Tuberculosis (TB) is an infectious disease caused by Mycobacterium tuberculosis (M.tb.). Our integrative analysis aims to identify the transcriptional profiling and gene expression signature that distinguish individuals with active TB (ATB) disease, and those with latent tuberculosis infection (LTBI). In the present study, we reanalyzed a microarray dataset (GSE37250) from GEO database and explored the data for differential gene expression analysis between those with ATB and LTBI derived from Malawi and South African cohorts. We used BRB array tool to distinguish DEGs (differentially expressed genes) between ATB and LTBI. Pathway enrichment analysis of DEGs was performed using DAVID bioinformatics tool. The protein–protein interaction (PPI) network of most upregulated genes was constructed using STRING analysis. We have identified 375 upregulated genes and 152 downregulated genes differentially expressed between ATB and LTBI samples commonly shared among Malawi and South African cohorts. The constructed PPI network was significantly enriched with 76 nodes connected to 151 edges. The enriched GO term/pathways were mainly related to expression of IFN stimulated genes, interleukin-1 production, and NOD-like receptor signaling pathway. Downregulated genes were significantly enriched in the Wnt signaling, B cell development, and B cell receptor signaling pathways. The short-listed DEGs were validated in a microarray data from an independent cohort (GSE19491). ROC curve analysis was done to assess the diagnostic accuracy of the gene signature in discrimination of active and latent tuberculosis. Thus, we have derived a seven-gene signature, which included five upregulated genes FCGR1B, ANKRD22, CARD17, IFITM3, TNFAIP6 and two downregulated genes FCGBP and KLF12, as a biomarker for discrimination of active and latent tuberculosis. The identified genes have a sensitivity of 80–100% and specificity of 80–95%. Area under the curve (AUC) value of the genes ranged from 0.84 to 1. This seven-gene signature has a high diagnostic accuracy in discrimination of active and latent tuberculosis.

We examined 25 breast tumor samples for somatic mutations in exon 20 and exon 9 of PIK3CA gene in South Indian population. Genomic DNA was isolated and amplified for PIK3CA gene, followed by direct sequencing of purified polymerase chain reaction products. We identified PI3K3CA mutations in 5 of 25 (20%), including four of the mutations in p.H1047R and one in p.H1047L. Nucleotide base substitution A to G (c.3140A > G) and A to T (c.3140A > T) results in p.H1047R and p.H1047L mutation in exon 20 of PIK3CA gene. We did not observe any mutation in exon 9 of PIK3CA gene. Furthermore, we investigated the effect of mutations on protein structure and function by the combination of sequence and structure-based in silico prediction methods. This determined the underlying relationship between the mutation and its phenotypic effects. Next step, we complemented by molecular dynamics simulation analysis (30 ns) of native and mutant structures that measured the effect of mutation on protein structure. The obtained results support that the application of computational methods helps predict the biological significance of mutations.

Cytochrome P450 drug metabolizing enzymes are implicated in personalized medicine for two main reasons. First, inter-individual variability in CYP3A4 expression is a confounding factor during cancer treatment. Second, inhibition or induction of CYP3A4 can trigger adverse drug–drug interactions. However, inflammation can downregulate CYP3A4 and other drug metabolizing enzymes and lead to altered metabolism of drugs and essential vitamins and lipids. Little is known about effects of inflammation on expression of CYP450 genes controlling drug metabolism in the skin. Therefore, we analyzed seven published microarray datasets, and identified differentially-expressed genes in two inflammatory skin diseases (melanoma and psoriasis). We observed opposite patterns of expression of genes regulating metabolism of specific vitamins and lipids in psoriasis and melanoma samples. Thus, genes controlling the turnover of vitamin D (CYP27B1, CYP24A1), vitamin A (ALDH1A3, AKR1B10), and cholesterol (CYP7B1), were up-regulated in psoriasis, whereas melanomas showed downregulation of genes regulating turnover of vitamin A (AKR1C3), and cholesterol (CYP39A1). Genes controlling abnormal keratinocyte differentiation and epidermal barrier function (CYP4F22, SULT2B1) were up-regulated in psoriasis. The up-regulated CYP24A1, CYP4F22, SULT2B1, and CYP7B1 genes are potential drug targets in psoriatic skin. Both disease samples showed diminished drug metabolizing capacity due to downregulation of the CYP1B1 and CYP3A5 genes. However, melanomas showed greater loss of drug metabolizing capacity due to downregulation of the CYP3A4 gene.

Background: Mangrove plants have high potential in medical research and they have been used in traditional medicine for any diseases. Squalene, a natural 30-carbon triterpenoid compound, was originally obtained from Shark and for the first time isolated from mangrove plant species. From the historical background, it was known that squalene display protective actions against several diseases and carcinogens. Objective: Herein, we desire to report the in vitro evaluation of squalene on AGS cell line. In the present investigation, after 24 h incubation, the inhibitory effect of squalene was found to have significant activity on AGS cell lines proliferation. Materials and Methods: Mangrove plant isolated squalene compound was treated with gastric adenocarcinoma cancer cell line AGS for 24 h with control. The cells were treated at varying concentration range 10, 30, and 50 μg/mL. The cytotoxicity effect of squalene was studied by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-tetrazolium bromide, mitochondria membrane potential, etc., Results: Among the tested concentrations, squalene at 50 μg/mL showed a higher level of mitochondrial depolarization, DNA fragmentation, and induced apoptosis in AGS cells when compared to control. A similar but lower activity was observed in minimum doses of 20 and 30 μg/mL compared to maximum dose of 50 μg/mL. A 50% and 100% cell viability was observed at 30 and 50 μg/mL, respectively. Likewise, there was a significant reduction in thiobarbituric acid reactive substrate and lipid hydroperoxides levels, while antioxidant enzymes like superoxide dismutase. Catalase, glutathione (GSH) peroxidase, reduced GSH, Vitamin-C (Vit-C), and Vitamin-E were increased on squalene treatment in a dose-dependent manner. Conclusion: On the basis of results, it was concluded that isolated compound (squalene) from Rhizophora mucronata had a potent antigastric carcinogenic effect at 50 μg/mL in AGS cell lines and appeared to be more sensitive toward the AGS cell line. Abbreviations used: PBS: Phosphate-buffered saline; FBS: Fetal bovine serum; DMEM: Dulbecco's modified eagle medium; MTT: 3-(4, 5-dimethyl-2-thiazolyl)-2, 5-diphenyl-tetrazolium bromide; DCFH-DH-7: Diacetyl dichlorofluorescein; Rh 123: Rhodamine 123; EB: Ethidium bromide; AO: Acridine orange; TBA: Thiobarbituric acid; NBT: Nitro blue tetrazolium; PMS: Phenazine methosulfate; DTNB-5: 5-dithiobis 2-nitrobenzoic acid; GSH: Reduced glutathione.

Ficus hispida Linn. (Family Moraceae), well-known beneficial medicinal shrub, has been traditionally used for the treatment of various diseases such as leukoderma. The aim of the present study is to investigate the efficacy of F. hispida ethanolic leaves extract for antiproliferative, apoptotic, cell cycle blockade, and wound healing. F. hispida leaves extract was treated with colorectal adenocarcinoma cancer cell line HT29 for 24 h with control. The cells were treated at varying concentration ranges of 15, 31, 62, 125, and 250 μg/ml each The cytotoxicity effect of leaves extract was studied by 3-[4, 5-dimethylthiazol-2-yl]-2, 5 diphenyltetrazolium bromide assay and their anticancer activity was further evaluated using cell cycle analysis and wound scratch assay. The end antiproliferative result showed that HT-29 cell viability decreases in a concentration-dependent manner and the growth inhibitory effect (IC50) values are obtained at a concentration of 125 μg. The increase in number of apoptotic cell was observed after treating HT-29 cells with the sample in double-staining methods. G0/G1 phase of the cell cycle was significantly blocked by the test sample followed by the G2/M phase in a negligible manner. In vitro cell wound closure or contracture was not significant when compared the sample against control group. F. hispida Linn. ethanolic leaves extract had shown to possess excellent cytotoxic effect through inducing apoptosis, especially causing cell cycle arrest at the G0/G1 phase. The experiment tries to evaluate the effectiveness of F. hispida leaves extract as an antiproliferative, apoptotic, cell cycle inhibitor and wound healing agent. Results showed that F. hispida Linn extract own cytotoxic property by inducing apoptosis through cell cycle arrest. Abbreviations used: HT 29: Human adenocarcinoma colorectal cell line; PBS: Phosphate Buffered Saline; FBS: Fetal Bovine Serum; DMEM: Dulbecco's Modified Eagles Medium; MTT: 3 [4, 5 dimethylthiazol 2 yl] 2, 5 diphenyltetrazolium bromide; NCCS: National Centre for Cell Sciences; DMSO: DiMethyl SulfOxide; PI: Propidium Iodide; AO: Acridine Orange;EB: Ethidium Bromide; IC: Inhibitory Concentration.

A total of 480 suspected blood samples were collected from cattle (n=254) and buffaloes (n=226) during the study period from September 2011 to December 2014 for determination of prevalence of haemoprotozoan parasites from South Western Gujarat (Junagadh). The conventional optical microscopy of Giemsa stained blood smears revealed that 37% of cattle and 38.93% of buffaloes were infected with haemoprotozoan parasites including Anaplasma marginale, Babesia bigemina, Trypanosoma evansi and Theileria annulata. The animals infected with haemoprotozoan diseases showed lower total erythrocyte count (TEC), haemoglobin (Hb), packed cell volume (PCV), mean corpuscular haemoglobin concentration (MCHC) and higher total leukocyte count (TLC) and mean corpuscular volume (MCV). Incidence of haemoprotozoan infection between the breeds differed significantly (P<0.05). Haemoprotozoan infections were recorded significantly higher (P0.05). The prevalence of B. bigemina in bovines was associated with various risk factors namely age, season and breed (p£0.05). Sex wise females recorded apparently higher infection rates than males. The multivariate logistic regression models showed that the risk of babesiosis was significantly higher in rainy season (OR=5.18, P=0.003) followed by summer (OR=3.9, P=0.019) compared to winter season. Conversely, in buffaloes, the risk of babesiosis was significantly higher in summer season (OR=9.0, P=0.004) followed by rainy (OR=7.43, P=0.008) compared to winter season. The risk for anaplasmosis in buffaloes increased by 3.46 times (OR=3.64, p=0.027) in non descriptive breed compared to well defined breed.