Lipocalin 2(LCN2)plays a pivotal role in iron metabolism,particularly in the context of microbial infection resistance(e.g.,viruses,bacteria,parasites,etc.).LCN2 combats microbial infection by directly assisting the b...Lipocalin 2(LCN2)plays a pivotal role in iron metabolism,particularly in the context of microbial infection resistance(e.g.,viruses,bacteria,parasites,etc.).LCN2 combats microbial infection by directly assisting the body in competing with microorganisms for iron,inducing immune cells to secrete various cytokines to enhance systemic immune responses,or recruiting neutrophils to infectious sites.The liver serves as the primary organ for LCN2 secretion during microbial infections.This review encapsulates recent advances in dynamic changes,clinical values,and the effects of LCN2 in infectious liver diseases caused by various microbial microorganisms.展开更多
Purpose: The study was to evaluate the efficacy of cyanoacrylate tissue adhesive (CTA) application in corneal perforations. Method: This was a prospective study on 20 patients of corneal perforations who received cyan...Purpose: The study was to evaluate the efficacy of cyanoacrylate tissue adhesive (CTA) application in corneal perforations. Method: This was a prospective study on 20 patients of corneal perforations who received cyanoacrylate tissue adhesive application as treatment between March 2021 and March 2022 at Preah Ang Duong Hospital. The primary outcome measure was success rate of CTA application, while the secondary outcome was to measure postoperative best-corrected visual acuity (BCVA) and ocular complications. Results: The mean age of patients was 44.15 ± 16.05 years old and 7 (35%) were female. Causes of perforation were microbial infection in 12 patients (60%), trauma in 5 patients (25%), and sterile melting in 3 patients (15%). The perforation of size smaller than 1.5 mm was in 8 patients (40%) while 12 patients (60%) had perforated size between 1.5 mm to 3 mm. The perforation was 60% (12 patients) central, 25% (5 patients) paracentral, and 15% (3 patients) peripherally. Out of 20 patients, 5 patients (25%) received CTA application more than 1 time. The mean glue retention was 57.60 ± 31.84 days. Success rate of glue application (defined as intact globe without surgical intervention regardless of number of CTA applications) was 85%. At the last visit, 7 patients (35%) had BCVA of 6/120 or better. Common complications were uveitis (45%), ocular hypertension (30%), cataract (25%) and neovascularization (20%). No serious complications were found. Conclusion: Cyanoacrylate tissue adhesive is an effective treatment option in sealing corneal perforations with no serious complications. .展开更多
Background: Chronic ulcers are responsible for considerable morbidity and significantly contribute to the escalation in the cost of health care. Chronic leg ulcers (CLUs) are susceptible to microbial infections and se...Background: Chronic ulcers are responsible for considerable morbidity and significantly contribute to the escalation in the cost of health care. Chronic leg ulcers (CLUs) are susceptible to microbial infections and serious complications such as tissue necrosis and osteomyelitis, can result without the timely control of infections. Recent studies have also reported an increase in the association of fungal infections with chronic non-healing ulcers. Aim: To determine the prevalence of bacterial and fungal infections among patients reporting with chronic leg ulcers in participants without co-morbidities. Methods: A prospective cross-sectional study was conducted among patients with chronic leg ulcers at the National Reconstructive Plastic Surgery and Burns Centre, Korle-Bu Teaching Hospital (NRPS/BC-KBTH) and those who consented were enrolled. Characteristics of the wound as well as micro-organisms cultured from wound swabs were recorded. Results: A total of 50 participants were enrolled for the study with the mean (SD) age of 40.7 (10.7) years. Eighty percent of the participants presented with post traumatic leg ulcers with 80% being artisans and traders in the age group 31 - 50 years. There was no statistically significant association between sex and the organism cultured for post traumatic and cellulitis (p-value > 0.05). The prevalence of bacterial and fungal infection was 79.3% and 20.7% respectively. Pseudomonas species was the most isolated bacteria (61.5%) while Aspergillus niger was the most isolated fungi (41%). Conclusion: From this study, fungal infections should be included in managing chronic leg ulcers, especially among artisans, famers and gardeners even though there was a significantly higher burden of bacterial infections.展开更多
The most common complication of orthopedic surgery is implant failure, which can result in catastrophic injury and a significant financial burden for patients. Implant failure can be caused by a variety of factors, th...The most common complication of orthopedic surgery is implant failure, which can result in catastrophic injury and a significant financial burden for patients. Implant failure can be caused by a variety of factors, the most common of which are peri–implant infection(or implantrelated infection), excessive inflammatory response which caused pain and aseptic loosening. Orthopedic surgeons now have a variety of options for treating these issues, including revision surgery, which has demonstrated to be effective. If excessive inflammatory reaction caused by the corrosion and peri–implant infection can be avoided, it will be of enormous social benefits. This review will provide a summary of corrosion and the inflammation reactions due to the corrosion and antimicrobial properties of Mg alloy-based implants covering both in vitro and in vivo studies. The strategies on hindering/overcoming the excessive inflammatory response and enhancing the antimicrobial activity are discussed in this review.展开更多
Broad-spectrum antibacterial drugs often lack specificity,leading to indiscriminate bactericidal activity,which can disrupt the normal microbial balance of the host flora and cause unnecessary cytotoxicity during syst...Broad-spectrum antibacterial drugs often lack specificity,leading to indiscriminate bactericidal activity,which can disrupt the normal microbial balance of the host flora and cause unnecessary cytotoxicity during systemic administration.In this study,we constructed a specifically targeted antimicrobial peptide against Staphylococcus aureus by introducing a phage-displayed peptide onto a broad-spectrum antimicrobial peptide and explored its structure–function relationship through one-factor modification.SFK2 obtained by screening based on the selectivity index and the targeting index showed specific killing ability against S.aureus.Moreover,SFK2 showed excellent biocompatibility in mice and piglet,and demonstrated significant therapeutic efficacy against S.aureus infection.In conclusion,our screening of phage-derived heptapeptides effectively enhances the specific bactericidal ability of the antimicrobial peptides against S.aureus,providing a theoretical basis for developing targeted antimicrobial peptides.展开更多
Diarrheal diseases can be transmitted via both primary infection due to exposures to contaminated materials from the environment and secondary infection due to person- to-person contacts. Usually, the importance of se...Diarrheal diseases can be transmitted via both primary infection due to exposures to contaminated materials from the environment and secondary infection due to person- to-person contacts. Usually, the importance of secondary infection is empirically assessed by fitting mathematical models to the epidemic curves. However, these empirical models may not be applicable to other epidemic cases because they are developed only for the target epidemics and they don't consider the detail routes of infection. In our previous study, we developed a theoretical model taking into account the various routes of infection that commonly occur in households (e.g., shaking hands, food handling, and changing diapers). This model was made flexible and applicable to any epidemics by means of adjusting model parameters. In this study, we proposed a new index "Vulnerability indicator to secondary infection (VISI)", which expressed a ratio of secondary infection to primary infection risks and calculated this index in a simulated norouirus (NOV) epidemic that involved I0,000 households. The results demonstrated that households composed of more than three members including infant(s) had much higher levels of VlSl (5-45) than two-member-households with VlSI (0.1-4). These results concluded that the infants were likely to be a hub of secondary infections in highly dense families and therefore careful handling of diapers was deemed indispensible in such families to effectively control the secondary infections.展开更多
Due to the limitations of existing approaches,a rapid,sensitive,accurate,comprehensive,and generally applicable strategy to diagnose and treat bacterial and fungal infections remains a major challenge.Here,based on th...Due to the limitations of existing approaches,a rapid,sensitive,accurate,comprehensive,and generally applicable strategy to diagnose and treat bacterial and fungal infections remains a major challenge.Here,based on the ramanome technology platform,we propose a culture‐free,one cell resolution,phenome‐genome‐combined strategy called single‐cell identification,viability and vitality tests and source tracking(SCIVVS).For each cell directly extracted from a clinical specimen,the fingerprint region of the D2O‐probed single cell Raman spectrum(SCRS)enables species‐level identification based on a reference SCRS database of pathogen species,whereas the C‐D band accurately quantifies viability,metabolic vitality,phenotypic susceptibility to antimicrobials,and their intercellular heterogeneity.Moreover,to source track a cell,Raman‐activated cell sorting followed by sequencing or cultivation proceeds,producinging an indexed,high coverage genome assembly or a pure culture from precisely one pathogenic cell.Finally,an integrated SCIVVS workflow that features automated profiling and sorting of metabolic and morphological phenomes can complete the entire process in only a few hours.Because it resolves heterogeneity for both the metabolic phenome and genome,targets functions,can be automated,and is orders‐of‐magnitude faster while cost‐effective,SCIVVS is a new technological and data framework to diagnose and treat bacterial and fungal infections in various clinical and disease control settings.展开更多
Peptidoglycan recognition proteins (PGRPs) are a family of innate immune receptors that specifically recognize peptidoglycans (PGNs) on the surface of a number of pathogens. Here, we have identified and characteri...Peptidoglycan recognition proteins (PGRPs) are a family of innate immune receptors that specifically recognize peptidoglycans (PGNs) on the surface of a number of pathogens. Here, we have identified and characterized six PGRPs from endoparasitoid wasp, Microplitis mediator (MmePGRPs). To understand the roles of PGRPs in parasitoid wasps, we analyzed their evolutionary relationship and orthology, expression profiles during different developmental stages, and transcriptional expression following infection with Gram-positive and -negative bacteria and a fungus. MmePGRP-S1 was significantly induced in response to pathogenic infection. This prompted us to evaluate the effects of RNA interference mediated gene specific knockdown ofMmePGRP-S1. The knockdown of MmePGRP-S1 (iMmePGRP-S1) dramatically affected wasps' survival following challenge by Micrococcus luteus, indicating the involvement of this particular PGRP in immune responses against Gram-positive bacteria. This action is likely to be mediated by the Toll pathway, but the mechanism remains to be determined. MmePGRP-S 1 does not play a significant role in anti-fungal immunity as indicated by the survival rate of iMmePGRP-S wasps. This study provides a comprehensive characterization of PGRPs in the economically important hymenopteran species M. mediator.展开更多
The utilization of biomaterials in implanted blood-contacting medical devices often induces a persistent problem of microbial infection,which results from bacterial adhesion and biofilm formation on the surface of bio...The utilization of biomaterials in implanted blood-contacting medical devices often induces a persistent problem of microbial infection,which results from bacterial adhesion and biofilm formation on the surface of biomaterials.In this research,we developed new fluorinated alkoxyphosphazene materials,specifically poly[bis(octafluoropentoxy)phosphazene](OFP)and crosslinkable OFP(X–OFP),with improved mechanical properties,and further modified the surface topography with ordered pillars to improve the antibacterial properties.Three X–OFP materials,X–OFP3.3,X–OFP8.1,X–OFP13.6,with different crosslinking densities were synthesized,and textured films with patterns of 500/500/600 nm(diameter/spacing/height)were fabricated via a two stage soft lithography molding process.Experiments with 3 bacterial strains:Staphylococcal epidermidis,Staphylococcal aureus,and Pseudomonas aeruginosa showed that bacterial adhesion coefficients were significantly lower on OFP and X–OFP smooth surfaces than on the polyurethane biomaterial,and surface texturing further reduced bacterial adhesion due to the reduction in accessible surface contact area.Furthermore the anti-bacterial adhesion effect shows a positive relationship with the crosslinking degree.Biofilm formation on the substrates was examined using a CDC biofilm reactor for 7 days and no biofilm formation was observed on textured X–OFP biomaterials.The results suggested that the combination of fluorocarbon chemistry and submicron topography modification in textured X–OFP materials may provide a practical approach to improve the biocompatibility of current biomaterials with significant reduction in risk of pathogenic infection.展开更多
Bovine colostrum is defined as first milk by milching animals responsible for providing the innate immunity to the neonatal and possess many immunoglobulins for preventing the calf from diseases. Colostrum consist of ...Bovine colostrum is defined as first milk by milching animals responsible for providing the innate immunity to the neonatal and possess many immunoglobulins for preventing the calf from diseases. Colostrum consist of many bioactive compounds like proteins, enzymes, growth factors, immunoglobulins and nucleotides that provides several benefits to human health. Numerous clinical and pre-clinical studies have demonstrated the therapeutic benefits of the bovine colostrum. This review focusses on bioactive compounds, their health benefits, potential of colostrum for developing several health foods and prevention of respiratory and gastrointestinal tract disorders. Processing can also be done to extend shelf-life and extraction of bioactive constituents either as encapsulated or as extracts. The products derived from bovine colostrum are high-end supplements possessing high nutraceutical value.展开更多
文摘Lipocalin 2(LCN2)plays a pivotal role in iron metabolism,particularly in the context of microbial infection resistance(e.g.,viruses,bacteria,parasites,etc.).LCN2 combats microbial infection by directly assisting the body in competing with microorganisms for iron,inducing immune cells to secrete various cytokines to enhance systemic immune responses,or recruiting neutrophils to infectious sites.The liver serves as the primary organ for LCN2 secretion during microbial infections.This review encapsulates recent advances in dynamic changes,clinical values,and the effects of LCN2 in infectious liver diseases caused by various microbial microorganisms.
文摘Purpose: The study was to evaluate the efficacy of cyanoacrylate tissue adhesive (CTA) application in corneal perforations. Method: This was a prospective study on 20 patients of corneal perforations who received cyanoacrylate tissue adhesive application as treatment between March 2021 and March 2022 at Preah Ang Duong Hospital. The primary outcome measure was success rate of CTA application, while the secondary outcome was to measure postoperative best-corrected visual acuity (BCVA) and ocular complications. Results: The mean age of patients was 44.15 ± 16.05 years old and 7 (35%) were female. Causes of perforation were microbial infection in 12 patients (60%), trauma in 5 patients (25%), and sterile melting in 3 patients (15%). The perforation of size smaller than 1.5 mm was in 8 patients (40%) while 12 patients (60%) had perforated size between 1.5 mm to 3 mm. The perforation was 60% (12 patients) central, 25% (5 patients) paracentral, and 15% (3 patients) peripherally. Out of 20 patients, 5 patients (25%) received CTA application more than 1 time. The mean glue retention was 57.60 ± 31.84 days. Success rate of glue application (defined as intact globe without surgical intervention regardless of number of CTA applications) was 85%. At the last visit, 7 patients (35%) had BCVA of 6/120 or better. Common complications were uveitis (45%), ocular hypertension (30%), cataract (25%) and neovascularization (20%). No serious complications were found. Conclusion: Cyanoacrylate tissue adhesive is an effective treatment option in sealing corneal perforations with no serious complications. .
文摘Background: Chronic ulcers are responsible for considerable morbidity and significantly contribute to the escalation in the cost of health care. Chronic leg ulcers (CLUs) are susceptible to microbial infections and serious complications such as tissue necrosis and osteomyelitis, can result without the timely control of infections. Recent studies have also reported an increase in the association of fungal infections with chronic non-healing ulcers. Aim: To determine the prevalence of bacterial and fungal infections among patients reporting with chronic leg ulcers in participants without co-morbidities. Methods: A prospective cross-sectional study was conducted among patients with chronic leg ulcers at the National Reconstructive Plastic Surgery and Burns Centre, Korle-Bu Teaching Hospital (NRPS/BC-KBTH) and those who consented were enrolled. Characteristics of the wound as well as micro-organisms cultured from wound swabs were recorded. Results: A total of 50 participants were enrolled for the study with the mean (SD) age of 40.7 (10.7) years. Eighty percent of the participants presented with post traumatic leg ulcers with 80% being artisans and traders in the age group 31 - 50 years. There was no statistically significant association between sex and the organism cultured for post traumatic and cellulitis (p-value > 0.05). The prevalence of bacterial and fungal infection was 79.3% and 20.7% respectively. Pseudomonas species was the most isolated bacteria (61.5%) while Aspergillus niger was the most isolated fungi (41%). Conclusion: From this study, fungal infections should be included in managing chronic leg ulcers, especially among artisans, famers and gardeners even though there was a significantly higher burden of bacterial infections.
文摘The most common complication of orthopedic surgery is implant failure, which can result in catastrophic injury and a significant financial burden for patients. Implant failure can be caused by a variety of factors, the most common of which are peri–implant infection(or implantrelated infection), excessive inflammatory response which caused pain and aseptic loosening. Orthopedic surgeons now have a variety of options for treating these issues, including revision surgery, which has demonstrated to be effective. If excessive inflammatory reaction caused by the corrosion and peri–implant infection can be avoided, it will be of enormous social benefits. This review will provide a summary of corrosion and the inflammation reactions due to the corrosion and antimicrobial properties of Mg alloy-based implants covering both in vitro and in vivo studies. The strategies on hindering/overcoming the excessive inflammatory response and enhancing the antimicrobial activity are discussed in this review.
基金supported by the National Key R&D Program of China(2022YFD1300404)the National Natural Science Foundation of China(31930106 and U22A20514)+1 种基金the 2115 Talent Development Program of China Agricultural University(1041-00109019)the Pinduoduo-China Agricultural University Research Fund(PC2023A01001).
文摘Broad-spectrum antibacterial drugs often lack specificity,leading to indiscriminate bactericidal activity,which can disrupt the normal microbial balance of the host flora and cause unnecessary cytotoxicity during systemic administration.In this study,we constructed a specifically targeted antimicrobial peptide against Staphylococcus aureus by introducing a phage-displayed peptide onto a broad-spectrum antimicrobial peptide and explored its structure–function relationship through one-factor modification.SFK2 obtained by screening based on the selectivity index and the targeting index showed specific killing ability against S.aureus.Moreover,SFK2 showed excellent biocompatibility in mice and piglet,and demonstrated significant therapeutic efficacy against S.aureus infection.In conclusion,our screening of phage-derived heptapeptides effectively enhances the specific bactericidal ability of the antimicrobial peptides against S.aureus,providing a theoretical basis for developing targeted antimicrobial peptides.
基金supported by JST-CREST, JSPS-KAKENHI (No. 26241025)MEXT-GRENE
文摘Diarrheal diseases can be transmitted via both primary infection due to exposures to contaminated materials from the environment and secondary infection due to person- to-person contacts. Usually, the importance of secondary infection is empirically assessed by fitting mathematical models to the epidemic curves. However, these empirical models may not be applicable to other epidemic cases because they are developed only for the target epidemics and they don't consider the detail routes of infection. In our previous study, we developed a theoretical model taking into account the various routes of infection that commonly occur in households (e.g., shaking hands, food handling, and changing diapers). This model was made flexible and applicable to any epidemics by means of adjusting model parameters. In this study, we proposed a new index "Vulnerability indicator to secondary infection (VISI)", which expressed a ratio of secondary infection to primary infection risks and calculated this index in a simulated norouirus (NOV) epidemic that involved I0,000 households. The results demonstrated that households composed of more than three members including infant(s) had much higher levels of VlSl (5-45) than two-member-households with VlSI (0.1-4). These results concluded that the infants were likely to be a hub of secondary infections in highly dense families and therefore careful handling of diapers was deemed indispensible in such families to effectively control the secondary infections.
基金National Key R&D Program of China,Grant/Award Number:2022YFA1304101CAS,Grant/Award Number:XDB29050400+1 种基金National Natural Science Foundation of China,Grant/Award Number:32030003Shenzhen‐Hong Kong Innovation Circle Plan,Grant/Award Number:SGDX2019081623060946。
文摘Due to the limitations of existing approaches,a rapid,sensitive,accurate,comprehensive,and generally applicable strategy to diagnose and treat bacterial and fungal infections remains a major challenge.Here,based on the ramanome technology platform,we propose a culture‐free,one cell resolution,phenome‐genome‐combined strategy called single‐cell identification,viability and vitality tests and source tracking(SCIVVS).For each cell directly extracted from a clinical specimen,the fingerprint region of the D2O‐probed single cell Raman spectrum(SCRS)enables species‐level identification based on a reference SCRS database of pathogen species,whereas the C‐D band accurately quantifies viability,metabolic vitality,phenotypic susceptibility to antimicrobials,and their intercellular heterogeneity.Moreover,to source track a cell,Raman‐activated cell sorting followed by sequencing or cultivation proceeds,producinging an indexed,high coverage genome assembly or a pure culture from precisely one pathogenic cell.Finally,an integrated SCIVVS workflow that features automated profiling and sorting of metabolic and morphological phenomes can complete the entire process in only a few hours.Because it resolves heterogeneity for both the metabolic phenome and genome,targets functions,can be automated,and is orders‐of‐magnitude faster while cost‐effective,SCIVVS is a new technological and data framework to diagnose and treat bacterial and fungal infections in various clinical and disease control settings.
基金Acknowledgments This work was supported by National Basic Research Program of China (No. 2014CB138405), Strategic Priority Research Program of CAS (No. XDB 11030600), National Natural Science Foundation of China (No. 31472008, 31401804, 31272497), Open Research Fund Program of State Key Laboratory of Integrated Pest Management (Chinese IPM1407, 1304).
文摘Peptidoglycan recognition proteins (PGRPs) are a family of innate immune receptors that specifically recognize peptidoglycans (PGNs) on the surface of a number of pathogens. Here, we have identified and characterized six PGRPs from endoparasitoid wasp, Microplitis mediator (MmePGRPs). To understand the roles of PGRPs in parasitoid wasps, we analyzed their evolutionary relationship and orthology, expression profiles during different developmental stages, and transcriptional expression following infection with Gram-positive and -negative bacteria and a fungus. MmePGRP-S1 was significantly induced in response to pathogenic infection. This prompted us to evaluate the effects of RNA interference mediated gene specific knockdown ofMmePGRP-S1. The knockdown of MmePGRP-S1 (iMmePGRP-S1) dramatically affected wasps' survival following challenge by Micrococcus luteus, indicating the involvement of this particular PGRP in immune responses against Gram-positive bacteria. This action is likely to be mediated by the Toll pathway, but the mechanism remains to be determined. MmePGRP-S 1 does not play a significant role in anti-fungal immunity as indicated by the survival rate of iMmePGRP-S wasps. This study provides a comprehensive characterization of PGRPs in the economically important hymenopteran species M. mediator.
基金Research reported in this publication was supported by the National Institute of Allergy and Infectious Disease of NIH under award number R21 AI139706.
文摘The utilization of biomaterials in implanted blood-contacting medical devices often induces a persistent problem of microbial infection,which results from bacterial adhesion and biofilm formation on the surface of biomaterials.In this research,we developed new fluorinated alkoxyphosphazene materials,specifically poly[bis(octafluoropentoxy)phosphazene](OFP)and crosslinkable OFP(X–OFP),with improved mechanical properties,and further modified the surface topography with ordered pillars to improve the antibacterial properties.Three X–OFP materials,X–OFP3.3,X–OFP8.1,X–OFP13.6,with different crosslinking densities were synthesized,and textured films with patterns of 500/500/600 nm(diameter/spacing/height)were fabricated via a two stage soft lithography molding process.Experiments with 3 bacterial strains:Staphylococcal epidermidis,Staphylococcal aureus,and Pseudomonas aeruginosa showed that bacterial adhesion coefficients were significantly lower on OFP and X–OFP smooth surfaces than on the polyurethane biomaterial,and surface texturing further reduced bacterial adhesion due to the reduction in accessible surface contact area.Furthermore the anti-bacterial adhesion effect shows a positive relationship with the crosslinking degree.Biofilm formation on the substrates was examined using a CDC biofilm reactor for 7 days and no biofilm formation was observed on textured X–OFP biomaterials.The results suggested that the combination of fluorocarbon chemistry and submicron topography modification in textured X–OFP materials may provide a practical approach to improve the biocompatibility of current biomaterials with significant reduction in risk of pathogenic infection.
文摘Bovine colostrum is defined as first milk by milching animals responsible for providing the innate immunity to the neonatal and possess many immunoglobulins for preventing the calf from diseases. Colostrum consist of many bioactive compounds like proteins, enzymes, growth factors, immunoglobulins and nucleotides that provides several benefits to human health. Numerous clinical and pre-clinical studies have demonstrated the therapeutic benefits of the bovine colostrum. This review focusses on bioactive compounds, their health benefits, potential of colostrum for developing several health foods and prevention of respiratory and gastrointestinal tract disorders. Processing can also be done to extend shelf-life and extraction of bioactive constituents either as encapsulated or as extracts. The products derived from bovine colostrum are high-end supplements possessing high nutraceutical value.