Chinese herbal medicine decreases incidence of hepatocellular carcinoma in diabetes mellitus patients with regular insulin management

BACKGROUND Type 2 diabetes mellitus(DM)is an independent risk factor for hepatocellular carcinoma(HCC),while insulin is a potent mitogen.Identifying a new therapeutic modality for preventing insulin users from developing HCC is a critical goal for researchers.AIM To investigate whether regular herbal medicine use can decrease HCC risk in DM patients with regular insulin control.METHODS We used data acquired from the Taiwan,Chinaese National Health Insurance research database between 2000 and 2017.We identified patients with DM who were prescribed insulin for>3 months.The herb user group was further defined as patients prescribed herbal medication for DM for>3 months per annum during RESULTS We initially enrolled 657144 DM patients with regular insulin use from 2000 to 2017.Among these,46849 patients had used a herbal treatment for DM,and 140547 patients were included as the matched control group.The baseline variables were similar between the herb users and nonusers.DM patients with regular herb use had a 12%decreased risk of HCC compared with the control group[adjusted hazard ratio(aHR)=0.88,95%CI=0.80–0.97].The cumulative incidence of HCC in the herb users was significantly lower than that of the nonusers.Patients with a herb use of>5 years cumulatively exhibited a protective effect against development of HCC(aHR=0.82,P<0.05).Of patients who developed HCC,herb users exhibited a longer survival time than nonusers(aHR=0.78,P=0.0001).Additionally,we report the top 10 herbs and formulas in prescriptions and summarize the potential pharmacological effects of the constituents.Our analysis indicated that Astragalus propinquus(Huang Qi)plus Salvia miltiorrhiza Bunge(Dan Shen),and Astragalus propinquus(Huang Qi)plus Trichosanthes kirilowii Maxim.(Tian Hua Fen)were the most frequent combination of single herbs.Meanwhile,Ji Sheng Shen Qi Wan plus Dan Shen was the most frequent combination of herbs and formulas.CONCLUSION This large-scale retrospective cohort study reveals that herbal medicine may decrease HCC risk by 12%in DM patients with regular insulin use.

The current development of the application of abdominal diagnosis in traditional Chinese medicine in the massage therapy diagnosis and treatment

Objective:Abdominal diagnosis is one of the traditional diagnostic methods in traditional Chinese medicine(TCM),which explains the unique diagnostic and therapeutic characteristics.In massage clinical practice,the integrated diagnostic and treatment approach exhibits immediacy,accuracy,simplicity,and replicability.Methods:This article reviews the ancient literature and modern research on abdominal diagnosis,summarizing its development process,theoretical basis,and clinical application status of abdominal diagnosis in massage.Results:It is proposed that abdominal diagnosis should be deeply studied in terms of mechanism,indicators,and standards to promote the development of abdominal diagnosis standards and enable it to be more widely applied in massage clinical practice.Conclusion:The unique diagnostic and therapeutic characteristics of abdominal diagnosis have signifcant advantages in massage clinical pratice.Further research and standardization can facilitate its wider application in clinical practice.

Research progress in the treatment of diabetic foot with traditional Chinese medicine

Diabetic foot is one of the chronic complications of diabetes,which is serious and expensive to treat.As an effective method for treating diabetic foot,Chinese medicine plays an important role in improving the clinical symptoms and reducing the suffering of diabetic foot patients.The methods of traditional Chinese medicine to treat diabetic foot include internal treatment method,external treatment method and comprehensive therapy.This article reviews the research results of traditional Chinese medicine treatment of diabetic foot in order to provide reference for the treatment of diabetic foot.

Effect of Traditional Chinese Medicine Antiviral Capsules On Animal Model Genital Herpes and HSV-2 in Cell Culture

Objective: To study the effect of traditional Chinese medicine antiviral capsules in the treatment of genital herpes. Methods: Using female guinea pig genital herpes as the animal model, this study used oral administration of two formulations of antiviral capsules (AC) and observed the effect on vaginal HSV-2 titers and vulvar symptoms. Cell cultures were also used to examine the direct inactivation of HSV-2 by the antiviral capsules and the suppression of HSV-2 via three drug administration methods. Results: There was no significant difference of mean vaginal virus titers between the antiviral capsule groups and that of the positive acyclovir (ACV) control (P>0.05). Mean vulvarsymptom scores of the two antiviral capsule groups were also significantly lower than that of the saline negative control group on days 2, 3, 5, 7 and 8 (P<0.05) and similar to that of the ACV control (P>0.05). Cell culture showed the minimum inhibitory concentrations of antiviral capsules No. 1 and No. 2 were 0.390625 mg/ml and 1.5625 mg/ml, respectively. Conclusion: The traditional Chinese medicine antiviral capsules had suppressive effects on HSV-2 in both animal model GH and in vitro cell culture.

Traditional Chinese herbal medicine plus triple therapy in treating Helicobacter pylori-induced chronic atrophic gastritis: a meta-analysis and cumulative meta-analysis

Objectives:To evaluate the benefits of traditional Chinese herbal medicine(TCHM)plus triple therapy(TT)in the management of Helicobacter pylori(H.pylori)-induced chronic atrophic gastritis(CAG).Methods:A comprehensive access and electronic database search were carried out from inception to June 2020.Prospective randomized trials(TCHM plus TT vs.TT)were selected to assess the eradication rate of H.pylori(ER of H.pylori),clinical symptom relief rate(SRR),treatment-related adverse reactions(TRAR)and 95%confidence intervals(CI)in the meta-analysis and cumulative meta-analysis(CMA).Meta-regression analysis was used to analyze heterogeneity between studies and publication bias.Results:33 studies contained 3,226 participants were included.Compared with the TT group,TCHM plus TT group showed a significantly higher ER of H.pylori(OR=4.14,95%CI:3.21-5.35;P=0.000)and SRR(OR=4.50,95%CI:3.59-5.64).Meanwhile,the TRAR of TCHM plus TT remedy was significantly lower than TT monopoly(RR=0.43,95%CI:0.29-0.64;P=0.000).The results of the CMA,sorted by publication year,duration of treatment,and sample size,confirmed that combined treatment remedy was superior to TT monopoly in respect of ER of H.pylori and SRR.Conclusions:The present study obtained reliable and convincing evidence suggesting that TCHM plus TT remedy was efficacious and safe in treating H.pylori-induced CAG.

Reduced risk of dementia in patients with type 2 diabetes mellitus using Chinese herbal medicine:A nested case-control study

BACKGROUND Dementia is a prevalent condition in type 2 diabetes mellitus(T2DM)patients.While Chinese herbal medicine(CHM)is often employed as complementary therapy for glycemic control,its effect in controlling likelihood of dementia has not yet been fully elucidated.AIM To compare the risk of dementia between T2DM patients with and without CHM treatment.METHODS We undertook a nested case-control study and obtained data on patients 20-70 years of age who received medical care for T2DM between 2001 and 2010 from the National Health Insurance Research database in Taiwan.Cases,defined as those with dementia that occurred at least one year after the diagnosis of T2DM,were randomly matched to controls without dementia from the study cohort at a 1:1 ratio.We applied conditional logistic regression to explore the associations between CHM treatment and dementia.RESULTS A total of 11699 dementia cases were matched to 11699 non-dementia controls.We found that adding CHM to conventional care was related to a lower risk of dementia[adjusted odds ratio(OR)=0.51],and high-intensity CHM treatment was associated with an adjusted OR of 0.22.CONCLUSION This study shows that the cumulative CHM exposure was inversely associated with dementia risk in an exposureresponse manner,implying that CHM treatment may be embraced as a disease management approach for diabetic patients to prevent dementia.

Re-evaluating the role of pelvic radiation in the age of modern precision medicine and systemic therapy

The efficacy of pelvic radiation in the management of locally advanced stage rectal cancer has come under scrutiny in the context of modern precision medicine and systemic therapy as evidenced by recent clinical trials such as FOWARC(J Clin Oncol 2019;37:3223-3233),NCT04165772(N Engl J Med 2022;386:2363-2376),and PROSPECT(N Engl J Med 2023;389:322-334).In this review,we comprehensively assess these pivotal trials and offer additional insights into the evolving role of pelvic radiation in contemporary oncology.

Research p rogress on Chinese herbal drugs in the TGF- β signaling pathway involved in epithelial-mesenchymal transition

Epithelial-mesenchymal transition is a well-defined,reversible process in which epithelial cells lose their epithelial phenotype and acquire mesenchymal-like features.Epithelial-mesenchymal transition contributes significantly to the metastasis,invasion,and development of treatment resistance in cancer cells.There have been many studies on suppression of tumor epithelial-mesenchymal transition by Chinese medicine in recent years,mainly based on Chinese herbal drug monomers and compounds.In this review,we aim to describe the research progress on Chinese medicine in the t ransforming growth factor beta(T GF-β)sig naling pathway,we hope these will provide some guidance for further research on Chinese medicine targeting epithelial-mesenchymal transition.

Microplastic and nanoplastic exposure and risk of diabetes mellitus

The issue of plastic pollutants has become a growing concern.Both microplastics(MPs)(particle size<5 mm)and nanoplastics(NPs)(particle size<1μm)can cause DNA damage,cytotoxicity,and oxidative stress in various organisms.The primary known impacts of microplastic/nanoplastic are observed in the liver and respiratory system,leading to hepatotoxicity and chronic obstructive pulmonary disease.Although research on the effects of MPs and NPs on diabetes is still in its early stages,there are potential concerns.This editorial highlights the risk to diabetics from co-exposure to contaminants and MPs/NPs,supported by evidence from animal studies and the various chemical compositions of MPs/NPs.

Bi-Directional Regulation by Chinese Herbal Formulae to Host and Parasite for Multi-Drug Resistant <i>Staphylococcus aureus</i>in Humans and Rodents

A decline in the immunopotential of the host plays acritical factor(s) in the occurrence of infections with methicillin-resistant Staphylococcus aureus (MRSA) or microorganisms by opportunistic infection. In such an infection, no way out for therapeutic concept, therefore bi-directional trial was the final choice. So we selected aformula, Dang Gui Liu Huang Tang (dLHT), which could both augmentimmune factorsin host and exert bacteriostatic effect. We sought to break through the epidemic by MRSA especially in elderly patient, by the fundamental and clinical trial by employing minor TCM, characterizing bidirectional ability of the decoction by western methods. Animal Experiment: Mitomycin-C (MMC)-treated mice with or without the infection of MRSA were made. The experimental design was made up to examine the bacteriostatic action as well as the immunopo-tentiating bias of the promising Chinese herbal medicine, dLHT, which was first proved for its immune potentiating activities as well as their sensitivity to antibiotics, but not direct aseptic effect was clear for MRSA. Both basic and clinical data showed that this formula was effective on repelling from the infectious focus after the treatment of MRSA infection. After the administration of dLHT, the number of white blood cells in MMC-treated mice recovered to 80% of the normal level. In addition, the phagocytic activity of macrophages increased to 70% in the dLHT-treated group, while that of the non-treated group was only 20%. The bactericidal activity also recovered to the level close to the normal value by dLHT. The ratio of neutrophils in the dLHT-administered group increased to 2.2% (normal mice, 2.6%), whereas that in the non-terated group was only 0.5%. The bacterial count in the liver of MRSA-challenged mice reached the peak at six hours after the challenge in both dLHT-treated and non-treated mice. However, the number of bacteria in dLHT group was much greater than that in the non-treated group. The bacterial count in the blood showed an increase 12 and 24 hours after the challenge. Even 24 hours after the challenge, a significant number of bacteria existed in the blood of dLHT-administered group, whereas only a small number of bacteria detectable 6 hours after the challenge and the number gradually decreased thereafter in the dLHT-administered group. MRSA-challenged MMC-treated mice were treated by dLHT, vancomycin, or dLHT and vancomycin. All of non-treated mice died 8 days after the MRSA challenge, whereas the survival rates were 60% after dLHT treatment, 40% after vancomycin treatment, and 80% after dLHT and vancomycin treatment. All of MMC-treated mice, to which the phagocytic cells prepared from MMC-treated mice with dLHT administration had adoptively been transferred, survived from MRSA challenge. On the other hand, the survival rate of MMC-treated mice, to which the lymphocytes prepared from the same mice had adoptively been transferred, was 40%. Clinical Trial: All cases with dLHT treatment showed negative culture results for MRSA after the dLHT administration. The culture generally became negative less than 50 days after the initial administration, whereas one control case needed more than 100 days and the other was dead of the infection. One representative case, who was a 78-year-old woman suffering from hypertension, atrial fibrillation, and cerebral bleeding in the right occipital lobe, infected with MRSA during the antibiotic therapy for Streptococcus pneumoniae. The antibiotic therapy was halted and the dLHT administration started. Three weeks later, the culture result became negative. In addition, serum protein and albumin values also returned to the level that they had had before the infection of MRSA.

Efficacy and safety of Guipi Decoction combined with conventional Western medicine in the treatment of insomnia with deficiency of heart and spleen:a meta-analysis

Objective:To systematically evaluate the efficacy and safety of Guipi Decoction combined with Western medicine in the treatment of insomnia with deficiency of heart and spleen.Methods:English databases(PubMed,Web of Science,The Cochrane Library,EMBASE)and Chinese databases(CNKI,Wanfang database,China Biomedical Literature Service System,VIP database)were searched by computer.Randomized controlled trials of Guipi Decoction on insomnia with deficiency of heart and spleen were searched from the database construction to November 2021.After the first and second authors independently screened the literature,extracted the data and evaluated the risk of bias in the included studies,meta-analysis was performed using RevMan5.3 software.Results:A total of 9 RCTS were included after screening,including 914 patients.Meta-analysis results showed that:Total effective rate[RR=1.22,95%CI(1.16,1.30),P<0.00001],total PSQI score[MD=-3.05,95%CI(-3.96,-2.14),P=0.008],number of night awakening times[[MD=-1.18,95%CI(-1.42,-0.94),P<0.00001],adverse reaction rate[RR=0.32,95%CI(0.21,0.51),P<0.00001]were better than the control group,and the differences were statistically significant.Conclusion:The current evidence shows that,compared with pure using conventional western medicine,belongs to the spleen decoction combined western medicine therapy,cases both deficiency type of insomnia in the total effective rate,reducing the total PSQI score(improve sleep quality,sleep efficiency,sleep disorder,daytime function,etc.),reducing frequency of nighttime awakening,security,have more advantages.However,due to the limitation of the quality and quantity of articles included in the study,more randomized,double-blind,large-sample clinical studies are needed to confirm the above conclusions.

Study on the mechanism of two related Chinese herbs Chenpi-Banxia in the treatment of coronary microvascular dysfunction based on network pharmacology

Objective:By the method of network pharmacology to study the main active compounds,main target genes,critical path and mechanism of the two classical Chinese herbs Chenpi-Banxia in the treatment of Coronary Microvascular Dysfunction(CMD).Methods:Obtaining potential active compounds of Chenpi-Banxia from TCMSP,while the targets for CMD were obtained from DrugBank and OMIM databases.Using UniProt database to query the corresponding gene name.The key target of Chenpi-Banxia in the treatment of Coronary Microvascular Dysfunction can be obtained by using the intersection of VENNY.The PPI network was screened for the major targets by String and Cytoscape3.7.1.The GO enrichment analysis and KEGG Pathway analyses of major targets were performed by using the DAVID database and use Binformatics to draw bubble map.Finally,the ingredient-major arget-key pathway network was constructed by Cytoscape3.7.1.Results:There were 16 compounds such as naringenin,nobiletin,baicalein.beta-sitosterol etc,and 56 predictive target genes such as AKT1、VEGFA、BCL2、BAX、JUN etc,as well as 20 key pathways including inflammation-related pathway(TNF signaling pathway),pathways related to cardiovascular system(PI3K-Akt signaling pathway),Vascular endothelial growth factor signaling pathway(VEGF signaling pathway),Apoptosis related pathways(Apoptosis)and Hypoxia cell stress signaling pathway(HIF-1 signaling pathway)in the Compounds-Target-Pathway network.Conclusion:The study verified the characteristics of multi-components,multi-targets and integral regulation for Chenpi-Banxia with the application of network pharmacology.It predicted that Chenpi-Banxia couldtreat Coronary Microvascular Dysfunction mainly by protecting endothelial cell function of coronary microcirculation,inhibiting cell apoptosis and affecting inflammatory reaction.

A Study on the Emotional State of College Students with Functional Constipation

Objective:Functional constipation(FC)is a common problem in college students.In this study,we aimed to analyze emotional state and psychological well-being of college students.Methods:500 college students in Changqing University City of Jinan were selected for questionnaire survey.According to the Roma III diagnosis criteria,139 students were diagnosed patients with FC.Qiqing Assessment Scale Questionnaire was used to assess the emotional state of students with FC.Results:The prevalence rate of FC in college students was 32.5%.The psychological well-being score of normal students was higher than that of college students with FC.Significant difference was also observed in terms of mean score of emotional state dimensions in college students with FC.The score of worry was the highest,followed by anxiety and fright in college students with FC.Joy,as the only upward emotion in the seven emotions,had the lowest score.The scores of female students with FC were higher than those of men in anger,anxiety,sadness and worry.Conclusion:There is a close relationship between emotional factors and FC in college students.Emotional factors should be paid attention to in the prevention and treatment of FC.

The efficacy and safety of Shuxuening injection combined with western medicine in vascular dementia treatment:a meta-analysis

Background:To systematically evaluate the efficacy and safety of the Chinese patent medicine Shuxuening injection combined with western medicine in vascular dementia treatment.Methods:Randomized controlled trials of the Chinese patent medicine Shuxuening injection in vascular dementia treatment is searched in the databases of CNKI,Wanfang,VIP,CBM,PubMed,The Cochrane Library,Embase and Web of Science from the establishment time to December 2020.After screen the literature,extract the data and evaluate the bias risk of studies included;tRevMan5.3 was used for met-analysis.Results:Nine randomized controlled trials including 932 patients were included.The results of meta-analysis included:(1)the total effective rate(RR=1.27,95%CI(1.18,1.36),P<0.00001);(2)MMSE score(MD=4.78,95%CI(1.75,7.80),P=0.002);(3)ADL score(MD=8.87,95%CI(6.70,11.05),P<0.00001);(4)NIHSS score(MD=−6.60,95%CI(−7.04,−6.16).P<0.00001).The results of meta-analysis of the test group are better than those in the control group.Conclusion:The Chinese patent medicine Shuxuening injection combined with conventional western medicine has showed some advantages in the total effective rate,MMSE score,ADL score,NIHSS score than conventional western medicine without more side effects in vascular dementia treatment.More randomized,double-blind,large sample clinical studies are needed to confirm the above conclusions.

To explore the mechanism of Yigong San anti-gastric cancer and immune regulation

BACKGROUND Yigong San(YGS)is a representative prescription for the treatment of digestive disorders,which has been used in clinic for more than 1000 years.However,the mechanism of its anti-gastric cancer and regulate immunity are still remains unclear.AIM To explore the mechanism of YGS anti-gastric cancer and immune regulation.METHODS Firstly,collect the active ingredients and targets of YGS,and the differentially expressed genes of gastric cancer.Secondly,constructed a protein-protein interaction network between the targets of drugs and diseases,and screened hub genes.Then the clinical relevance,mutation and repair,tumor microenvironment and drug sensitivity of the hub gene were analyzed.Finally,molecular docking was used to verify the binding ability of YGS active ingredient and hub genes.RESULTS Firstly,obtained 55 common targets of gastric cancer and YGS.The Kyoto Encyclopedia of Genes and Genomes screened the microtubule-associated protein kinase signaling axis as the key pathway and IL6,EGFR,MMP2,MMP9 and TGFB1 as the hub genes.The 5 hub genes were involved in gastric carcinogenesis,staging,typing and prognosis,and their mutations promote gastric cancer progression.Finally,molecular docking results confirmed that the components of YGS can effectively bind to therapeutic targets.CONCLUSION YGS has the effect of anti-gastric cancer and immune regulation.

Effects of Yigan Capsule on the expression of HMGB1,RAGE and NF-κB protein in rats with drug-induced liver injury

Objective:To study the effect of Yigan capsule on the expression of high mobility group protein B1(HMGB1),nuclear factor-B(NF-κB)and receptor for advanced glycation end products(RAGE)in anti-tuberculosis drug-induced liver injury(ATB-DILI),and to explore its protective effect and mechanism on ATB-DILI,so as to provide experimental basis for the clinical application of Yigan capsule.Methods:Twenty-four rats were divided into two groups.Except for the blank group(n=6),the other 18 rats were given isoniazid(INH)+rifampicin(RFP)(50 mg/kg.d)for 4 weeks.Then 18 rats were randomly divided into three groups(model group,low dose group of Yigan capsule and high dose group of Yigan capsule)according to 6 rats in each group.The blank group and the model group were given 0.9%sodium chloride solution by intragastric administration.The low dose group of Yigan capsule was 0.468 g/kg,and the high dose group of Yigan capsule was 1.872 g/kg[1].After 4 weeks,the pathological changes of liver were observed by HE staining.The contents of ALT,AST,ALP,γ-GT and TBIL were detected.The expression of HMGB1,NF-κBp65 and RAGE protein was detected by IHC.The expression levels of HMGB1,NF-κBp65,RAGE,TNF-αand IL-1βwere detected by WB.Result:HE staining showed that the structure of the liver in the model group was disordered,the liver cells showed swelling and fusion,the number of inflammatory cells increased and accompanied by punctate necrosis,while the above pathological changes in each treatment group of Yigan capsule were significantly improved.The contents of ALT,AST,ALP,γ-GT and TBIL in the model group were higher than those in the blank group(P<0.05).The contents of ALT,AST,ALP,γ-GT and TBIL in each treatment group were significantly lower than those in the model group(P<0.05).Compared with the blank group,the expression levels of TNF-αand IL-1βin the model group were increased(P<0.05),and the expression levels of HMGB1,NF-κBp65 and RAGE were increased(P<0.05).Compared with the model group,the expression levels of TNF-αand IL-1βin each treatment group of Yigan capsule decreased(P<0.05),and the expression of HMGB1,NF-κBp65 and RAGE decreased(P<0.05).Conclusion:Yigan capsule may inhibit the secretion of inflammatory factors through HMGB1/RAGE/NF-κBp65 signaling pathway,thus protecting ATB-DILI.

Molecular mechanisms of Buqing granule for the treatment of diabetic retinopathy:Network pharmacology analysis and experimental validation

BACKGROUND Diabetic retinopathy(DR)is a common microvascular complication of diabetes mellitus.Its blindness rate is high;therefore,finding a reasonable and safe treatment plan to prevent and control DR is crucial.Currently,there are abundant and diverse research results on the treatment of DR by Chinese medicine Traditional Chinese medicine compounds are potentially advantageous for DR prevention and treatment because of its safe and effective therapeutic effects.AIM To investigate the effects of Buqing granule(BQKL)on DR and its mechanism from a systemic perspective and at the molecular level by combining network pharmacology and in vivo experiments.METHODS This study collected information on the drug targets of BQKL and the therapeutic targets of DR for intersecting target gene analysis and protein-protein interactions(PPI),identified various biological pathways related to DR treatment by BQKL through Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses,and preliminarily validated the screened core targets by molecular docking.Furthermore,we constructed a diabetic rat model with a high-fat and high-sugar diet and intraperitoneal streptozotocin injection,and administered the appropriate drugs for 12 weeks after the model was successfully induced.Body mass and fasting blood glucose and lipid levels were measured,and pathological changes in retinal tissue were detected by hematoxylin and eosin staining.ELISA was used to detect the oxidative stress index expression in serum and retinal tissue,and immunohistochemistry,real-time quantitative reverse transcription PCR,and western blotting were used to verify the changes in the expression of core targets.RESULTS Six potential therapeutic targets of BQKL for DR treatment,including Caspase-3,c-Jun,TP53,AKT1,MAPK1,and MAPK3,were screened using PPI.Enrichment analysis indicated that the MAPK signaling pathway might be the core target pathway of BQKL in DR treatment.Molecular docking prediction indicated that BQKL stably bound to these core targets.In vivo experiments have shown that compared with those in the Control group,rats in the Model group had statistically significant(P<0.05)severe retinal histopathological damage;elevated blood glucose,lipid,and malondialdehyde(MDA)levels;increased Caspase-3,c-Jun,and TP53 protein expression;and reduced superoxide dismutase(SOD)and glutathione peroxidase(GSH-Px)levels,ganglion cell number,AKT1,MAPK1,and MAPK3 protein expression.Compared with the Model group,BQKL group had reduced histopathological retinal damage and the expression of blood glucose and lipids,MDA level,Caspase-3,c-Jun and TP53 proteins were reduced,while the expression of SOD,GSH-Px level,the number of ganglion cells,AKT1,MAPK1,and MAPK3 proteins were elevated.These differences were statistically significant(P<0.05).CONCLUSION BQKL can delay DR onset and progression by attenuating oxidative stress and inflammatory responses and regulating Caspase-3,c-Jun,TP53,AKT1,MAPK1,and MAPK3 proteins in the MAPK signaling pathway mediates these alterations.

Potential application of Nardostachyos Radix et Rhizoma-Rhubarb for the treatment of diabetic kidney disease based on network pharmacology and cell culture experimental verification

BACKGROUND Diabetic kidney disease(DKD)is one of the serious complications of diabetes mellitus,and the existing treatments cannot meet the needs of today's patients.Traditional Chinese medicine has been validated for its efficacy in DKD after many years of clinical application.However,the specific mechanism by which it works is still unclear.Elucidating the molecular mechanism of the Nardostachyos Radix et Rhizoma-rhubarb drug pair(NRDP)for the treatment of DKD will provide a new way of thinking for the research and development of new drugs.AIM To investigate the mechanism of the NRDP in DKD by network pharmacology combined with molecular docking,and then verify the initial findings by in vitro experiments.METHODS The Traditional Chinese Medicine Systems Pharmacology(TCMSP)database was used to screen active ingredient targets of NRDP.Targets for DKD were obtained based on the Genecards,OMIM,and TTD databases.The VENNY 2.1 database was used to obtain DKD and NRDP intersection targets and their Venn diagram,and Cytoscape 3.9.0 was used to build a"drug-component-target-disease"network.The String database was used to construct protein interaction networks.Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analysis and Gene Ontology analysis were performed based on the DAVID database.After selecting the targets and the active ingredients,Autodock software was used to perform molecular docking.In experimental validation using renal tubular epithelial cells(TCMK-1),we used the Cell Counting Kit-8 assay to detect the effect of NRDP on cell viability,with glucose solution used to mimic a hyperglycemic environment.Flow cytometry was used to detect the cell cycle progression and apoptosis.Western blot was used to detect the protein expression of STAT3,p-STAT3,BAX,BCL-2,Caspase9,and Caspase3.RESULTS A total of 10 active ingredients and 85 targets with 111 disease-related signaling pathways were obtained for NRDP.Enrichment analysis of KEGG pathways was performed to determine advanced glycation end products(AGEs)-receptor for AGEs(RAGE)signaling as the core pathway.Molecular docking showed good binding between each active ingredient and its core targets.In vitro experiments showed that NRDP inhibited the viability of TCMK-1 cells,blocked cell cycle progression in the G0/G1 phase,and reduced apoptosis in a concentrationdependent manner.Based on the results of Western blot analysis,NRDP differentially downregulated p-STAT3,BAX,Caspase3,and Caspase9 protein levels(P<0.01 or P<0.05).In addition,BAX/BCL-2 and p-STAT3/STAT3 ratios were reduced,while BCL-2 and STAT3 protein expression was upregulated(P<0.01).CONCLUSION NRDP may upregulate BCL-2 and STAT3 protein expression,and downregulate BAX,Caspase3,and Caspase9 protein expression,thus activating the AGE-RAGE signaling pathway,inhibiting the vitality of TCMK-1 cells,reducing their apoptosis.and arresting them in the G0/G1 phase to protect them from damage by high glucose.

Potential pharmacological mechanisms of digallate in the treatment of enteritis based on network pharmacology and molecular docking

Background:In order to investigate the possible pharmacological mechanism of digallate in Galla Chinensis for treating enteritis,providing reference for the search and exploration of effective drugs for treating enteritis.Method:Traditional Chinese Medicines Systems Pharmacology Database and Analysis Platform,PharmMapper,DisGeNET,DrugBank,and GeneCards databases were used to obtain drug and disease-related target information.Gene ontology functional annotation and Kyoto Encyclopedia of Genes and Genomes pathway enrichment were performed,and the main therapeutic pathways and targets were identified by combining protein-protein interaction networks and cytoHubba plug-in.Molecular docking was used to validate the results.Result:297 drug related targets,2436 disease related targets,and 66 target points related to digallate were predicted to be associated with enteritis.10 related signal pathways and 10 key genes were identified.Conclusion:Digallate may be utilized to treat enteritis by acting on similar pathways,such those related to pathways in cancer,lipid and atherosclerosis,proteoglycans in cancer,Rap1 signaling pathway,PI3K-Akt signaling pathway and other targets such as IGF1,EGFR,SRC,IGF1R,PPARG.

Retinal vein occlusion coinciding with paracentral acute middle maculopathy in patient with menorrhagia causing life-threatening anemia

Dear Editor,We present two cases of retinal vein occlusion,one central retinal vein occlusion(CRVO)and one branch retinal vein occlusion(BRVO)respectively,coinciding with paracentral acute middle maculopathy(PAMM)on optical coherence tomography(OCT)in patients with menorrhagia causing life-threatening anemia.PAMM is considered a manifestation of acute ischemia affecting the deep macular capillary plexus.