Safety, tolerability, pharmacokinetics, and pharmacodynamics of a soluble guanylate cyclase stimulator, HEC95468, in healthy volunteers: a randomized, double-blinded, placebo-controlled phase 1 trial.

Heart failure is the most costly cardiovascular disorder. New treatments are urgently needed. This study aims to evaluate the safety, pharmacokinetics, and pharmacodynamic profile of HEC95468, a soluble guanylate cyclase (sGC) stimulator, in healthy volunteers.

Safety, pharmacokinetics, and pharmacodynamics in healthy Chinese volunteers treated with SC0062, a highly selective endothelin-A receptor antagonist.

This study evaluated the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD), and food effects (FE) of SC0062, a highly active endothelin-A (ET ) receptor antagonist, in healthy subjects. The primary objectives of this first-in-human phase I study, comprised of single-ascending-dose, multiple-ascending-dose, and FE parts, were to characterize the safety and tolerability of SC0062, and FE. The secondary objectives were to determine the PK behavior of SC0062 and its major active metabolite M18, whereas exploratory objectives focused on PD effects, principally effects on endothelin-1 (ET-1) and total bile acids (TBA).

Safety, immunogenicity, and efficacy of a modified COVID-19 mRNA vaccine, SW-BIC-213, in healthy people aged 18 years and above: a phase 3 double-blinded, randomized, parallel controlled clinical trial in Lao PDR (Laos).

Background: The mRNA vaccine has demonstrated significant effectiveness in protecting against SARS-CoV-2 during the pandemic, including against severe forms of the disease caused by emerging variants. In this study, we examined safety, immunogenicity, and relative efficacy of a heterologous booster of the lipopolyplex (LPP)-based mRNA vaccine (SW-BIC-213) versus a homologous booster of an inactivated vaccine (BBIBP) in Laos.

Methods: In this phase 3 clinical trial, which was randomized, parallel controlled and double-blinded, healthy adults aged 18 years and above were recruited from the Southern Savannakhet Provincial Hospital and Champhone District Hospital.

A phase I study comparing the pharmacokinetics and safety of HS628 (tocilizumab biosimilar) and reference tocilizumab in healthy male subjects.

This study aimed to evaluate the pharmacokinetic (PK) similarity of the proposed biosimilar HS628 compared with the reference tocilizumab (Actemra®) and also to demonstrate similar safety and immunogenicity profiles in healthy Chinese male subjects. Eighty eligible subjects were randomized into two treatment groups in a 1:1 ratio to receive a single intravenous infusion of HS628 or tocilizumab at 4 mg/kg over 60 min. Blood samples were collected at the scheduled time points for PK and immunogenicity analysis.

Safety and immunogenicity of a modified COVID-19 mRNA vaccine, SW-BIC-213, as a heterologous booster in healthy adults: an open-labeled, two-centered and multi-arm randomised, phase 1 trial.

Background: We assessed the safety and immunogenicity of a core-shell structured lipopolyplex (LPP) based COVID-19 mRNA vaccine, SW-BIC-213, as a heterologous booster in healthy adults.

Methods: We conducted an open-labeled, two-centered, and three-arm randomised phase 1 trial. Healthy adults, who had completed a two-dose of inactivated COVID-19 vaccine for more than six months, were enrolled and randomized to receive a booster dose of COVILO (inactivated vaccine) (n = 20) or SW-BIC-213-25μg (n = 20), or SW-BIC-213-45μg (n = 20).

Foam Cells in Atherosclerosis: Novel Insights Into Its Origins, Consequences, and Molecular Mechanisms.

Foam cells play a vital role in the initiation and development of atherosclerosis. This review aims to summarize the novel insights into the origins, consequences, and molecular mechanisms of foam cells in atherosclerotic plaques. Foam cells are originated from monocytes as well as from vascular smooth muscle cells (VSMC), stem/progenitor cells, and endothelium cells.

Development and validation of a ligand-binding assay for quantification of the F(ab') antivenom of Daboia russelii siamensis in human serum and its application to a phase I clinical study.

Daboia russelii siamensis accounts for most of snakebite mortalities in China, yet, specific treatment against the venom toxins is absent in clinical practice. The F(ab') antivenom of Daboia russelii siamensis is manufactured and approved for the clinical trial in China. To satisfy the need for clinical pharmacokinetic research, this study aimed to develop a ligand binding assay (LBA) for the quantification of F(ab') antivenom of Daboia russelii siamensis in human serum.

Liquid chromatography-tandem mass spectrometric assay for TPN171 in human plasma.

A simple, rapid and accurate method for quantitative analysis of a highly selective phosphodiesterase-5 inhibitor (PDE5), TPN171 by high performance liquid chromatography and tandem mass spectrometry in human plasma was proposed and validated successfully using D-TPN171 as internal standards (ISTD). An aliquot of 100 μL of plasma was mixed with internal standard and was precipitated with acetonitrile. Gradient elution was performed on a ACQUITY HSS T3 column (50 × 2.

Direct analysis in real time-mass spectrometry for rapid quantification of five anti-arrhythmic drugs in human serum: application to therapeutic drug monitoring.

Therapeutic drug monitoring (TDM) is necessary for the optimal administration of anti-arrhythmic drugs in the treatment of heart arrhythmia. The present study aimed to develop and validate a direct analysis in real time tandem mass spectrometry (DART-MS/MS) method for the rapid and simultaneous determination of five anti-arrhythmic drugs (metoprolol, diltiazem, amiodarone, propafenone, and verapamil) and one metabolite (5-hydroxy(OH)-propafenone) in human serum. After the addition of isotope-labeled internal standards and protein precipitation with acetonitrile, anti-arrhythmic drugs were ionized by DART in positive mode followed by multiple reaction monitoring (MRM) detection.

A novel small molecule liver X receptor transcriptional regulator, nagilactone B, suppresses atherosclerosis in apoE-deficient mice.

Aims: Atherosclerosis is the most common cause of cardiovascular diseases, such as myocardial infarction and stroke. We hypothesized that nagilactone B (NLB), a small molecule extracted from the root bark of Podocarpus nagi (Podocarpaceae), suppresses atherosclerosis in an atherosclerotic mouse model.

Methods And Results: Male apoE-deficient mice on C57BL/6J background received NLB (10 and 30 mg/kg) for 12 weeks.

Development and validation of an HPLC-MS/MS method to determine clopidogrel in human plasma.

A quantitative method for clopidogrel using online-SPE tandem LC-MS/MS was developed and fully validated according to the well-established FDA guidelines. The method achieves adequate sensitivity for pharmacokinetic studies, with lower limit of quantifications (LLOQs) as low as 10 pg/mL. Chromatographic separations were performed on reversed phase columns Kromasil Eternity-2.

Determination of the novel antiarrhythmic drug sulcardine sulfate in human plasma by liquid chromatography tandem mass spectrometry and its application in a clinical pharmacokinetic study.

Sulcardine sulfate (Sul), a novel antiarrhythmic agent, is currently in phase I and phase II clinical trials. To elucidate its clinical pharmacokinetic characteristics, a rapid and accurate liquid chromatography-tandem mass spectrometry (LC-MS/MS) method has been developed and validated for the quantification of Sul in human plasma. Plasma samples were precipitated by acetonitrile and isotope-labeled sulcardine was added as internal standard.

MG132, a proteasome inhibitor, enhances LDL uptake in HepG2 cells in vitro by regulating LDLR and PCSK9 expression.

Aim: Expression of liver low-density lipoprotein receptor (LDLR), a determinant regulator in cholesterol homeostasis, is tightly controlled at multiple levels. The aim of this study was to examine whether proteasome inhibition could affect LDLR expression and LDL uptake in liver cells in vitro.

Methods: HepG2 cells were examined.

Sodium tanshinone IIA silate inhibits high glucose-induced vascular smooth muscle cell proliferation and migration through activation of AMP-activated protein kinase.

The proliferation of vascular smooth muscle cells may perform a crucial role in the pathogenesis of diabetic vascular disease. AMPK additionally exerts several salutary effects on vascular function and improves vascular abnormalities. The current study sought to determine whether sodium tanshinone IIA silate (STS) has an inhibitory effect on vascular smooth muscle cell (VSMC) proliferation and migration under high glucose conditions mimicking diabetes without dyslipidemia, and establish the underlying mechanism.

Phase I study on the pharmacokinetics and tolerance of ZT-1, a prodrug of huperzine A, for the treatment of Alzheimer's disease.

Aim: Huperzine A isolated from the Chinese herb Huperzia serrata (Thunb) Trev is a novel reversible and selective AChE inhibitor. The aim of this study was to evaluate the pharmacokinetics and tolerance of single and multiple doses of ZT-1, a novel analogue of huperzine A, in healthy Chinese subjects.

Methods: This was a double-blinded, placebo-controlled, randomized, single- and multiple-dose study.

Liquid chromatography tandem mass spectrometry method for determination of N-acetylcysteine in human plasma using an isotope-labeled internal standard.

A liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed to determine total N-acetylcysteine in human plasma. Mass spectrometric detection was achieved in positive electrospray ionization and multiple reaction monitoring mode. The mass transition pairs of N-acetylcysteine and the isotope-labeled internal standard d3-N-acetylcysteine were 164 → 122 and 167 → 123, respectively.

Development and validation of a liquid chromatography-isotope dilution tandem mass spectrometry for determination of olanzapine in human plasma and its application to bioavailability study.

A simple, reliable and sensitive liquid chromatography-isotope dilution mass spectrometry (LC-ID/MS) was developed and validated for quantification of olanzapine in human plasma. Plasma samples (50 microL) were extracted with tert-butyl methyl ether and isotope-labeled internal standard (olanzapine-D3) was used. The chromatographic separation was performed on XBridge Shield RP 18 (100 mm x 2.

Development of a liquid chromatography-isotope dilution mass spectrometry method for quantification of fentanyl in human plasma.

Fentanyl is a potent analgesic drug in relieving chronic pain in patients. In this report, we present a simple, reliable and sensitive LC-ID/MS method for the quantification of fentanyl in human plasma. LC-ID/MS analysis was carried out on a triple quadrupole mass spectrometer operated in positive electrospray ionization multiple-reaction-monitoring using the transitions m/z 337.