1.Sanren Runchang Formula Regulates Brain-gut Axis to Treat IBS-C: A Randomized Controlled Trial
Teng LI ; Xinrong FAN ; He YAN ; Zhuozhi GONG ; Mengxi YAO ; Na YANG ; Yuhan WANG ; Huikai HU ; Wei WEI ; Tao LIU
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(2):154-161
ObjectiveTo observe the clinical efficacy of Sanren Runchang formula in treating constipation-predominant irritable bowel syndrome (IBS-C) by regulating the brain-gut axis and the effects of the formula on serum levels of 5-hydroxytryptamine (5-HT), vasoactive intestinal peptide (VIP), and substance P (SP). MethodsA randomized controlled design was adopted, and 72 IBS-C patients meeting Rome Ⅳ criteria were randomized into observation and control groups (36 cases).The observation group received Sanren Runchang formula granules twice daily, and the control group received lactulose oral solution daily for 4 weeks. IBS Symptom Severity Scale (IBS-SSS), IBS Quality of Life Scale (IBS-QOL), and Bristol Stool Form Scale (BSFS) were used to assess clinical symptoms, and bowel movement frequency was recorded. The Self-Rating Anxiety Scale (SAS) and Self-Rating Depression Scale (SDS) were employed to evaluate psychological status. ELISA was employed to measure the serum levels of 5-HT, VIP, and SP. ResultsThe total response rate in the observation group was 91.67% (33/36), which was higher than that (77.78%, 28/36) in the control group (χ2=4.50, P<0.05). After treatment, both groups showed increased defecation frequency and BSFS scores, decreased IBS-SSS total score, abdominal pain and bloating scores, IBS-QOL health anxiety, anxiety, food avoidance, and behavioral disorders scores, SAS and SDS scores, serum 5-HT and VIP levels, and increased SP levels (P<0.05, P<0.01). Moreover, the observation group showed more significant changes in the indicators above than the control group (P<0.05, P<0.01). The SP level showed no significant difference between the two groups. During the 4-week follow-up, the recurrence rate was 5.88% in the observation group and 31.25% in the control group. No adverse events occurred in observation group, and 2 cases of mild diarrhea occurred in the control group. ConclusionSanren Runchang formula demonstrated definitive efficacy in alleviating gastrointestinal symptoms and improving the psychological status and quality of life in IBS-C patients, with a low recurrence rate. The formula can regulate serum levels of neurotransmitters such as 5-HT and VIP, suggesting its potential regulatory effect on the brain-gut axis through modulating neurotransmitters and neuropeptides. However, its complete mechanism of action requires further investigation through detection of additional brain-gut axis-related biomarkers.
2.Treatment Principles and Paradigm of Diabetic Microvascular Complications Responding Specifically to Traditional Chinese Medicine
Anzhu WANG ; Xing HANG ; Lili ZHANG ; Xiaorong ZHU ; Dantao PENG ; Ying FAN ; Min ZHANG ; Wenliang LYU ; Guoliang ZHANG ; Xiai WU ; Jia MI ; Jiaxing TIAN ; Wei ZHANG ; Han WANG ; Yuan XU ; .LI PINGPING ; Zhenyu WANG ; Ying ZHANG ; Dongmei SUN ; Yi HE ; Mei MO ; Xiaoxiao ZHANG ; Linhua ZHAO
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(5):272-279
To explore the advantages of traditional Chinese medicine (TCM) and integrative TCM-Western medicine approaches in the treatment of diabetic microvascular complications (DMC), refine key pathophysiological insights and treatment principles, and promote academic innovation and strategic research planning in the prevention and treatment of DMC. The 38th session of the Expert Salon on Diseases Responding Specifically to Traditional Chinese Medicine, hosted by the China Association of Chinese Medicine, was held in Beijing, 2024. Experts in TCM, Western medicine, and interdisciplinary fields convened to conduct a systematic discussion on the pathogenesis, diagnostic and treatment challenges, and mechanism research related to DMC, ultimately forming a consensus on key directions. Four major research recommendations were proposed. The first is addressing clinical bottlenecks in the prevention and control of DMC by optimizing TCM-based evidence evaluation systems. The second is refining TCM core pathogenesis across DMC stages and establishing corresponding "disease-pattern-time" framework. The third is innovating mechanism research strategies to facilitate a shift from holistic regulation to targeted intervention in TCM. The fourth is advancing interdisciplinary collaboration to enhance the role of TCM in new drug development, research prioritization, and guideline formulation. TCM and integrative approaches offer distinct advantages in managing DMC. With a focus on the diseases responding specifically to TCM, strengthening evidence-based support and mechanism interpretation and promoting the integration of clinical care and research innovation will provide strong momentum for the modernization of TCM and the advancement of national health strategies.
3.Advances in early diabetic neuroretinopathy
International Eye Science 2025;25(1):76-81
Diabetic retinopathy(DR)is a late-stage peripheral micro-neurovascular complication of chronic hyperglycemia, leading to blood-retinal barrier impairment and retinal dysfunction. Recent studies have found that diabetic neuroretinopathy(DN)may be one of the earliest events in diabetic retinal alterations. The main features include defective electroretinographic responses in newly diagnosed patients, early self-activation of microglia and Müller cells, reduced activity of neurotransmitters(e.g., DOPA/GABA), and early mitochondrial dysfunction, such as persistent Drp1-Fis1 fission and mtDNA methylation mismatches. Understanding the molecular basis of DN is essential for elucidating its pathogenesis and developing early treatments. This review summarizes pathological changes and mechanisms of retinal function, glial cells, neurotransmitters, mitochondria, and other factors in early diabetes mellitus, in order to provide a theoretical foundation for investigating early DN mechanisms and developing targeted therapies.
4.Analysis of Differential Compounds of Poria cocos Medicinal Materials by Integrated Qualitative Strategy Based on UPLC-Q-Orbitrap-MS
Jiayuan WANG ; Xiaohan FAN ; Xiaoxiao WEI ; Rong CAO ; Jin WANG ; Lei WANG ; Fengqing XU ; Shunwang HUANG ; Deling WU ; Hongsu ZHAO
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(7):148-156
ObjectiveTo establish a rapid analytical method for identifying the differential components in Poria cocos medicinal materials based on ultra performance liquid chromatography-quadrupole-electrostatic field orbital trap high-resolution mass spectrometry(UPLC-Q-Orbitrap-MS), combined with mass defect filtering(MDF) and molecular network integration techniques. MethodsUPLC-Q-Orbitrap-MS was used for MS data acquisition and identification of P. cocos medicinal materials, with the help of MDF for the study of cleavage behavior and structural identification of triterpenoids. According to the similarity of MS/MS fragmentation patterns of each component, global natural product social molecular network(GNPS) was established, and Cytoscape 3.6.1 was used to screen molecular clusters with similar structures and the the structure of main compound classes were identified and confirmed. Multivariate statistical analyses such as principal component analysis(PCA) and orthogonal partial least squares-discriminant analysis(OPLS-DA) were used to screen the differential components of the five P. cocos medicinal materials with the variable importance in the projection(VIP) value>1 and P<0.05 as the criteria. ResultsA total of 66 compounds were identified by database comparison, 8 compounds were newly identified by MDF, 28 compounds were newly identified by GNPS, and a total of 102 chemical compounds were identified, including 43 triterpenoids, 16 saccharides, 26 amino acids and peptides, 3 nucleosides, and 14 other compounds. Triterpenoids were predominant in Poriae Cutis and wild Fushen, amino acids and peptides were the most abundant in Poria and cultivated Fushen, carbohydrates were the most abundant in Poriae Cutis. Type Ⅰ and Ⅱ triterpenoids had higher amounts in Poria and cultivated Fushen, type Ⅲ triterpenoids were more abundant in Poriae Cutis, all four types of triterpenoids were higher in Fushenmu, and type Ⅰ, Ⅱ, and Ⅳ triterpenoids were higher in wild Fushen. A total of 12 common differential chemical constituents were screened, including serine, guanosine, gallic acid, 2-octenal, maltotriose, trametenolic acid, dehydroeburicoic acid, dehydrotrametenolic acid, poricoic acid A, poricoic acid B, poricoic acid E and G, but the relative contents of them varied significantly among different medicinal materials. ConclusionAmong the five P. cocos medicinal materials, the types of constituents are generally similar, but their relative contents differed significantly among these medicinal materials, especially in the distribution of triterpenoids. The integration of UPLC-Q-Orbitrap-MS, MDF and GNPS can provide a reference for the rapid qualitative analysis of other Chinese medicines.
5.Analysis of Differential Compounds of Poria cocos Medicinal Materials by Integrated Qualitative Strategy Based on UPLC-Q-Orbitrap-MS
Jiayuan WANG ; Xiaohan FAN ; Xiaoxiao WEI ; Rong CAO ; Jin WANG ; Lei WANG ; Fengqing XU ; Shunwang HUANG ; Deling WU ; Hongsu ZHAO
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(7):148-156
ObjectiveTo establish a rapid analytical method for identifying the differential components in Poria cocos medicinal materials based on ultra performance liquid chromatography-quadrupole-electrostatic field orbital trap high-resolution mass spectrometry(UPLC-Q-Orbitrap-MS), combined with mass defect filtering(MDF) and molecular network integration techniques. MethodsUPLC-Q-Orbitrap-MS was used for MS data acquisition and identification of P. cocos medicinal materials, with the help of MDF for the study of cleavage behavior and structural identification of triterpenoids. According to the similarity of MS/MS fragmentation patterns of each component, global natural product social molecular network(GNPS) was established, and Cytoscape 3.6.1 was used to screen molecular clusters with similar structures and the the structure of main compound classes were identified and confirmed. Multivariate statistical analyses such as principal component analysis(PCA) and orthogonal partial least squares-discriminant analysis(OPLS-DA) were used to screen the differential components of the five P. cocos medicinal materials with the variable importance in the projection(VIP) value>1 and P<0.05 as the criteria. ResultsA total of 66 compounds were identified by database comparison, 8 compounds were newly identified by MDF, 28 compounds were newly identified by GNPS, and a total of 102 chemical compounds were identified, including 43 triterpenoids, 16 saccharides, 26 amino acids and peptides, 3 nucleosides, and 14 other compounds. Triterpenoids were predominant in Poriae Cutis and wild Fushen, amino acids and peptides were the most abundant in Poria and cultivated Fushen, carbohydrates were the most abundant in Poriae Cutis. Type Ⅰ and Ⅱ triterpenoids had higher amounts in Poria and cultivated Fushen, type Ⅲ triterpenoids were more abundant in Poriae Cutis, all four types of triterpenoids were higher in Fushenmu, and type Ⅰ, Ⅱ, and Ⅳ triterpenoids were higher in wild Fushen. A total of 12 common differential chemical constituents were screened, including serine, guanosine, gallic acid, 2-octenal, maltotriose, trametenolic acid, dehydroeburicoic acid, dehydrotrametenolic acid, poricoic acid A, poricoic acid B, poricoic acid E and G, but the relative contents of them varied significantly among different medicinal materials. ConclusionAmong the five P. cocos medicinal materials, the types of constituents are generally similar, but their relative contents differed significantly among these medicinal materials, especially in the distribution of triterpenoids. The integration of UPLC-Q-Orbitrap-MS, MDF and GNPS can provide a reference for the rapid qualitative analysis of other Chinese medicines.
6.Epidemiological Characteristics and Risk Factors of Non-alcoholic Fatty Liver Disease in Jincheng between 2015 and 2020
Nina ZHANG ; Junfang CUI ; Aiguo ZHANG ; Xueke FAN ; Yuting CHEN ; Shumei ZHANG ; Sha WEI
Journal of Public Health and Preventive Medicine 2025;36(1):110-113
Objective To investigate the epidemiological characteristics and risk factors of non-alcoholic fatty liver disease in Jincheng between 2015 and 2020. Methods Clinical data of 8,578 medical check-ups at Physical Examination Center of ou hospital from January 2015 to December 2020 were retrospectively selected. The prevalence of non-alcoholic fatty liver disease in the last 5 years was recorded, and Logistic regression was utilized to identify the risk factors for the development of non-alcoholic fatty liver disease. Results The overall prevalence of non-alcoholic fatty liver disease in Jincheng was 14.57% in 2015-2020. The prevalence of non-alcoholic fatty liver disease was higher in men than in women (16.99% vs 10.98%) and highest in the 40-59 age group (18.76%). No statistical difference was reported in blood urea nitrogen (BUN) and serum creatinine (Scr) between groups (P>0.05), while statistical difference was found in diabetes, hypertension, body mass index (BMI), waist circumference, weekly exercise frequency, daily vegetable intake, triglycerides (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), alanine aminotransferase (ALT) and uric acid (UA) between two groups (P<0.05). Multivariate Logistic regression analysis denoted that BMI (OR=2.794, 95% CI: 1.745-4.550), waist circumference (OR=2.586, 95% CI: 1.585-4.299), diabetes (OR=0.644, 95% CI: 1.425-2.781), hypertension (OR=1.479, 95% CI: 1.121-2.290), weekly exercise ≥6h (OR=0.617, 95% CI: 0.519-0.709), daily vegetable intake ≥300g (OR=0.590, 95% CI: 0.467-0.652), TG (OR=1.481, 95% CI: 1.122-1.996), TC (OR=1.562, 95% CI:1.143-2.135), LDL-C (OR=1.440, 95% CI: 1.139-2.048), HDL-C (OR=0.656 , 95% CI: 0.587-0.783) , ALT (OR=1.591, 95% CI: 1.056-2.183), and UA (OR=1.412, 95% CI: 1.009-1.887) were risk factors for non-alcoholic fatty liver disease (P<0.05) . Conclusion The prevalence of non-alcoholic fatty liver disease in Jincheng City from 2015 to 2020 is 14.57%, the prevalence of males is higher than that of females, and the prevalence rate is the highest in the 40-59 age group. Moreover , diabetes mellitus , hypertension , BMI , waist circumference , weekly exercise , daily vegetable intake , serum TG, TC, LDL-C, HDL-C, ALT, and UA are all associated with the risk of the disease.
7.Clinical Observation of Modified Zhigancao Tang in Treating Patients with Liver and Kidney Deficiency of Parkinson's Disease and Its Effect on Neuronal Signal-related Proteins
Yifo WEI ; Furong LYU ; Jia YAO ; Guonian LI ; Xianyi LUO ; Meng LUO ; Zhengzheng WEN ; Qiuqi LI ; Yihan LIU ; Linlin YANG ; Rui ZUO ; Wenxin DANG ; Fang MI ; Xiaoyan WANG ; Zhigang CHEN ; Fan LIU
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(4):166-173
ObjectiveMicrotube associated protein-2 (MAP-2), alpha-tubulin (α-tubulin), and synaptophysin (SYP) are important proteins in neuronal signal communication. This paper observed the effects of modified Zhigancao Tang on the expression of serum α-Synuclein (α-Syn) and its oligomers, MAP-2, α-tubulin, and SYP of patients with liver and kidney deficiency of Parkinson's disease (PD), analyzed their correlation, and evaluated the therapeutic effect of modified Zhigancao Tang in patients with liver and kidney deficiency of PD based on α-Syn transmission pathway mediated by neuronal communication in vivo. MethodsA total of 60 patients with PD who met the inclusion criteria were randomly divided into a treatment group (30 cases) and a control group (30 cases). Both groups were treated on the basis of PD medicine, and the treatment group was treated with modified Zhigancao Tang. Both groups were treated for 12 weeks. The changes in UPDRS score, TCM syndrome score, and expression of serum α-Syn and its oligomers, MAP-2, α-tubulin, and SYP were observed before and after 12 weeks of treatment in each group. The correlation between the above-mentioned serum biological indexes and the levels of serum α-Syn and its oligomers was analyzed. ResultsAfter treatment, the TCM syndrome score, UPDRS score, UPDRS-Ⅱ score, and UPDRS-Ⅲ score of the treatment group were significantly decreased (P<0.05, P<0.01). The UPDRS score, UPDRS-Ⅱ score, and UPDRS-Ⅲ scores in the treatment group were significantly decreased compared with those in the control group after treatment (P<0.05). After treatment, the total effective rate of the control group was 63.3% (19/30), and that of the treatment group was 86.7% (26/30). The clinical effect of the observation group was better than the control group (Z=-2.03, P<0.05). The total effective rate of the observation group was better than that of the control group, and the difference was statistically significant (χ2=5.136, P<0.05). After treatment, the oligomer level of serum α-Syn and MAP-2 level in the treatment group were significantly decreased (P<0.05, P<0.01). The levels of serum α-Syn and its oligomers, as well as α-tubulin in the treatment group, were significantly decreased compared with those in the control group after treatment (P<0.05, P<0.01). Serum α-Syn was correlated with serum MAP-2 and α-Syn oligomer in patients with PD (P<0.05, P<0.01) but not correlated with serum SYP . Serum α-Syn oligomers of patients with PD were correlated with serum MAP-2 and α-tubulin (P<0.05, P<0.01) but not correlated with serum SYP level. Serum SYP of patients with PD was correlated with serum MAP-2 (P<0.05). ConclusionModified Zhigancao Tang has a therapeutic effect on patients with liver and kidney deficiency of PD by inhibiting the production of α-Syn oligomers and intervening α-Syn microtubule transport pathway in vivo.
8.Expert Consensus on Clinical Application of Qinbaohong Zhike Oral Liquid in Treatment of Acute Bronchitis and Acute Attack of Chronic Bronchitis
Jian LIU ; Hongchun ZHANG ; Chengxiang WANG ; Hongsheng CUI ; Xia CUI ; Shunan ZHANG ; Daowen YANG ; Cuiling FENG ; Yubo GUO ; Zengtao SUN ; Huiyong ZHANG ; Guangxi LI ; Qing MIAO ; Sumei WANG ; Liqing SHI ; Hongjun YANG ; Ting LIU ; Fangbo ZHANG ; Sheng CHEN ; Wei CHEN ; Hai WANG ; Lin LIN ; Nini QU ; Lei WU ; Dengshan WU ; Yafeng LIU ; Wenyan ZHANG ; Yueying ZHANG ; Yongfen FAN
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(4):182-188
The Expert Consensus on Clinical Application of Qinbaohong Zhike Oral Liquid in Treatment of Acute Bronchitis and Acute Attack of Chronic Bronchitis (GS/CACM 337-2023) was released by the China Association of Chinese Medicine on December 13th, 2023. This expert consensus was developed by experts in methodology, pharmacy, and Chinese medicine in strict accordance with the development requirements of the China Association of Chinese Medicine (CACM) and based on the latest medical evidence and the clinical medication experience of well-known experts in the fields of respiratory medicine (pulmonary diseases) and pediatrics. This expert consensus defines the application of Qinbaohong Zhike oral liquid in the treatment of cough and excessive sputum caused by phlegm-heat obstructing lung, acute bronchitis, and acute attack of chronic bronchitis from the aspects of applicable populations, efficacy evaluation, usage, dosage, drug combination, and safety. It is expected to guide the rational drug use in medical and health institutions, give full play to the unique value of Qinbaohong Zhike oral liquid, and vigorously promote the inheritance and innovation of Chinese patent medicines.
9.The mechanism of Laggerae Herba in improving chronic heart failure by inhibiting ferroptosis through the Nrf2/SLC7A11/GPX4 signaling pathway
Jinling XIAO ; Kai HUANG ; Xiaoqi WEI ; Xinyi FAN ; Wangjing CHAI ; Jing HAN ; Kuo GAO ; Xue YU ; Fanghe LI ; Shuzhen GUO
Journal of Beijing University of Traditional Chinese Medicine 2025;48(3):343-353
Objective:
To investigate the role and mechanism of the heat-clearing and detoxifying drug Laggerae Herba in regulating the nuclear factor-erythroid 2-related factor-2(Nrf2)/solute carrier family 7 member 11 (SLC7A11)/glutathione peroxidase 4 (GPX4) signaling pathway to inhibit ferroptosis and improve chronic heart failure induced by transverse aortic arch constriction in mice.
Methods:
Twenty-four male ICR mice were divided into the sham (n=6) and transverse aortic arch constriction groups (n=18) according to the random number table method. The transverse aortic arch constriction group underwent transverse aortic constriction surgery to establish models. After modeling, the transverse aortic arch constriction group was further divided into the model, captopril, and Laggerae Herba groups according to the random number table method, with six mice per group. The captopril (15 mg/kg) and Laggerae Herba groups (1.95 g/kg) received the corresponding drugs by gavage, whereas the sham operation and model groups were administered the same volume of ultrapure water by gavage once a day for four consecutive weeks. After treatment, the cardiac function indexes of mice in each group were detected using ultrasound. The heart mass and tibia length were measured to calculate the ratio of heart weight to tibia length. Hematoxylin and eosin staining were used to observe the pathological changes in myocardial tissue. Masson staining was used to observe the degree of myocardial fibrosis. Wheat germ agglutinin staining was used to observe the degree of myocardial cell hypertrophy. Prussian blue staining was used to observe the iron deposition in myocardial tissue. An enzyme-linked immunosorbent assay was used to detect the amino-terminal pro-brain natriuretic peptide (NT-proBNP) and glutathione (GSH) contents in mice serum. Colorimetry was used to detect the malondialdehyde (MDA) content in mice serum. Western blotting was used to detect the Nrf2, GPX4, SLC7A11, and ferritin heavy chain 1 (FTH1) protein expressions in mice cardiac tissue.
Results:
Compared with the sham group, in the model group, the ejection fraction (EF) and fractional shortening (FS) of mice decreased, the left ventricular end-systolic volume (LVESV) and left ventricular end-systolic diameter (LVESD) increased, the left ventricular anterior wall end-systolic thickness (LVAWs) and left ventricular posterior wall end-systolic thickness (LVPWs) decreased, the ratio of heart weight to tibia length increased, the myocardial tissue morphology changed, myocardial fibrosis increased, the cross-sectional area of myocardial cells increased, iron deposition appeared in myocardial tissue, the serum NT-proBNP and MDA levels increased, the GSH level decreased, and Nrf2, GPX4, SLC7A11, and FTH1 protein expressions in cardiac tissue decreased (P<0.05). Compared with the model group, in the captopril and Laggerae Herba groups, the EF, FS, and LVAWs increased, the LVESV and LVESD decreased, the ratio of heart weight to tibia length decreased, the myocardial cells were arranged neatly, the degree of myocardial fibrosis decreased, the cross-sectional area of myocardial cells decreased, the serum NT-proBNP level decreased, and the GSH level increased. Compared with the model group, the LVPWs increased, the iron deposition in myocardial tissue decreased, the serum MDA level decreased, and Nrf2, GPX4, SLC7A11, and FTH1 protein expressions in cardiac tissue increased (P<0.05) in the Laggerae Herba group.
Conclusion
Laggerae Herba improves the cardiac function of mice with chronic heart failure caused by transverse aortic arch constriction, reduces the pathological remodeling of the heart, and reduces fibrosis. Its mechanism may be related to Nrf2/SLC7A11/GPX4 pathway-mediated ferroptosis.
10.Role of ATG12 in The Development of Disease
Wei LIU ; Rui TIAN ; Ce-Fan ZHOU ; Jing-Feng TANG
Progress in Biochemistry and Biophysics 2025;52(5):1081-1098
Autophagy, a highly conserved cellular degradation mechanism, maintains intracellular homeostasis by removing damaged organelles and abnormal proteins. Its dysregulation is closely associated with various diseases. Autophagy-related protein 12 (ATG12), a core member of the ubiquitin-like protein family, covalently binds to ATG5 through a ubiquitin-like conjugation system to form the ATG12-ATG5-ATG16L1 complex. This complex directly regulates the formation and maturation of autophagosomes, making ATG12 a key molecule in the initiation of autophagy. Recent studies have revealed that ATG12 functions extend far beyond the classical autophagy context. It promotes apoptosis by binding to anti-apoptotic proteins of the Bcl-2 family (e.g., Bcl-2 and Mcl-1) and enhances host antiviral immunity by regulating the NF-κB and interferon signaling pathways. Moreover, ATG12 deficiency can lead to mitochondrial biogenesis impairment, energy metabolism disorders, and substrate-dependent metabolic shifts, underscoring its pivotal role in cellular metabolic homeostasis. At the disease level, dysregulation of ATG12 expression is closely linked to tumorigenesis and cancer progression. By modulating the dynamic balance between autophagy and apoptosis, ATG12 influences cancer cell proliferation, metastasis, and chemoresistance. Notably, ATG12 is abnormally overexpressed in multiple cancers, including breast, liver, and gastric cancer, highlighting its potential as a therapeutic target. Furthermore, in neurodegenerative diseases such as Parkinson’s disease, ATG12 mitigates protein toxicity by enhancing mitochondrial autophagy. In cardiovascular diseases, it alleviates ischemia-reperfusion injury by regulating cardiomyocyte autophagy and apoptosis, demonstrating its broad regulatory role across various pathological conditions. Genetic studies further underscore the clinical significance of ATG12. Polymorphisms in the ATG12 gene (e.g., rs26537 and rs26538) have been significantly associated with the risk of head and neck squamous cell carcinoma, hepatocellular carcinoma, and atrophic gastritis. Notably, the risk allele of rs26537 enhances ATG12 promoter activity, leading to its overexpression and promoting tumorigenesis. These findings provide a molecular basis for individualized risk assessment and targeted interventions based on ATG12 genotype. Despite significant progress, many aspects of ATG12 biology remain unclear. The precise regulatory mechanisms of its post-translational modifications (e.g., ubiquitination and acetylation) are yet to be fully elucidated. Additionally, the molecular pathways underlying its non-canonical functions, such as metabolic regulation and immune modulation, require further investigation. Moreover, the functional heterogeneity of ATG12 in different tumor microenvironments and its role in drug resistance warrant in-depth exploration. Future research should integrate advanced technologies such as cryo-electron microscopy, single-cell sequencing, and organoid models to decipher the intricate regulatory network of ATG12. Additionally, developing small-molecule inhibitors or gene-editing tools targeting its protein interaction interfaces (e.g., the ATG12-ATG3 binding domain) may help overcome current therapeutic challenges. Through interdisciplinary collaboration and clinical translation, ATG12 holds promise as a next-generation molecular target for precision intervention in autophagy-related diseases. This review summarizes the structure and function of ATG12, its role in autophagy initiation, its physiological functions, and its involvement in disease pathogenesis. Furthermore, it discusses future research directions and potential challenges, emphasizing ATG12’s potential as a biomarker and therapeutic target in autophagy-related diseases.


Result Analysis
Print
Save
E-mail