1.Tanyu Tongzhi Youhua Prescription Regulates cGAS/STING Signaling Pathway to Inhibit Inflammation and Ameliorate No-reflow Phenomenon in Myocardial Ischemia/Reperfusion Injury
Sijia WU ; Yingying LI ; Haonan WU ; Xiang LI ; Lingfeng ZHOU ; Huamin ZHANG ; Danli TANG
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(8):99-107
ObjectiveThis paper aims to investigate the protective effects of the Tanyu Tongzhi Youhua prescription(TYTZP) against myocardial ischemia/reperfusion injury in rats via regulation of the cyclic GMP-AMP synthase (cGAS)/stimulator of interferon genes (STING) signaling pathway. MethodsFifty-six 8-week-old male Sprague-Dawley (SD) rats were randomly divided into sham group, model group, ticagrelor group (32.4 mg·kg-1), RU320521 (RU.521cGAS inhibitors) group (5 mL·kg-1), groups of TYTZP with low dose (3.6 g·kg-1), medium dose (7.2 g·kg-1), and high dose (14.4 g·kg-1), with eight rats per group. The ticagrelor group and groups of TYTZP with different doses received pre-treatment for seven days according to their respective protocols. The RU.521 group received an intraperitoneal injection one hour before modeling. A rat model of the no-reflow phenomenon in myocardial ischemia/reperfusion injury was established by ligating the left anterior descending coronary artery in situ. Myocardial no-reflow area was determined by thioflavin staining. Histopathological morphology of myocardial tissue was observed via hematoxylin and eosin (HE) staining. Cardiac function was detected by echocardiography. Myocardial microcirculation function change was observed by using real-time myocardial contrast echocardiography. The myocardial enzyme levels in the serum were measured by serum biochemical analysis. The double-stranded DNA (dsDNA) levels were detected by using PicoGreen. The protein expression of cGAS, STING, and nuclear factor-κB (NF-κB) p65 in myocardial tissue was detected by Western blot. The levels of cardiac troponin Ⅰ (cTNⅠ), cardiac troponin T (cTNT), interleukin-6 (IL-6), interleukin-1β (IL-1β), and tumor necrosis factor-α (TNF-α) in the peripheral blood were measured by enzyme-linked immunosorbent assay (ELISA). ResultsCompared with the sham group, the model group showed a significantly increased myocardial no-reflow area (P<0.01). Myocardial fiber rupture and disarray and inflammatory cell infiltration were observed by HE staining. The ultrasound results indicated that left ventricular ejection fraction (LVEF) and left ventricular fractional shortening (LVFS) (P<0.01) were significantly decreased. Real-time myocardial contrast echocardiography showed that the peak time of myocardial blood perfusion was significantly prolonged (P<0.01), and the levels of creatine kinase (CK), creatine kinase isoenzyme (CK-MB), lactate dehydrogenase (LDH), cTNⅠ, cTNT, and dsDNA were significantly elevated (P<0.01). Western blot results showed that the myocardial protein expressions of cGAS, STING, and NF-κB p65 were upregulated (P<0.01). ELISA results showed that the inflammatory factors in the serum such as IL-6, IL-1β, and TNF-α were increased (P<0.01). Compared with the model group, the group of the TYTZP significantly reduced the levels of myocardial enzyme, troponins, and dsDNA (P<0.01, P<0.05), improved cardiac function and myocardial microcirculation, alleviated histopathological morphology and inflammatory infiltration, inhibited activation of the cGAS/STING pathway, reduced the expression of NF-κB p65 (P<0.01, P<0.05), and inhibited inflammatory response. ConclusionThe TYTZP mitigates the no-reflow phenomenon in myocardial ischemia/reperfusion injury, and its mechanism is associated with inhibiting the activation of the cGAS/STING pathway and attenuating inflammatory responses.
2.Tanyu Tongzhi Youhua Prescription Regulates cGAS/STING Signaling Pathway to Inhibit Inflammation and Ameliorate No-reflow Phenomenon in Myocardial Ischemia/Reperfusion Injury
Sijia WU ; Yingying LI ; Haonan WU ; Xiang LI ; Lingfeng ZHOU ; Huamin ZHANG ; Danli TANG
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(8):99-107
ObjectiveThis paper aims to investigate the protective effects of the Tanyu Tongzhi Youhua prescription(TYTZP) against myocardial ischemia/reperfusion injury in rats via regulation of the cyclic GMP-AMP synthase (cGAS)/stimulator of interferon genes (STING) signaling pathway. MethodsFifty-six 8-week-old male Sprague-Dawley (SD) rats were randomly divided into sham group, model group, ticagrelor group (32.4 mg·kg-1), RU320521 (RU.521cGAS inhibitors) group (5 mL·kg-1), groups of TYTZP with low dose (3.6 g·kg-1), medium dose (7.2 g·kg-1), and high dose (14.4 g·kg-1), with eight rats per group. The ticagrelor group and groups of TYTZP with different doses received pre-treatment for seven days according to their respective protocols. The RU.521 group received an intraperitoneal injection one hour before modeling. A rat model of the no-reflow phenomenon in myocardial ischemia/reperfusion injury was established by ligating the left anterior descending coronary artery in situ. Myocardial no-reflow area was determined by thioflavin staining. Histopathological morphology of myocardial tissue was observed via hematoxylin and eosin (HE) staining. Cardiac function was detected by echocardiography. Myocardial microcirculation function change was observed by using real-time myocardial contrast echocardiography. The myocardial enzyme levels in the serum were measured by serum biochemical analysis. The double-stranded DNA (dsDNA) levels were detected by using PicoGreen. The protein expression of cGAS, STING, and nuclear factor-κB (NF-κB) p65 in myocardial tissue was detected by Western blot. The levels of cardiac troponin Ⅰ (cTNⅠ), cardiac troponin T (cTNT), interleukin-6 (IL-6), interleukin-1β (IL-1β), and tumor necrosis factor-α (TNF-α) in the peripheral blood were measured by enzyme-linked immunosorbent assay (ELISA). ResultsCompared with the sham group, the model group showed a significantly increased myocardial no-reflow area (P<0.01). Myocardial fiber rupture and disarray and inflammatory cell infiltration were observed by HE staining. The ultrasound results indicated that left ventricular ejection fraction (LVEF) and left ventricular fractional shortening (LVFS) (P<0.01) were significantly decreased. Real-time myocardial contrast echocardiography showed that the peak time of myocardial blood perfusion was significantly prolonged (P<0.01), and the levels of creatine kinase (CK), creatine kinase isoenzyme (CK-MB), lactate dehydrogenase (LDH), cTNⅠ, cTNT, and dsDNA were significantly elevated (P<0.01). Western blot results showed that the myocardial protein expressions of cGAS, STING, and NF-κB p65 were upregulated (P<0.01). ELISA results showed that the inflammatory factors in the serum such as IL-6, IL-1β, and TNF-α were increased (P<0.01). Compared with the model group, the group of the TYTZP significantly reduced the levels of myocardial enzyme, troponins, and dsDNA (P<0.01, P<0.05), improved cardiac function and myocardial microcirculation, alleviated histopathological morphology and inflammatory infiltration, inhibited activation of the cGAS/STING pathway, reduced the expression of NF-κB p65 (P<0.01, P<0.05), and inhibited inflammatory response. ConclusionThe TYTZP mitigates the no-reflow phenomenon in myocardial ischemia/reperfusion injury, and its mechanism is associated with inhibiting the activation of the cGAS/STING pathway and attenuating inflammatory responses.
3.Research progress in treating cardiovascular diseases with the principle of treating phlegm and stasis together
Xiang LI ; Huamin ZHANG ; Lin TONG ; Lei ZHANG ; Danli TANG
International Journal of Traditional Chinese Medicine 2020;42(7):708-711
This paper reviews the recent literatures about the clinical and mechanism researches on the treatment of cardiovascular diseases with the principles of treating phlegm and blood stasis together, which showed that phlegm and blood stasis are the key factors for the occurrence and exacerbation of cardiovascular diseases. This method is often used to treat angina pectoris, acute coronary syndrome, hypertension and hyperlipidemia, which could improve the condition of myocardial ischemia, resist myocardial cell apoptosis, improve vascular endothelial function, regulate the level of inflammatory cytokines, improve myocardial energy metabolism and reduce the level of myocardial injury markers. However, there still lacks of large-scale RCT, the effective components and mechanism of effective compound are not clear and the mechanism research lacks TCM characteristics.
4.Primary reconstruction with titanium mesh in comminuted and open skull fracture:long-term follow-up to verify its feasibility
Xiang ZHANG ; Zengliang WANG ; Danli CHEN ; Ganchun WU ; Danshu XU ; Yongxin WANG
Chinese Journal of Tissue Engineering Research 2014;(43):7012-7017
BACKGROUND:At present, scholars general y believe that the physical and chemical properties of titanium mesh are fine as easy plastic, easy cutting, good corrosion resistance and wear resistance, non-magnetic, less effect on CT or MRI results, good histocompatibility and resistance to stress. The titanium mesh is regarded as an ideal material for cranioplasty. <br> OBJECTIVE:To explore the clinical feasibility of primary reconstruction of comminuted and open skul fracture with titanium mesh. <br> METHODS:Sixty-two cases of comminuted and open skul fracture were analyzed retrospectively, including 49 males and 13 females, aged 7-69 years. Among these 62 patients, 30 patients underwent debridement and then after 6-12 months, they received titanium mesh reconstruction, serving as control group. Another 32 cases underwent debridement and titanium mesh reconstruction in the same time as observation group. Al the cases were fol owed-up for 1-2 years to observe wound healing, complications and hospitalization cost. <br> RESULTS AND CONCLUSION:During the fol ow-up, no wound infection and intracranial infection occurred in the two groups. The incidence of intracranial hematoma, epilepsy, and other complications was higher in the control group than the observation group (P<0.05), and the hospitalization cost was also higher in the control group than the observation group (P<0.05). These findings indicate that primary reconstruction with titanium mesh is feasible in the treatment of comminuted and open skul fracture and can significantly reduce the incidence of complications and hospitalization costs.
5.Drug susceptibility testing and randomly amplified polymorphic DNA analysis of Staphylococcus aureus from 178 children with impetigo
Caiyun BIAN ; Yonghong LU ; Peimei ZHOU ; Min WANG ; Ming CHEN ; Cunhuo JIANG ; Qi CAI ; Xuan LI ; Dawei ZHANG ; Qin RAN ; Haitao XU ; Qianming CHEN ; Yan LIU ; Bo WU ; Zhenyuan WANG ; Nayi CHEN ; Danli XIANG ; Xulei HUANG ; Yong BAO ; Yan LV ; Yafei YIN
Chinese Journal of Dermatology 2012;(11):767-770
Objective To test the antimicrobial susceptibility of Staphylococcus aureus from children with impetigo,and to assess the differences in randomly amplified polymorphic DNA profiles between sensitive and resistant Staphylococcus aureus strains.Methods Secretion specimens were obtained from the impetiginous lesions of 178 children,and subjected to bacterial culture.The susceptibility of 162 Staphylococcus aureus isolates against 21 antibiotics was tested.Randomly amplified polymorphic DNA PCR(RAPD-PCR)was performed to characterize the genotype of Staphylococcus aureus.Results Totally,180 bacterial strains were isolated from 178 children with impetigo in Chengdu,including 162(90.00%)Staphylococcus aureus strains.Of the 162 Staphylococcus aureus strains,148 were methicillin sensitive Staphylococcus aureus(MSSA),14 methicillin resistant Staphylococcus aureus(MRSA).The most active antibiotic was minocycline,followed by teicoplanin,quinupristin,vancomycin and nitrofurantoin,while the resistance rate to penicillin was highest,followed by that to erythromycin,clindamycin,compound sulfamethoxazole and tetracycline.All the Staphylococcus aureus isolates were sensitive to fusidic acid,nitrofurantoin,vancomycin,minocycline and teicoplanin.According to RAPD-PCR,the 162 Staphylococcus aureus strains were divided into 8 genotypes,with the three most prevalent genotypes being Ⅲ(31.48%),Ⅱ(26.54%)and Ⅵ(25.93%),which accounted for 65.43%(106/162)in all the strains.The 148 MSSA strains fell into 8 genotypes,with genotype Ⅲ(50 strains,33.78%),Ⅵ(39 strains,26.35%)and Ⅱ(33 strains,22.30%)being the most prevalent genotypes;the 14 MRSA strains fell into 3 genotypes,i.e.,genotype Ⅱ(10 strains,71.43%),Ⅵ(3 strains,21.43%),and Ⅲ(1 strain,7.14%).Conclusions Staphylococcus aureus is the most prevalent pathogenic bacteria in children with impetigo in Chengdu area,which is highly sensitive to minocycline,teicoplanin and quinupristin,and falls into 8 genotypes according to RAPD-PCR with genotype Ⅲ being the most common genotype.

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