Sequential Epidemiological Analyses of Real-World Data: A Tool for Prospective Drug Safety Surveillance from the Rofecoxib Example.

Introduction: Large administrative healthcare databases can be used for near real-time sequential safety surveillance of drugs as an alternative approach to traditional reporting-based pharmacovigilance. The study aims to build and empirically test a prospective drug safety monitoring setup and perform a sequential safety monitoring of rofecoxib use and risk of cardiovascular outcomes.

Methods: We used Danish population-based health registers and performed sequential analysis of rofecoxib use and cardiovascular outcomes using case-time-control and cohort study designs from January 2000 to September 2004.

Protective effect of valsartan alone and in combination with neprilysin inhibitor (valsartan + sacubitril) against hepatic ischemia-reperfusion injury: targeting angiotensin II receptor-neprilysin and modulating SMAD-4/NF-κβ/JNK pathways in rats.

Ischemia-reperfusion injury (IRI) is a common pathogenic situation that arises throughout all liver surgeries, including liver transplants. We aimed to compare the preventive effects of valsartan (VST) against valsartan + sacubitril (LCZ696) on hepatic injury caused by IRI. A total of thirty-six male Westar albino rats were split into six groups randomly: sham, IRI, VST + IRI, LCZ696 + IRI, VST, and LCZ696.

Presence of sibutramine and sildenafil in weight loss dietary supplements: a case series with analytical and clinical investigation.

Introduction: The use of weight loss supplements is increasing, often driven by online marketing. However, many of these supplements are adulterated with undeclared pharmaceutical substances, potentially posing significant health risks. We investigated the presence of sibutramine and sildenafil in weight loss supplements and assessed the associated clinical outcomes.

Efficacy of PARPi re-maintenance therapy for recurrent ovarian cancer.

Objective: The current clinical data regarding the re-administration of PARPi maintenance therapy in platinum sensitive recurrent ovarian cancer (PSROC) is limited. This study aims to investigate the efficacy and associated factors of PARPi re-maintenance therapy in PSROC patients in China.

Methods: In this study, there were 201 patients with PSROC who had received maintenance therapy previously and achieved complete or partial response after platinum-based chemotherapy upon recurrence.

Safety and Efficacy of Baricitinib, Upadacitinib, and Sarilumab Implementation in Moderately-to-Severely Active Rheumatoid Arthritis: A Systematic Review and Meta-Analysis of Current Evidence.

This study aims to assess the efficacy and safety of newly approved Janus kinase (JAK) and interleukin-6 (IL-6) inhibitors in patients with moderately-to-severely active rheumatoid arthritis (RA) with inadequate response to or intolerance of conventional disease-modifying antirheumatic drugs. We conducted a systematic review and meta-analysis of all placebo-controlled randomized trials assessing baricitinib, sarilumab, and upadacitinib treatment in RA, published in PubMed and CENTRAL (Cochrane Central Register of Controlled Trials) databases up to October 2023. The study outcomes involved the American College of Rheumatology (ACR) 20%, 50%, and 70% responses, Health Assessment Questionnaire-Disability Index (HAQ-DI), Disease Activity Score in 28 joints (DAS28), serious adverse events, and adverse events leading to drug discontinuation.

CircKIAA0182 Enhances Lung Cancer Progression and Chemoresistance through Interaction with YBX1.

Lung cancer, particularly non-small cell lung cancer (NSCLC), remains a leading cause of cancer-related mortality. Resistance to platinum-based chemotherapy, such as cisplatin, significantly limits treatment efficacy. Circular RNAs (circRNAs) have emerged as key regulators of cancer progression and chemotherapy resistance due to their stable structure, which protects them from degradation.

Effect of Staggered vs. Simultaneous Co-Administration of Bempedoic Acid on Pharmacokinetics of Pravastatin: Randomized, Cross-Over Clinical Trial in Healthy Volunteers.

: Bempedoic acid (BA) is a novel cholesterol-lowering agent with proven positive effects on cardiovascular endpoints. Because it is an inhibitor of the hepatic transporters OATP1B1 and OATP1B3, two uptake transporters regulating the intrahepatic availability of statins, it increases the systemic exposure of co-administered statins. This interaction could raise the risk of myopathy.

Therapeutic Efficacy of Intranasal -Acetyl-L-Cysteine with Cell-Penetrating Peptide-Modified Polymer Micelles on Neuropathic Pain in Partial Sciatic Nerve Ligation Mice.

: We previously demonstrated that the intranasal administration of cell-penetrating Tat peptide-modified carrier, PEG-PCL-Tat, improves drug delivery to the central nervous system. This study aimed to evaluate the potential of the post-onset intranasal administration of -acetyl-L-cysteine (NAC) combined with PEG-PCL-Tat (NAC/PPT) for neuropathic pain. : Neuropathic pain was induced by partial sciatic nerve ligation (PSNL) in mice.

Phenolic Compounds and Pharmacological Potential of Extracts for the Treatment of Neurodegenerative Diseases.

The search for neuroprotective compounds in lavender is driven by its traditional use for brain health, with antioxidant activity serving as a key mechanism in reducing oxidative stress and supporting cognitive function. Lavender's potential to protect neurons is based on its calming, anti-stress properties, which increase the brain's resistance to neurodegeneration. Although lavender is not a traditional medicinal plant in Ukraine, it is increasingly recognised for its medicinal properties and is widely cultivated in the country.

Correction: Saber et al. BD-AcAc2 Mitigates Chronic Colitis in Rats: A Promising Multi-Pronged Approach Modulating Inflammasome Activity, Autophagy, and Pyroptosis. 2023, , 953.

[...

Effects of Aging on Intramuscular Collagen-Related Factors After Injury to Mouse Tibialis Anterior Muscle.

Collagen I is the most abundant type of intramuscular collagen. Lysyl oxidase promotes collagen cross-link formation, which helps stabilize the extracellular matrix. Furthermore, matrix metalloproteinases, responsible for collagen degradation, maintain typical muscle structure and function through remodeling.

Epigenetic Regulation of Stromal and Immune Cells and Therapeutic Targets in the Tumor Microenvironment.

The tumor microenvironment (TME) plays a pivotal role in neoplastic initiation and progression. Epigenetic machinery, governing the expression of core oncogenes and tumor suppressor genes in transformed cells, significantly contributes to tumor development at both primary and distant sites. Recent studies have illuminated how epigenetic mechanisms integrate external cues and downstream signals, altering the phenotype of stromal cells and immune cells.

A Clinical Practice-Based Comparison of Conventional and Individualized Dosing Strategies for Therapeutic Enoxaparin.

To understand differences in anti-factor-Xa levels produced by two different dosing strategies (conventional and individualized) for therapeutic enoxaparin in a cohort of hospital inpatients. A multicenter, retrospective cohort study over a two- and a half-year period for inpatients with stable renal function and on therapeutic enoxaparin. Anti-factor-Xa levels were taken 3-5 h after enoxaparin administration and a minimum of 48 h of dosing.

Drug-Induced Liver Injury Associated With Emerging Cancer Therapies.

Targeted therapies and immunotherapies have shown great promise as best-in-class treatments for several cancers with respect to efficacy and safety. While liver test abnormalities are rather common in patients treated with kinase inhibitors or immunotherapy, events of severe hepatotoxicity in these patients are rare in comparison with those associated with chemotherapeutics. The underlying mechanisms and risk factors for severe hepatotoxicity with novel oncology therapies are not well understood, complicating the drug-induced liver injury (DILI) risk assessment in the preclinical and clinical phases of drug development.

Phase 2 Randomised Study of Bulevirtide as Monotherapy or Combined With Peg-IFNα-2a as Treatment for Chronic Hepatitis Delta.

Background And Aim: Bulevirtide (BLV) leads to beneficial virologic and biochemical responses when given alone to treat hepatitis delta virus (HDV) infection, which causes the most severe form of chronic viral hepatitis. We evaluated 48 weeks of BLV monotherapy, BLV + tenofovir disoproxil fumarate (TDF) and BLV + pegylated interferon alfa-2a (Peg-IFNα-2a), with 24-week follow-up.

Methods: Ninety patients were enrolled into six arms of 15 each (A-F); 60 patients were included in the main randomisation (arms A-D), and 30 patients (arms E-F) were randomised to the extension phase: (A) Peg-IFNα-2a 180 μg once weekly (QW); (B) BLV 2 mg once daily (QD) + Peg-IFNα-2a 180 μg QW; (C) BLV 5 mg QD + Peg-IFNα-2a 180 μg QW; (D) BLV 2 mg QD; (E) BLV 10 mg QD + Peg-IFNα-2a 180 μg QW and (F) BLV 10 mg (5 mg twice daily) + TDF QD.

CUL4-Based Ubiquitin Ligases in Chromatin Regulation: An Evolutionary Perspective.

Ubiquitylation is a post-translational modification that modulates protein function and stability. It is orchestrated by the concerted action of three types of enzymes, with substrate specificity governed by ubiquitin ligases (E3s), which may exist as single proteins or as part of multi-protein complexes. Although Cullin (CUL) proteins lack intrinsic enzymatic activity, they participate in the formation of active ubiquitin ligase complexes, known as Cullin-Ring ubiquitin Ligases (CRLs), through their association with ROC1 or ROC2, along with substrate adaptor and receptor proteins.

single nucleotide polymorphism reduces dabigatran acylglucuronide formation in humans.

Background: Dabigatran etexilate (DABE), a prodrug of dabigatran (DAB), is a direct thrombin inhibitor used to prevent ischemic stroke and thromboembolism during atrial fibrillation. The effect of genetic polymorphisms on its metabolism, particularly , has not been extensively explored in humans. This study aimed to investigate the effects of , , and polymorphisms on the pharmacokinetics of DAB and its acylglucuronide metabolites in healthy subjects.

LINC00626 drives tamoxifen resistance in breast cancer cells by interaction with UPF1.

Although tamoxifen is commonly utilized as adjuvant therapy for Estrogen Receptor alpha (ERα)-positive breast cancer patients, approximately 30-50% of individuals treated with tamoxifen experience relapse. Therefore, it is essential to investigate additional factors besides ERα that influence the estrogen response. In this study, cross-analysis of databases were performed, and the results revealed a significant association between LINC00626 and ERα signaling as well as increased expression levels of this gene in tamoxifen-resistant cells.

β-Sitosterol modulates osteogenic and adipogenic balance in BMSCs to suppress osteoporosis via regulating mTOR-IMP1-Adipoq axis.

Background: Osteoporosis (OP) is a prevalent global health concern, impacting millions of individuals, especially the elderly. The etiology of senile OP is associated with the imbalance of osteogenic and adipogenic differentiation in the bone marrow mesenchymal stem cells (BMSCs). The imbalance of BMSCs differentiation fate will leading to bone loss and lipids accumulation.

Pharmacist-led deprescribing of cardiovascular and diabetes medication within a clinical medication review: the LeMON study (Less Medicines in Older Patients in the Netherlands), a cluster randomized controlled trial.

Background: Deprescribing inappropriate cardiovascular and antidiabetic medication has been shown to be feasible and safe. Healthcare providers often perceive the deprescribing of cardiovascular and antidiabetic medication as a challenge and therefore it is still not widely implemented in daily practice.

Aim: The aim was to assess whether training focused on conducting a deprescribing-oriented clinical medication review (CMR) results in a reduction of the inappropriate use of cardiovascular and antidiabetic medicines.

Comparing haploidentical transplantation with post-transplantation cyclophosphamide and umbilical cord blood transplantation using targeted busulfan in children and adolescents with hematologic malignancies.

Purpose: This study compared the outcomes of haploidentical-related donor (HRD) and umbilical cord blood (UCB) hematopoietic stem cell transplantation (HSCT) in pediatric patients with hematologic malignancies.

Methods: Data on patients who underwent HRD HSCT with post-transplant cyclophosphamide (n = 41) and UCB HSCT (n = 24) after targeted busulfan-based myeloablative conditioning with intensive pharmacokinetic monitoring between 2009 and 2018 were retrospectively analyzed.

Results: The median follow-up durations in the HRD and UCB groups were 7.

Chlorogenic Acid Ameliorates CCl4-induced Liver Fibrosis by Modulating the PI3K/AKT/mTOR Autophagy Pathway.

Background: Liver fibrosis represents a serious risk to global health by impairing quality of life and elevating the chances of hepatocellular carcinoma, while the intricate role of autophagy can either alleviate or worsen fibrosis depending on its functioning.

Objective: Herein, we aimed to investigate the therapeutic effect of chlorogenic acid in CCl4-induced hepatic fibrosis and explore the autophagy pathway as the possible molecular target of chlorogenic acid.

Methods: Rats were injected with carbon tetrachloride (1ml/kg) to induce liver fibrosis for 10 weeks.

Cytokine Hemoadsorption versus Standard Care in Cardiac Surgery Using the Oxiris® Membrane: the OXICARD single center randomized trial.

Background: Cardiac surgery can lead to dysregulation with a pro-inflammatory state, resulting in adverse outcomes. Hemadsorption using the AN69 membrane (Oxiris membrane) has the properties to chelate inflammatory cytokines. We hypothesized that in patients at high risk of inflammation, the use of the Oxiris membrane could decrease inflammation, preserve endothelial function, and improve postoperative outcomes.

Variable temocillin protein binding and pharmacokinetics in different clinical conditions: Implications for target attainment.

Aims: The beta-lactam antibiotic temocillin is increasingly used to treat extended-spectrum beta-lactamase (ESBL-producing) strains; however, its protein binding is complex. This study aims to predict unbound temocillin concentrations in various participant groups to determine its impact on the probability of target attainment (PTA) and to improve dosing recommendations.

Methods: The plasma pharmacokinetics were analysed using non-linear mixed-effects modelling.

Ayahuasca-assisted meaning reconstruction therapy for grief: a non-randomized clinical trial protocol.

Background: Psychotherapy for Prolonged Grief Disorder (PGD), a condition characterized by an intense and persistent grief response, has received increased attention over the past decades. Evidence-based approaches to prevent PGD are currently scarce, and not always effective. This paper introduces a protocol for a clinical trial exploring the effectiveness of a Meaning Reconstruction psychotherapy approach (MR) assisted with ayahuasca, a traditional indigenous medicine.