We investigated whether Panax notoginseng saponin (PNS-R1) attenuates allergic rhinitis (AR) through AMPK/Drp1-mediated mitochondrial fission. AR model was established in mice by Ovalbumin (OVA). In vitro, human nasal epithelial cells (HNEpCs) were stimulated using recombinant human interleukin 13 (IL-13). PNS-R1 was administrated in vivo and in vitro. Then, HE staining of nasal tissue, ELISA detection of immunoglobulin E (IgE) and proinflammatory cytokine levels in serum and nasal lavage fluid, flow cytometry analysis of Th1/Th2 ratio and apoptosis, TUNEL staining, Western blot, detection of reactive oxygen species (ROS) and mitochondrial ROS, immunofluorescence analysis of Tom20 and mitochondrial fission protein Drp1 co-localization, and mitochondrial membrane potential detection, were performed. PNS-R1 attenuated allergic symptoms in AR mice, decreased OVA-specific IgE, IL-4, IL-6, IL-8, IL-13, and TNF-α levels, and restored the Th1/Th2 imbalance. Meanwhile, we found that PNS-R1 treatment significantly reduced apoptosis, ROS production, and co-localization of Tom20 and Drp1 in the nasal epithelium of AR mice. In vitro, we found that PNS-R1 upregulated mitochondrial membrane potential and reduced ROS and mitochondrial ROS production as well as Cleaved-caspase-3/9, Bax, Cyt-c, Apaf-1 expression and mitochondrial fission. Mechanistically, we found that PNS-R1 downregulated Drp1 phosphorylation (Ser 616) and Drp1 translocation in an AMPK-dependent manner, promoted MFN2 expression, and reduced TXNIP, NLRP3, Caspase-1, and IL-1β expression. PNS-R1 may protect mitochondrial integrity by inhibiting AMPK/Drp1 and TXNIP/NLRP3 signaling pathway, thereby alleviating AR symptoms in mice. PNS-R1 may have great potential as a therapeutic agent for AR.
目的 研究玫瑰花总黄酮(total flavonoids from Rosa rugosa,TFR)对大鼠脑缺血/再灌注损伤(cerebral ischemia reperfusion injury,CIRI)的影响,探讨TFR是否通过磷脂酰肌醇-3-激酶/蛋白激酶B(phosphoinositide 3-kinase/protein ki-nase B,PI3K/AKT)信号通路和内质网应激(endoplasmic re-ticulum stress,ERS)途径调控神经细胞凋亡.方法 将SD大鼠随机分成假手术组、模型组、TFR低、中、高剂量组(50、100、200 mg·kg-1·d-1)组,灌胃7 d,末次给药1 h后线栓法制备大脑中动脉阻塞/再灌注(middle cerebral artery occlu-sion/reperfusion,MCAO/R)模型.24 h后检测大鼠神经行为学变化、脑梗死面积、脑组织含水量;HE和尼氏染色观察病理相关指标;TUNEL染色观察神经细胞凋亡情况;Western blot检测Bcl-2、Bax、cleaved Caspase-3、PI3K、p-PI3K、AKT、p-AKT、GRP78、CHOP和Caspase-12的蛋白表达水平.结果 与MCAO/R组比,中、高剂量TFR给药组大鼠神经行为学功能改善,脑梗死面积下降,脑水肿程度降低,脑皮质区病理损伤减轻,神经细胞凋亡率明显减少,抗凋亡蛋白Bcl-2表达升高,促凋亡蛋白Bax和cleaved Caspase-3表达降低,p-PI3K/PI3K、p-AKT/AKT表达升高.ERS相关蛋白GRP78、CHOP、Caspase-12表达降低.结论 TFR可通过调控PI3K/AKT信号通路和ERS途径抑制神经细胞凋亡,从而发挥对CIRI大鼠的保护作用.
Aim To observe the effect of corticotropin-releasing factor(CRF)-expressing neurons on presym-pathetic neurons in hypothalamic paraventricular nucle-us(PVN)of normotensive Wistar Kyoto(WKY)rats or spontaneously hypertensive rats(SHR),and to elu-cidate the underlying neuronal circuit mechanism of central sympathetic hyperexcitability.Methods The expression levels of CRF protein in WKY rats and SHR PVN were determined by Western blot.Meanwhile,the WKY and SHR PVN CRF-expressing neurons and presympathetic neurons were observed by immunofluo-rescent staining.Adult WKY rats and SHR were used in this study.By microinjection of Cre-dependent ade-no-associated viruses(AAV)that specifically recog-nized the CRF promoter and AAV of chemogenetics in-to the PVN,CRF-expressing neurons expressed desig-ner receptors exclusively activated by designer drugs(DREADDs).Human M3 muscarinic DREADD cou-pled to Gq receptor(hM3Dq)was specifically ex-pressed in PVN CRF-expressing neurons in WKY rats,while human M4 muscarinic DREADD coupled to Gi receptor(hM4Di)was specifically expressed in PVN CRF-expressing neurons in SHR.Clozapine-N-oxide(CNO),as a designer ligand,would couple to excita-tory hM3Dq or inhibitory hM4Di to regulate the excita-bility of PVN CRF-expressing neurons.Then the PVN presympathetic neurons were retrogradely labeled by microinjection of fluosecent tracer into the intermedio-lateral column(IML)of spinal cord.Lastly,whole cell patch clamp was used to determine the effect of CNO(10 μmol·L-1)on spontaneous excitatory postsynaptic currents(sEPSCs)and current-evoked firing of PVN presympathtic neurons of WKY rats and SHR.Results The expression of CRF protein in the PVN of SHR was significantly higher than that of WKY rats,and the activity and number of CRF-expressing neurons in the PVN of SHR were increased.PVN CRF-expressing neurons were expressed with chemoge-netic DREADDs and PVN presympathetic neurons were retrogradely labeled with fluorescent tracer in WKY rats and SHR.In SHR expressed with chemogenetic inhibi-tory hM4Di-mCherry of PVN CRF-expressing neurons,bath application of CNO to the brain slices resulted in a significant decrease in sEPSCs frequency,but no change in their amplitude of labeled PVN presympa-thetic neurons.In contrast,in WKY rats expressed with excitatory hM3Dq-eGFP of PVN CRF-expressing neurons,CNO had no obvious effect on the sEPSCs frequency and amplitude in PVN presympathetic neu-rons.Furthermore,bath application of CNO had no significant effect on current-evoked firing of PVN pres-ympathetic neurons of either WKY rats with hM3Dq-eGFP expression in CRF neurons or SHR with hM4Di-mCherry expression in CRF neurons.Conclusions The activity and number of PVN CRF-expressing neu-rons are increased in SHR,and CRF-expressing neu-rons enhance the excitability of presympathetic neu-rons,which acts as a regulatory neuronal microcircuit between CRF neurons and presympathetic neurons in the PVN.
Mother-to-child transmission of hepatitis B virus(HBV)is one of the main ways of transmission and the main cause of chronic hepatitis B after infection.Therefore,preven-ting mother-to-child transmission of HBV is particularly impor-tant in reducing the incidence of chronic hepatitis B.Currently,nucleoside(acid)analoids(Nas)used for mother-to-child blocking of HBV include lamivudine(LAM),tibivudine(LdT)and tenofovir fumarate(TDF).Propofol tenofovir fumarate(TAF)has also been used in pregnant chronic hepatitis B pa-tients.This paper summarizes the efficacy,safety and antiviral treatment indications and termination time of the above-men-tioned drugs in mother-to-child preventing to provide suggestions for the selection and rational application of mother-to-child pre-venting Nas.
Aim To study the effect of baicalin on the activation of NLRP3 inflammasomes in human fibro-blast like synoviocytes of rheumatoid arthritis(HFLS-RA)and its mechanism.Methods To confirm that baicalin alleviated the activation of NLRP3 inflamma-some in HFLS-RA,immunofluorescence was used to observe the expression of NLRP3 before and after ba-icalin treatment.Western blot was used to detect the protein expression of p-PI3K,p-Akt,NF-κB p65,NL-RP3,ASC and caspase-1 after baicalin treatment for 48 h,and ELISA was employed to detect the contents of IL-1 and IL-18 in the supernatents.In order to ex-plore the mechanism of baicalin alleviating the activa-tion of NLRP3 inflammasome,double luciferin and Westen blot analysis were applied to verify the corre-sponding relationship between let-7i-3p and PIK3CA.RT-qPCR was utilized to determine the expression of let-7i-3p and PI3K before and after baicalin interven-tion.let-7i-3p interference was used to verify whether baicalin mitigated the activation of enhanced NLRP3 inflammasomes.Results Baicalin(50,100 mg· L-1)significantly reduced the activation of NLRP3 in-flammasomes,inhibited the protein expressions of p-PI3K,p-Akt,NF-κB p65,NLRP3,ASC and caspase-1,and the secretion of IL-1 and IL-18.let-7i-3p and PIK3CA had a targeted correspondence,and baicalin up-regulated the expression of let-7i-3p and down-reg-ulated the expression of PIK3CA.Baicalin attenuated the activation of NLRP3 inflammasomes enhanced by let-7i-3p interference.Conclusions Baicalin can up-regulate let-7i-3p expression,inhibit PI3K/Akt/NF-κB signal transduction,and thus reduce the activation of NLRP3 inflammasomes in HFLS-RA.
Neurovascular coupling is the function of regulating blood flow of the central nervous system at the level of neurovas-cular units.The central nervous system diseases related to neu-rovascular coupling mainly include cerebrovascular diseases such as chronic cerebral ischemia and neurodegenerative diseases such as Alzheimer's disease,Parkinson's disease and Lewy body dementia.The main mechanism of neurovascular coupling dys-function leading to the above diseases is cerebrovascular dys-function or loss,which leads to serious damage to neuronal ische-mia and affects its function.Therefore,this paper reviews the re-search status of neurovascular coupling and its related central nervous system diseases,in order to guide the follow-up re-search.The purpose of this paper is to provide a basis for the prevention,relief and treatment of central nervous system disea-ses related to neurovascular coupling through the mechanism of neurovascular coupling.
Aim To investigate the mechanism of Qizhu anti-cancer prescription(QZACP)inthe treat-ment of primary liver cancer using network pharmacolo-gy and molecular docking.Methods Drugs and pri-mary liver cancer(PLC)-related targets were found ac-cording to TCMSP database and disease databases such as GeneCard,the key chemical components and core targets were screened by Cytoscape 3.9.1 and String platform respectively,and a network relationship dia-gram of traditional Chinese medicine-active component-target was constructed by using Cytoscape 3.9.1.GO functional analysis and KEGG pathway analysis were performed using DAVID platform,visualized by R 4.1.1 software,and finally the core clustered proteins were analyzed by CytoNCA plug-in to obtain the core action targets,and the core components and key targets were verified by using molecular docking technology and the pharmacodynamic mechanism of QZACP was further verified by animal experiments.Results The active ingredients of QZACP in the treatment of primary liver cancer may be quercetin,glycyrrhizin,Denudatin B,isoflavanone,sanguinarol,etc.;the potential targets were STAT3,EGFR,AKT1 etc.;the related pathways were mainly PI3K-Akt signaling pathway,MAPK signa-ling pathway,etc.;molecular docking showed that the core compounds had better integrating conformation with the key targets.In addition,QZACP could inhibit the growth of tumor in nude mice and decrease the ex-pression of STAT3,EGFR and AKT1.Conclusions Qizhu anti-cancer prescription may have some positive significance in the treatment of primary liver cancer,which may be related to the regulation of PI3K/Akt signaling pathway.
Aim To explore the effect of Liuwei Di-huang decoction(LWDHD)on the expression of β-catenin,E-cadherin,α-SMA,the pathological changes of renal tissue,and the changes of an epithelial-mesen-chymal transformation(EMT)in renal tissue of rats with unilateral ureteral obstruction(UUO).Methods Forty-eight SPF grade SD rats were randomly divided into sham group(Sham),model group(UUO),Li-uwei Dihuang decoction low,medium,and high groups(LWDHD 3.375,6.75,13.5 g·kg-1)and enalapril group(10 mg·kg-1),with eight rats in each group.HE and Masson staining were used to observe the path-ological changes and collagen fiber deposition in the af-fected renal tissue of the six groups.Immunohisto-chemistry and Western blot were employed to detect the expression of E-cadherin,β-catenin,and α-SMA in re-nal tissue of rats in each group.Results Compared with the sham group,the UUO group showed glomeru-lar sclerosis,tubular dilatation,and more severe inter-stitial fibrosis.The expression of β-catenin and α-SMA protein increased,while the expression of E-cadherin protein decreased(P＜0.05).Compared with the UUO group,the pathological changes and collagen deposition of renal tissue in the LWDHD group and en-alapril group were significantly improved,the protein levels of β-catenin and α-SMA decreased,while the protein level of E-cadherin increased(P＜0.05).Conclusions LiuWei Dihuang decoction may down-regulate β-catenin expression,and then inhibit EMT,thus playing a role in alleviating renal fibrosis.
Aim To explore whether sea-buckthorn slows down-regulation of hepatic cytochrome P450 2C(CYP 2C)in mice with liver injury by BCG vaccine(BCG)-induced via PXR/NF-κB pathway.Methods The mouse model of liver injury was induced by a single tail vein injection of BCG 125 mg·kg-1 for hepatitis B research,and the mice were randomly di-vided into control group,BCG group,BCG+sea-buckthorn granules(SG)group(gavage 50,100,200 mg·kg-1,twice a day),BCG+PCN group(intraper-itoneal injection 100 mg·kg-1,once a day).The levels of serum transaminase and TNF-α and IL-1β in liver tissue were detected by ELISA.The nuclear pro-tein expression NF-κB p65 and the total protein expres-sion of pregnane X receptor(PXR),CYP2C in liver were detected by Western blot.Liver pathological changes were observed by HE staining.Results Sea-buckthorn inhibited overexpression of TNF-α,IL-1βand NF-κB p65,alleviated the down-regulation of CYP2C and PXR protein expression,and improved liv-er pathology and serum transaminase in a dose-depend-ent manner.After intervention with PCN,a mouse specific agonist of PXR,it was similar to the high dose group of SG.Conclusion Sea-buckthorn slows down-regulation of CYP2C in mice with liver injury by BCG-induced via PXR/NF-κB pathway.
Aim To explore the effects of carvedilol on atherogenesis in mice.Methods Eight-week-old ApoE-/-mice were placed on an atherogenic chow and randomly divided into control and carvedilol group.The mice in both groups were intraperitoneally adminis-tered with vehicle or carvedilol 12.5 mg·kg-1 once daily,respectively.After 10 weeks,histopathological alterations of brachiocephalic trunk,liver,pancreas and adipose tissues were assessed by hematoxylin and eosin and oil red O staining,the level of blood glu-cose,blood lipids,aspartate aminotransferase(AST),alanine aminotransferase(ALT),and liver fatty acidβ-oxidase were determined,and glucose tolerance/in-sulin tolerance tests were performed as well.In addi-tion,hepatic mRNA and protein expression of ACAD10 and mTOR were detected by real-time PCR and Western blot,respectively.Results Compared with the control group,the area of atherosclerotic plaque(P＜0.01)and intima-to-media ratio(P＜0.05)in the carvedilol group all significantly de-creased,aortic damages were obviously improved,glu-cose and insulin tolerance were remarkably enhanced;moreover,HDL-C concentration in serum increased(P＜0.05).Notably,HE and oil red 0 staining revealed that carvedilol almost completely reversed hepatic steatosis,increased liver fatty acid beta oxidase levels(P＜0.01),along with the reduction in ALT(P＜0.01)and AST(P＜0.01)levels,even improvement of pancreatic and adipose impairments in ApoE-/-mice.In carvedilol group,the mRNA(P＜0.01)and protein expression levels(P＜0.05)of ACAD 10 were significantly up-regulated,while mTOR was signifi-cantly down-regulated compared with that in the control group(P＜0.01).Conclusions Our results indicate that carvedilol regulates mTOR and ACAD 10 in liver,which may contribute to the alleviation of fatty liver,and even atherogenesis.
Aim To study the effects of high-fat diet on testicular germ cell apoptosis in mice through endoplas-mic reticulum stress.Methods C57BL/6J male mice were assigned into normal group and high-fat diet group randomly,with six mice in each group.The mice in normal group or high-fat diet group were fed with regu-lar or high-fat diet continuously for five months.The mice were weighed,anesthetized,and euthanized to col-lect testicular and epididymal tissue for analysis.The testicular tissue was weighed and their indices were calculated.Epididymal tissue was collected for semen analysis.The morphological alterations of testicular tis-sue were observed using hematoxylin-eosin(HE)stai-ning.The apoptosis of germ cells was detected by TUNEL staining and the apoptotic indices were calcu-lated.The expression levels of apoptosis and endoplas-mic reticulum stress-related proteins in testicular tissue were detected by Western blot.The protein expression and localization of GRP78 in testicular tissue were fur-ther detected by immunofluorescence.Results The results showed that compared to the normal group,the high-fat diet group had a significant increase in body weight,a significant decrease in testicular index,sperm concentration,and sperm vability,loose arrangement of germ cells,significant thinning of the seminiferous epi-thelium,no significant change in the diameter of semi-niferous tubules,a significant increase in germ cell ap-optosis,with an increased apoptosis index,and signifi-cant increase in expression of Bax and cleaved-caspase-12,and a significant decrease in Bcl-2 protein expres-sion.The expression levels of GRP78,p-IRE1,XBP1,and ATF6α proteins were significantly up-regulated,while p-PERK,p-eIF2α,ATF4 protein expression showed no significant changes.Immunofluorescence re-sults further showed a significant increase in the ex-pression of GRP78 protein in the testicular tissue,with no significant changes in the expression location.Con-clusions High-fat diet can induce the apoptosis of mouse testicular germ cells,and the mechanism may be related to the activation of endoplasmic reticulum stress IRE1 and ATF6 signaling pathway.
Aim To investigate whether Linggui Zhu-gan Decoction(LGZGD)can inhibit ventricular re-modeling and prevent heart failure in rats after myocar-dial infarction by regulating Nrf2/BNIP3 pathway.Methods The model of heart failure after myocardial infarction was established by left coronary artery liga-tion in rats.Two weeks after modeling,all rats were randomly divided into model group,LGZGD group,and captopril group.Meanwhile sham operation group was set up.The rats were given continuous intragastric administration with drug or distilled water for 28 days,once a day.The behavioral signs of rats in each group were observed.The cardiac function of rats in each group was examined by echocardiography.Serum BNP and NT-ProBNP content were detected by enzyme-linked immunoassay;The changes of myocardial his-topathological and collagen fibers in rats were detected using sirius staining.The contents of oxidative stress index including ROS,SOD in myocardial tissue of rats in each group were observed by DCFH-DA fluorescent probe and Enzyme-linked immunoassay.The ultra-structure of mitochondria was observed by transmission electron microscopy.Expressions of apopt otic proteins(mitochondrial CytC,cytoplasmic CytC)were detec-ted by Western blot.Expression of proteins related to the Nrf2/BNIP3 pathway were examined by immunoflu-orescence and Western blot.Results LGZGD could significantly improve the cardiac function of rats,re-duce the contents of BNP and NT-ProBNP,inhibit the excessive deposition of collagen in myocardial interstiti-um,reduce ROS,increase the content of SOD,im-prove mitochondrial structure damage,up-regulate the expression of Nrf2 and nuclear translocation,and re-duce the expression of BNIP3.Conclusions LGZGD can inhibit the ventricular remodeling and prevent the occurrence of heart failure after myocardial infarction.Its pharmacological effects are mainly related to regula-ting the Nrf2/BNIP3 pathway,activating Nrf2,promo-ting its nuclear transfer,and further down-regulating BNIP3,protecting mitochondrial function,and reduc-ing cardiomyocyte apoptosis.
Aim To investigate the therapeutic effect of lanthanum hydroxide on renal injury and vascular calcification in rats caused by chronic kidney disease(CKD)and the underlying mechanism.Methods A CKD model was constructed by adenine,and the rats were randomly divided into model group,lanthanum hydroxide low,medium and high dose groups,lantha-num carbonate group and calcium carbonate group.Af-ter eight weeks,serum phosphorus(Pi),calcium(Ca),serum creatinine(Scr),blood urea nitrogen(BUN),parathyroid hormone(PTH),fibroblast growth factor 23(FGF23)and tartrate-resistant acid phosphatase 5b(TARP-5b)levels were measured.Histopathological staining was used to assess the degree of calcification of blood vessels,and the expressions of smooth muscle protein 22 α(SM22α),Runt-related transcription factor 2(RUNX2),hypoxia inducible factor 1(HIF-1)pathway mRNA and protein expres-sion in blood vessels were detected.Results Lantha-num hydroxide can significantly reduce the levels of Pi,Scr,BUN,PTH,FGF23 and TARP-5b in the ser-um of CKD rats,significantly reduce the calcium depo-sition of the thoracic aorta of CKD rats,the expression of BMP-2,VEGF in the cytoplasm,the expression of RUNX2,HIF-1 α in the nucleus,and increase the mRNA and protein expression of SM22.Conclusion Lanthanum hydroxide can markedly improve hyper-phosphatemia in CKD rats,and can improve vascular calcification in CKD rats by blocking HIF-1 α signaling pathway.
Aim To investigate the role of autophagy regulated by the AMPK/mTOR pathway in the preven-tion of oxygen-glucose deprivation/reperfusion injury(OGD/R)in astrocytes using oxymatrine(OMT).Methods The isolated and purified astrocytes(AS)were randomly divided into control group(CON group),OGD/R group and OGD/R+OMT group(0.1,0.2,0.4 mmol·L-1).MTT assay was used to detect cell survival rate.Apoptosis was detected by Hoechst 33342 and Annexin V-FITC.The content of reactive oxygen species(ROS)was detected by flow cytometry.The expressions of p-AMPK,AMPK,p-mTOR,mTOR,Beclin 1,LC3B,p62 and β-actin were detected by Western blot.Meanwhile,the role of autophagy in the effect of OMT was explored by adding autophagy inhibitor 3-methyladenine(3-MA).Results Compared with CON group,the survival rate of OGD/R group significantly decreased(P＜0.01),cell apoptosis rate and intracellular ROS production significantly increased(P＜0.01),and the ratio of p-AMPK/AMPK and LC3B Ⅱ/Ⅰ,and the content of beclin 1 increased(P＜0.01).p-mTOR/mTOR ratio and p62 content decreased(P＜0.01).Compared with OGD/R group,the cell survival rate in OGD/R+OMT group significantly increased(P＜0.01),the cell apoptosis rate decreased(P＜0.01),the intracel-lular ROS production decreased(P＜0.01),and the ratio of p-AMPK/AMPK and LC3B Ⅱ/Ⅰ,and the content of Beclin 1 decreased(P＜0.01).p-mTOR/mTOR ratio and p62 content increased(P＜0.01).Compared with OGD/R group,the cell survival rate of OGD/R+3-MA group significantly increased(P＜0.01),and cell survival rate of OGD/R+3-MA group also had significant difference compared with OGD/R+OMT group and OGD/R+OMT+3-MA group.Conclusions OMT has a protective effect on OGD/R-induced AS injury,which is related to the inhibition of AMPK/mTOR signaling pathway and the amelioration of autophagy.
Aim To explore the possibility of resvera-trol(RES)combined with irinotecan(IRI)in the treatment of colorectal cancer(CRC)and the underly-ing molecular mechanism of RES ameliorating IRI che-moresistance of CRC cells.Methods CRC cells used in this study were HT-29 and RKO cells.The effects of RES,IRI and their combination on the proliferation of CRC cells were analyzed by MTT assay and colony for-mation assay.The effects of RES,IRI and their combi-nation on the migration of CRC cells were assessed by Wound-healing assay.On this basis,the role of RES in regulating IRI chemoresistance of CRC cells and the underlying molecular mechanisms were further ex-plored.Results The proliferation and migration abili-ty of CRC cells in the RES and IRI combined treatment group were significantly lower than those in the IRI treated group,which showed that RES could enhance the inhibiting effect of IRI on the proliferation and mi-gration of CRC cells,indicating that RES was able to a-meliorate the chemoresistance of CRC cells to IRI.And remarkably lower marker proteins expression levels of EGFR/AKT/mTOR signaling pathway in the RES and IRI combined treatment group was observed.Mo-reover,both EGFR activator(NSC 228155)and AKT activator(SC79)could reverse the ameliorating effect of RES on IRI chemoresistance of CRC cells,whereas AKT inhibitor(MK2206)could partially reverse the effect of NSC 228155.Conclusions RES can inhibit the proliferation and migration of CRC cells by down-regulating EGFR/AKT/mTOR signaling pathway,so as to ameliorate the chemoresistance of CRC cells to IRI,suggesting that RES combined with IRI can be a prom-ising novel treatment for CRC.
Inflammatory bowel disease(IBD)is a chronic pro-gressive inflammation of the gastrointestinal tract that damages the mucous membrane of the gastrointestinal tract.A growing number of studies have demonstrated that dysfunctional cell death occurs at inflammatory sites,leading to the destruction of the intestinal mechanical barrier and aggravation of inflammatory responses.Ferroptosis is a newly discovered form of programmed cell death mediated by iron-dependent lipid oxidation.There have been many articles that reported intestinal abnormal related factors of ferroptosis in patients with IBD.In view of the unclear current IBD specific pathogenesis and the many limitations in treatment,we summarize the research progress of ferroptosis mechanism in recent years,and expound the potential role of fer-roptosis in the pathogenesis of IBD,aiming to provide direction for the future study of the pathogenesis of IBD and the develop-ment and application of therapeutic drugs.
Inflammatory bowel disease(IBD),as an idiopathic inflammatory disease of the intestinal tract,consisting mainly of Crohn's disease and ulcerative colitis,which can involve the rec-tum,colon and ileum,and whose pathogenesis is still not fully understood.The initiation of intestinal inflammation associated with IBD and its chronicity begins with increased intestinal per-meability caused by intestinal epithelial barrier disruption.The anti-permeability of the intestinal epithelial barrier is maintained by tight junction in the apical region of the intestinal epithelial cells,and disruption of the tight junction structure is closely as-sociated with intestinal epithelial barrier damage and the devel-opment of IBD.Therefore,it is significant to find drugs for the prevention and treatment of IBD using tight junctions as regulato-ry targets.In recent years,many small molecules of natural product origin have been reported to improve the effects of IBD.In particular,we review the compounds that have the function of repairing intestinal epithelial barrier and protecting tight junction structure,in order to provide research ideas for the design and development of new drugs for the prevention and treatment of IBD.
Keloid is a fibrous proliferative disease of the skin,and its pathological essence is excessive wound healing caused by excessive fibrosis.Its pathological mechanism is complex and unclear.At present,it is believed that the cellular mechanism of keloids mainly involves inflammatory cells and fibrosis-related cells,as well as cytokines such as growth factors,interleukins,tumor necrosis factor,and matrix metalloproteinase;the molecu-lar mechanism mainly involves TGF-β/Smad pathway,NF-Mo-lecular mechanisms such as κB pathway,STAT3 signaling path-way,MAPK signaling pathway,and focal adhesion kinase.This article reviews the latest research progress on the pathological mechanism of keloids from the perspectives of cells,cytokines,and molecular signaling pathways.
依托咪酯(etomidate,ET)是一种作用强,且在临床麻醉中得到广泛应用的短效非巴比妥类静脉麻醉药,其麻醉机制与抑制多个脑区神经元活动与突触传递环路功能有关.ET抑制在体小鼠小脑浦肯野细胞放电活动,下调颗粒细胞感觉信息传递,提示ET影响小鼠小脑皮层神经环路突触传递长时程可塑性,但其影响机制尚不清楚.
Aim To investigate the pharmacological mechanism of the couplet medicines"Cangzhu-Yiy-iren"in treating adenoid hypertrophy(AH)of children based on network pharmacology.Methods To screen the active ingredient and relevant targets of the couplet medicines"Cangzhu-Yiyiren",a visual network map of"Drug-Component-Target"was constructed;related targets of AH were retrieved and standardized,and A PPI network to treat AH of children by"Cangzhu-Yiy-iren"was constructed.Enrichment analysis was per-formed for the core targets,and a"targets-pathways"network was constructed.The expression of target pro-teins from spleen tissues of different groups was deter-mined by Western blot to verify that atractylone regula-ted the expression of inflammatory factors by HIF-1 α-SUMOylation.Results A total of 71 drug-related tar-gets and 337 disease-related targets for AH in children were obtained,and there were 30"Drug-Disease"in-tersection targets.The main active components of the couplet medicines"Cangzhu-Yiyiren"were stigmaster-ol,atractylone and so on.The biological processes mainly involved in were tube morphogenesis,response to hormone,the main cellular components involved in were membrane raft,transcription regulator complex,and the molecular function of related targets were main-ly enriched in the transcription factor binding,protein domain specific binding,etc.The enrichment analysis indicated that it was associated with apoptosis-multiple species,VEGF signaling pathway,and HIF-1 signaling pathway,etc.The results of animal experiments showed that SUMO-1,HIF-1 α,VEGF and VEGF-R protein ex-pression were all down-regulated compared with the model group(P＜0.05).Conclusions The treat-ment of pediatric AH which takes the"Activating Spleen Treatment of Nasa"as the guiding ideology,is realized through multi-components,multi-target,multi-pathways,and mainly from the anti-inflammatory,im-mune regulation,antioxidant and other aspects to play its role in the treatment of children with AH.
