Regenex Pharmaceuticals (China)

The traditional polypyrrole (PPy) electrode for supercapacitors usually consists of PPy nanoparticles, carbon black and a binder. The PPy electrode inevitably suffers from structural rupture and active PPy particles' detachment during repeated doping/de-doping processes and results in low practical capacitance. Exploring the self-supported electrode without adding any binder or conductive agent is a smart and promising method to avoid the above problems. Herein, a flexible and tailorable polypyrrole/GelMA (PPy/GEL) composite film electrode was prepared via a novel confined interfacial electropolymerization at the interface of GelMA gel film and a conductive glass substrate (FTO). This method leverages spatial confinement to guide PPy growth into a continuous film, as confirmed by cross-sectional SEM analysis. This method can well confine the growth direction of the PPy chain so that PPy grows laterally to easily form a flexible and smooth two-dimensional film. The PPy/GEL-based supercapacitor not only exhibits a high areal capacitance of 260 mF cm−2 at a current density of 1 mA cm−2, which is almost 3 times higher than the pure PPy-based supercapacitor (76 mF cm−2), but also shows high cycling stability with 98% capacitance retention even after 30 000 cycles. Furthermore, the device demonstrates remarkable mechanical durability, retaining its electrochemical performance without significant degradation after being subjected to 100 repeated 180-degree folding cycles, underscoring its potential for wearable applications. This work provides a good strategy for the preparation of high performance PPy self-supported film electrodes.

Diagram showing a drug development process using AI. Left panel depicts molecular structures of teixobactin and clovibactin. Middle section illustrates pharmacochemistry, ADMET pharmacokinetics, and pharmacodynamics targeting with clinical trial simulation using AI. Right section covers side effects, prognosis, and diagnosis using multimodal electronic health records.

This phase I trial aimed to assess the pharmacokinetics (PK), safety, and preliminary efficacy of a single dose of HR20013 (mixed formulation of fosrolapitant and palonosetron) plus dexamethasone in patients with malignant solid tumors. Solid tumor patients who were naive to cisplatin-based chemotherapy and scheduled to receive the single-day cisplatin-based chemotherapy were enrolled. Patients would receive a single intravenous infusion of HR20013 (Day 1) before cisplatin-based chemotherapy, alongside oral dexamethasone (Day 1, 12mg, once a day; Day 2-4, 3.75mg, twice a day). Primary endpoints were PK parameters of fosrolapitant, rolapitant, M19 (a major active metabolite of rolapitant), palonosetron, and dexamethasone. Twenty-four patients were enrolled, and 22 received study treatment. Fosrolapitant reached maximum plasma concentration (Cmax) immediately at the end of the infusion of HR20013 (1h), followed by a short terminal phase, and it was completely hydrolyzed into rolapitant. Mean elimination half-lives of rolapitant and palonosetron were 188.2 and 51.5h, respectively. M19 reached Cmax at approximately 166.2h. After a single oral administration of dexamethasone at 12mg, when combined with HR20013, dexamethasone reached Cmax at approximately 1.5h, with a mean Cmax of 106.0ng/mL. Treatment-related adverse events occurred in 54.5% of patients, with constipation (22.7%), increased blood pressure (18.2%), abdominal distension (13.6%), injection site reaction (9.1%), and increased neutrophil count (9.1%) being most common. Complete response rates (no emesis/rescue therapy) were 90.9% at the overall phase (0-120h) and 86.4% at the beyond delayed phase (120-168h). HR20013 plus dexamethasone had a favorable PK profile, manageable safety, and durable antiemetic efficacy. ClinicalTrials.gov, NCT05465681.

Ferroptosis, an iron- and ROS-dependent form of regulated cell death. Cuproptosis is a novel form of cellular demise mode. Quercetin, a natural flavonoid, has demonstrated a range of pharmacological activities, including anti-cancer, anti-inflammatory, and antioxidant properties. In this research, we investigated the quercetin effect on cisplatin-induced acute kidney and its mechanism associated ferroptosis and cuproptosis. The HK-2 cells were used in this research. Cell viability was evaluated using the CCK-8 assay. Acute kidney injury (AKI) models were established to perform in vivo experiments. Renal tissue homogenate was used to determine ROS, LPO, MDA, PA, etc., to assess ferroptosis and cuproptosis. To perform bioinformatic analysis, microarray data from the GEO database was utilized. Real-time PCR analysis and ELISA was explored the mechanism of ferroptosis and cuproptosis. We found that ferroptosis and cuproptosis in AKI were abnormally activated caused by cisplatin, and that quercetin attenuated AKI by inhibiting ferroptosis and cuproptosis. QCT suppressed ferroptosis by reducing malondialdehyde (MDA) and ROS levels and increasing glutathione (GSH) levels and alleviated cuproptosis by reducing copper ion, pyruvate (PA) and HSP70 levels. Moreover, bioinformatic analysis revealed that the ferroptosis-related gene SLC7A11 and the cuproptosis-related genes ATP7B and GLS were the differential expression genes. And QCT significantly increased the expression or activity of SLC7A11, GPX4, ATP7B, and GLS in Cis-AKI mice. Our findings highlight the clinical importance of quercetin, which guards against cisplatin-induced acute kidney injury by suppressing ferroptosis and cuproptosis.

Pinocembrin (PCB) is 5,7-dihydroxyl flavanone and has multiple pharmacological activities, namely, anti-inflammation, anti-osteoporotic, and so on. However, low water solubility and bioavailability have hindered its application. Herein, we aimed to increase its bioavailability through preparation of F127/MPEG-PDLLA polymer micelles (PCB-M). We characterized the micelles through appropriate attributes such as analysis of particle size (PS), polydispersity (PDI), transmission electron microscopic (TEM) image, stability test, and evaluation of in vitro release of drug. After physical characterization, the respective PS, PDI, and entrapment efficiency (EE) of PCB-M were estimated to be 27.63 ± 0.17nm, 0.055 ± 0.02, and 90.53 ± 0.01%. Fluorescence probe method was employed to measure critical micelle concentration (CMC) of PCB-M, we observed CMC was low, thereby suggesting that PCB-M had good stability. In vitro release analysis indicated that the rate of cumulative PCB release from PCB-M was greater than 90% in each medium compared with free PCB, which was less than 40%, thus pointing to a significantly improved solubility of PCB. In vivo pharmacokinetic results showed that oral biological availability of PCB-M increased 5.3 folds comparable to free PCB. The effects of PCB on osteoblasts and ALP activities were investigated; subsequently, zebrafish osteoporotic model was established with prednisolone to study the anti-osteoporotic effects of PCB and PCB-M. The results showed that PCB improved osteoporosis with PCB-M being more effective than free PCB. Finally, PCB-M can be used as a promising method to improve the solubility of PCB, while the bioavailability and anti-osteoporotic effect of PCB could be improved, thus laying a foundation for clinical use in the future.

The main objective of the study was to evaluate the bioequivalence of two rosuvastatin calcium tablets in healthy Chinese subjects under fasted and fed conditions. The study was carried out using a randomized, open-label, two-formulation, two-sequence, two-period, single-dose crossover design, with a washout period of 7days. Both the fasted study and fed study enrolled 28 subjects. In each study period, the subjects were administrated a single oral dose of the test product or reference product of rosuvastatin 10mg. Blood samples were collected from pre-dose to 72hours after administration with 16 time points in total. Bioequivalence evaluation was performed using ln-transformed pharmacokinetic parameters of rosuvastatin, including Cmax , AUC0-t , and AUC0-∞ . In the present study, 95% confidence intervals (CIs) of test/reference geometric mean ratios (GMRs) of Cmax , AUC0-t , and AUC0-∞ under the fasted and fed conditions were all within the acceptance range of 80%-125%. Additionally, only one subject experienced one adverse event (AE). High-fat meals reduced the Cmax , AUC0-t , and AUC0-∞ , but had no significant effects on the λz, t1/2 , or Tmax of rosuvastatin. In the current study, the test product was bioequivalent to the reference product, and a single dose of rosuvastatin (10mg) was well-tolerated. Food decreased the systemic exposure of rosuvastatin without the effects on the Tmax or elimination rate.