Background:The development of gastric cancer(GC)encompasses precancerous conditions like chronic atrophic gastritis(CAG)and premalignant lesions of gastric cancer(PLGC).In these situations,abnormal Notch signaling res...Background:The development of gastric cancer(GC)encompasses precancerous conditions like chronic atrophic gastritis(CAG)and premalignant lesions of gastric cancer(PLGC).In these situations,abnormal Notch signaling results in mucosal impairment and the initiation of cancer.Banxia Xiexin Decoction(BXD),a well-known formula in traditional Chinese medicine(TCM),shows promise in treating gastric disorders,but its mechanisms in gastric restoration remain unclear.Methods:Using MNNG-induced CAG and PLGC rat models,BXD was administered for 12 weeks.Gastric mucosal pathology was assessed via hematoxylin-eosin staining.Proliferation(Ki-67)and angiogenesis(VEGFA)markers were evaluated by immunohistochemistry.Network pharmacology identified BXD’s targets and pathways.Notch pathway components(Notch1,Jagged1,Dll4,Hes1)were analyzed via qPCR,Western blot,and immunohistochemistry.Results:BXD significantly ameliorated mucosal atrophy,glandular structural disorder,and dysplasia in CAG and PLGC rats.Network pharmacology revealed 323 overlapping targets between BXD and PLGC,with Notch signaling as a central pathway.BXD downregulated Notch1,Jagged1,Dll4,and Hes1 expression at transcriptional and protein levels,suppressed Ki-67(proliferation)and VEGFA(angiogenesis)overexpression,and restored gastric mucosal integrity.Conclusion:BXD inhibits Notch signaling,reduces aberrant proliferation and angiogenesis,and interrupts Correa’s gastric carcinogenesis cascade.This study provides mechanistic evidence supporting BXD as a TCM-based intervention for gastric precancerous lesions.展开更多
AI applications have already-irreversibly-entered the fields of Humanities,Classics,and archaeological research,but are rarely taught in class.This paper attempts to encourage teachers and students of Classical Archae...AI applications have already-irreversibly-entered the fields of Humanities,Classics,and archaeological research,but are rarely taught in class.This paper attempts to encourage teachers and students of Classical Archaeology,Classics,Art History,and related fields,to practically explore,evaluate,and critically discuss pattern recognition(here focusing on Greek vase-painting),without requiring previously acquired coding skills.For this task,I will outline the potential of the open access program“Orange Data Mining”for academic teaching,based on a seminar taught by myself at Heidelberg University in the winter semester of 2024/25.I will introduce four different pattern recognition exercises(“Image Grid,”“Image Clustering,”“Image Classification,”and“Prediction”)that are easily accessible for classicists(please,try this at home!)and report the results and experiences which came out of our seminar.Furthermore,I will evaluate how the“hands-on”use of Orange Data Mining in class enables students to access the current debate on the chances and limitations of AI for research in ancient studies.展开更多
Obesity has become a global threat to health;however,the available drugs for treating obesity are limited.We investigated the anti-obesity effect of hydroxy-α-sanshool(HAS),an amide derived from the fruit of Zanthoxy...Obesity has become a global threat to health;however,the available drugs for treating obesity are limited.We investigated the anti-obesity effect of hydroxy-α-sanshool(HAS),an amide derived from the fruit of Zanthoxylum bungeanum,which promotes the management of obesity by triggering the browning of white adipose tissue(WAT)targeting the membrane receptor of transient receptor potential vanilloid 1(TRPV1).However,HAS easily undergoes configuration transformation and oxidative degradation.The short peptide CKGGRAKDC or adipose-targeting sequence(ATS)binds specifically to prohibitin on the surface of WAT cells and can be used as recognition assembly to enhance adipocyte targetability.Furthermore,mesoporous silica nanoparticles(MSNs)are widely used in drug delivery systems because of their large specific surface area and pore volume.Therefore,HAS-loaded adipose-targeted MSNs(MSNs-ATS)were developed to enhance the adipocyte targetability,safety,and efficacy of HAS,and tested on mature 3T3-L1 cells and obese mouse models.MSNs-ATS showed higher specificity for adipocyte targetability without obvious toxicity.HAS-loaded MSNs-ATS showed anti-obesity effects superior to those of HAS alone.In conclusion,we successfully developed adipocyte-targeted,HAS-loaded MSNs with good safety and anti-obesity effects.展开更多
The author of this book passionately recounts the tumultuous Life of Han Yu through microscopic,on-the-ground historical descriptions and analyses,also touching upon the literati and politicians of Han Yu's era,as...The author of this book passionately recounts the tumultuous Life of Han Yu through microscopic,on-the-ground historical descriptions and analyses,also touching upon the literati and politicians of Han Yu's era,as well as the political and Literary climate of the mid-Tang,guiding the reader into a truly tangible,vivid,and morally rich portrayal of the Confucian scholar Han Yu.展开更多
Ye Tianshi was a renowned expert in classical formulas during the Qing Dynasty.He created the Light Bitterness and Mild Pungency Method,which is formulated based on the compatibility of“Xing(bitter almond),Kou(Fructu...Ye Tianshi was a renowned expert in classical formulas during the Qing Dynasty.He created the Light Bitterness and Mild Pungency Method,which is formulated based on the compatibility of“Xing(bitter almond),Kou(Fructus amomi rotundus),Ju(tangerine peel),and Jie(platycodon root)”.This method regulates the dispersion and descent of lung Qi to dispel warm-heat pathogens and smooth the Qi movement of the triple energizer.In the treatment of lung system diseases,Ye classified them into two major categories based on etiology and pathogenesis:excess syndrome of nutrient-defense and deficiency syndrome of nutrient-defense.When discussing the treatment of cough caused by phlegm-fluid retention,he frequently referred to Synopsis of the Golden Chamber and attached great importance to summarizing and absorbing the academic thoughts of predecessors.As an accomplished expert in classical formulas,Ye Tianshi followed the academic essence of Xuanyuan and Qi Bo(founders of TCM theory)and respected the principles of Zhang Zhongjing’s classical formulas,integrating these theories in a coherent manner.With his masterful application of classical formulas to achieve remarkable curative effects,Ye’s academic viewpoints on treating lung system diseases still exert a profound influence on the modern clinical diagnosis and treatment of related diseases.展开更多
Background:Damp-heat syndrome(DHS)is a complex condition in traditional Chinese medicine(TCM)that can cause various issues in circulation,digestion,and the respiratory system.This syndrome is believed to be closely li...Background:Damp-heat syndrome(DHS)is a complex condition in traditional Chinese medicine(TCM)that can cause various issues in circulation,digestion,and the respiratory system.This syndrome is believed to be closely linked to environmental factors such as high temperature and high humidity environments.Tingzhen Lu,a prominent physician during the Qing Dynasty,proposed the efficacy of Huanglian Wengdan Decoction(HLWDT)in addressing ailments stemming from high-temperature and high-humidity conditions.Nevertheless,the specific therapeutic effects of this decoction on DHS and its underlying mechanisms remain incompletely understood.Methods:To clarify the composition of HLWDT,mass spectrometry was utilized to identify the constituent compounds.Moreover,DHS rats induced by high humidity-temperature combined with a high sugar-fatty diet were treated with Huanglian Wendan decoction,the efficacy of which was evaluated based on serum biochemical indices and histopathological analyses.The expression of corresponding proteins was verified using western blotting.The mechanism of DHS relief by HLWDT was investigated by integration of network pharmacology and non-targeted metabolomics.Results:The HLWDT contained nearly 1,315 ingredients,the majority of which were flavonoids.Moreover,HLWDT not only regulated gastrointestinal motility and oxidative stress in DHS rats but also alleviated their inflammatory state.Metabolomics and network pharmacology analysis revealed that HLWDT primarily affects bile secretion,linoleic acid metabolism,PPAR,and MAPK signaling pathways.Furthermore,the PPAR signaling pathway was confirmed.HLWDT decreased the expression of NF-κB p65 and promoted MAPK phosphorylation and PPARγexpression in DHS rats.Conclusion:The therapeutic effect of HLWDT on DHS is potentially attributable to activation of the PPARγ-NF-κB/MAPK signaling pathway and regulation of oxidative stress and inflammatory responses.This experiment preliminarily elucidated the impact and mechanisms of HLWDT on DHS through pharmacodynamics,network pharmacology,and metabolomics.展开更多
Background:Chaihu Guizhi Decoction(CGD)is a classical prescription in traditional Chinese medicine(TCM)that has been shown to be effective against infection and depression.However,the mechanisms of action of CGD in tr...Background:Chaihu Guizhi Decoction(CGD)is a classical prescription in traditional Chinese medicine(TCM)that has been shown to be effective against infection and depression.However,the mechanisms of action of CGD in treating patients with depression who are also infected with a virus remain unknown.This study investigated the pharmacological mechanisms of CGD in treating depression-like mice infected with influenza A virus(IAV).Methods:The acute depression-like mouse model infected with IAV was established.The effects of CGD on alleviating depression-like symptoms were observed using the sucrose preference test and monoamine neurotransmitter expression.Additionally,the effectiveness of CGD against infection was assessed by examining the relative expression of the M gene and pathological changes.To evaluate the anti-inflammatory effects of CGD,the levels of cytokines were measured,and the Th17/Treg ratio was analyzed to evaluate the immunomodulatory effects of CGD.Results:The study results show that CGD enhanced the rates of sucrose preference and raised the contents of neurotransmitters dopamine(DA)and norepinephrine(NE).CGD treatment led to a reduction in lung index and the relative expression of the M gene,along with improvements in pathological changes caused by IAV.Furthermore,the levels of cytokines were decreased after treatment with CGD,and the imbalance in the ratio of Th17/Treg was corrected via a reduction in the number of Th17 cells after treatment.Conclusions:CGD has a therapeutic effect in mice with depression-like symptoms infected with IAV,increasing the levels of DA and NE,downregulating M gene expression,calming the cytokine storm,and preserving the homeostasis of Th17/Treg cells.展开更多
Liver disease(LD)is a global health problem caused by multiple factors.At present,there are still obvious problems with limited efficacy and strong side effects of drugs used in the clinical treatment of LD.Therefore,...Liver disease(LD)is a global health problem caused by multiple factors.At present,there are still obvious problems with limited efficacy and strong side effects of drugs used in the clinical treatment of LD.Therefore,it is of great significance to search for effective hepatoprotective drugs from natural products.Geniposide(GS)is a cyclic ether terpenoid compound and a key component in the traditional Chinese medicine Gardenia jasminoides.It has a significant inhibitory effect on LD.However,there is currently no literature systematically analyzing its mechanism of action.To adapt to the environment of new drug research and the need for precision medication,this article summarizes the pathways and possible mechanisms of action discovered by GS in the treatment of LD,based on recent research literature:regulating bile stasis,antioxidant and anti-apoptosis,improving amino acid metabolism,improving energy metabolism,regulating lipid metabolism,anti-inflammatory and analgesic effects,etc.It also summarizes the pharmacokinetics of GS in vivo and discusses the liver toxicity of GS that is positively correlated with dosage.In addition,the existing problems in current research and possible future development directions were also discussed,to lay the foundation for the clinical development of natural product GS.展开更多
Objective:Arrhythmia-induced cardiomyopathy(AIC)is a reversible dilated cardiomyopathy induced by rapid or irregular heartbeat.Acupuncture has a long history of use in the treatment of cardiac diseases,and Xinshu(BL15...Objective:Arrhythmia-induced cardiomyopathy(AIC)is a reversible dilated cardiomyopathy induced by rapid or irregular heartbeat.Acupuncture has a long history of use in the treatment of cardiac diseases,and Xinshu(BL15)is a key acupoint.However,the underlying mechanism of acupuncture at BL15 in the treatment of AIC has not yet been elucidated.Methods:AIC was induced in adult male Sprague-Dawley(SD)rats by continuous administration of acetylcholine(ACh)-CaCl2 and treatment with electroacupuncture(EA)at bilateral BL15.Echocardiography was used to evaluate cardiac function;the rotarod test for motor coordination and performance;hematoxylin and eosin(HE)staining for the morphology of ventricles;electrocardiogram for susceptibility,inducibility,and duration of atrial fibrillation(AF);and electrical and optical mapping in isolated rat hearts maintained by the Langendorff perfusion system for electrical conduction and intracellular handling,respectively.Reverse transcription quantitative polymerase chain reaction(RT-qPCR)and Western blotting were used to determine the levels of cardiac conduction and intracellular calcium-handling proteins in the ventricle.Results:The results showed that EA improved the ejection factor and morphological indices on echocardiography,restored motor coordination and performance,and alleviated ventricular dilation and AF onset.EA alleviates atrial conduction disorders,shortens APD80,and decreases calcium handling in rats with AIC.Cx43 was downregulated and CaMKII was upregulated,and both effects were reversed by EA treatment.Conclusion:Our study provides a novel AIC model with abnormal electrical propagation and calcium handling that can be protected by EA at BL15.This potential mechanism may be associated with the modulation of Cx43 and CaMKII expression.展开更多
Colorectal inflammatory cancer transformation poses a major risk to patients with colitis.Patients with chronic intestinal inflammation have an approximately 2–3 fold increased risk of developing colorectal cancer(CR...Colorectal inflammatory cancer transformation poses a major risk to patients with colitis.Patients with chronic intestinal inflammation have an approximately 2–3 fold increased risk of developing colorectal cancer(CRC).Unfortunately,there is currently no effective intervention available.Huangqin decoction(HQD),a well-known traditional Chinese medicine(TCM)formula,is frequently clinically prescribed for treating patients with colitis,and its active ingredients have effective antitumour efficacy.Nonetheless,the mechanism of HQD-mediated prevention of colorectal inflammatory cancer transformation remains unclear.A strategy integrating metagenomic,lipidomic,and messenger RNA(mRNA)sequencing analysis was used to investigate the regulatory effects of HQD on the gut microbiome,metabolism and potential mechanisms involved in colorectal inflammatory cancer transformation.Our study revealed that HQD suppressed colorectal inflammatory cancer transformation,which was associated with enhanced intestinal barrier function,decreased the inflammatory response,and regulation of the gut microbiome.Notably,cohousing experiments revealed that the transfer of the gut microbiome from HQD-treated mice largely inhibited the pathological transformation of colitis.Moreover,gut microbiome transfer from HQD-treated mice primarily resulted in the altered regulation of fatty acid metabolism,especially the remodeling of arachidonic acid metabolism,which was associated with the amelioration of pathological transformation.Arachidonic acid metabolism and the key metabolic enzyme arachidonic acid 12-lipoxygenase(ALOX12)were affected by HQD treatment,and no obvious protective effect of HQD was observed in Alox12−/−mice,which revealed that ALOX12 was a critical mediator of HQD protection against colorectal inflammatory cancer transformation.In summary,multiple omics analyses were applied to produce valuable data and theoretical support for the application of HQD as a promising intervention for the transformation of inflammatory CRC.展开更多
Highlights The RT-RAA-VF assay developed for the NiV P gene can perform rapid detection of NiV within 20 min at 42℃ with high specificity.This assay is capable of attaining sensitivity to a single copy of NiV RNA tra...Highlights The RT-RAA-VF assay developed for the NiV P gene can perform rapid detection of NiV within 20 min at 42℃ with high specificity.This assay is capable of attaining sensitivity to a single copy of NiV RNA transcripts.This assay effectively avoids false positives caused by aerosol contamination with a sealed disposable nucleic acid visualization test paper device.展开更多
Background:Previously,a chronic social defeat stress(CSDS)model has been widely-adopted for assessing depressive-like behaviors in animals.However,there is still room for improvement in the CSDS model to safeguard stu...Background:Previously,a chronic social defeat stress(CSDS)model has been widely-adopted for assessing depressive-like behaviors in animals.However,there is still room for improvement in the CSDS model to safeguard study accuracy and the wel-fare of lab rodents.Our study team developed a novel,standardized apparatus to induce CSDS in rodents and assessed the model's practical adaptability.Methods:An innovative CSDS cage apparatus and water bottle was designed.To evaluate the effectiveness of the newly developed tools,a variety of animal models,including the tail suspension test(TST),sucrose preference test,forced swimming test(FST),novelty-suppressed feeding test,female urine sniffing test,and open field test(OFT),were adopted to assess depressive-like behaviors in mice.Fluoxetine treat-ment was also administered to observe the reversal effect,as part of the validation.Results:The CSDS cage apparatus resulted in the manifestation of depressive-like behaviors in the model mice.Significant reductions in sucrose preference and urine sniffing time were observed,while the OFT revealed decreased central zone total distance,residence time,and frequency of entry.Moreover,increased immobility was found in the FST and TST.Fluoxetine treatment was found to successfully reverse the modeling effect.Conclusion:The CSDS cage apparatus was validated for enhanced usability and ad-dressed the previous challenges of water bottle leakage and lab rodent welfare is-sues.The consistent results from multiple behavioral tests also supported real-world application of the apparatus,offering researchers a promising alternative to conven-tional rodent cages.展开更多
Stress studies frequently utilize physical stressors to establish animal models of stress. In the majority of cases, these models are not consistent with human circumstances. The present study simulated a social isola...Stress studies frequently utilize physical stressors to establish animal models of stress. In the majority of cases, these models are not consistent with human circumstances. The present study simulated a social isolation plus resident intruder stress model in the rat. The rats were subjected to daily social isolation and resident intruder stress for 2 weeks. Behaviors were then tested. Rats subjected to social stress exhibited different aggressive behavior styles; some rats had greater scores on composite aggression behaviors, as well as locomotor and exploratory activity, but lower scores on latency than others. The high-aggressive group exhibited predominantly anger-out, while the low-aggressive group exhibited anger-in. Results suggest that social isolation plus resident intruder may serve as an appropriate model for anger-in and anger-out emotion modeling in the rat.展开更多
OBJECTIVE: To elucidate the mechanisms underlying the treatment of Alzheimer’s disease(AD) with Traditional Chinese Medicine(TCM), by examining the active components, potential targets and synthetic pathways of Bulao...OBJECTIVE: To elucidate the mechanisms underlying the treatment of Alzheimer’s disease(AD) with Traditional Chinese Medicine(TCM), by examining the active components, potential targets and synthetic pathways of Bulao Elixir(BLE).METHODS: The Absorption, Distribution, Metabolism, Excretion(ADME)/Toxicology(T) calculation was used to screen the active components of Bulao Elixir. Based on the TCM Systems Pharmacology Analysis Platform(TCMSP database) and a text mining tool(GoPubMed database), we predicted and screened the active components of Bulao Elixir and its therapeutic targets for AD. Using the Database for Annotation, Visualization and Integrated Discovery(DAVID), we obtained the targets for AD. Cytoscape software was used to establish a network map of the active component-target and target-pathway of Bulao Elixir. Gene function, related biological processes and signaling pathways were analyzed using the DAVID database.RESULTS: Twelve active components were selected from 196 components of Bulao Elixir. Among 2209 targets, 102 effective targets were selected, and 30 important targets were identified via matching with the disease targets. After further analysis, 14 core targets were identified. Enrichment analysis revealed that most of these important targets were involved in multiple biological processes, including apoptosis, inflammatory reactions, and cell regulation cycles. The synthetic pathways for AD treatment were identified after analyzing and confirming the relevant pathways, providing potentially useful information for diagnosis and treatment methods for AD.CONCLUSION: The current study elucidated the potential treatment mechanisms of Bulao Elixir in AD using network pharmacology, providing a foundation for further clarification of its treatment targets.展开更多
OBJECTIVE: To evaluate the effectiveness of Sini powder for the treatment of non-alcoholic fatty liver disease(NAFLD) in rats and the molecular mechanisms involved.METHODS: A rat model of stress-induced NAFLD was esta...OBJECTIVE: To evaluate the effectiveness of Sini powder for the treatment of non-alcoholic fatty liver disease(NAFLD) in rats and the molecular mechanisms involved.METHODS: A rat model of stress-induced NAFLD was established by a combination of long-term tethering and feeding of a high-fat, high-calorie diet. These rats were then intragastrically administered with either simvastatin, Sini powder, or vehicle for 1 week. The body mass and field test scores for each group were recorded weekly. Serum aspartate aminotransferase and alanine aminotransferase activities, and triglyceride, total cholesterol,and free fatty acid concentrations were measured.Liver tissue histopathology was examined on hematoxylin and eosin-stained paraffin sections and oil red O-stained frozen sections. The hepatic m RNA expression of nuclear factor kappa-B(NF-κB),NOD-, LRR-, and pyrin domain-containing protein 3(NLRP3), apoptosis-associated speck-like protein containing CARD(ASC), and caspase-1 were measured by reverse transcription-polymerase chain reaction(RT-PCR). The hepatic protein concentrations of NF-κB and NLRP3, ASC, caspase-1, interleukin-1β(IL-1β), interleukin-6(IL-6), and the serum concentrations of IL-1β and IL-6 were measured by enzyme-linked immunosorbent assay.RESULTS: Compared with the Blank group, rats in the Compound model group showed significant pathologic manifestations of NAFLD, and the expression of NF-κB, NLRP3, ASC, caspase-1, IL-1βand IL-6 were significantly higher(all P < 0.01). Both simvastatin and Sini powder significantly ameliorated the NAFLD pathology and the abnormal expression of NF-κB, NLRP3, ASC, caspase-1, IL-1β, and IL-6(all P < 0.01).CONCLUSION: Sini powder inhibits the inflamma-tory response in rats with NAFLD, which is mediated by NF-κB/NLRP3, IL-1β, and IL-6, reduces the effects of psychological stress, and improves lipid metabolism. Therefore, Sini powder may be effective for the treatment of stress-related NAFLD through multiple mechanisms.展开更多
The syndrome of dampness stagnancy due to spleen deficiency(DSSD)is relatively common globally.Although the pathogenesis of DSSD remains unclear,evidence has suggested that the gut microbiota might play a significant ...The syndrome of dampness stagnancy due to spleen deficiency(DSSD)is relatively common globally.Although the pathogenesis of DSSD remains unclear,evidence has suggested that the gut microbiota might play a significant role.Radix Astragali,used as both medicine and food,exerts the effects of tonifying spleen and qi.Astragalus polysaccharide(APS)comprises a macromolecule substance extracted from the dried root of Radix Astragali,which has many pharmacological functions.However,whether APS mitigates the immune disorders underlying the DSSD syndrome via regulating gut microbiota and the relevant mechanism remains unknown.Here,we used DSSD rats induced by high-fat and low-protein(HFLP)diet plus exhaustive swimming,and found that APS of moderate molecular weight increased the body weight gain and immune organ indexes,decreased the levels of interleukin-1β(IL-1β),IL-6,and endotoxin,and suppressed the Toll-like receptor 4/nuclear factor-κB(TLR4/NF-κB)pathway.Moreover,a total of 27 critical genera were significantly enriched according to the linear discriminant analysis effect size(LEfSe).APS increased the diversity of the gut microbiota and changed its composition,such as reducing the relative abundance of Pseudoflavonifractor and Paraprevotella,and increasing that of Parasutterella,Parabacteroides,Clostridium XIVb,Oscillibacter,Butyricicoccus,and Dorea.APS also elevated the contents of short-chain fatty acids(SCFAs).Furthermore,the correlation analysis indicated that 12 critical bacteria were related to the body weight gain and immune organ indexes.In general,our study demonstrated that APS ameliorated the immune disorders in DSSD rats via modulating their gut microbiota,especially for some bacteria involving immune and inflammatory response and SCFA production,as well as the TLR4/NF-κB pathway.This study provides an insight into the function of APS as a unique potential prebiotic through exerting systemic activities in treating DSSD.展开更多
OBJECTIVE:To investigate the targets and mechanisms of action of Qingkailing injection(清开灵注射液,QKL)in the treatment of cholestatic hepatitis.METHODS:A network pharmacology method was implemented using drug and di...OBJECTIVE:To investigate the targets and mechanisms of action of Qingkailing injection(清开灵注射液,QKL)in the treatment of cholestatic hepatitis.METHODS:A network pharmacology method was implemented using drug and disease databases to target QKL and cholestasis hepatitis,respectively.The functional protein association network STRING database was used to construct a protein-protein interaction network using R language and the Bioconductor toolkit.The org.Hs.eg.db and cluster Profiler packages were used for gene ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis,which explored biological functions and pathways of potential targets.Targets were then visualized using Cytoscape 3.6.0 software.RESULTS:We screened 121 compounds in QKL and identified 112 targets for the treatment of cholestatic hepatitis.QKL played a role in the treatment of cholestatic hepatitis through 305 biology process terms,15 cellular component and 29 molecular function terms.The mechanism of QKL action was mainly related to tumor necrosis factor,mitogen-activated protein kinase,and PI3 K-Akt signaling pathways.CONCLUSION:The treatment of cholestatic hepatitis by QKL involved multiple targets,biological functions,and signaling pathways that are closely associated with the disease.展开更多
Objective: MicroRNAs(miRNAs) may be viable targets for treating renal interstitial fibrosis(RIF). Fuzheng Huayu recipe(FZHY), a traditional Chinese compound herbal medicine, is often used in China to treat fibrosis. T...Objective: MicroRNAs(miRNAs) may be viable targets for treating renal interstitial fibrosis(RIF). Fuzheng Huayu recipe(FZHY), a traditional Chinese compound herbal medicine, is often used in China to treat fibrosis. This study sought to assess the mechanisms through which FZHY influences miRNAs to treat RIF.Methods: RIF was induced in rats by mercury chloride and treated with FZHY. Hydroxyproline content,Masson’s staining and type I collagen expression were used to evaluate renal collagen deposition.Renal miRNA profiles were evaluated using a miRNA microarray. Those miRNAs that were differentially expressed following FZHY treatment were identified and subjected to bioinformatic analyses. The miR-21 target gene phosphatase and tensin homolog(PTEN) expression and AKT phosphorylation in kidney tissues were assessed via Western blotting. In addition, HK-2 human proximal tubule epithelial cells were treated using angiotensin II(Ang-II) to induce epithelial-to-mesenchymal transition(EMT), followed by FZHY exposure. miR-21 and PTEN expressions were evaluated via quantitative reverse transcriptionpolymerase chain reaction(qRT-PCR), while E-cadherin and a-smooth muscle actin(a-SMA) expressions were assessed by immunofluorescent staining and qRT-PCR. Western blotting was used to assess PTEN and AKT phosphorylation.Results: FZHY significantly decreased kidney collagen deposition, hydroxyproline content and type I collagen level. The miRNA microarray identified 20 miRNAs that were differentially expressed in response to FZHY treatment. Subsequent bioinformatic analyses found that miR-21 was the key fibrosis-related miRNA regulated by FZHY. FZHY also decreased PTEN expression and AKT phosphorylation in fibrotic kidneys. Results from in vitro tests also suggested that FZHY promoted E-cadherin upregulation and inhibited a-SMA expression in Ang-II-treated HK-2 cells, effectively reversing Ang-II-mediated EMT. We also determined that FZHY reduced miR-21 expression, increased PTEN expression and decreased AKT phosphorylation in these cells.Conclusion: miR-21 is the key fibrosis-related miRNA regulated by FZHY. The ability of FZHY to modulate miR-21/PTEN/AKT signaling may be a viable approach for treating RIF.展开更多
In 2012,a lacquer figure was unearthed from the Han dynasty tomb(188 BC-87 BC) at Chengdu Laoguanshan.The lines intaglioed on the Laoguan mountain lacquer figure were similar to the meridians.Objective:To investigate ...In 2012,a lacquer figure was unearthed from the Han dynasty tomb(188 BC-87 BC) at Chengdu Laoguanshan.The lines intaglioed on the Laoguan mountain lacquer figure were similar to the meridians.Objective:To investigate the relationship between the lines on this Laoguanshan lacquer figure and the regular meridians so as to explore the development of meridian system in ancient China.Methods:Based on collecting the photos of the Laoguan mountain lacquer figure and the representative acupuncture classics,the double evidence method(combining the unearthed relics/literature and extant literature) was performed to investigate the relationship between the lines on this Laoguanshan lacquer figure and the regular meridians.Furthermore,the development of regular meridians theory was analyzed from the number,distribution,direction and branches.Results:The routes of the 28 longitudinal white lines on the Laoguan mountain lacquer figure are similar to the regular meridians in the ancient literature including Huángdì Nèijīng 《黄帝内经》 Yellow Emperor’s Inner Classic).The number,distribution and branches of the meridians intaglioed on the Laoguanshan lacquer figure suggested the evolution of the regular-meridian system from the eleven-meridian system to the twelve-meridian system.Conclusions:The meridian system of Laoguanshan lacquer figure was a link connecting the preceding and the following.The Laoguanshan lacquer figure played an important role in the development of the early meridian theory.展开更多
基金supported by the National Natural Science Foundation of China(Grant No.82274442)the Key Research Project in Traditional Chinese Medicine of Tianjin Municipal Health Commission(Grant No.202007)the Integrated Traditional Chinese and Western Medicine Research Project of Tianjin Municipal Health Commission(Grant No.2023134).
文摘Background:The development of gastric cancer(GC)encompasses precancerous conditions like chronic atrophic gastritis(CAG)and premalignant lesions of gastric cancer(PLGC).In these situations,abnormal Notch signaling results in mucosal impairment and the initiation of cancer.Banxia Xiexin Decoction(BXD),a well-known formula in traditional Chinese medicine(TCM),shows promise in treating gastric disorders,but its mechanisms in gastric restoration remain unclear.Methods:Using MNNG-induced CAG and PLGC rat models,BXD was administered for 12 weeks.Gastric mucosal pathology was assessed via hematoxylin-eosin staining.Proliferation(Ki-67)and angiogenesis(VEGFA)markers were evaluated by immunohistochemistry.Network pharmacology identified BXD’s targets and pathways.Notch pathway components(Notch1,Jagged1,Dll4,Hes1)were analyzed via qPCR,Western blot,and immunohistochemistry.Results:BXD significantly ameliorated mucosal atrophy,glandular structural disorder,and dysplasia in CAG and PLGC rats.Network pharmacology revealed 323 overlapping targets between BXD and PLGC,with Notch signaling as a central pathway.BXD downregulated Notch1,Jagged1,Dll4,and Hes1 expression at transcriptional and protein levels,suppressed Ki-67(proliferation)and VEGFA(angiogenesis)overexpression,and restored gastric mucosal integrity.Conclusion:BXD inhibits Notch signaling,reduces aberrant proliferation and angiogenesis,and interrupts Correa’s gastric carcinogenesis cascade.This study provides mechanistic evidence supporting BXD as a TCM-based intervention for gastric precancerous lesions.
基金the European Union’s Horizon 2020 research and innovation programme.
文摘AI applications have already-irreversibly-entered the fields of Humanities,Classics,and archaeological research,but are rarely taught in class.This paper attempts to encourage teachers and students of Classical Archaeology,Classics,Art History,and related fields,to practically explore,evaluate,and critically discuss pattern recognition(here focusing on Greek vase-painting),without requiring previously acquired coding skills.For this task,I will outline the potential of the open access program“Orange Data Mining”for academic teaching,based on a seminar taught by myself at Heidelberg University in the winter semester of 2024/25.I will introduce four different pattern recognition exercises(“Image Grid,”“Image Clustering,”“Image Classification,”and“Prediction”)that are easily accessible for classicists(please,try this at home!)and report the results and experiences which came out of our seminar.Furthermore,I will evaluate how the“hands-on”use of Orange Data Mining in class enables students to access the current debate on the chances and limitations of AI for research in ancient studies.
基金supported by the Natural Science Foundation of Sichuan Province(No.2022NSFSC0720)Research Center for the Development of the Comprehensive Health Industry and Rural Revitalization of Sichuan TCM(No.DJKYB202306)State Administration of Traditional Chinese Medicine of Sichuan Province of China(No.2020HJZX001).
文摘Obesity has become a global threat to health;however,the available drugs for treating obesity are limited.We investigated the anti-obesity effect of hydroxy-α-sanshool(HAS),an amide derived from the fruit of Zanthoxylum bungeanum,which promotes the management of obesity by triggering the browning of white adipose tissue(WAT)targeting the membrane receptor of transient receptor potential vanilloid 1(TRPV1).However,HAS easily undergoes configuration transformation and oxidative degradation.The short peptide CKGGRAKDC or adipose-targeting sequence(ATS)binds specifically to prohibitin on the surface of WAT cells and can be used as recognition assembly to enhance adipocyte targetability.Furthermore,mesoporous silica nanoparticles(MSNs)are widely used in drug delivery systems because of their large specific surface area and pore volume.Therefore,HAS-loaded adipose-targeted MSNs(MSNs-ATS)were developed to enhance the adipocyte targetability,safety,and efficacy of HAS,and tested on mature 3T3-L1 cells and obese mouse models.MSNs-ATS showed higher specificity for adipocyte targetability without obvious toxicity.HAS-loaded MSNs-ATS showed anti-obesity effects superior to those of HAS alone.In conclusion,we successfully developed adipocyte-targeted,HAS-loaded MSNs with good safety and anti-obesity effects.
文摘The author of this book passionately recounts the tumultuous Life of Han Yu through microscopic,on-the-ground historical descriptions and analyses,also touching upon the literati and politicians of Han Yu's era,as well as the political and Literary climate of the mid-Tang,guiding the reader into a truly tangible,vivid,and morally rich portrayal of the Confucian scholar Han Yu.
文摘Ye Tianshi was a renowned expert in classical formulas during the Qing Dynasty.He created the Light Bitterness and Mild Pungency Method,which is formulated based on the compatibility of“Xing(bitter almond),Kou(Fructus amomi rotundus),Ju(tangerine peel),and Jie(platycodon root)”.This method regulates the dispersion and descent of lung Qi to dispel warm-heat pathogens and smooth the Qi movement of the triple energizer.In the treatment of lung system diseases,Ye classified them into two major categories based on etiology and pathogenesis:excess syndrome of nutrient-defense and deficiency syndrome of nutrient-defense.When discussing the treatment of cough caused by phlegm-fluid retention,he frequently referred to Synopsis of the Golden Chamber and attached great importance to summarizing and absorbing the academic thoughts of predecessors.As an accomplished expert in classical formulas,Ye Tianshi followed the academic essence of Xuanyuan and Qi Bo(founders of TCM theory)and respected the principles of Zhang Zhongjing’s classical formulas,integrating these theories in a coherent manner.With his masterful application of classical formulas to achieve remarkable curative effects,Ye’s academic viewpoints on treating lung system diseases still exert a profound influence on the modern clinical diagnosis and treatment of related diseases.
基金supported by the National Natural Science Foundation of China(No.82360897)Natural Science Foundation of Jiangxi Province of China(No.20212BAB216007)Administration of Traditional Chinese Medicine of Jiangxi Province of China(No.2022A328).
文摘Background:Damp-heat syndrome(DHS)is a complex condition in traditional Chinese medicine(TCM)that can cause various issues in circulation,digestion,and the respiratory system.This syndrome is believed to be closely linked to environmental factors such as high temperature and high humidity environments.Tingzhen Lu,a prominent physician during the Qing Dynasty,proposed the efficacy of Huanglian Wengdan Decoction(HLWDT)in addressing ailments stemming from high-temperature and high-humidity conditions.Nevertheless,the specific therapeutic effects of this decoction on DHS and its underlying mechanisms remain incompletely understood.Methods:To clarify the composition of HLWDT,mass spectrometry was utilized to identify the constituent compounds.Moreover,DHS rats induced by high humidity-temperature combined with a high sugar-fatty diet were treated with Huanglian Wendan decoction,the efficacy of which was evaluated based on serum biochemical indices and histopathological analyses.The expression of corresponding proteins was verified using western blotting.The mechanism of DHS relief by HLWDT was investigated by integration of network pharmacology and non-targeted metabolomics.Results:The HLWDT contained nearly 1,315 ingredients,the majority of which were flavonoids.Moreover,HLWDT not only regulated gastrointestinal motility and oxidative stress in DHS rats but also alleviated their inflammatory state.Metabolomics and network pharmacology analysis revealed that HLWDT primarily affects bile secretion,linoleic acid metabolism,PPAR,and MAPK signaling pathways.Furthermore,the PPAR signaling pathway was confirmed.HLWDT decreased the expression of NF-κB p65 and promoted MAPK phosphorylation and PPARγexpression in DHS rats.Conclusion:The therapeutic effect of HLWDT on DHS is potentially attributable to activation of the PPARγ-NF-κB/MAPK signaling pathway and regulation of oxidative stress and inflammatory responses.This experiment preliminarily elucidated the impact and mechanisms of HLWDT on DHS through pharmacodynamics,network pharmacology,and metabolomics.
基金Jinan City-University Integration Development Strategy Project,Grant/Award Number:JNSX2023054Shandong Province Technological Innovation Guidance Program,Grant/Award Number:YDZX2023044+4 种基金Independent Cultivation of Innovation Team,Grant/Award Number:2021GXRC028Shandong Provincial Natural Science Foundation,Grant/Award Number:ZR2021LZY012National Natural Science Foundation of China,Grant/Award Number:82274397Discipline Construction Project of Highlevel Traditional Chinese Medicine by National Administration of Traditional Chinese Medicine,Grant/Award Number:ZYYZDXK-2023119Shandong University of Traditional Chinese Medicine Research Fund,Grant/Award Number:KY2024Z04。
文摘Background:Chaihu Guizhi Decoction(CGD)is a classical prescription in traditional Chinese medicine(TCM)that has been shown to be effective against infection and depression.However,the mechanisms of action of CGD in treating patients with depression who are also infected with a virus remain unknown.This study investigated the pharmacological mechanisms of CGD in treating depression-like mice infected with influenza A virus(IAV).Methods:The acute depression-like mouse model infected with IAV was established.The effects of CGD on alleviating depression-like symptoms were observed using the sucrose preference test and monoamine neurotransmitter expression.Additionally,the effectiveness of CGD against infection was assessed by examining the relative expression of the M gene and pathological changes.To evaluate the anti-inflammatory effects of CGD,the levels of cytokines were measured,and the Th17/Treg ratio was analyzed to evaluate the immunomodulatory effects of CGD.Results:The study results show that CGD enhanced the rates of sucrose preference and raised the contents of neurotransmitters dopamine(DA)and norepinephrine(NE).CGD treatment led to a reduction in lung index and the relative expression of the M gene,along with improvements in pathological changes caused by IAV.Furthermore,the levels of cytokines were decreased after treatment with CGD,and the imbalance in the ratio of Th17/Treg was corrected via a reduction in the number of Th17 cells after treatment.Conclusions:CGD has a therapeutic effect in mice with depression-like symptoms infected with IAV,increasing the levels of DA and NE,downregulating M gene expression,calming the cytokine storm,and preserving the homeostasis of Th17/Treg cells.
基金supported by the National Natural Science Foundation of China Key Project(81830110)。
文摘Liver disease(LD)is a global health problem caused by multiple factors.At present,there are still obvious problems with limited efficacy and strong side effects of drugs used in the clinical treatment of LD.Therefore,it is of great significance to search for effective hepatoprotective drugs from natural products.Geniposide(GS)is a cyclic ether terpenoid compound and a key component in the traditional Chinese medicine Gardenia jasminoides.It has a significant inhibitory effect on LD.However,there is currently no literature systematically analyzing its mechanism of action.To adapt to the environment of new drug research and the need for precision medication,this article summarizes the pathways and possible mechanisms of action discovered by GS in the treatment of LD,based on recent research literature:regulating bile stasis,antioxidant and anti-apoptosis,improving amino acid metabolism,improving energy metabolism,regulating lipid metabolism,anti-inflammatory and analgesic effects,etc.It also summarizes the pharmacokinetics of GS in vivo and discusses the liver toxicity of GS that is positively correlated with dosage.In addition,the existing problems in current research and possible future development directions were also discussed,to lay the foundation for the clinical development of natural product GS.
基金supported by the National Key R&D Program of China(2022YFC3500405,2019YFC1712105)The National Science Foundation of China(82374075)+1 种基金The National Comprehensive Traditional Chinese Medicine Reform Demonstration Zone Science and Technology Collaborative Development Project(GZY-KJS-SD-2024-046)Taishan Scholar Youth Project of Shandong Province(tsqn202306188).
文摘Objective:Arrhythmia-induced cardiomyopathy(AIC)is a reversible dilated cardiomyopathy induced by rapid or irregular heartbeat.Acupuncture has a long history of use in the treatment of cardiac diseases,and Xinshu(BL15)is a key acupoint.However,the underlying mechanism of acupuncture at BL15 in the treatment of AIC has not yet been elucidated.Methods:AIC was induced in adult male Sprague-Dawley(SD)rats by continuous administration of acetylcholine(ACh)-CaCl2 and treatment with electroacupuncture(EA)at bilateral BL15.Echocardiography was used to evaluate cardiac function;the rotarod test for motor coordination and performance;hematoxylin and eosin(HE)staining for the morphology of ventricles;electrocardiogram for susceptibility,inducibility,and duration of atrial fibrillation(AF);and electrical and optical mapping in isolated rat hearts maintained by the Langendorff perfusion system for electrical conduction and intracellular handling,respectively.Reverse transcription quantitative polymerase chain reaction(RT-qPCR)and Western blotting were used to determine the levels of cardiac conduction and intracellular calcium-handling proteins in the ventricle.Results:The results showed that EA improved the ejection factor and morphological indices on echocardiography,restored motor coordination and performance,and alleviated ventricular dilation and AF onset.EA alleviates atrial conduction disorders,shortens APD80,and decreases calcium handling in rats with AIC.Cx43 was downregulated and CaMKII was upregulated,and both effects were reversed by EA treatment.Conclusion:Our study provides a novel AIC model with abnormal electrical propagation and calcium handling that can be protected by EA at BL15.This potential mechanism may be associated with the modulation of Cx43 and CaMKII expression.
基金supported by National Nature Science Foundation of China(Grant Nos.:82320108022,82322076,and 822104466)Shanghai Rising-Star Program,China(Grant No.:20QA1409300)+1 种基金the National Funding Program for Postdoctoral Researchers,China(C gradeProgram No.:GZC20231707).
文摘Colorectal inflammatory cancer transformation poses a major risk to patients with colitis.Patients with chronic intestinal inflammation have an approximately 2–3 fold increased risk of developing colorectal cancer(CRC).Unfortunately,there is currently no effective intervention available.Huangqin decoction(HQD),a well-known traditional Chinese medicine(TCM)formula,is frequently clinically prescribed for treating patients with colitis,and its active ingredients have effective antitumour efficacy.Nonetheless,the mechanism of HQD-mediated prevention of colorectal inflammatory cancer transformation remains unclear.A strategy integrating metagenomic,lipidomic,and messenger RNA(mRNA)sequencing analysis was used to investigate the regulatory effects of HQD on the gut microbiome,metabolism and potential mechanisms involved in colorectal inflammatory cancer transformation.Our study revealed that HQD suppressed colorectal inflammatory cancer transformation,which was associated with enhanced intestinal barrier function,decreased the inflammatory response,and regulation of the gut microbiome.Notably,cohousing experiments revealed that the transfer of the gut microbiome from HQD-treated mice largely inhibited the pathological transformation of colitis.Moreover,gut microbiome transfer from HQD-treated mice primarily resulted in the altered regulation of fatty acid metabolism,especially the remodeling of arachidonic acid metabolism,which was associated with the amelioration of pathological transformation.Arachidonic acid metabolism and the key metabolic enzyme arachidonic acid 12-lipoxygenase(ALOX12)were affected by HQD treatment,and no obvious protective effect of HQD was observed in Alox12−/−mice,which revealed that ALOX12 was a critical mediator of HQD protection against colorectal inflammatory cancer transformation.In summary,multiple omics analyses were applied to produce valuable data and theoretical support for the application of HQD as a promising intervention for the transformation of inflammatory CRC.
基金supported by the National Key Research and Development Program of China(2021YFF0703600)。
文摘Highlights The RT-RAA-VF assay developed for the NiV P gene can perform rapid detection of NiV within 20 min at 42℃ with high specificity.This assay is capable of attaining sensitivity to a single copy of NiV RNA transcripts.This assay effectively avoids false positives caused by aerosol contamination with a sealed disposable nucleic acid visualization test paper device.
基金National Natural Science Foundation of China,Grant/Award Number:82204958 and 82305065Natural Science Foundation of Shandong Province,Grant/Award Number:ZR2020ZD17+2 种基金Traditional Chinese Medicine Emotional Disease and Brain Steady State Regulation Innovation Team,Grant/Award Number:2023KJ191Medical and Health Science and Technology Development Plan Project of Shandong Province,Grant/Award Number:202105010467Traditional Chinese Medicine Science and Technology Project of Shandong Province,Grant/Award Number:Q-2022059。
文摘Background:Previously,a chronic social defeat stress(CSDS)model has been widely-adopted for assessing depressive-like behaviors in animals.However,there is still room for improvement in the CSDS model to safeguard study accuracy and the wel-fare of lab rodents.Our study team developed a novel,standardized apparatus to induce CSDS in rodents and assessed the model's practical adaptability.Methods:An innovative CSDS cage apparatus and water bottle was designed.To evaluate the effectiveness of the newly developed tools,a variety of animal models,including the tail suspension test(TST),sucrose preference test,forced swimming test(FST),novelty-suppressed feeding test,female urine sniffing test,and open field test(OFT),were adopted to assess depressive-like behaviors in mice.Fluoxetine treat-ment was also administered to observe the reversal effect,as part of the validation.Results:The CSDS cage apparatus resulted in the manifestation of depressive-like behaviors in the model mice.Significant reductions in sucrose preference and urine sniffing time were observed,while the OFT revealed decreased central zone total distance,residence time,and frequency of entry.Moreover,increased immobility was found in the FST and TST.Fluoxetine treatment was found to successfully reverse the modeling effect.Conclusion:The CSDS cage apparatus was validated for enhanced usability and ad-dressed the previous challenges of water bottle leakage and lab rodent welfare is-sues.The consistent results from multiple behavioral tests also supported real-world application of the apparatus,offering researchers a promising alternative to conven-tional rodent cages.
基金the National Natural Science Foundation of China,No.30973688the National Program of Key Basic Research Project(973Program),No.2006CB504804
文摘Stress studies frequently utilize physical stressors to establish animal models of stress. In the majority of cases, these models are not consistent with human circumstances. The present study simulated a social isolation plus resident intruder stress model in the rat. The rats were subjected to daily social isolation and resident intruder stress for 2 weeks. Behaviors were then tested. Rats subjected to social stress exhibited different aggressive behavior styles; some rats had greater scores on composite aggression behaviors, as well as locomotor and exploratory activity, but lower scores on latency than others. The high-aggressive group exhibited predominantly anger-out, while the low-aggressive group exhibited anger-in. Results suggest that social isolation plus resident intruder may serve as an appropriate model for anger-in and anger-out emotion modeling in the rat.
基金Supported by the National Natural Science Foundation of China(No.20100714200121000071220002+2 种基金20100721200202010072220008 and 20180072020005)the Classical Prescription Basic Research Team of Beijing University of Chinese Medicine。
文摘OBJECTIVE: To elucidate the mechanisms underlying the treatment of Alzheimer’s disease(AD) with Traditional Chinese Medicine(TCM), by examining the active components, potential targets and synthetic pathways of Bulao Elixir(BLE).METHODS: The Absorption, Distribution, Metabolism, Excretion(ADME)/Toxicology(T) calculation was used to screen the active components of Bulao Elixir. Based on the TCM Systems Pharmacology Analysis Platform(TCMSP database) and a text mining tool(GoPubMed database), we predicted and screened the active components of Bulao Elixir and its therapeutic targets for AD. Using the Database for Annotation, Visualization and Integrated Discovery(DAVID), we obtained the targets for AD. Cytoscape software was used to establish a network map of the active component-target and target-pathway of Bulao Elixir. Gene function, related biological processes and signaling pathways were analyzed using the DAVID database.RESULTS: Twelve active components were selected from 196 components of Bulao Elixir. Among 2209 targets, 102 effective targets were selected, and 30 important targets were identified via matching with the disease targets. After further analysis, 14 core targets were identified. Enrichment analysis revealed that most of these important targets were involved in multiple biological processes, including apoptosis, inflammatory reactions, and cell regulation cycles. The synthetic pathways for AD treatment were identified after analyzing and confirming the relevant pathways, providing potentially useful information for diagnosis and treatment methods for AD.CONCLUSION: The current study elucidated the potential treatment mechanisms of Bulao Elixir in AD using network pharmacology, providing a foundation for further clarification of its treatment targets.
基金Supported by the General Program of the National Natural Science Foundation of China(No.81774122):Exploring the Role of Psychological Stress in the Pathogenesis of NASH and the Intervention Mechanism of Sini Powder from the"NLRP3/IL-1β"Signaling Pathway and the Young and Middle-aged Teachers Project of Beijing University of Chinese Medicine(No.2017-JYB-JS-002)Psychological Stress Induced by GC/NLRP3 Pathway in Molecular Mechanism of Non-Alcoholic Fatty Liver Disease and Treatment Mechanism of Chaihu Jiangzhi Decoction。
文摘OBJECTIVE: To evaluate the effectiveness of Sini powder for the treatment of non-alcoholic fatty liver disease(NAFLD) in rats and the molecular mechanisms involved.METHODS: A rat model of stress-induced NAFLD was established by a combination of long-term tethering and feeding of a high-fat, high-calorie diet. These rats were then intragastrically administered with either simvastatin, Sini powder, or vehicle for 1 week. The body mass and field test scores for each group were recorded weekly. Serum aspartate aminotransferase and alanine aminotransferase activities, and triglyceride, total cholesterol,and free fatty acid concentrations were measured.Liver tissue histopathology was examined on hematoxylin and eosin-stained paraffin sections and oil red O-stained frozen sections. The hepatic m RNA expression of nuclear factor kappa-B(NF-κB),NOD-, LRR-, and pyrin domain-containing protein 3(NLRP3), apoptosis-associated speck-like protein containing CARD(ASC), and caspase-1 were measured by reverse transcription-polymerase chain reaction(RT-PCR). The hepatic protein concentrations of NF-κB and NLRP3, ASC, caspase-1, interleukin-1β(IL-1β), interleukin-6(IL-6), and the serum concentrations of IL-1β and IL-6 were measured by enzyme-linked immunosorbent assay.RESULTS: Compared with the Blank group, rats in the Compound model group showed significant pathologic manifestations of NAFLD, and the expression of NF-κB, NLRP3, ASC, caspase-1, IL-1βand IL-6 were significantly higher(all P < 0.01). Both simvastatin and Sini powder significantly ameliorated the NAFLD pathology and the abnormal expression of NF-κB, NLRP3, ASC, caspase-1, IL-1β, and IL-6(all P < 0.01).CONCLUSION: Sini powder inhibits the inflamma-tory response in rats with NAFLD, which is mediated by NF-κB/NLRP3, IL-1β, and IL-6, reduces the effects of psychological stress, and improves lipid metabolism. Therefore, Sini powder may be effective for the treatment of stress-related NAFLD through multiple mechanisms.
基金supported by the National Natural Science Foundation of China(No.81903947)the Key Research and Development Project of Shandong Province(No.2019GSF108209),China.
文摘The syndrome of dampness stagnancy due to spleen deficiency(DSSD)is relatively common globally.Although the pathogenesis of DSSD remains unclear,evidence has suggested that the gut microbiota might play a significant role.Radix Astragali,used as both medicine and food,exerts the effects of tonifying spleen and qi.Astragalus polysaccharide(APS)comprises a macromolecule substance extracted from the dried root of Radix Astragali,which has many pharmacological functions.However,whether APS mitigates the immune disorders underlying the DSSD syndrome via regulating gut microbiota and the relevant mechanism remains unknown.Here,we used DSSD rats induced by high-fat and low-protein(HFLP)diet plus exhaustive swimming,and found that APS of moderate molecular weight increased the body weight gain and immune organ indexes,decreased the levels of interleukin-1β(IL-1β),IL-6,and endotoxin,and suppressed the Toll-like receptor 4/nuclear factor-κB(TLR4/NF-κB)pathway.Moreover,a total of 27 critical genera were significantly enriched according to the linear discriminant analysis effect size(LEfSe).APS increased the diversity of the gut microbiota and changed its composition,such as reducing the relative abundance of Pseudoflavonifractor and Paraprevotella,and increasing that of Parasutterella,Parabacteroides,Clostridium XIVb,Oscillibacter,Butyricicoccus,and Dorea.APS also elevated the contents of short-chain fatty acids(SCFAs).Furthermore,the correlation analysis indicated that 12 critical bacteria were related to the body weight gain and immune organ indexes.In general,our study demonstrated that APS ameliorated the immune disorders in DSSD rats via modulating their gut microbiota,especially for some bacteria involving immune and inflammatory response and SCFA production,as well as the TLR4/NF-κB pathway.This study provides an insight into the function of APS as a unique potential prebiotic through exerting systemic activities in treating DSSD.
基金Supported by a grant from the National Natural Science Foundation of China(Study on Qingkailing’s Intervention Mechanism on"No Reflow"Phenomenon after Cerebral Infarction and Pericyte"Rho A/ROCK"Pathway,No.81973789)。
文摘OBJECTIVE:To investigate the targets and mechanisms of action of Qingkailing injection(清开灵注射液,QKL)in the treatment of cholestatic hepatitis.METHODS:A network pharmacology method was implemented using drug and disease databases to target QKL and cholestasis hepatitis,respectively.The functional protein association network STRING database was used to construct a protein-protein interaction network using R language and the Bioconductor toolkit.The org.Hs.eg.db and cluster Profiler packages were used for gene ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis,which explored biological functions and pathways of potential targets.Targets were then visualized using Cytoscape 3.6.0 software.RESULTS:We screened 121 compounds in QKL and identified 112 targets for the treatment of cholestatic hepatitis.QKL played a role in the treatment of cholestatic hepatitis through 305 biology process terms,15 cellular component and 29 molecular function terms.The mechanism of QKL action was mainly related to tumor necrosis factor,mitogen-activated protein kinase,and PI3 K-Akt signaling pathways.CONCLUSION:The treatment of cholestatic hepatitis by QKL involved multiple targets,biological functions,and signaling pathways that are closely associated with the disease.
基金supported by the National Natural Science Foundation of China (No. 81573810,81270053,81530101)China Postdoctoral Science Foundation (No. 2015T80445)National Science&Technology Major Project “Key New Drug Creation and Manufacturing Program” of China (No. 2019ZX09201001)。
文摘Objective: MicroRNAs(miRNAs) may be viable targets for treating renal interstitial fibrosis(RIF). Fuzheng Huayu recipe(FZHY), a traditional Chinese compound herbal medicine, is often used in China to treat fibrosis. This study sought to assess the mechanisms through which FZHY influences miRNAs to treat RIF.Methods: RIF was induced in rats by mercury chloride and treated with FZHY. Hydroxyproline content,Masson’s staining and type I collagen expression were used to evaluate renal collagen deposition.Renal miRNA profiles were evaluated using a miRNA microarray. Those miRNAs that were differentially expressed following FZHY treatment were identified and subjected to bioinformatic analyses. The miR-21 target gene phosphatase and tensin homolog(PTEN) expression and AKT phosphorylation in kidney tissues were assessed via Western blotting. In addition, HK-2 human proximal tubule epithelial cells were treated using angiotensin II(Ang-II) to induce epithelial-to-mesenchymal transition(EMT), followed by FZHY exposure. miR-21 and PTEN expressions were evaluated via quantitative reverse transcriptionpolymerase chain reaction(qRT-PCR), while E-cadherin and a-smooth muscle actin(a-SMA) expressions were assessed by immunofluorescent staining and qRT-PCR. Western blotting was used to assess PTEN and AKT phosphorylation.Results: FZHY significantly decreased kidney collagen deposition, hydroxyproline content and type I collagen level. The miRNA microarray identified 20 miRNAs that were differentially expressed in response to FZHY treatment. Subsequent bioinformatic analyses found that miR-21 was the key fibrosis-related miRNA regulated by FZHY. FZHY also decreased PTEN expression and AKT phosphorylation in fibrotic kidneys. Results from in vitro tests also suggested that FZHY promoted E-cadherin upregulation and inhibited a-SMA expression in Ang-II-treated HK-2 cells, effectively reversing Ang-II-mediated EMT. We also determined that FZHY reduced miR-21 expression, increased PTEN expression and decreased AKT phosphorylation in these cells.Conclusion: miR-21 is the key fibrosis-related miRNA regulated by FZHY. The ability of FZHY to modulate miR-21/PTEN/AKT signaling may be a viable approach for treating RIF.
基金Supported by the Youth Project of National Social Science Fund of China:14CKG008the Project of Chengdu Science and Technology:2014-RK00-00078-ZFthe Project of Sichuan Provincial Administration of Traditional Chinese Medicine:2014K091。
文摘In 2012,a lacquer figure was unearthed from the Han dynasty tomb(188 BC-87 BC) at Chengdu Laoguanshan.The lines intaglioed on the Laoguan mountain lacquer figure were similar to the meridians.Objective:To investigate the relationship between the lines on this Laoguanshan lacquer figure and the regular meridians so as to explore the development of meridian system in ancient China.Methods:Based on collecting the photos of the Laoguan mountain lacquer figure and the representative acupuncture classics,the double evidence method(combining the unearthed relics/literature and extant literature) was performed to investigate the relationship between the lines on this Laoguanshan lacquer figure and the regular meridians.Furthermore,the development of regular meridians theory was analyzed from the number,distribution,direction and branches.Results:The routes of the 28 longitudinal white lines on the Laoguan mountain lacquer figure are similar to the regular meridians in the ancient literature including Huángdì Nèijīng 《黄帝内经》 Yellow Emperor’s Inner Classic).The number,distribution and branches of the meridians intaglioed on the Laoguanshan lacquer figure suggested the evolution of the regular-meridian system from the eleven-meridian system to the twelve-meridian system.Conclusions:The meridian system of Laoguanshan lacquer figure was a link connecting the preceding and the following.The Laoguanshan lacquer figure played an important role in the development of the early meridian theory.
