BHUx: A Patent Polyherbal Formulation to Prevent Atherosclerosis

Ayurvedic medicine is a time-tested system of medicine which has been in clinical use for centuries in India. Being a time-tested system, it has an edge over other existing systems of health management, especially for dealing with chronic disorders such as coronary artery disease, which is of a complex multi-etiological nature. Recently, we have shown that BHUx, a patented polyherbal formulation consisting of the aqueous fraction of five medicinal plants of the ayurvedic system, has significant anti-inflammatory properties through inhibition of cyclooxygenase-2 and lipoxygenase-15. Here we have investigated its effect on diet-induced atherosclerosis in albino rabbits. BHUx was given orally for 3 months to rabbits pre-treated with an atherogenic diet for 3 months. After 6 months, the dorsal aorta was processed for histological studies for calcium and collagen content. The results demonstrated a remarkable reduction in intimal thickening in the treated animals. In addition, there was less calcification at the intima–medial interface and increased intensity of collagen cap on the surface along with an increase in survival, compared with the sham control. We suggest that BHUx is a potent, multi-factorial formulation against atherosclerosis

Molecular characterization of senescence marker protein-30 gene promoter: Identification of repressor elements and functional nuclear factor binding sites

<p>Abstract</p> <p>Background</p> <p>Senescence marker protein-30 (SMP30), whose expression declines during aging in rat liver, has been proposed as an important aging marker. Besides apoptosis, SMP30 also protects cells against various other injuries by enhancement of membrane calcium-pump activity. The mechanism of this differential gene expression mechanism is not known. DNA-protein interactions, mutation analysis and luciferase reporter assay studies have been performed to elucidate the mechanism of transcriptional regulation of SMP30 gene.</p> <p>Results</p> <p>We have characterized up to -2750 bp of the promoter by DNA-protein interactions studies. Twenty eight transcription factor binding sites have been identified by DNase I footprinting and electrophoretic mobility shift assay (EMSA). Transient transfection of 5' and 3' -deleted promoter-reporter constructs and luciferase assay illustrated the region between -128/+157 bp is sufficient to drive promoter activity. We have mapped an essential regulatory region between -513 to -352 bp which causes a drastic decline of reporter activity. This region contains CdxA, GATA2 and SRY transcription factor binding sites. Individual mutation of these three sites showed increase in reporter activity. Mutation in SRY site (-403/-368) showed maximum increase in reporter activity among these three sites. Therefore, we suggest that SRY like protein may be acting as a strong repressor of SMP30 gene along with CdxA and GATA-2. We also report that mutation of both Sp1 (172/-148 bp) and a C/EBPβ (-190/-177 bp) transcription binding site located adjacent to each other on SMP30 gene promoter, causes a significant enhancement in reporter activity than individual mutation, thus may be causing the repression of SMP30 promoter activity.</p> <p>Conclusion</p> <p>These studies provide novel insights into the mechanism that regulate SMP30 gene expression.</p

Differential splicing of neuronal genes in a Trem2*R47H mouse model mimics alterations associated with Alzheimer\u27s disease.

BACKGROUND: Molecular characterization of late-onset Alzheimer\u27s disease (LOAD), the leading cause of age-related dementia, has revealed transcripts, proteins, and pathway alterations associated with disease. Assessing these postmortem signatures of LOAD in experimental model systems can further elucidate their relevance to disease origins and progression. Model organisms engineered with human genetic factors further link these signatures to disease-associated variants, especially when studies are designed to leverage homology across species. Here we assess differential gene splicing patterns in aging mouse models carrying humanized APOE4 and/or the Trem2*R47H variant on a C57BL/6J background. We performed a differential expression of gene (DEG) and differential splicing analyses on whole brain transcriptomes at multiple ages. To better understand the difference between differentially expressed and differentially spliced genes, we evaluated enrichment of KEGG pathways and cell-type specific gene signatures of the adult brain from each alteration type. To determine LOAD relevance, we compared differential splicing results from mouse models with multiple human AD splicing studies. RESULTS: We found that differentially expressed genes in Trem2*R47H mice were significantly enriched in multiple AD-related pathways, including immune response, osteoclast differentiation, and metabolism, whereas differentially spliced genes were enriched for neuronal related functions, including GABAergic synapse and glutamatergic synapse. These results were reinforced by the enrichment of microglial genes in DEGs and neuronal genes in differentially spliced genes in Trem2*R47H mice. We observed significant overlap between differentially spliced genes in Trem2*R47H mice and brains from human AD subjects. These effects were absent in APOE4 mice and suppressed in APOE4.Trem2*R47H double mutant mice relative to Trem2*R47H mice. CONCLUSIONS: The cross-species observation that alternative splicing observed in LOAD are present in Trem2*R47H mouse models suggests a novel link between this candidate risk gene and molecular signatures of LOAD in neurons and demonstrates how deep molecular analysis of new genetic models links molecular disease outcomes to a human candidate gene

PHYSICOCHEMICAL CHARACTERISTICS OF FERTILIZER INDUSTRY EFFLUENT AND ITS TOXICOLOGICAL IMPACT ON THE ACTIVITY OF ACETYLCHOLINESTERASE (AChE) IN FRESHWATER TELEOSTS Heteropneustes fossilis AND Labeo rohita

Industrijska revolucija je dobar pokazatelj gospodarskog razvoja države, međutim, može biti i prijetnja za floru i faunu ako se u prirodu ispuštaju nepročišćene otpadne vode industrije. Cilj ovog istraživanja je procijeniti toksikološke učinke pročišćenih i nepročišćenih industrijskih otpadnih voda na aktivnost acetilkolinesteraze (AChE) kod Heteropneustes fossilis i Labeo rohita, jestivih riba različitih karakteristika poput razlika u morfologiji, staništu, ishrani, itd. Analizirani su fizikalno-kemijski parametri otpadnih voda kao što su: pH, električna vodljivost (EC), alkalitet, tvrdoća, otopljeni kisik (DO), fosfati, sulfati, nitrati, slobodni amonijak, kloridi, cink, željezo, krom i kalij jer ti parametri nisu bili u rasponu prema ISO smjernicama. Vrijednost LC50 za nepročišćene vode iznosila je 2,34% (v/v) i 0,80% (v/v) tijekom 96 h kod H. fossilis i L. rohita. Smrtnost riba u obrađenim otpadnim vodama nije zabilježena. Tijekom izlaganja subletalnim koncentracijama (1/15, 1/(10 ), 1/5 LC50) kod obje vrste riba aktivnost AChE u metabolički osjetljivim organima (mozak, mišići, škrge) je bila smanjena. Daljnja istraživanja biokemijskih i molekularnih pokazatelja mogla bi približiti mehanizam njihovog djelovanja.Industrial revolution is a good indicator of economic development of a country; however, it can be a threat to the flora and fauna if the untreated effluent of an industry is discharged. The present study is aimed to assess the comparative toxicological impacts of treated and untreated industrial effluents on acetylcholinesterase (AChE) activity in Heteropneustes fossilisand Labeo rohita, the most common edible fishes having diverse characters which include differences in morphology, habitat, food and feeding, etc. The physico-chemical parameters such as pH, electrical conductivity (EC), alkalinity, hardness, dissolved oxygen (DO), phosphate, sulphate, nitrate, free ammonia, chloride, zinc, iron, chromium and potassium of both untreated and treated effluent from the fertilizer industry were also analyzed as these parameters were not in range as per ISO guidelines. The LC50 value for untreated effluent was 2.34% (v/v) and 0.80% (v/v) for 96 h in H. fossilis and L. rohita, respectively, while no mortality was recorded in the treated effluent. The AChE activity in both fish species was found to decline in metabolically responsive organs like brain, muscle and gills through exposure to sub-lethal concentrations (1/15th, 1/10th and 1/5th of LC50 value) of the untreated effluent for 96 h. Further studies on biochemical and molecular aspects may reveal the mechanism of their action

HOMOLOGY MODELLING AND MOLECULAR DOCKING STUDY OF ORGANOPHOSPHATES AND PYRETHROIDS IN TERMS OF POTENTIAL TOXICITY

Objective: Though the adverse effects of pesticides used in agriculture may not immediately be visible in the human population however its long term exposure may cause detrimental effects by biomagnifications and bioaccumulation. Nowadays bioinformatics serves as an in silico tool not only for homology alignment but also for prediction of quaternary structures of biochemicals. The present study was aimed to compare the potential toxicities of triazophos and chlorpyrifos (organophosphates; OPs) and cypermethrin and deltamethrin (pyrethroids) and their interactions with cytochrome P450 functioning. Methods: The authors performed the BLAST for homology alignment for cytochrome P450 of human and Zebra fish and further proceeded for docking analysis of all the pesticides with cytochrome P450. Results: It was noted that 99% of query cover with 32% of homology in the sequences of cytochrome P450 between human and Zebra fish. Upon docking, the pesticide deltamethrin showed the highest interaction with cytochrome P450 with highest binding energy and least dissociation constant for Deltamethrin which was found to be 8.233 [kcal/mol] and 922849.687 [pM].Conclusion: Our preliminary results thus encompass/indicate that the deltamethrin is not only having detrimental effect on enzyme kinetics in general but also such similar effects be apprehended for human also

Non-destructive Quality Monitoring of Fresh Fruits and Vegetables

Quality determines the shelf life as well as selling price of fresh fruit or vegetable and therefore, quality monitoring and testing of fresh commodities have paramount importance in their postharvest handling and supply chain management. Most of the methods used to assess fruits and vegetables quality are destructive in nature. Now-a-days, various mechanical, optical, electromagnetic, and dynamic non-destructive methods are gaining importance due to ease in operations, faster turn over and reliability. Some of the non-destructive techniques (NDT) are currently being used in laboratories, research institutions and food packaging and processing industries, whereas, some methods are still at developmental stage. Various NDT with respect to their principle and applications such as impact test, electronic nose, time-resolved reflectance spectrometry (TSR), near infrared spectroscopy (NIR), nuclear magnetic resonance (NMR), X-Ray, ultra sonic, acoustic impulse response method, electrical conductivity methods etc., are discussed in this review