Molecular testing

The endocrine system functions by interactions between ligands and receptors. Ligands exhibit potency for binding to and interacting with receptors. Potency is the product of affinity and efficacy. Potency and physiological concentration determine the ability of a ligand to produce physiological effects. The kinetic behavior of ligand-receptor interactions conforms to the laws of mass action. The laws of mass action define the relationship between the affinity of a ligand and the fraction of cognate receptors that it occupies at any physiological concentration...

Autism spectrum disorder is a neurodevelopmental condition marked by restricted interests and difficulty with social communication. ASD is characterized by heightened neuroinflammation and irregular neuronal connections. ASD is more frequent in male than female with male-female ratio of around 4:1. ASD affects 2.8% or 1 in 36 8-year-olds, based on the CDC's Morbidity and Mortality Weekly Report. Various factors like Environmental, Genetic, Epigenetic and Developmental factors are linked with genesis of ASD...

BACKGROUND: Despite advancements in chronic myeloid leukemia (CML) therapy with tyrosine kinase inhibitors (TKIs), resistance and intolerance remain significant challenges. Leukemia stem cells (LSCs) and TKI-resistant cells rely on altered mitochondrial metabolism and oxidative phosphorylation. Targeting rewired energy metabolism and inducing non-apoptotic cell death, along with the release of damage-associated molecular patterns (DAMPs), can enhance therapeutic strategies and immunogenic therapies against CML and prevent the emergence of TKI-resistant cells and LSC persistence...

BACKGROUND: Infections caused by linezolid-resistant enterococci (LRE) are clinically difficult to treat and threaten patient health. However, there is a lack of studies on long time-span LRE strains in China. For this reason, our study comprehensively revealed the resistance mechanisms of LRE strains collected in a Chinese tertiary care hospital from 2011 to 2022. METHODS: Enterococcal strains were screened and verified after retrospective analysis of microbial data...

BACKGROUND: Side effects associated with antimicrobial drugs, as well as their high cost, have prompted a search for low-cost herbal medicinal substances with fewer side effects. These substances can be used as supplements to medicine or to strengthen their effects. The current study investigated the effect of oleuropein on the inhibition of fungal and bacterial biofilm in-vitro and at the molecular level. MATERIALS AND METHODS: In this experimental study, antimicrobial properties were evaluated using microbroth dilution method...

L-asparaginase is an important therapeutic enzyme that is frequently utilized in the chemotherapy regimens of adults as well as pediatric patients with acute lymphoblastic leukemia. However, a high rate of hypersensitivity with prolonged use has limited its utilization. Stenotrophomonas maltophilia (S. maltophilia) EMCC2297 isolate was reported as a novel and promising source for L- asparaginase. The present study aimed at the production, purification, and characterization of L- asparaginase from S. maltophilia EMCC2297 isolate...

INTRODUCTION: DNA extracted from malignant pleural effusion (PE) sediments is the traditional source of tumor DNA for predictive biomarker molecular testing (MT). Few recent studies have proposed the utility of cell-free DNA (cfDNA) extracted from effusion cytology centrifuged supernatants (CCS) in MT. The aim of this study was to assess the feasibility and utility of molecular testing on cfDNA extracted from PE CCS in lung cancer patients. METHOD: The study was of prospective design...

AIM: To review the changes in the new version of the FIGO 2023 staging system for endometrial cancer. METHODS AND RESULTS: The new FIGO 2023 endometrial cancer staging system provides key updates for the diagnosis and treatment of endometrial cancer. An important step in diagnosis is molecular classification, which allows more accurate risk stratification for recurrence and the identification of targeted therapies. The new staging system, based on the recommendations of the international societies ESGO, ESTRO and ESP, incorporates not only the description of the pathological and anatomical extent of the disease, but also the histopathological characteristics of the tumour, including the histological type and the presence of lymphovascular space invasion...

The Asian palm weevil, Rhynchophorus ferrugineus, is a tremendously important agricultural pest primarily adapted to palm trees and causes severe destruction, threatening sustainable palm cultivation worldwide. The host plant selection of this weevil is mainly attributed to the functional specialization of odorant receptors (ORs) that detect palm-derived volatiles. Yet, ligands are known for only two ORs of R. ferrugineus, and we still lack information on the mechanisms of palm tree detection. This study identified a highly expressed antennal R...

BACKGROUND: The activity of von Willebrand factor (VWF) in facilitating platelet adhesion and aggregation correlates with its multimer size. Traditional ristocetin-dependent functional assays lack sensitivity to multimers sizes. Recently nanobodies targeting the autoinhibitory module and activating VWF were identified. OBJECTIVE: To develop an assay that can differentiate the platelet-binding activity of VWF multimers. METHODS: An ELISA-based assay (VWF:GPIbNab) utilizing a VWF-activating nanobody was developed...

BACKGROUND: Immunotherapy combined with chemotherapy significantly improves progression-free survival compared to first-line chemotherapy alone in advanced endometrial cancer, with a much larger effect size in microsatellite-instability high (MSI-H) cases. New biomarkers might help to select patients that may have benefit among those with a microsatellite-stable (MSS) tumor. METHODS: In a pre-planned translational analysis of the MITO END-3 trial, we assessed the significance of genomic abnormalities in patients randomized to standard carboplatin/paclitaxel without or with avelumab...

BACKGROUND: Sevoflurane (SEV) has been found to induce neurotoxicity and cognitive impairment, leading to the development of degenerative diseases. Protein kinase C delta (PRKCD) is upregulated in the hippocampus of SEV-treated mice and may be related to SEV-related neurotoxicity. However, the underlying molecular mechanisms by which SEV mediates neurotoxicity via PRKCD remain unclear. METHODS: Normal mice and PRKCD knockout (KO) mice were exposed to SEV. Hippocampal neurons were isolated from mice hippocampal tissues...

Acute promyelocytic leukemia (APL) with variant RARA translocation is linked to over 15 partner genes. Recent publications encompassing six cases have expanded the spectrum of RARA partners to torque teno mini virus (TTMV). This entity is likely under-recognized due to lack of clinician and pathologist familiarity, inability to detect the fusion using routine testing modalities, and informatic challenges in its recognition within next-generation sequencing (NGS) data. We describe a clinicopathologic approach and provide necessary tools to screen and diagnose APL with TTMV::RARA using existing clinical DNA or RNA-based NGS assays, which led to identification of four cases, all without other known cytogenetic/molecular drivers...

The brown dog tick or Rhipicephalus sanguineus sensu lato is an ixodid tick, responsible for the dissemination of pathogens that cause canine infectious diseases besides inflicting the direct effects of tick bite. The hot humid climate of Kerala, a south Indian state, is favorable for propagation of tick vectors and acaricides are the main stay of tick control. Though the resistance against synthetic pyrethroids is reported among these species, the status of amitraz resistance in R. sanguineus s. l. in the country is uncertain due to the lack of molecular characterization data and scarce literature reports...

This study delves into the eco-endocrinological dynamics concerning the impact of dexamethasone (DXE) on the interrenal axis in juvenile carp, Cyprinus carpio. Through a comprehensive analysis, we investigated the effects of DXE exposure on oxidative stress, biochemical biomarkers, gene expression, and bioaccumulation within the interrenal axis. Results revealed a concentration-dependent escalation of cellular oxidation biomarkers, including 1) hydroperoxides content (HPC), 2) lipid peroxidation level (LPX), and 3) protein carbonyl content (PCC), indicative of heightened oxidative stress...

Immunodiagnostic tests for detecting dengue virus infections encounter challenges related to cross-reactivity with other related flaviviruses. Our research focuses on the development of a synthetic multiepitope antigen tailored for dengue immunodiagnostics. Selected dengue epitopes involved structural linearity and dissimilarity from the proteomes of Zika and Yellow fever viruses which served for computationally modeling the three-dimensional protein structure, resulting in the design of two proteins: rDME-C and rDME-BR...

A transition metal coordination polymer (CP), [Cd(Hdpcp)]n (Cd-CP) was prepared based on 3-(2,4-dicarboxyphenyl)-6-carboxypyridine ligand (H3 dpcp), and then its composite Eu@Cd-CP was synthesized by the post-modification through loading Eu3+ ions on Cd-CP. Eu@Cd-CP has outstanding fluorescence stability in aqueous solution with a wide range of pH. Furthermore, Eu@Cd-CP can distinguish sodium salicylate (SS) and sodium dehydroacetate (SA) in some food additives by quenching the characteristic fluorescence of Eu3+ ion...

Major depressive disorder (MDD) is a severe disorder that causes enormous loss of quality of life, and among the factors underlying MDD is stress in maternal deprivation (MD). In addition, classic pharmacotherapy has presented severe adverse effects. Centella asiatica (C. asiatica) demonstrates a potential neuroprotective effect but has not yet been evaluated in MD models. This study aimed to evaluate the effect of C. asiatica extract and the active compound madecassic acid on possible depressive-like behavior, inflammation, and oxidative stress in the hippocampus and serum of young rats submitted to MD in the first days of life...

Enterococcus has emerged as an opportunistic pathogen because of its antibiotic resistance and virulence profile, which makes it a causative agent of several diseases like endocarditis, surgical site, and urinary tract infections. Currently, species of this genus are the 2nd most frequently isolated microorganisms from hospital-acquired infections. Significant association with hospitals and unhygienic conditions of the environments has made them resistant to a wide range of antibiotics. On the brighter side, enterococci have the ability to produce antimicrobial proteins (i...

Naturally occurring coatings on aluminum metal, such as its oxide or hydroxide, serve to protect the material from corrosion. Understanding the conditions under which these coatings mechanically fail is therefore expected to be an important aspect of predictive models for aluminum component lifetimes. To this end, we develop and apply a molecular dynamics (MD) modeling framework for conducting tension tests that is capable of isolating factors governing the mechanical strength as a function of coating chemistry, defect morphology, and variables associated with the loading path...