Urine proteomics defines an immune checkpoint-associated nephritis signature.

Immune checkpoint inhibitor (ICI) therapy is a cornerstone treatment for many cancers, but it can induce severe immunotoxicity, including acute interstitial nephritis (AIN). Currently, kidney biopsy is required to differentiate ICI-AIN from other causes of acute kidney injury (AKI). However, this invasive approach can lead to morbidity, delayed glucocorticoid treatment for patients with AIN, and unnecessarily prolonged suspension of ICI therapy in non-AIN patients.

Pharmacological Characterization of the Novel Selective Kappa Opioid Receptor Agonists 10-Iodo-Akuammicine and 10-Bromo-Akuammicine in Mice.

Akuammicine (AKC), an indole alkaloid, is a kappa opioid receptor (KOR) full agonist with a moderate affinity. 10-Iodo-akuammicine (I-AKC) and 10-Bromo-akuammicine (Br-AKC) showed higher affinities for the KOR with K values of 2.4 and 5.

Development of a Patient Reported Outcome Measure of Side Effects for Patients Taking Calcineurin Inhibitors: The FACIT-CNI-Ntx.

Rationale & Objective: Valid measures of side effects are important to inform clinical use of calcineurin inhibitors (CNIs). This study sought to develop and establish the content validity of a PRO measure to capture side effects among kidney transplant recipients taking CNIs.

Study Design: Qualitative interviews for concept elicitation and cognitive debriefing.

ARCH: Large-scale knowledge graph via aggregated narrative codified health records analysis.

Objective: Electronic health record (EHR) systems contain a wealth of clinical data stored as both codified data and free-text narrative notes (NLP). The complexity of EHR presents challenges in feature representation, information extraction, and uncertainty quantification. To address these challenges, we proposed an efficient Aggregated naRrative Codified Health (ARCH) records analysis to generate a large-scale knowledge graph (KG) for a comprehensive set of EHR codified and narrative features.

Sargassum fusiforme polysaccharides protect mice against Citrobacter rodentium infection via intestinal microbiota-driven microRNA-92a-3p-induced Muc2 production.

Sargassum fusiforme, widely consumed in Asian countries, has been proven to have various biological activities. However, the impacts and mechanisms of Sargassum fusiforme polysaccharides (SFPs) on intestinal bacterial infection are not yet fully understood. Our findings indicate that SFPs pretreatment ameliorates intestinal inflammation by reducing C.

Sivelestat sodium protects against renal ischemia/reperfusion injury by reduction of NETs formation.

Background: Ischemia-reperfusion injury (IRI) often results in renal impairment. While the presence of neutrophil extracellular traps (NETs) is consistently observed, their specific impact on IRI is not yet defined. Sivelestat sodium, an inhibitor of neutrophil elastase which is crucial for NET formation, may offer a therapeutic approach to renal IRI, warranting further research.

Rotating Hinge Revision Total Knee Arthroplasty With and Without Porous Cone Adjunct Fixation.

Introduction: As the number of revision total knee arthroplasties (rTKA) continues to rise, there is increasing interest in the use of contemporary rotating hinge prostheses. These devices often incorporate porous cones to fill bone defects and enhance long-term fixation. This study evaluated the clinical and functional outcomes and survivorship in rTKA patients utilizing a rotating hinge prosthesis with flexible titanium (FT) cones, porous tantalum (PT) cones, or no cones.

Longitudinal integrated proteomic and metabolomic skin changes in atopic dermatitis patients treated with dupilumab.

Background: Inhibition of IL-4/IL-13 driven inflammation by dupilumab has shown significant clinical benefits in treatment of atopic dermatitis (AD).

Objective: To assess longitudinal protein and metabolite composition in AD skin during dupilumab treatment.

Methods: Skin tape strip (STS) were collected from lesional/non-lesional skin of 20 AD patients during 16-week dupilumab treatment and from 20 healthy volunteers (HV) followed for 16-weeks.

Allergen-induced activation of epithelial P2Y receptors promotes ATP exocytosis and type 2 immunity in airways.

Background: Environmental allergens induce the release of danger signals from the airway epithelium that trigger type 2 immune responses and promote airway inflammation.

Objective: To investigate the role of allergen-stimulated P2Y receptor activation in regulating ATP, IL-33 and DNA release by human bronchial epithelial (hBE) cells and mouse airways.

Methods: hBE cells were exposed to Alternaria alternata extract and secretion of ATP, IL-33 and DNA were studied in vitro.

Potential therapeutic effect of dimethyl fumarate on Treg/Th17 cell imbalance in biliary atresia.

The imbalance between Tregs and proinflammatory Th17 cells in children with biliary atresia (BA) causes immune damage to cholangiocytes. Dimethyl fumarate (DMF), an immunomodulatory drug, regulates the Treg/Th17 balance in diseases like multiple sclerosis (MS). This study explores DMF's effect on Treg/Th17 balance in BA and its potential mechanism.

Dichloroacetate: A metabolic game-changer in alleviating macrophage inflammation and enhancing recovery after myocardial infarction.

Background: Dichloroacetate (DCA) has shown potential in modulating cellular metabolism and inflammation, particularly in cardiac conditions. This study investigates DCA's protective effects in a mouse model of myocardial infarction (MI), focusing on its ability to enhance cardiac function, reduce inflammation, and shift macrophage polarization from the pro-inflammatory M1 to the anti-inflammatory M2 phenotype.

Methods: An acute MI model was created using left anterior descending coronary artery ligation.

Parathyroid hormone levels following denosumab vs. zoledronic acid therapy for osteoporosis.

The objective of this retrospective, database study was to characterize the rate, magnitude and timeline of increases in parathyroid hormone (PTH) levels post-denosumab (DMAb) vs. zoledronic acid (ZA) injection in patients with osteoporosis and near normal baseline PTH. Included were osteoporotic females, ≥50 years, initiating treatment with 60 mg DMAb or 5 mg ZA.

TARGETING LUNG HEME IRON BY AEROSOL HEMOPEXIN ADMINSTRATION IN SICKLE CELL DISEASE PULMONARY HYPERTENSION.

Lung tissue from human patients and murine models of sickle cell disease pulmonary hypertension (SCD-PH) show perivascular regions with excessive iron accumulation. The iron accumulation arises from chronic hemolysis and extravasation of hemoglobin (Hb) into the lung adventitial spaces, where it is linked to nitric oxide depletion, oxidative stress, inflammation, and tissue hypoxia, which collectively drive SCD-PH. Here, we tested the hypothesis that intrapulmonary delivery of hemopexin (Hpx) to the deep lung is effective at scavenging heme-iron and attenuating the progression of SCD-PH.

Breast cancer outcomes after skin- and nipple-sparing mastectomy in BRCA pathogenic mutation carriers versus non-BRCA carriers.

Unlabelled: Our previous study on BRCA breast cancer carriers disclosed a high local recurrence (LR) rate in patients who underwent skin sparing (SSM) or nipple sparing mastectomy (NSM) without postoperative radiation therapy (RT), compared to breast conservation surgery or mastectomy with RT. The current study compares the LR rates in BRCA versus non BRCA carriers after SSM/NSM in relation the receipt of RT.

Methods: The study was approved by the institutional ethics committee.

Preterm Births Attributable to Criteria Air Pollutant Exposure in Bangladesh During 2015-2019.

Criteria air pollutant exposure impacts human health through various pathways. Preterm birth (PTB) is one of the major adverse birth outcomes (ABO) associated with such exposure. Although numerous global and regional studies have been conducted on this issue, few have recently investigated the impact of major criteria air pollutant exposure on PTBs in Bangladesh, one of the world's most polluted countries with the highest relative PTB rate.

Safety and efficacy of satralizumab in patients with generalised myasthenia gravis (LUMINESCE): a randomised, double-blind, multicentre, placebo-controlled phase 3 trial.

Background: Evidence from preclinical studies suggests that IL-6 signalling has the potential to modulate immunopathogenic mechanisms upstream of autoantibody effector mechanisms in patients with generalised myasthenia gravis. We aimed to assess the safety and efficacy of satralizumab, a humanised monoclonal antibody targeting the IL-6 receptor, in patients with generalised myasthenia gravis.

Methods: LUMINESCE was a randomised, double-blind, placebo-controlled, multicentre, phase 3 study at 105 sites, including hospitals and clinics, globally.

Crossing the blood-brain barrier: emerging therapeutic strategies for neurological disease.

The blood-brain barrier is a physiological barrier that can prevent both small and complex drugs from reaching the brain to exert a pharmacological effect. For treatment of neurological diseases, drug concentrations at the target site are a fundamental parameter for therapeutic effect; thus, the blood-brain barrier is a major obstacle to overcome. Novel strategies have been developed to circumvent the blood-brain barrier, including CSF delivery, intracranial delivery, ultrasound-based methods, membrane transporters, receptor-mediated transcytosis, and nanotherapeutics.

Hidradenitis suppurativa.

Hidradenitis suppurativa is a chronic inflammatory disease characterised by painful, deep-seated nodules, abscesses, and draining tunnels in the skin of axillary, inguinal, genitoanal, or inframammary areas. In recent years, the body of knowledge in hidradenitis suppurativa has advanced greatly. This disorder typically starts in the second or third decade of life.

Recombinant probiotic Escherichia coli delivers the polymeric protein of swine influenza virus for protection.

Swine influenza virus invades the host through the respiratory mucosa, which severely restricts the development of the pig breeding industry. To construct monomeric and trimeric vaccines, we developed recombinant Escherichia coli Nissle 1917 (EcN) strains that express the receptor binding site (RBS) of the hemagglutinin (HA) antigen from H1N1 swine influenza virus. After the mucosal immunization of mice, we found that probiotics activated CD40 and CD86 in DCs and increased the levels of IL-4 and IFN-γ secretion by T cells.

Exploring the therapeutic potential of Abelmoschi Corolla in psoriasis: Mechanisms of action and inflammatory pathway disruption.

Background: Psoriasis is a prevalent chronic inflammatory skin condition for which existing treatments often fall short of fully addressing patient needs. Abelmoschi Corolla (AC), a traditional Chinese medicine, and its ethanol extract, huangkui capsule, are well established for the treatment of chronic kidney diseases. The therapeutic mechanisms of AC include anti-inflammatory effects and immune modulation, which align with psoriasis treatment strategies.

Integrated metabolomics and mass spectrometry imaging analysis reveal the efficacy and mechanism of Huangkui capsule on type 2 diabetic nephropathy.

Background: Huangkui capsule (HKC), a Chinese patent medicine, is clinically used for treating diabetic nephropathy. However, the core disease-specific biomarkers and targets of type 2 diabetic nephropathy (T2DN) and the therapeutic mechanism of HKC are not fully elucidated.

Purpose: This study aimed to investigate the therapeutic effects and underlying molecular mechanisms of HKC for T2DN.

A promising future for breast cancer therapy with hydroxamic acid-based histone deacetylase inhibitors.

Histone deacetylases (HDACs) play a critical role in chromatin remodelling and modulating the activity of various histone proteins. Aberrant HDAC functions has been related to the progression of breast cancer (BC), making HDAC inhibitors (HDACi) promising small-molecule therapeutics for its treatment. Hydroxamic acid (HA) is a significant pharmacophore due to its strong metal-chelating ability, HDAC inhibition properties, MMP inhibition abilities, and more.

Three-dimensional kinematics in patients with anterior shoulder instability - A systematic review with meta-analysis.

Anterior Shoulder Instability (ASI) is a common orthopedic condition often resulting in altered shoulder kinematics. Understanding the biomechanics of the unstable shoulder is critical to determine the most appropriate treatment. This study aims to conduct the first systematic review and meta-analysis of three-dimensional (3D) shoulder kinematic studies in ASI patients.