Drug Target Insights

Immunotherapy has become an integral part of a comprehensive treatment approach to metastatic colorectal cancer (mCRC). Nivolumab (Opdivo) is a human immunoglobulin G4 monoclonal antibody that blocks the interaction between the programmed cell death 1 (PD-1) receptor and its ligands 1/2 (PD-L1/PD-L2), leading to inhibition of T-cell proliferation, cytokine secretion, and enhanced immune response. The US Food and Drug Administration (FDA) has approved this drug for use in high microsatellite instability (MSI-high)/deficiencies in mismatch repair (dMMR) advanced CRC patients...

BACKGROUND: Non-compliance in the drafting of examination bulletins makes it difficult to perform them and interpret the results. With the aim of continuously improving laboratory services and guaranteeing the quality of urine cytobacteriological examination (ECBU) results, we initiated this study to evaluate non-compliance in the drafting of ECBU reports. MATERIALS AND METHODS: This was a retrospective descriptive cross-sectional study which focused on non-compliance in the drafting of ECBU reports analysed in the laboratory from January to December 2022...

Urinary tract infections (UTIs) are among the most common infections globally, imposing a substantial personal and economic burden on individuals and health resources. Despite international health concerns and sustained public awareness campaigns about the emergence of resistant microorganisms through the inappropriate therapeutic use of antimicrobial agents, the problem of antimicrobial resistance (AMR) is worsening, and AMR in UTIs represents a critical global healthcare issue. This narrative review summarizes evidence-based scientific material, recommendations from the current medical literature, and the latest clinical guidelines on antibiotic and antibiotic-sparing strategies for managing urological infections, including practical approaches to improve the management of patients with acute and recurrent UTIs (rUTIs) in routine clinical practice...

No abstract text is available yet for this article.

Optimal treatment for metastatic non-small cell lung cancer (NSCLC) with mesenchymal epithelial transition gene ( MET ) exon 14 skipping mutation has not been established yet. MET inhibitors were demonstrated to be effective and tolerated in patients with this condition, while evidence on safety and efficacy of immunotherapy and/or chemotherapy in this population is limited. Here we report the case of an 86-year-old male with metastatic NSCLC harboring MET exon 14 skipping mutation and with high programmed cell death ligand 1 (PD-L1) expression (tumor proportion score ≥50%)...

BACKGROUND: Antibiotic misuse is a major public health issue with long-term repercussions. OBJECTIVE: The purpose of this investigation was to evaluate the effects of pneumonia and diarrhea, with an emphasis on antibiotic misuse. METHODOLOGY: This study included 410 participants (217 fathers and 193 mothers), of whom 239 purchased antibiotics for their children without a prescription, whereas 171 had a prescription or were unsure if one was required...

INTRODUCTION: Antibiotic-resistant Pseudomonas aeruginosa strains cause considerable morbidity and mortality globally. Identification of novel targets in this notorious pathogen is urgently warranted to facilitate discovery of new anti-pathogenic agents against it. This study attempted to identify small-molecule inhibitors of two important proteins LasR and nitric oxide reductase (NOR) in P. aeruginosa . 'Las' system can be said to be the 'master' regulator of quorum sensing in P. aeruginosa , whose receptor protein is LasR...

BACKGROUND: Antimicrobial resistance (AMR) is a global health concern, with extended-spectrum β-lactamases (ESBLs) and carbapenemases being major contributors. Pleural infection (PI) is a severe condition in West Africa, complicated by AMR. This study aimed to investigate the prevalence and molecular characteristics of ESBL and carbapenemase-producing enterobacteria in pleural effusions in Mali. MATERIALS AND METHODS: Pleural fluid samples from 526 patients with pleuritis were analyzed...

In the CodeBreaK 100 phase 2 study, sotorasib was active for patients with metastatic non-small cell lung cancer (NSCLC) harboring Kirsten rat sarcoma viral oncogene homologue (KRAS) p.G12C mutation. However, patients with untreated and/or active brain metastases were excluded from the trial, and the activity of sotorasib in the setting of brain metastases should be further investigated. Here we report the case of a KRAS p.G12C mutant NSCLC patient with three brain metastases, of whom one was untreated and the other two had progressed after radiotherapy with symptoms requiring steroids, that responded to sotorasib...

BACKGROUND: Tuberculosis (TB) re mains a deadly disease affecting one-third population globally. Long turnaround time and poor sensitivity of the conventional diagnostics are the major impediments for faster diagnosis of Mycobacterial spp to prevent drug resistance. To overcome these issues, molecular diagnostics have been developed. They offer enhanced sensitivity but require sophisticated infrastructure, skilled manpower and remain expensive. METHODS: In that context, loop-mediated isothermal amplification (LAMP) assay, recommended by the WHO in 2016 for TB diagnosis, sounds as a promising alternative that facilitates visual read outs...

Periodontal disease is caused by specific pathogens which results in inflammation of the tooth-supporting structures and subsequently causes the continued breakdown of alveolar bone and periodontal ligament. Licorice ( Glycyrrhiza glabra ) is a perennial herb with substantial medicinal value. Licorice extract is derived from dried, unpeeled stolons and roots of Glycyrrhiza uralensis and G. glabra . The bioactive ingredients in licorice extract such as glycyrrhizin, licoricidin, glabridin, licochalcone A, and licorisoflavan A have anti-inflammatory, antimicrobial, and anti-adherence effects that are beneficial against periodontal disease...

INTRODUCTION: Antimicrobial resistance (AMR) is a serious global threat. Identification of novel antibacterial targets is urgently warranted to help antimicrobial drug discovery programs. This study attempted identification of potential targets in two important pathogens Pseudomonas aeruginosa and Staphylococcus aureus. METHODS: Transcriptomes of P. aeruginosa and S. aureus exposed to two different quorum-modulatory polyherbal formulations were subjected to network analysis to identify the most highly networked differentially expressed genes (hubs) as potential anti-virulence targets...

No abstract text is available yet for this article.

INTRODUCTION: Human immunodeficiency virus (HIV) infection and the long-term use of antiretroviral therapy, especially efavirenz (EFV)-based regimens, impact lipid profiles due to insulin resistance and lead to a higher risk of metabolic diseases. Dolutegravir (DTG) is an integrase inhibitor with better lipid profiles than EFV. However, data on treatment experience in Thailand are limited. The primary outcome was lipid profile changes at 24 weeks after switching therapy. METHODS: We conducted a prospective, open-label, cohort study in people with HIV aged ≥18 years who had undergone at least 6 months of EFV-based therapy, had HIV-1 ribonucleic acid levels <50 copies/mL for ≥6 months before switching, and were diagnosed with dyslipidemia or had risk factors for atherosclerosis cardiovascular disease based on modified National Cholesterol Education Program Adult Treatment Panel III guidelines...

INTRODUCTION: Mechanical ventilation (MV) is a life-saving approach in critically ill patients. However, it may affect the diaphragmatic structure and function, beyond the lungs. Levosimendan is a calcium sensitizer widely used in clinics to improve cardiac contractility in acute heart failure patients. In vitro studies have demonstrated that levosimendan increased force-generating capacity of the diaphragm in chronic obstructive pulmonary disease patients. Thus the aim of this study was to evaluate the effects of levosimendan administration in an animal model of ventilator-induced diaphragmatic dysfunction (VIDD) on muscle contraction and diaphragm muscle cell viability...

Cardiovascular diseases (CVDs) are inflammatory diseases of coronary arteries accompanying atheroma formation that can spawn impairment and, in severe cases, death. CVDs are the leading cause of death in the world. In recent decades, investigators have focused their impact on CVD by periodontal disease (PD). PD is a risk factor that can trigger the formation, maturation, and instability of atheroma in the arteries. Two mechanisms have been proposed to explain this relationship: periodontopathic pathogens explicitly invade the circulation or indirectly increase systemic levels of inflammatory mediators...

No abstract text is available yet for this article.

Drug administration through the vaginal tract is one of the oldest modalities of pharmacotherapy, and it is also one of the most explored. Since the vaginal cavity has a wide surface area, a plentiful blood supply, and a complex network of blood arteries, it can evade hepatic first-pass metabolism and obtain high local drug concentrations. Vaginal pills look to be a good dose form since they are simple to use, portable, and can easily deliver the required amount of medicine. Vaginal formulations, on the other hand, are vulnerable to rapid expulsion due to the vaginal tract’s self-cleaning action, which reduces the formulation’s efficiency...

INTRODUCTION: Detection and diagnosis of methicillin-resistant Staphylococcus aureus (MRSA) are important in ensuring a correct and effective treatment, further reducing its spread. A wide range of molecular approaches has been used for the diagnosis of antimicrobial resistance (AMR) in MRSA. This review aims to study and appraise widely used molecular diagnostic methods for detecting MRSA. METHODS: This meta-narrative review was performed by searching PubMed using the following search terms: (molecular diagnosis) AND (antimicrobial resistance) AND (methicillin-resistant Staphylococcus aureus)...

The enrichment and diversity of gut microbiota play an important role in sepsis, but the role of gut microbiota composition and early-life colonization in sepsis and septic shock has not yet been characterized. The impact of gut microbiota diversity on host immunological disorders and future treatments of inflammatory diseases are not yet fully elucidated. Further, the association between the microbiota and immune development in sepsis remains unknown, and the underlying mechanisms are not well understood. The altered composition of gut microbiota during sepsis is profoundly associated with a loss of commensal bacteria and an overgrowth of potentially pathogenic bacteria, especially AMR bacteria...