Metagenomics and bacterial culture were used to determine the normal skin microbiome of the Western mosquitofish (Gambusia affinis). This is the first study of G. affinis, and the most in-depth study of any fish skin,...Metagenomics and bacterial culture were used to determine the normal skin microbiome of the Western mosquitofish (Gambusia affinis). This is the first study of G. affinis, and the most in-depth study of any fish skin, utilizing a combination of 16S profile pyrosequencing and culture analysis. Over 1800 sequences obtained from three individuals reveal that over half of all sequences come from five invariant genera, Acinetobacter, Sphingomonas, Acidovorax, Enhydrobacter, and Aquabacterium. The microbiome is diverse but has low equitability, with a total of 81 genera detected. Challenge studies suggest that non-native bacteria cannot colonize the skin. This definition of the normal skin microbiome lays the foundation for future studies with this model system.展开更多
Abdominal surgical site infections(SSIs)are infections that occur after abdominal surgery.They can be superficial,involving the skin tissue only,or more profound,involving deeper skin tissues including organs and impl...Abdominal surgical site infections(SSIs)are infections that occur after abdominal surgery.They can be superficial,involving the skin tissue only,or more profound,involving deeper skin tissues including organs and implanted materials.Currently,SSIs are large global health problem with an incidence that varies significantly depending on the United Nations’Human Development Index.The purpose of this review is to provide a practical update on the latest available literature on SSIs,focusing on causative pathogens and treatment with an overview of the ongoing studies of new therapeutic strategies.展开更多
Porcine reproductive and respiratory syndrome (PRRS) is an economically devastating disease with worldwide distribution caused by Betaarterivirus suid (PRRSV). The virion has great genetic and antigenic variability wi...Porcine reproductive and respiratory syndrome (PRRS) is an economically devastating disease with worldwide distribution caused by Betaarterivirus suid (PRRSV). The virion has great genetic and antigenic variability with a marked increase in virulence. Vaccines tested to date have been of little use in controlling the problems caused by PRRSV, so the present study was conceived to evaluate the antiviral effect of polymeric nanoparticles (PNPs) made with glycyrrhizic acid (GA). Recent work has proven that this nanoparticle system is stable. These nanoparticles have good GA carrying capacity, a size < 250 nm, a spherical morphology, and a wide safety range. The integrity of cell morphology can be maintained for up to 72 h. The antiviral effect of this nanoparticle system was tested in cultures of MARC-145 cells in pre- and coinfection assays with PRRSV to evaluate changes in cell morphology and effects on cell viability. The use of PNPsGA with the real-time quantitative polymerase chain reaction (RT-qPCR) decreased viral infection by 38% in 3 amplification cycles. These results suggest that this system has an antiviral effect against PRRSV under the study conditions established.展开更多
Acute and chronic hepatitis B virus(HBV) infections remain to present a major global health problem. The infection can be associated with acute symptomatic or asymptomatic hepatitis which can cause chronic inflammatio...Acute and chronic hepatitis B virus(HBV) infections remain to present a major global health problem. The infection can be associated with acute symptomatic or asymptomatic hepatitis which can cause chronic inflammation of the liver and over years this can lead to cirrhosis and the development of hepatocellularcarcinomas. Currently available therapeutics for chronically infected individuals aim at reducing viral replication and to slow down or stop the progression of the disease. Therefore, novel treatment options are needed to efficiently combat and eradicate this disease. Here we provide a state of the art overview of gene therapeutic approaches to inhibit HBV replication. We discuss non-viral and viral approaches which were explored to deliver therapeutic nucleic acids aiming at reducing HBV replication. Types of delivered therapeutic nucleic acids which were studied since many years include antisense oligodeoxynucleotides and antisense RNA, ribozymes and DNAzymes, RNA interference, and external guide sequences. More recently designer nucleases gained increased attention and were exploited to destroy the HBV genome. In addition we mention other strategies to reduce HBV replication based on delivery of DNA encoding dominant negative mutants and DNA vaccination. In combination with available cell culture and animal models for HBV infection, in vitro and in vivo studies can be performed to test efficacy of gene therapeutic approaches. Recent progress but also challenges will be specified and future perspectives will be discussed. This is an exciting time to explore such approaches because recent successes of gene therapeutic strategies in the clinic to treat genetic diseases raise hope to find alternative treatment options for patients chronically infected with HBV.展开更多
Adenoviruses typically cause mild illnesses,but severe diseases may occur primarily in immunodeficient individuals,particularly children.Recently,adenoviruses have garnered significant interest as a versatile tool in ...Adenoviruses typically cause mild illnesses,but severe diseases may occur primarily in immunodeficient individuals,particularly children.Recently,adenoviruses have garnered significant interest as a versatile tool in gene therapy,tumor treatment,and vaccine vector development.Over the past two decades,the advent of recombineering,a method based on homologous recombination,has notably enhanced the utility of adenoviral vectors in therapeutic applications.This review summarizes recent advancements in the use of human adenoviral vectors in medicine and discusses the pivotal role of recombineering in the development of these vectors.Additionally,it highlights the current achievements and potential future impact of therapeutic adenoviral vectors.展开更多
More than 100 million people are facing a return to extreme poverty because of coronavirus disease 2019(COVID-19),while new estimates suggest that three nations—India,Nigeria,and the Democratic Republic of the Congo-...More than 100 million people are facing a return to extreme poverty because of coronavirus disease 2019(COVID-19),while new estimates suggest that three nations—India,Nigeria,and the Democratic Republic of the Congo-may suffer the greatest economic contractions.Such findings will have profound consequences in terms of our ability to control or eliminate the most widely prevalent neglected tropical diseases.展开更多
Background:Previously rare A2ML1 variants were identified to confer otitis media susceptibility in an indigenous Filipino community and in otitis-prone US children.The goal of this study is to describe differences in ...Background:Previously rare A2ML1 variants were identified to confer otitis media susceptibility in an indigenous Filipino community and in otitis-prone US children.The goal of this study is to describe differences in the middle ear microbiome between carriers and non-carriers of an A2ML1 duplication variant that increases risk for chronic otitis media among indigenous Filipinos with poor health care access.Methods:Ear swabs were obtained from 16 indigenous Filipino individuals with chronic otitis media,of whom 11 carry the A2ML1 duplication variant.Ear swabs were submitted for 16S rRNA gene sequencing.Results:Genotype-based differences in microbial richness,structure,and composition were identified,but were not statistically significant.Taxonomic analysis revealed that the relative abundance of the phyla Fusobacteria and Bacteroidetes,and genus Fusobacterium were nominally increased in carriers compared to non-carriers,but were non-significant after correction for multiple testing.We also detected rare bacteria including Oligella that was reported only once in the middle ear.Conclusions:These findings suggest that A2ML1-related otitis media susceptibility may be mediated by changes in the middle ear microbiome.Knowledge of middle ear microbial profiles according to genetic background can be potentially useful for therapeutic and prophylactic interventions for otitis media and can guide public health interventions towards decreasing otitis media prevalence within the indigenous Filipino community.展开更多
文摘Metagenomics and bacterial culture were used to determine the normal skin microbiome of the Western mosquitofish (Gambusia affinis). This is the first study of G. affinis, and the most in-depth study of any fish skin, utilizing a combination of 16S profile pyrosequencing and culture analysis. Over 1800 sequences obtained from three individuals reveal that over half of all sequences come from five invariant genera, Acinetobacter, Sphingomonas, Acidovorax, Enhydrobacter, and Aquabacterium. The microbiome is diverse but has low equitability, with a total of 81 genera detected. Challenge studies suggest that non-native bacteria cannot colonize the skin. This definition of the normal skin microbiome lays the foundation for future studies with this model system.
文摘Abdominal surgical site infections(SSIs)are infections that occur after abdominal surgery.They can be superficial,involving the skin tissue only,or more profound,involving deeper skin tissues including organs and implanted materials.Currently,SSIs are large global health problem with an incidence that varies significantly depending on the United Nations’Human Development Index.The purpose of this review is to provide a practical update on the latest available literature on SSIs,focusing on causative pathogens and treatment with an overview of the ongoing studies of new therapeutic strategies.
文摘Porcine reproductive and respiratory syndrome (PRRS) is an economically devastating disease with worldwide distribution caused by Betaarterivirus suid (PRRSV). The virion has great genetic and antigenic variability with a marked increase in virulence. Vaccines tested to date have been of little use in controlling the problems caused by PRRSV, so the present study was conceived to evaluate the antiviral effect of polymeric nanoparticles (PNPs) made with glycyrrhizic acid (GA). Recent work has proven that this nanoparticle system is stable. These nanoparticles have good GA carrying capacity, a size < 250 nm, a spherical morphology, and a wide safety range. The integrity of cell morphology can be maintained for up to 72 h. The antiviral effect of this nanoparticle system was tested in cultures of MARC-145 cells in pre- and coinfection assays with PRRSV to evaluate changes in cell morphology and effects on cell viability. The use of PNPsGA with the real-time quantitative polymerase chain reaction (RT-qPCR) decreased viral infection by 38% in 3 amplification cycles. These results suggest that this system has an antiviral effect against PRRSV under the study conditions established.
基金Supported by The Else-Kröner-Fresenius-Foundation(EKFS)and the UWH Forschungsförderung.
文摘Acute and chronic hepatitis B virus(HBV) infections remain to present a major global health problem. The infection can be associated with acute symptomatic or asymptomatic hepatitis which can cause chronic inflammation of the liver and over years this can lead to cirrhosis and the development of hepatocellularcarcinomas. Currently available therapeutics for chronically infected individuals aim at reducing viral replication and to slow down or stop the progression of the disease. Therefore, novel treatment options are needed to efficiently combat and eradicate this disease. Here we provide a state of the art overview of gene therapeutic approaches to inhibit HBV replication. We discuss non-viral and viral approaches which were explored to deliver therapeutic nucleic acids aiming at reducing HBV replication. Types of delivered therapeutic nucleic acids which were studied since many years include antisense oligodeoxynucleotides and antisense RNA, ribozymes and DNAzymes, RNA interference, and external guide sequences. More recently designer nucleases gained increased attention and were exploited to destroy the HBV genome. In addition we mention other strategies to reduce HBV replication based on delivery of DNA encoding dominant negative mutants and DNA vaccination. In combination with available cell culture and animal models for HBV infection, in vitro and in vivo studies can be performed to test efficacy of gene therapeutic approaches. Recent progress but also challenges will be specified and future perspectives will be discussed. This is an exciting time to explore such approaches because recent successes of gene therapeutic strategies in the clinic to treat genetic diseases raise hope to find alternative treatment options for patients chronically infected with HBV.
基金the DFG grant EH 192/5-3(to AE),the internal grant program(project IFF 2024-91)f the Faculty of Health at Witten/Herdecke University(WZ and KS)and the PhD program at Witten/Herdecke University(LK).
文摘Adenoviruses typically cause mild illnesses,but severe diseases may occur primarily in immunodeficient individuals,particularly children.Recently,adenoviruses have garnered significant interest as a versatile tool in gene therapy,tumor treatment,and vaccine vector development.Over the past two decades,the advent of recombineering,a method based on homologous recombination,has notably enhanced the utility of adenoviral vectors in therapeutic applications.This review summarizes recent advancements in the use of human adenoviral vectors in medicine and discusses the pivotal role of recombineering in the development of these vectors.Additionally,it highlights the current achievements and potential future impact of therapeutic adenoviral vectors.
文摘More than 100 million people are facing a return to extreme poverty because of coronavirus disease 2019(COVID-19),while new estimates suggest that three nations—India,Nigeria,and the Democratic Republic of the Congo-may suffer the greatest economic contractions.Such findings will have profound consequences in terms of our ability to control or eliminate the most widely prevalent neglected tropical diseases.
基金supported by:the National Organization for Hearing Research Foundation,the Hearing Health Foundation,and Action On Hearing Loss(to R.L.P.S.C.)the University of the Philippines Manila–National Institutes of Health(to G.T.A.)+1 种基金the Albert and Margaret Alkek Foundation(to J.F.P.)the United States National Institutes of Health-National Institute on Deafness and Other Communication Disorders grants K18 DC013564(to T.C.),R01 DC011651 and R01 DC003594(to S.M.L.)and R01 DC015004(to R.L.P.S.C.).
文摘Background:Previously rare A2ML1 variants were identified to confer otitis media susceptibility in an indigenous Filipino community and in otitis-prone US children.The goal of this study is to describe differences in the middle ear microbiome between carriers and non-carriers of an A2ML1 duplication variant that increases risk for chronic otitis media among indigenous Filipinos with poor health care access.Methods:Ear swabs were obtained from 16 indigenous Filipino individuals with chronic otitis media,of whom 11 carry the A2ML1 duplication variant.Ear swabs were submitted for 16S rRNA gene sequencing.Results:Genotype-based differences in microbial richness,structure,and composition were identified,but were not statistically significant.Taxonomic analysis revealed that the relative abundance of the phyla Fusobacteria and Bacteroidetes,and genus Fusobacterium were nominally increased in carriers compared to non-carriers,but were non-significant after correction for multiple testing.We also detected rare bacteria including Oligella that was reported only once in the middle ear.Conclusions:These findings suggest that A2ML1-related otitis media susceptibility may be mediated by changes in the middle ear microbiome.Knowledge of middle ear microbial profiles according to genetic background can be potentially useful for therapeutic and prophylactic interventions for otitis media and can guide public health interventions towards decreasing otitis media prevalence within the indigenous Filipino community.