China Pharmaceutical University (CPU) is a university in Nanjing, China that specializes in the pharmaceutical sciences. It is one of national key universities under the Double First Class University Plan and former “Project 211” and universities selected for the "985 Innovative Platforms for Key Disciplines Project" affiliated with the Chinese Ministry of Education, also, the university is included in the Double First Class University Plan designed by the Chinese central government.
Tau protein hyperphosphorylation and neuroinflammation playimportant roles in the onset and progression of Alzheimer's disease (AD). SIRT1has been implicated in the regulation of synaptic plasticity, cognitive function, andmemory, and is associated with the modulation of autophagy-and inflammation-related signaling pathways, including AMPK/mTOR/ULK1 and NF-κB. Resveratrol(RSV) has been reported to ameliorate cognitive impairment in AD models,primarily in the context of Aβ–related pathology; however, its potential effects andunderlying mechanisms in Tau-driven pathology remain incompletely understood. To investigate the effect of RSV on cognitive impairment in mice withTau mutation-induced Alzheimer's disease, and to explore its effects on autophagyand neuroinflammation. Tauopathy models were established using AAV-P301L-Tau. Cognitivefunction was assessed via behavioral tests; Hippocampal injury was evaluatedAccepted manuscriptACCEPTED MANUSCRIPTusing HE and Nissl staining, while autophagy was assessed byimmunofluorescence staining. Mechanisms were examined using Western blot,qRT-PCR, and CCK-8 assays. RSV treatment was associated with attenuation of neuronal damage,reduction of p-Tau accumulation, and improvement of cognitive impairment in ADmice. Consistent trends were observed in vitro, where RSV treatment wasassociated with increased cell viability and modulation of autophagy-relatedmarkers in AAV-P301L-Tau-induced BV2 cells. In addition, RSV administration wasaccompanied by coordinated changes in signaling components related to SIRT1,AMPK/mTOR/ULK1, and NF-κB pathways, along with reduced expression ofinflammatory mediators. RSV treatment was associated with coordinated modulation ofsignaling components related to the AMPK/mTOR/ULK1 and NF-κB pathways,together with improvements in cognitive performance in AD mice. These findingssupport the potential therapeutic relevance of RSV in Tau-drivenneurodegenerative pathology, while further studies are required to clarify theunderlying mechanisms.
BackgroundRomidepsin is a class I-selective histone deacetylase (HDAC) inhibitor indicated for the treatment of adult patients with cutaneous T-cell lymphoma (CTCL) who have received at least one prior systemic therapy and for adult patients with relapsed or refractory peripheral T-cell lymphoma (PTCL). Despite its clinical use, large-scale safety data remain limited. This study leverages the FDA Adverse Event Reporting System (FAERS) database to characterize romidepsin-associated adverse events (AEs) in real-world settings, aiming to enhance clinical risk management.MethodsData from the FAERS database, spanning from January 2014 to March 2025, served as the basis for this analysis. To evaluate the association between romidepsin and AEs, multiple disproportionality analyses were employed, including the reporting odds ratio (ROR), the proportional reporting ratio (PRR), the Bayesian confidence propagation neural network (BCPNN), and the multi-item gamma Poisson shrinker (MGPS).ResultsWithin the specified reporting period, 17,448,626 AE reports were recorded in the FAERS database, of which 1,285 events were associated with romidepsin. Based on four calculation methods, 101 preferred terms (PTs) related to romidepsin were determined. Common AEs included thrombocytopenia, pyrexia, anemia, electrocardiogram QT prolonged, and infections, aligning with the drug label. In addition, some unanticipated major AEs were detected, including cardiotoxicities beyond QT prolongation (acute cardiac failure, atrial fibrillation, sinus tachycardia, mitral valve incompetence, and bundle branch block left) alongside other significant AEs: hepatic failure, amenorrhea, mental status changes, glomerular filtration rate decreased, embolism, and retinal detachment.ConclusionThis study provides a systematic evaluation of AEs associated with romidepsin, confirming its established safety profile and identifying several emerging safety concerns in a real-world setting. These findings offer valuable insights to assist clinicians and pharmacists in better-managing romidepsin’s safety.
Children’s affect plays a crucial role in their mental health, academic performance, and social adjustment. However, previous studies on the relationship between life events and affect have primarily focused on adolescents or adults, leaving unclear how daily life events influence children’s affect in real school settings. This study used a 10-day daily diary design to examine the momentary relationships between life events and affect among 193 Chinese elementary school students (41.45
Abstract Background The formation of foam cells (FCs) is the major contributor to the development of atherosclerosis (AS). Gynostemma pentaphyllum is widely used to treat AS and exhibits biological activity against FCs formation. Narcissoside (Nar) is an important component from G. pentaphyllum flavonoids. This study aimed to reveal the beneficial effect and underlying mechanism of Nar on inhibiting the formation of FCs in AS. Methods The inhibitory effects of Nar on FCs formation were evaluated using Oil Red O staining and flow cytometry in ox-LDL-stimulated THP-1 and BMDMs. High-fat diet (HFD)-induced ApoE−/− mice were administered Nar for 9 weeks to assess its therapeutic efficacy in treating AS. Luciferase reporter gene assays, Western blot, and RT-qPCR were performed to investigate the mechanisms of action of Nar, which were further confirmed through in vitro experiments using siRNA of NR4A1 for reverse validation. Results In vitro, Nar attenuated FCs formation as evidenced by reduced intracellular lipid levels and ox-LDL uptake rates. In vivo, Nar effectively improved lipid profiles and serum inflammatory factors. Histological analysis showed that Nar reduced the area of the necrotic core and lipid accumulation in the aortic roots. Mechanistically, Nar inhibited CD36 transcription by enhancing the expression and nuclear translocation of NR4A1. Mutation of the NR4A1 binding site within the CD36 promoter abolished the inhibitory effect of Nar. Additionally, silencing NR4A1 eliminated Nar’s capacity to suppress ox-LDL uptake and downregulate CD36 expression. Conclusions Nar attenuated AS by inhibiting CD36-mediated FCs formation through upregulating the expression and nuclear translocation of NR4A1, highlighting it as a promising therapeutic candidate for AS.
BACKGROUND:Transdermal drug delivery (TDD) offers a convenient administration for treating local or systemic diseases. However, the dense "brick-mortar" structure of the stratum corneum hinders the skin permeation of most of bioactive molecules, which highly constrained the application of TDD. METHODS:This study analyzed stratum corneum disruption and enhanced permeation by gently rubbing calcium hydrogen phosphate (Chp) particles of varying sizes on skin. Enhanced anesthetic efficacy of Chp-containing microemulsion gel (MG) loaded with lidocaine-tetracaine eutectic was evaluated in guinea pigs using a needle-prick model. RESULTS:Using Chp as dermabrasion particle could effectively disrupt the barrier of stratum corneum after applying gently rubbing on the skin, which resulted in increasing skin permeation of both FITC, FITC-Dextran4000 and MG loaded with lidocaine-tetracaine eutectic. The enhanced skin permeation depended not only on the increase of particle size and amount of Chp in the MG, but also on the increase of rubbing pressure and duration after being applied to the skin, finally shortening the onset time and improving the efficacy of local anesthetics. CONCLUSIONS:The incorporation of Chp into the topical formulation, followed by rubbing them on the skin with appropriate pressure and a certain duration, can significantly disrupt the stratum corneum, enhance drug permeation through the skin, and shorten the onset time of local anesthetics. This study provided a potential strategy for improving the skin permeation with well tolerance, which could be further used to expand the range of bioactive molecules for TDD.
