神経障害性疼痛の原因受容体：リゾホスファチジン酸受容体１のコンピューター利用によるモデル化とリガンド結合状態の動力学的解析

長崎大学学位論文 [学位記番号]博（医歯薬）甲第715号 [学位授与年月日]平成26年9月19

Global mapping of research trends on antibacterial activity of green silver nanoparticles

Over the years, the quest for antibacterial agents from green nanoparticles has attracted great attention due to the global rise in the prevalence of multi-drug resistant bacteria. Although several studies on the antibacterial activity of plant-mediated silver nanoparticles have been documented, no bibliometric studies on the subject have been reported to date. As a result, the present study aimed to assess the global research trends on the antibacterial activity of green silver nanoparticles from 2000 to 2020. In the present study, we explored Science Citation Index Expanded (SCIE) to extract research articles written in English on the subject within the specified period. Two hundred and sixty-nine (269) eligible research articles were included in the bibliometric analysis and R-package “bibliometrix” was used to analyse the documents for annual scientific publications, authors’ impact, most relevant institutions, countries productivity, frequent words, co-occurrence network, co-citation network and authors/institutions/countries collaboration networks. Based on the analysis, the top three (3) authors, journals, institutions and countries were Kumar V (n = 5), Zangeneh MM (n = 5) and Oh BT (n = 4); King Saud University, Banaras Hindu University and Islamic Azad University; Journal of Cluster Science (n = 10), Applied Organometallic Chemistry (n = 8) and Microbial Pathogenesis (n = 8); India, Iran, and Korea. The study findings highlighted the gaps in a research collaboration that negate productivity. Therefore, we are optimitic that this study would enlighten researchers in the field about the research lapses and the need for research collaboration in future studies

Toxicogenetic Studies of Desplatsia dewevrei using Gene Expression of Blood, Pancreatic, and Intestinal Genes in Wistar rats

Background: Toxicity studies are relevant in assessing the side effects of chemical substances before they are incorporated into the process of drug development.Introduction: Desplatsia dewevrei is a scarce forest species believed by natives to be nutritive and therapeutic, without scientific evidence though. Thus, this study was aimed at investigating the possible toxicity of short- and long-term oral administration of D. dewevrei using Wistar rats.Methods: 0, 30 100, and 1000 mg/kg of D. dewevrei were daily administered p.o for 3 and 28 days to Wistar rats consisting of four animals (two females, two males) per group. Hemotoxicity and liver function tests were done using automated machines from ERMA Inc. RT-PCR method was used to study the regulation of intestinal glucose transporter 4 (GLUT4), glucose transporter 2 (GLUT2), glucagon-like peptide-1 (GLP-1), pancreatic insulin, KCJN5, and L-type voltage-gated calcium channel genes (CACNAIA).Results: No morphological or hematological signs of toxicity were observed. Liver function test showed an elevated level of high-density lipoprotein (HDL-C) in the treatment group (100 mg/kg). The lethal dose (LD50) of D. dewevrei extracts were above 1000 mg/kg as no mortality was observed at the highest regimen dose used. Up-regulation of pancreatic insulin and down-regulation of intestinal GLUT-2 suggest that the plant may contain therapeutic constituents.Conclusion: Short- or long-term administration of D. dewevrei is relatively safe

Meta-Analysis and Multivariate GWAS Analyses in 77,850 Individuals of African Ancestry Identify Novel Variants Associated with Blood Pressure Traits

High blood pressure (HBP) has been implicated as a major risk factor for cardiovascular diseases in several populations, including individuals of African ancestry. Despite the elevated burden of HBP-induced cardiovascular diseases in Africa and other populations of African descent, limited genetic studies have been carried out to explore the genetic mechanism driving this phenomenon. We performed genome-wide association univariate and multivariate analyses of both systolic (SBP) and diastolic blood pressure (DBP) traits in 77, 850 individuals of African ancestry. We used summary statistics data from six independent cohorts, including the African Partnership for Chronic Disease Research (APCDR), the UK Biobank, and the Million Veteran Program (MVP). FUMA was used to annotate, prioritize, visualize, and interpret our findings to gain a better understanding of the molecular mechanism(s) underlying the genetics of BP traits. Finally, we undertook a Bayesian fine-mapping analysis to identify potential causal variants. Our meta-analysis identified 10 independent variants associated with SBP and 9 with DBP traits. Whilst our multivariate GWAS method identified 21 independent signals, 18 of these SNPs have been previously identified. SBP was linked to gene sets involved in biological processes such as synapse assembly and cell-cell adhesion via plasma membrane adhesion. Of the 19 independent SNPs identified in the BP meta-analysis, only 11 variants had posterior probability (PP) of > 50%, including one novel variant: rs562545 (MOBP, PP = 77%). To facilitate further research and fine-mapping of high-risk loci/variants in highly susceptible groups for cardiovascular disease and other related traits, large-scale genomic datasets are needed. Our findings highlight the importance of including ancestrally diverse populations in large GWASs and the need for diversity in genetic research

Flavones scaffold of Chromolaena odorata as a potential xanthine oxidase inhibitor: Induced Fit Docking and ADME studies

Introduction: Gout is a type of painful inflammation initiated by the interactions between monosodium urate crystals and connective tissue. Xanthine oxidase (XO) catalyzes the oxidation of hypoxanthine to xanthine, then to uric acid. The primary treatments for gout include XO inhibitors. At present, allopurinol is the most used XO inhibitor for the treatment of gout. However, it can cause adverse effects commonly known as allopurinol hypersensitivity syndrome, thereby limiting its usage. Consequently, it is necessary to develop potent and less toxic inhibitors of XO. Chromolaena odorata is one of such plants under investigation for its diverse health benefits. Methods: Phytochemicals of C. odorata were screened against XO receptor, using molecular docking. The top five hit compounds of glide docking yield flavones scaffold which were subjected to induced fit docking (IFD) and absorption, distribution, metabolism, and excretion (ADME) studies. Results: The result showed that flavones scaffold of C. odorata can bind with higher affinity and lower free energy values when compared to that of the standard, allopurinol. The IFD scores of the flavones scaffold range from -1525.25 to -1527.99 kcal/mol. Conclusion: Our results have shown that flavones scaffold might have the potential to act as an effective drug candidate when compared to allopurinol in treating and/or preventing gout and some inflammatory condition

Additional file 1 of In-silico analysis reveals druggable single nucleotide polymorphisms in angiotensin 1 converting enzyme involved in the onset of blood pressure

Additional file 1: Table S1. Nonsynonymous Single Nucleotide Polymorphism of ACE1 gene retrieved from NCBI dbSNP database. Table S2. a Deleterious or disease-causing SNPs across the six in silico tools (SNPs&GO, PROVEAN, PhD-SNP, Polyphen-2, PANTHER and SIFT). b SIFT predictive result of deleterious of nsSNPs. c SNPs&GO deleterious nsSNPs prediction. d PROVEAN predictive result of deleterious or disease-causing nsSNPs. e Polyphen-2 predictive result of deleterious or disease-causing nsSNPs. Table S3. a INSP protein stability predictions for nsSNPs in ACE1. b MUpro stability prediction result for MUpro_NN and MUpro_SVM. c I-Mutant prediction result for ACE1 protein stability. d istable server protein stability prediction using MUpro_SVM, MUpro_NN, iPTREE- STAB and I-Mutant. Table S4. Consurf conservation prediction analysis

Additional file 1: Figure S1. of NMDA receptor agonists reverse impaired psychomotor and cognitive functions associated with hippocampal Hbegf-deficiency in mice

In Gng7 wt/cre and Hbegf flox/flox mice, used for mating to generate Hbegf cKO mice, lacZ positive cells were not observed in the dentate gyrus. (TIF 9882 kb

Modulatory Effect of Human Immunodeficiency Virus on Circulating p53, miR-21, and miR-125b: Any Diagnostic Implication?

Identifying immunocompromised women who are at risk of developing cervical cancer remains a challenge for clinicians. In an effort to identify the role of HIV in cervical carcinogenesis, this study evaluated the levels of normally downregulated oncomirs (miR-21, miR-146a, miR-155, miR-182, and miR-200c) and normally upregulated tumor suppressors (miR-let-7b, miR-125b, miR-143, miR-145, and p53 expression) associated with cervical cancer in the serum of women living with HIV (HIV+) and without HIV (HIV. Method: This case-control study included 173 women; confirmed HIV+ (n = 103) and HIV− (n = 70). Serum levels of miRNAs and p53 were determined using reverse transcriptase PCR. t-test and Pearson’s correlation analyses were carried out on the generated data. Result: A higher level of miR-21 was observed among HIV+ women compared with their HIV− counterpart (p = 0.028), whereas lower levels of miR-125, and p53 gene were observed among HIV+ women compared with HIV− women at p = 0.050 and 0.049, respectively. Significant direct relationships were observed between miR-21 and other oncomirs (p < 0.05) among HIV+ women. Conclusion: This study revealed that HIV contributes to cervical carcinogenesis by modulating circulating levels of miR-21, p53, and miR-125b. It suggests that these biomarkers could be used to identify at high risk for developing cervical cancer

Identification of novel chemical compounds targeting filovirus VP40-mediated particle production

The central role of Ebola virus (EBOV) VP40 in nascent virion assembly and budding from infected host cells makes it an important therapeutic target. The mechanism of dimerization, following oligomerization of VP40 leading to the production of virus-like particles (VLP) has never been investigated for the development of therapeutic candidates against Ebola disease. Molecular dynamics-based computational screening targeted VP40 dimer with 40,000,000 compounds selected 374 compounds. A novel in vitro screening assay selected two compounds, NUSU#1 and NUSU#2. Conventional VLP assays consistently showed that both compounds inhibited EBOV VP40-mediated VLP production. Intriguingly, NUSU#1 inhibited the VP40-mediated VLP pro-duction in other ebolavirus species and the Marburg virus, but did not inhibit Lassa virus Z-mediated VLP production. These results strongly suggested that the selected compounds are potential lead drug candidates against Filovirus disease via disruption of VP40-mediated particle production