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p38 MAPK inhibitor SB202190 suppresses ferroptosis in the glutamate-induced retinal excitotoxicity glaucoma model

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Neural Regeneration Research 2024年第10期19卷 2299-2309页

作者： Lemeng Feng Chao Wang Cheng Zhang Wulong Zhang Weiming Zhu Ye He Zhaohua Xia Weitao Song National Clinical Research center for Geriatric Diseases Xiangya Hospital of Central South UniversityChangshaHunan ProvinceChina Eye center of Xiangya hospital Central South UniversityChangshaHunan ProvinceChina Hunan Key Laboratory of Ophthalmology ChangshaHunan ProvinceChina

Glutamate excitotoxicity has been shown to play an important role in glaucoma, and glutamate can induce ferroptosis. The p38 mitogenactivated protein kinase(MAPK) pathway inhibitor SB202190 has a potential ability to suppress ferroptosis, and its downstream targets, such as p53, have been shown to be associated with ferroptosis. However, whether ferroptosis also occurs in retinal ganglion cells in response to glutamate excitotoxicity and whether inhibition of ferroptosis reduces the loss of retinal ganglion cells induced by glutamate excitotoxicity remain unclear. This study investigated ferroptosis in a glutamate-induced glaucoma rat model and explored the effects and molecular mechanisms of SB202190 on retinal ganglion cells. A glutamate-induced excitotoxicity model in R28 cells and an N-methyl-D-aspartate-induced glaucoma model in rats were used. In vitro experiments showed that glutamate induced the accumulation of iron and lipid peroxide and morphological changes of mitochondria in R28 cells, and SB202190 inhibited these changes. Glutamate induced the levels of p-p38 MAPK/p38 MAPK and SAT1 and decreased the expression levels of ferritin light chain, SLC7A11, and GPX4. SB202190 inhibited the expression of iron death-related proteins induced by glutamate. In vivo experiments showed that SB202190 attenuated N-methyl-D-aspartate-induced damage to rat retinal ganglion cells and improved visual function. These results suggest that SB202190 can inhibit ferroptosis and protect retinal ganglion cells by regulating ferritin light chain, SAT1, and SLC7A11/Gpx4 pathways and may represent a potential retina protectant.

关键词： ferroptosis glaucoma glutamate excitotoxicity p38 MAPK retinal ganglion cell SB202190

NIR-triggered on-site NO/ROS/RNS nanoreactor:Cascade-amplified photodynamic/photothermal therapy with local and systemic immune responses activation

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Opto-Electronic Advances 2024年第6期7卷 58-73页

作者： Ziqing Xu Yakun Kang Jie Zhang Jiajia Tang Hanyao Sun Yang Li Doudou He Xuan Sha Yuxia Tang Ziyi Fu Feiyun Wu Shouju Wang Laboratory of Molecular Imaging Department of RadiologyThe First Affiliated Hospital of Nanjing Medical UniversityNanjing 210029China Department of Breast Surgery The First Affiliated Hospital of Nanjing Medical UniversityNanjing 210029China Department of Women&Children Research center The First Affiliated HospitalNanjing Medical UniversityNanjing 210029China

Photothermal and photodynamic therapies(PTT/PDT)hold promise for localized tumor treatment,yet their full potential is hampered by limitations such as the hypoxic tumor microenvironment and inadequate systemic immune *** these challenges,we present a novel near-infrared(NIR)-triggered RNS nanoreactor(PBNO-Ce6)to amplify the photodynamic and photothermal therapy efficacy against triple-negative breast cancer(TNBC).The designed PBNOCe6 combines sodium nitroprusside-doped Prussian Blue nanoparticles with Chlorin e6 to enable on-site RNS production through NIR-induced concurrent NO release and ROS *** not only enhances tumor cell eradication but also potentiates local and systemic antitumor immune responses,protecting mice from tumor *** in vivo evaluations revealed that treatment with PBNO-Ce6 leads to a remarkable 2.7-fold increase in cytotoxic T lymphocytes and a 62%decrease in regulatory T cells in comparison to the control PB-Ce6(Prussian Blue nanoparticles loaded with Chlorin e6),marking a substantial improvement over traditional PTT/*** such,the PBNO-Ce6 nanoreactor represents a transformative approach for improving outcomes in TNBC and potentially other malignancies affected by similar barriers.

关键词： photothermal therapy photodynamic therapy nitric oxide reactive nitrogen species triple-negative breast cancer immune response nanoreactor

A new era of mutation rate analyses: Concepts and methods

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Zoological Research 2024年第4期45卷 767-780页

作者： Kun Wu Danqi Qin Yang Qian Haoxuan Liu center for Evolutionary&Organismal Biology and the Fourth Affiliated hospital of Zhejiang university Zhejiang University School of MedicineHangzhouZhejiang 310058China

The mutation rate is a pivotal biological characteristic,intricately governed by natural selection and historically garnering considerable *** advances in high-throughput sequencing and analytical methodologies have profoundly transformed our understanding in this domain,ushering in an unprecedented era of mutation rate *** paper aims to provide a comprehensive overview of the key concepts and methodologies frequently employed in the study of mutation *** examines various types of mutations,explores the evolutionary dynamics and associated theories,and synthesizes both classical and contemporary ***,this review comprehensively explores recent advances in understanding germline and somatic mutations in animals and offers an overview of experimental methodologies,mutational patterns,molecular mechanisms,and driving forces influencing variations in mutation rates across species and ***,it proposes several potential research directions and pressing questions for future investigations.

关键词： Mutation rate Somatic mutations Germline mutations Animal

Rbm8a regulates neurogenesis and reduces Alzheimer's disease-associated pathology in the dentate gyrus of 5×FAD mice

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Neural Regeneration Research 2024年第4期19卷 863-871页

作者： Chenlu Zhu Xiao Ren Chen Liu Yawei Liu Yonggang Wang Department of Neurology Lanzhou University Second Hospital Department of Neurology The First Affiliated Hospital of Nanchang University Department of Neurology Xiaogan City Central Hospital Health Service Department of the Guard Bureau of the General Office of the Central Committee of the Communist Party of China Headache center Department of NeurologyBeijing Tiantan HospitalCapital Medical University

Alzheimer’s disease is a prevalent and debilitating neurodegenerative condition that profoundly affects a patient’s daily functioning with progressive cognitive decline,which can be partly attributed to impaired hippocampal *** in the hippocampal dentate gyrus is likely to persist throughout life but declines with aging,especially in Alzheimer’s *** evidence indicated that RNA-binding protein 8A(Rbm8a)promotes the proliferation of neural progenitor cells,with lower expression levels observed in Alzheimer’s disease patients compared with healthy *** study investigated the hypothesis that Rbm8a overexpression may enhance neurogenesis by promoting the proliferation of neural progenitor cells to improve memory impairment in Alzheimer’s ***,Rbm8a overexpression was induced in the dentate gyrus of 5×FAD mice to validate this *** Rbm8a levels in the dentate gyrus triggered neurogenesis and abated pathological phenotypes(such as plaque formation,gliosis reaction,and dystrophic neurites),leading to ameliorated memory performance in 5×FAD *** sequencing data further substantiated these findings,showing the enrichment of differentially expressed genes involved in biological processes including neurogenesis,cell proliferation,and amyloid protein *** conclusion,overexpressing Rbm8a in the dentate gyrus of 5×FAD mouse brains improved cognitive function by ameliorating amyloid-beta-associated pathological phenotypes and enhancing neurogenesis.

关键词： Adora2a Alzheimer’s disease astrocyte cAMP signaling pathway dentate gyrus dystrophic neurites microglia neurogenesis plaque Rbm8a

Multilocular thymic cysts can be easily misdiagnosed as malignant tumor on computer tomography:A case report

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World Journal of Clinical Cases 2024年第8期12卷 1474-1480页

作者： Jun Sun Qing-Ning Yang Yi Guo Ping Zeng Long-Yan Ma Ling-Wen Kong Bo-Ying Zhao Chuan-Ming Li Department of Radiology Chongqing University Central HospitalChongqing Emergency Medical CenterChongqing 400014China Department of Pathology Chongqing University Central HospitalChongqing Emergency Medical CenterChongqing 400014China Department of Cardiothoracic Surgery Chongqing University Central HospitalChongqing Emergency Medical CenterChongqing 400014China

BACKGROUND Multilocular thymic cyst(MTC)is a rare mediastinal lesion which is considered to occur in the process of acquired *** is usually characterized by well-defined cystic density and is filled with transparent *** SUMMARY We report on a 39-year-old male with a cystic-solid mass in the anterior *** tomography(CT)imaging showed that the mass was irregular with unclear *** injection of contrast agent,there was a slight enhancement of stripes and *** to CT findings,it was diagnosed as thymic *** After surgery,MTC accompanied by bleeding and infection was confirmed by pathological *** main lesson of this case was that malignant thymic tumor and MTC of the anterior mediastinum sometimes exhibit similar CT *** is necessary in clinical work to avoid misdiagnosis.

关键词： Multilocular thymic cyst Computer tomography Misdiagnosis Hemorrhage Infection Case report

Predictive factors and model validation of post-colon polyp surgery Helicobacter pylori infection

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World Journal of Gastrointestinal Surgery 2024年第1期16卷 173-185页

作者： Zheng-Sen Zhang Health Management center Affiliated Hospital of Shaoxing University(Shaoxing Municipal Hospital)Shaoxing 312000Zhejiang ProvinceChina

BACKGROUND Recently,research has linked Helicobacter pylori(***)stomach infection to colonic inflammation,mediated by toxin production,potentially impacting colorectal cancer *** To investigate the risk factors for post-colon polyp surgery,*** infection,and its correlation with pathologic *** Eighty patients who underwent colon polypectomy in our hospital between January 2019 and January 2023 were retrospectively *** were then randomly split into modeling(n=56)and model validation(n=24)sets using *** modeling cohort was divided into an ***-infected group(n=37)and an ***-uninfected group(n=19).Binary logistic regression analysis was used to analyze the factors influencing the occurrence of *** infection after colon polyp surgery.A roadmap prediction model was established and ***,the correlation between the different pathological types of colon polyps and the occurrence of *** infection was analyzed after colon polyp *** Univariate results showed that age,body mass index(BMI),literacy,alcohol consumption,polyp pathology type,high-risk adenomas,and heavy diet were all influential factors in the development of *** infection after intestinal *** multifactorial logistic regression analysis showed that age,BMI,and type of polyp pathology were independent predictors of the occurrence of *** infection after intestinal *** area under the receiver operating characteristic curve was 0.969[95%confidence interval(95%CI):0.928–1.000]and 0.898(95%CI:0.773–1.000)in the modeling and validation sets,*** slope of the calibration curve of the graph was close to 1,and the goodness-of-fit test was P>0.05 in the two *** decision analysis curve showed a high rate of return in both *** results of the correlation analysis between different pathological types and the occurrence of *** infection after colon polyp surgery showed that hyperplastic

关键词： Colon polyps Helicobacter pylori Risk factors Pathologic type Columnar graphic modeling

Bioinspired metal-organic framework nanozyme reinforced with thermosensitive hydrogel for regulating inflammatory responses in Parkinson’s disease

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Nano Research 2024年第2期17卷 858-865页

作者： Xiaowan Fan Tao Zhang Xin Ding Yushuo Gu Qing Li Wei Jiang Kelong Fan Nanozyme Medical center Academy of Medical ScienceZhengzhou UniversityZhengzhou 450001China Department Central-China Branch of National Center for Cardiovascular DiseasesHean Cardiovascular Disease CenterFuwai Central-China HospitalCentral China Fuwai Hospital of Zhengzhou UniversityZhengzhou 450046China Application center for Precision Medicine the Second Affiliated Hospital of Zhengzhou UniversityZhengzhou 450052China CAS Engineering Laboratory for Nanozyme Key Laboratory of Protein and Peptide PharmaceuticalsInstitute of BiophysicsChinese Academy of SciencesBeijing 100101China university of Chinese Academy of Sciences Beijing 101408China Department of General Surgery Strategic Support Force Medical CenterBeijing 100101China Department of Anesthesiology Pain and Perioperative MedicineThe First Affiliated Hospital of Zhengzhou UniversityZhengzhou 450052China

Parkinson’s disease(PD)is a prevalent neurodegenerative disorder accompanied by movement disorders and neuroinflammatory ***-inflammatory intervention to regulate oxidative stress in the brain is beneficial for managing ***,traditional natural antioxidants have failed to meet the clinical treatment demands due to insufficient activity and ***,Cu-doping zeolite imidazolate framework-8(ZIF-8)nanozyme is designed to simulate Cu/Zn superoxide dismutase(SOD)by biomimetic *** nanozyme composite is then integrated into thermosensitive hydrogel(poly(lactic-co-glycolic acid)-poly(ethylene glycol)-poly(lactic-co-glycolic acid)(PLGA-PEG-PLGA))to form an effective antioxidant system(Cu-ZIF@Hydrogel).The thermosensitive hydrogel incorporating nanozymes demonstrate distinct viscoelastic properties aimed at enhancing local nanozyme adhesion,prolonging nanozyme retention time,and modulating antioxidant activity,thus significantly improving the bioavailability of *** the cellular and animal levels of PD,we find that Cu-ZIF@Hydrogel bypass the blood-brain barrier and efficiently accumulate in the nerve ***,the Cu-ZIF@Hydrogel significantly alleviate the PD’s behavioral and pathological symptoms by reducing the neuroinflammatory levels in the lesion ***,the hydrogel-incorporating nanozyme system holds great potential as a simple and reliable avenue for managing PD.

关键词： bioinspired nanozyme thermosensitive hydrogel Parkinson’s disease oxidative stress neuroinflammatory

Expert consensus on the diagnosis and therapy of endo-periodontal lesions

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International Journal of Oral Science 2024年第3期16卷 381-389页

作者： Bin Chen Yanan Zhu Minkui Lin Yangheng Zhang Yanfen Li Xiangying Ouyang Song Ge Jiang Lin Yaping Pan Yan Xu Yi Ding Shaohua Ge Faming Chen Zhongchen Song Shaoyun Jiang Jiang Sun Lijun Luo Junqi Ling Zhi Chen Lin Yue Xuedong Zhou Fuhua Yan Department of Periodontology Nanjing Stomatological HospitalAffiliated Hospital of Medical SchoolInstitute of StomatologyNanjing UniversityNanjingChina Department of Endodontics Nanjing Stomatological HospitalAffiliated Hospital of Medical SchoolInstitute of StomatologyNanjing UniversityNanjingChina Clinical Research center for Oral Tissue Deficiency Diseases of Fujian Province&Fujian Key Laboratory of Oral Diseases&Fujian Provincial Engineering Research center of Oral Biomaterial School and Hospital of StomatologyFujian Medical UniversityFuzhouChina Department of Periodontology Peking University School and Hospital of Stomatology&National Center for Stomatology&National Clinical Research Center for Oral Diseases&National Engineering Research Center of Oral Biomaterials and Digital Medical DevicesBeijingChina School and hospital of Stomatology Zunyi Medical UniversityZunyiChina Department of Stomatology Beijing TongRen HospitalCapital Medical UniversityBeijingChina Department of Periodontics School and Hospital of StomatologyChina Medical UniversityShenyangChina Department of Periodontology The Affiliated Stomatological Hospital of Nanjing Medical UniversityJiangsu Key Laboratory of Oral DiseasesNanjing Medical UniversityNanjingChina State Key Laboratory of Oral Diseases&National center for Stomatology&National Clinical Research center for Oral Diseases&Department of Periodontics West China Hospital of StomatologySichuan UniversityChengduChina Department of Periodontology School and Hospital of StomatologyShandong University&Shandong Key Laboratory of Oral Tissue Regeneration&Shandong Engineering Research Center of Dental Materials and Oral Tissue Regeneration&Shandong Provincial Clinical Research Center for Oral Diseases JinanJinanChina State Key Laboratory of Oral&Maxillofacial Reconstruction and Regeneration National Clinical Research Center for Oral DiseasesShaanxi International Joint Research Center for Oral DiseasesDepartment of periodontologySchool of StomatologyThe Fou

Endo-periodontal lesions(EPLs)involve both the periodontium and pulp tissue and have complicated etiologies and pathogenic mechanisms,including unique anatomical and microbiological characteristics and multiple contributing *** etiological complexity leads to difficulties in determining patient prognosis,posing great challenges in clinical ***,EPLaffected teeth require multidisciplinary therapy,including periodontal therapy,endodontic therapy and others,but there is still much debate about the appropriate timing of periodontal therapy and root canal *** compiling the most recent findings on the etiology,pathogenesis,clinical characteristics,diagnosis,therapy,and prognosis of EPL-affected teeth,this consensus sought to support clinicians in making the best possible treatment decisions based on both biological and clinical evidence.

关键词： diagnosis periodontal lesions

Efficacy and safety of Tianqi Pingchan Granule, a compound Chinese herbal medicine, for levodopa-induced dyskinesia in Parkinson's disease:A randomized double-blind placebo-controlled trial

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Journal of Integrative Medicine 2024年第5期22卷 545-551页

作者： Yu Zhang Xiao-bo Zhu Yang Zhao Gui-yun Cui Wen-tao Li Can-xing Yuan Jian-ping Huang Ying Wan Na Wu Lu Song Jia-hao Zhao Yan Liang Chuan-ying Xu Mei-juan Liu Chen Gao Xin-xin Chen Zhen-guo Liu Department of Neurology Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine Department of Neurology Nanjing Hospital of Chinese Medicine Affiliated to Nanjing University of Chinese Medicine Parkinson's Disease center the Affiliated Hospital of Xuzhou Medical University Department of Neurology Shanghai Municipal Hospital of Traditional Chinese Medicine Affiliated to Shanghai University of Traditional Chinese Medicine Department of Neurology Longhua HospitalShanghai University of Traditional Chinese Medicine Department of Neurology Wenzhou Central Hospital

Background: Patients with Parkinson's disease(PD) undergoing long-term levodopa therapy are prone to develop levodopa-induced dyskinesia(LID). Amantadine is the main drug recommended for the treatment of LID by current guidelines, but it is far from meeting clinical needs. Tianqi Pingchan Granule(TPG), a compound Chinese herbal medicine, has been developed to relieve symptom of ***: This randomized controlled trial evaluated the efficacy and safety of the combination of TPG and amantadine for ***, setting, participants and interventions: This is a randomized double-blind placebo-controlled trial,conducted from January 2020 to August 2021 at 6 sites in Jiangsu, Zhejiang and Shanghai, China. One hundred PD patients with ≥ 0.5 h of LID were randomly assigned to either the TPG plus amantadine group(TPG group) or the placebo plus amantadine group(placebo group), and treated for a period of12 weeks. To ensure unbiased results, all study participants, investigators and sponsors were unaware of group allocations. Additionally, the data analysts remained blinded until the analysis was *** outcome measures: The primary outcome was assessed using the Unified Dyskinesia Rating Scale(UDysRS)(Range 0–104). The key secondary end point was improvement of motor and non-motor symptoms. Safety analyses included all enrolled ***: One hundred patients were enrolled and randomized into the two treatment groups. The changes in UDysRS at week 12 were –11.02 for the TPG group and –4.19 for the placebo group(treatment difference –6.83 [–10.53 to –3.12]; P = 0.0004). Adverse events were reported for 2 of 50 patients(4.0%) in each of the ***: This study indicated that a 12-week treatment of amantadine plus TPG effectively reduced UDysRS scores and was well tolerated, demonstrating the efficacy and safety of TPG for the treatment of LID in PD.

关键词： Levodopa-induced dyskinesia Parkinson’s disease Tianqi Pingchan Granule