1.Trends in intestinal aging: From underlying mechanisms to therapeutic strategies.
Yajun WANG ; Xueni ZHANG ; Mengli QING ; Wen DANG ; Xuemei BAI ; Yingjie WANG ; Di ZHOU ; Lingjuan ZHU ; Degang QING ; Juan ZHANG ; Gang CHEN ; Ning LI
Acta Pharmaceutica Sinica B 2025;15(7):3372-3403
Intestinal aging is central to systemic aging, characterized by a progressive decline in intestinal structure and function. The core mechanisms involve dysregulation of epithelial cell renewal and gut microbiota dysbiosis. In addition to previous results in model organisms like Drosophila melanogaster, recent studies have shown that in mammalian models, aging causes increased intestinal permeability and intestinal-derived systemic inflammation, thereby affecting longevity. Therefore, anti-intestinal aging can be an important strategy for reducing frailty and promoting longevity. There are three key gaps remaining in the study of intestinal aging: (1) overemphasis on aging-related diseases rather than the primary aging mechanisms; (2) lack of specific drugs or treatments to prevent or treat intestinal aging; (3) limited aging-specific dysbiosis research. In this review, the basic structures and renewal mechanisms of intestinal epithelium, and mechanisms and potential therapies for intestinal aging are discussed to advance understanding of the causes, consequences, and treatments of age-related intestinal dysfunction.
2.CD38 regulates macrophagic cholesterol efflux by promoting lysosome reformation via TFEB
Hao XU ; Xueni SUN ; Tianqi WU ; Jinyuan LIU ; Qianlin HUANG ; Die MO ; Jiaxin WANG ; Shenxian CHEN ; Bodan DENG ; Xiaoyang XU
Chinese Journal of Pathophysiology 2024;40(1):28-37
AIM:To explore the effects of CD38 on lysosome reformation and cholesterol efflux in macro-phages.METHODS:Bone marrow-derived macrophages from low-density lipoprotein(LDL)receptor knockout(LDLr-/-)mice were cultured as cell model.Live cell imaging system was applied to evaluate the effect of nicotinic acid adenine di-nucleotide phosphate(NAADP)on lysosome number.ELISA was conducted to measure NAADP level in macrophages.After the cells were treated with nicotinic acid(NA),RT-qPCR was conducted to detect CD38 mRNA expression,and Western blot was conducted to observe CD38 protein expression and phosphorylated transcription factor EB(TFEB)level.Laser scanning confocal microscopy was applied to evaluate the influence of CD38/NAADP signaling on lysosome number and cholesterol egression.RESULTS:NAADP remarkably increased lysosome number(P<0.05),and this effect was significantly inhibited by NAADP antagonist NED-19,Ca2+ chelator BAPTA,and calcineurin inhibitor CsA(P<0.05).CD38 markedly enhanced NAADP synthesis in macrophages(P<0.05).NAADP synthetic substrate NA prominently ele-vated the expression of CD38 mRNA and protein(P<0.05).NA significantly decreased the phosphorylated TFEB level;this effect was also attenuated by NED-19,BAPTA and CsA(P<0.05).Disrupting CD38/NAADP signaling pathway markedly inhibited NA-induced enhancement of lysosome number,lysosomal free cholesterol and cytosol cholesterol ester efflux in macrophages(P<0.05).NA-induced enhancement of lysosome number,lysosomal free cholesterol and cytosol cholesterol ester efflux abolished in LDLr/CD38 DKO macrophages(P<0.05),whereas these effects induced by NA were recovered after CD38 gene rescue.CONCLUSION:CD38 triggers lysosome reformation via TFEB and consequently pro-motes the efflux of lysosomal free cholesterol and cytosol cholesterol ester.
3.Talaketides A-G,linear polyketides with prostate cancer cytotoxic activity from the mangrove sediment-derived fungus Talaromyces sp.SCSIO 41027
Chunmei CHEN ; Xueni WANG ; Wenxuan FANG ; Jiaqi LIANG ; Jian CAI ; Dehua YANG ; Xiaowei LUO ; Chenghai GAO ; Xiangxi YI ; Yonghong LIU ; Xuefeng ZHOU
Chinese Journal of Natural Medicines (English Ed.) 2024;22(11):1047-1056
Seven novel linear polyketides,talaketides A-G(1-7),were isolated from the rice media cultures of the mangrove sed-iment-derived fungus Talaromyces sp.SCSIO 41027.Among these,talaketides A-E(1-5)represented unprecedented unsaturated lin-ear polyketides with an epoxy ring structure.The structures,including absolute configurations of these compounds,were elucidated through detailed analyses of nuclear magnetic resonance(NMR)and high-resolution mass spectrometry(HR-MS)data,as well as elec-tronic custom distributors(ECD)calculations.In the cytotoxicity screening against prostate cancer cell lines,talaketide E(5)demon-strated a dose-dependent inhibitory effect on prostate cancer PC-3 cell lines,with an IC50 value of 14.44 μmol·L-1.Moreover,com-pound 5 significantly inhibited the cloning formation of PC-3 cell lines and arrested the cell cycle in S-phase,ultimately inducing ap-optosis.These findings indicate that compound 5 may serve as a promising lead compound for the development of a potential treat-ment for prostate cancer.
4.Validity and reliability of the Chinese version of the Sensitivity to Punishment and Sensitivity to Reward Questionnaire-Revised and Clarified(SPSRQ-RC)in patients with eating disorders
Xueying LIU ; Xueni LI ; Shuxia GENG ; Lei YANG ; Chao CHEN ; Qingmei KONG ; Tianmei SI
Chinese Mental Health Journal 2024;38(12):1045-1050
Objective:To evaluate the validity and reliability of the Chinese version of the Sensitivity to Pun-ishment and Sensitivity to Reward Questionnaire-Revised and Clarified(SPSRQ-RC)in patients with eating disor-ders.Methods:Totally 111 patients with eating disorders meeting diagnostic criteria of DSM-5 were assessed with SPSRQ-RC,Barratt Impulsiveness Scale-11(BIS-11),Trait Anxiety Inventory(TAI)and Eating Disorder Exami-nation Questionnaire 6.0(EDE-Q 6.0).Results:Three factors were extracted from the items by exploratory factor analysis with cumulative variance being 55.65%.The interclass correlation coefficient(ICC)of SR and BIS-11 was 0.26,the ICC of SP and TAI was 0.25,and the correlation coefficient of the SPSRQ-RC and EDE-Q 6.0 was 0.35.The Cronbach's α coefficient of the SPSRQ-RC was 0.83,the test-retest reliability of the scale was 0.82.Conclusion:The Chinese version of SPSRQ-RC shows good psychometric properties in patients with eating disor-ders.
5.Study of Ctsk knockout regulating type H blood vessel formation and tooth extraction socket healing in mice
Wuyang ZHANG ; Dengke LI ; Yiming WANG ; Yuan LI ; Yuzhe CHEN ; Xueni ZHENG ; Hongzhi ZHOU ; Kaijin HU ; Yang XUE
Journal of Practical Stomatology 2024;40(3):330-336
Objective:To study the effects of cathepsin K(CTSK)on the healing process of tooth extraction socket and type H blood vessel angiogenesis in mice.Methods:Ctsk knockout(Ctsk-/-)mice were generated by CRISPR/Cas9 technology,and genotype sequen-cing,general observation,Micro-CT and immunohistochemistry were performed to confirm successful knockout of Ctsk.Then 8 week-old WT and Ctsk-/-mice were used to establish the tooth extraction modle by extracting the left maxillary first molars,and the mice were sac-rificed at the day 7,10,14,21,28 and 35 respectively(n=3)after tooth extraction.Then samples were subjected to stereo microscope and Micro-CT examination.Immunofluorescence staining was used to study the effect of Ctsk knockout on type H blood vessel angiogene-sis.Results:Ctsk knockout did not affect the soft tissue healing of tooth extraction socket,but significantly promoted the bone healing process,and Ctsk deficency significantly enhanced type H blood vessel angiogenesis in the tooth extraction socket.Conclusion:Ctsk knockout can enhance type H vessel angiogenesis,and promote bone healing process of tooth extraction socket in mice.
6.Ocular biometric parameters among primary and secondary school students of Naxi,Bai and Han ethnicity in Yunnan Province
Qiang ZHANG ; Litao CHANG ; Peiqian LI ; Jie XIAO ; Dafeng HUANG ; Xueni XIE ; Jin-Jiao ZHANG ; Zixue MA ; Qianqian LI ; Xiao LUO ; Maosen CHEN ; Ying HUANG
Recent Advances in Ophthalmology 2024;44(5):365-369
Objective To assess ocular biometric parameters among primary and secondary school students from Naxi,Bai and Han ethnic groups in Yunnan Province.Methods The school-based study was conducted in October 2020.A total of 724 second-,third-and seventh-graders were selected from Dali and Lijiang,where Bai and Naxi ethnic groups inhabit,using a stratified cluster sampling method to receive questionnaire surveys and eye examinations.Non-cycloplegic spherical equivalent(SE),axial length(AL),anterior chamber depth(ACD),corneal radius of curvature(CR),central corneal thickness(CCT),white-to-white(WTW)distance,and the AL/CR ratio were measured.Covariance analysis was used to examine the differences in SE and ocular biometric parameters in terms of ethnicity,sex and grade,while Pearson correlation was used to test the associations among the said indicators.Results There were no significant differences in daily outdoor time,screen time and sleep time among the three ethnic groups regardless of grades(all P>0.05).The mean CCT of Naxi students was lower than that of Han and Bai students[grade 2 and grade 3:(542.48±39.76)μm vs.(553.81±31.83)μm and(559.27±32.79)μm;grade7:(538.86±34.91)μm vs.(547.41±33.55)μm and(548.26± 32.98)μm,all P<0.05],while no significant differences were found in the other ocular biometric parameters among the three ethnic groups(all P>0.05).Among the seventh-graders,the SE,AL and AL/CR ratio of Naxi students were signifi-cantly different from those of Han and Bai students(all P<0.05).The AL,CR,ACD,CCT,WTW distance,and mean SE were lower in girls than in boys(all P<0.05).Compared with grade 2 and grade 3,students of grade 7 had longer AL,deeper ACD and thinner CCT(all P<0.05),while no significant differences were found in CR and WTW distance(all P>0.05).Correlation analysis showed that the AL/CR ratio was highly correlated with SE(r=-0.78,P<0.05).Conclu-sion Multiethnic primary and secondary school students may face similar environmental risks.Yet,disparities in ocular biometric parameters caused by ethnicity,sex and age should be noted.
7.Discriminante analysis of risk factors Nomograms of myopia in children and adolescents in Yunnan Province
Chinese Journal of School Health 2023;44(9):1387-1391
Objective:
To explore the related factors of myopia among children and adolescents in Yunnan Province, and to predict and evaluate the influencing factors, so as to provide a scientific theoretical basis for the prevention and control of myopia.
Methods:
From March 9 to 14, 2023, 848 students from 6 primary and secondary schools in Dali and Lijiang of Yunnan Province were selected by multi stage stratified random cluster sampling method for visual acuity detection and questionnaire survey on myopia related factors. Multivariate Logistic regression analysis was used to establish a Nomogram prediction model for the selected influencing factors.
Results:
The overall myopia rate of the respondents was 68.3%, the myopia rate of boys (63.4%) was lower than that of girls (72.9%), and the myopia rate of primary school students (46.7%) was lower than that of junior high school students (81.1%), and the difference was statistically significant( χ 2=8.71, 108.07, P <0.05). Daily eye exercises, activities outside the teaching building during recess, having daily sleep time of 7-9 and >9 h, having both parents without myopia were negatively correlated with the occurrence of myopia in children and adolescents in Yunnan Province ( OR=0.64, 0.63, 0.56, 0.28, 0.48, P < 0.05 ). The reading and writing time after school ≥3 h per day and parents unrestricted time to play video games were positively correlated with myopia ( OR=1.94, 1.78, P <0.05). Based on the influencing factors, a Nomogram prediction model was established to quantitatively evaluate the risk of myopia. The results showed that greater risk for myopia was associated with sleep duration, parental history of myopia, and the time spent reading and writing after school every day.
Conclusion
Both genetic factors and environmental factors are related to myopia in children and adolescents. The prediction model of nomogram is beneficial for screening high risk factors of myopia and taking corresponding prevention and treatment measures.
8.Relationship between interleukin-1β and silicosis development
Junjin LIAO ; Xueni YU ; Junpeng CHI ; Luocheng SHAO ; Shizi WANG ; Zhen LIU ; Zhuo CHEN ; Huihui TAO
Chinese Journal of Primary Medicine and Pharmacy 2023;30(2):316-320
Silicosis is a diffuse pulmonary fibrosis disease caused by occupational exposure to silica, which is one of the occupational diseases with high incidence in developing countries. Up to now, there is no definite drug to relieve or reverse the lung injury caused by silicosis, so it is very important to prevent, diagnose and treat pulmonary fibrosis as soon as possible. Studies have shown that a chronic inflammatory environment contributes to pulmonary fibrosis to a certain extent. Interleukin-1β is a cytokine that increases the number of inflammatory factors in the microenvironment in the immune response and plays a key role in inflammatory reaction. Therefore, the release of interleukin-1β is of great significance in the pathogenesis of silicosis. This paper aims to systematically expound the development course of silicosis, the signal pathway of interleukin-1β production, and the relationship between them.
9.Protective Mechanism of Wenyang Fuyuan Prescription on Nerve Injury in Rats with Cerebral Ischemia-Reperfusion Injury Based on Ferroptosis
Junjun XIANG ; Liqin LI ; Jianzheng LI ; Xueni MO ; Wei CHEN ; Yueqiang HU
Traditional Chinese Drug Research & Clinical Pharmacology 2023;34(12):1649-1657
Objective To investigate the protective mechanism of Wenyang Fuyuan Prescription on nerve injury by improving brain iron metabolism in rats with cerebral ischemia-reperfusion injury(CIRI)based on ferroptosis.Methods A total of 72 SD rats were randomly divided into sham-operation group,CIRI model group,Wenyang Fuyuan Prescription group(18.0 g·kg-1,gavage),ferroptosis inducer group(100 mg·kg-1,intraperitoneal injection),Wenyang Fuyuan Prescription(18.0 g·kg-1,gavage)+ ferroptosis inducer group(intraperitoneal injection)and ferroptosis inhibitor group(5 mg·kg-1,intraperitoneal injection),12 rats in each group.All the procedures adopted in the sham group were the same as those in the model group.But nylon thread was inserted into the internal carotid artery at a depth of 9 mm and un-plugged middle cerebral artery.The rest of the groups were used to construct middle cerebral artery occlusion/reperfusion(MCAO/R)model by thread embolism method.Ferroptosis inducer(100 mg·kg-1)and ferroptosis inhibitor(5 mg·kg-1)were administered intraperitoneally to rats according to the grouping 24 hours before modeling.Wenyang Fuyuan Prescription(18.0 g·kg-1)was administered by gavage 2 hours after anesthesia and awakening.All intervention were given once daily for 7 consecutive days.The Longa scoring standard was used to evaluate the neurological deficit on 1,3,and 7 days after MCAO/R surgery,respectively.At the end of the treatment period,brain tissues were taken to observe the morphological changes of rat neurons in each group by hematoxylin eosin staining(HE).The ultrastructural changes of neuron mitochondria in each group were observed by transmission electron microscope.The biochemical kit was used to detect the content of iron ions(Fe2+)and reduced glutathione(GSH)in brain tissue.The protein and mRNA expressions of transferrin receptor 1(TFR1),iron regulatory protein 1(IRP1)and ferroportin(FPN)were detected by real-time quantitative polymerase chain reaction(RT-qPCR)and Western Blot.Results① Compared with sham group,the neurological deficit scores of rats in model group increased at each time point(P<0.01).HE staining showed neurons were sparse and disordered,the nuclei underwent pyknosis,and vacuoles appeared at the edges.Under electron microscopy,it was observed that the number of neuronal mitochondria decreased,the density of mitochondrial membranes increased,massive numbers of mitochondrial membranes ruptured and dissolved,and mitochondrial cristae disappeared.The content of Fe2+,both mRNA and protein expressions of TFR1 were significantly increased(P<0.01),while GSH content,as well as expressions of mRNA and protein for IRP1 and FPN were significantly decreased(P<0.05,P<0.01).② Compared with the model group,the neurological deficit scores of rats in the Wenyang Fuyuan Prescription group decreased at various time points(P<0.05).The number of neurons increased,their arrangement was relatively neat,the morphology of the nucleus is complete and clear,the mitochondrial structure of neurons was relatively complete,the mitochondrial membrane was relatively intact,and the mitochondrial cristae were clear.The content of Fe2+,both mRNA and protein expressions of TFR1 were decreased(P<0.05,P<0.01),while GSH content,as well as expressions of mRNA and protein for IRP1 and FPN increased(P<0.05,P<0.01).③ Compared with the Wenyang Fuyuan Prescription group,the neurological deficit scores of rats in ferroptosis inducer group and the Wenyang Fuyuan Prescription + ferroptosis inducer group increased at all time points(P<0.05).Distribution of neurons was in disorder,the nucleus shrinked,and vacuoles appeared at the edges.The density of mitochondrial membranes increased,some ruptured and dissolved mitochondrial membranes were found.The number of mitochondria decreased and mitochondrial cristae disappeared.The content of Fe2+,both TFR1 mRNA and protein expression increased(P<0.05,P<0.01),while the content of GSH,as well as expressions of mRNA and protein for IRP1 and FPN decreased(P<0.05,P<0.01).However,there was no statistically significant difference in all observed indicators between the ferroptosis inhibitor group and the Wenyang Fuyuan Prescription group(P>0.05).Conclusion Wenyang Fuyuan Prescription can improve the neurological function and pathological damage of CIRI rats.Its mechanism may be related to regulating the expression of IRP1 protein,improving the brain iron metabolism pathway,and inhibiting ferroptosis.
10.Relationship of pks gene islands with virulence genes and biofilm formation in Klebsiella pneumoniae
Chenshuo LUO ; Yanshu CHEN ; Yulan LIN ; Tongzhe DENG ; Xueni HU ; Bin YANG
Chinese Journal of Microbiology and Immunology 2022;42(11):888-893
Objective:To investigate the relationship of pks gene islands with virulence genes, capsular serotypes and biofilm formation in Klebsiella pneumoniae ( Kp). Methods:A total of 113 Kp clinical isolates were collected in the First Affiliated Hospital of Fujian Medical University and divided into two groups based on the presence of pks gene islands: pks+ and pks- groups. The hypermucoviscous (HM) phenotype was detected by string test. Five virulence genes ( peg-344, rmpA, rmpA2, iucA, iroB) and six common capsular serotypes (K1, K2, K5, K20, K54, K57) were detected by polymerase chain reaction (PCR). The biofilm formation ability was measured by crystal violet staining. Results:Among the 113 Kp isolates, 46 were pks+ strains and 67 were pks- strains. The detection rate of HM phenotype was higher in the pks+ group than in the pks- group [87.0% (40/46) vs 43.3% (29/67)]. The detection rates of virulence genes ( peg-344, rmpA, rmpA2, iucA, iroB) and K1 serotype in the pks+ group were also higher than those in the pks- group ( P<0.05). The biofilm formation ability of the pks+ strains was higher than the pks- strains ( P<0.05). Conclusions:Kp strains carrying pks gene islands were likely to display a HM phenotype and mainly belonged to the K1 serotype. Most of the pks+Kp strains carried the virulence genes of peg-344, rmpA, rmpA2, iucA and iroB, and had a greater ability to form biofilms.


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