COPD and Immune Checkpoint Inhibitors for Cancer: A Literature Review.

Purpose: Immune checkpoint inhibitors are a standard treatment option for many patients with cancer and are most frequently used to treat lung cancer. Chronic obstructive pulmonary disease (COPD) is the most common comorbidity of patients with lung cancer. As the cancer-specific survival of patients with lung cancer continues to increase with modern treatments, it is critical to optimize comorbidities to improve overall survival.

Reshaping the Landscape of Locoregional Treatments for Breast Cancer Liver Metastases: A novel, intratumoral, p21-targeted percutaneous therapy increases survival in BALB/c mice inoculated with 4T1 triple negative breast cancer cells in the liver.

Patients with disseminated metastatic disease from breast cancer are likely to have liver involvement in >50% of cases at some point during disease progression. These patients have a poor prognosis; and, when treated with the standard of care systemic therapy they have a median survival of <9-months. Increasing survival in breast cancer patients will likely require the administration of better therapies that are specifically targeted to treat distant metastases.

OST Catalytic Subunit Redundancy Enables Therapeutic Targeting of N-Glycosylation.

Protein asparagine (N)-glycosylation, which promotes folding and trafficking of cell surface receptors such as the EGFR, has not been considered a viable target in oncology due to the essential and non-redundant enzymatic activities required for glycan synthesis and transfer. In mammals an exception to this rule is the presence of the oligosaccharyltransferase (OST) catalytic subunit paralogs, STT3A and STT3B. Here we delineate the chemical biology of OST inhibitors and develop an approach for limited inhibition of N-glycosylation optimized for downstream effects on EGFR.

A model of inborn metabolism errors associated with adenine amyloid-like fiber formation reduces TDP-43 aggregation and toxicity in yeast.

TDP-43 is linked to human diseases such as amyotrophic lateral sclerosis (ALS) and frontotemporal degeneration (FTD). Expression of TDP-43 in yeast is known to be toxic, cause cells to elongate, form liquid-like aggregates, and inhibit autophagy and TOROID formation. Here, we used the yeast model of disorders of inborn errors of metabolism, previously shown to lead to intracellular adenine accumulation and adenine amyloid-like fiber formation, to explore interactions with TDP-43.

Tobacco Smoke Exposure and Lactation.

Tobacco smoke exposure remains a significant public health concern, particularly for lactating women and their infants. Despite widespread awareness of the harms of smoking during pregnancy, many women continue to smoke postpartum, directly impacting lactation success and infant health. Studies have shown that nicotine, the primary component of tobacco smoke, inhibits prolactin production and the milk ejection reflex, resulting in a decreased milk supply and poor breastfeeding outcomes.

Novel isatin conjugates endowed with analgesic and anti-inflammatory properties: design, synthesis and biological evaluation.

Aims: This study aimed to develop novel molecular hybrid conjugates integrating isatin, rhodanine, and phthalimide pharmacophores to create effective analgesic and anti-inflammatory agents with improved safety profiles over existing treatments.

Materials & Methods: A series of hybrid conjugates () were synthesized and evaluated through in vitro and in vivo biological assays. The most promising compound, , underwent extensive pharmacological and toxicological evaluations.

δ-Toxin Induces Ca Influx-Independent Degranulation of Murine Cultured Mast Cells.

Cutaneous colonization with Staphylococcus aureus (SA) is frequently observed in patients with atopic dermatitis. SA produces a wide variety of bacterial toxins, among which δ-toxin was found to induce degranulation of mast cells. Degranulation of mast cells could enhance bacterial clearance and protection from future SA infection but lead to exacerbation of atopic dermatitis.

Tracing Zinc's Role in Preterm Infants' Health: A Narrative Review.

Zinc (Zn) is a trace element involved in numerous physiological processes, including enzyme function, gene transcription, and cell signaling. Its importance is especially pronounced in preterm infants, who are at high risk of Zn deficiency due to disrupted transplacental transfer, high nutrient demands, and medical complications. The inherent risk of Zn deficiency in this population is further increased by poor Zn dietary intake.

Sleep deprivation alters hepatic UGT1A9 and propofol metabolism in mice.

Sleep deprivation (SD) causes circadian misalignment, and circadian clock disruption is associated with metabolic diseases such as obesity, insulin resistance, and diabetes. However, the underlying mechanism for SD-induced circadian clock disruption as well as metabolic enzyme changes is still lacking. Here, we developed SD sensitizes mice with disrupted circadian rhythms to demonstrate the regulation role and mechanism of SD in UDP-glucuronosyltransferases (UGTs) expression and the metabolism of corresponding substrates.

Definition, Classification, and Management of Primary Non-Cardiac Causes of Cardiogenic Shock.

Cardiogenic shock is a complex syndrome presenting with a critical state of cardiac output insufficient to support end-organ perfusion requirements. Contemporary cardiogenic shock classification recognizes broad categories of primary cardiac etiologies of cardiogenic shock, such as acute myocardial infarction and heart failure. Primary non-cardiac etiologies of cardiogenic shock, however, are poorly described in literature and have not been captured by any contemporary classification, leading to challenges in diagnosing and managing these cases.

Screening, identification and functional validation of Microcystin-LR direct binding target proteins based on thermal proteomics profiling.

Microcystin-LR (MC-LR) is one of the most common harmful cyanobacterial toxin and poses a serious threat to human health and ecosystems. The accepted toxic effect of MC-LR is to inhibit its enzymatic activity by covalently binding to protein phosphatase 2A (PP2A). However, numerous researches have revealed that the toxic effects of MC-LR are not solely dependent on PP2A.

Microchimerism: The mystery of multiple DNA and its implications in forensic sciences.

Microchimerism (MC) refers to the presence of small amounts of foreign cells or DNA in the tissues or circulation of an individual. It generally occurs through mother-fetus interaction, twin pregnancies, and intergenerational transmission. MC is influenced by genetic and environmental factors such as toxic conditions, immunological suppression, and various diseases (influenza, COVID-19, etc.

Computational simulation of bioaccumulation and trophic transfer of antibiotics mechanisms in aquatic food chain.

Numerous antibiotics have been detected in aquatic ecosystems and induced severe toxic effects on aquatic organisms. However, mechanisms of bioaccumulation and trophic transfer of antibiotics are not adequately discussed, to the best of our knowledge. In this context, the bidirectional selective effect values (BSEV) and trophic transfer efficiency ratio (TTER) of 24 antibiotics in a simulated food chain (Chlorella sorokiniana-Daphnia magna-Danio rerio) were first calculated to mirror the bioaccumulation and biomagnification.

Clinical impact of UV mutational signatures in Veterans with cancer.

Background: UV-related DNA damage signature (UVsig) is highly specific for cutaneous cancers. The prevalence of UVsig among tumors without a primary site and tumors of extracutaneous origin were previously reported, suggesting potential misclassification of cancers. Our study aims to assess if the knowledge of UVsig at diagnosis would change first-line treatment recommendation.

Host-microbiota interplay in arsenic metabolism: Implications on host glucose homeostasis.

Arsenic (As), a naturally occurring element with unique properties, has been recognized as the largest mass poisoning in the world by the World Health Organization (WHO). Approximately 200 million people worldwide are exposed to toxic levels of arsenic due to natural and anthropogenic activities. This widespread exposure necessitates a deeper understanding of microbe-arsenic interactions and their potential influence on host exposure and health risks.

Targeting tau in Alzheimer's and beyond: Insights into pathology and therapeutic strategies.

Tauopathies encompass a group of approximately 20 neurodegenerative diseases characterized by the accumulation of the microtubule-associated protein tau in brain neurons. The pathogenesis of intracellular neurofibrillary tangles, a hallmark of tauopathies, is initiated by hyperphosphorylated tau protein isoforms that cause neuronal death and lead to diseases like Alzheimer's, Parkinson's disease, frontotemporal dementia, and other complex neurodegenerative diseases. Current applications of tau biomarkers, including imaging, cerebrospinal fluid, and blood-based assays, assist in the evaluation and diagnosis of tauopathies.

Fomesafen induced ecotoxicological responses, bioaccumulation, and implications for soil ecosystems remediation in three ecotypes earthworms.

Fomesafen (FSA) is a herbicide commonly used in soybean fields, but its long half-life in the soil can pose pollution risks to the soil ecosystem. Earthworms, which have an indicative function for soil health and play a vital role in maintaining soil ecological functions, have not been fully studied in terms of their susceptibility to FSA. This study examined the effects of different concentrations of FSA on three ecotypes of earthworms (Eisenia fetida (epigeic), Metaphire guillelmi (anecic), and Aporrectodea caliginosa (endogeic)) and found varying trade-off strategy of their growth and reproduction.

Omeprazole and its analogs exhibit insecticidal potencies as inhibitors of insect choline acetyltransferase.

Choline acetyltransferase (ChAT) is crucial for acetylcholine synthesis and regulates diverse functions in numerous biological processes. Omeprazole, an inhibitor on human ChAT, was evaluated here on insect ChAT as a potential inhibitor, as well as its insecticidal potency on Nilaparvata lugens, a major insect pest on rice. The evaluation also included omeprazole analogs and α-NETA, in order to explore a superior leading compound targeting on insect ChAT.

Emamectin benzoate and nanoplastics induce PANoptosis of common carp (Cyprinus carpio) gill through MAPK pathway.

Emamectin benzoate (EMB) is a pesticide that is frequently used. Nanoplastics (NPs) are a recently identified class of pollutants that are ubiquitous in the environment. In the aquatic environment, NPs can appear together with EMB, which may exacerbates the damage to water and aquatic organisms.

Deltamethrin exposure caused renal inflammation and renal fibrosis via upregulating endoplasmic reticulum stress-mediated TXNDC5 level in mice.

Deltamethrin (DLM) is a type II pyrethroid insecticide that is extensively applied to agriculture, veterinary medicine and livestock pest control. Excessive accumulation of DLM in the body can lead to nephrotoxicity, but the precise toxic mechanism remains obscure. Therefore, we established in vivo models of DLM-exposed mice for 30 days and in vitro models of DLM-exposed renal tubular epithelial cells of mice.

Design, synthesis, and biological evaluation of novel 3-naphthylthiophene derivatives as potent SIRT2 inhibitors for the treatment of myocardial fibrosis.

SIRT2 (sirtuin2) is a NAD-dependent deacetylase implicated in fibrosis and inflammation of the liver, kidney, and heart. In this study, we designed and synthesized a series of 3-naphthylthiophene derivatives and evaluated their inhibitory activity against the SIRT2 enzyme. Among them, Z18 demonstrated outstanding SIRT2 inhibitory activity and selectivity.

Potential to reduce margins and Shrink targets in patients with intact cervical cancer treated on An MRI guided radiation therapy (MRgRT) system.

Introduction: Consensus contouring guidelines for intensity-modulated-radiation-therapy (IMRT) of patients with locally advanced cervix cancer (LACC) advise including the whole uterus in the target volume and adding generous planning-target-volumes (PTVs) to account for motion uncertainties of the gross-tumor-volume (GTV). The primary objective of this analysis was to assess the interfractional GTV motions using a magnetic-resonance-image (MRI) guided-Radiation-Therapy (MRgRT) system to investigate the margins required for MRgRT treatments.

Methods: 125 daily set-up MRIs from five patients with LACC who received MRgRT were analyzed.

Surface modification of particles/nanoparticles to improve the stability of Pickering emulsions; a critical review.

Pickering emulsions (PEs) are dispersions stabilized by solid particles, which are derived from various materials, both organic (proteins, polysaccharides, lipids) and inorganic (metals, silica, metal oxides). These colloidal particles play a critical role in ensuring the stability and functionality of PEs, making them highly valued across multiple industries due to their enhanced stability and lower toxicity compared to conventional emulsions. The stabilization mechanisms in PEs differ from those in emulsions stabilized by surfactants or biopolymers.

Integrated application of target-based and ligand-based drug-designing approaches for the identification of novel caspase-6 inhibitors.

Caspase-6 (CASP6) is an effector caspase that has been marked to possess various pathological attributes associated with neurodegeneration. It is widely expressed in the neurodegenerative brain and peripheral tissues. It plays a vital role in apoptotic cell death and also performs non-apoptotic functions like axon pruning which contribute to the degeneration of neurons.

Malnutrition and radiation therapy in head and neck cancers, a systematic review on reported definitions and associated factors.

Radiation therapy is a major treatment in head and neck cancers that can induce mucositis, pain, and dysgeusia that could impair oral intake and lead to weight loss and malnutrition. Intensity modulation has diminished toxicity of radiation therapy. We performed a review to assess the rate of malnutrition and how malnutrition was defined across cohorts of patients undergoing modern curative radiation therapy.