Objective: We developed and validated a sensitive and reliable UPLC-MS/MS method for simultaneous determination of dezocine (DEZ), midazolam (MDZ) and its metabolite 1-hydroxymidazolam (1-OH-MDZ) in beagle plasma and investigated the effect of dexmedetomidine (DEX) on the pharmacokinetics of DEZ, MDZ and 1-OH-MDZ in beagles. Materials and Methods: Diazepam was used as the internal standard (IS); the

Background: α2A-adrenoceptor (AR) is a potential target for the treatment of degenerative diseases of the central nervous system, and α2A-AR agonists are effective drugs for this condition. However, the lack of high selectivity for α2A-AR subtype of traditional drugs greatly limits their clinic usage. Methods: A series of homobivalent 4-aminoquinolines conjugated by two 4-aminoquinoline moieties via

Background: This study sought to investigate a novel effect of melatonin in reducing brain injury in an in vivo hyperglycemic intracerebral hemorrhage (ICH) model and further explore the mechanisms of protection. Methods: Hyperglycemia ICH was induced in Sprague-Dawley rats by streptozocin injection followed by autologous blood injection into the striatum. A combined approach including RNA-specific

Purpose: Prolonged use of proton pump inhibitors may cause bone loss, and limited therapeutic agents are available to prevent this skeletal side effect. The combination of annatto tocotrienol, a bone anabolic agent, with calcium presents a novel strategy to prevent bone loss caused by proton pump inhibitors. This study aims to compare the effects of calcium alone and in combination with annatto tocotrienol

Purpose: The mechanism of cardioprotection by Kv7.1– 5 (KCNQ1-5) channels inhibition by XE991 is unclear. We examined the impact of administration time on the cardioprotective efficacy of XE991, the involvement of key pro-survival kinases, and the importance of the Kv7 subchannels. Methods: Isolated perfused rat hearts were divided into five groups: 1) vehicle, 2) pre-, 3) post- or 4) pre- and post-ischemic

Purpose: Colorectal cancer (CRC) is one of the most commonly occurring cancers and is associated with high morbidity and mortality. Nevertheless, there is currently no safe and effective treatment for this condition. Thymol is a phenolic compound that is recognized as safe for use in food as well as medical and cosmetic fields. Increasing evidence has indicated that thymol exerts prominent antitumor

Purpose: The monocarbonyl analogs of curcumin (MCACs) have been widely studied for their promising antitumor activity. Pyrazole is a five-membered aromatic heterocyclic system with various bioactivities incorporated frequently in drugs. However, few of MCACs inspired pyrazole analogues were investigated. To search for more potent cytotoxic agents based on MCACs, a series of new 1,5-diaryl/heteroaryl-1

Attenuation of Myocardial Fibrosis with Curcumin Is Mediated by Modulating Expression of Angiotensin II AT1/AT2 Receptors and ACE2 in Rats [Corrigendum]

Abstract: Belimumab (Benlysta®) is a fully humanized monoclonal antibody that inhibits B lymphocyte stimulator (BLyS, also known as B cell-activating factor of the tumor necrosis factor family) and was approved by the US Food and Drug Administration (FDA) and the European Medicines Evaluation Agency for the treatment of autoantibody-positive systemic lupus erythematosus (SLE) in adults with moderate

Abstract: Type 2 diabetes mellitus (T2DM) is an emerging epidemic in Asian countries, especially in India. With the advent of the SGLT2 inhibitor class of drugs demonstrating benefits beyond glycemic control, viz. weight loss, blood pressure reduction, and cardiovascular and renal protection, the management of T2DM has taken a quantum leap. Remogliflozin etabonate (RE) is the latest addition to the

Background: Identification of laboratory parameter clinical safety signals depends on the terminology and scoring criteria. Grade 1 scoring criteria in the Common Terminology Criteria for Adverse Events (CTCAE) is typically based on the healthy volunteer reference range (HVRR). The objectives of this study were to determine 1) what laboratory parameters in individuals with diabetes are potentially

Background: Oral cancer (OC) is one of the most common cancers around the world. Despite the progress in treatment, the prognosis of OC remains poor, especially for patients with advanced diseases. It urges the development of novel therapeutic options against OC. Lycopene (LYC) is an antioxidant with chemoprotective properties against cancer. However, little is known about the mechanisms underlying

Purpose: Berberine (BBR) is an effective component of Huanglian and has shown to attenuate atherosclerosis (AS); however, the detailed mechanism of BBR-mediated protective actions against AS remains elusive. This study was undertaken to examine the effects of BBR on aortic atherosclerotic plaque stability and the expression of autophagy-related proteins in AS rats with damp-heat syndrome or yang deficiency

Background: Severe bleeding and perforation of the colon and rectum are complications of ulcerative colitis which can be treated by a targeted drug delivery system. Purpose: Development of colon-targeted delivery usually involves a complex formulation process and coating steps of pH-sensitive methacrylic acid based Eudragit®. The current work was purposefully designed to develop dicalcium phosphate

Abstract: Neoadjuvant chemotherapy is increasingly used in breast cancer, especially for downstaging the primary tumor in the breast and the metastatic axillary lymph node. Accurate evaluations of the response to neoadjuvant chemotherapy provide important information on the impact of systemic therapies on breast cancer biology, prognosis, and guidance for further therapy. Moreover, pathologic complete

Purpose: Acute myeloid leukemia (AML) is a complex malignancy characterized by the clonal expansion of immature myeloid precursors. The standard treatment for newly diagnosed AML is chemotherapy consisting of cytosine arabinoside (Ara-C) and anthracyclines with disappointing clinical outcomes and severe adverse effects, such as symptomatic bradycardia, neurotoxicity. Thus, it is promising to treat

Introduction: Currently, gastroesophageal reflux disease (GERD) is one of the most ubiquitous problems in clinical practice. An antacid-alginate combination (under the trade name Gaviscon) is a natural-based product that effectively suppresses GERD. This product acts via the formation of viscous gel that floats on the top of the gastric content. On the other hand, efficient management of Helicobacter

Introduction: Liver disease is common and often life-threatening. Sinomenine (SIN) is an active ingredient extracted from Sinomenium acutum. This study investigated the protective effect and mechanism of sinomenine (SIN) on acetaminophen (APAP)-induced liver injury from in vitro and in vivo. Methods: In vivo experiments, mice were randomly divided into six groups (n=10): control group, model group

Purpose: Patients with type 1 diabetes (T1D) are associated with a high risk of multiple complications, so the development of T1D treatment is urgently needed. This study was set out to explore the molecular mechanism of metformin in the treatment of T1D insulin resistance. Patients and Methods: Subcutaneous adipose tissues were collected from 68 T1D patients and 51 healthy controls. Insulin resistance

Introduction: Osteoarthritis (OA) is an age-related chronic degenerative disease. Accumulation of advanced glycation end products (AGEs) induces degradation of the articular extracellular matrix (ECM) and is considered a critical step toward the development and progression of OA. GPR40 is a well-known free fatty acid receptor, which possesses pleiotropic effects in different types of diseases. However

Aim: The aim of this study was to develop a GX1-modified nanostructured lipid carrier (NLCs) and to evaluate its ability to improve the anti-gastric cancer tumor effects of paclitaxel (PTX). Main Methods: The GX1-modified NLCs were synthesized and loaded with PTX (GX1-PTX-NLCs) by emulsion solvent evaporation technique. The anti-tumor activity and pharmacodynamics were then evaluated by in vitro cell

Purpose: Drug-induced liver injury (DILI) is the most common cause of acute liver failure. The aim of this study was to investigate the molecular mechanisms by which Ganoderma lucidum mushroom (GLM) may ameliorate cisplatin (CP)-induced hepatotoxicity theoretically and experimentally. Materials and Methods: Thirty-six male Sprague-Dawley (SD) rats were divided into six groups, two of them are normal

Background: Cholangiocarcinoma (CCA) is a slowly progressing but highly aggressive malignancy. Targeting the HER protein family represents a potential therapeutic strategy for CCA treatment. The pan-HER inhibitor varlitinib is being developed for the treatment of breast cancer, gastric cancer, and biliary tract cancer, which includes CCA. This study aims to evaluate the anti-tumor effect of varlitinib

Introduction: Transdermal drug delivery is gaining popularity as an alternative to traditional routes of administration. It can increase patient compliance because of its painless and noninvasive nature, aid compounds in bypassing presystemic metabolic effects, and reduce the likelihood of adverse effects through decreased systemic exposure. In silico physiological modeling is critical to predicting

Background: Subarachnoid hemorrhage (SAH) is a cerebral hemorrhage disease that severely damages the brain and causes cognitive impairment (CI). Therefore, accurate and appropriate treatment strategies are urgently needed. The application of nimodipine can not only improve blood circulation in patients with SAH but also repair ischemic neuron injury. Purpose: To investigate the effects of nimodipine

Abstract: Nontuberculous mycobacteria (NTM) can cause and perpetuate chronic inflammation and lung infection. Despite having the diagnostic criteria, as defined by the American Thoracic Society (ATS) and Infectious Diseases Society of America (IDSA), clinicians find it challenging to diagnose and treat NTM-induced lung disease. Inhaled antibiotics are suitable for patients with lung infection caused

Abstract: Astaxanthin is a carotenoid derived from oxygen-containing non-vitamin A sources and is mainly obtained from marine organisms. Studies have demonstrated that astaxanthin is a natural antioxidant product and it is widely used in the fields of medicine, health-care products and cosmetics. Studies have shown that astaxanthin has important preventive and therapeutic effects on liver fibrosis

Purpose: Lung cancer remains the leading cancer-associated deaths worldwide. Cisplatin (CDDP) was used in combination with curcumin (CUR) for the treatment of non-small cell lung cancer. The aim of this study was to prepare and characterize CDDP prodrug and CUR co-encapsulated layer-by-layer nanoparticles (CDDP-PLGA/CUR LBL NPs) to induce cooperative response, maximize the therapeutic effect, overcome

Purpose: Lung cancer is the leading cause of cancer mortality worldwide. Drug resistance is the major barrier for the treatment of non-small cell lung cancer (NSCLC). The aim of this research is to develop an aptamer-decorated hybrid nanoparticle for the co-delivery of docetaxel prodrug (DTXp) and cisplatin (DDP) and to treat lung cancer. Materials and Methods: Aptamer-conjugated lipid–polymer ligands

Introduction: Ziprasidone (ZP) is a novel atypical antipsychotic agent effective in the treatment of positive and negative symptoms of schizophrenia with low chances for extrapyramidal side effects (EPs) and cognitive deficits. ZP possesses poor oral bioavailability (∼ 50%), short biological half-life (∼ 2.5 h) and due to extensive first-pass metabolism, a repeated dose is administered which makes

Activation of Cholinergic Anti-Inflammatory Pathway in Peripheral Immune Cells Involved in Therapeutic Actions of α-Mangostin on Collagen-Induced Arthritis in Rats [Corrigendum]

Aim: Gastric cancer is a leading cause of cancer death worldwide. In-depth research of precancerous lesions of gastric carcinoma (PLGC) with malignant transformation potential is a key measure to prevent the development of gastric carcinoma. Recently, calycosin has been shown to have anticancer effects in vitro and in vivo. The molecular mechanism by which calycosin affects PLGC, however, has not yet

Purpose: Hyperuricemia is an independent risk factor for renal damage and can promote the progression of chronic kidney disease (CKD). In the present study, we employ a rat model to investigate the effects of rosiglitazone (RGTZ), a peroxisome proliferator-activated receptor-gamma agonist, on the development of hyperuricemic nephropathy (HN), and we elucidate the mechanisms involved. Methods: An HN

Purpose: The purpose of this study was to examine the effects of voriconazole on the pharmacokinetics of vonoprazan. Methods: Fifteen Sprague-Dawley rats were randomly divided into three groups: five rats in each group, including control group, single-dose group (a single dose of 30 mg/kg of voriconazole), and multiple-dose group (multiple doses of 30 mg/(kg•day) per dose of voriconazole). Each group

Background: There is a correlation between tumor and inflammation. The activity of 13-[CH2CO-Cys(Bzl)-OBzl]-berberine (13-Cys-BBR) slowing tumor growth is higher than that of BBR. Whether the anti-inflammation activity of 13-Cys-BBR is higher than that of BBR remains unknown. There is a correlation between thrombosis and inflammation. Whether 13-Cys-BBR is an inhibitor of thrombosis remains unknown

Background: Several published meta-analyses have confirmed that single-agent maintenance therapy in advanced non-small-cell lung cancer (NSCLC) can prolong time to disease progression and potentially increase overall survival (OS) in comparison to placebo. However, whether doublet maintenance therapy can improve the survival of advanced NSCLC remains undetermined. Methods: We searched several databases

Introduction: The current study was designed to synthesize derivatives of succinimide and compare their biological potency in anticholinesterase, alpha-glucosidase inhibition, and antioxidant assays. Methods: In this research, two succinimide derivatives including (S)-1-(2,5-dioxo-1-phenylpyrrolidin-3-yl) cyclohexanecarbaldehyde (Compound 1) and (R)-2-((S)-2,5-dioxo-1-phenylpyrrolidin-3-yl)-2-phenylpropanal

Purpose: To determine the impact of initiating enzyme replacement therapy (ERT) with agalsidase alfa early in the course of Fabry disease, we evaluated renal and cardiac outcomes for ≤ 10 years after ERT initiation in males from the Fabry Outcome Survey (FOS). Patients and Methods: Male patients from FOS were stratified into three cohorts by age at ERT initiation: ≤ 18 years (cohort 1), > 18 and ≤

Objective: This study aimed to evaluate the fundamental characteristics of coronavirus disease (COVID-19) clinical trials registered in China. Methods: COVID-19 clinical trials registered in China were analyzed from databases on ChiCTR and ClinicalTrials.gov. The study designs, samples, primary end points, and intervention measures were evaluated. Results: In total, 262 intervention clinical trials

In situ Delivery of Thermosensitive Gel-Mediated 5-Fluorouracil Microemulsion for the Treatment of Colorectal Cancer [Corrigendum]

Effect of Lactoferrin Protein on Red Blood Cells and Macrophages: Mechanism of Parasite–Host Interaction [Corrigendum]

Purpose Dioscin, a natural glycoside derived from many plants, has been proved to exert anti-cancer activity. Several studies have found that it reverses TGF-β1-induced epithelial-mesenchymal transition (EMT). Whether dioscin can reverse EMT by pathways other than TGF-β is still unknown. Methods We used network-based pharmacological methods to systematically explore the potential mechanisms by which

Objective To compare the efficacy of dexmedetomidine and midazolam in the prevention of postoperative nausea and vomiting (PONV) caused by hemabate in postpartum hemorrhage during cesarean delivery. Methods One hundred and five parturients with American Society of Anesthesiology (ASA) physical status I and II, aged 20-40 years, undergoing elective cesarean delivery under epidural anesthesia were randomly

Background Intervertebral disc degeneration (IDD) is the most common diagnosis of patients with lower back pain. IDD is the underlying lesion of many spinal degenerative diseases; however, the role of cGAS/Sting/NLRP3 pathway and epigallocatechin gallate (EGCG) in the development of IDD remained unclear. Methods The expressions of cGAS, Sting and NLRP3 mRNA of intervertebral disc (IVD) samples from

Background Leukemia threatens so many lives around the world. Dihydroartemisinin (DHA), as a typical derivative of artemisinin (ART), can efficiently inhibit leukemia, but the controversial mechanisms are still controversial. Many reports showed that tumor cells acquire energy through the glycolysis pathway, pyruvate kinase M2 (PKM2) plays a crucial role in regulating glycolysis. However, it is unclear

Purpose: Osteoarthritis (OA) is associated with chronic low-grade inflammation. Resveratrol exerts protective effects on OA through its anti-inflammatory property; however, the mechanism of resveratrol on anti-inflammatory signaling pathways has not been fully elucidated yet. The aim of the present study was to investigate whether resveratrol-mediated PI3K/Akt expression is linked to TLR4/NF-κB pathway

Objective Fimasartan, an angiotensin II type 1 receptor blocker, and linagliptin, a dipeptidyl-peptidase-4 inhibitor, are frequently coadministered to treat patients with hypertension and diabetes, respectively. This study sought to evaluate the pharmacokinetic interactions between fimasartan and linagliptin after co-administration in healthy Korean subjects. Methods The overall study was divided into

Introduction Peroxisome proliferator-activated receptor γ (PPARγ) plays a key role in glucose, which is a ligand-mediated transcription factor. The lipid homeostasis often serves as a pharmacological target for new drug discovery and development. Materials and Methods In the research, we synthesized a series of piperine derivatives and then used a fluorescence polarization-based PPARγ ligand screening

Background Gilteritinib, a novel, potent FLT3/AXL inhibitor, was recently approved in Japan and USA for the treatment of adult patients who have relapsed or refractory acute myeloid leukemia (AML) with a FLT3 mutation. Purpose and Methods In this study, we aimed to develop and validate a sensitive and simple ultra performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) method for the

Purpose Autophagy caused by ischemia/reperfusion (I/R) increases the extent of cardiomyocyte damage. Melatonin (Mel) diminishes cardiac injury through regulating autophagy and mitochondrial dynamics. However, illustrating the specific role of mitophagy in the cardioprotective effects of melatonin remains a challenge. The aim of our research was to investigate the impact and underlying mechanisms of

Introduction Targeted multimodal approaches need to be strategically developed to control tumour growth and prevent metastatic burden successfully. Breast cancer presents a unique clinical problem because of the variety of cellular subtypes that arise. The tumour stage and cellular subtypes often dictate the appropriate clinical treatment regimen. Also, the development of chemoresistance is a common

Purpose To explore the molecular mechanism of glycine in improving ischemic stroke. Patients and Methods The serum samples of patients with ischemic stroke and healthy people were compared. The ischemic stroke model of PC12 cells was established by oxygen-glucose deprivation (OGD). qPCR quantified miR-19a-3p and AMPK mRNA, and protein expression was detected by Western blot. MTT was used to detect

Introduction In this study, the encapsulation of fentanyl citrate as an opioid drug with hydrophobic nature in the nanostructured lipid carrier (NLC) is performed. Methods For encapsulation of fentanyl citrate drug, hot homogenization method is used. The pharmacokinetics of encapsulated fentanyl citrate for pain relief of rats are investigated. The influence of important variables such as the ratio

Background Studies have shown that α-mangostin (MG) could exert anti-rheumatic effects in vivo by restoring immunity homeostasis, and have indicated that activation of the choline anti-inflammatory pathway (CAP) may contribute to this immunomodulatory property. The current study was designed to further investigate the effects of MG on the CAP in peripheral immune cells and clarify its relevance to

Aim Lung injury is a common complication of acute pancreatitis (AP), which leads to the development of acute respiratory distress syndrome and causes high mortality. In the present study, we investigated the therapeutic effect of emodin on AP-induced lung injury and explored the molecular mechanisms involved. Materials and Methods Thirty male Sprague-Dawley rats were randomly divided into AP (n=24)

Background and Purpose Apatinib is a small-molecule tyrosine kinase inhibitor for the treatment of recurrent or progressive advanced-stage gastric adenocarcinoma or gastroesophageal junction cancer. The in vitro inhibition studies suggested that apatinib exerted potent inhibition on CYP3A4 and CYP2C9. To evaluate the potential of apatinib as a perpetrator in CYP450-based drug-drug interactions in vivo

Introduction In multiple studies, involvement of oxidative stress in the pathogenesis of methotrexate (MTX)-mediated liver damage has been confirmed. Use of many drugs has been examined experimentally in order to prevent or diminish oxidative stress. However, no study has yet examined the effects of ferulic acid (FA) on MTX-induced liver damage. This study aimed at evaluating the effects of FA on protection

Background The macrophage is one of the most important types of immune cells that protect against harmful stimuli. Macrophage activation plays a pivotal role in the progression and development of various inflammatory diseases. The neurokinin 1 receptor (NK-1R) is a G protein-coupled receptor that plays an important role in inflammatory diseases. Aprepitant is a kind of NK-1R antagonist. The purpose

Purpose A fixed-dose combination (FDC) of fimasartan and atorvastatin is used to treat hypertension and dyslipidemia. The peak plasma concentration (Cmax) of fimasartan and atorvastatin has a large intra-subject variability with a maximum coefficient of variation of 65% and 48%, respectively. Therefore, both drugs are classified as highly variable drugs. The purpose of this study was to compare the

Purpose Arsenic trioxide (ATO) has been shown to induce hepatic injury. Crocetin is a primary constituent of saffron, which has been verified to have antioxidant and anti-inflammatory effects. In the current experiment, we evaluated the efficacy of crocetin against ATO-induced hepatic injury and explored the potential molecular mechanisms in rats. Methods Rats were pretreated with 25 or 50 mg/kg crocetin