Epigenetic‑ncRNA crosstalk in atherosclerosis: Mechanisms, disease progression and therapeutic potential (Review).

Atherosclerosis is a chronic and progressive vascular disease involving the gradual accumulation of lipids, cholesterol, cellular debris, and fibrous elements within the arterial wall. This process leads to the thickening and hardening of arteries, resulting in restricted blood flow and reduced oxygen delivery to tissues. Over time, these pathological changes significantly elevate the risk of life‑threatening cardiovascular events, including myocardial infarction and ischemic stroke.

Pharmacokinetic Drug Interactions of TPN171 When Coadministration With Rifampicin or Itraconazole.

Purpose: TPN171, a novel, highly selective, and potent phosphodiesterase type 5 (PDE5) inhibitor, is currently under clinical development for the treatment of pulmonary arterial hypertension (PAH) and erectile dysfunction (ED). The drug is mainly metabolized by the cytochrome P450 (CYP) enzyme 3A4. We evaluated the pharmacokinetic (PK) profile and safety of TPN171, both alone and in combination with itraconazole (a CYP3A4 potent inhibitor) or rifampin (a CYP3A4 potent inducer), in healthy Chinese volunteers.

Efficacy and safety of simenafil in men with erectile dysfunction: a multicenter, randomized, double-blind, placebo-controlled, fixed dose, parallel group, phase 3 trial.

Background: Simenafil, a potent and highly selective oral phosphodiesterase type 5 (PDE5) inhibitor, is currently under investigation for erectile dysfunction (ED) treatment.

Aims: To evaluate the efficacy and safety of simenafil for ED treatment.

Methods: This was a multicenter, randomized, double-blind, placebo-controlled, parallel group, phase 3 study in men aged 18-75 years with a history of ED of 6 months or more.

Evaluation of the acute effects of single-dose TPN171 on semen quality in healthy Chinese male volunteers.

Aims: TPN171 is a novel phosphodiesterase type 5 inhibitor for the treatment of erectile dysfunction. This study aimed to assess the immediate impact of a single dose of TPN171 (10 mg) on semen quality in healthy male Chinese volunteers. Additionally, the study investigated the exposure of TPN171 in seminal plasma and observed the safety of TPN171 in the participants.

Hemodynamic and Pharmacokinetic Interactions of TPN171 with Alcohol in Healthy Male Subjects.

This study aimed to evaluate the effects of the concomitant administration of TPN171 and alcohol on hemodynamic and pharmacokinetic characteristics in healthy Chinese male subjects. Fifteen eligible subjects were randomly assigned to one of three sequences, each comprising three treatments: Treatment A (placebo +0.5 g/kg alcohol), Treatment B (TPN171 + 0.

Pharmacokinetics, mass balance, and metabolism of [C]TPN171, a novel PDE5 inhibitor, in humans for the treatment of pulmonary arterial hypertension.

TPN171 is a novel phosphodiesterase-5 (PDE5) inhibitor used to treat pulmonary arterial hypertension (PAH) and erectile dysfunction (ED), which currently is undergoing phase II clinical trials in China. In this single-center, single-dose, nonrandomized, and open design study, radiolabeled [C]TPN171 was used to investigate the metabolic mechanism, pharmacokinetic characteristics, and clearance pathways of TPN171 in 6 healthy Chinese male volunteers. Each volunteer was administered a single oral suspension of 10 mg (100 μCi) of [C]TPN171.

Safety, tolerability, and pharmacokinetics of VV116, an oral nucleoside analog against SARS-CoV-2, in Chinese healthy subjects.

VV116 (JT001) is an oral drug candidate of nucleoside analog against SARS-CoV-2. The purpose of the three phase I studies was to evaluate the safety, tolerability, and pharmacokinetics of single and multiple ascending oral doses of VV116 in healthy subjects, as well as the effect of food on the pharmacokinetics and safety of VV116. Three studies were launched sequentially: Study 1 (single ascending-dose study, SAD), Study 2 (multiple ascending-dose study, MAD), and Study 3 (food-effect study, FE).

Discovery of an Oleanolic Acid/Hederagenin-Nitric Oxide Donor Hybrid as an EGFR Tyrosine Kinase Inhibitor for Non-Small-Cell Lung Cancer.

Natural triterpenoids, such as oleanolic acid (OA) and hederagenin, display anti-lung cancer effects, and nitric oxide (NO) is associated with some oncogenic signaling pathways. Accordingly, 17 OA/hederagenin-NO donor hybrids were designed, synthesized, and evaluated against tumor cells. The most potent compound, , significantly inhibited the proliferation of five tumor cell lines (IC 4.

Cytotoxicity, Hemolytic Toxicity, and Mechanism of Action of Pulsatilla Saponin D and Its Synthetic Derivatives.

The strong hemolytic toxicity of pulsatilla saponin D (1, HD 6.3 μM) has hampered its clinical development as an injectable anticancer agent. To combat this challenge, 17 new derivatives of 1 with ring C, C-28, or C-3 modifications were synthesized and evaluated for cytotoxicity against several selected human tumor lines, as well as for hemolytic toxicity against rabbit erythrocytes.

The derivatives of Pulsatilla saponin A, a bioactive compound from Pulsatilla chinensis: Their synthesis, cytotoxicity, haemolytic toxicity and mechanism of action.

The strong haemolytic toxicity of Pulsatilla saponin A (PSA) has hampered its clinical development as an injectable anticancer agent. To circumvent this challenge, twenty PSA derivatives with C ring or C-28 or C-3 modifications were synthesized and evaluated for cytotoxicity against seven selected human tumor lines, as well as for haemolytic toxicity. Structure-activity relationship (SAR) and structure-toxicity relationship (STR) correlations were also elucidated.

Palladium-Catalyzed Domino Synthesis of 4-Amino-3-acyl-2- naphthols via Isocyanide Chemoselective Insertion.

A novel and efficient strategy for the synthesis of sterically hindered 4-amino-3-acyl-2-naphthols through a palladium-catalyzed coupling reaction involving isocyanide chemselective insertion and domino isomerization has been developed. The methodology, which is in accordance with the principle of "atom and step economy", efficiently constructs 4-amino-3-acyl-2-naphthols in moderate to good yields.

Palladium-catalyzed chemoselective synthesis of indane-1,3-dione derivatives via tert-butyl isocyanide insertion.

A simple and efficient strategy for the synthesis of indane-1,3-dione derivatives through a palladium(0)-catalyzed reaction incorporating tert-butyl isocyanide has been developed. In addition, by applying this protocol as the key step, indenopyrazole derivatives can be easily synthesized in high yields in a one-pot procedure. This methodology is tolerant of a wide range of substrates and applicable to library synthesis.

Synthesis, cytotoxicity and haemolytic activity of Pulsatilla saponin A, D derivatives.

The strong haemolytic activity of Pulsatilla saponin A (PSA), D (PSD) hampered their clinical development of antitumor agents. In order to solve this problem, C-28 position modification derivatives of PSA/PSD were synthesized. The cytotoxicity and haemolytic activity of these compounds were evaluated.

New polyoxygenated cyclohexene and polyoxygenated seco-cyclohexene from Uvaria boniana.

A new polyoxygenated cyclohexene bonianol A (1) and another new polyoxygenated seco-cyclohexene bonianol B (2) were isolated from the leaves of Uvaria boniana, and their structures were established on the basis of spectroscopic methods including IR, HR-ESI-MS, 1D, and 2D NMR.