Jinyinqingre Oral Liquid alleviates LPS-induced acute lung injury by inhibiting the NF-κB/NLRP3/GSDMD pathway.

Acute lung injury (ALI) is a prevalent and severe clinical condition characterized by inflammatory damage to the lung endothelial and epithelial barriers, resulting in high incidence and mortality rates. Currently, there is a lack of safe and effective drugs for the treatment of ALI. In a previous clinical study, we observed that Jinyinqingre oral liquid (JYQR), a Traditional Chinese Medicine formulation prepared by the Taihe Hospital, Affiliated Hospital of Hubei University of Medicine, exhibited notable efficacy in treating inflammation-related hepatitis and cholecystitis in clinical settings. However, the potential role of JYQR in ALI/acute respiratory distress syndrome (ARDS) and its anti-inflammatory mechanism remains unexplored. Thus, the present study aimed to investigate the therapeutic effects and underlying molecular mechanisms of JYQR in ALI using a mouse model of lipopolysaccharide (LPS)-induced ALI and an in vitro RAW264.7 cell model. JYQR yielded substantial improvements in LPS-induced histological alterations in lung tissues. Additionally, JYQR administration led to a noteworthy reduction in total protein levels within the BALF, a decrease in MPAP, and attenuation of pleural thickness. These findings collectively highlight the remarkable efficacy of JYQR in mitigating the deleterious effects of LPS-induced ALI. Mechanistic investigations revealed that JYQR pretreatment significantly inhibited NF-κB activation and downregulated the expressions of the downstream proteins, namely NLRP3 and GSDMD, as well as proinflammatory cytokine levels in mice and RAW2647 cells. Consequently, JYQR alleviated LPS-induced ALI by inhibiting the NF-κB/NLRP3/GSDMD pathway. JYQR exerts a protective effect against LPS-induced ALI in mice, and its mechanism of action involves the downregulation of the NF-κB/NLRP3/GSDMD inflammatory pathway.

Antioxidant capacity of flavonoids from Folium Artemisiae Argyi and the molecular mechanism in Caenorhabditis elegans.

ETHNOPHARMACOLOGICAL RELEVANCE: Folium Artemisiae Argyi (FAA) is one kind of Chinese herbal medicine with a long history. It has widespread pharmacological activities such as antibacterial, anti-inflammatory, antioxidative, and hemostatic, among others. FAA is traditionally used for the treatment of eczema, respiratory diseases and gynecological diseases for hundreds of years. Flavonoids are reported as the main components of them. Recent studies focused on the antioxidant effect of its flavonoids in vitro, while few studies focused on the antioxidant effect in vivo, and the underlying mechanisms have not yet been elucidated. AIM OF THE STUDY: The aim of this study was to evaluate the antioxidant activity of Folium Artemisia Argyi flavonoids (FAAF) and explore its possible molecular mechanism in Caenorhabditis elegans. The research and development of its medicinal value will beneficial to the resource utilization of FAA. MATERIALS AND METHODS: Firstly, FAAF was prepared, purified and then qualitatively and quantitatively analyzed using LC-DAD-MS. Then, 1,1-diphenyl-2-trinitrophenylhydrazine (DPPH), 2,2-azino-bis-(3-ethylbenzothiazoline-6-sulfonic acid (ABTS), hydroxyl radical and ferric reducing antioxidant power (FRAP) assays were applied to investigate the antioxidant effect of FAAF in vitro. Meanwhile, a stress resistance assay was carried out to evaluate the antioxidant effect of FAAF in vivo. Moreover, superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activities and reactive oxygen species (ROS) accumulation were determined to ascertain whether FAAF can increase the oxidant defense system of nematodes and reduce the accumulation of ROS. Lipofuscin and protein carbonylation assays were employed to test whether FAAF can increase the antioxidant capacity of nematodes to resist the growth health indicators related to antioxidation. At last, quantitative real-time polymerase chain reaction (qRT-PCR) was performed to evaluate the expression of genes related to antioxidation. The expression of green fluorescent protein (GFP) was further investigated using a fluorescence microscope in transgenic strains (SOD-3::GFP, GST-4::GFP, and HSP-16.2::GFP). RESULTS: FAAF exhibited a strong antioxidant capacity and enhanced stress resistance in C. elegans. FAAF reduced ROS accumulation and improved the antioxidant defense system under acute stress. Moreover, FAAF prevented the accumulation of lipofuscin and protein carbonylation in C. elegans. FAAF also upregulated the gene expression levels of hsp-16.2, gst-4, sod-3, skn-1, daf-16, ctl-2, hsf-1 and increased SOD-3::GFP and GST-4::GFP expression. CONCLUSION: These results demonstrated that FAAF exerted antioxidant activity in C. elegans. It was perhaps regulated by the insulin/insulin-like growth factor-1(IGF-1) signaling pathway.

Therapeutic evidence of umbilical cord-derived mesenchymal stem cell transplantation for cerebral palsy: a randomized, controlled trial.

BACKGROUND: Cerebral palsy (CP) is a syndrome of childhood movement and posture disorders. Clinical evidence is still limited and sometimes inconclusive about the benefits of human umbilical cord mesenchymal stem cells (hUC-MSCs) for CP. We conducted a randomized trial to evaluate the safety and efficacy of hUC-MSC transplantation concomitant with rehabilitation in patients with CP. METHODS: Eligible patients were allocated into the hUC-MSC group and control group. In addition to rehabilitation, the patients in the hUC-MSC group received four transfusions of hUC-MSCs intravenously, while the control group received a placebo. Adverse events (AEs) were collected for safety evaluation in the 12-month follow-up phase. Primary endpoints were assessed as activities of daily living (ADL), comprehensive function assessment (CFA), and gross motor function measure (GMFM) scales. In addition, cerebral metabolic activity was detected by 18F-FDG-PET/CT to explore the possible mechanism of the therapeutic effects. Primary endpoint data were analyzed by ANOVA using SPSS version 20.0. RESULTS: Forty patients were enrolled, and 1 patient withdrew informed consent. Therefore, 39 patients received treatments and completed the scheduled assessments. No significant difference was shown between the 2 groups in AE incidence. Additionally, significant improvements in ADL, CFA, and GMFM were observed in the hUC-MSC group compared with the control group. In addition, the standard uptake value of 18F-FDG was markedly increased in 3 out of 5 patients from the hUC-MSC group at 12 months after transplantation. CONCLUSIONS: Our clinical data showed that hUC-MSC transplantation was safe and effective at improving the gross motor and comprehensive function of children with CP when combined with rehabilitation. Recovery of cerebral metabolic activity might play an essential role in the improvements in brain function in patients with CP. The therapeutic window, transfusion route, and dosage in our study were considerable for reference in clinical application. TRIAL REGISTRATION: Chictr.org.cn, ChiCTR1800016554. Registered 08 June 2018-retrospectively registered. The public title was "Randomized trial of umbilical cord-derived mesenchymal stem cells for cerebral palsy."