1.Baicalein attenuates lipopolysaccharide-induced myocardial injury by inhibiting ferroptosis via miR-299b-5p/HIF1-α pathway.
Wen-Yan ZHOU ; Jian-Kui DU ; Hong-Hong LIU ; Lei DENG ; Kai MA ; Jian XIAO ; Sheng ZHANG ; Chang-Nan WANG
Journal of Integrative Medicine 2025;23(5):560-575
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*
2.Study on analgesic effect of anterior quadratus lumborum block at lateral supra-arcuate ligament and transversus abdominis plane block in analgesia in patients undergoing laparoscopic partial hepatectomy
Lingling JIANG ; Yun LI ; Kui SHENG ; Lili ZHANG ; Yang HU ; Ye ZHANG
Tianjin Medical Journal 2024;52(3):302-306
Objective To observe the effect of ultrasound-guided anterior quadratus lumborum block at lateral supra-arcuate ligament(QLB-LSAL)and transversus abdominis plane block(TAPB)on analgesia and recovery quality after laparoscopic partial hepatectomy(LPH).Methods Fifty-eight patients underwent elective LPH were selected and divided into the quadratus lumborum group or the transversus abdominis group randomly,with 29 patients in each group.The quadratus lumborum group received bilateral QLB-LSAL,and the transversus abdominis group received bilateral subcostal TAPB block before surgery.Both groups received 20 mL of 0.33%ropivacaine on each side.All patients used patient-controlled intravenous analgesia(PCIA)postoperatively.The numeric rating scale(NRS)scores for rest and movement were recorded at 2,4,6,12,24 and 48 hours postoperatively,as well as the Quality of Recovery-15(QoR-15)scores at 1 day preoperatively,1 and 3 days postoperatively.The perioperative anesthetic agent consumption,PCIA pressing frequency,remedial analgesia use in 48 h,postoperative nausea and vomiting(PONV)incidence and time of first out-of-bed mobilization were also recorded.Results Compared with the transversus abdominis group,the quadratus lumborum group had lower movement NRS scores at 2,4,6,12,24 and 48 hours postoperatively,and lower rest NRS scores at 2,4,6,12 and 24 hours postoperatively(P<0.05).The quadratus lumborum group had higher QoR-15 scores at 1 and 3 days postoperatively(P<0.05).Patients in the quadratus lumborum group had reduced perioperative remifentanil and sufentanil consumption,postoperative 48-hour rescue analgesia use,PCIA pressing frequency,PONV incidence and time of first out-of-bed mobilization(P<0.05).Conclusion QLB-LSAL block provides superior analgesic effects and recovery quality compared to TAPB block after LPH.
3.Research progress on inflammatory mechanism and treatment in aneurysmal subarachnoid hemorrhage
Ming ZHANG ; Xiao-Wei SONG ; Xiao-Kui GAN ; Yi-Ming FANG ; Bao-Sheng HUANG
Medical Journal of Chinese People's Liberation Army 2024;49(11):1336-1342
Aneurysmal subarachnoid hemorrhage(aSAH),primarily caused by the rupture of intracranial aneurysms with bleeding into the subarachnoid space,is an acute neurological disease associated with high disability and mortality.Brain injury after aSAH results from a combination of injury mechanisms,with early brain injury(EBI)occurring within 72 hours post-onset,laying the foundation for subsequent pathophysiological changes in the brain and poor prognosis of patients.Among them,the brain immunoinflammatory response,involving the interaction of various immune cells and active substances,plays a significant role in post-aSAH EBI,and is related to delayed brain injury and long-term prognosis.Systemic inflammatory response following aSAH can also affect the prognosis and outcome of patients.This review summarizes the role of local and systemic immune inflammatory responses in the occurrence and progression of aSAH,as well as the research progress on related inflammatory biomarkers and therapeutic prospects,aiming to provide a theoretical reference for new treatment for aSAH.
4.Effects of orientation and distance of goats on blast lung injury characteristics on a plateau above 4500-meter.
Zhao-Xia DUAN ; Guan-Hua LI ; Jie-Yuan ZHANG ; Meng-Sheng DENG ; Kui-Jun CHEN ; Liang-Chao ZHANG ; Xiang-Yun CHENG ; Jing CHEN ; Guang-Ming YANG ; Jian-Min WANG
Chinese Journal of Traumatology 2023;26(3):139-146
PURPOSE:
High explosives are used to produce blast waves to study their biological effects. The lungs are considered as the critical target organ in blast-effect studies. The degree of lung hemorrhaging is related to both the explosive power and the increased lung weight. We studied the characteristics of the biological effects from an air explosion of a thermobaric bomb in a high-altitude environment and the lethality and lung injury severity of goats in different orientations and distances.
METHODS:
Goats were placed at 2.5, 3, 4, and 5 m from the explosion center and exposed them to an air blast at an altitude of 4700-meter. A group of them standing oriented to the right side and the other group seated facing the explosion center vertically. The lung injuries were quantified according to the percentage of surface area contused, and using the pathologic severity scale of lung blast injury (PSSLBI) to score the 4 injury categories (slight, moderate, serious and severe) as 1, 2, 3, and 4, respectively. The lung coefficient (lung weight [g]/body weight [kg]) was the indicator of pulmonary edema and was related to lung injury severity. Blast overpressure data were collected using blast test devices placed at matching locations to represent loadings to goats. All statistical analyses were performed using SPSS, version 26.0, statistical software (SPSS, Inc., Chicago, IL, USA).
RESULTS:
In total, 127 goats were involved in this study. Right-side-standing goats had a significantly higher mortality rate than those seated vertical-facing (p < 0.05). At the 2.5 m distance, the goat mortality was nearly 100%, whereas at 5 m, all the goats survived. Lung injuries of the right-side-standing goats were 1 - 2 grades more serious than those of seated goats at the same distances, the scores of PSSLBI were significantly higher than the seated vertical-facing goats (p < 0.05). The lung coefficient of the right-side-standing goats were significantly higher than those of seated vertical-facing (p < 0.05). Mortality, PSSLBI, and the lung coefficient results indicated that the right-side-standing goats experienced severer injuries than the seated vertical-facing goats, and the injuries were lessened as the distance increased. The blast overpressure was consistent with these results.
CONCLUSION
The main killing factors of the thermobaric bomb in the high-altitude environment were blast overpressure, blast wind propulsions and burn. The orientation and distances of the goats significantly affected the blast injury severity. These results may provide a research basis for diagnosing, treating and protecting against injuries from thermobaric explosions.
Animals
;
Lung Injury/etiology*
;
Blast Injuries
;
Goats
;
Explosions
;
Lung/pathology*
5.Combination immunotherapy of glioblastoma with dendritic cell cancer vaccines,anti-PD-1 and poly I:C
Ping ZHU ; Shi-You LI ; Jin DING ; Zhou FEI ; Sheng-Nan SUN ; Zhao-Hui ZHENG ; Ding WEI ; Jun JIANG ; Jin-Lin MIAO ; San-Zhong LI ; Xing LUO ; Kui ZHANG ; Bin WANG ; Kun ZHANG ; Su PU ; Qian-Ting WANG ; Xin-Yue ZHANG ; Gao-Liu WEN ; Jun O.LIU ; Thomas-John AUGUST ; Huijie BIAN ; Zhi-Nan CHEN ; You-Wen HE
Journal of Pharmaceutical Analysis 2023;13(6):616-624
Glioblastoma(GBM)is a lethal cancer with limited therapeutic options.Dendritic cell(DC)-based cancer vaccines provide a promising approach for GBM treatment.Clinical studies suggest that other immu-notherapeutic agents may be combined with DC vaccines to further enhance antitumor activity.Here,we report a GBM case with combination immunotherapy consisting of DC vaccines,anti-programmed death-1(anti-PD-1)and poly I:C as well as the chemotherapeutic agent cyclophosphamide that was integrated with standard chemoradiation therapy,and the patient remained disease-free for 69 months.The patient received DC vaccines loaded with multiple forms of tumor antigens,including mRNA-tumor associated antigens(TAA),mRNA-neoantigens,and hypochlorous acid(HOCl)-oxidized tumor lysates.Furthermore,mRNA-TAAAs were modified with a novel TriVac technology that fuses TAAs with a destabilization domain and inserts TAAs into full-length lysosomal associated membrane protein-1 to enhance major histo-compatibility complex(MHC)class Ⅰ and Ⅱ antigen presentation.The treatment consisted of 42 DC cancer vaccine infusions,26 anti-PD-1 antibody nivolumab administrations and 126 poly I:C injections for DC infusions.The patient also received 28 doses of cyclophosphamide for depletion of regulatory T cells.No immunotherapy-related adverse events were observed during the treatment.Robust antitumor CD4+and CD8+T-cell responses were detected.The patient remains free of disease progression.This is the first case report on the combination of the above three agents to treat glioblastoma patients.Our results suggest that integrated combination immunotherapy is safe and feasible for long-term treatment in this patient.A large-scale trial to validate these findings is warranted.
6.Overexpression of Protein Phosphatase 2 Regulatory Subunit B"Alpha Promotes Glycolysis by Regulating Hexokinase 1 in Hepatocellular Carcinoma.
Ning JIAO ; Wan Sheng JI ; Biao ZHANG ; Yu Kui SHANG ; Yu Chen ZHANG ; Wei Qun YU ; Hai Long JIN ; Chao LI ; Cheng Ying ZHANG ; Cheng YAN ; Wen YUE ; Qing ZHANG
Biomedical and Environmental Sciences 2022;35(7):622-632
Objective:
To investigate the regulatory relationship of Protein Phosphatase 2 Regulatory Subunit B"Alpha ( PPP2R3A) and hexokinase 1 ( HK1) in glycolysis of hepatocellular carcinoma (HCC).
Methods:
In HepG2 and Huh7 cells, PPP2R3A expression was silenced by small interfering RNA (siRNA) and overexpression by plasmid transfection. The PPP2R3A-related genes were searched by RNA sequencing. Glycolysis levels were measured by glucose uptake and lactate production. QRT-PCR, ELISA, western blot and immunofluorescence assay were performed to detect the changes of PPP2R3A and HK1. Cell proliferation, migration and invasion assay were used to study the roles of HK1 regulation by PPP2R3A.
Results:
RNA sequencing data revealed that PPP2R3A siRNA significantly downregulated the expression of HK1. PPP2R3A gene overexpression promotes, while gene silencing suppresses, the level of HK1 and glycolysis in HCC cells. In HCC tissue samples, PPP2R3A and HK1 were colocalized in the cytoplasm, and their expression showed a positive correlation. HK1 inhibition abrogated the promotion of glycolysis, proliferation, migration and invasion by PPP2R3A overexpression in liver cancer cells.
Conclusion
Our findings showed the correlation of PPP2R3A and HK1 in the glycolysis of HCC, which reveals a new mechanism for the oncogenic roles of PPP2R3A in cancer.
Carcinoma, Hepatocellular/pathology*
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Cell Line, Tumor
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Cell Proliferation
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Gene Expression Regulation, Neoplastic
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Glycolysis
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Hexokinase/metabolism*
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Humans
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Liver Neoplasms/pathology*
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Protein Phosphatase 2/metabolism*
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RNA, Small Interfering/metabolism*
7. Distribution of gene polymorphism in folate metabolism pathway and its effect on serumhomocysteine concentration
Chunyan YANG ; Wen ZHANG ; Peipei WANG ; Jing PENG ; Jia JIANG ; Jing SONG ; Jun LIU ; Yueran LI ; Kui YANG ; Sheng WANG ; Zhenyu XU ; Jiajie LUAN
Chinese Journal of Clinical Pharmacology and Therapeutics 2021;26(11):1259-1264
AIM: To study the polymorphism distribution of methylenetetrahydrofolate reductase (MTHFR) and methionine synthase reductase (MTRR) genes and their influence on serum homocysteine (Hcy) concentration. METHODS: A total of 148 patients diagnosed with ischemic stroke from November 2020 to February 2021 in Yijishan Hospital of Wanan Medical College were selected for the study, and patients were typed for MTHFR 677C/T and MTRR 66A/G genes using fluorescent staining in situ hybridization technique. Serum Hcy concentrations were measured in 21 patients using a circulating enzyme assay. The distribution of MTHFR 677C/T and MTRR 66A/G gene polymorphisms were analyzed, and the differences in serum Hcy concentrations between patients with different genotypes were compared. RESULTS: The mutation rates of MTHFR 677C/T and MTRR 66A/G genes were 42.57% and 26.01%, respectively, and no significant differences in gene distribution frequencies were observed between men and women (P>0.05). The mean Hcy serum concentration was (16.04±4.34) μmol/L in 21 patients, including 8 patients (38.10%) with <15 μmol/L and 13 patients (61.90%) with ≥15 μmol/L. The Hcy serum concentrations in patients with different genotypes of MTHFR were TT (18.91±5.34) μmol/L, CT (14.38±1.84) μmol/L and CC (13.58±2.86) μmol/L, respectively, and were statistically different (P<0.001). Serum Hcy concentrations in patients with different genotypes of MTRR were not statistically different (P>0.05). CONCLUSION: MTHFR gene polymorphisms can affect serum Hcy concentrations. The MTHFR genotyping can be considered for individualized folic acid supplement. This conclusion should be further verified by expanding the clinical sample size.
8.Two newly recorded species of plants in Jiangxi province.
Chao CHEN ; Hua-Sheng PENG ; Hui-Ting ZENG ; Xiao-Bo ZHANG ; Yan-Kui CHENG ; Yuan YUAN ; Jin-Bao YU ; Lu-Qi HUANG
China Journal of Chinese Materia Medica 2021;46(5):1117-1119
Based on the investigation of wild medicinal plant resources in Dexing city, Jiangxi province, and the collected plant specimens, which were identified by taxonomy, two new record species of geographical distribution were found, which are Meehania zheminensis A. Takano, Pan Li & G.-H. Xia and Corydalis huangshanensis L.Q.Huang & H.S.Peng. The voucher specimens are kept in Dexing museum of traditional Chinese medicine. In this paper, the new distribution species were reported, which provides valuable information for further enriching and supplementing the species diversity of medicinal plant resources in Jiangxi province.
China
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Corydalis
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Humans
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Lamiaceae
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Medicine, Chinese Traditional
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Museums
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Plants, Medicinal
9.Closed folding apex manipulation combined with splinting for the treatment of double fractures of distal ulna and radius in children.
Hong-Feng SHENG ; Jian-Wei LU ; Qiao-Feng GUO ; Kai HUANG ; Yi-Yang LIU ; Zhen WU ; Bin-Feng JIANG ; Bin XU ; Kui ZHANG ; Pei-Xiang ZHANG ; Yang-Jun LAO
China Journal of Orthopaedics and Traumatology 2021;34(2):153-156
OBJECTIVE:
To investigate specific technique and clinical effects of closed folding top consolidation maneuver combined with splint fixation maneuver for consolidation and cedar bark external fixation splint for the treatment of double fractures of distal ulna and radius in children.
METHODS:
From January 2017 to December 2019, 17 children with double fractures of distal ulna and radius were treated with closed folded apex consolidation maneuver, including 13 males and 4 females, aged from 4 to 11 years old with an average of (7.29±2.34) years old. The fractures were fixed with cedar bark splint and followed up for 6 months, and alignment of fracture was evaluated according to the latest X-rays by follow up, and function of the affected limbs was evaluated by Anderson forearm function evaluation criteria.
RESULTS:
Fifteen of 17 children were successfully reset immediately, and 2 children were successfully reset again. The average fixed time was (25.00±3.35) days. At 6 months of follow up, 12 patients got excellent results, 3 good, 2 fair, and 0 poor according to Anderson forearm function evaluation criteria. The position of all children were larger than 3/4, and 10 children were received anatomical reduction, alignment of 4 children was less than 10°, 3 children was less than 15°. No complications such as fracture displacement, nonunion, compartment syndrome, and forearm rotation dysfunction occurred.
CONCLUSION
Restoration of distal radius double fracture in children with the combination of the closed folding and top fixation maneuver and splint fixation maneuver has advantages of higher success rate, lower complications, which could reduce operating difficultyand pain of patients.
Aged
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Child
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Child, Preschool
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Female
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Fracture Fixation
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Fracture Fixation, Internal
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Humans
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Male
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Radius
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Radius Fractures/therapy*
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Splints
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Treatment Outcome
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Ulna
;
Ulna Fractures
10. Analysis of influencing factors of metabolic syndrome in male occupational population in mineral industry
Le-yan ZHANG ; Chao XUE ; Han WANG ; Qing-lin LI ; Sheng-kui ZHANG ; Yong-bin WANG ; Ju-xiang YUAN
China Occupational Medicine 2021;48(01):73-76
OBJECTIVE: To study the prevalence and influencing factors of metabolic syndrome(MS) in male occupational population in the mineral industry. METHODS: A total of 2 654 male employees in the mining area of a mining group in Xingtai City were selected as the study subjects using the convenient sampling method. The general demographic data, behavior and lifestyle, work status, and biochemical examination results of the study subjects were collected, and the influencing factors of MS were analyzed by multi-factor logistic regression. RESULTS: The detection rate of MS was 16.0%(425/2 654) in these 2 654 male workers. The detection rate of MS increased with age and length of service(all P<0.05). The detection rate of MS in male workers with hypertension, high blood sugar, central obesity, high triglyceride and low high-density lipoprotein was higher than that in control workers(all P<0.01). The results of multivariate logistic regression analysis showed that age, work shifts, salt intake, dietary habit, alcohol drinking, sleep time, physical exercise, and body mass index were all influencing factors for MS(all P<0.05). CONCLUSION: Male workers have a high incidence of MS. Older age, shift work, high-salt diet, meat-based diet, alcohol drinking, severely insufficient sleep time, and overweight/obesity increase the risk of MS in male workers.

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