Dear Editor,We present this case report which discusses a patient who underwent flap amputation after repeated attempts to resolve persistent and severe epithelial ingrowth following laser-assisted in situ keratomileu...Dear Editor,We present this case report which discusses a patient who underwent flap amputation after repeated attempts to resolve persistent and severe epithelial ingrowth following laser-assisted in situ keratomileusis(LASIK)surgery.Epithelial ingrowth is a known complication of LASIK surgery,typically manageable with minimal measures.However,severe cases may necessitate more aggressive interventions,such as flap amputation[1].LASIK is a widely performed refractive surgery with high success rates and excellent visual outcome[2].展开更多
The dark blue pigment(DBP)is a health ingredient from Vaccinium bracteatum Thunb.leaves used as a functional food supplement.However,the details of transepithelial absorption on the intestinal epithelial cells are bar...The dark blue pigment(DBP)is a health ingredient from Vaccinium bracteatum Thunb.leaves used as a functional food supplement.However,the details of transepithelial absorption on the intestinal epithelial cells are barely understood.This study aimed to clarify the absorption properties of DBP in the Caco-2 cell monolayer model and evaluate the effect on the endo-metabolism and barrier function of Caco-2 cells.The results showed that the DBP did not show the dose-dependent toxic effect to Caco-2 cells between 0.25 and 1.5 mg/mL,which did not cause disorder in the normal cell metabolism and absorption activity.The Caco-2 cell monolayer model could absorb DBP by passive and active transport,and the absorptive pattern was dosedependent when the concentration was more than 0.25 mg/mL.During DBP absorption,an increase in m RNA and protein expressions of glucose transporters demonstrated that the glucose transporters were the potential transporter of DBP.But the glucose transport amounts were significantly lowered after 30 min of DBP treatment,indicating that DBP owned the inhibitory effect on glucose transportation.Furthermore,DBP also owned protective effects on the barrier function of intestinal epithelial cells.展开更多
Epithelial-mesenchymal transition(EMT)plays an irreplaceable role in the development of silicosis.However,molecular mechanisms of EMT induced by silica exposure still remain to be addressed.Herein,metabolic profiles o...Epithelial-mesenchymal transition(EMT)plays an irreplaceable role in the development of silicosis.However,molecular mechanisms of EMT induced by silica exposure still remain to be addressed.Herein,metabolic profiles of human alveolar type II epithelial cells(A549 cells)exposed directly to silica were characterized using non-targeted metabolomic approaches.A total of 84 differential metabolites(DMs)were identified in silica-treated A549 cells undergoing EMT,which were mainly enriched in metabolisms of amino acids(e.g.,glutamate,alanine,aspartate),purine metabolism,glycolysis,etc.The number of DMs identified in the A549 cells obviously increased with the elevated exposure concentration of silica.Remarkably,glutamine catabolism was significantly promoted in the silica-treated A549 cells,and the levels of related metabolites(e.g.,succinate)and enzymes(e.g.,α-ketoglutarate(α-KG)dehydrogenase)were substantially up-regulated,with a preference toα-KG pathway.Supplementation of glutamine into the cell culture could substantially enhance the expression levels of both EMT-related markers and Snail(zinc finger transcription factor).Our results suggest that the EMT of human alveolar epithelial cells directly induced by silica can be essential to the development of silicosis.展开更多
BACKGROUND Oral squamous cell carcinoma(OSCC)is a frequent cancer affecting the oral cavity.OSCC is usually preceded by occurrence of precursor lesions,which demonstrate a varying degree of malignant transformation po...BACKGROUND Oral squamous cell carcinoma(OSCC)is a frequent cancer affecting the oral cavity.OSCC is usually preceded by occurrence of precursor lesions,which demonstrate a varying degree of malignant transformation potential.Epithelialmesenchymal transition is a significant biological phenomenon that facilitates tumor growth and metastasis through the involvement of diverse epithelial and mesenchymal proteins.E-cadherin down regulation and over-expression of zincfinger E-box-binding homeobox 1(ZEB1)has been reported in several cancers.AIM To evaluate the role of E-cadherin and ZEB1 in oral leukoplakia and OSCC.METHODS A total of 60 cases i.e.,oral leukoplakia/oral epithelial dysplasia(OED)(n=30)and OSCC(n=30)were included.Immunohistochemistry was performed utilizing two markers:E-cadherin and ZEB1.The Mann-Whitney U test was employed to compare individual markers across the study groups.Spearman’s correlation was done followed by discriminant function analysis.RESULTS Reduction in the expression E-cadherin and altered localization were noted from OED to OSCC.Overexpression of ZEB1 along with cytoplasmic accumulation was noted in OED,with marked expression in OSCC.ZEB1 epithelium intensity and ZEB1 connective tissue percentage contributed to the discriminant function with an accuracy of 85%for the classification of OED from OSCC.CONCLUSION Loss of E-cadherin and up-regulation of ZEB1 from OED to OSCC,predisposes to induction of epithelial-mesenchymal transition.Discriminant formulas are developed to classify cases of OED and OSCC with 85%accuracy.展开更多
AIM:To investigate the effect of skullcapflavone II(SCF-II)on the epithelial-mesenchymal transition(EMT)induced by transforming growth factor beta(TGF-β)in human corneal epithelial cells(HCECs),as well as to identify...AIM:To investigate the effect of skullcapflavone II(SCF-II)on the epithelial-mesenchymal transition(EMT)induced by transforming growth factor beta(TGF-β)in human corneal epithelial cells(HCECs),as well as to identify the signaling pathways that may be involved.METHODS:HCECs were cultured in vitro.At a SCFII(5,10μmol/L)dose,cell viability was analysed with a cell counting kit-8(CCK-8)assay,and cell migration was monitored with wound healing and Transwell migration assays.There were 4 groups:SCF-II,TGF-β,SCF-II+TGF-βand Control.Western blotting and immunofluorescence were performed to show the expression of EMT markers and the translocation of nuclear factor kappa-B(NF-κB)into the nucleus in the 4 groups.RESULTS:Treatment with SCF-II decreased HCEC viability in a dose-dependent manner.A concentration below 10μmol/L did not present obvious cell toxicity,and survival rates were more than 70%at 48h.Treatment with SCF-II(5 and 10μmol/L)significantly impeded migration in wound healing and Transwell migration assays(P<0.05),and EMT markers and NF-κB translocation into the nucleus were inhibited.After both TGF-βand SCF-II treatment,the migration of TGF-β-treated HCECs were suppressed by SCF-II(P<0.05).The expression levels of the mesenchymal markers N-cadherin(P<0.05),α-smooth muscle actin(α-SMA;P<0.05)and NF-κB(P<0.05)in both TGF-β-and SCF-II-treated HCECs were lower than those in the HCECs treated with TGF-βalone and higher than those in HCECs treated with SCF-II alone.Immunofluorescence showed that the entry of NF-κB into the nucleus in both TGF-β-and SCF-IItreated HCECs was less than that in the TGF-β-treated HCECs.CONCLUSION:SCF-II inhibit TGF-β-induced EMT in HCECs by potentially regulating the NF-κB signalling pathway.Thus,SCF-II represents a candidate putative therapeutic agent in corneal fibrotic diseases.展开更多
AIM:To highlight the importance of microRNA(miRNA)-21-5p in directing the phosphatase and tensin homolog(PTEN)gene to control the phosphoinositide 3-kinase/protein kinase B/mammalian target of rapamycin(PI3K/Akt/mTOR)...AIM:To highlight the importance of microRNA(miRNA)-21-5p in directing the phosphatase and tensin homolog(PTEN)gene to control the phosphoinositide 3-kinase/protein kinase B/mammalian target of rapamycin(PI3K/Akt/mTOR)pathway in retinal pigment epithelial(RPE)cells in humans subjected to photodamage.METHODS:Human adult RPE cell line-19(ARPE-19)was cultured in vitro and randomly divided into control,damage,overexpression,negative,and PI3K/Akt blocker groups to establish a photodamage model of ARPE-19 cells.The models were subjected to 24h of light exposure,after which the corresponding indices were detected.The cell counting kit-8 assay quantified cell viability,while flow cytometry determined apoptosis rates.The miRNA-21 mimics and miRNA mimic NC were transfected into ARPE-19 cells using a transient transfection technique.Quantitative reverse transcription polymerase chain reaction(SYBR Green)and Western blotting analyzed expression levels of miRNA-21-5p,PTEN,p-PI3K/PI3K,p-mTOR/mTOR,and p-Akt/Akt.Statistical analyses comprised one-way analysis of variance and the Student-Newman-Keuls test for multiple group comparisons.RESULTS:The photodamage group demonstrated reduced cell survival rates than the control group(P<0.01).The overexpression group exhibited higher cell survival rates than the injury group(P<0.01).The negative group showed no difference in viability(P>0.05).The PI3K/Akt blocker group demonstrated lower cell viability,compared with the overexpression group(P<0.01).CONCLUSION:miRNA-21-5p significantly increases ARPE-19 cell survival after photodamage and inhibits lightinduced ARPE-19 cell apoptosis,suggesting that it may play a protective role in RPE by activating the PI3K/Akt/mTOR pathway while downregulating PTEN expression.展开更多
Multifocal epithelial hyperplasia(MEH),also known as Heck’s disease,is a rare and benign condition of the oral mucosa that is strongly associated with low-risk human papillomavirus(HPV)genotypes 13 and 32.This narrat...Multifocal epithelial hyperplasia(MEH),also known as Heck’s disease,is a rare and benign condition of the oral mucosa that is strongly associated with low-risk human papillomavirus(HPV)genotypes 13 and 32.This narrative review synthesizes recent findings regarding the epidemiology,viral mechanisms,clinical and histopathological features,diagnostic strategies-including molecular and immunohistochemical methods-and therapeutic approaches to MEH.This disease predominantly affects children and adolescents from Indigenous American countries,although cases have been increasingly reported in nonendemic regions.MEH manifests clinically as multiple,asymptomatic papules or nodules,typically exhibiting a characteristic cobblestone-like appearance.Histologically,it presents with epithelial hyperplasia,koilocytosis,and altered cytokeratin expression.Molecular techniques such as polymerase chain reaction and in situ hybridization are pivotal for accurate viral genotyping,while immunohistochemical markers such as CK4/13,Ki-67,and the absence of p16 can be useful adjuncts in differential diagnosis.Despite its self-limiting nature in most cases,treatment may be warranted in symptomatic or immunocompromised patients.This review highlights the need to improve diagnostic access,develop targeted vaccines,and implement public health strategies in vulnerable communities.It also highlights existing gaps in knowledge,particularly regarding host-virus interactions and the absence of standardized treatment protocols.展开更多
The oviduct epithelium is the initial maternal contact site for embryos after fertilization,offering the microenviron-ment before implantation.This early gestation period is particularly sensitive to stress,which can ...The oviduct epithelium is the initial maternal contact site for embryos after fertilization,offering the microenviron-ment before implantation.This early gestation period is particularly sensitive to stress,which can cause reduced fertil-ity and reproductive disorders in mammals.Nevertheless,the local impact of elevated stress hormones on the ovi-duct epithelium has received limited attention to date,except for a few reports on polyovulatory species like mice and pigs.In this study,we focused on the effects of chronic maternal stress on cattle,given its association with infertil-ity issues in this monoovulatory species.Bovine oviduct epithelial cells(BOEC)differentiated at the air–liquid interface(ALI)were stimulated with 250 nmol/L cortisol for 1 or 3 weeks.Subsequently,they were assessed for morphology,bioelectrical properties,and gene expression related to oviduct function,glucocorticoid pathway,cortisol metabo-lism,inflammation,and apoptosis.Results revealed adverse effects of cortisol on epithelium structure,featured by deciliation,vacuole formation,and multilayering.Additionally,cortisol exposure led to an increase in transepithelial potential difference,downregulated mRNA expression of the major glucocorticoid receptor(NR3C1),upregulated the expression of cortisol-responsive genes(FKBP5,TSC22D3),and significant downregulation of oviductal glycopro-tein 1(OVGP1)and steroid receptors PGR and ESR1.The systematic comparison to a similar experiment previously performed by us in porcine oviduct epithelial cells,indicated that bovine cultures were more susceptible to elevated cortisol levels than porcine.The distinct responses between both species are likely linked to their divergence in the cortisol-induced expression changes of HSD11B2,an enzyme controlling the cellular capacity to metabolise cortisol.These findings provide insights into the species-specific reactions and reproductive consequences triggered by maternal stress.展开更多
A lactating dairy cow mammary epithelial cell(DCMEC)model is useful for studying milk synthesis and lactation in the dairy cow mammary gland.However,the cells can only maintain their original characteristics for a lim...A lactating dairy cow mammary epithelial cell(DCMEC)model is useful for studying milk synthesis and lactation in the dairy cow mammary gland.However,the cells can only maintain their original characteristics for a limited period in vitro.Thus,the proliferative capacity and lactation pattern of subcultured DCMECs need to be characterized.In the present study,subcultured DCMECs appeared to proliferate without changes in morphology or growth pattern up to the 12th passage.Subculturing had no obvious effect on the lactation capacity of the subcultured DCMEC up to the 10th passage in vitro.These results indicated that the DCMEC line could be subpassaged up to 10 times and still maintain its original milk synthesis characteristics.Moreover,DCMECs were frozen using different methods,and the method of placing the vials in the foam box was determined after cryopreservation with the best adherence of 91.2%.This method was recommended for long-term cryopreservation for DCMECs.展开更多
Background Ferroptosis is characterized by increased production of reactive oxygen species(ROS)and membrane lipid peroxidation that can exacerbate inflammatory damage.Extracellular vesicles(EVs)isolated from bovine mi...Background Ferroptosis is characterized by increased production of reactive oxygen species(ROS)and membrane lipid peroxidation that can exacerbate inflammatory damage.Extracellular vesicles(EVs)isolated from bovine milk have many biological functions,including antioxidant properties.However,the role of EVs on Klebsiella pneumoniaeinduced ferroptosis and oxidative stress in bovine mammary epithelial cells(bMECs)and murine mammary tissue is unclear.In this study,EVs were isolated from bovine colostrum,mature milk and clinical mastitis milk(defined as C-EVs,M-EVs and CM-EVs,respectively)and assessed by transmission electron microscopy,Western blot and transcriptome sequencing.Effects of EVs on K.pneumoniae-induced ferroptosis and oxidative stress in bMECs were evaluated with immunofluorescence and Western blot.Results In bMECs,infection with K.pneumoniae induced oxidative stress,decreasing protein expression of Nrf2,Keap1 and HO-1 plus SOD activity,and increasing ROS concentrations.However,protein expression of GPX4,ACSL4 and S100A4 in bMECs,all factors that regulate ferroptosis,was downregulated by K.pneumoniae.Furthermore,this bacterium compromised tight junctions in murine mammary tissue,with low expression of ZO-1 and Occludin,whereas protein expression of Nrf2 and GPX4 was also decreased in mammary tissue.Adding C-EVs,M-EVs or CMEVs reduced oxidative stress and ferroptosis in K.pneumoniae-infected bMECs in vitro and murine mammary tissues in vivo.Conclusion In conclusion,all 3 sources of milk-derived EVs alleviated oxidative stress and ferroptosis in K.pneumoniae-infected bMECs and mammary tissues.展开更多
BACKGROUND Diabetic nephropathy(DN)is a leading cause of chronic kidney disease and endstage renal disease,and is a significant global healthcare burden.Although proximal tubular epithelial cells(PTECs)and podocytes a...BACKGROUND Diabetic nephropathy(DN)is a leading cause of chronic kidney disease and endstage renal disease,and is a significant global healthcare burden.Although proximal tubular epithelial cells(PTECs)and podocytes are involved in DN progression,the specific molecular interactions between these cells are not well understood.AIM To elucidate the role of interleukin-6(IL-6)/Rab5 signaling in mediating crosstalk between PTECs and podocytes,and to evaluate the protective effects of nicotinamide mononucleotide(NMN)against DN progression.METHODS We utilized in vitro and in vivo models to investigate the pathogenesis of DN.In vitro,human PTECs and murine podocytes were cultured under high-glucose conditions,and IL-6 neutralizing antibodies or NMN treatments were applied.Podocyte injury was assessed by measurements of nephrin endocytosis,Rab5 activity,cytoskeletal organization,cell adhesion,and cell-spreading assays.In vivo,DN was induced in mice using streptozotocin,and mice then received NMN,insulin,or both treatments over an 8-week period.Renal tissues were analyzed histologically,ultrastructurally,and immunochemically,and urinary albumin excretion was measured to assess renal function.Statistical analyses were conducted using one-way ANOVA and Tukey's test.RESULTS High-glucose conditions induced the epithelial-mesenchymal transition(EMT)in PTECs,increased IL-6 secretion,and activated Rab5 signaling in podocytes,leading to increased nephrin endocytosis and podocyte injury.Blocking IL-6 significantly attenuated these effects.NMN treatment of diabetic mice markedly reduced podocyte injury,glomerular hypertrophy,foot-process effacement,and urinary albumin excretion.Mechanistically,NMN suppressed the EMT and IL-6 secretion by PTECs,inhibited Rab5 activation in podocytes,and prevented nephrin endocytosis,thereby preserving the cytoskeletal integrity and function of podocytes.CONCLUSION Our findings reveal a novel pathogenic mechanism of DN in which IL-6 released from glucose-stressed PTECs activates Rab5 signaling in podocytes,followed by nephrin endocytosis and structural injury of podocytes.Importantly,NMN treatment effectively disrupted this pathological pathway of intercellular communication,and provided significant protection against DN progression.These results suggest that NMN supplementation and targeting the IL-6/Rab5 signaling axis has promise as a therapeutic strategy for managing DN.展开更多
BACKGROUND The pathogenesis of non-ampullary duodenal epithelial tumors(NADETs)is not fully understood.NADETs that express gastric-type mucin phenotypes(GNADETs)are noteworthy because of their high malignancy.Gastric ...BACKGROUND The pathogenesis of non-ampullary duodenal epithelial tumors(NADETs)is not fully understood.NADETs that express gastric-type mucin phenotypes(GNADETs)are noteworthy because of their high malignancy.Gastric foveolar metaplasia,from which G-NADETs originate,protects the duodenal mucosa from gastric acidity.As gastric acid secretion is affected by endoscopic gastric mucosal atrophy(EGMA),we hypothesized that EGMA would be associated with GNADETs.AIM To evaluate the association between EGMA and the occurrence of G-NADETs.METHODS This cross-sectional retrospective study investigated the relationship between EGMA and NADETs in 134 patients.The duodenum was divided into parts 1(bulb),2(superior duodenal angle to the papilla),and 3(anal side of the papilla to the horizontal part).The effects of gastric acidity and presence of Brunner’s glands were considered.EGMA was divided into types C(no or mild atrophy)and O(severe atrophy).Mucin phenotype expressions in NADETs were divided into gastric,intestinal,gastrointestinal,and unclassifiable.RESULTS When NADETs were classified according to EGMA,105 were classified as type C and 29 as type O.G-NADETs were present in 11.9%(16 cases)of all cases,and all 16 cases were of type C.Among G-NADETs,93.8%(15 cases)were present in part 1 or 2.There was an association between G-NADETs and type C in part 1,and 50.0%(eight of 16 cases)of G-NADETs were associated with a current or previous Helicobacter pylori infection status.Additionally,all eight cases occurred in part 1.CONCLUSION G-NADETs were significantly associated with type C.Gastric acidity and Brunner's gland growth may be associated with G-NADETs.展开更多
Diabetic kidney disease(DKD)has emerged as one of the leading causes of chronic kidney disease and end-stage renal disease worldwide.In the progression of DKD,renal tubular injury plays a pivotal role,with stress-indu...Diabetic kidney disease(DKD)has emerged as one of the leading causes of chronic kidney disease and end-stage renal disease worldwide.In the progression of DKD,renal tubular injury plays a pivotal role,with stress-induced senescence of renal tubular epithelial cells(RTECs)being a critical cellular event contributing to tubular damage in DKD.Recent studies have revealed that multiple mechanisms,including oxidative stress,mitochondrial autophagy,endoplasmic reticulum stress,and epigenetic modifications,can induce stress-induced senescence in RTECs,thereby driving the progression of DKD.In recent years,research has demonstrated that traditional Chinese medicine(TCM)can regulate these mechanisms through multiple targets and key pathways,inhibiting stress-induced senescence in RTECs and ameliorating the progression of DKD.TCM has been widely applied in clinical practice with proven efficacy.This article systematically summarizes the concept of cellular senescence,delves into the relationship between stress-induced senescence of RTECs and DKD,analyzes the mechanisms underlying the formation of stress-induced senescence in RTECs within the context of DKD,and reviews the research progress of TCM in anti-senescence treatment for DKD.The aim is to provide a reference for future research and the development of novel therapeutic strategies.展开更多
Objective To investigate the differential expression of microRNA-144-3p in endometrial cells exposed to copper ions in vitro.The specific mechanism by which microRNA-144-3p is involved in Cu^(2+)-induced damage to the...Objective To investigate the differential expression of microRNA-144-3p in endometrial cells exposed to copper ions in vitro.The specific mechanism by which microRNA-144-3p is involved in Cu^(2+)-induced damage to the human endometrial epithelial cells(HEECs)was explored.Methods HEECs were cultured in copper-containing culture medium to simulate changes in the endometrium after copper intrauterine device(Cu-IUD)implantation.Reverse transcription quantitative PCR(RT-qPCR)was used to detect the differential expression of miR-144-3p in HEECs after Cu^(2+)treatment.MiRNAs,siRNAs and related inhibitors were used to treat HEECs.The expression levels of related downstream genes were then analyzed by RT-qPCR,Western blotting and immunofluorescence to explore the specific mechanism involved.Results MiR-144-3p was significantly upregulated in the Cu^(2+)-treated HEECs.The expression of P-NF-κB,MMP9,TGF-β3 and P-SMAD3 was significantly decreased in HEECs treated with 10μg/mL Cu^(2+).MiR-144-3p regulated the expression of metallothionein 1A(MT1A)and thrombospondin-1(THBS-1)in Cu^(2+)-treated HEECs.The expression of P-NF-κB can be regulated by MT1A,and an inhibitor of P-NF-κB can significantly reduce the expression of MMP9 in Cu^(2+)-treated HEECs.The expression of TGF-β3 can be regulated by THBS-1,and a TGF-β3 inhibitor can significantly reduce the expression of SMAD3 in Cu^(2+)-treated HEECs.The proliferative capacity of HEECs treated with MMP9 or SMAD3 inhibitors was significantly reduced.Conclusions The increased Cu^(2+)concentration led to the upregulation of miR-144-3p,further reducing the expression levels of its target genes(MT1A and THBS-1),which in turn downregulated the expression of NF-κB,MMP9,TGF-β3 and SMAD3,ultimately leading to increased endometrial cell damage and decreased cell proliferation.展开更多
Idiopathic pulmonary fibrosis(IPF)is a progressive and fatal interstitial lung disease characterized by excessive fibrotic remodeling,for which effective therapeutic options remain severely limited.Among the pathogeni...Idiopathic pulmonary fibrosis(IPF)is a progressive and fatal interstitial lung disease characterized by excessive fibrotic remodeling,for which effective therapeutic options remain severely limited.Among the pathogenic mechanisms implicated in IPF,epithelial-to-mesenchymal transition(EMT)is recognized as a pivotal driver of fibroblast activation and extracellular matrix deposition.In this study,we aimed to develop low-molecular-weight dextran sulfate sodium(LMW-DSS)derivatives and assess their capacity to interfere with EMT,thereby offering novel therapeutic avenues for IPF management.Starting with dextran(2 kDa)as a precursor,we successfully synthesized two sulfated derivatives,DSS-LS and DSS-HS,via distinct sulfonation processes.Using a TGF-β1-stimulated A549 alveolar epithelial cell model,we demonstrated that LMW-DSS compounds exhibited no cytotoxicity,as validated by CCK-8 viability assays.Importantly,Transwell migration assays revealed that LMW-DSS markedly attenuated TGF-β1-induced A549 cell migration,indicating a potent anti-fibrotic effect.Moreover,qPCR and Western blotting analyses confirmed that LMW-DSS significantly suppressed the expression and secretion of key pro-fibrotic mediators,including TGF-β1 and VEGF-A,and downregulated critical EMT-associated markers such as Snail and vimentin.Notably,reducedα-SMA expression following LMW-DSS treatment further substantiated its role in hindering EMT progression.Collectively,these findings highlighted the capacity of LMW-DSS to effectively impede EMT and fibrotic processes,thereby delaying the progression of pulmonary fibrosis.This work not only underscored the therapeutic potential of LMW-DSS in IPF but also provided compelling experimental evidence to support its development as a promising anti-fibrotic agent for clinical application.展开更多
Objective:This study primarily focuses on analyzing the inductive effects of emotional disturbances on the malignant transformation process of mammary gland epithelial cells.Methods:A total of 42 patients with maligna...Objective:This study primarily focuses on analyzing the inductive effects of emotional disturbances on the malignant transformation process of mammary gland epithelial cells.Methods:A total of 42 patients with malignant transformation of mammary gland epithelial cells(breast cancer,observation group)and 42 patients without malignant transformation of mammary gland epithelial cells(non-breast tumors,control group)were selected as research subjects.The earliest consultation time was January 2022,and the latest was January 2024.The extent of psychological stress impact on these patients was compared.Results:Compared with the control group,the observation group experienced a higher frequency and intensity(LEU value)of adverse life events,with P<0.05.The intensity of adverse life events in the observation group,except for mild events,was significantly higher than that in the control group(P<0.05).In terms of the content distribution of adverse life events,the proportion of marital and family problems in the observation group was significantly higher than that in the control group(P<0.05).The negative coping score and positive coping score in the observation group were significantly different from those in the control group(P<0.05).Regarding social support,the objective support score in the observation group was higher than that in the control group(P<0.05).Conclusion:During the malignant transformation process of mammary gland epithelial cells,long-term emotional disturbances have a significant impact,indicating a close relationship between psychological stress and the occurrence of breast cancer.展开更多
Type 2 alveolar epithelial cell(AT2)senescence plays a crucial role in the onset andprogression of pulmonary fibrosis.Recent studies have revealed a close relationship betweenAT2 senescence and pulmonary fibrosis,sugg...Type 2 alveolar epithelial cell(AT2)senescence plays a crucial role in the onset andprogression of pulmonary fibrosis.Recent studies have revealed a close relationship betweenAT2 senescence and pulmonary fibrosis,suggesting that senescent cells have a dual role inthe injury repair process of lung tissue.On the one hand,senescent AT2 loses its repairfunction,and on the other hand,senescent cells exacerbate the inflammatory and fibroticprocesses by secreting senescence-associated secretory phenotype.In this paper,we willreview the biological mechanisms and pathological features of AT2 senescence and itsrelationship with the development of pulmonary fibrosis,and discuss current therapeuticintervention strategies,including the potential of small molecule drugs,cellular therapies,gene editing techniques,and traditional Chinese medicine.Finally,the paper summarizesthe challenges of current research and suggests future research directions.展开更多
BACKGROUND Thin endometrium,leading cause of recurrent implantation failure and infertility,has been found to respond to exosomes.AIM To investigate the efficacy of exosomes in addressing the issue of thin endometrium...BACKGROUND Thin endometrium,leading cause of recurrent implantation failure and infertility,has been found to respond to exosomes.AIM To investigate the efficacy of exosomes in addressing the issue of thin endometrium.METHODS RNA sequencing and reverse transcription-quantitative polymerase chain reaction were employed to identify differentially expressed microRNAs(miRNAs)in human umbilical cord mesenchymal stem cell(hucMSC)treated with exosomes enriched with endometrial cell-derived components.Additionally,Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses were conducted to highlight significant enrichment in specific biological pathways,molecular functions,and cellular components.Transwell and wound healing assays were performed to assess migratory potential,and western blotting was detected protein level.RESULTS A total of 53 differentially expressed miRNAs were identified in hucMSC treated with exosomes enriched with endometrial cell-derived components,comprising 27 upregulated and 26 downregulated miRNAs,which includes miR-137-3p.Enhanced migratory potential was observed in the Transwell and wound healing assays,and western blotting confirmed the epithelial differentiation of hucMSC and the increased p-signal transducer and activator of transcription 3.These effects were attributed to the upregulation of miR-137-3p.CONCLUSION miR-137-3p in exosomes from hypoxia-affected endometrial epithelial cell stimulates the signal transducer and activator of transcription 3 signaling pathway,enhancing the migration and differentiation of hucMSC into endometrial epithelial cell.展开更多
The effects of biodegradable Mg?6Zn alloy on tight junction of intestinal epithelial cells (IEC-6) were investigated. In the in vitro experiments, the cells were exposed to Mg?6Zn alloy extracts with different concent...The effects of biodegradable Mg?6Zn alloy on tight junction of intestinal epithelial cells (IEC-6) were investigated. In the in vitro experiments, the cells were exposed to Mg?6Zn alloy extracts with different concentrations (0, 20% and 40%) for 1, 3 and 5 d. The real-time polymerase chain reaction (PCR) results show that when the cells are treated with 40% and 20% extracts, the expression of Zona Occludens 1 (ZO-1) and Occludin increase as compared with those in the control group. In the in vivo experiments, Mg?6Zn alloy and titanium staples were implanted into rabbits’ intestinal tract for 1, 2 and 3 weeks. By immunohistochemical staining of peri-implant intestinal tissue, increased expression of Occludin and ZO-1 are observed in the Mg?6Zn alloy groups as compared with those in the titanium and control groups. The results show that Mg?6Zn alloy in intestine may promote the regeneration of tight junction, and the extract with a certain concentration can induce the expression of tight junction related genes in IEC-6 cells.展开更多
[Objective] The experiment aimed to set up a method for isolating and culturing endometrial stromal cells (BESC) and endometrial glandular epithelial cells(BEGEC) of buffalo as well as laid foundation for studying bio...[Objective] The experiment aimed to set up a method for isolating and culturing endometrial stromal cells (BESC) and endometrial glandular epithelial cells(BEGEC) of buffalo as well as laid foundation for studying biological mechanism of embryo implantation and uterine diseases. [Method] The enzymatic digestion method, scraping method, serial filtration and differential velocity adherent technique were used to isolate BESC and BEGEC, then immunocytochemical method and TRYPAN-Blue assay were used to determine the purity and survival rate of isolated cells. [Result] The BESC and BEGEC were successfully isolated and cultured while immunocytochemical method and cell count method demonstrated that the purity was over 90%. The result of TRYPAN-Blue assay shown that survival rate of BESC and BEGEC was 91% and 78% respectively. [Conclusion] The enzymatic digestion method, scraping method, serial filtration and differential velocity adherent technique could isolate BESC and BEGEC with high purity.展开更多
文摘Dear Editor,We present this case report which discusses a patient who underwent flap amputation after repeated attempts to resolve persistent and severe epithelial ingrowth following laser-assisted in situ keratomileusis(LASIK)surgery.Epithelial ingrowth is a known complication of LASIK surgery,typically manageable with minimal measures.However,severe cases may necessitate more aggressive interventions,such as flap amputation[1].LASIK is a widely performed refractive surgery with high success rates and excellent visual outcome[2].
基金supported by the China Postdoctoral Science Foundation(2021M701462)the National Natural Science Foundation of China(32072254)+2 种基金the Postdoctoral Research Funding Program of Jiangsu Province(2021K097A)the Fundamental Research Funds for the Central Universities(JUSRP121106)the“Qing Lan Project”of Jiangsu Province。
文摘The dark blue pigment(DBP)is a health ingredient from Vaccinium bracteatum Thunb.leaves used as a functional food supplement.However,the details of transepithelial absorption on the intestinal epithelial cells are barely understood.This study aimed to clarify the absorption properties of DBP in the Caco-2 cell monolayer model and evaluate the effect on the endo-metabolism and barrier function of Caco-2 cells.The results showed that the DBP did not show the dose-dependent toxic effect to Caco-2 cells between 0.25 and 1.5 mg/mL,which did not cause disorder in the normal cell metabolism and absorption activity.The Caco-2 cell monolayer model could absorb DBP by passive and active transport,and the absorptive pattern was dosedependent when the concentration was more than 0.25 mg/mL.During DBP absorption,an increase in m RNA and protein expressions of glucose transporters demonstrated that the glucose transporters were the potential transporter of DBP.But the glucose transport amounts were significantly lowered after 30 min of DBP treatment,indicating that DBP owned the inhibitory effect on glucose transportation.Furthermore,DBP also owned protective effects on the barrier function of intestinal epithelial cells.
基金supported by the National Natural Science Foundation of China(Nos.22206207,22127810,and 22276224)the Natural Science Foundation of Guangdong Province(Nos.2021A1515011546 and 2023A1515010085)the Science and Technology Planning Project of Guangzhou(No.202102080005)。
文摘Epithelial-mesenchymal transition(EMT)plays an irreplaceable role in the development of silicosis.However,molecular mechanisms of EMT induced by silica exposure still remain to be addressed.Herein,metabolic profiles of human alveolar type II epithelial cells(A549 cells)exposed directly to silica were characterized using non-targeted metabolomic approaches.A total of 84 differential metabolites(DMs)were identified in silica-treated A549 cells undergoing EMT,which were mainly enriched in metabolisms of amino acids(e.g.,glutamate,alanine,aspartate),purine metabolism,glycolysis,etc.The number of DMs identified in the A549 cells obviously increased with the elevated exposure concentration of silica.Remarkably,glutamine catabolism was significantly promoted in the silica-treated A549 cells,and the levels of related metabolites(e.g.,succinate)and enzymes(e.g.,α-ketoglutarate(α-KG)dehydrogenase)were substantially up-regulated,with a preference toα-KG pathway.Supplementation of glutamine into the cell culture could substantially enhance the expression levels of both EMT-related markers and Snail(zinc finger transcription factor).Our results suggest that the EMT of human alveolar epithelial cells directly induced by silica can be essential to the development of silicosis.
文摘BACKGROUND Oral squamous cell carcinoma(OSCC)is a frequent cancer affecting the oral cavity.OSCC is usually preceded by occurrence of precursor lesions,which demonstrate a varying degree of malignant transformation potential.Epithelialmesenchymal transition is a significant biological phenomenon that facilitates tumor growth and metastasis through the involvement of diverse epithelial and mesenchymal proteins.E-cadherin down regulation and over-expression of zincfinger E-box-binding homeobox 1(ZEB1)has been reported in several cancers.AIM To evaluate the role of E-cadherin and ZEB1 in oral leukoplakia and OSCC.METHODS A total of 60 cases i.e.,oral leukoplakia/oral epithelial dysplasia(OED)(n=30)and OSCC(n=30)were included.Immunohistochemistry was performed utilizing two markers:E-cadherin and ZEB1.The Mann-Whitney U test was employed to compare individual markers across the study groups.Spearman’s correlation was done followed by discriminant function analysis.RESULTS Reduction in the expression E-cadherin and altered localization were noted from OED to OSCC.Overexpression of ZEB1 along with cytoplasmic accumulation was noted in OED,with marked expression in OSCC.ZEB1 epithelium intensity and ZEB1 connective tissue percentage contributed to the discriminant function with an accuracy of 85%for the classification of OED from OSCC.CONCLUSION Loss of E-cadherin and up-regulation of ZEB1 from OED to OSCC,predisposes to induction of epithelial-mesenchymal transition.Discriminant formulas are developed to classify cases of OED and OSCC with 85%accuracy.
基金Supported by the National Natural Science Foundation of China(No.82103563)the Key Research and Development Program of Shaanxi Province(No.2020ZDLSF02-06).
文摘AIM:To investigate the effect of skullcapflavone II(SCF-II)on the epithelial-mesenchymal transition(EMT)induced by transforming growth factor beta(TGF-β)in human corneal epithelial cells(HCECs),as well as to identify the signaling pathways that may be involved.METHODS:HCECs were cultured in vitro.At a SCFII(5,10μmol/L)dose,cell viability was analysed with a cell counting kit-8(CCK-8)assay,and cell migration was monitored with wound healing and Transwell migration assays.There were 4 groups:SCF-II,TGF-β,SCF-II+TGF-βand Control.Western blotting and immunofluorescence were performed to show the expression of EMT markers and the translocation of nuclear factor kappa-B(NF-κB)into the nucleus in the 4 groups.RESULTS:Treatment with SCF-II decreased HCEC viability in a dose-dependent manner.A concentration below 10μmol/L did not present obvious cell toxicity,and survival rates were more than 70%at 48h.Treatment with SCF-II(5 and 10μmol/L)significantly impeded migration in wound healing and Transwell migration assays(P<0.05),and EMT markers and NF-κB translocation into the nucleus were inhibited.After both TGF-βand SCF-II treatment,the migration of TGF-β-treated HCECs were suppressed by SCF-II(P<0.05).The expression levels of the mesenchymal markers N-cadherin(P<0.05),α-smooth muscle actin(α-SMA;P<0.05)and NF-κB(P<0.05)in both TGF-β-and SCF-II-treated HCECs were lower than those in the HCECs treated with TGF-βalone and higher than those in HCECs treated with SCF-II alone.Immunofluorescence showed that the entry of NF-κB into the nucleus in both TGF-β-and SCF-IItreated HCECs was less than that in the TGF-β-treated HCECs.CONCLUSION:SCF-II inhibit TGF-β-induced EMT in HCECs by potentially regulating the NF-κB signalling pathway.Thus,SCF-II represents a candidate putative therapeutic agent in corneal fibrotic diseases.
文摘AIM:To highlight the importance of microRNA(miRNA)-21-5p in directing the phosphatase and tensin homolog(PTEN)gene to control the phosphoinositide 3-kinase/protein kinase B/mammalian target of rapamycin(PI3K/Akt/mTOR)pathway in retinal pigment epithelial(RPE)cells in humans subjected to photodamage.METHODS:Human adult RPE cell line-19(ARPE-19)was cultured in vitro and randomly divided into control,damage,overexpression,negative,and PI3K/Akt blocker groups to establish a photodamage model of ARPE-19 cells.The models were subjected to 24h of light exposure,after which the corresponding indices were detected.The cell counting kit-8 assay quantified cell viability,while flow cytometry determined apoptosis rates.The miRNA-21 mimics and miRNA mimic NC were transfected into ARPE-19 cells using a transient transfection technique.Quantitative reverse transcription polymerase chain reaction(SYBR Green)and Western blotting analyzed expression levels of miRNA-21-5p,PTEN,p-PI3K/PI3K,p-mTOR/mTOR,and p-Akt/Akt.Statistical analyses comprised one-way analysis of variance and the Student-Newman-Keuls test for multiple group comparisons.RESULTS:The photodamage group demonstrated reduced cell survival rates than the control group(P<0.01).The overexpression group exhibited higher cell survival rates than the injury group(P<0.01).The negative group showed no difference in viability(P>0.05).The PI3K/Akt blocker group demonstrated lower cell viability,compared with the overexpression group(P<0.01).CONCLUSION:miRNA-21-5p significantly increases ARPE-19 cell survival after photodamage and inhibits lightinduced ARPE-19 cell apoptosis,suggesting that it may play a protective role in RPE by activating the PI3K/Akt/mTOR pathway while downregulating PTEN expression.
文摘Multifocal epithelial hyperplasia(MEH),also known as Heck’s disease,is a rare and benign condition of the oral mucosa that is strongly associated with low-risk human papillomavirus(HPV)genotypes 13 and 32.This narrative review synthesizes recent findings regarding the epidemiology,viral mechanisms,clinical and histopathological features,diagnostic strategies-including molecular and immunohistochemical methods-and therapeutic approaches to MEH.This disease predominantly affects children and adolescents from Indigenous American countries,although cases have been increasingly reported in nonendemic regions.MEH manifests clinically as multiple,asymptomatic papules or nodules,typically exhibiting a characteristic cobblestone-like appearance.Histologically,it presents with epithelial hyperplasia,koilocytosis,and altered cytokeratin expression.Molecular techniques such as polymerase chain reaction and in situ hybridization are pivotal for accurate viral genotyping,while immunohistochemical markers such as CK4/13,Ki-67,and the absence of p16 can be useful adjuncts in differential diagnosis.Despite its self-limiting nature in most cases,treatment may be warranted in symptomatic or immunocompromised patients.This review highlights the need to improve diagnostic access,develop targeted vaccines,and implement public health strategies in vulnerable communities.It also highlights existing gaps in knowledge,particularly regarding host-virus interactions and the absence of standardized treatment protocols.
基金German research Foundation(DFG,grant numbers:CH2321/1–1 and SCHO1231/7–1)JH has received a scholarship from the Chinese Scholarship Council(CSC No.:201908350115).
文摘The oviduct epithelium is the initial maternal contact site for embryos after fertilization,offering the microenviron-ment before implantation.This early gestation period is particularly sensitive to stress,which can cause reduced fertil-ity and reproductive disorders in mammals.Nevertheless,the local impact of elevated stress hormones on the ovi-duct epithelium has received limited attention to date,except for a few reports on polyovulatory species like mice and pigs.In this study,we focused on the effects of chronic maternal stress on cattle,given its association with infertil-ity issues in this monoovulatory species.Bovine oviduct epithelial cells(BOEC)differentiated at the air–liquid interface(ALI)were stimulated with 250 nmol/L cortisol for 1 or 3 weeks.Subsequently,they were assessed for morphology,bioelectrical properties,and gene expression related to oviduct function,glucocorticoid pathway,cortisol metabo-lism,inflammation,and apoptosis.Results revealed adverse effects of cortisol on epithelium structure,featured by deciliation,vacuole formation,and multilayering.Additionally,cortisol exposure led to an increase in transepithelial potential difference,downregulated mRNA expression of the major glucocorticoid receptor(NR3C1),upregulated the expression of cortisol-responsive genes(FKBP5,TSC22D3),and significant downregulation of oviductal glycopro-tein 1(OVGP1)and steroid receptors PGR and ESR1.The systematic comparison to a similar experiment previously performed by us in porcine oviduct epithelial cells,indicated that bovine cultures were more susceptible to elevated cortisol levels than porcine.The distinct responses between both species are likely linked to their divergence in the cortisol-induced expression changes of HSD11B2,an enzyme controlling the cellular capacity to metabolise cortisol.These findings provide insights into the species-specific reactions and reproductive consequences triggered by maternal stress.
基金Supported by the National Natural Science Foundation of China(31601141)。
文摘A lactating dairy cow mammary epithelial cell(DCMEC)model is useful for studying milk synthesis and lactation in the dairy cow mammary gland.However,the cells can only maintain their original characteristics for a limited period in vitro.Thus,the proliferative capacity and lactation pattern of subcultured DCMECs need to be characterized.In the present study,subcultured DCMECs appeared to proliferate without changes in morphology or growth pattern up to the 12th passage.Subculturing had no obvious effect on the lactation capacity of the subcultured DCMEC up to the 10th passage in vitro.These results indicated that the DCMEC line could be subpassaged up to 10 times and still maintain its original milk synthesis characteristics.Moreover,DCMECs were frozen using different methods,and the method of placing the vials in the foam box was determined after cryopreservation with the best adherence of 91.2%.This method was recommended for long-term cryopreservation for DCMECs.
基金supported by the National Natural Science Foundation of China(32273082 and U21A20262).
文摘Background Ferroptosis is characterized by increased production of reactive oxygen species(ROS)and membrane lipid peroxidation that can exacerbate inflammatory damage.Extracellular vesicles(EVs)isolated from bovine milk have many biological functions,including antioxidant properties.However,the role of EVs on Klebsiella pneumoniaeinduced ferroptosis and oxidative stress in bovine mammary epithelial cells(bMECs)and murine mammary tissue is unclear.In this study,EVs were isolated from bovine colostrum,mature milk and clinical mastitis milk(defined as C-EVs,M-EVs and CM-EVs,respectively)and assessed by transmission electron microscopy,Western blot and transcriptome sequencing.Effects of EVs on K.pneumoniae-induced ferroptosis and oxidative stress in bMECs were evaluated with immunofluorescence and Western blot.Results In bMECs,infection with K.pneumoniae induced oxidative stress,decreasing protein expression of Nrf2,Keap1 and HO-1 plus SOD activity,and increasing ROS concentrations.However,protein expression of GPX4,ACSL4 and S100A4 in bMECs,all factors that regulate ferroptosis,was downregulated by K.pneumoniae.Furthermore,this bacterium compromised tight junctions in murine mammary tissue,with low expression of ZO-1 and Occludin,whereas protein expression of Nrf2 and GPX4 was also decreased in mammary tissue.Adding C-EVs,M-EVs or CMEVs reduced oxidative stress and ferroptosis in K.pneumoniae-infected bMECs in vitro and murine mammary tissues in vivo.Conclusion In conclusion,all 3 sources of milk-derived EVs alleviated oxidative stress and ferroptosis in K.pneumoniae-infected bMECs and mammary tissues.
基金Supported by Hubei Provincial Natural Science Foundation,No.2023AFB732and Scientific Research Project of Hubei Provincial Health Commission,No.WJ2023M053.
文摘BACKGROUND Diabetic nephropathy(DN)is a leading cause of chronic kidney disease and endstage renal disease,and is a significant global healthcare burden.Although proximal tubular epithelial cells(PTECs)and podocytes are involved in DN progression,the specific molecular interactions between these cells are not well understood.AIM To elucidate the role of interleukin-6(IL-6)/Rab5 signaling in mediating crosstalk between PTECs and podocytes,and to evaluate the protective effects of nicotinamide mononucleotide(NMN)against DN progression.METHODS We utilized in vitro and in vivo models to investigate the pathogenesis of DN.In vitro,human PTECs and murine podocytes were cultured under high-glucose conditions,and IL-6 neutralizing antibodies or NMN treatments were applied.Podocyte injury was assessed by measurements of nephrin endocytosis,Rab5 activity,cytoskeletal organization,cell adhesion,and cell-spreading assays.In vivo,DN was induced in mice using streptozotocin,and mice then received NMN,insulin,or both treatments over an 8-week period.Renal tissues were analyzed histologically,ultrastructurally,and immunochemically,and urinary albumin excretion was measured to assess renal function.Statistical analyses were conducted using one-way ANOVA and Tukey's test.RESULTS High-glucose conditions induced the epithelial-mesenchymal transition(EMT)in PTECs,increased IL-6 secretion,and activated Rab5 signaling in podocytes,leading to increased nephrin endocytosis and podocyte injury.Blocking IL-6 significantly attenuated these effects.NMN treatment of diabetic mice markedly reduced podocyte injury,glomerular hypertrophy,foot-process effacement,and urinary albumin excretion.Mechanistically,NMN suppressed the EMT and IL-6 secretion by PTECs,inhibited Rab5 activation in podocytes,and prevented nephrin endocytosis,thereby preserving the cytoskeletal integrity and function of podocytes.CONCLUSION Our findings reveal a novel pathogenic mechanism of DN in which IL-6 released from glucose-stressed PTECs activates Rab5 signaling in podocytes,followed by nephrin endocytosis and structural injury of podocytes.Importantly,NMN treatment effectively disrupted this pathological pathway of intercellular communication,and provided significant protection against DN progression.These results suggest that NMN supplementation and targeting the IL-6/Rab5 signaling axis has promise as a therapeutic strategy for managing DN.
文摘BACKGROUND The pathogenesis of non-ampullary duodenal epithelial tumors(NADETs)is not fully understood.NADETs that express gastric-type mucin phenotypes(GNADETs)are noteworthy because of their high malignancy.Gastric foveolar metaplasia,from which G-NADETs originate,protects the duodenal mucosa from gastric acidity.As gastric acid secretion is affected by endoscopic gastric mucosal atrophy(EGMA),we hypothesized that EGMA would be associated with GNADETs.AIM To evaluate the association between EGMA and the occurrence of G-NADETs.METHODS This cross-sectional retrospective study investigated the relationship between EGMA and NADETs in 134 patients.The duodenum was divided into parts 1(bulb),2(superior duodenal angle to the papilla),and 3(anal side of the papilla to the horizontal part).The effects of gastric acidity and presence of Brunner’s glands were considered.EGMA was divided into types C(no or mild atrophy)and O(severe atrophy).Mucin phenotype expressions in NADETs were divided into gastric,intestinal,gastrointestinal,and unclassifiable.RESULTS When NADETs were classified according to EGMA,105 were classified as type C and 29 as type O.G-NADETs were present in 11.9%(16 cases)of all cases,and all 16 cases were of type C.Among G-NADETs,93.8%(15 cases)were present in part 1 or 2.There was an association between G-NADETs and type C in part 1,and 50.0%(eight of 16 cases)of G-NADETs were associated with a current or previous Helicobacter pylori infection status.Additionally,all eight cases occurred in part 1.CONCLUSION G-NADETs were significantly associated with type C.Gastric acidity and Brunner's gland growth may be associated with G-NADETs.
基金supported by the Hebei Natural Science Foundation(Grant No.H2022110019).
文摘Diabetic kidney disease(DKD)has emerged as one of the leading causes of chronic kidney disease and end-stage renal disease worldwide.In the progression of DKD,renal tubular injury plays a pivotal role,with stress-induced senescence of renal tubular epithelial cells(RTECs)being a critical cellular event contributing to tubular damage in DKD.Recent studies have revealed that multiple mechanisms,including oxidative stress,mitochondrial autophagy,endoplasmic reticulum stress,and epigenetic modifications,can induce stress-induced senescence in RTECs,thereby driving the progression of DKD.In recent years,research has demonstrated that traditional Chinese medicine(TCM)can regulate these mechanisms through multiple targets and key pathways,inhibiting stress-induced senescence in RTECs and ameliorating the progression of DKD.TCM has been widely applied in clinical practice with proven efficacy.This article systematically summarizes the concept of cellular senescence,delves into the relationship between stress-induced senescence of RTECs and DKD,analyzes the mechanisms underlying the formation of stress-induced senescence in RTECs within the context of DKD,and reviews the research progress of TCM in anti-senescence treatment for DKD.The aim is to provide a reference for future research and the development of novel therapeutic strategies.
文摘Objective To investigate the differential expression of microRNA-144-3p in endometrial cells exposed to copper ions in vitro.The specific mechanism by which microRNA-144-3p is involved in Cu^(2+)-induced damage to the human endometrial epithelial cells(HEECs)was explored.Methods HEECs were cultured in copper-containing culture medium to simulate changes in the endometrium after copper intrauterine device(Cu-IUD)implantation.Reverse transcription quantitative PCR(RT-qPCR)was used to detect the differential expression of miR-144-3p in HEECs after Cu^(2+)treatment.MiRNAs,siRNAs and related inhibitors were used to treat HEECs.The expression levels of related downstream genes were then analyzed by RT-qPCR,Western blotting and immunofluorescence to explore the specific mechanism involved.Results MiR-144-3p was significantly upregulated in the Cu^(2+)-treated HEECs.The expression of P-NF-κB,MMP9,TGF-β3 and P-SMAD3 was significantly decreased in HEECs treated with 10μg/mL Cu^(2+).MiR-144-3p regulated the expression of metallothionein 1A(MT1A)and thrombospondin-1(THBS-1)in Cu^(2+)-treated HEECs.The expression of P-NF-κB can be regulated by MT1A,and an inhibitor of P-NF-κB can significantly reduce the expression of MMP9 in Cu^(2+)-treated HEECs.The expression of TGF-β3 can be regulated by THBS-1,and a TGF-β3 inhibitor can significantly reduce the expression of SMAD3 in Cu^(2+)-treated HEECs.The proliferative capacity of HEECs treated with MMP9 or SMAD3 inhibitors was significantly reduced.Conclusions The increased Cu^(2+)concentration led to the upregulation of miR-144-3p,further reducing the expression levels of its target genes(MT1A and THBS-1),which in turn downregulated the expression of NF-κB,MMP9,TGF-β3 and SMAD3,ultimately leading to increased endometrial cell damage and decreased cell proliferation.
基金the National Natural Science Foundation of China(Grant Nos.92478133,81930097,and 82151223)by the State Key Laboratory of Natural and Biomimetic Drugs(Grant No.K202430).
文摘Idiopathic pulmonary fibrosis(IPF)is a progressive and fatal interstitial lung disease characterized by excessive fibrotic remodeling,for which effective therapeutic options remain severely limited.Among the pathogenic mechanisms implicated in IPF,epithelial-to-mesenchymal transition(EMT)is recognized as a pivotal driver of fibroblast activation and extracellular matrix deposition.In this study,we aimed to develop low-molecular-weight dextran sulfate sodium(LMW-DSS)derivatives and assess their capacity to interfere with EMT,thereby offering novel therapeutic avenues for IPF management.Starting with dextran(2 kDa)as a precursor,we successfully synthesized two sulfated derivatives,DSS-LS and DSS-HS,via distinct sulfonation processes.Using a TGF-β1-stimulated A549 alveolar epithelial cell model,we demonstrated that LMW-DSS compounds exhibited no cytotoxicity,as validated by CCK-8 viability assays.Importantly,Transwell migration assays revealed that LMW-DSS markedly attenuated TGF-β1-induced A549 cell migration,indicating a potent anti-fibrotic effect.Moreover,qPCR and Western blotting analyses confirmed that LMW-DSS significantly suppressed the expression and secretion of key pro-fibrotic mediators,including TGF-β1 and VEGF-A,and downregulated critical EMT-associated markers such as Snail and vimentin.Notably,reducedα-SMA expression following LMW-DSS treatment further substantiated its role in hindering EMT progression.Collectively,these findings highlighted the capacity of LMW-DSS to effectively impede EMT and fibrotic processes,thereby delaying the progression of pulmonary fibrosis.This work not only underscored the therapeutic potential of LMW-DSS in IPF but also provided compelling experimental evidence to support its development as a promising anti-fibrotic agent for clinical application.
基金Bayan Nur Science and Technology Plan Project(Project No.:K202148)。
文摘Objective:This study primarily focuses on analyzing the inductive effects of emotional disturbances on the malignant transformation process of mammary gland epithelial cells.Methods:A total of 42 patients with malignant transformation of mammary gland epithelial cells(breast cancer,observation group)and 42 patients without malignant transformation of mammary gland epithelial cells(non-breast tumors,control group)were selected as research subjects.The earliest consultation time was January 2022,and the latest was January 2024.The extent of psychological stress impact on these patients was compared.Results:Compared with the control group,the observation group experienced a higher frequency and intensity(LEU value)of adverse life events,with P<0.05.The intensity of adverse life events in the observation group,except for mild events,was significantly higher than that in the control group(P<0.05).In terms of the content distribution of adverse life events,the proportion of marital and family problems in the observation group was significantly higher than that in the control group(P<0.05).The negative coping score and positive coping score in the observation group were significantly different from those in the control group(P<0.05).Regarding social support,the objective support score in the observation group was higher than that in the control group(P<0.05).Conclusion:During the malignant transformation process of mammary gland epithelial cells,long-term emotional disturbances have a significant impact,indicating a close relationship between psychological stress and the occurrence of breast cancer.
基金supported by the Tianjin Wuqing District Health and Health Research Project(WQWJ202403).
文摘Type 2 alveolar epithelial cell(AT2)senescence plays a crucial role in the onset andprogression of pulmonary fibrosis.Recent studies have revealed a close relationship betweenAT2 senescence and pulmonary fibrosis,suggesting that senescent cells have a dual role inthe injury repair process of lung tissue.On the one hand,senescent AT2 loses its repairfunction,and on the other hand,senescent cells exacerbate the inflammatory and fibroticprocesses by secreting senescence-associated secretory phenotype.In this paper,we willreview the biological mechanisms and pathological features of AT2 senescence and itsrelationship with the development of pulmonary fibrosis,and discuss current therapeuticintervention strategies,including the potential of small molecule drugs,cellular therapies,gene editing techniques,and traditional Chinese medicine.Finally,the paper summarizesthe challenges of current research and suggests future research directions.
基金Supported by the National High Level Hospital Clinical Research Funding,No.2022-PUMCH-B-080 and No.2022-PUMCH-C-064.
文摘BACKGROUND Thin endometrium,leading cause of recurrent implantation failure and infertility,has been found to respond to exosomes.AIM To investigate the efficacy of exosomes in addressing the issue of thin endometrium.METHODS RNA sequencing and reverse transcription-quantitative polymerase chain reaction were employed to identify differentially expressed microRNAs(miRNAs)in human umbilical cord mesenchymal stem cell(hucMSC)treated with exosomes enriched with endometrial cell-derived components.Additionally,Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses were conducted to highlight significant enrichment in specific biological pathways,molecular functions,and cellular components.Transwell and wound healing assays were performed to assess migratory potential,and western blotting was detected protein level.RESULTS A total of 53 differentially expressed miRNAs were identified in hucMSC treated with exosomes enriched with endometrial cell-derived components,comprising 27 upregulated and 26 downregulated miRNAs,which includes miR-137-3p.Enhanced migratory potential was observed in the Transwell and wound healing assays,and western blotting confirmed the epithelial differentiation of hucMSC and the increased p-signal transducer and activator of transcription 3.These effects were attributed to the upregulation of miR-137-3p.CONCLUSION miR-137-3p in exosomes from hypoxia-affected endometrial epithelial cell stimulates the signal transducer and activator of transcription 3 signaling pathway,enhancing the migration and differentiation of hucMSC into endometrial epithelial cell.
基金Project(30901422)supported by the National Natural Science Foundation of ChinaProject(YG2010MS45)supported by Shanghai Jiao Tong University Interdisciplinary(Biomedical Engineering)Research Fund,ChinaProject(09XJ21005)supported by School of Medicine Science and Technology Fund,Shanghai Jiao Tong University,China
文摘The effects of biodegradable Mg?6Zn alloy on tight junction of intestinal epithelial cells (IEC-6) were investigated. In the in vitro experiments, the cells were exposed to Mg?6Zn alloy extracts with different concentrations (0, 20% and 40%) for 1, 3 and 5 d. The real-time polymerase chain reaction (PCR) results show that when the cells are treated with 40% and 20% extracts, the expression of Zona Occludens 1 (ZO-1) and Occludin increase as compared with those in the control group. In the in vivo experiments, Mg?6Zn alloy and titanium staples were implanted into rabbits’ intestinal tract for 1, 2 and 3 weeks. By immunohistochemical staining of peri-implant intestinal tissue, increased expression of Occludin and ZO-1 are observed in the Mg?6Zn alloy groups as compared with those in the titanium and control groups. The results show that Mg?6Zn alloy in intestine may promote the regeneration of tight junction, and the extract with a certain concentration can induce the expression of tight junction related genes in IEC-6 cells.
基金Supported by the Innovation Foundation For Postgraduate of Guangxi University(2008105930905D001) the Tackle Key Program in Science and Technology of Science and Technology Bureau of Guangxi Province(0815008-2-4)~~
文摘[Objective] The experiment aimed to set up a method for isolating and culturing endometrial stromal cells (BESC) and endometrial glandular epithelial cells(BEGEC) of buffalo as well as laid foundation for studying biological mechanism of embryo implantation and uterine diseases. [Method] The enzymatic digestion method, scraping method, serial filtration and differential velocity adherent technique were used to isolate BESC and BEGEC, then immunocytochemical method and TRYPAN-Blue assay were used to determine the purity and survival rate of isolated cells. [Result] The BESC and BEGEC were successfully isolated and cultured while immunocytochemical method and cell count method demonstrated that the purity was over 90%. The result of TRYPAN-Blue assay shown that survival rate of BESC and BEGEC was 91% and 78% respectively. [Conclusion] The enzymatic digestion method, scraping method, serial filtration and differential velocity adherent technique could isolate BESC and BEGEC with high purity.
