Role of liquid membrane phenomenon in biological actions of ACE inhibitors, captopril and lisinopril

The liquid membrane phenomenon in angiotensin converting enzyme (ACE) inhibitors namely, captopril and lisinopril has been studied. Hydraulic permeability data have been obtained to demonstrate the existence of the liquid membrane in series with a supporting membrane generated by the ACE inhibitors. Data on the transport of the relevant permeants in presence of the liquid membrane formed by ACE inhibitors indicate that liquid membrane phenomenon is likely to play a significant role in the action of ACE inhibitors.     

Differences in binding specificity for the homologous gamma- and beta-chain "holes" on fibrinogen: exclusive binding of Ala-His-Arg-Pro-amide by the beta-chain hole

The beta-chain amino-terminal sequences of all known mammalian fibrins begin with the sequence Gly-His-Arg-Pro- (GHRP-), but the homologous sequence in chicken fibrin begins with the sequence Ala-His-Arg-Pro- (AHRP-). Nonetheless, chicken fibrinogen binds the synthetic peptide GHRPam, and a previously reported crystal structure has revealed that the binding is in exact conformance with that observed for the human GHRPam-fragment D complex. We now report that human fibrinogen, which is known not to bind APRP, binds the synthetic peptide AHRPam. Moreover, a crystal structure of AHRPam complexed with fragment D from human fibrinogen shows that AHRPam binds exclusively to the beta-chain hole and, unlike GHRPam, not at all to the homologous gamma-chain hole. The difference can be attributed to the methyl group of the alanine residue clashing with a critical carboxyl group in the gammaC hole but being accommodated in the roomier betaC hole where the equivalent carboxyl is situated more flexibly.     

Antiproliferative potential of gallic acid against diethylnitrosamine-induced rat hepatocellular carcinoma

One of the focuses in current cancer chemoprevention studies is the search for nontoxic chemopreventive agents that inhibit the initiation of malignant transformation. Cancer biomarkers are quantifiable molecules involved in the physiologic or pathologic events occurring between exposure to carcinogens and the development, progression of cancer. Biomarkers may be the consequence of a continuous process, such as increased cell mass, or a discrete event, such as genetic mutation. Analysis of tumor markers can be used as an indicator of tumor response to therapy. Gallic acid is a naturally available polyphenol, possess strong antioxidant activity with a capacity to inhibit the formation of tumors in several cancer models. In the present study, we investigated the antiproliferative effect of gallic acid during diethylnitrosamine (DEN)-induced hepatocellular carcinoma (HCC) in male wistar albino rats. DEN treatment resulted in increased levels of aspartate transaminase, alanine transaminase, alkaline phosphatase, acid phosphatase, lactate dehydrogenase, gamma-glutamyltransferase, 5'-nucleotidase, bilirubin, alpha-fetoprotein, carcinoembryonic antigen, argyophillic nucleolar organizing regions, and proliferating cell nuclear antigen. Gallic acid treatment significantly attenuated these alterations and decreased the levels of AgNORs and PCNA. These finding suggests that gallic acid is a potent antiproliferative agent against DEN-induced HCC.     

In silico analysis of expression pattern of a Wnt/β-catenin responsive gene ANLN in gastric cancer

Actin-binding protein anillin (ANLN) is primarily involved in the cytokinesis and known to be dysregulated in many cancers including gastric cancer (GC). However, the regulation and clinical significance of ANLN in GC are far less clear. In the present study, we aimed to investigate the clinical significance and possible regulators of ANLN in GC. We have identified the Wnt/β-catenin associated regulation of ANLN by analyzing the in vitro perturbed β-catenin mRNA expression profiles. Investigating the gastric tumors from publicly available genome-wide mRNA expression profiles, we have identified the over expression of ANLN in gastric tumors. Association between ANLN expression and clinical characteristics of GC showed elevated expression in intestinal type GC. Performing a single sample prediction method across GC mRNA expression profiles, we have identified the over expression of ANLN in proliferative type gastric tumors compared to the invasive and metabolic type gastric tumors. In silico pathway prediction analysis revealed the association between Wnt/β-catenin signaling and ANLN expression in gastric tumors. Our results highlight that expression of a Wnt/β-catenin responsive gene ANLN in GC is a molecular predictor of intestinal and proliferative type gastric tumors.     

Phylogenetic reconstruction of endophytic fungal isolates using internal transcribed spacer 2 (ITS2) region

Endophytic fungi are inhabitants of plants, living most part of their lifecycle asymptomatically which mainly confer protection and ecological advantages to the host plant. In this present study, 48 endophytic fungi were isolated from the leaves of three medicinal plants and characterized based on ITS2 sequence – secondary structure analysis. ITS2 secondary structures were elucidated with minimum free energy method (MFOLD version 3.1) and consensus structure of each genus was generated by 4SALE. ProfDistS was used to generate ITS2 sequence structure based phylogenetic tree respectively. Our elucidated isolates were belonging to Ascomycetes family, representing 5 orders and 6 genera. Colletotrichum/Glomerella spp., Diaporthae/Phomopsis spp., and Alternaria spp., were predominantly observed while Cochliobolus sp., Cladosporium sp., and Emericella sp., were represented by singletons. The constructed phylogenetic tree has well resolved monophyletic groups with >50% bootstrap value support. Secondary structures based fungal systematics improves not only the stability; it also increases the precision of phylogenetic inference. Above ITS2 based phylogenetic analysis was performed for our 48 isolates along with sequences of known ex-types taken from GenBank which confirms the efficiency of the proposed method. Further, we propose it as superlative marker for reconstructing phylogenetic relationships at different taxonomic levels due to their lesser length.     

Marker-trait association analysis for gall midge (Orseolia oryzae) resistance in a diverse rice population

Damage caused by insect herbivores, notably Asian rice gall midge, Orseolia oryzae is more prevalent in the rice-growing belts of India's southern and north-eastern states. As a prelude to resistant cultivar development, the identification of genomic regions for resistance in the source population is crucial. In the present investigation, 202 rice genotypes were phenotyped and assayed with genomic markers reported for gall midge resistance. Positive skewness and platykurtic distribution of response scores suggested the inheritance of gall midge resistance in the study population. The marker gm3del3 contributed the most genetic variation, followed by RM28574 and marker RM22709 explained minimal variation. A marker-trait association analysis with a single marker-trait linear regression approach was performed to discover gall midge resistant genomic region/genes. The marker RM17480 on chromosome 4 reported to be linked with gm3 gene was found significantly associated with the gall midge resistance genomic region with allelic effects in a negative direction favouring resistance reaction. The allelic effects of significantly associated markers were correlated significantly with the phenotypic variation of gall midge damage scores. Genes identified in the vicinity of this marker contribute to stress response reactions in rice plants. The 200 bp allele of the marker was associated with susceptibility, while the 250 bp allele was associated with resistance expression. This allelic association with trait variation suggests the importance of associated marker for utilisation in marker-assisted selection programmes to incorporate resistance alleles into elite rice genotypes.     

Microwave assisted synthesis of 2-(4-substituted piperazin-1-yl)-1,8-naphthyridine-3-carbonitrile as a new class of serotonin 5-HT3 receptor antagonists

A series of novel 2-(4-substituted piperazin-1-yl)-1,8-naphthyridine-3-carbonitrile 6 were prepared by microwave irradiation and conventional heating. The intermediate, 2-oxo-1,2-dihydro-1,8-naphthyridine-3-carbonitrile 3, was prepared from 2-aminonicotinaldehyde 1 and ethyl cyanoacetate 2 in the presence of piperidine under solvent free condition. The synthesized compounds were evaluated for 5-HT3 antagonisms in longitudinal muscle-myenteric plexus (LMMP) preparation from Guinea pig ileum against 5-HT3 agonist, 2-methyl-5-HT. Among the compounds tested, 2-(4-allylpiperazin-1-yl)-1,8-naphthyridine-3-carbonitrile 6d showed most favorable 5-HT3 receptor antagonism in the Guinea pig ileum.     

Transport studies through liquid membranes of ciprofloxacin and norfloxacin

Ciprofloxacin and norfloxacin, the widely used drugs have been shown to generate liquid membranes in series with a supporting membrane (Sartorius celluose acetate microfiltration membrane). Transport of dextrose and ions, such as NH4+, Mg2+, Ca2+, K+ and PO4(3-) has been studied in the presence of liquid membranes generated by these drugs. The data obtained on the modification in the permeability of dextrose and ions in the presence of liquid membrane indicate the significance of liquid membranes in passive transport.     

《生物安全法》实施背景下生物遗传资源的安全管理

生物安全是国家安全的重要组成部分,《中华人民共和国生物安全法》通过了全国人大常委会的审议,并自2021年4月15日起施行。生物遗传资源是国家可持续发展的重要战略资源和国家安全的重要物质保障,目前已成为世界各国资源争夺的新领域,随着生物技术、分子生物学、生物信息学的迅速发展,对生物遗传资源的安全管理,离不开法律法规等制度的规范。《生物安全法》的出台完善了中国的法律、法规等管理制度,但还需要进一步的细化。首先阐述了《生物安全法》的立法意义,介绍了《生物安全法》的层级地位及立法进程;然后,在《生物安全法》实施背景下简要分析了生物遗传资源的定义及其安全管理面临的问题、国内外生物遗传资源安全管理的现状,阐述了《生物安全法》的出台对完善中国生物遗传资源管理的重要意义;最后,从法律框架、法律法规内容和科学技术层面提出如何更好地推进与落实《生物安全法》出台后中国生物遗传资源的安全管理。     

Melatonin,immune function and aging

Aging is associated with a decline in immune function (immunosenescence), a situation known to correlate with increased incidence of cancer, infectious and degenerative diseases. Innate, cellular and humoral immunity all exhibit increased deterioration with age. A decrease in functional competence of individual natural killer (NK) cells is found with advancing age. Macrophages and granulocytes show functional decline in aging as evidenced by their diminished phagocytic activity and impairment of superoxide generation. There is also marked shift in cytokine profile as age advances, e.g., CD3+ and CD4+ cells decline in number whereas CD8+ cells increase in elderly individuals. A decline in organ specific antibodies occurs causing reduced humoral responsiveness. Circulating melatonin decreases with age and in recent years much interest has been focused on its immunomodulatory effect. Melatonin stimulates the production of progenitor cells for granulocytes-macrophages. It also stimulates the production of NK cells and CD4+ cells and inhibits CD8+ cells. The production and release of various cytokines from NK cells and T-helper lymphocytes also are enhanced by melatonin. Melatonin presumably regulates immune function by acting on the immune-opioid network, by affecting G protein-cAMP signal pathway and by regulating intracellular glutathione levels. Melatonin has the potential therapeutic value to enhance immune function in aged individuals and in patients in an immunocompromised state.