greenmedinfo--2020-07-29--Regular use of proton pump inhibitors was associated with increased risk of rheumatoid arthritis in

Regular use of proton pump inhibitors was associated with increased risk of rheumatoid arthritis in women.

BACKGROUND : Proton pump inhibitors ( PPIs ) have a significant impact on the gut microbiome , which in turn , might increase the risk of rheumatoid arthritis ( RA ) .
AIM : To evaluate regular use of PPIs and risk of RA .
METHODS : This is a prospective analysis of the US nurses who reported PPI use data , and were free of RA from the Nurses ' Health Study ( NHS 2002-2014 ) and NHS II ( 2003-2015 ) .
The exposure was regular use of PPI in the past 2 years , which was repeatedly @ @ @ @ @ @ @ confirmed by the 1987 or 2010 American College of Rheumatology criteria .
We estimated the hazard ratios ( HRs ) and confidence interval ( CIs ) with time-dependent Cox regression adjusting for potential confounders .
RESULTS : We documented 421 cases of RA over 1 753 879 person-years of follow-up .
Regular PPI users had a 44 % higher risk of RA as compared with non-regular users ( adjusted HR = 1.44 ; 95 % CI , 1.10-1.89 ) .
The risk of RA increased with the total duration of PPI use ( @ @ @ @ @ @ @ non-regular users , the adjusted HRs were 1.22 ( 95 % CI , 0.93-1.62 ) for women with > 0 to 4 years ' use and 1.73 ( 95 % CI , 1.14 to 2.61 ) for > 4 years ' use .
CONCLUSIONS : Regular use of PPI was associated with increased risk of RA in women , with a higher risk observed in individuals with a longer duration of PPI use .
Due to the observational study design , large prospective trials are still required to confirm our finding .

BACKGROUND: Proton pump inhibitors (PPIs) have a significant impact on the gut microbiome, which in turn, might increase the risk of rheumatoid arthritis (RA).
AIM: To evaluate regular use of PPIs and risk of RA.
METHODS: This is a prospective analysis of the US nurses who reported PPI use data, and were free of RA from the Nurses' Health Study (NHS 2002-2014) and NHS II (2003-2015). The exposure was regular use of PPI in the past 2 years, which was repeatedly evaluated in biennial surveys. RA was confirmed by the 1987 or 2010 American College of Rheumatology criteria. We estimated the hazard ratios (HRs) and confidence interval (CIs) with time-dependent Cox regression adjusting for potential confounders.
RESULTS: We documented 421 cases of RA over 1 753 879 person-years of follow-up. Regular PPI users had a 44% higher risk of RA as compared with non-regular users (adjusted HR = 1.44; 95%CI, 1.10-1.89). The risk of RA increased with the total duration of PPI use (P-trend = 0.008). Compared with non-regular users, the adjusted HRs were 1.22 (95%CI, 0.93-1.62) for women with>0 to 4 years' use and 1.73 (95% CI, 1.14 to 2.61) for>4 years' use.
CONCLUSIONS: Regular use of PPI was associated with increased risk of RA in women, with a higher risk observed in individuals with a longer duration of PPI use. Due to the observational study design, large prospective trials are still required to confirm our finding.


greenmedinfo--2020-07-29--Prolonged proton pump inhibitors use was associated with an increased risk of rosacea.

Proton pump inhibitors ( PPI ) are commonly used drugs .
However , little is known about the association between PPI use and rosacea .
This study aimed to investigate the association between PPI use and rosacea risk .
Patients with prior PPI therapy , including 1067 rosacea cases and 4268 matched controls , were identified from the National Health Insurance Research Database in Taiwan .
The cumulative defined daily dose ( cDDD ) was used to quantify the PPI use .
Logistic regression was used for the analyses .
After adjustment for potential confounders , PPI use with cDDD @ @ @ @ @ @ @ with an increased risk of rosacea ( odds ratio [ OR ] , 1.54 ; 95 % confidence interval [ CI ] , 1.10-2.15 ) .
Rosacea risk was significantly associated with PPI use of cDDD of more than 365 in women ( OR , 1.62 ; 95 % CI , 1.08-2.46 ) but not in men .
Stratified by PPI indications , risk of rosacea was significantly associated with PPI use of cDDD of more than 365 for peptic ulcer ( OR , 1.58 ; 95 % CI , 1.12-2.21 ) .
@ @ @ @ @ @ @ associated with an increased risk of rosacea , particularly in women and patients with peptic ulcers .

Proton pump inhibitors (PPI) are commonly used drugs. However, little is known about the association between PPI use and rosacea. This study aimed to investigate the association between PPI use and rosacea risk. Patients with prior PPI therapy, including 1067 rosacea cases and 4268 matched controls, were identified from the National Health Insurance Research Database in Taiwan. The cumulative defined daily dose (cDDD) was used to quantify the PPI use. Logistic regression was used for the analyses. After adjustment for potential confounders, PPI use with cDDD of more than 365 was significantly associated with an increased risk of rosacea (odds ratio [OR], 1.54; 95% confidence interval [CI], 1.10-2.15). Rosacea risk was significantly associated with PPI use of cDDD of more than 365 in women (OR, 1.62; 95% CI, 1.08-2.46) but not in men. Stratified by PPI indications, risk of rosacea was significantly associated with PPI use of cDDD of more than 365 for peptic ulcer (OR, 1.58; 95% CI, 1.12-2.21). In conclusion, prolonged PPI use was associated with an increased risk of rosacea, particularly in women and patients with peptic ulcers.


greenmedinfo--2020-07-29--Curcumin prevents neuronal loss and structural changes in the superior cervical (sympathetic) gangli

Curcumin prevents neuronal loss and structural changes in the superior cervical (sympathetic) ganglion induced by chronic sleep deprivation.

BACKGROUND : In modern societies , sleep deprivation is a serious health problem .
This problem could be induced by a variety of reasons , including lifestyle habits or neurological disorders .
Chronic sleep deprivation ( CSD ) could have complex biological consequences , such as changes in neural autonomic control , increased oxidative stress , and inflammatory responses .
The superior cervical ganglion ( SCG ) is an important sympathetic component of the autonomic nervous system .
CSD can lead to a wide range of neurological consequences in SCG , which mainly supply innervations to circadian system and other @ @ @ @ @ @ @ Curcuma longa , curcumin possesses many therapeutic properties ; including neuroprotective .
This study aimed to evaluate the effect of CSD on the SCG histomorphometrical changes and the protective effect of curcumin in preventing these changes .
METHODS : Thirty-six male rats were randomly assigned to the control , curcumin , CSD , CSD + curcumin , grid floor control , and grid floor + curcumin groups .
The CSD was induced by a modified multiple platform apparatus for 21 days and animals were sacrificed at the end of CSD or treatment , @ @ @ @ @ @ @ TUNEL evaluations and also spatial arrangement of neurons in this structure .
RESULTS : Concerning stereological findings , CSD significantly reduced the volume of SCG and its total number of neurons and satellite glial cells in comparison with the control animals ( P CONCLUSIONS : CSD could potentially induce neuronal loss and structural changes including random spatial distribution in the SCG neurons .
Deleterious effects of sleep deprivation could be prevented by the oral administration of curcumin .
Furthermore , the consumption of curcumin in a healthy person might lead to a reduction @ @ @ @

BACKGROUND: In modern societies, sleep deprivation is a serious health problem. This problem could be induced by a variety of reasons, including lifestyle habits or neurological disorders. Chronic sleep deprivation (CSD) could have complex biological consequences, such as changes in neural autonomic control, increased oxidative stress, and inflammatory responses. The superior cervical ganglion (SCG) is an important sympathetic component of the autonomic nervous system. CSD can lead to a wide range of neurological consequences in SCG, which mainly supply innervations to circadian system and other structures. As the active component of Curcuma longa, curcumin possesses many therapeutic properties; including neuroprotective. This study aimed to evaluate the effect of CSD on the SCG histomorphometrical changes and the protective effect of curcumin in preventing these changes.
METHODS: Thirty-six male rats were randomly assigned to the control, curcumin, CSD, CSD + curcumin, grid floor control, and grid floor + curcumin groups. The CSD was induced by a modified multiple platform apparatus for 21 days and animals were sacrificed at the end of CSD or treatment, and their SCGs removed for stereological and TUNEL evaluations and also spatial arrangement of neurons in this structure.
RESULTS: Concerning stereological findings, CSD significantly reduced the volume of SCG and its total number of neurons and satellite glial cells in comparison with the control animals (P < 0.05). Treatment of CSD with curcumin prevented these decreases. Furthermore, TUNEL evaluation showed significant apoptosis in the SCG cells in the CSD group, and treatment with curcumin significantly decreased this apoptosis (P < 0.01). This decrease in apoptosis was observed in all control groups that received curcumin. CSD also changed the spatial arrangement of ganglionic neurons into a random pattern, whereas treatment with curcumin preserved its regular pattern.
CONCLUSIONS: CSD could potentially induce neuronal loss and structural changes including random spatial distribution in the SCG neurons. Deleterious effects of sleep deprivation could be prevented by the oral administration of curcumin. Furthermore, the consumption of curcumin in a healthy person might lead to a reduction of cell death.


greenmedinfo--2020-07-29--Efficacy of high-dissolution turmeric-sesame formulation for pain relief in adult subjects with acut

Efficacy of high-dissolution turmeric-sesame formulation for pain relief in adult subjects with acute musculoskeletal pain compared to acetaminophen.

BACKGROUND : Acetaminophen ( paracetamol ) is one of the most commonly used over-the-counter for pain relief .
Management of acute pain with plant-based nutrients has remained suboptimal due to an absence of data supporting acute relief of pain .
In the present study , it was hypothesized that high-dissolution liquid treatment of black sesame extract oil , Curcuma longa and Boswellia serrata may provide pain relief in people with acute musculoskeletal pain as quickly as acetaminophen .
METHODS : In this randomized active controlled open label study , 88 healthy subjects with acute musculoskeletal pain were randomized to receive @ @ @ @ @ @ @ ) or 1,000 mg/d acetaminophen for 7 days .
Change in pain intensity and pain relief at first 6 hours , 3 days , and 7 days were measured .
The onset of analgesia was measured by perceptible pain relief and meaningful pain relief .
Other measures were McGill Pain Questionnaire and Patient Global Impression Change .
RESULTS : The treatment formulation resulted in average magnitude of pain relief comparable to the acetaminophen .
Sixty-six percent of subjects in the treatment group reported positive response in pain relief ( ≥50 % max TOTPAR @ @ @ @ @ @ @ hours , compared to 73 % of control .
Seventy-three percent of subjects on treatment were considered positive responders , compared to 80 % in the control group .
The average time of onset of analgesia was 1 hour for the treatment group , versus 0.83 hour forcontrol .
At the end of day 3 and 7 , there was significant improvement ( P CONCLUSION : The results showed that the treatment used in the study may act as a natural , fast acting , and safe alternative for acute pain relief comparable @ @ @

BACKGROUND: Acetaminophen (paracetamol) is one of the most commonly used over-the-counter for pain relief. Management of acute pain with plant-based nutrients has remained suboptimal due to an absence of data supporting acute relief of pain. In the present study, it was hypothesized that high-dissolution liquid treatment of black sesame extract oil, Curcuma longa and Boswellia serrata may provide pain relief in people with acute musculoskeletal pain as quickly as acetaminophen.
METHODS: In this randomized active controlled open label study, 88 healthy subjects with acute musculoskeletal pain were randomized to receive treatment capsule (Rhuleave-K; 1,000 mg/d) or 1,000 mg/d acetaminophen for 7 days. Change in pain intensity and pain relief at first 6 hours, 3 days, and 7 days were measured. The onset of analgesia was measured by perceptible pain relief and meaningful pain relief. Other measures were McGill Pain Questionnaire and Patient Global Impression Change.
RESULTS: The treatment formulation resulted in average magnitude of pain relief comparable to the acetaminophen. Sixty-six percent of subjects in the treatment group reported positive response in pain relief (≥50% max TOTPAR; total pain relief) after 6 hours, compared to 73% of control. Seventy-three percent of subjects on treatment were considered positive responders, compared to 80% in the control group. The average time of onset of analgesia was 1 hour for the treatment group, versus 0.83 hour forcontrol. At the end of day 3 and 7, there was significant improvement (P < .001 for day 3 and day 7) in the pain condition of treatment group and was comparable to control (P = .436 for day 3 and P = .529 for day 7). The total McGill Pain score showed significant reduction in pain with the treatment irrespective of the pain intensity statistically equal (P = .468) to control. Both the groups were equal in providing sensory pain relief (P = .942), but the treatment was 8.57 times significantly better (P = .027) than acetaminophen in reducing the unpleasantness and emotional aspects (affective domain) involved with acute pain.
CONCLUSION: The results showed that the treatment used in the study may act as a natural, fast acting, and safe alternative for acute pain relief comparable to acetaminophen.


greenmedinfo--2020-07-29--Discovery of natural products from Curcuma longa that protect cells from beta-amyloid insult.

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greenmedinfo--2020-07-29--Curcumin-free turmeric exhibits anti-inflammatory and anticancer activities.

Turmeric , a dried powder derived from the rhizome of Curcuma longa , has been used for centuries in certain parts of the world and has been linked to numerous biological activities including antioxidant , anti-inflammatory , anticancer , antigrowth , anti-arthritic , anti-atherosclerotic , antidepressant , anti-aging , antidiabetic , antimicrobial , wound healing , and memory-enhancing activities .
One component of turmeric is curcumin , which has been extensively studied , as indicated by more than 5600 citations , most of which have appeared within the past decade .
Recent research has identified numerous chemical entities from turmeric @ @ @ @ @ @ @ whether all of the activities ascribed to turmeric are due to curcumin or whether other compounds in turmeric can manifest these activities uniquely , additively , or synergistically with curcumin .
However , studies have indicated that turmeric oil , present in turmeric , can enhance the bioavailability of curcumin .
Studies over the past decade have indicated that curcumin-free turmeric ( CFT ) components possess numerous biological activities including anti-inflammatory , anticancer , and antidiabetic activities .
Elemene derived from turmeric is approved in China for the treatment of cancer .
The @ @ @ @ @ @ @ anti-inflammatory activities exhibited by CFT and by some individual components of turmeric , including turmerin , turmerone , elemene , furanodiene , curdione , bisacurone , cyclocurcumin , calebin A , and germacrone .

Turmeric, a dried powder derived from the rhizome of Curcuma longa, has been used for centuries in certain parts of the world and has been linked to numerous biological activities including antioxidant, anti-inflammatory, anticancer, antigrowth, anti-arthritic, anti-atherosclerotic, antidepressant, anti-aging, antidiabetic, antimicrobial, wound healing, and memory-enhancing activities. One component of turmeric is curcumin, which has been extensively studied, as indicated by more than 5600 citations, most of which have appeared within the past decade. Recent research has identified numerous chemical entities from turmeric other than curcumin. It is unclear whether all of the activities ascribed to turmeric are due to curcumin or whether other compounds in turmeric can manifest these activities uniquely, additively, or synergistically with curcumin. However, studies have indicated that turmeric oil, present in turmeric, can enhance the bioavailability of curcumin. Studies over the past decade have indicated that curcumin-free turmeric (CFT) components possess numerous biological activities including anti-inflammatory, anticancer, and antidiabetic activities. Elemene derived from turmeric is approved in China for the treatment of cancer. The current review focuses on the anticancer and anti-inflammatory activities exhibited by CFT and by some individual components of turmeric, including turmerin, turmerone, elemene, furanodiene, curdione, bisacurone, cyclocurcumin, calebin A, and germacrone.


greenmedinfo--2020-07-29--Calebin-A inhibits adipogenesis and hepatic steatosis in high-fat diet-induced obesity via activatio

Calebin-A inhibits adipogenesis and hepatic steatosis in high-fat diet-induced obesity via activation of AMPK signaling.

SCOPE : Diet-induced obesity and associated nonalcoholic fatty liver disease have increased and become a major health problem worldwide .
This study was conducted to investigate the chemopreventive effects of dietary Calebin-A , a curcuminoid , on differentiation of 3T3-L1 adipocytes and high-fat diet ( HFD ) induced obesity and hepatic steatosis .
Potential mechanisms contributing to these effects were also elucidated .
METHODS AND RESULTS : Calebin-A effectively and dose dependently suppressed accumulation of lipid droplets in adipocytes through the suppression of adipogenic specific factor peroxisome proliferator-activated receptor ( PPAR ) γ and fatty acid synthase and activated acetyl-CoA @ @ @ @ @ @ @ gain and relative perigonadal , retroperitoneal , and mesenteric fat weight in HFD-fed mice .
Furthermore , Calebin-A markedly reduced hepatic steatosis and the serum levels of glutamate oxaloacetate transaminase , glutamate pyruvate transaminase , total cholesterol , and triacylglycerol .
These effects were associated with the downregulation of PPARγ , sterol regulatory element-binding protein-1 , and particularly the activation of AMP-activated protein kinase α signaling found in both adipocytes and liver tissues .
CONCLUSION : Taken together , these results demonstrated for the first time that Calebin-A suppressed adipocyte differentiation , prevented @ @ @ @ @ @ @ , suggesting a novel application for the prevention and treatment of obesity and associated nonalcoholic fatty liver disease .

SCOPE: Diet-induced obesity and associated nonalcoholic fatty liver disease have increased and become a major health problem worldwide. This study was conducted to investigate the chemopreventive effects of dietary Calebin-A, a curcuminoid, on differentiation of 3T3-L1 adipocytes and high-fat diet (HFD) induced obesity and hepatic steatosis. Potential mechanisms contributing to these effects were also elucidated.
METHODS AND RESULTS: Calebin-A effectively and dose dependently suppressed accumulation of lipid droplets in adipocytes through the suppression of adipogenic specific factor peroxisome proliferator-activated receptor (PPAR)γ and fatty acid synthase and activated acetyl-CoA carboxylase. Dietary Calebin-A effectively decreased weight gain and relative perigonadal, retroperitoneal, and mesenteric fat weight in HFD-fed mice. Furthermore, Calebin-A markedly reduced hepatic steatosis and the serum levels of glutamate oxaloacetate transaminase, glutamate pyruvate transaminase, total cholesterol, and triacylglycerol. These effects were associated with the downregulation of PPARγ, sterol regulatory element-binding protein-1, and particularly the activation of AMP-activated protein kinase α signaling found in both adipocytes and liver tissues.
CONCLUSION: Taken together, these results demonstrated for the first time that Calebin-A suppressed adipocyte differentiation, prevented HFD-induced obesity, and improved hepatic steatosis, suggesting a novel application for the prevention and treatment of obesity and associated nonalcoholic fatty liver disease.


greenmedinfo--2020-07-29--Calebin A downregulates osteoclastogenesis through suppression of RANKL signalling.

Osteoporosis is a bone disease that is exacerbated by aging and age-associated chronic diseases such as cancer .
Cancer-induced bone loss is usually treated with bisphosphonates or denosumab , an antibody against receptor activator of nuclear factor ( NF ) -κB ligand ( RANKL ) .
Because these drugs are expensive and have numerous side effects and high rates of toxicity , safer , more effective , and more affordable therapies for osteoporosis are still needed .
We identified a compound , calebin A ( CA ) , derived from turmeric ( Curcuma longa ) that affects osteoclastogenesis through modulation @ @ @ @ @ @ @ CA 's effect on NF-κB activation was examined by electrophoretic mobility shift assay .
Using mouse macrophages in vitro model , we found that CA suppressed RANKL-induced osteoclast differentiation of macrophages into osteoclasts , and downregulate RANKL-induced osteoclastogenesis-related marker gene expression , including NFATc-1 , TRAP , CTR , and cathepsin K. CA also suppressed the osteoclastogenesis induced by multiple myeloma and breast cancer cells .
This effect of CA was correlated with suppression of the phosphorylation and degradation of inhibitor of κB and , thus , inhibition of NF-κB activation .
Furthermore @ @ @ @ @ @ @ peptide blocked RANKL-induced osteoclastogenesis , demonstrating that the NF-κB signalling pathway is mandatory for RANKL-induced osteoclastogenesis .
Our results conclusively indicate that CA downmodulates the osteoclastogenesis induced by RANKL and by tumour cells through suppression of NF-κB pathway .

Osteoporosis is a bone disease that is exacerbated by aging and age-associated chronic diseases such as cancer. Cancer-induced bone loss is usually treated with bisphosphonates or denosumab, an antibody against receptor activator of nuclear factor (NF)-κB ligand (RANKL). Because these drugs are expensive and have numerous side effects and high rates of toxicity, safer, more effective, and more affordable therapies for osteoporosis are still needed. We identified a compound, calebin A (CA), derived from turmeric (Curcuma longa) that affects osteoclastogenesis through modulation of the RANKL signalling pathway. The CA's effect on NF-κB activation was examined by electrophoretic mobility shift assay. Using mouse macrophages in vitro model, we found that CA suppressed RANKL-induced osteoclast differentiation of macrophages into osteoclasts, and downregulate RANKL-induced osteoclastogenesis-related marker gene expression, including NFATc-1, TRAP, CTR, and cathepsin K. CA also suppressed the osteoclastogenesis induced by multiple myeloma and breast cancer cells. This effect of CA was correlated with suppression of the phosphorylation and degradation of inhibitor of κB and, thus, inhibition of NF-κB activation. Furthermore, we found that an NF-κB-specific inhibitory peptide blocked RANKL-induced osteoclastogenesis, demonstrating that the NF-κB signalling pathway is mandatory for RANKL-induced osteoclastogenesis. Our results conclusively indicate that CA downmodulates the osteoclastogenesis induced by RANKL and by tumour cells through suppression of NF-κB pathway.


greenmedinfo--2020-07-29--Calebin A suppresses NF-κB regulated cell survival and inflammatory gene products leading to inhibit

Calebin A suppresses NF-κB regulated cell survival and inflammatory gene products leading to inhibition of cell growth and chemosensitization.

BACKGROUND : While the anti-inflammatory and anticancer potential of curcumin , which is derived from turmeric ( Curcuma longa ) , has been studied extensively , very little is known about Calebin A , another novel compound from the same source .
PURPOSE : To determine whether Calebin A exhibits anti-inflammatory and anticancer potential .
METHODS : We examined the anti-inflammatory potential of Calebin A by DNA binding of NF-κB .
Anticancer properties of Calebin were determined by MTT and FACS analysis and NF-κB regulated expression of proteins was assessed by western blotting .
RESULTS : Calebin A suppressed NF-κB @ @ @ @ @ @ @ inhibition of NF-κB activation was mediated through the suppression of direct binding of NF-κB/p65 to the DNA .
This inhibitory effect was reversed by a reducing agent , and mutation of the Cys38 of p65 to serine abolished the effect of Calebin A on this binding .
Suppression of NF-κB activation by Calebin A resulted in the down-regulation of the expression of proteins involved in tumor cell survival , proliferation , inflammation , and metastasis .
Furthermore , Calebin A inhibited proliferation and induced apoptosis in a wide variety of tumor cells , @ @ @ @ @ @ @ enhanced apoptosis induced by chemotherapeutic agents .
CONCLUSION : Our results demonstrate that Calebin A inhibits NF-κB activation pathway through interaction with p65 and potentiates apoptosis in cancer cells ; thus , it has potential in the treatment of cancer .
However , further in vivo studies are warranted to define its anti-inflammatory and anticancer potential .

BACKGROUND: While the anti-inflammatory and anticancer potential of curcumin, which is derived from turmeric (Curcuma longa), has been studied extensively, very little is known about Calebin A, another novel compound from the same source.
PURPOSE: To determine whether Calebin A exhibits anti-inflammatory and anticancer potential.
METHODS: We examined the anti-inflammatory potential of Calebin A by DNA binding of NF-κB. Anticancer properties of Calebin were determined by MTT and FACS analysis and NF-κB regulated expression of proteins was assessed by western blotting.
RESULTS: Calebin A suppressed NF-κB activation induced by various stimuli. This inhibition of NF-κB activation was mediated through the suppression of direct binding of NF-κB/p65 to the DNA. This inhibitory effect was reversed by a reducing agent, and mutation of the Cys38 of p65 to serine abolished the effect of Calebin A on this binding. Suppression of NF-κB activation by Calebin A resulted in the down-regulation of the expression of proteins involved in tumor cell survival, proliferation, inflammation, and metastasis. Furthermore, Calebin A inhibited proliferation and induced apoptosis in a wide variety of tumor cells,as examined by various assays. It enhanced apoptosis induced by chemotherapeutic agents.
CONCLUSION: Our results demonstrate that Calebin A inhibits NF-κB activation pathway through interaction with p65 and potentiates apoptosis in cancer cells; thus, it has potential in the treatment of cancer. However, further in vivo studies are warranted to define its anti-inflammatory and anticancer potential.


greenmedinfo--2020-07-29--Multitargeted Calebin A has an anti-cancer capability on TNF-β-induced malignities.

OBJECTIVE : Natural polyphenol Calebin A has been recently discovered as a novel derivate from turmeric with anti-cancer potential .
Pro-inflammatory cytokine TNF-β ( lymphotoxin α ) is a stimulant for cancer cell malignity via activation of NF-B pathway , also in colorectal cancer ( CRC ) .
Here , we investigated the potential of Calebin A to suppress TNF-β-induced NF-B signalling in CRC .
MATERIALS AND METHODS : Three distinct CRC cell lines ( HCT116 , RKO , SW480 ) were treated in monolayer or 3-dimensional alginate culture with TNF-β , Calebin A , curcumin , BMS-345541 , dithiothreitol @ @ @ @ @ @ @ ASO ) against NF-B .
RESULTS : Calebin A suppressed dose-dependent TNF-β-induced CRC cell vitality and proliferation in monolayer culture .
Further , in alginate culture , Calebin A significantly suppressed TNF-β-enhanced colonosphere development , as well as invasion and colony formation of all three CRC cell lines investigated .
Calebin A specifically blocked TNF-β-induced activation and nuclear translocation of p65-NF-B , similar to curcumin ( natural NF-B inhibitor ) , BMS-345541 ( specific IKK inhibitor ) and ASO-NF-B .
Moreover , Immunofluorescence and Immunoblotting showed that Calebin A , similar to curcumin @ @ @ @ @ @ @ translocation of p65-NF-B and the transcription of NF-B-promoted biomarkers associated with proliferation , migration and apoptosis , in a dose- and time-dependent manner .
Those findings were potentiated by the specific treatment of extracted nuclei with DTT , which abrogated Calebin A-mediated nuclear p65-NF-B-inhibition and restored p65-NF-B-activity in the nucleus .
CONCLUSION : Overall , these results demonstrate , for the first time , that multitargeted Calebin A has an anti-cancer capability on TNF-β-induced malignities through inhibitory targeting of NF-B activation in the cytoplasm , as well as by suppressing the binding of @ @ @ @

OBJECTIVE: Natural polyphenol Calebin A has been recently discovered as a novel derivate from turmeric with anti-cancer potential. Pro-inflammatory cytokine TNF-β (lymphotoxin α) is a stimulant for cancer cell malignity via activation of NF-B pathway, also in colorectal cancer (CRC). Here, we investigated the potential of Calebin A to suppress TNF-β-induced NF-B signalling in CRC.
MATERIALS AND METHODS: Three distinct CRC cell lines (HCT116, RKO, SW480) were treated in monolayer or 3-dimensional alginate culture with TNF-β, Calebin A, curcumin, BMS-345541, dithiothreitol (DTT) or antisense oligonucleotides-(ASO) against NF-B.
RESULTS: Calebin A suppressed dose-dependent TNF-β-induced CRC cell vitality and proliferation in monolayer culture. Further, in alginate culture, Calebin A significantly suppressed TNF-β-enhanced colonosphere development, as well as invasion and colony formation of all three CRC cell lines investigated. Calebin A specifically blocked TNF-β-induced activation and nuclear translocation of p65-NF-B, similar to curcumin (natural NF-B inhibitor), BMS-345541 (specific IKK inhibitor) and ASO-NF-B. Moreover, Immunofluorescence and Immunoblotting showed that Calebin A, similar to curcumin or BMS-345541 suppressed TNF-β-induced activation and nuclear translocation of p65-NF-B and the transcription of NF-B-promoted biomarkers associated with proliferation, migration and apoptosis, in a dose- and time-dependent manner. Those findings were potentiated by the specific treatment of extracted nuclei with DTT, which abrogated Calebin A-mediated nuclear p65-NF-B-inhibition and restored p65-NF-B-activity in the nucleus.
CONCLUSION: Overall, these results demonstrate, for the first time, that multitargeted Calebin A has an anti-cancer capability on TNF-β-induced malignities through inhibitory targeting of NF-B activation in the cytoplasm, as well as by suppressing the binding of p65-NF-B to DNA.


greenmedinfo--2020-07-29--Calebin A potentiates the effect of 5-FU and TNF-β against human colorectal cancer cells.

OBJECTIVE : The majority of chemotherapeutic agents stimulate NF-κB signaling that mediates cell survival , proliferation and metastasis .
The natural turmeric non-curcuminoid derivate Calebin A has been shown to suppress cell growth , invasion and colony formation in colorectal cancer cells ( CRC ) by suppression of NF-κB signaling .
Therefore , we hypothesized herethat Calebin A might chemosensitize the TNF-β-treated tumor cells and potentiates the effect of 5-Fluorouracil ( 5-FU ) in advanced CRC .
MATERIALS AND METHODS : CRC cells ( HCT116 ) and their clonogenic 5-FU chemoresistant counterparts ( HCT116R ) were cultured in monolayer or @ @ @ @ @ @ @ treated with/without Calebin A , TNF-β , 5-FU , BMS-345541 and DTT ( dithiothreitol ) .
RESULTS : The results showed that TNF-β increased proliferation , invasion and resistance to apoptosis in chemoresistant CRC cells .
Pretreatment with Calebin A significantly chemosensitized HCT116R to 5-FU and inhibited the TNF-β-induced enhanced efforts for survival , invasion and anti-apoptotic effects .
We found further that Calebin Asignificantly suppressed TNF-β-induced phosphorylation and nuclear translocation of p65-NF-κB , similar to BMS-345541 ( specific IKK inhibitor ) and NF-κB-induced tumor-promoting biomarkers ( NF-κB , β1-Integrin , MMP-9 , @ @ @ @ @ @ @ associated with increased apoptosis in HCT116 and HCT116R cells .
Furthermore , blocking of p65-NF-κB stimulation by Calebin A was imparted through the downmodulation of p65-NF-κB binding to the DNA and this suppression was turned by DTT .
CONCLUSION : Our findings indicate , for the first time , that Calebin A chemosensitizes human CRC cells to chemotherapy by targeting of the p65-NF-κB signaling pathway .

OBJECTIVE: The majority of chemotherapeutic agents stimulate NF-κB signaling that mediates cell survival, proliferation and metastasis. The natural turmeric non-curcuminoid derivate Calebin A has been shown to suppress cell growth, invasion and colony formation in colorectal cancer cells (CRC) by suppression of NF-κB signaling. Therefore, we hypothesized herethat Calebin A might chemosensitize the TNF-β-treated tumor cells and potentiates the effect of 5-Fluorouracil (5-FU) in advanced CRC.
MATERIALS AND METHODS: CRC cells (HCT116) and their clonogenic 5-FU chemoresistant counterparts (HCT116R) were cultured in monolayer or alginate-based 3D tumor environment culture and were treated with/without Calebin A, TNF-β, 5-FU, BMS-345541 and DTT (dithiothreitol).
RESULTS: The results showed that TNF-β increased proliferation, invasion and resistance to apoptosis in chemoresistant CRC cells. Pretreatment with Calebin A significantly chemosensitized HCT116R to 5-FU and inhibited the TNF-β-induced enhanced efforts for survival, invasion and anti-apoptotic effects. We found further that Calebin Asignificantly suppressed TNF-β-induced phosphorylation and nuclear translocation of p65-NF-κB, similar to BMS-345541 (specific IKK inhibitor) and NF-κB-induced tumor-promoting biomarkers (NF-κB, β1-Integrin, MMP-9, CXCR4, Ki67). This was associated with increased apoptosis in HCT116 and HCT116R cells. Furthermore, blocking of p65-NF-κB stimulation by Calebin A was imparted through the downmodulation of p65-NF-κB binding to the DNA and this suppression was turned by DTT.
CONCLUSION: Our findings indicate, for the first time, that Calebin A chemosensitizes human CRC cells to chemotherapy by targeting of the p65-NF-κB signaling pathway.


greenmedinfo--2020-07-29--Hypoglycemic and antioxidant effects of five commercial turmeric supplements.

We evaluate the hypoglycemic and antioxidant effects of five commercial turmeric ( Curcuma longa ) supplements : ( 1 ) bulk samples , ( 2 ) turmeric root from India , ( 3 ) curcuma turmeric Pronat , ( 4 ) turmeric & black pepper Swanson , and ( 5 ) C3 complexturmeric curcumin .
Glucose diffusion and enzymatic starch digestion assays , usingα-amylase and α-glucosidase , were performed .
The antioxidant activity of turmeric supplements was measured through lipid peroxidation inhibition and the scavenging radical assay .
A starch dose of 102 mg/Kg of body weight ( equivalent to @ @ @ @ @ @ @ to perform the oral starch tolerance test ( OSTT ) in Wistar male rats .
All turmeric supplements decreased glucose diffusion and α-glucosidase enzyme activity , and inhibited lipid peroxidation .
The rats that received bulk samples and CT showed significantly lower glucose levels than rats receiving acarbose and those of negative control group .
Our results show that biological activities of turmeric supplements vary according to the commercial presentation .
PRACTICAL APPLICATIONS : The study results suggest that the hypoglycemic and antioxidant effects of five commercial turmeric supplements vary among them .
@ @ @ @ @ @ @ physicians and individuals using these supplements .

We evaluate the hypoglycemic and antioxidant effects of five commercial turmeric (Curcuma longa) supplements: (1) bulk samples, (2) turmeric root from India, (3) curcuma turmeric Pronat, (4) turmeric&black pepper Swanson, and (5) C3 complexturmeric curcumin. Glucose diffusion and enzymatic starch digestion assays, usingα-amylase and α-glucosidase, were performed. The antioxidant activity of turmeric supplements was measured through lipid peroxidation inhibition and the scavenging radical assay. A starch dose of 102 mg/Kg of body weight (equivalent to 1 g/day in humans) was used to perform the oral starch tolerance test (OSTT) in Wistar male rats. All turmeric supplements decreased glucose diffusion and α-glucosidase enzyme activity, and inhibited lipid peroxidation. The rats that received bulk samples and CT showed significantly lower glucose levels than rats receiving acarbose and those of negative control group. Our results show that biological activities of turmeric supplements vary according to the commercial presentation. PRACTICAL APPLICATIONS: The study results suggest that the hypoglycemic and antioxidant effects of five commercial turmeric supplements vary among them. The information provided would be useful to physicians and individuals using these supplements.


greenmedinfo--2020-07-29--Benefits of turmeric supplementation for skin health in chronic diseases.

The skin is a physical barrier that protects the body from the external environment .
Through its immune system , it limits the attack of environmental threats .
Unregulated immune reactions , however , can cause chronic inflammatory skin diseases , requiring that effective treatment routes be sought .
Turmeric , a root originated from Southeast Asia , has a number of therapeutic benefits , including anti-inflammatory activity .
The aim of this review was to evaluate the effects of turmeric oral supplementation in the treatment of chronic inflammatory skin diseases .
Through PubMed , Scopus , and Web of @ @ @ @ @ @ @ relationship between turmeric , curcumin , and skin health in humans until September 2019 were systematically searched .
Evidence analysis were performed using robust tools to evaluate the risk of bias ( RoB 2.0 ) , ( ROBINS-I ) and methodological quality ( GRADE ) of the included studies .
A total of eleven studies were included .
The skin conditions examined include psoriasis , pruritus , oral lichen planus , facial redness , as well as types of skin cancers .
Overall , therapeutic benefits for skin health have been observed through @ @ @ @ @ @ @ studies , nevertheless , are limited , requiring continuity and improvement in the intervention methodology employed .

The skin is a physical barrier that protects the body from the external environment. Through its immune system, it limits the attack of environmental threats. Unregulated immune reactions, however, can cause chronic inflammatory skin diseases, requiring that effective treatment routes be sought. Turmeric, a root originated from Southeast Asia, has a number of therapeutic benefits, including anti-inflammatory activity. The aim of this review was to evaluate the effects of turmeric oral supplementation in the treatment of chronic inflammatory skin diseases. Through PubMed, Scopus, and Web of Science databases, clinical studies examining the relationship between turmeric, curcumin, and skin health in humans until September 2019 were systematically searched. Evidence analysis were performed using robust tools to evaluate the risk of bias (RoB 2.0), (ROBINS-I) and methodological quality (GRADE) of the included studies. A total of eleven studies were included. The skin conditions examined include psoriasis, pruritus, oral lichen planus, facial redness, as well as types of skin cancers. Overall, therapeutic benefits for skin health have been observed through oral turmeric supplementation. The current published studies, nevertheless, are limited, requiring continuity and improvement in the intervention methodology employed.


greenmedinfo--2020-07-29--Alzheimer's disease, inflammation, and the role of antioxidants.

The World Health Organization refers to Alzheimer 's disease ( AD ) as a global health priority .
As the @ @ @ @ @ 's population is increasing , so too is the rate of AD .
There are @ @ @ @ @ globally who have been diagnosed with AD dementia , and researchers have yet to figure @ @ @ @ @ All misfolded aggregate proteins that are involved in neurodegenerative disorders ( amyloid-β , Huntington 's @ @ @ @ @ oxidative stress .
It is that oxidative stress that leads to inflammation and , in @ @ @ @ @ tau hyperphosphorylation , progresses to and exacerbates AD .
The consumption of antioxidants and nutrients @ @ @ @ @ caffeine , and turmeric , may slow the progression of AD and can be found @ @ @ @ @ dietary foods .
This review explores the role of inflammation on AD , the antioxidants @ @ @ @ @ , and future directions of how the treatment of the disease can be better understood @

The World Health Organization refers to Alzheimer's disease (AD) as a global health priority. As the average age of the world's population is increasing, so too is the rate of AD. There are an estimated 47 million people globally who have been diagnosed with AD dementia, and researchers have yet to figure out the root cause. All misfolded aggregate proteins that are involved in neurodegenerative disorders (amyloid-β, Huntington's tau,-synuclein) induce oxidative stress. It is that oxidative stress that leads to inflammation and, in conjunction with amyloid protein and tau hyperphosphorylation, progresses to and exacerbates AD. The consumption of antioxidants and nutrients, specifically vitamin E, caffeine, and turmeric, may slow the progression of AD and can be found in a wide variety of dietary foods. This review explores the role of inflammation on AD, the antioxidants that can potentially combat it, and future directions of how the treatment of the disease can be better understood.


greenmedinfo--2020-07-29--Long-term use of proton pump inhibitors as a risk factor for various adverse manifestations.

The long-term use of proton pump inhibitors ( PPIs ) can lead to increased gastric pH , hypochlorhydria and in some cases to achlorhydria when compared to other acid-suppressing agents like histamine-2 ( H2 ) receptor blockers and antacids .
These consequences by the use of long-term PPIs may lead to significant vitamin ( Band C ) and mineral ( iron , calcium and magnesium ) deficiencies which needs gastric acid for their absorption and bioavailability .
Long-term use of PPIs by the pregnant patients may impose a potential risk of congenital malformations .
Various studies have recommended the life @ @ @ @ @ @ @ choice among pregnant womens by preserving PPIs ( omeprazole as a safe choice of PPI ) for severe conditions of gastroesophageal reflux disease .
The long-term acid suppression by PPIs can also lead to enteric , respiratory and urinary tract infections .
The hypochlorhydria by chronic PPIs use may induce hypergastrinemia , which ultimately mediates the gastric polyps , gastric carcinoids and gastric cancer .
The concomitant use of PPIs with antiplatelet drugs like clopidogrel can impose the patients to major adverse cardiac events .
This review has enlisted the comprehensive information regarding @ @ @ @ @ @ @ of PPIs and their possible relations .
Considerable studies like case-control , randomized trials , cohort studies and meta-analysis were reported in supporting these adverse effects .
The clinicians and patients should be cautious about these effects so that they can avoid the serious outcomes .
PPIs should be avoided for long-term use mainly in older adults unless there is a proper indication .

The long-term use of proton pump inhibitors (PPIs) can lead to increased gastric pH, hypochlorhydria and in some cases to achlorhydria when compared to other acid-suppressing agents like histamine-2 (H2) receptor blockers and antacids. These consequences by the use of long-term PPIs may lead to significant vitamin (Band C) and mineral (iron, calcium and magnesium) deficiencies which needs gastric acid for their absorption and bioavailability. Long-term use of PPIs by the pregnant patients may impose a potential risk of congenital malformations. Various studies have recommended the life style modifications and antacid use as first choice among pregnant womens by preserving PPIs (omeprazole as a safe choice of PPI) for severe conditions of gastroesophageal reflux disease. The long-term acid suppression by PPIs can also lead to enteric, respiratory and urinary tract infections. The hypochlorhydria by chronic PPIs use may induce hypergastrinemia, which ultimately mediates the gastric polyps, gastric carcinoids and gastric cancer. The concomitant use of PPIs with antiplatelet drugs like clopidogrel can impose the patients to major adverse cardiac events. This review has enlisted the comprehensive information regarding the adverse effects induced by long-term use of PPIs and their possible relations. Considerable studies like case-control, randomized trials, cohort studies and meta-analysis were reported in supporting these adverse effects. The clinicians and patients should be cautious about these effects so that they can avoid the serious outcomes. PPIs should be avoided for long-term use mainly in older adults unless there is a proper indication.


greenmedinfo--2020-07-29--White button mushroom and a probiotics mixture supplementation corrects dyslipidemia.

Consumption of foods rich in dietary fiber has attracted considerable attention for lowering blood cholesterol and triglycerides through attenuation of gut microbiome .
Diets rich in fiber may provide substrates for microbes to digest and proliferate .
In response , products of microbial digestion enter systemic circulation and support host energy homeostasis .
In the present study , rats with hypercholesterolemia ( HC ) were supplemented with probiotics ( PB ) and Agaricus bisporus mushroom to examine the antidyslipidemia effects .
Forty adult rats were divided into five treatment groups .
The rats in the control group were fed only @ @ @ @ @ @ @ n = 8 ) , whereas an atherogenic diet ( chow diet supplemented with 1.5 % cholesterol and 0.5 % cholic acid ) was offered to the remaining rats to induce hypercholesterolemia ( HC group ; n = 32 ) .
Rats developed HC following a 24-day continuous supplementation with the atherogenic diet .
From day 25 onward , the HC group was further divided into HC-CON , HC-PB ( supplemented with PB at 1 mg/rat/day ) , HC-AB ( supplemented with A. bisporus at 5 % of diet ) , and HC-AB.PB @ @ @ @ @ @ @ PB ) .
After 6 weeks of supplementation , rats were killed to collect blood to determine serum lipid profile , oxidative stress , and for metagenomics analysis of colon contents .
Results showed that all supplementations corrected HC-induced oxidative stress .
Furthermore , A. bisporus supplementation corrected HC-induced dyslipidemia ( P≤ .05 ) .
Blautia and Bifidobacterium were the most dominant bacterial genera in HC-AB and HC-PB groups , respectively .
Phylum Firmicutes and class Clostridia predominantly occupied the gut microbiome in all groups .
However , no significant differences were observed @ @ @ @ @ @ @ study groups .
In conclusion , supplementation of A. bisporus mushroom and probiotics can lower oxidative stress and dyslipidemia with partial effects on the phylogenetic makeup in the gut microbiome .

Consumption of foods rich in dietary fiber has attracted considerable attention for lowering blood cholesterol and triglycerides through attenuation of gut microbiome. Diets rich in fiber may provide substrates for microbes to digest and proliferate. In response, products of microbial digestion enter systemic circulation and support host energy homeostasis. In the present study, rats with hypercholesterolemia (HC) were supplemented with probiotics (PB) and Agaricus bisporus mushroom to examine the antidyslipidemia effects. Forty adult rats were divided into five treatment groups. The rats in the control group were fed only a chow maintenance diet (CON; n = 8), whereas an atherogenic diet (chow diet supplemented with 1.5% cholesterol and 0.5% cholic acid) was offered to the remaining rats to induce hypercholesterolemia (HC group; n = 32). Rats developed HC following a 24-day continuous supplementation with the atherogenic diet. From day 25 onward, the HC group was further divided into HC-CON, HC-PB (supplemented with PB at 1 mg/rat/day), HC-AB (supplemented with A. bisporus at 5% of diet), and HC-AB.PB (supplemented with both A. bisporus and PB). After 6 weeks of supplementation, rats were killed to collect blood to determine serum lipid profile, oxidative stress, and for metagenomics analysis of colon contents. Results showed that all supplementations corrected HC-induced oxidative stress. Furthermore, A. bisporus supplementation corrected HC-induced dyslipidemia (P≤ .05). Blautia and Bifidobacterium were the most dominant bacterial genera in HC-AB and HC-PB groups, respectively. Phylum Firmicutes and class Clostridia predominantly occupied the gut microbiome in all groups. However, no significant differences were observed in microbiome diversity and clustering patterns among study groups. In conclusion, supplementation of A. bisporus mushroom and probiotics can lower oxidative stress and dyslipidemia with partial effects on the phylogenetic makeup in the gut microbiome.


greenmedinfo--2020-07-29--Fucoidan ameliorates hepatocellular carcinoma.

Fucoidan is sulfated polysaccharide of brown seaweed .
It offers various pharmacological actions like anti-inflammatory , anti-bacterial and anti-tumor activities .
Therefore , we aimed to investigate the effect of targeting microRNA-143 and inflammatory pathway by Fucoidan on experimentally induced hepatocellular carcinoma ( HCC ) in rats .
HCC is experimentally induced in Sprague Dawley by thioacetamide .
Rats were treated with 100 mg/kg and 200 mg/kg Fucoidan .
Hepatic sections were stained with hematoxylin/esosin for investigation of cell integrity .
Moreover , hepatic sections were immunohistochemically stained with antibodies for ki67 , TNF-α , and IL-1β .
Finally , @ @ @ @ @ @ @ miR-143 , NF-κB , TNF-α , and IL-1β .
We found that treating HCC with Fucoidan significantly reduced HCC-induced elevation in oxidative stress .
Moreover , Fucoidan reduced HCC-induced in expression of miR-143 , NF-κB , TNF-α , and IL-1β .
Finally , Fucoidan attenuated pseudohepatic lobules , broad fibrous septa and vacuolar to ballooning degeneration associated with reduction of immunostaining of ki67 , TNF-α , and IL-1β .
Fucoidan elevated the survival of HCC rats and reduced their serum AFP .
In addition , Fucoidan treatment revealed reduction in the expression of @ @ @ @ @ @ @ HCC rats .

Fucoidan is sulfated polysaccharide of brown seaweed. It offers various pharmacological actions like anti-inflammatory, anti-bacterial and anti-tumor activities. Therefore, we aimed to investigate the effect of targeting microRNA-143 and inflammatory pathway by Fucoidan on experimentally induced hepatocellular carcinoma (HCC) in rats. HCC is experimentally induced in Sprague Dawley by thioacetamide. Rats were treated with 100 mg/kg and 200 mg/kg Fucoidan. Hepatic sections were stained with hematoxylin/esosin for investigation of cell integrity. Moreover, hepatic sections were immunohistochemically stained with antibodies for ki67, TNF-α, and IL-1β. Finally, hepatic tissues were investigated for expression of miR-143, NF-κB, TNF-α, and IL-1β. We found that treating HCC with Fucoidan significantly reduced HCC-induced elevation in oxidative stress. Moreover, Fucoidan reduced HCC-induced in expression of miR-143, NF-κB, TNF-α, and IL-1β. Finally, Fucoidan attenuated pseudohepatic lobules, broad fibrous septa and vacuolar to ballooning degeneration associated with reduction of immunostaining of ki67, TNF-α, and IL-1β. Fucoidan elevated the survival of HCC rats and reduced their serum AFP. In addition, Fucoidan treatment revealed reduction in the expression of miR-143 associated with antioxidant andanti-inflammatory activities in HCC rats.


greenmedinfo--2020-07-30--Parthenolide ameliorates colon inflammation through regulating Treg/Th17 balance in a gut microbiota

Parthenolide ameliorates colon inflammation through regulating Treg/Th17 balance in a gut microbiota-dependent manner.

Inflammatory bowel disease ( IBD ) is a global health problem in which gut microbiota dysbiosis plays an important pathogenic role .
However , the current drugs for IBD treatment are far from optimal .
Previous researches indicated that parthenolide ( PTL ) had not only anti-cancer properties but also strong anti-inflammatory activities .
: To investigate the protective effect of PTL on colon inflammation and demonstrate the underlying gut microbiota-dependent mechanism.Colon inflammation severity in mouse model was measured by body weight change , mortality , colon length , disease activity index ( DAI ) score , H & E @ @ @ @ @ @ @ alteration and short-chain fatty acids ( SCFAs ) production were analyzed through 16S rRNA sequencing and targeted metabolomics .
Luminex cytokine microarray and Enzyme-linked immunosorbent assay ( ELISA ) were conducted to measure the colon cytokines profile .
The frequency of immune cells in lamina propria ( LP ) and spleen were phenotyped by flow cytometry .
: The PTL-treated mice showed significantly relieved colon inflammation , as evidenced by a reduction in body weight loss , survival rate , shortening of colon length , DAI score , histology score and colonoscopy score @ @ @ @ @ @ @ was depleted using antibiotic cocktails , the protective effect of PTL on colon inflammation disappeared .
PTL treatment downregulated the level of proinflammatory cytokines , including IL-1β , TNF-α , IL-6 , and IL-17A and upregulated the immunosuppressive cytokine IL-10 in colon tissue .
16S rRNA sequencing indicated that PTL-treated mice exhibited much more abundant gut microbial diversity and flora composition .
Targeted metabolomics analysis manifested the increased SCFAs productionin PTL-treated mice .
Additionally , PTL administration selectively upregulated the frequency of colonic regulatory T ( Treg ) cells as well as downregulated @ @ @ @ @ @ @ 17 ( Th17 ) cells , improving the Treg/Th17 balance to maintain intestinal homeostasis .
Gut microbiota depletion and fecal microbiota transplantation ( FMT ) was performed to confirm this gut microbiota-dependent mechanism .
: PTL ameliorated colon inflammation in a gut microbiota-dependent manner .
The underlying protective mechanism was associated with the improved Treg/Th17 balance in intestinal mucosa mediated through the increased microbiota-derived SCFAs production .
Collectively , our results demonstrated the role of PTL as a potential gut microbiota modulator to prevent and treat IBD .

Inflammatory bowel disease (IBD) is a global health problem in which gut microbiota dysbiosis plays an important pathogenic role. However, the current drugs for IBD treatment are far from optimal. Previous researches indicated that parthenolide (PTL) had not only anti-cancer properties but also strong anti-inflammatory activities.: To investigate the protective effect of PTL on colon inflammation and demonstrate the underlying gut microbiota-dependent mechanism.Colon inflammation severity in mouse model was measured by body weight change, mortality, colon length, disease activity index (DAI) score, H&E staining and colonoscopy evaluation. Gut microbiota alteration and short-chain fatty acids (SCFAs) production were analyzed through 16S rRNA sequencing and targeted metabolomics. Luminex cytokine microarray and Enzyme-linked immunosorbent assay (ELISA) were conducted to measure the colon cytokines profile. The frequency of immune cells in lamina propria (LP) and spleen were phenotyped by flow cytometry.: The PTL-treated mice showed significantly relieved colon inflammation, as evidenced by a reduction in body weight loss, survival rate, shortening of colon length, DAI score, histology score and colonoscopy score. Notably, when the gut microbiota was depleted using antibiotic cocktails, the protective effect of PTL on colon inflammation disappeared. PTL treatment downregulated the level of proinflammatory cytokines, including IL-1β, TNF-α, IL-6, and IL-17A and upregulated the immunosuppressive cytokine IL-10 in colon tissue. 16S rRNA sequencing indicated that PTL-treated mice exhibited much more abundant gut microbial diversity and flora composition. Targeted metabolomics analysis manifested the increased SCFAs productionin PTL-treated mice. Additionally, PTL administration selectively upregulated the frequency of colonic regulatory T (Treg) cells as well as downregulated the ratio of colonic T helper type 17 (Th17) cells, improving the Treg/Th17 balance to maintain intestinal homeostasis. Gut microbiota depletion and fecal microbiota transplantation (FMT) was performed to confirm this gut microbiota-dependent mechanism.: PTL ameliorated colon inflammation in a gut microbiota-dependent manner. The underlying protective mechanism was associated with the improved Treg/Th17 balance in intestinal mucosa mediated through the increased microbiota-derived SCFAs production. Collectively, our results demonstrated the role of PTL as a potential gut microbiota modulator to prevent and treat IBD.


greenmedinfo--2020-07-30--Effect of exposure of plastic infant feeding bottle leached water on biochemical, morphological and

Effect of exposure of plastic infant feeding bottle leached water on biochemical, morphological and oxidative stress parameters.

Bisphenol A ( BPA ) is leached out from plastic infant feeding bottles that are filled with warm milk/water due to high temperatures , exposing the infants to BPA .
The present study aims to understand the effects of ingestion of BPA leached from plastic infant feeding bottle and delineate the underlying mechanisms in rats .
In this study , adult rats of Wistar strain were divided into 3 groups .
In the first group , the rats consumed normal food and tap water .
In the second group , the rats ingested BPA ( 20µg/kg bodyweight/day , orally ) @ @ @ @ @ @ @ rats drank water leached from plastic infant feeding bottles .
After 30days , tests involving biochemical parameters , histopathological examination , and oxidative stress enzyme markers were performed , and the levels of BPA in plastic-leached water were estimated by HPLC analysis .
There were significant biochemical changes in the form of increased alkaline phosphatase ( ALP ) , creatine kinase-muscle/brain ( CK-MB ) , and lactate dehydrogenase ( LDH ) levels in both treated groups as compared to control group , accompanied by structural damage to thevital organs , and lipid peroxidation @ @ @ @ @ @ @ were also high in the treated groups .
Further , the BPA concentration in plastic leached water was estimated to be 0.1 ± 0.02 µg/mL .

Bisphenol A (BPA) is leached out from plastic infant feeding bottles that are filled with warm milk/water due to high temperatures, exposing the infants to BPA. The present study aims to understand the effects of ingestion of BPA leached from plastic infant feeding bottle and delineate the underlying mechanisms in rats. In this study, adult rats of Wistar strain were divided into 3 groups. In the first group, the rats consumed normal food and tap water. In the second group, the rats ingested BPA (20µg/kg bodyweight/day, orally). In the third group, the rats drank water leached from plastic infant feeding bottles. After 30days, tests involving biochemical parameters, histopathological examination, and oxidative stress enzyme markers were performed, and the levels of BPA in plastic-leached water were estimated by HPLC analysis. There were significant biochemical changes in the form of increased alkaline phosphatase (ALP), creatine kinase-muscle/brain (CK-MB), and lactate dehydrogenase (LDH) levels in both treated groups as compared to control group, accompanied by structural damage to thevital organs, and lipid peroxidation, glutathione reductase, and catalase activity were also high in the treated groups. Further, the BPA concentration in plastic leached water was estimated to be 0.1 ± 0.02 µg/mL.


greenmedinfo--2020-07-30--Migration of phthalates from PET water bottle in events of repeated uses and associated risk assessm

Migration of phthalates from PET water bottle in events of repeated uses and associated risk assessment.

Phthalates are widely used as a plasticizer in manufacturing polyethylene terephthalate ( PET ) bottles to improve softness , flexibility @ @ @ @ @ and workability .
Phthalates are known in instigating profound human health hazards .
In many @ @ @ @ @ proper disposal facilities established for empty PET bottles and the absence of legislation on reuse @ @ @ @ @ them for storing potable water .
An experiment was conducted with two commercial brands of @ @ @ @ @ potential of phthalate migration when domestically refilled and reused in multiple times at two temperature @ @ @ @ @ ( 27 ± 2 °C ) and warm ( 60 ± 2 °C ) were @ @ @ @ @ because of the common practice by people .
For both brands , only bis ( @ @ @ @ @ ) levels were detected in refilled water in every event of reuse .
For both @ @ @ @ @ migrated to water at 60 ± 2 °C were significantly higher ( p

Phthalates are widely used as a plasticizer in manufacturing polyethylene terephthalate (PET) bottles to improve softness, flexibility, durability, longevity, and workability. Phthalates are known in instigating profound human health hazards. In many developing countries, lack of proper disposal facilities established for empty PET bottles and the absence of legislation on reuse invariably persuade people to reuse them for storing potable water. An experiment was conducted with two commercial brands of PET bottles to explore the potential of phthalate migration when domestically refilled and reused in multiple times at two temperature conditions. Temperatures of ambient (27 ± 2 °C) and warm (60 ± 2 °C) were selected as the refilling temperatures because of the common practice by people. For both brands, only bis(2-ethylhexyl) phthalate (DEHP) levels were detected in refilled water in every event of reuse. For both brands, mean DEHP levels migrated to water at 60 ± 2 °C were significantly higher (p < 0.05) compared to those at 27 ± 2 °C. Risk analyses carried out on human health suggested that there exist no definite acute or chronic health risks when the refilled water is consumed continuously for 30 years for both temperatures. Still, such risks were higher for the consumption of refilled water of warm temperatures than those of ambient temperature. However, this study elucidates that DEHP migration would be at an alarming rate when the events of reuse of a single bottle increase so that regulations banning the reuse of empty PET bottles are paramount, especially for developing countries.


greenmedinfo--2020-07-30--Benzyl butyl phthalate exposure may disturb neural tube development by strengthening oxidative stres

Benzyl butyl phthalate exposure may disturb neural tube development by strengthening oxidative stress.

Benzyl butyl phthalate ( BBP ) is a persistent environmental pollutant .
BBP exposure and the possible effects on human @ @ @ @ @ ) remain elusive .
In this study , we found that the detection ratio of @ @ @ @ @ in maternal urine was obviously higher in NTDs ' population than that in normal controls @ @ @ @ @ 0.05 , respectively ) .
Animal experiments showed that BBP treatment induced developmental toxicity in @ @ @ @ @ levels of oxidative stress and cell apoptosis ( 0.01 ) .
More interestingly , the @ @ @ @ @ CHO , 10 μg/mL ) could partially restore the teratogenic effects of BBP by inhibiting @ @ @ @ @ .
Our data collectively suggest that BBP exposure may disturb neural tube development by strengthening @ @ @ @ @ partially restore the toxicity effects of BBP .
This studymay provide new insight for NTD @ @

Benzyl butyl phthalate (BBP) is a persistent environmental pollutant. BBP exposure and the possible effects on human neural tube defects (NTDs) remain elusive. In this study, we found that the detection ratio of positive BBP and its metabolites in maternal urine was obviously higher in NTDs' population than that in normal controls by GC-MS ( 0.01, 0.05, respectively). Animal experiments showed that BBP treatment induced developmental toxicity in chick embryo by enhancing the levels of oxidative stress and cell apoptosis ( 0.01). More interestingly, the supplement of high-dose choline (CHO, 10 μg/mL) could partially restore the teratogenic effects of BBP by inhibiting the occurrence of oxidative stress. Our data collectively suggest that BBP exposure may disturb neural tube development by strengthening oxidative stress. CHO can partially restore the toxicity effects of BBP. This studymay provide new insight for NTD prevention.


greenmedinfo--2020-07-30--Di-2-ethylhexyl phthalate imposes acute and profound damage to spermatozoa

A growing number of studies point to reduced fertility upon chronic exposure to endocrine-disrupting chemicals ( EDCs ) such as phthalates and plasticizers .
These toxins are ubiquitous and are often found in food and beverage containers , medical devices , as well as in common household and personal care items .
Animal studies with EDCs , such as phthalates and bisphenol A have shown a dose-dependent decrease in fertility and embryo toxicity upon chronic exposure .
However , limited research has been conducted on the acute effects of these EDCs on male fertility .
Here we used a murine @ @ @ @ @ @ @ four ubiquitous environmental toxins : bisphenol A ( BPA ) , di-2-ethylhexyl phthalate ( DEHP ) , diethyl phthalate ( DEP ) , and dimethyl phthalate ( DMP ) on sperm fertilizing ability and pre-implantation embryo development .
The most potent of these toxins , di-2-ethylhexyl phthalate ( DEHP ) , was further evaluated for its effect on sperm ion channel activity , capacitation status , acrosome reaction and generation of reactive oxygen species ( ROS ) .
DEHP demonstrated a profound hazardous effect on sperm fertility by producing an altered capacitation profile @ @ @ @ @ @ @ , interestingly , also increasing ROS production .
These results indicate that in addition to its known chronic impact on reproductive potential , DEHP also imposes acute and profound damage to spermatozoa , and thus , represents a significant risk to male fertility .

A growing number of studies point to reduced fertility upon chronic exposure to endocrine-disrupting chemicals (EDCs) such as phthalates and plasticizers. These toxins are ubiquitous and are often found in food and beverage containers, medical devices, as well as in common household and personal care items. Animal studies with EDCs, such as phthalates and bisphenol A have shown a dose-dependent decrease in fertility and embryo toxicity upon chronic exposure. However, limited research has been conducted on the acute effects of these EDCs on male fertility. Here we used a murine model to test the acute effects of four ubiquitous environmental toxins: bisphenol A (BPA), di-2-ethylhexyl phthalate (DEHP), diethyl phthalate (DEP), and dimethyl phthalate (DMP) on sperm fertilizing ability and pre-implantation embryo development. The most potent of these toxins, di-2-ethylhexyl phthalate (DEHP), was further evaluated for its effect on sperm ion channel activity, capacitation status, acrosome reaction and generation of reactive oxygen species (ROS). DEHP demonstrated a profound hazardous effect on sperm fertility by producing an altered capacitation profile, impairing the acrosome reaction, and, interestingly, also increasing ROS production. These results indicate that in addition to its known chronic impact on reproductive potential, DEHP also imposes acute and profound damage to spermatozoa, and thus, represents a significant risk to male fertility.


greenmedinfo--2020-07-30--The present study suggests that dimethyl phthalate exposure increases the risk of high blood pressur

The present study suggests that dimethyl phthalate exposure increases the risk of high blood pressure.

BACKGROUND : Exposure to phthalate esters may be linked to the risk of high blood pressure ( HBP ) , but limited evidence is available in Chinese children .
OBJECTIVE : To investigate the associations between nine phthalate metabolites ( mPAEs ) and systolic/diastolic BP , pulse pressure ( PP ) , mean arterial pressure ( MAP ) , and the risk of HBP .
METHODS : In this cross-sectional study , a total of 1044 primary school children ( 6-8 years old ) were enrolled from Shenzhen , China , between 2016 and 2017 .
Nine mPAEs were analyzed @ @ @ @ @ @ @ tandem mass spectrometry .
A multivariable linear regression model was used to explore the associations between phthalate exposure and systolic/diastolic BP , PP , and MAP .
A binary logistic regression model was used to examine the associations between phthalate exposure and the risk of HBP .
RESULTS : Monomethyl phthalate ( MMP ) concentrations were significantly higher in HBP children than normal BP children .
MMP , monoisobutyl phthalate ( MiBP ) , monobutyl phthalate ( MnBP ) , mono ( 5-carboxy-2-ethylpentyl ) phthalate , mono- [ ( 2-carboxy methyl ) hexyl @ @ @ @ @ @ @ sum of four short-chain mPAEs ( ∑LMW ) , and the sum of all nine mPAEs ( ∑mPAEs ) were significantly positively associated with increases in systolic BP z-score , while only MMP was significantly positively associated with diastolic BP z-score .
MMP , MiBP , MnBP , MCMHP , ∑LMW , and ∑mPAEs were significantly associated with increases in PP , while MMP and MnBP were significantly associated with increases in MAP .
MMP was significantly associated with the risk of HBP , with an odds ratio of 1.87 ( 95 % @ @ @ @ @ @ @ CONCLUSIONS : The present study suggests that dimethyl phthalate exposure increases the risk of HBP .
And some types of phthalates are associated with elevations in systolic/diastolic BP z scores , PP , and MAP in Chinese children .

BACKGROUND: Exposure to phthalate esters may be linked to the risk of high blood pressure (HBP), but limited evidence is available in Chinese children.
OBJECTIVE: To investigate the associations between nine phthalate metabolites (mPAEs) and systolic/diastolic BP, pulse pressure (PP), mean arterial pressure (MAP), and the risk of HBP.
METHODS: In this cross-sectional study, a total of 1044 primary school children (6-8 years old) were enrolled from Shenzhen, China, between 2016 and 2017. Nine mPAEs were analyzed from urine using ultra-performance liquid chromatography and tandem mass spectrometry. A multivariable linear regression model was used to explore the associations between phthalate exposure and systolic/diastolic BP, PP, and MAP. A binary logistic regression model was used to examine the associations between phthalate exposure and the risk of HBP.
RESULTS: Monomethyl phthalate (MMP) concentrations were significantly higher in HBP children than normal BP children. MMP, monoisobutyl phthalate (MiBP), monobutyl phthalate (MnBP), mono(5-carboxy-2-ethylpentyl) phthalate, mono-[(2-carboxy methyl)hexyl] phthalate (MCMHP), the sum of four short-chain mPAEs (∑LMW), and the sum of all nine mPAEs (∑mPAEs) were significantly positively associated with increases in systolic BP z-score, while only MMP was significantly positively associated with diastolic BP z-score. MMP, MiBP, MnBP, MCMHP,∑LMW, and ∑mPAEs were significantly associated with increases in PP, while MMP and MnBP were significantly associated with increases in MAP. MMP was significantly associated with the risk of HBP, with an odds ratio of 1.87 (95% CI: 1.23, 2.85).
CONCLUSIONS: The present study suggests that dimethyl phthalate exposure increases the risk of HBP. And some types of phthalates are associated with elevations in systolic/diastolic BP z scores, PP, and MAP in Chinese children.


greenmedinfo--2020-07-30--Bisphenols and phthalates: Plastic chemical exposures can contribute to adverse cardiovascular healt

Bisphenols and phthalates: Plastic chemical exposures can contribute to adverse cardiovascular health outcomes.

Phthalates and bisphenols are high production volume chemicals that are used in the manufacturing of consumer and medical products .
@ @ @ @ @ and phthalate chemicals in the environment , biomonitoring studies routinely detect these chemicals in 75-90 @ @ @ @ @ .
Accumulating evidence suggests that such chemical exposures may influence human health outcomes , including @ @ @ @ @ are particularly worrisome for sensitive populations , including fetal , infant and pediatric groups-with underdeveloped @ @ @ @ @ systems .
In the presented article , we aimed to review the literature on environmental @ @ @ @ @ and phthalates , highlight experimental work that suggests that these chemicals may exert a negative @ @ @ @ @ and emphasize areas of concern that relate to vulnerable pediatric groups .
Gaps in our @ @ @ @ @ , so that future endeavors may resolve the relationship between chemical exposures and the impact @ @ @ @ @

Phthalates and bisphenols are high production volume chemicals that are used in the manufacturing of consumer and medical products. Given the ubiquity of bisphenol and phthalate chemicals in the environment, biomonitoring studies routinely detect these chemicals in 75-90% of the general population. Accumulating evidence suggests that such chemical exposures may influence human health outcomes, including cardiovascular health. These associations are particularly worrisome for sensitive populations, including fetal, infant and pediatric groups-with underdeveloped metabolic capabilities and developing organ systems. In the presented article, we aimed to review the literature on environmental and clinical exposures to bisphenols and phthalates, highlight experimental work that suggests that these chemicals may exert a negative influence on cardiovascular health, and emphasize areas of concern that relate to vulnerable pediatric groups. Gaps in our current knowledge are also discussed, so that future endeavors may resolve the relationship between chemical exposures and the impact on pediatric cardiovascular physiology.


greenmedinfo--2020-07-30--These results also suggested that serum levels of phthalate metabolites are a good predictor for mal

These results also suggested that serum levels of phthalate metabolites are a good predictor for male infertility.

Global decline in male fertility and their associations with ubiquitous exposure of phthalates ( PAEs ) have raised public concerns .
However , the current epidemiological data are limited and controversial .
Hence , we investigated possible associations between PAE exposure and male infertility .
Eleven phthalate metabolites ( mPAEs ) were determined in urine and serum samples collected from eighty-eight males diagnosed with infertility from Tianjin , China .
The median serum levels of mPAE were n.d. -3.63 ng/mL , which were 1-2 orders of magnitude lower than the urinary levels of n.d. -192 ng/mL .
Negative associations were @ @ @ @ @ @ @ ) and MiBP and serum MCMHP , as well as testosterone ( T ) and luteinizing hormone ( LH ) and the molar concentrations of ∑mPAE , while positive association was found between T and the serum molar concentrations of ∑mDEHP .
Positive associations were found between the molar concentrations of serum ∑mPAE and sperm concentration , sperm motility rate , and progressive motility , between mono ( 2-ethyl-5-carboxypentyl ) phthalate ( MECPP ) and semen volume and total sperm number , and between MCMHP and progressive motility , while negative association was @ @ @ @ @ @ @ ( MEOHP ) and progressive motility .
Moreover , FSH was found to mediate the association between serum concentrations of MCMHPand progressive motility ( mediation ratio = 41.6 % ) , and LH to mediate the associations between serum concentrations of ∑mPAE and sperm concentration ( mediation ratio = 45.7 % ) and sperm motility rate ( mediation ratio = 29.0 % ) .
These results also suggested that serum levels of mPAE are a goodpredictor for male infertility .
Further efforts need to be made on toxicological studies to systematically elaborate the @ @ @

Global decline in male fertility and their associations with ubiquitous exposure of phthalates (PAEs) have raised public concerns. However, the current epidemiological data are limited and controversial. Hence, we investigated possible associations between PAE exposure and male infertility. Eleven phthalate metabolites (mPAEs) were determined in urine and serum samples collected from eighty-eight males diagnosed with infertility from Tianjin, China. The median serum levels of mPAE were n.d. -3.63 ng/mL, which were 1-2 orders of magnitude lower than the urinary levels of n.d. -192 ng/mL. Negative associations were identified between urinary follicle-stimulating hormone (FSH) and MiBP and serum MCMHP, as well as testosterone (T) and luteinizing hormone (LH) and the molar concentrations of ∑mPAE, while positive association was found between T and the serum molar concentrations of ∑mDEHP. Positive associations were found between the molar concentrations of serum ∑mPAE and sperm concentration, sperm motility rate, and progressive motility, between mono (2-ethyl-5-carboxypentyl) phthalate (MECPP) and semen volume and total sperm number, and between MCMHP and progressive motility, while negative association was found between mono(2-ethyl-5-oxohexyl) phthalate (MEOHP) and progressive motility. Moreover, FSH was found to mediate the association between serum concentrations of MCMHPand progressive motility (mediation ratio = 41.6%), and LH to mediate the associations between serum concentrations of ∑mPAE and sperm concentration (mediation ratio = 45.7%) and sperm motility rate (mediation ratio = 29.0%). These results also suggested that serum levels of mPAE are a goodpredictor for male infertility. Further efforts need to be made on toxicological studies to systematically elaborate the internal mechanisms.


greenmedinfo--2020-07-30--Bisphenol-A and polycystic ovary syndrome: a review of the literature.

Polycystic ovary syndrome ( PCOS ) is the most common endocrine disorder among women of reproductive age with reproductive , metabolic and endocrine implications .
While the exact pathophysiological mechanisms of the syndrome are unknown , its heterogeneity suggests a multifactorial causal background .
In the last two decades , numerous environmental chemicals , including Bisphenol-A ( BPA ) that is used in the synthesis of polycarbonate plastics , have been proposed as potential contributors to the aetiology of PCOS .
This review provides a holistic overview of the available data regarding the possible relation of PCOS with BPA exposure @ @ @ @ @ @ @ of 24 studies .
Eleven human case-control and 13 animal studies provided data regarding this potential relation .
Accumulating evidence suggests that a correlation between high levels of BPA and the presence of PCOS may exist .
Contradicting results from human and animal studies , however , render it difficult to conclude on the exact role of BPA in the pathogenesis of PCOS .
BPA may constitute a consequence of the syndrome rather than a cause , but further research is still needed to clarify this .
Continued efforts to study the early @ @ @ @ @ @ @ , are required to identify the exact effect of BPA on women with PCOS .

Polycystic ovary syndrome (PCOS) is the most common endocrine disorder among women of reproductive age with reproductive, metabolic and endocrine implications. While the exact pathophysiological mechanisms of the syndrome are unknown, its heterogeneity suggests a multifactorial causal background. In the last two decades, numerous environmental chemicals, including Bisphenol-A (BPA) that is used in the synthesis of polycarbonate plastics, have been proposed as potential contributors to the aetiology of PCOS. This review provides a holistic overview of the available data regarding the possible relation of PCOS with BPA exposure. We have included a total number of 24 studies. Eleven human case-control and 13 animal studies provided data regarding this potential relation. Accumulating evidence suggests that a correlation between high levels of BPA and the presence of PCOS may exist. Contradicting results from human and animal studies, however, render it difficult to conclude on the exact role of BPA in the pathogenesis of PCOS. BPA may constitute a consequence of the syndrome rather than a cause, but further research is still needed to clarify this. Continued efforts to study the early origins of PCOS, using prospective-designed studies, are required to identify the exact effect of BPA on women with PCOS.


greenmedinfo--2020-07-29--Fetal exposure to bisphenols and phthalates and childhood bone mass.

BACKGROUND : Exposure to bisphenols and phthalates might influence bone health .
We hypothesized that exposure to bisphenols and phthalates during fetal life has persistent effects on bone development .
OBJECTIVES : To analyze the associations of fetal exposure to bisphenols and phthalates with bone health in school-aged children .
METHODS : Among 1,362 mother-child pairs participating in a population-based cohort study , we measured maternal urinary concentrations of bisphenols and phthalates at first , second and third trimester with high performance liquid chromatography electrospray ionization-tandem mass spectrometry .
Total body bone mineral density ( BMD ) and bone area @ @ @ @ @ @ @ X-ray absorptiometry ( DXA ) at 6 and 10 years , and were both used to calculate bone mineral content ( BMC ) and area-adjusted BMC ( aBMC , a measure of volumetric BMD ) .
RESULTS : Maternal bisphenol concentrations were not associated with childhood bone measures at 6 years .
After adjustment for covariates and multiple testing correction , an interquartile range increase in maternal first trimester bisphenol S ( BPS ) concentrations was associated with lower BMD and aBMC at 10 years ( -6.08 ( 95 % confidence interval ( @ @ @ @ @ @ @ mg/cmand -0.12 ( 95 % CI , -0.20 to -0.04 ) g ) .
Maternal third trimester low molecular weight ( LMW ) phthalate concentrations were associated with higher aBMC at 6 years whereas , maternal third trimester di-n-octylphthalate ( DNOP ) concentrations were associated with lower aBMC at 10 years .
However , these associations did not remain statistically significant after multiple testing correction .
DISCUSSION : Maternal first trimester BPS concentrations are associated with lower BMD and aBMC in school-aged children .
These findings should be considered as hypothesis generating and @ @ @ @ @ @ @ underlying mechanisms .

BACKGROUND: Exposure to bisphenols and phthalates might influence bone health. We hypothesized that exposure to bisphenols and phthalates during fetal life has persistent effects on bone development.
OBJECTIVES: To analyze the associations of fetal exposure to bisphenols and phthalates with bone health in school-aged children.
METHODS: Among 1,362 mother-child pairs participating in a population-based cohort study, we measured maternal urinary concentrations of bisphenols and phthalates at first, second and third trimester with high performance liquid chromatography electrospray ionization-tandem mass spectrometry. Total body bone mineral density (BMD) and bone area (BA) were measured using dual-energy X-ray absorptiometry (DXA) at 6 and 10 years, and were both used to calculate bone mineral content (BMC) and area-adjusted BMC (aBMC, a measure of volumetric BMD).
RESULTS: Maternal bisphenol concentrations were not associated with childhood bone measures at 6 years. After adjustment for covariates and multiple testing correction, an interquartile range increase in maternal first trimester bisphenol S (BPS) concentrations was associated with lower BMD and aBMC at 10 years (-6.08 (95% confidence interval (CI), -9.97 to -2.19) mg/cmand -0.12 (95% CI, -0.20 to -0.04) g). Maternal third trimester low molecular weight (LMW) phthalate concentrations were associated with higher aBMC at 6 years whereas, maternal third trimester di-n-octylphthalate (DNOP) concentrations were associated with lower aBMC at 10 years. However, these associations did not remain statistically significant after multiple testing correction.
DISCUSSION: Maternal first trimester BPS concentrations are associated with lower BMD and aBMC in school-aged children. These findings should be considered as hypothesis generating and need further replication and exploration of potential underlying mechanisms.


greenmedinfo--2020-07-29--Association of bisphenol A or bisphenol S exposure with oxidative stress and immune disturbance amon

Association of bisphenol A or bisphenol S exposure with oxidative stress and immune disturbance among unexplained recurrent spontaneous abortion women.

Human exposure to environmental chemicals might play a role in the pathogenesis of unexplained recurrent spontaneous abortion ( URSA ) .
Bisphenol A ( BPA ) and bisphenol S ( BPS ) have been suggested to affect reproductive health .
However , the mechanism remains unclear .
To explore the association between BPA and BPS exposure and oxidative stress and immune homeostasis , we conducted a cross-sectional study and revealed BPA and BPS levels in relation to these two factors which were supposed to be implicated in miscarriage .
111 URSA patients were recruited and we analyzed urinary BPA and @ @ @ @ @ @ @ 8-hydroxydeoxyguanosine and 8-isoprostane ) and serum immune balance biomarkers ( IL-1β , IL-2 , IL-4 , IL-6 , IL-8 , IL-10 , IL-12p70 , IL-13 , TNF-α , TGF-β and IFN-γ ) .
Multivariable linear regression models were used to evaluate the correlation between bisphenols exposure and outcome biomarkers .
After adjustment for age , BMI , menstrual cycle , and parity history , creatinine-adjusted BPAwas significantly associated with increases in 8-isoprostane ( β = 0.74 , 95 % CI = 0.07 , 1.41 ; p = 0.031 ) and IFN-γ ( β @ @ @ @ @ @ @ 0.00 , 0.36 ; p = 0.046 ) .
No statistical correlation between BPS and biomarkers of oxidative stress or immune balance was observed when all participantswere analyzed .
Further analysis revealed that in the subgroup of BPS > limit of detection ( 0.01 ng/ml ) , creatinine-adjusted BPS was significantly associated with increases in IL-10 ( β = 0.22 , 95 % CI = 0.00 , 0.45 ; p = 0.048 ) .
Our findings suggested that BPA and BPS exposure might be related to oxidative stress and immune imbalance in URSA @ @ @ @ @ @ @ suggest potential pathogenic and aetiological associations among the bisphenols , biomarkers and URSA , which offers hypotheses for further studies .

Human exposure to environmental chemicals might play a role in the pathogenesis of unexplained recurrent spontaneous abortion (URSA). Bisphenol A (BPA) and bisphenol S (BPS) have been suggested to affect reproductive health. However, the mechanism remains unclear. To explore the association between BPA and BPS exposure and oxidative stress and immune homeostasis, we conducted a cross-sectional study and revealed BPA and BPS levels in relation to these two factors which were supposed to be implicated in miscarriage. 111 URSA patients were recruited and we analyzed urinary BPA and BPS concentrations, oxidative stress biomarkers (8-hydroxydeoxyguanosine and 8-isoprostane) and serum immune balance biomarkers (IL-1β, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12p70, IL-13, TNF-α, TGF-β and IFN-γ). Multivariable linear regression models were used to evaluate the correlation between bisphenols exposure and outcome biomarkers. After adjustment for age, BMI, menstrual cycle, and parity history, creatinine-adjusted BPAwas significantly associated with increases in 8-isoprostane (β = 0.74, 95% CI = 0.07, 1.41; p = 0.031) and IFN-γ (β = 0.18, 95% CI = 0.00, 0.36; p = 0.046). No statistical correlation between BPS and biomarkers of oxidative stress or immune balance was observed when all participantswere analyzed. Further analysis revealed that in the subgroup of BPS > limit of detection (0.01 ng/ml), creatinine-adjusted BPS was significantly associated with increases in IL-10 (β = 0.22, 95% CI = 0.00, 0.45; p = 0.048). Our findings suggested that BPA and BPS exposure might be related to oxidative stress and immune imbalance in URSA patients. Overall, our work might suggest potential pathogenic and aetiological associations among the bisphenols, biomarkers and URSA, which offers hypotheses for further studies.


greenmedinfo--2020-07-31--Two case reports of intravenous honokiol in drug-resistant cancer.

Long-term patient survival in cancer is affected by drug resistance .
Honokiol ( HNK ) is a small-molecule polyphenol isolated from the bark and seed cones of .
HNK has been shown to enhance the effects of chemotherapy and inhibit drug resistance in preclinical models .
HNK was well tolerated in multiple animal models when administered orally , intravenously ( IV ) , and via intraperitoneal route .
However , there are limited human data on the use of HNK in general , and specifically via IV ( HNK-IV ) in cancer.We aim to assess the efficacy , safety , @ @ @ @ @ @ @ drug-resistant tumors.This is a case study of 2 cancer patients who utilized HNK-IV as part of their cancer treatment regimen .
The initial infusion of HNK was 10 mg/kg body weight , and subsequent treatments were increased up to 50 mg/kg according to individual tolerance , over 2 weeks.Positive clinical response was achieved in both patients , including improved symptoms and quality of life .
No serious adverse side effects occurred , and there were no adverse effects on laboratory parameters ( complete blood count , kidney , and liver function ) .
@ @ @ @ @ @ @ and resolved postinfusion.This is the first report of HNK-IV in human patients .
Given the positive clinical results , safety , and tolerability , the use of HNK-IV warrants further investigation regarding optimum formulation , and its use as adjunctive therapy in cancer patients .

Long-term patient survival in cancer is affected by drug resistance. Honokiol (HNK) is a small-molecule polyphenol isolated from the bark and seed cones of. HNK has been shown to enhance the effects of chemotherapy and inhibit drug resistance in preclinical models. HNK was well tolerated in multiple animal models when administered orally, intravenously (IV), and via intraperitoneal route. However, there are limited human data on the use of HNK in general, and specifically via IV (HNK-IV) in cancer.We aim to assess the efficacy, safety, and tolerability of HNK-IV in patients with drug-resistant tumors.This is a case study of 2 cancer patients who utilized HNK-IV as part of their cancer treatment regimen. The initial infusion of HNK was 10 mg/kg body weight, and subsequent treatments were increased up to 50 mg/kg according to individual tolerance, over 2 weeks.Positive clinical response was achieved in both patients, including improved symptoms and quality of life. No serious adverse side effects occurred, and there were no adverse effects on laboratory parameters (complete blood count, kidney, and liver function). Transient sedation and minor nausea were noted and resolved postinfusion.This is the first report of HNK-IV in human patients. Given the positive clinical results, safety, and tolerability, the use of HNK-IV warrants further investigation regarding optimum formulation, and its use as adjunctive therapy in cancer patients.


greenmedinfo--2020-07-31--Honokiol suppressed pancreatic cancer progression.

Background : Pancreatic cancer is one of the most aggressive malignancies .
The present study aimed to examine the anti-tumor effects of honokiol in pancreatic cancer and to explore the underlying molecular mechanisms .
Materials and Methods : In vitro functional assays determined pancreatic cancer cell proliferation , apoptosis and invasion .
Xenograft nude mice model determined the in vivo anti-cancer effects of honokiol .
Luciferase reporter assay determined the interaction between miR101 and myeloid cell leukemia-1 ( Mcl-1 ) .
Results : Honokiol concentration-dependently suppressed pancreatic cancer cell viability .
In addition , honokiol increased the caspase-3 activity and @ @ @ @ @ @ @ arrest at G0/G1 phase , and inhibited cell invasion in pancreatic cancer .
Interestingly , honokiol treatment induced up-regulation of miR-101 in pancreatic cancer cells .
Knockdown of miR-101 attenuated the honokiol-induced cell apoptosis and inhibition in cell invasion of pancreatic cancer cells .
On the other hand , miR-101 overexpression induced cell apoptosis and inhibited cell viability and invasion in pancreatic cancer .
Further mechanistic study verified that Mcl-1 was negatively regulated by miR-101 , and Mcl-1 overexpression counteracted the tumor-suppressive effects of honokiol on the pancreatic cancer cells .
In vivo @ @ @ @ @ @ @ growth of pancreatic cancer in the nude mice and up-regulated miR-101 expression but down-regulated Mcl-1 expression in tumor tissues .
Conclusion : Our data showed that honokiol suppressed pancreatic cancer progression via miR-101-Mcl-1 axis .
Honokiol could be a promising candidate for cancer prevention and/or therapeutic treatment for pancreatic cancer .

Background: Pancreatic cancer is one of the most aggressive malignancies. The present study aimed to examine the anti-tumor effects of honokiol in pancreatic cancer and to explore the underlying molecular mechanisms.
Materials and Methods: In vitro functional assays determined pancreatic cancer cell proliferation, apoptosis and invasion. Xenograft nude mice model determined the in vivo anti-cancer effects of honokiol. Luciferase reporter assay determined the interaction between miR101 and myeloid cell leukemia-1 (Mcl-1).
Results: Honokiol concentration-dependently suppressed pancreatic cancer cell viability. In addition, honokiol increased the caspase-3 activity and cell apoptotic rates, induced cell cycle arrest at G0/G1 phase, and inhibited cell invasion in pancreatic cancer. Interestingly, honokiol treatment induced up-regulation of miR-101 in pancreatic cancer cells. Knockdown of miR-101 attenuated the honokiol-induced cell apoptosis and inhibition in cell invasion of pancreatic cancer cells. On the other hand, miR-101 overexpression induced cell apoptosis and inhibited cell viability and invasion in pancreatic cancer. Further mechanistic study verified that Mcl-1 was negatively regulated by miR-101, and Mcl-1 overexpression counteracted the tumor-suppressive effects of honokiol on the pancreatic cancer cells. In vivo studies showed that honokiol dose-dependently suppressed tumor growth of pancreatic cancer in the nude mice and up-regulated miR-101 expression but down-regulated Mcl-1 expression in tumor tissues.
Conclusion: Our data showed that honokiol suppressed pancreatic cancer progression via miR-101-Mcl-1 axis. Honokiol could be a promising candidate for cancer prevention and/or therapeutic treatment for pancreatic cancer.


greenmedinfo--2020-07-31--Dietary supplement Magnolia officinalis extract could be used for the prevention against oral carcin

Dietary supplement Magnolia officinalis extract could be used for the prevention against oral carcinoma.

Among the three key active components ( KACs ) ofbark extract ( ME ) , 4 -- methylhonokiol and honokiol @ @ @ @ @ magnolol in the oral squamous cancer cell lines ( Cal-27 , SCC-9 , and SCC-4 @ @ @ @ @ ME-KACs were poor ( < 0.2 % ) in C57BL/6 mice primarily due to their @ @ @ @ @ and poor solubilities .
High plasma concentration of glucuronides upon oral administration and faster rate @ @ @ @ @ indicated intestine as one of the major metabolic organs for ME-KACs .
Despite the increase @ @ @ @ @ ∼8-10-fold ) and decrease in AUCof glucuronides ( ∼10-fold ) upon ME solubility enhancement , @ @ @ @ @ to improve meaningfully .
In conclusion , we propose a quality-controlled and chemically defined ME @ @ @ @ @ ratio of three KACs , delivered locally in the oral cavity as the most promising @ @ @ @ @ oral cancer chemopreventive dietary supplement .

Among the three key active components (KACs) ofbark extract (ME), 4--methylhonokiol and honokiol showed higher antiproliferation activities than magnolol in the oral squamous cancer cell lines (Cal-27, SCC-9, and SCC-4). Oral bioavailabilities of ME-KACs were poor (<0.2%) in C57BL/6 mice primarily due to their extensive first-pass phase II metabolism and poor solubilities. High plasma concentration of glucuronides upon oral administration and faster rate of glucuronidation by intestinal microsomes indicated intestine as one of the major metabolic organs for ME-KACs. Despite the increase in bioavailabilities of ME-KACs (∼8-10-fold) and decrease in AUCof glucuronides (∼10-fold) upon ME solubility enhancement, systemic exposure of ME-KACs failed to improve meaningfully. In conclusion, we propose a quality-controlled and chemically defined ME mixture, containing an optimized ratio of three KACs, delivered locally in the oral cavity as the most promising strategyfor ME use as an oral cancer chemopreventive dietary supplement.