Transcriptomic, mutational and structural bioinformatics approaches to explore the therapeutic role of FAP in predominant cancer types.

Fibroblast activating protein (FAP) is a cell surface marker of cancer-associated fibroblasts with a distinct pro-tumorigenic role. The present study analyzed the pan-cancer expression; and clinical and mutational profiles of the FAP coding gene. Molecular dynamics simulation (MDS) deciphered the backbone dynamics and energetics of FAP.

A Comprehensive Review of Antimicrobial Agents Against Clinically Important Bacterial Pathogens: Prospects for Phytochemicals.

Antimicrobial resistance (AMR) hinders the effective treatment of a range of bacterial infections, posing a serious threat to public health globally, as it challenges the currently available antimicrobial drugs. Among the various modes of antimicrobial action, antimicrobial agents that act on membranes have the most promising efficacy. However, there are no consolidated reports on the shortcomings of these drugs, existing challenges, or the potential applications of phytochemicals that act on membranes.

Powering up targeted protein degradation through active and passive tumour-targeting strategies: Current and future scopes.

Targeted protein degradation (TPD) has emerged as a prominent and vital strategy for therapeutic intervention of cancers and other diseases. One such approach involves the exploration of proteolysis targeting chimeras (PROTACs) for the selective elimination of disease-causing proteins through the innate ubiquitin-proteasome pathway. Due to the unprecedented achievements of various PROTAC molecules in clinical trials, researchers have moved towards other physiological protein degradation approaches for the targeted degradation of abnormal proteins, including lysosome-targeting chimeras (LYTACs), autophagy-targeting chimeras (AUTACs), autophagosome-tethering compounds (ATTECs), molecular glue degraders, and other derivatives for their precise mode of action.

Impact of air pollution and heavy metal exposure on sperm quality: A clinical prospective research study.

Exposure to air pollution poses significant risks to human health, including detrimental effects on the reproductive system, affecting both men and women. Our prospective clinical study aimed to assess the impact of prolonged air pollution exposure on sperm quality in male patients attending a fertility clinic. The current study was conducted at Sri Narayani Hospital and Research Centre in Vellore, Tamil Nadu, India, and the study examined sperm samples obtained from individuals with extended exposure to air pollution.

Designing multi-epitope vaccine against human cytomegalovirus integrating pan-genome and reverse vaccinology pipelines.

Human cytomegalovirus (HCMV) is accountable for high morbidity in neonates and immunosuppressed individuals. Due to the high genetic variability of HCMV, current prophylactic measures are insufficient. In this study, we employed a pan-genome and reverse vaccinology approach to screen the target for efficient vaccine candidates.

Cefiderocol susceptibility endows hope in treating carbapenem-resistant : insights from and evidence.

'High-risk' hypermutable clones of disseminating extensive drug-resistance (XDR) have raised global health concerns with escalating mortality rates in immunocompromised patients. Mutations in conventional drug-targets under antibiotic stress necessitate structural understanding to formulate sustainable therapeutics. In the present study, the major β-lactam antibiotic target, penicillin-binding protein-3 (PBP3) with mutations F533L and T91A, were identified in carbapenemase-positive isolates ( = 6) using whole genome sequencing.

Identifying Novel Therapeutics for the Resistant Mutant "F533L" in PBP3 of Using ML Techniques.

is a highly infectious and antibiotic-resistant bacterium, which causes acute and chronic nosocomial infections. exhibits multidrug resistance due to the emergence of resistant mutants. The bacterium takes advantage of intrinsic and acquired resistance mechanisms to resist almost every antibiotic.

Muco-Adhesive and Muco-Penetrative Formulations for the Oral Delivery of Insulin.

Insulin, a pivotal anabolic hormone, regulates glucose homeostasis by facilitating the conversion of blood glucose to energy or storage. Dysfunction in insulin activity, often associated with pancreatic β cells impairment, leads to hyperglycemia, a hallmark of diabetes. Type 1 diabetes (T1D) results from autoimmune destruction of β cells, while type 2 diabetes (T2D) stems from genetic, environmental, and lifestyle factors causing β cell dysfunction and insulin resistance.

Integrating pan-genome and reverse vaccinology to design multi-epitope vaccine against Herpes simplex virus type-1.

Unlabelled: Herpes simplex virus type-1 (HSV-1), the etiological agent of sporadic encephalitis and recurring oral (sometimes genital) infections in humans, affects millions each year. The evolving viral genome reduces susceptibility to existing antivirals and, thus, necessitates new therapeutic strategies. Immunoinformatics strategies have shown promise in designing novel vaccine candidates in the absence of a clinically licensed vaccine to prevent HSV-1.

Whole genome analysis reveals unique traits of SARS-CoV-2 in pediatric patients.

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) continues to challenge the global healthcare with emerging variants and higher infectivity as well as morbidities. This study investigated potential age-related variations through genomic characterization of the virus under common clinical settings. A cohort comprising 71 SARS-CoV-2 strains from both infected infants and accompanying adults, diagnosed via RT-PCR at a tertiary pediatric hospital and research center, underwent Illumina paired-end sequencing.

Anionic species from multivalent metal salts are differentially retained during aqueous ionic gelation of sodium alginate and could fine-tune the hydrogel properties.

The role of anionic counterions of divalent metal salts in alginate gelation and hydrogel properties has been thoroughly investigated. Three anions were selected from the Hofmeister series, namely sulphate, acetate and chloride, paired in all permutations and combinations with divalent metal cations like calcium, zinc and copper. Spectroscopic analysis revealed the presence of anions and their interaction with the respective metal cations in the hydrogel.

Coinfections in human papillomavirus associated cancers and prophylactic recommendations.

The Human Papillomavirus (HPV) infection is responsible for more than 80% of reported cervical cancer and other virus-associated tumours. Although this global threat can be controlled using effective vaccination strategies, a growing perturbation of HPV infection is an emerging coinfection likely to increase the severity of the infection in humans. Moreover, these coinfections prolong the HPV infections, thereby risking the chances for oncogenic progression.

Computational study of the piperidine and FtsZ interaction in Typhi: implications for disrupting cell division machinery.

FtsZ, a bacterial cell division protein, is essential for assembling the contractile Z-ring crucial in bacterial cytokinesis. Consequently, inhibiting FtsZ could impede proto-filaments, disrupting FtsZ and other associated proteins vital for cell division machinery. Conduct an drug interaction study to identify novel drug candidates that inhibit the FtsZ protein, aiming to prevent Multi-Drug Resistant (MDR) Typhi.

In silico screening of herbal phytochemicals to develop a Rasayana for immunity against Nipah virus.

Background: The first emergence of the Nipah virus (NiV) in 1998 from Malaysia became a major concern when it came to light and resurfaced on different occasions thereafter. NiV is a bat-borne zoonotic and pleomorphic virus that causes severe infection in human and animal hosts. Studies revealed fruit bats are the major reservoirs as natural hosts and pigs as intermediate hosts for the spread of this infection.

Designing a novel and combinatorial multi-antigenic epitope-based vaccine "MarVax" against Marburg virus-a reverse vaccinology and immunoinformatics approach.

Context: Marburg virus (MARV) is a member of the Filoviridae family and causes Marburg virus disease (MVD) among humans and primates. With fatality rates going up to 88%, there is currently no commercialized cure or vaccine to combat the infection. The National Institute of Allergy and Infectious Diseases (NIAID) classified MARV as priority pathogen A, which presages the need for a vaccine candidate which can provide stable, long-term adaptive immunity.

PER2 gene and its association with sleep-related disorders: A review.

The natural circadian rhythm in an individual governs the sleep-wake cycle over 24 h. Disruptions in this internal cycle can lead to major health hazards and sleep disorders. Reports suggest that at least 50 % of people worldwide suffer from sleep-related disorders.

Impact of PmrB mutations on clinical Klebsiella pneumoniae with variable colistin-susceptibilities: Structural insights and potent therapeutic solutions.

Carbapenem-resistant Klebsiella pneumoniae (CRKP) infections continue to impose high morbidity threats to hospitalized patients worldwide, limiting therapeutic options to last-resort antibiotics like colistin. However, the dynamic genomic landscape of colistin-resistant K. pneumoniae (COLR-Kp) invoked ardent exploration of underlying molecular signatures for therapeutic propositions/designs.

Elucidating the molecular role of MUC5B in progressive lung adenocarcinoma: Prospects for early diagnosis.

Gel-forming mucin MUC5B is significantly deregulated in lung adenocarcinoma (LUAD), however, its role in tumor progression is not yet clearly understood. Here, we used an integrated computational-pipeline-initiated with gene expression analysis followed by network, functional-enrichment, O-linked glycosylation analyses, mutational profiling, and immune cell infiltration estimation to functionally characterize MUC5B gene in LUAD. Thereafter, clinical biomarker validation was supported by the overall survival (OA) and comparative expression profiling across clinical stages using computational algorithms.

Understanding the Molecular Regulation of Serotonin Receptor 5-HTR-β-Arrestin1 Complex in Stress and Anxiety Disorders.

The serotonin receptor subtype 5-HTR is widely distributed in the brain with an important role in various behavioral implications including neurological conditions and psychiatric disorders. The neuromodulatory action of 5-HTR largely depends upon its arrestin mediated signaling pathway. In this study, we tried to investigate the role of unusually long intracellular loop 3 (ICL3) region of the serotonin receptor 5-HTR in interaction with β-arrestin1 (Arr2) to compensate for the absence of the long cytoplasmic tail.

FN1 and cancer-associated fibroblasts markers influence immune microenvironment in clear cell renal cell carcinoma.

Background: Altered tumor microenvironment (TME) is characterized in clear cell renal cell carcinoma (ccRCC) as a result of the heterogeneity observed in the TME. Modulations in TME have shown tumor metastasis promotion; hence, identifying TME-based biomarkers can be critical for theranostics application.

Methods: Here, we performed an integrated systems biology approach utilizing differential gene expression, network metrics and clinical samples cohorts to prioritize the major deregulated genes and their associated pathways specific for metastasis.

Comprehensive analysis on the diagnostic role of circulatory exosome-based miR-92a-3p for osteoblastic metastases in prostate adenocarcinoma.

Prostate adenocarcinoma (PRAD) is the second leading cause of death in men and the key factor that attributes to the severity and higher mortality rates is the tumor's ability to promote osteoblastic metastases (OM). Currently, no blood-based biomarkers are present that bridges the crosstalk between PRAD and OM progression. Conversely, circulatory microRNAs (miRNAs) are gaining interest among the scientific community for its potential as blood-based markers for cancer detection.

Cancer-biomarkers associated with sex hormone receptors and recent therapeutic advancements: a comprehensive review.

Hormones and its regulation plays vital role in causing breast, prostate, ovarian and endometrial cancers collectively known as hormone-sensitive cancers. This review discusses the various functions of the sex hormones and the biological pathways involved in causing hormone-associated cancer under differential regulation. We have also attempted to explore the biomarkers associated with the cancers and the current therapeutic availability to treat such cancers.

Impact of the COVID-19 pandemic on routine vaccine landscape: A global perspective.

The coronavirus disease (COVID-19) threat is subsiding through extensive vaccination worldwide. However, the pandemic imposed major disruptions in global immunization programs and has aggravated the risks of vaccine-preventable disease (VPD) outbreaks. Particularly, lower-middle-income regions with minimal vaccine coverage and circulating vaccine-derived viral strains, such as polio, suffered additional burden of accumulated zero-dose children, further making them vulnerable to VPDs.