Objective : To investigate the brain microvascular tissue block culture method for extracting primary rat brain microvascular endothelial cells and identify its effect. Methods : Brain tissue from 4-week-old Sprague Dawley rats was screened, pre-digested and solidified to obtain brain microvascular segments. These segments were subsequently placed in a CO2incubator for primary culture. The target cells were identified by cell morphology and immunocytochemical staining for factor Ⅷ-related antigen. Results : After a 48-hour culture periodin vitro, the short spindle cells crawled out from around the brain microvascular segments. After 72 hours, island-like cell culsters formed. After 96 hours the clusters fused and the cells formed a typical monolayer, cobble stone-like, and mosaic arrangement. Factor Ⅷ-related antigen immunocytochemical staining showed that the cytoplasm of the cells appeared brown-red, indicating positive expression; DAB stained the nucleus, showing blue-dark. Conclusion The brain microvascular tissue block culture method can isolate and culture primary rat brain microvascular endothelial cells.

Traumatic brain injury (TBI) is intricately linked to the most severe clinical manifestations of brain damage. It encompasses dynamic pathological mechanisms, including hemodynamic disorders, excitotoxic injury, oxidative stress, mitochondrial dysfunction, inflammation, and neuronal death. This review provides a comprehensive analysis and summary of biomaterial-based tissue engineering scaffolds and nano-drug delivery systems. As an example of functionalized biomaterials, nano-drug delivery systems alter the pharmacokinetic properties of drugs. They provide multiple targeting strategies relying on factors such as morphology and scale, magnetic fields, pH, photosensitivity, and enzymes to facilitate the transport of therapeutics across the blood-brain barrier and to promote selective accumulation at the injury site. Furthermore, therapeutic agents can be incorporated into bioscaffolds to interact with the biochemical and biophysical environment of the brain. Bioscaffolds can mimic the extracellular matrix environment, regulate cellular interactions, and increase the effectiveness of local treatments following surgical interventions. Additionally, stem cell-based and exosome-dominated extracellular vesicle carriers exhibit high bioreactivity and low immunogenicity and can be used to design therapeutic agents with high bioactivity. This review also examines the utilization of endogenous bioactive materials in the treatment of TBI.

Allergic rhinitis (AR), a globally prevalent immune-mediated inflammatory condition, is still an incurable disease. In the present study, we have validated the impact of the Kelch-like ECH associated protein 1 (Keap1)-related oxidative stress and inflammatory response in clinical AR patient peripheral blood and nasal swab samples, emphasizing the biological relevance of Keap1 and AR. Targeting Keap1 -nuclear factor erythroid 2-related factor 2 (Nrf2) related anti-oxidative stress may be effective for AR intervention. Drawing inspiration from the Keap1 homodimerization and the E3 ligase characteristics, we herein present a design of novel bivalent molecules for chemical knockdown of Keap1. For the first time, we characterized ternary complexes of Keap1 dimer and one molecule of bivalent compounds. The best bivalent molecule 8 encompasses robust capacity to degrade Keap1 as a homoPROTAC^KEAP1. It efficaciously suppresses inflammatory cytokines in extensively different cells, including human nasal epithelial cells. Moreover, in an AR mouse model, we confirmed that the chemical degradation induced by homoPROTAC^KEAP1 led to therapeutic benefits in managing AR symptoms, oxidative stress and inflammation. In summary, our findings underscore the efficacy of targeting the Keap1 system through the homoPROTAC-ing technology as an innovative and promising treatment strategy for the incurable allergic disorders.

OBJECTIVE: Baicalein has been reported to have wide therapeutic effects that act through its anti-inflammatory activity. This study examines the effect and mechanism of baicalein on sepsis-induced cardiomyopathy (SIC). METHODS: A thorough screening of a small library of natural products, comprising 100 diverse compounds, was conducted to identify the most effective drug against lipopolysaccharide (LPS)-treated H9C2 cardiomyocytes. The core target proteins and their associated signaling pathways involved in baicalein's efficacy against LPS-induced myocardial injury were predicted by network pharmacology. RESULTS: Baicalein was identified as the most potent protective agent in LPS-exposed H9C2 cardiomyocytes. It exhibited a dose-dependent inhibitory effect on cell injury and inflammation. In the LPS-induced septic mouse model, baicalein demonstrated a significant capacity to mitigate LPS-triggered myocardial deficits, inflammatory responses, and ferroptosis. Network pharmacological analysis and experimental confirmation suggested that hypoxia-inducible factor 1 subunit α (HIF1-α) is likely to be the crucial factor in mediating the impact of baicalein against LPS-induced myocardial ferroptosis and injury. By combining microRNA (miRNA) screening in LPS-treated myocardium with miRNA prediction targeting HIF1-α, we found that miR-299b-5p may serve as a regulator of HIF1-α. The reduction in miR-299b-5p levels in LPS-treated myocardium, compared to the control group, was reversed by baicalein treatment. The reverse transcription quantitative polymerase chain reaction, Western blotting, and dual-luciferase reporter gene analyses together identified HIF1-α as the target of miR-299b-5p in cardiomyocytes. CONCLUSION Baicalein mitigates SIC at the miRNA level, suggesting the therapeutic potential of it in treating SIC through the regulation of miR-299b-5p/HIF1-α/ferroptosis pathway. Please cite this article as: Zhou WY, Du JK, Liu HH, Deng L, Ma K, Xiao J, Zhang S, Wang CN. Baicalein attenuates lipopolysaccharide-induced myocardial injury by inhibiting ferroptosis via miR-299b-5p/HIF1-α pathway. J Integr Med. 2025; 23(5):560-575.
Flavanones/pharmacology* ; Animals ; MicroRNAs/genetics* ; Lipopolysaccharides ; Hypoxia-Inducible Factor 1, alpha Subunit/genetics* ; Ferroptosis/drug effects* ; Mice ; Myocytes, Cardiac/metabolism* ; Signal Transduction/drug effects* ; Rats ; Male ; Mice, Inbred C57BL ; Cardiomyopathies/etiology* ; Cell Line ; Sepsis/complications*

Gastric cancer ranks fifth in global cancer mortality,which is highly aggressive and heterogeneous.How-ever,the research and treatment of gastric cancer is hindered by short of research models that may characterize the developmental properties of gastric cancer.Gastric cancer organoid is a multicellular three-dimensional structure de-veloped in vitro,which can mimic the structure and function of native gastric cancer.Gastric cancer organoids have great application potential and development prospects in establishing gastric cancer research models,mimicking the tumor microenvironment,high-throughput screening of drugs,discovering new therapeutic targets,predicting clinical therapeutic responses,and guiding individualized treatment.In this paper,the progress of gastric cancer or-ganoids in basic research and clinical application is reviewed aiming for promoting the progress of preclinical re-search and supporting the clinical treatment of gastric cancer.

Efferocytosis refers to the process that phagocytes recognize and remove the apoptotic cells, which is essential for maintaining tissue homeostasis both in physiological and pathological conditions. Numerous studies have demonstrated that efferocytosis can prevent secondary necrosis and proinflammatory factor release, leading to the resolution of inflammation and tissue immunological tolerance in numerous diseases such as stroke. Stroke is a leading cause of death and morbidity for adults worldwide. Persistent inflammation triggered by the dead cells or cell debris is a major contributor to post-stroke brain damage. Effective efferocytosis might be an efficient strategy to minimize inflammation and restore brain homeostasis for neuronal regeneration and function recovery. In this review, we will discuss the phagocytes in the brain, the molecular mechanisms underlying efferocytosis, the role of efferocytosis in inflammation resolution, and the potential therapeutic applications targeting efferocytosis in stroke.
Humans ; Stroke ; Phagocytosis/physiology* ; Inflammation ; Apoptosis/physiology* ; Animals ; Phagocytes/physiology* ; Brain/metabolism* ; Efferocytosis

Objective:To observe the choroidal vascular changes of chronic central serous chorioretinopathy (cCSC), and analyze their correlations with central macular thickness (CMT).Methods:A cross-sectional study was adopted.Seventy-six eyes of 38 patients with monocular cCSC who were treated in Renmin Hospital of Wuhan University from March 2018 to December 2019 were enrolled, and 30 eyes of 30 normal control matched with age, gender, and spherical equivalent (SE) were included.Choroidal images of all subjects, and the CMT, subfoveal choroidal thickness (SFCT), choroidal vascularity index (CVI), total choroidal area (TCA), choroidal stromal area (SA), and choroidal luminal area (LA) were measured by Heidelberg enhanced depth imaging optical coherence tomography.The differences in SFCT, LA, SA, TCA, CMT and CVI between the cCSC eye, fellow eye and normal eye, as well as the correlation between SFCT and CVI, SFCT and CMT, and CVI and CMT were analyzed.This study adhered to the Declaration of Helsinki.The study protocol was approved by the Ethics Committee of Renmin Hospital of Wuhan University (No.WDRY2020-K234).Results:The CVI and the SFCT of the cCSC eyes, fellow eyes and normal eyes were (71.67±5.60)% and 483.82(409.01, 550.87)μm, (68.33±3.85)% and 444.66(351.25, 505.15)μm, (64.70±1.88)% and 373.46(327.98, 405.48)μm, respectively.The CMT, SFCT, TCA, LA, CVI in cCSC eyes were significantly higher than those in the contralateral eyes and normal control eyes, while SFCT, TCA, LA, CVI in the contralateral eyes were higher than those in normal control eyes (all at P<0.05). Pairwise comparison among the three groups showed no significant difference in SA (all at P>0.05). Correlation analysis showed that in cCSC eyes, SFCT was strongly positively correlated with CVI ( rs=0.703, P<0.001), and there was no correlation between CMT and SFCT ( rs=0.181, P=0.278), or CMT and CVI ( r=0.231, P=0.164). Conclusions:The SFCT and CVI are higher in cCSC and the fellow eyes compared with normal eyes, and the choroidal vessels are significantly dilated in cCSC patients.The SFCT and CVI of the cCSC eye are slightly higher in comparison with the fellow eye.CMT is not correlated with SFCT or CVI in cCSC eyes.

Object:To explore surgical treatments for duodenal fistula with intra-abdominal infection.Methods:The data of 19 patients with duodenal fistula treated at the Affiliated Tumor Hospital of Zhenzhou University between Jan 2015 and Dec 2021 were analyzed retrospectively. Surgery is performed with duodenostomy or modified duodenal shunt procedures.Result:All patients were accompanied by intra-abdominal infection, including 9 duodenal stump fistulas. All patients successfully completed the operation,11cases underwent duodenostomy, 8 case underwent modified duodenal shunt procedures. operating time was 110(60-140)min, postoperative hospitalization time was 29(9-103)d. Two patients died postoperatively. Fistula heals in other patients.Conclusion:Surgical intervention for duodenal fistula should focus on controlling the source of infection, strengthening intestinal and abdominal drainage, and reducing postoperative complications.

Objective:To investigate the effect of transorally inserted anvil (OrVil TM) in patients with relapsed or denovo carcinoma at the esophagogastric junction. Methods:The clinical data of 60 patients who underwent radical intent resection for locally relapsed or denovo esophagogastric junction adenocarcinoma at Zhengzhou University Cancer Hospital from Jan 2011 to Jun 2021 were retrospectively analyzed. The patients were divided into two groups according to whether transorally inserted anvil was used. Twenty-six patients who had used the system were assigned to the experimental group. Thirty-four patients without transorally inserted anvil were set to control group.Results:The incisor distance of the experimental group was shorter than that of the control group [36(34-40)cm vs. 39(36-41)cm, Z=-4.948, P<0.05]. Operation time in experimental group was 177 (145-260) min, compared to control group of 172 (140-225) min ( Z=-0.735, P=0.463). Intraoperative blood loss was 200 (100-900) ml in the experimental group and 300 (100-800) ml in the control group ( Z=-1.244, P=0.213). Postoperative upper margin distance of the experimental group was (3.6±1.7) cm compared to control group of (1.8±1.1) cm ( t=-0.735, P<0.01). The positive rate of margin in the experimental group was 4% vs. 15% in the control group ( χ2=1.931, P=0.165). The length of postoperative hospital stay in the experimental group was (18.6±5.2) d vs. (20.5±4.7) d ( t=-1.455, P=0.151). Surgery-related complications developed in 19% in the experimental group vs. 27% in the control group ( P>0.05). Conclusion:The application of the transorally inserted anvil in the operation of patients with locally relapsed or denovo esophagogastric junction cancer after initial operation reduces the difficulty of operation and decreases the positive rate of margin.

Humans ; Multiple Myeloma/drug therapy* ; Thalidomide/therapeutic use* ; Dexamethasone/therapeutic use* ; Antineoplastic Combined Chemotherapy Protocols ; Neoplasm Recurrence, Local/drug therapy*