1.Relationship between plasma proteins and pulmonary arterial hypertension and potential therapeutic targets
Cuicui ZHANG ; Huanyu CHEN ; Qiao YU ; Yuxuan HUANG ; Gengzhen YAO ; Xu ZOU
Chinese Journal of Tissue Engineering Research 2026;30(5):1331-1340
BACKGROUND:Pulmonary arterial hypertension is a destructive cardiopulmonary disease for which there is no cure.An association between plasma proteins and pulmonary arterial hypertension has been suggested,but the causal relationship has not been specifically elucidated.OBJECTIVE:To elucidate the causal relationship between plasma proteome and pulmonary arterial hypertension using a two-sample Mendelian randomization method,thereby searching for potential therapeutic targets for pulmonary arterial hypertension.METHODS:Plasma Protein Gene-Wide Association Analysis Statistics for 4 907 Aptamer Measurements in 35 559 Icelanders from the Icelandic Database;Genome-wide association analysis statistics for pulmonary arterial hypertension were obtained from the Finn Gen database,version R9,including 234 cases and 265 626 controls.Analyses were performed using Mendelian randomization and Bayesian co-localization analysis,the findings were examined using sensitivity analyses,and protein-protein interaction network maps were constructed to explore the causal relationship between plasma proteins and pulmonary arterial hypertension.RESULTS AND CONCLUSION:(1)The results of inverse variance weighting,maximum likelihood and Wald ratio methods showed 19 proteins causally associated with pulmonary arterial hypertension(P<0.05).Among them,10 plasma proteins,including Beta-1,3-N-acetylglucosaminyltransferase manic fringe(odds ratio[OR]=0.12,95%confidence interval[CI]0.02-0.61,P=0.01)and interferon alpha/beta receptor 1(OR=0.45,95%CI 0.24-0.84,P=0.012),might be associated with a reduced risk of pulmonary arterial hypertension.In contrast,nine plasma proteins,such as glucoside xylosyltransferase 1(OR=3.48,95%CI 1.51-8.00,P=0.003)and plasminogen(OR=42.78,95%CI 2.49-734.31,P=0.01),might be associated with an increased risk of pulmonary arterial hypertension.After the false discovery rate was corrected,19 proteins remained significantly associated with pulmonary arterial hypertension.(2)Multiple sensitivity analyses such as the MR-Egger intercept test and leave-one-out method showed no horizontal multiplicity or heterogeneity in the results of the study,indicating the stability of the study's results.(3)Bayesian co-localization analysis showed that six plasma proteins,including plasminogen(PPH4=1.0)and glucoside xylosyltransferase 1(PPH4=0.94),had PPH4>0.8,suggesting that plasma proteins and the genome-wide association study of pulmonary arterial hypertension had similar causal variance in terms of genetic association.(4)By constructing a protein-protein interaction network map,plasminogen,Annexin A1,fibrinogen gamma chain and matrix metalloproteinase 7 were found to be core proteins.(5)The article used Mendelian randomization analysis to reveal a potential causal association between 4 907 plasma proteins and pulmonary arterial hypertension,suggesting that plasma proteins may be potential therapeutic targets for pulmonary arterial hypertension.The core proteins identified in the study also provide a theoretical basis for further in-depth study of the pathophysiological mechanisms of pulmonary arterial hypertension.Secondly,analyses using the large-scale international databases of Iceland and FinnGen provide new research directions and treatment ideas for pulmonary arterial hypertension in specific populations and environments,as well as ideas and methods that can be used to prevent and treat pulmonary arterial hypertension in China.
2.Preparation,characterization and quantitative analysis of β-cyclodextrin inclusion complex with volatile oil from Qianghuo qushi qingwen granules
Yicheng SUN ; Lingrui QIN ; Kaiping ZOU ; Chenguang ZHAO ; Li DOU ; Shun LIU ; Lingang ZHAO
China Pharmacy 2026;37(6):746-751
OBJECTIVE To prepare the β -cyclodextrin ( β -CD) inclusion complex with volatile oil from Qianghuo qushi qingwen granules, and to characterize and quantitatively analyze the inclusion complex. METHODS The comprehensive scores calculated by inclusion rate and inclusion compound yield were used as indicators for screening the inclusion method. The single-factor experiments and Box-Behnken response surface experiments were used to op timize the inclusion conditions, with the above comprehensive score as response value, and taking the ratio of β -CD to volatile oil, inclusion temperature and inclusion time as indexes. The volatile oil inclusion complex of Qianghuo qushi qingwen granules was prepared according to the determined optimal process, followed by validation. Ultraviolet (UV)-visible spectroscopy, thin-layer chromatography (TLC), and microscopic imaging were also performed. Ultra-high performance liquid chromatography was used to determine the contents of perillaldehyde, pogostone and atractylodin. RESULTS The saturation aqueous solution method was adopted. The optimal inclusion process conditions were as follows: the ratio of β -CD to volatile oil was 7.5∶1, the inclusion temperature was 40 ℃, and the inclusion time was 2.2 h. In three verification experiments, the average inclusion rate was 72.32%, the average yield of inclusion compound was 74.45%, the average comprehensive score was 72.96 points, and the relative error with the predicted value (74.15 points) of the model was 1.61%. UV-visible spectroscopy, TLC and microscopic imaging showed that β -CD and volatile oil successfully formed a new inclusion complex. The average contents of perillaldehyde, pogostone and atractylodin were 4.498 2, 0.814 9, 0.905 7 mg/g, respectively, with RSDs of 0.31%, 0.56% and 0.63% ( n =3). CONCLUSIONS A stable and feasible preparation process of the volatile oil inclusion complex of Qianghuo qushi qingwen granules is successfully established.
3.Safety of using glucagon-like peptide-1 receptor agonists before gastrointestinal endoscopy:an overview of systematic reviews
Yuzhou LI ; Shuying ZOU ; Xiangnan ZHU ; Li TANG ; Peng LI ; Caixia XIE
China Pharmacy 2026;37(6):806-811
OBJECTIVE To conduct a systematic review concerning the safety of using glucagon-like peptide-1 receptor agonists (GLP-1RA) before gastrointestinal endoscopy. METHODS Chinese and English databases including CNKI, Wanfang Data, VIP, CBM, and PubMed were searched to collect systematic reviews and meta-analyses on the safety of using GLP-1RA before gastrointestinal endoscopy, with a search period from the inception to September 30, 2025. Report quality, methodological quality, risk of bias, and evidence quality were assessed using the PRISMA 2020 statement, AMSTAR 2 scale, ROBIS tool, and GRADE tool, respectively. Corrected covered area (CCA) was used to quantitatively evaluate the degree of outcome overlap, and a comprehensive quality analysis was performed on the quantitative results of systematic reviews/meta-analyses. RESULTS Ten studies were included. All 10 stu dies had some information deficiencies (15.5-19.5 points), and were at high risk of bias; 9 studies were extremely low methodological quality, while 1 study was low. In terms of evidence quality, among 88 outcome indexes, there was 1 moderate-level index, 28 low-level indexes, and 59 extremely low-level indexes. The CCA values of the incidence of residual gastric contents, aspiration, endoscopy interruption, repeated endoscopy, inadequate bowel preparation and Boston Bowel Preparation Scale scores were 37.30%, 35.00%, 35.00%, 50.00%, 29.60% and 20.00%, respectively. Results of comprehensive quality analysis showed that compared with the control group, the incidence of residual gastric contents, endoscopy interruption and repeated endoscopy were increased significantly in the intervention group, along with a notably prolonged gastric emptying time and a significantly lower score of Boston Bowel Preparation Scale ( P <0.05). However, the study results regarding the effects of GLP-1RA on the incidence of aspiration and inadequate bowel preparation were inconsistent. CONCLUSIONS The use of GLP-1RA before gastrointestinal endoscopy can increase certain safety risks, including residual gastric contents, endoscopy interruption and repeated endoscopy, prolong gastric emptying time, and reduce the quality of bowel preparation. However, the effects on aspiration and inadequate bowel preparation remain controversial. The reports included in systematic reviews/meta-analyses exhibited low quality in reporting, methodology and evidence, with high risk of bias. Therefore, conclusions should be interpreted with caution.
4.Epidemiological characteristics of scarlet fever in Pudong New Area of Shanghai in 2010 - 2023
Zou CHEN ; Anchen ZHOU ; Hong ZHANG ; Rongxin WU ; Chuchu YE ; Lipeng HAO
Journal of Public Health and Preventive Medicine 2026;37(2):26-29
Objective To analyze the epidemic characteristics of scarlet fever in Pudong New Area, Shanghai from 2010 to 2023, and to grasp the incidence of scarlet fever in time. Methods The information on the registration of scarlet fever in Pudong New Area, Shanghai from January 1, 2010 to December 31, 2023 was collected through the China Disease Prevention and Control Information System, and descriptive epidemiological methods and Joinpoint regression model were used for data analysis. Results From 2010 to 2023, a total of 5 669 cases of scarlet fever were reported in Pudong New Area, Shanghai, and no deaths were reported. The annual reported incidence rate was 7.2/100 000, and the overall trend was decreasing year by year. In terms of time distribution, the incidence peaks were in spring and winter. The incidence rate in males was higher than that in females, and it mainly affected children, especially those aged 2 to 10 years. Joinpoint regression model analysis showed that the annual percentage change (APC) and average annual percentage change (AAPC) of the reported incidence rate of scarlet fever from 2010 to 2023 showed that the incidence rate was fluctuating, and the incidence rate decreased significantly from 2019 to 2023 (APC was -53.7%). Conclusion The reported incidence rate of scarlet fever in Pudong New Area in Shanghai has decreased year by year from 2010 to 2023, and children remain the focus of prevention and control.
5.Current quality status and management countermeasures of occupational health technical services in Zhejiang Province
Qiuliang XU ; Feng HAN ; Peng WANG ; Zhen ZHOU ; Fei LI ; Hongwei XIE ; Yong HU ; Weiming YUAN ; Lifang ZHOU ; Hua ZOU
Journal of Environmental and Occupational Medicine 2026;43(3):341-346
Background The quality of occupational health technical services is directly linked to the protection of workers' health rights and the efficacy of occupational disease prevention and control. However, the industry still faces critical challenges: sporadic instances of institutional non-compliance and persistent irregularities in professional practice continue to undermine overall service performance. Objective To assess the current quality status of occupational health technical services in Zhejiang Province and propose countermeasures for quality improvement, providing a scientific basis for policy optimization and service delivery quality enhancement. Methods A total of 69 occupational health technical service institutions in Zhejiang Province that obtained formal accreditation as of April 30, 2024, were sampled, including 3 public institutions and 66 private institutions (comprising 3 formerly Class-A, 28 formerly Class-B, 11 formerly Class-C, and 24 newly certified institutions). Following the Technical Protocol for Quality Monitoring of Occupational Health Technical Service in Zhejiang Province and the Technical Protocol for Proficiency Testing of Occupational Health Detection in Zhejiang Province, a quality assessment task force comprising national and provincial experts was established. Evaluation was conducted across four dimensions: qualification maintenance and compliance, standardization of technical services, authenticity of technical services, and proficiency testing, utilizing a combination of document review, on-site inspections, and technical skill assessments. Results The occupational health technical service institutions in Zhejiang Province were predominantly private entities (82.5%), with significant disparities in overall service quality. The pass rates for qualification maintenance and compliance, technical service standardization, technical service authenticity, and the excellence rate for laboratory proficiency testing were 81.5%, 80.7%, 97.3%, and 90.4%, respectively. Regarding qualification maintenance, the pass rates for "environmental conditions" (49.8%, 56.7%) and "instrumentation and equipment" (58.2%、65.6%) were significantly lower for formerly Class-C and newly certified institutions compared to other categories. In terms of technical standardization, "standardized on-site inspections" recorded the lowest pass rate (67.4%), with newly certified institutions at only 48.0%. Regarding technical service authenticity, formerly Class-C institutions exhibited issues such as missing raw chromatograms for blank samples (85.7% pass rate). In laboratory proficiency testing, public and formerly Class-A institutions achieved 100% excellence rates, but the performance of formerly Class-C and newly certified institutions was comparatively weak; specifically, the failure rate for organic analysis in formerly Class-C institutions reached 20%; the failure rate for dust testing items in newly certified institutions was 10.3%. Conclusion The overall quality of occupational health technical services in Zhejiang Province still requires significant improvement, particularly in basic institutional conditions, the standardization of on-site inspections, and laboratory proficiency in organic and dust analysis. Formerly Class-C and newly certified institutions should be the primary focus of quality management efforts. Differentiated regulatory strategies are recommended, alongside strengthening interim and ex-post supervision to gradually enhance the quality of occupational health technical services across all institutions.
6.Mechanisms of Curcumol in Inhibiting Proliferation and Migration in Non-small Cell Lung Cancer via JAK2/STAT3 Signaling Pathway
Yu QI ; Yihan YU ; Linling HU ; Bo JIANG ; Yilong ZOU ; Cunyu FAN ; Yiling FAN ; Jixian ZHANG ; Bo XU
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(10):34-45
ObjectiveTo investigate the inhibitory effects of curcumol (Cur) on the proliferation and metastasis of non-small cell lung cancer (NSCLC) cells and to explore the underlying mechanisms. MethodsIn vivo, a subcutaneous tumor xenograft model was established to evaluate the antiproliferative effect of Cur. In vitro, the cell counting kit-8 (CCK-8) assay was used to assess the effects of Cur at concentrations of 0, 60, 120, 240, 360, 480, 600, 720, 840, 960 μmol·L-1 on the viability of NCI-A549 and NCI-H23 cells, and to evaluate its inhibitory effect on the proliferation of human bronchial epithelial BEAS-2B cells. Wound healing and Transwell migration assays were conducted to assess changes in cell migratory capacity following Cur treatment. Immunohistochemistry (IHC-P) was used to investigate the regulatory effect of Cur on the Janus kinase 2/signal transducer and activator of transcription 3 (JAK2/STAT3) signaling pathway in tumor tissues. Western blot was performed to determine the protein expression levels of phosphorylated JAK2 (p-JAK2), phosphorylated STAT3 (p-STAT3), proliferating cell nuclear antigen (PCNA), matrix metalloproteinase-2 (MMP-2), matrix metalloproteinase-9 (MMP-9), and vascular endothelial growth factor A (VEGFA) in tumor tissues and cells. To further verify the role of the JAK2/STAT3 signaling pathway in the pharmacological effects of Cur, rescue experiments were performed using the pathway agonist colivelin. ResultsIn vivo experiments showed that, compared with the model group, the tumor volumes of subcutaneous xenografts in nude mice in both low- and high-dose Cur groups were significantly reduced (P<0.05), and the tumor inhibition rates were significantly increased (P<0.05). The inhibitory effect in the high-dose group was comparable to that of the cisplatin group, and the body weight of mice in the Cur groups remained stable throughout the experiment. In vitro, compared with the control group, Cur at concentrations of 120 and 240 μmol·L-1 inhibited the proliferation of NCI-A549 and NCI-H23 cells in a concentration-dependent manner (P<0.05), with a significant inhibitory effect observed at 360 μmol·L-1 (P<0.01), while no significant effect on the viability of BEAS-2B cells was observed. Migration assays demonstrated that, compared with the control group, Cur treatment significantly reduced the migration rates of both cell lines in a concentration-dependent manner (P<0.05), with an inhibitory effect at 360 μmol·L-1 comparable to that of the cisplatin group. Mechanistic validation showed that, compared with the control group, the protein expression levels of p-JAK2 and p-STAT3 in tumor tissues and cells were significantly downregulated in the Cur groups (P<0.01), and the expression levels of downstream proteins PCNA, MMP-2, MMP-9, and VEGFA were also significantly decreased with increasing Cur concentration (P<0.05). In the rescue experiments, compared with the control group, colivelin pretreatment increased cell proliferation and migration rates (P<0.05) and upregulated the expression of related proteins (P<0.05). Compared with the Cur group, the colivelin+Cur group showed significantly increased proliferation and migration rates (P<0.05), along with significantly upregulated protein expression levels (P<0.05). ConclusionCur can significantly inhibit the proliferation and metastasis of NSCLC both in vivo and in vitro, and its mechanism of action is closely associated with the inhibition of JAK2/STAT3 signaling pathway activation.
7.Mechanisms of Oxyresveratrol in Inhibiting Epithelial-mesenchymal Transition in Non-small Cell Lung Cancer via PI3K/Akt Signaling Pathway
Linling HU ; Bo JIANG ; Yu QI ; Yilong ZOU ; Cunyu FAN ; Yiling FAN ; Yihan YU ; Bo XU
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(10):46-57
ObjectiveTo investigate the mechanisms by which oxyresveratrol (OXY) inhibits epithelial-mesenchymal transition (EMT) in non-small cell lung cancer (NSCLC) through the phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt) signaling pathway. MethodsCell counting kit-8 (CCK-8) assays were used to determine the survival rates of A549 and H1299 cells treated with different concentrations of OXY, and appropriate concentrations (0, 30, 60, 90 μmol·L-1) were selected. The effects of OXY on the proliferation of A549 and H1299 cells were evaluated using 5-ethynyl-2′-deoxyuridine (EdU) assays and colony formation assays. Wound healing assays and Transwell invasion assays were performed to assess the effects of OXY on cell migration and invasion. Western blot (WB) was used to detect the expression levels of Snail, E-cadherin, N-cadherin, and Vimentin in A549 and H1299 cells. Network pharmacology and molecular docking were applied to predict the mechanism of action of OXY, and WB was used to evaluate the effects of OXY on proteins in the PI3K/Akt signaling pathway. Rescue experiments were conducted using the PI3K/Akt signaling pathway agonist 740Y-P. Under activation of the PI3K/Akt pathway, the effect of OXY on proliferation, migration, and invasion phenotypes, as well as on the expression levels of PI3K/Akt pathway-related proteins and EMT markers (Snail, E-cadherin, N-cadherin, and Vimentin), were examined. ResultsIn the forward experiments, CCK-8 assay results showed that, compared with the control group, the survival rates of NSCLC cells in the OXY-treated groups (20-120 μmol·L-1) were significantly decreased (P<0.05). The half-maximal inhibitory concentration (IC50) values of A549 and H1299 cells after 48 h of OXY treatment were 113.6 μmol·L-1 and 92.53 μmol·L-1, respectively. Therefore, concentrations of 0, 30, 60, 90 μmol·L-1 were selected as the gradient for subsequent phenotypic and mechanistic studies. Compared with the control group, the proliferation rate, colony number, migration rate, and invasion number of NSCLC cells in the OXY groups (30, 60, and 90 μmol·L-1) were significantly decreased (P<0.01, P<0.05). WB results showed that, compared with the control group, the protein expression levels of Snail, N-cadherin, and Vimentin in NSCLC cells of the OXY groups were significantly decreased (P<0.05), whereas E-cadherin expression was significantly increased (P<0.01). Network pharmacology and molecular docking results indicated that OXY could act on the PI3K/Akt signaling pathway and exhibited good binding affinity with PI3K and Akt proteins. Further WB results showed that, compared with the control group, there were no statistically significant differences in the expression levels of PI3K and Akt proteins in NSCLC cells of the OXY groups, whereas the expression levels of phosphorylated PI3K (p-PI3K) and phosphorylated Akt (p-Akt) were significantly decreased (P<0.05). In the rescue experiments, compared with the control group, the proliferation rate, colony number, migration rate, and invasion number of NSCLC cells in the 740Y-P group (15 μmol·L-1) were significantly increased (P<0.01). Compared with the control + OXY group (90 μmol·L-1), these indices in the 740Y-P + OXY group (15 μmol·L-1 + 90 μmol·L-1) were also significantly increased (P<0.01). WB results showed that, compared with the control group, there were no statistically significant differences in the expression levels of PI3K and Akt proteins in the 740Y-P group. However, the expression levels of p-PI3K, p-Akt, Snail, N-cadherin, and Vimentin were significantly increased (P<0.05), while E-cadherin expression was significantly decreased (P<0.01). Compared with the control + OXY group, there were no statistically significant differences in PI3K and Akt protein expression in the 740Y-P + OXY group. However, the expression levels of p-PI3K, p-Akt, Snail, N-cadherin, and Vimentin were significantly increased (P<0.05), while E-cadherin expression was significantly decreased (P<0.05). ConclusionOXY inhibits the PI3K/Akt signaling pathway and suppresses the EMT process, thereby exerting anti-metastatic effects in NSCLC.
8.Anti-lung Cancer Mechanisms of Yang-warming Herbs and Formulas: A Review
Bo XU ; Yu QI ; Jixian ZHANG ; Linling HU ; Bo JIANG ; Yilong ZOU ; Cunyu FAN ; Yiling FAN ; Qing MIAO ; Yihan YU
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(10):70-79
Lung cancer, particularly non-small cell lung cancer (NSCLC), is the malignant tumor with the highest incidence and mortality in China and worldwide. In 2022, the global number of deaths reached 1.8 million, accounting for 18.7% of all cancer-related deaths, seriously threatening human health and life, and posing a severe challenge for prevention and treatment. Although treatment strategies for lung cancer have been continuously enriched in recent years, and progress has been made in targeted therapy and immunotherapy, long-term survival benefits remain limited due to primary or acquired drug resistance, low immune responsiveness, and chemotherapy-related toxicities. Therefore, there is an urgent need to explore safe and effective adjunctive therapeutic strategies. Traditional Chinese medicine (TCM), with its advantages of holistic regulation and individualized syndrome differentiation, has played an increasingly prominent role in comprehensive cancer treatment. TCM holds that "Yang deficiency leads to accumulation" is a key pathogenesis of tumors. Based on the theory that "Yang transforms Qi, while Yin forms substance", deficiency of Yang Qi results in impaired warming and transformation functions, leading to internal accumulation of Yin-cold. This is closely related to dysregulation of the immune microenvironment, "cold tumor" characteristics, and dysfunction of the neuroendocrine system in modern medicine. Accordingly, the therapeutic strategy of "warming Yang, supporting healthy Qi, and combating cancer" has gained increasing attention. In recent years, commonly used Yang-warming Chinese herbs, including Aconiti Lateralis Radix Praeparata, Zingiberis Rhizoma, Cinnamomi Cortex, Epimedii Folium, and Psoraleae Fructus, as well as their active constituents, have achieved notable progress in anti-lung cancer research by regulating multiple signaling pathways, inducing apoptosis, inhibiting metastasis, and reversing drug resistance. In addition, Yang-warming formulae such as Sini Tang and Yanghe Tang have shown promising effects in alleviating myelosuppression, improving cancer-related fatigue, managing malignant pleural effusion, and relieving cancer pain. These therapies exhibit toxicity-reducing and efficacy-enhancing effects, significantly improving patients' quality of life and survival benefits. To systematically summarize the roles and mechanisms of Yang-warming Chinese herbal medicines and compound formulae in lung cancer, this paper provides a comprehensive review of recent advances, aiming to offer insights for the clinical practice of TCM in the prevention and treatment of lung cancer.
9.Zuogui Jiangtang Shuxin Prescription Ameliorates Lipid Deposition in Diabetic Cardiomyopathy of MKR Mice by Regulating AMPK/FoxO1/CD36 Signaling Pathway
Xiu LIU ; Juping WANG ; Jiawang HUANG ; Junju ZOU ; Qin XIANG ; Yunfeng YU ; Rong YU
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(10):134-142
ObjectiveTo investigate the ameliorative effects and related mechanisms of the Zuogui Jiangtang Shuxin prescription (ZJSP) on glucose and lipid metabolism disorders in MKR mice with diabetic cardiomyopathy (DCM), with a focus on elucidating its regulatory role on the adenosine monophosphate-activated protein kinase (AMPK)/forkhead box protein O1 (FoxO1)/cluster of differentiation 36 (CD36) signaling pathway and lipid deposition. MethodsFifty 8-week-old male MKR mice were fed a high-fat diet for four weeks and then intraperitoneally injected with streptozotocin (STZ) while maintaining a high-fat diet to establish a DCM model. The mice were randomly divided into the model group, the low-dose(14.43 g·kg-1)and high-dose(28.86 g·kg-1) ZJSP groups, and the metformin group (0.25 g·kg-1), with age-matched FVB mice as a normal control group. Each group received intragastric administration of normal saline or corresponding concentrations of ZJSP at equal volumes. After four weeks, fasting blood glucose (FBG) and cardiac function were measured. Blood was collected from the eyeballs under anesthesia to detect fasting insulin (FINS) and blood lipid levels. Myocardial tissue morphology was observed by hematoxylin-eosin (HE) staining, and lipid deposition in the heart was assessed using oil red O staining. Real-time quantitative polymerase chain reaction (Real-time PCR) was used to measure the mRNA expression levels of AMPK, FoxO1, and CD36 in myocardial tissues. Western blot was employed to detect the protein expression levels of AMPK, p-AMPK, FoxO1, p-FoxO1, and CD36. ResultsCompared with the control group, the model group showed significantly increased levels of FBG and FINS (P<0.01), elevated levels of triglycerides (TG), total cholesterol (TC), and low-density lipoprotein cholesterol (LDL-C) (P<0.01), and significantly decreased left ventricular ejection fraction (EF) and fractional shortening (FS) values (P<0.01). HE staining revealed marked cardiomyocyte hypertrophy, disarray, and widened intercellular spaces in myocardial tissues. Oil Red O staining showed extensive red deposition areas and fine lipid droplet accumulation in the myocardial tissue. AMPK mRNA expression was decreased, while FoxO1 and CD36 mRNA expressions were significantly increased (P<0.01). The p-AMPK/AMPK protein expression ratio in myocardial tissues was significantly reduced, while the p-FoxO1/FoxO1 protein expression ratio and CD36 protein expression levels were significantly increased (P<0.01). Compared with the model group, all treatment groups exhibited significantly reduced FBG (P<0.01), decreased FINS and blood lipid levels (TG, TC, LDL-C) (P<0.05, P<0.01), improved cardiac function (P<0.05), noticeable amelioration of myocardial histopathological morphology and lipid deposition, increased AMPK mRNA expression (P<0.01), with significantly downregulated FoxO1 and CD36 mRNA expressions (P<0.01), elevated p-AMPK/AMPK protein expression levels in myocardial tissue (P<0.05), significantly decreased p-FoxO1/FoxO1 ratios (P<0.01), and downregulated CD36 protein expression levels (P<0.05, P<0.01). ConclusionZJSP exerts a protective effect on the heart in type 2 DCM of MKR mice, and its mechanism may be associated with the regulation of the AMPK/FoxO1/CD36 signaling pathway.
10.Mechanisms of Curcumol in Inhibiting Proliferation and Migration in Non-small Cell Lung Cancer via JAK2/STAT3 Signaling Pathway
Yu QI ; Yihan YU ; Linling HU ; Bo JIANG ; Yilong ZOU ; Cunyu FAN ; Yiling FAN ; Jixian ZHANG ; Bo XU
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(10):34-45
ObjectiveTo investigate the inhibitory effects of curcumol (Cur) on the proliferation and metastasis of non-small cell lung cancer (NSCLC) cells and to explore the underlying mechanisms. MethodsIn vivo, a subcutaneous tumor xenograft model was established to evaluate the antiproliferative effect of Cur. In vitro, the cell counting kit-8 (CCK-8) assay was used to assess the effects of Cur at concentrations of 0, 60, 120, 240, 360, 480, 600, 720, 840, 960 μmol·L-1 on the viability of NCI-A549 and NCI-H23 cells, and to evaluate its inhibitory effect on the proliferation of human bronchial epithelial BEAS-2B cells. Wound healing and Transwell migration assays were conducted to assess changes in cell migratory capacity following Cur treatment. Immunohistochemistry (IHC-P) was used to investigate the regulatory effect of Cur on the Janus kinase 2/signal transducer and activator of transcription 3 (JAK2/STAT3) signaling pathway in tumor tissues. Western blot was performed to determine the protein expression levels of phosphorylated JAK2 (p-JAK2), phosphorylated STAT3 (p-STAT3), proliferating cell nuclear antigen (PCNA), matrix metalloproteinase-2 (MMP-2), matrix metalloproteinase-9 (MMP-9), and vascular endothelial growth factor A (VEGFA) in tumor tissues and cells. To further verify the role of the JAK2/STAT3 signaling pathway in the pharmacological effects of Cur, rescue experiments were performed using the pathway agonist colivelin. ResultsIn vivo experiments showed that, compared with the model group, the tumor volumes of subcutaneous xenografts in nude mice in both low- and high-dose Cur groups were significantly reduced (P<0.05), and the tumor inhibition rates were significantly increased (P<0.05). The inhibitory effect in the high-dose group was comparable to that of the cisplatin group, and the body weight of mice in the Cur groups remained stable throughout the experiment. In vitro, compared with the control group, Cur at concentrations of 120 and 240 μmol·L-1 inhibited the proliferation of NCI-A549 and NCI-H23 cells in a concentration-dependent manner (P<0.05), with a significant inhibitory effect observed at 360 μmol·L-1 (P<0.01), while no significant effect on the viability of BEAS-2B cells was observed. Migration assays demonstrated that, compared with the control group, Cur treatment significantly reduced the migration rates of both cell lines in a concentration-dependent manner (P<0.05), with an inhibitory effect at 360 μmol·L-1 comparable to that of the cisplatin group. Mechanistic validation showed that, compared with the control group, the protein expression levels of p-JAK2 and p-STAT3 in tumor tissues and cells were significantly downregulated in the Cur groups (P<0.01), and the expression levels of downstream proteins PCNA, MMP-2, MMP-9, and VEGFA were also significantly decreased with increasing Cur concentration (P<0.05). In the rescue experiments, compared with the control group, colivelin pretreatment increased cell proliferation and migration rates (P<0.05) and upregulated the expression of related proteins (P<0.05). Compared with the Cur group, the colivelin+Cur group showed significantly increased proliferation and migration rates (P<0.05), along with significantly upregulated protein expression levels (P<0.05). ConclusionCur can significantly inhibit the proliferation and metastasis of NSCLC both in vivo and in vitro, and its mechanism of action is closely associated with the inhibition of JAK2/STAT3 signaling pathway activation.


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