IN SILICO AND IN VIVO PHARMACOLOGICAL STUDIES OF CLOZAPINE AND D-AMINO ACID OXIDASE INHIBITOR FOR COGNITIVE ENHANCEMENT

Objective: D-amino acid oxidase inhibitors (DAAOIs) are of particular focus for cognition study. Atypical antipsychotics are known DAAO inhibitors. The present examination was done to check out the binding affinity of atypical antipsychotics by docking toward the DAAO protein; in conclusion, the picked antipsychotic drug was checked for their cognition enhancing activity with scopolamine-induced amnesia.Methods: The crystal structure of DAAO was obtained from Protein Data Bank, the energy minimization was performed with CHARMM program, then active site prediction was made out using Ramachandran plot, and finally, docking examination was finished using Autodock 4.2 tool. For in vivo study, the mice were divided into three groups. Group I - vehicle (Saline) treated, Group II – saline +scopolamine (1 mg/kg, intraperitoneal [i.p]) treated, and Group III - clozapine (20 mg/kg, i.p) + scopolamine (1 mg/kg, i.p).Results: The Autodock examination shows significant binding affinity of - 5.22 for brexpiprazole and least or positive binding affinity of +1 for iloperidone. Clozapine with binding energy of - 2.87 was decided for completing the in vivo cognition study. The in vivo shows up that clozapine (20 mg/kg, i.p) exhibits a change in the impairment of spatial memory.Conclusion: The results recommend that the clozapine produces cognitive enhancement through both DAAOI and antipsychotic action. Clozapine has cognitive improvement potential, favoring its usage in reducing toxic impacts of scopolamin

D-AMINO ACID OXIDASE: A REVIEW

ABSTRACTOver many years, D-serine and glycine were found to be the endogenous ligands for glycine-binding site for N-methyl-D-aspartate receptors. D-serinebefore being used up by the cells undergoes oxidative deamination by the enzyme D-amino acid oxidase (DAAO) and makes D-serine levels reduced inthe brain, thereby affecting brain functions. In this review, we will discuss about the synthesis, location, therapeutic potential of DAAO function, rolein cognition, and neuropathic pain.Keywords: D-serine, Glycine, N-methyl-D-aspartate receptors, D-amino acid oxidase, Cognition, Neuropathy

EFFECT OF ORAL AZITHROMYCIN AND METRONIDAZOLE AS AN ADJUNCT TO SCALING AND ROOT PLANING ON GLYCEMIC CONTROL IN TYPE II DIABETIC PATIENTS WITH CHRONIC PERIODONTITIS

ABSTRACTObjective: Periodontitis, a chronic inflammatory disease characterized by destruction of the periodontal ligament and alveolar bone is the sixthcomplication of diabetes mellitus. Periodontal treatment that reduces gingival inflammation aids in the control of hyperglycemia. Therefore, thepresent study was designed to determine the effect of treating chronic periodontitis with oral antibiotics azithromycin and metronidazole on the levelof serum glycated hemoglobin in type-II diabetic patients.Methods: This prospective observational study was carried out in the dental department of a tertiary care hospital for 9 months. Clinical andbiochemistry reports of 90 patients were collected in designed case report forms. All statistical analyses were performed using IBM Statistical Packagefor Social Sciences 17 and Graph Pad Prism 7.0.Results: Significant reduction in all the clinical and dental parameters was comparatively higher in patients who received azithromycin than inpatients who received metronidazole and scaling and root planning alone.Conclusion: Periodontal therapy with oral azithromycin can be employed as a supportive strategy for the management of diabetes mellitus.Henceforth, prevention and control of periodontal disease along with antibiotics must be considered an integral part of glycemic control. However,due to the lesser sample size in this study, further investigations are required to confirm the effect of periodontal therapy on systemic diseases.Keywords: Periodontitis, Azithromycin, Metronidazole, Glycemic control, Diabetes mellitus

Talent retention and organizational citizenship behaviour (OCB): a case study of healthcare professionals in Tamil Nadu, India

The COVID-19 pandemic has severely impacted the employment system, which has instilled in workers a dread of job insecurity. This study's objective is to investigate the fluctuation of levels of organizational citizenship behaviour (OCB) in the healthcare sector in Chennai and Coimbatore, Tamil Nadu, India, which is influenced by talent retention. This study used a mixed methodology to gather its data, i.e., a triangulation with both quantitative survey questions and qualitative semi-structured interview questions. The independent variable was job insecurity, while the dependent variable was the employees' level of organizational citizenship behaviour, and the moderating variable was Talent Retention. Additionally, in order to understand the interactive impact of job insecurity and talent retention on Organizational Citizenship Behaviour, we performed Ordinary Least Squares (OLS) regression analysis. By interacting these two variables, it was found that there is a strong positive influence on OCB. Thus, this study can help organizations understand how to use job insecurity as a talent retention tool to encourage Organisational Citizenship Behaviour among healthcare workers

Design, Synthesis and Anticancer Screening of Novel Piperidine ydroxamate as HDAC Inhibitors.

Thirteen compounds were synthesized with piperidine in linker region and hydroxamate as Zinc Binding Group (ZBG). They were screened against (HeLa) human cervical cancer cell-line. Of those, compound 3l (N-hydroxy-1-{[(2E)-2-(2-hydroxybenzylidene) hydrazinyl] carbonothioyl} piperidine-4-carboxamide) was found a lead compound with promising IC50 value of 5.83nM. Further the lead compound would be evaluated against a panel of cancer cell lines and establish its possible mechanism through enzyme inhibition assay

HINOKITIOL-AMELIORATED DIETHYLNITROSAMINE-INDUCED HEPATOCARCINOGENESIS THROUGH ANTIOXIDANT MECHANISM IN RATS: IN VITRO AND IN VIVO STUDY

Objective: Chemoprevention seems to be the best strategy for lowering the incidence of liver cancer. Therefore, this study has been initiated to investigate the hinokitiol (HIOL) supplementation which could prevent oxidative stress induced by hepatocarcinogen, diethylnitrosamine (DEN) in rats.Methods: The biochemical parameters such as tissue damaging enzymes, namely, alanine transaminase (ALT), alkaline phosphatase (ALP), aspartate aminotransferase (AST), and attack-free period and enzymatic antioxidants, namely, glutathione (GSH), catalase (CAT), glutathione peroxidase (GPx), glutathione-S-transferase (GST), glutathione reductase (GR), superoxide dismutase (SOD), and histopathological changes were estimated.Results: DEN-treated rats shows increased ALT, ALP, and AST and decreased GSH, GST, CAT, GPx, GR, and SOD activities in liver tissues. The DEN-treated group (200 mg/kg body weight single intraperitoneal injection) with phenobarbital 0.05% orally showed the severe histopathological lesions in liver tissue. Whereas, the groups received HIOL along with DEN shown a comparatively lesser damage. Here, the HIOL supplementation ameliorated the biochemical parameters as well as evoked enzymatic antioxidants in DEN-induced rats to the control values.Conclusion: The HIOL possesses potent antioxidant property, in this credence to that conception, the treatment with HIOL may prevent the development of chemical-induced hepatocarcinogenesis in rats by free radical scavenging mechanism

Combined Effects of Simulated Microgravity and Radiation Exposure on Osteoclast Cell Fusion

The loss of bone mass and alteration in bone physiology during space flight are one of the major health risks for astronauts. Although the lack of weight bearing in microgravity is considered a risk factor for bone loss and possible osteoporosis, organisms living in space are also exposed to cosmic radiation and other environmental stress factors. As such, it is still unclear as to whether and by how much radiation exposure contributes to bone loss during space travel, and whether the effects of microgravity and radiation exposure are additive or synergistic. Bone is continuously renewed through the resorption of old bone by osteoclast cells and the formation of new bone by osteoblast cells. In this study, we investigated the combined effects of microgravity and radiation by evaluating the maturation of a hematopoietic cell line to mature osteoclasts. RAW 264.7 monocyte/macrophage cells were cultured in rotating wall vessels that simulate microgravity on the ground. Cells under static 1g or simulated microgravity were exposed to rays of varying doses, and then cultured in receptor activator of nuclear factor-B ligand (RANKL) for the formation of osteoclast giant multinucleated cells (GMCs) and for gene expression analysis. Results of the study showed that radiation alone at doses as low as 0.1 Gy may stimulate osteoclast cell fusion as assessed by GMCs and the expression of signature genes such as tartrate resistant acid phosphatase (Trap) and dendritic cell-specific transmembrane protein (Dcstamp). However, osteoclast cell fusion decreased for doses greater than 0.5 Gy. In comparison to radiation exposure, simulated microgravity induced higher levels of cell fusion, and the effects of these two environmental factors appeared additive. Interestingly, the microgravity effect on osteoclast stimulatory transmembrane protein (Ocstamp) and Dcstamp expressions was significantly higher than the radiation effect, suggesting that radiation may not increase the synthesis of adhesion molecules as much as microgravity

Thymosin beta 4 gene silencing decreases stemness and invasiveness in glioblastoma

Glioblastomas are incurable malignant primary brain tumours. Wirsching etal. investigate the effects of altered expression of thymosin beta 4 (TB4), a polypeptide implicated in neural development and wound healing, in glioma models. TB4 silencing inhibited migration and invasion of glioma cells invitro, and enhanced survival of glioma-bearing mic

A Glial Signature and Wnt7 Signaling Regulate Glioma-Vascular Interactions and Tumor Microenvironment.

Gliomas comprise heterogeneous malignant glial and stromal cells. While blood vessel co-option is a potential mechanism to escape anti-angiogenic therapy, the relevance of glial phenotype in this process is unclear. We show that Olig2+ oligodendrocyte precursor-like glioma cells invade by single-cell vessel co-option and preserve the blood-brain barrier (BBB). Conversely, Olig2-negative glioma cells form dense perivascular collections and promote angiogenesis and BBB breakdown, leading to innate immune cell activation. Experimentally, Olig2 promotes Wnt7b expression, a finding that correlates in human glioma profiling. Targeted Wnt7a/7b deletion or pharmacologic Wnt inhibition blocks Olig2+ glioma single-cell vessel co-option and enhances responses to temozolomide. Finally, Olig2 and Wnt7 become upregulated after anti-VEGF treatment in preclinical models and patients. Thus, glial-encoded pathways regulate distinct glioma-vascular microenvironmental interactions