Population aging is one of the common challenges in the current world.As people age,the body’s tissues including cells,and molecules inevitably degrade,and their functions gradually decline,causing various age-relate...Population aging is one of the common challenges in the current world.As people age,the body’s tissues including cells,and molecules inevitably degrade,and their functions gradually decline,causing various age-related diseases like Alzheimer’s disease,osteoporosis,low immunity,glucose and lipid metabolism disorders,and cardiovascular diseases.With the continuous increase of the elderly population,the pressure on the medical industry is increasing.To lower the burden on the medical industry and increase the average age of the elderly,it is vital to explore effective anti-aging materials.Ginseng Radix et Rhizoma(Renshen),as a traditional and precious Chinese medicinal herb,is known as the“king of all herbs”.It is famous for its effects of“tonifying Qi,restoring pulse”(helping with the generation of Qi(the fundamental,vital energy that continuously flows within the body)and the circulation of blood)and strengthening the body,nourishing the spleen and lungs,generating fluids and nourishing blood,calming the mind and improving intelligence.Recently,its anti-aging effect has received increasing attention from modern scientific research.This study summarizes the pharmacological effects of the main active ingredients of Renshen(ginsenosides,polysaccharides,etc.)on resisting aging,including preventing neuroaging,suppressing skin aging,mitigating ovarian aging,inhibiting osteoporosis and arthritis,enhancing the immune system of the elderly,protecting the cardiovascular system,resisting aging-induced fatigue and exerting the anti-tumor effects.Through network pharmacology and molecular docking,the anti-aging active ingredients of Renshen were screened,and the key targets and pathways of anti-aging active ingredients in Renshen were determined.Using network pharmacology,totally 106 drug targets and 3,479 disease targets were screened,and 79 common targets between aging and Renshen were identified.Three core targets were identified in the PPI network,including TNF,AKT1,and IL-1β.Molecular docking was used to obtain further verification.This study emphasizes the potential of Renshen as a source of anti-aging activity,which can be developed into a novel drug for the treatment of age-related diseases.展开更多
BACKGROUND Colorectal cancer(CRC)is the third most common cancer globally,causing over 900000 deaths annually.Risk factors include aging,diet,obesity,sedentary lifestyle,tobacco use,genetic predisposition,and inflamma...BACKGROUND Colorectal cancer(CRC)is the third most common cancer globally,causing over 900000 deaths annually.Risk factors include aging,diet,obesity,sedentary lifestyle,tobacco use,genetic predisposition,and inflammatory bowel disease.Despite current treatments,survival rates for advanced CRC remain low,highlighting the need for better therapeutic strategies.AIM To evaluate both the clinical significance and the pathological implications of the Kinesin family member 14(KIF14)expression within CRC specimens.Additionally,this study aims to investigate the interaction between nitidine chloride(NC)and KIF14,considering their potential as therapeutic targets.METHODS The expression of the KIF14 protein in CRC was analyzed using immunohistochemical staining.The integration of multicenter high-throughput data facilitated the calculation of the standardized mean difference(SMD)for KIF14 mRNA levels.The assessment of clinical and pathological impact was enhanced by analyzing combined receiver operating characteristic curves,along with measures of sensitivity,specificity,and likelihood ratios.Additionally,clustered regularly interspaced short palindromic repeats knockout screening for cell growth and single-cell sequencing were employed to validate the significance of KIF14 expression in CRC.Survival analysis established the prognostic value of KIF14 in CRC.The molecular mechanism of NC against CRC was elucidated through whole-genome sequencing and enrichment analysis,and molecular docking was utilized to explore the targeting affinity between NC and KIF14.RESULTS KIF14 was highly expressed in 208 CRC patients.Data from 17 platforms involving 2436 CRC samples and 1320 noncancerous colorectal tissue controls indicated that KIF14 expression was significantly higher in CRC samples,with an SMD of 1.92(95%CI:1.49-2.35).The area under the curve was 0.94(95%CI:0.92-0.96),with a sensitivity of 0.85(95%CI:0.78-0.90)and a specificity of 0.90(95%CI:0.85-0.93).The positive and negative likelihood ratios were 8.38(95%CI:5.39-13.02)and 0.17(95%CI:0.11-0.26),respectively.At the single-cell level,significant overexpression of KIF14 was observed in CRC cells(P<0.001),with 35 CRC cell lines dependent on KIF14 for growth.The K-M plots demonstrated that KIF14 possesses prognostic value in CRC patients within the GSE71187 and GSE103679 datasets(P<0.05).Binding energy calculations indicated that KIF14 is a potential target for NC(binding energy:10.3 kcal/mol).CONCLUSION KIF14 promotes the growth of CRC cells and acts as an oncogenic factor,potentially serving as a therapeutic target for NC in the treatment of CRC.展开更多
Ethiprole is widely used as a second-generation phenyl pyrazole insecticide.Previous studies indicated that ethiprole exhibited thyroid toxicity while two main metabolites(ethiprole sulfone(M1)and ethiprole sulfide(M2...Ethiprole is widely used as a second-generation phenyl pyrazole insecticide.Previous studies indicated that ethiprole exhibited thyroid toxicity while two main metabolites(ethiprole sulfone(M1)and ethiprole sulfide(M2))of ethiprole showed higher acute toxicity than ethiprole.Therefore,assessing the thyroid toxicity of its metabolites is crucial for safety assessment.In this study,the thyroid toxicity and underlying mechanisms of ethiprole and its metabolites were explored using in silico,in vitro,and in vivo assays,with the aim of conducting a comparative study on thyroid toxicity.Molecular docking analysis showed that ethiprole,M1 and M2 could bind with thyroid receptor isoforms and exhibited higher binding affinity compared to 3,3,5-triiodothyronine(T3).GH3 cell proliferation assays revealed that ethiprole,M1 and M2 all served as thyroid hormone antagonists to hinder the T3-induced cell proliferation.Using the zebrafish model,we further investigated that exposure to ethiprole,M1,and M2 disrupted thyroid hormone levels and the transcriptional expressions of hypothalamus-pituitary-thyroid(HPT)axis-related genes.Ethiprole induced thyroid disrupting effects by binding with the thyroid receptor beta,M1 mainly through binding with the corticotropin releasing factor receptor-1,and M2 exposure firstly inhibited the thyroid peroxidase enzyme activity.M2 showed the highest developmental toxicity and thyroid disrupting effects,which significantly reducing hatching rates,increasing deformity rates,exhibiting the lowest lethal concentration 50 value and showing the most serious transcription inhibitory effects on the HPT axis.This study suggested the risk assessment of metabolites should be considered in assessing potential environmental risk of ethiprole.展开更多
BACKGROUND The stearoyl-coenzyme A desaturase(SCD)gene influences colorectal cancer(CRC)pathogenesis,with its expression linked to tumor cell survival and resistance,necessitating further investigation into its role i...BACKGROUND The stearoyl-coenzyme A desaturase(SCD)gene influences colorectal cancer(CRC)pathogenesis,with its expression linked to tumor cell survival and resistance,necessitating further investigation into its role in CRC.AIM To explore the clinical and pathological significance of SCD expression in CRC tissues and to evaluate the affinity between nitidine chloride(NC)and SCD as a target.METHODS Multi-center high-throughput data related to CRC were integrated to calculate the standardized mean difference of SCD mRNA expression levels.Immunohistochemical staining results,Clustered Regularly Interspaced Short Palindromic Repeats knockout screening results of cell growth,and single-cell sequencing were employed to verify the significance of SCD expression in CRC.The clinical and pathological significance of SCD was assessed using pooled receiver operating characteristic curves,sensitivity,specificity,and likelihood ratios.The molecular mechanism of NC against CRC was clarified using the SwissTarget Prediction and functional enrichment,and molecular docking techniques were utilized to explore the targeting affinity between NC and SCD.RESULTS Data from 18 platforms,including 2482 CRC samples and 1334 non-cancerous colorectal tissue controls.SCD expression was significantly upregulated in CRC,with a standardized mean difference of 2.05[95%confidence interval(CI):1.69-2.41].The area under the pooled receiver operating characteristic curve was 0.95(95%CI:0.92-0.96),with a sensitivity of 0.86(95%CI:0.81-0.90)and a specificity of 0.90(95%CI:0.87-0.93).Positive and negative likelihood ratios were 9.02(95%CI:6.49-12.51)and 0.15(95%CI:0.10-0.22),respectively.High SCD protein expression was noted in 208 CRC patients,significantly associated with vascular invasion(P<0.001).At the singlecell level,SCD was significantly overexpressed in CRC cells(P<0.001).A total of 33 CRC cell lines depended on SCD for growth.The potential mechanism of NC against CRC might involve modulation of the cell cycle,positioning SCD as a potential target for NC.CONCLUSION SCD promotes CRC cell growth and thus acts as an oncogenic factor,making it a potential therapeutic target for NC in CRC treatment.展开更多
Background:Gastric cancer(GC)remains a global health burden and is often characterized by heterogeneous molecular profiles and resistance to conventional therapies.The phosphoinositide 3-kinase and PI3K and Janus kina...Background:Gastric cancer(GC)remains a global health burden and is often characterized by heterogeneous molecular profiles and resistance to conventional therapies.The phosphoinositide 3-kinase and PI3K and Janus kinase(JAK)signal transducer and activator of transcription(JAK-STAT)pathways play pivotal roles in GC progression,making them attractive targets for therapeutic interventions.Methods:This study applied a computational and molecular dynamics simulation approach to identify and characterize SBL-JP-0004 as a potential dual inhibitor of JAK2 and PI3KCD kinases.KATOIII and SNU-5 GC cells were used for in vitro evaluation.Results:SBL-JP-0004 exhibited a robust binding affinity for JAK2 and PI3KCD kinases,as evidenced by molecular docking scores and molecular dynamics simulations.Binding interactions and Gibbs binding free energy estimates confirmed stable and favorable interactions with target proteins.SBL-JP-0004 displayed an half-maximal inhibitory concentration(IC_(50))value of 118.9 nM against JAK2 kinase and 200.9 nM against PI3KCD enzymes.SBL-JP-0004 exhibited potent inhibition of cell proliferation in KATOIII and SNU-5 cells,with half-maximal growth inhibitory concentration(GI50)values of 250.8 and 516.3 nM,respectively.A significant elevation in the early phase apoptosis(28.53%in KATOIII cells and 26.85%in SNU-5 cells)and late phase apoptosis(17.37%in KATOIII cells and 10.05%in SNU-5 cells)were observed with SBL-JP-0004 treatment compared to 2.1%and 2.83%in their respective controls.Conclusion:The results highlight SBL-JP-0004 as a promising dual inhibitor targeting JAK2 and PI3KCD kinases for treating GC and warrant further preclinical and clinical investigations to validate its utility in clinical settings.展开更多
Background:Pistacia chinensis Bunge has been traditionally used to manage various conditions,including asthma,pain,inflammation,hepatoprotection,and diabetes.The study was conducted to investigate the antioxidant and ...Background:Pistacia chinensis Bunge has been traditionally used to manage various conditions,including asthma,pain,inflammation,hepatoprotection,and diabetes.The study was conducted to investigate the antioxidant and anti-lipoxygenase(LOX)properties of the isolated compound 2-(3,4-dihydroxyphenyl)-5,7-dihydroxy-4H-chromen-4-one from Pistacia chinensis.Methods:LOX assay and antioxidant activity using 2,2-diphenyl-1-picrylhydrazyl(DPPH)assay were performed.Molecular docking studies were conducted using a molecular operating environment.Results:The LOX assay revealed significant inhibitory effects at 0.2µM concentration,with an IC50 value of 37.80µM.The antioxidant effect demonstrated dose-dependency across 5 to 100µg/mL concentrations,reaching 93.09%at 100µg/mL,comparable to ascorbic acid’s 95.43%effect.Molecular docking studies highlighted strong interactions with the lipoxygenase enzyme,presenting an excellent docking score of-10.98 kcal/mol.Conclusion:These findings provide valuable insights into Pistacia chinensis’chemical components and biological effects,reinforcing its traditional medicinal applications.展开更多
The anti-hair loss mechanism of Aquilaria sinensis leaf extract(ASE)has been studied by using metabolomics and network pharmacology.Metabolomics was utilized to comprehensively identify the active constituents of ASE,...The anti-hair loss mechanism of Aquilaria sinensis leaf extract(ASE)has been studied by using metabolomics and network pharmacology.Metabolomics was utilized to comprehensively identify the active constituents of ASE,and the network pharmacology was used to elucidate their anti-hair loss mechanism,which was verified by molecular docking technology.572 active compounds were identified from the ASE by metabolomics methods,where there are 1447 corresponding targets and 492 targets related to hair loss,totaling 88 targets.20 core active substances were identified by constructing a network between common targets and active substances,which include vanillic acid,chorionic acid,caffeic acid and apigenin.The five key targets of TNF,TP53,IL6,PPARG,and EGFR were screened out by the PPI network analysis on 88 common targets.The GO and KEGG pathway enrichment analysis showed that the inflammation,hormone balance,cell growth,proliferation,apoptosis,and oxidative stress are involved.Molecular docking studies have confirmed the high binding affinity between core active compounds and key targets.The drug similarity assessment on these core compounds suggested that they have the potential to be used as potential hair loss treatment drugs.This study elucidates the complex molecular mechanism of ASE in treating hair loss,and provides a reference for the future applications in hair care products.展开更多
Objective To evaluate the protective effect of Lonicerae Japonicae Flos(LJF)extract against doxorubicin(DOX)-induced cardiotoxicity(DIC)and explore the possible mechanisms.Methods Network pharmacology,bioinformatics a...Objective To evaluate the protective effect of Lonicerae Japonicae Flos(LJF)extract against doxorubicin(DOX)-induced cardiotoxicity(DIC)and explore the possible mechanisms.Methods Network pharmacology,bioinformatics analysis and molecular docking were used to predict the targets of the core components of LJF.In a mouse model of DOX-induced myocardial injury,the protective effects of different doses of LJF extract were evaluated and the underlying mechanisms were explored by detecting the changes in mouse myocardial functions,myocardial enzymes,myocardial pathologies,and the expressions of inflammatory factors and pyroptosis-related proteins.Results The 10 core ingredients of LJF showed strong binding to AKT,EGFR,and GSK3β.In the animal experiment,the DOX-treated mice,compared with the sham-treated mice,had significantly decreased cardiac output,stroke volume,left ventricular ejection fraction,left ventricular fraction shorting,elevated serum levels of CK-MB and LDH,increased myocardial expressions of IL-18 and IL-1β,obvious myocardial damage,increased expression levels of NLRP3,caspase-1,GSDMD and GSDMD-N,and reduced expressions of EGFR,p-AKT and p-GSK3βproteins in the myocardial tissues.LJF treatment obviously improved myocardial function,decreased myocardial expressions of IL-18,IL-1β,NLRP3,caspase-1,GSDMD and GSDMD-N proteins,and increased the expressions EGFR,p-AKT and p-GSK3βproteins in DOX-treated mice.Conclusion LJF extract alleviates DOX-induced myocardial injury in mice possibly by reducing myocardial inflammation and pyroptosis via targeting EGFR,AKT and GSK3βto regulate the ErbB signaling pathway.展开更多
The Solanum genus is known for its diverse bioactive compounds,yet its diuretic potential remains understudied.This research commenced with an analysis of polyphenol and flavonoid content in Solanum elaeagnifolium lea...The Solanum genus is known for its diverse bioactive compounds,yet its diuretic potential remains understudied.This research commenced with an analysis of polyphenol and flavonoid content in Solanum elaeagnifolium leaf extract(SEFE)using colorimetric techniques,followed by HPLC-DAD to delineate its chemical composition.The aqueous extract revealed prominent constituents:naringin(12.38%),quercetin 3-O-B-D-Glucoside(27.25%),and flavone(15.26%).A 15-day study on normal rats investigated the diuretic potential of SEFE at repeated doses.SEFE significantly increased urine volume and urinary sodium/potassium levels without inducing hypokalaemia,contrasting with furosemide,a standard diuretic that induced hypokalaemia.Conversely,furosemide,a standard diuretic,increased urinary sodium and potassium while inducing hypokalaemia.It was evident that the diuretic effect of S.elaeagnifolium is dose-dependent,with a dosage of 500 mg/kg body weight exerting a more potent diuretic effect compared to furosemide.The diuretic activity of this plant was supported by an in silico study of the diuretic effect.The findings demonstrate how S.elaeagnifolium leaves have a potent diuretic impact on rats.However,more in-depth studies are needed to examine the following aspects:identifying the specific molecules responsible for the diuretic effect,understanding the molecular and cellular mechanisms underlying this activity,and assessing the long-term safety and clinical efficacy of this plant in different contexts.展开更多
Trehalose is an autophagy-promoting disaccharide,which can improve and delay chronic diseases like neurodegenerative diseases and atherosclerosis,but its bioavailability is severely restricted by endogenous trehalase ...Trehalose is an autophagy-promoting disaccharide,which can improve and delay chronic diseases like neurodegenerative diseases and atherosclerosis,but its bioavailability is severely restricted by endogenous trehalase in mammals.Trehalase inhibitor is a promising and effective way to enhance trehalose bioavailability by preventing trehalose from hydrolyzing.However,previously reported trehalase inhibitors still face safety of long-term use and promiscuous inhibition on intestinal glycosidases.This study carried out a high-throughput virtual screening through molecular pool-based molecular docking combined with in vitro inhibition experiments to screen trehalase inhibitors naturally derived from foods.Out of 1769 small molecules,which include 115 analogs of trehalose,natural monosaccharides,disaccharides,trisaccharides,imidazoles and their derivatives,as well as 20 natural amino acids and their 400 dipeptides,isomaltose,α-isomaltulose,and isomaltitol exhibited the best inhibitory activities,beyond as traditional sweetener and prebiotic.Best of all,isomaltose showed the half maximal inhibitory concentration(IC50)and inhibition constant(Ki)values on trehalase of 5.59 and(2.1760±0.3431)mmol/L,respectively.Moreover,isomaltose was resistant to the simulated digestive environment and did not affect intestinal glycosidases such asα-glucosidase and glucoamylase,making it a reliable edible candidate for a trehalase inhibitor.This study provides new insights into the virtual screening-based identification of new food-derived trehalase inhibitors for enhanced integrity and bioavailability of orally administered trehalose,especially repurposing a prebiotic for another new use as trehalase inhibitor.展开更多
Objective:To examine the effect of the methanolic extract of Salacia fruticosa in a zebrafish model of scopolamine-induced Alzheimer’s disease.Methods:High-resolution liquid chromatography-mass spectrometry was used ...Objective:To examine the effect of the methanolic extract of Salacia fruticosa in a zebrafish model of scopolamine-induced Alzheimer’s disease.Methods:High-resolution liquid chromatography-mass spectrometry was used to characterize the phytochemical constituents of Salacia fruticosa methanolic extract.The drug-likeness of these compounds was determined via the DruLiTo tool,and their acetylcholinesterase(AChE)binding affinities were studied by molecular docking.In in vivo studies,adult zebrafish were treated with 3.125,6.25,and 12.5 mg/L of the extract for seven days and then immersed in scopolamine(100μM/L)to induce cognitive deficits.T-maze and novel object recognition tests were used for behavioral studies.In addition,the activities of AChE,antioxidant enzymes,and myeloperoxidase were determined in brain tissue of zebrafish.Results:High-resolution liquid chromatography-mass spectrometry revealed that 40 phytoconstituents were present in the methanolic extract of Salacia fruticosa,and 27 compounds met Lipinski's rule of five,indicating good drug-likeness.Some compounds such as stylopine,p-coumaroylagmatine,and(-)-heliannuol E,demonstrated high AChE binding affinity.Moreover,pretreatment with the extract significantly mitigated zebrafish cognitive decline,as indicated by increased time spent at the novel object in novel object recognition test,as well as increased time spent and decreased latency in the green arm(P<0.001).The extract also markedly lowered malondialdehyde and myeloperoxidase levels and AChE activity,and enhanced glutathione peroxidase and superoxide dismutase activities(P<0.001)in zebrafish with scopolamine-induced Alzheimer’s disease.Histopathological studies revealed that Salacia fruticosa extract ameliorated scopolamine-induced abnormalities in neuronal cell morphology.Conclusions:Pretreatment with the methanolic extract of Salacia fruticosa reduces cognitive impairment,enhances antioxidants,and attenuates oxidative stress,highlighting its potential as a preventive agent for Alzheimer’s disease.展开更多
Phytophthora infestans control is a long-standing problem that has caused ongoing difficulties and brought limited success for over a century.Traditional methods,such as fungicides,have drawbacks including high cost,r...Phytophthora infestans control is a long-standing problem that has caused ongoing difficulties and brought limited success for over a century.Traditional methods,such as fungicides,have drawbacks including high cost,restrictions on organic farming,potential risks to the environment and human health,and the development of resistant strains.In this study,we employed cutting-edge computer-based techniques,including Quantitative Structure-Activity Relationship(QSAR)modeling and molecular docking simulations,to uncover new fungicidal compounds and gain insights into their specific mechanisms of action against P.infestans.QSAR modeling on the number of compounds tested as P.infestans inhibitors was performed using an interactive OCHEM web platform.The predictive ability of the developed classification models had a balanced accuracy(BA)of 77–85%for the training set and BA?89–93%for the validation external test set.During the in vitro testing against P.infestans,thirteen synthesized 2-oxoimidazolidine-4-sulfonamides demonstrated inhibition rates,ranging from 23.6%to 87.4%.The fungicidal potential of six of these fungicides ranged from 79.3%to 87.4%,which is comparable to the activity of known fungicides.Acute toxicity results using the well-known aquatic marker Daphnia magna showed that the most active sulfonamides 3d,3f,3h,3j,3k,and 3l,with LC_(50) values ranging from 13.7 to 52.9 mg/L,are low-toxicity compounds.The molecular docking results demonstrated a potential mechanism of the antifungal action of the studied 2-oxoimidazolidin-4-sulfonamide derivatives via the inhibition of fungal CYP51,a sterol biosynthesis enzyme.展开更多
AIM:To investigate the effects of nintedanib on epithelial-mesenchymal transition(EMT)in cells derived from pterygium,aiming to explore its potential as a pharmacological intervention for pterygium treatment.METHODS:P...AIM:To investigate the effects of nintedanib on epithelial-mesenchymal transition(EMT)in cells derived from pterygium,aiming to explore its potential as a pharmacological intervention for pterygium treatment.METHODS:Primary human pterygium epithelial cells(hPEC)and human conjunctival epithelial(hCJE)cells were isolated from patients,cultured,and characterized.The impact of nintedanib on transforming growth factor beta(TGF-β)-induced EMT was assessed by examining the expression of EMT markers such as vimentin and E-cadherin.Additionally,the modulation of the miR-23b-3p/transforming growth factor beta receptor 2(TGFBR2)/Smad2 pathway by nintedanib was investigated to elucidate its potential antifibrotic mechanism.RESULTS:The expression of miR-23b-3p gene in hCJE cells was significantly higher than that in hPEC cells.Nintedanib effectively mitigated TGF-β-induced EMT in cells derived from pterygium,as evidenced by the downregulation of vimentin and upregulation of E-cadherin.When the nintedanib concentration exceeded 1μmol/L,it significantly suppressed the proliferation of hPEC cells and significantly inhibited the migration distance of hPEC cells within 48h(P<0.01).The immunoprecipitation experiment showed that nintedanib modulated the TGFBR2 protein’s response to TGF-βindependently of miR-23b-3p.Both nintedanib and transfection with miR-23b-3p mimic significantly inhibited the expression levels of phosphorylated Smad2,snail homolog 1(Drosophila,SNAIL),and SNAI2(also known as SLUG,snail family transcriptional repressor 2)proteins.CONCLUSION:Nintedanib is found to modulate the miR-23b-3p/TGFBR2/Smad2 pathway,suggesting a novel antifibrotic mechanism.These findings collectively highlight nintedanib’s therapeutic potential in managing pterygium,marking a significant step toward non-surgical treatment options.Nintedanib may offer a targeted pharmacological treatment that could complement or reduce the need for surgical interventions.展开更多
To investigate the targets and mechanism of Hedysarum Multijugum Maxim(HMM)in treatment of bladder cancer(BC).Based on Traditional Chinese Medicine Systems Pharmacology(TCMSP)and gene databases,active substances and p...To investigate the targets and mechanism of Hedysarum Multijugum Maxim(HMM)in treatment of bladder cancer(BC).Based on Traditional Chinese Medicine Systems Pharmacology(TCMSP)and gene databases,active substances and potential targets of HMM were screened,and the HMM-active substances-targets-BC(HATB)regulatory network and PPI network were constructed.Hub targets were screened by Cytoscape.The main active substances and Hub targets were molecularly docked with AutoDock and visualized by PyMOL.12 Hub targets were screened.Molecular docking showed that active substances mainly acted on MAPK14,MAPK1 and CCND1.The bindings of calycosin to MAPK14,formononetin to MAPK14,and calycosin to CCND1 were stable.展开更多
Helicoverpa armigera is one of the most destructive agricultural pests worldwide,noted for its wide host range,high fecundity,and rapid development of resistance to synthetic insecticides.To address this threat,sustai...Helicoverpa armigera is one of the most destructive agricultural pests worldwide,noted for its wide host range,high fecundity,and rapid development of resistance to synthetic insecticides.To address this threat,sustainable botanical alternatives are urgently needed.In this study,Nerium oleander,a toxic ornamental plant rich in secondary metabolites,was evaluated as a potential botanical insecticide through in silico assays.Methanolic extracts were subjected to phytochemical screening,confirming the presence of alkaloids,saponins,cardiac glycosides,coumarins,and terpenoids.Gas Chromatography-Mass Spectrometry(GC-MS)profiling identified 20 major compounds,including terpenoids,fatty acids,sterols,and phenolics,with 2-methoxy-4-vinylphenol(2.7%),neophytadiene(1.7%),and phytol(0.9%)among the key constituents.Cytochrome P450,a central detoxification enzyme in insects,was chosen as the molecular target.Docking analysis revealed strong binding affinities,with phytol(−6.92 kcal/mol,Ki 8.12μM),neophytadiene(−6.43 kcal/mol,Ki 14.57μM),and 2-methoxy-4-vinylphenol(5.87 kcal/mol,Ki 45.13μM)demonstrating significant inhibitory potential.These findings indicate that N.oleander metabolites may disrupt detoxification pathways in H.armigera,providing a mechanistic basis for their insecticidal action and supporting the plant's promise as a candidate for integrated pest management.展开更多
Bioinformatics,an interdisciplinary field that integrates computer science,biology,information technology,and statistics,plays a pivotal role in analyzing and interpreting biological data.It has become an indispensabl...Bioinformatics,an interdisciplinary field that integrates computer science,biology,information technology,and statistics,plays a pivotal role in analyzing and interpreting biological data.It has become an indispensable tool in the design and discovery of novel drugs by facilitating the analysis of biological datasets and aiding in the identification of potential therapeutic targets.With the rise of antibiotic resistance among bacterial species,the demand for new drug development has intensified.However,the process of drug discovery remains labor-intensive,costly,and time-consuming.The identification of new drugs involves multiple critical stages,including target identification,structural analysis of the target protein,selection of potential drug candidates,safety and efficacy assessments,drug optimization,and ultimately,validation.Bioinformatics contributes significantly to each of these phases.For instance,through the analysis of protein sequences and genetic data,researchers can pinpoint potential drug targets.Once a target protein is identified,bioinformatics tools enable detailed structural analysis of the protein.Upon locating the potential ligand-binding site,large compound databases can be screened to discover viable drug candidates.Simulations further aid in examining the interaction between the target protein and biomolecules,providing valuable insights into the drug’s safety and efficacy.Moreover,bioinformatics-driven drug optimization helps improve both safety and effectiveness.Recent advances,such as pharmacophore modeling and molecular docking techniques,have accelerated the screening process,narrowing thousands of candidate molecules down to a select few with promising therapeutic potential.In this study,bioinformatics was leveraged within the framework of network pharmacology to design and discover new drugs.展开更多
基金supported by the Jilin Science and Technology Development Talent Special Project,Nos.20240601086RC,23JQ08(all to ZH)YDZJ202502CXJD077+1 种基金JLARS-2025-0802-09YDZJ202501ZYTS706.
文摘Population aging is one of the common challenges in the current world.As people age,the body’s tissues including cells,and molecules inevitably degrade,and their functions gradually decline,causing various age-related diseases like Alzheimer’s disease,osteoporosis,low immunity,glucose and lipid metabolism disorders,and cardiovascular diseases.With the continuous increase of the elderly population,the pressure on the medical industry is increasing.To lower the burden on the medical industry and increase the average age of the elderly,it is vital to explore effective anti-aging materials.Ginseng Radix et Rhizoma(Renshen),as a traditional and precious Chinese medicinal herb,is known as the“king of all herbs”.It is famous for its effects of“tonifying Qi,restoring pulse”(helping with the generation of Qi(the fundamental,vital energy that continuously flows within the body)and the circulation of blood)and strengthening the body,nourishing the spleen and lungs,generating fluids and nourishing blood,calming the mind and improving intelligence.Recently,its anti-aging effect has received increasing attention from modern scientific research.This study summarizes the pharmacological effects of the main active ingredients of Renshen(ginsenosides,polysaccharides,etc.)on resisting aging,including preventing neuroaging,suppressing skin aging,mitigating ovarian aging,inhibiting osteoporosis and arthritis,enhancing the immune system of the elderly,protecting the cardiovascular system,resisting aging-induced fatigue and exerting the anti-tumor effects.Through network pharmacology and molecular docking,the anti-aging active ingredients of Renshen were screened,and the key targets and pathways of anti-aging active ingredients in Renshen were determined.Using network pharmacology,totally 106 drug targets and 3,479 disease targets were screened,and 79 common targets between aging and Renshen were identified.Three core targets were identified in the PPI network,including TNF,AKT1,and IL-1β.Molecular docking was used to obtain further verification.This study emphasizes the potential of Renshen as a source of anti-aging activity,which can be developed into a novel drug for the treatment of age-related diseases.
基金Natural Science Foundation of Shandong Province,No.ZR2020QH185Scientific Research Nurturing Fund of The First Affiliated Hospital of Shandong First Medical University&Shandong Provincial Qianfoshan Hospital,No.QYPY2020NSFC0803+2 种基金Guangxi Zhuang Autonomous Region Health Commission Scientific Research Project,No.Z-A20220415Guangxi Medical University Teacher Teaching Ability Development Project,No.2022JFA02Guangxi Medical University Undergraduate Education and Teaching Reform Project,No.2023Y05.
文摘BACKGROUND Colorectal cancer(CRC)is the third most common cancer globally,causing over 900000 deaths annually.Risk factors include aging,diet,obesity,sedentary lifestyle,tobacco use,genetic predisposition,and inflammatory bowel disease.Despite current treatments,survival rates for advanced CRC remain low,highlighting the need for better therapeutic strategies.AIM To evaluate both the clinical significance and the pathological implications of the Kinesin family member 14(KIF14)expression within CRC specimens.Additionally,this study aims to investigate the interaction between nitidine chloride(NC)and KIF14,considering their potential as therapeutic targets.METHODS The expression of the KIF14 protein in CRC was analyzed using immunohistochemical staining.The integration of multicenter high-throughput data facilitated the calculation of the standardized mean difference(SMD)for KIF14 mRNA levels.The assessment of clinical and pathological impact was enhanced by analyzing combined receiver operating characteristic curves,along with measures of sensitivity,specificity,and likelihood ratios.Additionally,clustered regularly interspaced short palindromic repeats knockout screening for cell growth and single-cell sequencing were employed to validate the significance of KIF14 expression in CRC.Survival analysis established the prognostic value of KIF14 in CRC.The molecular mechanism of NC against CRC was elucidated through whole-genome sequencing and enrichment analysis,and molecular docking was utilized to explore the targeting affinity between NC and KIF14.RESULTS KIF14 was highly expressed in 208 CRC patients.Data from 17 platforms involving 2436 CRC samples and 1320 noncancerous colorectal tissue controls indicated that KIF14 expression was significantly higher in CRC samples,with an SMD of 1.92(95%CI:1.49-2.35).The area under the curve was 0.94(95%CI:0.92-0.96),with a sensitivity of 0.85(95%CI:0.78-0.90)and a specificity of 0.90(95%CI:0.85-0.93).The positive and negative likelihood ratios were 8.38(95%CI:5.39-13.02)and 0.17(95%CI:0.11-0.26),respectively.At the single-cell level,significant overexpression of KIF14 was observed in CRC cells(P<0.001),with 35 CRC cell lines dependent on KIF14 for growth.The K-M plots demonstrated that KIF14 possesses prognostic value in CRC patients within the GSE71187 and GSE103679 datasets(P<0.05).Binding energy calculations indicated that KIF14 is a potential target for NC(binding energy:10.3 kcal/mol).CONCLUSION KIF14 promotes the growth of CRC cells and acts as an oncogenic factor,potentially serving as a therapeutic target for NC in the treatment of CRC.
基金supported by the National Natural Science Foundation of China(Nos.42207320 and 22076214).
文摘Ethiprole is widely used as a second-generation phenyl pyrazole insecticide.Previous studies indicated that ethiprole exhibited thyroid toxicity while two main metabolites(ethiprole sulfone(M1)and ethiprole sulfide(M2))of ethiprole showed higher acute toxicity than ethiprole.Therefore,assessing the thyroid toxicity of its metabolites is crucial for safety assessment.In this study,the thyroid toxicity and underlying mechanisms of ethiprole and its metabolites were explored using in silico,in vitro,and in vivo assays,with the aim of conducting a comparative study on thyroid toxicity.Molecular docking analysis showed that ethiprole,M1 and M2 could bind with thyroid receptor isoforms and exhibited higher binding affinity compared to 3,3,5-triiodothyronine(T3).GH3 cell proliferation assays revealed that ethiprole,M1 and M2 all served as thyroid hormone antagonists to hinder the T3-induced cell proliferation.Using the zebrafish model,we further investigated that exposure to ethiprole,M1,and M2 disrupted thyroid hormone levels and the transcriptional expressions of hypothalamus-pituitary-thyroid(HPT)axis-related genes.Ethiprole induced thyroid disrupting effects by binding with the thyroid receptor beta,M1 mainly through binding with the corticotropin releasing factor receptor-1,and M2 exposure firstly inhibited the thyroid peroxidase enzyme activity.M2 showed the highest developmental toxicity and thyroid disrupting effects,which significantly reducing hatching rates,increasing deformity rates,exhibiting the lowest lethal concentration 50 value and showing the most serious transcription inhibitory effects on the HPT axis.This study suggested the risk assessment of metabolites should be considered in assessing potential environmental risk of ethiprole.
基金Supported by Natural Science Foundation of Shandong Province,No.ZR2020QH185Scientific Research Nurturing Fund of the First Affiliated Hospital of Shandong First Medical University&Shandong Provincial Qianfoshan Hospital,No.QYPY2020NSFC0803Guangxi Zhuang Autonomous Region Health Commission Scientific Research Project,No.Z20210442.
文摘BACKGROUND The stearoyl-coenzyme A desaturase(SCD)gene influences colorectal cancer(CRC)pathogenesis,with its expression linked to tumor cell survival and resistance,necessitating further investigation into its role in CRC.AIM To explore the clinical and pathological significance of SCD expression in CRC tissues and to evaluate the affinity between nitidine chloride(NC)and SCD as a target.METHODS Multi-center high-throughput data related to CRC were integrated to calculate the standardized mean difference of SCD mRNA expression levels.Immunohistochemical staining results,Clustered Regularly Interspaced Short Palindromic Repeats knockout screening results of cell growth,and single-cell sequencing were employed to verify the significance of SCD expression in CRC.The clinical and pathological significance of SCD was assessed using pooled receiver operating characteristic curves,sensitivity,specificity,and likelihood ratios.The molecular mechanism of NC against CRC was clarified using the SwissTarget Prediction and functional enrichment,and molecular docking techniques were utilized to explore the targeting affinity between NC and SCD.RESULTS Data from 18 platforms,including 2482 CRC samples and 1334 non-cancerous colorectal tissue controls.SCD expression was significantly upregulated in CRC,with a standardized mean difference of 2.05[95%confidence interval(CI):1.69-2.41].The area under the pooled receiver operating characteristic curve was 0.95(95%CI:0.92-0.96),with a sensitivity of 0.86(95%CI:0.81-0.90)and a specificity of 0.90(95%CI:0.87-0.93).Positive and negative likelihood ratios were 9.02(95%CI:6.49-12.51)and 0.15(95%CI:0.10-0.22),respectively.High SCD protein expression was noted in 208 CRC patients,significantly associated with vascular invasion(P<0.001).At the singlecell level,SCD was significantly overexpressed in CRC cells(P<0.001).A total of 33 CRC cell lines depended on SCD for growth.The potential mechanism of NC against CRC might involve modulation of the cell cycle,positioning SCD as a potential target for NC.CONCLUSION SCD promotes CRC cell growth and thus acts as an oncogenic factor,making it a potential therapeutic target for NC in CRC treatment.
文摘Background:Gastric cancer(GC)remains a global health burden and is often characterized by heterogeneous molecular profiles and resistance to conventional therapies.The phosphoinositide 3-kinase and PI3K and Janus kinase(JAK)signal transducer and activator of transcription(JAK-STAT)pathways play pivotal roles in GC progression,making them attractive targets for therapeutic interventions.Methods:This study applied a computational and molecular dynamics simulation approach to identify and characterize SBL-JP-0004 as a potential dual inhibitor of JAK2 and PI3KCD kinases.KATOIII and SNU-5 GC cells were used for in vitro evaluation.Results:SBL-JP-0004 exhibited a robust binding affinity for JAK2 and PI3KCD kinases,as evidenced by molecular docking scores and molecular dynamics simulations.Binding interactions and Gibbs binding free energy estimates confirmed stable and favorable interactions with target proteins.SBL-JP-0004 displayed an half-maximal inhibitory concentration(IC_(50))value of 118.9 nM against JAK2 kinase and 200.9 nM against PI3KCD enzymes.SBL-JP-0004 exhibited potent inhibition of cell proliferation in KATOIII and SNU-5 cells,with half-maximal growth inhibitory concentration(GI50)values of 250.8 and 516.3 nM,respectively.A significant elevation in the early phase apoptosis(28.53%in KATOIII cells and 26.85%in SNU-5 cells)and late phase apoptosis(17.37%in KATOIII cells and 10.05%in SNU-5 cells)were observed with SBL-JP-0004 treatment compared to 2.1%and 2.83%in their respective controls.Conclusion:The results highlight SBL-JP-0004 as a promising dual inhibitor targeting JAK2 and PI3KCD kinases for treating GC and warrant further preclinical and clinical investigations to validate its utility in clinical settings.
文摘Background:Pistacia chinensis Bunge has been traditionally used to manage various conditions,including asthma,pain,inflammation,hepatoprotection,and diabetes.The study was conducted to investigate the antioxidant and anti-lipoxygenase(LOX)properties of the isolated compound 2-(3,4-dihydroxyphenyl)-5,7-dihydroxy-4H-chromen-4-one from Pistacia chinensis.Methods:LOX assay and antioxidant activity using 2,2-diphenyl-1-picrylhydrazyl(DPPH)assay were performed.Molecular docking studies were conducted using a molecular operating environment.Results:The LOX assay revealed significant inhibitory effects at 0.2µM concentration,with an IC50 value of 37.80µM.The antioxidant effect demonstrated dose-dependency across 5 to 100µg/mL concentrations,reaching 93.09%at 100µg/mL,comparable to ascorbic acid’s 95.43%effect.Molecular docking studies highlighted strong interactions with the lipoxygenase enzyme,presenting an excellent docking score of-10.98 kcal/mol.Conclusion:These findings provide valuable insights into Pistacia chinensis’chemical components and biological effects,reinforcing its traditional medicinal applications.
文摘The anti-hair loss mechanism of Aquilaria sinensis leaf extract(ASE)has been studied by using metabolomics and network pharmacology.Metabolomics was utilized to comprehensively identify the active constituents of ASE,and the network pharmacology was used to elucidate their anti-hair loss mechanism,which was verified by molecular docking technology.572 active compounds were identified from the ASE by metabolomics methods,where there are 1447 corresponding targets and 492 targets related to hair loss,totaling 88 targets.20 core active substances were identified by constructing a network between common targets and active substances,which include vanillic acid,chorionic acid,caffeic acid and apigenin.The five key targets of TNF,TP53,IL6,PPARG,and EGFR were screened out by the PPI network analysis on 88 common targets.The GO and KEGG pathway enrichment analysis showed that the inflammation,hormone balance,cell growth,proliferation,apoptosis,and oxidative stress are involved.Molecular docking studies have confirmed the high binding affinity between core active compounds and key targets.The drug similarity assessment on these core compounds suggested that they have the potential to be used as potential hair loss treatment drugs.This study elucidates the complex molecular mechanism of ASE in treating hair loss,and provides a reference for the future applications in hair care products.
文摘Objective To evaluate the protective effect of Lonicerae Japonicae Flos(LJF)extract against doxorubicin(DOX)-induced cardiotoxicity(DIC)and explore the possible mechanisms.Methods Network pharmacology,bioinformatics analysis and molecular docking were used to predict the targets of the core components of LJF.In a mouse model of DOX-induced myocardial injury,the protective effects of different doses of LJF extract were evaluated and the underlying mechanisms were explored by detecting the changes in mouse myocardial functions,myocardial enzymes,myocardial pathologies,and the expressions of inflammatory factors and pyroptosis-related proteins.Results The 10 core ingredients of LJF showed strong binding to AKT,EGFR,and GSK3β.In the animal experiment,the DOX-treated mice,compared with the sham-treated mice,had significantly decreased cardiac output,stroke volume,left ventricular ejection fraction,left ventricular fraction shorting,elevated serum levels of CK-MB and LDH,increased myocardial expressions of IL-18 and IL-1β,obvious myocardial damage,increased expression levels of NLRP3,caspase-1,GSDMD and GSDMD-N,and reduced expressions of EGFR,p-AKT and p-GSK3βproteins in the myocardial tissues.LJF treatment obviously improved myocardial function,decreased myocardial expressions of IL-18,IL-1β,NLRP3,caspase-1,GSDMD and GSDMD-N proteins,and increased the expressions EGFR,p-AKT and p-GSK3βproteins in DOX-treated mice.Conclusion LJF extract alleviates DOX-induced myocardial injury in mice possibly by reducing myocardial inflammation and pyroptosis via targeting EGFR,AKT and GSK3βto regulate the ErbB signaling pathway.
文摘The Solanum genus is known for its diverse bioactive compounds,yet its diuretic potential remains understudied.This research commenced with an analysis of polyphenol and flavonoid content in Solanum elaeagnifolium leaf extract(SEFE)using colorimetric techniques,followed by HPLC-DAD to delineate its chemical composition.The aqueous extract revealed prominent constituents:naringin(12.38%),quercetin 3-O-B-D-Glucoside(27.25%),and flavone(15.26%).A 15-day study on normal rats investigated the diuretic potential of SEFE at repeated doses.SEFE significantly increased urine volume and urinary sodium/potassium levels without inducing hypokalaemia,contrasting with furosemide,a standard diuretic that induced hypokalaemia.Conversely,furosemide,a standard diuretic,increased urinary sodium and potassium while inducing hypokalaemia.It was evident that the diuretic effect of S.elaeagnifolium is dose-dependent,with a dosage of 500 mg/kg body weight exerting a more potent diuretic effect compared to furosemide.The diuretic activity of this plant was supported by an in silico study of the diuretic effect.The findings demonstrate how S.elaeagnifolium leaves have a potent diuretic impact on rats.However,more in-depth studies are needed to examine the following aspects:identifying the specific molecules responsible for the diuretic effect,understanding the molecular and cellular mechanisms underlying this activity,and assessing the long-term safety and clinical efficacy of this plant in different contexts.
基金supported by the National Natural Science Foundation of China(32360564)the Guangxi Science and Technology Major Project(2021AA17011)the Nanning Government Specially-invited Expert Program,and Guangxi University Natural Science and Technological Innovation Development Multiplication Plan Project(2022BZRC010).
文摘Trehalose is an autophagy-promoting disaccharide,which can improve and delay chronic diseases like neurodegenerative diseases and atherosclerosis,but its bioavailability is severely restricted by endogenous trehalase in mammals.Trehalase inhibitor is a promising and effective way to enhance trehalose bioavailability by preventing trehalose from hydrolyzing.However,previously reported trehalase inhibitors still face safety of long-term use and promiscuous inhibition on intestinal glycosidases.This study carried out a high-throughput virtual screening through molecular pool-based molecular docking combined with in vitro inhibition experiments to screen trehalase inhibitors naturally derived from foods.Out of 1769 small molecules,which include 115 analogs of trehalose,natural monosaccharides,disaccharides,trisaccharides,imidazoles and their derivatives,as well as 20 natural amino acids and their 400 dipeptides,isomaltose,α-isomaltulose,and isomaltitol exhibited the best inhibitory activities,beyond as traditional sweetener and prebiotic.Best of all,isomaltose showed the half maximal inhibitory concentration(IC50)and inhibition constant(Ki)values on trehalase of 5.59 and(2.1760±0.3431)mmol/L,respectively.Moreover,isomaltose was resistant to the simulated digestive environment and did not affect intestinal glycosidases such asα-glucosidase and glucoamylase,making it a reliable edible candidate for a trehalase inhibitor.This study provides new insights into the virtual screening-based identification of new food-derived trehalase inhibitors for enhanced integrity and bioavailability of orally administered trehalose,especially repurposing a prebiotic for another new use as trehalase inhibitor.
基金funded by King Saud University,Riyadh,Saudi Arabia,Project Number(RSPD2025R709).
文摘Objective:To examine the effect of the methanolic extract of Salacia fruticosa in a zebrafish model of scopolamine-induced Alzheimer’s disease.Methods:High-resolution liquid chromatography-mass spectrometry was used to characterize the phytochemical constituents of Salacia fruticosa methanolic extract.The drug-likeness of these compounds was determined via the DruLiTo tool,and their acetylcholinesterase(AChE)binding affinities were studied by molecular docking.In in vivo studies,adult zebrafish were treated with 3.125,6.25,and 12.5 mg/L of the extract for seven days and then immersed in scopolamine(100μM/L)to induce cognitive deficits.T-maze and novel object recognition tests were used for behavioral studies.In addition,the activities of AChE,antioxidant enzymes,and myeloperoxidase were determined in brain tissue of zebrafish.Results:High-resolution liquid chromatography-mass spectrometry revealed that 40 phytoconstituents were present in the methanolic extract of Salacia fruticosa,and 27 compounds met Lipinski's rule of five,indicating good drug-likeness.Some compounds such as stylopine,p-coumaroylagmatine,and(-)-heliannuol E,demonstrated high AChE binding affinity.Moreover,pretreatment with the extract significantly mitigated zebrafish cognitive decline,as indicated by increased time spent at the novel object in novel object recognition test,as well as increased time spent and decreased latency in the green arm(P<0.001).The extract also markedly lowered malondialdehyde and myeloperoxidase levels and AChE activity,and enhanced glutathione peroxidase and superoxide dismutase activities(P<0.001)in zebrafish with scopolamine-induced Alzheimer’s disease.Histopathological studies revealed that Salacia fruticosa extract ameliorated scopolamine-induced abnormalities in neuronal cell morphology.Conclusions:Pretreatment with the methanolic extract of Salacia fruticosa reduces cognitive impairment,enhances antioxidants,and attenuates oxidative stress,highlighting its potential as a preventive agent for Alzheimer’s disease.
基金supported by the BASF Open Innovative Platform(Project OI39).
文摘Phytophthora infestans control is a long-standing problem that has caused ongoing difficulties and brought limited success for over a century.Traditional methods,such as fungicides,have drawbacks including high cost,restrictions on organic farming,potential risks to the environment and human health,and the development of resistant strains.In this study,we employed cutting-edge computer-based techniques,including Quantitative Structure-Activity Relationship(QSAR)modeling and molecular docking simulations,to uncover new fungicidal compounds and gain insights into their specific mechanisms of action against P.infestans.QSAR modeling on the number of compounds tested as P.infestans inhibitors was performed using an interactive OCHEM web platform.The predictive ability of the developed classification models had a balanced accuracy(BA)of 77–85%for the training set and BA?89–93%for the validation external test set.During the in vitro testing against P.infestans,thirteen synthesized 2-oxoimidazolidine-4-sulfonamides demonstrated inhibition rates,ranging from 23.6%to 87.4%.The fungicidal potential of six of these fungicides ranged from 79.3%to 87.4%,which is comparable to the activity of known fungicides.Acute toxicity results using the well-known aquatic marker Daphnia magna showed that the most active sulfonamides 3d,3f,3h,3j,3k,and 3l,with LC_(50) values ranging from 13.7 to 52.9 mg/L,are low-toxicity compounds.The molecular docking results demonstrated a potential mechanism of the antifungal action of the studied 2-oxoimidazolidin-4-sulfonamide derivatives via the inhibition of fungal CYP51,a sterol biosynthesis enzyme.
基金Supported by the Ningbo Natural Science Foundation(No.2023J212)Zhejiang Medical and Health Technology Program(No.2023KY1141).
文摘AIM:To investigate the effects of nintedanib on epithelial-mesenchymal transition(EMT)in cells derived from pterygium,aiming to explore its potential as a pharmacological intervention for pterygium treatment.METHODS:Primary human pterygium epithelial cells(hPEC)and human conjunctival epithelial(hCJE)cells were isolated from patients,cultured,and characterized.The impact of nintedanib on transforming growth factor beta(TGF-β)-induced EMT was assessed by examining the expression of EMT markers such as vimentin and E-cadherin.Additionally,the modulation of the miR-23b-3p/transforming growth factor beta receptor 2(TGFBR2)/Smad2 pathway by nintedanib was investigated to elucidate its potential antifibrotic mechanism.RESULTS:The expression of miR-23b-3p gene in hCJE cells was significantly higher than that in hPEC cells.Nintedanib effectively mitigated TGF-β-induced EMT in cells derived from pterygium,as evidenced by the downregulation of vimentin and upregulation of E-cadherin.When the nintedanib concentration exceeded 1μmol/L,it significantly suppressed the proliferation of hPEC cells and significantly inhibited the migration distance of hPEC cells within 48h(P<0.01).The immunoprecipitation experiment showed that nintedanib modulated the TGFBR2 protein’s response to TGF-βindependently of miR-23b-3p.Both nintedanib and transfection with miR-23b-3p mimic significantly inhibited the expression levels of phosphorylated Smad2,snail homolog 1(Drosophila,SNAIL),and SNAI2(also known as SLUG,snail family transcriptional repressor 2)proteins.CONCLUSION:Nintedanib is found to modulate the miR-23b-3p/TGFBR2/Smad2 pathway,suggesting a novel antifibrotic mechanism.These findings collectively highlight nintedanib’s therapeutic potential in managing pterygium,marking a significant step toward non-surgical treatment options.Nintedanib may offer a targeted pharmacological treatment that could complement or reduce the need for surgical interventions.
基金2025 Open Experimental Special Fund of Beijing Institute of Technology, “Applications and Practices of R Language in Bioinformatics”。
文摘To investigate the targets and mechanism of Hedysarum Multijugum Maxim(HMM)in treatment of bladder cancer(BC).Based on Traditional Chinese Medicine Systems Pharmacology(TCMSP)and gene databases,active substances and potential targets of HMM were screened,and the HMM-active substances-targets-BC(HATB)regulatory network and PPI network were constructed.Hub targets were screened by Cytoscape.The main active substances and Hub targets were molecularly docked with AutoDock and visualized by PyMOL.12 Hub targets were screened.Molecular docking showed that active substances mainly acted on MAPK14,MAPK1 and CCND1.The bindings of calycosin to MAPK14,formononetin to MAPK14,and calycosin to CCND1 were stable.
文摘Helicoverpa armigera is one of the most destructive agricultural pests worldwide,noted for its wide host range,high fecundity,and rapid development of resistance to synthetic insecticides.To address this threat,sustainable botanical alternatives are urgently needed.In this study,Nerium oleander,a toxic ornamental plant rich in secondary metabolites,was evaluated as a potential botanical insecticide through in silico assays.Methanolic extracts were subjected to phytochemical screening,confirming the presence of alkaloids,saponins,cardiac glycosides,coumarins,and terpenoids.Gas Chromatography-Mass Spectrometry(GC-MS)profiling identified 20 major compounds,including terpenoids,fatty acids,sterols,and phenolics,with 2-methoxy-4-vinylphenol(2.7%),neophytadiene(1.7%),and phytol(0.9%)among the key constituents.Cytochrome P450,a central detoxification enzyme in insects,was chosen as the molecular target.Docking analysis revealed strong binding affinities,with phytol(−6.92 kcal/mol,Ki 8.12μM),neophytadiene(−6.43 kcal/mol,Ki 14.57μM),and 2-methoxy-4-vinylphenol(5.87 kcal/mol,Ki 45.13μM)demonstrating significant inhibitory potential.These findings indicate that N.oleander metabolites may disrupt detoxification pathways in H.armigera,providing a mechanistic basis for their insecticidal action and supporting the plant's promise as a candidate for integrated pest management.
文摘Bioinformatics,an interdisciplinary field that integrates computer science,biology,information technology,and statistics,plays a pivotal role in analyzing and interpreting biological data.It has become an indispensable tool in the design and discovery of novel drugs by facilitating the analysis of biological datasets and aiding in the identification of potential therapeutic targets.With the rise of antibiotic resistance among bacterial species,the demand for new drug development has intensified.However,the process of drug discovery remains labor-intensive,costly,and time-consuming.The identification of new drugs involves multiple critical stages,including target identification,structural analysis of the target protein,selection of potential drug candidates,safety and efficacy assessments,drug optimization,and ultimately,validation.Bioinformatics contributes significantly to each of these phases.For instance,through the analysis of protein sequences and genetic data,researchers can pinpoint potential drug targets.Once a target protein is identified,bioinformatics tools enable detailed structural analysis of the protein.Upon locating the potential ligand-binding site,large compound databases can be screened to discover viable drug candidates.Simulations further aid in examining the interaction between the target protein and biomolecules,providing valuable insights into the drug’s safety and efficacy.Moreover,bioinformatics-driven drug optimization helps improve both safety and effectiveness.Recent advances,such as pharmacophore modeling and molecular docking techniques,have accelerated the screening process,narrowing thousands of candidate molecules down to a select few with promising therapeutic potential.In this study,bioinformatics was leveraged within the framework of network pharmacology to design and discover new drugs.
