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Accumulating evidence demonstrates that the host genome's epigenetic modifications are essential for living organisms to adapt to extreme conditions. DNA methylation, covalent modifications of histone and interassociation of noncoding RNAs facilitate the cellular manifestation of epigenetic changes in the genome. Out of various factors involved in the epigenetic programming of the host, noncoding RNAs (ncRNAs) such as microRNA (miRNA), long noncoding RNA (lncRNA), circular RNA, snoRNA and piRNA are new generation noncoding molecules that influence a variety of cellular processes like immunity, cellular differentiation and tumor development. During tumor development, temporal changes in miRNA/lncRNA rheostat influence sterile inflammatory responses accompanied by the changes in the carcinogenic signaling in the host. At the cellular level, this is manifested by the upregulation of inflammasome and inflammatory pathways, which promotes cancer-related inflammation. Given this, we discuss the potential of lncRNAs, miRNAs, circular RNA, snoRNA and piRNA in regulating inflammation and tumor development in the host.

The biological applications of germylenes remain an unconceivable domain owing to their unstable nature. We report the isolation of air, water, and culture-medium stable germylene DPMGeOH (3) and its potential biological application (DPM = dipyrromethene ligand). Compound 3 exhibits antiproliferative effects comparable to that of cisplatin in human cancer cells. The cytotoxicity of compound 3 on normal epithelial cells is minimal and is similar to that of the currently used anti-cancer drugs. These findings provide a framework for a plethora of biological studies using germylenes and have important implications for low-valent main group chemistry.

Silver coating of different thicknesses ranging from 5 to 20 nm was deposited on the Ti6Al4V substrate using DC sputtering followed by thermal annealing at 750 °C for 15 min in an ambient environment. The surface topography and elemental composition of annealed samples were analyzed using different characterization techniques. The silver ions (Ag+) concentration released from the modified titanium surface was calculated through inductive coupled plasma mass spectroscopy (ICP-MS). The plate counting method was used to quantify the bacteria-killing potential of modified titanium surface against Escherichia coli (E. coli), Staphylococcus aureus (S. aureus), Fluoroquinolones-resistant Salmonella typhi (FRST) and Methicillin-resistant Staphylococcus aureus (MRSA) bacteria. The cell membrane integrity study of E. coli and S. aureus bacterium was done qualitatively using scanning electron microscopy and further confirmed with fluorescence microscopy. Due to thermal annealing, polygonal shaped oxide nanoparticles were formed on the titanium substrate. Moreover, the surface topography of modified titanium surface changes with the thickness of the silver film. In order to check the cytotoxic effect of modified titanium surface, mouse fibroblast cells (NIH3T3) were used for 3‑(4,5‑dimethylthiazol‑2‑yl)‑2,5‑diphenyltetrazolium bromide (MTT) assay. The limited (

Breast cancer is the most common cancer among Indian women with a significant increase in incidence in young women. To identify risk factors for breast cancer in young women, study of BRCA1 and BRCA2 germ line mutations was done in a cohort of 204 Indian breast cancer patients. The study showed a total of 18 mutations in 2.94% of the tested patients, 44% BRCA1 and 78% BRCA2 mutations were found unique to the Indian population. Association of low penetrance genes mainly CYP17, VDR gene and AR-CAG repeat polymorphisms with breast cancer risk showed CYP17 A2 and VDR Poly-A L as high risk alleles, the risk of developing breast cancer among women carrying three high-risk alleles is 4.68 (95% confidence interval [CI]: 0.77–28.0; p for trend = 0.10) compared with women carrying none. CYP17 A2 allele was also found associated with development of breast cancer at young age and can also serve as a target for therapy. Betel quid chewing has been found as a significant and independent risk factor for developing breast cancer in North East Indian women which induces genetic alterations leading to breast carcinogenesis. Studies to assess the predictive role of various tumor markers showed that expression of p-glycoprotein in pretreatment biopsy predicts a poor clinical response to neoadjuvant chemotherapy (NACT) in patients having locally advanced breast cancer. The chemotherapy-induced toxicity (vomiting and alopecia) correlated significantly with clinical and immunohistochemical response (reduction in bcl2/bax ratio) and were found to be a cost-effective and reliable predictor of response to NACT. Androgen receptor (AR) has been identified as independent predictive marker for response to NACT in locally advanced breast cancer cases and can serve as novel therapeutic target for triple negative breast cancers.

Perturbation in the microbial population/colony index has harmful consequences on human health. Both biological and social factors influence the composition of the gut microbiota and also promote gastric diseases. Changes in the gut microbiota manifest in disease progression owing to epigenetic modification in the host, which in turn influences differentiation and function of immune cells adversely. Uncontrolled use of antibiotics, chemotherapeutic drugs, and any change in the diet pattern usually contribute to the changes in the colony index of sensitive strains known to release microbial content in the tissue micromilieu. Ligands released from dying microbes induce Toll-like receptor (TLR) mimicry, skew hypoxia, and cause sterile inflammation, which further contributes to the severity of inflammatory, autoimmune, and tumorous diseases. The major aim and scope of this review is both to discuss various modalities/interventions across the globe and to utilize microbiota-based therapeutic approaches for mitigating the disease burden.

Perturbation in the microbial population/colony index has harmful consequences on human health. Both biological and social factors influence the composition of the gut microbiota and promote gastric diseases. Changes in the gut microbiota manifest in disease progression owing to epigenetic modification in host which influences differentiation and function of immune cells adversely. Uncontrolled use of antibiotics; chemotherapeutic drugs and change in the diet pattern usually contribute to the changes in the colony index of sensitive strains known to release microbial content in the tissue micromillieu. Ligands released from dying microbes induce TLR mimicry on interaction with TLR abnormally which skew hypoxia and sterile inflammation contributing to severity of disease like IBD autoimmunity and cancer. Various modalities/interventions practiced across the globe and future strategies for microbiota based therapeutic approaches with special emphasis on tumor and inflammatory diseases are reviewed here. Therefore the major aim and scope of this manuscript is to both discuss various modalities/interventions across the globe and to design future microbiota based therapeutic approaches for mitigating the burden with special emphasis on tumor and Inflammatory diseases.

The method for fast fabrication of superhydrophobic surfaces was proposed to resist the formation of biofilm of Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus) for orthopedic and dental implants. Laser beam machining with nanosecond pulsed laser (Nd:YAG) was used to fabricate pit structure on Grade-5 Ti–6Al–4V alloy followed by annealing (at 300 °C with different time scales) in order to reduce the transition time from hydrophilic to superhydrophobic surface generation. Field emission scanning electron microscopy (FE-SEM) and X-ray diffraction (XRD) techniques were used to characterize the textured samples. The surface wettability of plain and textured samples was measured by the sessile drop method using goniometer. The biofilm formation was qualitatively and quantitatively evaluated by FE-SEM and crystal violet binding assay, respectively. The biofilm formation was observed on plain (hydrophilic) surface for both the types of bacteria, whereas significantly less biofilm formation was observed on the laser textured (superhydrophobic) surfaces. The proposed method helps in reducing the risk of infection associated with implants without using cytotoxic bactericidal agents.

The clinical course of HIV-1 varies greatly among infected individuals. Despite extensive research, virus factors associated with slow-progression remain poorly understood. Identification of unique HIV-1 genomic signatures linked to slow-progression remains elusive. We investigated CpG dinucleotide content in HIV-1 envelope gene as a potential virus factor in disease progression. We analysed 1808 HIV-1 envelope gene sequences from three independent longitudinal studies; this included 1280 sequences from twelve typical-progressors and 528 sequences from six slow-progressors. Relative abundance of CpG dinucleotides and relative synonymous codon usage (RSCU) for CpG-containing codons among HIV-1 envelope gene sequences from typical-progressors and slow-progressors were analysed. HIV-1 envelope gene sequences from slow-progressors have high-CpG dinucleotide content and increased number of CpG-containing codons as compared to typical-progressors. Our findings suggest that observed differences in CpG-content between typical-progressors and slow-progressors is not explained by differences in the mononucleotide content. Our results also highlight that the high-CpG content in HIV-1 envelope gene from slow-progressors is observed immediately after seroconversion. Thus CpG dinucleotide content of HIV-1 envelope gene is a potential virus-related factor that is linked to disease progression. The CpG dinucleotide content of HIV-1 envelope gene may help predict HIV-1 disease progression at early stages after seroconversion.

The major challenge faced in biomedical field is the formation of biofilm on polymer devices like catheters. It is important to functionalize the biomedical devices with a bactericidal agent through an easy and safe process in order to protect them from bacterial attack. In this article, the new method of impregnation of silver nanoparticles (AgNPs) into polymer film was proposed and tested against bacterial cells. The different sizes of silver nanoparticles were embedded in polystyrene film using thermal annealing and soft molding technique. Silver films having different thickness were deposited on the highly polished machinable glass ceramic (MACOR) substrate using direct current (DC) sputtering and subjected to at 750 °C for 15 min. After the heat treatment, AgNPs were formed on MACOR sample. It was then characterized using field emission scanning electron microscope (FE-SEM). Image-J software was used to analysed shape, size and distribution of AgNPs. The spin coating method was adopted to coat polystyrene film on to MACOR substrate supported AgNPs and allow it to cure for 24 h. After curing, the polystyrene film was peeled off and finally, AgNPs got transferred to polystyrene film. The AgNPs embedded polystyrene film was analyzed using FE-SEM and atomic force microscopy (AFM). Spread plate (plate counting) method was used to evaluate the bacterial killing potential of modified polystyrene film against Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus) bacteria. The modified polystyrene film shows effective antibacterial ability against both the types of bacteria compared to the plain polystyrene surface.

Widespread use of tobacco and betel quid consumption and a high incidence of tobacco-associated aerodigestive tract cancers have been reported in different ethnic groups from several regions of Northeast (NE) India. This study was done to explore the possibility of phase II metabolic enzymes being responsible for the high prevalence of cancers in this region of India.Samples from 370 cases with oral, gastric, and lung cancers and 270 controls were analyzed for polymorphism of glutathione-S-transferase (GST) genes using polymerase chain reaction-restriction fragment length polymorphism-based methods.Tobacco smoking and betel quid chewing were found to be high risk factors for oral and lung cancers but not for gastric cancer, whereas tobacco chewing was found to be a risk factor for oral cancer but not for gastric or lung cancer. The variant genotypes of GSTP1 were not associated with any of the aerodigestive tract cancers. GSTT1 and GSTM1 null genotypes appeared to play a protective role for lung cancer (odds ratio [OR] = 0.47, 95% confidence interval [95% CI]: 0.24-0.93, p = 0.03) and (OR = 0.52, 95% CI: 0.28-0.96, p = 0.04), but they were not associated with oral and gastric cancers. However, when data was analyzed in different geographic regions the GSTT1 null genotype was found to be a significant risk factor for oral (OR = 2.58, 95% CI 1.01-6.61, p = 0.05) as well as gastric cancer (OR = 3.08, 95% CI 1.32-7.19, p = 0.009) in samples obtained from the Assam region of NE India. This is the first study on the association of GST polymorphisms and aerodigestive tract cancers in the high-risk region of NE India.

Detoxifying glutathione S-transferase (GST) gene polymorphisms show variation in different ethnic populations. GST detoxifies and metabolizes carcinogens, including oxygen free radicals. GST polymorphisms have been associated with susceptibility to different diseases. In the current study, allelic polymorphisms of GSTM1 and GSTT1 were analyzed in three ethnic groups of North East (NE) India where a high prevalence of various cancers and other diseases such as hypertension, tuberculosis, and asthma have been reported.We compared the prevalence of GSTT1 and GSTM1 deletion genotypes, which were determined by multiplex polymerase chain reaction, in 422 voluntary, healthy NE Indians with those of other populations. The data was statistically analyzed.The GSTT1-null genotype was found in 51%, 34.3%, and 15.7% of individuals (from Mizoram, Sikkim, and Assam regions of NE India, respectively), whereas the GSTM1-null genotype was found in 46.9%, 46%, and 35% of individuals from the same areas.The NE Indians differ from the rest of the Indian population with reference to genotypic distribution of GST polymorphisms but the frequency was found to be similar to that which has been reported from China. This may explain the hypothesis of the common ancestral origin of both the NE Indians and the Chinese and a higher frequency of cancers such as gastric, esophageal, and oral cancers, which has been reported from these regions. This study establishes baseline frequency data for GST polymorphisms for future case control studies on the role these polymorphisms play with regard to diseases. The results presented here provide the first report on GST polymorphisms in the NE Indian population.

Polymorphisms in DNA repair and cell cycle genes contribute to increased breast cancer (BC) risk. Their association and interaction in relation to betel quid and tobacco chewing habits need exhaustive multi-analytical investigation to explain BC predisposition due to DNA damage. Polymorphism in TP53-72Arg>Pro, RAD51-135G>C, BRCA2, and CCND1-G870A were examined in 204 BC cases and 217 controls from Northeast Indian population. Multifaceted analytic approaches were used to explore relationships between polymorphisms, tobacco history, and BC susceptibility. Betel quid chewing was identified as the predominant risk factor. CCND-AA and dominant model showed protection towards BC in betel quid chewer (BQC) [(0.28 (0.10–0.77), 0.01 and 0.32 (0.12–0.81), 0.01)] and non-betel quid chewers (NBQC) [(0.26 (0.09–0.78), 0.01 and 0.37 (0.16–0.87), 0.02)]. TP53-Pro/Pro genotype showed protection towards BC in NBQC (0.29 (0.10–0.81), p = 0.01) and (0.51 (0.32–0.80), p = 0.003, respectively). RAD51-C allele was associated with BC risk (2.03 (1.26–3.30) 0.002) in BQC. Two BQC cases had BRCA2 8415G>T:K2729N mutation in Exon18. MDR analysis showed best four locus model with TBA 0.6765 (0.005) and CVC of 10/10 in NBQC. Interaction diagram concurred the interactions between TP53 and RAD51 (1.32 %) with independent effect (1.89 %) of CCND1in NBQC. In CART analysis, BQC with CCND1 GG genotype were at risk (OR = 33.0; 95 % CI = 6.08–179.07), p

Betel Quid (BQ) chewing independently contributes to oral, hepatic and esophageal carcinomas. Strong association of breast cancer risk with BQ chewing in Northeast Indian population has been reported where this habit is prodigal. We investigated genomic alterations in breast cancer patients with and without BQ chewing exposure. Twenty six BQ chewers (BQC) and 17 non BQ chewer (NBQC) breast cancer patients from Northeast India were analyzed for genomic alterations and pathway networks using SNP array and IPA. BQC tumors showed significantly (P30%) were seen in 27 regions. Three networks were significant in common regions with key roles of PTK2, RPN2, EMR3, VAV1, NNAT, MUC16, MYC and YWHAZ genes. These data show that breast cancer arising by environmental carcinogens exemplifies genetic alterations differing from those observed in the non exposed ones. A number of genetic changes are shared in both tumor groups considered as crucial in breast cancer progression.

Complex disease such as cancer results from interactions of multiple genetic and environmental factors. Studying these factors singularly cannot explain the underlying pathogenetic mechanism of the disease. Multi-analytical approach, including logistic regression (LR), classification and regression tree (CART) and multifactor dimensionality reduction (MDR), was applied in 188 lung cancer cases and 290 controls to explore high order interactions among xenobiotic metabolizing genes and environmental risk factors. Smoking was identified as the predominant risk factor by all three analytical approaches. Individually, CYP1A1*2A polymorphism was significantly associated with increased lung cancer risk (OR = 1.69;95%CI = 1.11–2.59,p = 0.01), whereas EPHX1 Tyr113His and SULT1A1 Arg213His conferred reduced risk (OR = 0.40;95%CI = 0.25–0.65,p

Polymorphisms in genes encoding detoxification enzymes have been suggested as susceptibility factors for many solid tumors. However, their association with hematological malignancies is controversial. A case-control study was done to determine the association between glutathione S-transferase M1 (GSTM1), GSTT1, GSTP1, EPHX1, and p53 codon 72 polymorphisms as risk factors in 120 adult acute myeloid leukemia (AML) cases and 202 healthy controls by polymerase chain reaction-restriction fragment length polymorphism techniques. Data were analyzed using χ(2) and conditional logistic regression model. None of the polymorphisms studied alone was associated with increased risk for AML. However, the frequency of GSTT1 null genotype was higher among controls (28.7%) than AML cases (21.6%), which showed a protective effect of the null genotype (odds ratio = 0.58, 95% confidence interval: 0.33-1.05, p = 0.07). In a combined analysis, both EPHX1 (His113His) and GSTP1 (Ile/Val) genes imparted a fourfold risk for adult AML but did not reach statistical significance (odds ratio = 4.22, 95% confidence interval: 0.992-17.99, p = 0.05). These findings suggest that the etiology of adult AML cannot be explained by polymorphism at a single locus, perhaps because of complexity involved in the metabolism of diverse xenobiotic compounds, and therefore, multiple gene-gene interactions should be investigated to predict the risk of AML.

Northeast region of India shows high incidence of tobacco-related cancer with widespread consumption of betel quid and tobacco in different forms. There is an increasing incidence of breast cancer and eminent use of tobacco in females in this region. Thus, we analysed the role of tobacco exposure and polymorphisms in detoxification enzymes in breast cancer risk. Polymorphisms in five gene variants (GSTT1, GSTM1, GSTP1, TP53 and CYP17) and four environmental exposure variables (tobacco smoking, tobacco chewing, betel quid chewing, alcohol) were analysed in 117 breast cancer cases and 174 cancer free controls. Multifactor dimensionality reduction identified betel quid chewing as the single main risk factor and women with betel quid chewing history had five times the risk of developing breast cancer [4.78 (2.87–8.00) 0.001]. In logistic regression analysis, GSTT1 null and GSTM1 null genotypes conferred 41% less [0.59 (0.34–1.03) 0.06] and 55% less [0.58 (0.30–1.02) 0.05] reduced risk to breast cancer, respectively. However, the risk increased in women with GSTP1 variant G allele which conferred 1.43 times [(0.96–2.11) 0.07] more risk to breast cancer. In conclusion this study suggests betel quid chewing as a significant risk factor for developing breast cancer. Moreover, the lack of detoxification enzymes GSTT1 and GSTM1 are associated with reduced breast cancer risk.

SUMMARY The incidence of esophageal squamous cell carcinoma (ESCC) is very high in the northeast region of India. An earlier study from China and Iran suggested that mutations in BRCA2 gene may play a role in the etiology of familial ESCC. However, the frequency of BRCA2 gene germ line mutations and its contribution to risk of familial aggregation of ESCC in high-risk region of India are not known. In the current study of 317 cases of esophageal cancer, 92 (29%) cases had a family history of esophageal and/or other cancers. Of these 92 patients, 45 (49%) patients had a family history of esophageal cancer. The risk of developing esophageal cancer was higher in cases where family history showed occurrence of cancers in first-degree relatives (odds ratio [OR]: 3.1; confidence interval [CI]: 1.9–5.3) than in second-degree relatives (OR: 1.3; CI: 0.25–3.2). Moreover, the risk of developing esophageal cancer was higher in subjects whose predegree suffered from esophageal cancer (OR: 2.4; CI: 1.1–4.1) than from any other cancers (OR: 1.1; CI: 0.32–3.3). The subjects with family history of cancer were more likely to develop ESCC if they were tobacco chewers (OR: 4.2; CI: 2.1–5.8) and betel quid users (OR: 3.6; CI: 1.8–4.6). Screening for mutations of the BRCA2 gene in the germ line DNA was carried out for 20 familial and 80 nonfamilial ESCC patients. One hundred unrelated healthy controls from the same population were included in this study. Nonsynonymous variants in exon 18 (K2729N) and exon 27 (I3412V) of BRCA2 gene were found in 3 of 20 patients with familial ESCC. No sequence alterations were found in 80 nonfamilial ESCC cases (P= 0.01) and 100 healthy controls (P= 0.0037), suggesting that germ line BRCA2 gene mutation may play a role in familial aggregation of ESCC in high-risk region of India.

Background A large number of distinct mutations in the BRCA1 and BRCA2 genes have been reported worldwide, but little is known regarding the role of these inherited susceptibility genes in breast cancer risk among Indian women. We investigated the distribution and the nature of BRCA1 and BRCA2 germline mutations and polymorphisms in a cohort of 204 Indian breast cancer patients and 140 age-matched controls. Method Cases were selected with regard to early onset disease (≤40 years) and family history of breast and ovarian cancer. Two hundred four breast cancer cases along with 140 age-matched controls were analyzed for mutations. All coding regions and exon-intron boundaries of the BRCA1 and BRCA2 genes were screened by heteroduplex analysis followed by direct sequencing of detected variants. Results In total, 18 genetic alterations were identified. Three deleterious frame-shift mutations (185delAG in exon 2; 4184del4 and 3596del4 in exon 11) were identified in BRCA1, along with one missense mutation (K1667R), one 5'UTR alteration (22C>G), three intronic variants (IVS10-12delG, IVS13+2T>C, IVS7+38T>C) and one silent substitution (5154C>T). Similarly three pathogenic protein-truncating mutations (6376insAA in exon 11, 8576insC in exon19, and 9999delA in exon 27) along with one missense mutation (A2951T), four intronic alterations (IVS2+90T>A, IVS7+75A>T, IVS8+56C>T, IVS25+58insG) and one silent substitution (1593A>G) were identified in BRCA2. Four previously reported polymorphisms (K1183R, S1613G, and M1652I in BRCA1, and 7470A>G in BRCA2) were detected in both controls and breast cancer patients. Rare BRCA1/2 sequence alterations were observed in 15 out of 105 (14.2%) early-onset cases without family history and 11.7% (4/34) breast cancer cases with family history. Of these, six were pathogenic protein truncating mutations. In addition, several variants of uncertain clinical significance were identified. Among these are two missense variants, one alteration of a consensus splice donor sequence, and a variant that potentially disrupts translational initiation. Conclusion BRCA1 and BRCA2 mutations appear to account for a lower proportion of breast cancer patients at increased risk of harboring such mutations in Northern India (6/204, 2.9%) than has been reported in other populations. However, given the limited extent of reported family history among these patients, the observed mutation frequency is not dissimilar from that reported in other cohorts of early onset breast cancer patients. Several of the identified mutations are unique and novel to Indian patients.

[corrected] Mifepristone is a synthetic antiprogestin which terminates early pregnancy. Since it interferes with the progesterone maintained decidua, we compared the effect of mifepristone on oestrogen and progesterone receptors, and on the biotransformation of these hormones in normal and deciduous uterus.Ovariectomized rats were treated with an oestrogen-progesterone hormone regimen and deciduoma was induced by trauma in one horn of the rat uterus while the other served as a control under an identical hormonal milieu. Hormone receptor and biotransformation studies were done using radiolabelled oestradiol and progesterone with high specific activity.The artificially formed decidual tissue was comparable with that of early pregnancy. Mifepristone replenished oestrogen and progesterone receptors which were suppressed by progesterone in both the normal and decidualized uterine horns. Inhibition of oestrogen receptors by progesterone correlated with decreased oestradiol levels at the site of action. Metabolism of progesterone to less potent compounds was promoted by mifepristone. The enzymatic activities of 17beta-hydroxysteroid dehydrogenase (which metabolizes oestradiol), and 20alpha-hydroxysteroid dehydrogenase and 5alpha-reductase (which metabolize progesterone) were altered by mifepristone.The effect of mifepristone in varying the hormone receptor population and the availability of different levels of active metabolites of ovarian hormones have an Important role in the antiprogestin action of mifepristone.

Background North-east India has always been a ‘hotspot’ for population geneticists because of its unique, strategic geographic location and the presence of linguistically, culturally and demographically diverse populations practicing various tobacco habits. This region reports a high incidence of breast cancer in females with a history of extensive exposure to tobacco. Therefore, this population is constantly exposed to a high level of genotoxic stress. Accumulation of multiple and discrete genetic events during tobacco exposure can combine to drive breast cancer pathogenesis. Direct analysis of the tumor genome can reveal the genomic events accumulated during tumor progression. Hence, we investigated genomic alterations in breast cancer patients with tobacco exposure.