Gallbladder carcinoma(GBC)is the most common malignant tumor of biliary tract,with poor prognosis due to its aggressive nature and limited therapeutic options.Early detection of GBC is a major challenge,with most GBCs...Gallbladder carcinoma(GBC)is the most common malignant tumor of biliary tract,with poor prognosis due to its aggressive nature and limited therapeutic options.Early detection of GBC is a major challenge,with most GBCs being detected accidentally during cholecystectomy procedures for gallbladder stones.This letter comments on the recent article by Deqing et al in the World Journal of Gastrointestinal Oncology,which summarized the various current methods used in early diagnosis of GBC,including endoscopic ultrasound(EUS)examination of the gallbladder for high-risk GBC patients,and the use of EUS-guided elasto-graphy,contrast-enhanced EUS,trans-papillary biopsy,natural orifice translu-minal endoscopic surgery,magnifying endoscopy,choledochoscopy,and confocal laser endomicroscopy when necessary for early diagnosis of GBC.However,there is a need for novel methods for early GBC diagnosis,such as the use of artificial intelligence and non-coding RNA biomarkers for improved screening protocols.Additionally,the use of in vitro and animal models may provide critical insights for advancing early detection and treatment strategies of this aggressive tumor.展开更多
Diabetes mellitus,particularly type 2 diabetes mellitus(T2DM),poses a significant global health challenge.Traditional management strategies primarily focus on glycemic control;however,there is a growing need for compr...Diabetes mellitus,particularly type 2 diabetes mellitus(T2DM),poses a significant global health challenge.Traditional management strategies primarily focus on glycemic control;however,there is a growing need for comprehensive approaches addressing the complex pathophysiology of diabetes complications.The recent study by Attia et al explores the potential of a novel therapy combining metformin with cholecalciferol(vitamin D3)and taurine to mitigate T2DM-related complications in a rat model.The findings indicate that this treatment combination improves glycemic control and reduces oxidative stress,inflammation,and lipid abnormalities.However,the study is limited by a lack of safety profile data and in-depth molecular mechanism insights.This editorial critically highlights the study's strengths and weaknesses,compares it against other combination therapy research in T2DM,and underscores the need to explore further the mechanisms underpinning the observed therapeutic effects and investigate the safety profile of this novel approach.展开更多
Perianal fistulizing Crohn’s disease(PFCD)is a common presentation of CD,which affects the patients’quality of life,including social and sexual function.The management of PFCD remains a critical challenge in inflamm...Perianal fistulizing Crohn’s disease(PFCD)is a common presentation of CD,which affects the patients’quality of life,including social and sexual function.The management of PFCD remains a critical challenge in inflammatory bowel disease,primarily due to limited understanding of the mechanisms involved in its pathogenesis,complicating medical treatment.Increased production of inflammatory cytokines such as tumor necrosis factor and interleukin-13 by infiltrating macrophages and other inflammatory cells stimulate the epithelial-to-mesenchymal transition,resulting in activation of myofibroblasts and elevation of matrix metalloproteinases,leading to fistula formation.Given the potential for malignant transformation,PFCD screening is critical.Cytokine and inflammationtargeted therapies can help control this disease,but recurrence is a common complication.Surgical interventions such as fistulotomy represent viable therapeutic options,with magnetic resonance imaging serving as an important diagnostic tool for delineating fistula tract anatomy.Animal models and clinical trials demonstrate that injection of mesenchymal stem cells(MSCs)into the fistula results in suppression of the inflammatory cells and cytokines and complete resolution of PFCD.Recently,MSC-derived extracellular vesicles were found to stimulate fistula healing,with encouraging results.In this article,we comment on the review article by Pacheco et al,summarizing the various lines of PFCD treatment and highlighting the role of screening for this disease.Importantly,we focus on the various mechanisms involved in the pathogenesis of PFCD,the therapeutic roles of MSCs and related extracellular vesicles,and explore the potential role of autophagy in enhancing the therapeutic efficacy of these cells,which may help in the treatment of this disease.展开更多
Diabetes mellitus(DM)is a metabolic disorder characterized by persistent hyperglycemia and other symptoms,which pose significant challenges to individual health,life expectancy,and public healthcare systems.The escala...Diabetes mellitus(DM)is a metabolic disorder characterized by persistent hyperglycemia and other symptoms,which pose significant challenges to individual health,life expectancy,and public healthcare systems.The escalating global prevalence of diabetes underscores the need for innovative therapeutic interventions.In this article,we critically comment on the study by Wang et al,published in the World Journal of Diabetes,which elucidates the therapeutic potential of Plantamajoside(PMS)in type 2 DM(T2DM)management.The authors provide evidence for the mechanism of action of PMS in T2DM models,demonstrating prevention of endoplasmic reticulum stress and apoptosis of pancreaticβ-cells via activation of DNAJC1.This manuscript provides a brief review of the pathogenesis of T2DM,explores the various roles of PMS in disease therapy in addition to the DNAJC-related apoptotic and autophagic functions,critically evaluates the experimental approaches employed by Wang et al,and provides recommendations for advancing future research.展开更多
Primary biliary cholangitis(PBC)is an autoimmune disease characterized by the selective destruction of intrahepatic small bile ducts,primarily by infiltrating lymphocytes,and has limited therapeutic options.A growing ...Primary biliary cholangitis(PBC)is an autoimmune disease characterized by the selective destruction of intrahepatic small bile ducts,primarily by infiltrating lymphocytes,and has limited therapeutic options.A growing body of evidence suggests that nanoparticles encapsulating rapamycin(ImmTOR)can suppress autoreactive lymphocytes and reduce inflammatory cytokine levels in various autoimmune diseases.In a recent study,Yang et al investigated the therapeutic effects of ImmTOR in a mouse model of PBC.ImmTOR treatment reduced the expression and number of CD4+T cells,CD8+T cells,and B cells isolated from the liver and spleen,improved liver inflammation and enzyme levels,and was associated with a concomitant decrease in anti-mitochondrial antibody levels.In this editorial,we highlight the significance of these findings,focusing on the potential mechanisms by which ImmTOR suppresses hepatic autoreactive T cells and reduces anti-mitochondrial antibody levels,ultimately improving liver pa-thology,through pathways such as mammalian target of rapamycin inhibition and autophagy restoration.We also offer a perspective on future research di-rections for PBC in both animal models and in vitro studies.展开更多
Perianal fistulizing Crohn’s disease(PFCD)is a complication of CD that signi-ficantly impacts patients’quality of life,particularly their social and sexual well-being.Despite advances in therapy,its treatment remain...Perianal fistulizing Crohn’s disease(PFCD)is a complication of CD that signi-ficantly impacts patients’quality of life,particularly their social and sexual well-being.Despite advances in therapy,its treatment remains a major challenge in the field of inflammatory bowel disease.The pathogenesis of PFCD involves in-creased production of inflammatory cytokines by infiltrating macrophages and lymphocytes,stimulation of the epithelial-to-mesenchymal transition,activation of myofibroblasts,and elevated levels of matrix metalloproteinases.Mesenchymal stem cells(MSCs)are multipotent stromal cells with self-renewal and differen-tiation capabilities.Evidence from animal models and clinical trials indicates that MSC injection into PFCD lesions suppresses the infiltration of inflammatory cells and cytokines,resulting in complete fistula healing.More recently,MSC-derived extracellular vesicles(EVs)have shown promising results in promoting fistula healing,particularly in cases of refractory or relapsing fistulas.Notably,the activation of macroautophagy(hereafter referred to as autophagy)in MSCs has been shown to accelerate the healing process.This narrative review discusses the mechanisms underlying PFCD pathogenesis,the therapeutic roles of MSCs and their EVs,and the potential role of autophagy upregulation in enhancing MSC function and EV production.展开更多
Excessive alcohol intake may induce hepatic apoptosis, steatosis, fibrosis, cirrhosis and even cancer. Ethanolinduced activation of general or selective autophagy as mitophagy or lipophagy in hepatocytes is generally ...Excessive alcohol intake may induce hepatic apoptosis, steatosis, fibrosis, cirrhosis and even cancer. Ethanolinduced activation of general or selective autophagy as mitophagy or lipophagy in hepatocytes is generally considered a prosurvival mechanism. On the other side of the coin, upregulation of autophagy in nonhepatocytes as stellate cells may stimulate fibrogenesis and subsequently induce detrimental effects on the liver. The autophagic response of other non-hepatocytes as macrophages and endothelial cells is unknown yet and needs to be investigated as these cells play important roles in ethanol-induced hepatic steatosis and damage. Selective pharmacological stimulation of autophagy in hepatocytes may be of therapeutic importance in alcoholic liver disease.展开更多
Tuberculosis(TB)remains a leading cause of death among infectious diseases,particularly in poor countries.Viral infections,multidrug-resistant and ex-tensively drug-resistant TB strains,as well as the coexistence of c...Tuberculosis(TB)remains a leading cause of death among infectious diseases,particularly in poor countries.Viral infections,multidrug-resistant and ex-tensively drug-resistant TB strains,as well as the coexistence of chronic illnesses such as diabetes mellitus(DM)greatly aggravate TB morbidity and mortality.DM[particularly type 2 DM(T2DM)]and TB have converged making their control even more challenging.Two contemporary global epidemics,TB-DM behaves like a syndemic,a synergistic confluence of two highly prevalent diseases.T2DM is a risk factor for developing more severe forms of multi-drug resistant-TB and TB recurrence after preventive treatment.Since a bidirectional relationship exists between TB and DM,it is necessary to concurrently treat both,and promote recommendations for the joint management of both diseases.There are also some drug-drug interactions resulting in adverse treatment outcomes in TB-DM patients including treatment failure,and reinfection.In addition,autophagy may play a role in these comorbidities.Therefore,the TB-DM comorbidities present several health challenges,requiring a focus on multidisciplinary collaboration and integrated strategies,to effectively deal with this double burden.To effectively manage the comorbidity,further screening in affected countries,more suitable drugs,and better treatment strategies are required.展开更多
Dysfunctional mitochondria may produce excessive reactive oxygen species, thus inducing DNA damage, which may be oncogenic if not repaired. As a major role of the PINK1-Parkin pathway involves selective autophagic cle...Dysfunctional mitochondria may produce excessive reactive oxygen species, thus inducing DNA damage, which may be oncogenic if not repaired. As a major role of the PINK1-Parkin pathway involves selective autophagic clearance of damaged mitochondria via a process termed mitophagy, Parkin-mediated mitophagy may be a tumorsuppressive mechanism. As an alternative mechanism for tumor inhibition beyond mitophagy, Parkin has been reported to have other oncosuppressive functions such as DNA repair, negative regulation of cell proliferation and stimulation of p53 tumor suppressor function. The authors recently reported that acute ethanol-induced mitophagy in hepatocytes was associated with Parkin mitochondrial translocation and colocalization with accumulated 8-OHd G(a marker of DNA damage and mutagenicity). This finding suggests:(1) the possibility of Parkin-mediated repair of damaged mitochondrial DNA in hepatocytes of ethanol-treated rats(ETRs) as an oncosuppressive mechanism; and(2) potential induction of cytoprotective mitophagy in ETR hepatocytes if mitochondrial damage is too severe to be repaired. Below is a summary of the various roles Parkin plays in tumor suppression, which may or may not be related to mitophagy. A proper understanding of the various tasks performed by Parkin in tumorigenesis may help in cancer therapy by allowing the PINK1-Parkin pathway to be targeted.展开更多
Macroautophagy(hereafter referred to as autophagy)is a prosurvival mechanism for the clearance of damaged cellular components,specifically related to exposure to various stressors such as starvation,excessive ethanol ...Macroautophagy(hereafter referred to as autophagy)is a prosurvival mechanism for the clearance of damaged cellular components,specifically related to exposure to various stressors such as starvation,excessive ethanol intake,and chemotherapy.This editorial reviews and comments on an article by Zhao et al,to be published in World J Gastrointestinal Oncology in 2024.Based on various molecular biology methodologies,they found that humanβ-defensin-1 reduced the proliferation of colon cancer cells,which was associated with the inhibition of the mammalian target of rapamycin,resulting in autophagy activation.The activation of autophagy is evidenced by increased levels of Beclin1 and LC3II/I proteins and mediated by the upregulation of long non-coding RNA TCONS_00014506.Our study discusses the impact of autophagy activation and mechanisms of autophagy,including autophagic flux,on cancer cells.Additionally,we emphasize the importance of describing the detailed methods for isolating long noncoding RNAs TCONS_00014506.Our review will benefit the scientific community and improve the overall clarity of the paper.展开更多
In this letter,we comment on a recent case report by Sun et al in the World Journal of Cardiology.The report describes the successful management of a rare complication:The unloading or detachment of a bioresorbable st...In this letter,we comment on a recent case report by Sun et al in the World Journal of Cardiology.The report describes the successful management of a rare complication:The unloading or detachment of a bioresorbable stent(BRS)during percutaneous coronary intervention(PCI)in a male patient.The unloading of BRS was detected via angiography and intravascular ultrasound(IVUS)imaging of the left coronary artery and left anterior descending artery.Although this case is interesting,the authors’report lacked crucial details.Specifically,insufficient information about the type of BRS used,potential causes of BRS unloading,or whether optical coherence tomography(OCT)imaging for coronary arteries was performed before,during,or after PCI.The OCT imaging of coronary arteries before PCI can potentially prevent BRS unloading due to its higher resolution compared to IVUS.In addition,despite detecting myocardial bridging during the PCI,the authors did not provide any details regarding this variation.Here we discuss the various types of BRS,the importance of OCT in PCI,and the clinical relevance of myocardial bridging.展开更多
In this letter,we comment on a recent publication by Mei et al,in the World Journal of Hepatology,investigating the hepatoprotective effects of the modified Xiaoyao San(MXS)formula in a male rat model of non-alcoholic...In this letter,we comment on a recent publication by Mei et al,in the World Journal of Hepatology,investigating the hepatoprotective effects of the modified Xiaoyao San(MXS)formula in a male rat model of non-alcoholic steatohepatitis(NASH).The authors found that MXS treatment mitigated hepatic steatosis and inflam-mation in the NASH model,as evidenced by the reduction in lipid droplets(LDs),fibrosis markers and lipogenic factors.Interestingly,these hepatoprotective effects were associated with androgen upregulation(based on metabolomics analysis of male steroid hormone metabolites),adenosine 5’-monophosphate-activated protein kinase(AMPK)activation,and restoration of phosphatase and tensin homolog(PTEN)expression.However,the authors did not clearly discuss the relationships between MXS-induced hepatic steatosis reduction in the NASH model,and androgen upregulation,AMPK activation,and restoration of PTEN expression.This editorial emphasizes the reported mechanisms and explains how they act or interact with each other to reduce hepatic steatosis and inflammation in the NASH model.As a perspective,we propose additional mechanisms(such as autophagy/lipophagy activation in hepatocytes)for the clearance of LDs and suppression of hepatic steatosis by MXS in the NASH model.A proper understanding of the mechanisms of MXS-induced reduction of hepatic steatosis might help in the treatment of NASH and related diseases.展开更多
Autophagy is a prosurvival mechanism for the clearance of accumulated abnormal proteins,damaged organelles,and excessive lipids within mammalian cells.A growing body of data indicates that autophagy is reduced in agin...Autophagy is a prosurvival mechanism for the clearance of accumulated abnormal proteins,damaged organelles,and excessive lipids within mammalian cells.A growing body of data indicates that autophagy is reduced in aging cells.This reduction leads to various diseases,such as myocardial hypertrophy,infarction,and atherosclerosis.Recent studies in animal models of an aging heart showed that fasting-induced autophagy improved cardiac function and longevity.This improvement is related to autophagic clearance of damaged cellular components via either bulk or selective autophagy(such as mitophagy).In this editorial,we summarize the mechanisms of autophagy in normal and aging hearts.In addition,the protective effect of fasting-induced autophagy in cardiac aging has been highlighted.展开更多
The retroesophageal right subclavian artery may be associated with multiple neurovascular variations, which may impact various cervicothoracic surgeries. During the dissection of 27 cadavers, the authors detected a re...The retroesophageal right subclavian artery may be associated with multiple neurovascular variations, which may impact various cervicothoracic surgeries. During the dissection of 27 cadavers, the authors detected a retroesophageal right subclavian artery in old man arising from distal aortic arch, crossed ventrally by left recurrent laryngeal nerve and dorsally by thoracic duct. On the right side, the aberrant subclavian artery was associated with nonrecurrent laryngeal nerve crossing a large tortuous inferior thyroid artery at multiple intersection points. Importantly, the nonrecurrent laryngeal nerve gave rise to extra laryngeal branch passing over Zuckerkandl’s tubercle of thyroid gland before its termination into the larynx. The relationships of the aberrant subclavian artery in the present case to thoracic duct, recurrent and nonrecurrent laryngeal nerves may have clinical relevance to various operations such as thyroidectomy, esophagectomy and surgical correction of the aberrant vessel. Therefore, these relationships should be well known by surgeons for prevention of iatrogenic damage of essential neurovascular structures during various surgeries.展开更多
Anomalous muscles in carpal tunnel (CT) may cause carpal tunnel syndrome (CTS), and may be also associated with neurovascular abnormalities, altering the diagnosis and surgical interventions for CTS. The authors repor...Anomalous muscles in carpal tunnel (CT) may cause carpal tunnel syndrome (CTS), and may be also associated with neurovascular abnormalities, altering the diagnosis and surgical interventions for CTS. The authors report a case of bilateral Gantzer’s muscles (GMs) inserted into the tendons of flexor digitorum profundus within the CTs in an old male cadaver. The left GM was associated with enlarged lumbrical muscles in the CT and bifid median nerve (MN) communicating with ulnar nerve in the hand. The right GM was associated with perforation of MN branches in the hand by superficial palmar arch. This unreported coexistence of anomalous GMs and the associated neurovascular variations may have clinical relevance to etiology, diagnosis and treatment of CTS.展开更多
In this editorial,we comment on a recent publication,which highlights the important findings from the study,including the antitumor and anti-inflammatory effects of isothiocyanates,their underlying mechanisms,and impl...In this editorial,we comment on a recent publication,which highlights the important findings from the study,including the antitumor and anti-inflammatory effects of isothiocyanates,their underlying mechanisms,and implications.Additionally,a related perspective is discussed.展开更多
文摘Gallbladder carcinoma(GBC)is the most common malignant tumor of biliary tract,with poor prognosis due to its aggressive nature and limited therapeutic options.Early detection of GBC is a major challenge,with most GBCs being detected accidentally during cholecystectomy procedures for gallbladder stones.This letter comments on the recent article by Deqing et al in the World Journal of Gastrointestinal Oncology,which summarized the various current methods used in early diagnosis of GBC,including endoscopic ultrasound(EUS)examination of the gallbladder for high-risk GBC patients,and the use of EUS-guided elasto-graphy,contrast-enhanced EUS,trans-papillary biopsy,natural orifice translu-minal endoscopic surgery,magnifying endoscopy,choledochoscopy,and confocal laser endomicroscopy when necessary for early diagnosis of GBC.However,there is a need for novel methods for early GBC diagnosis,such as the use of artificial intelligence and non-coding RNA biomarkers for improved screening protocols.Additionally,the use of in vitro and animal models may provide critical insights for advancing early detection and treatment strategies of this aggressive tumor.
文摘Diabetes mellitus,particularly type 2 diabetes mellitus(T2DM),poses a significant global health challenge.Traditional management strategies primarily focus on glycemic control;however,there is a growing need for comprehensive approaches addressing the complex pathophysiology of diabetes complications.The recent study by Attia et al explores the potential of a novel therapy combining metformin with cholecalciferol(vitamin D3)and taurine to mitigate T2DM-related complications in a rat model.The findings indicate that this treatment combination improves glycemic control and reduces oxidative stress,inflammation,and lipid abnormalities.However,the study is limited by a lack of safety profile data and in-depth molecular mechanism insights.This editorial critically highlights the study's strengths and weaknesses,compares it against other combination therapy research in T2DM,and underscores the need to explore further the mechanisms underpinning the observed therapeutic effects and investigate the safety profile of this novel approach.
文摘Perianal fistulizing Crohn’s disease(PFCD)is a common presentation of CD,which affects the patients’quality of life,including social and sexual function.The management of PFCD remains a critical challenge in inflammatory bowel disease,primarily due to limited understanding of the mechanisms involved in its pathogenesis,complicating medical treatment.Increased production of inflammatory cytokines such as tumor necrosis factor and interleukin-13 by infiltrating macrophages and other inflammatory cells stimulate the epithelial-to-mesenchymal transition,resulting in activation of myofibroblasts and elevation of matrix metalloproteinases,leading to fistula formation.Given the potential for malignant transformation,PFCD screening is critical.Cytokine and inflammationtargeted therapies can help control this disease,but recurrence is a common complication.Surgical interventions such as fistulotomy represent viable therapeutic options,with magnetic resonance imaging serving as an important diagnostic tool for delineating fistula tract anatomy.Animal models and clinical trials demonstrate that injection of mesenchymal stem cells(MSCs)into the fistula results in suppression of the inflammatory cells and cytokines and complete resolution of PFCD.Recently,MSC-derived extracellular vesicles were found to stimulate fistula healing,with encouraging results.In this article,we comment on the review article by Pacheco et al,summarizing the various lines of PFCD treatment and highlighting the role of screening for this disease.Importantly,we focus on the various mechanisms involved in the pathogenesis of PFCD,the therapeutic roles of MSCs and related extracellular vesicles,and explore the potential role of autophagy in enhancing the therapeutic efficacy of these cells,which may help in the treatment of this disease.
文摘Diabetes mellitus(DM)is a metabolic disorder characterized by persistent hyperglycemia and other symptoms,which pose significant challenges to individual health,life expectancy,and public healthcare systems.The escalating global prevalence of diabetes underscores the need for innovative therapeutic interventions.In this article,we critically comment on the study by Wang et al,published in the World Journal of Diabetes,which elucidates the therapeutic potential of Plantamajoside(PMS)in type 2 DM(T2DM)management.The authors provide evidence for the mechanism of action of PMS in T2DM models,demonstrating prevention of endoplasmic reticulum stress and apoptosis of pancreaticβ-cells via activation of DNAJC1.This manuscript provides a brief review of the pathogenesis of T2DM,explores the various roles of PMS in disease therapy in addition to the DNAJC-related apoptotic and autophagic functions,critically evaluates the experimental approaches employed by Wang et al,and provides recommendations for advancing future research.
文摘Primary biliary cholangitis(PBC)is an autoimmune disease characterized by the selective destruction of intrahepatic small bile ducts,primarily by infiltrating lymphocytes,and has limited therapeutic options.A growing body of evidence suggests that nanoparticles encapsulating rapamycin(ImmTOR)can suppress autoreactive lymphocytes and reduce inflammatory cytokine levels in various autoimmune diseases.In a recent study,Yang et al investigated the therapeutic effects of ImmTOR in a mouse model of PBC.ImmTOR treatment reduced the expression and number of CD4+T cells,CD8+T cells,and B cells isolated from the liver and spleen,improved liver inflammation and enzyme levels,and was associated with a concomitant decrease in anti-mitochondrial antibody levels.In this editorial,we highlight the significance of these findings,focusing on the potential mechanisms by which ImmTOR suppresses hepatic autoreactive T cells and reduces anti-mitochondrial antibody levels,ultimately improving liver pa-thology,through pathways such as mammalian target of rapamycin inhibition and autophagy restoration.We also offer a perspective on future research di-rections for PBC in both animal models and in vitro studies.
文摘Perianal fistulizing Crohn’s disease(PFCD)is a complication of CD that signi-ficantly impacts patients’quality of life,particularly their social and sexual well-being.Despite advances in therapy,its treatment remains a major challenge in the field of inflammatory bowel disease.The pathogenesis of PFCD involves in-creased production of inflammatory cytokines by infiltrating macrophages and lymphocytes,stimulation of the epithelial-to-mesenchymal transition,activation of myofibroblasts,and elevated levels of matrix metalloproteinases.Mesenchymal stem cells(MSCs)are multipotent stromal cells with self-renewal and differen-tiation capabilities.Evidence from animal models and clinical trials indicates that MSC injection into PFCD lesions suppresses the infiltration of inflammatory cells and cytokines,resulting in complete fistula healing.More recently,MSC-derived extracellular vesicles(EVs)have shown promising results in promoting fistula healing,particularly in cases of refractory or relapsing fistulas.Notably,the activation of macroautophagy(hereafter referred to as autophagy)in MSCs has been shown to accelerate the healing process.This narrative review discusses the mechanisms underlying PFCD pathogenesis,the therapeutic roles of MSCs and their EVs,and the potential role of autophagy upregulation in enhancing MSC function and EV production.
文摘Excessive alcohol intake may induce hepatic apoptosis, steatosis, fibrosis, cirrhosis and even cancer. Ethanolinduced activation of general or selective autophagy as mitophagy or lipophagy in hepatocytes is generally considered a prosurvival mechanism. On the other side of the coin, upregulation of autophagy in nonhepatocytes as stellate cells may stimulate fibrogenesis and subsequently induce detrimental effects on the liver. The autophagic response of other non-hepatocytes as macrophages and endothelial cells is unknown yet and needs to be investigated as these cells play important roles in ethanol-induced hepatic steatosis and damage. Selective pharmacological stimulation of autophagy in hepatocytes may be of therapeutic importance in alcoholic liver disease.
文摘Tuberculosis(TB)remains a leading cause of death among infectious diseases,particularly in poor countries.Viral infections,multidrug-resistant and ex-tensively drug-resistant TB strains,as well as the coexistence of chronic illnesses such as diabetes mellitus(DM)greatly aggravate TB morbidity and mortality.DM[particularly type 2 DM(T2DM)]and TB have converged making their control even more challenging.Two contemporary global epidemics,TB-DM behaves like a syndemic,a synergistic confluence of two highly prevalent diseases.T2DM is a risk factor for developing more severe forms of multi-drug resistant-TB and TB recurrence after preventive treatment.Since a bidirectional relationship exists between TB and DM,it is necessary to concurrently treat both,and promote recommendations for the joint management of both diseases.There are also some drug-drug interactions resulting in adverse treatment outcomes in TB-DM patients including treatment failure,and reinfection.In addition,autophagy may play a role in these comorbidities.Therefore,the TB-DM comorbidities present several health challenges,requiring a focus on multidisciplinary collaboration and integrated strategies,to effectively deal with this double burden.To effectively manage the comorbidity,further screening in affected countries,more suitable drugs,and better treatment strategies are required.
文摘Dysfunctional mitochondria may produce excessive reactive oxygen species, thus inducing DNA damage, which may be oncogenic if not repaired. As a major role of the PINK1-Parkin pathway involves selective autophagic clearance of damaged mitochondria via a process termed mitophagy, Parkin-mediated mitophagy may be a tumorsuppressive mechanism. As an alternative mechanism for tumor inhibition beyond mitophagy, Parkin has been reported to have other oncosuppressive functions such as DNA repair, negative regulation of cell proliferation and stimulation of p53 tumor suppressor function. The authors recently reported that acute ethanol-induced mitophagy in hepatocytes was associated with Parkin mitochondrial translocation and colocalization with accumulated 8-OHd G(a marker of DNA damage and mutagenicity). This finding suggests:(1) the possibility of Parkin-mediated repair of damaged mitochondrial DNA in hepatocytes of ethanol-treated rats(ETRs) as an oncosuppressive mechanism; and(2) potential induction of cytoprotective mitophagy in ETR hepatocytes if mitochondrial damage is too severe to be repaired. Below is a summary of the various roles Parkin plays in tumor suppression, which may or may not be related to mitophagy. A proper understanding of the various tasks performed by Parkin in tumorigenesis may help in cancer therapy by allowing the PINK1-Parkin pathway to be targeted.
文摘Macroautophagy(hereafter referred to as autophagy)is a prosurvival mechanism for the clearance of damaged cellular components,specifically related to exposure to various stressors such as starvation,excessive ethanol intake,and chemotherapy.This editorial reviews and comments on an article by Zhao et al,to be published in World J Gastrointestinal Oncology in 2024.Based on various molecular biology methodologies,they found that humanβ-defensin-1 reduced the proliferation of colon cancer cells,which was associated with the inhibition of the mammalian target of rapamycin,resulting in autophagy activation.The activation of autophagy is evidenced by increased levels of Beclin1 and LC3II/I proteins and mediated by the upregulation of long non-coding RNA TCONS_00014506.Our study discusses the impact of autophagy activation and mechanisms of autophagy,including autophagic flux,on cancer cells.Additionally,we emphasize the importance of describing the detailed methods for isolating long noncoding RNAs TCONS_00014506.Our review will benefit the scientific community and improve the overall clarity of the paper.
文摘In this letter,we comment on a recent case report by Sun et al in the World Journal of Cardiology.The report describes the successful management of a rare complication:The unloading or detachment of a bioresorbable stent(BRS)during percutaneous coronary intervention(PCI)in a male patient.The unloading of BRS was detected via angiography and intravascular ultrasound(IVUS)imaging of the left coronary artery and left anterior descending artery.Although this case is interesting,the authors’report lacked crucial details.Specifically,insufficient information about the type of BRS used,potential causes of BRS unloading,or whether optical coherence tomography(OCT)imaging for coronary arteries was performed before,during,or after PCI.The OCT imaging of coronary arteries before PCI can potentially prevent BRS unloading due to its higher resolution compared to IVUS.In addition,despite detecting myocardial bridging during the PCI,the authors did not provide any details regarding this variation.Here we discuss the various types of BRS,the importance of OCT in PCI,and the clinical relevance of myocardial bridging.
文摘In this letter,we comment on a recent publication by Mei et al,in the World Journal of Hepatology,investigating the hepatoprotective effects of the modified Xiaoyao San(MXS)formula in a male rat model of non-alcoholic steatohepatitis(NASH).The authors found that MXS treatment mitigated hepatic steatosis and inflam-mation in the NASH model,as evidenced by the reduction in lipid droplets(LDs),fibrosis markers and lipogenic factors.Interestingly,these hepatoprotective effects were associated with androgen upregulation(based on metabolomics analysis of male steroid hormone metabolites),adenosine 5’-monophosphate-activated protein kinase(AMPK)activation,and restoration of phosphatase and tensin homolog(PTEN)expression.However,the authors did not clearly discuss the relationships between MXS-induced hepatic steatosis reduction in the NASH model,and androgen upregulation,AMPK activation,and restoration of PTEN expression.This editorial emphasizes the reported mechanisms and explains how they act or interact with each other to reduce hepatic steatosis and inflammation in the NASH model.As a perspective,we propose additional mechanisms(such as autophagy/lipophagy activation in hepatocytes)for the clearance of LDs and suppression of hepatic steatosis by MXS in the NASH model.A proper understanding of the mechanisms of MXS-induced reduction of hepatic steatosis might help in the treatment of NASH and related diseases.
文摘Autophagy is a prosurvival mechanism for the clearance of accumulated abnormal proteins,damaged organelles,and excessive lipids within mammalian cells.A growing body of data indicates that autophagy is reduced in aging cells.This reduction leads to various diseases,such as myocardial hypertrophy,infarction,and atherosclerosis.Recent studies in animal models of an aging heart showed that fasting-induced autophagy improved cardiac function and longevity.This improvement is related to autophagic clearance of damaged cellular components via either bulk or selective autophagy(such as mitophagy).In this editorial,we summarize the mechanisms of autophagy in normal and aging hearts.In addition,the protective effect of fasting-induced autophagy in cardiac aging has been highlighted.
文摘The retroesophageal right subclavian artery may be associated with multiple neurovascular variations, which may impact various cervicothoracic surgeries. During the dissection of 27 cadavers, the authors detected a retroesophageal right subclavian artery in old man arising from distal aortic arch, crossed ventrally by left recurrent laryngeal nerve and dorsally by thoracic duct. On the right side, the aberrant subclavian artery was associated with nonrecurrent laryngeal nerve crossing a large tortuous inferior thyroid artery at multiple intersection points. Importantly, the nonrecurrent laryngeal nerve gave rise to extra laryngeal branch passing over Zuckerkandl’s tubercle of thyroid gland before its termination into the larynx. The relationships of the aberrant subclavian artery in the present case to thoracic duct, recurrent and nonrecurrent laryngeal nerves may have clinical relevance to various operations such as thyroidectomy, esophagectomy and surgical correction of the aberrant vessel. Therefore, these relationships should be well known by surgeons for prevention of iatrogenic damage of essential neurovascular structures during various surgeries.
文摘Anomalous muscles in carpal tunnel (CT) may cause carpal tunnel syndrome (CTS), and may be also associated with neurovascular abnormalities, altering the diagnosis and surgical interventions for CTS. The authors report a case of bilateral Gantzer’s muscles (GMs) inserted into the tendons of flexor digitorum profundus within the CTs in an old male cadaver. The left GM was associated with enlarged lumbrical muscles in the CT and bifid median nerve (MN) communicating with ulnar nerve in the hand. The right GM was associated with perforation of MN branches in the hand by superficial palmar arch. This unreported coexistence of anomalous GMs and the associated neurovascular variations may have clinical relevance to etiology, diagnosis and treatment of CTS.
文摘In this editorial,we comment on a recent publication,which highlights the important findings from the study,including the antitumor and anti-inflammatory effects of isothiocyanates,their underlying mechanisms,and implications.Additionally,a related perspective is discussed.
