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Reduced efficacy of single-dose albendazole against Ascaris lumbricoides, and Trichuris trichiura, and high reinfection rate after cure among school children in southern Ethiopia: a prospective cohort study

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Infectious Diseases of Poverty 2024年第1期13卷 95-96页

作者： Tigist Dires Gebreyesus Eyasu Makonnen Tafesse Tadele Kalkidan Mekete Habtamu Gashaw Heran Gerba Eleni Aklillu Department of Global Public Health Karolinska Institutet Karolinska University Hospital Stockholm Sweden Ethiopian Food and drug Authority Addis Ababa Ethiopia center for innovative drug development and therapeutic trials for africa College of Health Sciences Addis Ababa University Addis Ababa Ethiopia Departments of Pharmacology and Clinical Pharmacy College of Health Sciences Addis Ababa University Addis Ababa Ethiopia College of Medicine and Health Sciences Hawassa University Hawassa Ethiopia Ethiopian Public Health Institute Addis Ababa Ethiopia

Background Mass drug administration(MDA)program of albendazole to at-risk populations as preventive chemo-therapy is the core public health intervention to control soil-transmitted helminths(STHs).Achieving this goal relies on drug effectiveness in reducing the parasite reservoirs in the community and preventing *** assessed the effcacy of albendazole against STH parasite infection and reinfection status after *** A total of 984 schoolchildren infected with at least one type of STH parasite(hookworm,Ascaris lumbri-coides,Trichuris trichiura)in southern Ethiopia were enrolled and received albendazole and praziquantel in MDA campaign conducted from January to March *** exams at week-4 and at week-8 of post-MDA were done using Kato Katz *** primary outcome was effcacy assessed by cure rate(CR)and fecal egg reduction rates(ERRs)at four weeks of *** secondary outcome was reinfection status defined as parasite egg positivity at eight weeks among those who were cured at 4 weeks of *** comparisons in CR and related factors were assessed with chi-square or Fisher's exact *** of CR were examined through univariate and multi-variate regression *** The overall CR and ERR for hookworm infection were 97.2%(95%CI:94.6-99.4)and 97.02%,*** overall CR and ERR for *** were 71.5%(95%CI:68.3-74.6)and 84.5% *** overall CR and ERR and for *** were 49.5%(95%CI:44.8-54.2)and 68.3%,*** CR among moderate *** infec-tion intensity was 28.6%.Among children cured of hookworm,*** and *** at week 4 post-MDA,4.6%,18.3% and 52.4% became reinfected at week-8 post-MDA,*** lower CR(36.6%)and higher reinfection after cure(60.6%)among *** and *** coinfected children than *** only(CR=69.6%,reinfection rate=15.1%)or *** only infected children(CR=55.6%,reinfection rate=47.1%)was obse

关键词： Soil transmitted helminths Neglected tropical diseases Preventive chemotherapy Albendazole School age children Ethiopia

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Allogenic microglia replacement:A novel therapeutic strategy for neurological disorders

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Fundamental Research 2024年第2期4卷 237-245页

作者： Yanxia Rao Bo Peng Department of Laboratory Animal Science MOE Frontiers Center for Brain ScienceFudan UniversityShanghai 200032China Department of Neurosurgery Huashan HospitalInstitute for Translational Brain ResearchState Key Laboratory of Medical NeurobiologyMOE Frontiers Center for Brain ScienceMOE Innovative Center for New Drug Development of Immune Inflammatory DiseasesFudan UniversityShanghai 200000China Co-Innovation center of Neuroregeneration Nantong UniversityNantongJiangsu 226001China

Microglia are resident immune cells in the central nervous system(CNS)that play vital roles in CNS development,homeostasis and disease *** defects in microglia lead to microglial dysfunction,which in turn leads to neurological *** correction of the specific genetic defects in microglia in these disorders can lead to therapeutic *** genetic defect correction approaches are dependent on viral vectorbased genetic defect ***,the viruses used in these approaches,including adeno-associated viruses,lentiviruses and retroviruses,do not primarily target microglia;therefore,viral vector-based genetic defect corrections are ineffective in *** replacement is a novel approach to correct microglial genetic defects via replacing microglia of genetic defects with allogenic healthy *** this paper,we systematically review the history,rationale and therapeutic perspectives of microglia replacement,which would be a novel strategy for treating CNS disorders.

关键词： Microglia Replacement Microglia replacement Microglia depletion Microglia-free niche CSF1R

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Reynosin protects neuronal cells from microglial neuroinflammation by suppressing NLRP3 inflammasome activation mediated by NADPH oxidase

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Chinese Journal of Natural Medicines 2024年第6期22卷 486-500页

作者： YANG Yanqiu CHE Yue FANG Mingxia YAO Xiaohu ZHOU Di WANG Feng CHEN Gang LIANG Dong LI Ning HOU Yue Key Laboratory of Bioresource Research and development of Liaoning Province College of Life and Health SciencesNorth-eastern UniversityShenyang 110000China National Frontiers Science center for Industrial Intelligence and Systems Optimization Key Laboratory of Data Analytics and Optimization for Smart IndustryMinistry of EducationNortheastern UniversityShenyang 110000China School of Traditional Chinese Materia Medica Key Laboratory of Innovative Traditional Chinese Medicine for Major Chronic Diseases of Liaoning provinceKey Laboratory for TCM Material Basis Study and Innovative Drug Development of Shenyang CityShenyang Pharmaceutical UniversityShenyang 110000China State Key Laboratory for Chemistry and Molecular Engineering of Medicinal Resources School of Chemistry and Pharmaceutical SciencesGuangxi Normal UniversityGuilin 541000China

Neuroinflammation,mediated by the nucleotide-binding oligomerization domain-like receptor family pyrin domain-containing-3(NLRP3)inflammasome,is a significant contributor to the pathogenesis of neurodegenerative diseases(NDDs).Reynos-in,a natural sesquiterpene lactone(SL),exhibits a broad spectrum of pharmacological effects,suggesting its potential therapeutic ***,the effects and mechanism of reynosin on neuroinflammation remain *** current study explores the effects and mechanisms of reynosin on neuroinflammation using mice and BV-2 microglial cells treated with lipopolysaccharide(LPS).Our findings reveal that reynosin effectively reduces microglial inflammation in vitro,as demonstrated by decreased CD11b expression and lowered interleukin-1 beta(IL-1β)and interleukin-18(IL-18)mRNA and protein ***,in vivo,results showed a re-duction in the number of Iba-1 positive cells and alleviation of morphological alterations,alongside decreased expressions of IL-1βand *** analysis indicates that reynosin inhibits NLRP3 inflammasome activation,evidenced by reduced transcription of NLRP3 and caspase-1,diminished NLRP3 protein expression,inhibited apoptosis-associated speck-like protein containing a CARD(ASC)oli-gomerization,and decreased caspase-1 ***,reynosin curtailed the activation of nicotinamide adenine dinuc-leotide phosphate(NADPH)oxidase,demonstrated by reduced NADP^(+)and NADPH levels,downregulation of gp91^(phox) mRNA,pro-tein expression,suppression of p47^(phox) expression and translocation to the ***,reynosin exhibited a neuroprotective effect against microglial inflammation in vivo and in *** collective findings underscore reynosin’s capacity to mitigate mi-croglial inflammation by inhibiting the NLRP3 inflammasome,thus highlighting its potential as a therapeutic agent for managing neuroinflammation.

关键词： Microglia NLRP3 inflammasome Reactive oxygen species NADPH oxidase Neuron Reynosin

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A novel marine-derived anti-acute kidney injury agent targeting peroxiredoxin 1 and its nanodelivery strategy based on ADME optimization

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Acta Pharmaceutica Sinica B 2024年第7期14卷 3232-3250页

作者： Ping Yu Tanwei Gu Yueyang Rao Weimin Liang Xi Zhang Huanguo Jiang Jindi Lu Jianglian She Jianmin Guo Wei Yang Yonghong Liu Yingfeng Tu Lan Tang Xuefeng Zhou Guangdong Provincial Key Laboratory of New drug Screening Guangdong-Hong Kong-Macao Joint Laboratory for New Drug ScreeningSchool of Pharmaceutical SciencesSouthern Medical UniversityGuangzhou 510515China CAS Key Laboratory of Tropical Marine Bio-Resources and Ecology Guangdong Key Laboratory of Marine Materia MedicaSouth China Sea Institute of OceanologyChinese Academy of SciencesGuangzhou 510301China NMPA Key Laboratory for Research and Evaluation of drug Metabolism School of Pharmaceutical SciencesSouthern Medical UniversityGuangzhou 510515China Guangdong Lewwin Pharmaceutical Research Institute Co. Ltd.Guangdong Provincial Key Laboratory of Drug Non-Clinical Evaluation and ResearchGuangdong Engineering Research Center for Innovative Drug Evaluation and ResearchGuangzhou 510990China

Insufficient therapeutic strategies for acute kidney injury(AKI)necessitate precision therapy targeting its *** study reveals the new mechanism of the marine-derived anti-AKI agent,piericidin glycoside S14,targeting peroxiredoxin 1(PRDX1).By binding to Cys83 of PRDX1 and augmenting its peroxidase activity,S14 alleviates kidney injury efficiently in Prdx1-overexpression(Prdx1-OE)***,S14 also increases PRDX1 nuclear translocation and directly activates the Nrf2/HO-1/NQO1 pathway to inhibit ROS *** to the limited druggability of S14 with low bioavailability(2.6%)and poor renal distribution,a pH-sensitive kidney-targeting dodecanaminechitosan nanoparticle system is constructed to load S14 for precise treatment of AKI.L-Serine conjugation to chitosan imparts specificity to kidney injury molecule-1(Kim-1)-overexpressed *** developed S14-nanodrug exhibits higher therapeutic efficiency by improving the in vivo behavior of S14 *** encapsulation with micelles,the AUC_(0-t),half-life time,and renal distribution of S14 increase 2.5-,1.8-,and 3.1-fold,*** main factors contributing to the improved druggability of S14 nanodrugs include the lower metabolic elimination rate and UDPglycosyltransferase(UGT)-mediated *** summary,this study identifies a new therapeutic target for the marine-derived anti-AKI agent while enhancing its ADME properties and druggability through nanotechnology,thereby driving advancements in marine drug development for AKI.

关键词： Acute kidney injury Piericidin glycoside Peroxiredoxin 1 Nanodrug Kim-1 targeted ADME Marine drug druggability

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Enzyme-activatable disk-shaped nanocarriers augment tumor permeability for breast cancer combination therapy

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Nano Research 2024年第7期17卷 6400-6410页

作者： Hanming Zhang Honglin Gao Yicong Zhang Yikun Han Qing Lin Tao Gong Xun Sun Zhirong Zhang Ling Zhang Shiqi Huang Key Laboratory of drug-Targeting and drug Delivery System of the Education Ministry West China School of PharmacySichuan UniversityChengdu 610041China Med-X center for Materials College of Polymer Science and EngineeringSichuan UniversityChengdu 610065China

Unique physiopathological characteristics of tumor tissues impose obstacles to the sufficient penetration of traditional nanomedicines,resulting in undesirable drug delivery efficacy and therapeutic ***,we constructed TRAIL-[NDHCPT]^(GAC),a synergistic hydroxycamptothecin(HCPT)and tumor necrosis factor-related apoptosis-inducing ligand(TRAIL)protein co-loaded disk-shaped nanocarrier withγ-glutamyl transpeptidase *** the novel nanodisks extravasated into the tumor interstitium,theγ-glutamyl transpeptidase overexpressed on the tumor cell membranes cleaved theγ-glutamyl portions of the nanodisk surface to produce positively charged amino *** a result,the cationic nanodisks possessed stronger tumor infiltration ability through transcytosis than anionic *** and TRAIL exerted synergistic antitumor effects with better overall therapeutic *** TRAIL-[ND-HCPT]^(GAC)system performed significantly better than free HCPT and remarkably prolonged the survival of breast tumor-bearing mice with no significant toxicity.

关键词： tumor penetration combination therapy charge reversal γ-glutamyl transpeptidase nanodisk

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Anti-osteosarcoma trimodal synergistic therapy using NiFe-LDH and MXene nanocomposite for enhanced biocompatibility and efficacy

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Acta Pharmaceutica Sinica B 2024年第3期14卷 1329-1344页

作者： Yani Xu Lan Yang Min Li Haozhou Shu Na Jia Yunzhen Gao Rongying Shi Xiaojia Yang Zhirong Zhang Ling Zhang Key Laboratory of drug-Targeting and drug Delivery System of the Education Ministry West China School of PharmacySichuan UniversityChengdu 610041China Med-X center for Materials College of Polymer Science and EngineeringSichuan UniversityChengdu 610065China

Osteosarcoma is usually resistant to immunotherapy and,thus primarily relies on surgical resection and high-dosage ***,less invasive or toxic therapies such as photothermal therapy(PTT)and chemodynamic therapy(CDT)generally failed to show satisfactory *** multimodal therapies with proper safety profiles may provide better solutions for ***,a simple nanocomposite that synergistically combines CDT,PTT,and chemotherapy for osteosarcoma treatment was *** this composite,small 2D Ni Fe-LDH flakes were processed into 3D hollow nanospheres via template methods to encapsulate 5-Fluorouracil(5-FU)with high loading *** nanospheres were then adsorbed onto larger 2D Ti3C2MXene monolayers and finally shielded by bovine serum albumin(BSA)to form 5-FU@Ni Fe-LDH/Ti3C2/BSA nanoplatforms(5NiTiB).Both in vitro and in vivo data demonstrated that the 5-FU induced chemotherapy,Ni Fe-LDH driven chemodynamic effects,and MXene-based photothermal killing collectively exhibited a synergistic“all-in-one”anti-tumor effect.5NiTiB improved tumor suppression rate fromtherapeutic platform achieved higher therapeutic efficacy with a lower agent dose,thereby minimizing side ***,the composite is simple to produce,enabling the fine-tuning of dosages to suit different ***,the platform is versatile and efficient,with potential for further development.

关键词： Osteosarcoma NiFe-LDH MXene Chemodynamic therapy Photothermal therapy Chemotherapy 5-Fluorouracil Nanocomposite

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Traditional Chinese medicines derived natural inhibitors of ferroptosis on ischemic stroke

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Chinese Journal of Natural Medicines 2024年第8期22卷 746-755页

作者： WANG Yongliang LAN Xiaobing LIU Ning MA Lin DU Juan WEI Wei HAI Dongmei WU Jing YU Jianqiang LIU Yue School of Pharmacy Ningxia Medical UniversityYinchuan 750000China Ningxia Key Laboratory of drug development and Generic drug Research Ningxia Medical UniversityYinchuan 750000China Ningxia Characteristic Traditional Chinese Medicine Modern Engineering Research center Ningxia Medical UniversityYinchuan 750000China College of Basic Medical Sciences Ningxia Medical UniversityYinchuan 750000China

Ischemic stroke(IS)is a globally prevalent cerebrovascular disorder resulting from cerebral vessel occlusion,leading to significant morbidity and *** intricate pathological mechanisms underlying IS complicate the development of effective therapeutic ***,a form of programmed cell death(PCD)characterized by iron overload and accumulation of lipid peroxidation products,has been increasingly recognized as a key contributor to IS *** Chinese medicines(TCMs)have long been utilized in the management of IS,prompting extensive research into their potential as sources of natural ferroptosis *** review investigates the critical role of ferroptosis in IS and provides a comprehensive analysis of current research on natural ferroptosis inhibitors identified in TCMs,aiming to lay a theoretical groundwork for the development of innovative anti-IS therapies.

关键词： Ischemic stroke Traditional Chinese medicines Natural inhibitors Ferroptosis

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development of SV2A Ligands for Epilepsy Treatment:A Review of Levetiracetam,Brivaracetam,and Padsevonil

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Neuroscience Bulletin 2024年第5期40卷 594-608页

作者： Peng-Peng Wu Bi-Rong Cao Fu-Yun Tian Zhao-Bing Gao center for Neurological and Psychiatric Research and drug Discovery Shanghai Institute of Materia MedicaChinese Academy of SciencesShanghai201203China University of Chinese Academy of Sciences Beijing100049China Zhongshan Institute for drug Discovery Shanghai Institute of Materia MedicaChinese Academy of SciencesZhongshan528400China

Epilepsy is a common neurological disorder that is primarily treated with antiseizure medications(ASMs).Although dozens of ASMs are available in the clinic,approximately 30%of epileptic patients have medically refractory seizures;other limitations in most traditional ASMs include poor tolerability and drug-drug ***,there is an urgent need to develop alternative ***(LEV)is a first-line ASM that is well tolerated,has promising efficacy,and has little drug-drug *** it is widely accepted that LEV acts through a unique therapeutic target synaptic vesicle protein(SV)2A,the molecular basis of its action remains *** so,the next-generation SV2A ligands against epilepsy based on the structure of LEV have achieved clinical *** review highlights the research and development(R&D)process of LEV and its analogs,brivaracetam and padsevonil,to provide ideas and experience for the R&D of novel ASMs.

关键词： Levetiracetam Epilepsy Antiseizure medications Synaptic vesicle protein 2A Brivaracetam Padsevonil

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Biological factors driving colorectal cancer metastasis

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World Journal of Gastrointestinal Oncology 2024年第2期16卷 259-272页

作者： Shuai-Xing An Zhao-Jin Yu Chen Fu Min-Jie Wei Long-Hai Shen Department of Pharmacology School of PharmacyChina Medical UniversityShenyang 110122Liaoning ProvinceChina Liaoning Key Laboratory of Molecular Targeted Antitumor drug development and Evaluation Liaoning Cancer Immune Peptide Drug Engineering Technology Research CenterKey Laboratory of Precision Diagnosis and Treatment of Gastrointestinal Tumors(China Medical University)Ministry of EducationShenyang 110122Liaoning ProvinceChina BD Department Greenpine Pharma Group Co.LtdTianjin 300020China center of Oncology Genertec Liaoyou Gem Flower HospitalPanJin 124010Liaoning ProvinceChina

Approximately 20%of colorectal cancer(CRC)patients present with metastasis at *** Stage I-III CRC patients who undergo surgical resection,18%typically suffer from distal metastasis within the first three years following initial *** median survival duration after the diagnosis of metastatic CRC(mCRC)is only 9 *** is traditionally considered to be an advanced stage malignancy or is thought to be caused by incomplete resection of tumor tissue,allowing cancer cells to spread from primary to distant organs;however,increa-sing evidence suggests that the mCRC process can begin early in tumor *** patients present with high heterogeneity and diverse cancer phenotypes that are classified on the basis of molecular and morphological *** genomic and nongenomic events can induce subclone diversity,which leads to cancer and *** the course of mCRC,metastatic cascades are associated with invasive cancer cell migration through the circulatory system,extravasation,distal seeding,dormancy,and reactivation,with each step requiring specific molecular ***,cancer cells presenting neoantigens can be recognized and eliminated by the immune *** this review,we explain the biological factors that drive CRC metastasis,namely,genomic instability,epigenetic instability,the metastatic cascade,the cancer-immunity cycle,and external lifestyle *** remarkable progress in CRC research,the role of molecular classification in therapeutic intervention remains *** review shows the driving factors of mCRC which may help in identifying potential candidate biomarkers that can improve the diagnosis and early detection of mCRC cases.

关键词： cancer Metastasis cascade Cancer immunity Genomic variation Epigenetic instability Lifestyle factor

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Id2 epigenetically controls CD8^(+)T-cell exhaustion by disrupting the assembly of the Tcf3-LSD1 complex

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Cellular & Molecular Immunology 2024年第3期21卷 292-308页

作者： Yiming Li Mingwei Han Haolin Wei Wan Huang Zhinan Chen Tianjiao Zhang Meirui Qian Lin Jing Gang Nan Xiuxuan Sun Shuhui Dai Kun Wang Jianli Jiang Ping Zhu Liang Chen Department of Cell Biology of National Translational Science center for Molecular Medicine and Department of Clinical Immunology of Xijing Hospital Fourth Military Medical UniversityXi’anShaanxi 710032China State Key Laboratory of New Targets Discovery and drug development for Major Diseases GanzhouJiangxi341000Xi’anShaanxi 710032China School of Medicine Shanghai UniversityShanghai 200444China

CD8^(+)T-cell exhaustion is a state of dysfunction that promotes tumor progression and is marked by the generation of Slamf6^(+)progenitor exhausted(Tex^(prog))and Tim-^(3+)terminally exhausted(Tex^(term))*** of DNA binding protein 2(Id2)has been shown to play important roles in T-cell development and CD8^(+)T-cell ***,the role of Id2 in CD8^(+)T-cell exhaustion is ***,we found that Id2 transcriptionally and epigenetically regulates the generation of Texprog cells and their conversion to Texterm *** deletion of Id2 dampens CD8^(+)T-cell-mediated immune responses and the maintenance of stem-like CD8^(+)T-cell subpopulations,suppresses PD-1 blockade and increases tumor ***,through its HLH domain,Id2 binds and disrupts the assembly of the Tcf3-Tal1 transcriptional regulatory complex,and thus modulates chromatin accessibility at the Slamf6 promoter by preventing the interaction of Tcf3 with the histone lysine demethylase ***,Id2 increases the abundance of the permissive H3K4me2 mark on the Tcf3-occupied E-boxes in the Slamf6 promoter,modulates chromatin accessibility at the Slamf6 promoter and epigenetically regulates the generation of Slamf6+Texprog *** LSD1 inhibitor GSK2879552 can rescue the Id2 knockout phenotype in tumor-bearing *** of LSD1 increases the abundance of Slamf6^(+)Tim-3^(−)Tex^(prog) cells in tumors and the expression level of Tcf1 in Id2-deleted CD8+T *** study demonstrates that Id2-mediated transcriptional and epigenetic modification drives hierarchical CD8^(+)T-cell exhaustion,and the mechanistic insights gained may have implications for therapeutic intervention with tumor immune evasion.

关键词： Id2 T-cell exhaustion Epigenetic modification Immune evasion

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