greenmedinfo--2020-04-30--Rapid delivery of gold nanoparticles into colon cancer HT-29 cells by electroporation: in-vitro stud

Rapid delivery of gold nanoparticles into colon cancer HT-29 cells by electroporation: in-vitro study.

Background : Electroporation has become a routine technique for rapid drug delivery for the treatment of cancer .
Because of its simplicity and wide range of application , it has been applied for the transfer of gold-nanoparticles and can facilitate entry into target cancer cells .
Objective : The aim of this study is finding optimal conditions in order to obtain high GNPs- uptake and cell viability by means of electroporation .
Materials and Methods : In this in vitro study , exponential electrical pulse with electric field intensity ranging from 0.2 -2 kV/cm , pulse length of 100µs and @ @ @ @ @ @ @ .
Electroporated cell viability was investigated using MTS assay and GNPs-cellular uptake was assayed using graphite furnace atomic absorption spectrometry ( GFAAS ) .
Finally , electroporation results were compared with passive method .
Results : The maximum uptake occurred at 1.2 to 2 kV/cm and passive method happened .
The cell viability of 1.2 kV/cm and passive method was about 90 % , while the cell viability in 2 kV/cm drastically decreased to 50 % .
The findings showed that using two pulses of 1.2 kV/cm and 100µs is a convenient way @ @ @ @ @ @ @ GNPs into cells .
Conclusion : It is concluded that the electroporation-GNPs method could create an opportunistic context for colon cancer therapy .
This type of treatment is especially attractive for highly immunogenic types of cancers in patients who are otherwise not surgical candidates or whose tumors are unresectable .

Background: Electroporation has become a routine technique for rapid drug delivery for the treatment of cancer. Because of its simplicity and wide range of application, it has been applied for the transfer of gold-nanoparticles and can facilitate entry into target cancer cells.
Objective: The aim of this study is finding optimal conditions in order to obtain high GNPs- uptake and cell viability by means of electroporation.
Materials and Methods: In this in vitro study, exponential electrical pulse with electric field intensity ranging from 0.2 -2 kV/cm, pulse length of 100µs and the pulse number of 2 was used. Electroporated cell viability was investigated using MTS assay and GNPs-cellular uptake was assayed using graphite furnace atomic absorption spectrometry (GFAAS). Finally, electroporation results were compared with passive method.
Results: The maximum uptake occurred at 1.2 to 2 kV/cm and passive method happened. The cell viability of 1.2 kV/cm and passive method was about 90%, while the cell viability in 2 kV/cm drastically decreased to 50%. The findings showed that using two pulses of 1.2 kV/cm and 100µs is a convenient way and surrogate of passive method for internalizing GNPs into cells.
Conclusion: It is concluded that the electroporation-GNPs method could create an opportunistic context for colon cancer therapy. This type of treatment is especially attractive for highly immunogenic types of cancers in patients who are otherwise not surgical candidates or whose tumors are unresectable.


greenmedinfo--2020-04-30--The present data indicate that ashwagandha root extract could prevent thyroid dysfunction and reduce

The present data indicate that ashwagandha root extract could prevent thyroid dysfunction and reduce its complications on the nervous system.

The current aim is to evaluate the effect of ashwagandha root extract ( AE ) on the neurochemical changes induced in the cortex and hippocampus as a consequence of thyroid dysfunction induced by propylthiouracil ( PTU ) .were divided into ; control , AE treated rats , rat model of hypothyroidism and rat model of hypothyroidism treated with either AE or L-thyroxine ( T4 ) for 1 month .
Rat model of hypothyroidism showed a significant decrease in serum levels of tri-iodothyronine ( T3 ) and T4 and a significant increase in cortical and hippocampal lipid peroxidation ( MDA ) @ @ @ @ @ @ @ superoxide dismutase ( SOD ) and catalase ( CAT ) .
However , reduced glutathione ( GSH ) decreased significantly .
This was associated with a significant increase in hippocampal tumor necrosis factor-α ( TNF-α ) and cortical dopamine levels .
Both L-thyroxine and AE restored T3 and T4 levels .
In the hippocampus L-Thyroxine prevented the increase in MDA and restored GSH but failed to restore the increased NO and TNF-α .
In the cortex L-thyroxine did n't change the increased MDA and NO and the decreased GSH induced by PTU .
@ @ @ @ @ @ @ CAT .
AE prevented the increased hippocampal MDA , NO and TNF-α and the decreased GSH level induced by PTU .
In the cortex AE failed to restore MDA and NO but prevented the decrease in GSH .
The increase in cortical dopamine level induced by PTU was ameliorated by L-thyroxine and improved by AE .
The present data indicate that AE could prevent thyroid dysfunction and reduce its complications on the nervous system including oxidative stress and neuroinflammation .

The current aim is to evaluate the effect of ashwagandha root extract (AE) on the neurochemical changes induced in the cortex and hippocampus as a consequence of thyroid dysfunction induced by propylthiouracil (PTU).were divided into; control, AE treated rats, rat model of hypothyroidism and rat model of hypothyroidism treated with either AE or L-thyroxine (T4) for 1 month. Rat model of hypothyroidism showed a significant decrease in serum levels of tri-iodothyronine (T3) and T4 and a significant increase in cortical and hippocampal lipid peroxidation (MDA), nitric oxide (NO), superoxide dismutase (SOD) and catalase (CAT). However, reduced glutathione (GSH) decreased significantly. This was associated with a significant increase in hippocampal tumor necrosis factor-α (TNF-α) and cortical dopamine levels. Both L-thyroxine and AE restored T3 and T4 levels. In the hippocampus L-Thyroxine prevented the increase in MDA and restored GSH but failed to restore the increased NO and TNF-α. In the cortex L-thyroxine didn't change the increased MDA and NO and the decreased GSH induced by PTU. L-thyroxine increased cortical and hippocampal SOD and CAT. AE prevented the increased hippocampal MDA, NO and TNF-α and the decreased GSH level induced by PTU. In the cortex AE failed to restore MDA and NO but prevented the decrease in GSH. The increase in cortical dopamine level induced by PTU was ameliorated by L-thyroxine and improved by AE. The present data indicate that AE could prevent thyroid dysfunction and reduce its complications on the nervous system including oxidative stress and neuroinflammation.


greenmedinfo--2020-04-30--Bacteriocin-capped silver nanoparticles for enhanced antimicrobial efficacy against food pathogens.

Bacteriocins produced by lactic acid bacteria are safer alternatives to the more popularly used chemical preservatives which exhibit several adverse effects .
The bacteriocins have an advantage of being efficient in controlling food pathogens without possessing any side-effects .
However , the bacteriocins have a limitation of exhibiting a narrow antimicrobial spectrum and having a high-dosage requirement .
With an aim to combat these limitations , the present study involved the biosynthesis of bacteriocin-capped nanoparticles , using two bacteriocins ( Bac4463 and Bac22 ) extracted and purified fromstrains .
Nanoconjugates synthesised at optimum conditions were characterized using various physico-chemical techniques @ @ @ @ @ @ @ with the pathogenic bacteria was observed using scanning electron microscopy , wherein the deformed and elongated cells were clearly visible.antimicrobial efficacy of both Bac4463-capped silver nanoparticles and Bac22-capped silver nanoparticles against different food pathogens was observed to be enhanced in comparison to the antimicrobial activity of bacteriocins alone .
Minimum inhibitory concentration was observed to be as low as 8 μg/ml for Bac4463-capped silver nanoparticles against , and 2 μg/ml for Bac22-capped silver nanoparticles against .
This study , therefore , recommends the use of bacteriocin-capped nanoparticles as food preservatives to control the @ @ @ @ @ @

Bacteriocins produced by lactic acid bacteria are safer alternatives to the more popularly used chemical preservatives which exhibit several adverse effects. The bacteriocins have an advantage of being efficient in controlling food pathogens without possessing any side-effects. However, the bacteriocins have a limitation of exhibiting a narrow antimicrobial spectrum and having a high-dosage requirement. With an aim to combat these limitations, the present study involved the biosynthesis of bacteriocin-capped nanoparticles, using two bacteriocins (Bac4463 and Bac22) extracted and purified fromstrains. Nanoconjugates synthesised at optimum conditions were characterized using various physico-chemical techniques. The interaction of bacteriocin-capped silver nanoparticles with the pathogenic bacteria was observed using scanning electron microscopy, wherein the deformed and elongated cells were clearly visible.antimicrobial efficacy of both Bac4463-capped silver nanoparticles and Bac22-capped silver nanoparticles against different food pathogens was observed to be enhanced in comparison to the antimicrobial activity of bacteriocins alone. Minimum inhibitory concentration was observed to be as low as 8 μg/ml for Bac4463-capped silver nanoparticles against, and 2 μg/ml for Bac22-capped silver nanoparticles against. This study, therefore, recommends the use of bacteriocin-capped nanoparticles as food preservatives to control the growth of food spoiling bacteria.


greenmedinfo--2020-04-30--Biogenic synthesis of silver nanoparticles: Antibacterial and cytotoxic potential.

In green chemistry , the application of a biogenic material as a mediator in nanoparticles formation is an innovative nanotechnology .
Our current investigation aimed at testing the cytotoxic potential and antimicrobial ability of silver nanoparticles ( AgNPs ) that were prepared usingroots andleaf extracts as stabilizing and reducing agents .
An agar well diffusion technique was employed to detect synthesized AgNPs antibacterial ability on , andbacterial strains .
Furthermore , their cytotoxic capability against LoVo , MDA-MB231 and HepG2 ca cells was investigated .
For phyto-chemical detection in the biogenic AgNPs the Fourier-transform infrared spectroscopy ( FT-IR ) was @ @ @ @ @ @ @ Transmission Electron Microscope ) and FE-SEM ( Field Emission Scanning Electron Microscope ) were used to detect biogenic AgNPs ' size and morphology .
The current results showed the capability of tested plant extract for conversion of Ag ions to AgNPs with a mean size ranging between 90.8 ± 0.8 and 183.2 ± 0.7 nm in diameter .
Furthermore , prepared AgNPs exhibited apoptotic potential against HepG2 , LoVo , and MDA-MB 231cell with ICranging between 10.9 and 21.4 μg/ml and antibacterial ability in the range of 16.0 ± 0.1 to 22.0 ± @ @ @ @ @ @ @ in AgNPs treated cells could be the main indicator for their positive effect causing apoptosis .
The current investigation suggested that the green production of AgNPs could be a suitable substitute to large-scale production of AgNPs , since stable and active nanoparticles could be obtained .

In green chemistry, the application of a biogenic material as a mediator in nanoparticles formation is an innovative nanotechnology. Our current investigation aimed at testing the cytotoxic potential and antimicrobial ability of silver nanoparticles (AgNPs) that were prepared usingroots andleaf extracts as stabilizing and reducing agents. An agar well diffusion technique was employed to detect synthesized AgNPs antibacterial ability on, andbacterial strains. Furthermore, their cytotoxic capability against LoVo, MDA-MB231 and HepG2 ca cells was investigated. For phyto-chemical detection in the biogenic AgNPs the Fourier-transform infrared spectroscopy (FT-IR) was considered. Zeta sizer, TEM (Transmission Electron Microscope) and FE-SEM (Field Emission Scanning Electron Microscope) were used to detect biogenic AgNPs' size and morphology. The current results showed the capability of tested plant extract for conversion of Ag ions to AgNPs with a mean size ranging between 90.8 ± 0.8 and 183.2 ± 0.7 nm in diameter. Furthermore, prepared AgNPs exhibited apoptotic potential against HepG2, LoVo, and MDA-MB 231cell with ICranging between 10.9 and 21.4 μg/ml and antibacterial ability in the range of 16.0 ± 0.1 to 22.0 ± 1.8 mm diameter. Activation of caspases in AgNPs treated cells could be the main indicator for their positive effect causing apoptosis. The current investigation suggested that the green production of AgNPs could be a suitable substitute to large-scale production of AgNPs, since stable and active nanoparticles could be obtained.


greenmedinfo--2020-04-30--Curcumin as a therapeutic agent in leukemia.

Leukemia comprises a group of hematological malignancies responsible for 8 % of all cancers and is the most common cancer @ @ @ @ @ improvements in leukemia treatment , the efficacy of conventional chemotherapeutic agents is low and the @ @ @ @ @ with frequent relapses and high mortality .
Curcumin is a yellow polyphenol compound with diverse @ @ @ @ @ antioxidant , antidiabetic , anti-inflammatory , immunomodulatory , hepatoprotective , lipid-regulating , antidepressant , and @ @ @ @ @ experimental studies have reported the benefits of curcumin in treating leukemia .
Curcumin 's anticancer @ @ @ @ @ mechanisms .
Here , we review the effects of curcumin on various types of leukemia @ @ @ @ @ action .

Leukemia comprises a group of hematological malignancies responsible for 8% of all cancers and is the most common cancer in children. Despite significant improvements in leukemia treatment, the efficacy of conventional chemotherapeutic agents is low and the disease carries a poor prognosis with frequent relapses and high mortality. Curcumin is a yellow polyphenol compound with diverse pharmacological actions including anticancer, antioxidant, antidiabetic, anti-inflammatory, immunomodulatory, hepatoprotective, lipid-regulating, antidepressant, and antiarthritic. Many cellular and experimental studies have reported the benefits of curcumin in treating leukemia. Curcumin's anticancer effects are exerted via various mechanisms. Here, we review the effects of curcumin on various types of leukemia whilst considering its mechanisms of action.


greenmedinfo--2020-04-30--Curcumin and intestinal inflammatory diseases: molecular mechanisms of protection.

Intestinal inflammatory diseases , such as Crohn 's disease , ulcerative colitis , and necrotizing enterocolitis , are becoming increasingly prevalent .
While knowledge of the pathogenesis of these related diseases is currently incomplete , each of these conditions is thought to involve a dysfunctional , or overstated , host immunological response to both bacteria and dietary antigens , resulting in unchecked intestinal inflammation and , often , alterations in the intestinal microbiome .
This inflammation can result in an impaired intestinal barrier allowing for bacterial translocation , potentially resulting in systemic inflammation and , in severe cases , sepsis @ @ @ @ @ @ @ in the case of inflammatory bowel disease , can even spur cancer growth in the longer-term .
Recent research has indicated certain natural products with anti-inflammatory properties , such as curcumin , can help tame the inflammation involved in intestinal inflammatory diseases , thus improving intestinal barrier function , and potentially , clinical outcomes .
In this review , we explore the potential therapeutic properties of curcumin on intestinal inflammatory diseases , including its antimicrobial and immunomodulatory properties , as well as its potential to alter the intestinal microbiome .
Curcumin may play @ @ @ @ @ @ @ treatment in the future , particularly as an adjuvant therapy .

Intestinal inflammatory diseases, such as Crohn's disease, ulcerative colitis, and necrotizing enterocolitis, are becoming increasingly prevalent. While knowledge of the pathogenesis of these related diseases is currently incomplete, each of these conditions is thought to involve a dysfunctional, or overstated, host immunological response to both bacteria and dietary antigens, resulting in unchecked intestinal inflammation and, often, alterations in the intestinal microbiome. This inflammation can result in an impaired intestinal barrier allowing for bacterial translocation, potentially resulting in systemic inflammation and, in severe cases, sepsis. Chronic inflammation of this nature, in the case of inflammatory bowel disease, can even spur cancer growth in the longer-term. Recent research has indicated certain natural products with anti-inflammatory properties, such as curcumin, can help tame the inflammation involved in intestinal inflammatory diseases, thus improving intestinal barrier function, and potentially, clinical outcomes. In this review, we explore the potential therapeutic properties of curcumin on intestinal inflammatory diseases, including its antimicrobial and immunomodulatory properties, as well as its potential to alter the intestinal microbiome. Curcumin may play a significant role in intestinal inflammatory disease treatment in the future, particularly as an adjuvant therapy.


greenmedinfo--2020-05-01--Effects of fish n-3 PUFAs on intestinal microbiota and immune system.

Studies over several decades have documented the beneficial actions of n-3 polyunsaturated fatty acids ( PUFAs ) , which are plentiful in fish oil , in different disease states .
Mechanisms responsible for the efficacy of n-3 PUFAs include : ( 1 ) Reduction of triglyceride levels ; ( 2 ) anti-arrhythmic and antithrombotic effects , and ( 3 ) resolution of inflammatory processes .
The human microbiota project and subsequent studies using next-generation sequencing technology have highlighted that thousands of different microbial species are present in the human gut , and that there has been a significant variability of @ @ @ @ @ @ @ .
Several factors ( gestational age , mode of delivery , diet , sanitation and antibiotic treatment ) influence the bacterial community in the human gastrointestinal tract , and among these diet habits play a crucial role .
The disturbances in the gut microbiota composition , i.e.
, gut dysbiosis , have been associated with diseases ranging from localized gastrointestinal disorders to neurologic , respiratory , metabolic , ocular , and cardiovascular illnesses .
Many studies have been published about the effects of probiotics and prebiotics on the gut microbiota/microbioma .
On the @ @ @ @ @ @ @ have been less well defined .
However , experimental studies suggested that gut microbiota , n-3 PUFAs , and host immune cells work together to ensure the intestinal wall integrity .
This review discussed current evidence concerning the links among gut microbiota , n-3 PUFAs intake , and human inflammatory disease .

Studies over several decades have documented the beneficial actions of n-3 polyunsaturated fatty acids (PUFAs), which are plentiful in fish oil, in different disease states. Mechanisms responsible for the efficacy of n-3 PUFAs include: (1) Reduction of triglyceride levels; (2) anti-arrhythmic and antithrombotic effects, and (3) resolution of inflammatory processes. The human microbiota project and subsequent studies using next-generation sequencing technology have highlighted that thousands of different microbial species are present in the human gut, and that there has been a significant variability of taxa in the microbiota composition among people. Several factors (gestational age, mode of delivery, diet, sanitation and antibiotic treatment) influence the bacterial community in the human gastrointestinal tract, and among these diet habits play a crucial role. The disturbances in the gut microbiota composition, i.e., gut dysbiosis, have been associated with diseases ranging from localized gastrointestinal disorders to neurologic, respiratory, metabolic, ocular, and cardiovascular illnesses. Many studies have been published about the effects of probiotics and prebiotics on the gut microbiota/microbioma. On the contrary, PUFAs in the gut microbiota have been less well defined. However, experimental studies suggested that gut microbiota, n-3 PUFAs, and host immune cells work together to ensure the intestinal wall integrity. This review discussed current evidence concerning the links among gut microbiota, n-3 PUFAs intake, and human inflammatory disease.


greenmedinfo--2020-05-01--n-3 PUFAs attenuated anti-viral CD8+ T cell responses against acute viral infection and could be use

n-3 PUFAs attenuated anti-viral CD8+ T cell responses against acute viral infection and could be used to alleviate immunopathology mediated by viral infection.

Omega-3 ( -3 ) polyunsaturated fatty acids ( PUFAs ) have been known to exert anti-inflammatory effects on various disease @ @ @ @ @ effect on CD8T cell-mediated immunopathology upon viral infection has not been well elucidated yet .
@ @ @ @ @ investigated the possible implication of-3 PUFAs in CD8T cell responses against an acute viral infection @ @ @ @ @ mice that are capable of synthesizing-3 PUFAs from-6 PUFAs with lymphocytic choriomeningitis virus ( LCMV @ @ @ @ @ of anti-viral CD8T cell responses .
Interestingly , expansion of adoptively transferred wild-type ( WT @ @ @ @ @ ( TCR ) transgenic CD8 ( P14 ) T cells into FAT-1 mice was significantly @ @ @ @ @ of anti-viral CD4helper T cells was reduced in FAT-1 mice .
Importantly , P14 cells @ @ @ @ @ transferred into WT mice exhibited a substantially decreased ability to proliferate and produce cytokines against @ @ @ @ @ -3 PUFAs attenuated anti-viral CD8T cell responses against an acute viral infection and thus could @ @ @ @ @ mediated by the viral infection .

Omega-3 (-3) polyunsaturated fatty acids (PUFAs) have been known to exert anti-inflammatory effects on various disease states. However, its effect on CD8T cell-mediated immunopathology upon viral infection has not been well elucidated yet. In this study, we investigated the possible implication of-3 PUFAs in CD8T cell responses against an acute viral infection. Infection of FAT-1 transgenic mice that are capable of synthesizing-3 PUFAs from-6 PUFAs with lymphocytic choriomeningitis virus (LCMV) resulted in significant reduction of anti-viral CD8T cell responses. Interestingly, expansion of adoptively transferred wild-type (WT) LCMV-specific T cell receptor (TCR) transgenic CD8(P14) T cells into FAT-1 mice was significantly decreased. Also, activation of anti-viral CD4helper T cells was reduced in FAT-1 mice. Importantly, P14 cells carrying thegene that were adoptively transferred into WT mice exhibited a substantially decreased ability to proliferate and produce cytokines against LCMV infection. Together,-3 PUFAs attenuated anti-viral CD8T cell responses against an acute viral infection and thus could be used to alleviate immunopathology mediated by the viral infection.


greenmedinfo--2020-05-01--Depressed Cancer Survivors Have Increased Risk of Death, Opioid Use

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This website is for information purposes only. By providing the information contained herein we are not diagnosing, treating, curing, mitigating, or preventing any type of disease or medical condition. Before beginning any type of natural, integrative or conventional treatment regimen, it is advisable to seek the advice of a licensed healthcare professional.
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greenmedinfo--2020-04-30--Depressed Cancer Survivors Have Increased Risk of Death, Opioid Use

Receiving a cancer diagnosis can be a trigger for feelings of depression and anxiety , and you also need to manage pain .
But mental health conditions may not only increase opioid use but also risk of death .
Learn how this common pain medication may become deadly when you 're depressed The need to properly screen pain patients for underlying mental health conditions before prescribing opioids is not a subject that gets much attention , despite the growing concern over the use of opioids in the U.S .
But a large-scale retrospective study has shined a discomforting spotlight on @ @ @ @ @ @ @ and increased risk of death from opioids prescribed to treat chronic pain .
Conducted by a team of researchers from the University of Virginia School of Medicine , the focus study [ i ] analyzed more than 10,000 women with first-time breast cancer diagnoses that were hormone receptor-positive , meaning cancer that grows in response to estrogen and/or progesterone .
[ ii ] The focus group included first-time users of a commonly prescribed therapy for hormonal cancers called adjuvant endocrine therapy ( AET ) , which is associated with painful side effects in @ @ @ @ @ @ @ understand the relationship among opioid use , risk of death and mental health conditions among breast cancer patients .
Nearly Half of Cancer Survivors Struggle With Mental Health Breast cancer is one of the most commonly diagnosed cancers among women in the U.S. and is responsible for more than 40,000 deaths annually .
[ iii ] AET is credited with improved breast cancer survival rates and is part of the American Society of Clinical Oncology 's ( ASCO ) practice guidelines for preventing recurrence of breast cancer .
[ iv ] However , @ @ @ @ @ @ @ such as musculoskeletal and joint pain [ v ] that are often addressed by prescriptions for opioid pain medications .
In a prior study , co-author Xi Tan found evidence suggesting that AET is significantly associated with opioid use among breast cancer survivors .
[ vi ] It was also known that prolonged opioid use is associated with lower survival rates in breast cancer survivors .
[ vii ] This led the research team to focus on how a mental health comorbidity ( secondary chronic condition ) may impact risk of death for @ @ @ @ @ @ @ using opioids for pain management .
According to researchers , approximately 40 % of patients with breast cancer have some type of mental health condition .
[ viii ] Anxiety and depression are considered normal responses to a cancer diagnosis , which can obscure diagnosis as a serious co-risk factor when it comes to opioid use .
The focus study , published in the July 2019 Journal of Oncology Practice , spotlights the need for physicians to use increasing caution when prescribing opioids to patients with any type of mental health condition .
@ @ @ @ @ @ @ true informed consent for patients who may not fully understand the increased risks of their mental health on potential health outcomes , including an increased risk of death .
With a keen awareness of these multiple risk factors , the research team asked the question , Is there an association between mental health conditions such as anxiety and depression with opioid use and survival in elderly breast cancer survivors using AET ?
Methods for this retrospective cohort study involved analyzing medical case histories on 10,452 adult women who received a new and primary @ @ @ @ @ @ @ 2011 .
Data was obtained from the SEER-Medicare linked database .
SEER refers to the Surveillance , Epidemiology , and End Results program of the National Cancer Institute , a source of epidemiologic information on the incidence and survival rates of cancer in the U.S. [ ix ] Patients met the study criteria if they initiated AET within one year of their cancer diagnosis .
The final requirement for inclusion was that patients had a two-year-or-greater follow-up period after the date of filling their first AET prescription .
The study measured those patients @ @ @ @ @ @ @ a mental health condition and who used opioids after starting AET and their subsequent health outcomes at the end of the study period .
Researchers were specifically interested in survival rates for this population group .
Opioid use among the focus group was defined as `` yes '' or `` no '' based on intake of any oral and transdermal opioids during the two-year period after the initiation of AET .
Commonly prescribed opioids include codeine , fentanyl , hydrocodone , hydromorphone , meperidine , morphine , methadone , oxycodone , xymorphone , @ @ @ @ @ @ @ well as any combinations of these drugs .
Researchers took a conservative approach to determining the mental health comorbidity factor .
Participants were placed in this group if they had received treatment for depression and/or anxiety for at least two days as an outpatient , or at least one day as an inpatient before receiving their cancer diagnosis .
If participants did not meet this stipulation , they were placed in the `` no mental health comorbid '' test group .
Opioid Use by Breast Cancer Survivors May Lead to Higher Rates of @ @ @ @ @ @ @ found that mental health comorbidities such as depression and anxiety were associated with higher hazards of mortality in women with breast cancer .
According to study authors , `` these differences were statistically significant .
`` [ x ] In addition , breast cancer survivors with mental health comorbidities were more likely to use opioids than survivors without mental health challenges , which suggests the increased risk of death may be related to opioid use .
Researchers also performed a secondary analysis of the groups by stratification according to their opioid use .
@ @ @ @ @ @ @ that used opioids had a higher hazard of mortality .
Research indicates that patients with breast cancer and comorbid mental health conditions have higher opioid use and reduced survival rates overall .
[ xi ] According to a paper published in the peer-reviewed journal Oncology , AET `` provides substantial benefit by reducing breast cancer recurrences and improving associated mortality in early-stage endocrine-responsive breast cancers ( estrogen receptor - and/or progesterone receptor-positive ) .
`` [ xii ] Since this standard of treatment has a high risk of associated pain , it is @ @ @ @ @ @ @ therapies that treat the whole person .
Opioids can not be a one-size-fits-all prescription for pain .
Researchers suggested that physicians limit the prescription of opioids and instead encourage AET patients with associated pain to engage alternative therapies like massage , acupuncture , cognitive behavioral or physical therapy and other holistic methods for dealing with pain .
[ 1 ] For minor to moderate pain , you can also explore the opioid-like effects of certain foods on GreenMedInfo.com 's natural health database .
[ i ] Mental Health Comorbidities and Elevated Risk of @ @ @ @ @ @ @ Using Adjuvant Endocrine Treatments .
Raj Desai , et al .
Journal of Oncology Practice 2019 15:9 , e777-e786 .
doi : 10.1200/JOP.18.00781 [ iv ] Burstein HJ , Lacchetti C , Anderson H , et al : Adjuvant endocrine therapy for women with hormone receptor-positive breast cancer : American Society of Clinical Oncology clinical practice guideline update on ovarian suppression .
J Clin Oncol 34:1689-1701 , 2016 [ vi ] Tan X , Camacho TF , LeBaron VT , et al : Opioid use among female breast cancer patients using different adjuvant @ @ @ @ @ @ @ Treat 165:455-465 , 2017 [ vii ] Mental Health Comorbidities and Elevated Risk of Opioid Use in Elderly Breast Cancer Survivors Using Adjuvant Endocrine Treatments .
Raj Desai , et al .
Journal of Oncology Practice 2019 15:9 , e777-e786 .
doi : 10.1200/JOP.18.00781 [ viii ] Mehnert A , Brahler E , Faller H , et al : Four-week prevalence of mental disorders in patients with cancer across major tumor entities .
J Clin Oncol 32:3540-3546 , 2014 [ x ] Mental Health Comorbidities and Elevated Risk of Opioid Use in Elderly @ @ @ @ @ @ @ .
Raj Desai , et al .
Journal of Oncology Practice 2019 15:9 , e777-e786 .
doi : 10.1200/JOP.18.00781 [ xi ] Mental Health Comorbidities and Elevated Risk of Opioid Use in Elderly Breast Cancer Survivors Using Adjuvant Endocrine Treatments .
Raj Desai , et al .
Journal of Oncology Practice 2019 15:9 , e777-e786 .
doi : 10.1200/JOP.18.00781 [ xii ] Cancer Network , Oncology , Extending Adjuvant Endocrine Therapy in Breast Cancer : Who , What , Why ?
Accessed : 9 Mar 2020 , https : //www.cancernetwork.com/breast-cancer/extending-adjuvant-endocrine-therapy-breast-cancer-who-what-why [ 1 ] @ @ @ @ @ @ @ Opioid Use in Elderly Breast Cancer Survivors Using Adjuvant Endocrine Treatments .
Raj Desai , et al .
Journal of Oncology Practice 2019 15:9 , e777-e786 .
doi : 10.1200/JOP.18.00781

Visit our Re-post guidelines This article is copyrighted by GreenMedInfo LLC, 2020
Receiving a cancer diagnosis can be a trigger for feelings of depression and anxiety, and you also need to manage pain. But mental health conditions may not only increase opioid use but also risk of death. Learn how this common pain medication may become deadly when you're depressed
The need to properly screen pain patients for underlying mental health conditions before prescribing opioids is not a subject that gets much attention, despite the growing concern over the use of opioids in the U.S. But a large-scale retrospective study has shined a discomforting spotlight on the link between common mental health conditions and increased risk of death from opioids prescribed to treat chronic pain.
Conducted by a team of researchers from the University of Virginia School of Medicine, the focus study[i] analyzed more than 10,000 women with first-time breast cancer diagnoses that were hormone receptor-positive, meaning cancer that grows in response to estrogen and/or progesterone.[ii]
The focus group included first-time users of a commonly prescribed therapy for hormonal cancers called adjuvant endocrine therapy (AET), which is associated with painful side effects in some patients. This study aimed to understand the relationship among opioid use, risk of death and mental health conditions among breast cancer patients.
Nearly Half of Cancer Survivors Struggle With Mental Health
Breast cancer is one of the most commonly diagnosed cancers among women in the U.S. and is responsible for more than 40,000 deaths annually.[iii] AET is credited with improved breast cancer survival rates and is part of the American Society of Clinical Oncology's (ASCO) practice guidelines for preventing recurrence of breast cancer.[iv] However, AET is also associated with adverse effects such as musculoskeletal and joint pain[v] that are often addressed by prescriptions for opioid pain medications.
In a prior study, co-author Xi Tan found evidence suggesting that AET is significantly associated with opioid use among breast cancer survivors.[vi] It was also known that prolonged opioid use is associated with lower survival rates in breast cancer survivors.[vii] This led the research team to focus on how a mental health comorbidity (secondary chronic condition) may impact risk of death for survivors on an AET regimen who are using opioids for pain management.
According to researchers, approximately 40% of patients with breast cancer have some type of mental health condition.[viii] Anxiety and depression are considered normal responses to a cancer diagnosis, which can obscure diagnosis as a serious co-risk factor when it comes to opioid use.
The focus study, published in the July 2019 Journal of Oncology Practice, spotlights the need for physicians to use increasing caution when prescribing opioids to patients with any type of mental health condition. It also speaks to the need for true informed consent for patients who may not fully understand the increased risks of their mental health on potential health outcomes, including an increased risk of death.
Study Highlights Depression's Association With Negative Health Outcomes
With a keen awareness of these multiple risk factors, the research team asked the question, Is there an association between mental health conditions such as anxiety and depression with opioid use and survival in elderly breast cancer survivors using AET?
Methods for this retrospective cohort study involved analyzing medical case histories on 10,452 adult women who received a new and primary diagnosis of breast cancer between 2007 and 2011. Data was obtained from the SEER-Medicare linked database. SEER refers to the Surveillance, Epidemiology, and End Results program of the National Cancer Institute, a source of epidemiologic information on the incidence and survival rates of cancer in the U.S.[ix]
Patients met the study criteria if they initiated AET within one year of their cancer diagnosis. The final requirement for inclusion was that patients had a two-year-or-greater follow-up period after the date of filling their first AET prescription. The study measured those patients who also had a clinical diagnosis of a mental health condition and who used opioids after starting AET and their subsequent health outcomes at the end of the study period. Researchers were specifically interested in survival rates for this population group.
Opioid use among the focus group was defined as "yes" or "no" based on intake of any oral and transdermal opioids during the two-year period after the initiation of AET. Commonly prescribed opioids include codeine, fentanyl, hydrocodone, hydromorphone, meperidine, morphine, methadone, oxycodone, xymorphone, tapentadol, tramadol and pentazocine, as well as any combinations of these drugs.
Researchers took a conservative approach to determining the mental health comorbidity factor. Participants were placed in this group if they had received treatment for depression and/or anxiety for at least two days as an outpatient, or at least one day as an inpatient before receiving their cancer diagnosis. If participants did not meet this stipulation, they were placed in the "no mental health comorbid" test group.
Opioid Use by Breast Cancer Survivors May Lead to Higher Rates of Death
After analyzing the data, researchers found that mental health comorbidities such as depression and anxiety were associated with higher hazards of mortality in women with breast cancer. According to study authors, "these differences were statistically significant."[x] In addition, breast cancer survivors with mental health comorbidities were more likely to use opioids than survivors without mental health challenges, which suggests the increased risk of death may be related to opioid use.
Researchers also performed a secondary analysis of the groups by stratification according to their opioid use. In both groups, the survivor group that used opioids had a higher hazard of mortality. Research indicates that patients with breast cancer and comorbid mental health conditions have higher opioid use and reduced survival rates overall.[xi]
According to a paper published in the peer-reviewed journal Oncology, AET "provides substantial benefit by reducing breast cancer recurrences and improving associated mortality in early-stage endocrine-responsive breast cancers (estrogen receptor - and/or progesterone receptor-positive)."[xii] Since this standard of treatment has a high risk of associated pain, it is incumbent upon physicians to evaluate integrative pain therapies that treat the whole person. Opioids cannot be a one-size-fits-all prescription for pain.
Researchers suggested that physicians limit the prescription of opioids and instead encourage AET patients with associated pain to engage alternative therapies like massage, acupuncture, cognitive behavioral or physical therapy and other holistic methods for dealing with pain.[1] For minor to moderate pain, you can also explore the opioid-like effects of certain foods on GreenMedInfo.com's natural health database.
References
[i] Mental Health Comorbidities and Elevated Risk of Opioid Use in Elderly Breast Cancer Survivors Using Adjuvant Endocrine Treatments. Raj Desai, et al. Journal of Oncology Practice 2019 15:9, e777-e786. doi: 10.1200/JOP.18.00781


greenmedinfo--2020-04-30--Krill oil might be a new candidate for treatment of iron overload-induced toxicity.

Krill oil ( KO ) is a recent supplement which is rich in eicosapentaenoic acid ( EPA ) and docosahexaenoic acid ( DHA ) .
These fatty acids are found in both krill oil and fish oil .
In krill oil , they esterified to phospholipids , but in fish oil , they are esterified to triacylglycerols .
The target of this study was to investigate whether KO could help against iron overload-induced toxicity in liver and spleen .
Rats were randomly assigned into 3 categories : control rats , rats received iron in a drinking water for 8 weeks @ @ @ @ @ @ @ 40 mg/kg ) treatment for an extra 8 weeks .
Extent of hepatic and splenic injury was assessed via biochemical , histopathological and immunohistochemical evaluations .
KO effectively improved the microscopic features of liver and spleen .
Moreover , it decreased the increased levels of serum transaminases , ALP , LDH , iron , and ferritin and increased albumin serum level as well .
In addition , it restored the balance between oxidants and antioxidants in the hepatic and splenic tissues .
Furthermore , it decreased HO-1 levels , upregulated the production of @ @ @ @ @ @ @ MMP9 .
These findings altogether suggest that KO might be a new candidate for treatment of iron overload-induced toxicity .
Graphical abstract Graphical abstract .

Krill oil (KO) is a recent supplement which is rich in eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). These fatty acids are found in both krill oil and fish oil. In krill oil, they esterified to phospholipids, but in fish oil, they are esterified to triacylglycerols. The target of this study was to investigate whether KO could help against iron overload-induced toxicity in liver and spleen. Rats were randomly assigned into 3 categories: control rats, rats received iron in a drinking water for 8 weeks followed by either vehicle or KO (40 mg/kg) treatment for an extra 8 weeks. Extent of hepatic and splenic injury was assessed via biochemical, histopathological and immunohistochemical evaluations. KO effectively improved the microscopic features of liver and spleen. Moreover, it decreased the increased levels of serum transaminases, ALP, LDH, iron, and ferritin and increased albumin serum level as well. In addition, it restored the balance between oxidants and antioxidants in the hepatic and splenic tissues. Furthermore, it decreased HO-1 levels, upregulated the production of Nrf2, and limited the expression of MMP9. These findings altogether suggest that KO might be a new candidate for treatment of iron overload-induced toxicity. Graphical abstract Graphical abstract.


greenmedinfo--2020-04-30--Daily meal supplemented with astaxanthin-enriched yolk has mitigative effects against hypertension.

The aim of this study was to investigate the effects of egg yolk powder enriched with astaxanthin ( ASX-E ) on blood pressure in spontaneously hypertensive rats ( SHR ) and to verify the benefits of ASX-E as a functional food .
To investigate the antihypertensive effect , SHR were fed with an ASX-E mixed diet before hypertension development .
Blood pressures were determined periodically during the study by the tail-cuff method .
At the end of the study , animals were euthanized , and their thoracic aortas were collected to determine vascular conductance .
The thoracic aorta tension was @ @ @ @ @ @ @ Concentration-dependent response relationships were determined by cumulative addition of 10-10M Carbamoylcholine ( Cch ) .
Blood pressures of the SHR in the ASX-E mixed diet group were ASX-dose-dependently lower than that of those in the control group .
In SHR fed with an ASX-E mixed diet , Cch induced vasorelaxation in the thoracic aorta with endothelium lining but not without endothelium .
However , the antihypertensive effect of ASX-E was not observed on blood pressures in SHR that were fed with ASX-E only after the development of hypertension .
Results suggest that ASX-E @ @ @ @ @ @ @ development of hypertension .
Hence , the results of our research indicate that daily consumption of ASX-E has a potential benefit on human health .

The aim of this study was to investigate the effects of egg yolk powder enriched with astaxanthin (ASX-E) on blood pressure in spontaneously hypertensive rats (SHR) and to verify the benefits of ASX-E as a functional food. To investigate the antihypertensive effect, SHR were fed with an ASX-E mixed diet before hypertension development. Blood pressures were determined periodically during the study by the tail-cuff method. At the end of the study, animals were euthanized, and their thoracic aortas were collected to determine vascular conductance. The thoracic aorta tension was measured with a force displacement transducer. Concentration-dependent response relationships were determined by cumulative addition of 10-10M Carbamoylcholine (Cch). Blood pressures of the SHR in the ASX-E mixed diet group were ASX-dose-dependently lower than that of those in the control group. In SHR fed with an ASX-E mixed diet, Cch induced vasorelaxation in the thoracic aorta with endothelium lining but not without endothelium. However, the antihypertensive effect of ASX-E was not observed on blood pressures in SHR that were fed with ASX-E only after the development of hypertension. Results suggest that ASX-E protects endothelial function and thereby prevents the development of hypertension. Hence, the results of our research indicate that daily consumption of ASX-E has a potential benefit on human health.


greenmedinfo--2020-05-01--Fucoidan induces apoptosis of HT-29 cells.

Fucoidan has a variety of pharmacological activities , but the understanding of the mechanism of fucoidan-induced apoptosis of colorectal cancer cells remains limited .
The results of the present study demonstrated that the JNK signaling pathway is involved in the activation of apoptosis in colorectal cancer-derived HT-29 cells , and fucoidan induces apoptosis by activation of the DR4 at the transcriptional and protein levels .
The survival rate of HT-29 cells was approximately 40 % in the presence of 800μg/mL of fucoidan , but was increased to 70 % after DR4 was silenced by siRNA .
Additionally , fucoidan has @ @ @ @ @ @ @ potential and destroy the integrity of mitochondrial membrane .
In the presence of an inhibitor of cytochrome C inhibitor and DR4 siRNA or the presence of cytochrome C inhibitor only , the cell survival rate was significantly higher than when cells were treated with DR4 siRNA only .
These data indicate that both the DR4 and the mitochondrial pathways contribute to fucoidan-induced apoptosis of HT-29 cells , and the extrinsic pathway is upstream ofthe intrinsic pathway .
In conclusion , the current work identified the mechanism of fucoidan-induced apoptosis and provided a novel @ @ @ @ @ @ @ clinical applications of fucoidan as a drug .

Fucoidan has a variety of pharmacological activities, but the understanding of the mechanism of fucoidan-induced apoptosis of colorectal cancer cells remains limited. The results of the present study demonstrated that the JNK signaling pathway is involved in the activation of apoptosis in colorectal cancer-derived HT-29 cells, and fucoidan induces apoptosis by activation of the DR4 at the transcriptional and protein levels. The survival rate of HT-29 cells was approximately 40% in the presence of 800μg/mL of fucoidan, but was increased to 70% after DR4 was silenced by siRNA. Additionally, fucoidan has been shown to reduce the mitochondrial membrane potential and destroy the integrity of mitochondrial membrane. In the presence of an inhibitor of cytochrome C inhibitor and DR4 siRNA or the presence of cytochrome C inhibitor only, the cell survival rate was significantly higher than when cells were treated with DR4 siRNA only. These data indicate that both the DR4 and the mitochondrial pathways contribute to fucoidan-induced apoptosis of HT-29 cells, and the extrinsic pathway is upstream ofthe intrinsic pathway. In conclusion, the current work identified the mechanism of fucoidan-induced apoptosis and provided a novel theoretical basis for the future development of clinical applications of fucoidan as a drug.


greenmedinfo--2020-05-01--Shikonin suppresses NEAT1 and Akt signaling in treating paclitaxel-resistant non-small cell of lung

Shikonin suppresses NEAT1 and Akt signaling in treating paclitaxel-resistant non-small cell of lung cancer.

BACKGROUND : The development of paclitaxel-resistance led to the tumor relapse and treatment failure of non-small cell lung cancer .
@ @ @ @ @ show anti-cancer activity in many cancer types .
The present study aimed to investigate the @ @ @ @ @ paclitaxel-resistant non-small cell lung cancer treatment .
RESULTS : Shikonin decreased paclitaxel-resistant NSCLC cell viability @ @ @ @ @ xenograft tumor .
Shikonin induced apoptotic cell death of paclitaxel-resistant NSCLC cell lines and suppressed @ @ @ @ @ Akt signaling of paclitaxel-resistant NSCLC cell lines and xenograft tumors .
Either low dose or @ @ @ @ @ suppressed the cell growth and induced the cell apoptotic death in NEAT1 knockdown A549/PTX cells @ @ @ @ @ decreased .
CONCLUSIONS : Shikonin could be a promising candidate for paclitaxel-resistant NSCLC treatment .

BACKGROUND: The development of paclitaxel-resistance led to the tumor relapse and treatment failure of non-small cell lung cancer. Shikonin has been demonstrated to show anti-cancer activity in many cancer types. The present study aimed to investigate the anti-cancer activity of shikonin in paclitaxel-resistant non-small cell lung cancer treatment.
METHODS: MTT, clonogenic assay, apoptotic cell death analysis, western blot, qRT-PCR, gene knockdown and overexpression, xenograft experiment, immunohistochemistry were performed.
RESULTS: Shikonin decreased paclitaxel-resistant NSCLC cell viability and inhibited the growth of xenograft tumor. Shikonin induced apoptotic cell death of paclitaxel-resistant NSCLC cell lines and suppressed the level of NEAT1 and Akt signaling of paclitaxel-resistant NSCLC cell lines and xenograft tumors. Either low dose or high dose of shikonin considerably suppressed the cell growth and induced the cell apoptotic death in NEAT1 knockdown A549/PTX cells, and p-Akt expression was decreased.
CONCLUSIONS: Shikonin could be a promising candidate for paclitaxel-resistant NSCLC treatment.


greenmedinfo--2020-05-01--Shikonin is a promising candidate for treatment of postmenopausal osteoporosis.

BACKGROUND : Postmenopausal osteoporosis results from estrogen withdrawal and is characterized mainly by bone resorption .
Shikonin is a bioactive constitute of Chinese traditional herb which plays a role in antimicrobial and antitumor activities .
The study was designed to investigate the role of shikonin on postmenopausal osteoporosis and explore its underlying mechanisms .
METHODS : Immunofluorescence staining was performed to evaluate the effects of shikonin on actin ring formation .
The expression levels of the nuclear factor kappa-B ( NF-κB ) and mitogen-activated protein kinase ( MAPK ) pathway were determined by Western blot analysis .
To determine whether @ @ @ @ @ @ @ factor-κB ligand ( RANKL ) -induced association between receptor activator of NF-κB ( RANK ) and tumor necrosis factor receptor associated factor 6 ( TRAF6 ) , immunofluorescence staining and immunoprecipitation experiments were performed .
During our validation model , histomorphometric examination and micro-computed tomography ( CT ) were conducted to assess the morphology of osteoporosis .
RESULTS : Shikonin prevented bone loss by inhibiting osteoclastogenesis in vitro and improving bone loss in ovariectomized mice in vivo .
At the molecular level , Western blot analysis indicated that shikonin inhibited the phosphorylation of @ @ @ @ @ @ @ P50 , P65 , extracellular regulated protein kinases ( ERK ) , c-Jun N-terminal kinase ( JNK ) , and P38 .
Interaction of TRAF6 and RANK was prevented , and downstream MAPK and NF-κB signaling pathways were downregulated .
CONCLUSION : Osteoclastic bone resorption was reduced in the presence of shikonin in vitro and in vivo .
Shikonin is a promising candidate for treatment of postmenopausal osteoporosis .

BACKGROUND: Postmenopausal osteoporosis results from estrogen withdrawal and is characterized mainly by bone resorption. Shikonin is a bioactive constitute of Chinese traditional herb which plays a role in antimicrobial and antitumor activities. The study was designed to investigate the role of shikonin on postmenopausal osteoporosis and explore its underlying mechanisms.
METHODS: Immunofluorescence staining was performed to evaluate the effects of shikonin on actin ring formation. The expression levels of the nuclear factor kappa-B (NF-κB) and mitogen-activated protein kinase (MAPK) pathway were determined by Western blot analysis. To determine whether shikonin influences the receptor activator of nuclear factor-κB ligand (RANKL)-induced association between receptor activator of NF-κB (RANK) and tumor necrosis factor receptor associated factor 6 (TRAF6), immunofluorescence staining and immunoprecipitation experiments were performed. During our validation model, histomorphometric examination and micro-computed tomography (CT) were conducted to assess the morphology of osteoporosis.
RESULTS: Shikonin prevented bone loss by inhibiting osteoclastogenesis in vitro and improving bone loss in ovariectomized mice in vivo. At the molecular level, Western blot analysis indicated that shikonin inhibited the phosphorylation of inhibitor of NF-κB (IκB), P50, P65, extracellular regulated protein kinases (ERK), c-Jun N-terminal kinase (JNK), and P38. Interaction of TRAF6 and RANK was prevented, and downstream MAPK and NF-κB signaling pathways were downregulated.
CONCLUSION: Osteoclastic bone resorption was reduced in the presence of shikonin in vitro and in vivo. Shikonin is a promising candidate for treatment of postmenopausal osteoporosis.


greenmedinfo--2020-05-01--Shikonin could be a promising antioxidant candidate for age-associated neurodegenerative diseases.

Oxidative stress acts as the major causative factor for various age-associated neurodegenerative diseases , triggering cognitive and memory impairments .
In the present study , the underlying neuroprotective mechanism governing how shikonin acts against D-galactose ( D-gal ) -induced memory impairment , neuroinflammation and neuron damage was examined .
The results revealed that chronic administration of D-gal [ 150 mg/kg intraperitoneally ( i.p . )
] in mice caused cognitive and memory impairments , as determined by Morris water-maze test .
Shikonin treatment , however , alleviated D-gal-induced memory impairment and reversed the D-gal-induced neural damage and apoptosis .
Furthermore @ @ @ @ @ @ @ morphological analysis revealed that shikonin treatments markedly reduced D-gal induced neuroinflammation through inhibition of astrocytosis as determined by glial fibrillary acidic protein ( GFAP ) detection , and downregulating other inflammatory mediators , including tumor necrosis factor-α ( TNF-α ) , interleukin-1β ( IL-1β ) , and IL-6 .
Moreover , shikonin treatment led to inhibition of the activation of nuclear factor-κB ( NF-κB ) and the phosphorylation of mitogen-activated protein kinases ( MAPKs ) , preventing neurodegeneration .
Hence , taken together , the results of the present study suggested that shikonin @ @ @ @ @ @ @ neurodegeneration , possibly via the NF-κB/mitogen-activated protein kinase ( MAPK ) pathway .
Our data suggest that shikonin could be a promising , endogenous and compatible antioxidant candidate for age-associated neurodegenerative diseases , including Alzheimer 's disease .

Oxidative stress acts as the major causative factor for various age-associated neurodegenerative diseases, triggering cognitive and memory impairments. In the present study, the underlying neuroprotective mechanism governing how shikonin acts against D-galactose (D-gal)-induced memory impairment, neuroinflammation and neuron damage was examined. The results revealed that chronic administration of D-gal [150 mg/kg intraperitoneally (i.p.)] in mice caused cognitive and memory impairments, as determined by Morris water-maze test. Shikonin treatment, however, alleviated D-gal-induced memory impairment and reversed the D-gal-induced neural damage and apoptosis. Furthermore, western blotting and the results of morphological analysis revealed that shikonin treatments markedly reduced D-gal induced neuroinflammation through inhibition of astrocytosis as determined by glial fibrillary acidic protein (GFAP) detection, and downregulating other inflammatory mediators, including tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and IL-6. Moreover, shikonin treatment led to inhibition of the activation of nuclear factor-κB (NF-κB) and the phosphorylation of mitogen-activated protein kinases (MAPKs), preventing neurodegeneration. Hence, taken together, the results of the present study suggested that shikonin attenuated D-gal-induced memory impairment, neuroinflammation and neurodegeneration, possibly via the NF-κB/mitogen-activated protein kinase (MAPK) pathway. Our data suggest that shikonin could be a promising, endogenous and compatible antioxidant candidate for age-associated neurodegenerative diseases, including Alzheimer's disease.


greenmedinfo--2020-05-01--Shikonin inhibits growth, invasion and glycolysis of nasopharyngeal carcinoma cells.

Nasopharyngeal carcinoma ( NPC ) is a malignant tumor which is commonly found in East Asia and Africa .
The present clinical treatment of NPC is still mainly based on chemotherapeutics and is prone to drug resistance and adverse reactions .
Shikonin has been demonstrated to play the antitumor effect in various cancers .
However , the specific effects and related regulatory mechanism of Shikonin in NPC have not been clearly declared yet .
Cell viability was valued through 3- ( 4,5-dimethylthiazol-2-yl ) -2,5-diphenyltetrazolium bromide ( MTT ) assay , and cell proliferation was detected through colony formation assay and @ @ @ @ @ @ @ 33258 staining was used to value cell apoptosis .
Cell migration and invasion were valued through wound healing and transwell invasion assay , respectively .
Glucose uptake , lactate release , ATP level and pyruvate kinase M2 isoform ( PKM2 ) activity were measured using corresponding assay kits .
Western blotting was used to examine the expression of proteins related to cell proliferation , cell apoptosis , cell migration and the phosphatidylinositol 3 kinase ( PI3K ) /AKT signal pathway .
We found that Shikonin treatment effectively suppressed cell proliferation and induced obvious @ @ @ @ @ @ @ Besides , Shikonin treatment suppressed cell migration and invasion effectively .
The detection about glycolysis showed that Shikonin treatment suppressed cell glucose uptake , lactate release and ATP level .
The activity of PKM2 was also largely inhibited by Shikonin .
Further study revealed that the PI3K/AKT signal pathway was inactivated by Shikonin treatment .
In addition , the inducer of the PI3K/AKT signal pathway largely abolished the antitumor effect of Shikonin on cell proliferation , cell apoptosis , cell mobility and aerobic glycolysis in NPC cells .
Shikonin inhibits growth and invasion @ @ @ @ @ @ @ signal pathway .

Nasopharyngeal carcinoma (NPC) is a malignant tumor which is commonly found in East Asia and Africa. The present clinical treatment of NPC is still mainly based on chemotherapeutics and is prone to drug resistance and adverse reactions. Shikonin has been demonstrated to play the antitumor effect in various cancers. However, the specific effects and related regulatory mechanism of Shikonin in NPC have not been clearly declared yet. Cell viability was valued through 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, and cell proliferation was detected through colony formation assay and Bromodeoxyuridine (BrdU) assay. Hochest 33258 staining was used to value cell apoptosis. Cell migration and invasion were valued through wound healing and transwell invasion assay, respectively. Glucose uptake, lactate release, ATP level and pyruvate kinase M2 isoform (PKM2) activity were measured using corresponding assay kits. Western blotting was used to examine the expression of proteins related to cell proliferation, cell apoptosis, cell migration and the phosphatidylinositol 3 kinase (PI3K)/AKT signal pathway. We found that Shikonin treatment effectively suppressed cell proliferation and induced obvious cell apoptosis compared with the control. Besides, Shikonin treatment suppressed cell migration and invasion effectively. The detection about glycolysis showed that Shikonin treatment suppressed cell glucose uptake, lactate release and ATP level. The activity of PKM2 was also largely inhibited by Shikonin. Further study revealed that the PI3K/AKT signal pathway was inactivated by Shikonin treatment. In addition, the inducer of the PI3K/AKT signal pathway largely abolished the antitumor effect of Shikonin on cell proliferation, cell apoptosis, cell mobility and aerobic glycolysis in NPC cells. Shikonin inhibits growth and invasion of NPC cells through inactivating the PI3K/AKT signal pathway.


greenmedinfo--2020-05-01--Shikonin attenuated a high fat diet-induced nonalcoholic fatty liver disease.

Shikonin , a natural plant pigment , is known to have anti-obesity activity and to improve insulin sensitivity .
This @ @ @ @ @ effect of shikonin on hepatic steatosis , focusing on the AMP-activated protein kinase ( AMPK @ @ @ @ @ Hepa 1-6 cells and in high-fat fed mice .
Shikonin increased AMPK phosphorylation in a @ @ @ @ @ and inhibition of AMPK with compound C inhibited this activation .
In an oleic acid-induced @ @ @ @ @ shikonin suppressed oleic acid-induced lipid accumulation , increased AMPK phosphorylation , suppressed the expression of @ @ @ @ @ fatty acid oxidation-related genes .
Shikonin administration for four weeks decreased body weight gain and @ @ @ @ @ in the liver of high-fat fed mice .
Furthermore , shikonin promoted energy expenditure by @ @ @ @ @ In addition , shikonin increased the expression of PPARγ coactivator-1α ( PGC-1α ) , carnitine @ @ @ @ @ other mitochondrial function-related genes .
These results suggest that shikonin attenuated a high fat diet-induced @ @ @ @ @ stimulating fatty acid oxidation and energy expenditure via AMPK activation .

Shikonin, a natural plant pigment, is known to have anti-obesity activity and to improve insulin sensitivity. This study aimed to examine the effect of shikonin on hepatic steatosis, focusing on the AMP-activated protein kinase (AMPK) and energy expenditure in Hepa 1-6 cells and in high-fat fed mice. Shikonin increased AMPK phosphorylation in a dose- and time-dependent manner, and inhibition of AMPK with compound C inhibited this activation. In an oleic acid-induced steatosis model in hepatocytes, shikonin suppressed oleic acid-induced lipid accumulation, increased AMPK phosphorylation, suppressed the expression of lipogenic genes, and stimulated fatty acid oxidation-related genes. Shikonin administration for four weeks decreased body weight gain and the accumulation of lipid droplets in the liver of high-fat fed mice. Furthermore, shikonin promoted energy expenditure by activating fatty acid oxidation. In addition, shikonin increased the expression of PPARγ coactivator-1α (PGC-1α), carnitine palmitoyltransferase-1 (CPT1) and other mitochondrial function-related genes. These results suggest that shikonin attenuated a high fat diet-induced nonalcoholic fatty liver disease by stimulating fatty acid oxidation and energy expenditure via AMPK activation.


greenmedinfo--2020-05-01--Benefits of Chlorogenic Acids Found in Coffee


greenmedinfo--2020-05-01--Curcumin reduces lung inflammation via Wnt/β-catenin signaling in mouse model of asthma.

OBJECTIVES : Asthma is a chronic inflammatory , heterogeneous airway disease affecting millions of people around the world .
Curcumin has been found to have anti-inflammatory and antifibrosis effects .
Researchers reported that curcumin regulated Wnt/β-catenin signaling in lots of cells .
However , whether curcumin regulates the levels of Wnt/β-Catenin signaling in lung tissues and DCs ( dendritic cells ) remains unclear .
In this study , we assessed the effects of curcumin on DCs and asthma .
METHODS : C57BL/6 mice immunized with OVA ( ovalbumin ) were challenged thrice with an aerosol of OVA every second day @ @ @ @ @ @ @ was administered intraperitoneally to OVA-immunized C57BL/6 mice on day 24 once a day for 9 days .
Mice were analyzed for effects of curcumin on asthma , inflammatory cell infiltration and cytokine levels in lung tissue .
DCs were isolated from mouse bone morrow .
Thesurface markers CD40 , CD86 and CD11c of DCs was detected by FACS ( fluorescence activated cell sorting ) and the function of DCs was detected by mixed lymphocyte reaction .
The expression of GSK-3β and β-catenin was detected by Western Blot .
RESULTS : Results showed that @ @ @ @ @ @ @ in BALF ( bronchoalveolar lavage fluid ) , elevated lung inflammation scores in mice .
Curcumin dose-dependently reversed the alterations induced by OVA in the asthmatic mice .
Curcumin activated Wnt/β-catenin signaling pathway in DCs and asthmatic mouse lungs .
CONCLUSIONS : Curcumin could influence the morphology and function of DCs , ease asthma symptom and inflammatory reaction through the activation of Wnt/β-catenin signaling .
These results provide new evidence new evidence for application of curcumin on asthma .

OBJECTIVES: Asthma is a chronic inflammatory, heterogeneous airway disease affecting millions of people around the world. Curcumin has been found to have anti-inflammatory and antifibrosis effects. Researchers reported that curcumin regulated Wnt/β-catenin signaling in lots of cells. However, whether curcumin regulates the levels of Wnt/β-Catenin signaling in lung tissues and DCs (dendritic cells) remains unclear. In this study, we assessed the effects of curcumin on DCs and asthma.
METHODS: C57BL/6 mice immunized with OVA (ovalbumin) were challenged thrice with an aerosol of OVA every second day for 8 days. Dexamethasone or curcumin was administered intraperitoneally to OVA-immunized C57BL/6 mice on day 24 once a day for 9 days. Mice were analyzed for effects of curcumin on asthma, inflammatory cell infiltration and cytokine levels in lung tissue. DCs were isolated from mouse bone morrow. Thesurface markers CD40, CD86 and CD11c of DCs was detected by FACS (fluorescence activated cell sorting) and the function of DCs was detected by mixed lymphocyte reaction. The expression of GSK-3β and β-catenin was detected by Western Blot.
RESULTS: Results showed that OVA increased the number of inflammatory factors in BALF (bronchoalveolar lavage fluid), elevated lung inflammation scores in mice. Curcumin dose-dependently reversed the alterations induced by OVA in the asthmatic mice. Curcumin activated Wnt/β-catenin signaling pathway in DCs and asthmatic mouse lungs.
CONCLUSIONS: Curcumin could influence the morphology and function of DCs, ease asthma symptom and inflammatory reaction through the activation of Wnt/β-catenin signaling. These results provide new evidence new evidence for application of curcumin on asthma.


greenmedinfo--2020-05-01--Curcumin alleviates macrophage activation and lung inflammation induced by influenza virus infection

Curcumin alleviates macrophage activation and lung inflammation induced by influenza virus infection.

BACKGROUND : Influenza A viruses ( IAV ) result in severe public health problems with worldwide each year .
Overresponse of immune system to IAV infection leads to complications , and ultimately causing morbidity and mortality .
OBJECTIVE : Curcumin has been reported to have anti-inflammatory ability .
However , its molecular mechanism in immune responses remains unclear .
METHODS : We detected the pro-inflammatory cytokine secretion and nuclear factor kappa-light-chain-enhancer of activated B cell ( NF-κB ) -related protein expression in human macrophages or mice infected by IAV with or without curcumin treatment .
RESULTS : We found that @ @ @ @ @ @ @ of pro-inflammatory cytokine productions of human macrophages and mice immune cells .
However , curcumin treatment after IAV infection downregulated these cytokines production in a dose-dependent manner .
Moreover , the NF-κB has been activated in human macrophages after IAV infection , while administration of curcumin inhibited NF-κB signaling pathway via promoting the expression of nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor , alpha ( IκBα ) , and inhibiting the translocation of p65 from cytoplasm to nucleus .
CONCLUSIONS : In summary , IAV infection could result in @ @ @ @ @ @ @ especially macrophages .
Curcumin has the therapeutic potentials to relieve these inflammatory responses through inhibiting the NF-κB signaling pathway .

BACKGROUND: Influenza A viruses (IAV) result in severe public health problems with worldwide each year. Overresponse of immune system to IAV infection leads to complications, and ultimately causing morbidity and mortality.
OBJECTIVE: Curcumin has been reported to have anti-inflammatory ability. However, its molecular mechanism in immune responses remains unclear.
METHODS: We detected the pro-inflammatory cytokine secretion and nuclear factor kappa-light-chain-enhancer of activated B cell (NF-κB)-related protein expression in human macrophages or mice infected by IAV with or without curcumin treatment.
RESULTS: We found that the IAV infection caused a dramatic enhancement of pro-inflammatory cytokine productions of human macrophages and mice immune cells. However, curcumin treatment after IAV infection downregulated these cytokines production in a dose-dependent manner. Moreover, the NF-κB has been activated in human macrophages after IAV infection, while administration of curcumin inhibited NF-κB signaling pathway via promoting the expression of nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor, alpha (IκBα), and inhibiting the translocation of p65 from cytoplasm to nucleus.
CONCLUSIONS: In summary, IAV infection could result in the inflammatory responses of immune cells, especially macrophages. Curcumin has the therapeutic potentials to relieve these inflammatory responses through inhibiting the NF-κB signaling pathway.


greenmedinfo--2020-05-01--Curcumin ameliorates asthmatic airway inflammation.

Previous studies have shown that curcumin alleviates asthma in vivo .
However , the relationship between curcumin and the nuclear factor-E2-related factor 2 ( Nrf2 ) /haem oxygenase ( HO ) -1 pathway in asthma treatment remains unknown .
The aim of the present study was to investigate the mechanisms of curcumin involved in the amelioration of airway inflammation in a mouse asthma model .
Curcumin was administrated to asthmatic mice , and bronchoalveolar lavage fluid was collected .
Inflammatory cell infiltration was measured by Giemsa staining .
Immunoglobulin E production in bronchoalveolar lavage fluid was measured by enzyme-linked immunosorbent @ @ @ @ @ @ @ haematoxylin-eosin and periodic acid-Schiff staining .
Airway hyperresponsiveness was examined by whole-body plethysmography .
Nuclear factor-E2-related factor 2 , HO-1 , nuclear factor-κB and inhibitory κB/p-inhibitory κB levels in lung tissues were detected by western blot , and Nrf2 activity was measured by electrophoretic mobility shift assay .
Tumour necrosis factor-α , interleukin ( IL ) -1β , and IL-6 levels in the small interfering RNA-transfected cells were detected by enzyme-linked immunosorbent assay .
Curcumin treatment significantly reduced immunoglobulin E production , attenuated inflammatory cell accumulation and goblet cell hyperplasia , and ameliorated @ @ @ @ @ @ @ factor-E2-related factor 2 and HO-1 levels in lung tissues were significantly increased .
Meanwhile , Nrf2 activity was enhanced .
Nuclear factor-κB and p-inhibitory κB levels were elevated in the lung tissue of ovalbumin-challenged mice .
Both were restored to normal levels after curcumin treatment .
Haem oxygenase-1 and nuclear Nrf2 levels were enhanced indose- and time-dependent manners in curcumin-treated RAW264.7 cells .
Curcumin blocked lipopolysaccharide-upregulated expression of tumour necrosis factor-α , IL-1β , and IL-6 .
After the cells were transfected with HO-1 or Nrf2 small interfering RNA , lipopolysaccharide-induced pro-inflammation cytokine @ @ @ @ @ @ @ , curcumin might alleviate airway inflammation in asthma through the Nrf2/HO-1 pathway , potentially making it an effective drug in asthma treatment .

Previous studies have shown that curcumin alleviates asthma in vivo. However, the relationship between curcumin and the nuclear factor-E2-related factor 2 (Nrf2)/haem oxygenase (HO)-1 pathway in asthma treatment remains unknown. The aim of the present study was to investigate the mechanisms of curcumin involved in the amelioration of airway inflammation in a mouse asthma model. Curcumin was administrated to asthmatic mice, and bronchoalveolar lavage fluid was collected. Inflammatory cell infiltration was measured by Giemsa staining. Immunoglobulin E production in bronchoalveolar lavage fluid was measured by enzyme-linked immunosorbent assay. Histological analyses were evaluated with haematoxylin-eosin and periodic acid-Schiff staining. Airway hyperresponsiveness was examined by whole-body plethysmography. Nuclear factor-E2-related factor 2, HO-1, nuclear factor-κB and inhibitory κB/p-inhibitory κB levels in lung tissues were detected by western blot, and Nrf2 activity was measured by electrophoretic mobility shift assay. Tumour necrosis factor-α, interleukin (IL)-1β, and IL-6 levels in the small interfering RNA-transfected cells were detected by enzyme-linked immunosorbent assay. Curcumin treatment significantly reduced immunoglobulin E production, attenuated inflammatory cell accumulation and goblet cell hyperplasia, and ameliorated mucus secretion and airway hyperresponsiveness. Nuclear factor-E2-related factor 2 and HO-1 levels in lung tissues were significantly increased. Meanwhile, Nrf2 activity was enhanced. Nuclear factor-κB and p-inhibitory κB levels were elevated in the lung tissue of ovalbumin-challenged mice. Both were restored to normal levels after curcumin treatment. Haem oxygenase-1 and nuclear Nrf2 levels were enhanced indose- and time-dependent manners in curcumin-treated RAW264.7 cells. Curcumin blocked lipopolysaccharide-upregulated expression of tumour necrosis factor-α, IL-1β, and IL-6. After the cells were transfected with HO-1 or Nrf2 small interfering RNA, lipopolysaccharide-induced pro-inflammation cytokine expression was significantly restored. In summary, curcumin might alleviate airway inflammation in asthma through the Nrf2/HO-1 pathway, potentially making it an effective drug in asthma treatment.


greenmedinfo--2020-05-01--Emodin alleviated LPS-induced pulmonary inflammation in rat lung tissues.

OBJECTIVE AND DESIGN : This study aimed to investigate the anti-pulmonary inflammation effect of emodin on Wistar rats with lipopolysaccharide ( LPS ) -induced acute lung injury ( ALI ) and RAW264.7 cells through the mammalian target of rapamycin ( mTOR ) /hypoxia-inducible factor-1α ( HIF-1α ) /vascular endothelial growth factor ( VEGF ) signaling pathway .
TREATMENT : LPS was used to induce inflammation in rats or RAW264.7 cells and emodin was given once a day before LPS stimulation and continued for a certain number of days .
METHODS : Lung tissues and bronchoalveolar lavage fluid ( BALF ) @ @ @ @ @ @ @ , while cells and supernatant were collected for the in vitro experiment .
Pathological changes in the lung tissues were assessed by hematoxylin and eosin staining .
The levels of inflammatory factors , including TNF-α , IL-1β , and IL-6 , were determined by enzyme-linked immunosorbent assay .
The expression levels of p-mTOR , HIF-1α , and VEGF proteins were measured by Western blot analysis and immunohistochemistry .
The mRNA levels of p70S6K , eIF4E-BP1 , and eIF4E were measured by quantitative polymerase chain reaction .
RESULTS : Emodin ameliorated pathological changes and @ @ @ @ @ @ @ It also significantly reduced the expression of inflammatory factors , including TNF-α , IL-1β , and IL-6 , in BALF and downregulated the expression of p-mTOR , HIF-1α , and VEGF proteins in the lung tissues .
Similar anti-inflammatory effects and the downregulation of the mTOR/HIF-1α/VEGF signaling pathway were found in RAW264.7 cells .
The mRNA levels of p70S6K , eIF4E-BP1 , and eIF4Ealso decreased in the macrophages .
CONCLUSION : Emodin alleviated LPS-induced pulmonary inflammation in rat lung tissues and RAW264.7 cells through inhibiting the mTOR/HIF-1α/VEGF signaling pathway , which accounted for @ @ @ @ @ @ @ .

OBJECTIVE AND DESIGN: This study aimed to investigate the anti-pulmonary inflammation effect of emodin on Wistar rats with lipopolysaccharide (LPS)-induced acute lung injury (ALI) and RAW264.7 cells through the mammalian target of rapamycin (mTOR)/hypoxia-inducible factor-1α (HIF-1α)/vascular endothelial growth factor (VEGF) signaling pathway.
SUBJECTS: Wistar rats and RAW264.7 cells were studied.
TREATMENT: LPS was used to induce inflammation in rats or RAW264.7 cells and emodin was given once a day before LPS stimulation and continued for a certain number of days.
METHODS: Lung tissues and bronchoalveolar lavage fluid (BALF) were collected for the in vivo experiment, while cells and supernatant were collected for the in vitro experiment. Pathological changes in the lung tissues were assessed by hematoxylin and eosin staining. The levels of inflammatory factors, including TNF-α, IL-1β, and IL-6, were determined by enzyme-linked immunosorbent assay. The expression levels of p-mTOR, HIF-1α, and VEGF proteins were measured by Western blot analysis and immunohistochemistry. The mRNA levels of p70S6K, eIF4E-BP1, and eIF4E were measured by quantitative polymerase chain reaction.
RESULTS: Emodin ameliorated pathological changes and infiltrated inflammatory cells in LPS-induced ALI. It also significantly reduced the expression of inflammatory factors, including TNF-α, IL-1β, and IL-6, in BALF and downregulated the expression of p-mTOR, HIF-1α, and VEGF proteins in the lung tissues. Similar anti-inflammatory effects and the downregulation of the mTOR/HIF-1α/VEGF signaling pathway were found in RAW264.7 cells. The mRNA levels of p70S6K, eIF4E-BP1, and eIF4Ealso decreased in the macrophages.
CONCLUSION: Emodin alleviated LPS-induced pulmonary inflammation in rat lung tissues and RAW264.7 cells through inhibiting the mTOR/HIF-1α/VEGF signaling pathway, which accounted for the therapeutic effects of emodin on ALI.


greenmedinfo--2020-05-01--Aloe-emodin induces breast tumor cell apoptosis.

Purpose : Aloe-emodin ( AE ) is a natural compound derived from aloe vera and palmatum rhubarb and shows anticancer activities in various cancers .
Bcl-2 family is the main regulator of cell death or cell survival .
This study describes the effects of AE on proliferation of breast tumor ( BT ) cells .
Methods : MCF-10A , MCF-10AT , MCF-7 , and MDA-MB-231 cell lines were exposed to AE .
Cell proliferation and apoptosis were assessed by CCK-8 and flow cytometry .
Protein levels were measured by Western blotting .
The levels of mRNA and miRNA were examined @ @ @ @ @ @ @ screen miRNAs that bind to 3'-UTR of mRNA .
Results : The results showed that AE selective activity inhibited the proliferation and induced apoptosis of MCF-10AT and MCF-7 cells but exhibited no significant inhibition in MCF10A and MDA-MB-231 cells .
Mechanistically , AE dose-dependently decreased the protein expression of Bcl-2 and Bcl-xl , while it increased Bax protein expression in MCF-10AT and MCF-7 cells .
The levels of Bcl-xl and Bax mRNA were altered by AE treatment , which was consistent with the protein expression results .
However , Bcl-2 mRNA levels were @ @ @ @ @ @ @ suggesting that AE may modulate the protein translation of Bcl-2 through miRNAs .
In all candidate miRNAs that bind to 3'-UTR of Bcl-2 , miR-15a and miR-16-1 were dose-dependently downregulated by AE .
Moreover , inhibition of miR-15a/16-1 could eliminate the inhibition of MCF-10AT and MCF-7 cells growth by AE and could reverse the downregulation of AE-induced Bcl-2 protein level .
Conclusion : Our research provides an important basis that AE induces BT cell apoptosis through upregulation of miR-15a/miR-16-1 that suppresses BCL2 .

Purpose: Aloe-emodin (AE) is a natural compound derived from aloe vera and palmatum rhubarb and shows anticancer activities in various cancers. Bcl-2 family is the main regulator of cell death or cell survival. This study describes the effects of AE on proliferation of breast tumor (BT) cells.
Methods: MCF-10A, MCF-10AT, MCF-7, and MDA-MB-231 cell lines were exposed to AE. Cell proliferation and apoptosis were assessed by CCK-8 and flow cytometry. Protein levels were measured by Western blotting. The levels of mRNA and miRNA were examined by RT-PCR. Bioinformatics was applied to screen miRNAs that bind to 3'-UTR of mRNA.
Results: The results showed that AE selective activity inhibited the proliferation and induced apoptosis of MCF-10AT and MCF-7 cells but exhibited no significant inhibition in MCF10A and MDA-MB-231 cells. Mechanistically, AE dose-dependently decreased the protein expression of Bcl-2 and Bcl-xl, while it increased Bax protein expression in MCF-10AT and MCF-7 cells. The levels of Bcl-xl and Bax mRNA were altered by AE treatment, which was consistent with the protein expression results. However, Bcl-2 mRNA levels were not affected in either cell line, suggesting that AE may modulate the protein translation of Bcl-2 through miRNAs. In all candidate miRNAs that bind to 3'-UTR of Bcl-2, miR-15a and miR-16-1 were dose-dependently downregulated by AE. Moreover, inhibition of miR-15a/16-1 could eliminate the inhibition of MCF-10AT and MCF-7 cells growth by AE and could reverse the downregulation of AE-induced Bcl-2 protein level.
Conclusion: Our research provides an important basis that AE induces BT cell apoptosis through upregulation of miR-15a/miR-16-1 that suppresses BCL2.


greenmedinfo--2020-05-01--Aloe-emodin exerts cholesterol-lowering effects by inhibiting proprotein convertase subtilisin/kexin

Aloe-emodin exerts cholesterol-lowering effects by inhibiting proprotein convertase subtilisin/kexin type 9.

Hyperlipidemia ( HPL ) characterized by metabolic disorder of lipids and cholesterol is one of the important risk factors for cardiovascular diseases .
Proprotein convertase subtilisin/kexin type 9 ( PCSK9 ) is a potent circulating regulator of LDL through its ability to induce degradation of the low-density lipoprotein cholesterol receptor ( LDLR ) in the lysosome of hepatocytes .
Aloe-emodin ( AE ) is one of potentially bioactive components of Chinese traditional medicine Daming capsule .
In this study we evaluated the HPL-lowering efficacy of AE in both in vivo and in vitro HPL models .
High-fat diet-induced rats were @ @ @ @ @ @ @ day , ig ) for 6 weeks .
We found that AE administration significantly decreased the levels of total cholesterol ( TC ) and LDL in the serum and liver tissues .
Moreover , AE administration ameliorated HPL-induced hepatic lipid aggregation .
But AE administration did not significantly inhibit HMG-CoA reductase activity in the liver of HPL rats .
A cellular model of HPL was established in human hepatoma ( HepG2 ) cells treated with cholesterol ( 20 μg/mL ) and 25-hydroxycholesterol ( 2 μg/mL ) , which exhibited markedly elevated cholesterol levels @ @ @ @ @ @ @ reversed by subsequent treatment with AE ( 30 μM ) .
In both the in vivo and in vitro HPL models , we revealed that AE selectively suppressed the sterol-regulatory element-binding protein-2 ( SREBP-2 ) and hepatocyte nuclear factor ( HNF ) 1α-mediated PCSK9 signaling , which in turn upregulated LDL receptor ( LDLR ) and promoted LDL uptake .
This study demonstrates that AE reduces cholesterol content in HPL rats by inhibiting the hepatic PCSK9/LDLR pathway .

Hyperlipidemia (HPL) characterized by metabolic disorder of lipids and cholesterol is one of the important risk factors for cardiovascular diseases. Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a potent circulating regulator of LDL through its ability to induce degradation of the low-density lipoprotein cholesterol receptor (LDLR) in the lysosome of hepatocytes. Aloe-emodin (AE) is one of potentially bioactive components of Chinese traditional medicine Daming capsule. In this study we evaluated the HPL-lowering efficacy of AE in both in vivo and in vitro HPL models. High-fat diet-induced rats were treated with AE (100 mg/kg per day, ig) for 6 weeks. We found that AE administration significantly decreased the levels of total cholesterol (TC) and LDL in the serum and liver tissues. Moreover, AE administration ameliorated HPL-induced hepatic lipid aggregation. But AE administration did not significantly inhibit HMG-CoA reductase activity in the liver of HPL rats. A cellular model of HPL was established in human hepatoma (HepG2) cells treated with cholesterol (20 μg/mL) and 25-hydroxycholesterol (2 μg/mL), which exhibited markedly elevated cholesterol levels. The increased cholesterol levels could be reversed by subsequent treatment with AE (30 μM). In both the in vivo and in vitro HPL models, we revealed that AE selectively suppressed the sterol-regulatory element-binding protein-2 (SREBP-2) and hepatocyte nuclear factor (HNF)1α-mediated PCSK9 signaling, which in turn upregulated LDL receptor (LDLR) and promoted LDL uptake. This study demonstrates that AE reduces cholesterol content in HPL rats by inhibiting the hepatic PCSK9/LDLR pathway.


greenmedinfo--2020-05-01--Aloe emodin inhibits telomerase activity in breast cancer cells: transcriptional and enzymological m

Aloe emodin inhibits telomerase activity in breast cancer cells: transcriptional and enzymological mechanism.

BACKGROUND : Telomerase plays an essential role in cancer cell proliferation .
In this study , we investigated inhibition mechanism of aloe emodin ( AE ) on three different types of breast cancer cell lines , MDA-MB-453 , MDA-MB-231 and MCF-7 .
METHODS : The cells were treated with different concentrations of AE .
Relative length of telomere and human telomerase reverse-transcriptase ( hTERT ) mRNA level was analyzed by quantitative PCR ( qPCR ) .
Protein level was assayed by Western blot .
Sodium bisulfite methylation sequencing was performed to assess the methylation status of gene promoter .
Enzymology @ @ @ @ @ @ @ between AE and telomerase .
Ultraviolet-visible titration and fluorescence resonance energy transfer ( FRET ) melting experiment were carried out to study the interaction between AE and telomeric DNA .
RESULTS : Continuous AE exposure of these cells for 48 h results in shortening of telomeres and inhibition of telomerase .
The transcription of hTERT was repressed by activation of E2F1 and inactivation of c-myc proteins .
Significant demethylation of CpG islands in hTERT gene promoter was observed in MDA-MB-453 and MCF-7 cells .
AE competed with dNTP for occupation of the enzyme @ @ @ @ @ @ @ G-quadruplex structure stabilizer as indicated by titration test and FRET experiments .
CONCLUSIONS : AE was a competitive inhibitor of telomerase and a G-quadruplex structure stabilizer .
AE decreased the transcription of hTERT gene in the three breast cancer cell lines via up-regulation E2F1 and down-regulation c-myc expressions .
The suppressed transcription was also related to the demethylation of the gene promoter .

BACKGROUND: Telomerase plays an essential role in cancer cell proliferation. In this study, we investigated inhibition mechanism of aloe emodin (AE) on three different types of breast cancer cell lines, MDA-MB-453, MDA-MB-231 and MCF-7.
METHODS: The cells were treated with different concentrations of AE. Relative length of telomere and human telomerase reverse-transcriptase (hTERT) mRNA level was analyzed by quantitative PCR (qPCR). Protein level was assayed by Western blot. Sodium bisulfite methylation sequencing was performed to assess the methylation status of gene promoter. Enzymology kinetics was applied to reveal the interaction between AE and telomerase. Ultraviolet-visible titration and fluorescence resonance energy transfer (FRET) melting experiment were carried out to study the interaction between AE and telomeric DNA.
RESULTS: Continuous AE exposure of these cells for 48 h results in shortening of telomeres and inhibition of telomerase. The transcription of hTERT was repressed by activation of E2F1 and inactivation of c-myc proteins. Significant demethylation of CpG islands in hTERT gene promoter was observed in MDA-MB-453 and MCF-7 cells. AE competed with dNTP for occupation of the enzyme active site. AE was a telomeric G-quadruplex structure stabilizer as indicated by titration test and FRET experiments.
CONCLUSIONS: AE was a competitive inhibitor of telomerase and a G-quadruplex structure stabilizer. AE decreased the transcription of hTERT gene in the three breast cancer cell lines via up-regulation E2F1 and down-regulation c-myc expressions. The suppressed transcription was also related to the demethylation of the gene promoter.


greenmedinfo--2020-05-01--Inhibition of curcumin on influenza A virus infection and influenzal pneumonia.

Oxidative stress , Nrf2-HO-1 and TLR-MAPK/NF-κB signaling pathways have been proved to be involved in influenza A virus ( IAV ) replication and influenzal pneumonia .
In the previous studies , we have performed several high-throughput drug screenings based on the TLR pathways .
In the present study , through plaque inhibition test , luciferase reporter assay , TCID , qRT-PCR , western blotting , ELISA and siRNA assays , we investigated the effect and mechanism of action of curcumin against IAV infection in vitro and in vivo .
The results showed that curcumin could directly inactivate IAV , blocked @ @ @ @ @ @ @ As for the underlying mechanisms , we found that curcumin could significantly inhibit IAV-induced oxidative stress , increased Nrf2 , HO-1 , NQO1 , GSTA3 and IFN-β production , and suppressed IAV-induced activation of TLR2/4/7 , Akt , p38/JNK MAPK and NF-κB pathways .
Suppression of Nrf2 via siRNA significantly abolished the stimulatory effect of curcumin on HO-1 , NQO1 , GSTA3 and IFN-β production and meanwhile blocked the inhibitory effect of curcumin on IAVM2 production .
Oxidant HOand TLR2/4 , p38/JNK and NF-κB agonists could significantly antagonize the anti-IAV activity of curcumin @ @ @ @ @ @ @ increased the survival rate of mice , reduced lung index , inflammatory cytokines and lung IAV titer , and finally improved pulmonary histopathological changes after IAV infection .
In conclusion , curcumin can directly inactivate IAV , inhibits IAV adsorption and replication ; and its inhibition on IAV replication may be via activating Nrf2 signal and inhibiting IAV-induced activation of TLR2/4 , p38/JNK MAPK and NF-κB pathways .

Oxidative stress, Nrf2-HO-1 and TLR-MAPK/NF-κB signaling pathways have been proved to be involved in influenza A virus (IAV) replication and influenzal pneumonia. In the previous studies, we have performed several high-throughput drug screenings based on the TLR pathways. In the present study, through plaque inhibition test, luciferase reporter assay, TCID, qRT-PCR, western blotting, ELISA and siRNA assays, we investigated the effect and mechanism of action of curcumin against IAV infection in vitro and in vivo. The results showed that curcumin could directly inactivate IAV, blocked IAV adsorption and inhibited IAV proliferation. As for the underlying mechanisms, we found that curcumin could significantly inhibit IAV-induced oxidative stress, increased Nrf2, HO-1, NQO1, GSTA3 and IFN-β production, and suppressed IAV-induced activation of TLR2/4/7, Akt, p38/JNK MAPK and NF-κB pathways. Suppression of Nrf2 via siRNA significantly abolished the stimulatory effect of curcumin on HO-1, NQO1, GSTA3 and IFN-β production and meanwhile blocked the inhibitory effect of curcumin on IAVM2 production. Oxidant HOand TLR2/4, p38/JNK and NF-κB agonists could significantly antagonize the anti-IAV activity of curcumin in vitro. Additionally, curcumin significantly increased the survival rate of mice, reduced lung index, inflammatory cytokines and lung IAV titer, and finally improved pulmonary histopathological changes after IAV infection. In conclusion, curcumin can directly inactivate IAV, inhibits IAV adsorption and replication; and its inhibition on IAV replication may be via activating Nrf2 signal and inhibiting IAV-induced activation of TLR2/4, p38/JNK MAPK and NF-κB pathways.


greenmedinfo--2020-05-01--Curcumin ameliorates severe influenza pneumonia via attenuating lung injury and regulating macrophag

Curcumin ameliorates severe influenza pneumonia via attenuating lung injury and regulating macrophage cytokines production.

Curcumin , an active phenolic agent extract from the Curcuma longa , exhibits excellent anti-cancer , anti-inflammation , and neuroprotective @ @ @ @ @ investigate the anti-influenza role of curcumin in vitro and in vivo .
The effect of @ @ @ @ @ A virus ( IAV ) was examined in human lung cancer cell line A549 , @ @ @ @ @ mouse model .
Curcumin could inhibit IAV in vitro and alleviate the severity of the @ @ @ @ @ infection with IAV .
The results also indicated that curcumin could trigger expression of Heme @ @ @ @ @ IAV-induced injury to the lung tissue .
Furthermore , curcumin could regulate immune response following @ @ @ @ @ of local inflammatory cytokines .
In addition , curcumin was found to inhibit NF-κB signalling @ @ @ @ @ as the subsequent production of cytokines/chemokines responding to IAV infection , by enhancing IκBα and @ @ @ @ @ supports the potential of curcumin as a promising treatment against IAV infection , whose effect @ @ @ @ @ immune response to prevent injury to the lung tissue .

Curcumin, an active phenolic agent extract from the Curcuma longa, exhibits excellent anti-cancer, anti-inflammation, and neuroprotective effects. We aimed to investigate the anti-influenza role of curcumin in vitro and in vivo. The effect of curcumin on replication of influenza A virus (IAV) was examined in human lung cancer cell line A549, as well as in a mouse model. Curcumin could inhibit IAV in vitro and alleviate the severity of the disease in the mouse after infection with IAV. The results also indicated that curcumin could trigger expression of Heme oxygenase-1 in vivo and attenuate IAV-induced injury to the lung tissue. Furthermore, curcumin could regulate immune response following IAV infection through inhibiting production of local inflammatory cytokines. In addition, curcumin was found to inhibit NF-κB signalling in macrophages, as well as the subsequent production of cytokines/chemokines responding to IAV infection, by enhancing IκBα and AMPK. Our current study supports the potential of curcumin as a promising treatment against IAV infection, whose effect may be mediated by regulating immune response to prevent injury to the lung tissue.


greenmedinfo--2020-05-01--Anti-tumor bioactivities of curcumin on mice loaded with gastric carcinoma.

Curcumin , a derivative from the dried rhizome of curcuma longa , has been proven to possess anti-tumor effects .
However , the detailed molecular mechanisms have not been fully elucidated .
In this study , we aimed to explore the anti-tumor mechanisms of curcumin in treating gastric cancer .
BALB/C mice grafted with a mouse gastric adenocarcinoma cell line ( MFC ) were used as the experimental model .
Mice received different doses of curcumin after grafting .
Tumor size was measured and tumor weight was determined after tumor inoculation .
TUNEL assay and flow cytometric analysis were applied @ @ @ @ @ @ @ cells .
Serum cytokines IFN-γ , TNF-α , granzyme B and perforin were detected by ELISA assay .
The anti-tumor effect was determined using cytotoxic T-lymphocyte ( CTL ) assays and in vivo tumor prevention tests .
The expression of DEC1 , HIF-1α , STAT3 and VEGF in tumor tissues was examined by immunostaining and analyzed using an Image J analysis system .
Compared with controls , tumor growth ( size and weight ) was significantly inhibited by curcumin treatment ( P < 0.05 ) .
The apoptotic index in gastric cancer cells @ @ @ @ @ @ @ group .
Splenocyte cells from mice treated with curcumin exhibited higher cytolytic effects on MFC cancer cells than those from mice treated with saline ( P < 0.01 ) .
The expression of DEC1 , HIF-1α , STAT3 and VEGF in tumor tissues was down-regulated after curcumin treatment .
Our results indicate that curcumin inhibits the proliferation of gastric carcinoma by inducing the apoptosis of tumor cells , activating immune cells to secrete a large amount of cytokines , and down-regulating the DEC1 , HIF-1α , VEGF and STAT3 signal transduction pathways .

Curcumin, a derivative from the dried rhizome of curcuma longa, has been proven to possess anti-tumor effects. However, the detailed molecular mechanisms have not been fully elucidated. In this study, we aimed to explore the anti-tumor mechanisms of curcumin in treating gastric cancer. BALB/C mice grafted with a mouse gastric adenocarcinoma cell line (MFC) were used as the experimental model. Mice received different doses of curcumin after grafting. Tumor size was measured and tumor weight was determined after tumor inoculation. TUNEL assay and flow cytometric analysis were applied to evaluate the apoptosis of the cancer cells. Serum cytokines IFN-γ, TNF-α, granzyme B and perforin were detected by ELISA assay. The anti-tumor effect was determined using cytotoxic T-lymphocyte (CTL) assays and in vivo tumor prevention tests. The expression of DEC1, HIF-1α, STAT3 and VEGF in tumor tissues was examined by immunostaining and analyzed using an Image J analysis system. Compared with controls, tumor growth (size and weight) was significantly inhibited by curcumin treatment (P<0.05). The apoptotic index in gastric cancer cells was significantly increased in the curcumin treatment group. Splenocyte cells from mice treated with curcumin exhibited higher cytolytic effects on MFC cancer cells than those from mice treated with saline (P<0.01). The expression of DEC1, HIF-1α, STAT3 and VEGF in tumor tissues was down-regulated after curcumin treatment. Our results indicate that curcumin inhibits the proliferation of gastric carcinoma by inducing the apoptosis of tumor cells, activating immune cells to secrete a large amount of cytokines, and down-regulating the DEC1,HIF-1α, VEGF and STAT3 signal transduction pathways.