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Hydrogen sulfide reduces oxidative stress in Huntington's disease via Nrf2

Neural Regeneration Research 2025年第6期20卷 1776-1788页

作者： Zige Jiang Dexiang Liu Tingting Li Chengcheng Gai Danqing Xin Yijing Zhao Yan Song Yahong Cheng Tong Li Zhen Wang department of Physiology School of Basic Medical SciencesCheeloo College of MedicineShandong UniversityJinanShandong ProvinceChina department of Medical Psychology and Ethics School of Basic Medicine SciencesCheeloo College of MedicineShandong UniversityJinanShandong ProvinceChina department of Neurosurgery Surgery Qingdao Municipal HospitalQingdaoShandong ProvinceChina

The pathophysiology of Huntington's disease involves high levels of the neurotoxin quinolinic acid. Quinolinic acid accumulation results in oxidative stress, which leads to neurotoxicity. However, the molecular and cellular mechanisms by which quinolinic acid contributes to Huntington's disease pathology remain unknown. In this study, we established in vitro and in vivo models of Huntington's disease by administering quinolinic acid to the PC12 neuronal cell line and the striatum of mice, respectively. We observed a decrease in the levels of hydrogen sulfide in both PC12 cells and mouse serum, which was accompanied by down-regulation of cystathionine β-synthase, an enzyme responsible for hydrogen sulfide production. However, treatment with NaHS(a hydrogen sulfide donor) increased hydrogen sulfide levels in the neurons and in mouse serum, as well as cystathionine β-synthase expression in the neurons and the mouse striatum, while also improving oxidative imbalance and mitochondrial dysfunction in PC12 cells and the mouse striatum. These beneficial effects correlated with upregulation of nuclear factor erythroid 2-related factor 2 expression. Finally, treatment with the nuclear factor erythroid 2-related factor 2inhibitor ML385 reversed the beneficial impact of exogenous hydrogen sulfide on quinolinic acid-induced oxidative stress. Taken together, our findings show that hydrogen sulfide reduces oxidative stress in Huntington's disease by activating nuclear factor erythroid 2-related factor 2,suggesting that hydrogen sulfide is a novel neuroprotective drug candidate for treating patients with Huntington's disease.

关键词： apoptosis cystathionine-β-synthase nuclear factor erythroid 2-related factor 2 Huntington's disease hydrogen sulfide mitochondrion neuroplasticity oxidative stress quinolinic acid reactive oxygen species

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Altered 3D genome reorganization mediates precocious myeloid differentiation of aged hematopoietic stem cells in inflammation

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Science China Life Sciences 2025年

作者： Xinyu Cui Yu Dong Qiang Zhan Yixin Huang Qianshu Zhu Zihao Zhang Guang Yang Liping Wang Shijun Shen Jia Zhao Zhiyi Lin Jiatong Sun Zhongqu Su Yihan Xiao Chuyu Zhang Yuwei Liang Lu Shen Lichen Ji Xuguang Zhang Jiqing Yin Hong Wang Zhiyang Chen Zhenyu Ju Cizhong Jiang Rongrong Le Shaorong Gao Clinical and Translational Research Center of Shanghai First Maternity & Infant hospital Frontier Science Center for Stem Cells School of Life Sciences and Technology Tongji University Key Laboratory of Spine and Spinal Cord Injury Repair and Regeneration of Ministry of Education Orthopaedic Department of Tongji Hospital School of Life Sciences and Technology Tongji University Key Laboratory of Regenerative medicine of Ministry of Education Institute of Aging and Regenerative Medicine Department of Developmental & Regenerative Medicine College of Life Science and Technology Jinan University shandong Key Laboratory of Animal Bioengineering and Disease Prevention College of Animal Science and Technology Shandong Agricultural University department of Joint Surgery Shanghai East Hospital Tongji University School of Medicine Shanghai Institute of nutrition and Health Chinese Academy of Sciences

Inflammation is a driving force of hematopoietic stem cells(HSCs) aging, causing irreversible exhaustion of functional HSCs. However, the underlying mechanism of HSCs erosion by inflammatory insult remains poorly understood. Here, we find that transient LPS exposure primes aged HSCs to undergo accelerated differentiation at the expense of self-renewal, leading to depletion of HSCs. Meanwhile, the central regulator nuclear factor kappa B(NF-κB) mediating functional impairment by inflammation insult induces differential transcriptional response in aged HSCs compared with young HSCs, with precocious activation of myeloid lineage genes. Altered compartmentalization and chromatin loop formation are associated with aging-related differential transcriptional response in HSCs upon lipopolysaccharide(LPS)stimulation. Mechanistically, enhancer and promoter regions of myeloid lineage genes in aged HSCs are more accessible and display more rapid and prominent CTCF occupancy upon LPS stimulation. Our study provides comprehensive resources for the three-dimensional(3D)genome structure of HSCs and sheds light into the ordered genome organization and the associated transcriptome signature underlying HSCs aging.

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Systematical identification of regulatory GPCRs by single-cell trajectory inference reveals the role of ADGRD1 and GPR39 in adipogenesis

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Science China Life Sciences 2025年

作者： Chuan Ye Xuemei Wang Jun Lin Chenyang Wu Yuhua Gao Chenghao Guo Yunxi Liao Ziyan Rao Shaodong Huang Weixuan Chen Ying Huang Jinpeng Sun Dongyu Zhao Changtao Jiang Center of Basic Medical Research Institute of Medical Innovation and ResearchPeking University Third Hospital department of Physiology and Pathophysiology School of Basic Medical SciencesPeking University department of Biomedical Informatics School of Basic Medical SciencesPeking University State Key Laboratory of Vascular Homeostasis and Remodeling Peking University Center for Obesity and Metabolic Disease Research School of Basic Medical SciencesPeking University State Key Laboratory of Female Fertility Promotion Center for Reproductive MedicineDepartment of Obstetrics and GynecologyPeking University Third Hospital National Clinical Research Center for Obstetrics and Gynecology Peking University Third Hospital department of Endocrinology and Metabolism Peking University Third Hospital Key Laboratory Experimental Teratology of the Ministry of Education Department of Biochemistry and Molecular BiologySchool of Basic Medical SciencesCheeloo College of MedicineShandong University department of Immunology School of Basic Medical SciencesPeking University

Adipogenesis is the healthy expansion of white adipose tissue (WAT),serving as a compensatory response to maintain metabolic homeostasis in the presence of excess energy in the ***,the identification of novel regulatory molecules in adipogenesis,specifically membrane receptors such as G protein-coupled receptors (GPCRs),holds significant clinical *** receptors can serve as viable targets for pharmaceuticals,offering potential for restoring metabolic homeostasis in individuals with *** utilized trajectory inference methods to analyze three distinct single-nucleus sequencing (sNuc-seq) datasets of adipose tissue and systematically identified GPCRs with the potential to regulate *** verification in primary adipose progenitor cells (APCs) of mice,we discovered that ADGRD1 promoted the differentiation of APCs,while GPR39 inhibits this *** the obese mouse model induced by a high-fat diet(HFD),both gain-of-function and loss-of-function studies validated that ADGRD1 promoted adipogenesis,thereby improving metabolic homeostasis,while GPR39 inhibited adipogenesis,leading to metabolic ***,through the analysis of 2,400 ChIP-seq data and 1,204 bulk RNA-seq data,we found that the transcription factors (TFs) MEF2D and TCF12 regulated the expression of ADGRD1and GPR39,*** study revealed the regulatory role of GPCRs in adipogenesis,providing novel targets for clinical intervention of metabolic dysfunction in obese patients.

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Neural stem cell-conditioned medium upregulated the PCMT1 expression and inhibited the phosphorylation of MST1 in SHSY5Y cells induced by Aβ_(25-35)

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BIOCELL 2022年第2期46卷 471-478页

作者： XINWEI WU GUOYONG JIA HONGNA YANG CONGCONG SUN YING LIU ZENGYAN DIAO department of Geriatrics Qilu HospitalCheeloo College of MedicineShandong UniversityJinanChina department of Neurology Qilu HospitalCheeloo College of MedicineShandong UniversityJinanChina department of Critical-Care medicine Qilu HospitalCheeloo College of MedicineShandong UniversityJinanChina

A progressive neurodegenerative disease,Alzheimer’s disease(AD).Studies suggest that highly expressed protein isoaspartate methyltransferase 1(PCMT1)in brain *** the current study,we explored the effects of neural stem cell-conditioned medium(NSC-CDM)on the PCMT1/MST1 pathway to alleviate Aβ_(25-35)-induced damage in SH-SY5Y *** data suggested that Aβ_(25-35) markedly inhibited cell ***-CDM or Neural stem cell-complete medium(NSC-CPM)had a suppression effect on toxicity when treatment with Aβ_(25-35),with a greater effect observed with NSC-CDM.Aβ_(25-35)+NSC-CDM group exhibited an increase in PCMT1 ***-PCMT1 markedly decreased cell proliferation and suppressed the protective role of NSC-CDM through the induction of apoptosis and improved p-MST1 *** of PCMT1 reversed the Aβ_(25-35)-induced decrease in cell proliferation and *** summary,our findings suggest that NSC-CDM corrects the Aβ_(25-35)-induced damage to cells by improving PCMT1 expressions,which in turn reduces phosphorylation of MST1.

关键词： Neural stem cell conditioned medium Protein isoaspartate methyltransferase 1 MST1 Amyloidβ_(25-35) Apoptosis

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Glucocorticoid receptor modulates myeloid-derived suppressor cell function via mitochondrial metabolism in immune thrombocytopenia

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Cellular & Molecular Immunology 2022年第7期19卷 764-776页

作者： Yu Hou Jie Xie Shuwen Wang Daqi Li Lingjun Wang Haoyi Wang Xiaofei Ni Shaoqiu Leng Guosheng Li Ming Hou Jun Peng department of Hematology Qilu HospitalCheeloo College of MedicineShandong UniversityJinanChina shandong Provincial Key Laboratory of Immunohematology Qilu HospitalCheeloo College of MedicineShandong UniversityJinanChina Jinan Central hospital Cheeloo College of MedicineShandong UniversityJinanChina Leading Research Group of Scientific Innovation Department of Science and Technology of Shandong ProvinceQilu HospitalCheeloo College of MedicineShandong UniversityJinanChina Advanced Medical Research Institute Shandong UniversityJinanChina

Myeloid-derived suppressor cells(MDSCs)are a heterogeneous population of immature cells and natural inhibitors of adaptive *** metabolic changes in MDSCs exert a direct immunological influence on their suppressive *** previous study demonstrated that high-dose dexamethasone(HD-DXM)corrected the functional impairment of MDSCs in immune thrombocytopenia(ITP);however,the MDSC population was not restored in nonresponders,and the mechanism remained *** this study,altered mitochondrial physiology and reduced mitochondrial gene transcription were detected in MDSCs from HD-DXM nonresponders,accompanied by decreased levels of carnitine palmitoyltransferase-1(CPT-1),a rate-limiting enzyme in fatty acid oxidation(FAO).Blockade of FAO with a CPT-1 inhibitor abolished the immunosuppressive function of MDSCs in HD-DXM *** also report that MDSCs from ITP patients had lower expression of the glucocorticoid receptor(GR),which can translocate into mitochondria to regulate the transcription of mitochondrial DNA(mtDNA)as well as the level of oxidative *** was confirmed that the expression of CPT-1 and mtDNA-encoded genes was downregulated in GR-siRNA-treated murine ***,by establishing murine models of active and passive ITP via adoptive transfer of DXM-modulated MDSCs,we confirmed that GR-silenced MDSCs failed to alleviate thrombocytopenia in mice with *** conclusion,our study indicated that impaired aerobic metabolism in MDSCs participates in the pathogenesis of glucocorticoid resistance in ITP and that intact control of MDSC metabolism by GR contributes to the homeostatic regulation of immunosuppressive cell function.

关键词： immune thrombocytopenia myeloid-derived suppressor cell HD-DXM glucocorticoid receptor

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Management of hepatocellular carcinoma patients with portal vein tumor thrombosis:A narrative review

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Hepatobiliary & Pancreatic Diseases International 2022年第2期21卷 134-144页

作者： Zi-Wen Tao Bao-Quan Cheng Tao Zhou Yan-Jing Gao department of Gastroenterology Qilu HospitalCheeloo College of MedicineShandong UniversityJinan 250012China

Background: Hepatocellular carcinoma(HCC) is one of the main reasons for malignancy-related death. Portal vein tumor thrombosis(PVTT) is the most common form of macrovascular invasion related to HCC occurring in 10%-60% of patients. HCC with PVTT is usually characterized by worsening liver function, vulnerability to blood metastasis, higher incidence of complications associated with portal hypertension, and intolerance to treatment when compared with that without PVTT. If only treated with supportive care, the median survival of HCC with PVTT is about 2.7 months. In the past, sorafenib was the only recommended therapy by guidelines with limited effectiveness. This narrative review aimed to describe the current management options for HCC with PVTT. Data sources: We have reviewed literature from Pub Med on the treatment of HCC with PVTT and compiled evidence-based facts on effective therapies available for different types of PVTT. Results: Sorafenib monotherapy is not much effective, but combining it with other methods can improve survival. Each type of PVTT can beneft from the combination of transarterial chemoembolization and sorafenib than sorafenib monotherapy. The tumor downstaging can be realized possibly after transarterial chemoembolization, but tumor invasion into the main trunk of the portal vein greatly impairs efficacy. Although surgery is a curative approach, it is often not recommended for Vp4 PVTT. Some new methods can broaden the indication, but further explorations are needed. Radiotherapy can decrease the possibility of Vp3 progression to Vp4, but building a forecast model of best radiation dose and response is necessary. Systemic chemotherapy, hepatic arterial infusion chemotherapy, radiofrequency ablation, portal stenting, and traditional Chinese medicine are also benefcial in Vp3-4 PVTT. The accurate diagnosis of PVTT can be made by radiomics, and prognostic classifcation models can be used to design personalized treatments. The application of new

关键词： Hepatocellular carcinoma Portal vein tumor thrombosis Transarterial chemoembolization Radiotherapy Surgery Sorafenib

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Prior transfusion of umbilical cord mesenchymal stem cells can effectively alleviate symptoms of motion sickness in mice through interleukin 10 secretion

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World Journal of Stem Cells 2021年第2期13卷 177-192页

作者： Hua-Su Zhu Dong Li Cong Li Jin-Xian Huang Shan-Shan Chen Lan-Bo Li Qing Shi Xiu-Li Ju department of Pediatrics Qilu HospitalCheeloo College of MedicineShandong UniversityJinan 250012Shandong ProvinceChina Stem Cell and Regenerative medicine Research Center Qilu HospitalCheeloo College of MedicineShandong UniversityJinan 250012Shandong ProvinceChina department of Animal Laboratory Qilu HospitalCheeloo College of MedicineShandong UniversityJinan 250012Shandong ProvinceChina department of Pediatrics Qilu Hospital of Shandong UniversityJinan 250012Shandong ProvinceChina

BACKGROUND Motion sickness(MS)is a disease that occurs during unbalanced movement,characterized by gastrointestinal symptoms and autonomic nervous system *** clinical treatments for MS are *** evidence indicates that the levels of pro-inflammatory cytokines increase during MS and are associated with an inner ear immune *** the present study,mesenchymal stem cells(MSCs)have been shown to exert strong immunosuppressive *** To explore whether umbilical cord-derived mesenchymal stem cells(UC-MSCs)can prevent the occurrence of MS,and the underlying mechanism regulated by MSCs in a mouse model of *** A total of 144(equal numbers of males and females)5wkold BALB/c mice were randomly divided into five groups:Normal group(n=16),MS group(n=32),MSCs group(n=32),MS+MSCs group(n=32),and MS+AS101/MSCs group(n=32).The MSCs group(n=32),MS+MSCs group(n=32),and MS+AS101/MSCs group(n=32)were preventively transplanted with UC-MSCs or AS101-treated UC-MSCs(1×106 cells/mouse).Mice in the MS(n=32),MS+MSCs,and MS+AS101/MSCs groups were subjected to rotation on a centrifuge for 10 min at 8×g/min for MS model establishment on days 3,5,8,and 10 after UC-MSCs *** Morris water maze(MWM)test was used to observe the symptom of ***-linked immunosorbent assay(ELISA)and reverse transcription-quantitative polymerase chain reaction(RT-qPCR)were used to detect the levels of inflammatory cytokines in mice peripheral blood and the petrous part of the temporal bone *** blot analysis was performed to analyze the JAK2/STAT3 signaling pathway in the cochlear *** examination was performed by hematoxylin and eosin(HE)staining for conventional morphological evaluation in the petrous part of temporal bone *** The MWM test demonstrated that UC-MSCs improved the symptoms of *** MS+MSCs group was faster than the MS group on days 3 and 5(P=0.036 and P=0.002,respectively).ELISA and RT-qPCR showed that

关键词： Mesenchymal stem cell Motion sickness Inflammation Immune microenvironment Interleukin-10 JAK2/STAT3

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Immunotherapy combined with antiangiogenic agents in patients with advanced malignant pleural mesothelioma: A case report

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World Journal of Clinical Cases 2022年第23期10卷 8284-8290页

作者： Tian-Tian Xuan Guang-Yi Li Si-Bo Meng Zhan-Mei Wang Lin-Li Qu department of Medical Oncology Qilu Hospital(Qingdao)Cheeloo College of MedicineShandong UniversityQingdao 266035Shandong ProvinceChina department of Respiratory Qilu Hospital(Qingdao)Cheeloo College of MedicineShandong UniversityQingdao 266035Shandong ProvinceChina

BACKGROUND Malignant pleural mesothelioma has limited therapeutic options and a poor outcome. Antiangiogenic agents might increase the efficacy of immunotherapy as second-line treatment of advanced-stage *** SUMMARY A patient with stage ⅢB pleural mesothelioma received second-line treatment with a combination of pembrolizumab, bevacizumab and chemotherapy following standard chemotherapy under the guidance of second-generation sequencing. He achieved a partial response after four cycles of treatment with progression-free survival of 5 mo. Pembrolizumab was suspended due to grade 2 immunerelated pneumonia, which was resolved by oral ***, disease progression was observed after immunotherapy rechallenge and anlotinib therapy. The patient had disease progression, multiorgan dysfuntion and died suddenly in October *** The combination of immune checkpoint inhibitor, anti-angiogenic agents and chemotherapy showed effective response for advanced pleural mesothelioma, but with adverse reactions.

关键词： Pleural mesothelioma Immune checkpoint inhibitor Next-generation Sequencing Immunerelated pneumonia Immunotherapy rechallenge Case report

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Regenerative antibacterial hydrogels from medicinal molecule for diabetic wound repair

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Bioactive Materials 2023年第7期25卷 541-554页

作者： Chunxiao Chai Pengfei Zhang Lin Ma Qi Fan Zhicheng Liu Xiang Cheng Yunpeng Zhao Weiwei Li Jingcheng Hao Key Laboratory of Colloid and Interface Chemistry(shandong university) Ministry of EducationJinan250100PR China department of Orthopaedic Surgery Qilu HospitalCheeloo College of MedicineShandong UniversityJinan250012PR China cheeloo college of medicine Shandong UniversityJinan250012PR China department of Pathology Qilu HospitalCheeloo College of MedicineShandong UniversityJinan250012PR China Laboratory of Basic Medical Sciences Qilu HospitalCheeloo College of MedicineShandong UniversityJinan250012PR China

Hydrogel products for chronic diabetic wounds,a serious and prevalent complication of diabetes,show limited effects on disability and remain ***,improvements in the usage of pharmaceutical molecule in the hydrogels are highly desirable to increase the therapeutic effect of *** this study,thioctic acid(a common medicine molecule in diabetes treatment)is used for preparing regenerative antibacterial hydrogels(RAH)which contains in situ synthesized silver nanoparticles(AgNPs).The RAH shows regenerative,self-healing and injectable ability,because of the reversible hydrogen and coordination *** good regenerative capacity,RAH can be stored as powder to avoid the water loss and facilitate storage *** to the antioxidant properties of thioctic acid,the RAH can decrease the oxidative damage and retain cell proliferation *** to the in situ synthesized AgNPs,the RAH also exhibits extraordinary antimicrobial capacities against MDR *** of these superiorities enable RAH to be a promising therapy for chronic diabetic wounds.

关键词： Diabetic wound healing Antibacterial hydrogel Thioctic acid Antioxidant Regeneration

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Impact of intravenous dexmedetomidine on postoperative bowel movement recovery after laparoscopic nephrectomy: A consortprospective, randomized, controlled trial

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World Journal of Clinical Cases 2021年第26期9卷 7762-7771页

作者： Shan-Shan Huang Fu-Xi Song Shao-Zhong Yang Shuai Hu Lian-Ying Zhao Shu-Qin Wang Qi Wu Xin Liu Feng Qi department of Anesthesiology Qilu HospitalCheeloo College of MedicineShandong UniversityJinan 250012Shandong ProvinceChina department of Anesthesiology The Second HospitalCheeloo College of MedicineShandong UniversityJinan 250033Shandong ProvinceChina

BACKGROUND Postoperative ileus is a frequent postoperative complication,especially after abdominal *** excitation is the primary factor for postoperative *** activation becomes increased by surgical stress,postoperative pain,and ***(DEX)can inhibit sympathetic nerve activity,inflammation,and *** To observe whether DEX promotes bowel movements in patients after laparoscopic *** One hundred and twenty patients undergoing laparoscopic nephrectomy were assigned to three groups:C(normal saline infusion),D1(DEX 0.02μg/kg/h),and D2(DEX 0.04μg/kg/h).The primary outcomes were the recorded times to first flatus,defecation,and eating after *** secondary outcomes were postoperative pain,assessed using the numerical rating scale(NRS),adverse effects,and the duration of the postoperative hospital *** The times to first flatus,defecation,and eating in groups D1 and D2 were significantly shorter than those in group C(P0.05).CONCLUSION Postoperative infusion of DEX at 0.04μg/kg/h facilitates bowel movements in patients undergoing laparoscopic nephrectomy.

关键词： Dexmedetomidine Bowel movement Recovery Flatus Postoperative

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