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Supercritical fluid technology:A game-changer for biomacromolecular nanomedicine preparation and biomedical application

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Chinese Chemical Letters 2024年第7期35卷 89-99页

作者： Yating Zheng Yulan Huang Jing Luo Xuqi Peng Xiran Gui Gang Liu Yang Zhang State Key laboratory of Vaccines for infectious diseases Xiang An Biomedicine LaboratoryNational Innovation Platform for Industry-Education Integration in Vaccine ResearchState Key Laboratory of Molecular Vaccinology and Molecular DiagnosticsCenter for Molecular Imaging and Translational MedicineSchool of Public HealthXiamen UniversityXiamen 361102China Shen Zhen Research Institute of Xiamen University Shenzhen 518057China division of Urology and Department of Surgery Brigham and Women's HospitalHarvard Medical SchoolBostonMA 02115United States Innovation laboratory for Sciences and Technologies of Energy Materials of Fujian Province(IKKEM) Xiamen 361102China

Biomacromolecules are attractive in biomedical applications as therapeutic agents and potential drug carriers due to their natural active components,good biocompatibility,and high ***,their large relative molecular weight,complex structure,susceptibility to degradation,and poor stability limit their *** can address these issues by improving the therapeutic value,bioavailability,permeability,and absorption of biomacromolecules while regulating their retention time in the ***,compelling evidence has been reported that supercritical fluid(SCF)technology has emerged as an alternative that maintains the integrity of biomacromolecules and reduces environmental *** this review,we highlight a set of unique nanosizing strategies based on SCF technology for biomacromolecular nanomedicine,and extensively discuss their characteristics and *** particular,the protein-based,nucleic acid-based,and polysaccharide-based nanomedicine preparations via SCF technology and their biomedical applications are summarized,and the potential for industrial production of biomacromolecular drugs is also *** further provide perspectives on the opportunities and challenges in this excellent field of biomacromolecular drugs nanotechnology.

关键词： Biomacromolecules Supercritical fluid technology Therapeutic proteins Gene therapy Nanomedicine

The interplay of drug therapeutics and immune responses to SARS-CoV-2

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Cellular & molecular Immunology 2024年第2期21卷 197-200页

作者： Valeria Fumagalli Matteo Iannacone division of Immunology Transplantationand Infectious DiseasesIRCCS San Raffaele Scientific InstituteMilanItaly Vita-Salute San Raffaele University MilanItaly Experimental Imaging Centre IRCCS San Raffaele Scientific InstituteMilanItaly

The SARS-CoV-2 pandemic has necessitated rapid therapeutic and preventative *** vaccines form the frontline of defense,antiviral treatments such as nirmatrelvir have emerged as vital adjunctive measures,particularly for those unable or unwilling to be *** review delves into the potential influence of nirmatrelvir on enduring *** parallel,the potential of drug repurposing is explored,with bisphosphonates being examined for their possible effects against COVID-19 due to their immunomodulatory *** importance of rigorous clinical trials and careful interpretation of preliminary data is emphasized.

关键词： SARS-CoV-2 Nirmatrelvir Bisphosphonates Adaptive immunity Drug repurposing

Design,synthesis,and biological evaluation of 1,2,4-triazole derivatives as potent antitubercular agents

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Chinese Chemical Letters 2024年第3期35卷 326-331页

作者： Yu Wen Shichun Lun Yuxue Jiao Wei Zhang Tianyu Hu Ting Liu Fan Yang Jie Tang Bing Zhang William R.Bishai Li-Fang Yu Shanghai Engineering Research Center of molecular Therapeutics and New Drug Development School of Chemistry and Molecular EngineeringEast China Normal UniversityShanghai 200062China Center for Tuberculosis Research Department of MedicineDivision of Infectious DiseaseJohns Hopkins School of MedicineBaltimoreMD21231-1044United States Shanghai Institute for Advanced Immunochemical Studies and School of Life Science and Technology ShanghaiTech UniversityShanghai 201210China Shanghai Key laboratory of Green Chemistry and Chemical Process School of Chemistry and Molecular EngineeringEast China Normal UniversityShanghai 200062China

Inhibition of mycobacterial membrane protein large 3(MmpL3)thereby affecting the mycolic acid biosynthetic pathway has been proven to be an effective strategy for developing antitubercular *** on the X-ray crystal structure of MmpL3 inhibitor complexes,a series of novel 1,2,4-triazole derivatives were designed,synthesized and evaluated antitubercular activity against Mtb strain *** structure–activity relationship exploration resulted in the identification of compounds 21 and 28,which possess potent antitubercular activity against Mtb strain H37Rv[minimum inhibitory concentration(MIC)=0.03–0.13μg/mL]and the clinical isolates of multidrug resistance(MDR)and extensive drug resistance(XDR)tuberculosis(MIC=0.06–1.0μg/mL).Moreover,compounds 21 and 28 showed neglectable cytotoxicity(IC_(50)≥32μg/mL)to the mammalian Vero cells and favorable physicochemical and pharmacokinetic properties according to the in silico absorption,distribution,metabolism and excretion(ADME)***,the potential target of representative 1,2,4-triazole 28 was identified to be MmpL3 using a microscale thermophoresis(MST)assay.

关键词： Tuberculosis MDR and XDR-TB MmpL3 inhibitor 1 2 4-Triazole Structure-based drug design

Manipulating the Gut Microbiome to Alleviate Steatotic Liver Disease:Current Progress and Challenges

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Engineering 2024年第9期40卷 51-60页

作者： Ernesto Saenz Nathally Espinosa Montagut Baohong Wang Christoph Stein-Thöringer Kaicen Wang Honglei Weng Matthias Ebert Kai Markus Schneider Lanjuan Li Andreas Teufel division of Hepatology Division of Clinical BioinformaticsDepartment of Medicine IIMedical Faculty MannheimHeidelberg UniversityMannheim 68167Germany Clinical Cooperation Unit Healthy Metabolism Center for Preventive Medicine and Digital HealthMedical Faculty MannheimHeidelberg UniversityMannheim 68167Germany School of Medicine Universidad de Los AndesBogotá111711Colombia State Key laboratory for Diagnosis and Treatment of infectious diseases National Clinical Research Center for Infectious DiseasesCollaborative Innovation Center for Diagnosis and Treatment of Infectious DiseasesThe First Affiliated HospitalZhejiang University School of MedicineHangzhou 310003China Internal MedicineⅠ University Clinic Tuebingen&CoE CMFI(Controlling Microbes to Fight Infections)Tuebingen 72074Germany Department of MedicineⅡ Medical Faculty MannheimHeidelberg UniversityMannheim 68167Germany DKFZ Hector Cancer Institute at the University Medical Center Mannheim 69120Germany molecular Medicine Partnership Unit European Molecular Biology LaboratoryHeidelberg 69117Germany Department of MedicineⅢ University Hospital RWTH AachenAachen 52074Germany

The prevalence of metabolic-dysfunction-associated steatotic liver disease(MASLD)is alarmingly high;it is estimated to affect up to a quarter of the global population,making it the most common liver disorder *** is characterized by excessive hepatic fat accumulation and is commonly associated with comorbidities such as obesity,dyslipidemia,and insulin resistance;however,it can also manifest in lean ***,it is crucial to develop effective therapies for this complex ***,there are no approved medications for MASLD treatment,so there is a pressing need to investigate alternative *** research has characterized MASLD as a multifaceted disease,frequently linked to metabolic disorders that stem from dietary *** suggests that changes in the gut microbiome play a fundamental role in the development and progression of MASLD from simple steatosis to steatohepatitis and even hepatocellular carcinoma(HCC).In this review,we critically examine the literature on the emerging field of gut-microbiota-based therapies for MASLD and metabolicdysfunction-associated steatohepatitis(MASH),including interventions such as fecal microbiota transplantation(FMT),probiotics,prebiotics,short-chain fatty acids,antibiotics,metabolic pathway targeting,and immune checkpoint kinase blockade.

关键词： Microbiome Fecal microbiota transplantation Metabolic-dysfunction-associated steatotic liver disease Fatty liver

Antibodies Targeting a Conserved Surface Polysaccharide Are Protective Against a Wide Range of Microbial Pathogens Producing β-1-6-Linked Poly-N-Acetylglucosamine(PNAG)

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Engineering 2024年第7期38卷 69-76页

作者： Xi Lu Guoqing Li Jing Pang Xinyi Yang Colette Cywes-Bentley Xuefu You Gerald B.Pier Beijing Key laboratory of Antimicrobial Agents Institute of Medicinal BiotechnologyChinese Academy of Medical Sciences&Peking Union Medical CollegeBeijing 100050China division of infectious diseases Department of MedicineBrigham and Women’s HospitalHarvard Medical SchoolBostonMA 02115USA

The b-1-6-linked poly-N-acetylglucosamine(PNAG)polymer is a conserved surface polysaccharide produced by many bacteria,fungi,and protozoan(and even filarial)*** wide-ranging expression makes PNAG an attractive target for vaccine development,as it potentially encompasses a broad range of *** progress has been made in discovering important properties of the biology of PNAG expression in recent *** molecular characterization and regulation of operons for the production of PNAG biosynthetic proteins and enzymes have been studied in many *** addition,the physiological function of PNAG has been further ***-based vaccines and PNAG-targeting antibodies have shown great efficacy in preclinical ***,clinical tests for both vaccines and antibodies have been carried out in humans and economically important animals,and the results are *** it is not destined to be a smooth road,we are optimistic about new vaccines and immunotherapeutics targeting PNAG becoming validated and eventually licensed for clinical use against multiple infectious agents.

关键词： Poly-N-acetylglucosamine Conjugate vaccine Monoclonal antibody

Genetic diversity and occult hepatitis B infection in Africa: A comprehensive review

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World Journal of Hepatology 2024年第5期16卷 843-859页

作者： Michee M Bazie Mahamoudou Sanou Florencia Wendkuuni Djigma Tegwinde Rebeca Compaore Dorcas Obiri-Yeboah Benoît Kabamba Bolni Marius Nagalo Jacques Simpore Rasmata Ouédraogo Department of Medicine Transmissible Diseases LaboratoryUniversitéJoseph KI-ZERBOOuagadougou 0000Burkina Faso Department of Biochemistry and Microbiology Molecular Biology and Genetics LaboratoryUniversity Joseph KI-ZERBOOuagadougou 0000Burkina Faso infectious and parasitic disease laboratory Health Sciences Research InstituteIRSS/CNRSTNational Center for Scientific and Technological ResearchOuagadougou 0000Burkina Faso Department of Microbiology and Immunology School of Medical SciencesUniversity of Cape CoastPMBCape Coast 0000Ghana Department of Clinical Biology Virology LaboratoryCliniques Universitaires Saint LucUniversitéCatholique de LouvainBruxelles 0000Belgium division of Hematology and Oncology Mayo ClinicAZ 0000United States

BACKGROUND Occult hepatitis B infection(OBI)is a globally prevalent infection,with its frequency being influenced by the prevalence of hepatitis B virus(HBV)infection in a particular geographic region,including *** can be transmitted th-rough blood transfusions and organ transplants and has been linked to the development of hepatocellular carcinoma(HCC).The associated HBV genotype influences the *** To highlight the genetic diversity and prevalence of OBI in *** This systematic review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines and involved a comprehensive search on PubMed,Google Scholar,Science Direct,and African Journals Online for published studies on the prevalence and genetic diversity of OBI in *** The synthesis included 83 articles,revealing that the prevalence of OBI varied between countries and population groups,with the highest prevalence being 90.9%in patients with hepatitis C virus infection and 38%in blood donors,indicating an increased risk of HBV transmission through blood *** of OBI reactivation have been reported following *** D is the predominant,followed by genotypes A and *** This review highlights the prevalence of OBI in Africa,which varies across countries and population *** study also demonstrates that genotype D is the most prevalent.

关键词： Occult hepatitis B infection Blood transfusion Genetic diversity

Detection of ARV-Resistant Mutants in HIV-1-Infected Individuals in a Context of Systematic Switching to an Association Based on Dolutegravir in Abidjan, Côte d’Ivoire

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American Journal of molecular Biology 2024年第3期14卷 138-151页

作者： Odegue Kpadraux Danielle Kakou-Ngazoa Solange Dechi Jean-Jacques Renaud Diallo Zelica Sina Kouamé Mireille Sylla Aboubacar Tossea Koui Stéphane Kouakou Venance Adagba Marius Apia N’Chouo Kouamé Basile Touré Offianan André Dosso Mireille molecular Biology Platform Institut Pasteur Abidjan Cte dIvoire laboratory of the Regional Blood Transfusion Center Yamoussoukro Cte dIvoire Department of infectious and Tropical diseases University Hospital Treichville Abidjan Cte dIvoire laboratory of the Regional Blood Transfusion Center San-Pdro Cte dIvoire Department of Epidemic Virus Institut Pasteur Abidjan Cte dIvoire Department of parasitology Mycology Institut Pasteur Abidjan Cte dIvoire Department of Bacteriology-Virology Institut Pasteur Abidjan Cte dIvoire

The emergence of antiretroviral resistance mutations represents a major threat to the achievement of national and global goals for the elimination of HIV-1 infection. The global strategy in 2019 in Cte d'Ivoire is a new national policy for the management of people living with HIV with the administration of dolutegravir (DTG)-based fixed-dose combination. The aim of our study was to evaluate HIV-1 resistance to antiretrovirals (ARVs) in infected adult subjects in Cte d’Ivoire in the context of a systematic switch to a DTG-based combination. Between February 2022 and October 2023, a cross-sectional survey with random sampling was conducted in 06 services caring for people living with HIV. A total of 139 participants were included in the study. Adults with a viral load ≥ 1000 copies/mL were tested for HIV-1 ARV resistance mutations. molecular analyses were performed using protocol of ANRS-MIE (National Agency for Research on AIDS and emerging infectious diseases). The interpretation is performed by HIVGRAD (https://***/cms/grade/). The frequencies of HIV-1 resistance to non-nucleotide reverse transcriptase inhibitors (NNRTIs), nucleotide reverse transcriptase inhibitors (NRTIs), integrase inhibitors (IINTs) and protease inhibitors (PIs) were 82%, 73%, 19% and 11% respectively. The main mutations observed in the different classes were K103N (45%), M184V (64%), E157Q (19%) and L10V/M46I/A71V/I54V (6%) respectively. This study reveals the emergence of resistance to DTG-based fixed-dose combinations, favored by high rates of resistance to NRTIs and NNRTIs. This finding underlines the need for enhanced viral load monitoring and HIV-1 genotyping tests to guide the choice of NRTIs for combination therapy. In addition, monitoring for mutations to second-generation NRTIs is essential, given the scale-up of DTG-based regimens currently underway in Cte d’Ivoire.

关键词： Resistant Mutants Dolutegravir HIV-1 Antiretrovirals Côte d’Ivoire

STAT3-Dependent Effects of Polymeric Immunoglobulin Receptor in Regulating Interleukin-17 Signaling and Preventing Autoimmune Hepatitis

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Engineering 2024年第5期36卷 209-222页

作者： Ting Li Tongtong Pan Nannan Zheng Xiong Ma Xiaodong Wang Fang Yan Huimian Jiang Yuxin Wang Hongwei Lin Jing Lin Huadong Zhang Jia Huang Lingming Kong Anmin Huang Qingxiu Liu Yongping Chen Dazhi Chen Hepatology Diagnosis and Treatment Center The First Affiliated Hospital of Wenzhou Medical University&Zhejiang Provincial Key Laboratory for Accurate Diagnosis and Treatment of Chronic Liver DiseasesWenzhou 325035China Department of Clinical Medicine Hangzhou Medical CollegeHangzhou 310053China State Key laboratory for Oncogenes and Related Genes Renji HospitalSchool of MedicineShanghai Jiao Tong UniversityShanghai 200001China Wenzhou Medical University Wenzhou 325035China division of infectious diseases Lishui People’s HospitalLishui 323000China

One-third of patients with autoimmune hepatitis(AIH)have cirrhosis at the time of *** relevance of these variables,although unknown,is believed to be critical in AIH because of suspected interactions between the gut microbiome and genetic *** of the gut flora and elevated polymeric immunoglobulin receptor(pIgR)levels have been observed in both patients and mouse ***,there is a direct relationship between pIgR expression and transaminase levels in patients with *** this study,we aimed to explore how pIgR influences the secretion of regenerating islet-derived 3 beta(Reg3b)and the flora composition in AIH using in vivo experiments involving patients with AIH and a concanavalin A-induced mouse model of ***3b expression was reduced in pIgR gene(Pigr)-knockout mice compared to that in wild-type mice,leading to increased microbiota ***,exogenous pIgR supplementation increased Reg3b expression and maintained microbiota *** sequencing revealed the participation of the interleukin(IL)-17 signaling pathway in the regulation of Reg3b through ***,the introduction of external pIgR could not restore the imbalance in gut microbiota in AIH,and the decrease in Reg3b expression was not apparent following the inhibition of signal transducer and activator of transcription 3(STAT3).In this study,pIgR facilitated the upregulation of Reg3b via the STAT3 pathway,which plays a crucial role in preserving the balance of the intestinal microbiota in *** this research,we discovered new molecular targets that can be used for the diagnosis and treatment of AIH.

关键词： Autoimmune hepatitis Polymeric immunoglobulin receptor Regenerating islet-derived 3 beta Intestinal microbiota Signal transducer and activator of transcription 3

molecular Detection of Pathogens Involved in Sexually Transmitted Infections in Brazzaville, Congo

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Open Journal of Medical Microbiology 2024年第3期14卷 190-205页

作者： Jeanine Mireille Sita Maboundou Bitsi Nina Esther Ngoyi Ontsira Edith Sophie Kombo Bayonne Tanguy Mieret Geril Sekangue Obili Herlen Tsoumou Lina Foungou Kessengue Samantha Potokoue Mpia Chloé Dupont Guilhem Conquet Gickel Mpika Bitsene Bienvenu Roland Ibara Ossibi Axel Aloumba Etienne Nguimbi Sylvain Godreuil Faculty of Sciences and Technology Marien NGOUABI University Brazzaville Republic of the Congo Faculty of Health Sciences Marien NGOUABI University Brazzaville Republic of the Congo Bacteriology-Virology laboratory University Hospital Center Brazzaville Republic of the Congo Department of infectious diseases Referral Hospital Center of Talanga Brazzaville Republic of the Congo parasitology-Mycology laboratory University Hospital Center Brazzaville Republic of the Congo Department of Gynecology-Obstetrics University Hospital Center Brazzaville Republic of the Congo UMR IRD224-CNRS5290-UM MIVEGEC Infectious Diseases and Vectors: Ecology Genetics Evolution and Control CREES (Reshearch Center in Ecology and Evolution Health) Montpellier France Bacteriology laboratory Arnaud de Villeneuve University Hospital CHU of Montpellier Montpellier France Department of infectious diseases University Hospital Center Brazzaville Republic of the Congo

The objective of this multicentric study was to assess the prevalence of Chlamydia trachomatis, Neisseria gonorrhoeae, Mycoplasma génitalium and Trichomonas vaginalis infections in Brazzaville, in the Republic of Congo, using molecular methods. From January to December 2021, the sexually transmitted disease risk participants were recruited from six centers: The Association of Young HIV-Positive People of Congo, The Congolese Association for Family Welfare, The Association for Support to Vulnerable Groups, Talangaï hospital, Brazzaville university hospital (outpatient service) and the private clinic COGEMO (outpatient service). The real-time multiplex PCR was carried out to detect these pathogens. Each patient had at least one specimen (urine, urethral, anal and/or vaginal samples). The patients were considered infected when one of their samples was positive. 287 participants made of 227 women and 60 men were tested. The general prevalence of these infections was: Chlamydia trachomatis 2.79%, Neisseria gonorrhoeae 3.14%, Mycoplasma génitalium 3.45% and Trichomonas vaginalis 2.97. The prevalence rates according to sex were: C. trachomatis, M. génitalium, N. gonorrhea and T. vaginalis were 1.32%, 2.05%, 1.32% and 3.42% in women and 8.33%, 7.02%, 10% and 1.75% in men, respectively. Most infected patients were asymptomatic. Prevalence rates were higher in bisexual individuals, with the exception of T. vaginalis which showed higher prevalence in heterosexual patients. The bisexual and homosexual individuals represent a major public health problem in sexually active young adults, particularly among men having sex with men. These sexually transmitted infections are mainly asymptomatic, their diagnosis and management remain difficult in developing countries.

关键词： Prevalence Chlamydia trachomatis Neisseria gonorrhoeae Mycoplasma génitalium Trichomonas vaginalis