Practical management of adverse events in patients receiving tarlatamab, a delta-like ligand 3-targeted bispecific T-cell engager immunotherapy, for previously treated small cell lung cancer.

Tarlatamab is a bispecific T-cell engager immunotherapy targeting delta-like ligand 3 (DLL3) and the cluster of differentiation 3 (CD3) molecule. In the phase 2 DeLLphi-301 trial of tarlatamab for patients with previously treated small cell lung cancer, tarlatamab 10 mg every 2 weeks achieved durable responses and encouraging survival outcomes. Analyses of updated safety data from the DeLLphi-301 trial demonstrated that the most common treatment-emergent adverse events were cytokine release syndrome (53%), pyrexia (38%), decreased appetite (36%), dysgeusia (32%), and an emia (30%).

Cysteine S-conjugate sulfoxide β-lyase activity for human ACCS.

1-Aminocyclopropane-1-carboxylate synthase (ACCS) catalyzes the conversion of S-adenosyl-methionine to 1-aminocyclopropane-1-carboxylate (ACC), a rate-limiting step in ethylene biosynthesis. A gene encoding a putative ACCS protein was identified in the human genome two decades ago. It has been shown to not exhibit any canonical ACC synthase activity and its true function remains obscure.

Cognitive dysfunction in diabetes - the 'forgotten' diabetes complication: a narrative review.

Background: In addition to peripheral neuropathy of various kinds, diabetes can also cause central neuropathy, which among other things can manifest itself as premature cognitive dysfunction, often linked to vascular dysfunction. Although the link between diabetes and cognitive dysfunction was discovered more than 100 years ago and has important clinical implications, this diabetes complication remains relatively unknown. Recent years have seen research that has clarified cerebral insulin resistance and defective insulin signaling as examples of pathogenic factors behind this cognitive impairment in diabetes.

The AhR pathway regulation in phthalates-induced cancer promotion, progression and metastasis: a scoping review.

Background: Cancer remains a leading cause of death worldwide. Environmental factors, specifically endocrine-disrupting chemicals (EDCs), like phthalates, are increasingly being linked to cancer development. Phthalates, widely used in consumer products, can activate the aryl hydrocarbon receptor (AhR).

Effects of intra-class peer mentorship intervention programme on the academic performances of academically underperforming medical students in Nigeria.

Background: A significant gap exists in understanding the effectiveness of intra-class (same-class) level peer mentorship programmes designed to enhance academic performance, well-being, and student involvement among underperforming medical students. This study assessed the effectiveness of intra-class (same-class) peer mentorship programme on the academic performances, subjective well-being and school engagement of academically underperforming medical students in Nigeria.

Methods: This was a quasi-experimental research consisting of the pretest-posttest control design at Nnamdi Azikiwe University, Awka, Nigeria.

Investigating the role of intratumoral Streptococcus mitis in gastric cancer progression: insights into tumor microenvironment.

Growing evidence implicates that intratumoral microbiota are closely linked to cancer progression; however, research on the role of these microbiota in the development of gastric cancer remains limited. Here, using 16 S rRNA sequencing, tumor tissue proteomics and serum cytokines analysis, we identified enrichment of specific microbial communities within tumors of gastric cancer patients, possibly affecting the tumor microenvironment by immune modulation, metabolic processes, and inflammatory responses. Based on the results of in vivo experiments and intratumoral microbiota analysis, we found that Streptococcus mitis can inhibit gastric cancer progression via suppressing M2 macrophage polarization and infiltration, as well as altering the intratumoral microbial community.

Intestinal neutrophil extracellular traps promote gut barrier damage exacerbating endotoxaemia, systemic inflammation and progression of diabetic retinopathy in type 2 diabetes.

Aims/hypothesis: Within the small intestine, neutrophils play an integral role in preventing bacterial infection. Upon interaction with bacteria or bacteria-derived antigens, neutrophils initiate a multi-staged response of which the terminal stage is NETosis, formation of protease-decorated nuclear DNA into extracellular traps. NETosis has a great propensity to elicit ocular damage and has been associated with diabetic retinopathy and diabetic macular oedema (DME) progression.

Different essential oils can inhibit Candida albicans biofilm formation on acrylic resin by suppressing aspartic proteinase: In vitro and in silico approaches.

Introduction: Cymbopogon martini, Syzygium aromaticum, and Cupressus sempervirens are used for antimicrobial purposes in the worldwide. Both their extracts and essential oil contents are rich in active ingredients.

Objective: The aim of this study was to investigate the inhibitory effect of Cymbopogon martini essential oil (CMEO), Syzygium aromaticum essential oil (SAEO) and Cupressus sempervirens essential oil (CSEO) on Candida albicans biofilm formation on heat-polymerized polymethyl methacrylate (PMMA) samples in vitro and in silico.

A human metabolic map of pharmacological perturbations reveals drug modes of action.

Understanding a small molecule's mode of action (MoA) is essential to guide the selection, optimization and clinical development of lead compounds. In this study, we used high-throughput non-targeted metabolomics to profile changes in 2,269 putative metabolites induced by 1,520 drugs in A549 lung cancer cells. Although only 26% of the drugs inhibited cell growth, 86% caused intracellular metabolic changes, which were largely conserved in two additional cancer cell lines.

Effectiveness of Pelvic Floor Muscle and Education-based Therapies on Bladder, Bowel, Vaginal, Sexual, Psychological Function, Quality of Life, and Pelvic Floor Muscle Function in Females Treated for Breast Cancer: A Systematic Review.

Purpose Of Review: Breast malignancy is the most common cancer in females. Symptoms of pelvic floor disorders and sexual dysfunction secondary to systemic cancer treatment may occur. Non-surgical, non-pharmaceutical conservative therapies, namely pelvic floor muscle (PFM) and education-based therapies, could be beneficial to reduce these symptoms in this population.

Ginsenoside Rd protects against acute liver injury by regulating the autophagy NLRP3 inflammasome pathway.

Ginsenoside Rd (Rd) is a bioactive compound predominantly found in Panax ginseng C.A. Meyer and Panax notoginseng (Burkill) F.

Assessment of retinal pigment epithelium tears in eyes with submacular hemorrhage secondary to age-related macular degeneration.

To assess retinal pigment epithelium (RPE) tears in eyes which underwent pars plana vitrectomy (PPV) for submacular hemorrhage (SMH) secondary to age-related macular degeneration and to investigate the prognostic factors of visual outcomes. This study was a retrospective, observational case series that included 24 eyes of 24 patients who underwent PPV with subretinal tissue plasminogen activator and air for SMH. RPE tears were investigated using spectral-domain or swept-source optical coherence tomography images with raster scan, combined confocal scanning laser ophthalmoscope near-infrared images and color fundus photographs.

Characterization of Bozitinib as a potential therapeutic agent for MET-amplified gastric cancer.

Hyperactive c-Met signaling pathway caused by altered MET is a common mechanism underlying gastric cancer and represents an attractive target for the treatment of gastric cancer with MET alterations. However, no c-Met kinase inhibitors are currently approved specifically for the treatment of c-Met-amplified gastric cancer. Recently, bozitinib, a highly selective c-Met kinase inhibitor, has shown remarkable potency in selectively inhibiting MET-altered non-small cell lung cancer and secondary glioblastoma.

α-Copaene is a potent repellent against the Asian Citrus Psyllid Diaphorina citri.

The Asian Citrus Psyllid (ACP), Diaphorina citri, severely threatens citrus production worldwide by transmitting the greening (= Huanglongbing)-causing bacterium Candidatus Liberibacter asiaticus. There is growing evidence that the push-pull strategy is suitable to partially mitigate HLB by repelling ACP with transgenic plants engineered to produce repellents and attracting the vector to plants with a minimal disease transmission rate. Species that pull ACP away from commercial citrus plants have been identified, and transgenic plants that repel ACP have been developed.

PARP inhibition-associated heterochromatin confers increased DNA replication stress and vulnerability to ATR inhibition in SMARCA4-deficient cells.

DNA replication stress (RS), a prevalent feature of various malignancies, arises from both genetic mutations and genotoxic exposure. Elevated RS levels increase the vulnerability of cancer cells to ataxia telangiectasia and Rad3-related kinase inhibitors (ATRis). Here, we screened for DNA damage response inhibitors that enhance ATRi-induced cytotoxicity using SWI/SNF complex-deficient cells and identified a potent synergy between ATRi and poly(ADP-ribose) polymerase inhibitor (PARPi), particularly in SMARCA4-deficient cells.

The role of nutritional vitamin D in CKD-MBD in children and adults with CKD, on dialysis and after kidney transplantation - a European consensus statement.

Vitamin D deficiency is common in patients with chronic kidney disease (CKD) and associates with poor outcomes. Current clinical practice guidelines recommend supplementation with nutritional vitamin D as for the general population. However, recent large-scale, clinical trials in the general population failed to demonstrate a benefit of vitamin D supplementation on skeletal or non-skeletal outcomes, fueling a debate on the rationale for screening for and correcting vitamin D deficiency, both in non-CKD and CKD populations.

Lipid nanoparticle-mediated intracameral mRNA delivery facilitates gene expression and editing in the anterior chamber of the eye.

Lipid nanoparticles (LNPs) have shown great potential in the field of gene therapy for retinal diseases. To expand on this application, we investigated LNP-mediated mRNA delivery to the anterior chamber of the eye via the intracameral (IC) route of administration. Here, we show that IC injections of LNPs facilitated protein expression and gene editing in the trabecular meshwork (TM).

Metallofullerenol Gd@C(OH) preserves human erythrocyte plasma membrane integrity from AAPH-induced oxidative stress: molecular mechanisms and antioxidant activity.

Metallofullerenols and fullerenols have attracted attention due to their remarkable ability to interact with various biologically relevant molecules, paving the way for biomedical applications, ranging from medical imaging techniques to drug carriers, acting with increased efficiency and reduced side effects. In this work, we investigated the effects of two fullerene derivatives, Gd@C(OH) and C(OH), on erythrocyte membrane components under oxidative stress conditions induced by 2,2'-azobis(2-amidinopropane) dihydrochloride (AAPH) as a source of peroxyl radicals. The results demonstrated that gadolinium encapsulation within the fullerene cage enhanced the electron affinity of Gd@C(OH), resulting in stronger antioxidant activity.

Deep eutectic solvents in analysis, delivery and chemistry of pharmaceuticals.

Deep eutectic solvents (DES) have an emerging scientific role, assisting modern pharmaceutics. They are uniquely supporting the resolution of crucial issues, such as the effective extraction and isolation of bio-actives. They act as media and catalysts for pharmaceutical drug synthesis, and as green solvents and modifiers in pharmaceutical analysis.

Formulation screening of lyophilized mRNA-lipid nanoparticles.

Lipid nanoparticles (LNPs) have demonstrated their therapeutic potential as safe and effective drug delivery systems for nucleic acids during the COVID-19 pandemic. However, one of the main challenges during technical CMC (Chemistry, Manufacturing, and Controls) development is their long-term stability at temperatures of 2-8 °C or higher, which may be improved by the removal of water by lyophilization. In this study, we identified lyo-/cryo-protectants for freeze-dried mRNA-LNP formulations beyond conventional excipients such as sucrose and trehalose as T-modifiers using polyA as a surrogate.

Abiraterone acetate fixed-dosed combinations with ibuprofen-based therapeutic eutectic and deep eutectic solvents.

In recent years, deep eutectic solvents (DESs) with their outstanding solubilization properties have emerged as strong candidates for oral enabling formulations of poorly soluble drugs. This study explores the use of drug-based therapeutic DESs (THEDESs) to solubilize a poorly soluble compound with the aim of providing a fixed-dose combination of two complementary therapeutic agents. Specifically, potential anticancer effects of ibuprofen (IBU) are harnessed in a novel type of THEDES to dissolve higher amounts of abiraterone acetate (AbAc), an antitumor agent.

IN SILICO AND IN VITRO ASSESSMENT OF ANTI-Leishmania infantum ACTIVITY OF A NOVEL CYCLOHEXYL-1,2,4-OXADIAZOLE DERIVATIVE.

Globally, an estimated 1 billion people reside in endemic areas, and over 12 million individuals are infected with leishmaniasis. Despite its prevalence, leishmaniasis continues to be a neglected disease, mainly affecting underdeveloped countries. In Brazil, the available treatments are pentavalent antimonials and Amphotericin B, which are outdated, toxic, require prolonged parenteral administration and have limited efficacy.

The GLP-1 Agonist Semaglutide Ameliorates Cognitive Regression in P301S Tauopathy Mice Model via Autophagy/ACE2/SIRT1/FOXO1-Mediated Microglia Polarization.

Tau hyper-phosphorylation has been recognized as an essential contributor to neurodegeneration in Alzheimer's disease (AD) and related tauopathies. In the last decade, tau hyper-phosphorylation has gained considerable concern in AD therapeutic development. Tauopathies are manifested with a broad spectrum of symptoms, from dementia to cognitive decline and motor impairments.

Design, Synthesis, and biological evaluation of 7H-Pyrrolo[2,3-d]pyrimidines as potent HPK1 kinase inhibitors.

Hematopoietic progenitor kinase 1 (HPK1) has emerged as a promising target for cancer immunotherapy due to its critical role as a negative regulator of T cell receptor (TCR) signaling. Despite this potential, no HPK1 inhibitors have been approved for cancer treatment, underscoring the need for structurally novel inhibitors. Herein, we describe the design, synthesis and biological evaluation of a series of potent HPK1 inhibitors based on our previously identified hit 9.