TGFβ signaling sensitizes MEKi-resistant human melanoma to targeted therapy-induced apoptosis.

The TGFβ signaling pathway is known for its pleiotropic functions in a plethora of biological processes. In melanoma, TGFβ signaling promotes invasiveness and metastasis formation. However, its involvement in the response to therapy is controversial.

Safety and efficacy of GLP-1/FGF21 dual agonist HEC88473 in MASLD and T2DM: a randomized, double-blind, placebo-controlled study.

Background And Aims: Glucagon-like peptide-1 (GLP-1) and fibroblast growth factor 21 (FGF21) are key regulators of glucose and lipid metabolism. In the present study, we assessed the safety and efficacy of a novel GLP-1/FGF21 dual agonist HEC88473 for the treatment of metabolic dysfunction-associated steatotic liver disease (MASLD) combined with type 2 diabetes mellitus (T2DM).

Methods: This was a randomized, double-blind, placebo-controlled, multiple-ascending-dose phase 1b/2a trial.

Development of a high-throughput platform for quantitation of histone modifications on a new QTOF instrument.

Histone post-translational modifications (PTMs) regulate gene expression patterns through epigenetic mechanisms. The 5 histone proteins (H1, H2A, H2B, H3, and H4) are extensively modified, with over 75 distinct modification types spanning more than 200 sites. Despite strong advances in mass spectrometry-based approaches, identification and quantification of modified histone peptides remains challenging due to factors such as isobaric peptides, pseudo-isobaric PTMs, and low stoichiometry of certain marks.

Photothermal-responsive nanocomposite injectable hydrogel capable of programed peroxidase-mimicking catalysis and immunomodulation and revascularization enables efficient drug-resistant bacterial elimination and comprehensive tissue regeneration.

Intractable infected wound caused by drug-resistant bacteria remains a severe healthcare problem. Reactive oxygen species (ROS)-based nanocatalytic therapy (ROS-NT) is harnessed to combat drug-resistant bacterial infection. However, it can also cause immune imbalance and excessive inflammatory responses, postponing subsequent wound healing process.

Comparison of urinary excretion patterns among exposures to cosmetic preservative, herbicide, and nootropic stimulant in anti-doping analysis.

Doping with meclofenoxate, a nootropic stimulant prohibited in-competition by the World Anti-Doping Agency (WADA), is identified through the primary marker of urinary 4-chlorophenoxyacetic acid (4-CPA). However, the presence of 4-CPA can also arise from permissible sources. This study ventured into comparing urinary excretion patterns among exposures to permitted chemicals (chlorphenesin and 4-CPA) and the banned stimulant (meclofenoxate) and interpreting the analytical findings according to the reporting requirements.

Direct injection UPLC-MS/MS method for analysing 77 compounds including human biomarkers, illicit drugs, new psychoactive substances and metabolites in wastewater.

Wastewater analysis technology has emerged as a promising tool for monitoring illicit drug consumption. However, the current reliance on the solid-phase extraction (SPE) pre-treatment method presents significant challenges for widespread adoption and high-throughput monitoring, as it consumes a large amount of time and labor as well as requires specialized instruments. This study has developed a direct injection (DI) technique for UPLC-MS/MS, enabling the detection of 77 compounds encompassing metabolites of human biomarkers, illicit drugs, and new psychoactive substances.

A versatile and automatic on-line screening method: Transverse diffusion of laminar flow profiles-based capillary electrophoresis for exploring PTP1B inhibitors in natural products.

Natural products (NPs) play an important role in drug discovery and drug development due to their diverse chemical properties and biological activities. In the present work, an on-line capillary electrophoresis (CE) method was developed and applied to screen protein tyrosine phosphatase 1B (PTP1B) inhibitors in NPs. As a generic technique, transverse diffusion of laminar flow profiles (TDLFP) was utilized to mix all reactants in the capillary for on-line enzymatic reaction.

Increased Infectious Risk Donor Status and Equity-Relevant Predictors of Organ Donation Organization Approach and Caregiver Consent for Deceased Organ Donation in a Canadian Province (2015-2021).

Background: Current donor risk assessments to identify risk of infectious transmission through transplantation have been criticized as unnecessarily discriminatory for sexual and gender minorities. Little is known about how increased infectious risk donor (IIRD) patients transition through the deceased donation system. We sought to evaluate how IIRD status and other equity-relevant identities impacted the likelihood of a caregiver of a deceased donor being approached for organ donation and the likelihood of caregiver consent.

Population Pharmacokinetics of Epcoritamab Following Subcutaneous Administration in Relapsed or Refractory B Cell Non-Hodgkin Lymphoma.

Background And Objectives: Epcoritamab is a CD3xCD20 bispecific antibody approved for the treatment of adults with different types of relapsed or refractory (R/R) B cell non-Hodgkin lymphoma (B-NHL) after ≥ 2 lines of systemic therapy. Here we report the first results from a population pharmacokinetic model-based analysis using data from 2 phase 1/2 clinical trials (EPCORE NHL-1, NCT03625037 and EPCORE NHL-3, NCT04542824) evaluating epcoritamab in patients with R/R B-NHL.

Methods: Plasma concentration-time data included 6819 quantifiable pharmacokinetic samples from 327 patients with R/R B-NHL.

5-Fluorouracil-methotrexate conjugate enhances the efficacy of 5-fluorouracil in colorectal cancer therapy.

To extend the short half-life of fluorouracil (Fu), enhance its tumor targeting, improve efficacy, and reduce side effects, providing a new approach for colorectal cancer treatment. Fluorouracil was hydroxylated and conjugated with methotrexate to form a 5-fluorouracil-methotrexate conjugate (MF). This was complexed with sulfobutyl ether-β-cyclodextrin (MF-SEBCD) using a stirring method to create an injectable formulation.

Memantine/Rosuvastatin Therapy Abrogates Cognitive and Hippocampal Injury in an Experimental Model of Alzheimer's Disease in Rats: Role of TGF-β1/Smad Signaling Pathway and Amyloid-β Clearance.

Alzheimer's disease (AD) is a multifactorial neurodegenerative disorder of complex pathogenesis and multiple interacting signaling pathways where amyloidal-β protein (Aβ) clearance plays a crucial role in cognitive decline. Herein, the current study investigated the possible modulatory effects of memantine/ rosuvastatin therapy on TGF-β1/p-Smad/p21 signaling pathway and their correlation to the blood brain barrier transporters involved in Aβ-clearance and microRNAs as a novel molecular mechanism in AD treatment. AD was induced by a single intracerebroventricular streptozotocin injection (ICV-STZ, 3 mg/kg) in rats and drug therapy was continued for 28 days after AD induction.

Combined fractional CO2 laser 10,600 nm with methotrexate 1% gel versus methotrexate 1% gel alone in the treatment of nail psoriasis: a randomized comparative study.

Methotrexate injections intralesionally as a treatment for psoriatic nails proved to be effective in large-scale studies as well as individual case reports, but the process is painful and time-consuming. The objective of this study was to compare the efficacy and safety of combined fractional CO2 laser (Fr. CO2) 10,600 nm and methotrexate gel versus methotrexate 1% gel alone in treatment of nail psoriasis.

Vitamin D supplementation alleviates high fat diet-induced metabolic associated fatty liver disease by inhibiting ferroptosis pathway.

Purpose: Recently, a significant negative correlation has been found between vitamin D (VD) and metabolic associated fatty liver disease (MAFLD), suggesting a potential beneficial role of VD in preventing of MAFLD, while underscoring the importance of exploring its mechanisms.

Methods: The experiment comprised two parts: male C57BL/6J mice (6 weeks) were fed a high-fat diet (HFD) and intraperitoneally injected with vitamin D (VD) (1.68 IU/g/week) for 16 weeks.

Tolerability and efficacy of botulinum toxin injection in the treatment of bromhidrosis: a systematic review and meta-analysis of clinical trials.

This review evaluates the risks and benefits of botulinum toxin (BTX) therapy for treating bromhidrosis. A search was conducted across six databases, including clinical trials comparing BTX therapy with BTX-free controls. The analyzed outcomes included pooled adverse events (AEs), treatment success, ≥ 50% overall improvement, and recurrence rates.

Hesperidin ameliorates thioacetamide-induced liver fibrosis via antioxidative and anti-inflammatory mechanisms targeting TGF-β/α-SMA pathways in rats.

Our study intended to explore Hesp antioxidant and anti-inflammatory effects against TAA hepatic fibrosis in rats. Hesperidin (Hesp), is a pharmacologically active flavonoid, found abundantly in citrus species. Our present research attempts to inspect the potential hepatoprotective role of Hesp against thioacetamide (TAA)-induced hepatic fibrosis.

Influence of Azadirachta indica leaf extracts on tumor necrosis factor-α and interleukin-6 in albino rats and its computational analysis.

The current study was designed to investigate the effect of A. indica (Neem) leaf extracts (ethanolic and aqueous) in yeast-induced pyrexia and acetic acid-induced writhing in rat models to evaluate the antipyretic and analgesic biomarkers and its phytochemical screening with computational analysis. For the antipyretic activity model 60 albino rats (160-200g) of either sex were divided into 4 groups and all groups were injected with yeast to induce pyrexia.

Effectiveness for adding or switching from other incretin-related drugs to oral semaglutide in type 2 diabetes.

Aims/introduction: This study aimed to evaluate and compare the effectiveness of oral semaglutide after adding to or switching from incretin-related drugs by assessing the changes in HbA1c and body weight (BW) in participants with type 2 diabetes in clinical settings.

Materials And Methods: A total of 368 participants were divided into groups according to antidiabetic medications before oral semaglutide treatment; incretin-related drug-naïve (naïve), switching from dipeptidyl peptide-4 inhibitors (DPP-4i) or glucagon-like peptide-1 receptor agonist (GLP-1 RA) groups. Adjusted mean changes in HbA1c and BW at 6 months after oral semaglutide administration were compared among the three groups.

Progress and challenges in the elimination of hepatitis C among people who inject drugs in Germany: results of a pilot study for a national monitoring system, 10 years after the first data collection.

Background: People who inject drugs (PWID) are at high risk of blood-borne infections, and injection drug use contributes significantly to hepatitis C virus (HCV) transmission. The WHO has therefore set targets of reducing HCV incidence and prevalence among PWID and increasing treatment coverage to eliminate HCV by 2030. The DRUCK study (2011-2014) found high HCV prevalence and low treatment coverage among PWID in Germany.

Targeted lipid nanoparticles distributed in hydrogel treat osteoarthritis by modulating cholesterol metabolism and promoting endogenous cartilage regeneration.

Osteoarthritis (OA) is the most common disease in aging joints and has characteristics of cartilage destruction and inflammation. It is currently considered a metabolic disease, and the CH25H-CYP7B1-RORα axis of cholesterol metabolism in chondrocytes plays a crucial catabolic regulatory role in its pathogenesis. Targeting of this axis in chondrocytes may provide a therapeutic approach for OA treatment.

Developing an ethical framework for the recruitment of people who inject drugs experiencing incarceration in HIV prevention research: a qualitative study.

Background: HIV disproportionately impacts people who experience incarceration. Incarceration represents an opportunity to engage in HIV prevention care for individuals who often experience a number of barriers accessing health services in the community. The development of evidence-based practices promoting pre-exposure prophylaxis for HIV prevention (PrEP) is crucial for ending the HIV epidemic within this highly marginalized population.

Practical solutions to resolve social barriers to hepatitis C treatment initiation among people who inject drugs: a qualitative study.

Background: We aimed to identify motivators for people who inject drugs to pursue treatment for hepatitis C virus (HCV) infection and uncover opportunities that could make treatment more appealing.

Methods: Between November 2023 and January 2024, we conducted semi-structured interviews with 15 HCV RNA-positive individuals with a history of injecting drug use and self-reported as either untreated or treated but delayed treatment for more than 6 months. Thematic and framework data analysis was employed and interpreted using the Capability, Opportunity and Motivation (COM-B) framework of behaviour change.

Berberine promotes primordial follicle activation and increases ovulated oocyte quantity in aged mice.

Background: Primordial follicle activation is vital for the reproduction of women with advanced age and premature ovarian insufficiency (POI). But there is a lack of effective and safe therapeutic options to activate their primordial follicles in vivo. Berberine (BBR) possesses multiple pharmacological properties, but its impact on primordial follicle activation remains unclear.

Baicalin improves isoproterenol-induced cardiac remodeling by regulating the Nrf2-dependent signaling pathway.

Background: Cardiovascular disease carries the highest mortality rate among diseases, and pharmacological interventions have limited efficacy. Baicalin (Bai) promotes biological metabolic processes, eliminates oxygen free radicals, and is anti-inflammatory. This study aimed to investigate the effect of Bai on the cardiac injury model induced by isoproterenol in mice.

Minocycline prevents monocrotaline-induced pulmonary hypertension through the attenuation of endothelial dysfunction and vascular wall thickening.

Pulmonary hypertension (PH) is a progressive disease with a poor prognosis in which high pulmonary artery pressure leads to right heart failure, therefore, there is an urgent need to elucidate pathological mechanisms and to develop new treatment for PH. Minocycline has not only antibacterial effects but also anti-inflammatory effects in various tissues. We hypothesize that minocycline could prevent PH development in rats.

Okanin alleviates symptoms of nociceptive-like responses in diabetic peripheral neuropathy in type 1 diabetic Wistar rats by regulating the AGEs/NF-κB/Nrf-2 pathway.

Elevated reactive species and AGEs contribute to deregulation of transcription factors e.g., NF-κB and Nrf2 in diabetic peripheral neuropathy (DPN).