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Computational analysis of dual targeting of β1-adrenergic and AT1 receptors by bisoprolol fumarate and candesartan cilexetil for hypertensive modulation.

This study explores a dual-action approach for hypertension management based on a co-formulated suspension containing Candesartan cilexetil (CC) - Bisoprolol fumarate (BF) system, combining FTIR characterisation with computational modelling to evaluate molecular compatibility, binding behaviour, and pharmacokinetic properties.Direct in situ FTIR-ATR spectral analysis confirmed the successful interfacial wetting and co-dispersion of both drugs within the surfactant matrix, driven by robust hydrophobic interactions and cooperative hydrogen bonding. Hirshfeld surface analysis revealed complementa

The impact of copper status on lubabegron fumarate-induced growth and adipose immune cell infiltration in beef feedlot steers.

The objective of this study was to evaluate the effect of copper (Cu) status on response to lubabegron fumarate (LUB; Experior, Elanco, Greenfield, IN) and adipose tissue physiology. Forty-eight Angus crossbred steers (469 ± 31 kg) were enrolled in a 77-day finishing study, housed in pens of six, with a GrowSafe bunk (GrowSafe Systems, Ltd, Airdrie, AB, Canada) in each pen and implanted (Revalor-200, Merck Animal Health, Madison, NJ; 200 mg TBA + 20 mg E2) on day 0. A 2 × 2 factorial arrangement was applied to Cu status (Cu0, no supplemental Cu; or Cu10, 10 mg supplemental Cu/kg DM as CuSO4) a

Multi-Omics Integration Uncovers That Tenofovir Disoproxil Fumarate Is Linked to Hepatic Metabolic Reprogramming Independent of Viral Infection.

BACKGROUND AND AIMS: TDF is a first-line antiviral for CHB with pleiotropic effects including immunomodulation and fibrosis regression, but its virus-independent mechanisms are unclear. This study delineates TDF's direct molecular and metabolic landscape in vivo using multi-omics. METHODS: Wild-type mice received TDF or vehicle for 4 months. Liver tissues underwent RNA-seq and targeted metabolomics, followed by integrative systems biology. RESULTS: TDF caused no hepatotoxicity but induced transcriptomic reprogramming: broad upregulation of immune/inflammatory pathways and suppression of meta

Screening of Sepsis Diagnostic Biomarkers Based on Fumarate Metabolism-Related Genes with Analysis of Immune Infiltration and Subtype Identification.

BACKGROUND: Sepsis is a major global health challenge characterized by a complex pathogenesis involving an early hyperinflammatory phase followed by a subsequent immunosuppressive state. Recent studies have revealed that dysregulation of fumarate metabolism plays a central role in immune dysregulation during sepsis, making related genes promising candidates as novel diagnostic biomarkers and therapeutic targets. METHODS: Three sepsis datasets (GSE65682, GSE95233, GSE131761) were analyzed to identify differentially expressed fumarate metabolism-related genes. Key genes were selected via machin

Urea cycle fumarate limits fibrosis post-myocardial infarction by reducing fibroblast mitochondrial adenosine triphosphate production.

AIMS: Cardiac fibrosis, a common pathological outcome of various heart diseases including myocardial infarction (MI), is primarily driven by the activation and trans-differentiation of cardiac fibroblasts that demand substantial adenosine triphosphate production (ATP) for energy. Although sodium-glucose co-transporter 2 (SGLT2) inhibitors such as dapagliflozin have been shown to improve outcomes in heart failure, their direct impact on cardiac fibrosis, particularly through the modulation of fibroblast energy metabolism remains unexplored. METHODS AND RESULTS: We employed an integrated strate

Impact of Switching from Tenofovir Disoproxil Fumarate to Tenofovir Alafenamide or Entecavir in Older Patients with Chronic Hepatitis B.

INTRODUCTION: Tenofovir disoproxil fumarate (TDF) is highly effective for chronic hepatitis B (CHB) but may induce progressive renal impairment and proximal tubular dysfunction. Switching to tenofovir alafenamide (TAF) or entecavir (ETV) may reduce TDF-related nephrotoxicity. This study evaluated renal and metabolic changes before and after switching from TDF to TAF or ETV in a real-world cohort of older patients. METHODS: This retrospective longitudinal cohort study included adults with CHB who switched from TDF to TAF or ETV at a tertiary center (2012-2023). Eligible patients had ≥ 2 years

Dimethyl Fumarate and Cobalt Protoporphyrin IX Inhibit Fibromyalgia-like Pain by Modulating Region-Specific Redox Pathways.

Fibromyalgia is a chronic nociplastic pain disorder characterized by widespread pain and affective disturbances, in which oxidative stress and neuroinflammation are now recognized as central pathogenic mechanisms. However, current therapies provide only limited symptomatic relief. This study compared the therapeutic and molecular effects of dimethyl fumarate (DMF), an activator of nuclear factor erythroid 2-related factor 2 (NRF2), and cobalt protoporphyrin IX (CoPP), an inducer of heme oxygenase-1 (HO-1), in a reserpine-induced mouse model of fibromyalgia-like pain. Male and female C57BL/6J m

Clinical Insights and Therapeutic Strategies for Fumarate Hydratase-Deficient Renal Cell Carcinoma: A Case Report with Literature Review.

BACKGROUND: Fumarate Hydratase-deficient Renal Cell Carcinoma (FH-d RCC) is a rare autosomal dominant malignancy caused by germline mutations in the fumarate hydratase gene. This aggressive renal cell carcinoma subtype predominantly affects young patients, exhibiting features of type II papillary renal cell carcinoma with early metastatic potential. CASE PRESENTATION: We present a case of a 38-year-old male diagnosed with FH-d RCC accompanied by retroperitoneal lymph node and vertebral bone metastases. Initial contrast-enhanced computed tomography revealed a 2-cm solid-cystic lesion in the up

Resistance Analyses of Lenacapavir, Emtricitabine/Tenofovir Alafenamide and Emtricitabine/Tenofovir Disoproxil Fumarate in the PURPOSE 1 and 2 Studies.

BACKGROUND: Lenacapavir (LEN) is an HIV-1 capsid inhibitor being evaluated for pre-exposure prophylaxis (PrEP). The PURPOSE trials assessed the efficacy of LEN and emtricitabine/tenofovir disoproxil fumarate (F/TDF) in cisgender women (PURPOSE 1; P1) and in cisgender men, transgender women, transgender men and gender non-binary persons (PURPOSE 2; P2). Emtricitabine/tenofovir alafenamide (F/TAF) was also assessed in P1. Both studies demonstrated the superiority of LEN to F/TDF. We describe resistance analyses from P1 and P2, which provide the first data regarding emergent drug resistance in th

Simulation-Based Predictions to Support the Development of a Pediatric Fixed-Dose Combination of Dolutegravir/Emtricitabine/Tenofovir Alafenamide Fumarate.

BACKGROUND AND OBJECTIVE: Approximately 1.4 million children (aged 0-14 years) are living with human immunodeficiency virus, most infected through mother-to-child transmission. Despite the availability of combination antiretroviral treatment, only 57% of children had access to combination antiretroviral treatment in 2023, with suboptimal formulations contributing to high mortality. Limited access to age-appropriate formulations is a key barrier, particularly in low- and middle-income countries. This study presents stochastic simulations with previously published population pharmacokinetic mode

Dimethyl fumarate ameliorates behavioural and brain oscillatory alterations induced by prenatal valproic acid exposure in female rats.

Sex differences in the prevalence, age of onset of symptoms, and symptom presentation have been widely described in autism spectrum disorders, yet the mechanisms underlying these sex differences remain poorly characterized. Exposing rats prenatally to valproic acid (VPA) is widely used as a model to study autism-like phenotypes. Using this model, sex-specific neuroanatomical and functional characteristics were examined in adolescent rats. We found sex differences in cortical pyramidal neuron complexity, spine density, and morphology in VPA-prenatally exposed animals. The expression of autism h

Dimethyl fumarate modulates M1/M2 macrophage polarization to ameliorate periodontal destruction by increasing TUFM-mediated mitophagy.

Periodontitis is a common oral disease characterized by progressive alveolar bone resorption and inflammation of the periodontal tissues. Dimethyl fumarate (DMF) has been used in the treatment of various immune-inflammatory diseases due to its excellent anti-inflammatory and antioxidant functions. Here, we investigated for the first time the therapeutic effect of DMF on periodontitis. In vivo studies showed that DMF significantly inhibited periodontal destruction, enhanced mitophagy, and decreased the M1/M2 macrophage ratio. In vitro studies showed that DMF inhibited macrophage polarization to

Real-World Outcomes in Patients with COPD Initiating Budesonide/Glycopyrronium/Formoterol Fumarate Dehydrate in Spain: ORESTES Study.

INTRODUCTION: Chronic obstructive pulmonary disease (COPD) often results in progressive airflow limitation and is a major cause of morbidity, mortality, and healthcare resource utilization (HCRU). Single-inhaler triple therapy with budesonide/glycopyrronium/formoterol fumarate dehydrate (BGF) is recommended for maintenance in adults with moderate-to-severe COPD not adequately controlled by dual therapy. The ORESTES study aimed to describe the occurrence of exacerbations, clinical characteristics, and HCRU in patients with COPD initiating BGF in a real-life setting in Spain. METHODS: Observati

The Cytopathological Diagnosis of Fumarate Hydratase (FH)-Deficient Renal Cell Carcinoma in Two Patients With FH Gene Mutation.

Fumarate hydratase-deficient renal cell carcinoma (FH-dRCC) is a high-grade renal cell carcinoma characterised by mutations in the FH gene. FH-dRCC is highly aggressive and has a poor prognosis, underscoring the importance of accurate diagnosis. Although the histopathological features of this neoplasm have been reported in previous studies, descriptions of its cytopathological features are limited. Here, we report the cytopathological morphologies of two cases of metastatic FH-dRCC in male patients aged 48 and 35 years. Case 1 presented with a cystic solid mass in the right retroperitoneal lum

Cost-effectiveness of tenofovir alafenamide fumarate for treatment of chronic hepatitis B: Evidence from a tertiary hospital in Vietnam.

BackgroundThis study aims to evaluate the cost-effectiveness of tenofovir alafenamide fumarate (TAF) versus tenofovir disoproxil fumarate (TDF) for chronic hepatitis B treatment from a payer's perspective in a limited-income context like Vietnam.MethodsA Markov model was developed to estimate the lifetime cost and effectiveness (measured in quality-adjusted life year, QALY) of TAF compared to TDF in the HbeAg+ patient population. Efficacy data came from clinical trials, and costs were based on 2023 data from an exit survey of 94 inpatients and 464 outpatients in Bach Mai hospital. Other clinic

Assessment of the risk of discontinuation of tenofovir disoproxil fumarate after delivery and the benefit of continued treatment in patients with immune tolerance.

BACKGROUND: Both domestic and foreign guidelines recommend that chronic hepatitis B virus (HBV) infection pregnant women in the immune tolerance phase (ITP) discontinue antiviral therapy after delivery, this study aimed to investigate the risk of postpartum drug withdrawal and the pros and cons of continuing treatment of tenofovir dipivoxil fumarate (TDF) in ITP pregnant women. METHODS: The study group consisted of 116 naive pregnant women in ITP, the control group included 81 naive chronic hepatitis B (CHB) pregnant women with HBeAg-positive and high viral load. The study aimed to compare th

Anti-CD20 versus Dimethyl Fumarate as First-Line Treatment for Pediatric Multiple Sclerosis: A Retrospective Cohort Study.

Consensus on the first-line treatment of pediatric-onset multiple sclerosis (POMS) remains unresolved. Recently, dimethyl fumarate (DMF) and anti-CD20 therapies have been among the favorable options for pediatric multiple sclerosis (MS).This study aimed to determine the effectiveness and safety of DMF versus anti-CD20 therapies for POMS.We conducted a retrospective cohort study from July 2012 to July 2022 in the Isfahan MS clinic. MS cases under the age of 18 years old who received DMF or anti-CD20 agents as first-line treatment and were followed for at least 12 months were included.About 124

ДиметилФумарат Аттенуаты циклофосфамидозные повреждения мочевого пузыря и усиление цитотоксичной активности против клеток SH-SY5Y.

Острый кистит, вызванный циститом цилофосфамида (КХ), является изнурительной дисфункцией мочевого пузыря, которая, как правило, наблюдается у больных раком, главным образом в результате окислительных повреждений и воспаления тканей мочевого пузыря. Диметилфумарат (DMF) — эстер фумарной кислоты, утвержденный для лечения множественных склерозов в силу его антиоксидантов и противовоспалительных свойств. Таким образом, мы намеревались изучить многообразное воздействие ДМФ, включая как его потенциальное синергетическое воздействие с ХП на клетки SH-SY5Y, так и его незащищенное воздействие на острый

Совпадение в полном тексте источника
… Dimethyl fumarate (DMF) is an FDA‐approved drug used to treat psoriasis and multiple sclerosis. DMF is a pro‐drug that rapidly hydrolysed to its pharmacologically active metabolite, monomethyl fumarate [ 14 ]. … Although the exact mechanism of action of these fumaric acid derivatives has not yet been fully elucidated, both fumarates have been reported to enhance the antioxidant defense mechanism in various cell types by acting through the nuclear factor erythroid 2‐related factor 2 (Nrf2) [ 15 , 16 ]. …

Fumarate Hydratase-Deficient Renal Cell Carcinoma With Predominant Tubulocystic Features Mimics Tubulocystic Renal Cell Carcinoma.

CONTEXT.—: Fumarate hydratase (FH)-deficient renal cell carcinoma (RCC) rarely exhibits a predominant tubulocystic architecture with few other components. RCC with pure tubules and cysts lined by eosinophilic tumor cells with prominent nucleoli would raise the diagnosis of tubulocystic RCC. It is important to differentiate the 2 entities because they lead to different outcomes. OBJECTIVE.—: To address this concern, a multicenter study was implemented to explore useful clinicopathologic features in differentiation between tubulocystic FH-deficient RCC and tubulocystic RCC. DESIGN.—: Clinical