greenmedinfo--2020-07-22--6-gingerol showed efficacy in the treatment of DSS-induced ulcerative colitis.

Background : Ulcerative colitis ( UC ) is a non-specific chronic intestinal inflammatory disease with unclear etiology .
Previous studies have suggested that the imbalance of Treg/Thl7 cells may be involved in the development of UC .
It was found that 6-gingerol can alleviate the intestinal inflammatory damage and improve the weight loss of colitis mice .
However , whether 6-gingerol can regulate the balance of Th17/Treg cells and inhibit the intestinal inflammatory response remains to be clarified .
Methods : In this study , a dextran sulfate sodium ( DSS ) -induced colitis mouse model was established , and @ @ @ @ @ @ @ the balance of Th17/Treg cells were observed usingserial assays , including enzyme-linked immunosorbent assay ( ELISA ) , quantitative real time-polymerase chain reaction ( qPCR ) , and Western blotting .
Results : DSS caused the damage of bowel tissue and a 100 % weight loss rate in colitis mice .
The treatment of 6-gingerol can significantly relieve bowel damage and reduce incidence of weight loss to 16.7 % at a low or high dose ( P < 0.05 ) , which was similar to the therapeutic effect of mesalazine .
It was @ @ @ @ @ @ @ levels of IL-6 and IL-17 in serum ( by qPCR ) , and the serum and bowel levels of IL-6 and IL-17 ( by ELISA ) ; these levels were significantly different from those of the blank group ( P < 0.05 ) .
Furthermore , 6-gingerol was found to inhibit the increase of mRNA levels and serum and bowel levels of IL-6 and IL-17 induced by DSS , which is similar with mesalazine .
It was also found that DSS can down-regulate the mRNA level of IL-10 in serum , along with @ @ @ @ @ @ @ , with this being significantly different from the levels of the blank group ( P < 0.05 ) .
6-gingerol could also inhibit the decrease of mRNA levels and serum and bowel levels of IL-10 induced by DSS , which is also similar to mesalazine .
In addition , DSS could increase Th17 cell count and decrease Treg cell count in blood , with significant difference from that of the blank group ( P < 0.05 ) .
6-gingerol could significantly ( P < 0.05 ) inhibit the increase of Th17 cells and @ @ @ @ @ @ @ DSS , which is similar to the effect of mesalazine .
The detection of expression levels of transcription factors RORγT for Th17 and FOXP3 for Treg at both mRNA and protein levels showed that DSS can up-regulate the mRNA and protein levels of RORγT , and down-regulate the mRNA and protein levels of FOXP3 .
Furthermore , 6-gingerol could significantly ( P < 0.05 ) inhibit the up-regulation of RORγT mRNA and protein , and the down-regulation of FOXP3 mRNA and protein induced by DSS , which is similar to the effect of @ @ @ @ @ @ @ in the treatment of DSS-induced UC in mice , by regulating the cell balance of Th17/Treg , and by relieving inflammatory responses both systematically and locally .

Background: Ulcerative colitis (UC) is a non-specific chronic intestinal inflammatory disease with unclear etiology. Previous studies have suggested that the imbalance of Treg/Thl7 cells may be involved in the development of UC. It was found that 6-gingerol can alleviate the intestinal inflammatory damage and improve the weight loss of colitis mice. However, whether 6-gingerol can regulate the balance of Th17/Treg cells and inhibit the intestinal inflammatory response remains to be clarified.
Methods: In this study, a dextran sulfate sodium (DSS)-induced colitis mouse model was established, and the effects of 6-gingerol on cytokines and the balance of Th17/Treg cells were observed usingserial assays, including enzyme-linked immunosorbent assay (ELISA), quantitative real time-polymerase chain reaction (qPCR), and Western blotting.
Results: DSS caused the damage of bowel tissue and a 100% weight loss rate in colitis mice. The treatment of 6-gingerol can significantly relieve bowel damage and reduce incidence of weight loss to 16.7% at a low or high dose (P<0.05), which was similar to the therapeutic effect of mesalazine. It was found that DSS can up-regulate the mRNA levels of IL-6 and IL-17 in serum (by qPCR), and the serum and bowel levels of IL-6 and IL-17 (by ELISA); these levels were significantly different from those of the blank group (P<0.05). Furthermore, 6-gingerol was found to inhibit the increase of mRNA levels and serum and bowel levels of IL-6 and IL-17 induced by DSS, which is similar with mesalazine. It was also found that DSS can down-regulate the mRNA level of IL-10 in serum, along with the serum and bowel level of IL-10, with this being significantly different from the levels of the blank group (P<0.05). 6-gingerol could also inhibit the decrease of mRNA levels and serum and bowel levels of IL-10 induced by DSS, which is also similar to mesalazine. In addition, DSS could increase Th17 cell count and decrease Treg cell count in blood, with significant difference from that of the blank group (P<0.05). 6-gingerol could significantly (P<0.05) inhibit the increase of Th17 cells and the decrease of Treg cells induced by DSS, which is similar to the effect of mesalazine. The detection of expression levels of transcription factors RORγT for Th17 and FOXP3 for Treg at both mRNA and protein levels showed that DSS can up-regulate the mRNA and protein levels of RORγT, and down-regulate the mRNA and protein levels of FOXP3. Furthermore, 6-gingerol could significantly (P<0.05) inhibit the up-regulation of RORγT mRNA and protein, and the down-regulation of FOXP3 mRNA and protein induced by DSS, which is similar to the effect of mesalazine.
Conclusions: 6-gingerol showed efficacy in the treatment of DSS-induced UC in mice, by regulating the cell balance of Th17/Treg, and by relieving inflammatory responses both systematically and locally.


greenmedinfo--2020-07-22--10-gingerol targets lipid rafts associated PI3K/Akt signalling in radio-resistant triple negative br

10-gingerol targets lipid rafts associated PI3K/Akt signalling in radio-resistant triple negative breast cancer cells.

10-gingerol is a major phenolic lipid found in the rhizomes of ginger ( Zingiber officinale ) .
Being amphiphilic in nature , phenolic lipids have the ability to incorporate into cell membranes and modulate membrane properties .
The purpose of the present study was to evaluate the effects of 10-gingerol on lipid raft/membrane raft modulation in radio-resistant triple negative breast cancer ( MDA-MB-231/IR ) cells .
The effects of 10-gingerol on MDA-MB-231/IR cells ' proliferation , clonogenic growth , migration , and invasion were assayed using MTT , colony formation , cell migration , and invasion assays , respectively .
@ @ @ @ @ @ @ extract lipid rafts .
Western blotting and immunofluorescence were employed to assess the effects of 10-gingerol on lipid raft/membrane raft modulation and lipid rafts-associated PI3K/Akt signaling .
Cholesterol measurements were carried out using a commercially available kit .
10-gingerol suppressed the proliferation , migration , invasion , and induced apoptosis through targeting the PI3K/Akt signaling pathway in MDA-MB-231/IR cells .
Moreover , 10-gingerol was found to modulate the lipid rafts of MDA-MB-231/IR cells and attenuate the key PI3K/Akt signaling components in lipid rafts .
The cholesterol content of the lipid rafts and rafts-resident @ @ @ @ @ @ @ to 10-gingerol .
The results of the present study highlight rafts-associated PI3K/Akt signaling as a new target of 10-gingerol in MDA-MB-231/IR cells , thus rationalizing a new rafts-mediated treatment approach for radio-resistant triple negative breast cancer cells .

10-gingerol is a major phenolic lipid found in the rhizomes of ginger (Zingiber officinale). Being amphiphilic in nature, phenolic lipids have the ability to incorporate into cell membranes and modulate membrane properties. The purpose of the present study was to evaluate the effects of 10-gingerol on lipid raft/membrane raft modulation in radio-resistant triple negative breast cancer (MDA-MB-231/IR) cells. The effects of 10-gingerol on MDA-MB-231/IR cells' proliferation, clonogenic growth, migration, and invasion were assayed using MTT, colony formation, cell migration, and invasion assays, respectively. Sucrose density gradient centrifugation was used to extract lipid rafts. Western blotting and immunofluorescence were employed to assess the effects of 10-gingerol on lipid raft/membrane raft modulation and lipid rafts-associated PI3K/Akt signaling. Cholesterol measurements were carried out using a commercially available kit. 10-gingerol suppressed the proliferation, migration, invasion, and induced apoptosis through targeting the PI3K/Akt signaling pathway in MDA-MB-231/IR cells. Moreover, 10-gingerol was found to modulate the lipid rafts of MDA-MB-231/IR cells and attenuate the key PI3K/Akt signaling components in lipid rafts. The cholesterol content of the lipid rafts and rafts-resident Akt signaling were also affected by exposure to 10-gingerol. The results of the present study highlight rafts-associated PI3K/Akt signaling as a new target of 10-gingerol in MDA-MB-231/IR cells, thus rationalizing a new rafts-mediated treatment approach for radio-resistant triple negative breast cancer cells.


greenmedinfo--2020-07-22--6-gingerol alleviates inflammatory injury in DSS-induced ulcerative colitis.

BACKGROUND : The imbalance of Treg/Thl7 cells and inflammatory injury are believed to be involved in the development of ulcerative colitis ( UC ) .
Meanwhile , 6-gingerol has been reported to alleviate intestinal inflammatory damage in mice models , but the underlying mechanism remains elusive .
METHODS : In this study , dextran sulfate sodium ( DSS ) -induced colitis mice models were established to examine the effects of 6-gingerol on IL-17 and IL-10 secretion , and the activation of NF-κB signaling was evaluated using enzyme-linked immunosorbent assay ( ELISA ) , Western blotting , and immunohistochemistry .
RESULTS @ @ @ @ @ @ @ loss caused by DSS in mice models ( P < 0.05 ) , which is similar to the therapeutic drug , mesalazine .
Immunohistochemistry showed that 6-gingerol can repair the damaged glandular structure gradually caused by DSS , significantly decrease the IL-17 level , and increase IL-10 level in bowel tissue .
ELISA revealed that 6-gingerol could significantly decrease the IL17 level and increase IL-10 level in both serum and bowel tissue , and the differences were all statistically significant ( P < 0.05 ) .
In addition , 6-gingerol could suppress the @ @ @ @ @ @ @ which was up-regulated by DSS .
Further analysis with immunohistochemistry indicated p-p65 staining was mainly in the nucleus with some in the cytoplasm after DSS treatment , and the treatment with 6-gingerol could significantly weaken the density of p-p65 both in the cytoplasm and nucleus .
CONCLUSIONS : Our study suggests that 6-gingerol may alleviate inflammatory injury in UC mice by regulating NF-κB signaling pathway .

BACKGROUND: The imbalance of Treg/Thl7 cells and inflammatory injury are believed to be involved in the development of ulcerative colitis (UC). Meanwhile, 6-gingerol has been reported to alleviate intestinal inflammatory damage in mice models, but the underlying mechanism remains elusive.
METHODS: In this study, dextran sulfate sodium (DSS)-induced colitis mice models were established to examine the effects of 6-gingerol on IL-17 and IL-10 secretion, and the activation of NF-κB signaling was evaluated using enzyme-linked immunosorbent assay (ELISA), Western blotting, and immunohistochemistry.
RESULTS: 6-gingerol could significantly reduce the weight loss caused by DSS in mice models (P<0.05), which is similar to the therapeutic drug, mesalazine. Immunohistochemistry showed that 6-gingerol can repair the damaged glandular structure gradually caused by DSS, significantly decrease the IL-17 level, and increase IL-10 level in bowel tissue. ELISA revealed that 6-gingerol could significantly decrease the IL17 level and increase IL-10 level in both serum and bowel tissue, and the differences were all statistically significant (P<0.05). In addition, 6-gingerol could suppress the phosphorylation level of IκBα and p65, which was up-regulated by DSS. Further analysis with immunohistochemistry indicated p-p65 staining was mainly in the nucleus with some in the cytoplasm after DSS treatment, and the treatment with 6-gingerol could significantly weaken the density of p-p65 both in the cytoplasm and nucleus.
CONCLUSIONS: Our study suggests that 6-gingerol may alleviate inflammatory injury in UC mice by regulating NF-κB signaling pathway.


greenmedinfo--2020-07-22--6-Gingerol attenuates microglia-mediated neuroinflammation and ischemic brain injuries.

Neuroinflammation is critical for the pathogenesis of ischemia brain damage .
Over-activated microglia-mediated inflammation plays a very important role in ischemia cerebral injuries .
6-Gingerol , obtained from edible ginger ( Zingiber Officinale ) exhibits protective effects against inflammation .
In this study , we found that 6-Gingerol could reduce the size of infarction ( P = 0.0184 ) and improve neurological functions ( P = 0.04 ) at the third day after ischemic brain injury in vitro .
Since 6-Gingerol has the anti-inflammatory effects , we further investigated its impacts on neuroinflammation mediated by microglia both in vivo and @ @ @ @ @ @ @ levels of pro-inflammatory cytokines Interleukin-1 beta ( IL-1β , P = 0.0213 ) , Interleukin-6 ( IL-6 , P = 0.0316 ) , and inducible NO synthase ( iNOS , P = 0.0229 ) in the infarct penumbra were lower in 6-Gingerol treated groups .
Furthermore , microglia induced pro-inflammatory cytokines , such as IL-6 , IL-1β , incremental intercellular nitric oxide ( NO ) , as well as iNOS were blocked by the treatment of 6-Gingerol in lipopolysaccharide ( LPS ) stimulated microglia .
In terms of mechanism , 6-Gingerol potently suppressed @ @ @ @ @ @ @ ) - mammalian target of rapamycin ( mTOR ) - signal transducer and activator of transcription 3 ( STAT3 ) in LPS-treated microglia .
Taken together , the present study suggested that 6-Gingerol improved cerebral ischemia injury by suppressing microglia-mediated neuroinflammation by down-regulating Akt-mTOR-STAT3 pathway .

Neuroinflammation is critical for the pathogenesis of ischemia brain damage. Over-activated microglia-mediated inflammation plays a very important role in ischemia cerebral injuries. 6-Gingerol, obtained from edible ginger (Zingiber Officinale) exhibits protective effects against inflammation. In this study, we found that 6-Gingerol could reduce the size of infarction (P = 0.0184) and improve neurological functions (P = 0.04) at the third day after ischemic brain injury in vitro. Since 6-Gingerol has the anti-inflammatory effects, we further investigated its impacts on neuroinflammation mediated by microglia both in vivo and in vitro. We found that the levels of pro-inflammatory cytokines Interleukin-1 beta (IL-1β, P = 0.0213), Interleukin-6 (IL-6, P = 0.0316), and inducible NO synthase (iNOS, P = 0.0229) in the infarct penumbra were lower in 6-Gingerol treated groups. Furthermore, microglia induced pro-inflammatory cytokines, such as IL-6, IL-1β, incremental intercellular nitric oxide (NO), as well as iNOS were blocked by the treatment of 6-Gingerol in lipopolysaccharide (LPS) stimulated microglia. In terms of mechanism, 6-Gingerol potently suppressed phosphorylation of serine-threonine protein kinase (Akt) - mammalian target of rapamycin (mTOR) - signal transducer and activator of transcription 3 (STAT3) in LPS-treated microglia. Taken together, the present study suggested that 6-Gingerol improved cerebral ischemia injury by suppressing microglia-mediated neuroinflammation by down-regulating Akt-mTOR-STAT3 pathway.


greenmedinfo--2020-07-22--Effect of shikonin on the proliferation and apoptosis of human ovarian cancer cell SKOV3.

BACKGROUND : This study will investigate the effect of shikonin on the proliferation and apoptosis of human ovarian cancer cell SKOV3 ( HOCC-SKOV3 ) .
METHODS : We will retrieve potential studies from inception to the March 1 , 2020 in Cochrane Library , MEDLINE , EMBASE , Scopus , Cumulative Index to Nursing and Allied Health Literature , WANGFANG , and China National Knowledge In-frastructure .
There are not restrictions related to the language and publication status .
This study will include case-controlled studies ( CCSs ) or randomized controlled studies ( RCSs ) that examine the effect of @ @ @ @ @ @ @ HOCC-SKOV3 .
Two researchers will independently identify literatures , extract data , and appraise study quality .
Any disagreements will be resolved by discussion with another researcher .
RevMan 5.3 software will be placed to perform statistical analysis .
RESULTS : This study will summarize the present evidence to test the effect of shikonin on the proliferation and apoptosis of HOCC-SKOV3 .
CONCLUSION : It will provide evidence to investigate the effect of shikonin on the proliferation and apoptosis of HOCC-SKOV3 , and will supply reference for further study.Systematic review registration : INPLASY202040146 @

BACKGROUND: This study will investigate the effect of shikonin on the proliferation and apoptosis of human ovarian cancer cell SKOV3 (HOCC-SKOV3).
METHODS: We will retrieve potential studies from inception to the March 1, 2020 in Cochrane Library, MEDLINE, EMBASE, Scopus, Cumulative Index to Nursing and Allied Health Literature, WANGFANG, and China National Knowledge In-frastructure. There are not restrictions related to the language and publication status. This study will include case-controlled studies (CCSs) or randomized controlled studies (RCSs) that examine the effect of shikonin on the proliferation and apoptosis of HOCC-SKOV3. Two researchers will independently identify literatures, extract data, and appraise study quality. Any disagreements will be resolved by discussion with another researcher. RevMan 5.3 software will be placed to perform statistical analysis.
RESULTS: This study will summarize the present evidence to test the effect of shikonin on the proliferation and apoptosis of HOCC-SKOV3.
CONCLUSION: It will provide evidence to investigate the effect of shikonin on the proliferation and apoptosis of HOCC-SKOV3, and will supply reference for further study.Systematic review registration: INPLASY202040146.


greenmedinfo--2020-07-22--Proteomic analysis revealed ROS-mediated growth inhibition of Aspergillus terreus by shikonin.

Aspergillus terreus is an emerging fungal pathogen in immunocompromised patients .
Due to the intrinsic resistance of AmB against A. terreus and acquiring resistance to azoles , an alternative antifungal strategy needs investigation .
Thus , we explored the activity of phytochemicals such as shikonin , gallic acid , coumaric acid and quercetin against A. terreus .
Among these , shikonin showed significant inhibition at MIC ; 2 μg/ml .
SEM analyses revealed delayed swelling and distorted cell wall organization in shikonin treated A. terreus conidia .
Further , we performed differential proteome profiling using nLC-ESI-MS/MS , qRT-PCR and catalase @ @ @ @ @ @ @ terreus .
Protein data generated using Proteome Discoverer showed 882 differentially expressed proteins ( 680 up- and 202 down-regulated ) .
GO analysis showed proteins from signaling pathways , oxidative stress , energy metabolism , and cytoskeleton organization .
qRT-PCR of selected genes from ROS detoxification ( catalase-peroxidase , superoxide dismutase ) , respiration ( succinate-dehydrogenase , NADH-ubiquinone oxidoreductase ) , signaling ( protein kinase C , Mitogen-activated protein kinase , cAMP-dependent protein kinase , ras-1 ) , and 1 , 3-β-glucanosyltransferase , rho-1 , β-hexosaminidase showed correlation with expressed proteins .
We @ @ @ @ @ @ @ fluorescence ROS assay correlating with low catalase-peroxidase activity in shikonin treated A. terreus .
Modulation of ROS homeostasis and the metabolic shift could be instrumental in shikonin- mediated growth inhibition of A. terreus .
SIGNIFICANCE : Aspergillosis caused by A. terreus requires more attention due to the development of drug resistance .
In this report , we employed nLC-ESI-MS/MS to identify the differential proteome in A. terreus in response to shikonin .
The identified proteins involved in pathways influenced by shikonin could be helpful to understand the molecular mechanism on how shikonin/ phytochemicals @ @ @ @ @ @ @ and may enable the discovery of novel or synergistic drug targets .

Aspergillus terreus is an emerging fungal pathogen in immunocompromised patients. Due to the intrinsic resistance of AmB against A. terreus and acquiring resistance to azoles, an alternative antifungal strategy needs investigation. Thus, we explored the activity of phytochemicals such as shikonin, gallic acid, coumaric acid and quercetin against A. terreus. Among these, shikonin showed significant inhibition at MIC; 2 μg/ml. SEM analyses revealed delayed swelling and distorted cell wall organization in shikonin treated A. terreus conidia. Further, we performed differential proteome profiling using nLC-ESI-MS/MS, qRT-PCR and catalase assay with and without shikonin treated A. terreus. Protein data generated using Proteome Discoverer showed 882 differentially expressed proteins (680 up- and 202 down-regulated). GO analysis showed proteins from signaling pathways, oxidative stress, energy metabolism, and cytoskeleton organization. qRT-PCR of selected genes from ROS detoxification (catalase-peroxidase, superoxide dismutase), respiration (succinate-dehydrogenase, NADH-ubiquinone oxidoreductase), signaling (protein kinase C, Mitogen-activated protein kinase, cAMP-dependent protein kinase, ras-1), and 1, 3-β-glucanosyltransferase, rho-1, β-hexosaminidase showed correlation with expressed proteins. We also observed elevated reactive oxygen species using fluorescence ROS assay correlating with low catalase-peroxidase activity in shikonin treated A. terreus. Modulation of ROS homeostasis and the metabolic shift could be instrumental in shikonin- mediated growth inhibition of A. terreus. SIGNIFICANCE:Aspergillosis caused by A. terreus requires more attention due to the development of drug resistance. In this report, we employed nLC-ESI-MS/MS to identify the differential proteome in A. terreus in response to shikonin. The identified proteins involved in pathways influenced by shikonin could be helpful to understand the molecular mechanism on how shikonin/ phytochemicals or other antifungal agents inhibit fungal growth and may enable the discovery of novel or synergistic drug targets.


greenmedinfo--2020-07-22--Evaluation of green tea polyphenols as novel corona virus main protease (Mpro) inhibitors.

Coronavirus disease 2019 ( COVID-19 ) is a viral respiratory disease which caused global health emergency and announced as pandemic disease by World Health Organization .
Lack of specific drug molecules or treatment strategy against this disease makes it more devastating .
Thus , there is an urgent need of effective drug molecules to fight against COVID-19 .
The main protease ( Mpro ) of SARS CoV-2 , a key component of this viral replication , is considered as a prime target for anti-COVID-19 drug development .
In order to find potent Mpro inhibitors , we have selected eight polyphenols @ @ @ @ @ @ @ already known to exert antiviral activity against many RNA viruses .
We have elucidated the binding affinities and binding modes between these polyphenols including a well-known Mpro inhibitor N3 ( having binding affinity -7.0 kcal/mol ) and Mpro using molecular docking studies .
All eight polyphenols exhibit good binding affinity toward Mpro ( -7.1 to -9.0 kcal/mol ) .
However , only three polyphenols ( epigallocatechin gallate , epicatechingallate and gallocatechin-3-gallate ) interact strongly with one or both catalytic residues ( His41 and Cys145 ) of Mpro .
Molecular dynamics simulations ( 100 @ @ @ @ @ @ @ further reveal that these complexes are highly stable , experience less conformational fluctuations and share similar degree of compactness .
Estimation of total number of intermolecularH-bond and MM-GBSA analysis affirm the stability of these three Mpro-polyphenol complexes .
Pharmacokinetic analysis additionally suggested that these polyphenols possess favorable drug-likeness characteristics .
Altogether , our study shows that these three polyphenols can be used as potential inhibitors against SARS CoV-2 Mpro and are promising drug candidates for COVID-19 treatment.Communicated by Ramaswamy H. Sarma .

Coronavirus disease 2019 (COVID-19) is a viral respiratory disease which caused global health emergency and announced as pandemic disease by World Health Organization. Lack of specific drug molecules or treatment strategy against this disease makes it more devastating. Thus, there is an urgent need of effective drug molecules to fight against COVID-19. The main protease (Mpro) of SARS CoV-2, a key component of this viral replication, is considered as a prime target for anti-COVID-19 drug development. In order to find potent Mpro inhibitors, we have selected eight polyphenols from green tea, as these are already known to exert antiviral activity against many RNA viruses. We have elucidated the binding affinities and binding modes between these polyphenols including a well-known Mpro inhibitor N3 (having binding affinity -7.0 kcal/mol) and Mpro using molecular docking studies. All eight polyphenols exhibit good binding affinity toward Mpro (-7.1 to -9.0 kcal/mol). However, only three polyphenols (epigallocatechin gallate, epicatechingallate and gallocatechin-3-gallate) interact strongly with one or both catalytic residues (His41 and Cys145) of Mpro. Molecular dynamics simulations (100 ns) on these three Mpro-polyphenol systems further reveal that these complexes are highly stable, experience less conformational fluctuations and share similar degree of compactness. Estimation of total number of intermolecularH-bond and MM-GBSA analysis affirm the stability of these three Mpro-polyphenol complexes. Pharmacokinetic analysis additionally suggested that these polyphenols possess favorable drug-likeness characteristics. Altogether, our study shows that these three polyphenols can be used as potential inhibitors against SARS CoV-2 Mpro and are promising drug candidates for COVID-19 treatment.Communicated by Ramaswamy H. Sarma.


greenmedinfo--2020-07-22--Identification of potential natural inhibitors of SARS-CoV2 main protease by molecular docking and s

Identification of potential natural inhibitors of SARS-CoV2 main protease by molecular docking and simulation studies.

Coronaviruses are contagious pathogens primarily responsible for respiratory and intestinal infections .
Research efforts to develop antiviral agents against coronavirus demonstrated the main protease ( Mpro ) protein may represent effective drug target .
X-ray crystallographic structure of the SARS-CoV2 Mpro protein demonstrated the significance of Glu166 , Cys141 , and His41 residues involved in protein dimerization and its catalytic function .
We performedscreening of compounds fromL .
( Zingiberaceae family ) against Mpro protein inhibition .
Employing a combination of molecular docking , scoring functions , and molecular dynamics simulations , 267 compounds were screened by docking on Mpro @ @ @ @ @ @ @ profile analysis exhibited strong binding on the Mpro catalytic domain with compounds C ( 1E,6E ) -1,2,6,7-tetrahydroxy-1,7-bis ( 4-hydroxy-3-methoxyphenyl ) hepta-1,6-diene-3,5-dione ) and C ( 4Z,6E ) -1,5-dihydroxy-1,7-bis ( 4-hydroxyphenyl ) hepta-4,6-dien-3-one as lead agents .
Compound Cand Cshowed minimum binding score ( -9.08 and -8.07 kcal/mole ) against Mpro protein in comparison to shikonin and lopinavir ( ≈ -5.4 kcal/mole ) a standard Mpro inhibitor .
Furthermore , principal component analysis , free energy landscape and protein-ligand energy calculation studies revealed that these two compounds strongly bind to the catalyticcore of the @ @ @ @ @ @ @ , a standard antiretroviral of the protease inhibitor class .
Taken together , this structure based optimization has provided lead on two natural Mpro inhibitors for further testing and development as therapeutics against human coronavirus.Communicated by Ramaswamy H. Sarma .

Coronaviruses are contagious pathogens primarily responsible for respiratory and intestinal infections. Research efforts to develop antiviral agents against coronavirus demonstrated the main protease (Mpro) protein may represent effective drug target. X-ray crystallographic structure of the SARS-CoV2 Mpro protein demonstrated the significance of Glu166, Cys141, and His41 residues involved in protein dimerization and its catalytic function. We performedscreening of compounds fromL. (Zingiberaceae family) against Mpro protein inhibition. Employing a combination of molecular docking, scoring functions, and molecular dynamics simulations, 267 compounds were screened by docking on Mpro crystallographic structure. Docking score and interaction profile analysis exhibited strong binding on the Mpro catalytic domain with compounds C(1E,6E)-1,2,6,7-tetrahydroxy-1,7-bis(4-hydroxy-3-methoxyphenyl)hepta-1,6-diene-3,5-dione) and C(4Z,6E)-1,5-dihydroxy-1,7-bis(4-hydroxyphenyl)hepta-4,6-dien-3-one as lead agents. Compound Cand Cshowed minimum binding score (-9.08 and -8.07 kcal/mole) against Mpro protein in comparison to shikonin and lopinavir (≈ -5.4 kcal/mole) a standard Mpro inhibitor. Furthermore, principal component analysis, free energy landscape and protein-ligand energy calculation studies revealed that these two compounds strongly bind to the catalyticcore of the Mpro protein with higher efficacy than lopinavir, a standard antiretroviral of the protease inhibitor class. Taken together, this structure based optimization has provided lead on two natural Mpro inhibitors for further testing and development as therapeutics against human coronavirus.Communicated by Ramaswamy H. Sarma.


greenmedinfo--2020-07-22--5G Radiation May Cause Coronavirus Infection, New Study Suggests

A new paper published in the Journal of Biological Regulators & Homeostatic Agents posits there may be a unique , causally connected relationship between 5G millimeter wave exposure and Coronavirus ; an idea which though widely discussed early on in the global COVID crisis , was eventually dismissed as “ conspiracy theory ” by the mainstream media and government officials , resulting in widespread censorship on social media platforms .
The new study titled , “ 5G Technology and induction of coronavirus in skin cells , ” authored by an international collaboration of scientists from Italy , the US , @ @ @ @ @ @ @ may be absorbed by dermatologic cells which act like antennas , * thereby transferring its effects to other cells , including activating DNA-based biosynthetic processes within the nucleus of the cell , resulting in the de novo synthesis of coronaviruses in biological cells .
The authors describe how this may work as follows : “ DNA is built from charged electrons and atoms and has an inductor-like structure .
This structure could be divided into linear , toroid and round inductors .
Inductors interact with external electromagnetic waves , move and produce some @ @ @ @ @ @ @ shapes of these waves are similar to shapes of hexagonal and pentagonal bases of their DNA source .
These waves produce some holes in liquids within the nucleus .
To fill these holes , some extra hexagonal and pentagonal bases are produced .
These bases could join to each other and form virus-like structures such as Coronavirus .
To produce these viruses within a cell , it is necessary that the wavelength of external waves be shorter than the size of the cell .
Thus 5G millimeter waves could be good candidates for @ @ @ @ @ @ @ Coronaviruses ( COVID-19 ) within cells.
” The idea that one of the causes of illness associated with the coronavirus crisis derives from non-native electromagnetic radiation exposure , including from 5G millimeter waves , was proposed by Dr. Thomas Cowan , in the highly controversial presentation below that resulted in being labeled as “ false and harmful ” information on a variety of social media and global mainstream media platforms .
According to Dr. Cowan , 5G millimeter waves may induce cell damage which results in the excretion of cellular contents , which @ @ @ @ @ @ @ nanoparticles produced within cells as natural forms of intercellular communication ) .
These debris , which he describes as part of the detoxification of the damaged cells ( `` cellularl pooping '' ) may be mistakenly identified as exogenous viruses such as coronavirus and may result in false positives on RT-PCR tests which are notoriously ineffective at positivity distinguishing specific strains of viruses and identifying them with any certainty .
While this idea differs slightly from the one proposed by the study authors , they overlap in significant ways .
In both explanations @ @ @ @ @ @ @ which are identified as being caused by `` COVID virus . ''
Whether or not there is a de novo synthesis of coronaviruses as a result of 5G radiation exposure , or whether or not the damage to the cell produces debris containing COVID virus like nucleic acid , remains to be determined .
But in both scenarios , what is perceived as a COVID illness from the outside in may in fact be the byproduct of cellular changes resulting from EMF exposure and not an exogenous viral infection , as commonly assumed @ @ @ @ @ @ @ this topic and discovered that what the global , mainstream medical establishment and media are identifying as “ COVID-19 ” is likely our own exosomes being secreted by either healthy or damaged cells .
I highly recommend viewing his presentation below , and you can obtain more presentations of this kind in section two of www.QuestioningCovid.com titled , Questioning Germ Theory , Contagion and Viral Testing .
My take on it , which I explore in the video below “ COVID-19 -- is it really about a virus ?
” is that exosomal @ @ @ @ @ @ @ simulate infectious processes , but rather than being simply a sign of pathology and imminent morbidity and mortality , are designed to support the collective health of a group of individuals or species , or even between species .
In this view , what is commonly understood to be infection and contagion is actually a surface misunderstanding of a process of horizontal information exchange designed to facilitate enhanced detoxification , xenohormesis , and the activation of resiliency pathways within a species , and is the very origin of what is known as “ @ @ @ @ @ @ @ back up an important topic that has been all but suppressed and censored today , namely , that health problems associated with infections such as coronavirus involve a wide range of factors , including foremost the role of the so-called “ bioterrain ” of the cell in determining susceptibility to infection and illness .
Viruses do not exist in a vacuum , and don ’ t simply attack helpless bodies .
When the cellular terrain is healthy and resilient infections tend not to take hold , or , have effects that confer lasting @ @ @ @ @ @ @ of the human microbiome ( and the total set of viruses or viral-like components of the microbiome known as the human virome ) , reveals that classical germ theory is bankrupt , and that what we once believed were invisible viral threats “ out there ” are surprisingly similar if not identical to endogenous viral-like elements within our cells known as exosomes , and often can not be distinguished from them .
For example , the widespread use of RT-PCR tests to identify “ covid ” may simply be identifying our bodies ’ @ @ @ @ @ @ @ thereby generating “ false positives ” which justify the continual implementation of allopathic approaches that result in profound iatrogenic damage to the body falsely described as “ caused by COVID.
” I highly recommend that those interested in understanding the true nature of viruses and their indispensable role in establishing immunological self-tolerance , homeostasis , and ultimately health , watch distinguished NIH speaker and virome expert Dr. Herbert Virgin 's presentation : Also , learn more about the New Biology and its impact on our understanding of infectious disease by reading : • @ @ @ @ @ @ @ Vaccine Policy , and Patriarchy • Why Everything You Learned About Viruses is WRONG *Incidentally , the notion that the harms of 5G radiation extend beyond the surface of the skin , as commonly paroted by the telecom industry and its would-be regulators , and that human skin may act as a 5G radiation receiver was recently discussed in a paper published in 2018 titled , “ The human skin as a sub-THz receiver – Does 5G pose a danger to it or not ?
”

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A now withdrawn paper published in the Journal of Biological Regulators & Homeostatic Agents posits there may be a unique, causally connected relationship between 5G millimeter wave exposure and coronavirus -- an idea which, though widely discussed early on in the global COVID crisis, was eventually dismissed as "conspiracy theory" by the mainstream media and government officials, resulting in widespread censorship on social media platforms
The now retracted study, titled, "5G Technology and induction of coronavirus in skin cells," authored by an international collaboration of scientists from Italy, the U.S. and Russia, suggests that 5G radiation may be absorbed by dermatologic cells that act like antennas,* thereby potentially transferring its effects to other cells, including activating DNA-based biosynthetic processes within the nucleus of the cell, possibly resulting in the de novo synthesis of coronaviruses in biological cells.
The authors describe how this may work as follows:
"DNA is built from charged electrons and atoms and has an inductor-like structure. This structure could be divided into linear, toroid and round inductors. Inductors interact with external electromagnetic waves, move and produce some extra waves within the cells. The shapes of these waves are similar to shapes of hexagonal and pentagonal bases of their DNA source. These waves produce some holes in liquids within the nucleus. To fill these holes, some extra hexagonal and pentagonal bases are produced. These bases could join to each other and form virus-like structures such as Coronavirus. To produce these viruses within a cell, it is necessary that the wavelength of external waves be shorter than the size of the cell. Thus 5G millimeter waves could be good candidates for applying in constructing virus-like structures such as Coronaviruses (COVID-19) within cells."
As for why the study was retracted, it's stated:
"This article has been retracted at the request of the Editor. After a thorough investigation the Editor-in-Chief has retracted this article as it showed evidence of substantial manipulation of the peer review."
However, the idea that one of the causes of illness associated with the coronavirus crisis derives from non-native electromagnetic radiation exposure, including from 5G millimeter waves, was proposed by Dr. Thomas Cowan, in the highly controversial presentation below. This has been labeled as "false and harmful" information on a variety of social media and global mainstream media platforms.
According to Cowan, 5G millimeter waves may induce cell damage that results in the excretion of cellular contents, which include nucleic acids and exosomes (virus-like nanoparticles produced within cells as natural forms of intercellular communication).
This debris, which he describes as part of the detoxification of the damaged cells ("cellular pooping"), may be mistakenly identified as exogenous viruses such as coronavirus and may result in false positives on RT-PCR tests, which are notoriously ineffective at positively distinguishing specific strains of viruses and identifying them with any certainty.
While this idea differs slightly from the one proposed by the study authors, they overlap in significant ways. In both explanations, 5G associated radiation induces cell changes that are identified as being caused by "COVID virus."
Whether or not there is a de novo synthesis of coronaviruses as a result of 5G radiation exposure, or whether or not the damage to the cell produces debris containing COVID virus like nucleic acid, remains to be determined. But in both scenarios, what is perceived as a COVID illness from the outside in may in fact be the byproduct of cellular changes resulting from EMF exposure and not an exogenous viral infection, as commonly assumed.
Dr. Andrew Kaufman has also explored this topic and discovered that what the global mainstream medical establishment and media are identifying as "COVID-19" is likely our own exosomes being secreted by either healthy or damaged cells.
I highly recommend viewing his presentation below, and you can obtain more presentations of this kind in section two of QuestioningCovid.com, titled, Questioning Germ Theory, Contagion and Viral Testing.
My take on it, which I explore in the video below -- "COVID-19 -- is it really about a virus?" -- is that exosomal processes within the body and between bodies simulate infectious processes, but rather than being simply a sign of pathology and imminent morbidity and mortality, are designed to support the collective health of a group of individuals or species, or even between species.
In this view, what is commonly understood to be infection and contagion is actually a surface misunderstanding of a process of horizontal information exchange designed to facilitate enhanced detoxification, xenohormesis and the activation of resiliency pathways within a species, and is the very origin of what is known as "herd immunity."
This latest paper opens back up an important topic that has been all but suppressed and censored today, namely, that health problems associated with infections such as coronavirus involve a wide range of factors, including foremost the role of the so-called "bioterrain" of the cell in determining susceptibility to infection and illness.
Viruses do not exist in a vacuum and don't simply attack helpless bodies. When the cellular terrain is healthy and resilient infections tend not to take hold, or even have effects that confer lasting health benefits.
Moreover, the discovery of the human microbiome (and the total set of viruses or viral-like components of the microbiome known as the human virome) reveals that classical germ theory is bankrupt, and that what we once believed were invisible viral threats "out there" are surprisingly similar, if not identical, to endogenous viral-like elements within our cells known as exosomes, and often cannot be distinguished from them.
For example, the widespread use of RT-PCR tests to identify "COVID" may simply be identifying our bodies' own viral or exosomal contents, and thereby generating "false positives," which justify the continual implementation of allopathic approaches that result in profound iatrogenic damage to the body, falsely described as "caused by COVID."
I highly recommend that those interested in understanding the true nature of viruses and their indispensable role in establishing immunological self-tolerance, homeostasis, and ultimately health, watch distinguished National Institutes of Health (NIH) speaker and virome expert Dr. Herbert Virgin's presentation:
Also, you can learn more about the New Biology and its impact on our understanding of infectious disease by reading:
*Incidentally, the notion that the harms of 5G radiation extend beyond the surface of the skin, as commonly paroted by the telecom industry and its would-be regulators, and that human skin may act as a 5G radiation receiver was discussed in a paper published in 2018 titled, "The human skin as a sub-THz receiver - Does 5G pose a danger to it or not?"


greenmedinfo--2020-07-22--Inhibition of the STAT3 signalling pathway contributes to the anti-melanoma activities of shikonin.

Background : Malignant melanoma is an extremely aggressive and metastatic cancer , and highly resistant to conventional therapies .
Signal transducer and activator of transcription 3 ( STAT3 ) signaling promotes melanoma development and progression , which has been validated as an effective target in melanoma treatment .
Natural naphthoquinone shikonin is reported to exert anti-melanoma effects .
However , the underlying mechanisms have not been fully elucidated .
Purpose : This study aims to evaluate the anti-melanoma activities of shikonin and explore the involvement of STAT3 signaling in these effects .
Methods : Zebrafish tumor model was established to @ @ @ @ @ @ @ .
MTT assay and colony formation assay were employed to investigate the anti-proliferative effects of shikonin on human melanoma A375 and A2058 cells .
Flow cytometry was used to analyze cell cycle distribution and apoptosis induction .
Wound healing assay and Transwell chamber assay were conducted to examine the cell migratory and invasive abilities .
Immunofluorescence assay was used to observe F-actin , Tubulin , and STAT3 localization .
Western blotting was used to determine the expression levels of proteins associated with apoptosis and key proteins in the STAT3 signaling pathway .
Immunoblotting @ @ @ @ @ @ @ determine the homo-dimerization of STAT3 .
Gelatin zymography was employed to evaluate the enzymatic activity of MMP-2 and MMP-9 .
Transient transfection was used to overexpress STAT3 in cell models .
Results : Shikonin suppressed melanoma growth in cultured cells and in zebrafish xenograft models .
Shikonin induced melanoma cells apoptosis , inhibited cell migration and invasion .
Mechanistic study indicated that shikonin inhibited the phosphorylation and homo-dimerization of STAT3 , thus reduced its nuclear localization .
Further study showed that shikonin decreased the levels of STAT3-targeted genes Mcl-1 , Bcl-2 , MMP-2 @ @ @ @ @ @ @ are involved in melanoma survival , migration , and invasion .
More importantly , overexpression of constitutively active STAT3 partially abolished the anti-proliferative , anti-migratory , and anti-invasive effects of shikonin .
Conclusion : The anti-melanoma activity of shikonin is at least partially attributed to the inhibition on STAT3 signaling .
These findings provide new insights into the anti-melanoma molecular mechanisms of shikonin , suggesting its potential in melanoma treatment .

Background: Malignant melanoma is an extremely aggressive and metastatic cancer, and highly resistant to conventional therapies. Signal transducer and activator of transcription 3 (STAT3) signaling promotes melanoma development and progression, which has been validated as an effective target in melanoma treatment. Natural naphthoquinone shikonin is reported to exert anti-melanoma effects. However, the underlying mechanisms have not been fully elucidated.
Purpose: This study aims to evaluate the anti-melanoma activities of shikonin and explore the involvement of STAT3 signaling in these effects.
Methods: Zebrafish tumor model was established to evaluate the anti-human melanoma effects of shikonin. MTT assay and colony formation assay were employed to investigate the anti-proliferative effects of shikonin on human melanoma A375 and A2058 cells. Flow cytometry was used to analyze cell cycle distribution and apoptosis induction. Wound healing assay and Transwell chamber assay were conducted to examine the cell migratory and invasive abilities. Immunofluorescence assay was used to observe F-actin, Tubulin, and STAT3 localization. Western blotting was used to determine the expression levels of proteins associated with apoptosis and key proteins in the STAT3 signaling pathway. Immunoblotting was performed in DSS cross-linked cells to determine the homo-dimerization of STAT3. Gelatin zymography was employed to evaluate the enzymatic activity of MMP-2 and MMP-9. Transient transfection was used to overexpress STAT3 in cell models.
Results: Shikonin suppressed melanoma growth in cultured cells and in zebrafish xenograft models. Shikonin induced melanoma cells apoptosis, inhibited cell migration and invasion. Mechanistic study indicated that shikonin inhibited the phosphorylation and homo-dimerization of STAT3, thus reduced its nuclear localization. Further study showed that shikonin decreased the levels of STAT3-targeted genes Mcl-1, Bcl-2, MMP-2, vimentin, and Twist, which are involved in melanoma survival, migration, and invasion. More importantly, overexpression of constitutively active STAT3 partially abolished the anti-proliferative, anti-migratory, and anti-invasive effects of shikonin.
Conclusion: The anti-melanoma activity of shikonin is at least partially attributed to the inhibition on STAT3 signaling. These findings provide new insights into the anti-melanoma molecular mechanisms of shikonin, suggesting its potential in melanoma treatment.


greenmedinfo--2020-07-22--Clinical trials on pain lowering effect of ginger: A narrative review

Ginger has a pain-reducing effect and it can modulate pain through various mechanisms : inhibition of prostaglandins via the COX and LOX-pathways , antioxidant activity , inibition of the transcription factor nf-kB , or acting as agonist of vanilloid nociceptor .
This narrative review summarizes the last 10-year of randomized controlled trials ( RCTs ) , in which ginger was traditionally used as a pain reliever for dysmenorrhea , delayed onset muscle soreness ( DOMS ) , osteoarthritis ( AO ) , chronic low back pain ( CLBP ) , and migraine .
Regarding dysmenorrhea , six eligible studies suggest @ @ @ @ @ @ @ As concerned with DOMS , the four eligible RCTs suggested a reduction of inflammation after oral and topical ginger administration .
Regarding knee AO , nine RCTs agree in stating that oral and topical use of ginger seems to be effective against pain , while other did not find significant differences .
One RCT considered the use of ginger in migraine and suggested its beneficial activity .
Finally , one RCT evaluated the effects of Swedish massage with aromatic ginger oil on CLBP demonstrated a reduction in pain .
The use of ginger @ @ @ @ @ @ @ and promising , even though more studies are needed to create a consensus about the dosage of ginger useful for long-term therapy .

Ginger has a pain-reducing effect and it can modulate pain through various mechanisms: inhibition of prostaglandins via the COX and LOX-pathways, antioxidant activity, inibition of the transcription factor nf-kB, or acting as agonist of vanilloid nociceptor. This narrative review summarizes the last 10-year of randomized controlled trials (RCTs), in which ginger was traditionally used as a pain reliever for dysmenorrhea, delayed onset muscle soreness (DOMS), osteoarthritis (AO), chronic low back pain (CLBP), and migraine. Regarding dysmenorrhea, six eligible studies suggest a promising effect of oral ginger. As concerned with DOMS, the four eligible RCTs suggested a reduction of inflammation after oral and topical ginger administration. Regarding knee AO, nine RCTs agree in stating that oral and topical use of ginger seems to be effective against pain, while other did not find significant differences. One RCT considered the use of ginger in migraine and suggested its beneficial activity. Finally, one RCT evaluated the effects of Swedish massage with aromatic ginger oil on CLBP demonstrated a reduction in pain. The use of ginger for its pain lowering effect is safe and promising, even though more studies are needed to create a consensus about the dosage of ginger useful for long-term therapy.


greenmedinfo--2020-07-22--The efficacy of electro-acupuncture added to standard therapy in the management of Bell palsy.

OBJECTIVE : To investigate the comparative efficacy of electro-acupuncture when added to standard therapy in patients with Bell palsy in terms of clinical and neurophysiologic outcomes .
METHODS : A total of 88 patients with Bell palsy who received standard treatment ( ST group ; n = 40 , mean ± standard deviation age : 39.2 ± 6.6 years , 60.0 % were males ) or standard treatment plus electro-acupuncture ( ST-EA group ; n = 48 , mean ± standard deviation age : 39.5 ± 6.9 years , 58.3 % were males ) were included .
Data on patient @ @ @ @ @ @ @ 3-month outcomes on treatment response assessed via House-Brackmann grading system and facial nerve recovery profile and electromyography were recorded .
RESULTS : Application of ST-EA versus ST was associated with a significantly higher rate of normal nerve function on 12th week electromyography ( 66.7 % versus 25.0 % , P = 0.020 ) , higher frequency of patients with House-Brackmann grade ≤2 in the 3rd week ( 79.2 % versus 45.0 % , P = 0.029 ) , 6th week ( 87.5 % versus 45.0 % , P = 0.004 ) , and @ @ @ @ @ @ @ % , P = 0.001 ) , and those with facial nerve recovery profile scores ≥8 in the 6th week ( 83.3 % versus 45.0 % , P = 0.011 ) and 12th week ( 87.5 % versus 50.0 % , P = 0.009 ) of treatment .
CONCLUSION : In conclusion , our findings in patients with Bell palsy revealed superiority of electro-acupuncture added to standard therapy over standard therapy alone in terms of improvement of nerve dysfunction , decrease in paralysis severity , and better functional recovery .
This seems to @ @ @ @ @ @ @ a safe and promising adjunct in the achievement of more satisfactory clinical outcomes in the management of Bell palsy when used in combination with standard medical and physiotherapy .

OBJECTIVE: To investigate the comparative efficacy of electro-acupuncture when added to standard therapy in patients with Bell palsy in terms of clinical and neurophysiologic outcomes.
METHODS: A total of 88 patients with Bell palsy who received standard treatment (ST group; n = 40, mean ± standard deviation age: 39.2 ± 6.6 years, 60.0% were males) or standard treatment plus electro-acupuncture (ST-EA group; n = 48, mean ± standard deviation age: 39.5 ± 6.9 years, 58.3% were males) were included. Data on patient demographics, symptoms, comorbidities, and 3-month outcomes on treatment response assessed via House-Brackmann grading system and facial nerve recovery profile and electromyography were recorded.
RESULTS: Application of ST-EA versus ST was associated with a significantly higher rate of normal nerve function on 12th week electromyography (66.7% versus 25.0%, P = 0.020), higher frequency of patients with House-Brackmann grade ≤2 in the 3rd week (79.2% versus 45.0%, P = 0.029), 6th week (87.5% versus 45.0%, P = 0.004), and 12th week (95.8% versus 50.0%, P = 0.001), and those with facial nerve recovery profile scores ≥8 in the 6th week (83.3% versus 45.0%, P = 0.011) and 12th week (87.5% versus 50.0%, P = 0.009) of treatment.
CONCLUSION: In conclusion, our findings in patients with Bell palsy revealed superiority of electro-acupuncture added to standard therapy over standard therapy alone in terms of improvement of nerve dysfunction, decrease in paralysis severity, and better functional recovery. This seems to indicate the likelihood of electro-acupuncture to be a safe and promising adjunct in the achievement of more satisfactory clinical outcomes in the management of Bell palsy when used in combination with standard medical and physiotherapy.


greenmedinfo--2020-07-22--Effects and mechanisms of acupuncture and electroacupuncture for functional dyspepsia.

BACKGROUND : Functional dyspepsia ( FD ) is a common digestive disease with limited therapeutic options .
According to evidence-based clinical practice , acupuncture or electroacupuncture ( EA ) seems to be a promising therapy for patients with FD .
However , there is still a lack of systematic reviews that have analyzed current clinical trials for a better understanding of mechanisms involved in the ameliorating effect of acupuncture and EA on FD .
AIM : To evaluate the results and qualities of existing clinical evidence for researching the underlying mechanisms of acupuncture/EA in treating FD .
METHODS : A @ @ @ @ @ @ @ to identify randomized controlled trials in which research on the mechanism of acupuncture or EA was conducted in FD patients .
Databases searched included PubMed , EMBASE , Cochrane Library , and Web of Science .
Data extraction and quality assessment were completed by two investigators independently and the results of quality evaluation were exported through Review Manager V5.3 .
RESULTS : Eight studies were included in this review with a total of 17 items for detecting techniques for mechanistic research .
Positive effects of acupuncture and EA were observed in regulating gastric @ @ @ @ @ @ @ , gastrointestinal hormones , and central and autonomic functions while improving dyspeptic symptoms and quality of life .
CONCLUSION : The key findings of this systematic review support the potential of acupuncture and EA in altering the heterogeneous pathophysiology in patients with FD .
However , high-quality studies with well-planned designs are necessary to provide more credible evidence .

BACKGROUND: Functional dyspepsia (FD) is a common digestive disease with limited therapeutic options. According to evidence-based clinical practice, acupuncture or electroacupuncture (EA) seems to be a promising therapy for patients with FD. However, there is still a lack of systematic reviews that have analyzed current clinical trials for a better understanding of mechanisms involved in the ameliorating effect of acupuncture and EA on FD.
AIM: To evaluate the results and qualities of existing clinical evidence for researching the underlying mechanisms of acupuncture/EA in treating FD.
METHODS: A systematic search of the literature was performed to identify randomized controlled trials in which research on the mechanism of acupuncture or EA was conducted in FD patients. Databases searched included PubMed, EMBASE, Cochrane Library, and Web of Science. Data extraction and quality assessment were completed by two investigators independently and the results of quality evaluation were exported through Review Manager V5.3.
RESULTS: Eight studies were included in this review with a total of 17 items for detecting techniques for mechanistic research. Positive effects of acupuncture and EA were observed in regulating gastric motility, gastric accommodation, mental status, gastrointestinal hormones, and central and autonomic functions while improving dyspeptic symptoms and quality of life.
CONCLUSION: The key findings of this systematic review support the potential of acupuncture and EA in altering the heterogeneous pathophysiology in patients with FD. However, high-quality studies with well-planned designs are necessary to provide more credible evidence.


greenmedinfo--2020-07-22--Electroacupuncture inhibits neuronal autophagy and apoptosis via the PI3K/AKT Pathway following isch

Electroacupuncture inhibits neuronal autophagy and apoptosis via the PI3K/AKT Pathway following ischemic stroke.

Electroacupuncture ( EA ) is a safe and effective therapy for ischemic stroke in both clinical and laboratory settings .
However , the underlying mechanism behind EA treatment for stroke remains unclear .
Here , we aimed to evaluate whether EA treatment at the acupoints of Zusanli ( ST36 ) and Quchi ( LI11 ) exerted a neuroprotective effect on ischemic stroke rats by modulating autophagy and apoptosisthe PI3K/AKT/mTOR signaling pathway .
EA was performed at 24 h following brain ischemia/reperfusion ( I/R ) for 30 min per day for 3 days .
Our results indicated that EA treatment significantly @ @ @ @ @ @ @ in ischemic stroke rats .
Also , EA intervention markedly reduced neuronal apoptosis by suppressing the activation of cleaved caspase-3 ( CCAS3 ) at 72 h following I/R , as shown by a Western blot analysis .
Furthermore , EA treatment after ischemic stroke suppressed the ischemia activated expression level of LC3II/I and Atg7 and increased the ischemia inhibited expression level of PI3K , phosphorylation of mTOR , phosphorylation of AKT , P62 and LAMP1 , hence mediating the autophagy level of the neurocyte , which was reversed by the PI3K inhibitor Dactolisib @ @ @ @ @ @ @ that the protective effects of EA treatment at points of Quchi ( LI11 ) and Zusanli ( ST36 ) in rats following cerebral I/R injury was associated with the inhibition of neuronal apoptosis and autophagyactivating the PI3K/AKT/mTOR signaling pathway .

Electroacupuncture (EA) is a safe and effective therapy for ischemic stroke in both clinical and laboratory settings. However, the underlying mechanism behind EA treatment for stroke remains unclear. Here, we aimed to evaluate whether EA treatment at the acupoints of Zusanli (ST36) and Quchi (LI11) exerted a neuroprotective effect on ischemic stroke rats by modulating autophagy and apoptosisthe PI3K/AKT/mTOR signaling pathway. EA was performed at 24 h following brain ischemia/reperfusion (I/R) for 30 min per day for 3 days. Our results indicated that EA treatment significantly decreased neurological deficits and cerebral infarct volume in ischemic stroke rats. Also, EA intervention markedly reduced neuronal apoptosis by suppressing the activation of cleaved caspase-3 (CCAS3) at 72 h following I/R, as shown by a Western blot analysis. Furthermore, EA treatment after ischemic stroke suppressed the ischemia activated expression level of LC3II/I and Atg7 and increased the ischemia inhibited expression level of PI3K, phosphorylation of mTOR, phosphorylation of AKT, P62 and LAMP1, hence mediating the autophagy level of the neurocyte, which was reversed by the PI3K inhibitor Dactolisib. In summary, our results indicate that the protective effects of EA treatment at points of Quchi (LI11) and Zusanli (ST36) in rats following cerebral I/R injury was associated with the inhibition of neuronal apoptosis and autophagyactivating the PI3K/AKT/mTOR signaling pathway.


greenmedinfo--2020-07-22--Electro-acupuncture inhibits p66Shc-mediated oxidative stress to facilitate functional recovery afte

Electro-acupuncture inhibits p66Shc-mediated oxidative stress to facilitate functional recovery after spinal cord injury.

Oxidative stress is the core problem in improving secondary spinal cord injury ( SCI ) .
To investigate the effect of electro-acupuncture with different frequencies on neuroinflammation , oxidative stress injury , as well as related signaling pathways , male Sprague-Dawley ( SD ) rats were induced using operation for model SCI and then treated with electrical stimulation at low frequency ( 2 mA , 0.2 Hz ) , medium frequency ( 2 mA , 50 Hz ) , and high frequency ( 2 mA , 100 Hz ) , respectively .
Here , we first demonstrated that the JNK/p66signal @ @ @ @ @ @ @ anti-oxidation effect of FoxO3a to induce oxidative stress damage after SCI and the mechanism of electro-acupuncture in anti-oxidative stress .
Electro-acupuncture facilitated functional recovery after SCI and improved the apoptosis of neurons .
Furthermore , p38MAPK-mediated microglia activation and inflammatory reaction and JNK/p66-mediated ROS generation and oxidative stress damage were both attenuated by electro-acupuncture .
However , the inhibitory effect of electro-acupuncture on p38MAPK was enslaved to the acupuncture frequency , but the ROS generation and phosphorylation of p66were effectively inhibited by electro-acupuncture .
Therefore , the activation of JNK/p66promoted the ROS-induced oxidative @ @ @ @ @ @ @ the phosphorylation of p66-mediated oxidative stress was the key target of electro-acupuncture to facilitate functional recovery SCI , but not p38MAPK .

Oxidative stress is the core problem in improving secondary spinal cord injury (SCI). To investigate the effect of electro-acupuncture with different frequencies on neuroinflammation, oxidative stress injury, as well as related signaling pathways, male Sprague-Dawley (SD) rats were induced using operation for model SCI and then treated with electrical stimulation at low frequency (2 mA, 0.2 Hz), medium frequency (2 mA, 50 Hz), and high frequency (2 mA, 100 Hz), respectively. Here, we first demonstrated that the JNK/p66signal pathway promoted ROS generation and inhibited the anti-oxidation effect of FoxO3a to induce oxidative stress damage after SCI and the mechanism of electro-acupuncture in anti-oxidative stress. Electro-acupuncture facilitated functional recovery after SCI and improved the apoptosis of neurons. Furthermore, p38MAPK-mediated microglia activation and inflammatory reaction and JNK/p66-mediated ROS generation and oxidative stress damage were both attenuated by electro-acupuncture. However, the inhibitory effect of electro-acupuncture on p38MAPK was enslaved to the acupuncture frequency, but the ROS generation and phosphorylation of p66were effectively inhibited by electro-acupuncture. Therefore, the activation of JNK/p66promoted the ROS-induced oxidative stress damage after SCI, and inhibiting the phosphorylation of p66-mediated oxidative stress was the key target of electro-acupuncture to facilitate functional recovery SCI, but not p38MAPK.


greenmedinfo--2020-07-22--Effects of electroacupuncture on stress-induced gastric dysrhythmia and mechanisms involving autonom

Effects of electroacupuncture on stress-induced gastric dysrhythmia and mechanisms involving autonomic and central nervous systems in functional dyspepsia.

Electroacupuncture ( EA ) is widely used as an effective method to treat stress-related disorders .
However , its mechanisms remain largely unknown .
The aim of this study was to investigate the effects and mechanisms of EA on gastric slow wave ( GSW ) dysrhythmia and c-Fos expression in the nucleus of the solitary tract ( NTS ) induced by stress in a rodent model of functional dyspepsia ( FD ) .
Rats in the neonatal stage were treated using intragastric iodoacetamide .
Eight weeks later , the rats were implanted with electrodes in the stomach for the measurement @ @ @ @ @ @ @ for EA .
Autonomic functions were assessed by spectral analysis of heart rate variability .
Rats were placed for 30 min in a cylindrical plastic tube for acute restraint stress .
The involvement of a central afferent pathway was assessed by measuring c-Fos-immunoreactive cells in the NTS . )
EA normalized restraint stress-induced impairment of GSW in FD rats . )
EA significantly increased vagal activity ( = 0.002 ) and improved sympathovagal balance ( = 0.004 ) under stress in FD rats . )
In FD rats under restraint stress , plasma @ @ @ @ @ @ @ 0.01 ) , which was suppressed with EA . )
The EA group showed increased c-Fos-positive cell counts in the NTS compared with the sham EA group ( < 0.05 ) in FD rats .
Acute restraint stress induces gastric dysrhythmia in a rodent model of FD .
EA at ST36 improves GSW under stress in FD rats mediated via the central and autonomic pathways , involving the NTS and vagal efferent pathway .

Electroacupuncture (EA) is widely used as an effective method to treat stress-related disorders. However, its mechanisms remain largely unknown. The aim of this study was to investigate the effects and mechanisms of EA on gastric slow wave (GSW) dysrhythmia and c-Fos expression in the nucleus of the solitary tract (NTS) induced by stress in a rodent model of functional dyspepsia (FD). Rats in the neonatal stage were treated using intragastric iodoacetamide. Eight weeks later, the rats were implanted with electrodes in the stomach for the measurement of GSW and electrodes into accupoints ST36 for EA. Autonomic functions were assessed by spectral analysis of heart rate variability. Rats were placed for 30 min in a cylindrical plastic tube for acute restraint stress. The involvement of a central afferent pathway was assessed by measuring c-Fos-immunoreactive cells in the NTS.) EA normalized restraint stress-induced impairment of GSW in FD rats.) EA significantly increased vagal activity (= 0.002) and improved sympathovagal balance (= 0.004) under stress in FD rats.) In FD rats under restraint stress, plasma norepinephrine concentration was increased substantially (<0.01), which was suppressed with EA.) The EA group showed increased c-Fos-positive cell counts in the NTS compared with the sham EA group (<0.05) in FD rats. Acute restraint stress induces gastric dysrhythmia in a rodent model of FD. EA at ST36 improves GSW under stress in FD rats mediated via the central and autonomic pathways, involving the NTS and vagal efferent pathway.


greenmedinfo--2020-07-22--Electroacupuncture relieves irritable bowel syndrome.

OBJECTIVE : To investigate the effect of electroacupuncture ( EA ) on irritable bowel syndrome ( IBS ) in mice @ @ @ @ @ protein-like receptor family pyrin domain containing 6 ( NLRP6 ) .
METHODS : Water-avoidance stress @ @ @ @ @ was used to investigate the effects and the mechanism of EA .
Abdominal withdrawal reflex @ @ @ @ @ , and intestinal motility test were used to evaluate visceral sensitivity , anxiety , and @ @ @ @ @ The expressions of NLRP6 , Mucin-2 ( MUC2 ) and E-cadherin were determined using immunofluorescence @ @ @ @ @ RESULTS : EA significantly upregulated the expression of NLRP6 in the intestine of mice .
@ @ @ @ @ expressions of MUC2 and E-cadherin in WAS mice .
CONCLUSION : Our study found that @ @ @ @ @ by EA may involve the increase in the expression of NLRP6 in WAS mice .

OBJECTIVE: To investigate the effect of electroacupuncture (EA) on irritable bowel syndrome (IBS) in mice through regulating nucleotide-binding oligomerization domain protein-like receptor family pyrin domain containing 6 (NLRP6).
METHODS: Water-avoidance stress (WAS) mice model was used to investigate the effects and the mechanism of EA. Abdominal withdrawal reflex test, open field test, and intestinal motility test were used to evaluate visceral sensitivity, anxiety, and intestinal motility in mice. The expressions of NLRP6, Mucin-2 (MUC2) and E-cadherin were determined using immunofluorescence and Western blotting assays.
RESULTS: EA significantly upregulated the expression of NLRP6 in the intestine of mice. Moreover, EA increased the expressions of MUC2 and E-cadherin in WAS mice.
CONCLUSION: Our study found that the relief of IBS symptoms by EA may involve the increase in the expression of NLRP6 in WAS mice.


greenmedinfo--2020-07-22--Electroacupuncture pretreatment as a novel avenue to protect heart against ischemia and reperfusion

Electroacupuncture pretreatment as a novel avenue to protect heart against ischemia and reperfusion injury.

In recent years , the efficacy of electroacupuncture ( EA ) pretreatment generating ischemic tolerance mimicking ischemic pretreatment ( IP ) has been continuously confirmed , which was first found in the brain and then in the heart .
Furthermore , researchers have observed the intensive cardioprotection impact of EA pretreatment on patients undergoing percutaneous coronary intervention ( PCI ) and heart valve replacement , indicating that EA pretreatment tends to be a valuable and advantageous avenue for preventing acute myocardial ischemia/reperfusion ( I/R ) injury or treatment of ischemic heart disease ( IHD ) .
In reality , the @ @ @ @ @ @ @ robust and pleiotropic , of which the regulatory molecular pathways are involved in multichannel , multilevel , and multitarget , including energy metabolism , inflammatory response , calcium overload , oxidative stress , autophagy , and apoptosis .
Through a growing number of clinical tests and basic experiments with animal models , researchers progressively explored the optimal acupoints and parameters , where EA pretreatment induced acute and delayed ischemic tolerance for myocardial protection .
Thereby , this article aims to collect the relevant evidence on EA pretreatment against myocardial ischemia/reperfusion injury ( MIRI @ @ @ @ @ @ @ of EA pretreatment to provide ideas and methods for further clinical applications .

In recent years, the efficacy of electroacupuncture (EA) pretreatment generating ischemic tolerance mimicking ischemic pretreatment (IP) has been continuously confirmed, which was first found in the brain and then in the heart. Furthermore, researchers have observed the intensive cardioprotection impact of EA pretreatment on patients undergoing percutaneous coronary intervention (PCI) and heart valve replacement, indicating that EA pretreatment tends to be a valuable and advantageous avenue for preventing acute myocardial ischemia/reperfusion (I/R) injury or treatment of ischemic heart disease (IHD). In reality, the heart protection mechanism of EA pretreatment is robust and pleiotropic, of which the regulatory molecular pathways are involved in multichannel, multilevel, and multitarget, including energy metabolism, inflammatory response, calcium overload, oxidative stress, autophagy, and apoptosis. Through a growing number of clinical tests and basic experiments with animal models, researchers progressively explored the optimal acupoints and parameters, where EA pretreatment induced acute and delayed ischemic tolerance for myocardial protection. Thereby, this article aims to collect the relevant evidence on EA pretreatment against myocardial ischemia/reperfusion injury (MIRI) and summarize the mechanism of cardioprotection of EA pretreatment to provide ideas and methods for further clinical applications.


greenmedinfo--2020-07-22--These results suggested enteric nervous system may be a new treatment approach to obesity.

BACKGROUND AND OBJECTIVES : The enteric nervous system ( ENS ) dominates the onset of obesity and has been shown @ @ @ @ @ energy metabolism .
METHODS AND STUDY DESIGN : This study was performed to investigate the @ @ @ @ @ ENS function in obese mice .
Obese mice were obtained by high-fat diet .
16S @ @ @ @ @ , quantitative PCR , and neurotransmitter analysis were used for this purpose .
RESULTS : @ @ @ @ @ , serum lipid , leptin , and adiponectin levels , and other basic indices were @ @ @ @ @ .
The pathological ENS scores , serum neurotransmitter levels , and intestinal transit rate were @ @ @ @ @ .
Moreover , electroacupuncture promoted the diversity of gut microbiota .
No significant differences were @ @ @ @ @ after electroacupuncture .
CONCLUSIONS : These results suggested ENS may be a new treatment approach @ @ @

BACKGROUND AND OBJECTIVES: The enteric nervous system (ENS) dominates the onset of obesity and has been shown to regulate nutrient absorption and energy metabolism.
METHODS AND STUDY DESIGN: This study was performed to investigate the role of electroacupuncture in regulating ENS function in obese mice. Obese mice were obtained by high-fat diet. 16S rRNA pyrosequencing, Western blotting, quantitative PCR, and neurotransmitter analysis were used for this purpose.
RESULTS: Body weight, Lee index, serum lipid, leptin, and adiponectin levels, and other basic indices were significantly ameliorated after electroacupuncture intervention. The pathological ENS scores, serum neurotransmitter levels, and intestinal transit rate were markedly changed in obese mice. Moreover, electroacupuncture promoted the diversity of gut microbiota. No significant differences were observed 21 and 28 days after electroacupuncture.
CONCLUSIONS: These results suggested ENS may be a new treatment approach to obesity.


greenmedinfo--2020-07-22--Electroacupuncture alleviates intestinal inflammation and barrier dysfunction by activating dopamine

Electroacupuncture alleviates intestinal inflammation and barrier dysfunction by activating dopamine in a rat model of intestinal ischaemia.

BACKGROUND : To investigate whether the mechanism underlying the anti-inflammatory effects of electroacupuncture ( EA ) at ST36 involves dopamine ( DA ) and its receptor and whether it is mediated by the vagus nerve in a rat model of intestinal ischaemia-reperfusion ( I/R ) injury .
METHODS : Rats were subjected to gut ischaemia for 30 min and then received EA for 30 min with or without abdominal vagotomy or intraperitoneal administration of butaclamol ( D1 receptor antagonist ) or spiperone ( D2 receptor antagonist ) .
Plasma levels of DA and tumour necrosis factor ( TNF ) -α @ @ @ @ @ @ @ reperfusion .
Myeloperoxidase ( MPO ) activity and malondialdehyde ( MDA ) content in intestinal tissues were assessed using enzyme-linked immunosorbent assay ( ELISA ) kits .
Intestinal tissue injury was assessed by observation of the pathological lesions and permeability to4 kDa fluorescein isothiocyanate ( FITC ) -dextran .
RESULTS : EA significantly increased levels of DA and lowered levels of TNF-α .
EA also inhibited intestinal levels of MPO and MDA and intestinal tissue injury and decreased intestinal permeability to FITC-dextran .
Abdominal vagotomy and intraperitoneal administration of butaclamol ( but not @ @ @ @ @ @ @ .
CONCLUSION : These findings suggest that EA at ST36 could attenuate intestinal I/R-induced inflammatory injury and that the underlying mechanism may involve EA-induced increases in levels of DA , mediated by the vagus nerve and D1 receptors .

BACKGROUND: To investigate whether the mechanism underlying the anti-inflammatory effects of electroacupuncture (EA) at ST36 involves dopamine (DA) and its receptor and whether it is mediated by the vagus nerve in a rat model of intestinal ischaemia-reperfusion (I/R) injury.
METHODS: Rats were subjected to gut ischaemia for 30 min and then received EA for 30 min with or without abdominal vagotomy or intraperitoneal administration of butaclamol (D1 receptor antagonist) or spiperone (D2 receptor antagonist). Plasma levels of DA and tumour necrosis factor (TNF)-α were assessed 1 or 4 h after reperfusion. Myeloperoxidase (MPO) activity and malondialdehyde (MDA) content in intestinal tissues were assessed using enzyme-linked immunosorbent assay (ELISA) kits. Intestinal tissue injury was assessed by observation of the pathological lesions and permeability to4 kDa fluorescein isothiocyanate (FITC)-dextran.
RESULTS: EA significantly increased levels of DA and lowered levels of TNF-α. EA also inhibited intestinal levels of MPO and MDA and intestinal tissue injury and decreased intestinal permeability to FITC-dextran. Abdominal vagotomy and intraperitoneal administration of butaclamol (but not spiperone) inhibited the effects of EA.
CONCLUSION: These findings suggest that EA at ST36 could attenuate intestinal I/R-induced inflammatory injury and that the underlying mechanism may involve EA-induced increases in levels of DA, mediated by the vagus nerve and D1 receptors.


greenmedinfo--2020-07-22--These results indicated that the 2 Hz electroacupuncture treatment had a good effect on dysphagia af

These results indicated that the 2 Hz electroacupuncture treatment had a good effect on dysphagia after stroke.

The aim of this study was to determine the optimum frequency of electroacupuncture ( EA ) for the treatment of @ @ @ @ @ C57BL/6 J mice were randomly divided into five groups : normal , model , 2 @ @ @ @ @ and 100 Hz groups .
All mice received a photochemical ischemia , except the normal @ @ @ @ @ were 1 mA for 15 min , with different frequencies ( 2 , 50 , @ @ @ @ @ .
After a three day treatment , neuronal activation was detected by the expression of @ @ @ @ @ technique was used to assess the discharge of contralateral neurons and the neuron types in @ @ @ @ @ of brain-derived neurotrophic factor ( BDNF ) in the contralateral neurons was also examined .
@ @ @ @ @ of swallowing in mice was calculated according to the lick counts and the lick-lick interval @ @ @ @ @ time .
The number of c-Fos neurons ( P

The aim of this study was to determine the optimum frequency of electroacupuncture (EA) for the treatment of dysphagia after stroke. Male C57BL/6 J mice were randomly divided into five groups: normal, model, 2 Hz, 50 Hz, and 100 Hz groups. All mice received a photochemical ischemia, except the normal group. The EA parameters were 1 mA for 15 min, with different frequencies (2, 50, and 100 Hz) applied. After a three day treatment, neuronal activation was detected by the expression of c-Fos. A multi-channel electrophysiological technique was used to assess the discharge of contralateral neurons and the neuron types in each group. The concentration of brain-derived neurotrophic factor (BDNF) in the contralateral neurons was also examined. In addition, the dysfunction of swallowing in mice was calculated according to the lick counts and the lick-lick interval within a certain period of time. The number of c-Fos neurons (P < 0.05) and the expression of BDNF (P < 0.05) increased after the 2 Hz EA treatment. The total frequency of neuron discharge in the 2 Hz group increased compared with the model group (P < 0.05). The pattern of sorted neuron populations was similar between the normal and 2 Hz groups. Consistent with these results, the lick counts increased (P < 0.05) and the lick-lick interval decreased after the 2 Hz EA treatment, which indicated a functional improvement in swallowing. These results indicated that the 2 Hz EA treatment had a good effect on dysphagia after stroke.


greenmedinfo--2020-07-23--Treatment with lycopene led to improvement in the symptoms of oral submucous fibrosis in the present

Treatment with lycopene led to improvement in the symptoms of oral submucous fibrosis in the present study.

BACKGROUND : Long-term follow-ups after receiving lycopene therapy for management of Oral Submucous Fibrosis ( OSMF ) are scarce .
The study aimed to assess the long-term efficacy of lycopene for management of OSMF symptoms .
METHODS : In this prospective clinical study , 400 clinically diagnosed early OSMF patients were assessed for the efficacy of lycopene in alleviation of burning sensation ( BS ) and reduced mouth opening ( MO ) symptoms in comparison to placebo .
After one year follow up , group A ( lycopene group ) was divided equally into Group A1 and Group A2 .
@ @ @ @ @ @ @ and the A2 group was followed without retreatment .
After 2 years follow up , the Group A2 patients were advised retreatment but not followed as most of the patient did not agree for follow-up .
However , group A1 patients were continued to follow up every 6 months for a total 3 years .
Statistical analysis was by independent sample t-test and p-value less than 0.05 were considered as significant .
RESULTS : A statistically significant difference ( p < 0.05 ) in BS and MO was found between group A and @ @ @ @ @ @ @ At one year follow up , a statistically significant recurrence in the symptoms was found ( p < 0.05 ) in lycopene group ( group A ) .
After the second intervention , there was a statistically significant difference in the improvement of symptoms between the group A1 and A2 at 6-months and one year ( p < 0.05 ) with group A1 ( retreatment ) showing better results .
CONCLUSIONS : Treatment with lycopene led to improvement in the symptoms of OSMF in the present study .
The results highlight the importance @ @ @ @ @ @ @ effect on alleviation the symptoms of OSMF .

BACKGROUND: Long-term follow-ups after receiving lycopene therapy for management of Oral Submucous Fibrosis (OSMF) are scarce. The study aimed to assess the long-term efficacy of lycopene for management of OSMF symptoms.
METHODS: In this prospective clinical study, 400 clinically diagnosed early OSMF patients were assessed for the efficacy of lycopene in alleviation of burning sensation (BS) and reduced mouth opening (MO) symptoms in comparison to placebo. After one year follow up, group A (lycopene group) was divided equally into Group A1 and Group A2. Group A1 patients were retreated with lycopene and the A2 group was followed without retreatment. After 2 years follow up, the Group A2 patients were advised retreatment but not followed as most of the patient did not agree for follow-up. However, group A1 patients were continued to follow up every 6 months for a total 3 years. Statistical analysis was by independent sample t-test and p-value less than 0.05 were considered as significant.
RESULTS: A statistically significant difference (p<0.05) in BS and MO was found between group A and B with lycopene showing better results. At one year follow up, a statistically significant recurrence in the symptoms was found (p<0.05) in lycopene group (group A). After the second intervention, there was a statistically significant difference in the improvement of symptoms between the group A1 and A2 at 6-months and one year (p<0.05) with group A1 (retreatment) showing better results.
CONCLUSIONS: Treatment with lycopene led to improvement in the symptoms of OSMF in the present study. The results highlight the importance of retreatment of lycopene for its long-term effect on alleviation the symptoms of OSMF.


greenmedinfo--2020-07-23--Lycopene inhibits imiquimod -induced psoriasis-like inflammation.

Lycopene is the most abundant carotenoid in tomatoes , which has been identified to have the properties of anti-inflammation in @ @ @ @ @ inhibit the expression of adhesion molecules .
Intercellular adhesion molecules play a critical role in @ @ @ @ @ Here , we report that the topical use of a lycopene decreased imiquimod ( IMQ @ @ @ @ @ , the progress of which was based on adhesion molecules .
In vitro analysis showed @ @ @ @ @ monocyte adhesion .
Evidence suggests that intercellular adhesion molecule-1 ( ICAM-1 ) is a main @ @ @ @ @ Therefore , it will be interesting to investigate the factors that contribute to the lycopene-mediated @ @ @ @ @ psoriasis .
We expect that lycopene will with potential value in the treatment of psoriasis @

Lycopene is the most abundant carotenoid in tomatoes, which has been identified to have the properties of anti-inflammation in addition to the capability to inhibit the expression of adhesion molecules. Intercellular adhesion molecules play a critical role in the pathogenesis of psoriasis. Here, we report that the topical use of a lycopene decreased imiquimod (IMQ)-induced psoriasis-like inflammatory responses, the progress of which was based on adhesion molecules. In vitro analysis showed that lycopene decreased keratinocyte and monocyte adhesion. Evidence suggests that intercellular adhesion molecule-1 (ICAM-1) is a main mediator of psoriasis pathogenesis. Therefore, it will be interesting to investigate the factors that contribute to the lycopene-mediated inhibition of ICAM-1 expression in psoriasis. We expect that lycopene will with potential value in the treatment of psoriasis.


greenmedinfo--2020-07-23--Magnesium-Rich Foods and Why You Need Them

This website is for information purposes only .
By providing the information contained herein we are not diagnosing , treating @ @ @ @ @ or preventing any type of disease or medical condition .
Before beginning any type of @ @ @ @ @ treatment regimen , it is advisable to seek the advice of a licensed healthcare professional @

This website is for information purposes only. By providing the information contained herein we are not diagnosing, treating, curing, mitigating, or preventing any type of disease or medical condition. Before beginning any type of natural, integrative or conventional treatment regimen, it is advisable to seek the advice of a licensed healthcare professional.
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greenmedinfo--2020-07-23--Cucurbitacin E inhibits esophageal carcinoma cell proliferation, migration, and invasion.

As an oxygenated tetracyclic triterpenoid , Cucurbitacin E ( CuE ) possesses potential antitumor properties in sorts of malignancies .
However , its effect on human esophageal carcinoma cells has not been previously unearthed , and the mechanism underlying its anticarcinoma activity remains vague .
Hence , this study was arranged to probe the function of CuE on esophageal carcinoma cells and its specific mechanism .
Human esophageal carcinoma cells ( ECA109 and EC9706 ) and human normal esophageal epithelial cells ( Het-1A ) were selected for subsequent experiments .
The expression levels of Rac1 in esophageal carcinoma cells were @ @ @ @ @ @ @ pCDNA3.1-Rac1 , esophageal carcinoma cells were exposed to CuE .
Then , 3- ( 4,5-dimethylthiazol-2-yl ) -2,5-diphenyltetrazolium bromide assay and 5-ethynyl-2'-deoxyuridine staining were utilized for measurement of cell proliferation ability , cell scratch assay for inspection of cell migration rate , and Transwell for detection of cell invasion ability .
The phosphorylation levels of protein kinase B and mTOR were analyzed by Western blot .
Rac1 was highly expressed in esophageal carcinoma cells .
Transfection of sh-Rac1 in esophageal carcinoma cells resulted in suppression on cell proliferation , migration , and invasion , @ @ @ @ @ @ @ AKT and mammalian target of rapamycin ( mTOR ) in esophageal carcinoma cells , while transfection of pCDNA3.1-Rac1 had an opposite effect , implicating that Rac1 can promote the viability of esophageal carcinoma cells .
Esophageal carcinoma cells subjected to CuE treatment had decreased expression of Rac1 , suppressed cell viability , and decreased phosphorylation levels of AKT and mTOR .
Transfection of pCDNA3.1-Rac1 and CuE treatment in esophageal carcinoma cells enhanced viability of esophageal carcinoma cells and promoted the phosphorylation levels of AKT and mTOR in comparison with cells treated with CuE @ @ @ @ @ @ @ , and migration of esophageal carcinoma cells via downregulating Rac1 to block the phosphoinositide 3-kinase/AKT/mTOR pathway .

As an oxygenated tetracyclic triterpenoid, Cucurbitacin E (CuE) possesses potential antitumor properties in sorts of malignancies. However, its effect on human esophageal carcinoma cells has not been previously unearthed, and the mechanism underlying its anticarcinoma activity remains vague. Hence, this study was arranged to probe the function of CuE on esophageal carcinoma cells and its specific mechanism. Human esophageal carcinoma cells (ECA109 and EC9706) and human normal esophageal epithelial cells (Het-1A) were selected for subsequent experiments. The expression levels of Rac1 in esophageal carcinoma cells were measured. After transfection of sh-Rac1 or pCDNA3.1-Rac1, esophageal carcinoma cells were exposed to CuE. Then, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay and 5-ethynyl-2'-deoxyuridine staining were utilized for measurement of cell proliferation ability, cell scratch assay for inspection of cell migration rate, and Transwell for detection of cell invasion ability. The phosphorylation levels of protein kinase B and mTOR were analyzed by Western blot. Rac1 was highly expressed in esophageal carcinoma cells. Transfection of sh-Rac1 in esophageal carcinoma cells resulted in suppression on cell proliferation, migration, and invasion, as well as downregulated phosphorylation levels of AKT and mammalian target of rapamycin (mTOR) in esophageal carcinoma cells, while transfection of pCDNA3.1-Rac1 had an opposite effect, implicating that Rac1 can promote the viability of esophageal carcinoma cells. Esophageal carcinoma cells subjected to CuE treatment had decreased expression of Rac1, suppressed cell viability, and decreased phosphorylation levels of AKT and mTOR. Transfection of pCDNA3.1-Rac1 and CuE treatment in esophageal carcinoma cells enhanced viability of esophageal carcinoma cells and promoted the phosphorylation levels of AKT and mTOR in comparison with cells treated with CuE alone. CuE inhibits proliferation, invasion, and migration of esophageal carcinoma cells via downregulating Rac1 to block the phosphoinositide 3-kinase/AKT/mTOR pathway.


greenmedinfo--2020-07-23--In vitro antitumor effect of cucurbitacin E on human lung cancer cell line and its molecular mechani

In vitro antitumor effect of cucurbitacin E on human lung cancer cell line and its molecular mechanism.

Cucurbitacin E ( CuE ) is previously reported to exhibit antitumor effect by several means .
In this study , CuE acted as a tyrosine kinase inhibitor interfering with the epidermal growth factor receptor/mitogen-activated protein kinase ( EGFR/MAPK ) signaling pathway and subsequently induced apoptosis and cell cycle arrest in non-small-cell lung cancer ( NSCLC ) cell line A549 .
The apoptosis regulators , cleaved Caspases-3 and Caspases-9 , were observed to be increased with the treatment of CuE .
The activated transcription factor STAT3 and the apoptosis inhibitor protein survivin were also observed to be reduced .
The cell @ @ @ @ @ @ @ CyclinD1 and CyclinE , were also investigated and the results suggested that the cell cycle was arrested at G1/G0 phase .
Treatment of CuE also altered the existence status of most of the participants in the EGFR/MAPK signaling .
Phosphorylation of EGFR enhanced significantly , leading to the alteration of members downstream , either total amount or phosphorylation level , notably , MEK1/2 and ERK1/2 .
Moreover , the results of molecular simulation brought an insight on the interaction mechanism between CuE and EGFR .
In summary , CuE exhibited anti-proliferative effect against @ @ @ @ @ @ @ pathway .

Cucurbitacin E (CuE) is previously reported to exhibit antitumor effect by several means. In this study, CuE acted as a tyrosine kinase inhibitor interfering with the epidermal growth factor receptor/mitogen-activated protein kinase (EGFR/MAPK) signaling pathway and subsequently induced apoptosis and cell cycle arrest in non-small-cell lung cancer (NSCLC) cell line A549. The apoptosis regulators, cleaved Caspases-3 and Caspases-9, were observed to be increased with the treatment of CuE. The activated transcription factor STAT3 and the apoptosis inhibitor protein survivin were also observed to be reduced. The cell cycle regulators, CyclinA2, cylinB1, CyclinD1 and CyclinE, were also investigated and the results suggested that the cell cycle was arrested at G1/G0 phase. Treatment of CuE also altered the existence status of most of the participants in the EGFR/MAPK signaling. Phosphorylation of EGFR enhanced significantly, leading to the alteration of members downstream, either total amount or phosphorylation level, notably, MEK1/2 and ERK1/2. Moreover, the results of molecular simulation brought an insight on the interaction mechanism between CuE and EGFR. In summary, CuE exhibited anti-proliferative effect against A549 cells by targeting the EGFR/MAPK signaling pathway.


greenmedinfo--2020-07-23--Encapsulation of cucurbitacin B into lipid polymer hybrid nanocarriers induced apoptosis of MDAMB231

Encapsulation of cucurbitacin B into lipid polymer hybrid nanocarriers induced apoptosis of MDAMB231 cells.

In the present study , we developed the lipid polymer hybrid nanoparticles of cucurbitacin B ( CuB ) and evaluated its effects on triple negative breast cancer cells .
The 3factorial design was utilized to understand the influence of input variables including PEG-conjugated phospholipid/biodegradable polymer ratio and the total lipids/lecithin molar percentage ratio .
The hybrid formulation at the center point of design was specified as optimal hybrid nanocarrier due to its superior features .
CuB loaded nanoparticles ( CuB-NP ) inhibited cell growth through a cell cycle arrest at G0/G1 phase .
The studies investigating the efficacy of CuB-NP @ @ @ @ @ @ @ the annexin v-bound cell population was 20.66 ± 1.99 % , and the depolarized cell population was higher in CuB-NP treated cells .
The pro-apoptotic bax , Iκb-α and cleaved PARP levels increased in CuB-NP treated cells , while anti-apoptotic Bcl-2 and NF-κB levels decreased .
The caspase ( + ) cell population was higher in nanoparticle-treated group as 14.20 ± 0.56 % and the findings obtained from the caspase assay were also compatible with western blot data .
Overall , both CuB and CuB-NP demonstrated anticancer activity , while the lipid polymer @ @ @ @ @ @ @ the nanoparticle formulation has more promising effect for the treatment of breast cancer .

In the present study, we developed the lipid polymer hybrid nanoparticles of cucurbitacin B (CuB) and evaluated its effects on triple negative breast cancer cells. The 3factorial design was utilized to understand the influence of input variables including PEG-conjugated phospholipid/biodegradable polymer ratio and the total lipids/lecithin molar percentage ratio. The hybrid formulation at the center point of design was specified as optimal hybrid nanocarrier due to its superior features. CuB loaded nanoparticles (CuB-NP) inhibited cell growth through a cell cycle arrest at G0/G1 phase. The studies investigating the efficacy of CuB-NP on apoptosis of cancer cells showed that the annexin v-bound cell population was 20.66 ± 1.99%, and the depolarized cell population was higher in CuB-NP treated cells. The pro-apoptotic bax, Iκb-α and cleaved PARP levels increased in CuB-NP treated cells, while anti-apoptotic Bcl-2 and NF-κB levels decreased. The caspase (+) cell population was higher in nanoparticle-treated group as 14.20 ± 0.56% and the findings obtained from the caspase assay were also compatible with western blot data. Overall, both CuB and CuB-NP demonstrated anticancer activity, while the lipid polymer hybrid nanoparticle formulation of CuB indicated that the nanoparticle formulation has more promising effect for the treatment of breast cancer.


greenmedinfo--2020-07-23--Best Essential Oils to Reduce Stress

Best Essential Oils to Reduce Stress