ObjectiveThis exploratory pilot study aimed to investigate the associations of anger-related irritability symptoms with gut microbiota and circulating metabolites in patients with type 2 diabetes mellitus (T2DM) using multi-omics analysis.MethodsWe conducted a cross-sectional study, in which T2DM patients were categorized into a self-reported irritable T2DM group (IDM, n = 29) and a self-reported non-irritable DM group (NIDM, n = 28) based on Visual Analog Scale (VAS) scores, with a healthy control group (HC, n = 30) also established. Fecal 16S rRNA gene sequencing and UPLC-MS/MS-based untargeted metabolomic profiling of blood samples were performed. Differences in microbial community structure between groups were analyzed using alpha and beta diversity metrics and linear discriminant analysis effect size (LEfSe) analysis. Differentially abundant genera were identified by MaAsLin2 with adjustment for confounders. Exploratory metabolite markers were screened based on thresholds for p < 0.05, variable importance in projection (VIP) > 1, |log2 fold change (FC)| > 1. Associations between differentially abundant genera and exploratory metabolite markers were explored using Spearman correlation analysis. Functional prediction was conducted based on differentially represented KEGG orthology (KO) and clusters of orthologous groups (COG) entries to identify altered metabolic pathways.ResultsBoth beta diversity and LEfSe analyses revealed differences in gut microbial community structure and potential discriminatory taxa among the three groups. Five differentially abundant genera and twelve exploratory metabolite markers were identified between IDM and NIDM. A combined model incorporating microbial and metabolomic markers demonstrated superior diagnostic performance (AUC = 0.872) compared with models using either type of marker alone. Twelve statistically significant microbiota–metabolite associations were found in Spearman analysis. Functional prediction analysis indicated enrichment of bile acid and tryptophan metabolism pathways.ConclusionVAS-defined irritability symptoms were associated with specific gut microbial and metabolomic alterations in T2DM, providing exploratory evidence for future studies on emotion-related metabolic dysregulation.

Ethnopharmacological relevance: Fuling-Zexie (FZ) formula, a traditional Chinese herbal prescription composed of Poria cocos (Schwan.) Wolf. (Poria), Pueraria lobate (Willd.) Howe. (Puerariae Lobatae Radix), Alisma orientale (Sam.) Julep. (Alismatis Rhizoma), and Atractylodes lancea (Thunb.) Dc. (Atractylodis Rhizoma), has been clinically used to ameliorate hyperuricemia (HUA) and its associated renal injury. Aim of study: This study aims to explore the action and mechanism of FZ on renal inflammation and dysfunction caused by HUA. Materials and methods: FZ was orally administered to rapid HUA mouse induced by potassium oxonate (PO) and hypoxanthine (HX) for 7 days. Serum levels of uric acid (UA), creatinine (CRE), blood urea nitrogen (BUN), xanthine oxidase (XOD), adenosine deaminase (ADA), alanine aminotransferase (ALT), aspartate aminotrans-ferase (AST), urine levels of UA, CRE and urinary albumin were determined by biochemical assays. Serum levels of interleukin (IL)-1 beta and IL-6 were tested by ELISA. Hematoxylin-eosin and Masson staining were used to examine kidney and liver histopathological alterations. The expressions of renal glucose transporter 9 (GLUT9), ATP-binding cassette subfamily G member 2 (ABCG2), organic anion transporter 1 (OAT1), phospho-janus kinase 2 (p-JAK2), p-signal transducer and activator of transcription 3 (p-STAT3), suppression of cytokine signaling 3 (SOCS3), NLR family pyrin domain containing 3 (NLRP3), apoptosis-associated speck-like protein (ASC), and cleaved-cysteinyl aspartate specific proteinase-1 (cleaved-Cas-1) were detected by western blots. The potential protein targets and pathways of FZ intervention on HUA were predicted by network pharmacology. The con-stituents in FZ aqueous extract were analyzed by UPLC-MS. Results: FZ reduced serum UA, CRE, BUN, and urinary albumin and increased urine UA, CRE levels in HUA mice. In addition, the treatment with FZ to HUA mice inhibited the elevated serum levels of XOD and ADA, and regulated renal urate transports including OAT1, GLUT9 and ABCG2. FZ also attenuated kidney inflammation and fibrosis and downregulated the expressions of IL-1 beta, p-JAK2, p-STAT3, SOCS3, IL-6, NLRP3, ASC, and cleaved-Cas-1. Thirteen compounds were identified in the FG, including L-phenylalanine, D-tryptophan, 3 '- hydroxypuerarin, Puerarin, 3 '-Methoxy Puerarin, Daidzin, Pueroside A, formononetin-8-C-[xylosyl (1 -> 6)]-glucoside, Ononin, Alisol I 23-acetate, 16-oxo-alisol A, Alisol C and Alisol A.Conclusion: FZ inhibits serum UA generation and promotes urine UA excretion as well as attenuates kidney inflammation and fibrosis in HUA mouse with nephropathy. The underlying mechanism of its action may be associated with suppression of the JAK2/STAT3 signaling pathway and NLRP3 inflammasome activation. This formula may offer a novel source for developing anti-HUA drugs.

Introduction: Jiangtang Sanhao Formula (JTSHF), composed of Panax ginseng, Atractylodes macrocephala, Coptis chinensis, Salvia miltiorrhiza and several other herbs, is a traditional Chinese medicine formula commonly used to treat type 2 diabetes. This compound shows significant clinical efficacy in the treatment of diabetic, however, its target and pharmacological mechanism are still unclear. The present study explored the therapeutic effect of JTSHF on diabetic mice and conducted RNA sequencing to investigate the potential mechanism. Methods: The T2DM mice model was established using a high-fat diet combined with an intraperitoneal injection of low-dose STZ. Fasting blood glucose (FBG), serum insulin, glucose tolerance, and blood lipids in mice from different groups were examined. Then the effects of JTSHF on oxidative stress and liver histopathology in diabetic mice were observed. Next, transcriptome analysis was performed to identify differentially expressed genes (DEG), which were validated using real-time quantitative PCR (RT-qPCR). By using pathway enrichment analysis, we identified several key pathways which are essential in the JTSHF effect on T2DM. Finally, we constructed ceRNA network to illustrate the regulatory effect of JTSHF on transcriptional profile in diabetic liver. Results: JTSHF reduced FBG level and blood lipid contents, ameliorated glucose tolerance and improved insulin sensitivity in diabetic mice. It also showed protective effects on fatty livers induced by high-fat diet and diabetes. For the first time, we revealed that JTSHF exerts anti-T2DM role in the liver of diabetic mice, which is associated with multiple molecular targets and signaling pathways. Enrichment analysis and treatment-based mRNA-ncRNA-miRNA ceRNA networks revealed that JTSHF might exerts therapeutic effect by modulating lipid metabolism. Discussion: Our research found that JTSHF exerts anti-T2DM effect by affecting multiple pathways. Among these, lipid metabolism and oxidative stress might be involved. The present study provided novel insights for the mechanism of JTSHF, and the differentially expressed genes identified can be potential therapeutic targets in the treatment of T2DM in future.

Objective: To observe the effect of electro-acupuncture（EA） on testicular morphology and the expression of testicular spermatogenic cell apoptosis-related proteins Bcl-2 and Bax in STZ rats, and to explore the mechanism of EA in reducing blood sugar to improve spermatogenic cell apoptosis in rats with type 2 diabetes mellitus（T2DM）. Methods: 12 male Wistar rats were established T2DM model by high-sugar and high-fat diets combined with intraperitoneal injection of 2% streptozotocin（STZ） solution（35 mg/kg）. The successful model was determined by blood sugar higher than 16.67 mmol/L and fasting blood-glucose（FBG） higher than 11.1mmol/L. The successful modeling was randomly divided into the model group and the EA group according to blood glucose levels, and were fed with high-sugar and high-fat diets subsequently. Another 6 normal rats were taken as the blank control and fed with common fodder. The EA group was treated with needling bilateral Weiwanxiashu（EX-B3）, Pishu（BL20）, Zusanli（ST36） and Sanyinjiao（SP6）, and among which EX-B3 and ST36 on one side were connected to EA apparatus. The treatment was 6 times a week for 6 weeks. FBG was detected before and after the intervention in each group. Serum levels of insulin（INS） and testosterone（T） were detected by Elisa method. HE staining was used to observe the morphological changes of the testis of the rats in each group. Western Blot method was applied to detect the protein expressions of Bcl-2 and Bax in the testis of the rats in each group. Grayscale of the bands was determined by ImageJ software. Results: Before the intervention, the value of FBG was significantly higher in the model group and the EA group than that in the blank group（P＜0.01）, and there was no statistical difference in the value of FBG between the model group and the EA group（P＞0.05）. After 6 weeks of intervention, compared with those in the blank group, the value of FBG was significantly increased（P＜0.01）, the serum levels of INS and T were significantly decreased（P ＜ 0.01）, and the protein expression of Bcl-2 in the testis was significantly decreased（P＜0.01）, and the Bax protein expression was increased in the model group（P＜0.05）; compared with those in the model group, the value of FBG was significantly decreased（P＜0.01）, the serum levels of INS and T were increased（P＜0.05, P＜0.01）, the protein expression of Bcl-2 was increased（P＜0.05）, and the protein expression of Bax was decreased in the EA group（P＜0.05）. HE staining showed that the pathological changes of the model group were more obvious than those of the blank group, and the overall condition of the EA group was better than that of the model group. Conclusion: Under hyperglycemia, the serum level of testosterone decreased, and the spermatogenic cell apoptosis increased in male rats. EA can significantly reduce FBG levels in the rats with T2DM, alleviate the internal pathological changes of seminiferous tubules in rats under hyperglycemia, and protect sperm develop normally, the mechanism may be related to the function of EA in down-regulating the expression of the pro-apoptotic factor Bax, up-regulating the expression of the anti-apoptotic factor Bcl-2, and inhibiting the apoptosis of spermatogenic cells.

MicroRNAs (miRNAs) and transfer RNA-derived small RNAs (tsRNAs) play critical roles in the regulation of different biological processes, but their underlying mechanisms in diabetes mellitus (DM) are still largely unknown. This study aimed to gain a better understanding of the functions of miRNAs and tsRNAs in the pathogenesis of DM. A high-fat diet (HFD) and streptozocin (STZ)-induced DM rat model was established. Pancreatic tissues were obtained for subsequent studies. The miRNA and tsRNA expression profiles in the DM and control groups were obtained by RNA sequencing and validated with quantitative reverse transcription-PCR (qRT-PCR). Subsequently, bioinformatics methods were used to predict target genes and the biological functions of differentially expressed miRNAs and tsRNAs. We identified 17 miRNAs and 28 tsRNAs that were significantly differentiated between the DM and control group. Subsequently, target genes were predicted for these altered miRNAs and tsRNAs, including Nalcn, Lpin2 and E2f3. These target genes were significantly enriched in localization as well as intracellular and protein binding. In addition, the results of KEGG analysis showed that the target genes were significantly enriched in the Wnt signaling pathway, insulin pathway, MAPK signaling pathway and Hippo signaling pathway. This study revealed the expression profiles of miRNAs and tsRNAs in the pancreas of a DM rat model using small RNA-Seq and predicted the target genes and associated pathways using bioinformatics analysis. Our findings provide a novel aspect in understanding the mechanisms of DM and identify potential targets for the diagnosis and treatment of DM.

OBJECTIVE:To observe the effect of electroacupuncture (EA) on liver protein kinase B (Akt)/forkhead box transcription factor 1 (FoxO1) signaling pathway in Zucker diabetic fatty (ZDF) rats, and to explore the possible mechanism of EA on improving liver insulin resistance of type 2 diabetes mellitus.METHODS:Twelve male 2-month-old ZDF rats were fed with high-fat diet for 4 weeks to establish diabetes model. After modeling, the rats were randomly divided into a model group and an EA group, with 6 rats in each group. In addition, six male Zucker lean (ZL) rats were used as the blank group. The rats in the EA group were treated with EA at bilateral "Zusanli" (ST 36), "Sanyinjiao" (SP 6), "Weiwanxiashu" (EX-B 3), and "Pishu" (BL 20). The ipsilateral "Zusanli" (ST 36) and "Weiwanxiashu" (EX-B 3) were connected to EA device, continuous wave, frequency of 15 Hz, 20 min each time, once a day, six times a week, for a total of 4 weeks. The fasting blood glucose (FBG) in each group was compared before modeling, before intervention and after intervention; the serum levels of insulin (INS) and C-peptide were measured by radioimmunoassay method, and the insulin resistance index (HOMA-IR) was calculated; HE staining method was used to observe the liver tissue morphology; Western blot method was used to detect the protein expression of Akt, FoxO1 and phosphoenolpyruvate carboxykinase (PEPCK) in the liver.RESULTS:Before intervention, compared with the blank group, FBG was increased in the model group and the EA group (P<0.01); after intervention, compared with the model group, FBG in the EA group was decreased (P<0.01). Compared with the blank group, the serum levels of INS and C-peptide, HOMA-IR, and the protein expression of hepatic FoxO1 and PEPCK were increased (P<0.01), while the protein expression of hepatic Akt was decreased (P<0.01) in the model group. Compared with the model group, the serum levels of INS and C-peptide, HOMA-IR, and the protein expression of hepatic FoxO1 and PEPCK were decreased (P<0.01), while the protein expression of hepatic Akt was increased (P<0.01) in the EA group. In the model group, the hepatocytes were structurally disordered and randomly arranged, with a large number of lipid vacuoles in the cytoplasm. In the EA group, the morphology of hepatocytes tended to be normal and lipid vacuoles were decreased.CONCLUSION:EA could reduce FBG and HOMA-IR in ZDF rats, improve liver insulin resistance, which may be related to regulating Akt/FoxO1 signaling pathway.

目的 探讨人参皂苷Rb1、小檗碱及其联合应用对高脂饮食诱导肥胖小鼠肠道菌群的影响.方法 42 只SPF级雄性C57BL/6J小鼠高脂饲料喂养12 周建立肥胖小鼠模型.将符合肥胖标准的32 只肥胖小鼠任意分为4 组:对照组、人参皂苷Rb1 组(20 mg/kg)、小檗碱组(50 mg/kg)、人参皂苷Rb1+小檗碱组(人参皂苷Rb1 20 mg/kg + 小檗碱50 mg/kg),每组8 只.连续灌胃给药8 周,给药期间小鼠继续给予高脂饲料喂养.每周记录各组小鼠的体质量,每 2 周检测小鼠空腹血糖.实验结束后留取粪便,进行16 S rDNA测序,观察各组小鼠肠道菌群变化.结果 与对照组比较,人参皂苷Rb1组、小檗碱组和人参皂苷Rb1+小檗碱组第4～6 周小鼠体质量降低,第4、6、8 周小鼠空腹血糖降低(均P＜0.05).人参皂苷Rb1 组、小檗碱组和人参皂苷Rb1+小檗碱组高脂饮食诱导的肠道生态失调均改善,拟杆菌门/厚壁菌门值增加,脱铁杆菌门、小螺菌属、螺杆菌属、多尔菌属、瘤胃球菌属和臭气杆菌属等有害菌群的相对丰度降低.结论 人参皂苷Rb1、小檗碱及其联合应用可降低高脂饮食诱导的肥胖小鼠体质量,作用机制可能与其调节肠道菌群的结构有关.

Abstract Insulin resistance (IR) in skeletal muscle is a well-documented pathologic characteristic in the development of type 2 diabetes mellitus (T2DM), with GLUT4 being a key protein involved in this process. Jiangtang Sanhao formula, (JTSHF), a proven effective prescription for treating T2DM in clinic, has been shown to have a beneficial effect on alleviation of skeletal muscle IR. However, the underlying mechanism still need to be explored. Herein, we investigated the potential benefits and mechanism of JTSHF-containing serum in combating IR induced by palmitate in C2C12 skeletal muscle cells. The results demonstrated that JTSHF-containing serum significantly enhanced glucose consumption and uptake in IR-C2C12 cells at noncytotoxic concentration. Moreover, the JTSHF-containing serum reduced the malondialdehyde level and increase superoxide dismutase activity. Further investigations showed the function of JTSHF-containing serum in up-regulating the expression of key factors involved in glucose transport and metabolism, including GLUT4, phosphorylated AMPKα, SIRT1, PGC-1α, PPARα, PPARγ, and UCP3, as well as GLUT4 translocation. Notably, these positive effects were substantially diminished when we used an AMPK inhibitor, named Compound C, suggesting that AMPK/SIRT1/PGC-1α signaling pathway may be involved in JTSHF’s ability to rescue palmitate-induced reductions in GLUT4 expression and translocation in IR-C2C12 cells. In summary, our study provides evidence that JTSHF may effectively regulate GLUT4 and counteracte IR in skeletal muscle cells, and it highlights the potential involvement of the AMPK/SIRT1/PGC-1α signaling pathway in mediating these beneficial effects.

[目的]观察降糖消渴颗粒对2型糖尿病小鼠肝脏中内质网应激和脂质代谢相关指标表达的影响,研究其改善糖尿病肝脏脂质代谢紊乱的可能机制.[方法]雄性8周龄KK-Ay小鼠,高脂饲料喂养,诱导2型糖尿病模型,以空腹血糖≥13.9 mmol/L作为成模标准.成模后小鼠随机分为模型组、吡格列酮组、降糖消渴颗粒高、中、低(7,3.5,1.75 g/kg)剂量组,并设正常对照组,C57BL/6J小鼠,普通饲料喂养.治疗10周后,摘取各组小鼠肝脏,剪取肝脏相同部位组织,生理盐水冲洗,10％福尔马林固定液固定待检,余下肝组织液氮保存备用.逆转录-聚合酶链反应(RT-PCR)法检测小鼠肝脏IRE1α、XBP1、SREBP-1c、SREBP2、Insig-1、FAS的mRNA表达情况;免疫组化法检测小鼠肝脏中p-eIF2α、GRP78的蛋白表达情况.[结果]模型组小鼠肝脏中SREBP-1c、SREBP2、IRE1α、XBP1的mRNA表达明显上调(P<0.01),Insig-1的mRNA表达明显下调(P<0.01),FAS的mRNA表达也有所增高(P<0.05).高剂量(7 g/kg)降糖消渴颗粒可显著下调SREBP-1c的mRNA表达量(P<0.01);低、中剂量(1.75,3.5 g/kg)作用比较广泛且突出,均可减少SREBP-1c和SREBP2的mRNA表达(P<0.01)以及FAS的基因表达量(P<0.05).除此之外,中剂量还具有下调IRE1α的mRNA表达(P<0.05),增加Insig-1的mRNA表达量(P<0.05)的作用.低、中、高剂量降糖消渴颗粒均可显著降低p-eIF2α、GRP78的蛋白表达量(P<0.01).[结论]2型糖尿病小鼠肝脏的脂质合成作用与内质网应激反应具有相关性.低、中(1.75,3.5 g/kg)剂量降糖消渴颗粒可在一定程度上下调实验小鼠肝脏中脂质代谢相关因子的表达,以减少肝脏脂质的过度合成,同时减轻肝脏内质网应激反应,共同起到改善糖尿病肝脏脂质代谢紊乱的作用.

目的:检测降糖消渴颗粒干预后的2型糖尿病小鼠肝组织胰岛素信号通路、腺苷酸活化蛋白激酶α(AMPKα)信号通路、核因子κB(NF-κB)信号通路相关指标表达的变化,探讨其改善糖尿病状态下肝脏脂代谢的可能途径.方法:40只8周龄雄性KK-Ay小鼠,高脂饲料喂养4周,诱导2型糖尿病发生,尾静脉取血测量空腹血糖,以空腹血糖≥13.9mmol/L作为糖尿病成模标准.将40只糖尿病小鼠随机分为模型组、吡格列酮组及降糖消渴颗粒低(1.75 g/kg)、中(3.50 g/kg)、高(7.00 g/kg)剂量组,每组8只,灌胃给药治疗10周.8只同周龄雄性C57BL/6J小鼠作为正常组,普通饲料喂养.治疗结束后,肝组织取材,实时荧光定量聚合酶链反应(RT-qPCR)检测小鼠肝脏胰岛素受体底物-1(IRS-1)、蛋白激酶Ce(PKCε)、腺苷酸活化蛋白激酶α(AMPKα)、过氧化物酶体增殖物激活受体α(PPARα)、NF-κB、肿瘤坏死因子-α(TNF-α)、白细胞介素-1β(IL-1β)的mRNA表达情况.结果:与正常组比较,模型组NF-κB、TNF-α mRNA上升,IRS-1、AMPKα、PPARα mRNA降低,差异均有统计学意义(P＜0.01).与模型组比较,吡格列酮组IRS-1、AMPKα mRNA上升,差异均有统计学意义(P＜0.01);降糖消渴颗粒高剂量组PKCe mRNA降低,PPARα mRNA上升,差异均具有统计学意义(P＜0.01);降糖消渴颗粒中剂量组AMPKα mRNA上升,NF-κB、TNF-α mRNA降低,差异均有统计学意义(P＜0.01或P＜0.05);降糖消渴颗粒低剂量组AMPKα mRNA上升,NF-κB、TNF-α mRNA降低,差异均具有统计学意义(P＜0.01或P＜0.05).结论:降糖消渴颗粒可上调糖尿病状态下小鼠肝细胞内AMPKα mRNA的表达,同时抑制NF-κB炎症信号通路的激活,调节肝脏脂质代谢;其中低、中剂量降糖消渴颗粒综合效果较好.

[目的]通过检测2型糖尿病小鼠肝糖原含量及相关指标的变化,探讨降糖消渴颗粒对糖尿病状态下肝糖原合成及储备的影响.[方法]选取雄性8周龄KK-Ay小鼠,予以高脂饲料喂养,诱导建立2型糖尿病模型,以空腹血糖≥13.9 mmol/L为成模标准;C57BL/6J小鼠予以正常饲料喂养,作为对照组.将成模后小鼠随机分为模型组、吡格列酮组、降糖消渴颗粒低、中、高(1.75、3.50、7.00 g/kg)剂量组,口服给药10周后,计算各组小鼠日均进食量及体质量增长率的变化;过碘酸雪夫染色法检测小鼠肝脏中糖原含量的变化;逆转录-聚合酶链式反应(RT-PCR)法检测小鼠肝脏IRS-2 mRNA、Akt mRNA、GSK-3αmRNA的表达情况.[结果]中剂量(3.50 g/kg)降糖消渴颗粒可显著提高肝组织中IRS-2 mRNA、Akt mRNA,降低GSK-3αmRNA的表达(P<0.01),增加肝脏中糖原的储备量(P<0.05);高剂量(7.00 g/kg)也具有提高肝组织中IRS-2 mRNA,降低GSK-3αmRNA表达(P<0.01)的作用.[结论]降糖消渴颗粒可增加糖尿病小鼠肝脏胰岛素受体与糖代谢相关基因的表达,从而促进肝脏利用血糖合成糖原,增加肝脏糖原储备,改善糖尿病糖代谢紊乱状态.

在专业课程中融入思想政治教育,实现课程思政教学具有时代必然性,同时也面临一些问题.将共情理念运用到课程思想政治教育的"改革""创新"工作中,有利于贯彻落实新时代"以人为本"教育理念.结合重大事件、社会热点、情景模拟、经典案例、科学创新、身边故事,以及真实数据的共情方案,探讨了"中医学基础"课程思政的思想政治教育元素的挖掘、课程设计与方法,以及教学评价和改进建议,以期有效推动和优化"中医学基础"课程思政的本科教学.

OBJECTIVE:This study was aimed at examining the effects of lycopene on bone metabolism in high-fat diet (HFD)- induced obese mice and to identify the potential underlying mechanisms.METHODS:Mice were fed a HFD for 12 weeks and then continue with or without lycopene intervention (15 mg/kg) for additional 10 weeks. The effects of lycopene on blood glucose and lipid metabolism, as well as serum levels of total antioxidant capacity (T-AOC), superoxide dismutase (SOD), and malondialdehyde (MDA) were determined by biochemical assays. Bone histomorphological features and osteoclast activity were assessed by hematoxylin/eosin and tartrate-resistant acid phosphatase staining. Bone microstructure at the proximal tibial metaphysis and diaphysis was determined by microcomputed tomography. Tibial biomechanical strength and material profiles were measured by a three-point bending assay and Fourier transform infrared spectroscopy. Protein expressions involved in the AGE/RAGE/NF-кB signaling pathway were determined by western blot and/or immunohistochemical staining.RESULTS:Lycopene consumption reduced body weight gain and improved blood glucose and lipid metabolism in HFD-induced obese mice. In addition, lycopene treatment preserved bone biomechanical strength, material profiles, and microarchitecture in obese mice. Moreover, these alterations were associated with an increase in serum levels of T-AOC and SOD, and a decline in serum levels of MDA, as well as a reduction of AGEs, RAGE, cathepsin K, and p-NF-кBp65 and NF-кBp65 expressions in the femurs and tibias of obese mice.CONCLUSION:Lycopene may improve bone quality through its antioxidant properties, which may be linked with the regulation of the AGE/RAGE/NF-кB signaling pathway in obese mice. These results suggest that lycopene consumption may be beneficial for the management of obesity-induced osteoporosis.

Ethnopharmacological relevance: BaZiBuShen formula (BZBS) is clinically used to counteract mental fatigue and to retard the aging process. Brain aging echoes in major risks of human sufferings and has become one of the main challenges to our societies and the health-care systems. Aim of the study: To investigate the effect and mode of action of BZBS on aging-associated cognitive impairments. Materials and methods: BZBS was orally administered to D-galactose and NaNO2-induced aging mice. Premature senescence was assessed using the Morris water maze, step-down type passive avoidance, and pole-climbing tests. Telomere length was examined by qPCR analysis. Telomerase activity was assessed using PCR ELISA assay. Mitochondrial complex IV activity was examined by biochemical test. The levels of redox and immune status were determined by ELISA or biochemical assay. The expressions of sirtuin 6 (Sirt6), peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PGC-1 alpha), P53, telomerase reverse transcriptase (TERT), heme oxygenase-1 (HO-1), phospho(p)-nuclear factor erythroid-2 related factor 2 (NRF2), caspase-3, Bcl-2 associated x (Bax), and B-cell lymphoma-2 (Bcl-2) in the cerebral cortex were examined by Western blot and/or immunohistochemical staining. Results: BZBS intervention ameliorated reduced brain performances in aging mice, including memory, cognitive, and motor functions. In addition, BZBS administration to aging mice preserved redox homeostasis, attenuated immunosenescence, and maintained telomerase activity and telomere length. Moreover, BZBS treatment were associated with a declines in P53, caspase-3, Bax expressions and an increase in Sirt6, p-HO-1, p-NRF2, PGC-1 alpha, and Bcl-2 expressions in the brains of this rapid aging mouse. Conclusions: BZBS attenuates premature senescence possibly via the preservation of redox homeostasis and telomere integrity, and inhibition of apoptosis in rapid aging mouse. The mechanism governing the alterations may be associated with through the activation of Sirt6/NRF2/HO-1 and Sirt6/P53-PGC-1 alpha-TERT signaling pathways. The results suggest that BZBS may provide a novel strategy for confronting aging and age-associated diseases.

Jiangtang Sanhao formula (JTSHF), one of the prescriptions for treating the patients with diabetes mellitus (DM) in traditional Chinese medicine clinic, has been demonstrated to effectively ameliorate the clinical symptoms of diabetic patients with overweight or hyperlipidemia. The preliminary studies demonstrated that JTSHF may enhance insulin sensitivity and improve glycolipid metabolism in obese mice. However, the action mechanism of JTSHF on skeletal muscles in diabetic mice remains unclear. To this end, high-fat diet (HFD) and streptozotocin (STZ)-induced diabetic mice were subjected to JTSHF intervention. The results revealed that JTSHF granules could reduce food and water intake, decrease body fat mass, and improve glucose tolerance, lipid metabolism, and insulin sensitivity in the skeletal muscles of diabetic mice. These effects may be linked to the stimulation of GLUT4 expression and translocation via regulating AMPKα/SIRT1/PGC-1α signaling pathway. The results may offer a novel explanation of JTSHF to prevent against diabetes and IR-related metabolic diseases.

思维导图作为一种思维工具,模拟大脑功能,有利于促进学习,因此被引入教育教学领域,成为众多国家教育改革的策略之一.目前,思维导图已被引入中医学课程教育教学改革之中."中医学基础"是中医学必修课程,在实际教学活动中应用思维导图建构"中医学基础"知识体系,符合该课程特色及人才培养目标,也有利于提高教学质量,激发学生的学习热情,有助于学生理解中医理论,也能为其以后学习其他医学知识奠定基础.

The Jiang Tang Xiao Ke (JTXK) granule is a classic Chinese herbal formula that has been put into clinical use in the treatment of type 2 diabetes mellitus for decades. However, whether its ability to ameliorate skeletal muscle insulin resistance (IR) is through modulation of the AMPK/SIRT1/PGC-1α signaling pathway remains unknown. Therefore, we aimed to investigate the effects of JTXK granules on IR in skeletal muscle of high-fat diet-induced diabetic mice and C2C12 cells and analyze the underlying mechanisms. In the present study, we showed that JTXK granules attenuated body weight gain, reduced body fat mass, improved body lean mass, and enhanced muscle performance of diabetic mice. JTXK granules also improved glucose metabolism and skeletal muscle insulin sensitivity and partially reversed abnormal serum lipid levels, which might be related to the regulation of the AMPK/SIRT1/PGC-1α pathway, both in skeletal muscle tissue of diabetic mice and in C2C12 cells. Furthermore, drug-containing serum of JTXK granules was capable of enhancing glucose uptake and mitochondrial respiration in C2C12 cells, and AMPKα was proven to be closely involved in this process. Taken together, these results suggest that the JTXK granule ameliorates skeletal muscle IR through activation of the AMPK/SIRT1/PGC-1α signaling pathway, which offers a novel perspective of this formula to combat IR-related metabolic diseases.

ETHNOPHARMACOLOGICAL RELEVANCE:Sperm infertility and testicular atrophy are symptoms associated with aging. BaZiBuShen formula (BZBS), a patented Chinese herbal prescription composed of Semen Cuscutae, Fructus Lycii, Epimedii Folium, Fructus Schisandrae Sphenantherae, Fructus Cnidii, Fructus Rosae Laevigatae, Semen Allii Tuberosi., Radix Morindae Officinalis, Herba Cistanches, Fructus Rubi, Radix Rehmanniae Recens, Radix Cyathulae, Radix Ginseng, Cervi Cornu Pantotrichum, Hippocampus, and Fuctus Toosendan, has been used as a kidney-tonifying and anti-aging drug as well as for the treatment of impotence and male infertility in traditional Chinese medicine. AIM OF THE STUDY:We aimed at investigating whether BZBS preserves sperm and testes morphology in aging mice, and to explore the underlying mechanisms. MATERIALS AND METHODS:BZBS was orally administered to aging mice induced by D-galactose (D-gal) and NaNO2 for 65 days. Sperm quality and testes pathophysiological alterations were examined by a Semen Analysis System, hematoxylin-eosin staining, transmission electron microscopy, and mitochondrial complex IV activity. In addition, serum levels of total antioxidant capacity (TAC), malondialdehyde (MDA), 8-hydroxy-desoxyguanosine (8-OH-dG), reduced glutathione (GSH), oxidized glutathione disulfide (GSSG), testosterone (T), follicle stimulating hormone (FSH), luteinizing hormone (LH), estradiol (E2) and tumor necrosis factor-α (TNF-α) were determined by ELISA. The expressions of P450 aromatase (CYP19), sirtuin 6 (Sirt6), P53, inducible nitric oxide synthase (iNOS), nuclear factor-kappa B (NF-κB)-p65, and phospho-NF-κB-p65 (NF-κB-pp65) in the testes were examined by western blot and/or immunohistochemical staining. RESULTS:Sustained exposure to D-gal/NaNO2 caused a deterioration of sperm quality and testes morphology in this rapid aging mouse model. BZBS treatment curtailed these alterations. These beneficial effects were associated with increased serum levels of TAC, GSH/GSSG, T, E2, and FSH, and decreased levels of MDA, TNF-α, and 8-OH-dG. BZBS treatment also downregulated the expressions of P53, iNOS, and NF-κB-pp65, as well as upregulated the expressions of Sirt6 and CYP19 in aging testes. CONCLUSIONS:BZBS preserves testicular morphology and spermatogenesis possibly via inhibition of oxidative stress and the modulation of the Sirt6/P53 and Sirt6/NF-κB signaling pathways. The results shed light on the beneficial effect of BZBS on sperm quality and fertility in aging males.

Accumulating evidence suggests that mitochondrial dysfunction and adipocyte differentiation promote lipid accumulation in the development of obesity and diabetes. Curcumin is an active ingredient extracted from Curcuma longa that has been shown to exhibit antioxidant and anti-inflammatory potency in metabolic disorders. However, the underlying mechanisms of curcumin in adipocytes remain largely unexplored. We studied the effects of curcumin on adipogenic differentiation and mitochondrial oxygen consumption and analysed the possible mechanisms. 3T3-L1 preadipocytes were used to assess the effect of curcumin on differentiation of adipocytes. The Mito Stress Test measured by Seahorse XF Analyzer was applied to investigate the effect of curcumin on mitochondrial oxygen consumption in 3T3-L1 adipocytes. The effect of curcumin on the morphology of both white and brown adipose tissue (WAT and BAT) was evaluated in a high-fat diet-induced obese mice model. We found that curcumin dose-dependently (10, 20 and 35 µM) induced adipogenic differentiation and the intracellular fat droplet accumulation. Additionally, 10 µM curcumin remarkably enhanced mature adipocyte mitochondrial respiratory function, specifically, accelerating basic mitochondrial respiration, ATP production and uncoupling capacity via the regulation of peroxisome proliferator-activated receptor γ (PPARγ) ( p < 0.01). Curcumin administration also attenuated the morphological changes in adipose tissues in high-fat diet-induced obese mice. Moreover, curcumin markedly increased the mRNA and protein expressions of mitochondrial uncoupling protein 1 (UCP1), PPARγ, peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α) and PR domain protein 16 (PRDM16) in vivo and in vitro . Collectively, the results demonstrate that curcumin promotes the adipogenic differentiation of preadipocytes and mitochondrial oxygen consumption in 3T3-L1 mature adipocytes by regulating UCP1, PRDM16, PPARγ and PGC-1α expression.

胰岛素抵抗(Insulin Resistance,IR)是2型糖尿病的重要病理特征,其发病机制复杂,包括肥胖、遗传等因素引起的多种激素水平紊乱,慢性轻度炎症反应,氧化应激和能量代谢障碍导致线粒体功能受损等,基本可分为受体前、受体和受体后3个环节.中药复方、中成药、单味中药或其有效成分、针灸等疗法都能在一定程度上改善IR,从细胞、分子水平展开的相关研究也越来越细致、深入.