Insights for precision oncology from the integration of genomic and clinical data of 13,880 tumors from the 100,000 Genomes Cancer Programme.

The Cancer Programme of the 100,000 Genomes Project was an initiative to provide whole-genome sequencing (WGS) for patients with cancer, evaluating opportunities for precision cancer care within the UK National Healthcare System (NHS). Genomics England, alongside NHS England, analyzed WGS data from 13,880 solid tumors spanning 33 cancer types, integrating genomic data with real-world treatment and outcome data, within a secure Research Environment. Incidence of somatic mutations in genes recommended for standard-of-care testing varied across cancer types. For instance, in glioblastoma multiforme, small variants were present in 94% of cases and copy number aberrations in at least one gene in 58% of cases, while sarcoma demonstrated the highest occurrence of actionable structural variants (13%). Homologous recombination deficiency was identified in 40% of high-grade serous ovarian cancer cases with 30% linked to pathogenic germline variants, highlighting the value of combined somatic and germline analysis. The linkage of WGS and longitudinal life course clinical data allowed the assessment of treatment outcomes for patients stratified according to pangenomic markers. Our findings demonstrate the utility of linking genomic and real-world clinical data to enable survival analysis to identify cancer genes that affect prognosis and advance our understanding of how cancer genomics impacts patient outcomes.

Interplay between PI3K/AKT pathway and heart disorders.

The PI3K/AKT signaling has crucial role in the regulation of numerous physiological functions through activation of downstream effectors and modulation of cell cycle transition, growth and proliferation. This pathway participates in the pathogenesis of several human disorders such as heart diseases through regulation of size and survival of cardiomyocytes, angiogenic processes as well as inflammatory responses. Moreover, PI3K/AKT pathway participates in the process of myocardial injury induced by a number of substances such as H2O2, Mercury, lipopolysaccharides, adriamycin, doxorubicin and epirubicin. In this review, we describe the contribution of this pathway in the pathoetiology of myocardial ischemia/reperfusion injury and myocardial infarction, heart failure, cardiac hypertrophy, cardiomyopathy and toxins-induced cardiac injury.

Whole-genome sequencing reveals host factors underlying critical COVID-19.

Critical COVID-19 is caused by immune-mediated inflammatory lung injury. Host genetic variation influences the development of illness requiring critical care1 or hospitalization2-4 after infection with SARS-CoV-2. The GenOMICC (Genetics of Mortality in Critical Care) study enables the comparison of genomes from individuals who are critically ill with those of population controls to find underlying disease mechanisms. Here we use whole-genome sequencing in 7,491 critically ill individuals compared with 48,400 controls to discover and replicate 23 independent variants that significantly predispose to critical COVID-19. We identify 16 new independent associations, including variants within genes that are involved in interferon signalling (IL10RB and PLSCR1), leucocyte differentiation (BCL11A) and blood-type antigen secretor status (FUT2). Using transcriptome-wide association and colocalization to infer the effect of gene expression on disease severity, we find evidence that implicates multiple genes-including reduced expression of a membrane flippase (ATP11A), and increased expression of a mucin (MUC1)-in critical disease. Mendelian randomization provides evidence in support of causal roles for myeloid cell adhesion molecules (SELE, ICAM5 and CD209) and the coagulation factor F8, all of which are potentially druggable targets. Our results are broadly consistent with a multi-component model of COVID-19 pathophysiology, in which at least two distinct mechanisms can predispose to life-threatening disease: failure to control viral replication; or an enhanced tendency towards pulmonary inflammation and intravascular coagulation. We show that comparison between cases of critical illness and population controls is highly efficient for the detection of therapeutically relevant mechanisms of disease.

Pharmacological effects of Raphanus caudatus in inflammation and hematopoitic system: an in vitro and in vivo investigation.

The pods of Radish are known as Raphanus caudatus that belongs to the family Brassicaceae. They are commonly known as Mungra or Sungra in Pakistan, while the common English name for this species is Rat-tailed radish. This variety of radish is unique and less tested for pharmacological as well as toxicological potential. In the current research, the ethanol extract of pods was assessed for anti-inflammatory potential in vitro and in vivo. Furthermore the effect of plant on hematological parameters was also investigated. For in vitro study, luminol-enhanced chemiluminescence method was used while in vivo study was carried out via Acetic acid- induced Paw Edema Test in wistar rats. The extract of Raphanus caudatus indicated significant anti-inflammatory effects regarding in vitro assay. Administered tested doses (250mg, 500mg and 1000mg/kg) of plant extract showed significant reduction in rat's paw but highest in vivo anti-inflammatory effect was observed at the dose of 1000mg/kg. Moreover, in the case of hematological study, noticeable elevation of white blood cell count was observed at 500 and 1000 mg/kg. However the number of platelets was reduced in dose dependent manner.

Relationship of Obsessive-Compulsive Disorders with Religion and Psychosocial attitude among Local Medical College Students of Karachi: An epidemiological study.

OBJECTIVE: To evaluate the awareness, prevalence and attitude of medical students towards obsessive compulsive disorder. METHOD: The cross-sectional study was conducted at different medical institutions in Karachi from August to October 2018, and comprised medical students who were selected using random sampling. The participants were asked to fill demographic form as well as the obsessive compulsive disorder Yale-Brown scale-based questionnaire. Data was analysed using SPSS 23. RESULTS: Of the 1172 subjects, 602(51.4%) were aware of obsessive compulsive disorder, while 570(48.6%) were unaware. Washing, counting and arranging were higher among females than in males (p<0.004). Fear, shame and stigma were of major concerns (p<0.05). CONCLUSIONS: Awareness level of medical students regarding obsessive compulsive disorder was very low.

Repeatedly heated mix vegetable oils-induced atherosclerosis and effects of Murraya koenigii.

BACKGROUND: Statins are considered as standard drugs to control cholesterol levels, but their use is also associated with renal hypertrophy, hemorrhagic stroke, hepatomegaly, and myopathy. Murraya koenigii is an herb that is used in traditional cuisine and as a medicine in South Asia. Here we assessed the antidyslipidemic and antiatherosclerotic effects of this spice in repeated heated mix vegetable oils (RHMVO)-induced atherosclerotic models. METHODS: Aqueous extract of M. koenigii leaves (Mk LE) was prepared and its phytoconstituents were determined. Rabbits were divided into 5 groups (n = 10). Except for the control group, all the other four groups were treated with RHMVO for 16 weeks (dose = 2 ml/kg/day) to induce dyslipidemia and atherosclerosis. These groups were further treated for 10 weeks either with 300 and 500 mg/kg/day Mk LE, lovastatin, RHMVO, or left untreated. Body and organ weights were measured along with oxidative stress and tissue damage parameters. Lipid profile and hepatic function markers were studied. Atheroma measurement and histopathological examination were also performed in control and treated groups. RESULTS: Mk LE significantly (p < 0.05) attenuated RHMVO-induced dyslipidemia and atheroma formation. Furthermore, fat accumulation and lipid peroxidation in hepatic tissues were reduced by Mk LE in a dose-dependent manner. Our results indicated that the antidyslipidemic effects of Mk LE in 500 mg/kg/day dose were comparable to lovastatin. Additionally, oxidative stress markers were reduced much more significantly in Mk LE-500 than in the statin group (p < 0.05). CONCLUSIONS: This study recommends Mk LE as a potent antioxidant and lipid-lowering natural medicine that can attenuate the RHMVO-induced atherosclerotic in optimal doses and duration. Therefore, Mk LE can be accessible, cheap, and free of adverse effects alternate to statins.

Association of long-term consumption of repeatedly heated mix vegetable oils in different doses and hepatic toxicity through fat accumulation.

BACKGROUND: Hepatic diseases are one of the chief reasons for worldwide morbidity and mortality. The increased incidence in Asian countries is driving researchers to explore preventive ways from nature. It is more practical to go with healthy routine edibles like vegetable oils to avoid environmental and chemical hepatic injuries. With the use of thermally oxidized oils overproduction of reactive oxygen species (ROS) with overwhelmed cellular antioxidants defense system results in oxidative stress, the known cause of cardiovascular diseases (CVDs), cancers and neurodegenerative disorders. Little is investigated about the effect of daily used oxidized cooking oils on hepatic function changes with oxidative stress especially in the animal model that mimics the human situation. METHODS: In this study, healthy adult male rabbits of local strain were divided into 4 groups (n = 12). First, two sets of rabbits were treated with 1 and 2 ml/kg/day of repeatedly heated mix vegetable oils (RHMVO) respectively. The third set of rabbits was given 1 ml/kg/day of single time heated mix vegetable oils (STHMVO) and the fourth set of rabbits served as controls and fed with normal rabbit diet to for 16 weeks. Serum liver function markers including total-protein, albumin, serum glutamic-oxaloacetic transaminase (SGOT), serum glutamic-pyruvic transaminase (SGPT) and alkaline phosphatase (ALP) along with the activity of hepatic antioxidant-enzymes including superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) and malondialdehyde (MDA) for lipid peroxidation were compared among different groups of rabbits. Histopathological examination was performed for all four groups. RESULTS: Significantly (p < 0.05) elevated hepatic enzymes and MDA levels, with lower total protein, serum albumin, GPx, SOD and CAT levels were found in high and low doses RHMVO treated groups, in comparison to control. In the STHMVO group, all mentioned markers were insignificantly changed. Accumulation of liver fat in low and high dose oil-treated groups was further confirmed under the microscopic examination of liver tissues, presented significant fat accumulation in liver tissues, in addition, 40-60% increased oxidative stress compared to control, in a dose-dependent manner. CONCLUSIONS: These results conclude that consumption of thermally oxidized mix vegetable oils for longer duration can impair the liver function and destroy its histological structure significantly through fat accumulation and oxidative stress both in high as well as low doses.

Substance P: A neuropeptide involved in the psychopathology of anxiety disorders.

Substance P (SP) is the most widely distributed neuropeptide in central nervous system (CNS) where it participates in numerous physiological and pathophysiological processes including stress and anxiety related behaviors. In line with this notion, brain areas that are thought to be involved in anxiety regulation contains SP and its specific NK1 receptors. SP concentration in different brain regions alters with the exposure of stressful stimulus and affected NK1 receptor binding is observed. SP is released in response to a stressor, which produces anxiogenic effects via activation of hypothalamic-pituitary-adrenal (HPA) axis, resulting in the liberation of cortisol. Moreover, SP is also involved in the activation of the sympathetic nervous system via stimulation of locus coeruleus (LC). This sympathetic surge initiates cortisol discharge by activation of HPA axis, representing the indirect anxiogenic effect of SP. Besides the aforementioned regions, SP also has an impact on other brain regions known to be involved in stress and anxiety mechanisms, including amygdala, lateral septum (LS), periaqueductal gray (PAG), ventromedial nucleus of the hypothalamus (VMH), and bed nucleus of stria terminalis (BNST). Thus, SP acts as an important neuromodulator in various brain regions in stress and anxiety response. Consistent with the above statement, SP makes a robust link in the psychopathology of anxiety disorders. As SP concentration is found elevated in stressed conditions, several studies have reported that the pharmacological antagonism or genetic depletion of NK-1 receptors results in the anxiolytic response making them a suitable therapeutic target for the treatment of stress and anxiety related disorders.

Oxidative stress and lipid per-oxidation with repeatedly heated mix vegetable oils in different doses in comparison with single time heated vegetable oils.

Cardiovascular diseases and cancer are the leading cause of death worldwide, changed lifestyle and eating habits are the major contributing factors. Daily consumption cooking oils is one of the nutritional sources in today's life. Oils are available in market in the blend of two or more oils to get the maximum health benefits. There are number of factors which decide the pathogenic or protective effects of these oils, like fatty acids(FAs) composition, duration and extent of thermal exposure, daily intake and consumption duration. While processing the food cooking oils are thermally oxidized, that exert deleterious health effects, when taken for long time. The present study designed to evaluate the lipid peroxidation and level of oxidative stress in rabbits treated with repeatedly heated mix vegetable oils, in low (L-RHMVO) and high doses (H-RHMVO) in comparison with single time heated olive (STH-OO), canola (STH-CO), sunflower (STH-SO) oils individually and in mixture (STH-MVO) collected from Karachi (Pakistan).Six groups of animals treated with all these processed oils for 16 weeks along with normal diet .Control group was kept on normal rabbit diet. Animal body and organ weight was recorded. Blood samples were collected to measure plasma Malondialdehyde (MDA), Homocysteine(H-Cys), Creatine phosphokinase (CPK), Lactate dehydrogenase (LDH),C-reactive protein (CRP) and lipid profile (TGs, Total-cholesterol, HDL-cholesterol, LDL-cholesterol and VLDL-cholesterol).Statistically highly significant (p<0.005) increased body and organ weight along with Total-cholesterol, TGs, LDL-cholesterol, VDLD-Cholesterol, H-Cys, MDA,CPK,LDH & CRP and decreased HDL-cholesterol was found in H-RHMVO and L-RHMVO groups in dose dependent manner compared to control and single time heated oils groups. Among the single time heated oils STH-SO fed animals had significant (p<0.05) increase in lipid periodization and oxidative stress parameters. STH-OO showed least variation from control with significant increase in HDL-cholesterol level. The finding of this study not only confirms health deleterious effect of vegetable oils when used in thermally oxidized condition but also suggests induced-metabolic changes with oxidative stress. So more advance studies simulating real-life exposure to multiple hazardous substances is required.

Vitamin D-Related Genes, Blood Vitamin D Levels and Colorectal Cancer Risk in Western European Populations.

Higher circulating 25-hydroxyvitamin D levels (25(OH)D) have been found to be associated with lower risk for colorectal cancer (CRC) in prospective studies. Whether this association is modified by genetic variation in genes related to vitamin D metabolism and action has not been well studied in humans. We investigated 1307 functional and tagging single-nucleotide polymorphisms (SNPs; individually, and by gene/pathway) in 86 vitamin D-related genes in 1420 incident CRC cases matched to controls from the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. We also evaluated the association between these SNPs and circulating 25(OH)D in a subset of controls. We confirmed previously reported CRC risk associations between SNPs in the VDR, GC, and CYP27B1 genes. We also identified additional associations with 25(OH)D, as well as CRC risk, and several potentially novel SNPs in genes related to vitamin D transport and action (LRP2, CUBN, NCOA7, and HDAC9). However, none of these SNPs were statistically significant after Benjamini-Hochberg (BH) multiple testing correction. When assessed by a priori defined functional pathways, tumor growth factor ß (TGFß) signaling was associated with CRC risk (P ≤ 0.001), with most statistically significant genes being SMAD7 (PBH = 0.008) and SMAD3 (PBH = 0.008), and 18 SNPs in the vitamin D receptor (VDR) binding sites (P = 0.036). The 25(OH)D-gene pathway analysis suggested that genetic variants in the genes related to VDR complex formation and transcriptional activity are associated with CRC depending on 25(OH)D levels (interaction P = 0.041). Additional studies in large populations and consortia, especially with measured circulating 25(OH)D, are needed to confirm our findings.

Evaluation of pharmacological and toxic effects of ethanolic extract of radish pods in albino rabbits: A biochemical and histopathological study.

Radish pods are known as vegetable eaten as a part of diet. Though the pharmacologic potential of radish has been well known but there are fewer reports regarding pharmacological and toxic effects of radish pods. On account of this reason, the current study was aimed to evaluate the pharmacological and toxic effects of ethanol extract of Raphanus caudatus (radish pods) in rabbits after 60 days of administration. The plant extract was administered in 250, 500 and 1000mg/kg doses and effect was observed on hepatic, renal, cardiac and lipid profile. The extract was found to be hepatoprotective, nephroprotective and cardioprotective. Also it showed hypocholestrolemic potential at 1000 mg/kg. However at higher doses the extract presented chronic gastritis. Conversely, no indication of histological alterations was seen in other vital organs such as liver, kidneys, heart. Thus there is critical requirement to identify toxic constituent/s inducing gastritis so that safety profile of the plant can be established for effective therapeutic use.

Association of Selenoprotein and Selenium Pathway Genotypes with Risk of Colorectal Cancer and Interaction with Selenium Status.

Selenoprotein genetic variations and suboptimal selenium (Se) levels may contribute to the risk of colorectal cancer (CRC) development. We examined the association between CRC risk and genotype for single nucleotide polymorphisms (SNPs) in selenoprotein and Se metabolic pathway genes. Illumina Goldengate assays were designed and resulted in the genotyping of 1040 variants in 154 genes from 1420 cases and 1421 controls within the European Prospective Investigation into Cancer and Nutrition (EPIC) study. Multivariable logistic regression revealed an association of 144 individual SNPs from 63 Se pathway genes with CRC risk. However, regarding the selenoprotein genes, only TXNRD1 rs11111979 retained borderline statistical significance after adjustment for correlated tests (PACT = 0.10; PACT significance threshold was P < 0.1). SNPs in Wingless/Integrated (Wnt) and Transforming growth factor (TGF) beta-signaling genes (FRZB, SMAD3, SMAD7) from pathways affected by Se intake were also associated with CRC risk after multiple testing adjustments. Interactions with Se status (using existing serum Se and Selenoprotein P data) were tested at the SNP, gene, and pathway levels. Pathway analyses using the modified Adaptive Rank Truncated Product method suggested that genes and gene x Se status interactions in antioxidant, apoptosis, and TGF-beta signaling pathways may be associated with CRC risk. This study suggests that SNPs in the Se pathway alone or in combination with suboptimal Se status may contribute to CRC development.

Laser capture microdissection of human pancreatic islets reveals novel eQTLs associated with type 2 diabetes.

OBJECTIVE: Genome wide association studies (GWAS) for type 2 diabetes (T2D) have identified genetic loci that often localise in non-coding regions of the genome, suggesting gene regulation effects. We combined genetic and transcriptomic analysis from human islets obtained from brain-dead organ donors or surgical patients to detect expression quantitative trait loci (eQTLs) and shed light into the regulatory mechanisms of these genes. METHODS: Pancreatic islets were isolated either by laser capture microdissection (LCM) from surgical specimens of 103 metabolically phenotyped pancreatectomized patients (PPP) or by collagenase digestion of pancreas from 100 brain-dead organ donors (OD). Genotyping (> 8.7 million single nucleotide polymorphisms) and expression (> 47,000 transcripts and splice variants) analyses were combined to generate cis-eQTLs. RESULTS: After applying genome-wide false discovery rate significance thresholds, we identified 1,173 and 1,021 eQTLs in samples of OD and PPP, respectively. Among the strongest eQTLs shared between OD and PPP were CHURC1 (OD p-value=1.71 × 10-24; PPP p-value = 3.64 × 10-24) and PSPH (OD p-value = 3.92 × 10-26; PPP p-value = 3.64 × 10-24). We identified eQTLs in linkage-disequilibrium with GWAS loci T2D and associated traits, including TTLL6, MLX and KIF9 loci, which do not implicate the nearest gene. We found in the PPP datasets 11 eQTL genes, which were differentially expressed in T2D and two genes (CYP4V2 and TSEN2) associated with HbA1c but none in the OD samples. CONCLUSIONS: eQTL analysis of LCM islets from PPP led us to identify novel genes which had not been previously linked to islet biology and T2D. The understanding gained from eQTL approaches, especially using surgical samples of living patients, provides a more accurate 3-dimensional representation than those from genetic studies alone.

The Radish, Raphanus sativus L. Var. caudatus reduces anxiety-like behavior in mice.

Inclusion of vegetables in the diet not only provides dietary fiber, vitamins, minerals, trace elements but also significantly reduces the risk of several diseases. Raphanus sativus L. Var. caudatus belongs to the family Brassicaceae are pods of Radish, and are commonly known as Mungra or Sungra in Pakistan and India. The English name for this species is Rat-tailed radish. This variety of radish is unique, less familiar to the population, and not commonly used as a food source. Furthermore there have been very few studies that report on the potential antioxidant and anti-cancer capabilities of this radish. The present study was designed to evaluate anxiolytic potential of Raphanus caudatus in mice using different behavioral paradigms. The ethanol extract of the plant was evaluated at three different doses i.e. 250, 500 and 1000 mg/kg. The extract at doses of 250 and 500 mg/kg produced a significant (p < 0.05) reduction of anxiety-like behavior in mice and results are comparable to standard anxiolytic drug diazepam.

Systems biology of the IMIDIA biobank from organ donors and pancreatectomised patients defines a novel transcriptomic signature of islets from individuals with type 2 diabetes.

AIMS/HYPOTHESIS: Pancreatic islet beta cell failure causes type 2 diabetes in humans. To identify transcriptomic changes in type 2 diabetic islets, the Innovative Medicines Initiative for Diabetes: Improving beta-cell function and identification of diagnostic biomarkers for treatment monitoring in Diabetes (IMIDIA) consortium ( www.imidia.org ) established a comprehensive, unique multicentre biobank of human islets and pancreas tissues from organ donors and metabolically phenotyped pancreatectomised patients (PPP). METHODS: Affymetrix microarrays were used to assess the islet transcriptome of islets isolated either by enzymatic digestion from 103 organ donors (OD), including 84 non-diabetic and 19 type 2 diabetic individuals, or by laser capture microdissection (LCM) from surgical specimens of 103 PPP, including 32 non-diabetic, 36 with type 2 diabetes, 15 with impaired glucose tolerance (IGT) and 20 with recent-onset diabetes (<1 year), conceivably secondary to the pancreatic disorder leading to surgery (type 3c diabetes). Bioinformatics tools were used to (1) compare the islet transcriptome of type 2 diabetic vs non-diabetic OD and PPP as well as vs IGT and type 3c diabetes within the PPP group; and (2) identify transcription factors driving gene co-expression modules correlated with insulin secretion ex vivo and glucose tolerance in vivo. Selected genes of interest were validated for their expression and function in beta cells. RESULTS: Comparative transcriptomic analysis identified 19 genes differentially expressed (false discovery rate ≤0.05, fold change ≥1.5) in type 2 diabetic vs non-diabetic islets from OD and PPP. Nine out of these 19 dysregulated genes were not previously reported to be dysregulated in type 2 diabetic islets. Signature genes included TMEM37, which inhibited Ca2+-influx and insulin secretion in beta cells, and ARG2 and PPP1R1A, which promoted insulin secretion. Systems biology approaches identified HNF1A, PDX1 and REST as drivers of gene co-expression modules correlated with impaired insulin secretion or glucose tolerance, and 14 out of 19 differentially expressed type 2 diabetic islet signature genes were enriched in these modules. None of these signature genes was significantly dysregulated in islets of PPP with impaired glucose tolerance or type 3c diabetes. CONCLUSIONS/INTERPRETATION: These studies enabled the stringent definition of a novel transcriptomic signature of type 2 diabetic islets, regardless of islet source and isolation procedure. Lack of this signature in islets from PPP with IGT or type 3c diabetes indicates differences possibly due to peculiarities of these hyperglycaemic conditions and/or a role for duration and severity of hyperglycaemia. Alternatively, these transcriptomic changes capture, but may not precede, beta cell failure.

Decreased STARD10 Expression Is Associated with Defective Insulin Secretion in Humans and Mice.

Genetic variants near ARAP1 (CENTD2) and STARD10 influence type 2 diabetes (T2D) risk. The risk alleles impair glucose-induced insulin secretion and, paradoxically but characteristically, are associated with decreased proinsulin:insulin ratios, indicating improved proinsulin conversion. Neither the identity of the causal variants nor the gene(s) through which risk is conferred have been firmly established. Whereas ARAP1 encodes a GTPase activating protein, STARD10 is a member of the steroidogenic acute regulatory protein (StAR)-related lipid transfer protein family. By integrating genetic fine-mapping and epigenomic annotation data and performing promoter-reporter and chromatin conformational capture (3C) studies in ß cell lines, we localize the causal variant(s) at this locus to a 5 kb region that overlaps a stretch-enhancer active in islets. This region contains several highly correlated T2D-risk variants, including the rs140130268 indel. Expression QTL analysis of islet transcriptomes from three independent subject groups demonstrated that T2D-risk allele carriers displayed reduced levels of STARD10 mRNA, with no concomitant change in ARAP1 mRNA levels. Correspondingly, ß-cell-selective deletion of StarD10 in mice led to impaired glucose-stimulated Ca2+ dynamics and insulin secretion and recapitulated the pattern of improved proinsulin processing observed at the human GWAS signal. Conversely, overexpression of StarD10 in the adult ß cell improved glucose tolerance in high fat-fed animals. In contrast, manipulation of Arap1 in ß cells had no impact on insulin secretion or proinsulin conversion in mice. This convergence of human and murine data provides compelling evidence that the T2D risk associated with variation at this locus is mediated through reduction in STARD10 expression in the ß cell.

Evaluation of antiviral activity of plant extracts against foot and mouth disease virus in vitro.

The aim of this study was to evaluate antiviral activity of chloroformic leaves extracts of three plants: Azadirachta indica, Moringa oleifera and Morus alba against Foot and Mouth disease virus using MTT assay (3-(4, 5-Dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide). Antiviral and cytotoxic activity of each extract was evaluated as cell survival percentage and results were expressed as Means ± S.D. The concentrations which resulted in cell survival percentages of greater than 50% are considered to be effective antiviral concentrations. From the tested plant extracts, Moringa oleifera showed potent antiviral activity (p<0.05) while Azadirachta indica showed significant antiviral activity in the range of 1-50µ/ml & 12-100µ/ml respectively. In contrast no antiviral activity was observed by Morus alba as all the tested concentration resulted in significant reduction (p<0.05) in cell survival percentage.

Identification of a novel susceptibility locus at 13q34 and refinement of the 20p12.2 region as a multi-signal locus associated with bladder cancer risk in individuals of European ancestry.

Candidate gene and genome-wide association studies (GWAS) have identified 15 independent genomic regions associated with bladder cancer risk. In search for additional susceptibility variants, we followed up on four promising single-nucleotide polymorphisms (SNPs) that had not achieved genome-wide significance in 6911 cases and 11 814 controls (rs6104690, rs4510656, rs5003154 and rs4907479, P < 1 × 10(-6)), using additional data from existing GWAS datasets and targeted genotyping for studies that did not have GWAS data. In a combined analysis, which included data on up to 15 058 cases and 286 270 controls, two SNPs achieved genome-wide statistical significance: rs6104690 in a gene desert at 20p12.2 (P = 2.19 × 10(-11)) and rs4907479 within the MCF2L gene at 13q34 (P = 3.3 × 10(-10)). Imputation and fine-mapping analyses were performed in these two regions for a subset of 5551 bladder cancer cases and 10 242 controls. Analyses at the 13q34 region suggest a single signal marked by rs4907479. In contrast, we detected two signals in the 20p12.2 region-the first signal is marked by rs6104690, and the second signal is marked by two moderately correlated SNPs (r(2) = 0.53), rs6108803 and the previously reported rs62185668. The second 20p12.2 signal is more strongly associated with the risk of muscle-invasive (T2-T4 stage) compared with non-muscle-invasive (Ta, T1 stage) bladder cancer (case-case P ≤ 0.02 for both rs62185668 and rs6108803). Functional analyses are needed to explore the biological mechanisms underlying these novel genetic associations with risk for bladder cancer.

ABO blood group alleles and prostate cancer risk: Results from the breast and prostate cancer cohort consortium (BPC3).

BACKGROUND: ABO blood group has been associated with risk of cancers of the pancreas, stomach, ovary, kidney, and skin, but has not been evaluated in relation to risk of aggressive prostate cancer. METHODS: We used three single nucleotide polymorphisms (SNPs) (rs8176746, rs505922, and rs8176704) to determine ABO genotype in 2,774 aggressive prostate cancer cases and 4,443 controls from the Breast and Prostate Cancer Cohort Consortium (BPC3). Unconditional logistic regression was used to calculate age and study-adjusted odds ratios and 95% confidence intervals for the association between blood type, genotype, and risk of aggressive prostate cancer (Gleason score ≥8 or locally advanced/metastatic disease (stage T3/T4/N1/M1). RESULTS: We found no association between ABO blood type and risk of aggressive prostate cancer (Type A: OR = 0.97, 95%CI = 0.87-1.08; Type B: OR = 0.92, 95%CI =n0.77-1.09; Type AB: OR = 1.25, 95%CI = 0.98-1.59, compared to Type O, respectively). Similarly, there was no association between "dose" of A or B alleles and aggressive prostate cancer risk. CONCLUSIONS: ABO blood type was not associated with risk of aggressive prostate cancer.

Integration of multiethnic fine-mapping and genomic annotation to prioritize candidate functional SNPs at prostate cancer susceptibility regions.

Interpretation of biological mechanisms underlying genetic risk associations for prostate cancer is complicated by the relatively large number of risk variants (n = 100) and the thousands of surrogate SNPs in linkage disequilibrium. Here, we combined three distinct approaches: multiethnic fine-mapping, putative functional annotation (based upon epigenetic data and genome-encoded features), and expression quantitative trait loci (eQTL) analyses, in an attempt to reduce this complexity. We examined 67 risk regions using genotyping and imputation-based fine-mapping in populations of European (cases/controls: 8600/6946), African (cases/controls: 5327/5136), Japanese (cases/controls: 2563/4391) and Latino (cases/controls: 1034/1046) ancestry. Markers at 55 regions passed a region-specific significance threshold (P-value cutoff range: 3.9 × 10(-4)-5.6 × 10(-3)) and in 30 regions we identified markers that were more significantly associated with risk than the previously reported variants in the multiethnic sample. Novel secondary signals (P < 5.0 × 10(-6)) were also detected in two regions (rs13062436/3q21 and rs17181170/3p12). Among 666 variants in the 55 regions with P-values within one order of magnitude of the most-associated marker, 193 variants (29%) in 48 regions overlapped with epigenetic or other putative functional marks. In 11 of the 55 regions, cis-eQTLs were detected with nearby genes. For 12 of the 55 regions (22%), the most significant region-specific, prostate-cancer associated variant represented the strongest candidate functional variant based on our annotations; the number of regions increased to 20 (36%) and 27 (49%) when examining the 2 and 3 most significantly associated variants in each region, respectively. These results have prioritized subsets of candidate variants for downstream functional evaluation.