裙带菜多糖保护异丙肾上腺素诱导的心脏纤维化研究

目的：探讨裙带菜多糖在异丙肾上腺素（ISO）诱导的心脏纤维化中的作用。方法将40只C57BL／6J小鼠随机分为对照组、ISO组、ISO＋裙带菜多糖组、裙带菜多糖组。ISO组连续皮下注射ISO 14 d（前3 d 10 mg·kg－1·d－1,后11 d 5 mg· kg－1·d－1）,ISO＋裙带菜多糖组除做上述ISO处理外,ISO处理前7 d开始给予裙带菜多糖200 mg·kg－1·d－1灌胃,持续到ISO皮下注射第14天;裙带菜多糖组连续21 d裙带菜多糖200 mg·kg－1·d－1灌胃;对照组以生理盐水代替ISO皮下注射。心脏超声检测各组小鼠心功能的改变,病理染色检测心脏纤维化程度,实时定量PCR检测转化生长因子-β（TGF-β）、Ⅰ型胶原α（CollagenⅠα）和Ⅲ型胶原（CollagenⅢ）的mRNA表达量的变化,Western Blot检测各组小鼠心脏自噬的改变。结果裙带菜多糖明显改善心功能,减少ISO诱导的心脏纤维化程度,心脏胶原蛋白CollagenⅠα和CollagenⅢ的mRNA表达量比ISO组显著降低（P＜0．05）,且裙带菜多糖能减少ISO诱导的心脏自噬。结论裙带菜能减轻ISO诱导的心脏纤维化,其主要是通过降低ISO诱导的心脏自噬而发挥作用的。     

Astragalus polysaccharide attenuates isoproterenol-induced cardiac hypertrophy by regulating TNF-α/PGC-1α signaling mediated energy biosynthesis

We previously reported that Astragalus polysaccharide (APS) extracted from Chinese medicine Astragalus membranaceus (Fisch.) Bge, attenuates hypertrophy of neonatal rat ventricular myocytes (NRVMs) induced by isoproterenol (Iso). The present study was designed to investigate the effects and the possible mechanism of APS on Iso-induced hypertrophy in rats and NRVMs with focus on tumor necrosis factor α (TNF-α)/peroxisome proliferator-activated receptor-γ coactivator 1α (PGC-1α) signaling mediated energy biosynthesis. 36-Week old rats were randomly divided into 3 groups: (1) Control, rats received vehicle; (2) Iso, rats received isoproterenol injections; (3) Iso+APS, rats received isoproterenol injections and APS. NRVMs were divided into similar groups as rats. The results showed that combination of APS with Iso significantly attenuated the pathological changes, reduced the ratios of heart weight/body weight (HW/BW) and left ventricular weight/BW (LVW/BW), improved the cardiac hemodynamics, down-regulated mRNA and protein expression of atrial natriuretic peptide (ANP), increased the ratios of ATP/ADP and ATP/AMP, and decreased the content of free fatty acid (FFA) in heart tissue of rats compared with Iso alone. In addition, pretreatment with APS significantly decreased the surface area and protein content, down-regulated mRNA and protein expression of ANP, increased the ratios of ATP/ADP and ATP/AMP, and decreased the content of FFA in NRVMs compared with Iso alone. Furthermore, APS increased the protein expressions of ATP5D, the σ subunit of ATP synthase, PGC-1α and pyruvate dehydrogenase kinase 4 (PDK4) in tissue and NRVMs respectively and inhibited the production of TNF-α in serum and culture medium compared with Iso alone. The results suggested that APS attenuates Iso-induced cardiac hypertrophy through regulating TNF-α/PGC-1α signaling mediated energy biosynthesis.     

PneuMum: Impact from a randomised controlled trial of maternal 23-valent pneumococcal polysaccharide vaccination on middle ear disease amongst Indigenous infants,Northern Territory,Australia

BackgroundWe assessed maternal 23-valent pneumococcal polysaccharide (23vPPV) vaccine efficacy (VE) against middle ear disease and pneumococcal carriage amongst Australian Indigenous infants.MethodsIn an open label, allocation concealed, outcome-assessor blinded, community stratified, randomised controlled trial, healthy pregnant Indigenous women aged 17–39 years in the Northern Territory of Australia received the 23vPPV (1:1:1) at: 30–36 weeks gestation, birth, or were unvaccinated (ClinicalTrials.gov NCT00714064). Co-primary outcomes were the point prevalences of infant middle ear disease and 23vPPV-type carriage at age 7 months.ResultsThe consent rate was 50% (313/632). Among 227 eligible participants randomised, retention rates were 86% (66/77) controls; 89% (67/75) pregnancy vaccinees; 88% (66/75) birth vaccinees. At infant age 7 months, ear disease prevalence was: 71% (47/66) controls, 63% (42/67) pregnancy vaccinees, 76% (50/66) birth vaccinees; and 23vPPV-type carriage was: 26% (17/66) controls, 18% (12/67) pregnancy vaccinees, 18% (12/66) birth vaccinees. For pregnancy vaccinees, VE was 12% (95% CI −12% to 31%) against infant ear disease and 30% (95% CI −34% to 64%) against 23vPPV-type carriage. In a post-hoc analysis, VE against infant ear disease concurrent with carriage of 23vPPV or related types was 51% (95% CI −2% to 76%). There were no serious adverse effects following receipt of the 23vPPV in pregnancy or at birth.ConclusionsIn a high risk population, our study was unable to demonstrate efficacy of 23vPPV in pregnancy against the co-primary outcomes of either all-cause infant ear disease or 23vPPV-type nasopharyngeal carriage at age 7 months. Efficacy against ear disease concurrent with carriage of vaccine-related serotypes (a more specific outcome) suggests 23vPPV in pregnancy may complement childhood pneumococcal vaccination programs.     

琼枝麒麟菜多糖抗单纯疱疹病毒2型活性研究

目的：探讨琼枝麒麟菜多糖（EGP）抗单纯疱疹病毒2型（HSV-2）的活性及其作用机制。方法：采用观察细胞病变效应（CPE）法和MTT法评价EGP对Vero细胞的毒性。空斑减数实验检测EGP对HSV-2的综合抗病毒活性、直接灭活作用、吸附及穿刺过程的抑制作用、和感染后的治疗作用。Real-time PCR检测EGP对HSV-2基因表达及其DNA复制的影响。结果： EGP浓度低于125 μg/mL对Vero细胞无毒性。EGP具有较强的综合抗病毒活性,在实验所用最低浓度（1.95 μg/mL）下,EGP可达到80 %的HSV-2病毒抑制率。EGP对HSV-2具有很强的直接灭活和抑制吸附作用,治疗作用相对较弱。同时,EGP可以下调HSV-2早期基因UL52和晚期基因UL27的表达,但是对病毒的DNA复制过程无影响。结论：麒麟菜多糖具有显著的抗HSV-2感染活性,主要通过干扰病毒对细胞的粘附、侵入而发挥作用。     

不同提取工艺对鄂产绿茶多糖体外降糖活性的影响

目的 探讨不同提取方法对鄂产绿茶多糖降糖活性的影响.方法 分别采用酶法、热水提取法、冷水提取法提取鄂产绿茶的茶多糖.通过体外实验观察不同提取方法所得绿茶多糖对α-葡萄糖苷酶、α-淀粉酶、蔗糖酶活性影响,选出对酶抑制作用最强的多糖.结果 3种提取方法所得绿茶多糖对α-葡萄糖苷酶的抑制作用无明显差别;酶法所提绿茶多糖对α-淀粉酶、蔗糖酶活性强于热水提取法、冷水提取法所得的绿茶多糖.结论 酶法提取的绿茶多糖具有较好的体外降血糖活性.     

非疫苗血清型肺炎链球菌发生机制及疫苗新策略

肺炎链球菌(Streptococcus pneumoniae,Sp)是社区获得性肺炎以及侵袭性疾病如脑膜炎和败血症的主要致病菌之一,到目前为止,关于肺炎链球菌感染性疾病的预防仍以肺炎链球菌多糖疫苗(pneumococcal polysaccharide vaccine,PPV)和肺炎链球菌多糖蛋白结合疫苗(pneumococcal conjugate vaccine,PCV)为主。然而靶向特定荚膜多糖的肺炎链球菌疫苗的选择性压力在一定程度上诱导了肺炎链球菌荚膜转换,导致了不同荚膜抗原突变体的产生,进而造成非疫苗血清型(non-vaccine type,NVT)及无荚膜肺炎链球菌(nonencapsulated streptococcus pneumoniae,NESp)的增加,使现有的疫苗不能有效预防肺炎链球菌的感染。本文重点介绍了肺炎链球菌非疫苗血清型的发生机制,为制备新型肺炎链球菌疫苗提供思路与策略。     

山茱萸多糖对青霉素致痫幼鼠学习记忆能力及海马组织脑源性神经因子、神经生长因子表达的影响

目的:探讨山茱萸多糖对青霉素致痫幼鼠学习记忆能力及海马组织脑源性神经因子(BDNF)、神经生长因子(NGF)表达的影响。方法:将30只日龄21 d龄幼鼠随机分为生理盐水对照组、青霉素点燃模型组、山茱萸多糖处理组各10只。生理盐水对照组只接受生理盐水灌胃,不造模;山茱萸多糖处理组在造模成功后灌胃0.05 g/mL山茱萸多糖;青霉素点燃模型组造模成功后灌胃等量生理盐水;连续灌胃28 d。采用Morris水迷宫检测各组幼鼠学习记忆能力;RT-PCR法检测海马组织BDNF mRNA、NGF mRNA表达;Western-blot法检测海马组织BDNF与NGF蛋白含量。结果:与生理盐水对照组比较,青霉素点燃模型组幼鼠学习记忆能力明显降低(P<0.01);与模型组比较,山茱萸多糖处理组学习记忆能力明显升高(P<0.01)。与生理盐水对照组比较,青霉素点燃模型组幼鼠BDNF、NGF mRNA和蛋白表达明显降低(P<0.01);与模型组比较,山茱萸多糖处理组BDNF、NGF mRNA和蛋白表达明显升高(P<0.01)。结论:山茱萸多糖具有提高青霉素点燃幼鼠学习记忆能力的作用,其机制可能是通过上调BDNF和NGF基因表达。     

灵芝多糖通过上调STAT4促进人外周血淋巴细胞中Th1细胞的分化

目的 探讨灵芝多糖(GLP)对外周血淋巴细胞免疫分群的影响及其作用机制.方法 取肿瘤患者和正常人的外周血,分离外周血单个核细胞(PBMC)后,用不同剂量的GLP(10 ng/ml、50ng/ml和100 ng/ml)刺激后,用流式细胞仪检测DC细胞表面分子(HLA-DR、CD83和CD11c)、Th1细胞、Th2细胞和NK(CD3-CD56+)细胞数;并进一步用免疫磁珠分选出正常人外周血CD4+ Th细胞后用不同浓度GLP刺激24h后,荧光实时定量Q-PCR检测Th1和Th2细胞因子的表达水平,Westernblot分析Th1分化相关的转录因子水平.结果 灵芝多糖可以在体外呈浓度依赖性增加外周血中Th1细胞亚群和DC共刺激分子的表达(P＜0.01),并且增加STAT4的表达和IL-12、IFN-γ和TNF-α的mRNA的表达水平(P＜0.01).结论 灵芝多糖可能通过增加Th细胞STAT4的表达水平,促进其向Th1细胞分化,并增加Th1的分泌细胞因子.     

Mammalian arylsulfatase A functions as a novel component of the extracellular matrix

Inherited deficiency for arylsulfatase (Ars) leads to lysosomal storage of sulfated compounds and to serious diseases such as growth retardation, heart failure, and demyelination in the central nervous system. Ars has been regarded as a lysosomal enzyme because of its hydrolytic activity on synthetic aromatic substrates and the lysosomal localization of its enzymatic activity. We previously demonstrated that a large portion of the mammalian arylsulfatase A (ArsA) protein exists on the cell surface of vascular endothelial cells, suggesting that ArsA plays a role in the components of the extracellular matrix. Here we show that ArsA functions as a substrate on which cells adhere and form protrusions. Coating culture plates with recombinant mouse ArsA (rmArsA) stimulates adhesion of human microvascular endothelial cells to the plate followed by the formation of cell protrusions as well as lamellipodia. rmArsA affects the architecture of the cytoskeleton, with a high density of actin filaments localized to peripheral regions of the cells and the extension of bundles of microtubules into the tips of cellular protrusions. rmArsA also affects the distribution pattern of the cell adhesion-associated proteins, integrin α2β1, and paxillin. rmArsA seems to modulate signaling of basic fibroblast growth factor (bFGF) stimulating cytoskeletal rearrangement. We also show that rmArsA tightly binds to sulfated polysaccharides. We suggest that mammalian ArsA plays a role as a novel component of the extracellular matrix. This viewpoint of Ars could be very useful for clarifying the mechanisms underpinning syndromes caused by the deficiency of the function of Ars genes.     

Achyranthes bidentata polysaccharide enhances immune response in weaned piglets

The acquired immunity is underdeveloped at 3–4 weeks of age when piglets are usually weaned on commercial farms, and weaning is associated with compromised immunity. Dietary supplementation with immunomodulatory phytochemicals may enhance immune responses in the weaned piglets. This study is conducted to investigate the effects of dietary supplemental achyranthes bidentata polysaccharide (ABP) on proliferation activity of lymphocytes, and production of antibodies, complements and cytokines in weaned piglets. Results showed that lymphocyte proliferation activity in piglets fed diets supplementing with 1000 and 1500?mg/kg ABP increased (P?<?0.05) on days 14 and 28 compared with the non-additive piglets, as well as serum contents of IgG, IgA, IgM, C₃, C₄, IL (interleukin)-2 and IFN (interferon)-γ. The ABP had dose-dependent immunomodulatory activity and the dose of 1500?mg/kg presented the strongest stimulating activity in vivo. In addition, the ABP increased (P?<?0.05) the proliferation activity and production of IL-2 and IFN-γ of cultured lymphocytes in dose- or time-dependent manner. The proliferation activity of peripheral T cells and splenic lymphocytes in 400?μg/ml of ABP group arrived at their peak values, as well as the production of IL-2 and IFN-γ at 72 and 12?h after the treatment, respectively. Collectively, these findings suggested that dietary supplementation with ABP to weaned piglets enhances cellular and humoral immune responses, and ABP addition to culture medium also increases the proliferation activity and cytokine production of lymphocytes cultured in vitro, which indicate that dietary supplementation with the herbal polysaccharide may offer an effective alternative to antibiotics for weaned piglets.