Wnt1-inducible signaling protein 1 regulates laryngeal squamous cell carcinoma glycolysis and chemoresistance via the YAP1/TEAD1/GLUT1 pathway

Wnt1-inducible signaling protein 1 (WISP1) is a matricellular protein and downstream target of Wnt/β-catenin signaling. This study sought to determine the role of WISP1 in glucose metabolism and chemoresistance in laryngeal squamous cell carcinoma. WISP1 expression was silenced or upregulated in Hep-2 cells by the transfection of WISP1 siRNA or AdWISP1 vector. Ectopic WISP1 expression regulated glucose uptake and lactate production in Hep-2 cells. Subsequently, the expression of glucose transporter 1 (GLUT1) was significantly modulated by WISP1. Furthermore, WISP1 increased cell survival rates, diminished cell death rates, and suppressed ataxia-telangiectasia-mutated (ATM)-mediated DNA damage response pathway in cancer cells treated with cisplatin through GLUT1. WISP1 also promoted cancer cell tumorigenicity and growth in mice implanted with Hep-2 cells. Additionally, WISP1 activated the YAP1/TEAD1 pathway that consequently contributed to the regulation of GLUT1 expression. In summary, WISP1 regulated glucose metabolism and cisplatin resistance in laryngeal cancer by regulating GLUT1 expression. WISP1 may be used as a potential therapeutic target for laryngeal cancer.     

Phosphoinositide-dependent kinase 1–associated glycolysis is regulated by miR-409-3p in clear cell renal cell carcinoma

Clear cell renal cell carcinoma (ccRCC) is the most popular kidney cancer in adults. Metabolic shift toward aerobic glycolysis is a fundamental factor for ccRCC therapy. MicroRNAs (miRNAs) are thought to be important regulators in ccRCC development and progression. Phosphoinositide-dependent kinase 1 (PDK1) is required for metabolic activation; however, the role of PDK1-induced glycolytic metabolism regulated by miRNAs is unclear in ccRCC. So, the purpose of the current study is to elucidate the underlying mechanism in ccRCC cell metabolism mediated by PDK1. Our results revealed that miR-409-3p inhibited glycolysis by regulating PDK1 expression in ccRCC cells. We also found that miR-409-3p was regulated by hypoxia. Our results indicated that PDK1 facilitated ccRCC cell glycolysis, regulated by miR-409-3p in hypoxia.     

不同强度有氧跑有助于改善IGR老年人的症状

为了探讨不同强度持续跑步干预对糖调节受损(impaired glucose regulation,IGR)人群胰岛素敏感性、骨密度、糖调节、激素分泌的影响效果差异,为研发促进IGR人群糖调节能力恢复的运动处方提供实证参考,本研究选定90名糖调节受损老年人为本研究实验对象,进行随机分组,随机分为Fatmax强度跑步组(F组,n=30);AT强度跑步组(A组,n=30);对照组(C组,n=30)。在干预开始前1周内对受试者进行前测(BMD,骨代谢,FPG,OGTT-2h,HOMA-IR,IGF-1,生长激素分泌指标)。干预前3天,F组进行FATMAX强度测试、A组进行AT强度测试,各组按照运动计划进行为期24周的干预,运动干预结束后测。通过24周干预,F组和A组受试者的BMI、体脂率后测结果显著低于前测结果(p<0.05),而C组BMI和体脂率前后测结果对比没有显著性差异(p>0.05);F组、A组的FPG和OGTT-2h后测结果显著低于前测,且显著低于C组后测结果(p<0.05);F组和A组受试者的血清GH、IGF-1以及BGP的后测结果明显高于其前测结果和C组后测结果(p<0.05),而C组GH、IGF-1和BGP前后测结果对比没有显著性差异(p>0.05)。F组和A组受试者股骨颈BMD、大转子骨BMD、Ward’s三角区BMD后测结果显著高于前测结果和C组后测结果(p<0.05)。IGR老年人长期进行以Fatmax和AT强度进行长时间有氧跑步,不仅能够增加其下肢骨密度、促进骨生产和改善骨代谢,而且降低FPG、缓解胰岛素抵抗、促进GH、IGF-1分泌。其机制可能是IGR老年人长期进行中低强度有氧跑会提升血清GH、IGF-1浓度,而GH和IGF-1能够促进胰岛素的分泌合成以及促进成骨细胞工作,从而缓解IGR老年人的胰岛素抵抗和增加下肢BMD。     

哺乳期需氧菌性阴道炎患者定期补充乳杆菌的疗效

目的分析在有效抗炎基础上定期补充乳杆菌活菌胶囊对哺乳期需氧菌性阴道炎患者的疗效及对远期复发率的影响。方法选择2019年4月至2020年3月于大连市妇女儿童医疗中心(集团)行产后42 d检查时发现的需氧菌性阴道炎患者共120例,按照随机自愿原则将所选患者分为观察组及对照组,各60例。全部患者均使用红核妇洁洗液及克林霉素磷酸酯阴道凝胶抗炎治疗7 d,观察组患者于第8天开始给予阴道用乳杆菌活菌胶囊每日睡前上药1粒,治疗10 d,停药后1周对两组患者进行临床疗效评估并了解不良反应发生情况。于首次治疗结束后第3个月及第6个月进行定期随诊,了解两组患者阴道炎的复发情况。且观察组患者于治疗后第3个月随诊结束后再次给予阴道用乳杆菌活菌胶囊补充上药1疗程。记录并比较两组患者治疗前、治疗后1周、治疗后第3个月及第6个月阴道pH值及H₂O₂情况。结果两组患者治疗期间均未发生明显不良反应。治疗后1周观察组患者治愈率(66.7%)显著高于对照组(36.7%),差异有统计学意义(P<0.05);观察组总有效率(95.0%)与对照组(86.7%)比较差异无统计学意义(P>0.05)。观察组治疗后第3个月复发率(5.0%)及第6个月复发率(11.7%)均明显低于同时段对照组(30.0%,56.7%),差异均有统计学意义(均P<0.05)。治疗后1周观察组患者阴道pH值正常率(95.0%)与对照组(86.7%)比较,差异无统计学意义(P>0.05),但观察组H₂O₂正常率(91.7%)明显高于对照组(63.3%),差异有统计学意义(P<0.05)。治疗后第3个月及第6个月观察组患者阴道pH值正常率(90.0%,85.0%)及H₂O₂正常率(86.7%,81.7%)均明显高于同时段对照组(53.3%、28.3%;45.0%、21.7%),差异均有统计学意义(均P<0.05)。结论在有效抗炎治疗基础上定期给予阴道用乳杆菌活菌胶囊补充治疗,能明显提高哺乳期需氧菌性阴道炎患者的治愈率,改善阴道pH值及H₂O₂情况,从而促进阴道微生态平衡,降低其复发率,值得临床应用。     

Glucose—a sweet way to die

TRAIL, a putative anticancer cytokine, induces extrinsic cell death by activating the caspase cascade directly (Type I cells) via the death-inducing signaling complex (DISC) or indirectly (Type II cells) by caspase-8 cleavage of Bid and activation of the mitochondrial cell death pathway. Cancer cells are characterized by their dependence on aerobic glycolysis, which, although inefficient in terms of ATP production, facilitates tumor metabolism. Our studies show that TRAIL-induced cell death is significantly affected by the metabolic status of the cell. Inhibiting glycolysis with 2-deoxyglucose potentiates TRAIL-induced cell death, whereas glucose deprivation can paradoxically inhibit apoptosis. These conflicting responses to glycolysis inhibition are modulated by the balance between the Akt and AMPK pathways and their subsequent downstream regulation of mTORC1. This results in marked changes in protein translation, in which the equilibrium between anti- and pro-apoptotic Bcl-2 family member proteins is decided by their individual degradation rates. This regulates the mitochondrial cell death pathway and alters its sensitivity not only to TRAIL, but to ABT-737, a Bcl-2 inhibitor. Taken together, our studies show that the sensitivity of cancer cells to apoptosis can be modulated by targeting their unique metabolism in order to enhance sensitivity to apoptotic agents.     

瓦氏效应——哺乳动物生殖过程中的有氧糖酵解

糖代谢是生物体赖以生存的基本生化过程之一.哺乳动物体内不同细胞对葡萄糖的利用方式不同.摄氧充足时,细胞通过氧化磷酸化在线粒体中进行有氧呼吸;缺氧的细胞则选择抑制氧化磷酸化,通过糖酵解产生乳酸.但有些细胞在有氧条件下也能进行糖酵解,从而产生大量的乳酸,这种糖酵解途径称为瓦氏效应.以前认为瓦氏效应主要存在于肿瘤细胞中,但近来发现在哺乳动物的生殖过程中也存在瓦氏效应.本文综述了哺乳动物生殖发育过程的瓦氏效应及其与一些生殖疾病的关系.     

Two-way communication between the metabolic and cell cycle machineries: the molecular basis

The relationship between cellular metabolism and the cell cycle machinery is by no means unidirectional. The ability of a cell to enter the cell cycle critically depends on the availability of metabolites. Conversely, the cell cycle machinery commits to regulating metabolic networks in order to support cell survival and proliferation. In this review, we will give an account of how the cell cycle machinery and metabolism are interconnected. Acquiring information on how communication takes place among metabolic signaling networks and the cell cycle controllers is crucial to increase our understanding of the deregulation thereof in disease, including cancer.     

Relationship of aerobic and anaerobic parameters with 400 m front crawl swimming performance

The aims of the present study were to investigate the relationship of aerobic and anaerobic parameters with 400 m performance, and establish which variable better explains long distance performance in swimming. Twenty-two swimmers (19.1±1.5 years, height 173.9±10.0 cm, body mass 71.2±10.2 kg; 76.6±5.3% of 400 m world record) underwent a lactate minimum test to determine lactate minimum speed (LMS) (i.e., aerobic capacity index). Moreover, the swimmers performed a 400 m maximal effort to determine mean speed (S400m), peak oxygen uptake (V.O2PEAK) and total anaerobic contribution (C_ANA). The C_ANA was assumed as the sum of alactic and lactic contributions. Physiological parameters of 400 m were determined using the backward extrapolation technique (V.O2PEAK and alactic contributions of C_ANA) and blood lactate concentration analysis (lactic anaerobic contributions of C_ANA). The Pearson correlation test and backward multiple regression analysis were used to verify the possible correlations between the physiological indices (predictor factors) and S400m (independent variable) (p < 0.05). Values are presented as mean ± standard deviation. Significant correlations were observed between S400m (1.4±0.1 m·s^-1) and LMS (1.3±0.1 m·s^-1; r = 0.80), V.O2PEAK (4.5±3.9 L·min^-1; r = 0.72) and C_ANA (4.7±1.5 L·O₂; r= 0.44). The best model constructed using multiple regression analysis demonstrated that LMS and V.O2PEAK explained 85% of the 400 m performance variance. When backward multiple regression analysis was performed, C_ANA lost significance. Thus, the results demonstrated that both aerobic parameters (capacity and power) can be used to predict 400 m swimming performance.