A range of neurodegenerative disorders,collectively termed parkinsonian disorders,present with a complex array of both motor and non-motor symptoms.Included in this group are Parkinson’s disease(PD),dementia with Lew...A range of neurodegenerative disorders,collectively termed parkinsonian disorders,present with a complex array of both motor and non-motor symptoms.Included in this group are Parkinson’s disease(PD),dementia with Lewy bodies(DLB),multiple system atrophy(MSA),corticobasal syndrome(CBS),and progressive supranuclear palsy(PSP).These disorders are differentiated neuropathologically by their dominant protein pathologies involvingα-synuclein(α-syn)and/or tau,the types of brain cells affected,such as neurons,oligodendroglia,and astrocytes,and the specific brain regions involved(Tolosa et al.,2021).展开更多
Objectives: The objective of the study is to observe the effects of ginsenoside Rb1 on indexes of body weight, body composition, blood lipid, skeletal muscle endurance, and insulin sensitivity in obese mice, probe int...Objectives: The objective of the study is to observe the effects of ginsenoside Rb1 on indexes of body weight, body composition, blood lipid, skeletal muscle endurance, and insulin sensitivity in obese mice, probe into its pharmacological action, and further explore its effects on adenosine monophosphate-activated protein kinase(AMPK) signaling pathway in skeletal muscle. Materials and Methods: Eight-week-old C57 BL/6 J mice were fed with high-fat diet for 12 weeks to establish obese mouse model. The model-establishment obese mice were randomly divided into three groups including model control group, metformin group, and ginsenoside Rb1 group. In the normal control group, normal diet was administered. The intervention period was 8 weeks. Body weight and food intake of the mice were measured regularly every week. The treadmill test was performed at weeks 3 and 7, and the oral glucose tolerance test was carried out at weeks 4 and 8. Body composition of the mice was detected by applying NMR Animal Body Composition Analyzer at week 8. Four parameters of blood lipids and free fatty acid(FFA)levels were detected. The m RNA expression of AMPKα and proliferator-activated receptor gamma coactivator-1α(PGC-1α) in skeletal muscle was examined by real-time fluorescence quantitative polymerase chain reaction, and the influence of ginsenoside Rb1 on protein expression of AMPKα, p-AMPKα, and PGC-1α was observed by western blotting. Results: The body weight(since the 5 th week of drug administration)and food intake of the mice in the ginsenoside Rb1 group were significantly lower than those in the model control group(P < 0.05) in a time-dependent manner. Ginsenoside Rb1 could significantly reduce the levels of triglyceride and low-density lipoprotein cholesterol, while increase the high-density lipoprotein cholesterol level(P < 0.05). In addition, ginsenoside Rb1 could reduce the serum FFA level(P < 0.05).After the administration of ginsenoside Rb1 for 8 weeks, the body fat mass of obese mice decreased and the lean mass increased(P < 0.05).The skeletal muscle endurance and the oral glucose tolerance of the obese mice improved using ginsenoside Rb1. At the molecular level,ginsenoside Rb1 could up-regulate the mRNA and protein expression of AMPKα in skeletal muscle, and increase the content of p-AMPK protein significantly(P < 0.01). At the same time, the mRNA and protein level of PGC-1α was also un-regulated, correspondingly(P < 0.01).Conclusion: Ginsenoside Rb1 exerts effects on reducing body weight, decreasing blood lipid levels, enhancing the skeletal muscle endurance,and increasing the insulin sensitivity in obese mice by activating the related proteins in AMPK signaling pathway in skeletal muscle.展开更多
Background:To date,there is no approved blood-based biomarker for breast cancer detection.Herein,we aimed to assess semaphorin 4C(SEMA4C),a pivotal protein involved in breast cancer progression,as a serum diagnostic b...Background:To date,there is no approved blood-based biomarker for breast cancer detection.Herein,we aimed to assess semaphorin 4C(SEMA4C),a pivotal protein involved in breast cancer progression,as a serum diagnostic biomarker.Methods:We included 6,213 consecutive inpatients from Tongji Hospital,Qilu Hospital,and Hubei Cancer Hospital.Training cohort and two validation cohorts were introduced for diagnostic exploration and validation.A pan-cancer cohort was used to independently explore the diagnostic potential of SEMA4C among solid tumors.Breast cancer patients who underwent mass excision prior to modified radical mastectomy were also analyzed.We hypothesized that increased pretreatment serum SEMA4C levels,measured using optimized in-house enzymelinked immunosorbent assay kits,could detect breast cancer.The endpoints were diagnostic performance,including area under the receiver operating characteristic curve(AUC),sensitivity,and specificity.Post-surgery pathological diagnosis was the reference standard and breast cancer staging followed the TNM classification.There was no restriction on disease stage for eligibilities.Results:We included 2667 inpatients with breast lesions,2378 patients with other solid tumors,and 1168 healthy participants.Specifically,118 patients with breast cancer were diagnosed with stage 0(5.71%),620 with stage I(30.00%),966 with stage II(46.73%),217 with stage III(10.50%),and 8 with stage IV(0.39%).Patients with breast cancer had significantly higher serum SEMA4C levels than benign breast tumor patients and normal controls(P<0.001).Elevated serum SEMA4C levels had AUC of 0.920(95%confidence interval[CI]:0.900–0.941)and 0.932(95%CI:0.911–0.953)for breast cancer detection in the two validation cohorts.The AUCs for detecting early-stage breast cancer(n=366)and ductal carcinoma in situ(n=85)were 0.931(95%CI:0.916–0.946)and 0.879(95%CI:0.832–0.925),respectively.Serum SEMA4C levels significantly decreased after surgery,and the reduction was more striking after modified radical mastectomy,compared with mass excision(P<0.001).The positive rate of enhanced serum SEMA4C levels was 84.77%for breast cancer and below 20.75%for the other 14 solid tumors.Conclusions:Serum SEMA4C demonstrated promising potential as a candidate biomarker for breast cancer diagnosis.However,validation in prospective settings and by other study groups is warranted.展开更多
文摘A range of neurodegenerative disorders,collectively termed parkinsonian disorders,present with a complex array of both motor and non-motor symptoms.Included in this group are Parkinson’s disease(PD),dementia with Lewy bodies(DLB),multiple system atrophy(MSA),corticobasal syndrome(CBS),and progressive supranuclear palsy(PSP).These disorders are differentiated neuropathologically by their dominant protein pathologies involvingα-synuclein(α-syn)and/or tau,the types of brain cells affected,such as neurons,oligodendroglia,and astrocytes,and the specific brain regions involved(Tolosa et al.,2021).
基金supported by Natural Science Foundation of China (NSFC81503540&NSFC81274041)Chaoyang District Science and Technology Commission Collaborative Innovation Project (CYXC1513)+1 种基金Major New Drug Creation Sub-project (2012ZX09103201-005)Beijing Joint Construction Project (0101216-14&0101216-2013)
文摘Objectives: The objective of the study is to observe the effects of ginsenoside Rb1 on indexes of body weight, body composition, blood lipid, skeletal muscle endurance, and insulin sensitivity in obese mice, probe into its pharmacological action, and further explore its effects on adenosine monophosphate-activated protein kinase(AMPK) signaling pathway in skeletal muscle. Materials and Methods: Eight-week-old C57 BL/6 J mice were fed with high-fat diet for 12 weeks to establish obese mouse model. The model-establishment obese mice were randomly divided into three groups including model control group, metformin group, and ginsenoside Rb1 group. In the normal control group, normal diet was administered. The intervention period was 8 weeks. Body weight and food intake of the mice were measured regularly every week. The treadmill test was performed at weeks 3 and 7, and the oral glucose tolerance test was carried out at weeks 4 and 8. Body composition of the mice was detected by applying NMR Animal Body Composition Analyzer at week 8. Four parameters of blood lipids and free fatty acid(FFA)levels were detected. The m RNA expression of AMPKα and proliferator-activated receptor gamma coactivator-1α(PGC-1α) in skeletal muscle was examined by real-time fluorescence quantitative polymerase chain reaction, and the influence of ginsenoside Rb1 on protein expression of AMPKα, p-AMPKα, and PGC-1α was observed by western blotting. Results: The body weight(since the 5 th week of drug administration)and food intake of the mice in the ginsenoside Rb1 group were significantly lower than those in the model control group(P < 0.05) in a time-dependent manner. Ginsenoside Rb1 could significantly reduce the levels of triglyceride and low-density lipoprotein cholesterol, while increase the high-density lipoprotein cholesterol level(P < 0.05). In addition, ginsenoside Rb1 could reduce the serum FFA level(P < 0.05).After the administration of ginsenoside Rb1 for 8 weeks, the body fat mass of obese mice decreased and the lean mass increased(P < 0.05).The skeletal muscle endurance and the oral glucose tolerance of the obese mice improved using ginsenoside Rb1. At the molecular level,ginsenoside Rb1 could up-regulate the mRNA and protein expression of AMPKα in skeletal muscle, and increase the content of p-AMPK protein significantly(P < 0.01). At the same time, the mRNA and protein level of PGC-1α was also un-regulated, correspondingly(P < 0.01).Conclusion: Ginsenoside Rb1 exerts effects on reducing body weight, decreasing blood lipid levels, enhancing the skeletal muscle endurance,and increasing the insulin sensitivity in obese mice by activating the related proteins in AMPK signaling pathway in skeletal muscle.
基金National Science and Technology Major Sub-Project,Grant/Award Number:2018ZX10301402-002National Natural Science Foundation of China,Grant/Award Numbers:81772787,81902653,82072889+2 种基金Technical Innovation Special Project of Hubei Province,Grant/Award Number:2018ACA138Fundamental Research Funds for the Central Universities,Grant/Award Number:2019kfyXMBZ024Municipal Health Commission Project ofWuhan,Grant/Award Number:WX18Q16。
文摘Background:To date,there is no approved blood-based biomarker for breast cancer detection.Herein,we aimed to assess semaphorin 4C(SEMA4C),a pivotal protein involved in breast cancer progression,as a serum diagnostic biomarker.Methods:We included 6,213 consecutive inpatients from Tongji Hospital,Qilu Hospital,and Hubei Cancer Hospital.Training cohort and two validation cohorts were introduced for diagnostic exploration and validation.A pan-cancer cohort was used to independently explore the diagnostic potential of SEMA4C among solid tumors.Breast cancer patients who underwent mass excision prior to modified radical mastectomy were also analyzed.We hypothesized that increased pretreatment serum SEMA4C levels,measured using optimized in-house enzymelinked immunosorbent assay kits,could detect breast cancer.The endpoints were diagnostic performance,including area under the receiver operating characteristic curve(AUC),sensitivity,and specificity.Post-surgery pathological diagnosis was the reference standard and breast cancer staging followed the TNM classification.There was no restriction on disease stage for eligibilities.Results:We included 2667 inpatients with breast lesions,2378 patients with other solid tumors,and 1168 healthy participants.Specifically,118 patients with breast cancer were diagnosed with stage 0(5.71%),620 with stage I(30.00%),966 with stage II(46.73%),217 with stage III(10.50%),and 8 with stage IV(0.39%).Patients with breast cancer had significantly higher serum SEMA4C levels than benign breast tumor patients and normal controls(P<0.001).Elevated serum SEMA4C levels had AUC of 0.920(95%confidence interval[CI]:0.900–0.941)and 0.932(95%CI:0.911–0.953)for breast cancer detection in the two validation cohorts.The AUCs for detecting early-stage breast cancer(n=366)and ductal carcinoma in situ(n=85)were 0.931(95%CI:0.916–0.946)and 0.879(95%CI:0.832–0.925),respectively.Serum SEMA4C levels significantly decreased after surgery,and the reduction was more striking after modified radical mastectomy,compared with mass excision(P<0.001).The positive rate of enhanced serum SEMA4C levels was 84.77%for breast cancer and below 20.75%for the other 14 solid tumors.Conclusions:Serum SEMA4C demonstrated promising potential as a candidate biomarker for breast cancer diagnosis.However,validation in prospective settings and by other study groups is warranted.