The results of this study demonstrate the therapeutic potential of this novel polyherbal formulation for the management and treatment of SDAT.

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CTCF-mediated chromatin interactions influence organization and function of mammalian genome in diverse ways. We analyzed the interactions among CTCF binding sites (CBS) at the murine TCRb locus to discern the role of CTCFmediated interactions in the regulation of transcription and VDJ recombination. Chromosome conformation capture analysis revealed thymocyte-specific long-range intrachromosomal interactions among various CBS across the locus that were relevant for defining the limit of the enhancer Eb-regulated recombination center (RC) and for facilitating the spatial proximity of TCRb variable (V) gene segments to the RC. Ectopic CTCF binding in the RC region, effected via genetic manipulation, altered CBS-directed chromatin loops, interfered with RC establishment, and reduced the spatial proximity of the RC with Trbv segments. Changes in chromatin loop organization by ectopic CTCF binding were relatively modest but influenced transcription and VDJ recombination dramatically. Besides revealing the importance of CTCF-mediated chromatin organization for TCRb regulation, the observed chromatin loops were consistent with the emerging idea that CBS orientations influence chromatin loop organization and underscored the importance of CBS orientations for defining chromatin architecture that supports VDJ recombination. Further, our study suggests that in addition to mediating long-range chromatin interactions, CTCF influences intricate configuration of chromatin loops that govern functional interactions between elements.KEYWORDS antigen receptor loci, CTCF, VDJ recombination, chromatin loop, chromatin organization S patial and temporal regulation of nuclear processes is intricately related to chromatin structure and organization since it can influence the interactions among regulatory elements. The mechanisms underlying these complex interactions are not completely understood. CTCF was identified to be the trans-acting factor that can organize an insulator and block enhancer-promoter interaction in a position dependent manner (1-3). Subsequently, CTCF has emerged as an important architectural protein that can influence interchromosomal and intrachromosomal interactions and impact nuclear functions largely in collaboration with cohesin (4, 5). Genome-wide investigations, including chromatin immunoprecipitation (ChIP), 4C, Hi-C, and chromatin interaction analysis by paired-end tag sequencing (ChIA-PET), etc., have established an important role of CTCF in organization of topologically associated domains (TADs) (6, 7). In addition, CTCF binding sites (CBS) located within TADs can contribute to celltype-specific chromatin loop organization by facilitating, as well as inhibiting, the interactions between regulatory elements. Locus-specific genetic analysis relying on deletion and inversion of CBS has revealed CBS orientation-dependent chromatin loop organization and its influence on transcriptional regulation (8-11). However, several aspects regarding the ability of CBS to organize chromatin and regulate function

It is important to monitor the quality of the phytopharmaceutical product as its therapeutic potential depends on standardized delivery of active ingredients present in the botanical source. Minimal presence of toxic impurities like heavy metals (HMs) is warranted to ensure product safety and prevent hazardous health impacts. In the present study, conducted as part of the development of a novel phytopharmaceutical product, the chemical profile of 13 heavy metals (Fe, Cu, Mn, Zn, Ni, Co, Mo, V, Cr, As, Pb, Hg, and Cd) was studied in the whole plant, fruit, and rhizome of Bacopa monnieri, Hippophae rhamnoides, and Dioscorea bulbifera, respectively, from environmentally diverse regions in India. Most samples had HM profiles within permissible limits as established by regulatory authorities, with the exception of Cd and Hg in low-altitude regions. This study indicates geographical regions in India suitable for procuring raw materials to develop and manufacture phytopharmaceutical products.

CitationDubey GP, Sadhu A, Upadhyay P, et al. Combination treatment with a novel polyherbal formulation and metformin: a single blind placebocontrolled study in patients with T2DM and cognitive impairments. ABSTRACTBackground: Older people suffering from Type 2 Diabetes Mellitus (T2DM) are at major risk for age related cognitive dysfunction and dementia, mainly due to vascular complications. Studies have shown that T2DM is also associated with Alzheimer's Disease (AD) and is responsible for accelerating the pathology through insulin resistance. A polyherbal drug containing Bacopa Monnieri, Hippophae rhamnoides and Dioscorea bulbifera has shown a potent neuroprotective effect in management of cognitive deficits in elderly; and metformin a well-accepted antidiabetic agent responsible for lowering blood glucose in T2DM, can together provide an intriguing potential combination therapy for prevention and amelioration of cognitive impairments in T2DM patients. Objective: The present study is aimed to evaluate the combined effect of a polyherbal drug and metformin on improving cognitive functions in patients suffering from T2DM. Method: Elderly patients with an age range of 60-75 years diagnosed for T2DM were enrolled in the study and randomized into two groups; Group I=T2DM patients given metformin and placebo, Group II=T2DM patients given metformin and polyherbal drug. The subjects received the combination therapy of metformin (500 mg) and placebo or metformin (500 mg) and polyherbal drug (500 mg) twice daily for a period of 24 weeks. Estimation of Mini Mental State Examination (MMSE) score, blood glucose, HbA1c, insulin, lipid profile (total cholesterol, LDL-c, HDL-c, triglycerides), homocysteine, Interleukin-6 (IL-6), TNF-α and C-reactive protein (CRP) were measured at baseline and were repeated at three months and six months. The primary end point was a change from baseline to week 24 in MMSE score. Key secondary end points included change from baseline to week 24 in Digital Symbol Substitution (DSS); subtest of the Wechsler Adult Intelligence Scale-Revised), word recall (digital memory apparatusMedicaid systems, Chandigarh, India), attention span (Attention Span Apparatus -Medicaid systems, Chandigarh, India), Functional Activity Questionnaire (FAQ) and Hamilton Depression Scale (HDS) score. Further inflammatory markers and level of oxidative stress were analysed using standard biochemical tests. Result: The trial was performed in 120 elderly diabetic patients out of whom 112 patients