A mitochondrial DNA variant 10398G>A in breast cancer among South Indians: An original study with meta-analysis

The m.10398G > A polymorphism in the MT-ND3 gene has been linked to the manifestation of several neurodegenerative disorders and cancers. Several research groups have analyzed the association between m.10398G > A polymorphism and breast cancer; however, the results do not follow a consensus. We have studied this polymorphism in three Dravidian populations from South India. Analysis on 716 cases and 724 controls found no association between m.10398G > A polymorphism and breast cancer [OR = 0.916 (0.743–1.128); P = 0.409]. Menopausal stratification also revealed no significant association in either pre-menopausal or post-menopausal breast cancer groups. In addition, we undertook a meta-analysis on 16 study groups, comprising a total of 7202 cases and 7490 controls. The pooled odds ratio suggested no significant association of m.10398G > A substitution with breast cancer [OR = 1.016 (0.85–1.22); P = 0.86]. In conclusion, there is no evidence of association between m.10398G > A polymorphism and breast cancer risk among South Indian women. Meta-analysis suggested no overall correlation between this polymorphism and breast cancer risk.     

Strong Impact of TGF-β1 Gene Polymorphisms on Breast Cancer Risk in Indian Women: A Case-Control and Population-Based Study

Introduction

TGF-β1 is a multi-functional cytokine that plays an important role in breast carcinogenesis. Critical role of TGF-β1 signaling in breast cancer progression is well documented. Some TGF-β1 polymorphisms influence its expression; however, their impact on breast cancer risk is not clear.

Methods

We analyzed 1222 samples in a candidate gene-based genetic association study on two distantly located and ethnically divergent case-control groups of Indian women, followed by a population-based genetic epidemiology study analyzing these polymorphisms in other Indian populations. The c.29C>T (Pro10Leu, rs1982073 or rs1800470) and c.74G>C (Arg25Pro, rs1800471) polymorphisms in the TGF-β1 gene were analyzed using direct DNA sequencing, and peripheral level of TGF-β1 were measured by ELISA.

Results

c.29C>T substitution increased breast cancer risk, irrespective of ethnicity and menopausal status. On the other hand, c.74G>C substitution reduced breast cancer risk significantly in the north Indian group (p = 0.0005) and only in the pre-menopausal women. The protective effect of c.74G>C polymorphism may be ethnicity-specific, as no association was seen in south Indian group. The polymorphic status of c.29C>T was comparable among Indo-Europeans, Dravidians, and Tibeto-Burmans. Interestingly, we found that Tibeto-Burmans lack polymorphism at c.74G>C locus as true for the Chinese populations. However, the Brahmins of Nepal (Indo-Europeans) showed polymorphism in 2.08% of alleles. Mean TGF-β1 was significantly elevated in patients in comparison to controls (p<0.001).

Conclusion

c.29C>T and c.74G>C polymorphisms in the TGF-β1 gene significantly affect breast cancer risk, which correlates with elevated TGF-β1 level in the patients. The c.29C>T locus is polymorphic across ethnically different populations, but c.74G>C locus is monomorphic in Tibeto-Burmans and polymorphic in other Indian populations.     

Carvacrol modulates instability of xenobiotic metabolizing enzymes and downregulates the expressions of PCNA,MMP-2, and MMP-9 during diethylnitrosamine-induced hepatocarcinogenesis in rats

Vascular calcification (VC) is highly associated with increased morbidity and mortality in patients with advanced chronic kidney disease. Paracrine/autocrine factors such as vasoactive peptides are involved in VC development. Here, we investigated the expression of the novel peptide C-type natriuretic peptide (CNP) in the vasculature, tested its ability to prevent VC in vivo and in vitro, and examined the mechanism involved. Rat aortic VC was induced by vitamin D3 plus nicotine (VDN). CNP (500 ng/kg/h) was administered by mini-osmotic pump. Calcification was examined by von Kossa staining; CNP and cyclic guanosine monophosphate (cGMP) contents were detected by radioimmunoassay, and mRNA and protein levels were examined by real-time PCR and Western blot analysis in aortas and calcified vascular smooth muscle cells (VSMCs). VDN-treated rat aortas showed higher CNP content and decreased expression of its receptor natriuretic peptide receptor B, along with increased vascular calcium deposition and alkaline phosphatase (ALP) activity. Low CNP levels were accompanied by increased vascular calcium deposition and ALP activity in VDN-treated rats when compared to vehicle treatment, which was further confirmed in cultured VSMCs. Administration of CNP greatly reduced VC in VDN-treated aortas compared with controls, which was confirmed in calcified VSMCs. The decrease in alpha-actin expression was ameliorated by CNP in vitro. Moreover, protein expression levels of osteopontin (OPN) were significantly up-regulated in calcified aortas, and CNP increased OPN expression in calcified aortas. Furthermore, CNP downregulated OPN and bone morphogenic protein 2 (BMP-2) expression in calcified aortas and VSMCs. Modulation of OPN and BMP-2 expression by CNP and the beneficial effects of CNP on calcified VSMCs were blocked significantly by protein kinase G inhibitor H7. Impaired local endogenous CNP and its receptor system may be associated with increased mineralization in vivo in rat aortas with VC, and administration of CNP inhibits VC development in vivo and in vitro, at least in part, via a cGMP/PKG pathway.     

Effect of long chain fatty acids on triacylglycerol accumulation,fatty acid composition and related gene expression in primary cultured bovine satellite cells

Abstract

This study was conducted to determine the effects of long chain fatty acids (LCFAs) on triacylglycerol (TAG) content, as well as on genes associated with lipid synthesis and fatty acid composition in bovine satellite cells. Both saturated (palmitic and stearic) and unsaturated (oleic and linoleic) fatty acids stimulated the TAG accumulation at a concentration of 100?µM and oleate increased it significantly more than stearate and palmitate. The results revealed that the lipid droplet formation was markedly stimulated by linoleate and oleate at 100?µM. Compared to control, the expressions of adipose triglyceride lipase, carnitine acyltransferase 1 and the fatty acid translocase 36 were upregulated by LCFAs. All the fatty acids also significantly increased diacylglycerol acyltransferase 2 than the untreated control (p?<?0.05). The monounsaturated fatty acids significantly increased (p?<?0.05) in response to oleate and linoleate compared to the control as did the polyunsaturated fatty acids (p?<?0.05), in addition to stearate, linoleate and oleate. In contrast, saturated fatty acids were significantly decreased in the oleate and linoleate-treated groups. The study results contribute to our enhanced understanding of LCFAs’ regulatory roles on the bovine cell lipid metabolism.     

Deterioration of cashewnuts in Kerala state of India due to insect infestation along with the fungal incidence

During the months of Feburary–March 2007, infected and diseased samples of cashewnuts were collected from the Kerala district of India in and around Cochin and Ernaculum. Severe damage of the nuts was observed due to the insect Trogoderma granarium which feeds on the entire soft portion of the kernel. The nuts were also observed to be infected by a fungal organism Alternaria geophila which made this nutritious nut unfit for human consumption.     

Peri-natal growth retardation rate and fat mass accumulation in mice lacking Dip2A is dependent on the dietary composition

Disco-interacting protein 2 is a highly conserved three-domain protein with two tandem Adenylate-forming domains. It is proposed to influence the processes involved in neuronal development by influencing lipid metabolism and remains to be characterized. In this study, we show that Disco-interacting protein 2a null mice do not exhibit overt phenotype defects. However, the body composition differences were observed in these mice under different dietary regimens. The neutral lipid composition of two different diets was characterized, and it was observed that the new-born mice grow relatively slower than the wild-type mice with delayed appearance of features such as dentition when fed with high-triacylglycerol NIN-formulation diet. The high-diacylglycerol Safe-formulation diet was found to accumulate more fat mass in mice than those fed with high-triacylglycerol NIN-formulation diet beyond 10 months. These findings point to a proposed relationship between dietary components (particularly the lipid composition) and body composition along with the growth of neonates in mice lacking the gene Disco-interacting protein 2a.

     

Molecular docking analysis of COX-2 for potential inhibitors

Cyclooxygenase-2 (COX-2) is liked with breast cancer. Therefore, it is of interest to design and develop new yet effective compounds against COX-2 from medicinal plants such as the natural alkaloid compounds. We document the optimal binding features of aristolochicacid with COX-2 protein for further consideration.     

In vitro antioxidant activity of banana (Musa spp. ABB cv. Pisang Awak)

The methanolic extract of Musa ABB cv Pisang Awak was investigated for the polyphenolic contents and antioxidant activity. The total phenol and flavonoid contents of the fruit extract were found to be 120 mg gallic acid equivalents (GAE) and 440 mg quercetin equivalents (QE)/100 g of sample dry weight, respectively. The antioxidant activity of the Pisang Awak methanol extract (PAME) (20-500 microg/ml) was determined using 1,1-diphenyl-2-picryl hydrazyl (DPPH) radical scavenging activity, reducing capacity, 2-2'-azinobis-3-ethylbenzothiozoline-6-sulfonic acid (ABTS) radical cation decolourization and hydroxyl radical scavenging capacity (OH*). The EC50 values of DPPH, ABTS and OH* activities of the PAME and butylated hydroxy toluene (BHT) were found to be 65 and 9 microg/ml, 29 and 6 microg/ml, 36 and 42 microg/ml respectively. The reducing capacity increased with increasing concentration (31.5-1000 mg/ml) of the fruit extract and the activity was comparable with the standard BHT. The high performance thin layer chromatography (HPTLC) analysis of the extract revealed the presence of polyphenols. The strong and positive correlations were obtained between total phenol/flavonoid contents (R2 = 0.693-1.0) and free radical scavenging ability was attributed to the polyphenols as the major antioxidants.     

Chemopreventive and therapeutic modulation of green tea polyphenols on drug metabolizing enzymes in 4-Nitroquinoline 1-oxide induced oral cancer

Oral cancer is one of the most common cancers in the world. Drugs can modulate the expression of drug metabolizing enzymes and are useful in chemoprevention as well as therapy in cancer. 4-Nitroquinoline 1-oxide (4-NQO) is used to induce oral cancer in the present study. In the present investigation, the effect of green tea polyphenols (GTP) on the activities of cytochrome b5, cytochrome P450, cytochrome b5 reductase (cyt b5 R), cytochrome P450 reductase (cyt P450 R), arryl hydrocarbon hydroxylase (AHH), DT-diaphorase (DTD)(Phase I enzymes) and glutathione-S-transferase (GST) and UDP-glucuronyl transferase (UDP-GT) (Phase II enzymes) were assessed in tongue and oral cavity. In induced rats, there was a decrease in the activity of Phase II enzymes and an increase in the activity of Phase I enzymes. On supplementation of GTP by both simultaneous and post treatment mode (200mg/kg) there was a significant increase in the activity of GST and UDP-GT and a significant decrease in the activity of Phase I enzymes. There was a significant decline in the number of tumors, tumor volume and oral squamous cell carcinoma in both simultaneous and post GTP treated animals relative to 4-NQO induced animals; on comparing simultaneous and post GTP treated animals the number of tumors, tumor volume and oral squamous cell carcinoma was significantly reduced in post treated animals. Thus inhibition of Phase I enzymes could be attributed to the protective efficacy of GTP which deactivates carcinogen and GTP induced the expression of Phase II enzymes that detoxifies the 4-NQO. It can be proposed that GTP plays role as a detoxifying agent by which its modulating role prevented/inhibited the formation of tumor.