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
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
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
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
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
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.