BACKGROUND Gastric cancer is one of the most common cancers worldwide,especially in East Asia.AIM To explore the clinical outcomes and progression-related factors of low-grade intraepithelial neoplasia(LGIN)in the gas...BACKGROUND Gastric cancer is one of the most common cancers worldwide,especially in East Asia.AIM To explore the clinical outcomes and progression-related factors of low-grade intraepithelial neoplasia(LGIN)in the gastric mucosa and provide valuable guidance for improving treatment efficacy.METHODS A total of 357 patients diagnosed with LGIN based on initial pathological examination in Anhui Provincial Hospital or three other medical consortium units between January 2022 and June 2024 were included.Among them,296 patients were followed up with endoscopic and biopsy pathology.Logistic regression was utilized to analyze the relevant risk factors for LGIN progression in the gastric mucosa.RESULTS The distribution sites of LGIN among the 357 patients were as follows:Gastric antrum(54.6%),gastric cardia(24.1%),gastric angulus(8.7%),gastric body(4.8%),gastric fundus(4.8%),and multiple sites(3.1%).Additionally,of the 357 patients with LGIN,112(31.4%)developed ulceration and 59(16.5%)experienced gastric polyps.Furthermore,231 of the 357(64.71%)patients with LGIN tested positive for Helicobacter pylori(H.pylori)infection.The H.pylori infection rates of the patients with LGIN with accompanying atrophy,intestinal metaplasia,and gastric ulcer were 51.95%,59.31%,and 28.57%,respectively.Multivariate logistic regression analysis showed that age≥60 years[odds ratio(OR)=3.063,95%confidence interval(CI):1.351-6.945,P=0.007],H.pylori infection(OR=3.560,95%CI:1.158-10.949,P=0.027),multiple locations(OR=10.136,95%CI:2.045-50.237,P=0.005),lesion size≥2 cm(OR=3.921,95%CI:1.664-9.237,P=0.002),and gastric ulcer(OR=2.730,95%CI:1.197-6.223,P=0.017)were predictive factors for LGIN progression.CONCLUSION LGIN progression is closely related to age,H.pylori positivity,multiple locations,lesion size≥2 cm,and gastric ulcer.Thus,actively identifying these risk factors in patients with LGIN may have certain clinical significance in preventing further tumor progression.展开更多
Lipocalin-2(LCN2)is a member of the lipocalin superfamily with multiple functions and can participate in the transport of a variety of small lipophilic ligands in vivo.LCN2 is significantly expressed in various tumors...Lipocalin-2(LCN2)is a member of the lipocalin superfamily with multiple functions and can participate in the transport of a variety of small lipophilic ligands in vivo.LCN2 is significantly expressed in various tumors and plays an important role in regulating tumor cell proliferation,invasion,and metastasis.The specific actions of LCN2 in tumors may vary depending on the particular type of cancer involved.In this review,we provide an extensive overview of the transcriptional and post-transcriptional regulation of LCN2 in health and disease.Furthermore,we summarize the impact of LCN2 dysregulation in a broad range of tumors.Lastly,we examine the mechanisms of action of LCN2 during tumorigenesis,progression,and metastasis.Understanding the complex relationships between LCN2 and tumor development,progression,and metastasis is vital for advancing our knowledge of cancer biology,developing biomarkers for diagnosis and clinical decision-making,and creating therapeutic strategies to improve the management of patients with cancer.展开更多
In the article“LncRNA PCGEM1 facilitates cervical cancer progression via miR-642a-5p/KIF5B axis”(Oncology Research,2024,Vol 32,No.7,pp.1221-1229.doi:10.32604/or.2024.047454),there were some errors in the content.In ...In the article“LncRNA PCGEM1 facilitates cervical cancer progression via miR-642a-5p/KIF5B axis”(Oncology Research,2024,Vol 32,No.7,pp.1221-1229.doi:10.32604/or.2024.047454),there were some errors in the content.In order to ensure the scientific and rigorous nature of our academic publications,we deleted the incorrect content that is not related to this study,supplemented the details of the method.展开更多
Ovarian cancer(OC),a highly lethal gynaecological malignancy,is often diagnosed at advanced stages,resulting in a poor prognosis.Sialylation,an important form of glycosylation,significantly contributes to the progress...Ovarian cancer(OC),a highly lethal gynaecological malignancy,is often diagnosed at advanced stages,resulting in a poor prognosis.Sialylation,an important form of glycosylation,significantly contributes to the progression of various solid tumours,including OC.Aberrant sialylation promotes tumour progression and metastasis by altering the structure and function of glycoproteins.Although its role in several solid tumours is well documented,the role of abnormal sialylation in OC and its potential as a therapeutic target remain poorly understood.This review highlights sialylation as a key regulator of the progression,metastasis,and drug resistance of OC.A deeper understanding of altered sialylation can contribute to the identification of novel therapeutic strategies for OC.展开更多
Splenic histiocytic sarcoma(SHS)is a rare,aggressive hematological malignancy with unclear progression and management.Our case illustrates the progression and pathophysiological processes of SHS and provides key data ...Splenic histiocytic sarcoma(SHS)is a rare,aggressive hematological malignancy with unclear progression and management.Our case illustrates the progression and pathophysiological processes of SHS and provides key data for the diagnosis,treatment and management of SHS.A 60-year-old female with incidentally detected splenic mass(6.0 cm×5.7 cm)underwent splenectomy,confirmed as SHS in 2020.Post-op imatinib therapy was given.In 2022,hepatic metastases(2.4 cm×2.9 cm)with pancytopenia led to supportive care.Lesions enlarged to 4.3 cm×2.7 cm,leading to multi-organ failure and death at 33 months.The case was categorized into three distinct stages based on the pathophysiology of SHS:Early-stage splenic tumor growth,mid-stage liver metastasis with hematological abnormalities,and late-stage tumor infiltration leading to multiorgan failure.For SHS,this case highlights the pivotal role of early intervention and the value of personalized treatment strategies.展开更多
Candida albicans(C.albicans)represents one of the most prevalent opportunistic fungal pathogens in cancer patients.Although the association between C.albicans and cancer has been recognized for decades,the causal rela...Candida albicans(C.albicans)represents one of the most prevalent opportunistic fungal pathogens in cancer patients.Although the association between C.albicans and cancer has been recognized for decades,the causal relationship,whether C.albicans infection is a consequence of cancer or a direct contributor to cancer development-remains a subject of intensive investigation.Recently,the complex interplay between microbes and cancer has garnered significant attention within the scientific community,with growing interest in elucidating the underlying molecular mechanisms.This review systematically examines the biological characteristics of C.albicans,its multifaceted interactions with the host,and its relationship with the intestinal microbiota.Additionally,it provides a comprehensive analysis of the association between C.albicans and the development of various malignancies,with particular emphasis on digestive tract cancers.The review also identifies critical knowledge gaps and apparent contradictions in existing research,highlighting potential avenues for breakthroughs that will advance the efficient and accurate screening,diagnosis,and treatment of cancer.展开更多
Alzheimer’s disease(AD)is a slow,progressive neurodegenerative disease with clinical symptoms that typically emerge in the elderly,leading to deterioration of cognitive functions over time.Memory loss is the primary ...Alzheimer’s disease(AD)is a slow,progressive neurodegenerative disease with clinical symptoms that typically emerge in the elderly,leading to deterioration of cognitive functions over time.Memory loss is the primary symptom,eventually leading to significant declines in executive and cognitive functions,along with psychiatric and behavioral changes,and alterations in personality.展开更多
Objective Glioma is a highly heterogeneous and malignant intracranial tumor that presents challenges for clinical treatment.ELMO domain containing 2(ELMOD2)is a GTPase-activating protein that regulates a range of cell...Objective Glioma is a highly heterogeneous and malignant intracranial tumor that presents challenges for clinical treatment.ELMO domain containing 2(ELMOD2)is a GTPase-activating protein that regulates a range of cellular biological processes.However,its specific role and prognostic value in tumorigenesis are still unknown.This study aimed to assess the prognostic relevance and signaling function of ELMOD2 in gliomas.Methods The Chinese Glioma Genome Atlas(CGGA)and The Cancer Genome Atlas(TCGA)databases were utilized to conduct a comprehensive analysis of the expression profile of ELMOD2 in gliomas,elucidating its associations with clinicopathological parameters and patient prognosis.Single-cell analysis was performed to characterize ELMOD2 expression across distinct glioma cell subpopulations.Gene Ontology(GO),Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analyses,and Gene Set Variation Analysis(GSVA)were employed to evaluate the potential biological functions of ELMOD2 in gliomagenesis.Specific small interfering RNAs(siRNAs)were used to knock down ELMOD2 in the glioma cell lines U251 and A172 to assess their cellular behaviors and examine the levels of multiple key signaling molecules associated with the occurrence of gliomas.Results ELMOD2 was overexpressed in gliomas,and this upregulation was correlated with tumor grade,isocitrate dehydrogenase mutation,and 1p/19q codeletion status.Notably,ELMOD2 expression was elevated in classical and mesenchymal subtypes,and single-cell resolution analysis revealed predominant enrichment within malignant cells.Functionally,ELMOD2 regulated cell cycle progression,and its overexpression was related to independent adverse outcomes.In vitro experiments revealed that ELMOD2 was located in the cytoplasm and nucleoplasm.Furthermore,ELMOD2 knockdown reduced proliferation,migration,and invasion and increased apoptosis in U251 and A172 cell lines.Finally,ELMOD2 knockdown significantly decreased p-Erk1/2.Conclusions ELMOD2 expression in glioma is positively correlated with tumorigenesis and is a crucial independent prognostic marker.Thus,ELMOD2 is a promising biomarker and therapeutic target for glioma treatment.展开更多
BACKGROUNDColorectal cancer(CRC)typically progresses from benign colorectal polyps,whichrepresent a precursor to malignancy.Identifying the factors influencing thisprogression is crucial for early intervention and pre...BACKGROUNDColorectal cancer(CRC)typically progresses from benign colorectal polyps,whichrepresent a precursor to malignancy.Identifying the factors influencing thisprogression is crucial for early intervention and prevention.Although genetic andenvironmental factors have been widely studied,the role of lifestyle factors suchas physical activity,diet,smoking,sleep,and stress remains underexplored,especially in patients with early stage CRC or polyps.Recent evidence suggeststhat lifestyle behaviors may influence cancer progression by modulating inflammatorypathways,metabolic health,and immune function.For instance,highlevels of physical activity are linked to a reduced risk of CRC development,whereas poor dietary habits,smoking,and inadequate sleep have all beenimplicated in increased cancer risk and progression.Moreover,early-stage CRCpatients,who are often asymptomatic or have minimal symptoms,may particularlybenefit from lifestyle modifications to slow disease progression andimprove overall prognosis.The gap in understanding the specific influence ofthese lifestyle factors on colorectal polyps and early stage cancer progressionunderscores the need for comprehensive studies.By assessing several modifiablelifestyle factors and their association with disease progression,clinicians canidentify practical intervention points.These interventions could ultimately reducethe need for more aggressive treatments and improve the long-term outcomes inaffected patients.AIMTo investigate the association between lifestyle factors and disease progression inpatients with colorectal polyps and early stage cancer.METHODSIn this observational study conducted from January 2022 to December 2023,werecruited 120 patients with colorectal polyps or early stage cancer from Jiangshan People's Hospital.Lifestyle factors,including physical activity,dietary patterns,smoking status,sleep quality,andstress levels,were assessed using validated questionnaires.Disease progression was evaluated using standardizedfollow-up colonoscopies and pathological examinations.Cox proportional hazards models were used to analyzethe association between lifestyle factors and disease progression after adjusting for potential confounders.RESULTSDuring the median follow-up of 18.4 months,42(35.0%)patients experienced disease progression.High levels ofphysical activity were associated with reduced progression risk[adjusted hazard ratio(HR)0.55,95%confidenceinterval(CI):0.38-0.80,P=0.002]compared to low activity levels.High adherence to a healthy dietary patternshowed similar protective effects(adjusted HR 0.62,95%CI:0.43-0.89,P=0.009).Current smoking(adjusted HR1.92,95%CI:1.35-2.73,P<0.001)and poor sleep quality(adjusted HR 1.38,95%CI:1.05-1.82,P=0.021)wereassociated with increased progression risk.The impact of lifestyle factors was particularly pronounced in patientsyounger than 60 years and those with multiple polyps at baseline.CONCLUSIONThis study demonstrated significant associations between lifestyle factors and disease progression in colorectalpolyps and early stage cancer.Physical activity,dietary patterns,smoking status,and sleep quality have emergedas key modifiable factors influencing disease progression.These findings support the integration of lifestyleassessments and modifications in the clinical management of patients with colorectal neoplasia.展开更多
BACKGROUND Uncertainty in illness(UI)and fear of progression(FoP)are significant psycho-logical challenges for lung cancer patients.Coping styles and social support are critical mediators,influencing patients'abil...BACKGROUND Uncertainty in illness(UI)and fear of progression(FoP)are significant psycho-logical challenges for lung cancer patients.Coping styles and social support are critical mediators,influencing patients'ability to manage the emotional and psy-chological burden of UI and FoP.However,limited research has explored the chain mediation effect of these factors on the relationship between UI and FoP,particularly among Chinese lung cancer patients.Convenience sampling was used to recruit inpatients diagnosed with lung cancer at a tertiary hospital in Changde City between November and December 2023.A total of 320 participants completed the Mishel Uncertainty in Illness Scale,Simp-lified Coping Style Questionnaire,Mandarin Chinese Version of the Medical Outcomes Study Social Support Survey,and Fear of Progression Questionnaire-Short Form.The chain mediation analysis was performed using the PROCESS macro to examine the relationships between the variables.RESULTS The results revealed that UI had a significant direct effect on FoP(effect=0.224,95%CI:0.136-0.408).Additionally,three indirect pathways were identified:(1)Social support(effect=0.128,95%CI:0.045-0.153);(2)Coping style(effect=0.115,95%CI:0.048-0.157);and(3)Chain mediators involving social support and coping style(effect=0.072,95%CI:0.045-0.120).The total indirect effect of the three mediation paths is 31.5%.These results confirm that social support and coping style significantly mediate the relationship between UI and FoP.CONCLUSION Based on cross-sectional data and a chain mediation model,this study explored the mechanisms between UI,social support,coping style,and FOP.Patients with lung cancer have higher levels of FOP,and the results of this study revealed a correlation between these four factors.Social support and coping style partially mediated the effects of UI on FOP,and there was a chain-mediating effect between UI and FOP.Programs designed to strengthen social support networks should also incorporate training to develop adaptive coping strategies,ultimately reducing FOP and improving overall quality of life.展开更多
BACKGROUND IL-22 plays a pivotal role in the processes of inflammation and tissue healing.,but its role in cholangiocarcinoma(CCA)remains unclear.our study explored the IL-22/IL-22R1 pathway and its impact on CCA prog...BACKGROUND IL-22 plays a pivotal role in the processes of inflammation and tissue healing.,but its role in cholangiocarcinoma(CCA)remains unclear.our study explored the IL-22/IL-22R1 pathway and its impact on CCA progression through the ERK1/2 signaling cascade.AIM To determine the mechanism of the IL-22/IL-22R1 pathway in CCA and provide new directions for its clinical treatment.METHODS IL-22R1 expression was assessed in human and rat CCA tissues utilizing immunohistochemical techniques,Western blot analysis,and quantitative reverse transcription PCR.The impact of IL-22 on CCA cells was assessed in vitro via tests for proliferation,migration,invasion,and apoptosis assays.The rat models of thioacetamide-induced CCA and subcutaneous xenografts in nude mice were used to assess the in vivo effects.ERK1/2 inhibitors were applied to elucidate the mechanistic role of the pathway.RESULTS IL-22R1 was overexpressed in CCA cell lines and tissues.IL-22 treatment increased the phosphorylation of ERK1/2,promoting tumor cell proliferation,migration,invasion,and resistance to apoptosis.ERK1/2 inhibition considerably reversed these effects both in vitro and in vivo.CONCLUSION The IL-22/IL-22R1 axis promotes CCA progression by activating ERK1/2 signaling.Targeting this pathway with ERK1/2 inhibitors offers potential therapeutic strategies for CCA.展开更多
This study aims to understand the current status of fear of disease progression(FoP)in patients with coronary heart disease(CHD)following percutaneous coronary intervention(PCI),and to explore the relationship between...This study aims to understand the current status of fear of disease progression(FoP)in patients with coronary heart disease(CHD)following percutaneous coronary intervention(PCI),and to explore the relationship between FoP levels,perceived control,and medical coping strategies in these patients.A total of 360 CHD patients who underwent PCI at Xijing Hospital in Shaanxi Province between June and November 2024 were selected using a convenience sampling method.Surveys included a general information questionnaire,the Fear of Progression Questionnaire-Short Form(FoP-Q-SF),the revised Control Attitudes Scale(CAS-R),and the Medical Coping Modes Questionnaire(MCMQ).Pearson correlation analysis was used to examine the relationships between disease perception,positive coping strategies,and FoP.A total of 360 patients completed the study.The average score for FoP in patients with CHD after PCI was 31.64±4.61.FoP was negatively correlated with perceived control(r=-0.106,P<0.01)and medical coping(r=-0.194,P<0.01).Multivariate regression analysis showed that the type of intervention,family history of CHD,smoking status,perceived control,and total medical coping score were significant factors influencing FoP(P<0.01).Enhancing perceived control and identifying positive coping strategies can improve FoP levels in patients with CHD after PCI.Therefore,clinicians should focus on perceived control and medical coping levels in patients and develop targeted interventions to alleviate negative emotions related to FoP.展开更多
AIM:To investigate the prevalence and characteristics of myopia in school-aged students and effects of environmental and genetic factors on the progression of myopia.METHODS:A total of 2422 students aged between 5 and...AIM:To investigate the prevalence and characteristics of myopia in school-aged students and effects of environmental and genetic factors on the progression of myopia.METHODS:A total of 2422 students aged between 5 and 18y from nine schools in Baiyun District of Guangzhou,China were sampled using a stratified sampling method in 2020.Among them,1066 students participated in the follow-up survey the following year.Data were obtained based on ocular examinations and a questionnaire survey conducted during two visits.Factors potentially influencing the progression of myopia were analyzed.RESULTS:During the year assessed in this study,the percentage of students with myopia increased from 58.4%to 64.8%(P=0.002).Spherical equivalent(SE)progressed from-1.44±1.91 diopters(D)at baseline to-1.66±1.10 D(P=0.005).A generalized estimating equation(GEE)model revealed that age[adjusted odds ratio(aOR)=1.298,P<0.001],residential students(aOR=2.428,P=0.018),parental myopia(one myopic parent:aOR=1.553,both parents myopic:aOR=2.609,P<0.001),frequent reading of books or viewing of screens in direct sunlight(aOR=3.502,P=0.023),using only overhead lighting for reading and writing at night(aOR=1.633,P=0.011),parental restrictions on exercise time(aOR=2.286,P=0.012),and having less than 2h of outdoor exercise per day during the past week(aOR=1.584,P=0.019)were all identified as independent risk factors for progression of myopia.CONCLUSION:Our findings in this study indicate that age,residential students,parental myopia,indoor lighting environment,and physical activity have significant effects on the progression of myopia,providing evidence for further in-depth mechanistic interpretation and efficient intervention strategies for school-age children in this area.展开更多
Background:Lung cancer remains a major factor causing cancer-associated mortality globally.While there have been advancements in treatment options,advanced lung cancer patients still have poor outcomes.This study aims...Background:Lung cancer remains a major factor causing cancer-associated mortality globally.While there have been advancements in treatment options,advanced lung cancer patients still have poor outcomes.This study aims to investigate the potential role of Transmembrane protein 33(TMEM33)in the development of lung adenocarcinoma.Methods:We leveraged The Cancer Genome Atlas(TCGA)database to analyze the connection between TMEM33 expression to the prognosis of lung adenocarcinoma(LUAD).Cell proliferation,invasiveness,and sphere formation were analyzed by various experiments.The association of miR-214-3p with TMEM33 was explored using luciferase reporter assay,immunoblotting,and real-time quantitative PCR(RT-qPCR).Additionally,TMEM33’s biological role was confirmed in the mouse xenograft model through lung cancer transplantation and metastasis studies.Results:TMEM33 showed high expression within both LUAD tissues and cells,with its expression correlating with poor patient survival outcomes.Silencing TMEM33 resulted in significant reductions in cell proliferation,invasiveness,and stem-like properties.Further investigation suggested that miR-214-3p negatively regulated TMEM33.In both cellular and animal models,we further demonstrated that TMEM33 knockdown could effectively suppress the aggressiveness of lung cancer cells,impeding tumor growth and inhibiting metastasis in the mouse model.Moreover,reducing TMEM33 expression reduced key signaling molecules within the Wnt/β-catenin pathway,providing insights into TMEM33’s mechanistic role in LUAD.Conclusion:TMEM33 functions as an oncogene,which is under the negative regulation of miR-214-3p,to promote the LUAD malignant characteristics by engaging the Wnt/β-catenin cascade.展开更多
Background:U2AF homology motif kinase 1(UHMK1)has been associated with RNA processing and protein phosphorylation,thereby influencing tumor progression.The study aimed to explore its regulatory mechanisms and biologic...Background:U2AF homology motif kinase 1(UHMK1)has been associated with RNA processing and protein phosphorylation,thereby influencing tumor progression.The study aimed to explore its regulatory mechanisms and biological functions in human prostate cancer(PCa).Methods:In this study,we systematically evaluated the expression and prognostic significance of UHMK1 in public databases,followed by validation through immunohis-tochemistry(IHC)in PCa specimens.Both gain-of-function and loss-of-function experiments were conducted to elucidate the role of UHMK1 in vitro and in vivo.Additionally,a series of molecular and biochemical assays were performed to investigate the regulatory mechanisms underlying UHMK1 activity.Results:Our findings revealed that UHMK1 expression was significantly upregulated in PCa tissues and correlated with poor patient prognosis,as demonstrated by analysis of public datasets and confirmed by immunohistochemical staining.Functional studies showed that UHMK1 depletion suppressed tumor cell proliferation and metastasis,while its overexpression promoted these processes.Mechanistically,we identified that UHMK1 phosphorylates nuclear receptor coactivator 3(NCOA3),which subsequently activates activating transcription factor 4(ATF4)to upregulate methylenetetrahydrofolate dehy-drogenase 2(MTHFD2)transcription.Interestingly,MTHFD2 was found to reciprocally enhance UHMK1 expression,establishing a positive feedback loop.Conclusions:In conclusion,our data suggest that the UHMK1-MTHFD2 axis forms a positive feedback loop that drives PCa progression.Targeting this loop represents a promising therapeutic strategy for restraining prostate cancer development and progression.展开更多
Background:Hepatocellular carcinoma(HCC)is a prevalent liver malignancy.This study examined the roles of transforming growth factor beta(TGF-β)and cytochrome b5 domain containing 2(CYB5D2)in HCC etiology and their pr...Background:Hepatocellular carcinoma(HCC)is a prevalent liver malignancy.This study examined the roles of transforming growth factor beta(TGF-β)and cytochrome b5 domain containing 2(CYB5D2)in HCC etiology and their prognostic biomarker potential.Methods:Key modules and prognostic genes were identified by analyzing the GSE101685 dataset by weighted gene co-expression network analysis(WGCNA)and Least absolute shrinkage and selection operator(LASSO)Cox regression.The expression levels of CYB5D2 and TGF-βin HCC cell lines were quantified using Quantitative reverse transcription polymerase chain reaction(qRT-PCR)and Western blotting(WB)assays.Effects of CYB5D2 overexpression on cell proliferation,migration,invasion,and epithelial-mesenchymal transition(EMT)marker regulation were assessed in vitro,while in vivo tumorigenicity was evaluated using a xenograft model of HCC in nude mice.Results:In this study,WGCNA identified the turquoise module as significantly associated with HCC,containing 452 DEGs.LASSO Cox regression analysis revealed 9 key prognostic genes,with CYB5D2 being underexpressed in HCC cells and tissues.TGF-βwas negatively correlated with CYB5D2 expression,resulting in poor patient prognosis.Functional assays demonstrated that CYB5D2 overexpression inhibited proliferation,migration,and invasion of HCC cell lines,and altered EMT marker expression.Furthermore,the addition of TGF-βpartially reversed the suppressive effects caused by CYB5D2 overexpression.In vivo,CYB5D2 overexpression significantly reduced tumor growth,indicating its potential as a therapeutic target for HCC.Conclusion:The tumor suppressor function of CYB5D2 in HCC and its interaction with TGF-βoffered fresh information on the molecular pathophysiology of HCC and possible treatment avenues.展开更多
Background:Colorectal cancer(CRC)is common and deadly,often leading to metastasis,challenging treatment,and poor outcomes.Understanding its molecular basis is crucial for developing effective therapies.Aims:This study...Background:Colorectal cancer(CRC)is common and deadly,often leading to metastasis,challenging treatment,and poor outcomes.Understanding its molecular basis is crucial for developing effective therapies.Aims:This study aimed to investigate the role of Myosin Heavy Chain 11(MYH11)in CRC progression,especially its effects on epithelial-mesenchymal transition(EMT)and cell behavior,and to explore its potential regulation by the EMT transcription factor zinc finger E-box binding homeobox 1(ZEB1).Methods:Differential expression analysis was performed in the GSE123390 and TCGA-READ datasets,and 317 intersection genes were identified.The hub gene MYH11 was identified based on Protein-protein interaction(PPI)analysis and expression validation.The effects of MYH11 and the EMT transcription factor(ZEB1)on the behavior of CRC cells were investigated in vitro.Results:Bioinformatics research revealed that MYH11 was considerably downregulated in CRC samples as compared to normal samples.Overexpression of MYH11 inhibited the proliferation,migration,and invasion of CRC cells.Western blotting(WB)testing showed that MYH11 overexpression inhibited EMT by elevating E-cadherin levels while suppressing ZEB1,vimentin,and N-cadherin expressions.By contrast,overexpression of ZEB1 promoted EMT and enhanced migration,invasion,and proliferation of CRC cells.The negative impacts of MYH11 affecting EMT markers and cell behaviors were partially mitigated by co-overexpression of MYH11 and ZEB1,indicating that MYH11 regulates EMT and CRC progression through ZEB1.Conclusion:Our study shows MYH11 curbs CRC growth by blocking EMT and invasion,but ZEB1 overexpression reduces this effect.It uncovers key CRC pathways and suggests MYH11’s therapeutic potential.展开更多
Oral squamous cell carcinoma(OSCC)progresses from preneoplastic precursors via genetic and epigenetic alterations.Previous studies have focused on the treatment of terminally developed OSCC.However,the role of epigene...Oral squamous cell carcinoma(OSCC)progresses from preneoplastic precursors via genetic and epigenetic alterations.Previous studies have focused on the treatment of terminally developed OSCC.However,the role of epigenetic regulators as therapeutic targets during the transition from preneoplastic precursors to OSCC has not been well studied.Our study identified lysine-specific demethylase 1(LSD1)as a crucial promoter of OSCC,demonstrating that its knockout or pharmacological inhibition in mice reversed OSCC preneoplasia.LSD1 inhibition by SP2509 disrupted cell cycle,reduced immunosuppression,and enhanced CD4+and CD8+T-cell infiltration.In a feline model of spontaneous OSCC,a clinical LSD1 inhibitor(Seclidemstat or SP2577)was found to be safe and effectively inhibit the STAT3 network.Mechanistic studies revealed that LSD1 drives OSCC progression through STAT3 signaling,which is regulated by phosphorylation of the cell cycle mediator CDK7 and immunosuppressive CTLA4.Notably,LSD1 inhibition reduced the phosphorylation of CDK7 at Tyr170 and eIF4B at Ser422,offering insights into a novel mechanism by which LSD1 regulates the preneoplastic-to-OSCC transition.This study provides a deeper understanding of OSCC progression and highlights LSD1 as a potential therapeutic target for controlling OSCC progression from preneoplastic lesions.展开更多
Hepatitis B virus(HBV)reactivation is a clinically significant challenge in disease management.This review explores the immunological mechanisms underlying HBV reactivation,emphasizing disease progression and manageme...Hepatitis B virus(HBV)reactivation is a clinically significant challenge in disease management.This review explores the immunological mechanisms underlying HBV reactivation,emphasizing disease progression and management.It delves into host immune responses and reactivation’s delicate balance,spanning innate and adaptive immunity.Viral factors’disruption of this balance,as are interac-tions between viral antigens,immune cells,cytokine networks,and immune checkpoint pathways,are examined.Notably,the roles of T cells,natural killer cells,and antigen-presenting cells are discussed,highlighting their influence on disease progression.HBV reactivation’s impact on disease severity,hepatic flares,liver fibrosis progression,and hepatocellular carcinoma is detailed.Management strategies,including anti-viral and immunomodulatory approaches,are critically analyzed.The role of prophylactic anti-viral therapy during immunosuppressive treatments is explored alongside novel immunotherapeutic interventions to restore immune control and prevent reactivation.In conclusion,this compre-hensive review furnishes a holistic view of the immunological mechanisms that propel HBV reactivation.With a dedicated focus on understanding its implic-ations for disease progression and the prospects of efficient management stra-tegies,this article contributes significantly to the knowledge base.The more profound insights into the intricate interactions between viral elements and the immune system will inform evidence-based approaches,ultimately enhancing disease management and elevating patient outcomes.The dynamic landscape of management strategies is critically scrutinized,spanning anti-viral and immunomodulatory approaches.The role of prophylactic anti-viral therapy in preventing reactivation during immunosuppressive treatments and the potential of innovative immunotherapeutic interventions to restore immune control and proactively deter reactivation.展开更多
The study aimed to test if Briganti’s 2012 nomogram could be associated with the risk of prostate cancer (PCa) progression in European Association of Urology (EAU) intermediate-risk patients treated with robotic surg...The study aimed to test if Briganti’s 2012 nomogram could be associated with the risk of prostate cancer (PCa) progression in European Association of Urology (EAU) intermediate-risk patients treated with robotic surgery. From January 2013 to December 2021, 527 consecutive patients belonging to the EAU intermediate-risk class were selected. Briganti’s 2012 nomogram, which predicts the risk of pelvic lymph node invasion (PLNI), was assessed as a continuous and dichotomous variable that categorized up to the median of 3.0%. Disease progression defined as biochemical recurrence and/or metastatic progression was evaluated by Cox proportional hazards (univariate and multivariate analysis). After a median follow-up of 95.0 months (95% confidence interval [CI]: 78.5–111.4), PCa progression occurred in 108 (20.5%) patients who were more likely to present with an unfavorable nomogram risk score, independently by the occurrence of unfavorable pathology including tumor upgrading and upstaging as well as PLNI. Accordingly, as Briganti’s 2012 risk score increased, patients were more likely to experience disease progression (hazard ratio [HR] = 1.060;95% CI: 1.021–1.100;P = 0.002);moreover, it also remained significant when dichotomized above a risk score of 3.0% (HR = 2.052;95% CI: 1.298–3.243;P < 0.0001) after adjustment for clinical factors. In the studied risk population, PCa progression was independently predicted by Briganti’s 2012 nomogram. Specifically, we found that patients were more likely to experience disease progression as their risk score increased. Because of the significant association between risk score and tumor behavior, the nomogram can further stratify intermediate-risk PCa patients, who represent a heterogeneous risk category for which different treatment paradigms exist.展开更多
基金the Research Project of the Chinese Digestive Early Cancer Physicians’Joint Growth Program,No.GTCZ-2021-AH-34-0012.
文摘BACKGROUND Gastric cancer is one of the most common cancers worldwide,especially in East Asia.AIM To explore the clinical outcomes and progression-related factors of low-grade intraepithelial neoplasia(LGIN)in the gastric mucosa and provide valuable guidance for improving treatment efficacy.METHODS A total of 357 patients diagnosed with LGIN based on initial pathological examination in Anhui Provincial Hospital or three other medical consortium units between January 2022 and June 2024 were included.Among them,296 patients were followed up with endoscopic and biopsy pathology.Logistic regression was utilized to analyze the relevant risk factors for LGIN progression in the gastric mucosa.RESULTS The distribution sites of LGIN among the 357 patients were as follows:Gastric antrum(54.6%),gastric cardia(24.1%),gastric angulus(8.7%),gastric body(4.8%),gastric fundus(4.8%),and multiple sites(3.1%).Additionally,of the 357 patients with LGIN,112(31.4%)developed ulceration and 59(16.5%)experienced gastric polyps.Furthermore,231 of the 357(64.71%)patients with LGIN tested positive for Helicobacter pylori(H.pylori)infection.The H.pylori infection rates of the patients with LGIN with accompanying atrophy,intestinal metaplasia,and gastric ulcer were 51.95%,59.31%,and 28.57%,respectively.Multivariate logistic regression analysis showed that age≥60 years[odds ratio(OR)=3.063,95%confidence interval(CI):1.351-6.945,P=0.007],H.pylori infection(OR=3.560,95%CI:1.158-10.949,P=0.027),multiple locations(OR=10.136,95%CI:2.045-50.237,P=0.005),lesion size≥2 cm(OR=3.921,95%CI:1.664-9.237,P=0.002),and gastric ulcer(OR=2.730,95%CI:1.197-6.223,P=0.017)were predictive factors for LGIN progression.CONCLUSION LGIN progression is closely related to age,H.pylori positivity,multiple locations,lesion size≥2 cm,and gastric ulcer.Thus,actively identifying these risk factors in patients with LGIN may have certain clinical significance in preventing further tumor progression.
基金supported by the Program for Science Technology and Innovation Committee of Shenzhen(2021N062-JCYJ20210324115408023)Guangdong High-Level Hospital Construction Fund,Shenzhen High-Level Hospital Construction Fund。
文摘Lipocalin-2(LCN2)is a member of the lipocalin superfamily with multiple functions and can participate in the transport of a variety of small lipophilic ligands in vivo.LCN2 is significantly expressed in various tumors and plays an important role in regulating tumor cell proliferation,invasion,and metastasis.The specific actions of LCN2 in tumors may vary depending on the particular type of cancer involved.In this review,we provide an extensive overview of the transcriptional and post-transcriptional regulation of LCN2 in health and disease.Furthermore,we summarize the impact of LCN2 dysregulation in a broad range of tumors.Lastly,we examine the mechanisms of action of LCN2 during tumorigenesis,progression,and metastasis.Understanding the complex relationships between LCN2 and tumor development,progression,and metastasis is vital for advancing our knowledge of cancer biology,developing biomarkers for diagnosis and clinical decision-making,and creating therapeutic strategies to improve the management of patients with cancer.
文摘In the article“LncRNA PCGEM1 facilitates cervical cancer progression via miR-642a-5p/KIF5B axis”(Oncology Research,2024,Vol 32,No.7,pp.1221-1229.doi:10.32604/or.2024.047454),there were some errors in the content.In order to ensure the scientific and rigorous nature of our academic publications,we deleted the incorrect content that is not related to this study,supplemented the details of the method.
基金supported by Hubei Provincial Natural Science Foundation of China(No.2023AFB670).
文摘Ovarian cancer(OC),a highly lethal gynaecological malignancy,is often diagnosed at advanced stages,resulting in a poor prognosis.Sialylation,an important form of glycosylation,significantly contributes to the progression of various solid tumours,including OC.Aberrant sialylation promotes tumour progression and metastasis by altering the structure and function of glycoproteins.Although its role in several solid tumours is well documented,the role of abnormal sialylation in OC and its potential as a therapeutic target remain poorly understood.This review highlights sialylation as a key regulator of the progression,metastasis,and drug resistance of OC.A deeper understanding of altered sialylation can contribute to the identification of novel therapeutic strategies for OC.
基金Supported by the Program of General Hospital of Western Theater,No.2021-XZYG-C33.
文摘Splenic histiocytic sarcoma(SHS)is a rare,aggressive hematological malignancy with unclear progression and management.Our case illustrates the progression and pathophysiological processes of SHS and provides key data for the diagnosis,treatment and management of SHS.A 60-year-old female with incidentally detected splenic mass(6.0 cm×5.7 cm)underwent splenectomy,confirmed as SHS in 2020.Post-op imatinib therapy was given.In 2022,hepatic metastases(2.4 cm×2.9 cm)with pancytopenia led to supportive care.Lesions enlarged to 4.3 cm×2.7 cm,leading to multi-organ failure and death at 33 months.The case was categorized into three distinct stages based on the pathophysiology of SHS:Early-stage splenic tumor growth,mid-stage liver metastasis with hematological abnormalities,and late-stage tumor infiltration leading to multiorgan failure.For SHS,this case highlights the pivotal role of early intervention and the value of personalized treatment strategies.
文摘Candida albicans(C.albicans)represents one of the most prevalent opportunistic fungal pathogens in cancer patients.Although the association between C.albicans and cancer has been recognized for decades,the causal relationship,whether C.albicans infection is a consequence of cancer or a direct contributor to cancer development-remains a subject of intensive investigation.Recently,the complex interplay between microbes and cancer has garnered significant attention within the scientific community,with growing interest in elucidating the underlying molecular mechanisms.This review systematically examines the biological characteristics of C.albicans,its multifaceted interactions with the host,and its relationship with the intestinal microbiota.Additionally,it provides a comprehensive analysis of the association between C.albicans and the development of various malignancies,with particular emphasis on digestive tract cancers.The review also identifies critical knowledge gaps and apparent contradictions in existing research,highlighting potential avenues for breakthroughs that will advance the efficient and accurate screening,diagnosis,and treatment of cancer.
基金supported by the National Natural Science Foundation of China(82120108010 and 81930028).
文摘Alzheimer’s disease(AD)is a slow,progressive neurodegenerative disease with clinical symptoms that typically emerge in the elderly,leading to deterioration of cognitive functions over time.Memory loss is the primary symptom,eventually leading to significant declines in executive and cognitive functions,along with psychiatric and behavioral changes,and alterations in personality.
基金supported by grants from the Natural Science Foundation of Guangxi Province(Grant No:2022GXNSFAA035639 and 2023GXNSFBA026092)the National Natural Science Foundation of China(Grant No:81860445 and 82260554)the Innovation Project of Guangxi Graduate Education(Grant No:YCBZ2024118)。
文摘Objective Glioma is a highly heterogeneous and malignant intracranial tumor that presents challenges for clinical treatment.ELMO domain containing 2(ELMOD2)is a GTPase-activating protein that regulates a range of cellular biological processes.However,its specific role and prognostic value in tumorigenesis are still unknown.This study aimed to assess the prognostic relevance and signaling function of ELMOD2 in gliomas.Methods The Chinese Glioma Genome Atlas(CGGA)and The Cancer Genome Atlas(TCGA)databases were utilized to conduct a comprehensive analysis of the expression profile of ELMOD2 in gliomas,elucidating its associations with clinicopathological parameters and patient prognosis.Single-cell analysis was performed to characterize ELMOD2 expression across distinct glioma cell subpopulations.Gene Ontology(GO),Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analyses,and Gene Set Variation Analysis(GSVA)were employed to evaluate the potential biological functions of ELMOD2 in gliomagenesis.Specific small interfering RNAs(siRNAs)were used to knock down ELMOD2 in the glioma cell lines U251 and A172 to assess their cellular behaviors and examine the levels of multiple key signaling molecules associated with the occurrence of gliomas.Results ELMOD2 was overexpressed in gliomas,and this upregulation was correlated with tumor grade,isocitrate dehydrogenase mutation,and 1p/19q codeletion status.Notably,ELMOD2 expression was elevated in classical and mesenchymal subtypes,and single-cell resolution analysis revealed predominant enrichment within malignant cells.Functionally,ELMOD2 regulated cell cycle progression,and its overexpression was related to independent adverse outcomes.In vitro experiments revealed that ELMOD2 was located in the cytoplasm and nucleoplasm.Furthermore,ELMOD2 knockdown reduced proliferation,migration,and invasion and increased apoptosis in U251 and A172 cell lines.Finally,ELMOD2 knockdown significantly decreased p-Erk1/2.Conclusions ELMOD2 expression in glioma is positively correlated with tumorigenesis and is a crucial independent prognostic marker.Thus,ELMOD2 is a promising biomarker and therapeutic target for glioma treatment.
文摘BACKGROUNDColorectal cancer(CRC)typically progresses from benign colorectal polyps,whichrepresent a precursor to malignancy.Identifying the factors influencing thisprogression is crucial for early intervention and prevention.Although genetic andenvironmental factors have been widely studied,the role of lifestyle factors suchas physical activity,diet,smoking,sleep,and stress remains underexplored,especially in patients with early stage CRC or polyps.Recent evidence suggeststhat lifestyle behaviors may influence cancer progression by modulating inflammatorypathways,metabolic health,and immune function.For instance,highlevels of physical activity are linked to a reduced risk of CRC development,whereas poor dietary habits,smoking,and inadequate sleep have all beenimplicated in increased cancer risk and progression.Moreover,early-stage CRCpatients,who are often asymptomatic or have minimal symptoms,may particularlybenefit from lifestyle modifications to slow disease progression andimprove overall prognosis.The gap in understanding the specific influence ofthese lifestyle factors on colorectal polyps and early stage cancer progressionunderscores the need for comprehensive studies.By assessing several modifiablelifestyle factors and their association with disease progression,clinicians canidentify practical intervention points.These interventions could ultimately reducethe need for more aggressive treatments and improve the long-term outcomes inaffected patients.AIMTo investigate the association between lifestyle factors and disease progression inpatients with colorectal polyps and early stage cancer.METHODSIn this observational study conducted from January 2022 to December 2023,werecruited 120 patients with colorectal polyps or early stage cancer from Jiangshan People's Hospital.Lifestyle factors,including physical activity,dietary patterns,smoking status,sleep quality,andstress levels,were assessed using validated questionnaires.Disease progression was evaluated using standardizedfollow-up colonoscopies and pathological examinations.Cox proportional hazards models were used to analyzethe association between lifestyle factors and disease progression after adjusting for potential confounders.RESULTSDuring the median follow-up of 18.4 months,42(35.0%)patients experienced disease progression.High levels ofphysical activity were associated with reduced progression risk[adjusted hazard ratio(HR)0.55,95%confidenceinterval(CI):0.38-0.80,P=0.002]compared to low activity levels.High adherence to a healthy dietary patternshowed similar protective effects(adjusted HR 0.62,95%CI:0.43-0.89,P=0.009).Current smoking(adjusted HR1.92,95%CI:1.35-2.73,P<0.001)and poor sleep quality(adjusted HR 1.38,95%CI:1.05-1.82,P=0.021)wereassociated with increased progression risk.The impact of lifestyle factors was particularly pronounced in patientsyounger than 60 years and those with multiple polyps at baseline.CONCLUSIONThis study demonstrated significant associations between lifestyle factors and disease progression in colorectalpolyps and early stage cancer.Physical activity,dietary patterns,smoking status,and sleep quality have emergedas key modifiable factors influencing disease progression.These findings support the integration of lifestyleassessments and modifications in the clinical management of patients with colorectal neoplasia.
基金Supported by Hunan Provincial Natural Science Foundation of China,No.2024JJ9579 and No.2025JJ80410The Science and Technology Innovation Program of Changde City,No.2023YD23.
文摘BACKGROUND Uncertainty in illness(UI)and fear of progression(FoP)are significant psycho-logical challenges for lung cancer patients.Coping styles and social support are critical mediators,influencing patients'ability to manage the emotional and psy-chological burden of UI and FoP.However,limited research has explored the chain mediation effect of these factors on the relationship between UI and FoP,particularly among Chinese lung cancer patients.Convenience sampling was used to recruit inpatients diagnosed with lung cancer at a tertiary hospital in Changde City between November and December 2023.A total of 320 participants completed the Mishel Uncertainty in Illness Scale,Simp-lified Coping Style Questionnaire,Mandarin Chinese Version of the Medical Outcomes Study Social Support Survey,and Fear of Progression Questionnaire-Short Form.The chain mediation analysis was performed using the PROCESS macro to examine the relationships between the variables.RESULTS The results revealed that UI had a significant direct effect on FoP(effect=0.224,95%CI:0.136-0.408).Additionally,three indirect pathways were identified:(1)Social support(effect=0.128,95%CI:0.045-0.153);(2)Coping style(effect=0.115,95%CI:0.048-0.157);and(3)Chain mediators involving social support and coping style(effect=0.072,95%CI:0.045-0.120).The total indirect effect of the three mediation paths is 31.5%.These results confirm that social support and coping style significantly mediate the relationship between UI and FoP.CONCLUSION Based on cross-sectional data and a chain mediation model,this study explored the mechanisms between UI,social support,coping style,and FOP.Patients with lung cancer have higher levels of FOP,and the results of this study revealed a correlation between these four factors.Social support and coping style partially mediated the effects of UI on FOP,and there was a chain-mediating effect between UI and FOP.Programs designed to strengthen social support networks should also incorporate training to develop adaptive coping strategies,ultimately reducing FOP and improving overall quality of life.
基金National Natural Science Foundation of China,No.82372194.
文摘BACKGROUND IL-22 plays a pivotal role in the processes of inflammation and tissue healing.,but its role in cholangiocarcinoma(CCA)remains unclear.our study explored the IL-22/IL-22R1 pathway and its impact on CCA progression through the ERK1/2 signaling cascade.AIM To determine the mechanism of the IL-22/IL-22R1 pathway in CCA and provide new directions for its clinical treatment.METHODS IL-22R1 expression was assessed in human and rat CCA tissues utilizing immunohistochemical techniques,Western blot analysis,and quantitative reverse transcription PCR.The impact of IL-22 on CCA cells was assessed in vitro via tests for proliferation,migration,invasion,and apoptosis assays.The rat models of thioacetamide-induced CCA and subcutaneous xenografts in nude mice were used to assess the in vivo effects.ERK1/2 inhibitors were applied to elucidate the mechanistic role of the pathway.RESULTS IL-22R1 was overexpressed in CCA cell lines and tissues.IL-22 treatment increased the phosphorylation of ERK1/2,promoting tumor cell proliferation,migration,invasion,and resistance to apoptosis.ERK1/2 inhibition considerably reversed these effects both in vitro and in vivo.CONCLUSION The IL-22/IL-22R1 axis promotes CCA progression by activating ERK1/2 signaling.Targeting this pathway with ERK1/2 inhibitors offers potential therapeutic strategies for CCA.
文摘This study aims to understand the current status of fear of disease progression(FoP)in patients with coronary heart disease(CHD)following percutaneous coronary intervention(PCI),and to explore the relationship between FoP levels,perceived control,and medical coping strategies in these patients.A total of 360 CHD patients who underwent PCI at Xijing Hospital in Shaanxi Province between June and November 2024 were selected using a convenience sampling method.Surveys included a general information questionnaire,the Fear of Progression Questionnaire-Short Form(FoP-Q-SF),the revised Control Attitudes Scale(CAS-R),and the Medical Coping Modes Questionnaire(MCMQ).Pearson correlation analysis was used to examine the relationships between disease perception,positive coping strategies,and FoP.A total of 360 patients completed the study.The average score for FoP in patients with CHD after PCI was 31.64±4.61.FoP was negatively correlated with perceived control(r=-0.106,P<0.01)and medical coping(r=-0.194,P<0.01).Multivariate regression analysis showed that the type of intervention,family history of CHD,smoking status,perceived control,and total medical coping score were significant factors influencing FoP(P<0.01).Enhancing perceived control and identifying positive coping strategies can improve FoP levels in patients with CHD after PCI.Therefore,clinicians should focus on perceived control and medical coping levels in patients and develop targeted interventions to alleviate negative emotions related to FoP.
基金Supported by the Guangzhou Health Science and Technology Project(No.20221A010077)the Guangdong Provincial Medical Science and Technology Research Fund Project(No.A2020146).
文摘AIM:To investigate the prevalence and characteristics of myopia in school-aged students and effects of environmental and genetic factors on the progression of myopia.METHODS:A total of 2422 students aged between 5 and 18y from nine schools in Baiyun District of Guangzhou,China were sampled using a stratified sampling method in 2020.Among them,1066 students participated in the follow-up survey the following year.Data were obtained based on ocular examinations and a questionnaire survey conducted during two visits.Factors potentially influencing the progression of myopia were analyzed.RESULTS:During the year assessed in this study,the percentage of students with myopia increased from 58.4%to 64.8%(P=0.002).Spherical equivalent(SE)progressed from-1.44±1.91 diopters(D)at baseline to-1.66±1.10 D(P=0.005).A generalized estimating equation(GEE)model revealed that age[adjusted odds ratio(aOR)=1.298,P<0.001],residential students(aOR=2.428,P=0.018),parental myopia(one myopic parent:aOR=1.553,both parents myopic:aOR=2.609,P<0.001),frequent reading of books or viewing of screens in direct sunlight(aOR=3.502,P=0.023),using only overhead lighting for reading and writing at night(aOR=1.633,P=0.011),parental restrictions on exercise time(aOR=2.286,P=0.012),and having less than 2h of outdoor exercise per day during the past week(aOR=1.584,P=0.019)were all identified as independent risk factors for progression of myopia.CONCLUSION:Our findings in this study indicate that age,residential students,parental myopia,indoor lighting environment,and physical activity have significant effects on the progression of myopia,providing evidence for further in-depth mechanistic interpretation and efficient intervention strategies for school-age children in this area.
文摘Background:Lung cancer remains a major factor causing cancer-associated mortality globally.While there have been advancements in treatment options,advanced lung cancer patients still have poor outcomes.This study aims to investigate the potential role of Transmembrane protein 33(TMEM33)in the development of lung adenocarcinoma.Methods:We leveraged The Cancer Genome Atlas(TCGA)database to analyze the connection between TMEM33 expression to the prognosis of lung adenocarcinoma(LUAD).Cell proliferation,invasiveness,and sphere formation were analyzed by various experiments.The association of miR-214-3p with TMEM33 was explored using luciferase reporter assay,immunoblotting,and real-time quantitative PCR(RT-qPCR).Additionally,TMEM33’s biological role was confirmed in the mouse xenograft model through lung cancer transplantation and metastasis studies.Results:TMEM33 showed high expression within both LUAD tissues and cells,with its expression correlating with poor patient survival outcomes.Silencing TMEM33 resulted in significant reductions in cell proliferation,invasiveness,and stem-like properties.Further investigation suggested that miR-214-3p negatively regulated TMEM33.In both cellular and animal models,we further demonstrated that TMEM33 knockdown could effectively suppress the aggressiveness of lung cancer cells,impeding tumor growth and inhibiting metastasis in the mouse model.Moreover,reducing TMEM33 expression reduced key signaling molecules within the Wnt/β-catenin pathway,providing insights into TMEM33’s mechanistic role in LUAD.Conclusion:TMEM33 functions as an oncogene,which is under the negative regulation of miR-214-3p,to promote the LUAD malignant characteristics by engaging the Wnt/β-catenin cascade.
基金supported by the National Natural Science Foundation of China(Grant Nos.81902617 and 82100816)Guangdong Natural Science Foundation(Grant No.2021A1515012322)Guangzhou Basic and Applied Basic Research Subject-Young Doctor’s“Sailing”Project(Grant No.2024A04J4702).
文摘Background:U2AF homology motif kinase 1(UHMK1)has been associated with RNA processing and protein phosphorylation,thereby influencing tumor progression.The study aimed to explore its regulatory mechanisms and biological functions in human prostate cancer(PCa).Methods:In this study,we systematically evaluated the expression and prognostic significance of UHMK1 in public databases,followed by validation through immunohis-tochemistry(IHC)in PCa specimens.Both gain-of-function and loss-of-function experiments were conducted to elucidate the role of UHMK1 in vitro and in vivo.Additionally,a series of molecular and biochemical assays were performed to investigate the regulatory mechanisms underlying UHMK1 activity.Results:Our findings revealed that UHMK1 expression was significantly upregulated in PCa tissues and correlated with poor patient prognosis,as demonstrated by analysis of public datasets and confirmed by immunohistochemical staining.Functional studies showed that UHMK1 depletion suppressed tumor cell proliferation and metastasis,while its overexpression promoted these processes.Mechanistically,we identified that UHMK1 phosphorylates nuclear receptor coactivator 3(NCOA3),which subsequently activates activating transcription factor 4(ATF4)to upregulate methylenetetrahydrofolate dehy-drogenase 2(MTHFD2)transcription.Interestingly,MTHFD2 was found to reciprocally enhance UHMK1 expression,establishing a positive feedback loop.Conclusions:In conclusion,our data suggest that the UHMK1-MTHFD2 axis forms a positive feedback loop that drives PCa progression.Targeting this loop represents a promising therapeutic strategy for restraining prostate cancer development and progression.
基金National Natural Science Foundation of China Youth Training Project(2021GZR003)Medical-Engineering Interdisciplinary Research Youth Training Project(2022YGJC001).
文摘Background:Hepatocellular carcinoma(HCC)is a prevalent liver malignancy.This study examined the roles of transforming growth factor beta(TGF-β)and cytochrome b5 domain containing 2(CYB5D2)in HCC etiology and their prognostic biomarker potential.Methods:Key modules and prognostic genes were identified by analyzing the GSE101685 dataset by weighted gene co-expression network analysis(WGCNA)and Least absolute shrinkage and selection operator(LASSO)Cox regression.The expression levels of CYB5D2 and TGF-βin HCC cell lines were quantified using Quantitative reverse transcription polymerase chain reaction(qRT-PCR)and Western blotting(WB)assays.Effects of CYB5D2 overexpression on cell proliferation,migration,invasion,and epithelial-mesenchymal transition(EMT)marker regulation were assessed in vitro,while in vivo tumorigenicity was evaluated using a xenograft model of HCC in nude mice.Results:In this study,WGCNA identified the turquoise module as significantly associated with HCC,containing 452 DEGs.LASSO Cox regression analysis revealed 9 key prognostic genes,with CYB5D2 being underexpressed in HCC cells and tissues.TGF-βwas negatively correlated with CYB5D2 expression,resulting in poor patient prognosis.Functional assays demonstrated that CYB5D2 overexpression inhibited proliferation,migration,and invasion of HCC cell lines,and altered EMT marker expression.Furthermore,the addition of TGF-βpartially reversed the suppressive effects caused by CYB5D2 overexpression.In vivo,CYB5D2 overexpression significantly reduced tumor growth,indicating its potential as a therapeutic target for HCC.Conclusion:The tumor suppressor function of CYB5D2 in HCC and its interaction with TGF-βoffered fresh information on the molecular pathophysiology of HCC and possible treatment avenues.
基金funded by Outstanding Leaders Training Programof Pudong Health Commission of Shanghai(No.PWR12023-03)In-house Project of Shanghai Pudong NewArea People’sHospital(No.E24-02).
文摘Background:Colorectal cancer(CRC)is common and deadly,often leading to metastasis,challenging treatment,and poor outcomes.Understanding its molecular basis is crucial for developing effective therapies.Aims:This study aimed to investigate the role of Myosin Heavy Chain 11(MYH11)in CRC progression,especially its effects on epithelial-mesenchymal transition(EMT)and cell behavior,and to explore its potential regulation by the EMT transcription factor zinc finger E-box binding homeobox 1(ZEB1).Methods:Differential expression analysis was performed in the GSE123390 and TCGA-READ datasets,and 317 intersection genes were identified.The hub gene MYH11 was identified based on Protein-protein interaction(PPI)analysis and expression validation.The effects of MYH11 and the EMT transcription factor(ZEB1)on the behavior of CRC cells were investigated in vitro.Results:Bioinformatics research revealed that MYH11 was considerably downregulated in CRC samples as compared to normal samples.Overexpression of MYH11 inhibited the proliferation,migration,and invasion of CRC cells.Western blotting(WB)testing showed that MYH11 overexpression inhibited EMT by elevating E-cadherin levels while suppressing ZEB1,vimentin,and N-cadherin expressions.By contrast,overexpression of ZEB1 promoted EMT and enhanced migration,invasion,and proliferation of CRC cells.The negative impacts of MYH11 affecting EMT markers and cell behaviors were partially mitigated by co-overexpression of MYH11 and ZEB1,indicating that MYH11 regulates EMT and CRC progression through ZEB1.Conclusion:Our study shows MYH11 curbs CRC growth by blocking EMT and invasion,but ZEB1 overexpression reduces this effect.It uncovers key CRC pathways and suggests MYH11’s therapeutic potential.
基金NIH/NIDCR grant R01 DE031413 and CTSA pilot grant UL1TR001430 to Manish V.Bais.
文摘Oral squamous cell carcinoma(OSCC)progresses from preneoplastic precursors via genetic and epigenetic alterations.Previous studies have focused on the treatment of terminally developed OSCC.However,the role of epigenetic regulators as therapeutic targets during the transition from preneoplastic precursors to OSCC has not been well studied.Our study identified lysine-specific demethylase 1(LSD1)as a crucial promoter of OSCC,demonstrating that its knockout or pharmacological inhibition in mice reversed OSCC preneoplasia.LSD1 inhibition by SP2509 disrupted cell cycle,reduced immunosuppression,and enhanced CD4+and CD8+T-cell infiltration.In a feline model of spontaneous OSCC,a clinical LSD1 inhibitor(Seclidemstat or SP2577)was found to be safe and effectively inhibit the STAT3 network.Mechanistic studies revealed that LSD1 drives OSCC progression through STAT3 signaling,which is regulated by phosphorylation of the cell cycle mediator CDK7 and immunosuppressive CTLA4.Notably,LSD1 inhibition reduced the phosphorylation of CDK7 at Tyr170 and eIF4B at Ser422,offering insights into a novel mechanism by which LSD1 regulates the preneoplastic-to-OSCC transition.This study provides a deeper understanding of OSCC progression and highlights LSD1 as a potential therapeutic target for controlling OSCC progression from preneoplastic lesions.
文摘Hepatitis B virus(HBV)reactivation is a clinically significant challenge in disease management.This review explores the immunological mechanisms underlying HBV reactivation,emphasizing disease progression and management.It delves into host immune responses and reactivation’s delicate balance,spanning innate and adaptive immunity.Viral factors’disruption of this balance,as are interac-tions between viral antigens,immune cells,cytokine networks,and immune checkpoint pathways,are examined.Notably,the roles of T cells,natural killer cells,and antigen-presenting cells are discussed,highlighting their influence on disease progression.HBV reactivation’s impact on disease severity,hepatic flares,liver fibrosis progression,and hepatocellular carcinoma is detailed.Management strategies,including anti-viral and immunomodulatory approaches,are critically analyzed.The role of prophylactic anti-viral therapy during immunosuppressive treatments is explored alongside novel immunotherapeutic interventions to restore immune control and prevent reactivation.In conclusion,this compre-hensive review furnishes a holistic view of the immunological mechanisms that propel HBV reactivation.With a dedicated focus on understanding its implic-ations for disease progression and the prospects of efficient management stra-tegies,this article contributes significantly to the knowledge base.The more profound insights into the intricate interactions between viral elements and the immune system will inform evidence-based approaches,ultimately enhancing disease management and elevating patient outcomes.The dynamic landscape of management strategies is critically scrutinized,spanning anti-viral and immunomodulatory approaches.The role of prophylactic anti-viral therapy in preventing reactivation during immunosuppressive treatments and the potential of innovative immunotherapeutic interventions to restore immune control and proactively deter reactivation.
文摘The study aimed to test if Briganti’s 2012 nomogram could be associated with the risk of prostate cancer (PCa) progression in European Association of Urology (EAU) intermediate-risk patients treated with robotic surgery. From January 2013 to December 2021, 527 consecutive patients belonging to the EAU intermediate-risk class were selected. Briganti’s 2012 nomogram, which predicts the risk of pelvic lymph node invasion (PLNI), was assessed as a continuous and dichotomous variable that categorized up to the median of 3.0%. Disease progression defined as biochemical recurrence and/or metastatic progression was evaluated by Cox proportional hazards (univariate and multivariate analysis). After a median follow-up of 95.0 months (95% confidence interval [CI]: 78.5–111.4), PCa progression occurred in 108 (20.5%) patients who were more likely to present with an unfavorable nomogram risk score, independently by the occurrence of unfavorable pathology including tumor upgrading and upstaging as well as PLNI. Accordingly, as Briganti’s 2012 risk score increased, patients were more likely to experience disease progression (hazard ratio [HR] = 1.060;95% CI: 1.021–1.100;P = 0.002);moreover, it also remained significant when dichotomized above a risk score of 3.0% (HR = 2.052;95% CI: 1.298–3.243;P < 0.0001) after adjustment for clinical factors. In the studied risk population, PCa progression was independently predicted by Briganti’s 2012 nomogram. Specifically, we found that patients were more likely to experience disease progression as their risk score increased. Because of the significant association between risk score and tumor behavior, the nomogram can further stratify intermediate-risk PCa patients, who represent a heterogeneous risk category for which different treatment paradigms exist.
