CTX-M-producing bacteria are known as a resistant source against oxyimino-cephalosporin such as cefotaxime and ceftazidime;although laboratory diagnosis of this gene has not been properly defined. The aims of this stu...CTX-M-producing bacteria are known as a resistant source against oxyimino-cephalosporin such as cefotaxime and ceftazidime;although laboratory diagnosis of this gene has not been properly defined. The aims of this study are determining the rates of prevalence of CTX-M and CTX-M group 1 in the Escherichia coli (E. coli) obtained from urinary tract infections (UTI), and also determining their genetic relationship in the city of Sanandaj. In current study, 180 E. coli strains isolated from urinary tract infections were used. Sensitivity to common antibiotics was studied by the disc diffusion method. Phenotypic detection of isolated ESBL-producing starins was done by the combination disc test. CTX-M and CTX-M1 genes were detected using the PCR method and finally, the possible clonal relationship between isolates was determined using the REP-PCR method. 89 samples were ESBL-positive. The PCR assay used for detecting the CTX-M gene, showed that 48 samples out of 180 samples (26.66%) contained that gene;also among these 48 samples, 23 (12.77%) had CTX-M group 1. Based on the REP-PCR assay, 48 genotypes among 48 samples were CTX-M-positive. Results from the REP-PCR assay indicated that the clonal propagation theory of one epidemic strain of Escherichia coli is not apply, i.e. all CTX-M-producing species are not originated from one single strain and the gene is spread between different isolates. Therefore, hospitals and their employees must be more hygiene and, proper disposal of hospital waste can help to prevent the spread of different resistances.展开更多
BACKGROUND Diabetic intracerebral hemorrhage(ICH)is a serious complication of diabetes.The role and mechanism of bone marrow mesenchymal stem cell(BMSC)-derived exosomes(BMSC-exo)in neuroinflammation post-ICH in patie...BACKGROUND Diabetic intracerebral hemorrhage(ICH)is a serious complication of diabetes.The role and mechanism of bone marrow mesenchymal stem cell(BMSC)-derived exosomes(BMSC-exo)in neuroinflammation post-ICH in patients with diabetes are unknown.In this study,we investigated the regulation of BMSC-exo on hyperglycemia-induced neuroinflammation.AIM To study the mechanism of BMSC-exo on nerve function damage after diabetes complicated with cerebral hemorrhage.METHODS BMSC-exo were isolated from mouse BMSC media.This was followed by transfection with microRNA-129-5p(miR-129-5p).BMSC-exo or miR-129-5poverexpressing BMSC-exo were intravitreally injected into a diabetes mouse model with ICH for in vivo analyses and were cocultured with high glucoseaffected BV2 cells for in vitro analyses.The dual luciferase test and RNA immunoprecipitation test verified the targeted binding relationship between miR-129-5p and high-mobility group box 1(HMGB1).Quantitative polymerase chain reaction,western blotting,and enzyme-linked immunosorbent assay were conducted to assess the levels of some inflammation factors,such as HMGB1,interleukin 6,interleukin 1β,toll-like receptor 4,and tumor necrosis factorα.Brain water content,neural function deficit score,and Evans blue were used to measure the neural function of mice.RESULTS Our findings indicated that BMSC-exo can promote neuroinflammation and functional recovery.MicroRNA chip analysis of BMSC-exo identified miR-129-5p as the specific microRNA with a protective role in neuroinflammation.Overexpression of miR-129-5p in BMSC-exo reduced the inflammatory response and neurological impairment in comorbid diabetes and ICH cases.Furthermore,we found that miR-129-5p had a targeted binding relationship with HMGB1 mRNA.CONCLUSION We demonstrated that BMSC-exo can reduce the inflammatory response after ICH with diabetes,thereby improving the neurological function of the brain.展开更多
BACKGROUND Necrotising enterocolitis(NEC)is a critical gastrointestinal emergency affecting premature and low-birth-weight neonates.Serum amyloid A(SAA),procalcitonin(PCT),and high-mobility group box 1(HMGB1)have emer...BACKGROUND Necrotising enterocolitis(NEC)is a critical gastrointestinal emergency affecting premature and low-birth-weight neonates.Serum amyloid A(SAA),procalcitonin(PCT),and high-mobility group box 1(HMGB1)have emerged as potential biomarkers for NEC due to their roles in inflammatory response,tissue damage,and immune regulation.AIM To evaluate the diagnostic value of SAA,PCT,and HMGB1 in the context of NEC in newborns.METHODS The study retrospectively analysed the clinical data of 48 newborns diagnosed with NEC and 50 healthy newborns admitted to the hospital.Clinical,radiological,and laboratory findings,including serum SAA,PCT,and HMGB1 Levels,were collected,and specific detection methods were used.The diagnostic value of the biomarkers was evaluated through statistical analysis,which was performed using chi-square test,t-test,correlation analysis,and receiver operating characteristic(ROC)analysis.RESULTS The study demonstrated significantly elevated levels of serum SAA,PCT,and HMGB1 Levels in newborns diagnosed with NEC compared with healthy controls.The correlation analysis indicated strong positive correlations among serum SAA,PCT,and HMGB1 Levels and the presence of NEC.ROC analysis revealed promising sensitivity and specificity for serum SAA,PCT,and HMGB1 Levels as potential diagnostic markers.The combined model of the three biomarkers demonstrating an extremely high area under the curve(0.908).CONCLUSION The diagnostic value of serum SAA,PCT,and HMGB1 Levels in NEC was highlighted.These biomarkers potentially improve the early detection,risk stratification,and clinical management of critical conditions.The findings suggest that these biomarkers may aid in timely intervention and the enhancement of outcomes for neonates affected by NEC.展开更多
High-mobility group box 1 was first discovered in the calf thymus as a DNA-binding nuclear protein and has been widely studied in diverse fields,including neurology and neuroscience.High-mobility group box 1 in the ex...High-mobility group box 1 was first discovered in the calf thymus as a DNA-binding nuclear protein and has been widely studied in diverse fields,including neurology and neuroscience.High-mobility group box 1 in the extracellular space functions as a pro-inflammatory damage-associated molecular pattern,which has been proven to play an important role in a wide variety of central nervous system disorders such as ischemic stroke,Alzheimer’s disease,frontotemporal dementia,Parkinson’s disease,multiple sclerosis,epilepsy,and traumatic brain injury.Several drugs that inhibit high-mobility group box 1 as a damage-associated molecular pattern,such as glycyrrhizin,ethyl pyruvate,and neutralizing anti-high-mobility group box 1 antibodies,are commonly used to target high-mobility group box 1 activity in central nervous system disorders.Although it is commonly known for its detrimental inflammatory effect,high-mobility group box 1 has also been shown to have beneficial pro-regenerative roles in central nervous system disorders.In this narrative review,we provide a brief summary of the history of high-mobility group box 1 research and its characterization as a damage-associated molecular pattern,its downstream receptors,and intracellular signaling pathways,how high-mobility group box 1 exerts the repair-favoring roles in general and in the central nervous system,and clues on how to differentiate the pro-regenerative from the pro-inflammatory role.Research targeting high-mobility group box 1 in the central nervous system may benefit from differentiating between the two functions rather than overall suppression of high-mobility group box 1.展开更多
Eukaryotic chromatin consisting of nucleosomes connected by linker DNA is organized into higher order structures,which is facilitated by linker histone H1.Formation of chromatin compacts and protects the genome,but al...Eukaryotic chromatin consisting of nucleosomes connected by linker DNA is organized into higher order structures,which is facilitated by linker histone H1.Formation of chromatin compacts and protects the genome,but also hinders DNA transactions.Cells have evolved mechanisms to modify/remodel chromatin resulting in chromatin states suitable for genome functions.The high mobility group box(HMGB)proteins are non-histone chromatin architectural factors characterized by one or more HMGB motifs that bind DNA in a sequence nonspecific fashion.They play a major role in chromatin dynamics.The Saccharomyces cerevisiae(yeast hereafter)HMGB protein Hmo1 contains two HMGB motifs.However,unlike a canonical HMGB protein that has an acidic C-terminus,Hmo1 ends with a lysine rich,basic,C-terminus,resembling linker histone H1.Hmo1 exhibits characteristics of both HMGB proteins and linker histones in its multiple functions.For instance,Hmo1 promotes transcription by RNA polymerases I and II like canonical HMGB proteins but makes chromatin more compact/stable like linker histones.Recent studies have demonstrated that Hmo1 destabilizes/disrupts nucleosome similarly as other HMGB proteins in vitro and acts to maintain a common topological architecture of genes in yeast genome.This minireview reviews the functions of Hmo1 and the underlying mechanisms,highlighting recent discoveries.展开更多
Background: Extended-spectrum beta-lactamase (ESBL) producing bacteria are a real public health problem, particularly in Africa. Among these ESBLs, there are the Muenchen Cefotaximase (CTX-M) described all over the wo...Background: Extended-spectrum beta-lactamase (ESBL) producing bacteria are a real public health problem, particularly in Africa. Among these ESBLs, there are the Muenchen Cefotaximase (CTX-M) described all over the world of which the most frequent is the CTX-M of group 1 particularly the CTX-M-15 variant. The objective of this study was to determine the prevalence of CTX-M group 1 ESBL-producing Escherichia coli strains and to test their antibiotics susceptibility profile. Methodology: A retrospective cross-sectional descriptive study was conducted to detect ESBL-secreting Escherichia coli strains by the synergy test. Identification of CTX-M type ESBL from group 1 was performed using the NG-Test CTX-M rapid diagnostic test (NG-Biotech®). Antibiotic susceptibility profile was determined using CA-SFM/EUCAST guidelines 2019. Data entry and statistical analysis were performed with Excel version 2010 and SPSS 20.0 respectively. Results: Eighty-two ESBL-producing Escherichia coli strains were tested. A group 1 CTX-M ESBL was detected in 75.6% of the strains (n = 62). These strains were highly resistant to cefotaxim (100%), aztreonam (100%), ceftazidim (85.4%) and cefepim (66.1%). They were also resistant to quinolones, gentamycin and sulfadoxine-trimethoprim combination. However, these strains showed sensitivity to ertapenem (100%), cefoxitin (69.3%), tigecyclin (66%), and amikacin (66.1%). The combination of piperacillin and tazobactam was active on 30.6% of the strains against 6.4% for the combination of amoxicillin and clavulanic acid. Conclusion: The CTX-M type ESBL of group 1 was present in the majority of ESBL-producing Escherichia colis trains. Despite the production of this enzyme conferring resistance to most beta-lactam antibiotics, some antibiotics remain active to treat infections caused by these germs.展开更多
文摘CTX-M-producing bacteria are known as a resistant source against oxyimino-cephalosporin such as cefotaxime and ceftazidime;although laboratory diagnosis of this gene has not been properly defined. The aims of this study are determining the rates of prevalence of CTX-M and CTX-M group 1 in the Escherichia coli (E. coli) obtained from urinary tract infections (UTI), and also determining their genetic relationship in the city of Sanandaj. In current study, 180 E. coli strains isolated from urinary tract infections were used. Sensitivity to common antibiotics was studied by the disc diffusion method. Phenotypic detection of isolated ESBL-producing starins was done by the combination disc test. CTX-M and CTX-M1 genes were detected using the PCR method and finally, the possible clonal relationship between isolates was determined using the REP-PCR method. 89 samples were ESBL-positive. The PCR assay used for detecting the CTX-M gene, showed that 48 samples out of 180 samples (26.66%) contained that gene;also among these 48 samples, 23 (12.77%) had CTX-M group 1. Based on the REP-PCR assay, 48 genotypes among 48 samples were CTX-M-positive. Results from the REP-PCR assay indicated that the clonal propagation theory of one epidemic strain of Escherichia coli is not apply, i.e. all CTX-M-producing species are not originated from one single strain and the gene is spread between different isolates. Therefore, hospitals and their employees must be more hygiene and, proper disposal of hospital waste can help to prevent the spread of different resistances.
基金Supported by the National Natural Science Foundation of China,No.81900743Heilongjiang Province Outstanding Young Medical Talents Training Grant Project,China,No.HYD2020YQ0007.
文摘BACKGROUND Diabetic intracerebral hemorrhage(ICH)is a serious complication of diabetes.The role and mechanism of bone marrow mesenchymal stem cell(BMSC)-derived exosomes(BMSC-exo)in neuroinflammation post-ICH in patients with diabetes are unknown.In this study,we investigated the regulation of BMSC-exo on hyperglycemia-induced neuroinflammation.AIM To study the mechanism of BMSC-exo on nerve function damage after diabetes complicated with cerebral hemorrhage.METHODS BMSC-exo were isolated from mouse BMSC media.This was followed by transfection with microRNA-129-5p(miR-129-5p).BMSC-exo or miR-129-5poverexpressing BMSC-exo were intravitreally injected into a diabetes mouse model with ICH for in vivo analyses and were cocultured with high glucoseaffected BV2 cells for in vitro analyses.The dual luciferase test and RNA immunoprecipitation test verified the targeted binding relationship between miR-129-5p and high-mobility group box 1(HMGB1).Quantitative polymerase chain reaction,western blotting,and enzyme-linked immunosorbent assay were conducted to assess the levels of some inflammation factors,such as HMGB1,interleukin 6,interleukin 1β,toll-like receptor 4,and tumor necrosis factorα.Brain water content,neural function deficit score,and Evans blue were used to measure the neural function of mice.RESULTS Our findings indicated that BMSC-exo can promote neuroinflammation and functional recovery.MicroRNA chip analysis of BMSC-exo identified miR-129-5p as the specific microRNA with a protective role in neuroinflammation.Overexpression of miR-129-5p in BMSC-exo reduced the inflammatory response and neurological impairment in comorbid diabetes and ICH cases.Furthermore,we found that miR-129-5p had a targeted binding relationship with HMGB1 mRNA.CONCLUSION We demonstrated that BMSC-exo can reduce the inflammatory response after ICH with diabetes,thereby improving the neurological function of the brain.
文摘BACKGROUND Necrotising enterocolitis(NEC)is a critical gastrointestinal emergency affecting premature and low-birth-weight neonates.Serum amyloid A(SAA),procalcitonin(PCT),and high-mobility group box 1(HMGB1)have emerged as potential biomarkers for NEC due to their roles in inflammatory response,tissue damage,and immune regulation.AIM To evaluate the diagnostic value of SAA,PCT,and HMGB1 in the context of NEC in newborns.METHODS The study retrospectively analysed the clinical data of 48 newborns diagnosed with NEC and 50 healthy newborns admitted to the hospital.Clinical,radiological,and laboratory findings,including serum SAA,PCT,and HMGB1 Levels,were collected,and specific detection methods were used.The diagnostic value of the biomarkers was evaluated through statistical analysis,which was performed using chi-square test,t-test,correlation analysis,and receiver operating characteristic(ROC)analysis.RESULTS The study demonstrated significantly elevated levels of serum SAA,PCT,and HMGB1 Levels in newborns diagnosed with NEC compared with healthy controls.The correlation analysis indicated strong positive correlations among serum SAA,PCT,and HMGB1 Levels and the presence of NEC.ROC analysis revealed promising sensitivity and specificity for serum SAA,PCT,and HMGB1 Levels as potential diagnostic markers.The combined model of the three biomarkers demonstrating an extremely high area under the curve(0.908).CONCLUSION The diagnostic value of serum SAA,PCT,and HMGB1 Levels in NEC was highlighted.These biomarkers potentially improve the early detection,risk stratification,and clinical management of critical conditions.The findings suggest that these biomarkers may aid in timely intervention and the enhancement of outcomes for neonates affected by NEC.
基金supported by a grant of the M.D.-Ph.D./Medical Scientist Training Program through the Korea Health Industry Development Institute(KHIDI)funded by the Ministry of Health&Welfare,Republic of Korea(to HK)+3 种基金supported by National Research Foundation of Korea(NRF)grants funded by the Korean government(MSITMinistry of Science and ICT)(NRF2019R1A5A2026045 and NRF-2021R1F1A1061819)a grant from the Korean Health Technology R&D Project through the Korea Health Industry Development Institute(KHIDI),funded by the Ministry of Health&Welfare,Republic of Korea(HR21C1003)New Faculty Research Fund of Ajou University School of Medicine(to JYC)。
文摘High-mobility group box 1 was first discovered in the calf thymus as a DNA-binding nuclear protein and has been widely studied in diverse fields,including neurology and neuroscience.High-mobility group box 1 in the extracellular space functions as a pro-inflammatory damage-associated molecular pattern,which has been proven to play an important role in a wide variety of central nervous system disorders such as ischemic stroke,Alzheimer’s disease,frontotemporal dementia,Parkinson’s disease,multiple sclerosis,epilepsy,and traumatic brain injury.Several drugs that inhibit high-mobility group box 1 as a damage-associated molecular pattern,such as glycyrrhizin,ethyl pyruvate,and neutralizing anti-high-mobility group box 1 antibodies,are commonly used to target high-mobility group box 1 activity in central nervous system disorders.Although it is commonly known for its detrimental inflammatory effect,high-mobility group box 1 has also been shown to have beneficial pro-regenerative roles in central nervous system disorders.In this narrative review,we provide a brief summary of the history of high-mobility group box 1 research and its characterization as a damage-associated molecular pattern,its downstream receptors,and intracellular signaling pathways,how high-mobility group box 1 exerts the repair-favoring roles in general and in the central nervous system,and clues on how to differentiate the pro-regenerative from the pro-inflammatory role.Research targeting high-mobility group box 1 in the central nervous system may benefit from differentiating between the two functions rather than overall suppression of high-mobility group box 1.
文摘Eukaryotic chromatin consisting of nucleosomes connected by linker DNA is organized into higher order structures,which is facilitated by linker histone H1.Formation of chromatin compacts and protects the genome,but also hinders DNA transactions.Cells have evolved mechanisms to modify/remodel chromatin resulting in chromatin states suitable for genome functions.The high mobility group box(HMGB)proteins are non-histone chromatin architectural factors characterized by one or more HMGB motifs that bind DNA in a sequence nonspecific fashion.They play a major role in chromatin dynamics.The Saccharomyces cerevisiae(yeast hereafter)HMGB protein Hmo1 contains two HMGB motifs.However,unlike a canonical HMGB protein that has an acidic C-terminus,Hmo1 ends with a lysine rich,basic,C-terminus,resembling linker histone H1.Hmo1 exhibits characteristics of both HMGB proteins and linker histones in its multiple functions.For instance,Hmo1 promotes transcription by RNA polymerases I and II like canonical HMGB proteins but makes chromatin more compact/stable like linker histones.Recent studies have demonstrated that Hmo1 destabilizes/disrupts nucleosome similarly as other HMGB proteins in vitro and acts to maintain a common topological architecture of genes in yeast genome.This minireview reviews the functions of Hmo1 and the underlying mechanisms,highlighting recent discoveries.
文摘Background: Extended-spectrum beta-lactamase (ESBL) producing bacteria are a real public health problem, particularly in Africa. Among these ESBLs, there are the Muenchen Cefotaximase (CTX-M) described all over the world of which the most frequent is the CTX-M of group 1 particularly the CTX-M-15 variant. The objective of this study was to determine the prevalence of CTX-M group 1 ESBL-producing Escherichia coli strains and to test their antibiotics susceptibility profile. Methodology: A retrospective cross-sectional descriptive study was conducted to detect ESBL-secreting Escherichia coli strains by the synergy test. Identification of CTX-M type ESBL from group 1 was performed using the NG-Test CTX-M rapid diagnostic test (NG-Biotech®). Antibiotic susceptibility profile was determined using CA-SFM/EUCAST guidelines 2019. Data entry and statistical analysis were performed with Excel version 2010 and SPSS 20.0 respectively. Results: Eighty-two ESBL-producing Escherichia coli strains were tested. A group 1 CTX-M ESBL was detected in 75.6% of the strains (n = 62). These strains were highly resistant to cefotaxim (100%), aztreonam (100%), ceftazidim (85.4%) and cefepim (66.1%). They were also resistant to quinolones, gentamycin and sulfadoxine-trimethoprim combination. However, these strains showed sensitivity to ertapenem (100%), cefoxitin (69.3%), tigecyclin (66%), and amikacin (66.1%). The combination of piperacillin and tazobactam was active on 30.6% of the strains against 6.4% for the combination of amoxicillin and clavulanic acid. Conclusion: The CTX-M type ESBL of group 1 was present in the majority of ESBL-producing Escherichia colis trains. Despite the production of this enzyme conferring resistance to most beta-lactam antibiotics, some antibiotics remain active to treat infections caused by these germs.
