Pharmacology

INTRODUCTION: Our study aimed to investigate the effect of zonisamide (ZNS) on bone metabolism in the rat model. METHODS: Eight-week-old rats were divided into four groups. The sham-operated control group (SHAM) and the control group after orchidectomy (ORX) received the standard laboratory diet (SLD). The experimental group after orchidectomy (ORX+ZNS) and the sham-operated control group (SHAM+ZNS) received SLD enriched with ZNS for 12 weeks. Bone marker concentrations in serum of receptor activator of nuclear factor kappa B ligand, PINP, and osteoprotegerin, and the levels of sclerostin and bone alkaline phosphatase in bone homogenate, were measured using an enzyme-linked immunosorbent assay...

INTRODUCTION: Acid-related inflammatory damage to the esophageal epithelium is a key component in the development of gastroesophageal reflux disease. Melatonin (MT) is considered as a potential therapeutic agent, but its molecular mechanism is unknown. METHODS: The expression of HIF-1α and pyroptosis-related genes (NLRP3, caspase-1, IL-1β, and IL-18) was analyzed using bioinformatics methods in GSE63401 and validated using quantitative real-time polymerase chain reaction and Western blot in an HEEC inflammation model induced by deoxycholic acid (DCA)...

INTRODUCTION AND OBJECTIVE: Endothelial progenitor cells (EPCs) have been proven to exhibit a therapeutic effect in deep vein thrombosis, but are susceptible to microenvironment. Besides, Matrine has promotive effects on EPCs, but its effects on microRNA (miR)-126 remain obscure, which are therefore discussed in the study. METHODS: The cultured EPCs were extracted from Sprague-Dawley rats and identified by immunofluorescence assay. After being treated with Matrine or transfected with miR-126b inhibitor and small interfering RNA targeting forkhead box (FOXO) 4, the viability and apoptosis of EPCs were determined by cell counting kit-8 assay and flow cytometry...

INTRODUCTION: Tumor exosome-derived miRNAs play important roles in the human laryngocarcinoma. However, it is still unknown if exosome miR-552 is involved in the laryngocarcinoma. The aim of the current study was to explore exosome miR-552's role in laryngocarcinoma and its underlying mechanisms. METHODS: Hep-2 exosome was characterized by transmission electron microscopy and nanoparticle tracking technology. CCK-8 was used to determine cell viability, and a xenograft animal model was used to determine the tumorigenicity...

INTRODUCTION: Myeloid differentiation protein 1 (MD1), a negative regulator of toll-like receptor 4 (TLR4), is widely expressed in the heart. Recent studies have shown that MD1 plays an important role in cardiac remodelling. However, the effects and potential mechanisms underlying MD1-mediated atrial remodelling in diabetic cardiomyopathy (DCM) remain unclear. Therefore, this study was designed to explore the role of MD1 in DCM-related atrial remodelling. METHODS: MD1 knockout (MD1-KO) mice and wild-type (WT) littermates were injected with streptozotocin (STZ) to establish a diabetic mouse model...

INTRODUCTION: Nonsteroidal anti-inflammatory drug (NSAID)-induced small intestinal damage is a serious and escalating clinical problem without effective treatment. Lafutidine (LAF) is a novel histamine H2 receptor antagonist with a mucosal protective action. This study aimed to investigate the protective effect of LAF on indomethacin (IND)-induced enteropathy in rats. METHODS: Rats were treated with LAF for 10 days with concomitant IND treatment on the final 5 days...

INTRODUCTION: Soft tissue sarcomas (STSs) are malignant tumors arising from mesenchymal tissues. Patients with advanced and metastatic STSs have low overall survival rates and relatively limited treatment options. Oncostatin M (OSM) is a pleiotropic cytokine that was shown to carry both pro- and anti-tumorigenic properties in various cancer types. However, the role of OSM in STSs has not yet been elucidated. Moreover, the potential additive effects of combining OSM and anti-PD-1 therapy have not been carried out so far...

BACKGROUND: Autophagy is a lysosome-mediated catabolic process that maintains cell homeostasis and survival. It occurs not only in normal cells such as cardiac muscle cells, neurons, and pancreatic acinar cells but also in various benign and malignant tumors. The abnormal level of intracellular autophagy is closely related to multiple pathophysiological processes, including aging, neurodegeneration, infectious diseases, immune disorders, and cancer. Autophagy mainly plays a dual role in life and death by regulating cell survival, proliferation, and death, thus being involved in the occurrence, development, and treatment of cancer...

INTRODUCTION: Autoimmune thyroiditis seems to be associated with increased cardiometabolic risk. Statins, the mainstay of cardiovascular risk reduction and prevention, were found to reduce thyroid antibody titers. The aim of this study was to investigate plasma markers of cardiometabolic risk in statin-treated women with thyroid autoimmunity. METHODS: We compared two matched groups of euthyroid women with hypercholesterolemia receiving atorvastatin treatment: subjects with autoimmune (Hashimoto's) thyroiditis (group A, n = 29) and subjects without thyroid pathology (group B, n = 29)...

INTRODUCTION: A cerebral vasospasm (CVSP) is a potent vasoconstriction of the cerebral vasculature and the primary cause of morbidity and mortality following a subarachnoid hemorrhage. The middle cerebral artery (MCA) is commonly affected by CVSPs. Concomitant administration of dantrolene and nimodipine synergistically reduces vasospasms in aortic rings from Sprague Dawley rats. To determine if the effects observed in the systemic vasculature extend to the cerebral circulation, we investigated the effect of intravenous administration of dantrolene (2...

INTRODUCTION: Metformin reduces elevated levels of FSH and LH. In some studies, gonadotroph secretory function was inhibited by statins. The aim of the present study was to investigate whether statin therapy modulates the impact of metformin on hypothalamic-pituitary-gonadal axis activity in postmenopausal women. METHODS: The study population included 60 postmenopausal women with prediabetes, 40 of whom, because of high cardiovascular risk, received rosuvastatin (20-40 mg daily)...

The anti-inflammatory properties of the medicinal plant Withania somnifera (L.) Dunal (WS) are generally related to withanolides; consistently, several strategies are under investigation to increase the concentration of these compounds in WS extracts. However, a potential toxicity of withanolides has been highlighted, thus questioning the safety of such preparations. At variance, the relative contribution of alkaloids is underrated, in spite of preliminary evidence underlining a possible pharmacological relevance...

INTRODUCTION: Metformin was found to reduce elevated levels of anterior pituitary hormones. Its thyrotropin-lowering effect was more pronounced in individuals receiving myo-inositol. The aim of the present study was to investigate whether the concomitant supplementation of myo-inositol determines the impact of metformin on prolactin levels. METHODS: The study population consisted of two groups of women with mild-to-moderate hyperprolactinemia. Group 1 included 24 individuals receiving myo-inositol preparations (2 g daily for at least 6 months), while 24 inositol-naïve women belonged to group 2...

INTRODUCTION: DPP4 is thought to be involved in certain immune processes and plays an important role in allergic reactions in the lungs. The effect of the DPP4 inhibitor sitagliptin on the effector phase of allergic rhinitis (AR) in ovalbumin (OVA)-sensitized mice and on mast cell degranulation in vitro was assessed. METHODS: The AR mouse model was established by intraperitoneal injection combined with OVA intranasal method. OVA was injected intraperitoneally 3 times for the first 2 weeks, and the mice were subsequently given DPP4 inhibitors by oral gavage, accompanied by an OVA intranasal challenge...

INTRODUCTION: Multiple sclerosis (MS) is the most common chronic inflammatory, demyelinating disease of the central nervous system. Dimethyl fumarate (DMF) and monomethyl fumarate (MMF) belong to the disease-modifying drugs in treatment of MS. There is evidence that astrocytes and microglia are involved in MS pathology, but few studies are available about MMF and DMF effects on astrocytes and microglia. The aim of this study was to investigate the effects of MMF and DMF on microglial activation and morphology as well as potential effects on glial viability, Cx43, and AQP4 expressions in different set-ups of an in vitro astrocyte-microglia co-culture model of inflammation...

The nucleus basalis of Meynert (nBM) is the major source of cholinergic neurons in the basal forebrain, which require nerve growth factor (NGF) for their survival. Melatonin, a pleiotropic hormone, has been shown to exert neuroprotection in several experimental models, but its effect on nBM neurons is not well known. Thus, the aim of this study is to evaluate the effect of melatonin in organotypic brain slices of the nBM. Organotypic nBM slices were incubated for 2 weeks without (control) or with 100 ng/mL NGF, 1 μM melatonin, or a combination of both...

INTRODUCTION: Neutrophils are a pivotal cell type in the K/BxN mouse model of rheumatoid arthritis and play an essential role in the progression of the arthritis. They are readily activated by immune complexes (ICs) via their FcγRs to release IL-1β in addition to other cytokines, which are inducing cartilage destruction. Neutrophils also release neutrophil-active chemokines to recruit themselves in an autocrine manner to perpetuate tissue destruction. FcγR-expression on neutrophils is of crucial importance for the recognition of ICs...

INTRODUCTION: Worldwide, breast cancer is the most common cancer in women and is the main cause of death among all neoplasia in this group. Luminal A breast cancer represents approximately 70% of all breast cancers and is treated with hormone therapies targeting estrogen receptor alpha (ERα). Unfortunately, patients develop drug resistance leading to recurrence of neoplasia due to estrogen-independent ERα reactivation. Therefore, it is crucial to identify new molecular targets downstream ERα signaling pathway that allows the implementation of better treatments to improve the outcome of breast cancer patients...

INTRODUCTION: Metformin-treated patients may experience severe hyperlactatemia or lactic acidosis (LA). LA often requires intensive-care-unit (ICU) treatment, and mortality rates are high. Here, we investigate the impact of renal dysfunction and renal replacement therapy (RRT) on the outcomes of critically ill patients with metformin-associated LA (MALA). Furthermore, we assessed associations between mortality and metformin dose, metformin plasma/serum concentrations, lactate level, and arterial pH...

BACKGROUND: Thrombolytic agents and anticoagulants are the two classes of medication used in the treatment of acute pulmonary embolism (PE). There is continuous renewal and iteration of thrombolytic agents, and the efficacy and adverse effects of different agents have different effects on PE due to their different mechanisms of action. OBJECTIVES: The aim of the study was to evaluate the efficacy and safety of different thrombolytic agents in the treatment of all types of acute PE: hemodynamically unstable PE (massive PE) and hemodynamically stable PE (submassive PE and low-risk PE), using a network meta-analysis...