2.Baicalein attenuates lipopolysaccharide-induced myocardial injury by inhibiting ferroptosis via miR-299b-5p/HIF1-α pathway.
Wen-Yan ZHOU ; Jian-Kui DU ; Hong-Hong LIU ; Lei DENG ; Kai MA ; Jian XIAO ; Sheng ZHANG ; Chang-Nan WANG
Journal of Integrative Medicine 2025;23(5):560-575
OBJECTIVE:
Baicalein has been reported to have wide therapeutic effects that act through its anti-inflammatory activity. This study examines the effect and mechanism of baicalein on sepsis-induced cardiomyopathy (SIC).
METHODS:
A thorough screening of a small library of natural products, comprising 100 diverse compounds, was conducted to identify the most effective drug against lipopolysaccharide (LPS)-treated H9C2 cardiomyocytes. The core target proteins and their associated signaling pathways involved in baicalein's efficacy against LPS-induced myocardial injury were predicted by network pharmacology.
RESULTS:
Baicalein was identified as the most potent protective agent in LPS-exposed H9C2 cardiomyocytes. It exhibited a dose-dependent inhibitory effect on cell injury and inflammation. In the LPS-induced septic mouse model, baicalein demonstrated a significant capacity to mitigate LPS-triggered myocardial deficits, inflammatory responses, and ferroptosis. Network pharmacological analysis and experimental confirmation suggested that hypoxia-inducible factor 1 subunit α (HIF1-α) is likely to be the crucial factor in mediating the impact of baicalein against LPS-induced myocardial ferroptosis and injury. By combining microRNA (miRNA) screening in LPS-treated myocardium with miRNA prediction targeting HIF1-α, we found that miR-299b-5p may serve as a regulator of HIF1-α. The reduction in miR-299b-5p levels in LPS-treated myocardium, compared to the control group, was reversed by baicalein treatment. The reverse transcription quantitative polymerase chain reaction, Western blotting, and dual-luciferase reporter gene analyses together identified HIF1-α as the target of miR-299b-5p in cardiomyocytes.
CONCLUSION
Baicalein mitigates SIC at the miRNA level, suggesting the therapeutic potential of it in treating SIC through the regulation of miR-299b-5p/HIF1-α/ferroptosis pathway. Please cite this article as: Zhou WY, Du JK, Liu HH, Deng L, Ma K, Xiao J, Zhang S, Wang CN. Baicalein attenuates lipopolysaccharide-induced myocardial injury by inhibiting ferroptosis via miR-299b-5p/HIF1-α pathway. J Integr Med. 2025; 23(5):560-575.
Flavanones/pharmacology*
;
Animals
;
MicroRNAs/genetics*
;
Lipopolysaccharides
;
Hypoxia-Inducible Factor 1, alpha Subunit/genetics*
;
Ferroptosis/drug effects*
;
Mice
;
Myocytes, Cardiac/metabolism*
;
Signal Transduction/drug effects*
;
Rats
;
Male
;
Mice, Inbred C57BL
;
Cardiomyopathies/etiology*
;
Cell Line
;
Sepsis/complications*
3.Independent and Interactive Effects of Air Pollutants, Meteorological Factors, and Green Space on Tuberculosis Incidence in Shanghai.
Qi YE ; Jing CHEN ; Ya Ting JI ; Xiao Yu LU ; Jia le DENG ; Nan LI ; Wei WEI ; Ren Jie HOU ; Zhi Yuan LI ; Jian Bang XIANG ; Xu GAO ; Xin SHEN ; Chong Guang YANG
Biomedical and Environmental Sciences 2025;38(7):792-809
OBJECTIVE:
To assess the independent and combined effects of air pollutants, meteorological factors, and greenspace exposure on new tuberculosis (TB) cases.
METHODS:
TB case data from Shanghai (2013-2018) were obtained from the Shanghai Center for Disease Control and Prevention. Environmental data on air pollutants, meteorological variables, and greenspace exposure were obtained from the National Tibetan Plateau Data Center. We employed a distributed-lag nonlinear model to assess the effects of these environmental factors on TB cases.
RESULTS:
Increased TB risk was linked to PM 2.5, PM 10, and rainfall, whereas NO 2, SO 2, and air pressure were associated with a reduced risk. Specifically, the strongest cumulative effects occurred at various lags: PM 2.5 ( RR = 1.166, 95% CI: 1.026-1.325) at 0-19 weeks; PM 10 ( RR = 1.167, 95% CI: 1.028-1.324) at 0-18 weeks; NO 2 ( RR = 0.968, 95% CI: 0.938-0.999) at 0-1 weeks; SO 2 ( RR = 0.945, 95% CI: 0.894-0.999) at 0-2 weeks; air pressure ( RR = 0.604, 95% CI: 0.447-0.816) at 0-8 weeks; and rainfall ( RR = 1.404, 95% CI: 1.076-1.833) at 0-22 weeks. Green space exposure did not significantly impact TB cases. Additionally, low temperatures amplified the effect of PM 2.5 on TB.
CONCLUSION
Exposure to PM 2.5, PM 10, and rainfall increased the risk of TB, highlighting the need to address air pollutants for the prevention of TB in Shanghai.
China/epidemiology*
;
Humans
;
Air Pollutants/analysis*
;
Tuberculosis/epidemiology*
;
Incidence
;
Meteorological Concepts
;
Particulate Matter/adverse effects*
;
Environmental Exposure
;
Male
;
Female
;
Adult
;
Air Pollution
;
Middle Aged
4.Sex and age distribution of global disease burden of calcific aortic valve disease.
Xiangning DENG ; Xinyu SUI ; Nan LI ; Jieli FENG ; Shaomin CHEN ; Xinye XU ; Yida TANG ; Yupeng WANG
Journal of Zhejiang University. Medical sciences 2025;54(1):21-27
OBJECTIVES:
To analyze sex and age distribution of global disease burden of calcific aortic valve disease (CAVD) from 1990 to 2021.
METHODS:
CAVD data during 1990-2021 were obtained from the IHME website for Global Burden of Disease (GBD). The prevalence, mortality, years lived with disability (YLDs), and disability-adjusted life years (DALYs) were analyzed by gender and age groups. Joinpoint regression was used to calculate annual percentage change (APC) and average annual percentage change (AAPC).
RESULTS:
In 2021, there were 13.32 million CAVD patients and 142 000 deaths caused by CAVD globally. Age-standardized prevalence was higher in males (193.2/105) than that in females (128.9/105). Patients in 65-<85 age group accounted for 64.0% of total cases, while those ≥85 years old accounted for 16.1%. From 1990 to 2021, prevalence increased in both sexes with an AAPC of 0.72% for males and 0.57% for females, respectively. Prevalence grew fastest from 2000 to 2010, slowed thereafter, and declined from 2015 to 2021. In <65 years old, the mortality of males was 2.4 times higher than that of females, while in ≥85 years old, mortality of females (117.3/105) exceeded that of males (99.1/105). YLD rates increased with age, and were higher in males for all age groups. DALY rates decreased overall but increased in ≥85 years old, with a greater increase in females.
CONCLUSIONS
There are significant gender and age disparities in global disease burden of CAVD, with the elderly, especially super-elderly females deserving particular attention. It is recommended to develop personalized intervention strategies for these populations.
Humans
;
Male
;
Female
;
Aged
;
Calcinosis/mortality*
;
Prevalence
;
Global Burden of Disease
;
Aged, 80 and over
;
Middle Aged
;
Aortic Valve/pathology*
;
Aortic Valve Stenosis/epidemiology*
;
Age Distribution
;
Adult
;
Disability-Adjusted Life Years
;
Sex Distribution
;
Global Health
;
Aortic Valve Disease/epidemiology*
;
Sex Factors
5.Additional role of low-density lipoprotein cholesterol on the risk of osteoporosis in men with or without coronary heart disease: a real-world longitudinal study.
Jing ZENG ; Zi-Mo PAN ; Ting LI ; Ze-Yu CHEN ; Xiao-Yan CAI ; Mei-Liang GONG ; Xin-Li DENG ; Sheng-Shu WANG ; Nan LI ; Miao LIU ; Chun-Lin LI
Journal of Geriatric Cardiology 2025;22(2):219-228
BACKGROUND:
Early control of low-density lipoprotein cholesterol (LDL-C) is crucial for reducing the progress of cardiovascular disease. However, its additional role to the risk of primary osteoporosis in men with coronary heart disease was inconclusive. Our study aims to determine the association of LDL-C and its trajectories for osteoporosis risk in the middle-aged and aged men of China.
METHODS:
The retrospective cohort study of 1546 men aged 69.74 ± 11.30 years conducted in Beijing, China from 2015 to 2022. And the incidence of primary osteoporosis was annually recorded. LDL-C trajectories were further identified by latent class growth model using repeated measurements of LDL-C. The association of baseline LDL-C for osteoporosis was estimated using hazard ratio (HR) with 95% CI in Cox proportional hazard model, while mean level and trajectories of LDL-C for osteoporosis were evaluated using odds ratio (OR) with 95% CI in logistic regression model.
RESULTS:
During the median 6.2-year follow-up period, 70 men developed primary osteoporosis. The higher level of baseline LDL-C (HR = 1.539, 95% CI: 1.012-2.342) and mean LDL-C (OR = 2.190, 95% CI: 1.443-3.324) were associated with higher risk of osteoporosis in men with coronary heart disease after adjusted for covariates. Compared with those in the LDL-C trajectory of low-stable decrease, participants with medium-fluctuant trajectory, whose longitudinal LDL-C started with a medium LDL-C level and appeared an increase and then decrease, were negatively associated with osteoporosis risk (OR = 2.451, 95% CI: 1.152-5.216). And participants with initially high LDL-C level and then a rapid decrease demonstrated a tendency towards reduced risk (OR = 0.718, 95% CI: 0.212-2.437).
CONCLUSIONS
Elevated LDL-C level and its long-term fluctuation may increase the risk of primary osteoporosis in men. Early controlling a stable level of LDL-C is also essential for bone health.
6.Artificial intelligence in drug development for delirium and Alzheimer's disease.
Ruixue AI ; Xianglu XIAO ; Shenglong DENG ; Nan YANG ; Xiaodan XING ; Leiv Otto WATNE ; Geir SELBÆK ; Yehani WEDATILAKE ; Chenglong XIE ; David C RUBINSZTEIN ; Jennifer E PALMER ; Bjørn Erik NEERLAND ; Hongming CHEN ; Zhangming NIU ; Guang YANG ; Evandro Fei FANG
Acta Pharmaceutica Sinica B 2025;15(9):4386-4410
Delirium is a common cause and complication of hospitalization in the elderly and is associated with higher risk of future dementia and progression of existing dementia, of which 70% is Alzheimer's disease (AD). AD and delirium, which are known to be aggravated by one another, represent significant societal challenges, especially in light of the absence of effective treatments. The intricate biological mechanisms have led to numerous clinical trial setbacks and likely contribute to the limited efficacy of existing therapeutics. Artificial intelligence (AI) presents a promising avenue for overcoming these hurdles by deploying algorithms to uncover hidden patterns across diverse data types. This review explores the pivotal role of AI in revolutionizing drug discovery for AD and delirium from target identification to the development of small molecule and protein-based therapies. Recent advances in deep learning, particularly in accurate protein structure prediction, are facilitating novel approaches to drug design and expediting the discovery pipeline for biological and small molecule therapeutics. This review concludes with an appraisal of current achievements and limitations, and touches on prospects for the use of AI in advancing drug discovery in AD and delirium, emphasizing its transformative potential in addressing these two and possibly other neurodegenerative conditions.
7.Application of nanoprobe based on aggregation-induced luminescence in photothermal diagnosis and treatment of prostate cancer
Bin GUI ; Nan JIANG ; Xin HUANG ; Fanglu ZHONG ; Zhiwen WANG ; Qianhui LIU ; Yuxin GUO ; Yueying CHEN ; Huan PU ; Qing DENG
Chinese Journal of Tissue Engineering Research 2025;29(16):3400-3409
BACKGROUND:A novel aggregation induced luminescence fluorescence probe based on the mechanism of intramolecular motility restriction can be used for the detection of disease markers,tumor diagnosis,and bacterial imaging recognition.OBJECTIVE:To prepare a near-infrared Ⅱ nanoprobe called FA-DSPE-PEG-AIE@NPs based on aggregation-induced luminescence,and to explore its potential of targeted fluorescence imaging and photothermal therapy for prostate cancer.METHODS:Lecithin,polyethylene glycol phospholipids,folate polyethylene glycol phospholipids,and aggregation induced luminescent molecule 2TT-oC26B were used as raw materials.The folate-targeted nanoprobe FA-DSPE-PEG-AIE@NPs were prepared by nanoprecipitation method,and basic characterization of the nanoprobe was detected.PC3 human prostate cancer cells and human umbilical vein endothelial cells were selected as experimental objects.The cytotoxicity and phototoxicity of FA-DSPE-PEG-AIE@NPs were detected.PC3 human prostate cancer cells were selected as the experimental objects.Flow cytometry and calcein/propidium iodide staining were used to assess the efficacy of photothermal therapy.PC3 human prostate cancer cells were injected subcutaneously into the abdomen of BALB/C nude mice to establish a tumor model,and nanoprobes FA-DSPE-PEG-AIE@NPs were injected into the tail vein.The mice were immediately subjected to near-infraced Ⅱ fluorescence imaging.12 hours later,the tumor was irradiated by laser for 5 minutes,and the photothermal treatment effect was observed within 14 days.RESULTS AND CONCLUSION:(1)The nanoprobes FA-DSPE-PEG-AIE@NPs with a mean diameter of(171.0±0.3)nm showed a well-defined spherical morphology.The nanoprobe had a wide absorption spectrum and tail emission extending to the near-infrared Ⅱ which emitted a bright near-infrared Ⅱ fluorescence signal under laser irradiation.(2)The nanoprobes FA-DSPE-PEG-AIE@NPs had low cytotoxicity and high phototoxicity.The results of flow cytometry and calcein/propidium iodide staining showed that nanoprobes FA-DSPE-PEG-AIE@NPs had an obvious photothermal killing effect on human prostate cancer cells.(3)The nanoprobes FA-DSPE-PEG-AIE@NPs successfully achieved near-infrared Ⅱ fluorescence imaging of mouse blood vessels and the maximum enrichment time of the tumor was 12 hours.The vessel widths of the hind leg and single blood vessels of abdomen were estimated to be 0.63 mm and 0.42 mm.The tumor volume of mice was significantly smaller after 14 days of treatment.(4)The results show that nanoprobes FA-DSPE-PEG-AIE@NPs can achieve near-infrared Ⅱ fluorescence imaging and photothermal therapy of prostate cancer effectively,which may provide a new method for early diagnosis and combined treatment of prostate cancer.
8.Mechanism of action of Sterculiae Lychnophorae Semen against PM2.5-induced acute lung injury based on network pharmacology,molecular docking and experimental validation
Fan ZHANG ; Yi-fan DU ; Xiao-shu DENG ; Zu-feng ZHANG ; Xian-lei HAN ; Wei TIAN ; Xiu-mei LI ; Mian CHEN ; Fei LIU ; Nan WANG
Chinese Pharmacological Bulletin 2025;41(12):2362-2369
Aim To investigate the anti-acute lung injury(ALI)effect of Sterculiae Lychnophorae Semen(SLS)and its mechanism.Methods The main ac-tive components of SLS and their core targets and path-ways of action against ALI were obtained by network pharmacology methods.Subsequently,molecular doc-king technology and in vitro cellular experiments were applied for validation.Results A total of 19 core tar-gets were obtained,including HSP90AA1,CASP3,TNF,MAPK8 and MAPK14.The mechanisms may in-volve signaling pathways such as cancer,PI3K/Akt and MAPK.Molecular docking confirmed that the key targets of SLS formed a better binding activity with the relevant active ingredients.The in vitro results showed that SLS was able to protect the PM2.5-contaminated BEAS-2B cells,inhibit their NO,IL-1β and TNF-αlevels,and reduce the expression of p-p38 MAPK and p-JNK proteins.Conclusions The study successfully predicts the active ingredients,targets and signaling pathways of SLS against ALI,and in vitro experiments demonstrate that SLS might protect BEAS-2B cells from PM2.5 stimulus-induced inflammation and apoptosis by inhibiting the over-activation of p38 MAPK and JNK signaling pathways.
9.Application effects of horizontal Baduanjin exercise based on interactive standard reaching theory on rehabilitation of patients with chronic heart failure
Qian-qian DING ; Ya-nan WANG ; Nan-nan DENG ; Hai-xia XU ; Sheng TU
Chinese Journal of cardiovascular Rehabilitation Medicine 2025;34(4):510-515
Objective:To explore the effect of horizontal Baduanjin guided by interactive standard reaching theory(ISRT)on cardiac function and quality of life in patients with chronic heart failure(CHF).Methods:This random-ized controlled study enrolled 114 patients diagnosed with CHF in Bozhou People's Hospital between September 2024 and February 2025.Patients were randomly divided into control group(n=57,routine nursing care)and interven-tion group(n=57,horizontal Baduanjin under the guidance of interactive standard theory).Both groups were con-tinuously treated for 3 months.Cardiac function indexes,N-terminal pro-brain natriuretic peptide(NT-proB-NP),self-care ability,quality of life and incidence of major adverse cardiovascular events(MACE)were com-pared between the two groups.Results:Compared to patients in the control group,those in the intervention had significant higher left ventricular ejection fraction(LVEF)[(56.34±0.86)%vs.(46.69±0.91)%],6min walking distance(6MWD)[(477.16±6.62)m vs.(451.39±4.17)m]and the proportion of New York Heart Association(NYHA)class Ⅱ(70.18%vs.35.09%),and significant lower NT-proBNP[(237.76±6.41)pg/ml vs.(377.46±6.85)pg/ml],scores of the European heart failure self-care behavior scale 9(EHFSCB-9)[(12.61±1.81)points vs.(25.51±1.71)points],the physical domain[(3.96±0.91)points vs.(11.05±0.79)points],emotional domain[(4.00±0.85)points vs.(11.95±0.81)points]and other domain[(4.05±0.83)points vs.(13.47±1.15)points]of MLHFQ(P<0.001 all).Compared to those in the control group,patients in intervention group had significant lower incidence of MACE(7.02%vs.22.81%,P=0.035).Conclusion:Under the guidance of the interactive standard theory,the horizontal Baduanjin exercise may enhance the cardiac function,improve self-care ability and quality of life in patients with chronic heart failure.
10.Immediate Impact of Acute Visual Acuity Decline on the Gait of Hemiplegic Patients
Hongshuai LENG ; Qinghua MENG ; Luxing ZHOU ; Nan ZHANG ; Yijie DENG
Journal of Medical Biomechanics 2025;40(2):300-306,328
Objective To explore the immediate impact of acute vision changes in hemiplegic patients on their gait.Methods Thirty visually normal hemiplegic patients were recruited.Plane mirrors(0°),concave lenses(+150°,+450°)were selected to simulate normal vision,moderate myopia,and high myopia scenarios for straight line walking tests.The Qualisys three-dimensional(3D)motion capture system and Kistler 3D force platform were employed to collect kinematic and dynamic parameters of the patients,and the differences in related indicators before and after visual intervention were compared.Results Visual intervention affected the step length,walking speed,and joint angles of hemiplegic patients.Especially after acute vision changes,there was a significant difference in the stride length and ankle joint angles on the patient's affected side.Under high myopia,the step length and step length symmetry were better than those under moderate myopia,but at the expense of gait speed.Visual intervention led to asymmetric trends in step the length symmetry and joint angle symmetry.There were very significant differences in center of pressure(COP)and COP symmetry between normal vision and high myopia.Conclusions Acute vision changes can affect the gait of hemiplegic patients,especially in individuals with high myopia presenting both a notable decrease in walking speed and an increased ankle range of motion,and an increase in walking speed with moderate myopia.Meanwhile,the symmetry of the COP decreases,indicating that acute vision changes lead to a higher risk of falls for patients.Reasonable vision assessment and corresponding intervention measures are expected to improve walking ability and life quality of the patients.

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