TClC effectively suppresses the growth and metastasis of NSCLC via polypharmacology.

Despite significant advances in targeted therapies and immunotherapies, non-small cell lung cancer (NSCLC) continues to present a global health challenge, with a modest five-year survival rate of 28 %, largely due to the emergence of treatment-resistant and metastatic tumors. In response, we synthesized a novel bioactive compound, ethyl 6-chlorocoumarin-3-carboxylyl L-theanine (TClC), which significantly inhibited NSCLC growth, epithelial mesenchymal transition (EMT), migration, and invasion and tumor growth and metastasis without inducing toxicity. TClC disrupts autocrine loops that promote tumor progression, particularly in stem-like CD133-positive NSCLC (CD133+ LC) cells, which are pivotal in tumor metastasis.

Trends in naloxone co-prescriptions.

Background: The opioid epidemic remains a significant public health crisis in the United States. Naloxone has been identified as a critical component in combating this crisis. However, co-prescription rates among patients receiving opioids remain suboptimal, especially among certain high-risk populations.

Nano-enabled pharmacogenomics: revolutionizing personalized drug therapy.

The combination of pharmacogenomics and nanotechnology science of pharmacogenomics into a highly advanced single entity has given birth to personalized medicine known as nano-enabled pharmacogenomics. This review article covers all aspects starting from pharmacogenomics to gene editing tools, how these have evolved or are likely to be evolved for pharmacogenomic application, and how these can be delivered using nanoparticle delivery systems. In this prior work, we explore the evolution of pharmacogenomics over the years, as well as new achievements in the field of genomic sciences, the challenges in drug creation, and application of the strategy of personalized medicine.

Prioritization of Eleven-Nineteen-Leukemia Inhibitors as Orally Available Drug Candidates for Acute Myeloid Leukemia.

Acute myeloid leukemia (AML) is the second most prevalent and fatal form of leukemia. The growth of AML cells harboring oncogenic MLL rearrangements relies on the YEATS domain-containing protein ENL. Many small molecule inhibitors targeting ENL have been developed.

A comprehensive review of challenges and advances in exosome-based drug delivery systems.

Exosomes or so-called natural nanoparticles have recently shown enormous potential for targeted drug delivery systems. Several studies have reported that exosomes as advanced drug delivery platforms offer efficient targeting of chemotherapeutics compared to individual polymeric nanoparticles or liposomes. Taking structural constituents of exosomes, , proteins, nucleic acids, and lipids, into consideration, exosomes are the most promising carriers as genetic messengers and for treating genetic deficiencies or tumor progression.

Involvement of macromolecules in 3D printing for wound healing management: A narrative review.

Wound healing comprises four overlapping stages involving complex biochemical and cellular processes. Any lapse in this procedure causes irregular healing, which generates clinical and financial burdens for the health system. Personalized treatment is preferred to overcome the limitations of classical as well as modern methods of wound healing.

Directed Evolution of Pyrrolysyl-tRNA Synthetase for the Genetic Incorporation of Two Different Noncanonical Amino Acids in One Protein.

The genetic code expansion technique is a powerful chemical biology tool to install noncanonical amino acids (ncAAs) in proteins. As a key enzyme for this technique, pyrrolysyl-tRNA synthetase (PylRS), coupled with its cognate amber suppressor tRNA, has been engineered for the genetic incorporation of more than 200 ncAAs. Using PylRS clones from different archaeal origins, two ncAAs have also been genetically encoded in one protein.

Application of validated size-exclusion chromatography method for physicochemical characterization of topical gel formulation of deferoxamine conjugated with PEGylated carbon nanoparticles.

The focus of current research work was to develop and validate size-exclusion chromatography method and develop and evaluate gel formulation of deferoxamine conjugated with PEGylated carbon nanoparticles (DEF-PEG-CNP) for topical delivery. Size-exclusion chromatography-based method was validated as per ICH guidelines. Effect of Carbopol® 974P and Transcutol® on the nanoparticles' permeation was studied by 3-level full factorial design of experiment.

Development, Pharmacokinetics and Antimalarial Evaluation of Dose Flexible 3D Printlets of Dapsone for Pediatric Patients.

The focus of current studies was to fabricate dose flexible printlets of dapsone (DDS) for pediatric patients by selective laser sintering (SLS) 3D printing method, and evaluate its physicochemical, patient in-use stability, and pharmacokinetic attributes. Eight formulations were fabricated using Kollicoat IR, Eudragit L-100-55 and StarCapas excipients and evaluated for hardness, disintegration, dissolution, amorphous phase by differential scanning calorimetry and X-ray powder diffraction, in-use stability at 30 C/75% RH for a month, and pharmacokinetic study in Sprague Dawley rats. The hardness, and disintegration of the printlets varied from 2.

Novel alloxazine analogues: design, synthesis, and antitumour efficacy enhanced by kinase screening, molecular docking, and ADME studies.

This study describes the development of novel alloxazine analogues as potent antitumor agents with enhanced selectivity for tumour cells. Twenty-nine out of 45 newly compounds were investigated for their growth inhibitory activities, against two human tumour cell lines, namely, the human T-cell acute lymphoblastoid leukaemia cell line (CCRF-HSB-2) and human oral epidermoid carcinoma cell line (KB), and the antitumor agent "Ara-C" was used as a positive reference in this investigation. Compounds and were the highest among their analogues, against both tumour cell lines (CCRF-HSB-2 and KB).

Assessment of needs, challenges, and re-design considerations for culturally sensitive provision and delivery of palliative care supports and services for older adults who prefer to age and die in place in diverse India.

As the global older adult population continues to grow, challenges related to managing multiple chronic conditions (MCCs) or multimorbidity underscore the growing need for palliative care. Palliative care preferences and needs vary significantly based on context, location, and culture. As a result, there is a need for more clarity on what constitutes palliative care in diverse settings.

Safety Outcomes After Sacubitril/Valsartan Initiation in a Community Teaching Hospital: A Retrospective Observational Study.

Background: Sacubitril/valsartan is one of the main foundational medications in heart failure (HF), and recent data show that it provides a mortality benefit in this patient population. Some of the main safety concerns associated with this drug class include hypotension, hyperkalemia, angioedema, and acute kidney injury (AKI). Other studies have focused on sacubitril/valsartan effects on blood glucose levels, which is a newer concept that has not been as researched.

Mono-(2-ethylhexyl) phthalate induces trophoblast hypoxia and mitochondrial dysfunction through HIF-1α-miR-210-3p axis in HTR-8/SVneo cell line.

The exposure to the ubiquitous phthalate metabolite mono-(2-ethylhexyl) phthalate (MEHP) is connected to dysregulated trophoblast function and placenta health; however, the underlying mechanisms preluding this scenario remain to be elucidated. In this study, we explored the hypoxemic effects of MEHP on a human placental first-trimester trophoblast cell line (HTR-8/Svneo). MEHP-treated trophoblast cells displayed significantly increased levels of oxidative stress and hypoxia-inducible factor-1 alpha (HIF-1α) attributed by the induction of hypoxia.

Population Pharmacokinetics (PopPK) Support for Pediatric Dosing of Biological Products.

This study assesses the use of population pharmacokinetics (PopPK) in supporting pediatric dosing of novel biological drug products. The labeling for biologic drug products approved by the US Food and Drug Administration (FDA) from 2002 until 2021 was reviewed to identify those with a pediatric indication. For the drugs with a pediatric indication, the dosing regimen(s) based on age groups, dosing strategy, the use of PopPK to support the dose, and the types of pediatric clinical trials were reviewed.

Risk-Based Approach for Defining Retest Dates for Active Pharmaceutical Ingredients and Excipients.

Drug substances and excipients must be stored in recommended storage conditions and should comply with their specifications during the retest period for their use in the manufacture of drug products. The ICH (International Council for Harmonization of Technical Requirements for Pharmaceuticals for Human Use) and WHO (World Health Organization) regulatory guidelines mandate that after the retest period, the drug substances must be retested for compliance with the specification and then used immediately in the manufacture of the finished product. Although these substances can be retested multiple times, an emphasis is placed on immediate use following a retest and compliance with standards.

Expression of hsa-miRNA-15b, -99b, -181a and Their Relationship to Angiogenesis in Renal Cell Carcinoma.

Background: MicroRNAs (miRNAs) play a regulatory role in various human cancers. The roles of hsa-miR-15a-5p, hsa-miR-99b-5p, and hsa-miR-181a-5p have not been fully explored in the angiogenesis of renal cell carcinoma (RCC).

Aims: The present study aimed to evaluate the expression of these miRNAs in tumorous and adjacent healthy tissues of RCC.

Mass spectrometry-based proteomic profiling of extracellular vesicle proteins in diabetic and non-diabetic ischemic stroke patients: a case-control study.

Acute ischemic stroke is the most common cause of neurologic dysfunction caused by focal brain ischemia and tissue injury. Diabetes is a major risk factor of stroke, exacerbating disease management and prognosis. Therefore, discovering new diagnostic markers and therapeutic targets is critical for stroke prevention and treatment.