1.PDGF-C: an Emerging Target in The Treatment of Organ Fibrosis
Chao YANG ; Zi-Yi SONG ; Chang-Xin WANG ; Yuan-Yuan KUANG ; Yi-Jing CHENG ; Ke-Xin REN ; Xue LI ; Yan LIN
Progress in Biochemistry and Biophysics 2025;52(5):1059-1069
Fibrosis, the pathological scarring of vital organs, is a severe and often irreversible condition that leads to progressive organ dysfunction. It is particularly pronounced in organs like the liver, kidneys, lungs, and heart. Despite its clinical significance, the full understanding of its etiology and complex pathogenesis remains incomplete, posing substantial challenges to diagnosing, treating, and preventing the progression of fibrosis. Among the various molecular players involved, platelet-derived growth factor-C (PDGF-C) has emerged as a crucial factor in fibrotic diseases, contributing to the pathological transformation of tissues in several key organs. PDGF-C is a member of the PDGFs family of growth factors and is synthesized and secreted by various cell types, including fibroblasts, smooth muscle cells, and endothelial cells. It acts through both autocrine and paracrine mechanisms, exerting its biological effects by binding to and activating the PDGF receptors (PDGFRs), specifically PDGFRα and PDGFRβ. This binding triggers multiple intracellular signaling pathways, such as JAK/STAT, PI3K/AKT and Ras-MAPK pathways. which are integral to the regulation of cell proliferation, survival, migration, and fibrosis. Notably, PDGF-C has been shown to promote the proliferation and migration of fibroblasts, key effector cells in the fibrotic process, thus accelerating the accumulation of extracellular matrix components and the formation of fibrotic tissue. Numerous studies have documented an upregulation of PDGF-C expression in various fibrotic diseases, suggesting its significant role in the initiation and progression of fibrosis. For instance, in liver fibrosis, PDGF-C stimulates hepatic stellate cell activation, contributing to the excessive deposition of collagen and other extracellular matrix proteins. Similarly, in pulmonary fibrosis, PDGF-C enhances the migration of fibroblasts into the damaged areas of lungs, thereby worsening the pathological process. Such findings highlight the pivotal role of PDGF-C in fibrotic diseases and underscore its potential as a therapeutic target for these conditions. Given its central role in the pathogenesis of fibrosis, PDGF-C has become an attractive target for therapeutic intervention. Several studies have focused on developing inhibitors that block the PDGF-C/PDGFR signaling pathway. These inhibitors aim to reduce fibroblast activation, prevent the excessive accumulation of extracellular matrix components, and halt the progression of fibrosis. Preclinical studies have demonstrated the efficacy of such inhibitors in animal models of liver, kidney, and lung fibrosis, with promising results in reducing fibrotic lesions and improving organ function. Furthermore, several clinical inhibitors, such as Olaratumab and Seralutinib, are ongoing to assess the safety and efficacy of these inhibitors in human patients, offering hope for novel therapeutic options in the treatment of fibrotic diseases. In conclusion, PDGF-C plays a critical role in the development and progression of fibrosis in vital organs. Its ability to regulate fibroblast activity and influence key signaling pathways makes it a promising target for therapeutic strategies aiming at combating fibrosis. Ongoing research into the regulation of PDGF-C expression and the development of PDGF-C/PDGFR inhibitors holds the potential to offer new insights and approaches for the diagnosis, treatment, and prevention of fibrotic diseases. Ultimately, these efforts may lead to the development of more effective and targeted therapies that can mitigate the impact of fibrosis and improve patient outcomes.
2.Epidemiological Investigation of Dampness Syndrome Manifestations in the Population at Risk of Cerebrovascular Disease
Xiao-Jia NI ; Hai-Yan HUANG ; Qing SU ; Yao XU ; Ling-Ling LIU ; Zhuo-Ran KUANG ; Yi-Hang LI ; Yi-Kai ZHANG ; Miao-Miao MENG ; Yi-Xin GUO ; Xiao-Bo YANG ; Ye-Feng CAI
Journal of Guangzhou University of Traditional Chinese Medicine 2024;41(3):531-539
Objective To make an epidemiological investigation on traditional Chinese medicine(TCM)dampness syndrome manifestations in the population at risk of cerebrovascular diseases in Guangdong area.Methods A cross-sectional study was conducted to analyze the clinical data related to the risk of cerebrovascular diseases in 330 Guangdong permanent residents.The diagnosis of dampness syndrome,quantitative scoring of dampness syndrome and rating of the risk of stroke were performed for the investigation of the distribution pattern of dampness syndrome and its influencing factors.Results(1)A total of 306(92.73%)study subjects were diagnosed as dampness syndrome.The percentage of dampness syndrome in the risk group was 93.82%(258/275),which was slightly higher than that of the healthy group(48/55,87.27%),but the difference was not statistically significant(χ2 = 2.91,P = 0.112).The quantitative score of dampness syndrome in the risk group was higher than that of the healthy group,and the difference was statistically significance(Z =-2.24,P = 0.025).(2)Among the study subjects at risk of cerebrovascular disease,evaluation time(χ2 = 26.11,P = 0.001),stroke risk grading(χ2= 8.85,P = 0.031),and history of stroke or transient ischemic attack(TIA)(χ2 = 9.28,P = 0.015)were the factors influencing the grading of dampness syndrome in the population at risk of cerebrovascular disease.Conclusion Dampness syndrome is the common TCM syndrome in the population of Guangdong area.The manifestations of dampness syndrome are more obvious in the population with risk factors of cerebrovascular disease,especially in the population at high risk of stroke,and in the population with a history of stroke or TIA.The assessment and intervention of dampness syndrome should be taken into account for future project of stroke prevention in Guangdong.
3.Severity of loneliness and factors associated with social and emotional loneliness among the elderly in three districts in Shanghai
Yu-Wen ZHANG ; Ying WANG ; Zhao-Hua XIN ; Jia-Lie FANG ; Rui SONG ; Hao-Cen LI ; Jia-Wen KUANG ; Yu-Ting YANG ; Jing-Yi WANG
Fudan University Journal of Medical Sciences 2024;51(1):1-11
Objective To explore the severity of loneliness among the elderly in communities in Shanghai,and to identify factors associated with social and emotional loneliness respectively.Methods A cross-sectional study was conducted in older adults aged 65 years or above in Pudong New Area,Jing'an District and Huangpu District in Shanghai from Mar to Jun 2021.In Pudong New Area,multi-stage stratified random sampling was conducted based on the age and gender distribution of Shanghai,while in Huangpu District and Jing'an District convenience sampling was conducted.A total of 635 samples were included in the study.Loneliness was assessed using the De Jong Gierveld Loneliness Scale with social and emotional loneliness subscales.Logistic regression analyses were conducted to identify factors associated with social and emotional loneliness.Results Among the 635 participants,only 53 older adults(8.4%)were not lonely.Female(OR=0.46,95%CI:0.31-0.70),higher self-efficacy(OR=0.97,95%CI:0.94-1.00),more objective social support(OR=0.96,95%CI:0.93-0.99)were associated with less severe social loneliness.Meanwhile,higher level of education(secondary education,OR=0.56,95%CI:0.34-0.95;college or above,OR=0.30,95%CI:0.11-0.83)and higher self-efficacy(OR=0.96,95%CI:0.93-0.99)were associated with less severe emotional loneliness,while depression(OR=3.41,95%CI:1.76-6.60)and worse social capital(OR=2.02,95%CI:1.29-3.16)were associated with more severe emotional loneliness.Conclusion Up to 91.6%of the elderly in our study sample were moderately lonely or above.The factors associated with social loneliness include self-efficacy,gender and social support.The factors associated with emotional loneliness are self-efficacy,education level,depression,and social capital.
4.Analysis of the prevalence and related factors for comorbidity of myopia, obesity, and depression symptoms among middle school students in Beijing
LUO Huijuan, SUN Bingjie, ZHAO Hai, CHEN Dongni, WANG Lu, GAO Ruoyi, KUANG Huining, E Boran, GUO Xin
Chinese Journal of School Health 2024;45(7):1045-1049
Objective:
To analyze the current status and related factors of comorbidity of myopia, obesity, and depression symptoms among middle school students in Beijing, so as to provide a basis for comprehensive public health interventions for common diseases.
Methods:
Through stratified cluster random sampling in October 2022, a total of 11 262 junior high school, senior high school, and vocational high school students in 16 districts of Beijing were surveyed with self administered questionnaires, physical examinations and visual acuity examinations. The χ 2 test and binary Logistic regression model were used to analyze group differences in the comorbidity of myopia, obesity and depression symptoms and factors influencing the comorbidity. Stratified analysis was applied to analyze the associations between health risk behaviors and the comorbidity.
Results:
The detection rate of comorbidity of myopia, obesity, and depression symptoms among middle school students in Beijing was 3.35%, the comorbidity rate among vocational high school students (4.61%) was higher than that in junior high school students (2.80%) and senior high school students (3.41%). The comorbidity rate was higher among students in suburban areas (3.66%) than that in urban areas (2.92%), and the differences was statistically significant ( χ 2=15.02, 4.63, P <0.05). Binary Logistic regression analyses indicated that middle school students with poor dietary behaviors ( OR =1.59) and excessive screen time ( OR =1.70) were associated with elevated risk of comorbidity of myopia, obesity, and depression symptoms. Both boys and girls with poor dietary behaviors ( OR =1.63, 1.69) and excessive screen time ( OR =1.45, 2.23) had elevated likelihood of comorbidity of myopia, obesity and depression symptoms. Students in junior high school and senior high school with poor dietary behaviors ( OR =2.16, 1.47) and excessive screen time ( OR =2.20, 1.63 ) had elevated likelihood of comorbidity of myopia, obesity, and depression symptoms ( P <0.05).
Conclusions
The current status of comorbidity of myopia, obesity, and depression symptoms among middle school students in Beijing is concerning. Schools and parents should work together to guide students to develop healthy behaviors such as balanced diet and moderate video, in order to achieve the goal of controlling myopia, obesity and depression symptoms.
5.Co-morbidity of screening myopia and scoliosis among primary and secondary school students in Beijing and associated factors
GAO Ruoyi, SUN Bingjie, LUO Huijuan, E Boran, KUANG Huining, GUO Xin
Chinese Journal of School Health 2024;45(8):1195-1198
Objective:
To investigate the comorbidity of screening myopia and scoliosis among primary and secondary school students in Beijing from 2019 to 2022 and its influencing factors, in order to provide new ideas for comprehensive prevention and control of myopia and scoliosis in children and adolescents.
Methods:
From 2019 to 2022, 34 923, 34 321, 36 008 and 35 598 primary and secondary school students in Beijing were selected by stratified cluster random sampling method, and visual acuity examination, scoliosis examination and questionnaire survey were conducted on them. Chisquare test was used to analyze the intergroup differences between screening myopia and scoliosis among primary and secondary school students, and the correlation factors between screening myopia and scoliosis were analyzed by multivariate Logistic regression.
Results:
From 2019 to 2022, the prevalence of screening myopia increased by year,while scoliosis decreased by year, and the comorbidity rate in 2022 (0.69%) decreased by 1.62% compared with 2019 (2.31%). In 2022, screening myopia with scoliosis rates (0.98%) than urban suburbs (0.50%), high school students (1.65%) >professional high school students (1.21%) >junior middle school students (0.76%) >primary school students (0.22%) (χ2=28.97, 153.55, P<0.01). The results of multivariate Logistic analysis found that insufficient sleep time and parents did not limit the use of electronic screen time were the risk factors for screening myopia and scoliosis [OR(95%CI)=1.59(1.20-2.12), 1.34(1.02-1.76), P<0.05]. Teachers often or always remind that reading and writing posture and one hour or more of moderateintensity physical activity every day were protective factors for screening myopia and scoliosis [OR(95%CI)=0.70(0.52-0.96), 0.56(0.34-0.92), P<0.05].
Conclusions
The comorbidity of acadmic screening myopia and scdiosis is not optimistic in Beijing. Attention should be paid to the reading and writing posture and related behavioral habits of children and adolescents, and ensure that children in each school section have sufficient sleep time, so as to prevent the occurrence and development of screening myopia and scoliosis.
6.Correlation analysis of electronic screen use and myopia among primary and secondary school students in six provinces and cities of China
GAO Ruoyi, XU Huiyu, LUO Huijuan, ZHANG Jingshu, LI Ting, KUANG Huining, E Boran, GUO Xin
Chinese Journal of School Health 2024;45(6):882-886
Objective:
To study the correlation between electronic screen use and myopia among primary and secondary school students in six provinces and cities in China, in order to provide a scientific basis for comprehensive prevention and control of myopia.
Methods:
From November 2020 to June 2022, a total of 16 557 primary and secondary school students from six provinces and cities in China (Beijing City, Liaoning Province, Zhejiang Province, Henan Province, Shaanxi Province, Chongqing City) were selected by stratified cluster random sampling and probability smampling methods, and a questionnaire prepared by Beijing Center for Disease Control and Prevention was used to investigate their electronic screen use. According to Screening Criteria for Myopia in Children and Adolescents, 0.5% mass concentration of compound topicamide eye drops was used to paralyze the ciliary muscle and undergo slit lamp optometry. Chisquare test was used to compare the differences between groups, and binary Logistic regression was used to analyze the association between electronic screen use and myopia.
Results:
About 58.3% of primary and secondary school students used electronic screens for more than two hours a day on average, and 63.4% of primary and secondary school students used continuously electronic products for more than 15 minutes at a time for nonstudy purposes. After adjusting for confounding factors, parents unrestricted use of electronic screen time and electronic screen time ≥2 h/d were positively correlated with myopia (OR=1.27, 1.13, P<0.05). Gender stratified analysis showed that boys who used electronic screen time ≥2 h/d had a higher risk of myopia (OR=1.15, P<0.05). The results of grade stratification analysis showed that parents unrestricted electronic screen use time and electronic screen time ≥2 h/d were positively correlated with myopia in the lower grade of primary school students (OR=1.34, 1.18, P<0.05). Among the higher grade of primary school students, continuous use of electronic screens for nonstudy purposes for more than 15 minutes at one time was positively correlated with myopia (OR=1.18, P<0.05). There was a multiplicative interaction between total screen time and one continuous screen time (OR=1.04, P<0.05).
Conclusions
Primary and secondary students in six provinces and cities in China reports excessive electronic screen usage which is associated with myopia. Schools and parents should jointly limit the use of electronic screen among primary and secondary students to reduce the occurrence of myopia.
7.Clinical trial of Morinda officinalis oligosaccharides in the continuation treatment of adults with mild and moderate depression
Shu-Zhe ZHOU ; Zu-Cheng HAN ; Xiu-Zhen WANG ; Yan-Qing CHEN ; Ya-Ling HU ; Xue-Qin YU ; Bin-Hong WANG ; Guo-Zhen FAN ; Hong SANG ; Ying HAI ; Zhi-Jie JIA ; Zhan-Min WANG ; Yan WEI ; Jian-Guo ZHU ; Xue-Qin SONG ; Zhi-Dong LIU ; Li KUANG ; Hong-Ming WANG ; Feng TIAN ; Yu-Xin LI ; Ling ZHANG ; Hai LIN ; Bin WU ; Chao-Ying WANG ; Chang LIU ; Jia-Fan SUN ; Shao-Xiao YAN ; Jun LIU ; Shou-Fu XIE ; Mao-Sheng FANG ; Wei-Feng MI ; Hong-Yan ZHANG
The Chinese Journal of Clinical Pharmacology 2024;40(6):815-819
Objective To observe the efficacy and safety of Morinda officinalis oligosaccharides in the continuation treatment of mild and moderate depression.Methods An open,single-arm,multi-center design was adopted in our study.Adult patients with mild and moderate depression who had received acute treatment of Morinda officinalis oligosaccharides were enrolled and continue to receive Morinda officinalis oligosaccharides capsules for 24 weeks,the dose remained unchanged during continuation treatment.The remission rate,recurrence rate,recurrence time,and the change from baseline to endpoint of Hamilton Depression Scale(HAMD),Hamilton Anxiety Scale(HAMA),Clinical Global Impression-Severity(CGI-S)and Arizona Sexual Experience Scale(ASEX)were evaluated.The incidence of treatment-related adverse events was reported.Results The scores of HAMD-17 at baseline and after treatment were 6.60±1.87 and 5.85±4.18,scores of HAMA were 6.36±3.02 and 4.93±3.09,scores of CGI-S were 1.49±0.56 and 1.29±0.81,scores of ASEX were 15.92±4.72 and 15.57±5.26,with significant difference(P<0.05).After continuation treatment,the remission rate was 54.59%(202 cases/370 cases),and the recurrence rate was 6.49%(24 cases/370 cases),the recurrence time was(64.67±42.47)days.The incidence of treatment-related adverse events was 15.35%(64 cases/417 cases).Conclusion Morinda officinalis oligosaccharides capsules can be effectively used for the continuation treatment of mild and moderate depression,and are well tolerated and safe.
8.Cornus officinalis with high pressure wine steaming enhanced anti-hepatic fibrosis:Possible through SIRT3-AMPK axis
Han XIN ; Ning YAN ; Dou XINYUE ; Wang YIWEN ; Shan QIYUAN ; Shi KAO ; Wang ZEPING ; Ding CHUAN ; Hao MIN ; Wang KUILONG ; Peng MENGYUN ; Kuang HAODAN ; Yang QIAO ; Sang XIANAN ; Cao GANG
Journal of Pharmaceutical Analysis 2024;14(5):758-771
Cornus officinalis,a medicinal and edible plant known for its liver-nourishing properties,has shown promise in inhibiting the activation of hepatic stellate cells(HSCs),crucial indicators of hepatic fibrosis,especially when processed by high pressure wine steaming(HPWS).Herein,this study aims to investigate the regulatory effects of cornus officinalis,both in its raw and HPWS forms,on inflammation and apoptosis in liver fibrosis and their underlying mechanisms.In vivo liver fibrosis models were established by subcutaneous injection of CCl4,while in vitro HSCs were exposed to transforming growth factor-β(TGF-β).These findings demonstrated that cornus officinalis with HPWS conspicuously ameliorated his-topathological injury,reduced the release of proinflammatory factors,and decreased collagen deposition in CCl4-induced rats compared to its raw form.Utilizing ultra-high-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometer(UHPLC-QTOF-MS)combined with network analysis,we identified that the pharmacological effects of the changed components of cornus officinalis before and after HPWS,primarily centered on the adenosine phosphate(AMP)-activated protein kinase(AMPK)pathway.Of note,cornus officinalis activated AMPK and sirtuin 3(SIRT3),promoting the apoptosis of activated HSCs through the caspase cascade by regulating caspase3,caspase6 and caspase9.small interfering RNA(siRNA)experiments showed that cornus officinalis could regulate AMPK activity and its mediated-apoptosis through SIRT3.In conclusion,cornus officinalis exhibited the ability to reduce inflammation and apoptosis,with the SIRT3-AMPK signaling pathway identified as a potential mecha-nism underlying the synergistic effect of cornus officinalis with HPWS on anti-liver fibrosis.
9.Understanding cannabis use in Singapore: profile of users and drug progression.
Doris Xin Yi CHIA ; Charis Wei Ling NG ; Pezhummoottil Vasudevan Nair ASHARANI ; Sabina AU YONG ; Jun Wen TAN ; Noor Azizah Bte ZAINULDIN ; Samuel Kee GUAN CHUA ; Lambert Tchern KUANG LOW ; Christopher Cheng SOON CHEOK ; Gomathinayagam KANDASAMI
Singapore medical journal 2023;64(6):385-390
INTRODUCTION:
Cannabis has consistently been the third most commonly abused drug among drug arrestees in Singapore over the past few years. Accordingly, this study aimed to understand the profile of cannabis users in Singapore and explore the effects of cannabis use on drug progression.
METHODS:
A total of 450 participants who had used cannabis at least once in their lifetime were recruited from the National Addictions Management Service, prisons, the Community Rehabilitation Centre and halfway houses from August 2017 to May 2018. A face-to-face questionnaire was administered and descriptive analyses were conducted.
RESULTS:
The mean participant age was 40.9 ± 14.51 years, and 93.1% of them were male. The participants generally initiated cannabis use during adolescence, at a mean onset age of 16.5 ± 4.46 years. Most (89.6%) were introduced to cannabis by peers. Approximately half of them (46.9%) had used cannabis before other illicit drugs and 42.1% of them had used heroin as the succeeding drug.
CONCLUSION
In Singapore, cannabis use is often initiated during adolescence, largely under peer influence. Cannabis users may progress to other illicit drugs, particularly heroin, later in life.
Adolescent
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Humans
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Male
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Adult
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Middle Aged
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Child
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Young Adult
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Female
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Cannabis
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Singapore/epidemiology*
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Heroin
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Substance-Related Disorders/epidemiology*
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Illicit Drugs
10.Aureane-type sesquiterpene tetraketides as a novel class of immunomodulators with interleukin-17A inhibitory activity.
Xin TANG ; Chuanxi WANG ; Lei WANG ; Feifei REN ; Runqiao KUANG ; Zhenhua LI ; Xue HAN ; Yiming CHEN ; Guodong CHEN ; Xiuqing WU ; Jie LIU ; Hengwen YANG ; Xingzhong LIU ; Chen WANG ; Hao GAO ; Zhinan YIN
Acta Pharmaceutica Sinica B 2023;13(9):3930-3944
Interleukin (IL)-17A, a pro-inflammatory cytokine, is a fundamental function in the onset and advancement of multiple immune diseases. To uncover the primary compounds with IL-17A inhibitory activity, a large-scale screening of the library of traditional Chinese medicine constituents and microbial secondary metabolites was conducted using splenic cells from IL-17A-GFP reporter mice cultured under Th17-priming conditions. Our results indicated that some aureane-type sesquiterpene tetraketides isolated from a wetland mud-derived fungus, Myrothecium gramineum, showed remarkable IL-17A inhibitory activity. Nine new aureane-type sesquiterpene tetraketides, myrogramins A-I ( 1, 4- 11), and two known ones ( 2 and 3) were isolated and identified from the strain. Compounds 1, 3, 4, 10, and 11 exhibited significant IL-17A inhibitory activity. Among them, compound 3, with a high fermentation yield dose-dependently inhibited the generation of IL-17A and suppressed glycolysis in splenic cells under Th17-priming conditions. Strikingly, compound 3 suppressed immunopathology in both IL-17A-mediated animal models of experimental autoimmune encephalomyelitis and pulmonary hypertension. Our results revealed that aureane-type sesquiterpene tetraketides are a novel class of immunomodulators with IL-17A inhibitory activity, and hold great promise applications in treating IL-17A-mediated immune diseases.


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