A real-world disproportionality analysis of apalutamide: data mining of the FDA adverse event reporting system.

Apalutamide is a new drug class, which is approved to treat prostate cancer (PCa). The aim of our study was to assess the safety profiles of apalutamide in real-world through data mining of the United States Food and Drug Administration Adverse Event Reporting System (FAERS). We included adverse event (AE) reports regarding apalutamide submitted to the FAERS from 2018 quarter 1 (2018Q1) to 2022 quarter 1 (2022Q1).

Adverse event profiles of PCSK9 inhibitors alirocumab and evolocumab: Data mining of the FDA adverse event reporting system.

Background: Proprotein convertase subtilisin/kexin type (PCSK9) inhibitor is a new drug class approved for treating dyslipidemias. Herein, we aimed to investigate the safety profiles of PCSK9 inhibitors (alirocumab and evolocumab) using the Food and Drug Administration Adverse Event Reporting System (FAERS).

Methods: We included adverse event (AE) reports regarding alirocumab and evolocumab submitted to the FAERs between 2015Q3 to 2021Q1.

NKTR-358: A novel regulatory T-cell stimulator that selectively stimulates expansion and suppressive function of regulatory T cells for the treatment of autoimmune and inflammatory diseases.

Impaired interleukin-2 (IL-2) production and regulatory T-cell dysfunction have been implicated as immunological mechanisms central to the pathogenesis of multiple autoimmune and inflammatory diseases. NKTR-358, a novel regulatory T-cell stimulator, is an investigational therapeutic that selectively restores regulatory T-cell homeostasis in these diseases. We investigated NKTR-358's selectivity for regulatory T-cells, receptor-binding properties, vo and pharmacodynamics, ability to suppress conventional T-cell proliferation in mice and non-human primates, and functional activity in a murine model of systemic lupus erythematosus.

Efficacy and safety of thrombolysis for acute ischemic stroke with atrial fibrillation: a meta-analysis.

Background: The efficacy and safety of intravenous thrombolysis (IVT) for acute ischemic stroke with atrial fibrillation (AF) is still controversial.

Methods: We conducted a meta-analysis of all relevant studies, retrieved through systematic search of PubMed, Embase, and Cochrane databases up to December 31, 2019. Modified Rankin Scale (mRS) scores of 0-1 at 90 days, mRS of 0-2 at 90 days, overall mortality, and incidence of symptomatic intracranial hemorrhage (sICH) were collected as outcome measures.

Specific knockdown of hippocampal astroglial EphB2 improves synaptic function via inhibition of D-serine secretion in APP/PS1 mice.

Increasing evidence emphasizes the protective role of Eph receptors in synaptic function in the pathological development of Alzheimer's disease (AD); however, their roles in the regulation of hippocampal astrocytes remain largely unknown. Here, we directly investigated the function of astroglial EphB2 on synaptic plasticity in APP/PS1 mice. Using cell isolation and transgene technologies, we first isolated hippocampal astrocytes and evaluated the expression levels of ephrinB ligands and EphB receptors.

Regional Differences in Food Allergies.

The prevalence of food allergies is increasing worldwide. To understand the regional specificities of food allergies and develop effective therapeutic interventions, extensive regional epidemiological studies are necessary. While data regarding incidence, prevalence, regional variation, and treatment in food allergies are available for western countries, such studies may not be available in many Asian countries.

Serum STLT-1 and bilirubin levels in patients with acute coronary syndrome and correlation with prognosis.

The serum triggering receptor expressed on myeloid cell (TREM)-like transcription factor-1 [soluble TREM-like transcript-1 (STLT-1)] and bilirubin levels were investigated in patients with acute coronary syndrome and the correlation with prognosis. A total of 125 patients of acute coronary syndrome admitted to the Department of Cardiology in People's Hospital of Rizhao were selected, including 45 cases with ST-segment elevation myocardial infarction (STEMI), 36 cases with non-ST-elevation myocardial infarction (NSTEMI) and 44 cases with unstable angina pectoris (UAP), while 48 subjects were enrolled as the normal control. The serum STLT-1 and bilirubin levels on admission and on the 3rd, 7th and 10th day after admission of patients in each group were respectively determined, the level changes of these two indicators in serum during the initial stage of acute coronary syndrome were analyzed, and their effects on prognosis of patients were analyzed.

Clinical and economic impact of pharmacist interventions on sampled outpatient prescriptions in a Chinese teaching hospital.

Background: Limited studies have evaluated the effectiveness of pharmacist interventions on outpatient prescription. The goal of this study was to evaluate the clinical and economic impacts of pharmacist interventions on randomly sampled outpatient prescriptions.

Method: Outpatient prescriptions of our hospital were sampled automatically and reviewed by pharmacists since 2011.

Sphingosine kinase inhibitors: A patent review.

Sphingosine kinases (SphKs) catalyze the conversion of the sphingosine to the promitogenic/migratory product, sphingosine-1-phosphate (S1P). SphK/S1P pathway has been linked to the progression of cancer and various other diseases including allergic inflammatory disease, cardiovascular diseases, rejection after transplantation, the central nervous system, and virus infections. Therefore, SphKs represent potential new targets for developing novel therapeutics for these diseases.

Inhibitors targeting the SUMOylation pathway: A patent review 2012‑2015 (Review).

Small ubiquitin‑related modifier (SUMO) proteins bind to the lysine residue of target proteins to produce functionally mature proteins. The abnormal SUMOylation of certain target proteins is associated with diseases including cancer, heart disease, diabetes, arthritis, degenerative diseases and brain ischemia/stroke. Thus, there has been growing appreciation for the potential importance of the SUMO conjugation pathway as a target for treating these diseases.

Quercetin alleviates thermal and cold hyperalgesia in a rat neuropathic pain model by inhibiting Toll-like receptor signaling.

Neuropathic pain is caused by lesion or disease of the nervous system, which results in abnormal spontaneous and evoked pain. It's common in clinical practice and greatly impairs the life quality of patients, but the effective treatment is still lacking. In this study, we aimed to explore the effect of quercetin (QUE) on neuropathic pain and the underlying mechanisms.

miR-93 enhances hepatocellular carcinoma invasion and metastasis by EMT via targeting PDCD4.

Objectives: To clarify the potential biological function of miR-93 and its related molecular mechanism underlying metastasis in human hepatocellular carcinoma (HCC).

Results: miR-93 was significantly up-regulated in HCC tissues and was associated with poor 5-year overall survival in HCC patients. Transwell assays showed that over-expression of miR-93 increased HCC cell migration and invasion in vitro.

Expression and purification of a major allergen, Pla a 1, from Platanus acerifolia pollen and the preparation of its monoclonal antibody.

Platanus acerifolia pollen is considered an important source of airborne allergens in numerous cities. Pla a 1 is a major allergen from P. acerifolia pollen.

Expression, purification and epitope analysis of Pla a 3 allergen from Platanus acerifolia pollen.

Platanus acerifolia (P. acerifolia) is an important cause of pollinosis in cities. The use of allergen extracts on patients with allergic diseases is the most commonly applied method to attempt to treat pollinosis.

Selective deletion of apolipoprotein E in astrocytes ameliorates the spatial learning and memory deficits in Alzheimer's disease (APP/PS1) mice by inhibiting TGF-β/Smad2/STAT3 signaling.

Astrocytes and apolipoprotein E (apoE) play critical roles in cognitive function, not only under physiological conditions but also in some pathological situations, particularly in the pathological progression of Alzheimer's disease (AD). The regulatory mechanisms underlying the effect of apoE, derived from astrocytes, on cognitive deficits during AD pathology development are unclear. In this study, we generated amyloid precursor protein/apoE knockout (APP/apoE) and APP/glial fibrillary acidic protein (GFAP)-apoE mice (the AD mice model used in this study was based on the APP-familial Alzheimer disease overexpression) to investigate the role of apoE, derived from astrocytes, in AD pathology and cognitive function.

Etirinotecan pegol administration is associated with lower incidences of neutropenia compared to irinotecan administration.

Purpose: The relationship between incidences of neutropenia and 10-hydroxy-7-ethyl camptothecin (SN38) exposure was explored using SN38 pharmacokinetic and neutrophil count data from toxicology studies of etirinotecan pegol (EP) and irinotecan in beagle dogs.

Methods: Dogs received four weekly intravenous infusions of either vehicle control (n = 22), EP (6, 15, 20, 25, 40/25 mg/kg; n = 3-9 dogs/dose group/sex; n = 48), or irinotecan (20 or 25 mg/kg n = 3-4 dogs/dose group/sex; n = 14). Blood samples were collected up to 50 days post-dose for characterization of SN38 pharmacokinetics.

Omalizumab for the treatment of chronic spontaneous urticaria: A meta-analysis of randomized clinical trials.

Background: Chronic spontaneous urticaria (CSU) is defined by itchy hives, angioedema, or both for at least 6 weeks. Omalizumab, an anti-IgE antibody that affects mast cell and basophil function, is a promising new treatment option. As of now, however, the efficacy and safety of different doses of omalizumab used in clinical trials for CSU have not been systematically analyzed and summarized.

NKTR-214, an Engineered Cytokine with Biased IL2 Receptor Binding, Increased Tumor Exposure, and Marked Efficacy in Mouse Tumor Models.

Purpose: Aldesleukin, recombinant human IL2, is an effective immunotherapy for metastatic melanoma and renal cancer, with durable responses in approximately 10% of patients; however, severe side effects limit maximal dosing and thus the number of patients able to receive treatment and potential cure. NKTR-214 is a prodrug of conjugated IL2, retaining the same amino acid sequence as aldesleukin. The IL2 core is conjugated to 6 releasable polyethylene glycol (PEG) chains.

Non-use of health care service among empty-nest elderly in Shandong, China: a cross-sectional study.

Background: Empty-nest elderly refers to those elderly with no children or whose children have already left home. Few studies have focused on healthcare service use among empty-nest seniors, and no studies have identified the prevalence and profiles of non-use of healthcare services among empty-nest elderly. The purpose of this study is to compare the prevalence of non-use of healthcare services between empty-nest and non-empty-nest elderly and identify risk factors for the non-use of healthcare services among empty-nest seniors.

Novel genetic variants in the TPO gene cause congenital hypothyroidism.

Background: Mutations in the dual oxidase maturation factor 2 (DUOXA2) and thyroid peroxidase (TPO) genes have been reported to cause goitrous congenital hypothyroidism (GCH). The aim of this study was to determine the genetic basis of GCH in affected children.

Methods: Thirty children with GCH were enrolled for molecular analysis of the DUOXA2 and TPO genes.

Evaluation of inflammatory and oxidative biomarkers in children with well-controlled congenital hypothyroidism.

Objective: To investigate well-controlled congenital hypothyroidism on the markers associated with early kidney injury and oxidative DNA damage.

Methods: Twenty-three children with euthyroid congenital hypothyroidism aged 3-6 years and 19 age- and gender-matched controls were enrolled. Serum levels of albumin, C-reactive protein, cysteine C, globulin, pre-albumin, and total protein were detected.

(3S,12R,20S,24R)-20,24-Ep-oxy-dammarane-3,12,25-triol.

In the title mol-ecule, C(30)H(52)O(4), the three six-membered rings are in chair conformations, the cyclo-pentane ring is in an envelope form and the tetra-hydro-furan ring has a conformation inter-mediate between half-chair and sofa. In the crystal, mol-ecules are linked by inter-molecular O-H⋯O hydrogen bonds into helical chains along [100]. Two intra-molecular O-H⋯O hydrogen bonds are also present.