Overcoming Resistance in Cancer Therapy: Computational Exploration of PIK3CA Mutations, Unveiling Novel Non-Toxic Inhibitors, and Molecular Insights Into Targeting PI3Kα.

Phosphoinositide-3-kinases (PI3 K) are pivotal regulators of cell signaling implicated in various cancers. Particularly, mutations in the PIK3CA gene encoding the p110α catalytic subunit drive oncogenic signaling, making it an attractive therapeutic target. Our study conducted in silico exploration of 31 PIK3CA mutations across breast, endometrial, colon, and ovarian cancers, assessing their impacts on response to PI3Kα inhibitors and identifying potential non-toxic inhibitors and also elucidating their effects on protein stability and flexibility.

Targeting decaprenylphosphoryl-β-D-ribose 2'-epimerase for Innovative Drug Development Against Mycobacterium Tuberculosis Drug-Resistant Strains.

Tuberculosis (TB) remains a global health challenge with the emergence of drug-resistant Mycobacterium tuberculosis variants, necessitating innovative drug molecules. One potential target is the cell wall synthesis enzyme decaprenylphosphoryl-β-D-ribose 2'-epimerase (DprE1), crucial for virulence and survival. This study employed virtual screening of 111 Protein Data Bank (PDB) database molecules known for their inhibitory biological activity against DprE1 with known IC50 values.

Virtual docking screening and quantitative structure-activity relationship studies to explore AKT and PI3K inhibitors acting on mTOR in cancers by theoretical biology and medical modeling.

Introduction: The mechanistic target of rapamycin (mTOR) coordinates the growth and metabolism of eukaryotic cells with a central role in the regulation of many fundamental cellular processes. It is strongly connected to phosphatidylinositol 3-kinase (PI3K) and AKT signaling. Activation of the PI3K/AKT/mTOR pathway leads to a profound disruption in the control of cell growth and survival, which ultimately leads to competitive growth advantage, metastatic competence, angiogenesis and therapeutic resistance.

Selective Non-toxics Inhibitors Targeting DHFR for Tuberculosis and Cancer Therapy: Pharmacophore Generation and Molecular Dynamics Simulation.

Dihydrofolate reductase (DHFR) is a crucial enzyme that catalyzes the conversion of folic acid. Its reserved properties and significance in both human (h-DHFR) and mycobacterium (mt-DHFR) make it a challenging target for developing drugs against cancer and bacterial infections. Although methotrexate (MTX) is commonly used for cancer therapy and bacterial infections, it has a toxic profile.

Facing Antitubercular Resistance: Identification of Potential Direct Inhibitors Targeting InhA Enzyme and Generation of 3D-pharmacophore Model by in silico Approach.

Purpose: The enoyl-acyl carrier protein reductase (InhA) is one of the important key enzymes employed in mycolic acids biosynthesis pathway and an important component of mycobacterial cell walls. This enzyme has also been identified as major target of isoniazid drug, except that isoniazid needs to be activated first by the catalase peroxidase (KatG) protein to form the isonicotinoyl-NAD (INH-NAD) adduct that inhibits the action of InhA enzyme. However, this activation becomes more difficult and unreachable with the problem of mutation-related resistance caused mainly by acquired mutations in KatG and InhA protein.

In Silico Analyses of All STAT3 Missense Variants Leading to Explore Divergent AD-HIES Clinical Phenotypes.

Autosomal dominant hyper-IgE syndrome (AD-HIES) is linked to dominant negative mutations of the STAT3 protein whose molecular basis for dysfunction is unclear and presenting with a variety of clinical manifestations with only supportive treatment. To establish the relationship between the impact of STAT3 mutations in different domains and the severity of the clinical manifestations, 105 STAT3 mutations were analyzed for their impact on protein stability, flexibility, function, and binding affinity using in Silico approaches. Our results showed that 73% of the studied mutations have an impact on the physicochemical properties of the protein, altering the stability, flexibility and function to varying degrees.

Association of endometriosis with interstitial cystitis in chronic pelvic pain syndrome: Short narrative on prevalence, diagnostic limitations, and clinical implications.

Introduction: Chronic pelvic pain (CPP) is a diagnostic and therapeutic challenge affecting women of all ages globally. The syndrome is not well understood, but the association of interstitial cystitis (IC) with endometriosis in causing CPP should not be overlooked in managing this cohort. Herein, we present a mini review of this association to evaluate the literature in determining the prevalence of endometriosis and IC concomitantly in patients with CPP, diagnostic limitations, and clinical implications.

Role of systems science in preventing and controlling emerging infectious diseases: protocol for a scoping review.

Introduction: In recent history, many new infectious diseases have affected humans for the first time or have appeared in previously unaffected areas of the world; these diseases are known as emerging infectious diseases (EIDs). Examples of EIDs include COVID-19, Middle East respiratory syndrome and Ebola virus disease. EIDs are known for their complexity.