Acute lung injury (ALI) is a severe disease caused by viral infection that triggers an uncontrolled inflammatory response. This study investigated the capacity of jasurolignoside (JO), a natural compound, to bind to Toll-like receptor 4 (TLR4) and treat ALI. The anti-inflammatory properties of JO were evaluated in vitro through Western blotting, enzyme-linked immunosorbent assay (ELISA), immunofluorescence staining, and co-immunoprecipitation. The investigation utilized a lipopolysaccharide (LPS)-induced ALI animal model to examine the therapeutic efficacy and mechanism of JO in vivo. JO attenuated inflammatory symptoms in infected cells and tissues by modulating the NOD-like receptor family pyrin domain containing protein 3 (NLRP3) inflammasome and the nuclear factor κB (NF-κB)/mitogen-activated protein kinase (MAPK) pathway. Molecular docking simulations revealed JO binding to TLR4 active sites, confirmed by cellular thermal shift assay. Surface plasmon resonance (SPR) demonstrated direct interaction between JO and TLR4 with a Kd value of 35.1 μmol·L^-1. Moreover, JO inhibited tumor necrosis factor α (TNF-α), interleukin-1β (IL-1β), and IL-6 secretion and reduced leukocyte, neutrophil, lymphocyte, and macrophage infiltration in ALI-affected mice. JO also enhanced lung function and reduced ALI-related mortality. Immunohistochemical staining demonstrated JO's ability to suppress TLR4 expression in ALI-affected mouse lung tissue. This study establishes that JO can bind to TLR4 and effectively treat ALI, indicating its potential as a therapeutic agent for clinical applications.
Toll-Like Receptor 4/chemistry* ; Animals ; Acute Lung Injury/chemically induced* ; Mice ; Humans ; Ilex/chemistry* ; Molecular Docking Simulation ; Male ; NF-kappa B/immunology* ; Mice, Inbred C57BL ; NLR Family, Pyrin Domain-Containing 3 Protein/immunology* ; Tumor Necrosis Factor-alpha/genetics* ; Interleukin-1beta/genetics* ; RAW 264.7 Cells ; Disease Models, Animal

Objective To analyze and summarize the acupoint selection law of acupuncture and moxibustion for the treatment of temporomandibular joint dysfunction syndrome(TMD)using data mining technology.Methods Clinical literature about acupuncture and moxibustion for the treatment of TMD was retrieved from CNKI,Wanfang Data,VIP,CBM,PubMed,Web of Science,Embase and Cochrane Library from the establishment of the databases to March 1,2024.Excel 2021 was used to establish a prescription database of acupoints.SPSS Modeler 18.0 and SPSS Statistics 27.0 were used to analyze the frequency of use of acupoints,meridians,locations,specific acupoints,and the analysis of association rules,factor analysis,and clustering analysis.Results A total of 480 articles and 480 prescriptions were included in the study,containing 90 acupoints,with a total frequency of 2 290 times.The high-frequency acupoints were Xiaguan,Hegu,Jiache,Tinggong and Ashi point;the commonly used meridians were the stomach meridian,large intestine meridian,small intestine meridian,bile meridian,and triple-energizer meridian;the most frequently chosen acupoints were the Jiaohui acupoints,Yuan acupoints and Wushu acupoints;and mostly involved acupoints were located at the head and neck area,the upper limb area and the lower limb area.The association analysis showed that the top five combinations were"Xiaguan-Hegu","Xiaguan-Jiache","Xiaguan-Hegu-Jiache","Xiaguan-Tinggong","Xiaguan-Tinggong-Jiache";clustering analysis showed that five valid clusters were extracted;factor analysis extracted seven valid common factors.Conclusion The core acupoints of acupuncture and moxibustion for the treatment of TMD is Xiaguan-Hegu-Jiache-Tinggong,and mainly follows the principle of combining proximal and distal acupoints.

Functionalized liposomes can improve the in vivo process of drugs to achieve high-efficiency delivery by enhancing drug absorption， changing drug distribution and reducing the elimination， which is one of the hotspots in nanomedicine research with broad application prospects. However， the drug information published by official websites of National Medical Products Administration （NMPA）， the United States Food and Drug Administration （FDA）， and the European Medicines Agency （EMA） shows that there are few liposomal products on the market， and the domestic varieties are mainly generic drugs. Excepting for polyethylene glycolized （PEGylated） liposomes， no other functionalized liposomes have been approved for marketing， which indicates that the clinical translation of functionalized liposomes remains at a low level. Therefore， the relevant reports of functionalized liposomes in recent years were reviewed in this paper， their application advantages and main challenges in preparation research and development were discussed based on the in vivo process， and their low clinical translation mainly because of the insufficient clinical thinking， safety and efficacy of functional materials， inaccurate in vitro and in vivo analysis methods and difficulty in scaling up production. Meanwhile， the possible strategies such as introducing the concept of clinical multi-function to improve clinical acuity， focusing on examining the modification density of functional materials and the interaction between the modified materials， evaluating the drug delivery performance of functionalized liposomes from multiple perspectives and scenarios， and conducting cost and convenience-oriented formulation composition and preparation process optimization were proposed in order to provide a reference for the development of functionalized liposomes and other carrier-based nanomedicines.