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Salsolinol as an RNA m~6A methylation inducer mediates dopaminergic neuronal death by regulating YAP1 and autophagy

Neural Regeneration Research 2025年第3期20卷 887-899页

作者： Jianan Wang Yuanyuan Ran Zihan Li Tianyuan Zhao Fangfang Zhang Juan Wang Zongjian Liu Xuechai Chen Beijing International Science and Technology Cooperation base for Antiviral Drugs College of Chemistry and LifeBeijing University of TechnologyBeijingChina department of Rehabilitation Beijing Rehabilitation HospitalCapital Medical UniversityBeijingChina

Salsolinol(1-methyl-6,7-dihydroxy-1,2,3,4-tetrahydroisoquinoline,Sal)is a catechol isoquinoline that causes neurotoxicity and shares structural similarity with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine,an environmental toxin that causes Parkinson's ***,the mechanism by which Sal mediates dopaminergic neuronal death remains *** this study,we found that Sal significantly enhanced the global level of N~6-methyladenosine(m~6A)RNA methylation in PC12 cells,mainly by inducing the downregulation of the expression of m~6A demethylases fat mass and obesity-associated protein(FTO)and alk B homolog 5(ALKBH5).RNA sequencing analysis showed that Sal downregulated the Hippo signaling *** m~6A reader YTH domain-containing family protein 2(YTHDF2)promoted the degradation of m~6A-containing Yes-associated protein 1(YAP1)mRNA,which is a downstream key effector in the Hippo signaling ***,downregulation of YAP1 promoted autophagy,indicating that the mutual regulation between YAP1 and autophagy can lead to *** findings reveal the role of Sal on m~6A RNA methylation and suggest that Sal may act as an RNA methylation inducer mediating dopaminergic neuronal death through YAP1 and *** results provide greater insights into the neurotoxic effects of catechol isoquinolines compared with other studies and may be a reference for assessing the involvement of RNA methylation in the pathogenesis of Parkinson's disease.

关键词： ALKBH5 autophagy FTO Hippo pathway m~6A Parkinson's disease RNA methylation salsolinol YAP1 YTHDF2

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Shrinkage of ipsilateral taste buds and hyperplasia of contralateral taste buds following chorda tympani nerve transection

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Neural Regeneration Research 2015年第6期10卷 989-995页

作者： Yi-ke Li Juan-mei Yang Yi-bo Huang Dong-dong Ren Fang-lu Chi department of otology and skull base surgery Eye Ear Nose & Throat HospitalFudan University Shanghai Auditory Medical Center Key Laboratory of Hearing Science Ministry of Health department of Hearing and Speech Sciences Vanderbilt University

The morphological changes that occur in the taste buds after denervation are not well under- stood in rats, especially in the contralateral tongue epithelium. In this study, we investigated the time course of morphological changes in the taste buds following unilateral nerve transection. The role of the trigeminal component of the lingual nerve in maintaining the structural integrity of the taste buds was also examined. Twenty-four Sprague-Dawley rats were randomly divided into three groups： control, unilateral chorda tympani nerve transection and unilateral chorda tympani nerve transection ＋ lingual nerve transection. Rats were allowed up to 42 days of re- covery before being euthanized. The taste buds were visualized using a cytokeratin 8 antibody. Taste bud counts, volumes and taste receptor cell numbers were quantified and compared among groups. No significant difference was detected between the chorda tympani nerve transection and chorda tympani nerve transection ＋ lingual nerve transection groups. Taste bud counts, volumes and taste receptor cell numbers on the ipsilateral side all decreased significantly compared with control. On the contralateral side, the number of taste buds remained unchanged over time, but they were larger, and taste receptor cells were more numerous postoperatively. There was no evidence for a role of the trigeminal branch of the lingual nerve in maintaining the structural integrity of the anterior taste buds.

关键词： nerve regeneration gustation cytokeratin tongue epithelium immunohistochemistry taste bud trigeminal nerve disorder NSFC grants neural regeneration

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Cell proliferation during hair cell regeneration induced by Math1 in vestibular epithelia in vitro

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Neural Regeneration Research 2018年第3期13卷 497-501页

作者： Yi-bo Huang Rui Ma Juan-mei Yang Zhao Han Ning Cong Zhen Gao Dongdong Ren Jing Wang Fang-lu Chi department of otology and skull base surgery EYE & ENT Hospital of Fudan University Shanghai China Shanghai Clinical Medical Center of Hearing Medicine Shanghai China Key Laboratory of Hearing Medicine Ministry of Health Shanghai China

Hair cell regeneration is the fundamental method of correcting hearing loss and balance disorders caused by hair cell damage or loss. How to promote hair cell regeneration is a hot focus in current research. In mammals, cochlear hair cells cannot be regenerated and few vestibular hair cells can be renewed through spontaneous regeneration. However, Math1 gene transfer allows a few inner ear cells to be transformed into hair cells in vitro or in vivo. Hair cells can be renewed through two possible means in birds： supporting cell differentiation and transdifferentiation with or without cell division. Hair cell regeneration is strongly associated with cell proliferation. Therefore, this study explored the relationship between Math1-induced vestibular hair cell regeneration and cell division in mammals. The mouse vestibule was isolated to harvest vestibular epithelial cells. Ad-Math1-enhanced green fluorescent protein （EGFP） was used to track cell division during hair cell transformation.5-Bromo-2′-deoxyuridine （BrdU） was added to track cell proliferation at various time points. Immunocytochemistry was utilized to determine cell differentiation and proliferation. Results demonstrated that when epithelial cells were in a higher proliferative stage, more of these cells differentiated into hair cells by Math1 gene transfer. However, in the low proliferation stage, no BrdU-positive cells were seen after Math1 gene transfer. Cell division always occurred before Math1 transfection but not during or after Math1 transfection, when cells were labeled with BrdU before and after Ad-Math1-EGFP transfection. These results confirm that vestibular epithelial cells with high proliferative potential can differentiate into new hair cells by Math1 gene transfer, but this process is independent of cell proliferation.

关键词： erve regeneration cell proliferation cell division Math1 hair cells hair cell renewal supporting cell differentiation vestibular cells neural regeneration

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Otolithic organ function in patients with profound sensorineural hearing loss

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Journal of otology 2016年第2期11卷 73-77页

作者： Yujuan Zhou Yongzhen Wu Jing Wang department of otology and skull base surgery Eye Ear Nose & Throat Hospital Fudan University Shanghai Auditory Medical Center Key Laboratory of Hearing Science Ministry of Health

Profound sensorineural hearing loss (PSHL) is not uncommonly encountered in otology. In clinics, there is a high incidence of otolithic damage in patients with PSHL, but relevant reports are few. Sharing a continuous membranous structure and similar receptor cell ultrastructures, the cochlea and vestibule may be susceptible to the same harmful factors. Disorders of the inner ear may result in a variety of manifestations, including vertigo, spatial disorientation, blurred vision, impaired articulation, and hearing impairment. Considering the diversity of clinical symptoms associated with PSHL with otolithic dysfunction, it may be frequently misdiagnosed, and objective means of testing the function of otolithic organs should be recommended for hearing-impaired patients. Vestibular-evoked myogenic potentials (VEMPs) via air-conducted sound are of great importance for the diagnosis of otolithic function. Hearing devices such as cochlear implants are commonly accepted treatments for PSHL, and early identification and treatment of vestibular disorders may increase the success rate of cochlear implantation. Therefore, it is necessary to increase awareness of otolithic functional states in patients with PSHL.

关键词： Profound sensorineural hearing loss PSHL Otolithic organs Vestibular-evoked myogenic potential VEMP

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Advantages of Short-term Personalized Vestibular Rehabilitation at Home Guided by Professional Therapist for Treatment of Decompensated Vestibular Vertigo

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Current Medical Science 2021年第4期41卷 687-694页

作者： Chen-ru DING Ying-qi GAO Yu-juan ZHOU Jun GU Jing WANG department of otology and skull base surgery Eye Ear Nose&Throat HospitalFudan UniversityShanghai 200031China Shanghai Auditory Medical Center Shanghai 200031China Key laboratory of Hearing Science Ministry of HealthShanghai 200031China

Objective Patients suffered a lot from decompensated vestibular *** and vestibular rehabilitation training have been proven to be effective in prompting vestibular *** rehabilitation training is faced with the challenges of patients’compliance,completion,the average recuperation time and so *** study is aimed to investigate advantages of short-term personalized vestibular rehabihitation at home guided by professional *** A short-term personalized vestibular rehabilitation program(ST-PVR)was designed for patients with decompensated vestibular vertigo in this *** Patients experiencing the ST-PVR program showed significant improvement of Self-Rating Anxiety Scale(SAS),Dizziness Handicap Inventory(DHI),Activities-Specific Balance Confidence Scale(ABC)scores by the second follow-up(at 2nd week after treatment,P<0.05).However-improvement in the medication group occurred slightly later,DHI for 1 month and SAS for 2 months after treatment(P<0.05).Also,the improvement in the onset time of unilateral weakness(UW)at 2nd week after treatment in the personalized vestibular rehabilitation(PVR)group was faster than that in the medication *** In general,the short-term PVR program showed great advantages by prompting vestibular compensation quickly and putting forward future direction for clinical treatment on decompensated vestibular vertigo.

关键词： vertigo personalized program medication vestibular compensation therapy vestibular rehabilitation

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Bioactive materials from berberine-treated human bone marrow mesenchymal stem cells accelerate tooth extraction socket healing through the jaw vascular unit

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Science China Life Sciences 2025年

作者： Ruyu Wang Tianxiao Wang Ziyu Chen Jiandong Jiang Yifei Du Hua Yuan Yongchu Pan Yuli Wang department of Oral and Maxillofacial surgery The Affiliated Stomatological Hospital of Nanjing Medical University State Key Laboratory Cultivation Base of Research Prevention and Treatment for Oral Diseases Jiangsu Province Engineering Research Centre of Stomatological Translational Medicine Nanjing Medical University department of Stomatology Chongzhou People's Hospital Medical Basic Research Innovation Centre for Cardiovascular and Cerebrovascular Diseases Ministry of Education International Joint Laboratory for Drug Target of Critical Illnesses School of PharmacyNanjing Medical University Institute of Medicinal Biotechnology Chinese Academy of Medical Sciences & Peking Union Medical College department of Orthodontic The Affiliated Stomatological Hospital of Nanjing Medical University State Key Laboratory Cultivation Base of Research Prevention and Treatment for Oral Diseases Jiangsu Province Engineering Research Centre of Stomatological Translational Medicine Nanjing Medical University

Delayed tooth extraction socket(TES) healing can cause failure of subsequent oral implantation and increase socioeconomic burden on patients. Excessive amounts of M1 macrophages, apoptotic neutrophils(ANs), and neutrophil extracellular traps(NETs) impair alveolar bone regeneration during TES healing. In the present study, we first discovered that conditioned medium(CM) collected from berberine-treated human bone marrow mesenchymal stem cells(BBR-HB-CM) accelerated TES healing. BBR-HB-CM contained bioactive materials that promoted the polarization of macrophages from M1 to M2, impeded the formation of ANs and NETs, and modulated M2 macrophage efferocytosis in vivo and in vitro. Mechanistically, BBR-HB-CM promoted bone formation by inhibiting macrophage-myofibroblast transition and reprogrammed macrophage polarization through p85/AKT/mTOR pathway-dependent autophagy. The 3-methyladenine abolished the therapeutic effects of BBR-HB-CM. Further studies revealed that BBR-HB-CM accelerated TES healing in rats with type 2 diabetes mellitus. Overall, our results demonstrated that BBR-HB-CM had high potential to promote rapid TES healing.

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The misdiagnosis of external auditory canal carcinoma

The misdiagnosis of external auditory canal carcinoma

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全国耳鼻咽喉头颈外科中青年学术会议

作者： Ting Zhang Chunfu Dai Zhengmin Wang department of otology and skull base surgery Eye Ear Nose and Throat HospitalFudan University

Objective External auditory canal(EAC) carcinomas are frequently *** aim of this study was to conduct a review of misdiagnosed cases and analyze the factors involved. Study Design This study was a retrospective assess...

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Endoscopic Approach to Remove Intra-extracranial Tumors in Various skull base Regions： 10-year Experience of a Single Center

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Chinese Medical Journal 2017年第24期130卷 2933-2940页

作者： Qiu-Hang Zhang Zhen-Lin Wang Hong-Chuan Guo Feng Kong Bo Yan Ming-Chu Li Ge Chen Jian-Tao Liang Yu-Hai Bao Feng Ling department of Neurosurgery Skull Base Surgery Center Xuanwu Hospital Capital Medical University Beijing 100053 China department of Otorhinolaryngology Head and Neck surgery Skull Base Surgery Center Xuanwu Hospital Capital Medical University Beijing 100053 China

Background：Some problems have been found in the usually adopted combined approach for the removal of intra-extracranial tumors in skull ***,we described a pure endoscopic transnasal or transoral approach （ETA） for the removal of intra-extracranial tumors in various skull base ***：Retrospectively,clinical data,major surgical complications,pre-and postoperative images,and follow-up information of a series of 85 patients with intra-extracranial tumors in various skull base regions who were treated by surgery via ETA in our skull base center during the past 10 years were reviewed and ***：Gross total tumor removal was achieved in 80/85 cases （94.1%） in this *** 37 cases with tumors in anterior skull base and all 14 cases with tumors in jugular foramen received total tumor *** and three cases with tumors in clivus received total and subtotal tumor removal,*** and subtotal tumor removal was performed for 16 cases and 2 cases in lateral skull base,*** complications in this study included：cerebrospinal fluid leakage （n =3）,meningitis （n =3）,and new cranial nerve deficits （n =3;recovered in 3 months after surgery）.In the follow-up period of40-151 months （median：77 months）,seven patients （8.8%） out of the 80 cases of total tumor removal experienced ***：Complete resection of intra-extracranial growing tumors in various skull base regions can be achieved via the pure ETA in one stage in selected *** procedure for radical removal of tumors is feasible and safe.

关键词： Endoscopy: lntra-extracranial Growth Neoplasm skull base surgery

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Engineered Cancer Nanovaccines:A New Frontier in Cancer Therapy

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Nano-Micro Letters 2025年第2期17卷 134-168页

作者： Yijie Wang Congrui Liu Chao Fang Qiuxia Peng Wen Qin Xuebing Yan Kun Zhang Central Laboratory and department of Medical Ultrasound Sichuan Academy of Medical SciencesSichuan Provincial People’s HospitalSchool of MedicineUniversity of Electronic Science and Technology of ChinaNo.32West Second SectionFirst Ring RoadChengdu 610072People’s Republic of China department of Stomatology and Central Laboratory School of MedicineShanghai Tenth People’s HospitalTongji UniversityNO.301 Yan‑Chang‑Zhong RoadShanghai 200072People’s Republic of China Jiangsu Provincial Innovation and Practice base for Postdoctors Suining People’s HospitalAffiliated Hospital of Xuzhou Medical UniversityNo.2Bayi West RoadSuiningXu Zhou 221000Jiangsu ProvincePeople’s Republic of China

Vaccinations are essential for preventing and treating disease,especially cancer nanovaccines,which have gained considerable interest recently for their strong anti-tumor immune *** can prompt the immune system to generate antibodies and activate various immune cells,leading to a response against tumor tissues and reducing the negative effects and recurrence risks of traditional chemotherapy and *** enhance the flexibility and targeting of vaccines,nanovaccines utilize nanotechnology to encapsulate or carry antigens at the nanoscale level,enabling more controlled and precise drug delivery to enhance immune *** nanovaccines function by encapsulating tumor-specific antigens or tumor-associated antigens within *** small size of these nanomaterials allows for precise targeting of T cells,dendritic cells,or cancer cells,thereby eliciting a more potent anti-tumor *** this paper,we focus on the classification of carriers for cancer nanovaccines,the roles of different target cells,and clinically tested cancer nanovaccines,discussing strategies for effectively inducing cytotoxic T lymphocytes responses and optimizing antigen presentation,while also looking ahead to the translational challenges of moving from animal experiments to clinical trials.

关键词： Cancer nanovaccines Immunotherapy Nanobiotechnology Immune targets Signaling pathway

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Foreign Body Reaction After Cochlear Implantation： A Case Report

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Chinese Medical Journal 2015年第15期128卷 2124-2125页

作者： Yuan Xin Ya-Sheng Yuan Fang-Lu Chi Jing Wang Juan-Mei Yang department of Otolaryngology-Head and Neck surgery Shanghai Children's Medical Center and Shanghai Children Hearing and Speech Center Shangha Jiaotong University Shanghai 200127 China department of otology and skull base surgery Eye Ear Nose and Throat Hospital Fudan University Shanghai 200031 China Shanghai Auditory Medical Center Shanghai 200031 China

Foreign body reaction is a rare complication after cochlear *** such complications do occur,they may be intractable and difficult to be cured with antibiotics or surgical revision that may lead to cochlear reimplantation *** this article,we presented a patient with foreign body reaction who recovered well after cochlear reimplantation and has been in good health throughout the 6 years of follow-up at regular intervals in Affiliated Eye Ear Nose and Throat Hospital of Fudan University.

关键词： Cochlear Implantation Foreign Body Reaction

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