Drug

Accurate analysis of microRNAs (miRNAs) at the single-cell level is extremely important for deeply understanding their multiple and intricate biological functions. Despite some advancements in analyzing single-cell miRNAs, challenges such as intracellular interferences and insufficient detection limits still remain. In this work, an ultrasensitive nanopore sensor for quantitative single-cell miRNA-155 detection is constructed based on ionic current rectification (ICR) coupled with enzyme-free catalytic hairpin assembly (CHA)...

PURPOSES: This study investigated the feasibility of adalimumab (ADA) dose reduction and withdrawal strategy in children with stable pediatric non-infectious uveitis (PNIU). METHODS: This open-label prospective pilot trial recruited 18 stable PNIU patients (33 eyes) between two and eighteen years old who were treated with standard doses of ADA (20/40 mg every 2 weeks) plus oral methotrexate. The interval of ADA injection was extended to 4 weeks and followed up for 24 weeks...

PURPOSE: Datopotamab deruxtecan (Dato-DXd) is an antibody-drug conjugate consisting of a humanized antitrophoblast cell-surface antigen 2 (TROP2) monoclonal antibody linked to a potent, exatecan-derived topoisomerase I inhibitor payload via a plasma-stable, selectively cleavable linker. PATIENTS AND METHODS: TROPION-PanTumor01 (ClinicalTrials.gov identifier: NCT03401385) is a phase I, dose-escalation, and dose-expansion study evaluating Dato-DXd in patients with previously treated solid tumors...

Drug-induced liver injury (DILI) is a common liver disease with a high rate of morbidity, and its pathogenesis is closely associated with the overproduction of highly reactive hypochlorite (ClO- ) in the liver. However, bioluminescence imaging of endogenous hypochlorite in nontransgenic natural mice remains challenging. Herein, to address this issue, we report a strategy for imaging ClO- in living cells and DILI mice by harnessing a bioluminescent probe formylhydrazine luciferin ( ClO-Luc ) combined with firefly luciferase (fLuc) mRNA-loaded lipid nanoparticles (LNPs)...

This study was aimed at investigating the ability of extract of Annona muricata (AM) flower-petals in ameliorating the toxic effects of acetaminophen on the kidneys of albino rats. The biochemical results showed a marked increase in AM 200 mg (32.84 ± 0.14) and AM 400 mg (32.64 ± 0.78). Increase levels of total protein in AM 200 mg (77.00 ± 5.65) displays nephroprotective potential of the flower extract. Reduction of renal activities of serum urea in AM 400 mg group (6...

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Drug abuse is a severe social problem worldwide. Particularly, the issue of new psychoactive substances (NPSs) have increasingly emerged. NPSs are structural or functional analogs of traditional illicit drugs, such as cocaine, cannabis, and amphetamine; these molecules provide the same or more severe neurological effects. Usually, immunoassays are utilized in the preliminary screening method. However, NPSs have poor detectability in commercially available immunoassay kits. Meanwhile, various chromatography combined with the mass spectrometry platform have been developed to quantify NPSs...

Despite their widespread use as therapeutics, clinical development of small molecule drugs remains challenging. Among the many parameters that undergo optimization during the drug development process, increasing passive cell permeability (i.e., log(P)) can have some of the largest impact on potency. Cyclic peptides (CPs) have emerged as a viable alternative to small molecules, as they retain many of the advantages of small molecules (oral availability, target specificity) while being highly effective at traversing the plasma membrane...

Antiretroviral therapy (ART) treatment failure remains a major public health concern, with multidimensional consequences, including an increased risk of drug resistance, compromised quality of life, and high healthcare costs. However, little is known about the outcomes of second-line ART in Ethiopia. Therefore, this systematic review and meta-analysis aimed to determine the incidence and determinants of second-line ART treatment failure. Articles published in PubMed, Google Scholar, Science Direct, and Scopus databases were systematically searched...

BACKGROUND: Youth who experience homelessness engage in behaviors that place them at high risk for disease and injury. Despite their health risk behaviors, these youth display psychological capital, positive attributes of hope, efficacy, resilience, and optimism that motivate them to engage in health-promoting behaviors such as safer sex. However, this array of positive psychological attributes has not been studied in this vulnerable population. OBJECTIVES: The specific aim of this analysis was to determine whether factors of psychological capital mediated the relationship between background risk factors (e...

Endoscopic submucosal dissection (ESD) is an effective method for resecting early-stage tumors in the digestive system. To achieve a low injection pressure of the injected fluid and continuous elevation of the mucosa following injection during the ESD technique, we introduced an innovative injectable sodium-alginate-based drug-loaded microsphere (Cipro-ThSA) for ESD surgery, which was generated through an emulsion reaction involving cysteine-modified sodium alginate (ThSA) and ciprofloxacin. Cipro-ThSA microspheres exhibited notable adhesiveness, antioxidant activity, and antimicrobial properties, providing a certain level of postoperative wound protection...

Gliomas, the most prevalent primary brain tumors, pose considerable challenges due to their heterogeneity, intricate tumor microenvironment (TME), and blood-brain barrier (BBB), which restrict the effectiveness of traditional treatments like surgery and chemotherapy. This review provides an overview of engineered cell membrane technologies in glioma therapy, with a specific emphasis on targeted drug delivery and modulation of the immune microenvironment. This study investigates the progress in engineered cell membranes, encompassing physical, chemical, and genetic alterations, to improve drug delivery across the BBB and effectively target gliomas...

Shifts in the magnitude and nature of gut microbial metabolites have been implicated in Alzheimer's disease (AD), but the host receptors that sense and respond to these metabolites are largely unknown. Here, we develop a systems biology framework that integrates machine learning and multi-omics to identify molecular relationships of gut microbial metabolites with non-olfactory G-protein-coupled receptors (termed the "GPCRome"). We evaluate 1.09 million metabolite-protein pairs connecting 408 human GPCRs and 335 gut microbial metabolites...

Glioblastoma (GBM) is a deadly brain tumor, and the kinesin motor KIF11 is an attractive therapeutic target with roles in proliferation and invasion. Resistance to KIF11 inhibitors, which has mainly been studied in animal models, presents significant challenges. We use lineage-tracing barcodes and single-cell RNA sequencing to analyze resistance in patient-derived GBM neurospheres treated with ispinesib, a potent KIF11 inhibitor. Similar to GBM progression in patients, untreated cells lose their neural lineage identity and become mesenchymal, which is associated with poor prognosis...

Identification of seizure sources in the brain is of paramount importance, particularly for drug-resistant epilepsy patients who may require surgical operation. Interictal epileptiform discharges (IEDs), which may or may not be frequent, are known to originate from seizure networks. Delayed responses (DRs) to brain electrical stimulation have been recently discovered. If DRs and IEDs come from the same location and the DRs can be accurately localized, there will be a significant step in identification of the seizure sources...

BACKGROUND: Tulathromycin (TUL) is a triamilide antibacterial drug which has been approved for use in the European Union and the United States for the treatment and prevention of bovine respiratory diseases. The existing methods for determination of TUL in its pharmaceutical bulk form are very limited and suffer from major drawbacks. OBJECTIVES: The aim of this study was the development of two innovative microwell spectrophotometric methods (MW-SPMs) for determination of TUL in its pharmaceutical bulk form...

OBJECTIVES: Rheumatoid arthritis (RA) and atherosclerosis share many common inflammatory pathways. We studied whether a multi-biomarker panel for RA disease activity (MBDA) would associate with changes in arterial inflammation in an interventional trial. METHODS: In the TARGET Trial, RA patients with active disease despite methotrexate were randomly assigned to the addition of either a TNF inhibitor or sulfasalazine+hydroxychloroquine (triple therapy). Baseline and 24-week follow-up 18F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography scans were assessed for change in arterial inflammation measured as the maximal arterial target-to-blood background ratio of FDG uptake in the most diseased segment of the carotid arteries or aorta (MDS-TBRmax)...

OBJECTIVE: We explored the efficacy and safety of brentuximab vedotin, a chimeric anti-CD30 antibody drug conjugate, in patients with severe active diffuse cutaneous systemic sclerosis (dcSSc). METHODS: This phase II proof-of-concept, single center, open-label, single arm, investigator-initiated trial included patients ≥18 years, with dcSSc, modified Rodnan skin score (mRSS) ≥15 with <5 years since the first non-Raynaud's symptom and/or skin worsening despite immunosuppression who were treated with intravenous brentuximab vedotin 0...

l-threonine dehydrogenase (Tdh) is an enzyme that links threonine metabolism to epigenetic modifications and mitochondria biogenesis. In vitro studies show that it is critical for the regulation of trimethylation of histone H3 lysine 4 (H3K4me3) levels and cell fate determination of mouse embryonic stem cells (mESCs). However, whether Tdh regulates a developmental process in vivo and, if it does, whether it also primarily regulates H3K4me3 levels in this process as it does in mESCs, remains elusive. Here, we revealed that, in zebrafish hematopoiesis, tdh is preferentially expressed in neutrophils...

The article aimed to compare the efficiency and safety of aspirin with low-molecular-weight heparin (LMWH) for thromboprophylaxis in orthopaedic surgery patients. According to the inclusion and exclusion criteria, PubMed, Embase and Cochrane Library database were searched for studies comparing aspirin and LMWH in venous thromboembolism (VTE) prophylaxis until 25 April 2023. The outcome measures included deep venous thrombosis(DVT)/Pulmonary embolism(PE) events, major bleeding events, wound complications, wound infection and death...