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Efficacy and safety of human umbilical cord-derived mesenchymal stem cells in the treatment of refractory immune thrombocytopenia:a prospective,single arm,phase I trial

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Signal Transduction and Targeted therapy 2024年第5期9卷 2250-2259页

作者： Yunfei Chen Yanmei Xu Ying Chi Ting Sun Yuchen Gao Xueqing Dou Zhibo Han Feng Xue Huiyuan Li Wei Liu Xiaofan Liu Huan Dong Rongfeng Fu Mankai Ju Xinyue Dai Wentian Wang Yueshen Ma Zhen Song Jundong Gu Wei Gong Renchi Yang Lei Zhang State Key Laboratory of Experimental Hematology National Clinical Research Centre for Blood DiseasesHaihe Laboratory of Cell EcosystemTianjin Key Laboratory of Gene Therapy for Blood DiseasesCAMS Key Laboratory of Gene Therapy for Blood DiseasesInstitute of Hematology&Blood Diseases HospitalChinese Academy of Medical Sciences&Peking Union Medical CollegeTianjin 300020China Tianjin Institutes of Health Science Tianjin 301600China National Clinical Research Center for Hematologic Diseases Jiangsu Institute of HematologyThe First Affiliated Hospital of Soochow UniversitySuzhou 215006China National Engineering Research Centre of cell Products Tianjin Key Laboratory of Engineering Technologies for Cell PharmaceuticalAmCellGene Engineering Co.LtdTianjin 300457China School of Population Medicine and Public Health Chinese Academy of Medical Sciences and Peking Union Medical College100730 BeijingChina

Patients with refractory immune thrombocytopenia(ITP)frequently encounter substantial bleeding risks and demonstrate limited responsiveness to existing *** cord-derived mesenchymal stem cells(UC-MSCs)present a promising alternative,capitalizing on their low immunogenicity and potent immunomodulatory effects for treating diverse autoimmune *** prospective phase I trial enrolled eighteen eligible patients to explore the safety and efficacy of UC-MSCs in treating refractory *** research design included administering UC-MSCs at escalating doses of 0.5×10^(6)cells/kg,1.0×10^(6)cells/kg,and 2.0×10^(6)cells/kg weekly for four consecutive weeks across three cohorts during the dose-escalation phase,followed by a dose of 2.0×10^(6)cells/kg weekly for the dose-expansion *** events,platelet counts,and changes in peripheral blood immunity were monitored and recorded throughout the administration and follow-up ***,12(with an addition of three patients in the 2.0×10^(6)cells/kg group due to dose-limiting toxicity)and six patients were enrolled in the dose-escalation and dose-expansion phase,*** patients(13/18,72.2%)experienced one or more treatment emergent adverse *** adverse events occurred in four patients(4/18,22.2%),including gastrointestinal hemorrhage(2/4),profuse menstruation(1/4),and acute myocardial infarction(1/4).The response rates were 41.7%in the dose-escalation phase(5/12,two received 1.0×10^(6)cells/kg per week,and three received 2.0×10^(6)cells/kg per week)and 50.0%(3/6)in the dose-expansion *** overall response rate was 44.4%(8/18)among all enrolled *** sum up,UC-MSCs are effective and well tolerated in treating refractory ITP(*** ID:NCT04014166).

关键词： doses immunity treatment

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The BCL-2 inhibitor APG-2575 resets tumor-associated macrophages toward the M1 phenotype,promoting a favorable response to anti-PD-1 therapy via NLRP3 activation

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cellular & Molecular Immunology 2024年第1期21卷 60-79页

作者： Fan Luo Han Li Wenjuan Ma Jiaxin Cao Qun Chen Feiteng Lu Miaozhen Qiu Penghui Zhou Zengfei Xia Kangmei Zeng Jianhua Zhan Ting Zhou Qiuyun Luo Wentao Pan Lin Zhang Chaozhuo Lin Yan Huang Li Zhang Dajun Yang Hongyun Zhao State Key Laboratory of Oncology in South China Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and TherapyGuangdong Provincial Clinical Research Center for CancerSun Yat-sen University Cancer CenterGuangzhouChina Ascentage Pharma(Suzhou)Co ltd 218 Xinghu StreetSuzhouJiangsu ProvinceChina

The main challenges in the use of immune checkpoint inhibitors(ICIs)are ascribed to the immunosuppressive tumor microenvironment and the lack of sufficient infiltration of activated CD8+T *** the tumor microenvironment(TME)from“cold”to“hot”and thus more likely to potentiate the effects of ICIs is a promising strategy for cancer *** found that the selective BCL-2 inhibitor APG-2575 can enhance the antitumor efficacy of anti-PD-1 therapy in syngeneic and humanized CD34+mouse *** single-cell RNA sequencing,we found that APG-2575 polarized M2-like immunosuppressive macrophages toward the M1-like immunostimulatory phenotype with increased CCL5 and CXCL10 secretion,restoring T-cell function and promoting a favorable immunotherapy ***,we demonstrated that APG-2575 directly binds to NF-κB p65 to activate NLRP3 signaling,thereby mediating macrophage repolarization and the activation of proinflammatory caspases and subsequently increasing CCL5 and CXCL10 chemokine *** a result,APG-2575-induced macrophage repolarization could remodel the tumor immune microenvironment,thus improving tumor immunosuppression and further enhancing antitumor T-cell *** immunohistochemistry confirmed that patients with better immunotherapeutic efficacy had higher CD86,p-NF-κB p65 and NLRP3 levels,accompanied by lower CD206 expression on ***,these data provide evidence that further study on APG-2575 in combination with immunotherapy for tumor treatment is required.

关键词： BCL-2 APG-2575 ICIs Macrophages NLRP3

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Photocatalytic in situ H_(2)O_(2) production and activation for enhanced ciprofloxacin degradation over CeO_(2)-Co_(3)O_(4)/g-C_(3)N_(4):key role of CeO_(2)

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Rare Metals 2024年第6期43卷 2695-2707页

作者： Hong-Jie Zhu Yi-Kai Yang Ming-Hui Li Lu-Ning Zou Hai-Tao Zhao Shandong Provincial Key Laboratory of Chemical Energy Storage and Novel cell Technology School of Chemistry and Chemical Engin College of Ecology and Environment Anhui Normal UniversityWuhu241002China Liaocheng YiLu Advanced Materials Co. LtdLiaocheng 252000China

The abused ciprofloxacin antibiotics have caused significant environmental *** oxidative degradation of ciprofloxacin exhibits promising efficacy,it often entails excessive energy ***,it is necessary to explore an effective and ecologically sustainable degradation ***,we demonstrated that g-C_(3)N_(4) decorated with the coordinated CeO_(2)and Co_(3)O_(4)(CeO_(2)-Co_(3)O_(4)/CN)exhibited effective ciprofloxacin photodegradation via in situ H_(2)O_(2) production and activation *** indicate that the introduced CeO_(2) enhances the transference of photogenerated electrons to O_(2) by adjusting the oxygen vacancy of photocatalyst,thereby increasing the generation of superoxide radicals,which in turn generate H_(2)O_(2),resulting in a 22.4-fold increase in H_(2)O_(2) generation over g-C_(3)N_(4).Moreover,the in situ H_(2)O_(2)generation facilitated by CeO_(2) is confirmed to be essential for ciprofloxacin degradation via CeO_(2)-Co_(3)O_(4)/CN,as it provides enough oxidant for Co_(3)O_(4) to activate into hydroxyl radicals for the pollutants ***,CeO_(2)-Co_(3)O_(4)/CN achieves a ciprofloxacin degradation ratio of 97.7%within 80 *** study introduces a novel approach that combines H_(2)O_(2) generation and activation,offering an innovative perspective for achieving clean and efficient purification of antibiotic-contaminated water.

关键词： CeO_(2) In situ H_(2)O_(2)generation Ciprofloxacin degradation Photocatalyst

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Neutralization of SARS-CoV-2 infection by antibodies targeting diverse epitopes

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Genes & Diseases 2024年第4期11卷 134-137页

作者： Shusheng Wang Yunji Liao Kaiyong Yang Hang Ma Zhangyi Song Haiqiu Huang Li Zhang Ailing Wang Lei Han Jiawei Zhang Hui Chen Haiyang Yin Yantin Bian Hua Jiang Xiaodong Xiao Yueqing Xie Yunsheng Yuan Jianwei Zhu Engineering Research Center of cell and Therapeutic Antibody Ministry of EducationSchool of PharmacyShanghai Jiao Tong UniversityShanghai 200240China Jecho Laboratories Inc.FrederickMD 21704USA Jecho Institute Co. Ltd.Shanghai 200240China

The CoVID-19 pandemic that started in late 2019 is sweeping through the world,posing historic challenges to global health,and disrupting social and economic *** and recent studies indicate that monoclonal antibodies can be efficacious in preventing and treating SARSCoV-1 and SARS-CoV-2 *** a phage display platform,we have identified dozens of monoclonal antibodies that bind to diverse epitope groups on the SARS-CoV-2 spike *** of them bound to the receptor binding domain(RBD)and inhibited ACE2-RBD interaction.

关键词： antibodies inhibited monoclonal

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Long non-coding RNA H19 regulates neurogenesis of induced neural stem cells in a mouse model of closed head injury

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Neural Regeneration Research 2024年第4期19卷 872-880页

作者： Mou Gao Qin Dong Zhijun Yang Dan Zou Yajuan Han Zhanfeng Chen Ruxiang Xu Department of Neurosurgery Sichuan Academy of Medical Sciences and Sichuan Provincial People's HospitalSchool of MedicineUniversity of Electronic Science and Technology of China Department of Neurosurgery Chinese PLA General Hospital Zhongsai Stem cell Genetic Engineering Co. Ltd. Department of Neurology Fu Xing HospitalCapital Medical University

Stem cell-based therapies have been proposed as a potential treatment for neural regeneration following closed head *** previously reported that induced neural stem cells exert beneficial effects on neural regeneration via cell ***,the neural regeneration efficiency of induced neural stem cells remains *** this study,we explored differentially expressed genes and long non-coding RNAs to clarify the mechanism underlying the neurogenesis of induced neural stem *** found that H19 was the most downregulated neurogenesis-associated lnc RNA in induced neural stem cells compared with induced pluripotent stem ***,we demonstrated that H19 levels in induced neural stem cells were markedly lower than those in induced pluripotent stem cells and were substantially higher than those in induced neural stem cell-derived *** predicted the target genes of H19 and discovered that H19 directly interacts with mi R-325-3p,which directly interacts with Ctbp2 in induced pluripotent stem cells and induced neural stem *** H19 or Ctbp2 impaired induced neural stem cell proliferation,and mi R-325-3p suppression restored the effect of H19 inhibition but not the effect of Ctbp2 ***,H19 silencing substantially promoted the neural differentiation of induced neural stem cells and did not induce apoptosis of induced neural stem ***,silencing H19 in induced neural stem cell grafts markedly accelerated the neurological recovery of closed head injury *** results reveal that H19 regulates the neurogenesis of induced neural stem cells.H19 inhibition may promote the neural differentiation of induced neural stem cells,which is closely associated with neurological recovery following closed head injury.

关键词： closed head injury Ctbp2 induced neural stem cell lncRNA H19 miR-325-3p neurogenesis

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Sperm acrosin activity may be a useful factor in choosing between ICSI and IVF for infertile male patients

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Asian Journal of Andrology 2024年第1期26卷 85-90页

作者： Ye-Na Hu Liang Hu Xin-Yu Yin Huan Zhang Yang-Qin Peng Gang Liu Ge Lin Wei-Na Li The Institute of Reproductive and Stem cell Engineering School of Basic Medical ScienceCentral South UniversityChangsha 410008China Department of Andrology Reproductive and Genetic Hospital of CITiC-XiangyaChangsha 410013China Clinical Research Center for Reproduction and Genetics in Hunan Province Changsha 410013China Hunan Guangxiu Hi-tech Life Technology Co. Ltd.Changsha 410013China

The clinical applications of acrosin activity are *** analyzed 61578 male partners in infertile couples who visited the outpatient department of the Reproductive and Genetic Hospital of CITIC-Xiangya(Changsha,China)between August 2014 and December 2019 to determine the reference ranges and thresholds for acrosin activity in infertile Chinese men;to determine whether correlations exist between acrosin activity and age,sperm concentration,sperm morphology,or sperm motility;and to evaluate whether acrosin activity could serve as an effective prognostic indicator for choosing between in vitro fertilization(IvF)and intracytoplasmic sperm injection(icsl)in the *** cut-off value for the normal reference range of acrosin activity for male partners in infertile couples was 24.78μlU per 106 *** was no significant association between acrosin activity and age,sperm concentration,semen volume,total sperm count,progressive motility,or total motile spermatozoa.A weak positive correlation was found between acrosin activity and normal sperm *** was a statistically significant difference in abnormal acrosome morphology between the group with high acrosin activity(>24.78μlU per 106 sperm)and the group with low acrosin activity(<24.78μlU per 106 sperm).The group with a low IVF fertilization rate had a high index of abnormal acrosomal morphology at 21.2%,while the group with a high IVF fertilization rate had a low index of 0.2%.At an acrosin activity of<24.78μlU per 10 sperm,in one cycle of the same patient,the fertilization rate,normal fertilization rate,and good-quality embryo rate for Icsl were significantly higher than those for ***,the most promising application of acrosin activity could be in the selection of IcsI over IVF for infertile male patients with complete fertilization failure or a low fertilization rate.

关键词： acrosin activity fertilization rate ICSI IVF semen parameters

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Amyloid-beta and tau protein beyond Alzheimer's disease

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Neural Regeneration Research 2024年第6期19卷 1262-1276页

作者： Morteza Abyadeh Vivek Gupta Joao A.Paulo Arezoo Gohari Mahmoudabad Sina Shadfar Shahab Mirshahvaladi Veer Gupta Christine T.O.Nguyen David I.Finkelstein Yuyi You Paul A.Haynes Ghasem H.Salekdeh Stuart L.Graham Mehdi Mirzaei ProGene Technologies Pty ltd. 2. Department of Clinical Medicine Faculty of Medicine Health and Human Sciences Macquarie Medical School Macquarie University Department of cell Biology Harvard Medical School School of Medicine Deakin University Department of Optometry and Vision Sciences School of Health Sciences Faculty of Medicine Dentistry and Health Sciences University of Melbourne The Florey Institute of Neuroscience and Mental Health The University of Melbourne School of Natural Sciences Macquarie University

The aggregation of amyloid-beta peptide and tau protein dysregulation are implicated to play key roles in Alzheimer’s disease pathogenesis and are considered the main pathological hallmarks of this devastating disease. Physiologically, these two proteins are produced and expressed within the normal human body. However, under pathological conditions, abnormal expression, posttranslational modifications, conformational changes, and truncation can make these proteins prone to aggregation, triggering specific disease-related cascades. Recent studies have indicated associations between aberrant behavior of amyloid-beta and tau proteins and various neurological diseases, such as Alzheimer’s disease, Parkinson’s disease, and amyotrophic lateral sclerosis, as well as retinal neurodegenerative diseases like Glaucoma and age-related macular degeneration. Additionally, these proteins have been linked to cardiovascular disease, cancer, traumatic brain injury, and diabetes, which are all leading causes of morbidity and mortality. In this comprehensive review, we provide an overview of the connections between amyloid-beta and tau proteins and a spectrum of disorders.

关键词： amyloid-beta cancer cardiovascular diseases diabetes neurodegeneration Tau traumatic brain injury

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Visualizing traumatic brain injury:ocular clues for diagnosis and assessment

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Neural Regeneration Research 2025年第5期20卷 1399-1400页

作者： Morteza Abyadeh Vivek Gupta Yuyi You Joao A.Paulo Mehdi Mirzaei ProGene Technologies Pty ltd SydneyNSWAustralia Department of Clinical Medicine Faculty of MedicineHealth and Human SciencesMacquarie Medical SchoolMacquarie UniversityMacquarie ParkNorth RydeSydneyNSWAustralia Department of cell Biology Harvard Medical SchoolBostonMAUSA

Traumatic brain injury (TBI) is defined as damage to the brain resulting from an external sudden physical force or shock to the *** is considered a silent public health epidemic causing significant death and disability *** were 64,000 TBI related deaths reported in the USA in 2020,with about US$76 billion in direct and indirect medical costs annually.

关键词： diagnosis ocular injury

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Newcastle disease virus suppresses antigen presentation via inhibiting IL-12 expression in dendritic cells

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Journal of Zhejiang University-Science B(Biomedicine & Biotechnology) 2024年第3期25卷 254-270页

作者： Fulong NAN Wenlong NAN Xin YAN Hui WANG Shasha JIANG Shuyun ZHANG Zhongjie YU Xianjuan ZHANG Fengjun LIU Jun LI Xiaoqiong ZHOU Delei NIU Yiquan LI Wei WANG Ning SHI Ningyi JIN Changzhan XIE Xiaoni CUI He ZHANG Bin WANG Huijun LU Department of Special Medicine Department of Pathogenic BiologySchool of Basic MedicineQingdao UniversityQingdao 266071China China Animal Health and Epidemiology Center Qingdao 266032China Academician Workstation of Jilin Province Changchun University of Chinese MedicineChangchun 130117China Institute of Virology Wenzhou UniversityWenzhou 325035China College of Veterinary Medicine Jilin UniversityChangchun 130012China Changchun Veterinary Research Institute Chinese Academy of Agricultural SciencesChangchun 130122China Sino-cell Biomed Co. Ltd.Qingdao 266000China

As a potential vectored vaccine,Newcastle disease virus(NDV)has been subject to various studies for vaccine development,while relatively little research has outlined the immunomodulatory effect of the virus in antigen *** elucidate the key inhibitory factor in regulating the interaction of infected dendritic cells(DCs)and T cells,DCs were pretreated with the NDV vaccine strain LaSota as an inhibitor and stimulated with lipopolysaccharide(LPS)for further detection by enzyme-linked immunosorbent assay(ELISA),flow cytometry,immunoblotting,and quantitative real-time polymerase chain reaction(qRT-PCR).The results revealed that NDV infection resulted in the inhibition of interleukin(IL)-12p40 in DCs through a p38 mitogen-activated protein kinase(MAPK)-dependent manner,thus inhibiting the synthesis of IL-12p70,leading to the reduction in T cell proliferation and the secretion of interferon-(IFN-),tumor necrosis factor-α(TNF-α),and IL-6 induced by ***,downregulated cytokines accelerated the infection and viral transmission from DCs to T ***,several other strains of NDV also exhibited inhibitory *** current study reveals that NDV can modulate the intensity of the innate-adaptive immune cell crosstalk critically toward viral invasion improvement,highlighting a novel mechanism of virus-induced immunosuppression and providing new perspectives on the improvement of NDV-vectored vaccine.

关键词： Newcastle disease virus Dendritic cells Interleukin-12(IL-12) T cells Immunosuppression

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Hydrogen and nitrogen absorption properties of Ce-added Zr_(2)(Fe_(1-x)Ni_(x)) alloys

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Journal of Rare Earths 2024年第6期42卷 1136-1141,I0005页

作者： Kai Yin Xiaopeng Liu State Key Laboratory of Advanced Materials for Smart Sensing GRINM Group Co.Ltd.Beijing10088China GRIMAT Engineering Institute Co. Ltd.Beijing101407China General Research Institute of Nonferrous Metals Beijing100088China

To improve the nitriding resistance of Zr_(2)Fe alloy,the Ce-added Zr_(2)(Fe_(1-x)Ni_(x))(x=0,0.15,0.3,0.5)alloys were prepared by magnetic levitation melting *** effects of Ni substitution for Fe on the phase structure,hydrogen and nitrogen absorption properties of the alloys were investigated by X-ray diffraction,scanning electron microscopy and p-c isotherm *** experimental results show that Ni substitution can effectively inhibit the formation of both α-Zr and ZrFe_(2) phases and promote the formation of C16 structure Zr_(2)(Fe,Ni)phase,causing Ni-substituted alloys to exhibit low nitrogen absorption rate and *** 623 K under 0.5 MPa nitrogen pressure,the nitrogen absorption capacity of Ce-added Zr_(2)(Fe_(0.5)Ni_(0.5))alloy reaches to 0.8 mL/g,much lower than that of Zr_(2)Fe alloy(1.5 mL/g).Ni substitution decreases the crystal cell volume of the C_(16)Zr_(2)(Fe,Ni)phase,resulting in an increase in the hydrogen absorption equilibrium *** 623 K under 0.05 MPa hydrogen pressure,the hydrogen absorption capacity decreases from 1.46 wt%of Zr_(2)Fe alloy to 1.41 wt%of Ce-added Zr_(2)(Fe_(0.5)Ni_(0.5))alloy.

关键词： Zr_(2)Fe alloy Ce Pressure-composition isotherm Hydrogen absorption Nitrogen absorption Rare earths

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