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

Effect of Spondias mombin leaves’ extracts on chemically induced tumor

Background & Aim: A tumor is merely a mass of tissue that does not perform any physiological function; it can be either benign or malignant. Cancer is being regarded as a malignant ailment emerging from unrestricted cell division occurring in the body to make mass of tissues. Spondias mombin L. (Family- Anacardiaceae) grows in coastal areas and in the rain forest into a big tree of up to 15 – 22 m. This study investigated the efficacy of S. mombin aqueous and n-hexane extracts in chemically induced tumor-bearing animals. Experimental: Twenty-eight (28) healthy rats were used and grouped into seven (7). Six groups were induced with trichloroacetic acid and ethidium bromide leaving out normal control group for 28 days prior to treatments. LBH589 (standard anticancer drug, 500 mg/kg) served as positive control. At the termination of the experiments, the animals were sacrificed; solid tumor volume was determined, blood and tissue samples were collected for hematology and histopathology respectively. Results: The results showed very significant reduction in the solid tumour volumes of S. mombin leaves extracts treated groups compared to positive and untreated control groups. The result of hematological parameters showed that the hemoglobin content, red blood cell and white blood cell counts of all treated groups were near to normal control group. Normal histological features were observed in control group animals, the negative groups showed the manifestations of cancer, all the treatment groups showed significant levels of repair almost similar to normal features in control group particularly in intestines and lungs of the experimental animals. Recommended applications/industries: The present data provided substantial evidence that S. mombin leaves suppressed tumor growth in experimental animals and suggested that the extracts are potential antitumorigenic agent inhibiting chemically induced lung and intestinal tumors

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

Computational and drug target analysis of functional single nucleotide polymorphisms associated with Haemoglobin Subunit Beta (HBB) gene

There is overwhelming evidence implicating Haemoglobin Subunit Beta (HBB) protein in the onset of beta thalassaemia. In this study for the first time, we used a combined SNP informatics and computer algorithms such as Neural network, Bayesian network, and Support Vector Machine to identify deleterious non-synonymous Single Nucleotide Polymorphisms (nsSNPs) present in the HBB gene. Our findings highlight three major mutation points (R31G, W38S, and Q128P) within the HBB gene sequence that have significant statistical and computational associations with the onset of beta thalassaemia. The dynamic simulation study revealed that R31G, W38S, and Q128P elicited high structural perturbation and instability, however, the wild type protein was considerably stable. Ten compounds with therapeutic potential against HBB were also predicted by structure-based virtual screening. Interestingly, the instability caused by the mutations was reversed upon binding to a ligand. This study has been able to predict potential deleterious mutants that can be further explored in the understanding of the pathological basis of beta thalassaemia and the design of tailored inhibitors

Effects of crude ethanolic extract of Garcinia cambogia on the reproductive system of male wist ar rats (Rattus novergicus)

15 male rats were grouped and administered crude ethanolic extracts of Garcinia cambogia seeds to test the effects on the histology of the testis and sperm counts. Group A served as the control while Groups B and C received 100 and 200 mg/kg body weight of extracts, respectively. The administration was done orally once a day, six days a week for six weeks. The routine histological preparation at the end of administration revealed increase in the interstitial spaces, degeneration of the Ledgid cells and distortion in the arrangement of the cells of spermatogenic series. The sperm counts revealed a significant increase in the experimental groups when compared statistically with the control (p<0.05). It was 81.5 ± 13.62 ´ 10^6/ml and 70 ± 12.98 ´ 10^6 /ml in groups Band C, respectively, as compared to 59.8 ± 2.14 ´ 10^6/ml in the Control group

Molecular Docking and Quantitative Structure Activity Relationship for the Identification of Novel Phyto-inhibitors of Matrix Metalloproteinase-2

Cancer is a deadly disease that affects humans of all races, gender, and age. The matrix metalloproteinase-2 (MMP-2) protein is a good target when designing an anticancer drug. The expression of this protein influences cell growth and division. The activation of this protein opens the extracellular matrix and provides entry of the new cells into the body system. Phytochemicals are known to possess the ability to cure human diseases with little or no side effect. In this study, phytochemicals from yellow mombin, turmeric, green chiretta, African basil and ginger were evaluated against the MMP-2 orthosteric sites and three-dimensional quantitative structure activity relationship (3D-QSAR) was used to generate a model for MMP-2 inhibitors. The drug-like properties of the lead compounds and the standard drug were tested by employing the Lipinski rule of five. Azulene from ginger, Andrographidine A from green chiretta and Isovitexin from African basil with the docking scores of -7.3 kcal/mol, -9.3 kcal/mol, and - 8.2 kcal/mol, respectively, were found to be the lead compounds as potential MMP-2 inhibitors. A robust regression model for the inhibition of MMP-2 was generated. Andrographidine A with the highest docking score stood out as a potential inhibitor of MMP-2 by sharing selective interactions with his-120 and his-130. The QSAR model proposed herein was thoroughly validated and hence offers a tool for the identification of potential MMP-2 inhibitors in the future

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

Virgin coconut oil reverses behavioral phenotypes of letrozole-model of PCOS in Wistar rats via modulation of NRF2 upregulation

الملخص: أهداف البحث: متلازمة المبيض المتعدد الكيسات هي اضطراب في الغدد الصماء يظهر مع مقاومة الأنسولين وفرط الأندروجين والعقم الفرعي. تم الإبلاغ عن أن زيت جوز الهند البكر له فوائد صحية، مثل الخصائص المضادة للالتهابات ومضادات الأكسدة المضادة للفيروسات. تبحث هذه الدراسة في تأثيرات النظام الغذائي الفموي التكميلي لزيت جوز الهند على الذاكرة والضعف الإدراكي في متلازمة المبيض المتعدد الكيسات التي يسببها دواء ليتروزول. طريقة البحث: تم تقسيم ثلاثين من إناث الفئران بشكل عشوائي إلى خمس مجموعات. بصرف النظر عن المجموعة الضابطة، عولجت جميع الفئران الأخرى باستخدام ليتروزول لمدة 21 يوما للحث على متلازمة المبيض المتعدد الكيسات وعولجت بعد ذلك لمدة 14 يوما باستخدام 10 ٪ من زيت جوز الهند البكر وكلوميفين، وتم دمج الاثنين لعلاج المجموعة الأخيرة (زيت جوز الهند البكر + كلوميفين). تم إجراء ثلاثة اختبارات سلوكية عصبية هي ''اختبارات الارتفاع بالإضافة إلى المتاهة، ومتاهة واي، واختبارات التعرف على الأشياء الجديدة''. النتائج: أظهرت نتائجنا ارتفاعا إحصائيا في تركيز الهرمونات الجنسية في مصل الدم في فئران متلازمة المبيض المتعدد الكيسات مقارنة بمجموعات التحكم والمجموعات المعالجة. أيضا، عكست جميع المجموعات المعالجة انخفاضا ملحوظا في تركيز المصل المنخفض من الكاتلاز والتعبير الجيني الخاضع للتنظيم لـ''إن آر اف-2'' لعينات الحصين التي شوهدت في فئران متلازمة المبيض المتعدد الكيسات. بالإضافة إلى ذلك، أظهرت نتائجنا تعبيرا جينيا منظما لأستراز أستيل كولين في فئران متلازمة المبيض المتعدد الكيسات والتي تم إرجاعها بشكل ثابت بواسطة المجموعات المعالجة بزيت جوز الهند البكر. الاستنتاجات: تم توضيح السلوك الشبيه بالقلق وضعف الذاكرة قصيرة المدى في هذه الدراسة. ومع ذلك، عكست مكملات زيت جوز الهند البكر كل هذا عن طريق تعديل التعبير الجيني ''إن آر اف-2'' و '' إستيراز الأستيل كولين''. Abstract: Objectives: Polycystic ovarian syndrome (PCOS) is an endocrine disorder associated with insulin resistance, hyperandrogenism, and sub-infertility. Virgin coconut oil (VCO) has been reported to have health benefits, such as anti-inflammatory, anti-oxidant, and antiviral properties. This study investigated the effects of dietary VCO supplementation on memory and cognitive impairment in female rats with letrozole induced PCOS. Methods: Thirty female rats were randomly divided into five groups. All rats except controls were treated with letrozole for 21 days to induce PCOS and were subsequently treated for 14 days with 10% VCO, clomiphene (CLO), or VCO + CLO. Three neurobehavioral tests were conducted: elevated plus maze, Y maze, and novel object recognition tests. Results: Our results indicated statistically elevated serum concentrations of sex hormones in rats with PCOS, compared with the control and treated groups. In addition, all treated groups showed significant reversal of the low serum concentrations of catalase and down-regulated gene expression of Nrf2 in the hippocampus seen in the PCOS rats. In addition, gene expression of acetylcholine esterase was up-regulated in PCOS rats, and was statistically reverted in the VCO treated groups. Conclusion: Anxiety-like behavior and impaired short-term memory were observed in PCOS rats; however, VCO supplementation reversed these effects by modulating the gene expression of Nrf2 and AchE