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Protein arginine methyltransferase-6 regulates heterogeneous nuclear ribonucleoprotein-F expression and is a potential target for the treatment of neuropathic pain

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Neural Regeneration Research 2025年第9期20卷 2682-2696页

作者： Xiaoyu Zhang Yuqi Liu Fangxia Xu Chengcheng Zhou Kaimei Lu Bin Fang Lijuan Wang Lina Huang Zifeng Xu Department of Anesthesiology International Peace Maternity and Child Health HospitalSchool of MedicineShanghai Jiao Tong UniversityShanghaiChina Department of Anesthesiology Shanghai General HospitalSchool of MedicineShanghai Jiao Tong UniversityShanghaiChina Shanghai key laboratory of Embryo Original diseases ShanghaiChina

Protein arginine methyltransferase-6 participates in a range of biological functions,particularly RNA processing,transcription,chromatin remodeling,and endosomal ***,it remains unclear whether protein arginine methyl transferase-6 modifies neuropathic pain and,if so,what the mechanisms of this *** this study,protein arginine methyltransferase-6 expression levels and its effect on neuropathic pain were investigated in the spared nerve injury model,chronic constriction injury model and bone cancer pain model,using immunohistochemistry,western blotting,immunoprecipitation,and label-free proteomic *** results showed that protein arginine methyltransferase-6 mostly co-localized withβ-tubulinⅢin the dorsal root ganglion,and that its expression decreased following spared nerve injury,chronic constriction injury and bone cancer *** addition,PRMT6 knockout(Prmt6~(-/-))mice exhibited pain ***,the development of spared nerve injury-induced hypersensitivity to mechanical pain was attenuated by blocking the decrease in protein arginine methyltransferase-6 ***,when protein arginine methyltransferase-6 expression was downregulated in the dorsal root ganglion in mice without spared nerve injury,increased levels of phosphorylated extracellular signal-regulated kinases were observed in the ipsilateral dorsal horn,and the response to mechanical stimuli was ***,protein arginine methyltransferase-6 appeared to contribute to spared nerve injury-induced neuropathic pain by regulating the expression of heterogeneous nuclear ***,protein arginine methyltransfe rase-6-mediated modulation of hete rogeneous nuclear ribonucleoprotein-F expression required amino atids 319 to 388,but not classical H3R2 *** findings indicated that protein arginine methyltransferase-6 is a potential therapeutic target fo r the treatment of peripheral neuro pathic pain.

关键词： dorsal root ganglion heterogeneous nuclear ribonucleoprotein F neuropathic pain protein arginine methyltransferase-6 sensory neurons

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Increased excitatory amino acid transporter 2 levels in basolateral amygdala astrocytes mediate chronic stress–induced anxiety-like behavior

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Neural Regeneration Research 2025年第6期20卷 1721-1734页

作者： Xirong Xu Shoumin Xuan Shuai Chen Dan Liu Qian Xiao Jie Tu Shenzhen key laboratory of Neuroimmunomodulation for Neurological diseases Shenzhen-Hong Kong Institute of Brain ScienceShenzhen Institute of Advanced TechnologyChinese Academy of SciencesShenzhenGuangdong ProvinceChina CAS key laboratory of Brain Connectome and Manipulation Brain Cognition and Brain Disease Institute(BCBDI)Shenzhen Institute of Advanced TechnologyChinese Academy of SciencesShenzhenGuangdong ProvinceChina Guangdong Provincial key laboratory of Brain Connectome and Behavior the Brain Cognition and Brain Disease Institute(BCBDI)Shenzhen Institute of Advanced TechnologyChinese Academy of SciencesShenzhenGuangdong ProvinceChina University of Chinese of Academy of Sciences BeijingChina Faculty of Life and Health Sciences Shenzhen Institute of Advanced TechnologyChinese Academy of SciencesShenzhenGuangdong ProvinceChina

The conventional perception of astrocytes as mere supportive cells within the brain has recently been called into question by empirical evidence, which has revealed their active involvement in regulating brain function and encoding behaviors associated with ***, astrocytes in the basolateral amygdala have been found to play a role in the modulation of anxiety-like behaviors triggered by chronic stress. Nevertheless, the precise molecular mechanisms by which basolateral amygdala astrocytes regulate chronic stress–induced anxiety-like behaviors remain to be fully elucidated. In this study, we found that in a mouse model of anxiety triggered by unpredictable chronic mild stress, the expression of excitatory amino acid transporter 2 was upregulated in the basolateral amygdala. Interestingly, our findings indicate that the targeted knockdown of excitatory amino acid transporter 2 specifically within the basolateral amygdala astrocytes was able to rescue the anxiety-like behavior in mice subjected to stress. Furthermore, we found that the overexpression of excitatory amino acid transporter 2 in the basolateral amygdala, whether achieved through intracranial administration of excitatory amino acid transporter 2agonists or through injection of excitatory amino acid transporter 2-overexpressing viruses with GfaABC1D promoters, evoked anxiety-like behavior in mice. Our single-nucleus RNA sequencing analysis further confirmed that chronic stress induced an upregulation of excitatory amino acid transporter 2 specifically in astrocytes in the basolateral amygdala. Moreover, through in vivo calcium signal recordings, we found that the frequency of calcium activity in the basolateral amygdala of mice subjected to chronic stress was higher compared with normal *** knocking down the expression of excitatory amino acid transporter 2 in the basolateral amygdala, the frequency of calcium activity was not significantly increased, and anxiety-like behavior was ob

关键词： anxiety astrocytes basolateral amygdala behavior dihydrokainic acid excitatory amino acid transporter 2 fiber photometry glutamate LDN-212320 transporter

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Lanthanum promoting bone formation by regulating osteogenesis,osteoclastogenesis and angiogenesis

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Journal of Rare Earths 2024年第3期42卷 621-628,I0007页

作者： Dandan Zou Runlian Lin Yu Han Juan Jia Guoqiang Zhou Haisong Zhang Kun Ge hebei key laboratory of chronic Kidney diseases and Bone Metabolism Affiliated Hospital of Hebei UniversityBaoding071000China key laboratory of Medicinal Chemistry and Molecular Diagnosis of the Ministry of Education Key Laboratory of Chemical Biology of Hebei ProvinceCollege of Chemistry and Environmental ScienceHebei UniversityBaoding071002China

With lanthanum(La) in agriculture, medicine, and the chemical industry, La shows accumulation in the body, especially in the bone, because of its similar structure to calcium. Moreover, La has a direct role in bone formation regulating osteoblasts and osteoclasts. Nevertheless, bone formation is complex under the regulation of osteogenesis, osteoclastogenesis, and angiogenesis in the bone microenvironment. It is difficult to comprehensively understand the regulation of bone homeostasis from a single kind of ***, some bone microenvironment-related cells and mouse calvaria culture models were used to study the regulatory effect of La-based compound-lanthanum nitrate(La(NO_(3))_(3)) on bone ***(NO_(3))_(3) has good biological safety, and the osteogenic differentiation is significantly increased under La(NO_(3))_(3) treatment for bone marrow mesenchymal stem cells(BMMSC). In contrast, the differentiation,maturation, and bone erosion ability of osteoclasts are significantly decreased. Meanwhile, the angiogenesis ability of human umbilical vein endothelial cells(HUVEC) is significantly promoted when treated with La(NO_(3))_(3). Furthermore, bone metabolism and angiogenesis are improved under La(NO_(3))_(3) treatment in the calvaria ex vivo culture model and BMMSC-HUVEC co-culture system. These results suggest that La has the beneficial effect of promoting bone metabolism and improving bone formation in the bone microenvironment.

关键词： Lanthanum Bone microenvironment Osteogenic differentiation Angiogenesis Rare earths

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Inhibitory gamma-aminobutyric acidergic neurons in the anterior cingulate cortex participate in the comorbidity of pain and emotion

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Neural Regeneration Research 2025年第10期20卷 2838-2854页

作者： Lu Guan Mengting Qiu Na Li Zhengxiang Zhou Ru Ye Liyan Zhong Yashuang Xu Junhui Ren Yi Liang Xiaomei Shao Jianqiao Fang Junfan Fang Junying Du Department of Neurobiology and Acupuncture Research Third School of Clinical MedicineZhejiang Chinese Medical UniversityHangzhouZhejiang ProvinceChina key laboratory for Research of Acupuncture Treatment and Transformation of Emotional diseases Third School of Clinical MedicineZhejiang Chinese Medical UniversityHangzhouZhejiang ProvinceChina Fuchun Community Health Service Center of Fuyang District HangzhouZhejiang ProvinceChina

Pain is often comorbid with emotional disorders such as anxiety and *** of the anterior cingulate cortex has been implicated in pain and pain-related negative emotions that arise from impairments in inhibitory gamma-aminobutyric acid *** review primarily aims to outline the main circuitry(including the input and output connectivity)of the anterior cingulate cortex and classification and functions of different gamma-aminobutyric acidergic neurons;it also describes the neurotransmitters/neuromodulators affecting these neurons,their intercommunication with other neurons,and their importance in mental comorbidities associated with chronic pain *** understanding on their role in pain-related mental comorbidities may facilitate the development of more effective treatments for these ***,the mechanisms that regulate gamma-aminobutyric acidergic systems remain *** is also unclear as to whether the mechanisms are presynaptic or *** exploration of the complexities of this system may reveal new pathways for research and drug development.

关键词： anterior cingulate cortex anxiety chronic pain circuit communication comorbidity depression gamma-aminobutyric acidergic neurons parvalbumin neurons synaptic transmission

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Protective Effect of Angiotensin(1-7) on Silicotic Fibrosis in Rats

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Biomedical and Environmental Sciences 2019年第6期32卷 419-426页

作者： ZHANG Bo Nan XU Hong GAO Xue Min ZHANG Gui Zhen ZHANG Xin YANG Fang School of Public Health North China University of Science and Technology Tangshan 063210 Hebei China hebei key laboratory for Organ Fibrosis Medical Research Center North China University of Science and Technology Tangshan 063210 Hebei China hebei key laboratory for chronic diseases Tangshan Key Laboratory for Clinical and Basic Research on Chronic Diseases School of Basic Medical Sciences North China University of Science and Technology Tangshan 063210 Hebei China Basic Medical College Hebei Medical University Shijiazhuang 050017 Hebei China

Objective Silicosis, caused by inhalation of silica dust, is the most serious occupational disease in China and the aim of present study was to explore the protective effect of Ang(1-7) on silicotic fibrosis and myofibroblast differentiation induced by Ang II. Methods HOPE-MED 8050 exposure control apparatus was used to establish the rat silicosis model. Pathological changes and collagen deposition of the lung tissue were examined by H.E. and VG staining, respectively. The localizations of ACE2 and α-smooth muscle actin(α-SMA) in the lung were detected by immunohistochemistry. Expression levels of collagen type I, α-SMA, ACE2, and Mas in the lung tissue and fibroblasts were examined by western blot. Levels of ACE2, Ang(1-7), and Ang II in serum were determined by ELISA. Co-localization of ACE2 and α-SMA in fibroblasts was detected by immunofluorescence. Results Ang(1-7) induced pathological changes and enhanced collagen deposition in vivo. Ang(1-7) decreased the expressions of collagen type I and α-SMA and increased the expressions of ACE2 and Mas in the silicotic rat lung tissue and fibroblasts stimulated by Ang II. Ang(1-7) increased the levels of ACE2 and Ang(1-7) and decreased the level of Ang II in silicotic rat serum. A779 enhanced the protective effect of Ang(1-7) in fibroblasts stimulated by Ang II. Conclusion Ang(1-7) exerted protective effect on silicotic fibrosis and myofibroblast differentiation induced by Ang II by regulating ACE2-Ang(1-7)-Mas axis.

关键词： Silicosis Ang II Myofibroblasts Ang(1-7) A779

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Dynamic Variation of RAS on Silicotic Fibrosis Pathogenesis in Rats

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Current Medical Science 2019年第4期39卷 551-559页

作者： Bo-nan ZHANG Xin ZHANG Hong XU Xue-min GAO Gui-zhen ZHANG Hui ZHANG Fang YANG School of Public Health Tangshan Key Laboratory for Clinical and Basic Research on Chronic DiseasesSchool of Basic Medical SciencesNorth China University of Science and TechnologyTangshan 063210China hebei key laboratory for Organ Fibrosis Medical Research CenterTangshan Key Laboratory for Clinical and Basic Research on Chronic DiseasesSchool of Basic Medical SciencesNorth China University of Science and TechnologyTangshan 063210China hebei key laboratory for chronic diseases Tangshan Key Laboratory for Clinical and Basic Research on Chronic DiseasesSchool of Basic Medical SciencesNorth China University of Science and TechnologyTangshan 063210China Basic Medical College Hebei Medical UniversityShijiazhuang 050017China

The dynamic variation of renin-angiotensin system (RAS) in silicosis remains *** Wistar rats were divided into 7 groups including control group,silicosis groups (inhaling SiO2 for 2,4,8,16 and 24 weeks,respectively) and Captopril (Cap) *** lung primary fibroblasts were divided into control group,SiO2-stimulated group (0,0.5,1,3,6,12,24 and 48 h) and Cap *** silicotic nodules were formed and collagens were deposited gradually in silicosis group observed by haematoxylin and eosin (HE) staining and Van Gieson (VG) *** relieved the lung fibrosis and collagen *** indicated the positive expression of α-smooth muscle actin α-SMA) was increased gradually in silicotic rat lung *** blotting revealed the expression of collagen type Ⅰ(Col Ⅰ) and α-SMA was up-regulated in silicotic rat lung tissue and fibroblasts stimulated by *** decreased the expression of Col Ⅰ and α-SMA in silicotic rat lung tissue and fibroblasts stimulated by *** blotting also demonstrated the expression of angiotensin-converting enzyme (ACE) and angiotensin Ⅱ type 1 receptor (ATI) was increased,and the expression of ACE2 and Mas was decreased gradually in silicotic rat lung tissue and fibroblasts stimulated by *** showed the serum levels of ACE and angiotensin Ⅱ(Ang Ⅱ) were also increased and ACE2 and Ang (1 -7) were decreased in the silicosis *** with Cap decreased the expression levels of ACE,Ang Ⅱ and ATI,and increased the expression levels of ACE2,Ang (1-7) and *** findings suggested that an imbalance between ACE-Ang Ⅱ-AT1 axis and ACE2-Ang (l-7)-Mas axis may participate in the development of silicosis.

关键词： silicosis fibroblasts SiCh renin-angiotensin system α-smooth muscle actin

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Identification of a dual functional betulinic acid analog for the treatment of osteoarthritis by phenotypic screening

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Science China Life Sciences 2025年第1期68卷 300-302页

作者： Ze-Min Lin Mai Xiang Wen-Hui Wei Shu-Hui Fan Li Chen Jie Wang Xiao-Qian Yang Chun-Hao Yang Shi-Jun He Jian-Ping Zuo laboratory of Immunopharmacology State Key Laboratory of Drug ResearchShanghai Institute of Materia MedicaChinese Academy of Sciences School of Pharmacy University of Chinese Academy of Sciences School of Pharmacy Nanjing University of Chinese Medicine State key laboratory of Drug Research Department of Medicinal ChemistryShanghai Institute of Materia MedicaChinese Academy of Sciences Innovation Research Institute of Traditional Chinese Medicine Shanghai University of Traditional Chinese Medicine Experiment Center for Science and Technology Shanghai University of Traditional Chinese Medicine

Dear Editor, Phenotypic drug discovery, which observes compound effects on physiology,has given way to targeting specific molecules, but has revived by using modern methods to find drugs based on therapeutic outcomes in disease models(Vincent et al., 2022). Osteoarthritis(OA) is a prevalent chronic joint disorder, primarily affecting knee joints, with osteoclast activation due to low-grade inflammation resulting in increased bone resorption and structural changes in the joint(Katz et al.,2021).

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Dietary carbohydrate intake and risk of type 2 diabetes:a 16-year prospective cohort study

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Science China Life Sciences 2025年

作者： Lu Gan Yi Yang Bin Zhao Kai Yu Kehua Guo Fang Fang Zhiguang Zhou Demetrius Albanes Jiaqi Huang key laboratory of Diabetes Immunology Ministry of Education and Department of Metabolism and Endocrinology The Second Xiangya Hospital of Central South University CSU-Sinocare Research Center for Nutrition and Metabolic Health Xiangya School of Public Health Central South UniversityFurong Laboratory Division of Cancer Epidemiology and Genetics National Cancer Institute NIH Department of Health and Human Services School of Computer Science and Engineering Central South University Institute of Environmental Medicine Karolinska Institute National Clinical Research Center for Metabolic diseases Key Laboratory of Diabetes Immunology Ministry of Education and Department of Metabolism and Endocrinology The Second Xiangya Hospital of Central South University

Despite considerable research underscoring the importance of carbohydrate intake in relation to the risk of type 2 diabetes(T2D), a comprehensive assessment of this relationship is currently lacking. We aimed to examine the associations of various types and food sources of dietary carbohydrate intake with the risk of T2D, to evaluate potential effect modification by other factors, including genetic susceptibility,and to explore the potential mediators for such associations. The present study included 161,872 participants of the UK Biobank who were free of prevalent cancer, cardiovascular disease, or diabetes, and had at least one validated 24-h dietary recall assessment. Multivariableadjusted age-stratified Cox proportional hazard regression models were applied to estimate hazard ratios(HRs) and 95% confidence intervals(CI) for the associations of various types and food sources of dietary carbohydrate intake with risk of T2D. During a median follow-up of13.6 years, 4,176 incident cases of T2D were identified. In the multivariable-adjusted models, a greater intake of fiber, carbohydrates from whole grains, and carbohydrates from non-starchy vegetables was significantly associated with a lower risk of T2D(highest vs. lowest quantile, HR [95% CI]=0.70 [0.62–0.79], 0.74 [0.67–0.82], and 0.83 [0.75–0.92], respectively, all P for trend <0.005). In contrast, a higher intake of starch and carbohydrate from starchy vegetables was associated with an increased risk of T2D(highest vs. lowest quantile, HR [95%CI]=1.31 [1.16–1.48] and 1.19 [1.09–1.31], respectively, both P for trend <0.005). Replacing one serving of refined grains or starchy vegetables with an equal amount of whole grains or non-starchy vegetables was associated with 4% to 10% lower risk of T2D(all P values <0.001).The observed associations were generally similar across population subgroups, including individuals with different genetic susceptibility to T2D. Mediation analyses of the inverse association between T

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Nanoscale and hollow inorganic sulfide@porous organic network doped intelligent hydrogels for accelerating diabetes wound therapeutics

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Science China Chemistry 2025年

作者： Yanhong Li Qiang Zhang Quanbo Wang Junping Wang Xiaomei Zhang Caixia Yin School of Chemistry and Chemical Engineering Shandong University key laboratory of Chemical Biology and Molecular Engineering of Ministry of Education Shanxi University

Diabetic wound healing remains a major challenge due to the excess hyperglycemia microenvironment,massively bacterial infections,macrophage dysfunction,and persistent *** comprehensively solve these problems,novel multifunctional materials are highly ***,a versatile and intelligent hydrogel (Cu2S@FePPOPTPM@GOx@Gel) is ***2S@FePPOPTPM@GOx with hollow morphology and controllable size was rationally designed and fabricated by using Cu2S nanocubes as a template,followed by in situ growth of FePPOPTPMand loading glucose oxidase （GOx）,*** infection occurs,the Schiff base bonds in Cu2S@FePPOPTPM@GOx@Gel can controllably release Cu2S@FePPOPTPM@GOx based on its excellent dynamic pH-responsiveness,thereby synergically reducing blood glucose levels and killing bacteria achieved relying on the excellent catalytic activity of GOx towards glucose and its promoted peroxidelike activity of *** experiments on diabetic wound model in vivo demonstrated that Cu2S@FePPOPTPM@GOx@Gel promoted wound healing and skin regeneration,which was attributed to its antibacterial properties,alleviating inflammation,stimulating vascular regeneration,and encouraging M2 polarization of *** work provides a novel strategy for the construction of a microenvironment-responsive and antibiotics-free drug delivery platform to treat diabetic wounds,as well as broad prospects of nanomaterials in the clinical treatment of chronic wounds.

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Cryptotanshinone suppresses key onco-proliferative and drugresistant pathways of chronic myeloid leukemia by targeting STAT5 and STAT3 phosphorylation

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Science China(Life Sciences) 2018年第9期61卷 999-1009页

作者： Bowen Dong Zirui Liang Zhirong Chen Bin Li Lingling Zheng Jianhua Yang Hui Zhou Lianghu Qu key laboratory of Gene Engineering of the Ministry of Education State Key Laboratory for Biocontrol Sun Yat-sen University

C-Myc and signal transducer and activator of transcription(STAT) family proteins have been proposed to be important downstream genes of BCR-ABL, which characterizes most cases of chronic myeloid leukemia(CML). Here, we report a c-Myc pathway-targeted screening of seven natural anticancer compounds, in which we identified cryptotanshinone as a highly promising agent for CML therapy. Cryptotanshinone depletes c-Myc in CML by repressing the phosphorylation of *** viability of K562 cells correlated with p-STAT5 suppression. Unexpectedly, imatinib activates rather than inhibits the phosphorylation of STAT3 in K562 cells. We demonstrated that cryptotanshinone, as a dual inhibitor of p-STAT5 and p-STAT3,can effectively block IL-6-mediated STAT3 activation and reverse BCR-ABL kinase-independent drug resistance. Moreover, we showed that the epigenetic rebalance between decreased BCR-ABL/STAT5/c-Myc and enhanced STAT3/multi-drug resistance(MDR) pathways is characteristic of the cancer stem cell-like property of K562/ADR. Simultaneously suppressing these two pathways using cryptotanshinone proves to be critical for the malignant network redress and MDR reversal of K562/ADR. These studies reveal the dual functions of cryptotanshinone that suppress key oncogenic proliferation and drug-resistant pathways in CML cells by targeting p-STAT5 and p-STAT3, providing a new strategy for CML therapy that takes advantage of natural products.

关键词： p-STAT3/5 microRNA CML MDR

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