1.Mechanism of Shenfu Xiongze Prescription in Regulating Autophagy Level to Intervene in Myocardial Remodeling in Rats via AMPK/mTOR Signaling Pathway
Xueqing WANG ; Wei ZHONG ; Liangliang PAN ; Caihong LI ; Man HAN ; Xiaowei YANG ; Yuanwang YU
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(2):136-144
ObjectiveTo explore the mechanism by which the Shenfu Xiongze prescription regulates autophagy in rats with myocardial remodeling through the adenosine monophosphate-activated protein kinase (AMPK)/mammalian target of rapamycin (mTOR) signaling pathway. MethodsA rat model of myocardial remodeling induced by isoprenaline (ISO) was established. Rats were divided into the blank group,the model group,the low-,medium-, and high-dose groups of Shenfu Xiongze prescription,and the captopril group, 6 rats in each group. Except for the blank group,the rat model of myocardial remodeling was established in the other groups by intraperitoneal injection of 2.5 mg·kg-1 ISO for 3 consecutive weeks. At the same time of modeling, the low-,medium-, and high-dose groups of Shenfu Xiongze prescription were administered the corresponding doses of Shenfu Xiongze prescription solution (8.4,16.8,and 33.6 g·kg-1),and the captopril group was administered captopril solution (25 mg·kg-1). As for the blank group and the model group, the same volume of normal saline was given. The treatment was continued for 3 weeks. Echocardiography was used to observe the cardiac structure and function,and the heart weight index was detected. Masson staining and hematoxylin-eosin (HE) staining were used to observe the pathological morphology changes of myocardial tissue. The levels of interleukin-6 (IL-6) and B-type natriuretic peptide (BNP) in serum were detected by enzyme-linked immunosorbent assay (ELISA). The expression of type Ⅰ collagen (Collagen Ⅰ),type Ⅲ collagen (Collagen Ⅲ),and microtubule-associated protein 1 light chain 3 (LC3) proteins in myocardial tissue was determined by immunohistochemistry. Autophagy was observed by transmission electron microscopy. The mRNA expression of Collagen Ⅰ,Collagen Ⅲ,α-smooth muscle actin (α-SMA),LC3,yeast Atg6 homolog protein (Beclin-1),AMPK,and mTOR in myocardial tissue was detected by quantitative real-time polymerase chain reaction (real-time PCR). The protein expression of Collagen Ⅰ,α-SMA,transforming growth factor-β1 (TGF-β1),LC3,Beclin-1,p62, phosphorylation(p)-AMPK,p-mTOR,AMPK,and mTOR was detected by Western blot. ResultsCompared with the normal group,rats in the model group exhibited significantly decreased values of ejection fraction (EF) and left ventricular fractional shortening (FS) (P<0.01), significantly increased values of left ventricular end-diastolic diameter (LVIDd) and left ventricular end-systolic diameter (LVIDs) (P<0.01). Additionally, the model group also showed increased degrees of inflammatory infiltration and fibrosis of myocardial tissue, significantly elevated levels of serum IL-6 and BNP (P<0.01), significantly increased mRNA and protein levels of Collagen Ⅰ,Collagen Ⅲ,α-SMA,and mTOR (P<0.01),and markedly decreased mRNA and protein levels of LC3,Beclin-1,and AMPK (P<0.05,P<0.01). Compared with the model group, the low-,medium-, and high-dose groups of Shenfu Xiongze prescription presented significantly elevated EF and FS values (P<0.01) and lowered LVIDd and LVIDs (P<0.05). In these groups, the inflammation and fibrosis were alleviated significantly. They also exhibited decreased serum levels of IL-6 and BNP (P<0.01), significantly reduced protein expression of Collagen Ⅰ, α-SMA, TGF-β1, p62, and p-mTOR (P<0.01), significantly decreased mRNA expression of Collagen Ⅰ, Collagen Ⅲ, α-SMA, and mTOR (P<0.01), and significantly increased mRNA and protein levels of LC3, Beclin-1, and AMPK (P<0.05,P<0.01). ConclusionThe Shenfu Xiongze prescription can improve the myocardial remodeling induced by ISO in rats by regulating the autophagy level,enhance cardiac function,and reduce inflammatory and fibrotic levels. This effect may be achieved through the AMPK/mTOR signaling pathway.
2.Research progress on Hippo signaling pathway effector molecules in rheumatic immune system diseases
Jie GAO ; Caihong PI ; Junmei PAN ; Wei ZHOU
Journal of Zhejiang University. Medical sciences 2024;53(3):376-381
The core components of the Hippo signaling pathway encompass upstream regulatory molecules,core kinase cascade complexes,and downstream transcriptional regulation complexes.This pathway modulates cellular behaviors by influencing the effector molecules of its core components and plays a pivotal role in immune regulation.Effector molecules,such as Yes-associated protein(YAP),transcriptional coactivator with PDZ-binding motif(TAZ),transcriptional enhanced associate domain transcriptional factor(TEAD),monopolar spindle-one binder(MOB1),large tumor suppressor(LATS),can stimulate fibroblast-like synovial cell migration and invasion in rheumatoid arthritis,regulate osteoarthritis disease progression,promote pathological new bone formation in ankylosing spondylitis,sustain submandibular gland development while delaying Sjogren's syndrome progression,mediate alpha-smooth muscle actin in systemic sclerosis,and refine the regulation of target genes associated with pulmonary fibrosis.This article provides an overview of the regulatory mechanisms involving Hippo signaling pathway-related effector molecules in the pathogenesis and progression of rheumatic immune system diseases,to serve as a reference for exploring novel therapeutic targets of rheumatic immune system diseases.
3.Levonorgestrel-releasing intrauterine system-based therapies for early-stage endometrial cancer: a systematic review and meta-analysis
Hongyi WEI ; Ningning PAN ; Wen ZHANG ; Guangwu XIONG ; Wenping GUO ; Zhe DONG ; Caihong MA
Journal of Gynecologic Oncology 2023;34(2):e36-
Objective:
To conduct a systematic review and meta-analysis of studies evaluating the oncological and fertility outcomes of early-stage endometrial cancer (EC) treated with the levonorgestrel-releasing intrauterine system (LIUS)-based regimens.
Methods:
The Meta-analyses Of Observational Studies in Epidemiology statement for meta-analyses was followed. Searches were conducted on MEDLINE, Embase, PubMed, Preprints, and the Cochrane Central Register of Controlled Trials from January 1990 to August 4, 2022. The Joanna Briggs Institute Critical Appraisal Checklist was used for quality assessment. The primary endpoint was the complete response (CR) rate and the secondary endpoints were relapse, pregnancy, and live birth rate.
Results:
A total of 25 studies (821 women) were included. The CR rate of LIUS-based regimens was 63.4% (95% confidence interval [CI]=52.3%–73.2%), with 29.6% (95% CI=23.3%–36.8%) of cases experiencing recurrence during follow-up. In sensitivity analyses, patients younger than 45 years of age with a body mass index <30 kg/m2 who were treated with LIUS-based regimens achieved a high CR rate of 84.6% (95% CI=80.3%–88.1%) over a median follow-up of more than 24 months. Overall pregnancy and live birth rates were 37.9% (95% CI=24.1%–53.9%) and 39.3% (95% CI=24.0%–57.0%), respectively. No statistical differences were apparent in CR or relapse rates among the LIUS+GnRH agonist, LIUS+oral progesterone, or hysteroscopic resection followed by LIUS subgroups.
Conclusion
LIUS-based therapies are viable for the conservative management of early-stage endometrioid EC on CR and fertility outcome.
4.The effects of enteral immunonutrition on cell immune level and clinical efficacy in patients with severe tuberculous
Xiaohong PAN ; Minjie MAO ; Jiekun XU ; Lei PAN ; Caihong WANG ; Xiaoqing HUANG ; Junke QIU
Chinese Journal of Integrated Traditional and Western Medicine in Intensive and Critical Care 2018;25(1):66-69
Objective To evaluate the effects of enteral immunonutrition on cell immunity level and clinical efficacy in patients with severe tuberculosis. Methods Sixty patients with severe tuberculosis were admitted to the department of tuberculosis intensive care unit of Hangzhou Red Cross Hospital from June 2015 to June 2017, and they were randomly divided into a conventional enteral nutrition group (EN group) and a enteral immunonutrition group (EIN group), each group 30 cases. Based on the patients' gastrointestinal tolerance condition, the EN group was treated with therapies of normal nutrition support, anti-tuberculosis, anti-infection, etc.; the EIN group was treated with enteral immunonutrition (TPF-T), and simultaneously with anti-tuberculosis, anti-infection, etc. therapies according to the disease situation. The target energy maintained at 104.6 kJ·d-1·kg-1and the therapeutic course was 14 days in the two groups. The levels of interleukins (IL-6, IL-10) and interferon-γ (IFN-γ), white blood cell count (WBC), C-reactive protein (CRP), procalcitonin (PCT), cell immune indexes (T cell subgroup CD4+, CD8+) were observed before treatment and on day 14 after treatment in the patients of two groups; the changes of acute physiology and chronic health evaluation Ⅱ (APACHE Ⅱ) score before treatment and after treatment and 28-day mortality rate were recorded in the two groups. Results After treatment, the levels of WBC, CRP, PCT were obviously lower than those before treatment, while the levels of IL-6, IFN-γ, CD4+in the two groups were significantly higher than those before treatment, and the changes of the EIN group were more significant than those in the EN group [WBC (×109/L): 8.0±3.1 vs. 10.0±2.4, CRP (mg/L): 30.3±9.1 vs. 45.8±6.6, PCT (μg/L): 2.2±1.8 vs. 4.3±2.2, IL-6 (mg/L): 182.53±8.52 vs. 168.42±7.62, IFN-γ (mg/L): 32.52±3.5 vs. 25.41±2.6, CD4+: 0.56±0.06 vs. 0.45±0.08, all P < 0.05]. The level of CD8+after treatment in the two groups was higher than that before treatment (the EN group: 0.28±0.06 vs. 0.27±0.07, the EIN group: 0.27±0.08 vs. 0.26±0.09), the APACHE Ⅱ scores in the two groups were lower than those before treatment (the EN group: 11±6 vs. 18±4, the EIN group: 10±3 vs. 17±6), the 28-day mortality in the EIN group was lower than that in the EN group [13.3% (4/30) vs. 16.7% (5/30)], no statistical significant difference in CD8+, APACHE Ⅱscore, 28-day mortality between the two groups being found (all P > 0.05). Conclusion Enteral immunonutrition can improve the level of cell immunity and decrease the degree of inflammatory response, and increase the clinical curative effect in patients with severe tuberculosis.
5.Ticagrelor versus clopidogrel in patients with acute coronary syndromes and diabetes mellitus
Caihong PAN ; Zeping HU ; Bangning WANG
Acta Universitatis Medicinalis Anhui 2015;50(9):1351-1353
Patients diagnosed to have acute coronary syndromes( ACS) were included in the study. All ACS patients were divided into non-diabetes group(40 cases) and diabetes group(80 cases) . Blood coagulation function was de-termined for all patients. In the diabetes group eighty patients were randomly divided into ticagrelor group (48 ca-ses) and clopidogrel group (32 cases) . After 5 days′treatment, platelet function was detected. Our study aimed to examine the effects of ticagrelor and clopidogrel on the platelet function.
6.Significance of CDH17 expression and its single nucleotide polymorphisms in oncogenesis and progression of gastric carcinoma
Diling PAN ; Sheng ZHANG ; Xingfu WANG ; Yupeng CHEN ; Caihong REN ; Xiangna CHEN
Chinese Journal of Clinical Oncology 2015;42(19):957-962
Objective:To explore the relationship of CDH17 expression with clinico-pathological features and the correlation be-tween the single nucleotide polymorphisms (SNPs) of CDH17 gene and genetic susceptibility of gastric carcinoma (GC). Methods:A tissue microarray was performed to simulate the dynamic process of invasion and metastasis of GC. Immunohistochemical staining was performed to detect the expression of CDH17 protein, and PCR-based LDR was performed to detect the 2 SNP loci (rs2514813 and rs3214050) genotypes of CDH17 gene. Results: The expression of CDH17 protein in GC was more significantly up-regulated and greatly increased in the intestinal type than in the diffuse type. The expression of CDH17 protein in GC was positively correlated with the histological grading (P<0.01) and was not associated with the survival (P=0.209). With the progression of the cancer invasion, the expression of CDH17 protein in GC showed a downtrend from the gastric mucosa layer to the invasive front edge. The frequencies of the C and T alleles and the CC, CT, and TT genotypes at the CDH17 rs3214050 locus between the GC patients and the control groups were significantly different (P<0.01). However, no significant differences were observed at rs2514813 (P>0.05). The individuals with the T al-leles had longer survival time than those with the CC genotype (P<0.01). Conclusion:The up-regulation of CDH17 expression is in-volved in the maintenance of histological phenotype and progression of GC. Individuals with T alleles at the CDH17 rs3214050 locus have decreased risk of GC and had better prognosis (OR=0.762, 95%CI:0.619-0.937), thereby suggesting that screening for these alleles would help with the assessment of genetic susceptibility and prognosis of GC in the Fujian population.
7.The correlation of miR-106a expression with clinical characteristics and prognosis of colon cancer
Yingying FANG ; Yang PAN ; Caihong SONG ; Ying LI ; Qiang LI
Practical Oncology Journal 2014;(3):245-249
Objective To detect the correlations of miR -106 a expression with clinical features of pa-tients with colon cancer ,and to explore the significance of miR -106 a as a prognostic factor .Methods One hun-dred and five patients with primary colon cancer were retrospectively enrolled in this study including their clinical information and slices of FFPE.miR-106a expression was detected by qRT -PCR,and analyzed the correlation between the level of miR -106a and clinical features and survival .Results The level of miR -106a in tumor tissue was higher than adjacent normal tissue (1.142 vs.0.685,P<0.001).miR-106a was correlated with TNM stage and lymphnode metastasis .The higher miR -106a expression,the poorer survival patients were .The hazard risk was increased 3.390 folds(95%CI for HR:1.028 ~11.178)when compared high expression group with the low.Conclusion The aberrant expression of miR -106a may be associated with colon cancer .It will po-tentially be a therapeutic target and prognostic factors .

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