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Epidemiology of Mpox Outbreaks and Implications for Surveillance in Imo State, Nigeria

Advances in Infectious Diseases 2024年第1期14卷 206-212页

作者： Adeniyi A. Adeniran Ebubechi c. Eronini Olugbenga Asaolu Simisola Adedeji Adaeze Joy Ugwu Marcus Oludare Faith Ehiaghe Ugba Aibinuomo Ayomide Oluwaseyi Tella Adedamola Dania Oluyinka Olayiwola Olanike Suliat Oladele Tinuola Daniel Musa Haruna Adebayo O. Amao John O. Ibitoye Oluwagbemiga Obembe christopher Obanubi Abdulmalik Abubakar Department of Public and allied health Babcock University Ilishan-Remo Nigeria Department of Public health University of Suffolk Waterfront Building UK Department of Public health EUCLID University Greater Bajul The Gambia Department of Public health Liverpool John Moores University Liverpool UK college of Medicine Obafemi Awolowo University Ile-Ife Nigeria Department of Environmental health sciences University of Ibadan Ibadan Nigeria Department of Public health Texila American University Georgetown Guyana School of Public health University of Port Harcourt Port Harcourt Nigeria Department of community Medicine University College Hospital Ibadan Nigeria Department of Nursing Adeleke University Ede Nigeria Department of Public health Central University of Nicaragua Managua Nicaragua Faculty of basic clinical sciences Lagos State University College of Medicine Ikeja Nigeria catholic Relief Services Abuja Nigeria Department of Political Science Faculty of Social Sciences Bayero University Kano Kano Nigeria

Mpox disease is caused by a double-stranded DNA virus, genus Orthopoxvirus of the family Poxviridae. The incubation period is usually 6 to 13 days but can range from 5 to 21 days while symptoms and signs may persist for 2 to 5 weeks. Although, the clinical features are usually less severe when compared to the deadly smallpox, the disease can be fatal with case fatality rate between 1% and 10%. In Imo State, Nigeria, there has been a changing epidemiology of the disease in the last 6 years and the frequency and geographic distribution of cases have progressively increased. This study aims to conduct a review of the disease epidemiology between 2017 and 2023 and implications for surveillance in Imo State. Surveillance data from the Surveillance Outbreak Response and Management System (SORMAS) was extracted between January 2017 and December 2023 across the 27 Local Government Areas (LGAs) of Imo State. A line list of 231 suspected cases was downloaded into an excel template and analyzed using SPSS® version 20 software. Analysis was done using descriptive statistics and associations were tested using Fischer’s exact at 0.05 level of significance. Of the 231 suspected cases, 57.1% (132) were males, 42.9% (99) were females and the modal age group was between the ages of 0 - 4 (32.5%). Eight (8) LGAs (districts) accounted for 71% (n = 164) of all the suspected cases. 21.2% (49) were confirmed positive, 27 males (55.1%) and 22 females (44.9%) (p > 0.05). Modal age group was 20 - 24 (22.4%, n = 11), 18% (9) were children under 14 years, p > 0.05. case fatality rate was 8% (n = 4). There was no significant association between mortality and age group. Five (5) LGAs accounted for about 60% (29) of all confirmed cases. These LGAs contribute only 20% to the total population in the State. Only 5.6% and 4% of suspected and confirmed cases, respectively, had knowledge of contact with an infectious source. The study described the epidemiology of Mpox outbreaks between 2017

关键词： Mpox Epidemiology Outbreak Surveillance

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Functionalized lipid nanoparticles modulate the blood-brain barrier and eliminate α-synuclein to repair dopamine neurons

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Asian Journal of Pharmaceutical sciences 2024年第2期19卷 120-135页

作者： Xiaomei Wu Renxiang Yuan Yichong Xu Kai Wang Hong Yuan Tingting Meng Fuqiang Hu Department of pharmacy Ruijin HospitalSchool of MedicineShanghai Jiaotong UniversityShanghai 200000China college of Pharmaceutical Science Zhejiang UniversityHangzhou 310058China Jinhua Institute of Zhejiang University Jinhua 321299China

The challenge in the clinical treatment of Parkinson's disease lies in the lack of disease-modifying therapies that can halt or slow down the progression. Peptide drugs, such as exenatide (Exe), with potential disease-modifying efficacy, have difficulty in crossing the blood-brain barrier (bbb) due to their large molecular weight. Herein, we fabricate multi-functionalized lipid nanoparticles (LNP) Lpc-boSA/cSO with bbb targeting, permeability-increasing and responsive release functions. borneol is chemically bonded with stearic acid and, as one of the components of Lpc-boSA/cSO, is used to increase bbb permeability. Immunofluorescence results of brain tissue of 15-month-old c57bL/6 mice show that Lpc-boSA/cSO disperses across the bbb into brain parenchyma, and the amount is 4.21 times greater than that of conventional LNP. Motor symptoms of mice in Lpc-boSA/cSO-Exe group are significantly improved, and the content of dopamine is 1.85 times (substantia nigra compacta) and 1.49 times (striatum) that of PD mice. α-Synuclein expression and Lewy bodies deposition are reduced to 51.85% and 44.72% of PD mice, respectively. Immunohistochemical mechanism studies show AKT expression in Lpc-boSA/cSO-Exe is 4.23 times that of PD mice and GSK-3β expression is reduced to 18.41%. Lpc-boSA/cSO-Exe could reduce the production of α-synuclein and Lewy bodies through AKT/GSK-3β pathway, and effectively prevent the progressive deterioration of Parkinson's disease. In summary, Lpc-boSA/cSO-Exe increases the entry of exenatide into brain and promotes its clinical application for Parkinson's disease therapy.

关键词： blood-brain barrier Lipid nanoparticles brain delivery facilitation α-Symuclein Parkinson's disease

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Photo-induced crosslinked and anti-PD-L1 peptide incorporated liposomes to promote PD-L1 multivalent binding for effective immune checkpoint blockade therapy

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Acta Pharmaceutica Sinica b 2024年第3期14卷 1428-1440页

作者： Youngjoo Lee Sukyung Song Suah Yang Jinseong Kim Yujeong Moon Nayeon Shim Hong Yeol Yoon Sehoon Kim Man Kyu Shim Kwangmeyung Kim KU-KIST Graduate School of converging Science and Technology Korea UniversitySeoul 02841Republic of Korea Medicinal Materials Research center Biomedical Research DivisionKorea Institute of Science and Technology(KIST)Seoul 02792Republic of Korea college of pharmacy Graduate School of Pharmaceutical SciencesEwha Womans UniversitySeoul 03760Republic of Korea Department of bioengineering Korea UniversitySeoul 02841Republic of Korea

Immune checkpoint blockade(Icb)therapy targeting PD-L1 via monoclonal antibody(m Ab)has shown extensive clinical benefits in the diverse types of advanced ***,most patients are completely refractory to Icb therapy owing to the PD-L1 recycling ***,we propose photo-induced crosslinked and anti-PD-L1 peptide incorporated liposomes(immune checkpoint blockade liposomes;Icb-LPs)to promote PD-L1 multivalent binding for inducing lysosomal degradation of PD-L1 in tumor *** Icb-LPs are prepared by formulation of Dc_(8,9)Pc with photo-polymerized diacetylenic moiety,1,2-dipalmitoylphosphatidylcholine(DPPc)and anti-PD-L1peptide(D-form NYSKPTdrQYHF)-conjugated DSPE-PEG_(2k)(anti-PD-L1-DSPE-PEG_(2k))in a molar ratio of 45:45:10,followed by cross-linking of liposomal bilayer upon UV *** 10 mol% antiPD-L1-DSPE-PEG_(2k)incorporated Icb-LPs have a nano-sized lipid bilayer structure with an average diameter of 137.7±1.04 nm,showing a high stability in serum ***,the Icb-LPs efficiently promote the multivalent binding with PD-L1 on the tumor cell membrane,which are endocytosed with aim to deliver PD-L1 to the lysosomes,wherein the durable PD-L1 degradation is observed for72 h,in contrast to anti PD-L1 m Abs showing the rapid PD-L1 recycling within 9 *** in vitro coculture experiments with cD8^(+)T cells show that Icb-LPs effectively enhance the T cell-mediated antitumor immune responses against tumor cells by blocking the PD-L1/PD-1 *** Icb-LPs are intravenously injected into colon tumor-bearing mice,they efficiently accumulate within the targeted tumor tissues via both passive and active tumor targeting,inducing a potent T cell-mediated antitumor immune response by effective and durable PD-L1 ***,this study demonstrates the superior antitumor efficacy of crosslinked and anti-PD-L1 peptide incorporated liposome formulation that promotes PD-L1 multivalent binding for trafficking of PD-L1 toward

关键词： cancer immunotherapy Immune checkpoint blockade PEGylated liposome crosslinked lipid nanoparticles Anti-PD-L1 peptide Tumor-targeting PD-L1 multivalent binding Lysosomal PD-L1 degradation

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Polyaspers A and b,the First Ergosterol-Polyether Adducts with Unprecedented 6/6/6/5/5/6/6/6/6 Nonacyclic Architecture from Aspergillus ***507

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chinese Journal of chemistry 2024年第7期42卷 743-751页

作者： Hong Hu Lanqin Li Zhengyi Shi Xueqi Lan Yeting Zhang Xinye Huang Xincai Hao Qun Zhou Weiguang Sun changxing Qi Yonghui Zhang Hubei Key Laboratory of Natural Medicinal chemistry and Resource Evaluation Tongji Medical CollegeHuazhong University of Science and TechnologyWuhanHubei 430030China Institute of Organ Transplantation Tongji HospitalTongji Medical CollegeHuazhong University of Science and Technology Key Laboratory of Organ TransplantationMinistry of EducationNHC Key Laboratory of Organ TransplantationKey Laboratory of Organ TransplantationChinese Academy of Medical SciencesWuhanHubei 430030China Hubei Key Laboratory of Wudang Local chinese Medicine Research Hubei Engineering Technology Center for Comprehensive Utilization of Medicinal PlantsCollege of PharmacyHubei University of MedicineShiyanHubei 442000China

Psoriasis is a chronic immune-mediated inflammatory skin disease and the TNF-αis an important therapeutic target of this *** our continuous study of bioactive natural products from fungi,the first ergosterol-polyether adducts,polyaspers A(1)and b(2),along with two known ergosterols,(36,5α,6α,22E)-5,6-epoxy-3-hydroxyergosta-8,22-dien-7-one(3)and calvasterol b(4),were iso-lated from Aspergillus *** elucidation was accomplished by extensive spectroscopic analysis and single-crystal X-ray diffraction *** A and b possessing an unequalled 6/6/6/5/5/6/6/6/6 nonacyclic system,and their biosynthetic path-ways were proposed to include intermolecular cyclization and Diels-Alder *** screen of these isolates showed that 1-3 could improve the cell viability in an actinomycin D/TNF-αinduced L929 cells death model,with the Ec50 values of 49.85,46.75 and 4.99μmol/L,respectively,and the activity of 3 was even comparable with that of the positive control *** bioactive investigations discovered 3 could suppress the inflammatory response simulated with TNF-αin HacaT *** an imiquimod-induced psoriasis murine model,3 significantly restrained the development of psoriasis symptoms and reduced the expression of IL-17 and IL-23,presenting an anti-psoriatic *** such,those ergosterol derivatives,might serve as lead compounds for the development of novel TNF-αinhibitory agents in the clinical treatment of psoriasis.

关键词： Psoriasis Aspergillus sp.TJ507 TNF-α Ergosterol-polyether adducts Inflammatory skin disease

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The chromosome-scale assembly of the Notopterygium incisum genome provides insight into the structural diversity of coumarins

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Acta Pharmaceutica Sinica b 2024年第8期14卷 3760-3773页

作者： Qien Li Yiqun Dai Xin-cheng Huang Lanlan Sun Kaixuan Wang Xiao Guo Dingqiao Xu Digao Wan Latai An Zixuan Wang Huanying Tang Qi Qi Huihui Zeng Minjian Qin Jia-Yu Xue Yucheng Zhao Tibetan Medicine Research center of Qinghai University Tibetan Medical CollegeQinghai UniversityXining 810016China School of pharmacy Bengbu Medical UniversityBengbu 233030China Department of Resources Science of Traditional chinese Medicines School of Traditional Chinese PharmacyChina Pharmaceutical UniversityNanjing 210009China college of Horticulture Bioinformatics CenterAcademy for Advanced Interdisciplinary StudiesNanjing Agricultural UniversityNanjing 210095China Key Laboratory of Shaanxi Administration of Traditional chinese Medicine for TcM compatibility Shaanxi University of Chinese MedicineXi’an 712046China

coumarins,derived from the phenylpropanoid pathway,represent one of the primary metabolites found in *** alignment of the tetrahydropyran(THP)and tetrahydrofuran(THF)rings with the lactone structure results in the formation of at least four types of complex ***,the mechanisms underlying the structural diversity of coumarin remain poorly ***,we report the chromosome-level genome assembly of Notopterygium incisum,spanning 1.64 Gb,with a contig N50 value of 22.7 Mb and 60,021 annotated protein-coding ***,we identified the key enzymes responsible for shaping the structural diversity of coumarins,including two p-coumaroyl coA 2′-hydroxylases crucial for simple coumarins basic skeleton architecture,two UbiA prenyltransferases responsible for angular or linear coumarins biosynthesis,and five cYP736 cyclases involved in THP and THF ring ***,two bifunctional enzymes capable of catalyzing both demethylsuberosin and osthenol were identified for the first *** analysis implies that tandem and ectopic duplications of the cYP736 subfamily,specifically arising in the Apiaceae,contributed to the structural diversity of coumarins in ***,this study proposes a parallel evolution scenario for the complex coumarin biosynthetic pathway among different angiosperms and provides essential synthetic biology elements for the heterologous industrial production of coumarins.

关键词： Notopterygium incisum Parallel evolution biosynthesis Pyranocoumarins Furanocoumarins

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Inhibition of the NF-κb Signaling Pathway Improves cigarette Mainstream Smoke-Induced Lung Injury and Gut Microbiota Disturbance

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biomedical and Environmental sciences 2024年第6期37卷 676-681页

作者： Hong Huang Shengjie Li Lifang Zeng Yan Zhang Ying chen Yanbing Ma Jing Wei changwei Zou Tingtao chen School of Resources and Environment Nanchang UniversityNanchang 330031JiangxiChina National Engineering Research center for bioengineering drugs and the Technologies Institute of Translational MedicineJiangxi Medical CollegeNanchang UniversityNanchang 330031JiangxiChina School of pharmacy Jiangxi Medical CollegeNanchang UniversityNanchang 330006JiangxiChina

currently,cigarette smoke(cS)remains a major contributor to disease morbidity and *** can be divided into cigarette mainstream smoke(cMS)and side-stream smoke,depending on where it is produced by burning tobacco^([1]).cMS is inhaled by smokers from the filter end during cigarette combustion and is strongly associated with the development of several diseases^([2-4]).

关键词： smoke cMS cigarette

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New Antibacterial Dihydropyrones Induced by co-culture of Penicillium crustosum PRb-2 and Penicillium citrinum HDN11-186

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Journal of Ocean University of china 2024年第1期23卷 216-220页

作者： YU Guihong ZHOU Luning WU Guangwei LI Dehai Shandong Province Key Laboratory of Applied Mycology and Qingdao International Center on Microbes Utilizing BiogasSchool of Life SciencesQingdao Agricultural UniversityQingdao 266109China School of Medicine and pharmacy and Sanya Oceanographic InstitutionOcean University of ChinaQingdao 266003China college of chemical Engineering Nanjing Forestry UniversityNanjing 210037China Laboratory for Marine drugs and bioproducts Laoshan LaboratoryQingdao 266237China

Two new dihydropyrones,rhytismatones c(1)and D(2),and a known compound,penicillenol A1(3),were isolated from the co-culture broth of the deep-sea-derived fungus Penicillium crustosum PRb-2 and Suaeda salsa-derived endophytic fungus Peni-cillium citrinum *** structures were elucidated through comprehensive analysis of nuclear magnetic resonance(NMR)spectra and mass *** absolute configurations of new compounds were determined by calculating the electronic circular di-chroism(EcD)***-MS data showed that compounds 1–3 could only be detected in the media of co-culture,suggesting new biosynthetic pathways were activated in the co-cultured *** 1 showed obvious antibacterial activities against Pro-teus ***-1002 and bacillus subtilis MMbc-1004 with minimum inhibitory concentration(MIc)both at 25μmolL^(-1).

关键词： co-culture Penicillium crustosum Penicillium citrinum dihydropyrones antibacterial activity

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Insights into the anorexic mechanism of Khat:an integrated in vivo,ex vivo,and in silico investigations

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Traditional Medicine Research 2024年第10期9卷 36-51页

作者： Ahmed Ali Jerah Manal Mohamed Elhassan Taha Abdullah Farasani Sivakumar Sivagurunathan Moni Emad Sayed Shaheen Andleeb Khan Ibrahim Abdo Khardali Magbool Oraiby Heyam Mohamed Ali Sidahmed Siddig Ibrahim Abdelwahab Department of Medical Laboratory Technology College of Applied Medical SciencesJazan UniversityJazan 45142Saudi Arabia health Research centre Jazan UniversityJazan 45142Saudi Arabia Department of Pharmaceutics College of PharmacyJazan UniversityJazan 45142Saudi Arabia Department of biosciences Faculty of ScienceIntegral UniversityLucknow 226026India Poison control and Medical Forensic chemistry center General Directorate of Health AffairsJazan 45142Saudi Arabia Department of Pharmaceutical chemistry Faculty of PharmacyAl-Neelain UniversityKhartoum 16458Sudan

background:chewing Khat(catha edulis)releases cathine and cathinone,which may reduce appetite via an unknown *** study investigated the peripheral and central effects of fresh leaves and buds of catha edulis water extract(cEWE)on appetite biomarkers,gene expression,and body weight,using in vivo,ex vivo,and in silico ***:Rats of both sexes were orally administered cEWE at different doses and durations in three different *** chromatography-mass spectroscopy(Lc-MS)-MS was used to detect cathinone and cathine in the murine *** effect of Khat on serotonin receptors was studied in isolated rat fundus *** of the two Khat ligands was performed on G(The 5-hydroxytryptamine-type 2c receptor(5-HT2c)in an agonist-bound active conformation)and H(5-HT2c in an antagonist-bound inactive conformation)proteins to determine which ligands are most likely to act as agonists or ***:Significant differences(Pbody weight were observed between the cEWE-treated groups and the controls over eight ***,the plasma leptin and ghrelin levels did not change significantly(P>0.05).The expression of the ghrelin and leptin genes was also unaffected,but the expression of the 5-hydroxytryptamine(5-HT)gene decreased(PcEWE *** antagonizes 5-HT receptors in isolated rat fundus *** findings indicated that the khat ligands bound to 5-HT2c *** and cathinone levels in rat plasma were ***:Khat extract may suppress appetite by antagonizing the 5-HT *** research is required to understand its mechanism and potential applications.

关键词： catha edulis appetite leptin ghrelin 5-hydroxytryptamine molecular docking

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Study on the mechanism of SND in the treatment of anxiety disorders based on network pharmacology, molecular docking and experiment validation

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Pharmacology Discovery 2024年第2期4卷 10-23页

作者： Fei-Yan Wang Ping Yuan Mei-Ling Zheng Xiao-Di Guo Long Li Jin Wang Shan Miao Ya-Jun Shi Shan-bo Ma Xiao-Peng Shi college of pharmacy Shaanxi University of Chinese MedicineXianyang 712046China Department of pharmacy Xijing HospitalAir Force Medical UniversityXi’an 710032China Outpatient Department of University Hospital Northwestern Polytechnical University HospitalXi’an 710072China The college of Life sciences Northwest UniversityXi’an 710127China

background:Sini decoction(SND)is a classic traditional chinese medicine(TcM)formulation that can be used to treat anxiety-related disorders,but the active substance and underlying molecular mechanism of its anxiolytic effects are *** this study,network pharmacology,molecular docking research and experimental verification methods were used to preliminarily explore the bioactive compounds and potential target mechanisms of SND ***:The active components and corresponding targets of SND were collected by ***,OMIM,PharmGkb,TTD and drugbank were used to search for the targets of anxiety *** core target of SND in the treatment of anxiety was screened by PPI.R language was used to analyze the intersection targets of SND in the treatment of anxiety disorders by GO and KEGG enrichment *** Vina was used for molecular docking,and Discovery Studio was used for visual conformation analysis after *** anti-anxiety effect and molecular mechanism of SND were studied by in vivo ***:based on network pharmacological analysis,we obtained 112 active ingredients and 350 effective targets related to anxiety from *** PPI analysis,26 targets such as STAT3,MAPK3,MAPK1,MAPK14,SRc,HSP90AA1,TP53 and PIK3cA were identified as core *** and KEGG analysis showed that the anxiolytic mechanism of SND may be related to the neuroactive ligand-receptor interaction pathway and inflammatory *** docking showed that quercetin,naringenin,licochalcone A had high affinity with JAK2,MAPK14 and *** experiments have shown that SND reverses the upregulation of GluN2b(NMDAR)and GluA1(AMPAR)proteins,and SND improves anxiety disorders by regulating glutamate transmitter levels,which may be related to neuroactive ligand-receptor interaction pathways,particularly glutamate ***:This study shows that SND can improve FS-induced behavioral changes in mice and can modulate hippocampal synapse-asso

关键词： SND anxiety disorders network pharmacology molecular docking pharmacological mechanisms

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Encoding and display technologies for combinatorial libraries in drug discovery:The coming of age from biology to therapy

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Acta Pharmaceutica Sinica b 2024年第8期14卷 3362-3384页

作者： Yu Fan Ruibing Feng Xinya Zhang Zhen-Liang Wang Feng Xiong Shuihua Zhang Zhang-Feng Zhong Hua Yu Qing-Wen Zhang Zhang Zhang Yitao Wang Guodong Li Macao centre for Research and Development in chinese Medicine State Key Laboratory of Quality Research in Chinese MedicineInstitute of Chinese Medical SciencesUniversity of MacaoMacao SAR 999078China State Key Laboratory of Quality Research in chinese Medicine Institute of Chinese Medical SciencesUniversity of MacaoMacao SAR 999078China International cooperative Laboratory of Traditional chinese Medicine Modernization and Innovative drug Development Ministry of Education(MoE)of People’s Republic of ChinaCollege of PharmacyJinan UniversityGuangzhou 510632China Zhuhai UM Science and Technology Research Institute Zhuhai 519031China Department of pharmacy Guangzhou Red Cross HospitalFaculty of Medical ScienceJinan UniversityGuangzhou 510632China Geriatric Medicine First People’s Hospital of XinXiang and the Fifth Affiliated Hospital of Xinxiang Medical CollegeXinxiang 453100China Shenzhen Innovation center for Small Molecule drug Discovery co. Ltd.Shenzhen 518000China

drug discovery is a sophisticated process that incorporates scientific innovations and cuttingedge *** to traditional bioactivity-based screening methods,encoding and display technologies for combinatorial libraries have recently advanced from proof-of-principle experiments to promising tools for pharmaceutical hit discovery due to their high screening efficiency,throughput,and resource *** review systematically summarizes the development history,typology,and prospective applications of encoding and displayed technologies,including phage display,ribosomal display,mRNA display,yeast cell display,one-bead one-compound,DNA-encoded,peptide nucleic acidencoded,and new peptide-encoded technologies,and examples of preclinical and clinical *** discuss the progress of novel targeted therapeutic agents,covering a spectrum from small-molecule inhibitors and nonpeptidic macrocycles to linear,monocyclic,and bicyclic peptides,in addition to *** also address the pending challenges and future prospects of drug discovery,including the size of screening libraries,advantages and disadvantages of the technology,clinical translational potential,and market *** review is intended to establish a comprehensive high-throughput drug discovery strategy for scientific researchers and clinical drug developers.

关键词： drug screening Phage display DNA-encoded chemical libraries Peptide-encoded chemical libraries clinical drugs

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