1.Reduction in mitochondrial DNA methylation leads to compensatory increase in mitochondrial DNA content: novel blood-borne biomarkers for monitoring occupational noise.
Jia-Hao YANG ; Zhuo-Ran LI ; Zhuo-Zhang TAN ; Wu-Zhong LIU ; Qiang HOU ; Pin SUN ; Xue-Tao ZHANG
Environmental Health and Preventive Medicine 2025;30():40-40
BACKGROUND:
Prolonged occupational noise exposure poses potential health risks, but its impact on mitochondrial DNA (mtDNA) damage and methylation patterns remains unclear.
METHOD:
We recruited 306 factory workers, using average binaural high-frequency hearing thresholds from pure-tone audiometry to assess noise exposure. MtDNA damage was evaluated through mitochondrial DNA copy number (mtDNAcn) and lesion rate, and mtDNA methylation changes were identified via pyrophosphate sequencing.
RESULTS:
There was a reduction in MT-RNR1 methylation of 4.52% (95% CI: -7.43% to -1.62%) among workers with abnormal hearing, whereas changes in the D-loop region were not statistically significant (β = -2.06%, 95% CI: -4.44% to 0.31%). MtDNAcn showed a negative association with MT-RNR1 methylation (β = -0.95, 95% CI: -1.23 to -0.66), while no significant link was found with D-loop methylation (β = -0.05, 95% CI: -0.58 to 0.48). Mediation analysis indicated a significant increase in mtDNAcn by 10.75 units (95% CI: 3.00 to 21.26) in those with abnormal hearing, with MT-RNR1 methylation mediating 35.9% of this effect.
CONCLUSIONS
These findings suggest that occupational noise exposure may influence compensatory increases in mtDNA content through altered MT-RNR1 methylation.
Humans
;
DNA, Mitochondrial
;
DNA Methylation
;
Male
;
Adult
;
Noise, Occupational/adverse effects*
;
Middle Aged
;
Occupational Exposure/adverse effects*
;
Biomarkers/blood*
;
Female
2.Protein palmitoylation: A potential therapeutic target in cardiovascular diseases.
Sijia ZHAO ; Yanyan YANG ; Hong LI ; Pin SUN ; Xiangqin HE ; Chao WANG ; Jingjing ZHANG ; Yu TIAN ; Tao YU ; Zhirong JIANG
Acta Pharmaceutica Sinica B 2025;15(10):5127-5144
Palmitoylation, an essential covalent attachment of a fatty acid (usually C16 palmitate) to cysteine residues within proteins, is crucial for regulating protein functionality and enzymatic activities. This lipid modification facilitates the anchoring of proteins to cellular membranes, dictating their subcellular distribution and influencing protein transport dynamics and intracellular positioning. Additionally, it plays a role in regulating protein degradation through the ubiquitin-proteasome system. Palmitoylation is implicated in the pathogenesis and progression of cardiovascular diseases by modulating substrates and prompting additional post-translational modifications, as well as by interacting with other molecular alterations. Moreover, an intervention strategy focusing on palmitoylation processes is anticipated to offer novel therapeutic avenues for cardiovascular pathologies and address extant challenges in clinical settings. This review consolidates current research on the role and importance of palmitoylation in cardiovascular diseases by exploring its regulatory functions, the catalyzing enzymes, and the involved substrates. It highlights recent discoveries connecting palmitoylation-targeted therapies to cardiovascular health and examines potential approaches and future challenges in cardiovascular treatment.
3.Lcn2 secreted by macrophages through NLRP3 signaling pathway induced severe pneumonia.
Mingya LIU ; Feifei QI ; Jue WANG ; Fengdi LI ; Qi LV ; Ran DENG ; Xujian LIANG ; Shasha ZHOU ; Pin YU ; Yanfeng XU ; Yaqing ZHANG ; Yiwei YAN ; Ming LIU ; Shuyue LI ; Guocui MOU ; Linlin BAO
Protein & Cell 2025;16(2):148-155
4.Analysis of pregnancy outcomes after transplantation of frozen-thawed embryo transfer in PCOS patients
Huifen XIANG ; Pin ZHANG ; Zuying XU ; Zhenran LIU ; Yue HUANG ; Yuting HUANG ; Qiong WU ; Yiran LI ; Rong LI ; Yunxia CAO
Acta Universitatis Medicinalis Anhui 2024;59(4):684-689
Objective To investigate the factors influencing the pregnancy outcomes during frozen-thawed embryo transfer(FET)cycles in patients with polycystic ovary syndrome(PCOS).Methods A retrospective analysis was conducted on patients'data from 882 FET cycles.According to the pregnancy outcome,the patients were divided into non-implantation group(Group A),abortion group(Group B1)and live birth group(Group B2).Clinical data and laboratory parameters were compared among the three groups,and ordered Logistic regression analysis was used to study the factors influencing pregnancy outcomes after FET.Patients were also divided into four groups(C1-C4)based on the number of high-quality embryos obtained(0-3,4-6,7-10,≥11),and their clinical data and laboratory parameters were compared.Results The clinical pregnancy rate,live birth rate,and miscar-riage rate in the 882 treatment cycles were 71.09%(627/882),61.68%(544/882),and 13.24%(83/627),respectively.Single-factor analysis showed significant differences in body mass index(BMI),infertility type,hu-man chorionic gonadotropin(hCG)day estradiol(E2)level,number of retrieved oocytes,and number of high-quality embryos among Groups A,B1,and B2(P<0.05).Further multiple Logistic regression analysis revealed that BMI(OR=1.046,95%CI:1.001-1.093,P=0.044)and a history of previous pregnancy(OR=1.417,95%CI:1.030-1.950,P=0.032)were independent risk factors for successful FET in PCOS patients,while an in-creased number of high-quality embryos was an independent protective factor for successful pregnancy.Based on the results of Group B2,compared to Group A,OR=0.920,95%CI:0.880-0.962,P=0.000;compared to Group B1,OR=0.923,95%CI:0.862-0.988,P=0.022.Compared with the other three groups(C1-C3),the total amount of gonadotropin(Gn)in the C4 group was the lowest and the number of oocytes obtained was the high-est(P<0.05).Multiple comparisons showed that Group C4 had lower BMI,follicle-stimulating hormone(FSH),very low-density lipoprotein(vLDL)levels,a higher luteinizing hormone and follicle-stimulating hormone(LH/FSH)ratio compared to Group C1(P<0.05).Group C4 had lower fasting insulin(FINS)and homeostasis model assessment of insulin resistance(HOMA-IR)levels compared to Group C3,and higher high-density lipoprotein-cholesterol(HDL-C)and apolipoprotein A1(Apo A1)levels compared to Groups C2 and C3(P<0.05).Con-clusion BMI,the history of previous pregnancy and the number of high-quality embryos were both independent factors for predicting pregnancy outcomes in PCOS patients undergoing FET cycles.Patients with a higher number of high-quality embryos have a higher clinical pregnancy rate during FET cycles.
5.The Chinese guideline for management of snakebites
Lai RONGDE ; Yan SHIJIAO ; Wang SHIJUN ; Yang SHUQING ; Yan ZHANGREN ; Lan PIN ; Wang YONGGAO ; Li QI ; Wang JINLONG ; Wang WEI ; Ma YUEFENG ; Liang ZIJING ; Zhang JIANFENG ; Zhou NING ; Han XIAOTONG ; Zhang XINCHAO ; Zhang MAO ; Zhao XIAODONG ; Zhang GUOQIANG ; Zhu HUADONG ; Yu XUEZHONG ; Lyu CHUANZHU
World Journal of Emergency Medicine 2024;15(5):333-355
In 2009,the World Health Organization included snakebite on the list of neglected tropical diseases,acknowledging it as a common occupational hazard for farmers,plantation workers,and others,causing tens of thousands of deaths and chronic physical disabilities every year.This guideline aims to provide practical information to help clinical professionals evaluate and treat snakebite victims.These recommendations are based on clinical experience and clinical research evidence.This guideline focuses on the following topics:snake venom,clinical manifestations,auxiliary examination,diagnosis,treatments,and prevention.
6.Propensity score-matched comparison of the clinical efficacy between two approaches of robot-assisted radical prostatectomy
Zhenhao LI ; Zhaowei ZHU ; Pin ZHAO ; Jin TAO ; Peng LI ; Yafeng FAN ; Yunlong LIU ; Shuanbao YU ; Xuepei ZHANG
Journal of Modern Urology 2024;29(7):602-606,611
Objective To compare the clinical efficacy and postoperative urinary control between robot-assisted radical prostatectomy(RARP)with posterior-anterior-lateral(PAL)approach and with anterior(conventional)approach using propensity score matching method.Methods Clinical data of 145 patients undergoing RARP in our hospital during Jan.2020 and Jan.2023 were retrospectively analyzed,including 122 patients in the conventional group and 23 in the PAL group.The patients were matched by 2∶1 propensity score matching,including 46 cases in the conventional group and 23 in the PAL group.The perioperative outcomes were compared of prostate cancer(PCa)patients undergoing RARP surgery with different approaches before and after matching,including operation time,intraoperative blood loss,pelvic drainage time,hospitalization days,preservation of neurovascular bundles(NVB)during surgery,deep dorsal venous complex(DVC)suture,reconstruction of bladder neck,and postoperative urinary control recovery rate after extubation immediately,and 1,3,and 6 months after surgery.Results There were no significant differences in baseline data,operation time,bleeding volume,pelvic drainage time,hospitalization days,preservation of NVB,and reconstruction of bladder neck between the two groups(P>0.05).The PAL group used less DVC suture during surgery(30.4%vs.100%,P<0.001),but had better urinary control recovery rate immediately after extubation,1,3 and 6 months after surgery(P<0.05).Conclusion RARP with PAL approach is as safe and effective as the conventional approach,and has significant advantages in early postoperative urinary control.
7.Effects of MT-1207 on blood glucose,blood lipids and atherosclerosis in mice
Xiuping ZHANG ; Jiasheng TIAN ; Daoxin WANG ; Jiaxin LI ; Pin WANG ; Chaoyu MIAO
Journal of Pharmaceutical Practice and Service 2024;42(11):487-494
Objective To study the effect of MT-1207 on blood glucose,blood lipids and atherosclerosis in mice.Methods The apolipoprotein E knockout(ApoE-/-)mice were fed with normal feed,drug feed containing losartan and drug feed containing MT-1207 at a dosage of 30 mg/kg.The body weight,blood glucose and blood lipids were detected,and the plaque area of atherosclerotic was evaluated.8-week-old male C57 mice were fed a high fat diet and given intragastric administration of MT-1207 and losartan at a dose of 30 mg/kg per day.The body weight,blood glucose and lipids levels were also examined to further evaluate the effects of MT-1207 on blood glucose and lipids levels.Results ApoE-/-mice treated with MT-1207 and losartan gained weight faster.There was no significant improvement in blood glucose and lipid levels,and no significant change in atherosclerotic plaque area.MT-1207 and losartan had no significant improvement effect on blood glucose and blood lipids of C57 mice.Conclusion MT-1207 and losartan couldn't improve the levels of blood glucose,blood lipids and atherosclerosis,and couldn't aggravate atherosclerosis.
8.Identification of oxidative stress-related biomarkers in chronic rhinosinusitis with nasal polyps using WGCNA combined with machine learning algorithms
Ye YUAN ; Xueyun SHI ; Xinyi MA ; Xinyu XIE ; Changhua WU ; Liqiang ZHANG ; Xuezhong LI ; Pin WANG ; Xin FENG
Chinese Journal of Otorhinolaryngology Head and Neck Surgery 2024;59(6):560-572
Objective:To identify diagnostic markers related to oxidative stress in chronic rhinosinusitis with nasal polyps (CRSwNP) by analyzing transcriptome sequencing data, and to investigate their roles in CRSwNP.Methods:Utilizing four CRSwNP sequencing datasets, differentially expressed genes (DEGs) analysis, weighted gene co-expression network analysis (WGCNA), and three machine learning methods for Hub gene selection were performed in this study. Subsequent validation was carried out using external datasets, as well as real-time quantitative polymerase chain reaction (Real-time qPCR), and immunofluorescence staining of clinical samples. Moreover, the diagnostic efficacy of the genes was assessed by receiver operating characteristic (ROC) curve, followed by functional and pathway enrichment analysis, immune-related analysis, and cell population localization. Additionally, a competing endogenous RNA (CeRNA) network was constructed to predict potential drug targets. Statistical analysis and plotting were conducted using SPSS 26.0 and Graphpad Prism9 software.Results:Through data analysis and clinical validation, CP, SERPINF1 and GSTO2 were identified among 4 138 DEGs as oxidative stress markers related to CRSwNP. Specifically, the expression of CP and SERPINF1 increased in CRSwNP, whereas that of GSTO2 decreased, with statistically significant differences ( P<0.05). Additionally, an area under the curve (AUC)>0.7 indicated their effectiveness as diagnostic indicators. Importantly, functional analysis indicated that these genes were mainly related to lipid metabolism, cell adhesion migration, and immunity. Single-cell data analysis revealed that SERPINF1 was mainly distributed in epithelial cells, stromal cells, and fibroblasts, while CP was primarily located in epithelial cells, and GSTO2 was minimally present in the epithelial cells and fibroblasts of nasal polyps. Consequently, a CeRNA regulatory network was constructed for the genes CP and GSTO2. This construction allowed for the prediction of potential drugs that could target CP. Conclusion:This study successfully identifies CP, SERPINF1 and GSTO2 as diagnostic and therapeutic markers related to oxidative stress in CRSwNP.
9. Effects of metabolites of eicosapentaenoic acid on promoting transdifferentiation of pancreatic OL cells into pancreatic β cells
Chao-Feng XING ; Min-Yi TANG ; Qi-Hua XU ; Shuai WANG ; Zong-Meng ZHANG ; Zi-Jian ZHAO ; Yun-Pin MU ; Fang-Hong LI
Chinese Pharmacological Bulletin 2024;40(1):31-38
Aim To investigate the role of metabolites of eicosapentaenoic acid (EPA) in promoting the transdifferentiation of pancreatic α cells to β cells. Methods Male C57BL/6J mice were injected intraperitoneally with 60 mg/kg streptozocin (STZ) for five consecutive days to establish a type 1 diabetes (T1DM) mouse model. After two weeks, they were randomly divided into model groups and 97% EPA diet intervention group, 75% fish oil (50% EPA +25% DHA) diet intervention group, and random blood glucose was detected every week; after the model expired, the regeneration of pancreatic β cells in mouse pancreas was observed by immunofluorescence staining. The islets of mice (obtained by crossing GCG
10.Effect of Buzhong Yiqitang on Th17/Treg Immune Imbalance and Notch1 Signaling Pathway in AIT Mice
Zhuo ZHAO ; Nan SONG ; Ziyu LIU ; Pin LI ; Yue LUO ; Pengkun ZHANG ; Zhimin WANG ; Yuanping YIN ; Tianshu GAO ; Zhe JIN ; Xiao YANG
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(5):19-27
ObjectiveTo explore the effect of Buzhong Yiqitang on the immune imbalance of helper T cell 17 (Th17)/regulatory T cell (Treg) and Notch1 signaling pathway in mice with autoimmune thyroiditis (AIT). MethodA total of 60 8-week-old NOD.H-2h4 mice were randomly divided into the normal group, model group, western medicine group (selenium yeast tablet, 32.5 mg·kg-1), and low-dose (4.78 g·kg-1·d-1), middle-dose (9.56 g·kg-1·d-1), and high-dose (19 g·kg-1·d-1) Buzhong Yiqitang groups, with 10 mice in each group. The normal group was fed with distilled water, and the other groups were fed with water containing 0.05% sodium iodide for eight weeks. After the animal model of AIT was formed spontaneously, the mice were killed under anesthesia after intragastric administration for eight weeks. Serum anti-thyroglobulin antibodies (TGAb), thyroid-stimulating hormone (TSH), free triiodothyronine (FT3), and free thyroid hormone (FT4) were detected by enzyme-linked immunosorbent assay (ELISA), and thyroid tissue changes were observed by hematoxylin-eosin (HE) staining. The mRNA and protein expressions of retinoid-related orphan receptor-γt (RORγt), interleukin (IL)-17, forkhead box P3 (FoxP3), IL-10, Notch1, and hair division-related enhancer 1 (Hes1) in thyroid tissue were detected by Real-time fluorescence quantitative polymerase chain reaction (Real-time PCR) and Western blot, respectively. ResultCompared with the normal group, the thyroid structure of the model group was severely damaged, and lymphocytes were infiltrated obviously. The levels of serum TGAb, FT3, and FT4 contents were significantly increased, and TSH content was significantly decreased (P<0.01). The mRNA and protein expression levels of RORγt, IL-17, Notch1, and Hes1 were significantly increased, while those of FoxP3 and IL10 were significantly decreased in the model group (P<0.01). Compared with the model group, thyroid structural damage and lymphocyte infiltration were improved in the treatment groups, and serum TGAb, FT3, and FT4 contents were significantly decreased. TSH content was increased, and mRNA and protein expression levels of RORγt, IL-17, Notch1, and Hes1 were decreased. mRNA and protein expression levels of FoxP3 and IL-10 were increased to different degrees (P<0.05, P<0.01), and the middle-dose Buzhong Yiqitang group had the most significant intervention effect. ConclusionBuzhong Yiqitang can alleviate the thyroid structural damage in AIT mice, and its mechanism may be related to improving the abnormal differentiation of Th17/Treg immune cells and inhibiting the activation of the Notch1 signaling pathway.


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