Oxyquinoline-Dependent Changes in Claudin-Encoding Genes Contribute to Impairment of the Barrier Function of the Trophoblast Monolayer

Bulletin of Experimental Biology and Medicine - Natural response to hypoxia critically depends on rapid stabilization of hypoxia-inducible factor (HIF). Under normoxic conditions, HIF-prolyl...     

Comparative Analysis of Secretome of Human Umbilical Cord- and Bone Marrow-Derived Multipotent Mesenchymal Stromal Cells

Bulletin of Experimental Biology and Medicine - Production of cytokines and growth factors by cultured human umbilical cord tissue- and bone marrow-derived multipotent mesenchymal stromal cells was...     

Rare detection of hepatitis B and hepatitis C virus genomes by polymerase chain reaction in seronegative donors with elevated alanine aminotransferase

BACKGROUND: Since screening for antibody to hepatitis C virus (HCV) was introduced in 1990, posttransfusion hepatitis has been reduced to nearly background levels. This has led to reconsideration of the value of testing donated blood for elevated alanine aminotransferase (ALT). The contribution of ALT testing in detecting seronegative infection was evaluated by the performance of polymerase chain reaction (PCR) for hepatitis B virus (HBV) or HCV in plasma from ALT-elevated blood units. STUDY DESIGN AND METHODS: Testing was performed on 375 units of plasma, derived from an equivalent of 47,500 blood donations, with a highly sensitive hemi-nested PCR procedure. Using a triplet of primers directed at the conserved regions of HBV DNA and 5'-noncoding regions of HCV RNA, the hemi-nested PCR assay can reliably amplify 10 viral molecules to levels detectable in ethidium bromide-stained agarose gels. Pools of plasma from groups of four donors were screened with hemi-nested PCR. For any reactive pools, the plasma from individual donors was retested twice on different aliquots. RESULTS: Two of 375 units, both with midrange ALT elevation, were repeatedly reactive in hemi-nested PCR (one each for HBV DNA and HCV RNA). However, samples from the two suspect donors tested 9 and 5 months later revealed no seroconversion, elevated ALT, or viral genomes in hemi-nested PCR. CONCLUSION: The lack of confirmed HBV or HCV infection in this study representing an estimated 47,500 voluntary blood donations suggests that routine ALT testing for further prevention of posttransfusion hepatitis after exclusion of HBV- and/or HCV-seropositive blood may be superfluous.     

Resolution of infection status of human immunodeficiency virus (HIV)- seroindeterminate donors and high-risk seronegative individuals with polymerase chain reaction and virus culture: absence of persistent silent HIV type 1 infection in a high-prevalence area

To address concerns over the prevalence of silent (antibody-negative) infections among blood donors and high-risk populations, a combination of proviral amplification by polymerase chain reaction (PCR) and viral isolation by co-culture techniques was employed to resolve the human immunodeficiency virus type 1 (HIV-1) infection status of well-characterized groups of suspect blood donors and others identified in the blood bank setting. No silent infections were found in 65 follow-up samples from 26 persistently HIV-1-seroindeterminate blood donors, 16 persistently seronegative heterosexual partners of infected transfusion recipients, and 6 high-risk seronegative homosexual men identified through donor look-back investigations. In contrast, 21 seropositive controls tested positive. These results suggest a low prevalence of persistently silent infections in at-risk populations, even in high HIV prevalence regions. The PCR assay, with a co-detected internal positive control, and appropriate confirmatory algorithms, was found to be a useful direct assay to rule out infection, especially in concert with confirmatory virus isolation.     

急性心肌梗死大鼠梗死区血管内皮生长因子和缺氧诱导因子1αmRNA表达及人参皂苷Rg1的干预效应

目的:观察人参皂苷Rg1对急性心肌梗死后血管新生及梗死区血管内皮生长因子和缺氧诱导因子1αmRNA表达的影响及其机制。方法:实验于2005-10/2006-01在中国医科大学附属第一医院循环内科实验室完成。实验分组:健康雄性Wistar大鼠104只,体质量180～220g,随机抽签法分为假手术组8只,对照组、Rg1低剂量治疗组和Rg1高剂量治疗组各32只。实验方法:建立Wistar大鼠急性心肌梗死模型,假手术组开胸不结扎冠状动脉,3d后处死取材;对照组、Rg1低剂量治疗组和Rg1高剂量治疗组分别于术后即刻及术后每天腹腔注射生理盐水1mL、人参皂苷Rg11mg/kg和5mg/kg,术后3,7,10,14d分别取材,每组8只。实验评估:测定血清心肌酶、心肌梗死面积、梗死区微血管密度,逆转录-聚合酶链反应检测梗死区心肌组织血管内皮生长因子和缺氧诱导因子1α的mRNA表达。结果:纳入大鼠104只,均进入结果分析。①人参皂苷Rg1对大鼠心肌酶及心肌梗死面积的影响:Rg1低剂量治疗组、Rg1高剂量治疗组心肌酶较对照组明显降低[(62.25±10.79),(57.64±9.36),(78.63±11.34)μg/L;P<0.05],心肌梗死面积亦明显降低[14d:(12.15±3.68)%,(10.10±3.12)%,(13.94±3.54)%;P<0.05]。②人参皂苷Rg1对大鼠心肌梗死区微血管密度的影响:各组梗死区血管生成数量随着时间的延长呈持续增加的趋势,与对照组比较,差异有显著性意义[Rg1低剂量治疗组14d:(17.29±3.21)个/视野;Rg1高剂量治疗组14d:(23.27±3.42)个/视野;对照组14d:(9.36±3.54)个/视野;P<0.01]。③大鼠心肌梗死区血管内皮生长因子、缺氧诱导因子1αmRNA的表达:心肌梗死后血管内皮生长因子、缺氧诱导因子1αmRNA表达随缺血时间的延长有增高趋势,Rg1低剂量治疗组与Rg1高剂量治疗组明显升高,14d时血管内皮生长因子的增长出现停止或下降[Rg1低剂量治疗组14d:(1.1637±0.1786);Rg1高剂量治疗组14d:(1.7230±0.3102)];而缺氧诱导因子1α继续升高[Rg1低剂量治疗组14d:(1.7263±0.3417);Rg1高剂量治疗组14d:(2.7725±0.3219)]。结论:严重缺血可刺激心肌组织产生大量的血管内皮生长因子、缺氧诱导因子1α,人参皂苷Rg1增加其表达进而刺激心肌梗死区的血管生成,减轻缺血对心肌的损伤。     

Regenerative medicine of pancreatic islets

The pancreas became one of the first objects of regenerative medicine,since other possibilities of dealing with the pancreatic endocrine insufficiency were clearly exhausted.The number of people living with diabetes mellitus is currently approaching half a billion,hence the crucial relevance of new methods to stimulate regeneration of the insulin-secreting β-cells of the islets of Langerhans.Natural restrictions on the islet regeneration are very tight;nevertheless,the islets are capable of physiological regeneration via β-cell self-replication,direct differentiation of multipotent progenitor cells and spontaneous α-to or δ-to β-cell conversion(trans-differentiation).The existing preclinical models of β-cell dysfunction or ablation(induced surgically,chemically or genetically) have significantly expanded our understanding of reparative regeneration of the islets and possible ways of its stimulation The ultimate goal,sufficient level of functional activity of β-cells or their substitutes can be achieved by two prospective broad strategies β-cell replacement and β-cell regeneration.The "regeneration" strategy aims to maintain a preserved population of β-cells through in situ exposure to biologically active substances that improve β-cell survival,replication and insulin secretion,or to evoke the intrinsic adaptive mechanisms triggering the spontaneous non-β-to β-cell conversion.The "replacement" strategy implies transplantation of β-cells(as non-disintegrated pancreatic material or isolated donor islets) or β-like cells obtained ex vivo from progenitors or mature somatic cells(for example,hepatocytes or a-cells) under the action of small-molecule inducers or by genetic modification.We believe that the huge volume of experimental and clinical studies will finally allow a safe and effective solution to a seemingly simple goal-restoration of the functionally activeβ-cells, the innermost hope of millions of people globally.