Background:Diabetic retinopathy(DR)is currently the leading cause of blindness in elderly individuals with diabetes.Traditional Chinese medicine(TCM)prescriptions have shown remarkable effectiveness for treating DR.Th...Background:Diabetic retinopathy(DR)is currently the leading cause of blindness in elderly individuals with diabetes.Traditional Chinese medicine(TCM)prescriptions have shown remarkable effectiveness for treating DR.This study aimed to screen a novel TCM prescription against DR from patents and elucidate its medication rule and molecular mechanism using data mining,network pharmacology,molecular docking and molecular dynamics(MD)simulation.Method:TCM prescriptions for treating DR was collected from patents and a novel TCM prescription was identified using data mining.Subsequently,the mechanism of the novel TCM prescription against DR was explored by constructing a network of core TCMs-core active ingredients-core targets-core pathways.Finally,molecular docking and MD simulation were employed to validate the findings from network pharmacology.Result:The TCMs of the collected prescriptions primarily possessed bitter and cold properties with heat-clearing and supplementing effects,attributed to the liver,lung and kidney channels.Notably,a novel TCM prescription for treating DR was identified,composed of Lycii Fructus,Chrysanthemi Flos,Astragali Radix and Angelicae Sinensis Radix.Twenty core active ingredients and ten core targets of the novel TCM prescription for treating DR were screened.Moreover,the novel TCM prescription played a crucial role for treating DR by inhibiting inflammatory response,oxidative stress,retinal pigment epithelium cell apoptosis and retinal neovascularization through various pathways,such as the AGE-RAGE signaling pathway in diabetic complications and the MAPK signaling pathway.Finally,molecular docking and MD simulation demonstrated that almost all core active ingredients exhibited satisfactory binding energies to core targets.Conclusions:This study identified a novel TCM prescription and unveiled its multi-component,multi-target and multi-pathway characteristics for treating DR.These findings provide a scientific basis and novel insights into the development of drugs for DR prevention and treatment.展开更多
Objective:To examine the effect of icariin plus curcumol on prostate cancer cells PC3 and elucidate the underlying mechanisms.Methods:We employed the Cell Counting Kit 8 assay and colony formation assay to assess cell...Objective:To examine the effect of icariin plus curcumol on prostate cancer cells PC3 and elucidate the underlying mechanisms.Methods:We employed the Cell Counting Kit 8 assay and colony formation assay to assess cell viability and proliferation.Autophagy expression was analyzed using monodansylcadaverine staining.Immunofluorescence and Western blot analyses were used to evaluate protein expressions related to autophagy,pyroptosis,and the mTOR pathway.Cellular damage was examined using the lactate dehydrogenase assay.Moreover,cathepsin B and NLRP3 were detected by co-immunoprecipitation.Results:Icariin plus curcumol led to a decrease in PC3 cell proliferation and an enhancement of autophagy.The levels of LC3-Ⅱ/LC3-Ⅰand beclin-1 were increased,while the levels of p62 and mTOR were decreased after treatment with icariin plus curcumol.These changes were reversed upon overexpression of mTOR.Furthermore,3-methyladenine resulted in a decrease in inflammatory cytokines,pyroptosis-related protein levels,and lactate dehydrogenase concentration,compared to the icariin plus curcumol group.Inhibiting cathepsin B reversed the regulatory effects of icariin plus curcumol.Conclusions:Icariin plus curcumol demonstrates great potential as a therapeutic agent for castration-resistant prostate cancer by enhancing autophagy via the mTOR pathway and promoting pyroptosis mediated by cathepsin B.These findings provide valuable insights into the molecular mechanisms underlying the therapeutic potential of icariin and curcumol for prostate cancer treatment.展开更多
Background:Xuefu Zhuyu decoction(XFZY)could significantly improve the function of hypertensive vascular endothelial cells,but the targets and mechanism are not clear.This study is to analyze the pharmacological substa...Background:Xuefu Zhuyu decoction(XFZY)could significantly improve the function of hypertensive vascular endothelial cells,but the targets and mechanism are not clear.This study is to analyze the pharmacological substances and targets of Xuefu Zhuyu decoction in hypertensive vascular endothelial cells.Methods:This study used Xuefu Zhuyu decoction to intervene human umbilical vein endothelial cells incubated by hypertensive patients’serum,then detected the function of vascular endothelial cells.The aqueous extract of XFZY was analyzed and validated by liquid chromatography-mass spectrometry technology;Finally,macromolecular docking technology was used to analyze the potential active substances and targets of XFZY in the prevention and treatment of hypertension.Results:Compared with the model group,the XFZY group showed a significant increase in NO expression(P<0.01)and a significant decrease in ET-1 expression(P<0.001);and the expression of BIP,P-JNK,CHOP,and BAX in XFZY group cells was significantly decreased(P<0.001),while the expression of JNK and BCL2 was significantly increased(P<0.001).19 main compounds were identified in XFZY and there were 3 pairs of molecular complexes with high affinity for markers of the endoplasmic reticulum stress,including BIP-Hesperidin complex,BIP-HSYA complex and JNK-Naringin complex.Conclusion:This study analyzed the potential pharmacodynamic substance and targets of Xuefu Zhuyu decoction in improving the function of hypertensive vascular endothelial cells,which could provide a scientific basis for the future molecular mechanism of XFZY in treating hypertension.展开更多
Because of the continuous improvement of the quality of life,the population of gout patients is also increasing,which seriously affects the quality of life of patients.Traditional Chinese medicine compound has a long ...Because of the continuous improvement of the quality of life,the population of gout patients is also increasing,which seriously affects the quality of life of patients.Traditional Chinese medicine compound has a long history and remarkable clinical effect in treating gout patients,and has been widely used.Intestinal flora and its metabolites are the focus of current research,which can promote intestinal mucosal barrier,improve immunity and improve metabolism.The regulation of intestinal flora can reduce serum uric acid and inhibit inflammation to fight gouty arthritis.Moreover,the mechanism of intestinal flora is related to the spleen in Chinese medicine theory.Therefore,this study discusses the research mechanism and clinical application of traditional Chinese medicine compound in treating gout by regulating intestinal flora,and provides theoretical basis for the clinical application of traditional Chinese medicine and the expansion of new dosage forms.展开更多
Objective To analyze the intellectual structure,hotspots and trends of traditional Chinese medicine(TCM)in immune regulation research.Methods The data were extracted from the Web of Science Core Collection(WoSCC)and t...Objective To analyze the intellectual structure,hotspots and trends of traditional Chinese medicine(TCM)in immune regulation research.Methods The data were extracted from the Web of Science Core Collection(WoSCC)and the China National Knowledge Infrastructure(CNKI)and verified by two experienced TCM researchers.The time of literature retrieval is up to 2020.CiteSpace 5.7.R1 and Microsoft Excel 2016 were used for the statistical analysis and bibliometric diagrams,including the co-occurrence network of authors,institutions,countries,keywords,references,dual-map overlays of journals and citation bursts,etc.Results A total of 12270 publications related to TCM in immune regulation were included.The annual number of publications has increased in this field.There was close cooperation of countries and institutions,while the distribution of scholars was scattered.China was the core of the cooperation network.The dual-map overlays analysis of journals showed that core and marginal fields had increased.The keywords and references analysis showed that network pharmacology,metabolism and cancer were the most high-frequency keywords with high-intensity bursts.Conclusion TCM in immune regulation has attracted wider attention,with multi-country,multi-field,multi-disciplinary and multi-level research developing toward informatization.Network pharmacology,metabolism and cancer may be the focus of future research in this field.展开更多
Background:Huang-Pu-Tong-Qiao formula(HPTQ),a traditional Chinese herbal formula,has a variety of pharmacological effects.It has been used to treat Alzheimer’s disease(AD)for decades.This study aimed to screen differ...Background:Huang-Pu-Tong-Qiao formula(HPTQ),a traditional Chinese herbal formula,has a variety of pharmacological effects.It has been used to treat Alzheimer’s disease(AD)for decades.This study aimed to screen differentially expressed proteins in the hippocampus of AD model rats treated with HPTQ.Proteomic studies of the effects of HPTQ on AD are key to understanding the therapeutic mechanisms of HPTQ and identifying potential therapeutic targets.Methods:We hence used the isobaric tags for relative and absolute quantification(ITRAQ)approach to investigate the differentially expressed proteins in the hippocampus of AD model rats before and after HPTQ administration and to identify the potential therapeutic target proteins of HPTQ.In this study,the learning and memory abilities of AD rats were examined by the Morris water maze test.After HPTQ administration,the differentially expressed proteins in the hippocampus of AD rats were quantified and analyzed in silico.Furthermore,western blotting was used to verify the expression of related proteins.Results:The Morris water maze results showed that HPTQ could improve the learning and memory ability of AD model rats.The proteomics analysis results showed that 57 proteins were differentially expressed,of which 35 were up-regulated and 22 were down-regulated.Bioinformatics analysis indicated that proteins with altered expression after HPTQ treatment were involved in several biological processes that have the potential to exert neuroprotective effects.These included promoting the translation of ribosomes,improving the deposition of amyloid-beta(Aβ),regulating autophagy,regulating neuronal synaptic function and plasticity,and alleviating oxidative stress.Conclusion:In conclusion,we identified several potential therapeutic target proteins and related mechanistic pathways of HPTQ in the treatment of AD,laying the foundation for further investigation of the therapeutic effects of HPTQ.展开更多
The substantial global health burden of depression encourages the development of innovative and broadly effective interventions.This paper aimed to examine recent advancements by which exercise works as an antidepress...The substantial global health burden of depression encourages the development of innovative and broadly effective interventions.This paper aimed to examine recent advancements by which exercise works as an antidepressant and recommends optimal types and quantity of exercise as supplemental therapies in treating depression.Sedentary behavior and low physical activity significantly influence the onset of depression.Being an effective treatment option,exercise can significantly reduce depression risk.Exercise exerts antidepressant effects as it modulates neurotransmitters,neuroplasticity,the immune system,and hormone levels.Effective exercise forms include yoga,strength training,and walking/jogging.Tailored exercise regimens that consider individual preferences and tolerability can improve outcomes.Regular exercise enhances general well-being and reduces depressive symptoms.Additional research is needed to understand the complex basis of exercise's effects on depression.Exercise is a cost-effective and accessible intervention for depression management that needs additional exploration.Thus,customized exercise programs,as per each patient’s needs,are essential for their successful implementation clinically.展开更多
Background:Ginkgo biloba L.preparations(GBLPs)are a class of Chinese herbal medicine used in the adjuvant treatment of ischemic stroke(IS).Recently,several systematic reviews(SRs)and meta-analyses(MAs)of GBLPs for IS ...Background:Ginkgo biloba L.preparations(GBLPs)are a class of Chinese herbal medicine used in the adjuvant treatment of ischemic stroke(IS).Recently,several systematic reviews(SRs)and meta-analyses(MAs)of GBLPs for IS have been published.Objective:This overview aims to assess the quality of related SRs and MAs.Search strategy:Pub Med,Embase,Cochrane Library,Web of Science,Chinese Biological Medicine,China National Knowledge Infrastructure,Wanfang,and Chinese Science and Technology Journals databases were searched from their inception to December 31,2022.Inclusion criteria:SRs and MAs of randomized controlled trials(RCTs)that explored the efficacy of GBLPs for patients with IS were included.Data extraction and analysis:Two independent reviewers extracted data and assessed the methodological quality,risk of bias(ROB),reporting quality,and credibility of evidence of the included SRs and MAs using A Measurement Tool to Assess Systematic Reviews 2(AMSTAR 2),Risk of Bias in Systematic Reviews(ROBIS),the Preferred Reporting Items for Systematic Reviews and Meta-analyses(PRISMA),and the Grading of Recommendations Assessment,Development and Evaluation(GRADE),respectively.Additionally,descriptive analysis and data synthesis were conducted.Results:Twenty-nine SRs/MAs involving 119 outcomes were included in this review.The overall methodological quality of all SRs/MAs was critically low based on AMSTAR 2,and 28 had a high ROB based on the ROBIS.According to the PRISMA statement,the reporting items of the included SRs/MAs are relatively complete.The results based on GRADE showed that of the 119 outcomes,8 were rated as moderate quality,24 as low quality,and 87 as very low quality.Based on the data synthesis,GBLPs used in conjunction with conventional treatment were superior to conventional treatment alone for decreasing neurological function scores.Conclusion:GBLPs can be considered a beneficial supplemental therapy for IS.However,because of the low quality of the existing evidence,high-quality RCTs and SRs/MAs are warranted to further evaluate the benefits of GBLPs for treating IS.展开更多
The history of medical development shows that oriental medicine, or traditional medicine, was born through medical practice during the times when science and technology were immature and underdeveloped, whereas with t...The history of medical development shows that oriental medicine, or traditional medicine, was born through medical practice during the times when science and technology were immature and underdeveloped, whereas with the development of science and technology, Western medicine, or modern medicine, was born through experimental analysis and research. With the development of medicine, the pros and cons of both medical systems become increasingly evident. How to integrate them and learn from each other will be the direction of future development of medicine. The formation and development of integrated medicine will, inevitably, usher in a new era for medicine.展开更多
The productivity and health of seagrass depend on the combined inputs of nutrients from the water and sediments in which they grow and the microbiota with which they live intimately.However,little is known about the c...The productivity and health of seagrass depend on the combined inputs of nutrients from the water and sediments in which they grow and the microbiota with which they live intimately.However,little is known about the composition and diversity pattern of single-celled benthic eukaryotes in seagrass meadows.Here,we investigated how the structure and diversity of the benthic microeukaryotic community vary with respect to season,location,and seagrass colonization,by applying 18S rRNA gene amplicon sequencing for 96 surface sediment samples that were collected from three different seagrass habitats through four seasons.We found that benthic microeukaryotic communities associated with seagrass Zostera japonica exhibited remarkable spatial and seasonal variations,as well as differences between vegetated and unvegetated sediments.Diatoms and dinoflagellates predominated in the benthic microeukaryotic communities,but they were inversely correlated and displaced each other as the dominant microbial group in different seasons or habitats.Mucoromycota was more prevalent in vegetated sediments,whereas Lobulomycetales and Chytridiales had higher proportions in unvegetated sites.Total organic carbon and total organic nitrogen were the most important environmental factors in driving the microeukaryotic assemblages and diversity.Our study expands the available knowledge on the biogeographic distribution patterns and niche preferences for benthic microeukaryotes in seagrass systems.展开更多
Objective:To explore the protective effect of Linggui Zhugan Decoction(LGZGD)medicated serum on myocardial fibrosis induced by transforming growth factor-β1(TGF-β1).Methods:Using enzyme digestion method,combined wit...Objective:To explore the protective effect of Linggui Zhugan Decoction(LGZGD)medicated serum on myocardial fibrosis induced by transforming growth factor-β1(TGF-β1).Methods:Using enzyme digestion method,combined with differential adherence to isolate and culture Sprague-Dawley(SD)suckling mouse Cardiac fibroblasys(CFB)in vitro.Divided into:blank group,blank rat serum group,model group,and LGZGD medicated serum group(5%、10%、20%).Except for blank group and blank rat serum group,they were stimulated with 5 ng/ml TGF-β1 for 12 hours,and then then intervene with LGZGD medicated serum(5%、10%、20%)and continue to culture for 24 hours.Use immunofluorescence and Western blot(WB)to detect the expression ofα-smooth muscle actin(α-SMA),Enzyme-linked immunosorbent assay(ELISA)and WB to detect type Ⅰ collagen(Collagen Ⅰ),type Ⅰ collagen(Collagen Ⅲ)and fibronectin(FN)expression.Results:Compared with the blank group,the expressions of Collagen Ⅰ,Collagen Ⅲ,α-SMA and FN in the model group were significantly increased(P<0.01);Compared with the model group,the expressions of Collagen Ⅰ and Collagen Ⅲ in each concentration group of the experiment were significantly reduced(P<0.01);the expression ofα-SMA and FN were significantly reduced(P<0.01).Conclusions:LGZGD has an inhibitory effect on collagen synthesis and the expression ofα-SMA and FN,indicating that the anti-fibrosis effect of LGZGD is related to it.展开更多
The placenta plays an important role in nutrient transport to maintain the growth and development of the embryo.Gestational diabetes mellitus(GDM),the most common complication during pregnancy,highly affects placental...The placenta plays an important role in nutrient transport to maintain the growth and development of the embryo.Gestational diabetes mellitus(GDM),the most common complication during pregnancy,highly affects placental function in late gestation.Advanced glycation end-products(AGEs),a complex and heterogeneous group of compounds engaged by the receptor for AGEs(RAGE),are closely associated with diabetes-related complications.In this study,AGEs induced a decrease in the expression of tight junction(TJ)proteins in BeWo cells and increased the paracellular permeability of trophoblast cells by regulating RAGE/NF-κB.Sprague-Dawley(SD)rats injected with 100 mg/kg AGEs-rat serum albumin(RSA)via the tail vein from embryo day 2 were set as the placental barrier dysfunction model group(n=10).The effect of AGEs on placental permeability was determined using the Evans-Blue dye extravasation method.The ultrastructure of the placenta samples was observed by transmission electron microscopy.The effects of AGEs on the placenta were confirmed by treating rats with RAGE antagonist FPS-ZM1 and soluble forms of RAGE(sRAGE).AGEs treatment increased placental permeability and disrupted the tight junctions in pregnant rat placenta,but has no effect on blood glucose.The expression of TJ-related proteins,including ZO-1,Occludin,and Claudin 5,were downregulated after AGEs treatment.Further,AGEs treatment increased the expression of RAGE and nuclear factor-κB in the placenta of rats and upregulated the levels of vascular endothelial growth factor.The effects of AGEs on the placenta were blocked by RAGE antagonist FPS-ZM1 and sRAGE.This study demonstrates the mechanism underlying AGEs-induced disturbance in placental function in pregnant rats and highlights the potential of AGEs in the treatment of GDM.展开更多
Postoperative adhesion(PA)is currently one of the most unpleasant complications following surgical procedures.Researchers have developed several new strategies to alleviate the formation of PA to a great extent,but so...Postoperative adhesion(PA)is currently one of the most unpleasant complications following surgical procedures.Researchers have developed several new strategies to alleviate the formation of PA to a great extent,but so far,no single measure or treatment can meet the expectations and requirements of clinical patients needing complete PA prevention.Chinese medicine(CM)has been widely used for thousands of years based on its remarkable efficacy and indispensable advantages CM treatments are gradually being accepted by modern medicine.Therefore,this review summarizes the formating process of PA and the efficacy and action mechanism of CM treatments,including their pharmacological effects,therapeutic mechanisms and advantages in PA prevention.We aim to improve the understanding of clinicians and researchers on CM prevention in the development of PA and promote the in-depth development and industrialization process of related drugs.展开更多
Background:Oligoasthenospermia is one of the main causes of male infertility.Researchers usually use chemical drugs to directly damage germ cells to prepare oligoasthenospermia models,which disregards the adhesion and...Background:Oligoasthenospermia is one of the main causes of male infertility.Researchers usually use chemical drugs to directly damage germ cells to prepare oligoasthenospermia models,which disregards the adhesion and migration between spermatogenic cells and Sertoli cells.TAp73 is a critical regulator of the adhesin of germ cell;thus,we sought to explore a novel oligoasthenospermia model based on TAp73 gene suppression.Methods:Mice in the Pifithrin-αgroup were injected intraperitoneally with 2.5 mg/kg Pifithrin-α(TAp73 inhibitor)daily for 30 consecutive days.Reproductive hormone levels and epididymal sperm quality,as well as the network morphology of Sertoli cells were tested.Results:Sperm density,motility,and the relative protein and mRNA expression of TAp73 and Nectin 2 were obviously decreased in the Pifithrin-αgroup compared with the normal control group.No significant distinction was observed in the relative mRNA and protein expression of ZO-1.Furthermore,the tight junctions(TJs)and api-cal ectoplasmic specialization(ES)were destroyed in the Pifithrin-αgroup.Conclusion:The above results indicate that we successfully established a new oli-goasthenospermia mouse model.This study provides a foundation for further explo-ration of the roles of TAp73 genes during spermatogenesis and provides new research objects for further oligospermia research and future drug discovery.展开更多
The aim of this study was to investigate the effect of hypoxia on the sodium current of rat cardiomyocytes in order to explore ion channel mechanism of cardiomyocyte hypoxia.The rat cardiomyocytes were isolated by acu...The aim of this study was to investigate the effect of hypoxia on the sodium current of rat cardiomyocytes in order to explore ion channel mechanism of cardiomyocyte hypoxia.The rat cardiomyocytes were isolated by acute enzymatic hydrolysis.A group of untreated cells were used to record sodium currents using whole-cell patch-clamp technique,another group was subjected to hypoxia and record sodium currents using same technique.The results showed that the morphological trajectory of sodium hypoxia was not changed compared with that of normal cells.The I-V curve of hypoxic cells was significantly higher than that of normal cells,and the peak current of INa was 15.68%higher than that of normal cells(P<0.0001).Activation potential of normal and hypoxia cells was about-40mV,the maximum peak current corresponds to the stimulation voltage of-25mV.The above results suggest that rat cardiomyocytes sodium current increases in the case of hypoxia.展开更多
Heidan disease(black jaundice)is a kind of jaundice,which is caused by lingering and chronic jaundice,often with blood stasis and damp-heat,etc.The clinical symptoms of Heidan disease(black jaundice)are similar to tho...Heidan disease(black jaundice)is a kind of jaundice,which is caused by lingering and chronic jaundice,often with blood stasis and damp-heat,etc.The clinical symptoms of Heidan disease(black jaundice)are similar to those of cirrhosis caused by multiple chronic liver diseases in Western medicine.Heidan disease(black jaundice)generally belongs to yin jaundice type,and the pathogenesis is mostly related to blood stasis and dampness stagnation,often with damp-heat residue.According to Zhongjing Zhang,the prescription Xiaoshi Fanshi powder for the treatment of Heidan disease(black jaundice)is based on the understanding that the nature of Heidan disease(black jaundice)is inseparable from the two key pathological factors of dampness and blood stasis.The treatment of jaundice should be based on removing blood stasis and dampness,supplemented by soothing the liver and promoting the transportation function of spleen,removing blood stasis and harmonizing the collaterals,and promoting diuresis and reducing jaundice.In the treatment of jaundice,removing blood stasis and purging turbidity should be stressed,and powerful tonification should be used with caution.Since blood stasis and turbidity are always intermingling and often complicated with damp heat,the method of warm drying should be used with caution.For promoting blood circulation,removing blood stasis,and dredging the liver-biliarycollaterals,drasticmedicine shouldbeused withcaution.展开更多
The enhanced permeability retention(EPR)effect based nanomedicine has been widely used for tumor targeting during the past decades.Here we unexpectedly observed the similar"EPR effect"at the site of iniury.W...The enhanced permeability retention(EPR)effect based nanomedicine has been widely used for tumor targeting during the past decades.Here we unexpectedly observed the similar"EPR effect"at the site of iniury.We found that the temporary dilated and leaky blood vessels caused by the potent vasodilator histamine in response to injury allowed the injected nanoparticles to pass through the vasculature and reached the injured tissue.Our finding shows the potential underline mechanism of"EPR effect"at the injured site.By loading with antibiotics,we further demonstrated a new strategy for prevention of infection at the site of injury.展开更多
Polo-like kinase 1(PLK1)plays a crucial role in cell mitosis and has been associated with necroptosis.However,the role of PLK1 and necroptosis in lung adenocarcinoma(LA)remains unclear.In this study,we analyzed The Ca...Polo-like kinase 1(PLK1)plays a crucial role in cell mitosis and has been associated with necroptosis.However,the role of PLK1 and necroptosis in lung adenocarcinoma(LA)remains unclear.In this study,we analyzed The Cancer Genome Atlas(TCGA)and Genotype-Tissue Expression databases to evaluate the prognostic value and mechanistic role of PLK1 in LA.PLK1 was found to be highly expressed in LA and was positively associated with advanced disease staging and poor survival outcomes.Functional enrichment analysis showed that PLK1 was involved in cell mitosis,neurotransmitter transmission,and drug metabolism.Further analysis using single-sample gene set enrichment analysis and ESTIMATE algorithm revealed a correlation between PLK1 expression and immune infiltration in LA.Silencing of PLK1 using miRNA transfection in LA cells reduced cell proliferation and increased apoptosis,as well as upregulating the expression of necroptosis-related proteins,such as RIPK1,RIPK3,and MLKL.Additionally,nude mouse transplantation tumor experiments demonstrated that silencing PLK1 reduced the growth capacity of LA cells.These findings suggest that PLK1 plays a critical role in LA progression by regulating necroptosis and immune infiltration,and may serve as a potential therapeutic target for immunotherapy.Furthermore,PLK1 expression can be used as a prognostic biomarker for LA patients.展开更多
Objective:To investigate the effect of Huangqin Decoction(HQD)on nuclear factor erythroid 2 related-factor 2(Nrf2)/heme oxygenase(HO-1)signaling pathway by inducing the colitis-associated carcinogenesis(CAC)model mice...Objective:To investigate the effect of Huangqin Decoction(HQD)on nuclear factor erythroid 2 related-factor 2(Nrf2)/heme oxygenase(HO-1)signaling pathway by inducing the colitis-associated carcinogenesis(CAC)model mice with azoxymethane(AOM)/dextran sodium sulfate(DSS).Methods:The chemical components of HQD were analyzed by liquid chromatography-quadrupole-time-of-flight mass spectrometry(LC-Q-TOF-MS/MS)to determine the molecular constituents of HQD.Totally 48 C57BL/6J mice were randomly divided into 6 groups by a random number table,including control,model(AOM/DSS),mesalazine(MS),low-,medium-,and high-dose HQD(HQD-L,HQD-M,and HQD-H)groups,8 mice in each group.Except for the control group,the mice in the other groups were intraperitoneally injected with AOM(10 mg/kg)and administrated with 2.5%DSS orally for 1 week every two weeks(totally 3 rounds of DSS)to construct a colitis-associated carcinogenesis mouse model.The mice in the HQD-L,HQD-M and HQD-H groups were given HQD by gavage at doses of 2.925,5.85,and 11.7 g/kg,respectively;the mice in the MS group was given a suspension of MS at a dose of 0.043 g/kg(totally 11 weeks).The serum levels of malondialdehyde(MDA)and superoxide dismutase(SOD)were measured by enzyme-linked immunosorbent assay.The mRNA and protein expression levels of Nrf2,HO-1,and inhibitory KELCH like ECH-related protein 1(Keap1)in colon tissue were detected by quantitative real-time PCR,immunohistochemistry,and Westem blot,respectively.Results:LC-Q-TOF-MS/MS analysis revealed that the chemical constituents of HQD include baicalin,paeoniflorin,and glycyrrhizic acid.Compared to the control group,significantly higher MDA levels and lower SOD levels were observed in the model group(P<0.05),whereas the expressions of Nrf2 and HO-1 were significantly decreased,and the expression of Keap1 increased(P<0.01).Compared with the model group,serum MDA level was decreased and SOD level was increased in the HQD-M,HQD-H and MS groups(P<0.05).Higher expressions of Nrf2 and HO-1 were observed in the HQD groups.Conclusion:HQD may regulate the expression of Nrf2 and HO-1 in colon tissue,reduce the expression of MDA and increase the expression of SOD in serum,thus delaying the progress of CAC in AOM/DSS mice.展开更多
Acute postoperative pain is commonly treated with flurbiprofen(FBP),but conventional delivery methods are suboptimal.This study prepared a new non-burst release microneedles(MNs)using genipin cross-linked gelatin(cGel...Acute postoperative pain is commonly treated with flurbiprofen(FBP),but conventional delivery methods are suboptimal.This study prepared a new non-burst release microneedles(MNs)using genipin cross-linked gelatin(cGel).By adding varying amounts of genipin to modulate the crosslinking degree of cGel,the drug release behavior of the drug-loaded MNs in the skin can be altered.The crosslinking parameters that meet therapeutic requirements are selected,thus providing rapid and longlasting analgesic effects.cGel solutions were successfully cross-linked,altering matrix material microstructure,confirmed by scanning electron microscope imaging and fourier transform infrared spectroscopy.MNs demonstrated increasing mechanical strength with higher crosslinking.Drug release rates were rapid initially,then slowed,exhibiting a characteristic of decreased release rates with increasing degrees of crosslinking.In vivo,FBP/cGel MNs significantly reduced allodynia and hyperalgesia post-surgery,with the greatest effect observed at 2–3 h post-surgery,and can maintain analgesia for up to 6 h.Biosafety tests confirmed good biocompatibility.FBP/cGel MNs effectively penetrate the stratum corneum,safely delivering drugs with significant analgesic effects,excellent mechanical properties,and good biocompatibility,representing a promising strategy for managing acute postoperative pain.展开更多
基金supported by the National Natural Science Foundation of China(Grant No.82104701)Science Fund Program for Outstanding Young Scholars in Universities of Anhui Province(Grant No.2022AH030064)+3 种基金Key Project at Central Government Level:the Ability Establishment of Sustainable Use for Valuable Chinese Medicine Resources(Grant No.2060302)Foundation of Anhui Province Key Laboratory of Pharmaceutical Preparation Technology and Application(Grant No.2021KFKT10)China Agriculture Research System of MOF and MARA(Grant No.CARS-21)Talent Support Program of Anhui University of Chinese Medicine(Grant No.2020rcyb007).
文摘Background:Diabetic retinopathy(DR)is currently the leading cause of blindness in elderly individuals with diabetes.Traditional Chinese medicine(TCM)prescriptions have shown remarkable effectiveness for treating DR.This study aimed to screen a novel TCM prescription against DR from patents and elucidate its medication rule and molecular mechanism using data mining,network pharmacology,molecular docking and molecular dynamics(MD)simulation.Method:TCM prescriptions for treating DR was collected from patents and a novel TCM prescription was identified using data mining.Subsequently,the mechanism of the novel TCM prescription against DR was explored by constructing a network of core TCMs-core active ingredients-core targets-core pathways.Finally,molecular docking and MD simulation were employed to validate the findings from network pharmacology.Result:The TCMs of the collected prescriptions primarily possessed bitter and cold properties with heat-clearing and supplementing effects,attributed to the liver,lung and kidney channels.Notably,a novel TCM prescription for treating DR was identified,composed of Lycii Fructus,Chrysanthemi Flos,Astragali Radix and Angelicae Sinensis Radix.Twenty core active ingredients and ten core targets of the novel TCM prescription for treating DR were screened.Moreover,the novel TCM prescription played a crucial role for treating DR by inhibiting inflammatory response,oxidative stress,retinal pigment epithelium cell apoptosis and retinal neovascularization through various pathways,such as the AGE-RAGE signaling pathway in diabetic complications and the MAPK signaling pathway.Finally,molecular docking and MD simulation demonstrated that almost all core active ingredients exhibited satisfactory binding energies to core targets.Conclusions:This study identified a novel TCM prescription and unveiled its multi-component,multi-target and multi-pathway characteristics for treating DR.These findings provide a scientific basis and novel insights into the development of drugs for DR prevention and treatment.
基金supported by Natural Science Foundation of Hunan Province(No.2023JJ40511)Excellent Youth Project of Scientific Research Program of Hunan Education Department(No.22B0370)+2 种基金Project of Traditional Chinese Medicine Administration of Hunan Province(No.B2023034)Science and Technology Development Foundation of Beijing Hospital of Traditional Chinese Medicine Affiliated to Capital Medical University(No.LYYB202214)Hunan Provincial Hygiene and Health Commission Health Research Project(No.W20243165).
文摘Objective:To examine the effect of icariin plus curcumol on prostate cancer cells PC3 and elucidate the underlying mechanisms.Methods:We employed the Cell Counting Kit 8 assay and colony formation assay to assess cell viability and proliferation.Autophagy expression was analyzed using monodansylcadaverine staining.Immunofluorescence and Western blot analyses were used to evaluate protein expressions related to autophagy,pyroptosis,and the mTOR pathway.Cellular damage was examined using the lactate dehydrogenase assay.Moreover,cathepsin B and NLRP3 were detected by co-immunoprecipitation.Results:Icariin plus curcumol led to a decrease in PC3 cell proliferation and an enhancement of autophagy.The levels of LC3-Ⅱ/LC3-Ⅰand beclin-1 were increased,while the levels of p62 and mTOR were decreased after treatment with icariin plus curcumol.These changes were reversed upon overexpression of mTOR.Furthermore,3-methyladenine resulted in a decrease in inflammatory cytokines,pyroptosis-related protein levels,and lactate dehydrogenase concentration,compared to the icariin plus curcumol group.Inhibiting cathepsin B reversed the regulatory effects of icariin plus curcumol.Conclusions:Icariin plus curcumol demonstrates great potential as a therapeutic agent for castration-resistant prostate cancer by enhancing autophagy via the mTOR pathway and promoting pyroptosis mediated by cathepsin B.These findings provide valuable insights into the molecular mechanisms underlying the therapeutic potential of icariin and curcumol for prostate cancer treatment.
基金financially supported by Natural Science Foundation of Shandong Province(No.ZR2023QH037)Medical and Health Science and Technology Development Program of Shandong Province(No.202203010622)+1 种基金GuangDong Basic and Applied Basic Research Foundation(No.2020A1515111005)China Postdoctoral Science Foundation(No.2018M643053).
文摘Background:Xuefu Zhuyu decoction(XFZY)could significantly improve the function of hypertensive vascular endothelial cells,but the targets and mechanism are not clear.This study is to analyze the pharmacological substances and targets of Xuefu Zhuyu decoction in hypertensive vascular endothelial cells.Methods:This study used Xuefu Zhuyu decoction to intervene human umbilical vein endothelial cells incubated by hypertensive patients’serum,then detected the function of vascular endothelial cells.The aqueous extract of XFZY was analyzed and validated by liquid chromatography-mass spectrometry technology;Finally,macromolecular docking technology was used to analyze the potential active substances and targets of XFZY in the prevention and treatment of hypertension.Results:Compared with the model group,the XFZY group showed a significant increase in NO expression(P<0.01)and a significant decrease in ET-1 expression(P<0.001);and the expression of BIP,P-JNK,CHOP,and BAX in XFZY group cells was significantly decreased(P<0.001),while the expression of JNK and BCL2 was significantly increased(P<0.001).19 main compounds were identified in XFZY and there were 3 pairs of molecular complexes with high affinity for markers of the endoplasmic reticulum stress,including BIP-Hesperidin complex,BIP-HSYA complex and JNK-Naringin complex.Conclusion:This study analyzed the potential pharmacodynamic substance and targets of Xuefu Zhuyu decoction in improving the function of hypertensive vascular endothelial cells,which could provide a scientific basis for the future molecular mechanism of XFZY in treating hypertension.
文摘Because of the continuous improvement of the quality of life,the population of gout patients is also increasing,which seriously affects the quality of life of patients.Traditional Chinese medicine compound has a long history and remarkable clinical effect in treating gout patients,and has been widely used.Intestinal flora and its metabolites are the focus of current research,which can promote intestinal mucosal barrier,improve immunity and improve metabolism.The regulation of intestinal flora can reduce serum uric acid and inhibit inflammation to fight gouty arthritis.Moreover,the mechanism of intestinal flora is related to the spleen in Chinese medicine theory.Therefore,this study discusses the research mechanism and clinical application of traditional Chinese medicine compound in treating gout by regulating intestinal flora,and provides theoretical basis for the clinical application of traditional Chinese medicine and the expansion of new dosage forms.
基金We thank for the funding support from the National Natural Science Foundation of China(No.81874492)Key Scientific Research Projects of Hunan Provincial Department of Education(No.18A219)the Domestic First-Class Discipline Construction Project of Chinese Medicine of Hunan University of Chinese Medicine.
文摘Objective To analyze the intellectual structure,hotspots and trends of traditional Chinese medicine(TCM)in immune regulation research.Methods The data were extracted from the Web of Science Core Collection(WoSCC)and the China National Knowledge Infrastructure(CNKI)and verified by two experienced TCM researchers.The time of literature retrieval is up to 2020.CiteSpace 5.7.R1 and Microsoft Excel 2016 were used for the statistical analysis and bibliometric diagrams,including the co-occurrence network of authors,institutions,countries,keywords,references,dual-map overlays of journals and citation bursts,etc.Results A total of 12270 publications related to TCM in immune regulation were included.The annual number of publications has increased in this field.There was close cooperation of countries and institutions,while the distribution of scholars was scattered.China was the core of the cooperation network.The dual-map overlays analysis of journals showed that core and marginal fields had increased.The keywords and references analysis showed that network pharmacology,metabolism and cancer were the most high-frequency keywords with high-intensity bursts.Conclusion TCM in immune regulation has attracted wider attention,with multi-country,multi-field,multi-disciplinary and multi-level research developing toward informatization.Network pharmacology,metabolism and cancer may be the focus of future research in this field.
基金the National Natural Science Foundation of China(Grant No.81873351 and 82205235)the Academic Support Program for High School Discipline(Professional)Top Talent(Grant No.gxbjZD2022024)+1 种基金the Key Project Foundation of Natural Science Research in Universities of Anhui Province in China(grant Nos.KJ2020A0439 and KJ2020A0416)the Talent Support Program of Anhui University of Traditional Chinese Medicine(2022rcyb028).
文摘Background:Huang-Pu-Tong-Qiao formula(HPTQ),a traditional Chinese herbal formula,has a variety of pharmacological effects.It has been used to treat Alzheimer’s disease(AD)for decades.This study aimed to screen differentially expressed proteins in the hippocampus of AD model rats treated with HPTQ.Proteomic studies of the effects of HPTQ on AD are key to understanding the therapeutic mechanisms of HPTQ and identifying potential therapeutic targets.Methods:We hence used the isobaric tags for relative and absolute quantification(ITRAQ)approach to investigate the differentially expressed proteins in the hippocampus of AD model rats before and after HPTQ administration and to identify the potential therapeutic target proteins of HPTQ.In this study,the learning and memory abilities of AD rats were examined by the Morris water maze test.After HPTQ administration,the differentially expressed proteins in the hippocampus of AD rats were quantified and analyzed in silico.Furthermore,western blotting was used to verify the expression of related proteins.Results:The Morris water maze results showed that HPTQ could improve the learning and memory ability of AD model rats.The proteomics analysis results showed that 57 proteins were differentially expressed,of which 35 were up-regulated and 22 were down-regulated.Bioinformatics analysis indicated that proteins with altered expression after HPTQ treatment were involved in several biological processes that have the potential to exert neuroprotective effects.These included promoting the translation of ribosomes,improving the deposition of amyloid-beta(Aβ),regulating autophagy,regulating neuronal synaptic function and plasticity,and alleviating oxidative stress.Conclusion:In conclusion,we identified several potential therapeutic target proteins and related mechanistic pathways of HPTQ in the treatment of AD,laying the foundation for further investigation of the therapeutic effects of HPTQ.
基金Supported by Nanjing Municipal Sports Bureau Research Bureau Project-Building a Sports Hospital with Chinese Medicine Characteristics to Help Sports-Health Integration,No.NJTY2023-104Exploring a New Model of“Integration of Sport and Health”,No.JSYGY-3-2023-506.
文摘The substantial global health burden of depression encourages the development of innovative and broadly effective interventions.This paper aimed to examine recent advancements by which exercise works as an antidepressant and recommends optimal types and quantity of exercise as supplemental therapies in treating depression.Sedentary behavior and low physical activity significantly influence the onset of depression.Being an effective treatment option,exercise can significantly reduce depression risk.Exercise exerts antidepressant effects as it modulates neurotransmitters,neuroplasticity,the immune system,and hormone levels.Effective exercise forms include yoga,strength training,and walking/jogging.Tailored exercise regimens that consider individual preferences and tolerability can improve outcomes.Regular exercise enhances general well-being and reduces depressive symptoms.Additional research is needed to understand the complex basis of exercise's effects on depression.Exercise is a cost-effective and accessible intervention for depression management that needs additional exploration.Thus,customized exercise programs,as per each patient’s needs,are essential for their successful implementation clinically.
基金supported by the Traditional Chinese Medicine Ancient Book Documents and Characteristic Technology Inheritance Project of the National Administration of Traditional Chinese Medicine(No.GZY-KJS-2020-079)the Research and Transformation Application of Clinical Characteristic Diagnosis and Treatment Techniques in the Capital(No.Z221100007422081)the National Famous Old TCM Experts Baoliang Wang Inheritance Studio Construction Program,State TCM Office Human Education Letter(No.[2022]75)。
文摘Background:Ginkgo biloba L.preparations(GBLPs)are a class of Chinese herbal medicine used in the adjuvant treatment of ischemic stroke(IS).Recently,several systematic reviews(SRs)and meta-analyses(MAs)of GBLPs for IS have been published.Objective:This overview aims to assess the quality of related SRs and MAs.Search strategy:Pub Med,Embase,Cochrane Library,Web of Science,Chinese Biological Medicine,China National Knowledge Infrastructure,Wanfang,and Chinese Science and Technology Journals databases were searched from their inception to December 31,2022.Inclusion criteria:SRs and MAs of randomized controlled trials(RCTs)that explored the efficacy of GBLPs for patients with IS were included.Data extraction and analysis:Two independent reviewers extracted data and assessed the methodological quality,risk of bias(ROB),reporting quality,and credibility of evidence of the included SRs and MAs using A Measurement Tool to Assess Systematic Reviews 2(AMSTAR 2),Risk of Bias in Systematic Reviews(ROBIS),the Preferred Reporting Items for Systematic Reviews and Meta-analyses(PRISMA),and the Grading of Recommendations Assessment,Development and Evaluation(GRADE),respectively.Additionally,descriptive analysis and data synthesis were conducted.Results:Twenty-nine SRs/MAs involving 119 outcomes were included in this review.The overall methodological quality of all SRs/MAs was critically low based on AMSTAR 2,and 28 had a high ROB based on the ROBIS.According to the PRISMA statement,the reporting items of the included SRs/MAs are relatively complete.The results based on GRADE showed that of the 119 outcomes,8 were rated as moderate quality,24 as low quality,and 87 as very low quality.Based on the data synthesis,GBLPs used in conjunction with conventional treatment were superior to conventional treatment alone for decreasing neurological function scores.Conclusion:GBLPs can be considered a beneficial supplemental therapy for IS.However,because of the low quality of the existing evidence,high-quality RCTs and SRs/MAs are warranted to further evaluate the benefits of GBLPs for treating IS.
文摘The history of medical development shows that oriental medicine, or traditional medicine, was born through medical practice during the times when science and technology were immature and underdeveloped, whereas with the development of science and technology, Western medicine, or modern medicine, was born through experimental analysis and research. With the development of medicine, the pros and cons of both medical systems become increasingly evident. How to integrate them and learn from each other will be the direction of future development of medicine. The formation and development of integrated medicine will, inevitably, usher in a new era for medicine.
基金The National Key Research and Development Program under contract No.2020YFD0901003the National Natural Science Foundation of China under contract Nos 92051119,42077305 and 32070112+2 种基金the Special National Project on Investigation of Basic Resources of China under contract No.2019FY100700the Key Research Project of Frontier Science of Chinese Academy of Sciences under contract No.QYZDB-SSW-DQC041the Taishan Scholar Project Special Funding under contract No.Tspd20210317。
文摘The productivity and health of seagrass depend on the combined inputs of nutrients from the water and sediments in which they grow and the microbiota with which they live intimately.However,little is known about the composition and diversity pattern of single-celled benthic eukaryotes in seagrass meadows.Here,we investigated how the structure and diversity of the benthic microeukaryotic community vary with respect to season,location,and seagrass colonization,by applying 18S rRNA gene amplicon sequencing for 96 surface sediment samples that were collected from three different seagrass habitats through four seasons.We found that benthic microeukaryotic communities associated with seagrass Zostera japonica exhibited remarkable spatial and seasonal variations,as well as differences between vegetated and unvegetated sediments.Diatoms and dinoflagellates predominated in the benthic microeukaryotic communities,but they were inversely correlated and displaced each other as the dominant microbial group in different seasons or habitats.Mucoromycota was more prevalent in vegetated sediments,whereas Lobulomycetales and Chytridiales had higher proportions in unvegetated sites.Total organic carbon and total organic nitrogen were the most important environmental factors in driving the microeukaryotic assemblages and diversity.Our study expands the available knowledge on the biogeographic distribution patterns and niche preferences for benthic microeukaryotes in seagrass systems.
基金National natural science foundation of China(No.81973844)。
文摘Objective:To explore the protective effect of Linggui Zhugan Decoction(LGZGD)medicated serum on myocardial fibrosis induced by transforming growth factor-β1(TGF-β1).Methods:Using enzyme digestion method,combined with differential adherence to isolate and culture Sprague-Dawley(SD)suckling mouse Cardiac fibroblasys(CFB)in vitro.Divided into:blank group,blank rat serum group,model group,and LGZGD medicated serum group(5%、10%、20%).Except for blank group and blank rat serum group,they were stimulated with 5 ng/ml TGF-β1 for 12 hours,and then then intervene with LGZGD medicated serum(5%、10%、20%)and continue to culture for 24 hours.Use immunofluorescence and Western blot(WB)to detect the expression ofα-smooth muscle actin(α-SMA),Enzyme-linked immunosorbent assay(ELISA)and WB to detect type Ⅰ collagen(Collagen Ⅰ),type Ⅰ collagen(Collagen Ⅲ)and fibronectin(FN)expression.Results:Compared with the blank group,the expressions of Collagen Ⅰ,Collagen Ⅲ,α-SMA and FN in the model group were significantly increased(P<0.01);Compared with the model group,the expressions of Collagen Ⅰ and Collagen Ⅲ in each concentration group of the experiment were significantly reduced(P<0.01);the expression ofα-SMA and FN were significantly reduced(P<0.01).Conclusions:LGZGD has an inhibitory effect on collagen synthesis and the expression ofα-SMA and FN,indicating that the anti-fibrosis effect of LGZGD is related to it.
基金This work was financially supported by The Jiangsu Provincial Maternal and Child Health Key Talents Project(F202042).
文摘The placenta plays an important role in nutrient transport to maintain the growth and development of the embryo.Gestational diabetes mellitus(GDM),the most common complication during pregnancy,highly affects placental function in late gestation.Advanced glycation end-products(AGEs),a complex and heterogeneous group of compounds engaged by the receptor for AGEs(RAGE),are closely associated with diabetes-related complications.In this study,AGEs induced a decrease in the expression of tight junction(TJ)proteins in BeWo cells and increased the paracellular permeability of trophoblast cells by regulating RAGE/NF-κB.Sprague-Dawley(SD)rats injected with 100 mg/kg AGEs-rat serum albumin(RSA)via the tail vein from embryo day 2 were set as the placental barrier dysfunction model group(n=10).The effect of AGEs on placental permeability was determined using the Evans-Blue dye extravasation method.The ultrastructure of the placenta samples was observed by transmission electron microscopy.The effects of AGEs on the placenta were confirmed by treating rats with RAGE antagonist FPS-ZM1 and soluble forms of RAGE(sRAGE).AGEs treatment increased placental permeability and disrupted the tight junctions in pregnant rat placenta,but has no effect on blood glucose.The expression of TJ-related proteins,including ZO-1,Occludin,and Claudin 5,were downregulated after AGEs treatment.Further,AGEs treatment increased the expression of RAGE and nuclear factor-κB in the placenta of rats and upregulated the levels of vascular endothelial growth factor.The effects of AGEs on the placenta were blocked by RAGE antagonist FPS-ZM1 and sRAGE.This study demonstrates the mechanism underlying AGEs-induced disturbance in placental function in pregnant rats and highlights the potential of AGEs in the treatment of GDM.
基金Supported by the National Natural Science Foundation of China(Nos.82174394,81673982,81704084)the Science and Technology Development Fund,Macao SAR(No.0121/2022/A3)+5 种基金the Faculty Research Grants of Macao University of Science and Technology(No.FRG-22-110-FC)the Natural Science Foundation of JiangsuProvince(No.BK20201401)the Postgraduate Research&Practice Innovation Program of Jiangsu Province(No.KYCX21_1667)Chinese Medicine Technology Development Project of Jiangsu Province(No.QN202002)the Natural Science Foundation of Nanjing University of Chinese Medicine(No.NZY81704084)the Open Projects of the Discipline of Chinese Medicine of Nanjing University Supported by the Subject of Academic priority discipline of Jiangsu Higher Education Institutions(No.ZYX03KF63)。
文摘Postoperative adhesion(PA)is currently one of the most unpleasant complications following surgical procedures.Researchers have developed several new strategies to alleviate the formation of PA to a great extent,but so far,no single measure or treatment can meet the expectations and requirements of clinical patients needing complete PA prevention.Chinese medicine(CM)has been widely used for thousands of years based on its remarkable efficacy and indispensable advantages CM treatments are gradually being accepted by modern medicine.Therefore,this review summarizes the formating process of PA and the efficacy and action mechanism of CM treatments,including their pharmacological effects,therapeutic mechanisms and advantages in PA prevention.We aim to improve the understanding of clinicians and researchers on CM prevention in the development of PA and promote the in-depth development and industrialization process of related drugs.
基金This project was supported by the Natural Science Foundation of Anhui Provincial Department of Education(no.KJ2020A0386)National Natural Science Foundation of China(no.82174162).
文摘Background:Oligoasthenospermia is one of the main causes of male infertility.Researchers usually use chemical drugs to directly damage germ cells to prepare oligoasthenospermia models,which disregards the adhesion and migration between spermatogenic cells and Sertoli cells.TAp73 is a critical regulator of the adhesin of germ cell;thus,we sought to explore a novel oligoasthenospermia model based on TAp73 gene suppression.Methods:Mice in the Pifithrin-αgroup were injected intraperitoneally with 2.5 mg/kg Pifithrin-α(TAp73 inhibitor)daily for 30 consecutive days.Reproductive hormone levels and epididymal sperm quality,as well as the network morphology of Sertoli cells were tested.Results:Sperm density,motility,and the relative protein and mRNA expression of TAp73 and Nectin 2 were obviously decreased in the Pifithrin-αgroup compared with the normal control group.No significant distinction was observed in the relative mRNA and protein expression of ZO-1.Furthermore,the tight junctions(TJs)and api-cal ectoplasmic specialization(ES)were destroyed in the Pifithrin-αgroup.Conclusion:The above results indicate that we successfully established a new oli-goasthenospermia mouse model.This study provides a foundation for further explo-ration of the roles of TAp73 genes during spermatogenesis and provides new research objects for further oligospermia research and future drug discovery.
文摘The aim of this study was to investigate the effect of hypoxia on the sodium current of rat cardiomyocytes in order to explore ion channel mechanism of cardiomyocyte hypoxia.The rat cardiomyocytes were isolated by acute enzymatic hydrolysis.A group of untreated cells were used to record sodium currents using whole-cell patch-clamp technique,another group was subjected to hypoxia and record sodium currents using same technique.The results showed that the morphological trajectory of sodium hypoxia was not changed compared with that of normal cells.The I-V curve of hypoxic cells was significantly higher than that of normal cells,and the peak current of INa was 15.68%higher than that of normal cells(P<0.0001).Activation potential of normal and hypoxia cells was about-40mV,the maximum peak current corresponds to the stimulation voltage of-25mV.The above results suggest that rat cardiomyocytes sodium current increases in the case of hypoxia.
基金supported by the National Natural Science Foundation of China(81403407)Special Program of the International Cooperation in Chinese Medicine of the State Administration of Traditional Chinese Medicine(China-Australia Chinese Medicine Center[Melbourne]GZYYGJ2021024)。
文摘Heidan disease(black jaundice)is a kind of jaundice,which is caused by lingering and chronic jaundice,often with blood stasis and damp-heat,etc.The clinical symptoms of Heidan disease(black jaundice)are similar to those of cirrhosis caused by multiple chronic liver diseases in Western medicine.Heidan disease(black jaundice)generally belongs to yin jaundice type,and the pathogenesis is mostly related to blood stasis and dampness stagnation,often with damp-heat residue.According to Zhongjing Zhang,the prescription Xiaoshi Fanshi powder for the treatment of Heidan disease(black jaundice)is based on the understanding that the nature of Heidan disease(black jaundice)is inseparable from the two key pathological factors of dampness and blood stasis.The treatment of jaundice should be based on removing blood stasis and dampness,supplemented by soothing the liver and promoting the transportation function of spleen,removing blood stasis and harmonizing the collaterals,and promoting diuresis and reducing jaundice.In the treatment of jaundice,removing blood stasis and purging turbidity should be stressed,and powerful tonification should be used with caution.Since blood stasis and turbidity are always intermingling and often complicated with damp heat,the method of warm drying should be used with caution.For promoting blood circulation,removing blood stasis,and dredging the liver-biliarycollaterals,drasticmedicine shouldbeused withcaution.
基金This work was supported by grants from startup supports of Soochow University and the Program for Jiangsu Specially-Appointed Professors.This work was also supported by the National Natural Science Foundation of China(No.31900988)the Natural Science Foundation of Jiangsu Province(No.SBK2019040088).
文摘The enhanced permeability retention(EPR)effect based nanomedicine has been widely used for tumor targeting during the past decades.Here we unexpectedly observed the similar"EPR effect"at the site of iniury.We found that the temporary dilated and leaky blood vessels caused by the potent vasodilator histamine in response to injury allowed the injected nanoparticles to pass through the vasculature and reached the injured tissue.Our finding shows the potential underline mechanism of"EPR effect"at the injured site.By loading with antibiotics,we further demonstrated a new strategy for prevention of infection at the site of injury.
基金supported by the Natural Science Research Project of Colleges and Universities in Anhui Province(KJ2021A0557)the grants from the Opening Project of Zhejiang Provincial Preponderant and Characteristic Subject of Key University(Chinese Traditional Medicine)(ZYXZD2019004)+2 种基金Zhejiang Chinese Medical Universitythe National Natural Science Foundation of China(ZYXZD81973643)Zhejiang Chinese Medicine Science and Technology Project(No.2023ZL467).
文摘Polo-like kinase 1(PLK1)plays a crucial role in cell mitosis and has been associated with necroptosis.However,the role of PLK1 and necroptosis in lung adenocarcinoma(LA)remains unclear.In this study,we analyzed The Cancer Genome Atlas(TCGA)and Genotype-Tissue Expression databases to evaluate the prognostic value and mechanistic role of PLK1 in LA.PLK1 was found to be highly expressed in LA and was positively associated with advanced disease staging and poor survival outcomes.Functional enrichment analysis showed that PLK1 was involved in cell mitosis,neurotransmitter transmission,and drug metabolism.Further analysis using single-sample gene set enrichment analysis and ESTIMATE algorithm revealed a correlation between PLK1 expression and immune infiltration in LA.Silencing of PLK1 using miRNA transfection in LA cells reduced cell proliferation and increased apoptosis,as well as upregulating the expression of necroptosis-related proteins,such as RIPK1,RIPK3,and MLKL.Additionally,nude mouse transplantation tumor experiments demonstrated that silencing PLK1 reduced the growth capacity of LA cells.These findings suggest that PLK1 plays a critical role in LA progression by regulating necroptosis and immune infiltration,and may serve as a potential therapeutic target for immunotherapy.Furthermore,PLK1 expression can be used as a prognostic biomarker for LA patients.
基金Supported by the Natural Science Foundation Project of Nanjing University of Traditional Chinese Medicine(No.XZR2020030)Jiangsu Famous Traditional Chinese Medicine Inheritance Studio Project(Jiangsu Traditional Chinese Medicine Science and Education(No.20SGzs003)。
文摘Objective:To investigate the effect of Huangqin Decoction(HQD)on nuclear factor erythroid 2 related-factor 2(Nrf2)/heme oxygenase(HO-1)signaling pathway by inducing the colitis-associated carcinogenesis(CAC)model mice with azoxymethane(AOM)/dextran sodium sulfate(DSS).Methods:The chemical components of HQD were analyzed by liquid chromatography-quadrupole-time-of-flight mass spectrometry(LC-Q-TOF-MS/MS)to determine the molecular constituents of HQD.Totally 48 C57BL/6J mice were randomly divided into 6 groups by a random number table,including control,model(AOM/DSS),mesalazine(MS),low-,medium-,and high-dose HQD(HQD-L,HQD-M,and HQD-H)groups,8 mice in each group.Except for the control group,the mice in the other groups were intraperitoneally injected with AOM(10 mg/kg)and administrated with 2.5%DSS orally for 1 week every two weeks(totally 3 rounds of DSS)to construct a colitis-associated carcinogenesis mouse model.The mice in the HQD-L,HQD-M and HQD-H groups were given HQD by gavage at doses of 2.925,5.85,and 11.7 g/kg,respectively;the mice in the MS group was given a suspension of MS at a dose of 0.043 g/kg(totally 11 weeks).The serum levels of malondialdehyde(MDA)and superoxide dismutase(SOD)were measured by enzyme-linked immunosorbent assay.The mRNA and protein expression levels of Nrf2,HO-1,and inhibitory KELCH like ECH-related protein 1(Keap1)in colon tissue were detected by quantitative real-time PCR,immunohistochemistry,and Westem blot,respectively.Results:LC-Q-TOF-MS/MS analysis revealed that the chemical constituents of HQD include baicalin,paeoniflorin,and glycyrrhizic acid.Compared to the control group,significantly higher MDA levels and lower SOD levels were observed in the model group(P<0.05),whereas the expressions of Nrf2 and HO-1 were significantly decreased,and the expression of Keap1 increased(P<0.01).Compared with the model group,serum MDA level was decreased and SOD level was increased in the HQD-M,HQD-H and MS groups(P<0.05).Higher expressions of Nrf2 and HO-1 were observed in the HQD groups.Conclusion:HQD may regulate the expression of Nrf2 and HO-1 in colon tissue,reduce the expression of MDA and increase the expression of SOD in serum,thus delaying the progress of CAC in AOM/DSS mice.
基金the National Key Research and Development Program of China(Nos.2022YFB3205602 and 2022YFB3804703)the National Natural Science Foundation of China(Nos.52372174,61875015,and T2125003)+2 种基金the Beijing Natural Science Foundation(Nos.L212046 and L212010)the Fundamental Research Funds for the Central Universitiesthe Animal Experimentation Ethics Committee of the Cancer Hospital,Chinese Academy of Medical Sciences(Ethical Approval No.NCC2023A291).
文摘Acute postoperative pain is commonly treated with flurbiprofen(FBP),but conventional delivery methods are suboptimal.This study prepared a new non-burst release microneedles(MNs)using genipin cross-linked gelatin(cGel).By adding varying amounts of genipin to modulate the crosslinking degree of cGel,the drug release behavior of the drug-loaded MNs in the skin can be altered.The crosslinking parameters that meet therapeutic requirements are selected,thus providing rapid and longlasting analgesic effects.cGel solutions were successfully cross-linked,altering matrix material microstructure,confirmed by scanning electron microscope imaging and fourier transform infrared spectroscopy.MNs demonstrated increasing mechanical strength with higher crosslinking.Drug release rates were rapid initially,then slowed,exhibiting a characteristic of decreased release rates with increasing degrees of crosslinking.In vivo,FBP/cGel MNs significantly reduced allodynia and hyperalgesia post-surgery,with the greatest effect observed at 2–3 h post-surgery,and can maintain analgesia for up to 6 h.Biosafety tests confirmed good biocompatibility.FBP/cGel MNs effectively penetrate the stratum corneum,safely delivering drugs with significant analgesic effects,excellent mechanical properties,and good biocompatibility,representing a promising strategy for managing acute postoperative pain.
