For the last decade, low serum amylase(hypoamylasemia) has been reported in certain common cardiometabolic conditions such as obesity, diabetes(regardless of type), and metabolic syndrome, all of which appear to have ...For the last decade, low serum amylase(hypoamylasemia) has been reported in certain common cardiometabolic conditions such as obesity, diabetes(regardless of type), and metabolic syndrome, all of which appear to have a common etiology of insufficient insulin action due to insulin resistance and/or diminished insulin secretion. Some clinical studies have shown that salivary amylase may be preferentially decreased in obese individuals, whereas others have revealed that pancreatic amylase may be preferentially decreased in diabetic subjects with insulin dependence. Despite this accumulated evidence, the clinical relevance of serum, salivary, and pancreatic amylase and the underlying mechanisms have not been fully elucidated. In recent years, copy number variations(CNVs) in the salivary amylase gene(AMY1), which range more broadly than the pancreatic amylase gene(AMY2A and AMY2B), have been shown to be well correlated with salivary and serum amylase levels. In addition, low CNV of AMY1, indicating low salivary amylase, was associated with insulin resistance, obesity, low taste perception/satiety, and postprandial hyperglycemia through impaired insulin secretion at early cephalic phase. In most populations, insulin-dependent diabetes is less prevalent(minor contribution) compared with insulin-independent diabetes, and obesity is highly prevalent compared with low body weight. Therefore, obesity as a condition that elicits cardiometabolic diseases relating to insulin resistance(major contribution) may be a common determinant for low serum amylase in a general population. In this review, the novel interpretation of low serum, salivary, and pancreas amylase is discussed in terms of major contributions of obesity, diabetes, and metabolic syndrome.展开更多
Objective:Mcl-1 overexpression confers acquired resistance to Bcl-2 inhibitors in non-small cell lung cancer(NSCLC),but no direct Mcl-1 inhibitor is currently available for clinical use.Thus,novel therapeutic strategi...Objective:Mcl-1 overexpression confers acquired resistance to Bcl-2 inhibitors in non-small cell lung cancer(NSCLC),but no direct Mcl-1 inhibitor is currently available for clinical use.Thus,novel therapeutic strategies are urgently needed to target Mcl-1 and sensitize the anti-NSCLC activity of Bcl-2 inhibitors.Methods:Cell proliferation was measured using sulforhodamine B and colony formation assays,and apoptosis was detected with Annexin V-FITC staining.Gene expression was manipulated using siRNAs and plasmids.Real-time PCR and Western blot were used to measure mRNA and protein levels.Immunoprecipitation and immunofluorescence were used to analyze co-localization o f dual specificity tyrosine-phosphorylation-regulated kinase 1A(DYRK1A)and Mcl-1.Results:Suppression of DYRK1A resulted in reduced Mcl-1 expression in NSCLC cells,whereas overexpression of DYRK1A significantly increased Mcl-1 expression.Suppression of DYRK1A did not alter Mcl-1 mRNA levels,but did result in an accelerated degradation o f Mcl-1 protein in NSCLC cells.Furthermore,DYRK1A mediated proteasome-dependent degradation o f Mcl-1 in NSCLC cells,and DYRK1A co-localized with Mcl-1 in NSCLC cells and was co-expressed with Mcl-1 in tumor samples from lung cancer patients,suggesting that Mcl-1 may be a novel DYRK1A substrate.We showed that combined therapy with harmine and Bcl-2 antagonists significantly inhibited cell proliferation and induced apoptosis in NSCLC cell lines as well as primary NSCLC cells.Conclusions:Mcl-1 is a novel DYRK1A substrate,and the role of DYRK1A in promoting Mcl-1 stability makes it an attractive target for decreasing Bcl-2 inhibitor resistance.展开更多
Vitamin D, a fat-soluble vitamin and endocrine horm one, and it impacts various bone and extra-bone health, such as osteoporosis, diabetes, and cancer. The main circulating form of vitamin D is 25-hydroxyvitamin D [25...Vitamin D, a fat-soluble vitamin and endocrine horm one, and it impacts various bone and extra-bone health, such as osteoporosis, diabetes, and cancer. The main circulating form of vitamin D is 25-hydroxyvitamin D [25(OH)D] and it is a useful clinical biomarker of vitamin D status. The Institute of Medicine (IOM) defines as vitamin D deficiency (VDD) when serum 25(OH)D concentration is less than 20 ng/mL⑴.Worldwide, VDD is recognized as a severe public health problem. In 2007, Holick estimated that globally over one billion people suffered from VDD or vitamin D insufficiency (VDI). In China, it has bee n reported that the prevale nee of VDD ranged from 38.8% to 91.2% in different regions.展开更多
Objective:This study was designed to evaluate the clinical significance of the serum thymidine kinase 1(TK1)and prognosis nutrition index(PNI)in the prognosis of elderly patients with advanced non-small cell lung canc...Objective:This study was designed to evaluate the clinical significance of the serum thymidine kinase 1(TK1)and prognosis nutrition index(PNI)in the prognosis of elderly patients with advanced non-small cell lung cancer(NSCLC).Methods:A total of 126 elderly patients with advanced non-small cell lung cancer from Jan.2015 to Apr.2016 were enrolled.The clinical,pathological and survival information were collected.The serum TK1 level was measured as well as PNI was calculated when the patient was admitted to our hospital for the first time.The relationship between serum TK1,PNI,and clinical prognostic characteristics was analyzed.The clinical significance of serum TK1 and PNI in the prognosis of elderly patients with advanced non-small cell lung cancer was investigated.Results:The results showed that the survival time of the patients was related to TK1 and PNI.The further Kaplan-Meier method and log-rank tests showed that the long-term outcome of the high-TK1 group was significantly worse than low-TK1 group(mOS,27 m vs.15 m,P=0.047).Besides,the Kaplan-Meier method and log-rank tests also showed that the long-term outcome of high-PNI group was significantly better than low-PNI group(mOS,31.5 m vs.16 m,P=0.015).However,the Spearman’s correlation analysis showed there was no correlation between PNI and TK1.The univariate and multivariate analysis showed that TK1,PNI and the number of metastatic sites were independent prognostic factors.Conclusions:The study confirmed the TK1 and PNI were independent prognostic factors of advanced NSCLC in the elderly.More attention worth is paid in routine clinical practice for patients cell proliferation and nutritional status.展开更多
文摘For the last decade, low serum amylase(hypoamylasemia) has been reported in certain common cardiometabolic conditions such as obesity, diabetes(regardless of type), and metabolic syndrome, all of which appear to have a common etiology of insufficient insulin action due to insulin resistance and/or diminished insulin secretion. Some clinical studies have shown that salivary amylase may be preferentially decreased in obese individuals, whereas others have revealed that pancreatic amylase may be preferentially decreased in diabetic subjects with insulin dependence. Despite this accumulated evidence, the clinical relevance of serum, salivary, and pancreatic amylase and the underlying mechanisms have not been fully elucidated. In recent years, copy number variations(CNVs) in the salivary amylase gene(AMY1), which range more broadly than the pancreatic amylase gene(AMY2A and AMY2B), have been shown to be well correlated with salivary and serum amylase levels. In addition, low CNV of AMY1, indicating low salivary amylase, was associated with insulin resistance, obesity, low taste perception/satiety, and postprandial hyperglycemia through impaired insulin secretion at early cephalic phase. In most populations, insulin-dependent diabetes is less prevalent(minor contribution) compared with insulin-independent diabetes, and obesity is highly prevalent compared with low body weight. Therefore, obesity as a condition that elicits cardiometabolic diseases relating to insulin resistance(major contribution) may be a common determinant for low serum amylase in a general population. In this review, the novel interpretation of low serum, salivary, and pancreas amylase is discussed in terms of major contributions of obesity, diabetes, and metabolic syndrome.
基金the National Natural Science Foundation of China(Grant Nos.81702887,81272473)the Key Laboratory of Clinical Cancer Pharmacology and Toxicology Research of Zhejiang Province(Grant No.2020E10021)+6 种基金the Key Medical Disciplines of Zhejiang Province(Grant No.2018-2-3)the Hangzhou Major Science and Technology Project(Grant No.20172016A01)the Zhejiang Provincial Foundation of Natural Science(Grant No.LY19H310004)the Scientific and Technological Developing Scheme of Hangzhou City(Grant No.20191203B49)the Science Research Foundation of Zhejiang Health Bureau(Grant No.2020RC026)the High-level Talents Coming Back from Abroad Innovation,the Entrepreneurship Program in Hangzhouand the Teachers Research Fund of Zhejiang University City College(Grant No.J-19006).
文摘Objective:Mcl-1 overexpression confers acquired resistance to Bcl-2 inhibitors in non-small cell lung cancer(NSCLC),but no direct Mcl-1 inhibitor is currently available for clinical use.Thus,novel therapeutic strategies are urgently needed to target Mcl-1 and sensitize the anti-NSCLC activity of Bcl-2 inhibitors.Methods:Cell proliferation was measured using sulforhodamine B and colony formation assays,and apoptosis was detected with Annexin V-FITC staining.Gene expression was manipulated using siRNAs and plasmids.Real-time PCR and Western blot were used to measure mRNA and protein levels.Immunoprecipitation and immunofluorescence were used to analyze co-localization o f dual specificity tyrosine-phosphorylation-regulated kinase 1A(DYRK1A)and Mcl-1.Results:Suppression of DYRK1A resulted in reduced Mcl-1 expression in NSCLC cells,whereas overexpression of DYRK1A significantly increased Mcl-1 expression.Suppression of DYRK1A did not alter Mcl-1 mRNA levels,but did result in an accelerated degradation o f Mcl-1 protein in NSCLC cells.Furthermore,DYRK1A mediated proteasome-dependent degradation o f Mcl-1 in NSCLC cells,and DYRK1A co-localized with Mcl-1 in NSCLC cells and was co-expressed with Mcl-1 in tumor samples from lung cancer patients,suggesting that Mcl-1 may be a novel DYRK1A substrate.We showed that combined therapy with harmine and Bcl-2 antagonists significantly inhibited cell proliferation and induced apoptosis in NSCLC cell lines as well as primary NSCLC cells.Conclusions:Mcl-1 is a novel DYRK1A substrate,and the role of DYRK1A in promoting Mcl-1 stability makes it an attractive target for decreasing Bcl-2 inhibitor resistance.
基金supported by the National Nature Science Foundation of China [grants number 81872626,81573151,U1204823,and 81573243]Science and Technology Foundation for Innovation Talent of Henan Province [No.154200510010]
文摘Vitamin D, a fat-soluble vitamin and endocrine horm one, and it impacts various bone and extra-bone health, such as osteoporosis, diabetes, and cancer. The main circulating form of vitamin D is 25-hydroxyvitamin D [25(OH)D] and it is a useful clinical biomarker of vitamin D status. The Institute of Medicine (IOM) defines as vitamin D deficiency (VDD) when serum 25(OH)D concentration is less than 20 ng/mL⑴.Worldwide, VDD is recognized as a severe public health problem. In 2007, Holick estimated that globally over one billion people suffered from VDD or vitamin D insufficiency (VDI). In China, it has bee n reported that the prevale nee of VDD ranged from 38.8% to 91.2% in different regions.
文摘Objective:This study was designed to evaluate the clinical significance of the serum thymidine kinase 1(TK1)and prognosis nutrition index(PNI)in the prognosis of elderly patients with advanced non-small cell lung cancer(NSCLC).Methods:A total of 126 elderly patients with advanced non-small cell lung cancer from Jan.2015 to Apr.2016 were enrolled.The clinical,pathological and survival information were collected.The serum TK1 level was measured as well as PNI was calculated when the patient was admitted to our hospital for the first time.The relationship between serum TK1,PNI,and clinical prognostic characteristics was analyzed.The clinical significance of serum TK1 and PNI in the prognosis of elderly patients with advanced non-small cell lung cancer was investigated.Results:The results showed that the survival time of the patients was related to TK1 and PNI.The further Kaplan-Meier method and log-rank tests showed that the long-term outcome of the high-TK1 group was significantly worse than low-TK1 group(mOS,27 m vs.15 m,P=0.047).Besides,the Kaplan-Meier method and log-rank tests also showed that the long-term outcome of high-PNI group was significantly better than low-PNI group(mOS,31.5 m vs.16 m,P=0.015).However,the Spearman’s correlation analysis showed there was no correlation between PNI and TK1.The univariate and multivariate analysis showed that TK1,PNI and the number of metastatic sites were independent prognostic factors.Conclusions:The study confirmed the TK1 and PNI were independent prognostic factors of advanced NSCLC in the elderly.More attention worth is paid in routine clinical practice for patients cell proliferation and nutritional status.
