葛根素对U14宫颈癌小鼠血液流变学、脾淋巴细胞增殖及细胞毒性影响

摘要 目的：研究葛根素治疗对U14宫颈癌小鼠血液流变学、脾淋巴细胞增殖活性及对宫颈癌细胞毒性的影响。方法：45只雌性昆明小鼠随机分为对照组、模型组和葛根素组。模型组和葛根素组小鼠通过腋下注射U14小鼠宫颈癌细胞建立U14宫颈癌移植瘤小鼠,并且葛根素小鼠通过葛根素灌胃进行治疗,对照组和模型组小鼠给予等量生理盐水。比较各组小鼠血流变学、脾淋巴细胞增殖活性及对宫颈癌细胞毒性。结果：经葛根素治疗的葛根素组宫颈癌小鼠肿瘤重量显著低于模型组小鼠（P<0.05）,葛根素治疗宫颈癌小鼠的抑瘤率是（42.91±12.91）%。宫颈癌小鼠低切/高切全血粘度、血浆粘度值以及血细胞比容均显著升高（P<0.05）,而葛根素治疗可显著降低宫颈癌小鼠低切/高切全血粘度、血浆粘度值以及血细胞比容（P<0.05）。宫颈癌小鼠脾脏重量、脾脏指数和脾淋巴细胞体外增殖能力均显著下降（P<0.05）,而葛根素治疗可显著提高宫颈癌小鼠脾脏重量、脾脏指数和脾淋巴细胞体外增殖能力（P<0.05）。此外,经葛根素治疗的宫颈癌小鼠脾淋巴细胞对U14宫颈癌细胞细胞毒性显著高于模型组宫颈癌小鼠（P<0.05）。结论：葛根素治疗可降低U14宫颈癌小鼠血液粘度、改善血流变性质,并且可以提高脾淋巴细胞的增殖活性和对宫颈癌细胞的杀伤力。     

双歧杆菌对高胆固醇饮食小鼠血脂影响的研究

目的了解双歧杆菌对高胆固醇饮食水平异常的动物个体血脂及脂蛋白代谢的影响.方法将高胆固醇饮食小鼠分为2组,一组饮用双歧杆菌菌液,另一组常规饮水.经28 d喂养后,将全部动物处死,并立即取血,取上清液测定血脂及脂蛋白各项指标:血清总胆固醇(TC)、甘油三酯(TG)和高密度脂蛋白(HDL-C).结果高脂饮食 双歧杆菌组TG、TC水平显著低于高脂饮食组(P<0.01),HDL-C/TC显著高于高脂膳食组(P<0.01).结果表明灌胃双歧杆菌,小鼠血清中TC、TG浓度较高脂饮食显著降低(P＜0.01),同时HDL-C浓度有所增加.结论饮用双歧杆菌能显著改善高胆固醇饮食小鼠血脂及脂蛋白代谢状况.     

双歧杆菌培养上清调节D-半乳糖衰老小鼠血脂水平的实验研究

目的通过观察双歧杆菌培养上清（spent culture supernatant,SCS）对D-半乳糖所致亚急性衰老小鼠血脂指标和学习记忆行为的影响,探讨双歧杆菌培养上清减低血脂的机制,为进一步研究双歧杆菌培养上清中有效延缓衰老的成分提供理论依据。方法小鼠颈背部皮下注射生理盐水和D-半乳糖建立亚急性老年模型和正常对照,同时,对实验组小鼠腹腔注射双歧杆菌培养上清,连续培养42 d后称重,用跳台法对小鼠学习、记忆能力进行测试后断颈处死,检测血清中总胆固醇（TC）、甘油三酯（TG）和高密度脂蛋白（HDL-C）含量。结果与模型组相比,实验组小鼠血清TG、TC水平显著降低（P〈0.05）,血清HDL-C/TC水平明显提高,学习记忆能力较模型组也有明显提高。结论双歧杆菌上清能降低血清TG、TC含量,延缓D-半乳糖小鼠的衰老进程。     

杭白菊总黄酮对衰老小鼠学习记忆的影响

目的：探讨杭白菊总黄酮（TFCM）对衰老小鼠学习记忆能力及胆碱能系统的影响。方法：采用皮下注射D-半乳糖的方法制备衰老小鼠模型。ICR小鼠随机分为5组（n=10）：正常对照组,模型组,低、中、高剂量TFCM处理组。TFCM处理组于造模后第2周开始每天给予TFCM（50、100或150mg／kg）灌胃。用Morris水迷宫法检测小鼠学习记忆能力,用比色法测定血清和大脑组织中丙二醛（MDA）含量,以及超氧化物歧化酶（SOD）和乙酰胆碱酯酶（Ach E）活性。结果：与正常对照组相比,模型组学习记忆能力减退,MDA含量和Ach E活性增加,SOD活性降低。与模型组相比,中高浓度TFCM处理组（100、150mg／kg）小鼠学习记忆能力明显改善,MDA含量和Ach E活性明显降低,SOD活性增高。结论：TFEM能显著改善D-半乳糖衰老小鼠学习记忆能力,其机制可能与TFCM的抗氧化特性以及提高中枢胆碱能系统功能有关。     

三联益生菌对便秘小鼠肠道推进功能改善及其对 小鼠肠道菌群调节作用的研究

目的研究新型嗜酸乳杆菌NCFM-乳双歧杆菌Bi-07-鼠李糖乳杆菌NH001三联益生菌制剂对便秘小鼠小肠蠕动的促进作用,以及其对小鼠肠道菌群构成比例的调节作用。方法小肠推进率实验:将50只KM小鼠适应性饲养后随机分为空白对照组、模型对照组和低中高三个剂量组。空白对照组和模型对照组给予蒸馏水,低中高剂量组每天分别给予0.165、0.330、0.990g/(kg·bw)益生菌制剂,灌胃14d后使用复方地芬诺酯建立小鼠便秘模型观察小肠墨汁推进率;肠道菌群调节作用实验:将42只BALB/c小鼠中随机抽取10只作为自身对比空白组,适应性饲养后将所有小鼠随机分为空白对照组和低中高三个剂量组,空白对照组给予蒸馏水,各剂量组以相同剂量给予益生菌制剂灌胃。自身对比空白组于灌胃前无菌采集小鼠直肠粪便,所有小鼠灌胃30d后无菌采集直肠粪便,使用16SrDNA基因测序对粪便中菌群DNA进行多样性及各水平菌群物种测定。结果高剂量组便秘小鼠小肠推进率显著高于模型对照组(P0.05);各剂量组肠道菌群多样性、双歧杆菌属、乳杆菌属数量较灌胃前显著增加(P0.05),大肠埃希菌属、梭菌属、肠球菌属较灌胃前显著降低(P0.05)。结论三联益生菌能够有效促进便秘小鼠肠道蠕动能力,改善便秘症状;同时对小鼠肠道菌群结构有调节作用。     

肠球菌WZM05对高胆固醇血症小鼠载脂蛋白的影响

目的探讨肠球菌WZM05对高胆固醇血症小鼠血清学指标及高胆固醇血症形成的影响。方法采用灌胃法建立小鼠高胆固醇血症模型及肠球菌实验组（10^6、10^8、10^9CFU／m1）,实验40d后,进行血清血脂水平检测及载脂蛋白A1（apoAI）、载脂蛋白B（apoB）测定。结果肠球菌组的血清总胆固醇明显降低,高密度脂蛋白明显升高（P〈0．01）,血清apoAI升高及apoB降低（P〈0．05）。结论肠球菌WZM05具有降脂、调脂作用。     

田基黄总黄酮调节酒精性肝损伤小鼠肠道菌群及降低内毒素的研究

目的 使用中药田基黄调节酒精性肝病（ALD）小鼠的肠道菌群,降低小鼠血中内毒素（LPS）的含量,改善小鼠的肝脏功能,从而减少酒精对肝脏的损伤、降低ALD的发病率达到临床辅助治疗ALD的目的。方法 80只昆明小鼠（雌雄各半）,体质量26～37 g。正常饲养1周后,随机选取20只小鼠作为正常组,剩余小鼠作为酒精模型组,模型组小鼠灌胃56°北京红星二锅头白酒0.3 mL,2次/d,连续灌胃45 d,末次小鼠灌胃白酒后,禁食12 h但不禁水,于第46天早上随机选取模型组与正常组小鼠各10只,采用眼球采血法取小鼠血液,检测小鼠血清谷丙转氨酶（ALT）、谷草转氨酶（AST)活性及血LPS水平来验证模型。造模成功后模型组余下50只小鼠随机分为自然恢复组、丽珠肠乐组以及田基黄总黄酮低、中、高剂量干预组（田基黄总黄酮剂量分别为10、20、40 mg/mL）,每组10只。分别于造模成功第0天、灌药7 d后,于无菌条件下取小鼠粪便对小鼠粪便中的大肠埃希菌、肠球菌、双歧杆菌和乳杆菌进行平板培养并计数。先称量小鼠体质量,采血检测小鼠血清ALT、AST活性及血LPS水平;最后处死小鼠取其肝脏称重,计算肝体比。结果...     

复合益生菌粉对功能性便秘小鼠润肠通便的作用

目的 探究由乳双歧杆菌V9、干酪乳杆菌Zhang、植物乳杆菌P9组成的复合益生菌粉对便秘模型小鼠的排便情况、肠动力水平的改善及肠道菌群结构的调整作用。方法 将100只Balb/c小鼠随机分为A、B两大组,每组又随机分为空白组、模型组以及复合益生菌粉低剂量组、中剂量组、高剂量组,其中A组50只用于排便情况测定,B组50只用于结肠HE染色及肠道菌群的检测。实验共进行15 d,空白组与模型组小鼠灌胃蒸馏水15 d,复合益生菌粉各剂量组小鼠灌胃相应剂量的复合益生菌粉15 d;同时,除空白组外,于第7天、第15天灌胃盐酸洛哌丁胺（4 mg/kg）进行造模。结果 与空白组相比,模型组小鼠首次排便时间显著延长（P<0.01）,6 h内粪便质量显著减轻（P<0.05）,肠推进率显著降低（P<0.05）,提示造模成功;与模型组相比,复合益生菌粉低、高剂量组首次排黑便时间显著缩短（P<0.05）,肠推进率显著升高（P<0.05）,同时高剂量组小鼠6 h排便量增加（P<0.05）。HE结果显示,复合益生菌粉可以增厚结肠肌层,恢复受损的结肠黏膜组织,并且腺管排列恢复至正常水...     

黄连素对肥胖小鼠肠道菌群的影响及其机制

为了探索黄连素对肥胖小鼠肠道菌群的影响和作用机制,本研究将40只雄性昆明种小鼠随机分为空白组、模型组、黄连素高剂量组、黄连素中剂量组和黄连素低剂量组,每组8只,除空白组外,其余4组给予高脂饮食,建立实验性肥胖小鼠模型。造模14 d后,全部给予正常饮食,黄连素高、中、低剂量组灌胃给予每天0.1～0.3 mL/10 g的药物干预,空白组和模型组给予等剂量的生理盐水,给药持续14 d。每周称量两次体质量,并分别于实验第0、14、28天从眼眶取血测定血脂和炎性因子的含量,收集小鼠粪便测定乳酸杆菌和双歧杆菌的数量。研究结果表明:空白组和模型组小鼠的体质量在第14天时有明显差异,造模成功;实验第28天,黄连素各给药组小鼠的体质量与模型组相比有显著性差异。模型组双歧杆菌、乳酸菌的数量和血脂水平与空白组比较有显著性差异,黄连素给药组能显著改善肥胖小鼠的血脂水平和双歧杆菌、乳酸杆菌的数量。本研究结果初步得出结论认为:黄连素改善肥胖小鼠的作用机制可能与脂质代谢、炎性反应和肠道微环境的改变密切相关。     

双歧杆菌脂磷壁酸对化疗荷瘤小鼠免疫功能的影响

目的探讨双歧杆菌脂磷壁酸对5-氟尿嘧啶（5-FU）化疗肝癌H22荷瘤小鼠免疫的影响及其作用机制。方法双歧杆菌脂磷壁酸处理5-Fu化疗的H纶荷瘤Balb／c小鼠,MTT法检测NK细胞和CTL细胞杀伤活性;采用流式细胞仪检测荷瘤小鼠脾细胞中T亚群比例;用RT-PCR和Western Not方法分别检测荷瘤小鼠肿瘤组织Foxp3和TIM-3mRNA及蛋白的表达变化。结果荷瘤小鼠脾细胞中CD4^＋ CD25^＋Tmg比例高,并存在Foxp3和TIM-3 mRNA及蛋白的高表达,经双歧杆菌LTA和5．Fu处理后CD4^＋CD25^＋Tmg比例下降,Foxp3和TIM-3mRNA及蛋白表达水平也均呈下调趋势,但5-FU单独处理后的荷瘤小鼠脾细胞中CD4^＋细胞比例也减少,NK细胞和CTL杀伤率均降低,而双歧杆菌LTA处理后CD4^＋细胞比例,NK细胞和CTL杀伤率却明显增加。二者联合处理也能增加CD^＋细胞比例及NK细胞和CTL杀伤率。结论双歧杆菌脂磷壁酸联合5-FU可通过增强NK细胞和CTL杀伤能力,同时抑制TIM-3／TIM-3L途径,降低CD4^＋CD25^＋Tmg的免疫抑制活性,增强机体细胞免疫来提高化疗抗肿瘤效果,减轻化疗副作用,增强宿主对化疗的耐受性,从而提高抗肿瘤作用。     

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).