Transcriptomic insights into the anti-inflammatory mechanisms of Protaetia brevitarsis seulensis larvae in IL-1β-driven chondrosarcoma cells.

Osteoarthritis (OA) is a complex, degenerative, multi-factorial joint disease. Because of the difficulty in treating OA, developing new targeting strategies that can be used to understand its molecular mechanisms is critical. Protaetia brevitarsis seulensis larvae offer much therapeutic value; however, the presence of various active compounds and the multi-factorial risk factors for OA render the precise mechanisms of action unclear.

α-amanitin induces hepatotoxicity via PPAR-γ inhibition and NLRP3 inflammasome activation.

Mushroom poisoning, predominantly caused by α-amanitin, is a critical food safety concern in worldwide, with severe cases leading to hepatotoxicity and fatalities. This study delves into the hepatotoxic effects of α-amanitin, focusing on the NLRP3 inflammasome and PPAR-γ's regulatory role in inflammation. In vitro studies with L-02 cells showed that α-amanitin reduces cell viability and triggers NLRP3 inflammasome activation, increasing NF-κB phosphorylation and pro-inflammatory cytokines IL-18 and IL-1β.

Associations of Serum Urate and Cardiovascular Events in a Clinical Trial of Interleukin-1β Blockade.

Background: Serum urate (SU) associates with cardiovascular (CV) events, mortality, and gout.

Objectives: The purpose of this study was to assess whether SU predicts CV risk in a trial of interleukin (IL)-1β inhibition with canakinumab, and whether IL-1β blockade, kidney function, or gout alter these associations.

Methods: This study is a subanalysis of the Canakinumab Antiinflammatory Thrombosis Outcome Study (CANTOS), which randomized 10,061 patients with prior myocardial infarction and elevated high-sensitivity C-reactive protein to 3 doses of canakinumab or placebo.

Promoting longus colli muscle activation: Force direction in sitting matters.

Background: There is limited evidence to inform exercise prescription for deep neck flexor activation out of supine.

Objective: To compare activation of longus colli (LC) and sternocleidomastoid (SCM) from supine to sitting, and to compare the effect of craniocervical flexion (CCF) exercises in sitting on activation.

Methods: Twenty-four individuals without neck pain (mean age 28.

Evaluation of SB-83, a 2-amino-thiophene derivative, against Leishmania species that cause visceral leishmaniasis.

Visceral leishmaniasis is a systemic disease that affects various internal organs and represents the most severe and fatal form of leishmaniasis. Conventional treatment presents significant challenges, such as prolonged management in hospital settings, high toxicity, and an increasing growing number of cases of resistance. In previous studies, our research group demonstrated the effective and selective activity of the 2-amino-thiophene derivative SB-83 in preclinical models of cutaneous leishmaniasis.

Engineered extracellular vesicles for TGF-β encapsulation as a therapeutic strategy against LPS-induced systemic inflammation.

Inflammation underlies a wide variety of physiological and pathological processes, the Lipopolysaccharide (LPS)-induced inflammation model is widely recognized as a classical inflammatory paradigm, while Transforming growth factor-β (TGF-β) serves as a potent immunosuppressant capable of inhibiting immune responses and mitigating inflammation. However, its in vivo instability and the high cost associated with purification have imposed limitations on its clinical application. Therefore, we propose a therapeutic strategy for genetically modifying extracellular vesicles (HEVs) derived from HEK-293 T cells to incorporate TGF-β which holds potential for mitigating LPS-induced inflammation.

Expression and correlation analysis of VISTA in peripheral blood mononuclear cells of myasthenia gravis patients.

Myasthenia gravis (MG) is a T cell-dependent, B cell-mediated disorder strongly associated with antigen presentation by dendritic cells (DCs). In MG, mucosal tolerance is linked to increased expression of TGF-β mRNA in monocytes. Additionally, monocytic myeloid-derived suppressor cells (M-MDSCs) exhibit negative immunomodulatory effects by suppressing autoreactive T and B cells.

A biodegradable magnesium alloy promotes subperiosteal osteogenesis via interleukin-10-dependent macrophage immunomodulation.

In situ bone regeneration and vertical bone augmentation have been huge problems in clinical practice, always imposing a significant economic burden and causing patient suffering. Herein, MgZnYNd magnesium alloy rod implantation in mouse femur resulted in substantial subperiosteal new bone formation, with osteoimmunomodulation playing a pivotal role. Abundant macrophages were attracted to the subperiosteal new bone region and proved to be the most important regulation cells for bone regeneration.

Arctiin suppress Th17 cells response and ameliorates experimental autoimmune uveitis through JAK/STAT signaling.

Conventional treatments for autoimmune uveitis, such as corticosteroids and systemic immunosuppressants, often result in adverse side effects, prompting the need for therapies targeting specific molecular pathways. This study investigates the effects of Arctiin, known for its diverse biological properties, on experimental autoimmune uveitis (EAU) through its action on Th17 cells and the JAK/STAT signaling pathway. Our findings reveal that Arctiin significantly alleviates EAU by reducing clinical scores, inflammatory cell infiltration, and levels of inflammatory cytokines like IL-17 and TNF-α in the eye.

Association of malnutrition with surgical outcomes after spine surgery for spinal epidural abscess.

Background: Malnutrition is a predictor of poor surgical outcomes, but its specific effects in spinal epidural abscess (SEA) are understudied. This study aims to assess the association between nutritional status and post-operative outcomes.

Methods: We conducted a retrospective cohort study using the 2011-2022 American College of Surgeons (ACS) National Surgical Quality Improvement Program (NSQIP) database to identify adult SEA patients who underwent spinal surgery.

Effectiveness of Tralokinumab in Different Phenotypes of Atopic Dermatitis: A Real-World Study.

Introduction: Atopic dermatitis (AD) is a chronic inflammatory skin disease characterized by pruritus and a relapsing course, affecting approximately 25% of children and 4-7% of adults. This study evaluated the efficacy, safety, and quality-of-life impact of tralokinumab, a humanized monoclonal antibody targeting interleukin-13 (IL-13), in treating moderate-to-severe AD in a real-world setting, with a focus on different AD phenotypes.

Methods: An observational cohort of 30 adults treated with tralokinumab for ≥ 16 weeks was analyzed.

Pericytes mediate neuroinflammation via Fli-1 in endotoxemia and sepsis in mice.

Background: Sepsis-associated encephalopathy (SAE) often results from neuroinflammation. Recent studies have shown that brain platelet-derived growth factor receptor β (PDGFRβ) cells, including pericytes, may act as early sensors of infection by secreting monocyte chemoattractant protein-1 (MCP-1), which transmits inflammatory signals to the central nervous system. The erythroblast transformation-specific (ETS) transcription factor Friend leukemia virus integration 1 (Fli-1) plays a critical role in inflammation by regulating the expression of key cytokines, including MCP-1.

Selective phosphodiesterase 4 inhibitor roflumilast reduces inflammation and lung injury in models of betacoronavirus infection in mice.

Objective: We aimed to understand the potential therapeutic and anti-inflammatory effects of the phosphodiesterase-4 (PDE4) inhibitor roflumilast in models of pulmonary infection caused by betacoronaviruses.

Methods: Mice were infected intranasally with murine hepatitis virus (MHV-3) or severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Roflumilast was given to MHV-3-infected mice therapeutically at doses of 1 mg/kg or 10 mg/kg, or prophylactically at 10 mg/kg.

Bimekizumab efficacy and safety through 3 years in patients with moderate to severe plaque psoriasis: Long-term results from the BE RADIANT phase 3b trial open-label extension period.

Background: Overexpression of interleukin (IL)-17A and IL-17F significantly influences psoriasis pathology. Until recently, biologics targeting IL-17A alone, like secukinumab, were used to treat psoriasis. Bimekizumab is a monoclonal IgG1 antibody that targets both IL-17A and IL-17F.

Utilizing pharmacy technicians for medication adherence patient outreach in an ambulatory care setting.

Disclaimer: In an effort to expedite the publication of articles, AJHP is posting manuscripts online as soon as possible after acceptance. Accepted manuscripts have been peer-reviewed and copyedited, but are posted online before technical formatting and author proofing. These manuscripts are not the final version of record and will be replaced with the final article (formatted per AJHP style and proofed by the authors) at a later time.

2024 White Paper on Recent Issues in Bioanalysis: Three Way-Cross Validation; Urine Clinical Analysis; Automated Methods; Regulatory Queries on Plasma Protein Binding; Automated Biospecimen Management; ELN Migration; Ultra-Sensitivity Mass Spectrometry ( - Recommendations on Advanced Strategies for Mass Spectrometry Assays, Chromatography, Sample Preparation and BMV/Regulated Bioanalysis - Regulatory Agencies' Inputs on Regulated Bioanalysis/BMV).

The 18 Workshop on Recent Issues in Bioanalysis (18 WRIB) took place in San Antonio, TX, USA on May 6-10, 2024. Over 1100 professionals representing pharma/biotech companies, CROs, and multiple regulatory agencies convened to actively discuss the most current topics of interest in bioanalysis. The 18 WRIB included 3 Main Workshops and 7 Specialized Workshops that together spanned 1 week to allow an exhaustive and thorough coverage of all major issues in bioanalysis of biomarkers, immunogenicity, gene therapy, cell therapy and vaccines.

Detecting noncredible symptomology in ADHD evaluations using machine learning.

Introduction: Diagnostic evaluations for attention-deficit/hyperactivity disorder (ADHD) are becoming increasingly complicated by the number of adults who fabricate or exaggerate symptoms. Novel methods are needed to improve the assessment process required to detect these noncredible symptoms. The present study investigated whether unsupervised machine learning (ML) could serve as one such method, and detect noncredible symptom reporting in adults undergoing ADHD evaluations.

NHS-Galleri trial: Enriched enrolment approaches and sociodemographic characteristics of enrolled participants.

Background/aims: Certain sociodemographic groups are routinely underrepresented in clinical trials, limiting generalisability. Here, we describe the extent to which enriched enrolment approaches yielded a diverse trial population enriched for older age in a randomised controlled trial of a blood-based multi-cancer early detection test (NCT05611632).

Methods: Participants aged 50-77 years were recruited from eight Cancer Alliance regions in England.

SERT-Deficient Mice Fed Western Diet Reveal Altered Metabolic and Pro-Inflammatory Responses of the Liver: A Link to Abnormal Behaviors.

Background: The inheritance of the short allele, encoding the serotonin transporter (SERT) in humans, increases susceptibility to neuropsychiatric and metabolic disorders, with aging and female sex further exacerbating these conditions. Both central and peripheral mechanisms of the compromised serotonin (5-HT) system play crucial roles in this context. Previous studies on SERT-deficient (Sert) mice, which model human SERT deficiency, have demonstrated emotional and metabolic disturbances, exacerbated by exposure to a high-fat Western diet (WD).

HIF-1α and VEGF Immunophenotypes as Potential Biomarkers in the Prognosis and Evaluation of Treatment Efficacy of Atherosclerosis: A Systematic Review of the Literature.

Background: Hypoxia-inducible factor 1 alpha (HIF-1α) and its related vascular endothelial growth factor (VEGF) may play a significant role in atherosclerosis and their targeting is a strategic approach that may affect multiple pathways influencing disease progression. This study aimed to perform a systematic review to reveal current evidence on the role of HIF-1α and VEGF immunophenotypes with other prognostic markers as potential biomarkers of atherosclerosis prognosis and treatment efficacy.

Methods: We performed a systematic review of the current literature to explore the role of HIF-1α and VEGF protein expression along with the relation to the prognosis and therapeutic strategies of atherosclerosis.

Remimazolam Combined with Andrographolide Improve Postoperative Cognitive Dysfunction in Rats after Cardiopulmonary Bypass through the AMPK/SIRT1 Signaling Pathway.

Introduction: The effects of remimazolam (Re) in combination with andrographolide (AP) on learning, memory, and motor abilities in rats following cardiopulmonary bypass (CPB) surgery were studied.

Methods: We hypothesized that the combination of Re and AP could improve postoperative cognitive dysfunction (POCD) in rats after CPB by modulating nervous system inflammation. Cognitive function was assessed using the Morris Water Maze test, and the concentrations of tumor necrosis factor alpha (TNF-α), interleukin-1 beta (IL-1β), and interleukin-6 (IL-6) in serum were measured by enzyme-linked immunosorbent assay (ELISA).

An evaluation of mepolizumab as an add-on maintenance treatment for severe eosinophilic asthma.

Introduction: Clinical experience with anti-interleukin (IL)-5 biologic therapies for severe asthma has been increasing, alongside deeper and broader research focusing on the role of IL-5 and the IL-5 targeted mepolizumab. This review aims to provide an update of the evidence on the role of IL-5 and mepolizumab, with discussions of the benefits of mepolizumab and its future potential, to promote the comprehension of the pathophysiology and therapeutic approaches to asthma.

Areas Covered: For this narrative review, we conducted a database search in PubMed and Embase using the keywords 'IL-5' and 'mepolizumab,' focusing on randomized controlled trials and real-world studies up to September 2024.

COVID-19 and HIV: Clinical Outcomes and Inflammatory Markers in a Cohort from a Reference Hospital in Rio de Janeiro, Brazil.

Background: Severe COVID-19 presents a variety of clinical manifestations associated with inflammatory profiles. People living with HIV (PLWH) could face a higher risk of hospitalization and mortality from COVID-19, depending on their immunosuppression levels. This study describes inflammatory markers in COVID-19 clinical outcomes with and without HIV infection.

Correction: Rehman et al. Fabrication, In Vitro and In Vivo Assessment of Eucalyptol-Loaded Nanoemulgel as a Novel Paradigm for Wound Healing. 2022, 1971.

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