1.Traditional Chinese Medicine Regulates Related Signaling Pathways to Prevent and Control Breast Cancer and Precancerous Lesions: A Review
Yifei ZENG ; Di ZHAO ; Junyue WANG ; Mengjie WANG ; Yubo GUO ; Yu ZHOU ; Dongxiao ZHANG ; Wenjie ZHAO
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(5):290-301
Breast cancer has become the malignant tumor with the highest incidence rate among women, seriously threatening the life and health of women all over the world. The pathogenic factors and development mechanisms of breast cancer are complex and diverse. The development of breast cells from ordinary hyperplasia to atypical hyperplasia, and from pre-cancerous lesions to cancerous lesions, is a long-term progressive process. Therefore, early screening and prevention of breast cancer is particularly important. Western medicine has a relatively mature treatment program for breast cancer, which is mainly based on surgery and systemic treatment, whereas the ensuing complications and adverse reactions often bring a heavy burden to patients. For the precancerous lesions of breast cancer, surgery is also the mainstay of treatment. In recent years, traditional Chinese medicine (TCM) has increasingly highlighted its advantages in the prevention and treatment of breast cancer. Increasing studies have shown that in the prevention and treatment of breast cancer and pre-cancerous lesions, TCM compound prescriptions, single herbs or herb pairs, and active components are able to regulate a variety of intracellular signaling pathways through multi-targets to inhibit the proliferation and invasion, promote the apoptosis and autophagy of tumor cells, and regulate the cell cycle and the immune microenvironment, thus exerting anti-tumor effects. At the same time, they can significantly attenuate the toxic side effects of radiotherapy and drug resistance of patients. However, the specific mechanisms of TCM in the prevention and treatment of breast cancer and precancerous lesions have not been fully clarified. The available studies are tanglesome regarding the TCM inhibition of tumor development through the regulation of classical signaling pathways such as phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt)/mammalian target of rapamycin (mTOR), Wnt/β-catenin, and Notch, which still need to be verified by a large number of clinical and experimental studies. Therefore, this paper reviews the research progress in the prevention and treatment of breast cancer and precancerous lesions by TCM through interfering with the relevant signaling pathways in recent years, aiming to summarize the possible mechanisms of TCM in the prevention and treatment of breast cancer and provide references for subsequent studies.
2.Epidemiological characteristics and disease burden of liver cancer in Guangdong Province
Ying ZHANG ; Yixuan CHEN ; Rong CAO ; Yue GAO ; Yutong HAN ; Ye WANG ; Ruilin MENG ; Xueyan ZHENG ; Yu LIAO ; Zhuanping ZENG
Journal of Public Health and Preventive Medicine 2026;37(1):68-72
Objective To analyze the epidemiological characteristics and disease burden of liver cancer in Guangdong Province in 2020, and to provide a scientific foundation for the development of regionalized prevention and control strategies for liver cancer. Methods According to the cancer registry data of Guangdong Province, the incidence, mortality and age-standardized rate by Chinese standard population in 2020 were calculated to analyze the epidemiological characteristics of liver cancer. The disability adjusted life years (DALYs), year of life loss (YLL), year of lived with disability (YLD), and cause-eliminated life expectancy were used to assess the disease burden of liver cancer. Results In 2020, the crude incidence rate and the age-standardized incidence rate of liver cancer in Guangdong Province were 27.79/100 000 and 20.84/100 000,respectively, and the crude mortality rate and the age-standardized mortality rate of liver cancer were 25.49/100,000 and 17.64/100 000, respectively. The total DALY and DALY rate of liver cancer in Guangdong Province were 515 311 person-years and 513.83/100 000, respectively. After eliminating the causes of death from liver cancer, the life expectancy in Guangdong Province increased from 84.60 years to 84.99 years. All indicators consistently demonstrated that the burden of liver cancer was higher in males than that in females, and the burden of liver cancer was higher in rural areas than that in urban areas. Conclusion Liver cancer in Guangdong Province exhibits a high incidence, mortality and disease burden level in 2020. There are obvious differences of gender, age and region in cancer burden. It is necessary to strengthen liver cancer screening and diagnosis and treatment in men, the elderly and those in rural areas to reduce the burden of liver cancer gradually in Guangdong Province.
3.Epidemiological characteristics of lung cancer in cancer registration areas of Guangdong Province in 2020
CHEN Yixuan ; LIAO Yu ; ZHANG Ying ; GAO Yue ; WANG Ye ; LI Jiansen ; HAN Yutong ; WEI Wenqiang ; ZENG Zhuanping
Journal of Preventive Medicine 2025;37(10):1009-1013
Objective:
To investigate the epidemiological characteristics of lung cancer in cancer registration areas of Guangdong Province in 2020, so as to provide the evidence for improving prevention and control strategies of lung cancer.
Methods:
Data of incidence and mortality in 2020 from 30 cancer registries in Guangdong Province were collected from the Cancer Follow-up Registration System and the All-Cause Mortality Registration Reporting System of the Guangdong Provincial Center for Disease Control and Prevention. The crude incidence, crude mortality, and cumulative rate for 0 to 74 years were calculated. The Chinese population-standardized rate and world population-standardized rate were calculated using the age structure of the standard population from the Fifth National Population Census in 2000 and Segi's world standard population. The incidence and mortality characteristics of lung cancer in different genders, urban/rural areas and ages were described.
Results:
In 2020, there were 25 357 new cases of lung cancer in Guangdong Province. The crude incidence, Chinese population-standardized incidence, world population-standardized incidence, and cumulative incidence for 0 to 74 years were 60.40/100 000, 43.75/100 000, 43.26/100 000, and 5.30%, respectively. There were 14 366 lung cancer deaths. The crude mortality, Chinese population-standardized mortality, world population-standardized mortality, and cumulative mortality for 0 to 74 years were 38.82/100 000, 24.49/100 000, 24.36/100 000, and 2.88%, respectively. The crude incidence and crude mortality of lung cancer in males were higher than those in females (71.19/100 000 vs. 49.42/100 000, 52.94/100 000 vs. 24.36/100 000, both P<0.05). The crude incidence and crude mortality of lung cancer in urban areas were higher than those in rural areas (66.37/100 000 vs. 45.95/100 000, 40.68/100 000 vs. 35.07/100 000, both P<0.05). The crude incidence and crude mortality of lung cancer exhibited upward trends with increasing age (both P<0.05), peaking in the age of 80-<85 years (347.97/100 000 and 342.14/100 000).
Conclusions
Comparing to the national data, the incidence of lung cancer in registration areas of Guangdong Province remained relatively high, while mortality remained relatively low. Males, urban residents and the elderly constitute the key populations for lung cancer prevention and control. It is recommend to optimize the allocation of medical resources between urban and rural areas and strengthen lung cancer screening among high-risk groups.
4.Textual research on the evolution of the meridian-zangfu related theory in the Warring States, Qin and Han dynasties.
Xiaohong CHEN ; Dekun LIU ; Ruibin ZHANG ; Yahan ZENG ; Sha YANG ; Shuguang YU
Chinese Acupuncture & Moxibustion 2025;45(3):280-287
The paper reviews the evolution of the theory related to meridians and zangfu organs during the Warring States, Qin and Han dynasties, so as to reveal the rules and value of its development. By analyzing historical documents, especially Zubi Shiyimai Jiujing (Moxibustion Classics of Eleven Meridians of Legs and Arms), Yinyang Shiyimai Jiujing (Moxibustion Classic on Eleven Yin and Yang Meridians), Laoguanshan bamboo medical slips of Han Dynasty and lacquer figure of meridian points, the evolutionary stages, i.e. the germination, development, and maturity of meridian-zangfu theory, are explored. In the time of the Warring States, Qin and Han dynasties, the meridian-zangfu related theory was developed from the germination to the maturity. In the classics of the early time, Zubi Shiyimai Jiujing and Yinyang Shiyimai Jiujing demonstrated the preliminary relationship between meridians and zangfu organs, focusing on the physiological connection and pathogenesis of three yin meridians of foot and zangfu organs. In the literature of Laoguanshan bamboo medical slips of Han Dynasty and lacquer figure of meridian points, the physiological connection between the yin meridians of hand and foot, and five zang organs, as well as the related diseases were further clarified; additionally, the meridian-zangfu theory had been developed in the field of diagnosis and treatment. In the era of Chapter of Meridians in Lingshu (Miraculous Pivot), there were up to 31 descriptions relevant with the connection of meridian distribution and zangfu physiological functions. It marks the construction of the "circular" flow of meridians and the interior-exterior communication of zang and fu organs; and enriches the knowledge in diseases, diagnosis and treatment with meridians and zangfu organs involved. The review on the evolution of the meridian-zangfu theory is conductive to supplementing and improving the development history of this theory of early time, and further recognizing its development rules and value. The maturity of this theoretical system not only links the meridians with the five zang and six fu organs, but also provides an important theoretical basis for the diagnosis and treatment of traditional Chinese medicine.
Meridians
;
Humans
;
History, Ancient
;
China
;
History, Medieval
;
History, 19th Century
;
History, 20th Century
;
History, 18th Century
;
History, 17th Century
;
History, 16th Century
;
Medicine, Chinese Traditional/history*
5.Mechanism of electroacupuncture-induced macrophage polarization in promoting acute skeletal muscle injury repair in rats.
Yuting HUANG ; Yuye LIN ; Guojun ZHANG ; Chufan ZENG ; Xia ZHANG ; Jingyu ZHANG ; Yu KAN ; Yanping FANG ; Xianghong JING ; Jun LIAO
Chinese Acupuncture & Moxibustion 2025;45(6):791-800
OBJECTIVE:
To investigate the potential mechanism by which electroacupuncture (EA) induces macrophage polarization to promote muscle satellite cell proliferation and differentiation, accelerating the repair of acute skeletal muscle injury.
METHODS:
Forty-two SPF-grade SD rats were randomly divided into three groups: a blank group (n=6), a model group (n=18), and an EA group (n=18). The model and EA groups established acute blunt contusion model of the right gastrocnemius muscle using a self-made striking device. From day 1 after modeling, rats in the EA group received EA at "Chengshan" (BL57) and "Yanglingquan" (GB34) on the right side, using disperse-dense wave with a frequency of 2 Hz/100 Hz and a current of approximately 2 mA. The EA treatment was administered once daily for 30 minutes for 3, 7, or 14 days based on the designated sampling time points. Gait analysis was performed using the Cat Walk XTTM system. Hematoxylin-eosin (HE) staining was used to observe the morphological changes in the gastrocnemius muscle. Masson staining was applied to evaluate collagen fiber content. Immunofluorescence was used to detect the expression of proliferating cell nuclear antigen (PCNA) in muscle satellite cells. Immunohistochemistry was used to assess the expression levels of CD68 and CD206, markers of macrophages. Serum levels of pro-inflammatory cytokines (TNF-α, IL-1β) and anti-inflammatory cytokines (IL-10, IL-13) were detected using ELISA.
RESULTS:
Compared with the blank group, the model group showed a significant reduction in average movement speed on days 3 and 7 after modeling (P<0.05), and a decrease in the right hind limb stride length on day 3 (P<0.05). Compared with the model group, the EA group showed increased average movement speed and right hind limb stride length on day 7 (P<0.05). In the blank group, the gastrocnemius muscle on the right side showed uniform and consistent inter-fiber spacing, with neatly and regularly arranged muscle cells. In contrast, the model group exhibited enlarged inter-fiber spacing, edema, and significant infiltration of red blood cells and inflammatory cells, with progressively increasing fibrosis over time. By day 14 after modeling, the EA group showed a return to baseline levels of inflammatory cell infiltration, and the degree of fibrosis was significantly lower than that observed in the model group. Compared with the blank group, the ratio of collagen fibers in the gastrocnemius muscle of the model group increased significantly on days 3, 7, and 14 after modeling (P<0.05). Compared with the model group, the EA group exhibited a lower collagen fiber ratio on days 3, 7, and 14 (P<0.05). Compared with the blank group, PCNA positive expression in the gastrocnemius muscle of the model group was significantly increased on days 3, 7, and 14 after modeling (P<0.05). Compared with the model group, the EA group exhibited significantly higher PCNA positive expression on days 3 and 7 (P<0.05). Compared with the blank group, the model group showed a significant increase in CD68-positive macrophage expression in the gastrocnemius muscle on day 3 after modeling (P<0.05), while CD206-positive macrophage expression increased on days 3, 7, and 14 (P<0.05). Compared with the model group, CD68 expression was significantly lower in the EA group on day 3 (P<0.05), whereas CD206 expression was significantly higher on days 3 and 7 (P<0.05), peaking on day 7 with CD206 expression. Compared with the blank group, serum TNF-α levels were significantly elevated in the model group on days 3 and 7 after modeling (P<0.05), while serum IL-1β levels were increased on days 3, 7, and 14 (P<0.05). Serum IL-10 and IL-13 levels were significantly higher on day 7 after modeling (P<0.05). Compared with the model group, the EA group exhibited lower serum TNF-α level on day 3 (P<0.05) and reduced serum IL-1β levels on days 3 and 7 (P<0.05), while serum IL-10 and IL-13 levels were significantly increased on day 7 (P<0.05).
CONCLUSION
EA could promote the repair of acute blunt contusion-induced gastrocnemius muscle injury by regulating the proliferation and differentiation of muscle satellite cells. This process is closely related to macrophage polarization.
Animals
;
Electroacupuncture
;
Rats, Sprague-Dawley
;
Rats
;
Macrophages/immunology*
;
Muscle, Skeletal/immunology*
;
Male
;
Humans
;
Female
;
Tumor Necrosis Factor-alpha/immunology*
;
Cell Proliferation
6.Percutaneous coronary intervention vs . medical therapy in patients on dialysis with coronary artery disease in China.
Enmin XIE ; Yaxin WU ; Zixiang YE ; Yong HE ; Hesong ZENG ; Jianfang LUO ; Mulei CHEN ; Wenyue PANG ; Yanmin XU ; Chuanyu GAO ; Xiaogang GUO ; Lin CAI ; Qingwei JI ; Yining YANG ; Di WU ; Yiqiang YUAN ; Jing WAN ; Yuliang MA ; Jun ZHANG ; Zhimin DU ; Qing YANG ; Jinsong CHENG ; Chunhua DING ; Xiang MA ; Chunlin YIN ; Zeyuan FAN ; Qiang TANG ; Yue LI ; Lihua SUN ; Chengzhi LU ; Jufang CHI ; Zhuhua YAO ; Yanxiang GAO ; Changan YU ; Jingyi REN ; Jingang ZHENG
Chinese Medical Journal 2025;138(3):301-310
BACKGROUND:
The available evidence regarding the benefits of percutaneous coronary intervention (PCI) on patients receiving dialysis with coronary artery disease (CAD) is limited and inconsistent. This study aimed to evaluate the association between PCI and clinical outcomes as compared with medical therapy alone in patients undergoing dialysis with CAD in China.
METHODS:
This multicenter, retrospective study was conducted in 30 tertiary medical centers across 12 provinces in China from January 2015 to June 2021 to include patients on dialysis with CAD. The primary outcome was major adverse cardiovascular events (MACE), defined as a composite of cardiovascular death, non-fatal myocardial infarction, and non-fatal stroke. Secondary outcomes included all-cause death, the individual components of MACE, and Bleeding Academic Research Consortium criteria types 2, 3, or 5 bleeding. Multivariable Cox proportional hazard models were used to assess the association between PCI and outcomes. Inverse probability of treatment weighting (IPTW) and propensity score matching (PSM) were performed to account for potential between-group differences.
RESULTS:
Of the 1146 patients on dialysis with significant CAD, 821 (71.6%) underwent PCI. After a median follow-up of 23.0 months, PCI was associated with a 43.0% significantly lower risk for MACE (33.9% [ n = 278] vs . 43.7% [ n = 142]; adjusted hazards ratio 0.57, 95% confidence interval 0.45-0.71), along with a slightly increased risk for bleeding outcomes that did not reach statistical significance (11.1% vs . 8.3%; adjusted hazards ratio 1.31, 95% confidence interval, 0.82-2.11). Furthermore, PCI was associated with a significant reduction in all-cause and cardiovascular mortalities. Subgroup analysis did not modify the association of PCI with patient outcomes. These primary findings were consistent across IPTW, PSM, and competing risk analyses.
CONCLUSION
This study indicated that PCI in patients on dialysis with CAD was significantly associated with lower MACE and mortality when comparing with those with medical therapy alone, albeit with a slightly increased risk for bleeding events that did not reach statistical significance.
Humans
;
Percutaneous Coronary Intervention/methods*
;
Male
;
Female
;
Coronary Artery Disease/drug therapy*
;
Retrospective Studies
;
Renal Dialysis/methods*
;
Middle Aged
;
Aged
;
China
;
Proportional Hazards Models
;
Treatment Outcome
7.Complex associations among modifiable determinants of circadian syndrome among employed people in southwestern China.
Shujuan YANG ; Peng JIA ; Lei ZHANG ; Yuchen LI ; Peng YU ; Jiqi YANG ; Sihan WANG ; Honglian ZENG ; Bo YANG ; Bin YU
Chinese Medical Journal 2025;138(21):2804-2812
BACKGROUND:
Circadian syndrome (CircS) may be closely linked to lifestyle, psychological, and occupational factors, but evidence is lacking. This study aimed to explore complex associations between lifestyle, psychological and occupational factors and CircS among employed people in southwestern China.
METHODS:
In this study, network analysis was used to identify complex associations between lifestyle, psychological and occupational factors and CircS in employed people from the Chinese Cohort of Working Adults (CCWA). The centrality of each variable was estimated by strength centrality index, which was calculated by the sum of edge weights connected to the variable. Bridge in the network was identified as the variables in the top 80 th percentile of overall bridge strength, which was defined as the most strongly connected variables across lifestyle, psychological and occupational factors and CircS. The differences were assessed in network structures between subgroups divided by the median score of the variable with the strongest bridge strengthen.
RESULTS:
Among 31,105 participants from CCWA, 5213 (16.76%) had CircS. In the constructed network, anxiety (edge weights: 0.28), smoking (edge weights: 0.15), drinking (edge weights: 0.10), perceived noise at work (edge weights: 0.08), and implicit health attitude (edge weights: -0.02) were directly related to CircS, with 83.31% of the variance for CircS explained by these neighboring factors. Anxiety was the most central variable (strength centrality: 1.20) in the network and the strongest bridge (bridge strength: 0.84) connecting all domains of variables. A stronger association between anxiety and CircS was observed in the network of participants with more severe anxiety (edge weight: 0.23) than those with less severe anxiety (edge weight: 0.03).
CONCLUSION
Anxiety had the strongest association with CircS and was the central factor with the highest strength centrality, also the bridge with the highest bridge strength in the network.
Humans
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Male
;
Female
;
Adult
;
China
;
Middle Aged
;
Life Style
;
Chronobiology Disorders/epidemiology*
8.The interval of rescue treatment does not affect the efficacy and safety of Helicobacter pylori eradication: A prospective multicenter observational study.
Minjuan LIN ; Junnan HU ; Jing LIU ; Juan WANG ; Zhongxue HAN ; Xiaohong WANG ; Zhenzhen ZHAI ; Yanan YU ; Wenjie YUAN ; Wen ZHANG ; Zhi WANG ; Qingzhou KONG ; Boshen LIN ; Yuming DING ; Meng WAN ; Wenlin ZHANG ; Miao DUAN ; Shuyan ZENG ; Yueyue LI ; Xiuli ZUO ; Yanqing LI
Chinese Medical Journal 2025;138(12):1439-1446
BACKGROUND:
The effect of the interval between previous Helicobacter pylori (H. pylori) eradication and rescue treatment on therapeutic outcomes remains unknown. The aim of this study was to investigate the association between eradication rates and treatment interval durations in H. pylori infections.
METHODS:
This prospective observational study was conducted from December 2021 to February 2023 at six tertiary hospitals in Shandong, China. We recruited patients who were positive for H. pylori infection and required rescue treatment. Demographic information, previous times of eradication therapy, last eradication therapy date, and history of antibiotic use data were collected. The patients were divided into four groups based on the rescue treatment interval length: Group A, ≥4 weeks and ≤3 months; Group B, >3 and ≤6 months; Group C, >6 and ≤12 months; and Group D, >12 months. The primary outcome was the eradication rate of H. pylori . Drug compliance and adverse events (AEs) were also assessed. Pearson's χ2 test or Fisher's exact test was used to compare eradication rates between groups.
RESULTS:
A total of 670 patients were enrolled in this study. The intention-to-treat (ITT) eradication rates were 88.3% (158/179) in Group A, 89.6% (120/134) in Group B, 89.1% (123/138) in Group C, and 87.7% (192/219) in Group D. The per-protocol (PP) eradication rates were 92.9% (156/168) in Group A, 94.5% (120/127) in Group B, 94.5% (121/128) in Group C, and 93.6% (190/203) in Group D. There was no statistically significant difference in the eradication rates between groups in either the ITT ( P = 0.949) or PP analysis ( P = 0.921). No significant differences were observed in the incidence of AEs ( P = 0.934) or drug compliance ( P = 0.849) between groups.
CONCLUSION:
The interval duration of rescue treatment had no significant effect on H. pylori eradication rates or the incidence of AEs.
REGISTRATION
ClinicalTrials.gov , NCT05173493.
Humans
;
Helicobacter Infections/drug therapy*
;
Helicobacter pylori/pathogenicity*
;
Male
;
Female
;
Prospective Studies
;
Middle Aged
;
Anti-Bacterial Agents/adverse effects*
;
Adult
;
Aged
;
Treatment Outcome
;
Proton Pump Inhibitors/therapeutic use*
9.Expert consensus on clinical application of Suhuang Zhike Capsules in treatment of respiratory diseases.
Yu MING ; Chang-Rui HUANG ; Bang YU ; Wen-Jing CHANG ; Zeng-Tao SUN ; Wei CHEN ; Hong-Chun ZHANG
China Journal of Chinese Materia Medica 2025;50(3):817-823
Suhuang Zhike Capsules are widely used in clinical practice for the treatment of respiratory diseases and have been included in Medicine Catalogue for National Basic Medical Insurance, Work Injury Insurance, and Maternity Insurance and National Essential Medicines List. However, problems remain, such as unclear definitions of treatment courses and unidentified contraindications for certain populations. Therefore, this consensus was developed collaboratively by clinical experts in traditional Chinese medicine(TCM) related to pulmonary diseases, respiratory, and critical care medicine, as well as methodology and pharmacy experts, adhering strictly to the consensus development procedures established by the China Association of Chinese Medicine for clinical application of Chinese patent medicines, with the aim to guide the correct clinical use of Suhuang Zhike Capsules for the treatment of cough variant asthma, post-infectious cough, and other respiratory diseases. This consensus employed questionnaire surveys and expert interviews to identify clinical concerns based on the PICOS principle and conduct evidence evaluation and GRADE grading. Utilizing nominal group techniques and GRADE networking methods, it resulted in 17 recommendations and consensus suggestions. The consensus further clarifies the indications, TCM syndromes, usage, and clinical safety of Suhuang Zhike Capsules in the treatment of cough variant asthma and post-infectious cough, aiming to promote standardized medication use and facilitate the rational clinical application of Suhuang Zhike Capsules.
Humans
;
Drugs, Chinese Herbal/administration & dosage*
;
Consensus
;
Capsules
;
Respiratory Tract Diseases/drug therapy*
;
Medicine, Chinese Traditional
10.Study on mechanism of naringin in alleviating cerebral ischemia/reperfusion injury based on DRP1/LRRK2/MCU axis.
Kai-Mei TAN ; Hong-Yu ZENG ; Feng QIU ; Yun XIANG ; Zi-Yang ZHOU ; Da-Hua WU ; Chang LEI ; Hong-Qing ZHAO ; Yu-Hong WANG ; Xiu-Li ZHANG
China Journal of Chinese Materia Medica 2025;50(9):2484-2494
This study aims to investigate the molecular mechanism by which naringin alleviates cerebral ischemia/reperfusion(CI/R) injury through DRP1/LRRK2/MCU signaling axis. A total of 60 SD rats were randomly divided into the sham group, the model group, the sodium Danshensu group, and low-, medium-, and high-dose(50, 100, and 200 mg·kg~(-1)) naringin groups, with 10 rats in each group. Except for the sham group, a transient middle cerebral artery occlusion/reperfusion(tMCAO/R) model was established in SD rats using the suture method. Longa 5-point scale was used to assess neurological deficits. 2,3,5-Triphenyl tetrazolium chloride(TTC) staining was used to detect the volume percentage of cerebral infarction in rats. Hematoxylin-eosin(HE) staining and Nissl staining were employed to assess neuronal structural alterations and the number of Nissl bodies in cortex, respectively. Western blot was used to determine the protein expression levels of B-cell lymphoma-2 gene(Bcl-2), Bcl-2-associated X protein(Bax), cleaved cysteine-aspartate protease-3(cleaved caspase-3), mitochondrial calcium uniporter(MCU), microtubule-associated protein 1 light chain 3(LC3), and P62. Mitochondrial structure and autophagy in cortical neurons were observed by transmission electron microscopy. Immunofluorescence assay was used to quantify the fluorescence intensities of MCU and mitochondrial calcium ion, as well as the co-localization of dynamin-related protein 1(DRP1) with leucine-rich repeat kinase 2(LRRK2) and translocase of outer mitochondrial membrane 20(TOMM20) with LC3 in cortical mitochondria. The results showed that compared with the model group, naringin significantly decreased the volume percentage of cerebral infarction and neurological deficit score in tMCAO/R rats, alleviated the structural damage and Nissl body loss of cortical neurons in tMCAO/R rats, inhibited autophagosomes in cortical neurons, and increased the average diameter of cortical mitochondria. The Western blot results showed that compared to the sham group, the model group exhibited increased levels of cleaved caspase-3, Bax, MCU, and the LC3Ⅱ/LC3Ⅰ ratio in the cortex and reduced protein levels of Bcl-2 and P62. However, naringin down-regulated the protein expression of cleaved caspase-3, Bax, MCU and the ratio of LC3Ⅱ/LC3Ⅰ ratio and up-regulated the expression of Bcl-2 and P62 proteins in cortical area. In addition, immunofluorescence analysis showed that compared with the model group, naringin and positive drug treatments significantly decreased the fluorescence intensities of MCU and mitochondrial calcium ion. Meanwhile, the co-localization of DRP1 with LRRK2 and TOMM20 with LC3 in cortical mitochondria was also decreased significantly after the intervention. These findings suggest that naringin can alleviate cortical neuronal damage in tMCAO/R rats by inhibiting DRP1/LRRK2/MCU-mediated mitochondrial fragmentation and the resultant excessive mitophagy.
Animals
;
Rats, Sprague-Dawley
;
Reperfusion Injury/genetics*
;
Flavanones/administration & dosage*
;
Rats
;
Dynamins/genetics*
;
Male
;
Brain Ischemia/genetics*
;
Protein Serine-Threonine Kinases/genetics*
;
Signal Transduction/drug effects*
;
Humans
;
Drugs, Chinese Herbal/administration & dosage*


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