"高住低练"模拟高原训练对划船运动员血清CK、LDH和ALT活性的影响

目的:探讨"高住低练"(运动员睡在相当于2 500 m的高度,训练则在平原)过程中,低氧及运动时划船运动员血清酶的变化规律.方法:20名划船运动员随机分为高住低练组和低住低练组,每组10名.分别测定运动员在安静状态下及耐力负荷后血清肌酸激酶(CK)、乳酸脱氢酶(LDH)和谷丙转氨酶(ALT)的活性.结果:发现在高住低练的初期,高住低练组运动员血清CK、LDH活性明显高于对照组,而高住低练4周后,血清酶活性则明显低于对照组,并可连续到高住低练后2周;通过4周高住低练后,高住低练组运动员在耐力测试后即刻及恢复期血清CK、LDH活性均明显低于对照组.结论:提示运动员在2 500m高度进行4周高住低练,机体对缺氧负荷和运动负荷的适应后,能降低由于运动引起的血清酶活性的升高,对防止肌肉组织的损伤和增加细胞膜的稳定性有一定的作用.     

不同低氧训练模式对大鼠力竭运动后骨骼肌线粒体抗氧化能力及呼吸链酶复合体活性的影响

本研究旨在观察4种低氧训练模式对大鼠骨骼肌线粒体抗氧化能力及呼吸链酶复合体活性的影响。将雄性Wistar大鼠40只随机均分为5组(n=8):常氧训练组(LoLo)、高住高练组(HiHi)、高住低训组(HiLo)、低住高练组(LoHi)和高住高练低训组(HiHiLo)。各组大鼠分别在常氧(海拔1500m,大气压632mmHg)或/和低氧(模拟海拔3500m,大气压493mmHg)环境中居住及递增负荷训练5周,每周训练6天。各组大鼠在最后一次训练后,在常氧环境恢复3天,然后进行力竭运动,之后即刻取骨骼肌样本,用差速离心法提取骨骼肌线粒体,分光光度法测定丙二醛(malondialdehyde,MDA)含量及超氧化物歧化酶(su-peroxide dismutase,SOD)、谷胱甘肽过氧化物酶(glutathione peroxidase,GSH-Px)和过氧化氢酶(catalase,CAT)活性及呼吸链酶复合体Ⅰ～Ⅲ(CⅠ～Ⅲ)活性。结果显示,与LoLo组相比,HiHi和HiHiLo组骨骼肌组织MDA含量均显著升高(P<0.01),SOD、GSH-Px和CAT活性均显著升高(P<0.05或P<0.01)。与LoL...     

低氧对少突胶质前体细胞增殖的影响

目的：观察低氧／复氧和间歇性低氧时少突胶质前体细胞（O2A）增殖的影响。方法：取混合培养4d的胶质细胞。按实验分为低氧／复氧、间歇性低氧和常氧3组,低氧／复氧组细胞置低氧环境（3％O2）中分别培养1h、2h、3h、4h、8h、12h、24h、48h和72h后取出,恢复常氧培养至9d。间歇性低氧组每天上午定时将细胞置于低氧环境中分别培养1h、2h、3h、4h后取出。恢复常氧培养。每天一次,分别重复1～4次后。常氧培养至9d。然后同时取出各组细胞,进行O2A细胞的分离纯化和细胞计数。结果：低氧／复氧1h、2h、3h组和间歇性低氧1h、2h、3h组,O2A细胞数均较常氧组明显增多。结论：低氧／复氧和间歇性低氧都可促进体外培养的O2A细胞明显增殖。其机制尚有待于进一步研究。     

基于RNA测序分析不同低氧暴露模式对大鼠胫骨前肌差异基因表达的影响

目的 筛选慢性间歇低氧暴露和急性低氧暴露对大鼠胫骨前肌差异表达基因及其相关通路分析.方法 SD大鼠24只,分为常氧对照组(C组)、慢性间歇低氧组(IH组,氧浓度为12.4％,每天8 h,共4周)和急性低氧组(AH组,氧浓度为12.4％,每天24 h,共3 d).干预后,测试抓力和瘦体重,取胫骨前肌(TA)进行HE染色后...     

慢性间歇性低氧降低急性缺氧对大鼠肺动脉平滑肌细胞膜上电压门控性钾通道的抑制

为了从离子通道水平上探讨机体低氧适应的离子机制,本实验将雄性 SD 大鼠随机分为常氧对照组和慢性间歇性低氧组[氧浓度(10 ± 0.5) %, 间断缺氧每天 8 h]。用酶解法急性分离单个大鼠肺内动脉平滑肌细胞(pulmonary artery smoothmuscle cells, PASMCs),以全细胞膜片钳技术记录 PASMCs 膜上的电压门控性钾通道 (voltage-gated potassium channel, KV) 电流,观察急性缺氧对慢性间歇性低氧大鼠 PASMCs 的 KV 的影响, 为机体适应低氧能力提供实验依据。结果显示:⑴常氧对照组在电流钳下,急性缺氧可使膜电位明显去极化(由-47.2 ±2.6 mV 去极到 -26.7 ±1.2 mV ); 在电压钳下, 急性缺氧可显著抑制 KV电流( 60 mV 时, KV电流密度从 153.4 ± 9.5 pA/pF降到 70.1 ± 10.6 pA/pF), 峰电流的抑制率为(57.6 ± 3.3) %, 电流-电压关系曲线向右下移。⑵慢性间歇性低氧组KV电流密度随低氧时间延长而逐渐减少(慢性低氧10 d后就有显著性意义),电流- 电压关系曲线逐渐右下移。⑶急性缺氧对慢性间歇性低氧大鼠PASMCs KV电流的抑制作用随慢性间歇性低氧时间延长而逐渐减弱。上述观察结果提示慢性间歇性低氧减弱急性缺氧对 KV 的抑制, 这可能是机体低氧适应的一种重要机制。     

低氧中强度训练可通过上调HIF-1α来提高机体抗氧化能力

低氧环境和运动训练均可导致人体体重降低,然而,低氧结合中强度训练对肥胖人群能量代谢及氧化应激的影响尚不清楚。本研究招募了60名无系统运动训练史的健康男性大学生,将受试者分为低氧组和常氧组,每组30名。在一个110 m^2的训练室内通过低氧训练系统模拟人工低氧环境(海拔高度:2 500 m,氧浓度:15%)。两组受试者进行1个月的低氧/常氧中强度骑行训练。此外,对低氧和常氧中强度训练的大鼠进行力竭跑台运动测试,苏木精和伊红(HE)染色评价大鼠骨骼肌形态学变化,RT-PCR检测低氧诱导因子1α(HIF-1α) mRNA的表达。研究显示,运动后低氧组的体重、脂肪重量和BMI均显著低于常氧组(p<0.05)。运动后低氧组的血清TC、HDL-C和LDL-C含量均显著低于常氧组(p<0.05),而总TG含量与常氧组无显著差异(p>0.05)。运动后,低氧组的游离脂肪酸含量显著高于常氧组(p<0.05),两组血糖无显著差异(p>0.05)。运动后,低氧组的SOD和GSH-PX水平显著高于常氧组(p<0.05),而MDA水平显著低于常氧组(p<0.05)。运动后,低氧组的IL-1β、IL-6和TNF-α水平显著低于常氧组(p<0.05)。力竭运动后,低氧组大鼠的骨骼肌形态学改变异常情况明显低于常氧组。低氧组的HIF-1αm RNA水平显著高于常氧组。本研究表明,与常氧相比,低氧中强度训练可有效降低肥胖人群的血脂水平,促进脂肪动员,减弱氧化应激损伤,抑制促炎细胞因子表达,从而促进体重减轻,并防止糖尿病、高血脂等肥胖相关疾病的发生。此外,低氧中强度可通过上调HIF-1α来提高机体抗氧化能力并减弱运动损伤。     

低氧对胚胎干细胞增殖的影响

目的:观察间歇性低氧和持续性低氧对体外培养的胚胎干细胞(ES细胞)增殖的影响.方法:利用细胞记数法和BrdU (5-溴脱氧尿苷)掺入的流式细胞分析检测细胞增殖,并用RT -PCR的方法检测低氧诱导因子(HIF-1a)的表达变化.结果:①将ES细胞分别放在低氧(3%～10% O2)和常氧(20% O2)的环境中培养24 h后,在低氧环境中培养的ES细胞数较常氧组明显减少;②将ES细胞分别给予间歇性低氧刺激(3%～10% O2),每天10 min,连续4 d后,发现3%低氧组较常氧对照组的细胞增殖明显升高.③用RT-PCR方法观察HIF-1a的表达与细胞增殖的关系,发现在常氧环境中培养的ES即有HIF-1a的表达,ES细胞在持续低氧24 h或间歇性低氧(3%～10% O2)刺激4 d后对HIF-1a的表达均无明显影响.结论:间歇性低氧(3% O2)可明显促进体外培养的ES细胞增殖,而持续性低氧抑制ES细胞增殖,间歇性低氧(3% O2)刺激促进ES细胞增殖的机制尚有待于进一步的研究.     

低氧影响蛋白质合成和分解的平衡诱导骨骼肌萎缩

暴露在低氧环境下,可能会引起胃肠功能障碍和摄食量下降,打破骨骼肌蛋白质合成和分解平衡,造成骨骼肌萎缩。为探讨低氧环境下骨骼肌的萎缩是低氧环境引起的还是低氧诱发的摄食量减少所致,本研究检测大鼠腓肠肌中低氧时蛋白质合成与分解相关基因的蛋白质表达。将21只雄性SD大鼠,随机分为3组：常氧对照组、低氧组（氧浓度为12.4%,模拟海拔4 000 m高度）和配对组（大鼠的摄食量与低氧组前1 d的摄食量相同）,每组7只,每天记录大鼠体重和摄食量。4周后,HE染色法观察腓肠肌肌纤维形态,Western印迹测试相关蛋白质水平。低氧组和配对组摄食量在低氧干预初期,较常氧对照组有显著性下降(P<0.05),干预后期差异不明显;干预期间,低氧组大鼠体重平均增加量(102.10 g)、体重(341.20 ± 16.75 g)、肌肉总量（226.83 ± 8.33 g）和腓肠肌肌纤维横截面积(12.67 ± 1.83 mm)较常氧对照组（128.00 g;377.50 ± 20.75 g;260.50 ± 9.35 g;15.78 ± 2.38 mm）和配对组（119.40 g;375.86 ± 11.30 g;262.29 ± 7.90 g;15.71 ± 2.82 mm）均显著下降,配对组较常氧对照组无显著性差异;4周干预后,与常氧对照组相比,低氧组大鼠腓肠肌中与低氧相关的HIF1α显著增加(1.42 ± 0.19, P<0.05),Akt和p-Akt/Akt显著降低 (1.44 ± 0.13; 0.47 ± 0.08, P<0.05),配对组上述3种指标相对表达量均无显著性差异;在蛋白质合成方面,低氧组mTOR较常氧对照组显著下降(0.63 ± 0.18, P<0.05),配对组较常氧对照组差异不明显;低氧组腓肠肌中,4EBP1(1.14 ± 0.14)和p70S6K1(1.14 ± 0.11)较配对组显著下降(P<0.05)。在蛋白质分解方面,低氧组p-FoxO1和p-FoxO1/FoxO1比值较常氧对照组显著下降(0.71 ± 0.15; 0.78 ± 0.14, P<0.05);低氧组大鼠腓肠肌中,Atrogin1、MuRF1、Beclin1、LC3Ⅰ及LC3Ⅱ/Ⅰ比值均高于常氧对照组(1.35 ± 0.12; 1.30 ± 0.22; 1.17 ± 0.11; 1.03 ± 0.11; 1.35 ± 0.13, P<0.05);配对组与常氧对照组间无明显差异。低氧环境下骨骼肌中蛋白质合成相关基因表达减少,蛋白质分解相关基因表达增加,造成骨骼肌萎缩,体重下降,此变化与摄食量减少无关。     

低氧影响蛋白质合成和分解的平衡诱导骨骼肌萎缩

暴露在低氧环境下,可能会引起胃肠功能障碍和摄食量下降,打破骨骼肌蛋白质合成和分解平衡,造成骨骼肌萎缩。为探讨低氧环境下骨骼肌的萎缩是低氧环境引起的还是低氧诱发的摄食量减少所致,本研究检测大鼠腓肠肌中低氧时蛋白质合成与分解相关基因的蛋白质表达。将21只雄性SD大鼠,随机分为3组：常氧对照组、低氧组（氧浓度为12.4%,模拟海拔4 000 m高度）和配对组（大鼠的摄食量与低氧组前1 d的摄食量相同）,每组7只,每天记录大鼠体重和摄食量。4周后,HE染色法观察腓肠肌肌纤维形态,Western印迹测试相关蛋白质水平。低氧组和配对组摄食量在低氧干预初期,较常氧对照组有显著性下降(P<0.05),干预后期差异不明显;干预期间,低氧组大鼠体重平均增加量(102.10 g)、体重(341.20 ± 16.75 g)、肌肉总量（226.83 ± 8.33 g）和腓肠肌肌纤维横截面积(12.67 ± 1.83 mm)较常氧对照组（128.00 g;377.50 ± 20.75 g;260.50 ± 9.35 g;15.78 ± 2.38 mm）和配对组（119.40 g;375.86 ± 11.30 g;262.29 ± 7.90 g;15.71 ± 2.82 mm）均显著下降,配对组较常氧对照组无显著性差异;4周干预后,与常氧对照组相比,低氧组大鼠腓肠肌中与低氧相关的HIF1α显著增加(1.42 ± 0.19, P<0.05),Akt和p-Akt/Akt显著降低 (1.44 ± 0.13; 0.47 ± 0.08, P<0.05),配对组上述3种指标相对表达量均无显著性差异;在蛋白质合成方面,低氧组mTOR较常氧对照组显著下降(0.63 ± 0.18, P<0.05),配对组较常氧对照组差异不明显;低氧组腓肠肌中,4EBP1(1.14 ± 0.14)和p70S6K1(1.14 ± 0.11)较配对组显著下降(P<0.05)。在蛋白质分解方面,低氧组p-FoxO1和p-FoxO1/FoxO1比值较常氧对照组显著下降(0.71 ± 0.15; 0.78 ± 0.14, P<0.05);低氧组大鼠腓肠肌中,Atrogin1、MuRF1、Beclin1、LC3Ⅰ及LC3Ⅱ/Ⅰ比值均高于常氧对照组(1.35 ± 0.12; 1.30 ± 0.22; 1.17 ± 0.11; 1.03 ± 0.11; 1.35 ± 0.13, P<0.05);配对组与常氧对照组间无明显差异。低氧环境下骨骼肌中蛋白质合成相关基因表达减少,蛋白质分解相关基因表达增加,造成骨骼肌萎缩,体重下降,此变化与摄食量减少无关。     

模拟高原环境下高原肺水肿大鼠模型的建立

目的在人工实验舱模拟高原环境下,探讨建立高原肺水肿大鼠模型的条件。方法 Wistar大鼠,雌雄各半,随机分为5组:空白对照组、低氧24 h组、低氧48 h组、低氧72 h组、低氧7 d组,测定大鼠肺组织含水量,肺组织中TNF-α、IL-6含量及病理改变。结果与正常对照组相比,低氧24、48、72 h组大鼠肺组织含水量依次为(81.58±0.86)%、(82.13±0.57)%、(82.21±0.88)%,高于正常对照组(78.72±0.52)%,肺组织中IL-6依次为(329.30±133.58)、(323.92±127.42)、(506.29±197.19)pg/mL,TNF-α依次(221.08±20.26)、(208.05±20.33)、(244.63±51.53)pg/mL,高于正常对照组IL-6(187.26±69.49)pg/mL,TNF-α为(91.81±22.24)pg/mL。低氧7d组肺组织含水量(81.47±0.65)%、肺组织中IL-6(241.33±83.60)pg/mL、TNF-α(109.99±31.98)pg/mL,均显著低于低氧72h组,病理学结果显示72h组肺组织有炎性细胞浸润,肺泡壁有明显的充血和水肿。结论模拟海拔5000 m环境,建立大鼠肺水肿模型的较好的时间为72 h。     

Recent advances in the study of Kaposi's sarcoma-associated herpesvirus replication and pathogenesis

It has now been over twenty years since a novel herpesviral genome was identified in Kaposi's sarcoma biopsies. Since then, the cumulative research effort by molecular biologists, virologists, clinicians, and epidemiologists alike has led to the extensive characterization of this tumor virus, Kaposi's sarcoma-associated herpesvirus(KSHV; also known as human herpesvirus 8(HHV-8)), and its associated diseases. Here we review the current knowledge of KSHV biology and pathogenesis, with a particular emphasis on new and exciting advances in the field of epigenetics. We also discuss the development and practicality of various cell culture and animal model systems to study KSHV replication and pathogenesis.     

A Unique Protease Cleavage Site Predicted in the Spike Protein of the Novel Pneumonia Coronavirus (2019-nCoV) Potentially Related to Viral Transmissibility

正Dear Editor,In December 2019, a novel human coronavirus caused an epidemic of severe pneumonia(Coronavirus Disease 2019,COVID-19) in Wuhan, Hubei, China(Wu et al. 2020; Zhu et al. 2020). So far, this virus has spread to all areas of China and even to other countries. The epidemic has caused 67,102 confirmed infections with 1526 fatal cases     

Curcuminoids as inhibitors of thioredoxin reductase: A receptor based pharmacophore study with distance mapping of the active site

Curcumin is the yellow pigment of turmeric that interacts irreversibly forming an adduct with thioredoxin reductase (TrxR), an enzyme responsible for redox control of cell and defence against oxidative stress. Docking at both the active sites of TrxR was performed to compare the potency of three naturally occurring curcuminoids, namely curcumin, demethoxy curcumin and bis-demethoxy curcumin. Results show that active sites of TrxR occur at the junction of E and F chains. Volume and area of both cavities is predicted. It has been concluded by distance mapping of the most active conformations that Se atom of catalytic residue SeCYS498, is at a distance of 3.56 from C13 of demethoxy curcumin at the E chain active site, whereas C13 carbon atom forms adduct with Se atom of SeCys 498. We report that at least one methoxy group in curcuminoids is necessary for interation with catalytic residues of thioredoxin. Pharmacophore of both active sites of the TrxR receptor for curcumin and demethoxy curcumin molecules has been drawn and proposed for design and synthesis of most probable potent antiproliferative synthetic drugs.     

Synthesis and antimicrobial studies of hydrazone derivatives of 4-[3-(2,4-difluorophenyl)-4-formyl-1H-pyrazol-1-yl]benzoic acid and 4-[3-(3,4-difluorophenyl)-4-formyl-1H-pyrazol-1-yl]benzoic acid

Microbial resistance to antibiotics is an unresolved global concern, which needs urgent and coordinated action. One of the guidelines of the Centers for Disease Control and Preventions (CDC) to combat antibiotic resistance is the development of new antibiotics to treat drug-resistant bacteria. In our effort to find new antibiotics, we report the synthesis and antimicrobial studies of 30 new pyrazole derivatives. These novel molecules have been synthesized by using readily available starting materials and benign reaction conditions. Some of these molecules have shown activity with MIC values as low as 0.78?µg/mL against four bacterial strains; Staphylococcus aureus, methicillin-resistant S. aureus, Bacillus subtilis, and Acinetobacter baumannii. Furthermore, active molecules are non-toxic to mammalian cell line.

     

Comparative morphology of the carpel in the Liliaceae: Hewardieae, Petrosavieae, and Tricyrteae

The young pistils in the melanthioid tribes, Hewardieae, Petrosavieae and Tricyrteae, are uniformly tricarpellate and syncarpous. They lack raphide idioblasts. All are multiovulate, with bitegmic ovules. The Petrosavieae are marked by the presence of septal glands and incomplete syncarpy. Tepals and stamens adhere to the ovary in the Hewardieae and the Petrosavieae but not in the Tricyrteae. Two vascular bundles occur in the stamens of the Hewartlieae and Tricyrtis latifolia. Ventral bundles in the upper part of the ovary of the Hewardieae are continuous with compound septal bundles and placental bundles in the lower part. Putative ventral bundles occur in the alternate position in the Tricyrteae and putative placental bundles in the opposite. position in the Petrosavieae. The dichtomously branched stigma in each carpel of the Tricyrteae is supplied by a bifurcated dorsal bundle.     

Novel compounds with potent CDK9 inhibitory activity for the treatment of myeloma

Cyclin-dependent kinases (CDKs) and Polo-like kinases (PLKs) play key role in the regulation of the cell cycle. The aim of our study was originally the further development of our recently discovered polo-like kinase 1 (PLK1) inhibitors. A series of new 2,4-disubstituted pyrimidine derivatives were synthesized around the original hit, but their PLK1 inhibitory activity was very poor. However the novel compounds showed nanomolar CDK9 inhibitory activity and very good antiproliferative effect on multiple myeloma cell lines (RPMI-8226).