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The co.cept of gene therapy for glauco.a:the dream that has not co.e true yet

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Neural Regeneration Research 2024年第1期19卷 92-99页

作者： Robert Sulak Xiaonan Liu Adrian Smedowski Department of Physiology Faculty of Medical Sciences in KatowiceMedical University of Silesia in KatowiceKatowicePoland Institute of biotechnology HiLIFEUniversity of HelsinkiHelsinkiFinland Glauco.ech co. KatowicePoland

Gene therapies,despite of being a relatively new therapeutic approach,have a potential to beco.e an important alternative to current treatment strategies in *** glauco.a is not co.sidered a single gene disease,the identified goals of gene therapy would be rather to provide neuroprotection of retinal ganglion cells,especially,in intraocular-pressure-independent *** most co.monly reported type of vector for gene delivery in glauco.a studies is adeno-associated virus serotype 2 that has a high tro pism to retinal ganglion cells,res ulting in long-term expression and low immunogenic *** gene thera py studies recruit inducible and genetic animal models of optic neuropathy,like DBA/2J mice model of high-tension glauco.a and the optic nerve *** gene therapy-based neuroprotection of retinal ganglion cells is targeting specific genes translating to growth factors(i.e.,brain derived neurotrophic factor,and its receptor TrkB),regulation of apoptosis and neurodegeneration(i.e.,Bcl-xl,Xiap,FAS system,nico.inamide mononucleotide adenylyl transferase 2,Digit3 and Sarm1),immunomodulation(i.e.,Crry,C3 co.plement),modulation of neuroinflammation(i.e.,e rythropoietin),reduction of excitotoxicity(i.e.,co. KIlα)and transcription regulation(i.e.,Max,Nrf2).On the other hand,some of gene therapy studies focus on lowering intra ocular pressure,by impacting genes involved in both,decreasing aqueous humor production(i.e.,aquaporin 1),and increasing outflow facility(i.e.,co.2,prostaglandin F2a receptor,RhoA/RhoA kinase signaling pathway,MMP1,Myocilin).The goal of this review is to summarize the current stateof-art and the direction of development of gene therapy strategies for glauco.atous neuropathy.

关键词： adeno-associated virus gene editing gene therapy glauco.a IOP lowering IOP-independent mechanisms neuroprotection optic nerve optic neuropathy retinal ganglion cells

Engineered AAV13 variants with enhanced transduction and co.fined spread

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Zoological Research 2024年第4期45卷 781-790页

作者： Neng-Song Luo Yu-Xiang Cai Zeng-Peng Han Xiao-Kai Sui Wen-Jia Yuan Zi-Lian Zhang Hao-Dong Guo Jie Wang Kun-Zhang Lin Fu-Qiang Xu Wuhan National Laboratory for Optoelectronics Huazhong University of Science and TechnologyWuhanHubei 430074China Shenzhen Key Laboratory of Viral Vectors for Biomedicine Shenzhen-Hong Kong Institute of Brain ScienceShenzhen Institute of Advanced TechnologyChinese Academy of SciencesShenzhenGuangdong 518055China Key Laboratory of Magnetic Resonance in Biological Systems State Key Laboratory of Magnetic Resonance and Atomic and Molecular PhysicsNational Center for Magnetic Resonance in WuhanInnovation Academy for Precision Measurement Science and TechnologyChinese Academy of SciencesWuhanHubei 430071China Key Laboratory of Quality co.trol Technology for Virus-Based Therapeutics Guangdong Provincial Medical Products AdministrationNMPA Key Laboratory for Research and Evaluation of Viral Vector Technology in Cell and Gene Therapy Medicinal ProductsBrain Cognition and Brain Disease InstituteShenzhen Institute of Advanced TechnologyChinese Academy of SciencesShenzhenGuangdong 518055China University of Chinese Academy of Sciences Beijing 100049China Zhongnan Hospital Wuhan UniversityWuhanHubei 430072China brain case biotechnology co. Ltd.ShenzhenGuangdong 518107China co.lege of Life Sciences Wuhan UniversityWuhanHubei 430072China Center for Excellence in brain Science and Intelligence Technology Chinese Academy of SciencesShanghai 200031China

Precise targeting of specific regions within the central nervous system(CNS)is crucial for both scientific research and gene therapy in the co.text of brain ***-associated virus 13(AAV13)is known for its restricted diffusion range within the CNS,making it an ideal choice for precise labeling and administration within small brain ***,AAV13 mediates relatively low expression of target ***,we introduced specifically engineered modifications to the AAV13 capsid protein to enhance its transduction *** first co.structed AAV13-YF by mutating tyrosine to phenylalanine on the surface of the AAV13 *** then inserted the 7m8 peptide,known to enhance cell transduction,into positions 587/588 and 585/586 of the AAV13 capsid,resulting in two distinct variants named AAV13-587-7m8 and AAV13-585-7m8,*** found that AAV13-YF exhibited superior in vitro infectivity in HEK293T cells co.pared to AAV13,while AAV13-587-7m8 and AAV13-585-7m8 showed enhanced CNS infection capabilities in C57BL/6 mice,with AAV13-587-7m8 infection retaining a limited spread *** modified AAV13 variants hold promising potential for applications in gene therapy and neuroscience research.

关键词： Adeno-associated virus 13 AAV13-YF AAV13-587-7m8 AAV13-585-7m8 transduction efficiency

Nanoparticle drug delivery system for the treatment of brain tumors:Breaching the blood–brain barrier

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Acta Pharmaceutica Sinica B 2024年第6期14卷 2786-2789页

作者： Qiyu Tang Guo Zhao Hong Fang Yale Jiang Peiwen Ma Jiawei Zhoua Dongyan Liu Shujun Xing Gaoquan Li Nian Liu Huiyu Chen Shuhang Wang Ning Li Clinical Trial Center National Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100021China Chongqing Upgra biotechnology co. Ltd.Chongqing 401331China

To the Editor:Malignant brain tumors represent a substantial morbidity and mortality burden globally,with 308,102 new cases and 251,329 cancer-related deaths in *** tumors enco.pass primary tumors originating in the brain and brain metastases(BM)that have been spread from cancer lesions of other ***,BM are the most prevalent intracranial malignant tumor affecting approximately 20%-40%of cancer patients2.

关键词： Nanoparticle Drug delivery system Blood-brain barrier Tumor Glioma

Identification and Molecular Docking Mechanism of Novel Anti-Inflammatory Peptides from Lactobacillus paraplantarum Fermented Cannabis sativa L. (hemp) Seeds

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Food Science and Human Wellness 2024年

作者： LingYue Shan Akanksha Tyagi HunJu Ham Deog Hwan Oh Department of Food Science and biotechnology co.lege of Agriculture and Life Sciences Kangwon National University Future F Biotech co. Ltd Department of Biological Environment co.lege of Agriculture and Life Sciences Kangwon National University

The inflammatory response is a crucial physiological process that can lead to tissue damage and is co.sidered a causative factor for various chronic diseases， such as rheumatoid arthritis. Recent research has focused on exploring valuable nutrients derived from Cannabis sativa L. (hemp) seeds， particularly hemp seed proteins. Therefore， this study aimed to investigate the release of anti-inflammatory peptides from Lactobacillus paraplantarum-fermented hemp seed proteins. To co.firm the co.plete hydrolysis of hemp seed proteins during the fermentation process， SDS-PAGE was employed. Further， the isolation and purification of peptides were achieved through ultrafiltration. The identity of peptides was nextly established using ultra-high-performance liquid chromatography co.pled with hybrid quadrupole time-of-flight mass spectrometry (UHPLC-QTOF-MS). The results revealed a total of 39 identified peptides in fermented hemp seeds， with 9 peptides selected based on their relative quantity. Notably， AAELIGVP (P1)， AAVPYPQ (P2)， VFPEVAP (P4)， DVIGVPLG (P6)， and PVPKVL (P9) demonstrated strong anti-inflammatory abilities in LPS-induced Raw 264.7 macrophage cells. Molecular docking was used to understand the potential anti-inflammatory mechanism of these five peptides， and in silico.results indicated that P1， P2， P4， P6， and P9 co.ld bind to the active sites of TLR-4， NF-kB， and IKK with higher binding energies. Overall， these findings indicate that hemp seeds have potential to be a source of bioactive peptides for functional foods with anti-inflammatory properties.

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Generation of double knockout cattle via CRISPR-Cas9 ribonucleoprotein(RNP)electroporation

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Journal of Animal Science and biotechnology 2024年第1期15卷 456-462页

作者： Gyeong-Min Gim Kyeong-Hyeon Eom Dong-Hyeok Kwon Dae-Jin Jung Dae-Hyun Kim Jun-Koo Yi Jae-Jung Ha Ji-Hyun Lee Seong-Beom Lee Woo-Jae Son Soo-Young Yum Won-Wu Lee Goo Jang Laboratory of Theriogenology and biotechnology Department of Veterinary Clinical ScienceCollege of Veterinary Medicine and the Research Institute of Veterinary ScienceSeoul National UniversitySeoulRepublic of Korea LARTBio co. Ltd.SeoulRepublic of Korea Gyeongsangbukdo Livestock Research Institute YeongjuRepublic of Korea co.parative Medicine Disease Research Center Seoul National UniversitySeoulRepublic of Korea

Background Genome editing has been co.sidered as powerful tool in agricultural ***,genome editing progress in cattle has not been fast as in other mammal species,for some disadvantages including long gestational periods,single pregnancy,and high raising ***,technically demanding methods such as microinjection and somatic cell nuclear transfer(SCNT)are needed for gene editing in *** this point of view,electroporation in embryos has been risen as an *** First,editing efficiency of our electroporation methods were tested for *** of mutation on embryo was co.firmed by T7E1 *** first co.bination,mutation rates for MSTN and PRNP were 57.6%±13.7%and 54.6%±13.5%,*** case of MSTN/BLG,mutation rates were 83.9%±23.6%for MSTN,84.5%±18.0%for ***,the double-KO embryos were transferred to surrogates and mutation rate was identified in resultant calves by targeted deep *** recipients were transferred for MSTN/PRNP,4 calves were delivered,and one calf underwent an induction for double *** surrogates were given double-KO embryos for MSTN/BLG,and four of the six calves that were born had mutations in both *** These data demonstrated that production of genome edited cattle via electroporation of RNP co.ld be effectively ***,MSTN and PRNP from beef cattle and MSTN and BLG from dairy cattle have been born and they will be valuable resources for future precision breeding.

关键词： Beta-lactoglobulin Cattle CRISPR-Cas9 Electroporation Knockout MSTN PRNP

Highly sensitive nanozyme strip:An effective tool for forensic material evidence identification

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Nano Research 2024年第3期17卷 1785-1791页

作者： Juanji Hong Zhanjun Guo Dihan Duan Yi Zhang Xin Chen Yongjiu Li Zheng Tu Lei Feng Lei Chen Xiyun Yan Lizeng Gao Minmin Liang Demin Duan Experimental Center of Advanced Materials School of Materials Science&EngineeringBeijing Institute of TechnologyBeijing 100081China co.lege of Bioscience and biotechnology Shenyang Agricultural UniversityShenyang 110866China Chongqing kangjuquanhong biology science and technology co. ltdChongqing 400026China Key Laboratory of Forensic Genetics Institute of Forensic ScienceMinistry of Public SecurityBeijing 100038China CAS Engineering Laboratory for Nanozyme Key Laboratory of BiomacromoleculesInstitute of BiophysicsChinese Academic of ScienceBeijing 100101China

During criminal case investigations,blood evidence tracing is critical for criminal ***,the blood stains are often cleaned or co.ered up after the crime,resulting in trace residue and difficult ***,a highly sensitive and specific method for the rapid detection of human blood stains remains *** solve this problem,we established a nanozyme-based strip for rapid detection of blood evidence with high sensitivity and *** co.struct reliable nanozyme strips,we synthesized co.e_(2)O_(4) nanozymes with high peroxidase-like activity by scaling up to gram level,which can be supplied for six million tests,and co.jugated antibody as a detection probe in nanozyme *** developed co.e_(2)O_(4) nanozyme strip can detect human hemoglobin(HGB)at a co.centration as low as 1 ng/mL,which is 100 times lower than the co.mercially available co.loidal gold strips(100 ng/mL).Moreover,this co.e_(2)O_(4) nanozyme strip showed high generality on 12 substrates and high specificity to human HGB among 13 animal blood ***,we applied the developed co.e_(2)O_(4) nanozyme strip to successfully detect blood stains in three real cases,where the current co.mercial co.loidal gold strip failed to *** results suggest that the co.e_(2)O_(4) nanozyme strip can be used as an effective on-scene detection method for human blood stains,and can further be used as a long-term preserved material evidence for traceability inquiry.

关键词： co.e_(2)O_(4)nanozyme nanozyme strip peroxidase-like activity human hemoglobin blood evidence

Targeting tau in Alzheimer's disease:from mechanisms to clinical therapy

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Neural Regeneration Research 2024年第7期19卷 1489-1498页

作者： Jinwang Ye Huali Wan Sihua Chen Gong-Ping Liu Shenzhen Key Laboratory of Marine biotechnology and Eco.ogy College of Life Sciences and OceanographyShenzhen UniversityShenzhenGuangdong ProvinceChina Department of Laboratory Medicine Guangdong Provincial People’s Hospital(Guangdong Academy of Medical Sciences)Southern Medical UniversityGuangzhouGuangdong ProvinceChina co.innovation Center of Neurodegeneration Nantong UniversityNantongJiangsu ProvinceChina Department of Pathophysiology School of Basic Medicine and the Collaborative Innovation Center for Brain ScienceKey Laboratory of Ministry of Education of China and Hubei Province for Neurological DisordersTongji Medical CollegeHuazhong University of Science and TechnologyWuhanHubei ProvinceChina

Alzheimer’s disease is the most prevalent neurodegenerative disease affecting older *** features of Alzheimer’s disease include extra cellular aggregation of amyloid-βplaques and the accumulation of neurofibrillary tangles,fo rmed by tau protein,in the *** there are amyloid-β-ta rgeting therapies for the treatment of Alzheimer’s disease,these therapies are co.tly and exhibit potential negative side *** evidence suggests significant involvement of tau protein in Alzheimer’s disease-related *** an important microtubule-associated protein,tau plays an important role in maintaining the stability of neuronal microtubules and promoting axonal *** fact,clinical studies have shown that abnormal phosphorylation of tau protein occurs before accumulation of amyloid-βin the *** therapeutic strategies targeting tau protein have begun to emerge,and are co.sidered possible methods to prevent and treat Alzheimer’s ***,abnormalities in post-translational modifications of the tau protein,including aberrant phosphorylation,ubiquitination,small ubiquitin-like modifier(SUMO)ylation,acetylation,and truncation,co.tribute to its microtubule dissociation,misfolding,and subcellular *** causes mitochondrial damage,synaptic impairments,gliosis,and neuroinflammation,eventually leading to neurodegeneration and co.nitive *** review summarizes the recent findings on the underlying mechanisms of tau protein in the onset and progression of Alzheimer’s disease and discusses tau-targeted treatment of Alzheimer’s disease.

关键词： acetylation Alzheimer’s disease co.nitive deficits gliosis mitochondria damage neuroinflammation phosphorylation synaptic impairments tau tau immunotherapy

Human immunodeficiency virus-associated dementia co.plex with positive 14-3-3 protein in cerebrospinal fluid:A case report

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World Journal of Clinical cases 2024年第12期12卷 2065-2073页

作者： Yun-Sen He Xiao-Hong Qin Min Feng Qin-Jiang Huang Meng-Jun Zhang Li-Li Guo Ming-Bin Bao Ye Tao Hong-Yuan Dai Bo Wu Department of Neurosurgery Sichuan Lansheng Brain Hospital&Shanghai Lansheng Brain Hospital Investment Co.Ltd.Chengdu 610036Sichuan ProvinceChina Department of Psychiatry Sichuan Provincial Center for Mental HealthChengdu 610072Sichuan ProvinceChina Department of Geriatrics Municipal People’s Hospital in LuzhouLuzhou 646000Sichuan ProvinceChina Department of Neurosurgery Wenjiang District People’s Hospital of ChengduChengdu 611100Sichuan ProvinceChina Department of Neurosurgery Sichuan Provincial People's HospitalUniversity of Electronic Science and Technology of China ChengduChengdu 610072Sichuan ProvinceChina Department of Neurology Sichuan Provincial People’s HospitalUniversity of Electronic Science and Technology of ChinaChengdu 610072Sichuan ProvinceChina

BACKGROUND Human immunodeficiency virus(HIV)-associated dementia(HAD)is a subco.tical form of dementia characterized by memory deficits and psychomotor ***,HAD often presents with symptoms similar to those of Creutzfeldt-Jakob disease(CJD),particularly in patients with acquired immune deficiency syndrome(AIDS).case SUMMARY We report the case of a 54-year-old male who exhibited co.nitive dysfunction and seco.dary behavioral changes following HIV infection and suspected prion *** patient was diagnosed with HIV during hospitalization and his cerebrospinal fluid tested positive for 14-3-3 *** electroencephalogram showed a borderline-abnormal periodic triphasic wave ***-enhanced magnetic resonance imaging revealed moderate encephalatrophy and ***,symptomatic treatment and administration of amantadine were pursued for presumed CJD,but the patient’s co.dition co.tinued to *** co.trast,the patient’s co.dition improved following anti-HIV *** individual is also the only patient with this prognosis to have survived over 4 ***,the diagnosis was revised to *** In the diagnostic process of rapidly progressive dementia,it is crucial to rule out as many potential causes as possible and to co.sider an autopsy to diminish diagnostic *** 14-3-3 protein should not be regarded as the definitive marker for *** laboratory screening for infectious diseases is essential to enhance diagnostic precision,especially in AIDS patients with potential ***,a trial of diagnostic treatment may be co.sidered when additional testing is not feasible.

关键词： HIV-associated dementia co.nitive dysfunction Creutzfeld-Jakob disease Rapidly progressive dementia case report

The protective effects of fermented vinegar on acute alco.ol-induced hepatic and neuro-toxicity by regulating ethanol metabolism and gut microbiota

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Food Science and Human Wellness 2024年

作者： Yuan Meng Yunfan Liu Ting Xia Beibei Geng Yinglei Tian Hailong Cao Jin Yan Xiaoqi Pang Kai Liang Yufeng Yan Min Wang State Key Laboratory of Food Nutrition and Safety Key Laboratory of Industrial Fermentation Microbiology co.lege of biotechnology Tianjin University of Science and Technology Department of Gastroenterology and Hepatology General Hospital Tianjin Medical University National Key Clinical Specialty Tianjin Institute of Digestive Diseases Tianjin Key Laboratory of Digestive Diseases Shanxi Provincial Key Laboratory for Vinegar Fermentation Science and Engineering Shanxi Zilin Vinegar Industry co. Ltd.

Alco.ol abuse co.stitutes a significant health hazard， leading to various organ damage， notably the liver and brain. Shanxi aged vinegar (SAV) is one of the famous fermented and functional foods co.taining a variety of bioactive ingredients with beneficial effects on the human body. This study aimed to explore the potential protective effect of SAV in alleviating acute alco.ol intoxication (AAI) in mice. It was found that SAV at 2.5 mg/kg BW effectively ameliorated the decline in behavioral abilities following alco.ol co.sumption， characterized by a shortened sobering period. SAV reduces alco.ol-induced liver damage by inhibiting hepatic function enzymes and oxidative stress levels. Additionally， SAV mitigated the overactivation of microglia and the downregulation of neurotransmitter levels (AchE， 5-HT， and DA)， thereby reducing ethanol-induced brain damage. Meanwhile， SAV significantly decreased co.centrations of alco.ol and acetaldehyde in the blood and increased ADH and ALDH activities in the liver， indicating enhancement of ethanol metabolism. Moreover， we found that some gut microbiota including Verruco.icrobiota， Akkermansia， and Enteroco.cus were downregulated after SAV treatment in mice with AAI. These bacteria showed a negative co.relation with anti-oxidative markers (GSH and CAT) and enzymes related to ethanol metabolism pathways (ADH and ALDH)， and a positive co.relation with hepatic function markers (ALT， AST， and MDA)， alco.ol metabolites (alco.ol and acetaldehyde) and neurotransmitters (AchE， 5-HT， and DA). However， Bacteroidota， norank＿f＿Muribaculaceae， and Alistipes exhibited the opposite direction. These findings suggest that SAV possesses protective effects against hepatic and neuro-toxicity， and co.ld be a potential functional food for AAI prevention.

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