Green synthesis and characterization of silver nanoparticles using ethanolic extract of Mimosa Pudica linn leaves

479-484Green synthesis of metal nanoparticles using plant extract is an eco-friendly and cost-effective method for synthesizing metal nanoparticles. In this present work silver nanoparticles have been synthesized using ethanolic extract of Mimosa Pudica Linn plant (MPL) leaves. Green synthesized silver nanoparticles (AgNps) have been characterized by UV-Vis spectrometer, Fourier Transform Infra-Red ((FTIR) spectra, dynamic light scattering (DLS), Scanning Electron Microscopy (SEM) and X-ray diffraction (XRD) methods. UV-Vis spectrum of synthesized silver nanoparticles from Mimosa pudica Linn leaves extract shows a characteristic absorption peak at 421 nm. FTIR analysis reveals that presence of silver nanoparticles the presence of some biomolecules in extracts that act as reducing and capping agent for green synthesis of silver nanoparticles. DLS analysis showed AgNPs are drifted widely from 58.6 to 157.7 nm, with an average particle size of 104.7 nm. The particles are found to be polydisperse and slightly agglomerated due to the presence of phytochemicals present in the plant extract. Scanning electron microscope showed silver nanoparticles are spherical shaped. The XRD pattern revealed the presence of crystalline, dominantly spherical silver nanoparticles in the sample having size ranging from 42 to 50 nm. The XRD peaks 38.08, 44.22, 64.42, and 77.32 for leaves extract and 38.1, 44.3, 64.5, 77.5, and 81.33 for callus extract can be assigned the plane of silver crystals (111), (200), (220), and (311), respectively, and shows face-centered, cubic and crystalline nature of the silver nanoparticles. The green synthesized silver nanoparticles show significant antibacterial activity

Involvement of Essential Signaling Cascades and Analysis of Gene Networks in Diabesity

(1) Aims: Diabesity, defined as diabetes occurring in the context of obesity, is a serious health problem that is associated with an increased risk of premature heart attack, stroke, and death. To date, a key challenge has been to understand the molecular pathways that play significant roles in diabesity. In this study, we aimed to investigate the genetic links between diabetes and obesity in diabetic individuals and highlight the role(s) of shared genes in individuals with diabesity. (2) Methods: The interactions between the genes were analyzed using the Search Tool for the Retrieval of Interacting Genes (STRING) tool after the compilation of obesity genes associated with type 1 diabetes (T1D), type 2 diabetes (T2D), and maturity-onset diabetes of the young (MODY). Cytoscape plugins were utilized for enrichment analysis. (3) Results: We identified 546 obesity genes that are associated with T1D, T2D, and MODY. The network backbone of the identified genes comprised 514 nodes and 4126 edges with an estimated clustering coefficient of 0.242. The Molecular Complex Detection (MCODE) generated three clusters with a score of 33.61, 16.788, and 6.783, each. The highest-scoring nodes of the clusters were , , and genes. The genes from cluster 1 were enriched in FOXO-mediated transcription of oxidative stress, renin secretion, and regulation of lipolysis in adipocytes. The cluster 2 genes enriched in Src homology 2 domain-containing (SHC)-related events triggered by , regulation of lipolysis in adipocytes, and GRB2: SOS produce a link to mitogen-activated protein kinase (MAPK) signaling for integrins. The cluster 3 genes ere enriched in IGF1R signaling cascade and insulin signaling pathway. (4) Conclusion: This study presents a platform to discover potential targets for diabesity treatment and helps in understanding the molecular mechanism.The APC was funded by Qatar University Internal Grant number [QUST-2-CHS-2020-12

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Identification of Potential Inhibitors Targeting GTPase-Kirsten RAt Sarcoma Virus (K-Ras) Driven Cancers via E-Pharmacophore-Based Virtual Screening and Drug Repurposing Approach

Background: Mutations in the K-Ras gene are among the most frequent genetic alterations in various cancers, and inhibiting RAS signaling has shown promising results in treating solid tumors. However, finding effective drugs that can bind to the RAS protein remains challenging. This drove us to explore new compounds that could inhibit tumor growth, particularly in cancers that harbor K-Ras mutations. Methods: Our study used bioinformatic techniques such as E-pharmacophore virtual screening, molecular simulation, principal component analysis (PCA), extra precision (XP) docking, and ADMET analyses to identify potential inhibitors for K-Ras mutants G12C and G12D. Results: In our study, we discovered that inhibitors such as afatinib, osimertinib, and hydroxychloroquine strongly inhibit the G12C mutant. Similarly, hydroxyzine, zuclopenthixol, fluphenazine, and doxapram were potent inhibitors for the G12D mutant. Notably, all six of these molecules exhibit a high binding affinity for the H95 cryptic groove present in the mutant structure. These molecules exhibited a unique affinity mechanism at the molecular level, which was further enhanced by hydrophobic interactions. Molecular simulations and PCA revealed the formation of stable complexes within switch regions I and II. This was particularly evident in three complexes: G12C-osimertinib, G12D-fluphenazine, and G12D-zuclopenthixol. Despite the dynamic nature of switches I and II in K-Ras, the interaction of inhibitors remained stable. According to QikProp results, the properties and descriptors of the selected molecules fell within an acceptable range compared to sotorasib. Conclusions: We have successfully identified potential inhibitors of the K-Ras protein, laying the groundwork for the development of targeted therapies for cancers driven by K-Ras mutations.Udhaya Kumar. S, one of the authors, gratefully acknowledges the Indian Council of Medical Research (ICMR), India, for providing him a Senior Research Fellowship [ISRM/11(93)/2019]. In addition, the authors would like to thank the Vellore Institute of Technology, Vel-lore, India, and Qatar University, Doha, Qatar for providing the necessary research facilities and encouragement to carry out this work. Open Access funding provided by the Qatar National Library.Scopu

Integrative ontology and pathway-based approach identifies distinct molecular signatures in transcriptomes of esophageal squamous cell carcinoma

Esophageal squamous cell carcinoma (ESCC) remains a serious concern globally due to many factors that including late diagnosis, lack of an ideal biomarker for diagnosis and prognosis, and high rate of mortality. In this study, we aimed to identify the essential dysregulated genes and molecular signatures associated with the progression and development of ESCC. The dataset with 15 ESCCs and the 15 adjacent normal tissue samples from the surrounding histopathologically tumor-free mucosa was selected. We applied bioinformatics pipelines including various topological parameters from MCODE, CytoNCA, and cytoHubba to prioritize the most significantly associated DEGs with ESCC. We performed functional enrichment annotation for the identified DEGs using DAVID and MetaCore GeneGo platforms. Furthermore, we validated the essential core genes in TCGA and GTEx datasets between the normal mucosa and ESCC for their expression levels. These DEGs were primarily enriched in positive regulation of transferase activity, negative regulation of organelle organization, cell cycle mitosis/S-phase transition, spindle organization/assembly, development, and regulation of angiogenesis. Subsequently, the DEGs were associated with the pathways such as oocyte meiosis, cell cycle, and DNA replication. Our study identified the eight-core genes (AURKA, AURKB, MCM2, CDC20, TPX2, PLK1, FOXM1, and MCM7) that are highly expressed among the ESCC, and TCGA dataset. The multigene comparison and principal component analysis resulted in elevated signals for the AURKA, MCM2, CDC20, TPX2, PLK1, and FOXM1. Overall, our study reported GO profiles and molecular signatures that might help researchers to grasp the pathological mechanisms underlying ESCC development and eventually provide novel therapeutic and diagnostic strategies. 2022 Elsevier Inc.The authors would like to take this opportunity to thank the management of Vellore Institute of Technology (VIT), Vellore, India, Qatar University, Doha, Qatar, and Amity University, Haryana, Gurugram for providing the necessary facilities and encouragement to carry out this work. SUK, HZ, and CGPD were involved in the design of the study. SUK, AB, and VAP were involved in the data collection and conducted the experiment. SUK, AB, VAP, MKK, and CGPD were involved in the acquisition, analysis, and interpretation of the results. SUK and AB drafted the manuscript. CGPD and HZ supervised the entire study and were involved in study design, the acquisition, analysis, understanding of the data, and critically reviewed the manuscript. All authors edited and approved the submitted version of the article. The authors have declared that no conflicts of interest exist.Scopu

A systemic approach to explore the mechanisms of drug resistance and altered signaling cascades in extensively drug-resistant tuberculosis

Background and aim: The persistence of extensively drug-resistant (XDR) strains of Mycobacterium tuberculosis (MTB) continue to pose a significant challenge to the treatment and control of tuberculosis infections worldwide. XDR-MTB strains exhibit resistance against first-line anti-TB drugs, fluoroquinolones, and second-line injectable drugs. The mechanisms of drug resistance of MTB remains poorly understood. Our study aims at identifying the differentially expressed genes (DEGs), associated gene networks, and signaling cascades involved in rendering this pathogen resistant to multiple drugs, namely, isoniazid, rifampicin, and capreomycin. Methods: We used the microarray dataset GSE53843. The GEO2R tool was used to prioritize the most significant DEGs (top 250) of each drug exposure sample between XDR strains and non-resistant strains. The validation of the 250 DEGs was performed using volcano plots. Protein-protein interaction networks of the DEGs were created using STRING and Cytoscape tools, which helped decipher the relationship between these genes. The significant DEGs were functionally annotated using DAVID and ClueGO. The concomitant biological processes (BP) and molecular functions (MF) were represented as dot plots. Results and conclusion: We identified relevant molecular pathways and biological processes, such as cell wall biogenesis, lipid metabolic process, ion transport, phosphopantetheine binding, and triglyceride lipase activity. These processes indicated the involvement of multiple interconnected mechanisms in drug resistance. Our study highlighted the impact of cell wall permeability, with the dysregulation of the mur family of proteins, as essential factors in the inference of resistance. Additionally, upregulation of genes responsible for ion transport such as ctpF, arsC, and nark3, emphasizes the importance of transport channels and efflux pumps in potentially driving out stress-inducing compounds. This study investigated the upregulation of the Lip family of proteins, which play a crucial role in triglyceride lipase activity. Thereby illuminating the potential role of drug-induced dormancy and subsequent resistance in the mycobacterial strains. Multiple mechanisms such as carboxylic acid metabolic process, NAD biosynthetic process, triglyceride lipase activity, phosphopantetheine binding, organic acid biosynthetic process, and growth of symbiont in host cell were observed to partake in resistance of XDR-MTB. This study ultimately provides a platform for important mapping targets for potential therapeutics against XDR-MTB. 2021 Elsevier Inc.Mr. Udhaya Kumar. S, one of the authors, gratefully acknowledges the Indian Council of Medical Research (ICMR), India, for providing him a Senior Research Fellowship [ISRM/11(93)/2019]. The authors would like to take this opportunity to thank the management of VIT for providing the necessary facilities and encouragement to carry out this work. The authors have declared that no conflicts of interest exist.Scopu

An integrative analysis to distinguish between emphysema (EML) and alpha-1 antitrypsin deficiency-related emphysema (ADL)-A systems biology approach

Lung Emphysema is an abnormal enlargement of the air sacs followed by the destruction of alveolar walls without any prominent fibrosis. This study primarily identifies the differentially expressed genes (DEGs), interactions between them, and their significant involvement in the activated signaling cascades. The dataset with ID GSE1122 (five normal lung tissue samples, five of usual emphysema, and five of alpha-1 antitrypsin deficiency-related emphysema) from the gene expression omnibus (GEO) was analyzed using the GEO2R tool. The physical association between the DEGs were mapped using the STRING tool and was visualized in the Cytoscape software. The enriched functional processes were identified with the ClueGO plugin's help from Cytoscape. Further integrative functional annotation was performed by implying the GeneGo Metacore to distinguish the enriched pathway maps, process networks, and GO processes. The results from this analysis revealed the critical signaling cascades that have been either activated or inhibited due to identified DEGs. We found the activated pathways such as immune response IL-1 signaling pathway, positive regulation of smooth muscle migration, BMP signaling pathway, positive regulation of leukocyte migration, NIK/NF-kappB signaling, and cytochrome-c oxidase activity. Finally, we mapped four crucial genes (CCL5, ALK, TAC1, CD74, and HLA-DOA) by comparing the functional annotations that could be significantly influential in emphysema molecular pathogenesis. Our study provides insights into the pathogenesis of emphysema and helps in developing potential drug targets against emphysema. 2021 Elsevier Inc.Mr. Udhaya Kumar. S, one of the authors, gratefully acknowledges the Indian Council of Medical Research (ICMR), India, for providing him a Senior Research Fellowship [ISRM/11(93)/2019]. The authors would like to thank the Vellore Institute of Technology, India, and Qatar University, Qatar, for providing the necessary research facilities and encouragement to carry out this work. The authors have declared that no conflicts of interest exist. UKS, HZ, and GPDC, contributed to designing the study and data acquisition, analysis, and interpretation. UKS, TKD, MPN, VAP, VK, DN, SY, and MR are involved in the acquisition, analysis, and interpreting of the results. UKS, MPN, TKD, MR, VAP, VK, DN, SY, and CGPD contributed to data interpretation, conducted, and drafting the manuscript. CGPD and HZ supervised the entire study and studied, acquiring, analyzing, understanding the data, and drafting the manuscript. The manuscript was reviewed and approved by all the authors. No funding agency is involved in the present study.Scopu

Chromosome Xq23 is associated with lower atherogenic lipid concentrations and favorable cardiometabolic indices

Abstract Autosomal genetic analyses of blood lipids have yielded key insights for coronary heart disease (CHD). However, X chromosome genetic variation is understudied for blood lipids in large sample sizes. We now analyze genetic and blood lipid data in a high-coverage whole X chromosome sequencing study of 65,322 multi-ancestry participants and perform replication among 456,893 European participants. Common alleles on chromosome Xq23 are strongly associated with reduced total cholesterol, LDL cholesterol, and triglycerides (min P = 8.5 × 10−72), with similar effects for males and females. Chromosome Xq23 lipid-lowering alleles are associated with reduced odds for CHD among 42,545 cases and 591,247 controls (P = 1.7 × 10−4), and reduced odds for diabetes mellitus type 2 among 54,095 cases and 573,885 controls (P = 1.4 × 10−5). Although we observe an association with increased BMI, waist-to-hip ratio adjusted for BMI is reduced, bioimpedance analyses indicate increased gluteofemoral fat, and abdominal MRI analyses indicate reduced visceral adiposity. Co-localization analyses strongly correlate increased CHRDL1 gene expression, particularly in adipose tissue, with reduced concentrations of blood lipids

Management of coronary disease in patients with advanced kidney disease

BACKGROUND Clinical trials that have assessed the effect of revascularization in patients with stable coronary disease have routinely excluded those with advanced chronic kidney disease. METHODS We randomly assigned 777 patients with advanced kidney disease and moderate or severe ischemia on stress testing to be treated with an initial invasive strategy consisting of coronary angiography and revascularization (if appropriate) added to medical therapy or an initial conservative strategy consisting of medical therapy alone and angiography reserved for those in whom medical therapy had failed. The primary outcome was a composite of death or nonfatal myocardial infarction. A key secondary outcome was a composite of death, nonfatal myocardial infarction, or hospitalization for unstable angina, heart failure, or resuscitated cardiac arrest. RESULTS At a median follow-up of 2.2 years, a primary outcome event had occurred in 123 patients in the invasive-strategy group and in 129 patients in the conservative-strategy group (estimated 3-year event rate, 36.4% vs. 36.7%; adjusted hazard ratio, 1.01; 95% confidence interval [CI], 0.79 to 1.29; P=0.95). Results for the key secondary outcome were similar (38.5% vs. 39.7%; hazard ratio, 1.01; 95% CI, 0.79 to 1.29). The invasive strategy was associated with a higher incidence of stroke than the conservative strategy (hazard ratio, 3.76; 95% CI, 1.52 to 9.32; P=0.004) and with a higher incidence of death or initiation of dialysis (hazard ratio, 1.48; 95% CI, 1.04 to 2.11; P=0.03). CONCLUSIONS Among patients with stable coronary disease, advanced chronic kidney disease, and moderate or severe ischemia, we did not find evidence that an initial invasive strategy, as compared with an initial conservative strategy, reduced the risk of death or nonfatal myocardial infarction