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Sickle cell anemia (SCA) is the most common genetic disorder that is caused due to mutation of the β globin gene. Although SCA is a monogenic disorder, the clinical presentation varies greatly among patients. The present study was designed to be a cross sectional study, aimed at analysing the SCA severity and its association with different clinical, biochemical and hematological variables in SCA patients of Indian origin. About 190 random homozygous SCA patients confirmed by hemoglobin electrophoresis were used in the study. Routine biochemical laboratory (liver function test and Renal function test) and hematologic tests (Total hemoglobin, fetal hemoglobin, hematocrit, MCV and MCH) were done. Values pertaining to complete blood count (CBC), Hb-HPLC and clinical investigations were collected from patient’s records. The mean age of patients with severe disease was significantly lesser than the moderate and mild disease patients. The body mass index (BMI) was also significantly lower in severe disease patients compared to the moderate and mild disease. The patients with severe disease had low levels of red blood cells, total hemoglobin (tHb) and fetal hemoglobin (HbF) compared to the other groups. There is no significant difference in the kidney and liver function among various degrees of disease severity. In summary, this study demonstrates that the tHb and HbF and total leucocyte count (TLC) are major prognostic factors for several clinical complications in SCA. Baseline measurement of these important variables is paramount in predicting important aspects of clinical course and improves the quality lives of these children.

Epilepsy responds to pharmacotherapy in its initial stages. The response of some forms of epilepsy, like the refractory epilepsy, is extremely low. Surgical management of epilepsy is associated with complications, which necessitates the search for novel and modern strategies for the treatment of epilepsy. Neuroprotection and neuronal regeneration are the major targets that must be accomplished by the new strategies. Hematopoietic Stem Cell (HSCs) therapy for epilepsy has shown promising results in pre-clinical studies with marginal clinical effects. This review explores the characteristics, mechanism of action, and clinical significance of HSCs therapy for the treatment of epilepsy.

The novel coronavirus disease-2019 (COVID-19) is caused by a positive-sense single-stranded RNA virus which belongs to the Coronaviridae family. In March 2019 the World Health Organization declared that COVID-19 was a pandemic. COVID-19 patients typically have a fever, dry cough, dyspnea, fatigue, and anosmia. Some patients also report gastrointestinal (GI) symptoms, including diarrhea, nausea, vomiting, and abdominal pain, as well as liver enzyme abnormalities. Surprisingly, many studies have found severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral RNA in rectal swabs and stool specimens of asymptomatic COVID-19 patients. In addition, viral receptor angiotensin-converting enzyme 2 and transmembrane protease serine-type 2, were also found to be highly expressed in gastrointestinal epithelial cells of the intestinal mucosa. Furthermore, SARS-CoV-2 can dynamically infect and replicate in both GI and liver cells. Taken together these results indicate that the GI tract is a potential target of SARS-CoV-2. Therefore, the present review summarizes the vital information available to date on COVID-19 and its impact on GI aspects.

Sickle cell disease (SCD) is a severe hereditary blood disorder caused by a mutation of the beta-globin gene, which results in a substantial reduction in life expectancy. Many studies are focused on various novel therapeutic strategies that include re-activation of the γ-globin gene. Among them, expression therapy caused by the fetal hemoglobin (HbF) at a later age is highly successful. The induction of HbF is one of the dominant genetic modulators of the hematological and clinical characteristics of SCD. In fact, HbF compensates for the abnormal beta chain and has an ameliorant effect on clinical complications. Erythropoiesis is a multi-step process that involves the proliferation and differentiation of a small population of hematopoietic stem cells and is affected by several factors, including signaling pathways, transcription factors, and small non-coding RNAs (miRNAs). miRNAs play a regulatory role through complex networks that control several epigenetic mechanisms as well as the post-transcriptional regulation of multiple genes. In this review, we briefly describe the current understanding of interactions between miRNAs, their molecular targets, and their regulatory effects in HbF induction in SCD.

Influenza is a highly contagious respiratory infection caused by the circulating Swine flu virus. According to the World Health Organization (WHO), the unique blending strain of influenza A H1N1 2009 (Swine Flu) is a pandemic affecting several geographical regions, including India. Previous literature indicates that children are "drivers" of influenza pandemics. At present, satisfactory data were not available to accurately estimate the role of children in the spread of influenza (in particular 2009 pandemic influenza). However, the role of children in the spread of pandemics influenza is unclear. Several studies in children have indicated that the immunization program decreased the occurrence of influenza, emphasizing the significance of communities impacted by global immunization programs. This article provides a brief overview on how children are a key contributor to pandemic Influenza A (2009 H1N1) and we would like to draw your attention to the need for a new vaccine for children to improve disease prevention and a positive impact on the community.

Background: Breast cancer (BC) accounts for one of the most prevalent malignancies in the world. Inflammatory molecules modulate tumor microenvironment in BC that promotes tumor growth and metastasis. NF-κB (a transcription factor) that regulates multiple immune functions and acts as a crucial mediator of inflammatory responses. Objective: The present study is aimed to quantitatively summarize the relation of NFKB1-94 ATTG (I, insertion/D, deletion) variant and risk of BC. Methods: Further, the meta-analysis includes three independent case-control investigations that focus on NFKB1-94, ATTG I/D polymorphism, and BC patients. Web of Science, PubMed and Embase databases were used to retrieve relevant data. OR and 95% confidence interval of pooled studies were analyzed by using the MetaGenyo web tool. Results: This study revealed a high heterogeneity. In all three genetic comparison models, the NFKB1-94 ATTG I/D variant is not related to the risk of BC. Further, no publication bias on the connection between NFKB1-94 ATTG I/D variant and risk of BC was observed. Conclusion: To summarize, our meta-analysis demonstrates that the NFKB1-94 ATTG I/D polymorphism is not a major risk factor for BC.

Background The neuropeptide Y (NPY) is one of the most abundant neurotransmitters in the nervous system. NPY acts as a potent stimulator of angiogenesis, inflammation, and adipogenesis, through the NPY 2 receptor (NPY2R). Changes in the NPY signaling pathway have been linked to Acute Coronary Syndrome (ACS). Objectives The purpose of this study is to determine the association between variants in the NPY and NPY2R genes, as well as the severity of acute coronary syndrome (ACS). Methods Approximately 221 ACS patients and 278 healthy controls were selected for this study. Four variants in NPY and two variants in NPY2R genes were genotyped using Taqman allelic discrimination and sequencing. The Chi-square and Fisher's exact tests were used to verify the genotype frequencies. The logistic regression analyses were used for the evaluation of the studied variables. Haplotype analysis was used to evaluate the linkage disequilibrium (LD) between the variants (pC variant was found with the ACS group when compared to the healthy group. In the analysis between variants and risk factors in the ACS group, NPY c.84G>A was associated with hypertension. The analysis between TIMI risk showed a significance for NPY c.20T>C between the low and intermediate/high TIMI risk groups. In the haplotype analysis, strong linkage disequilibrium (LD) was found between the variants NPY c.150G>A and NPY c.-485T>C. Conclusion The NPY c.20T>C variant appears to contribute to the development of ACS. The NPY2R c.-1116A>G variant may contribute to the early development of ACS and the NPY c.84G>A variant appears to contribute to the development of hypertension. In addition, the NPY c.20T>C is associated with a protective effect in ACS severity.

Introduction: The neuropeptide-Y (NPY) is involved in the development of alcoholism through NPY receptors. A T>C mutation causes substitution of leucine to proline at codon 7 (L7P; rs16139) in the signal peptide of neuropeptide Y is known to cause a 42% increase in plasma NPY levels. Studies that analyzed the association between NPY rs16139 and alcoholism risk did not demonstrate conclusive evidence for this relationship. The present study aims to evaluate the association between NPY gene rs16139 variant and alcohol dependence.Method: An electronic search of databases including PubMed and Google Scholar was performed to retrieve studies investigating the association between NPY rs16139 and alcoholism. The pooled odds ratio (OR) with 95% confidence interval (CI) was calculated in allelic and dominant genetic models. Sensitivity analyses and publication bias were assessed in our meta-analysis. The meta-analysis was conducted using the MetaGenyo web tool.Result: Significant heterogeneity was observed across studies (p < 0.001). Our results have shown that there is no significant association between NPY rs16139 variant and the risk of alcoholism in allelic (OR = 0.98, 95% CI 0.70–1.38, p = 0.921) and dominant models (OR = 0.98, 95% CI 0.69–1.40, p = 0.919). Begg's funnel plot and Egger's test have not shown publication bias (p = 0.332).Conclusion: To the best of our knowledge, this is the first meta-analysis that evaluates the relationship between the NPY rs16139 polymorphism and the risk of alcoholism. Our large-scale meta-analysis suggests that NPY rs16139 polymorphism is not associated with alcoholism. However, further studies are needed to increase our understanding of the relationship between NPY variants in alcoholism.

Physical activity (PA) and nutrition are the essential components of a healthy lifestyle, as they can influence energy balance, promote functional ability of various systems and improve immunity. Infections and their associated symptoms are the common and frequent challenges to human health that are causing severe economic and social consequences around the world. During aging, human immune system undergoes dramatic aging-related changes/dysfunctions known as immunosenescence. Clinically, immunosenescence refers to the gradual deterioration of immune system that increases exposure to infections, and reduces vaccine efficacy. Such phenomenon is linked to impaired immune responses that lead to dysfunction of multiple organs, while lack of physical activity, progressive loss of muscle mass, and concomitant decline in muscle strength facilitate immunosenescence and inflammation. In the present review, we have discussed the role of nutrition and PA, which can boost the immune system alone and synergistically. Evidence suggests that long-term PA is beneficial in improving immune system and preventing various infections. We have further discussed several nutritional strategies for improving the immune system. Unfortunately, the available evidence shows conflicting results. In terms of interaction with food intake, PA does not tend to increase energy intake during a short time course. However, overcoming nutritional deficiencies appears to be the most practical recommendation. Through the balanced nutritious diet intake one can fulfill the bodily requirement of optimal nutrition that significantly impacts the immune system. Supplementation of a single nutrient as food is generally not advisable. Rather incorporating various fruits and vegetables, whole grains, proteins and probiotics may ensure adequate nutrient intake. Therefore, multi-nutrient supplements may benefit people having deficiency in spite of sufficient diet. Along with PA, supplementation of probiotics, bovine colostrum, plant-derived products and functional foods may provide additional benefits in improving the immune system.

Introduction: In spite of the substantial advances in clinical practice, Gastric cancer (GC) remains the third leading cause of cancer death worldwide. The incidence of drug resistance remains a hindrance to effective treatment for GC. Although the molecular mechanisms of chemoresistance have broadly studied, the gene regulation and expression mechanisms of miRNA have not entirely understood. Methods: Online databases of PubMed, Scopus, Google Scholar, and Embase databases were searched to retrieve relevant publications. The following keywords were used: MicroRNA, Noncoding RNA, miRNA, Gastric cancer, drug resistance, and chemoresistance. Results: miRNAs play a pivotal role in the initiation, progression of tumor and metastasis, as well as in the development of pathways mediating resistance to chemotherapy in GC. Unluckily, to date, there is no consistent, reliable biomarker available to predict the response of chemotherapy before the start of the treatment. Discussion: In this review, we would like to provide an overview of the miRNAs and miRNA facilitated chemoresistance machinery in GC to develop a personalized treatment to overcome GC drug resistance.

Introduction Periodontitis is a multifactorial host-mediated oral disease caused by microbes. Previous studies suggested that interleukin-6 (IL-6) gene promoter polymorphism (-174G > C) are associated with the risk of periodontitis, although the results were inconclusive. This study investigated the association between IL-6 -174G > C polymorphism and susceptibility to periodontitis. Method A comprehensive search was conducted in PubMed, EMBASE, Web of Science, and Google Scholar databases to retrieve relevant studies. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were calculated to assess the strength of the association between 174G > C polymorphism and the risk of periodontitis. Cochrane Q and I2 statistics were used to measure heterogeneity between studies. Publication bias was estimated using Begg's funnel plots and Egger's test. Results Our results showed significant differences in the allelic (C vs. G: OR = 0.82, CI = 0.65–1.03), recessive (CC vs. GC + GG: OR = 0.69, CI = 0.42–1.13), and dominant (GC + CC vs. GG: OR = 0.85, CI = 0.63–1.13) genetic models of the IL6 -174G > C polymorphism and risk of periodontitis. Further, subgroup analysis showed decreased susceptibility to periodontitis associated with IL6 -174 G > C in a Brazilian population (C vs. G: OR = 0.60, CI = 0.41–0.88; GC + CC vs. GG: OR = 0.57, CI = 0.42–0.78) but not in Asian or Caucasian populations. Conclusion The findings of this study revealed that the IL6 -174 “C" allele is protective against periodontitis in the Brazilian population.

Background/objective: Colorectal cancer (CRC) is aggressive and widespread (3rd among malignancies) in the United States. Recent studies suggest that metabolic pathways play an essential role in CRC. NQO1 is an enzyme that contributes to chemoprotection for CRC. Previous studies showed that the link between the NQO1 polymorphisms and CRC risk yielded conflicting results. The aim of this meta-analysis is to test the connection between NQO1 C609T polymorphisms and CRC risk. Methods: PubMed, Web of Science, and Google Scholar were used in bibliographic searches until July 17, 2021. For the NQO1 C609T analysis, a total of 18 studies (7568 CRC cases and 9003 controls) were considered. Data was gathered and subsequently calculated using the pooled odds ratio (OR) (95% confidence interval, CI). Results: The relation between NQO1 polymorphism and CRC risk (T vs. C: OR=1.17, 95% CI=1.07-1.29, p Conclusion: This study indicates that the C609T polymorphism of NQO1 is linked with CRC risk in Caucasian populations. Citation Format: Chaithanya Ganji, Raasil R. Basha, Lakkakula V.K.S. Bhaskar, Bassel F. El-Rayes. Meta-analysis of the NQO1 gene C609T polymorphism: Increased risk of colorectal cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 1439.

Hepatocellular carcinoma (HC) is a malignant primary liver cancer which has poor treatment outcomes in advanced stages, and many of the HC patients present with advanced stages. The incidence of death due to HC increase as a result of ineffective treatments for advanced stage disease. Early diagnosis and management has proven benefits in both survival and quality of life. Currently very few biomarkers are available to provide diagnostic and prognostic benefits in HC patients. The present review elaborates the association of cardiac markers in HC disease. The HC disease pathology includes many cardiovascular events like hypoxia and other parameters discussed in this review which have a role in disease advancement, and also may help as diagnostic and / or prognostic markers. The scientific lacuna in association / role of cardiac markers in HC disease is also stated in this review which may be helpful for future research studies and develop cost effective biomarker for early diagnosis of HC.

Novel coronavirus disease 2019 (COVID-19) is a positive-sense single-stranded RNA virus which belongs to the Coronaviridae family. COVID-19 outbreak became evident after the severe acute respiratory syndrome coronavirus and the Middle East respiratory syndrome coronavirus in the twenty-first century as the start of the third deadly coronavirus. Currently, research is at an early stage, and the exact etiological dimensions of COVID-19 are unknown. Several candidate drugs and plasma therapy have been considered and evaluated for the treatment of severe COVID-19 patients. These include clinically available drugs such as chloroquine, hydroxychloroquine, and lopinavir/ritonavir. However, understanding the pathogenic mechanisms of this virus is critical for predicting interaction with humans. Based on recent evidence, we have summarized the current virus biology in terms of the possible understanding of the various pathophysiologies, molecular mechanisms, recent efficient diagnostics, and therapeutic approaches to control the disease. In addition, we briefly reviewed the biochemistry of leading candidates for novel therapies and their current status in clinical trials. As information from COVID-19 is evolving rapidly, this review will help the researcher to consider new insights and potential therapeutic approaches based on up-to-date knowledge. Finally, this review illustrates a list of alternative therapeutic solutions for a viral infection.

Endometrial cancer (EMC) is the most common gynecological cancer, accounting for more than 2% of cancer deaths in women worldwide. The present meta-analysis deals with the association between the CYP1B1 rs1056836 variant and risk of EMC. For the collection of data, we rigorously searched Google Scholar, PubMed, and Embase for relevant published articles. The association between CYP1B1 rs1056836 and EMC was assessed by calculating odds ratios (ORs) with 95% confidence intervals (CIs). Values of I2 statistics were calculated with the help of the Cochrane Q test to determine heterogeneity of the study. To understand between-study heterogeneity, subgroup analysis and sensitivity analysis were performed. Funnel plots as well as Egger's tests were performed to determine publication bias. A total of 4804 cases of EMC and 7185 control patients involving the CYP1B1 rs1056836 polymorphism and EMC risk were investigated from 17 independent studies. Pooled analysis in a dominant genetic model showed that there is significant association between the CYP1B1 rs1056836 polymorphism and development of EMC (OR = 1.31; 95% CI 1.08–1.59; P = 0.005). There is significant heterogeneity between ethnic groups with no publication bias observed. In summary, this meta-analysis revealed that rs1056836 is a major risk factor for developing EMC. Further research is still needed to investigate the clinical and biological implications of these associations.

Numerous studies have provided novel insights into the potential role of genetic polymorphisms as prognostic markers in gynecologic cancers, particularly cervical cancer. Cervical cancer is the second most common and primary cause of cancer-related deaths in developing countries. Deep research into single-nucleotide polymorphisms (SNPs) may help to explain potential differences in distinct cancers. Candidate SNPs may be involved in immune cell regulation, cell-cycle control, DNA damage and repair, cancer metabolism, and apoptosis. In the present chapter, we have summarized important findings of genetic association studies exploring the role of glutathione-S-transferase (GST), interleukins (ILs), p53 codon 72, tumor necrosis factor A gene (TNFA), human leukocyte antigen (HLA), Fas gene polymorphism, murine double-minute two homologs (MDM2), and interferons-γ (IFNG) gene polymorphism with cervical cancer. Genetic association studies will require further validation to provide direction for future research leading to better clinical outcomes for patients with cervical cancer.

Breast and cervix cancers are major diseases among women with increasing incidence worldwide. Apart from disease burden, costs related to treatments and diagnoses of breast and cervical cancers put a major stress on the health and economic status of patients as well as the countries they are from. In most low- and middle-income countries, treatments of these diseases cause a larger economic burden on patients. The introduction of pharmacoeconomics reduces the economic burden of disease management on both patient and governments. This chapter discusses the worldwide cost burden and cost-effective treatments of breast and cervix cancer, which may be a pharmacoeconomic input.

Hepatocellular carcinoma (HCC) is one of the most common primary hepatic tumors, and it is ranked as the third most common cause of cancer-linked deaths. Although the precise etiology of HCC is unknown, inflammation has been considered the foremost cause of HCC. Previous studies indicated that tumor necrosis factor-alpha (TNF-α) is associated with increased risk of HCC, but the results are conflicting. In the present study, we assessed the correlation between TNF-α G-308A polymorphism as well as HCC risk via a meta-analysis. We searched databases such as PubMed, EMBASE, and Web of Science for articles related to this subject. To evaluate the correlation between TNF-α G-308A polymorphism and HCC, the odds ratios (ORs) with 95% confidence intervals (CIs) were calculated. Between-study heterogeneity was assessed using Cochrane Q test and I2 statistics. To assess the robustness of data, sensitivity analysis, publication bias, and subgroup analysis were conducted. Approximately 30 articles with 4,753 cases of HCC and 6,667 controls were included for the meta-analysis. Overall, the TNF-α G-308A polymorphism notably correlated with increased risk of HCC in the dominant model (OR = 1.41, 95% CI: 1.02-1.94, P = 0.036). Furthermore, a subgroup investigation showed significant correlation between TNF-α G-308A polymorphisms and HCC risk only in Asian populations (dominant model OR = 1.55, 95% CI: 1.05-2.23, P = 0.025). Studies in ethnic groups showed significant heterogeneity (I2 > 50%). Funnel plot and Eggers p values did not reveal publication bias. The present meta-analysis suggested that TNF-α G-308A polymorphisms are correlated with an elevated risk of HCC in Asian populations.

Background Coronavirus disease 2019 (COVID-19) is a major public health concern currently. To date, there are no approved antiviral drugs or vaccines against this transmissible disease. This report sheds light on available information for a better understanding of clinical trials and pharmacotherapy related to COVID-19. Methods MEDLINE, PubMed, EMBASE, Scopus databases, Web of Science, WHO, and EU clinical trial sites were used to perform comparative analysis. Information was collected on the use of therapeutic agents for human therapy in patients with COVID-19 up to May 2020. Results We have extracted data from 60 clinical trials. Amongst these trials, 34 were from the European Union database of clinical trials and 26 from the National Institute of health. The data selection procedure includes active, completion, and recruitment in progress status. Most of the clinical trials are ongoing and hence, there is a lack of precise results for the treatment. Conclusions There is a lack of high-quality clinical evidence. The protocol to be developed requires large randomized clinical trials with a combination of available drugs and prospective therapies. We propose the usage of a large number of cases and different statistical analyses to conduct systematic clinical trials. This could provide comprehensive information about the clinical trial and potential therapeutic progress.

Systemic lupus erythematosus (SLE) is an autoimmune disease triggered by a complex interaction of immunologic, environmental, and genetic factors. Like other diseases of autoimmune origin, SLE manifestations follow relapsing and remitting courses. Several lines of evidence have demonstrated the association of adaptive and innate immune responses with regulation in SLE pathogenesis. The immunological diagnosis primarily relies on detection of serum autoantibodies in SLE patients. A concordance rate of < 25% between monozygotic twins indicates potential involvement of environmental factors in SLE development. In addition, SLE is categorized by a wide range of clinical manifestations, partly related to the disease itself but also associated with comorbidities and adverse drug reactions. Because the common therapeutic strategies are connected with certain adverse events, immunosuppressive medications and biological agents are used on the basis of prevailing disease manifestations. Genome-wide association studies have identified 50 loci that influence SLE. However, the actual genetic polymorphism that imparts SLE risk is not fully known. Further understanding can help to expand quality of life in SLE individuals.

Lipoxygenases (LOXs) are dioxygenases that catalyze the peroxidation of linoleic acid (LA) or arachidonic acid (AA), in the presence of molecular oxygen. The existence of inflammatory component in the tumor microenvironment intimately links the LOXs to gastrointestinal (GI) cancer progression. Amongst the six-different human LOX-isoforms, 5-LOX is the most vital enzyme for leukotriene (LT) biosynthesis, which is the main inflammation intermediaries. As recent investigations have shown the association of 5-LOX with tumor metastasis, there has also been significant progress in discovering the function of 5-LOX pathway in GI cancer. Studies on GI cancer cells using the pharmacological drugs targeting 5-LOX pathway have shown antiproliferative and proapoptotic effects. Pharmacogenetic discoveries in other diseases have revealed strong heritable basis for the leukotriene pathway, which helps in exploring the mechanistic source of genetic alteration within the leukotriene pathway and offer insights into GI cancer pathogenesis and future prospects for treatment and prevention. This review recapitulates the current research status of 5-LOX activity in GI malignancies.

A single nucleotide polymorphism (SNP) rs2853669 (A>G) in the telomerase reverse transcriptase (TERT) promoter has recently been reported in chr5:1,295,349 T>C (T349C), and was shown to be associated with increased cancer risk and poor survival in a specific population. However, at present, the role of this particular SNP with TERT promoter driver mutations and its genetic association with human papilloma virus (HPV) in patients with cervical cancer has not been determined. In the present study, the genetic association of the functional SNP rs2853669 in the presence/absence of TERT promoter hotspot mutations and HPV in patients with cervical cancer of South Indian origin was evaluated. To understand and compare the frequency of the variant allele and its risk association in different cancer types of various populations, the SNP was genotyped in 257 cervical cancer samples and 295 controls, and its associations with TERT promoter hotspot mutations and HPV were analyzed. Furthermore, an extensive search of previously published articles in PubMed, Embase and Web of Science was conducted; a meta-analysis was carried out to elucidate the association of the SNP with different cancer types in global populations. The SNP analysis showed significantly high frequency (41%) of homozygous variant allele rs2853669 (GG) in patients with cervical cancer compared with control samples [Recessive allele model odds ratio (OR)=1.71; 95% CI=1.20-2.43; P=0.003]. No significant interaction was observed between the TERT SNP rs2853669 and HPV status as well as other hotspot TERT promoter (C228T and C250T) mutations determined in our previous study. In addition, the overall meta-analysis revealed a significant association of the SNP rs2853669 with other cancer types in different ethnic populations (OR=1.09; 95% CI=1.03-1.16; P=0.004). The present results suggested that the TERT SNP rs2853669 could play an important role in the risk of cervical cancer in a South Indian population.

Gastric cancer (GC) is the third most frequent cause of cancer-related deaths worldwide. The Molecular Mechanism of pathogenesis in GC is still unknown and unclear due to the Chemoresistance. Chemotherapy still remains only a single treatment for GC patients. Among those patients, most are becoming resisting to chemotherapeutic agents, nowadays chemoresistance causes recurrence and is a major challenge in the treatment of cancer because of the deregulations of numerous signaling pathways such as a tumor suppressor gene signaling, PI3K/Akt signaling, NF-кB signaling, Wnt/β-catenin signaling, mitogen-activated protein kinase (MAPK), Hedgehog signaling, Hippo signaling, Notch signaling pathways, and epidermal growth factor receptor (EGFR) have been found in GC. Epithelial-mesenchymal transition (EMT), as a major process during embryogenesis and tumor genesis, as well as is playing a vital role in chemoresistance of GC. In this chapter we summarize important molecular pathway aspects of multi-drug resistance (MDR). It is crucial for the identification of the new drug target, and combination therapy to clarify these complex molecular signaling mechanisms.

Interleukin-6 (IL-6) is a multifunctional cytokine, which plays a vital role in inflammation as well as tumorigenesis. Several studies have demonstrated that the association of IL6 -174 G/C (rs1800795) and -572 G/C (rs1800796) promoter polymorphisms influences transcription and has been found to trigger the risk of gastric tumor advancement with inconsistent and controversial result. The present study aims at collecting eligible articles through extensive search in PubMed, MEDLINE, and Embase databases. Additionally, the analysis also included 15 case–control investigations. MetaGenyo web tool was used to perform the meta-analysis. No substantial association was observed between IL6 polymorphisms and GC. In conclusion, our study signifies that polymorphisms of IL6, -174 G/C, and -572 G/C are not linked with GC risk.

Colorectal cancer (CRC) is very common malignancy all over the world. Adoption of Western diet (red meat and high fat foods) in many countries has increased the incidence of colorectal cancer. There are genetic factors as well as environmental factors contributed to the etiology of CRC. Current meta-analysis is envisioned to investigate the association between rs4779584 variant and risk of CRC. PubMed, Google Scholar, and Embase were used for the collection of publication to retrieve data. Odds ratios (ORs) with 95% confidence intervals (CIs) were calculated to evaluate the association between rs4779584 variant and risk of CRC. To determine heterogeneity, Cochrane Q test and I2 statistic were employed. Subgroup analysis and sensitivity analysis were performed to assess between-study heterogeneity. Publication bias was determined through Funnel plots and Egger’s test. Total 14 publications with 26 different studies comprising 25,469 CRC cases and 32,745 controls were finally considered for meta-analysis. Overall, a positive association of rs4779584 polymorphism with CRC risk was found in all genetic models (allelic model: OR = 1.13; 95% CI 1.08–1.18; p =

Several prospective cohort and case-control studies have provided strong evidence describing an association between alcohol consumption and risk of colorectal cancer (CRC). Studies on the association of ADH1B Arg47His and ALDH2 Glu487Lys variants with CRC risk were inconclusive. In this chapter we aimed to elucidate the genetic associations of the alcohol metabolic enzymes with CRC risk. An organized literature search was performed in PubMed, Embase and Google scholar bibliographic databases to retrieve various case-control studies associated with alcohol metabolism genes and CRC. A meta-analysis was performed based on the random-effect model to calculate the overall association of ADH1B Arg47His and ALDH2 Glu487Lys variants with CRC risk. No association was found between ADH1B and ALDH2 gene polymorphisms and susceptibility of CRC. Stratified analysis by ethnicity also did not reveal a significant association between these variants and CRC risk. Cochrane Q-test and I2 statistics revealed heterogeneity in association with these variants (P < 0.001). Publication bias tests did not reveal evidence for bias. Thus, ADH1B Arg47His and ALDH2 Glu487Lys genetic variants are not considered as risk factors for CRC.

Among all cancers, colorectal cancer (CRC) is the third most common cancer. Colorectal cancer is associated with various risk factors which may alter the physiological pathways and induce genetic mutations. The risk factors, genetic variations, gene related toxicities with treatment regimens of CRC, clinically relevant biomarker of CRC were discussed in this review. The aim of the present review is to provide a current update on the risk factors and their pathways, biomarkers and their association with treatment efficacy and toxicity in CRC, which may provide a view for the Precision Medicine in CRC.

The Tyr113His and His139Arg polymorphisms in microsomal epoxide gene (EPHX1) have been reported to be associated with colorectal cancer (CRC) risk, but the results are inconclusive. Considering the functional importance of these polymorphisms and heterogeneity in genetic association studies, we performed a meta-analysis to investigate the association between the EPHX1 Tyr113His and His139Arg polymorphisms and CRC susceptibility. A comprehensive literature search of PubMed, Embase, and Google Scholar databases were conducted before May 10, 2019. Twenty eligible studies were finally included in this meta-analysis. The pooled odds ratio (OR) with 95% confidence intervals (CIs) were calculated. In the overall analysis, both Tyr113His and His139Arg polymorphisms were not associated with CRC in allelic and dominant genetic models. On subgroup analysis, no significant associations were observed in Asians and Caucasians in any of the genetic models for these polymorphisms. Our results were confirmed by sensitivity analysis and no publication bias was found. Taken together, our data indicate that EPHX1 Tyr113His and His139Arg polymorphisms are not associated with the susceptibility to colorectal cancer. Further well-designed studies with large sample size are warranted to establish the role of EPHX1 polymorphisms in CRC, especially for Tyr113His and His139Arg.

Background:The introduction of Monoclonal Antibodies (mAbs) and small-molecule Tyrosine Kinase Inhibitors (TKIs) that target the Epidermal Growth Factor Receptor (EGFR), marks a huge step forward in the Pancreatic Cancer (PC) therapy. However, anti-EGFR therapy is found to be successful only in a fraction of patients. Although anti-EGFR agents have shown considerable clinical promise, a serious adverse event associated with anti- EGFR therapy has been challenging. At this juncture, there is still more to be done in the search for effective predictive markers with therapeutic applicability.Methods:A focused literature search was conducted to summarize the existing evidence on anti-EGFR agents in pancreatic cancer therapy.Results:This review discusses various anti-EGFR agents currently in use for PC therapy and potential adverse effects associated with it. Existing evidence on EGFR TKIs demonstrated better tolerant effects and outcomes with multiple toxic regimens. Anti-EGFR therapy in combination with chemotherapy is necessary to achieve the best clinical outcomes.Conclusion:Future prospective studies on the identification of additional biological agents and novel anti-EGFR agents are warranted.

Nanotechnology or Nano medicine has been identified as the dominant and most commercially invented technology that aims to improve the quality of health care strategies. Although nanotechnology has some limitations, many pharmaceutical and medical equipment companies have already adhered to medical nanotechnology. In some cases, drugs with high toxic potential, such as chemotherapeutic cancer drugs, can be administered with a better safety profile using nanotechnology. It is important to note that Living cells are tiny virtual machines involved in all biological activities, including cell signalling, metabolism, energy generation and nutrient transport. Therefore it can be considered a major candidate technology to deal with biology and medicine for therapeutic purposes. In this review, we discuss the importance of nanoscience with different nanotechnology platforms being used in other aspects of medicine. Besides, we are also addressing the future opportunities of nanotechnology in human health.

Background Sickle cell anemia (SCA) is characterized by chronic hemolysis and vaso-occlusive episodes. The endothelial dysfunction in SCA may be due to the deficiency of nitric oxide. The association between nitric oxide synthase (NOS3) gene polymorphisms (−786 T > C, 894G > T and intron 4a/b) and risk of vascular complications remains elusive. Objective Here we performed a meta-analysis to evaluate the relationship between NOS3 gene polymorphisms and vascular complications of SCA. Methods Ten previously published articles were retrieved from PubMed, and Embase bibliographic databases. This meta-analysis included, eight papers (463 SCA patients with complications and 333 without complications) that pertained to the NOS3 -786 T > C, five papers (235 SCA patients with complications and 191 without complications) that corresponded to the NOS3 894G > T polymorphism and six papers (391 SCA patients with complications and 292 without complications) that involved the NOS3 intron 4a/b polymorphism. Pooled analysis, sensitivity analysis and assessment of publication bias were performed. Results Results of pooled analysis revealed that the NOS3 intron 4a/b polymorphism was significantly associated with an increased risk of vascular complications (aa+ab Vs. bb: odds ratio = 3.28, 95% confidence interval = 1.19–9.02, p = 0.022, random-effect model). However, no significant association was found for NOS3 -786 T > C and 894G > T polymorphisms. Conclusion Despite some limitations, our meta-analysis suggests that NOS3 intron 4a/b polymorphism is associated with four fold-increased risk of vascular complications in sickle cell anemia.

PURPOSE: Sickle cell disease (SCD) is the most common and serious form of an inherited blood disorder that lead to higher risk of early mortality. SCD patients are at high risk for developing multiorgan acute and chronic complications linked with significant morbidity and mortality. Some of the ophthalmological complications of SCD include retinal changes, refractive errors, vitreous hemorrhage, and abnormalities of the cornea. MATERIALS AND METHODS: The present study includes 96 SCD patients. A dilated comprehensive eye examination was performed to know the status of retinopathy. Refractive errors were measured in all patients. In patients with >10 years of age, cycloplegia was not performed before autorefractometry. A subset of fifty patients’ genotyping was done for NOS3 27-base pair (bp) variable number of tandem repeat (VNTR) and IL4 intron-3 VNTR polymorphisms using polymerase chain reaction-electrophoresis. Chi-square test was performed to test the association between the polymorphisms and refractive errors. RESULTS: The results of the present study revealed that 63.5% of patients have myopia followed by 19.8% hyperopia. NOS3 27-bp VNTR genotypes significantly deviated from Hardy–Weinberg equilibrium (P < 0.0001). Although IL4 70-bp VNTR increased the risk of developing refractive errors, it is not statistically significant. However, NOS3 27-bp VNTR significantly reduced the risk of development of myopia. CONCLUSION: In summary, our study documents the prevalence of refractive errors along with some retinal changes in Indian SCD patients. Further, this study demonstrates that the NOS3 VNTR contributes to the susceptibility to development of myopia in SCD cases.

Breast cancer (BC) is considered to be one of the most malignant diseases. The microenvironment of BC is characterized as a hypoxic-like environment. Hypoxia inducible factor (HIF) is activated during hypoxic conditions, which can be generated by the BC microenvironment. Previous studies showed the relation between HIF genetic variations and BC, but were not well characterized. The objective of this meta-analysis is to analyze the relation of the HIF1A C1772T with BC by reviewing and analyzing established studies. All the data was gathered from nine studies that focused on HIF1A C1772T and BC. The literature was retrieved from electronic databases such as Web of Science, PubMed and Embase. All of the statistical data was subjected to either a fixed or random effects model to calculate OR and 95% confidence interval of pooled studies. The data was then analyzed by using the MetaGenyo web tool. This study did not find evidence for publication bias. The outcomes of the present study showed that HIF1A gene C1772T variant is not correlated with the risk of BC. However, sub-group studies by origin implied that the probability of BC was both strongly correlated with the HIF1A C1772T variant and significantly elevated among Asians. In summary, this study suggests that the probability of BC associated with the HIF1A C1772T variant was significantly higher in Asians compared to Caucasians.

Platelet derived growth factor -c (PDGF-C) plays a major role in embryogenesis especially during the neural crest cell induction. Animal studies revealed that PDGF signalling is required for orofacial development. Further, Pdgfc knockout mice also showed cleft face phenotype. The present study aims to evaluate the parental transmission effect of PDGF-C gene variants in the etiology of non-syndromic cleft lip with or without cleft palate (NSCL/P) in South Indian population. In the present study 148 triads (case-parents) were genotyped for five single nucleotide polymorphisms (SNPs) in PDGF-C gene (rs983473, rs10517653, rs17035464, rs28999109, rs1002091) using TaqMan allelic discrimination method. Haploview program 4.2 was used to test the alleleic associations by transmission disequilibrium test (TDT) and linkage disequilibrium (LD) between the SNPs. Haplotype transmission effects were analysed using FAMHAP package. Further, the possible parent-of-origin effects were assessed by likelihood based approaches. TDT analysis revealed significant excess transmission of “C” allele from rs983473 and “C” allele from rs1002091 SNPs to the affected child. The sliding window haplotype analysis method showed significant overtransmission of some haplotypes. The analysis of parent of origin effects showed an excess of maternal transmission for C allele of rs983473 SNP (5.48%) and paternal transmission for C allele of rs1002091 SNP (4.12%). The present study supported the parenteral transmission effects of PDGF-C genetic variations the pathogenesis of NSCL/P. As the number of triads included in the study are limited, further studies are needed to confirm this association in other populations with more triads and other markers of PDGF-C.

Gemcitabine (GEM) is a widely used chemotherapeutic agent for the treatment of various cancers. Very little is known about predictors of toxicity, response, and survival in patients treated with GEM. Several studies have been carried out to assess the predictive and prognostic values of genetic polymorphisms in the genes encoding the enzymes involved in the metabolism of GEM. The purpose of this chapter is to describe the comprehensive reports and draw conclusions with the available information on GEM pharmacogenetics. Overall, evidence indicates that SLC29A1, CDA, and RRM1 gene expressions and protein levels are strongly correlated with cancer patient response to GEM. However, polymorphisms in genes of these metabolizing enzymes offered very little information regarding the response or toxicity with GEM therapy. Due to the lack of strong evidence on the clinical utility of pharmacogenetic testing, more research is warranted to uncover clinically relevant SNPs associated with gemcitabine efficacy.

The association between type 2 diabetes mellitus (T2DM) and pancreatic cancer (PC) is complex bidirectional. Recent epidemiological data suggest that about 80% of PC patients have impaired glucose tolerance (IGT) or new onset of diabetes. Obesity, smoking, family history, genetic factors, insulin resistance (IR), and chronic pancreatitis are significant risk factors for PC. Several lines of evidences demonstrated that the production of insulin increases with increasing IR in diabetes patients. Hyperinsulinemia and IR are involved in the development of PC. Majority of studies suggested that risk ratio for diabetes in associated PC was higher in patients with small periods of diabetes as compared those with long periods of diabetes. Several studies also reported that antidiabetic drugs decrease risk for PC and increase survival in diabetes patients. In this chapter we describe the link between insulin resistance and pancreatic cancer risk.

Methylenetetrahydrofolate reductase (MTHFR) deficiency is the most common determinant of serum homocysteine and folate status that is associated with increased risk for many cancers. This MTHFR deficiency in pancreatic cancer (PC) pathogenesis has been attributed to genetic polymorphism of MTHFR 677C>T and 1298A>C, but the evidence is still unclear. We conducted a meta-analysis of studies evaluating the effect of these polymorphisms on PC. We searched databases such as PubMed, Embase, and Google Scholar to retrieve studies that investigated MTHFR 677C>T and 1298A>C polymorphism for PC risk. For MTHFR 677C>T analysis, a total of eight publications with 1680 cases and 2520 controls were included; and for MTHFR 1298A>C analysis, six studies with 1421 cases and 1641 controls were included. Genotypes retrieved were subjected to meta-analysis using a random- or fixed-effects model with odds ratios and 95% confidence intervals as effect measures. Our met-analysis in all genetic models showed that MTHFR polymorphisms were not associated with the risk for PC. MTHFR polymorphisms revealed significant heterogeneity between studies for MTHFR 677C>T (P = .003) but not for 1298A>C (P = .495). Furthermore, there was no evidence for publication bias for these polymorphisms. Because the distribution of MTHFR genetic polymorphism differs among ethnic groups, the results of this meta-analysis cannot be extrapolated to patients belonging to any other ethnic group.

Renal disturbances by coronavirus disease 2019 (COVID-19), consisted of acute kidney injury, due to acute tubular necrosis induced by sepsis, hydration, cytokine storm syndrome, rhabdomyolysis and hypoxia. As the direct cytopathic effect of virus on various renal cells has been detected in previous studies, direct virus invasion to the renal tubular cells and interstitium or glomeruli is possible. Previous studies showed that coronavirus enters into the cells by angiotensin-converting enzyme II receptors that are extensively presented in the renal cells. Further, acute kidney injury in COVID-19 is strongly associated with higher mortality and morbidity and is an indicator for survival with Coronavirus infection. In the overall approach to patients with COVID-19 infection, special attention should be paid to control of classical risk factors of kidney injury.

Aim was to analyze predictors of burden among primary caregivers (CGs) of Indian Parkinson's disease (PD) patients. 150 PD patients were administered using Unified Parkinson's Disease Rating Scale (UPDRS), Hoehn and Yahr Scale (H&Y), Montgomery Asberg Depression Rating Score (MADRS) and Mini Mental State Examination (MMSE) in this cross-sectional evaluation study. CG burden was assessed by Caregiver's Burden Scale (CBS), Hospital Anxiety and Depression Scale (HADS), SF-36 and 20-item Burden Assessment Schedule (BAS). Linear regression methods were used to evaluate factors contributing to burden and stress. Mean age of CG was 50.38±16.04 (range: 25-83 yrs). Marital status of CGs was noted to have significant relationship with CBS score (F=9.525, P

Gastrointestinal cancers are heterogeneous and complex among the most common human cancers. In spite of this complexity, certain types of genetic alterations are linked to specific pathological lesions. Genomic and transcriptomic analyses have disclosed molecular subtypes that are characterized by specific genetic aberrations and expression signatures. Identification of better molecular markers to assist detection and prognostic evaluation of the cancer is therefore required. Tyrosine kinases are enzymes responsible for the activation of many proteins by signal transduction cascades. Inhibitors of tyrosine kinases (TKIs) have been effectively used for clinical treatment of certain types of cancer. Chronic exposure to gradually increasing concentrations of the TKI over a period of time, cells by activating modified signaling pathway can replace the lack of signal in target therapy, leading to the development of drug resistance. In recent years, researchers have specified different subsets of tyrosine kinase inhibitors’ potential resistance mechanisms in various gastric cancers. This chapter intends to provide an overview of the most recently identified molecular mechanisms of acquired resistance to tyrosine kinase-targeted therapy in various gastrointestinal malignancies.

Diabetic nephropathy (DN) is a chronic microangiopathic complication of both type 1 (T1DM) and type 2 diabetes mellitus (T2DM). The TCF7L2 gene has been reported to be associated with type 2 diabetes risk. We aimed to investigate the impact of TCF7L2 gene on the susceptibility of T2DM and DN in a south Indian population. Plus to evaluate the association of rs7903146 in the TCF7L2 gene with T2DM in the Indian population. The subjects recruited for this included 55 diabetic cases with diabetic nephropathy, 68 diabetic cases without nephropathy, and 82 non-diabetic healthy controls. Genomic DNA was isolated from blood and genotyping of TCF7L2 rs7903146 was performed by PCR-RFLP analysis. A literature survey was carried out into the effect of rs7903146 on genetic susceptibility to T2DM in Indian populations and we then performed a meta-analysis in order to evaluate its association with T2DM. Analysis of TCF7L2 rs7903146 in normal controls and diabetics with or without nephropathy demonstrated that the ‘T’ allele is associated with both diabetes (p = 0.049) and DN (p = 0.024), but this association is not independent of T2DM. Meta-analysis showed that the mutant allele and genotypes are associated with T2DM in Indian populations. In summary, a significant association exists between the ‘T’ allele and DN, but this association is not independent of T2DM. Pooled meta-analysis of studies on rs7903146 and T2DM confirmed that rs7903146 is significantly associated with susceptibility to T2DM in Indian populations. (Endokrynol Pol 2014; 65 (4): 298–305)

BackgroundAlcohol dependence (AD) is one of the major elements that significantly influence drinking pattern that provoke the alcohol-induced organ damage. The structural and neurophysiologic abnormalities in the frontal lobes of chronic alcoholics were revealed by magnetic resonance imaging scans. It is well known that candidate genes involved in dopaminergic pathway are of immense interest to the researchers engaged in a wide range of addictive disorders. Dopaminergic pathway gene polymorphisms are being extensively studied with respect to addictive and behavioral disorders.MethodsFrom the broad literature available, the current review summarizes the specific polymorphisms of dopaminergic genes that play a role in alcohol dependence.ResultsNo evidence indicating any strong association between AD and polymorphisms of dopamine pathway genes has emerged from the literature.DiscussionFurther studies are warranted, considering a range of alcohol-related traits to determine the genes that influence alcohol dependence.

Non syndromic cleft lip and/or palate (NSCLP) is a complex congenital anomaly with varying incidence among patients of different geographical origins. Multiple contributing factors are known to trigger the cleft formation. There are several genes involved in the aetiology of NSCLP and they are different in different populations. The genetic components of clefts that underlie the susceptibility to respond to the environment still remain unclear. In this study, five microsatellite polymorphisms from five candidate genes were employed to analyze the association between these genes and NSCLP in 83 patients and 90 controls. Genotyping was performed by separating and visualizing the fluorescently-labeled polymerase chain reaction (PCR) products. The association of the five microsatellite polymorphisms with NSCLP was tested by using the CLUMP v1.9 program that uses the Monte Carlo method. The genotypic distribution is in Hardy-Weinberg equilibrium in the control group for only the MSX1 and DLX3 genes. The RARA microsatellite was significantly associated with NSCLP. Our results suggest that the RARA gene is involved in pathogenesis of cleft lip and palate in South Indians.

Polymorphisms in the immunoglobulin G Fc receptor II (FcGR) and tumor necrosis factor-α (TNFA) genes are known to influence pathogenesis and severity of several inflammatory conditions. Association of FcGR and TNFA gene polymorphisms with chronic periodontitis (CP) susceptibility has been found to be diverse among different ethnic populations. Objectives of the present study are to determine association of functional single nucleotide polymorphisms (SNPs) in FcGR and TNF-α genes with CP susceptibility in a cohort from South India.Polymorphisms of: 1) FCGR2A 131His/Arg (rs1801274); 2) FCGR2B 232Ile/Thr (rs1050501); 3) TNFA -1031T/C (rs1799964); and 4) TNFA -863C/A (rs1800630) were analyzed among patients with healthy gingiva (n = 176) and patients with CP (n = 177). Genotyping was performed using allele-specific real-time polymerase chain reaction assay. Association between CP and SNPs was examined by multivariable logistic regression analysis with adjustment for: 1) age; 2) sex; and 3) oral hygiene index (OHI). Epistatic interaction between FcGR polymorphisms and interleukin 1B (IL1B) +3954C/T (rs1143634) was assessed using multifactorial dimensionality reduction analysis.Among four SNPs analyzed, only FCGR2A 131His/Arg showed significant association with CP in a dominant model (odds ratio: 1.6; 95% confidence interval: 1.028 to 2.530). This significance disappeared after correcting for multiple comparisons using Bonferroni analysis, or after adjusting for age, sex, and OHI. A significant redundant interaction between IL1B +3954 C/T and FCGR2A 131His/Arg was observed.Study results suggest the variant form of the SNP in FCGR2A 131His/Arg, FCGR2B 232Ile/Thr, TNFA -1031T/C, and TNFA -863C/A are not associated with CP susceptibility in the selected cohort from South India.

It is well established that the central dopaminergic reward pathway is likely involved in alcohol intake and the progression of alcohol dependence. Dopamine transporter (DAT1) mediates the active re-uptake of DA from the synapse and is a principal regulator of dopaminergic neurotransmission. The gene for the human DAT1 displays several polymorphisms, including a 40-bp variable number of tandem repeats (VNTR) ranging from 3 to 16 copies in the 3′-untranslated region (UTR) of the gene. To assess the role of this gene in alcoholism, we genotyped the VNTR of DAT1 gene in a sample of 206 subjects from the Kota population (111 alcohol dependence cases and 95 controls) and 142 subjects from Badaga population (81 alcohol dependence cases and 61 controls). Both populations inhabit a similar environmental zone, but have different ethnic histories. Phenotype was defined based on the DSM-IV criteria. Genotyping was performed using PCR and electrophoresis. The association of DAT1 with alcoholism was tested by using the Clump v1.9 program which uses the Monte Carlo method. In both Kota and Badaga populations, the allele A10 was the most frequent allele followed by allele A9. The genotypic distribution is in Hardy–Weinberg equilibrium in both cases and control groups of Kota and Badaga populations. The DAT1 VNTR was significantly associated with alcoholism in Badaga population but not in Kota population. Our results suggest that the A9 allele of the DAT gene is involved in vulnerability to alcoholism, but that these associations are population specific. (Am J Addict 2012;00:1–5)