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Discoidin domain receptors, DDR1 and DDR2 are members of the receptor tyrosine kinase (RTK) family that serves as a non-integrin collagen receptor and were initially identified as critical regulators of embryonic development and cellular homeostasis. In recent years, numerous studies have focused on the role of these receptors in disease development, in particular, cancer where they have been reported to augment ECM remodeling, invasion, drug resistance to facilitate tumor progression and metastasis. Interestingly, accumulating evidence also suggests that DDRs promote apoptosis and suppress tumor progression in various human cancers due to which their functions in cancer remain ill-defined and presents a case of an interesting therapeutic target. The present review has discussed the role of DDRs in tumorigenesis and the metastasis.

Increasing herbal formulations have been used to treat several diseases including cancer. W. somnifera (Ashwagandha) is one such plant the extracts of which have been tested against a number of ailments including cancer, which remains as one of the most dreadful diseases on the globe. The ever-increasing number of cancer related mortality demands the development of novel chemopreventive agents with minimum side effects. Different compounds isolated from various parts of the plant like root, stem, and leaves have been reported to display significant anti-cancerous and immunomodulating properties and thus can be used alone or in combination with other chemotherapeutic drugs for cancer treatment. Through this review, we highlight the importance of W. somnifera in countering the potential oncogenic signaling mediators that are modulated by active constituents of W. somnifera in a variety of cancer types. Further, we hope that active constituents of W. somnifera will be tested in clinical trials so that they can be used as an important adjuvant in the near future for the effective treatment of cancer.

Imidazole-based epidermal growth factor receptor (EGFR) inhibitors were computationally designed and synthesized. All the compounds were assessed for their anti-proliferative activity against five cancer cell lines, viz., MDA-MB-231 (breast), T47D (breast) and MCF-7 (breast), A549 (lung) and HT-29 (colorectal). Compounds 2c and 2d emerged as better anticancer molecules with no toxicity towards normal cells. 2c and 2d inhibited EGFR enzymatic activity in vitro with IC50 values of 617.33 ± 0.04 nM and 710 ± 0.05 nM, respectively. In order to further improve the potency, we explored an unoccupied area of the ATP binding domain of EGFR and analysed an in silico interaction model of 2c and 2d-EGFR complexes that guided and allowed substitution of the 4-fluorophenyl ring (2c and 2d) with 4-(4-methylpiperazinyl)-3-nitrophenyl at the N-9 position, resulting in compound 3c with a better binding score and potent EGFR inhibitory activity (IC50: 236.38 ± 0.04 nM), which was comparable to the positive control erlotinib (239.91 ± 0.05 nM). 3c exhibited a great improvement in anticancer potency with inhibition of cell growth of all cancer cell lines at very low micromolar concentrations (IC50 = 1.98 to 4.07 μM). Further investigation revealed that 3c also induced an increase in ROS levels in cancer cells in a mitochondrial-independent manner and halted the cell cycle at the sub-G1 phase.

miRNAs are fascinating molecular players for gene regulation as individual miRNA can control multiple targets and a single target can be regulated by multiple miRNAs. Loss of miRNA regulated gene expression is often reported to be implicated in various human diseases like diabetes and cancer. Recently, geneticists across the world started reporting single nucleotide polymorphism (SNPs) in seed sequences of miRNAs. Similarly, SNPs are also reported in various target sequences of these miRNAs. Both the scenarios lead to dysregulated gene expression which may result in the progression of diseases. In the present paper, we explore SNPs in various miRNAs and their target sequences reported in various human cancers as well as diabetes. Similarly, we also present evidence of these mutations in various other human diseases.

Inflammation and caner are linked in a bidirectional manner. C-reactive protein (CRP) is an important inflammatory marker. The aim of the study was to test whether the inflammatory marker, CRP at the time of diagnosis of breast cancer is associated with metastasis, recurrence, and death in breast cancer patients from Malwa region of Punjab where breast cancer is widely feared.Two hundred and forty-two breast cancer patients and 242 age and sex matched controls were included in the study. CRP levels were estimated using fully automated bio analyzer Erba200. Follow up interviews were conducted at an interval of 3, 6, 9, 12, 15, 18, 21, 24, and 27 months to determine the outcome among breast cancer patients.Elevated levels of CRP were found among the diseased in comparison with controls (P0.0001). Higher CRP levels associated significantly with poor outcome including metastasis and recurrence among breast cancer patients [P = 0.03; 95% confidence interval; odds ratio: 2.954 (0.9125-9.561)].Elevated levels of CRP associated significantly with increased risk of breast cancer and poor outcome. CRP estimation may be a simple and inexpensive tool for the risk assessment and outcome of the disease in Malwa region of Punjab where incidence of breast cancer is reported to be very high.

Background: Malaria, one of the World’s biggest billers’ is on the schedule for biomedical research and public health policies. The introduction of the artemisinin, a Chinese traditional drug from Artemisia annua is a revolution in the treatment of malaria. Artemisinin-based combination treatment (ACT) is considered to be the best strategy for uncomplicated Falciparum malaria. The presence of 1,2,4-trioxane system in artemisinin is responsible for its antimalarial activity. Methods: In this study, twenty-nine analogues of artemisinin were taken into account for QSAR studies along with artemisinin. The most active analogue of artemisinin 21 was energy minimized. All the structures were prepared from the active conformer 21 and energy was minimized to the stable state using MMFF94 force field using ChemBioDraw-12. Genetic Algorithm is used to decide the descriptors best required for the model generation. The test set and training set division were done by using hierarchal clustering module available with NCSS statistical software. Results and Conclusion: The antimalarial activity of the artemisinin and its substituted analogues has been analyzed through the multiple linear regression (MLR) using various physiochemical and structural descriptors obtained from PADEL software. The models were prepared using the Sigma Plot version 11. The calculated 2D autocorrelation descriptors and the MLR model suggest that artemisinin and its analogues hold the scope in the optimization of antimalarial activity.

Platelets are anucleated blood constituents, vital for hemostasis and involved in the pathophysiology of several cardiovascular, neurovascular diseases as well as inflammatory processes and metastasis. Over the past few years, the molecular processes that regulate the function of platelets in hemostasis and thrombosis have emerged revealing platelets to be perhaps more complex than may have been expected. The most understood part of platelets is to respond to a blood vessel injury by altering shape, secreting granule contents, and aggregating. These responses, while advantageous for hemostasis, can become detrimental when they root ischemia or infarction. Only a few transcription and signaling factors involved in platelet biogenesis have been identified till date. Platelets encompass an astonishingly complete array of organelles and storage granules including mitochondria, lysosomes, alpha granules, dense granules, a dense tubular system (analogous to the endoplasmic reticulum of nucleated cells); a highly invaginated plasma membrane system known as the open canalicular system (OCS) and large fields of glycogen. Platelets as a model cells to study neurological disorders have been recommended by several researchers since several counterparts exist between platelets and the brain, which make them interesting for studying the neurobiology of various neurological disorders. This review has been compiled with an aim to integrate the latest research on platelet biogenesis, activation and aggregation focusing on the molecular pathways that power and regulate these processes. The dysregulation of important molecular players affecting fluctuating platelet biology and thereby resulting in neurovascular diseases has also been discussed.

Diabetes, the most common endocrine disorder, also known as a silent killer disease, is characterized by uncontrolled hyperglycemia. According to the International Diabetes Federation, there were 451 million people with diabetes mellitus worldwide in 2017. It is a multifactorial syndrome caused by genetic as well as environmental factors. Noncoding RNAs, especially the miRNAs, play a significant role in the development as well as the progression of the disease. This is on account of insulin resistance or defects in β cell function. Various miRNAs including miR-7, miR-9, miR-16, miR-27, miR-24, miR-29, miR-124a, miR-135, miR-130a, miR-144, miR-181a, and miR-375 and many more have been associated with insulin resistance and other pathogenic conditions leading to the development of the disease. These miRNAs play significant roles in various pathways underlying insulin resistance such as PI3K, AKT/GSK, and mTOR. The main target genes of these miRNAs are FOXO1, FOXA2, STAT3, and PTEN. The miRNAs carry out important functions in insulin target tissues like the adipose tissue, liver, and muscle. MiRNAs miR-9, miR-375, and miR-124a, are also associated with the secretion of insulin from pancreatic cells. There is an interplay between the miRNAs and pancreatic cell growth, especially the miRNAs affecting development and proliferation of these cells. Most of the miRNAs target more than one gene which not only justifies their use as biomarkers but also their therapeutic potential. The current review has been compiled with an aim to discuss the role of various miRNAs involved in various pathogenic mechanisms including insulin resistance, insulin secretion, and the β cell dysfunction.

In the present study we attempted a parent–child trio, whole exome sequencing (WES) approach to study Apert's syndrome. Clinical characteristics of the child were noted down and WES was carried out using Ion Torrent System that revealed the presence of previously reported P253R mutation in FGFR2 gene. Presence of two SNPs rs1047057 and rs554851880 in FGFR2 gene with an allelic frequency of 0.5113 and 0.001176 respectively and 161 complete damaging mutations were found. This study is the first reported case of exome sequencing approach on an Apert's syndrome patient aimed at providing better genetic counselling in a non-consanguineous relationship. Keywords: Apert syndrome, Craniosynostosis, Exome sequencing, FGFR2 gene, Parent–child trio study

Objective We investigated the null polymorphism in GSTM1 and GSTT1 genes and the antioxidant levels in oral submucous fibrosis (OSMF), leukoplakia and oral cancer patients along with healthy controls in a South Indian cohort. Methods Genotyping was done using multiplex PCR and the antioxidant levels were estimated using biochemical methods Association between genotypes and different diseased states was determined by odds ratio with 95% confidence interval (CI) and chi-square analysis and for antioxidant levels student’s t-test was used. Results The relative risk for GSTM1 and GSTT1 gene polymorphisms was statistically insignificant for the 3 patient groups vs. controls. Comparing the frequency of the null genotypes between the groups of patients only GSTM1 polymorphism revealed a significant difference between OSMF & oral cancer subjects (p = 0.02). Further, analysis of the antioxidant parameters shows ceruloplasmin levels to be significantly elevated between patient groups and controls and among OSMF vs. cancer patients (p Conclusion In conclusion, this study finds GSTM1 null genotype and antioxidants (ceruloplasmin and glutathione levels) to be significantly higher in oral cancers than in precancerous lesions, and suggesting that they might be associated with the malignant transformation of the oral precancers.

Structure-based design and synthesis of pyrimidine containing reversible epidermal growth factor receptor (EGFR) inhibitors 1a-d are reported. The compounds (1a-d) inhibited the EGFR kinase activity in vitro with IC50 range 740 nm to 3 μm. mRNA expression of EGFR downstream target genes, that is twist, c-fos and aurora were found to be altered upon treatment with compounds 1a-d. The compounds 1a-d exhibited excellent anticancer activity at low micromolar level (3.2-9 μm) in lung, colon and breast cancer cell lines. Furthermore, compounds induced the alteration in mitochondrial membrane potential and reactive oxygen species level and. Selected compound 1b was found to increase sub-G1 population indicative of cell death, the mode of cell death was apoptotic as evident from Annexin V verses propidium iodide assay. Molecular modelling further helped to investigate the binding recognition pattern of the compounds in ATP binding EGFR domain similar to erlotinib and dissimilar to WZ4002.

Stroke is the second largest cause of death worldwide. Angiotensin converting enzyme (ACE) gene has emerged as an important player in the pathogenesis of hypertension and consequently stroke. It encodes ACE enzyme that converts the inactive decapeptide angiotensin I to active octapeptide, angiotensin II (Ang II). Dysregulation in the expression of ACE gene, on account of genetic variants or regulation by miRNAs, alters the levels of ACE in the circulation. Variable expression of ACE affects the levels of Ang II. Ang II acts through different signal transduction pathways via various tyrosine kinases (receptor/non-receptor) and protein serine/threonine kinases, initiating a downstream cascade of molecular events. In turn these activated molecular pathways might lead to hypertension and inflammation thereby resulting in cardiovascular and cerebrovascular diseases including stroke. In order to regulate the overexpression of ACE, many ACE inhibitors and blockers have been developed, some of which are still under clinical trials.

Single-Cell omics has emerged as an important tool to study the biological heterogeneity of the cell. The technique involves the analysis of genome, methylome, transcriptome, and proteome of a single-cell. It provides cutting-edge prenatal testing including genetic diagnosis of preimplantation human embryos following in vitro fertilization. The developing embryos shed cells in the maternal blood; the potential to isolate and analyze these cells is broadening the scope as well as the precision of current noninvasive prenatal testing (NIPT) for circulating DNA in maternal plasma. Single-cell omics is evolving at a significant rate and many technical developments have been recently made in this field. Investigation of circulating tumor cells from solid tumors and tumor-cell-free DNA is also applied in guiding, diagnosis, prognosis, and treatment of cancer. Single-cell omics is also poised to transform the studies of many neuronal phenomena, which have been stalled for a long time by the immense cellular complexity of the brain. Fortunately, current biological science does possess technologies for determination of single-cell genetic and epigenetic profiling at all the hierarchical levels of the genome organization to rule out single-cell variations in neurons.

Single-cell genomics is an emerging technique used to study individuality of cells by using omics approaches. The technique actually evolved after the establishment of the Next Generation Sequencing and resulted into transformation of many fields of biological research. The functionality and properties of a cell in its naive conditions and analysis of genomic heterogeneity that exists within a cell during normal development and disease can be studied using single-cell genomics. Further, the sequencing of single molecular types (DNA, RNA, and protein) provides insights of cell's phenotype that can be used to establish the links with genotype in future. The process of single genome sequencing includes the preparation of cell suspension for isolation of single-cell followed by whole genome sequencing and then mapping the reads from reference genome to check alterations in the genome. The technique has various applications in the fields of oncology, prenatal diagnosis, tissue mosaicism, immunology, organogenesis, embryogenesis, germline transmission, microbiology, and neurobiology. The technology and its applications will be discussed in detail in this chapter.

Background & objectives: The amount of foetal haemoglobin that persists in adulthood affects the clinical severity of haemoglobinopathies including β-thalassaemia major and sickle cell anaemia (SCA). The present study was undertaken to analyse β-thalassaemia as well as SCA patients for the single nucleotide polymorphism (SNP), rs11886868 (T/C) in BCL11A gene and to evaluate the association between this polymorphism and severity of β-thalassaemia major and SCA. Methods: a total of 620 samples (420 β-thalassaemia major and 200 SCA cases) were analysed before blood transfusion using basic screening tests like complete blood analysis and osmotic fragility and further confirmed by high performance liquid chromatography (HPLC), amplification refractory mutation system-polymerase chain reaction (ARMS-PCR) and reverse dot blot techniques. All patients were transfusion dependent. Patients with β-thalassaemia and SCA were classified into mild, moderate, severe according to the severity score based on Hb levels, age of onset, age at which patients received their first blood transfusion, the degree of growth retardation and splenectomy. β-thalassaemia as well as SCA patients were analysed for the SNP, rs11886868 (T/C) in BCL11A gene and association between this polymorphism and severity of β-thalassaemia major as well as SCA was evaluated. Results: There was a significant difference in genotypic and allelic frequencies of BCL11A gene polymorphism between mild and moderate and mild and severe cases in both the groups. A significant (P

The failure of the Integrase Strand Transfer Inhibitors (INSTIs) due to the mutations occurring at the catalytic site of HIV integrase (IN) has led to the design of allosteric integrase inhibitors (ALLINIs). Lens epithelium derived growth factor (LEDGF/p75) is the host cellular cofactor which helps chaining IN to the chromatin. The protein-protein interactions (PPIs) were observed at the allosteric site (LEDGF/p75 binding domain) between LEDGF/p75 of the host cell and IN of virus. In recent years, many small molecules such as CX04328, CHIBA-3053 and CHI-104 have been reported as LEDGF/p75-IN interaction inhibitors (LEDGINs). LEDGINs have emerged as promising therapeutics to halt the PPIs by binding at the interface of both the proteins. In the present work, we correlated the docking scores for the reported LEDGINs containing quinoline scaffold with the in vitro biological data. The hierarchal clustering method was used to divide the compounds into test and training set. The robustness of the generated model was validated by q2 and r2 for the predicted set of compounds. The generated model between the docking score and biological data was assessed to predict the activity of the hits (quinoline scaffold) obtained from virtual screening of LEDGINs providing their structureactivity relationships to aim for the generation of potent agents.

Introduction: Several human and experimental studies have revealed that chronic inflammation may play a vital role in neurodegenerative processes including epilepsy. There is accumulating evidence that inflammatory processes affect the pathophysiology of different epilepsy types. Aim: To assess the concentrations of Homocysteine (Hcy) and High Sensitivity C-Reactive Protein (hs-CRP) in Idiopathic Generalised Epilepsy (IGE) patients and their association with IGE and duration of the Anti Epileptic Drugs (AEDs). Materials and Methods: This case-control study consisted of 100 IGE patients (50 tonic–clonic, 15 absence and 35 myoclonic seizures) and equal number of healthy controls. Hcy levels were assayed by Centaur XP using ADVIA centaur Hcy; whereas hsCRP levels by ELISA method using commercially available kits. Results: The Hcy and hs-CRP levels were significantly increased in both the patient groups (18 years). Significant difference in the levels of Hcy was observed between different epilepsy types of 18 years patients (5 years) (p=0.002 and p

BRCA2is the main susceptibility gene known to be involved in the pathogenesis of breast cancer. It plays an important role in maintaining the genome stability by homologous recombination through DNA double-strand breaks repairing, by interacting with various other proteins including RAD51, DSS1, RPA, MRE11, PALB2, and p53. BRCA2-deficient cells show the abnormalities of chromosome number. BRCA2 is also found to be involved in centrosome duplication specifically in the metaphase to anaphase transition. Inactivation or depletion of BRCA2 leads to centrosome amplification that results in unequal separation of chromosomes. BRCA2 localizes with central spindle and midbody during telophase and cytokinesis. Inactivation or depletion of BRCA2 leads to multinucleation of cell. Around 2000 mutations have been reported in BRCA2 gene. BRCA2-deficient tumors are being taking into consideration for targeted cancer therapy by using different inhibitors like poly ADP-ribose polymerase and thymidylate synthase. The present review focusses on the role of BRCA2 in various critical cellular processes based on the mechanistic approaches. Mutations reported in the BRCA2 gene in various ethnic groups till date have also been compiled with an insight into the functional aspects of these alterations. The therapeutic strategies for targeting BRCA2-deficient tumors have also been targeted.

Molecular farming provides an unprecedented approach for the production of metabolites or proteins of medicinal value from plants used previously only in agricultural setting. These plants act as protein factories that can synthesize a variety of proteins free from pathogens such as plasma proteins, growth factors, and vaccines. This method provides a novel, tempting, inexpensive, easy, and safe alternative to other techniques of protein or antigen production. With the advent of transgenic plants, it is possible to produce unlimited amounts of subunit vaccines (for oral use/edible and of parenteral use), protein used for pharmaceutical/medicinal purpose, recombinant proteins, antibodies, and industrial enzymes. Plants have numerous advantages over the production systems on account of scalability, safety, and are economic; for example, less cost of production is involved for Hepatitis B nucleocapsid antigen using transgenic tobacco. Biopharming or molecular farming provides an important resource for cheaper drug production used in the treatment of cancer, heart diseases, and infectious diseases. The pharmaceutical products are manufactured by genetically engineered plants that are extracted and purified, also known as pharmaceuticals produced by plants. Edible vaccines are cheaper in cost, easy to administer mostly by oral route, fail-safe, and are acceptable by society especially in developing countries. These vaccines are targeted to provide systemic as well as mucosal types of immunity. It has been predicted that in future children may get their immunization by munching on foods instead of getting enduring shots. The production of edible vaccines consists of the process of introducing the selected genes of desired quality into plant to induce these altered or transgenic plants to produce the encoded proteins in a natural way. These vaccines provide safer alternatives and help in reduction of cost of production and shipping and also decrease the potential hazards associated with conventional vaccines. However, becoming a reality and readily availability of edible vaccine is challenged by many problems of technical, regulatory, and nonscientific issues, which should be ruled out and rectified. This chapter provides insight into the current scenario and future applications of this new preventive modality.

Introduction: Oxidative stress resulting from excessive generation of Reactive Oxygen Species (ROS) plays a significant role in neurodegeneration associated with seizures/epilepsy. Aim: To evaluate oxidative stress markers and antioxidant enzymes in Genetic Generalised Epilepsy (GGE) and to know the extent of oxidative stress induced by Anti-Epileptic Drugs (AEDs) with the time duration of treatment. Materials and Methods: In this case-control study, 310 GGE patients (male:female=203:107), who were on AED treatment (n=235) and 75 untreated patients (male:female=49:26) along with 310 age and sex matched healthy controls were recruited. Oxidative stress markers such as Nitric Oxide (NO), Malondialdehyde (MDA) and antioxidant enzyme activities namely Superoxide Dismutase (SOD), Glutathione Peroxidase (GPx) and Catalase (CAT) were measured spectrophotometrically. Results: Significantly higher levels of serum NO, MDA and low levels of plasma Total Antioxidant Capacity (TAC) were found in patients as compared to controls (p5 years compared to other groups (≤ 1 year and 1-≤ 5 years) (p=0.02, p=0.01, p=0.001, p=0.01 and p=0.05 respectively). Further, significant increase in the levels of NO, MDA and decreased activities of SOD, CAT were found in treated patients compared to untreated patients (p

HER2 amplification/overexpression accounts for aggressive clinical features of HER2 positive breast cancer. Epigenetic changes including DNA methylation, histone modifications and ncRNAs/miRNAs are associated with regulation of DNA chromatin and specifically, gene transcription. Hence, these produce eminent effects upon proto-oncogenes, tumor-suppressors and key cancer-regulatory signaling pathways. Understanding of epigenomic regulation of HER2 overexpression and signaling may help uncover the unmatchable physiology of HER2 gene/protein. Moreover, this may also aid in resolving the major issue of resistance-development towards HER2 targeted agents (trastuzumab and lapatinib), since epigenetic alterations are important therapeutic markers and modulate the response towards HER2 targeted therapy. Therefore, in this review the information regarding various epigenetic markers implicated in HER2 positive breast cancer susceptibility and therapeutic-strategies has been compiled.

There are around 20 Cyclin-dependent kinases (CDKs) known till date, and various research groups have reported their role in different types of cancer. The X-ray structures of some CDKs especially CDK2 was exploited in the past few years, and several inhibitors have been found, e.g., flavopiridol, indirubicin, roscovitine, etc., but due to the specificity issues of these inhibitors (binding to all CDKs), these were called as pan inhibitors. The revolutionary outcome of palbociclib in 2015 as CDK4/6 inhibitor added a new charm to the specific inhibitor design for CDKs. Computer-aided drug design (CADD) tools added a benefit to the design and development of new CDK inhibitors by studying the binding pattern of the inhibitors to the ATP binding domain of CDKs. Herein, we have attempted a comparative analysis of structural differences between several CDKs ATP binding sites and their inhibitor specificity by depicting the important ligand-receptor interactions for a particular CDK to be targeted. This perspective provides futuristic implications in the design of inhibitors considering the spatial features and structural insights of the specific CDK.

HER2 positive breast cancer is characterized by the low survival rate in the metastatic patients. Development of resistance and disease-relapse are the major problems associated with the currently available therapies for HER2 positive breast cancer. There are two major targeted therapies for HER2 positive breast cancer viz. monoclonal antibodies and tyrosine-kinase inhibitors, and both of these therapies have their advantages and limitations. To address the limitations associated with the existing therapies, use of antibodies and TKIs as combination therapy proved to be more effective. Various chemical modifications can be performed on tyrosine-kinase inhibitors to develop novel ligands with increased selectivity for HER2 kinase. A number of tyrosine-kinase inhibitors are in various phases of clinical trials for the treatment of HER2 positive breast cancer. In the current review article, recent developments on various HER2 tyrosine-kinase inhibitors have been reported. Various structurally different scaffolds bind to the HER2 receptor and exhibit potent anti-cancer activities. The structural and pharmacophoric requirements of the scaffolds are discussed in detail so as to discover effective drug candidates for the treatment of HER2 positive breast cancer.

Apert syndrome is one of the several genetic syndromes associated with craniosynostosis, a condition that includes premature fusion of one or multiple cranial sutures. There has been significant clinical variation among different sutural synostoses and also within particular suture synostosis. Enormous progress has been made in identifying various mutations associated with Apert Syndrome. Although a causal gene has been defined, the precise role of this mutation in producing craniofacial dysmorphology and other related abnormalities is in the process of discovery. Most of the understanding regarding this rare disorder has been possible due to mouse models that have helped in deciphering the elements of this rare human disease. Thus, molecular and cellular understanding of the disease has taken a leap and further with the advent of technology definitive diagnosis of the syndrome is no more of an issue. In this review, we have discussed and consolidated the possible molecular studies that have contributed in understanding of this rare syndrome. This article may help clinicians and researchers to inform about the latest progress in Apert syndrome.

Introduction: Albumin in an important biomarker that indicates malnutrition as well as inflammation. The aim of the study was to evaluate the albumin levels in breast cancer patients and its association with overall survival among breast cancer patients of Malwa region of Punjab. Material and methods: The study was planned in Malwa region of Punjab. Sampling was done from Guru Gobind Singh Medical College and Hospital and Max Hospital. The estimation of albumin levels was done at Central University of Punjab. 250 patients with breast cancer and 250 age and sex matched controls were involved in the study. Albumin levels were estimated using fully automated bio analyzer Erba 200. Follow-up interviews were conducted at an interval of 3, 6, 12 and 15 months to determine the outcome among breast cancer patients. Results: Low levels of albumin was found among the diseased in comparison with controls (p 3.5 g/dl) are associated significantly with increased overall survival among breast cancer patients. Albumin estimation may be a simple and inexpensive tool for the risk assessment and outcome of the disease in Malwa region of Punjab where the incidence of breast cancer is reported to be very high.

The idiopathic generalized epilepsy (IGE) is a neurological disorder which accounts for approximately 30% of all epilepsy cases. Patients identified with IGE syndromes have pharmacoresponsive epilepsies without abnormal neurological symptoms, structural brain lesions and are of unknown origin. A genetic etiology to IGEs has been proposed. Gamma amino butyric acid (GABA), a major inhibitory neurotransmitter acts by binding to transmembrane GABAA and GABAB receptors of both pre- and postsynaptic neurons. Synapsin II (SynII), a neuron specific phosphoprotein plays a major role in synaptogenesis and neurotransmitter release. The present study was carried out with an aim to evaluate the association of GABRA6 (rs3219151) TC and Syn II (rs37733634) AG gene polymorphisms with IGE. Molecular analysis revealed that the frequency of 'CC' genotype and 'C'allele of GABRA6 (rs3219151) TC gene polymorphism was significantly higher in IGE patients compared to healthy controls [CC vs. TT, χ2=26; p0.001; Odds ratio=3.6 (95% CI; 2.1-5.9); C vs T, χ2=24.7; p0.001; Odds ratio=1.78 (95% CI; 1.4-2.2)]. The frequency of 'GG' genotype and 'G' allele of the intronic polymorphism AG in Syn II gene was also found to be significantly associated with the disease when compared to controls [GG vs AA, χ2=64.52; p0.001; Odds ratio=7.37 (95% CI; 4.4-12.3); G vs. A, χ2=65.78; p0.001; Odds ratio=2.57 (95% CI; 2.0-3.2)]. The generalized multifactor dimensionality reduction method was employed to detect gene-gene interactions. The gene-gene interaction at two loci involving GABRA6 and Syn II revealed a significant association [χ2=36.6, p0.001, Odds ratio=3.17 (95% CI; 2.2-4.6)] with IGE. Therefore, the present study clearly indicates that both GABRA6 (rs3219151) TC and Syn II (rs37733634) AG polymorphisms are important risk factors for the development of IGE in the South Indian population from Andhra Pradesh. The gene-gene interaction studies demonstrated significant interactive effects of these two loci in the development of the disease.

Several studies have implicated the role of interleukin-1 in various chronic diseases including periodontitis. The present study was carried out with an aim to evaluate the role of interleukin 1β polymorphisms, namely +3954C/T, -511C/T and -31T/C, in the development of chronic periodontitis.Twenty-nine chronic periodontitis patients and 31 healthy controls of North Indian origin from Chhattisgarh were recruited for the study. The genotypes for the three variants were determined using the PCR-RFLP technique and the strength of association between genotypes and periodontitis was determined by odds ratio with 95% confidence interval (CI) and chi-square analysis.Analysis for the +3954 allelic and genotypic frequencies of the polymorphism revealed a significant difference in the CT genotype between periodontitits patients and controls (p = 0.03). A significant difference was also observed in the allelic frequencies between the two groups (p = 0.02). For the -511 site, TT genotype revealed a significant association with the disease (p = 0.01). A significant association was also found following the co-dominant model (p = 0.007). However, the -31 polymorphism revealed no significant difference between patients and controls.In conclusion, the present study suggests a strong association of the TT genotype of -511 and CT genotype of +3954 variant of interleukin 1β with chronic periodontitis. However, the -31 variant did not show a significant association with the disease.

In the present study, we evaluated the association of 1059GC polymorphism in C-reactive protein (CRP) gene with the risk of ischemic and hemorrhagic strokes. We did not find a significant association of this polymorphism with stroke. However, 2 % of mutants were observed in hemorrhagic stroke patients with a 0.01 frequency for the C allele. We also estimated the high-sensitivity C-reactive protein (hsCRP) levels in hemorrhagic stroke and compared the levels with our already published data on ischemic stroke. The hsCRP level in hemorrhagic stroke was found to be significantly elevated in comparison with that in controls (p0.001). However, there was no difference in the mean value of hsCRP levels between types of stroke. In conclusion, the GC polymorphism in the promoter region of the CRP gene is not abundant in the population and cannot be connected with different hsCRP levels and stroke prediction. The CRP level is a useful marker in stroke, but cannot help in differentiating between types of stroke.

Date fruits are consumed as traditional and ideal food in Saudi Arabia. It provides a wide range of essential nutrients and potential health benefits. Twelve (12) most consumed varieties of date fruits and their seeds available in the open markets of Riyadh, Medina and Kharj were screened for the presence of bacteria and fungi. Our study reveals that these fruits carry a heavy load of both fungal and bacterial pathogens. The variety Sukhari was found to be the most contaminant fruit with fungi while the bacterial contamination was highest in the variety Mabroon. The Genus Aspergillus was represented by seven species, amongst which Aspergillus niger was the most predominant fungi. Potential pathogens like Staphylococcus aureus and Escherichia coli were isolated besides six species of the genus Bacillus. Fruits were more contaminated than their seeds. Key words: Date fruits, seed borne, fruit spoilage, open markets.

Haemoglobinopathies including β-thalassemia and sickle cell anaemia (SCA) are considered to be classical monogenic diseases. There is considerable clinical variability between patients inheriting identical β-globin mutations. The reasons for this variability are not well understood. Previous studies have suggested that a variety of genetic determents influence different clinical phenotypes. The genetic variants that modulate HbF levels have a very strong impact on ameliorating the clinical phenotype. In the present study 6,500 blood samples from suspected cases were analysed using HPLC, ARMS-PCR, RDB techniques. Patients with β-thalassemia and SCA were classified into mild, moderate, severe according to the severity score based on Hb levels, age of onset, age at which patients received their first blood transfusion, the degree of growth retardation and splenectomy. Patients with β-thalassemia and SCA were analysed for Xmn1 polymorphism and association between this polymorphism and severity of β-thalassemia and SCA was evaluated. We found a significant difference in genotypic and allelic frequencies of Xmn1 polymorphism between mild and moderate and mild and severe cases. There was a significant difference in high and low percentage of HbF in CC, CT and TT bearing individuals. The TT bearing individuals were found to have a high percentage of HbF in β-thalassemia as well as SCA. This study confirms that increased γG-globin expression associated with Xmn1 polymorphism ameliorates the clinical severity in β-thalassemia as well as SCA in the study population.

E-selectin is an important inflammatory cytokine involved in the pathogenesis of various diseases such as atherosclerosis and stroke. We investigated the association of E-selectin gene polymorphism (S128R) with ischemic stroke and its subtypes. We studied 610 patients with ischemic stroke and 610 age- and sex-matched healthy controls. The ischemic stroke was classified according to Trial of Org10172 in Acute Stroke Treatment (TOAST). E-selectin gene polymorphism (S128R) was determined by polymerase chain reaction–restriction fragment length polymorphism technique. We found statistically significant difference in the genotypic distribution between patients and controls (for AC vs. AA, χ 2 = 49.5; p

Previous studies have associated low serum albumin levels with poor outcome in ischemic stroke. Animal studies also demonstrated neuroprotective effects of serum albumin in focal ischemia. However, there are very limited studies on the association of serum albumin levels with stroke outcome in ischemic stroke divided into subtypes. The present study was carried out to investigate the association of serum albumin levels with outcome in ischemic stroke and its subtypes.The study involved 560 patients. Serum albumin levels were estimated and follow-up interviews were conducted at 3 mo postevent to determine stroke outcome. The association between serum albumin levels and stroke outcome was evaluated by multiple logistic regression analysis after adjustment for potential confounders.Low levels of albumin associated significantly with poor outcome (score of3 on the modified Rankin Scale). The adjusted odds ratio was 1.972 (95% confidence interval, 1.103-4.001; P 0.001). The recurrence of stroke and death rate also was high in patients with low levels of albumin compared with patients with elevated levels of albumin. The reduced level of serum albumin associated significantly with poor outcome in all the stroke subtypes classified according to TOAST (Trial of ORG 10172 in Acute Stroke Treatment).Relatively high serum albumin levels in acute stroke decrease poor outcome.

Nonalcoholic fatty liver disease (NAFLD) is the most common liver disease in the world today. Its incidence in adults and children is rising rapidly due to the ongoing epidemics of obesity and type 2 diabetes. Hence, it has become a global public health issue. Environmental factors have been found to play a major role in the etiology of NAFLD, especially for genetically susceptible populations. Among these, one of the most important factors is junk food, especially the typical "Western-style" diet rich in simple carbohydrates, saturated fat, and highly processed food materials. Genetic predisposition to NAFLD does occur; however, a precise definition of genetic factors responsible for NAFLD is still lacking. Specific variants of different genes have been shown to present a risk for NAFLD. Genetic studies might be helpful in the management of the disease by developing novel treatment strategies based on individual's genotype.

Background: Breast cancer is the most frequently diagnosed life-threatening malignancy among women, across the globe. HER2 positive is a distinct breast cancer subtype, on account of its unique biology and physiological behavior. Results: Amplification of HER2 oncogene/polysomy 17 leads to HER2 overexpression that is a significant causal implication in HER2 positive breast cancer. HER2 gene variants, as well as other genes/gene variants, are involved in its overexpression, disease prognosis and in predicting the susceptibility towards HER2 positive breast cancer. Trastuzumab (Herceptin) is the most commonly used therapy for treating patients with HER2 positive status. Genomic alterations are incriminated in the development of trastuzumab-resistance, which influences the response towards trastuzumab-therapy. Conclusion: In the current review article, we have summarized the genomic alterations that are responsible for overexpression of HER2 and therefore, increased risk of breast cancer. In addition, the gene variants affecting response towards trastuzumab-therapy have also been discussed.

An association between phosphodiesterase 4D (PDE4D) gene and risk of stroke has been suggested by deCODE group in an Icelandic population. In the present case-control study we investigated the association of SNP41 (rs12153798) and SNP56 (rs702553) with ischemic stroke and stroke subtypes. Five hundred and sixteen ischemic stroke patients and 513 healthy age and sex matched controls were included in the study. The genotypes were determined by subjecting the PCR products to sequencing. Both the SNPs 56 and 41 associated significantly with stroke [adjusted OR=1.97; 95% CI (1.262-3.082); p=0.003: adjusted OR=5.42; 95% CI (3.45-8.5); p0.001 respectively]. In addition to this, a novel SNP at position 59736747 TG was found while sequencing the PCR products including SNP56. This novel SNP was found in patients as well as controls but did not show a significant association with the disease. We found significant association of SNPs 56 and 41 with large artery atherosclerosis, lacunar and cardioembolic stroke. In conclusion PDE4D gene plays a key part in the pathogenesis of ischemic stroke in the South Indian population from Andhra Pradesh.

Statins reduce the risk of cardiovascular events by lowering the blood cholesterol. Many genes involved in the pharmacodynamic pathway of statins have been part of pharmacogenetic research in patients with hypercholesterolemia, with an emphasis on genes involved in the cholesterol pathway. The present study was carried out with an aim to evaluate the association between the genetic variants of lipoprotein lipase gene [HindIII (+/+)/HindIII (-/-)], multiple drug resistance gene (C3435T) and endothelial nitric oxide synthase gene (4a/4b) with clinical outcome including an increased risk of recurrent stroke or death in ischemic stroke patients on atorvastatin therapy. 525 stroke patients and 500 healthy controls were involved in the study. Follow-up telephone interviews were conducted with patients post-event to determine stroke outcome. Blood samples were collected and genotypes determined by polymerase chain reaction-restriction digestion technique. A significant association of MDR1 and LPL gene variants with bad outcome in stroke patients on atorvastatin therapy was found. However, there was no significant association of 27 bp VNTR polymorphism of eNOS gene with outcome. MDR analysis was carried out to analyze gene-gene interaction involving these gene variants contributing to clinical outcome of patients on stratin therapy but no significant interaction between these variants was observed. In conclusion the individuals with HindIII (-/-) genotype of LPL and CC genotype of MDR1 gene would benefit more from atorvastatin therapy.

Lipoprotein lipase (LPL) plays an important role in lipid metabolism by hydrolyzing triglycerides in chylomicrons and very low density lipoproteins. An increasing number of studies have suggested an association of LPL gene variants with the risk of cardiovascular and cerebrovascular diseases. The aim of this study was to test whether HindIII polymorphism of LPL gene is associated with ischemic stroke and its subtypes as well as plasma lipid levels in a South Indian population from Andhra Pradesh. Five hundred and twenty five ischemic stroke patients and 500 controls were enrolled in this case-control study. The LPL HindIII polymorphism was determined by PCR-RFLP technique and the lipid levels were estimated using commercially available kits. We found significant difference in the genotypic distribution between patients and controls [for HindIII (+/+) vs. HindIII (-/-), χ(2)=4.916; p=0.02; Odds ratio=1.59 (95%CI; 1.054-2.413); HindIII (+/+) vs. HindIII (-/-) and HindIII (+/-), χ(2)=5.25; p=0.02; Odds ratio=1.24 (95%CI; 1.03-1.503)]. A stepwise multiple logistic regression analysis confirmedthese findings. The relationship between HindIII genotypes and plasma levels of HDL, LDL, VLDL and triglycerides was analyzed using ANOVA and further confirmed by Post-hoc analysis. The levels of triglycerides were found to be elevated in individuals bearing HindIII (+/+) genotype in comparison with HindIII (-/-) genotype. HDL levels were found to be significantly reduced and triglyceride levels significantly elevated in HindIII (+/+) genotype in comparison with HindIII (-/-). However, there was no difference in the levels of LDL and VLDL between the two genotypes. Examining the association of LPL gene HindIII polymorphism with stroke subtypes, we found significant association of HindIII polymorphism with Intracranial large artery atherosclerosis [Odds ratio=2.12 955CI (1.656-2.848); p=0.009]. Our results suggest that the HindIII polymorphism of LPL is significantly associated with ischemic stroke risk and elevated levels of plasma triglycerides and reduced HDL levels. Further, this polymorphism is significantly associated with intracranial large artery atherosclerosis which is the most frequent subtype in our region.

Acute coronary syndrome (ACS) is an inflammatory disease. Cytokines are the central regulators of inflammation and may be a cause or marker of atherosclerosis. Accumulating evidence suggests that polymorphisms at promoter regions of various cytokine genes are known to be associated with their expression levels. In the present study we investigated whether variants at -1082G→A (rs1800896) and -592C→A (rs1800872) of interleukin-10 (IL-10), -1188A→C (rs3212227) of IL-12 p40, -308G→A of tumor necrosis factor-α (TNF-α) (rs1800629), -174G→C of IL-6 (rs1800795) and +874A→T of interferon-γ (IFN-γ) genes (rs2430561) are associated with ACS.DNA samples were collected from 1083 subjects and IL-10-1082G→A, -592A→C, TNF-α-308G→A, IL-12 p40-1188 A→C, and IFN-γ+874A→T polymorphisms were identified by amplified refractory mutation system polymerase chain reaction and IL-6-174 G/C, restriction fragment length polymorphism based on standard methods.Six hundred and fifty one ACS patients along with 432 age and sex matched controls were analyzed for various gene polymorphisms. The "low-producer" IL-10-1082 AA (χ(2)=9.45; p=0.0021; odds ratio [OR]=1.472; 95% confidence interval [CI]=1.15-1.884), "high producer" IL-10-592 CC (χ(2)=39.42; p=0.001, OR=2.26; 95% CI=1.748-2.292), "low producer"IFN-γ+874AA (χ(2)=28; p0.00154; OR=2.3695% CI=1.713-3.251), and "high producer" TNF-α -308AA (χ(2)=3.213, p=0.073; OR=1.515) genotypes may be responsible for the regulation of immune response leading to inflammation in ACS patients. However, -1188 of the IL-12 gene was not associated with the disease.The polymorphisms at -308G→A of TNF-α, -174G→C of IL-6, +874A→T of IFN-γ and -1082G→A, and -592C→A of IL-10 genes evaluated in the present study are important risk factors for the development of ACS in the South Indian population from Andhra Pradesh. The better understanding of these variants conferring susceptibility to ACS may aid in early diagnosis and development of new methods to create personalized medicine.

Natural products have become increasingly important in pharmaceutical discoveries, and traditional herbalism has been a pioneering specialty in biomedical science. The search for effective plant-derived anticancer agents has continued to gain momentum in recent years. The present study aimed to investigate the role of crude extracts of the aerial parts of Artemisia absinthium (AA) extract in modulating intracellular signaling mechanisms, in particular its ability to inhibit cell proliferation and promote apoptosis in a human breast carcinoma estrogenic-unresponsive cell line, MDA-MB-231, and an estrogenic-responsive cell line, MCF-7. Cells were incubated with various concentrations of AA, and anti-proliferative activity was assessed by MTT assays, fluorescence microscopy after propidium iodide staining, western blotting and cell cycle analysis. Cell survival assays indicated that AA was cytotoxic to both MDA-MB-231 and MCF-7 cells. The morphological features typical of nucleic staining and the accumulation of sub-G1 peak revealed that the extract triggered apoptosis. Treatment with 25 μg/mL AA resulted in activation of caspase-7 and upregulation of Bad in MCF-7 cells, while exposure to 20 μg/mL AA induced upregulation of Bcl-2 protein in a time-dependent response in MDA-MB-231 cells. Both MEK1/2 and ERK1/2 was inactivated in both cell lines after AA treatment in a time-dependent manner. These results suggest that AA-induced anti-proliferative effects on human breast cancer cells could possibly trigger apoptosis in both cell lines through the modulation of Bcl-2 family proteins and the MEK/ERK pathway. This might lead to its possible development as a therapeutic agent for breast cancer following further investigations.

To gain insight into the possible origin of the hemagglutinin of 2009 outbreak, we performed its comparative analysis with hemagglutinin of influenza viral strains from 2005 to 2008 and the past pandemics of 1977, 1968, 1957 and 1918. This insilico analysis showed a maximum sequence similarity between 2009 and 1918 pandemics. Primary structure analysis, antigenic and glycosylation site analyses revealed that this protein has evolved from 1918 pandemic. Phylogenetic analysis of HA amino acid sequence of 2009 influenza A(H1N1) viruses indicated that this virus possesses a distinctive evolutionary trait with 1918 influenza A virus. Although the disordered sequences are different among all the isolates, the disordered positions and sequences between 2009 and 1918 isolates show a greater similarity. Thus these analyses contribute to the evidence of the evolution of 2009 pandemic from 1918 influenza pandemic. This is the first computational evolutionary analysis of HA protein of 2009 H1N1 pandemic.

The inherited disorders of hemoglobin synthesis are the most common monogenic disorders worldwide. They include thalassemias, hemoglobin variants, and hereditary persistence of fetal hemoglobin. β-thalassemia is the most common monogenic disorder in India. Clinical manifestations of β-thalassemia are extremely variable in severity. The reasons for this heterogeneity are not very well understood. Previous studies have shown that the genetic variants that modulate HbF levels have a very strong impact on ameliorating the clinical phenotype. In the present study, 5570 blood samples from suspected cases were analyzed using HPLC, amplification refractory mutation system-PCR and reverse dot blot techniques. Of 5570 individuals, we found 676 cases of β-thalassemia disease. Molecular analysis revealed the presence of different β-thalassemia mutations in the population under study. Patients with β-thalassemia were classified into mild, moderate, and severe according to severity score based on Hb level, age of onset, age at which patients received their first blood transfusion, degree of growth retardation and splenectomy. Patients with β-thalassemia were analyzed for zinc finger and homeoboxes 2 (ZHX2) G779A polymorphism, and the association between ZHX2 gene polymorphism and severity of β-thalassemia was evaluated. We did not find a significant difference in genotypic and allelic frequency of ZHX2 gene between mild and moderate, mild and severe, and moderate and severe cases. There was no significant difference in high and low percentage of HbF in GG, GA, and AA bearing individuals showing that ZHX2 gene variant has no role in ameliorating the severity of β-thalassemia major in the South Indian population from Andhra Pradesh.

Within the past few years there has been increasing evidence that the genetic variation in the genes coding pro- and anti-inflammatory markers may play an important role in the pathogenesis of various human diseases, including stroke. The aim of the study was to evaluate the association of Interleukin-10 (IL-10)-1082 G/A, promoter polymorphism (rs1800896) with ischemic stroke in a South Indian population from Andhra Pradesh. In this study 480 ischemic stroke patients and 470 age and sex matched healthy controls were included. The ischemic stroke patients were classified according to TOAST classification. The region of interest in the IL-10 gene was amplified by polymerase chain reaction with the use of allele specific oligonucleotide primers flanking the polymorphic region. Association between genotypes and stroke was examined by Odds Ratio (OR) with 95% confidence interval (CI) and Chi-square analysis. Significant difference was observed between the patients and healthy controls, in genotypic distribution as well as allelic frequency (p0.05). Multiple logistic regression analysis with forward stepwise selection using the potential confounders (sex, age, diabetes, hypertension, smoking and alcoholism) and IL-10 gene variant revealed that -1082 G/A polymorphism in the promoter region of IL-10 gene is significantly [adjusted OR=2.26; 95% C.I. (1.24-4.15), p0.001] associated with ischemic stroke in the South Indian population from Andhra Pradesh. We found significant association of this polymorphism with stroke of undetermined etiology (p0.001). Moreover, hypertensive and diabetic individuals bearing A allele of IL-10 gene in high frequency were found to be more predisposed to stroke.

Stroke is a complex disease caused by combination of multiple risk factors. Recent findings have suggested that stroke has a strong genetic component. Evidence suggests that variations in the estrogen receptor α (ESR1) gene may influence stroke risk.The present study was carried out to investigate the role of ESR1 gene polymorphisms [PvuII (rs 2234693) and XbaI (rs 9340799)] with stroke in a South Indian population from Andhra Pradesh. The relationship between ESR1 genotypes with estradiol levels was also investigated in pre- and postmenopausal women.Four hundred patients with ischemic stroke and three hundred and eighty subjects were enrolled in this case-control study. Ischemic stroke subtypes were classified according to TOAST (Trial of Org 10172 in Acute Stroke Treatment) classification. The ESR1 PvuII and XbaI genotypes were determined by PCR-RFLP method. Serum estradiol was measured by ELISA.In case of PvuII polymorphism statistically significant difference was observed in the genotypic and allelic frequencies between patients and controls (joint analysis of men and women) (p=0.003 and 0.004 respectively). However, the XbaI genotypes and alleles did not show an association with stroke in the study population. When the analysis was carried out separately for men and women, the PvuII polymorphism did not show significant association with stroke in men; women showed a significant association. Further when women were grouped in to premenopausal and postmenopausal, the premenopausal group did not show a significant association with the polymorphism but significant association with stroke was found in postmenopausal women. A stepwise multiple logistic regression analysis confirmed these findings. Women with pp genotype had low estradiol levels in comparison with PP genotypic individuals (p0.05). Further evaluating the association of this polymorphism with stroke subtypes, we found significant association of PvuII polymorphism with extracranial atherosclerosis, lacunar and cardioembolic stroke.In conclusion our results suggest the PvuII gene polymorphism is significantly associated with stroke in postmenopausal women in a South Indian population from Andhra Pradesh. The pp genotypes have average 17β estradiol levels which are significantly low in comparison with PP genotypes. Therefore postmenopausal women with a high frequency of pp genotype are more predisposed to ischemic stroke. However, this is a preliminary study and the results need to be confirmed in a larger cohort.

Stroke is a complex disease caused by combination of multiple risk factors. Recent findings have suggested that stroke has a significant genetic component. Various types of genetic polymorphisms have been suggested to contribute to the risk of stroke. Gene polymorphisms of renin-angiontensin aldosterone system (RAAS) have been suggested to be risk factors for hypertension, cardiovascular diseases and stroke. In the present case-control study we investigated the association of -344C/T (rs1799998) [corrected] polymorphism in the promoter region of the human aldosterone (CYP11B2) gene with genetic predisposition to hypertension, ischemic stroke and stroke subtypes classified according to TOAST (Trial of Org 10172 in Acute Stroke Treatment) classification. Four hundred and three stroke patients (hypertensives:normotensives=219:184) and three hundred and ninety four, sex and age matched healthy controls (hypertensives:normotensives=118:276) were involved in the study. The region of interest in the CYP11B2 gene was amplified by polymerase chain reaction and genotypes determined by subjecting the PCR products to restriction digestion by the enzyme HaeIII. Significant difference was observed in the genotypic distribution and allelic frequency between the stroke patients and healthy controls. TT genotype and T allele associated significantly with hypertension and stroke (p

Plant epigenetics has become one of the hottest topics of research not only as a subject of basic research but also as a possible new source of beneficial traits for plant breeding. In addition, epigenetic mechanisms are also crucial to appropriate plant reactions to stress. Given the sessile lifestyle and the late differentiation of the germ line, plants can perceive stresses during vegetative growth and also memorize them, possibly by epigenetic mechanisms. Plants use three systems to initiate and regulate epigenetic gene regulation, like other higher organisms, which include DNA methylation, histone modifications, and RNA interference. New concepts are being evolved to show how these epigenetic components interact and stabilize each other. The role of epigenetic mechanisms in hybrid vigor and epigenetic transgene silencing is also being explored. In this chapter, we have tried to highlight the epigenetic mechanisms that play key roles in plants.