Integrated bioinformatics approach to unwind key genes and pathways involved in colorectal cancer.

BACKGROUND: Colorectal cancer (CRC) is the fifth leading cause of death in India. Until now, the exact pathogenesis concerning CRC signaling pathways is largely unknown; however, the diseased condition is believed to deteriorate with lifestyle, aging, and inherited genetic disorders. Hence, the identification of hub genes and therapeutic targets is of great importance for disease monitoring. OBJECTIVE: Identification of hub genes and targets for identification of candidate hub genes for CRC diagnosis and monitoring. MATERIALS AND METHODS: The present study applied gene expression analysis by integrating two profile datasets (GSE20916 and GSE33113) from NCBI-GEO database to elucidate the potential key candidate genes and pathways in CRC. Differentially expressed genes (DEGs) between CRC (195 CRC tissues) and healthy control (46 normal mucosal tissue) were sorted using GEO2R tool. Further, Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analysis were performed using Cluster Profiler in Rv. 3.6.1. Moreover, protein-protein interactions (PPI), module detection, and hub gene identification were accomplished and visualized through the Search Tool for the Retrieval of Interacting Genes, Molecular Complex Detection (MCODE) plug-in of Cytoscape v3.8.0. Further hub genes were imported into ToppGene webserver for pathway analysis and prognostic expression analysis was conducted using Gene Expression Profiling Interactive Analysis webserver. RESULTS: A total of 2221 DEGs, including 1286 up-regulated and 935down-regulated genes mainly enriched in signaling pathways of NOD-like receptor, FoxO, AMPK signalling and leishmaniasis. Three key modules were detected from PPI network using MCODE. Besides, top 20 high prioritized hub genes were selected. Further, prognostic expression analysis revealed ten of the hub genes, namely IL1B, CD44, Glyceraldehyde-3-phosphate dehydrogenase (GAPDH, MMP9, CREB1, STAT1, vascular endothelial growth factor (VEGFA), CDC5 L, Ataxia-telangiectasia mutated (ATM + and CDH1 to be differently expressed in normal and cancer patients. CONCLUSION: The present study proposed five novel therapeutic targets, i.e., ATM, GAPDH, CREB1, VEGFA, and CDH1 genes that might provide new insights into molecular oncogenesis of CRC.

A Machine Learning-Based Intrauterine Growth Restriction (IUGR) Prediction Model for Newborns.

Intrauterine growth restriction (IUGR) is a condition in which the fetal weight is below the 10th percentile for its gestational age. Prenatal exposure to metals can cause a decrease in fetal growth during gestation thereby reducing birth weight. Therefore, the aim of the present study was to develop a machine learning model for early prediction of IUGR. A total of 126 IUGR and 88 appropriate-for-gestational-age (AGA) samples were collected from the Gynecology Department, Safdarjung Hospital, New Delhi. The predictive models were developed using the Weka software. The models developed using all the features gave the highest accuracy of 95.5% with support vector machine (SMO) algorithm and 88.5% with multilayer perceptron (MLP) algorithm. Further, models developed after feature selection using 14 important and statistically significant variables also gave the highest accuracy of 98.5% with SMO algorithm and 99% with Naïve Bayes (NB) algorithm. The study concluded SMO_31, SMO_14, MLP_31, and NB_14 to be the better classifiers for IUGR prediction.

Current Overviews on COVID-19 Management Strategies.

The coronavirus pandemic hit the world lately and caused acute respiratory syndrome in humans. The causative agent of the disease was soon identified by scientists as SARS-CoV-2 and later called a novel coronavirus by the general public. Due to the severity and rapid spread of the disease, WHO classifies the COVID-19 pandemic as the 6th public health emergency even after taking efforts like worldwide quarantine and restrictions. Since only symptomatic treatment is available, the best way to control the spread of the virus is by taking preventive measures. Various types of antigen/antibody detection kits and diagnostic methods are available for the diagnosis of COVID-19 patients. In recent years, various phytochemicals and repurposing drugs showing a broad range of anti-viral activities with different modes of actions have been identified. Repurposing drugs such as arbidol, hydroxychloroquine, chloroquine, lopinavir, favipiravir, remdesivir, hexamethylene amiloride, dexamethasone, tocilizumab, interferon-ß, and neutralizing antibodies exhibit in vitro anti-coronaviral properties by inhibiting multiple processes in the virus life cycle. Various research groups are involved in drug trials and vaccine development. Plant-based antiviral compounds such as baicalin, calanolides, curcumin, oxymatrine, matrine, and resveratrol exhibit different modes of action against a wide range of positive/negative sense-RNA/DNA virus, and future researches need to be conducted to ascertain their role and use in managing SARS-CoV-2. Thus this article is an attempt to review the current understanding of COVID- 19 acute respiratory disease and summarize its clinical features with their prospective control and various aspects of the therapeutic approach.

Protein-protein interaction and in silico mutagenesis studies on IL17A and its peptide inhibitor.

Protein-protein interactions of Interleukin-17 (IL17) play vital role in the autoimmune and inflammatory diseases, such as rheumatoid arthritis, multiple sclerosis, and psoriasis. Potent therapeutics for these diseases could be developed by blocking or modulating these interactions through biologics, peptide inhibitors and small molecule inhibitors. Unlike biologics, peptide inhibitors are cost effective and can be orally available. Peptide inhibitors do not require a binding groove as that of small molecules either. Therefore, crystal structure of IL17A in complex with a high affinity peptide inhibitor (HAP) (1-IHVTIPADLWDWIN-14) is investigated with an aim to find hot spots that could improve its potency. An in silico mutagenesis strategy was implemented using FoldX PSSM to scan for positions tolerant to amino acid substitution. Three positions T4, A7, and N14 showed improved stability when mutated with 'F/M/Y', 'P' and 'F/M/Y', respectively. A set of 31 mutant peptides are designed through combinations of these tolerant mutations using Build Model application of FoldX. Binding affinity and interactions of 31 peptides are assessed through protein-peptide docking and binding free energy calculations. Two peptides namely, P1 ("1-IHVTIPPDLWDWIY-14") and P2 ("1-IHVMIPPDLWDWIF-14") showed better binding affinity to IL17A dimerization site compared to HAP. Interactions of P1, P2 and HAP are also analyzed through 100 ns molecular dynamics simulations using GROMACS v5.0. The results revealed that the P2 peptide likely to offer better potency compared to HAP and P1. Therefore, the P2 peptide can be synthesized to develop oral therapies for autoimmune and inflammatory diseases with further experimental evaluations. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s13205-021-02856-y.

Re-testing reported significant SNPs related to suicide in a historical high -risk isolated population from north east India.

BACKGROUND: Genetic diathesis of suicide is supported by family and twin studies. Few candidate gene pathways are known, but does not explain fully the complexity of suicide genetic risk. Recent investigations opting for Genome-Wide Association Studies (GWAS) resulted in finding additional targets, but replication remained a challenge. In this respect small isolated population approach in several complex disease phenotypes is found encouraging. The present study is an attempt to re-test some of the reported significant SNPs for suicide among a small historical high- risk isolated population from Northeast India. METHODS: Two hundred ten cases (inclusive of depressed, suicide attempter and depressed + suicide attempter) and 249 controls were considered in the present study which were evaluated for the psychiatric parameters. Sixteen reported significant SNPs for suicide behaviour were re-tested using association approach under various genetic models. Networking by GeneMANIA tool was used for function prediction of the associated genes. RESULTS: Seven SNPs (of 6 genes) remained significant in different genetic models. On networking genes with significant SNPs IL7, RHEB, CTNN3, KCNIP4, ARFGEF3 are found in interaction with already known candidate gene pathways while SNP rs1109089 (RHEB) gained further support from earlier expression studies. NUGGC gene is in complete isolation. CONCLUSIONS: Small population approach in replicating significant SNPs is useful in complex phenotypes like suicide. This study explored the region-specific demographics of India by identifying vulnerable population for suicide via genetic association analysis in bringing into academic and administrative forum, the importance of suicide as a disease and its biological basis.

Predicting risk of low birth weight offspring from maternal features and blood polycyclic aromatic hydrocarbon concentration.

Prenatal exposure to organic pollutants increases the risk of low birth weight (LBW) offspring. Women involved in the plucking of tea leaves can be exposed to polycyclic aromatic hydrocarbons (PAHs) during pregnancy through inhalation and diet. Therefore, the aim of the study was to investigate the association of maternal socio-demographic features and blood PAH concentration with LBW; also to develop a model for predicting LBW risk. The study was performed by recruiting 55 women who delivered LBW and 120 women with NBW (normal birth weight) babies from Assam Medical College. The placental tissue, maternal and cord blood samples were collected. A total of sixteen PAHs and cotinine were analysed by HPLC and GC-MS. Association of PAH concentration with weight was determined using correlation and multiple logistic regression analyses. Predictive model was developed using SVMlight and Weka software. Maternal features such as age, education, food habits, occupation, etc. were found to be associated with LBW deliveries (p-value<0.05). Overall, 9 PAHs and cotinine were detected in the samples. A multiple logistic regression depicted an increased likelihood of LBW by exposure to PAHs (pyrene, di-benzo (a,h) anthracene, fluorene and fluoranthene) and cotinine. Models based on the features and PAHs/ cotinine predicted LBW offspring with 84.35% sensitivity and 74% specificity. LBW prediction models are available at http://dev.icmr.org.in/plbw/ webserver. With machine learning gaining more importance in medical science; our webserver could be instrumental for researchers and clinicians to predict the state of the fetus.

Fusarium head blight in wheat: contemporary status and molecular approaches.

Fusarium head blight (FHB) disease that occurs in wheat is caused by Fusarium graminearum and is a major risk to wheat yield. Although several research efforts focusing on FHB have been conducted in the past several decades, conditions have become more critical due to the increase in its virulent forms. In such a scenario, conferring complete resistance in plants seems to be difficult for handling this issue. The phenotyping for FHB and finding a solution for it at the genetic level comprises a long-term process as FHB infection is largely affected by environmental conditions. Modern molecular strategies have played a crucial role in revealing the host-pathogen interaction in FHB. The integration of molecular biology-based methods such as genome-wide association studies and marker-based genomic selection has provided potential cultivars for breeding programs. In this review, we aim at outlining the contemporary status of the studies conducted on FHB in wheat. The influence of FHB in wheat on animals and human health is also discussed. In addition, a summary of the advancement in the molecular technologies for identifying and developing the FHB-resistant wheat genetic resources is provided. It also suggests the future measures that are required to reduce the world's vulnerability to FHB which was one of the main goals of the US Wheat and Barley Scab Initiative.

Psoriasis and cardiovascular disorders: association or epiphenomenon? Meta-analysis of observational studies.

Psoriasis is a chronic inflammatory disease believed to be correlated with numerous cardiovascular risk factors including increased blood pressure, elevated blood cholesterol level, diabetes, inactivity, high body mass index (obesity) and dyslipidaemia. The present meta-analysis intends to assess the association between psoriasis and cardiovascular risk factors. Three hundred and fifty articles were primarily screened using NCBI MEDLINE/PubMed and Cochrane library from its inception until June 30, 2018. Of these, 26 observational studies depending upon the inclusion and exclusion criteria were included in the study with 17,672 psoriasis patients and 66,407 non-psoriasis subjects. The psoriasis patients were found to be at significantly increased risk of systolic blood pressure (SBP) [ORs 2.31 (95% CI 1.12, 4.74)], diastolic blood pressure (DBP) [ORs 2.31 (95% CI 1.58, 3.38)], abdominal obesity [ORs 1.90 (95% CI 1.45, 2.50)] and triglycerides [ORs 1.80 (95% CI 1.29, 2.51)] as compared to non-psoriasis subjects. The subgroup analyses of studies based on the continents revealed that psoriasis patients from Middle East are prone to higher risk factors of CVD including increased levels of triglyceride, cholesterol, DBP, SBP, fasting blood sugar, body mass index and decreased HDL levels, whereas psoriasis patients from European population reported increased LDL-C and waist circumference. The present study supports a significant association between psoriasis and incidence of major adverse cardiovascular events. Contrary to the previous literature, our finding suggests that hypertension is a highly associative condition in psoriasis. The findings of this study could be validated amongst well-defined cohorts of patients with psoriasis individually in different regions to confirm the implication of the study.

Up-regulation of fibroblast growth factor receptor 1 due to prenatal tobacco exposure can lead to developmental defects in new born.

Introduction: Tobacco-smoking is one of the most important risk factor for preterm delivery, pregnancy loss, low birth weight, and fetal growth restriction. It is estimated that approximately 30% of growth-restricted neonates could be independently associated with maternal smoking.Methods: In this study, gene expression profile, GSE11798, was chosen from GEO database with an aim to perceive change in gene expression signature in new born due to maternal smoking. Enrichment analysis was performed to annotate differentially expressed genes (DEGs) through gene ontology and pathway analysis using DAVID. Protein-protein interactions and module detection of these DEGs were carried out using cytoscape v3.6.0. Thirty umbilical cord tissue samples from 15 smokers and 15 non-smokers pregnant women were included in this analysis.Results: Twenty-six differentially expressed genes (DEGs) between two groups were selected using GEO2R tool. The DEGs were observed to be participating in biological processes/pathways related to growth releasing hormone, angiogenesis, embryonic skeletal, and cardiac development. Fibroblast growth factor receptor-1 (FGFR1) was identified to be the hub node with 348 interacting partners, which regulates transcription, cell growth, differentiation, and apoptosis. The up-regulation of FGFR1 in umbilical cord tissue may lead to reproductive and developmental complications such as encephalocraniocutaneous lipomatosis, osteoglophonic dysplasia, and Pfeiffer syndrome in new-borns.Conclusion: The findings manifests the possibility of overcoming these adverse health effects in new born through FGFR1 modulating treatments during pregnancy.

Tau and mTOR: The Hotspots for Multifarious Diseases in Alzheimer's Development.

The hyperphosphorylation of tau protein and the overexpression of mTOR are considered to be the driving force behind Aß plaques and Neurofibrillay Tangles (NFT's), hallmarks of Alzheimer's disease (AD). It is now evident that miscellaneous diseases such as Diabetes, Autoimmune diseases, Cancer, etc. are correlated with AD. Therefore, we reviewed the literature on the causes of AD and investigated the association of tau and mTOR with other diseases. We have discussed the role of insulin deficiency in diabetes, activated microglial cells, and dysfunction of blood-brain barrier (BBB) in Autoimmune diseases, Presenilin 1 in skin cancer, increased reactive species in mitochondrial dysfunction and deregulated Cyclins/CDKs in promoting AD pathogenesis. We have also discussed the possible therapeutics for AD such as GSK3 inactivation therapy, Rechaperoning therapy, Immunotherapy, Hormonal therapy, Metal chelators, Cell cycle therapy, γ-secretase modulators, and Cholinesterase and BACE 1-inhibitors which are thought to serve a major role in combating pathological changes coupled with AD. Recent research about the relationship between mTOR and aging and hepatic Aß degradation offers possible targets to effectively target AD. Future prospects of AD aims at developing novel drugs and modulators that can potentially improve cell to cell signaling, prevent Aß plaques formation, promote better release of neurotransmitters and prevent hyperphosphorylation of tau.

Prognostic significance of soluble fas and soluble fas ligand in serum of patients with complete hydatidiform moles.

PROBLEM: Despite of advances in diagnosis and staging, the prognosis of hydatidiform mole (HM) remains intricate. HM possesses the substantial risk of developing persistent trophoblastic disease (PTD), which is considerably high for complete hydatidiform moles (CHMs). Significance of serum soluble Fas (sFas) and soluble FasL (sFasL) has been observed in various malignancies; however, there is no report till date on HM. METHOD OF STUDY: The serum levels of sFas and sFasL were measured using enzyme-linked immunosorbent assay in 62 patients with CHMs and 64 healthy controls. The protein concentrations were also correlated with clinicopathological parameters, ß-hCG level, and clinical outcome. RESULTS: The serum sFas and sFasL levels in patients with CHM were significantly higher than those in control group (mean±SD: 703.497±491.759 versus 348.141±175.24; P<0.004 and 31.17±18.758 versus 18.802± 6.775; P<0.0001, respectively). Patients who progressed to PTD demonstrated higher sFas and sFasL concentrations than those who regressed spontaneously (794.211±415.892 versus 446.69±161.382; P<0.046 and 37.55±20.337 versus 22.763±6.52; P<0.011, respectively). Furthermore, significant associations were observed among sFas, sFasL, and ß-hCG levels (P<0.0001 for all associations). CONCLUSION: Production of sFas and sFasL may play a crucial role in progression of CHM and may serve both as prognostic tool and therapeutic target in improving the clinical outcome.

Indoor fungal concentration in the homes of allergic/asthmatic children in Delhi, India.

Allergy to fungi has been linked to a wide range of illnesses, including rhinitis and asthma. Therefore, exposure to fungi in home environment is an important factor for fungal allergy. The present study was aimed to investigate types of airborne fungi inside and outside the homes of asthmatic children and control subjects (nonasthmatic children). The dominant fungi were evaluated for their quantitative distribution and seasonal variation. The air samples were collected from indoors and immediate outdoors of 77 selected homes of children suffering from bronchial asthma/allergic rhinitis using Andersen volumetric air sampler. The isolated fungal genera/species were identified using reference literature, and statistical analysis of the dominant fungi was performed to study the difference in fungal concentration between indoor and immediate outdoor sites as well as in between different seasons. A total of 4423 air samples were collected from two indoor and immediate outdoor sites in a 1-year survey of 77 homes. This resulted in the isolation of an average of 110,091 and 107,070 fungal colonies per metric cube of air from indoor and outdoor sites, respectively. A total of 68 different molds were identified. Different species of Aspergillus, Alternaria, Cladosporium, and Penicillium were found to be the most prevalent fungi in Delhi homes, which constituted 88.6% of the total colonies indoors. Highest concentration was registered in autumn and winter months. Total as well as dominant fungi displayed statistically significant differences among the four seasons (p < 0.001). The largest number of isolations were the species of Aspergillus (>40% to total colony-forming units in indoors as well as outdoors) followed by Cladosporium spp. Annual concentration of Aspergillus spp. was significantly higher (p < 0.05) inside the homes when compared with outdoors. Most of the fungi also occurred at a significantly higher (p < 0.001) rate inside the homes when compared with immediate outdoors. Asthmatic children in Delhi are exposed to a substantial concentration of mold inside their homes as well as immediate outdoor air. The considerable seasonal distributions of fungi provide valuable data for investigation of the role of fungal exposure as a risk for respiratory disorders among patients suffering from allergy or asthma in Delhi.

Natural rubber latex allergy.

Natural rubber latex (NRL) is a ubiquitous allergen as it is a component of > 40,000 products in everyday life. Latex allergy might be attributed to skin contact or inhalation of latex particles. Latex allergy is an IgE-mediated hypersensitivity to NRL, presenting a wide range of clinical symptoms such as angioedema, swelling, cough, asthma, and anaphylactic reactions. Until 1979, latex allergy appeared only as type IV delayed hypersensitivity; subsequently, the proportion of different allergy types drifted towards type IV contact allergy reactions. Several risk factors for sensitization to NRL are already known and well documented. Some authors have established a positive correlation between a history of multiple surgical interventions, atopy, spina bifida malformation, and latex allergy incidence. We suspect an increase in latex allergy incidence in association with increased atopy and sensitivity to environmental allergens in the industrial population. It is often postulated in literature that the groups of workers at risk for this allergy are essentially workers in the latex industry and healthcare professionals. In this population, direct internal and mucosal contact with NRL medical devices may be the route of sensitization as factors such as the number of procedures and use of NRL materials (catheters and tubes) were associated with increased risk of latex sensitization and allergy.