Pharmaceuticals

Schizophrenia is a serious mental disorder that significantly affects the social and professional life of patients, causing distortion of reality and loss of identity and cognitive abilities. Psychopharmacological treatment is an integral part of modern psychiatry, and the introduction of new "atypical" antipsychotic drugs has brought significant progress in the treatment of this disorder. One of these drugs is olanzapine, which has an effective effect on the productive symptoms of schizophrenia while having an almost minimal potential to cause extrapyramidal syndrome...

Pyroptosis, an innate immune response, plays a crucial role in the pathological process of inflammatory diseases. Although pyroptosis blockade is considered a potential therapeutic strategy, no ideal candidate drug has been identified. The natural product Chojaponilactone B (CJB) has demonstrated anti-inflammatory effects, but its role in macrophage pyroptosis has not been studied. This study aimed to investigate the effect and mechanism of CJB in inhibiting macrophage pyroptosis. Using an LPS/ATP-induced THP-1 macrophage pyroptosis model, we found that CJB significantly inhibited pyroptosis and reduced the levels of NLRP3, caspase 1, N-GSDMD, and inflammatory cytokines IL-1β and IL-18...

Glioblastoma, the most common and lethal primary adult brain tumor, cannot be successfully removed surgically due to its highly invasive nature. Therapeutically, approaches must be aimed at a systemic brain disease and not merely at a tumor located within the brain, unless a successful containment strategy can be found. Reelin, an extracellular matrix glycoprotein, plays an important role in neuronal migration and serves here as a natural stop signal. Interestingly, the expression of reelin is negatively associated with tumor grade and, within glioblastoma, correlates with increased overall survival...

The aim of this study was to determine the drug loading capacity of phosphatidylcholine-based formulations for four poorly water-soluble drug substances (clofazimine, fenofibrate, artemether, cannabidiol). Two self-dispersing lipid formulations were investigated, which consisted of soybean phospholipids, medium-chain triglycerides and ethanol with a different phospholipid-oil ratio. The direct loading of the bulk formulation was conducted with dual centrifugation, which proved to be a suitable method for screening experiments with the highly viscous formulations...

Cecropia is a genus of neotropical trees mainly distributed in Mexico and Central and South America. Currently, 63 species have been described, some of which have been used for centuries in traditional medicine to treat conditions such as diabetes, high blood pressure, and wound healing, among others. In recent times, modern phytochemical studies have succeeded in isolating individual compounds with potential specific medicinal applications. This review aims to examine the literature data regarding isolated terpenes and their correlation with pharmacological activities, with the goal of unveiling the future potential of the genus...

Lactoferrins and lactoferrin-derived peptides display numerous functions linked to innate immunity in mammalians, spanning from antimicrobial to anti-inflammatory and immunomodulatory actions, and even demonstrate antitumor properties. To date, the proposed mechanisms for their biological actions are varied, although the molecular basis that governs lactoferrin interactions with molecular targets has been clarified only in a limited number of specific cases. However, key in silico methods have recently moved the topic to the fore, thus greatly expanding the possibilities of large-scale investigations on macromolecular interactions involving lactoferrins and their molecular targets...

The present study provides evidence showing that adenosine (Ado) increases the expression of programmed death ligand 1 (PD-L1) in cervical cancer (CeCa) cells by interacting with A2A R/A2B R and that TGF-β1 acts in an autocrine manner to induce PD-L1 expression, enhancing the immunosuppressive effects of CeCa cells on activated T lymphocytes (ATLs) and CD8+ cytotoxic T lymphocytes (CTLs) specific for antigenic peptides derived from E6 and E7 proteins of HPV-16. Interestingly, the addition of the antagonists ZM241385 and MRS1754, which are specific for A2A R and A2B R, respectively, or SB-505124, which is a selective TGF-β1 receptor inhibitor, to CeCa cell cultures significantly inhibited PD-L1 expression...

Over the last several decades, a growing body of research has investigated the potential to repurpose the anti-diabetic drug metformin for breast cancer prevention and/or treatment. Observational studies in the early 2000s demonstrated that patients with diabetes taking metformin had decreased cancer risk, providing the first evidence supporting the potential role of metformin as an anti-cancer agent. Despite substantial efforts, two decades later, the exact mechanisms and clinical efficacy of metformin for breast cancer remain ambiguous...

Adverse drug reactions continue to be not only one of the most urgent problems in clinical medicine, but also a social problem. The aim of this study was a bibliometric analysis of the use of digital technologies to prevent adverse drug reactions and an overview of their main applications to improve the safety of pharmacotherapy. The search was conducted using the Web of Science database for the period 1991-2023. A positive trend in publications in the field of using digital technologies in the management of adverse drug reactions was revealed...

The recent introduction of the innovative therapy, onasemnogene abeparvovec (Zolgensma® ), has revolutionized the spinal muscular atrophy (SMA) therapeutic landscape. Although Zolgensma® therapy has proven to lead to functional improvements in SMA children, some gaps in its safety profile still need to be investigated. To better characterize the Zolgensma® safety profile, we conducted a retrospective observational study, analyzing all the Individual Case Safety Reports (ICSRs) referred to it and collected in the European pharmacovigilance database between 1 January 2019 and 22 September 2023...

Glutamate excitotoxicity and oxidative stress represent two major pathological mechanisms implicated in retinal disorders. In Diabetic Retinopathy (DR), oxidative stress is correlated to NADPH oxidase (NOX), a major source of Reactive Oxygen Species (ROS), and glutamate metabolism impairments. This study investigated the role of NOX2 and the novel NOX2 inhibitor, GLX7013170, in two models of a) retinal AMPA excitotoxicity [AMPA+GLX7013170 (10-4 M, intravitreally)] and b) early-stage DR paradigm (ESDR), GLX7013170: 14-day therapeutic treatment (topically, 20 μL/eye, 10 mg/mL (300 × 10-4 M), once daily) post-streptozotocin (STZ)-induced DR...

The development of BRD9 inhibitors involves the design and synthesis of molecules that can specifically bind the BRD9 protein, interfering with the function of the chromatin-remodeling complex ncBAF, with the main advantage of modulating gene expression and controlling cellular processes. Here, we summarize the work conducted over the past 10 years to find new BRD9 binders, with an emphasis on their structure-activity relationships, efficacies, and selectivities in preliminary studies. BRD9 is expressed in a variety of cancer forms, hence, its inhibition holds particular significance in cancer research...

Rheumatoid arthritis (RA) and osteoarthritis (OA) are the most common arthritic diseases. Medical ozone has demonstrated its effectiveness in combination therapy with methotrexate or non-steroidal anti-inflammatory drugs for RA and OA, respectively. Although RA and OA have been compared from different points of view, few studies have considered their redox status in spite of the oxidative processes that are involved in both diseases. The aim of this study was to compare RA with OA, evaluating their redox status and the effects of ozone on their clinical response to combined therapy with ozone...

The radionuclides 43 Sc, 44g/mSc, and 47 Sc can be produced cost-effectively in sufficient yield for medical research and applications by irradiating natTi and natV target materials with protons. Maximizing the production yield of the therapeutic 47 Sc in the highest cross section energy range of 24-70 MeV results in the co-production of long-lived, high-γ-ray-energy 46 Sc and 48 Sc contaminants if one does not use enriched target materials. Mass separation can be used to obtain high molar activity and isotopically pure Sc radionuclides from natural target materials; however, suitable operational conditions to obtain relevant activity released from irradiated natTi and natV have not yet been established at CERN-MEDICIS and ISOLDE...

Inappropriate expression of histone deacetylase (HDAC-6) and deregulation of the phosphatidylinositol 3-kinase (PI3K) signalling pathway are common aberrations observed in cancers. LASSBio-2208, has been previously described as a dual inhibitor in the nanomolar range of HDAC-6 and PI3Kα and is three times more potent in inhibiting HDAC-6. In this paper we described the cytotoxic and antiproliferative potency of LASSBio-2208 on different tumour cell lines, its possible synergism effect in association with PI3K and HDAC-6 inhibitors, and its drug metabolism and pharmacokinetics (DMPK) in vitro profile...

"Click reactions" are a very useful tool for the selective conjugation of different molecular subunits to produce complex structures in a simple way. In this paper, we present the application of Cu(I)-catalyzed biorthogonal reactions between alkynes and azides to the indirect radiofluorination of an estradiol derivative with potential applications in estrogen receptor imaging. The procedure was fully developed on an automated synthesis platform, and conditions were optimized to achieve the desired product with a reasonable yield without precipitation...

Tumor cell stemness stands out as a pivotal factor driving tumor recurrence or metastasis and significantly contributes to the mortality of patients with colorectal cancer (CRC). Recent research has unveiled a link between immune-active cells and the induction of tumor cell stemness, ultimately leading to heightened resistance to treatment. In this study, stemness in CRC cell lines was assessed after co-culture with natural killer (NK) cells, both with and without sulfarotene administration. Furthermore, a CRC xenograft model was utilized to scrutinize the in vivo efficacy of sulfarotene in overcoming stemness induced by NK cell activation...

The emergence of drug-resistant microorganisms presents a substantial global public health threat. The increase in pathogens resistant to commonly prescribed antibiotics underscores the urgent requirement to explore alternative treatment strategies. This study adopts a novel approach by harnessing natural resources, specifically essential oils (EO), to combat bacterial pathogenicity. The primary aim of this research was to analyze the chemical composition of the aerial part of the Matricaria aurea ( M. aureas ) EO and evaluate its potential for inhibiting quorum sensing (QS) and disrupting biofilm formation in Pseudomonas aeruginosa ( P ...

An increasing body of research has demonstrated the significant role of long non-coding RNAs (lncRNAs) in the pathogenesis of stroke. They can actively contribute to the disease's progression either by directly participating in its pathogenesis or by acting as mediators through competing endogenous RNA (ceRNA) mechanisms. Concurrently, epigenetics plays a pivotal role in the pathological mechanisms underlying stroke. Epigenetic factors serve as valuable markers for disease progression, diagnostic biomarkers, and novel therapeutic targets...

Ammodaucus leucotrichus exhibits promising pharmacological activity, hinting at anti-inflammatory and anti-arthritic effects. This study investigated seed extracts from Ammodaucus leucotrichus using methanol and n-hexane, focusing on anti-inflammatory and anti-arthritic properties. The methanol extract outperformed the n-hexane extract and diclofenac, a reference anti-inflammatory drug, in trypsin inhibition (85% vs. 30% and 64.67% at 125 μg/mL). For trypsin inhibition, the IC50 values were 82.97 μg/mL (methanol), 202...