Pub Date : 2025-04-05DOI: 10.1016/j.micpath.2025.107554
Hamid Sadeghi , Mehdi Bakht , Susan Khanjani , Masoumeh Aslanimehr , Farhad Nikkhahi , Fatemeh Fardsanei , Mohammad Reza Maleki , Sara Rahimi , Saeideh Gholamzadeh Khoei
Acinetobacter baumannii's resistance to antibiotics restricts treatment ways, and has enhanced its mortality rates approaching 35 %. Resistance to β-lactams in Acinetobacter baumannii, related to extended-spectrum β-lactamases (ESBLs), has become a worldwide concern. This study aimed to assess the prevalence of Extended-Spectrum Beta-Lactamase-Producing Acinetobacter baumannii in Iran.
Important databases (PubMed, Scopus, Wily Online Library, ScienceDirect and Google Scholar) were searched for related literature published from January 2010 to April 2024. The inclusion criteria were predefined based on PRISMA guidelines. A random-effects model was used according to the heterogeneity test. Publication bias was specified using Egger's weighted regression and Begg's rank correlation methods. The statistical analyses were carried out relying on the Comprehensive Meta-Analysis Software (CMA).
Among 2409 articles identified, 15 papers met the eligibility criteria. Among encoding genes of ESBLs, TEM, PER, SHV, CTX-M, VEB and GES were found with the prevalence of 25.0 % (95 % CI: 15.9–37.1 %), 16.1 % (95 % CI: 7.4–31.5 %), 14.3 % (95 % CI: 6.3–29.4 %), 11.1 % (95 % CI: 4.3–25.8 %), 9.9 % (95 % CI: 5.2–18.1 %) and 8.5 % (95 % CI: 1.4–37.2 %), respectively. A subgroup analysis based on province showed some differences in TEM prevalence. The evaluated pooled prevalence of TEM was highest in Ilam (53.4 %; 95 % CI: 42.0–64.5 %), however, it was based only on one study. It was 51.1 % (95 % CI: 33.7–68.3 %) in Tehran.
The present studies demonstrate a high prevalence of ESBL in Acinetobacter Baumannii in Iran which poses a serious concern in critically ill patients. As well as these findings can assist our conception of the real prevalence of ESBL to work on new strategies for the control and prevention of infection.
{"title":"Systematic review and meta-analysis on the prevalence of extended-spectrum β-lactamases-producing Acinetobacter baumannii in Iran: Evaluation of TEM, PER, SHV, CTX-M, VEB and GES","authors":"Hamid Sadeghi , Mehdi Bakht , Susan Khanjani , Masoumeh Aslanimehr , Farhad Nikkhahi , Fatemeh Fardsanei , Mohammad Reza Maleki , Sara Rahimi , Saeideh Gholamzadeh Khoei","doi":"10.1016/j.micpath.2025.107554","DOIUrl":"10.1016/j.micpath.2025.107554","url":null,"abstract":"<div><div><em>Acinetobacter baumannii's</em> resistance to antibiotics restricts treatment ways, and has enhanced its mortality rates approaching 35 %. Resistance to β-lactams in <em>Acinetobacter baumannii</em>, related to extended-spectrum β-lactamases (ESBLs), has become a worldwide concern. This study aimed to assess the prevalence of Extended-Spectrum Beta-Lactamase-Producing <em>Acinetobacter baumannii</em> in Iran.</div><div>Important databases (PubMed, Scopus, Wily Online Library, ScienceDirect and Google Scholar) were searched for related literature published from January 2010 to April 2024. The inclusion criteria were predefined based on PRISMA guidelines. A random-effects model was used according to the heterogeneity test. Publication bias was specified using Egger's weighted regression and Begg's rank correlation methods. The statistical analyses were carried out relying on the Comprehensive Meta-Analysis Software (CMA).</div><div>Among 2409 articles identified, 15 papers met the eligibility criteria. Among encoding genes of ESBLs, <em>TEM</em>, <em>PER</em>, <em>SHV</em>, <em>CTX-M</em>, <em>VEB</em> and <em>GES</em> were found with the prevalence of 25.0 % (95 % CI: 15.9–37.1 %), 16.1 % (95 % CI: 7.4–31.5 %), 14.3 % (95 % CI: 6.3–29.4 %), 11.1 % (95 % CI: 4.3–25.8 %), 9.9 % (95 % CI: 5.2–18.1 %) and 8.5 % (95 % CI: 1.4–37.2 %), respectively. A subgroup analysis based on province showed some differences in <em>TEM</em> prevalence. The evaluated pooled prevalence of <em>TEM</em> was highest in Ilam (53.4 %; 95 % CI: 42.0–64.5 %), however, it was based only on one study. It was 51.1 % (95 % CI: 33.7–68.3 %) in Tehran.</div><div>The present studies demonstrate a high prevalence of ESBL in <em>Acinetobacter Baumannii</em> in Iran which poses a serious concern in critically ill patients. As well as these findings can assist our conception of the real prevalence of ESBL to work on new strategies for the control and prevention of infection.</div></div>","PeriodicalId":18599,"journal":{"name":"Microbial pathogenesis","volume":"204 ","pages":"Article 107554"},"PeriodicalIF":3.3,"publicationDate":"2025-04-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143785178","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-04-04DOI: 10.1016/j.micpath.2025.107538
Ligia Beatriz Rizzanti Pereira, Breno Luis Nery Garcia, Carlos Eduardo Fidelis, Kristian da Silva Barbosa, Stéfani Thais Alves Dantas, Vera Lúcia Mores Rall, Marcos Veiga Dos Santos
Streptococcus agalactiae is a primary pathogen associated with subclinical mastitis in dairy herds, requiring accurate identification and characterization for effective management due to its highly contagious nature. This study evaluated the use of Matrix Assisted Laser Desorption/Ionization Time-of-Flight Mass Spectrometry (MALDI-TOF MS) for grouping S. agalactiae isolates from subclinical mastitis in cattle and buffaloes associating the antimicrobial susceptibility profiles of the isolates with the grouping results. A total of 198 milk samples were collected from three farms (Farm A: 67 cow isolates, Farm B: 101 cow isolates, Farm C: 30 buffalo isolates). Antimicrobial susceptibility testing using the Minimum Inhibitory Concentration (MIC) method was performed for 10 antimicrobials. High sensitivity (>90%) was observed for ceftiofur, penicillin, oxacillin, amoxicillin, cefquinome, gentamicin, and cefoxitin, while low sensitivity (<15%) was detected for enrofloxacin and cephalexin. Clustering was conducted using Random Amplified Polymorphic DNA (RAPD) and grouped by MALDI-TOF MS. RAPD identified 33 clusters at an 80% similarity breakpoint, while MALDI-TOF MS identified 8 distinct groups. MALDI-TOF MS successfully grouped all isolates, whereas RAPD clustered only 100. Both methods grouped isolates from the same herd with similar susceptibility profiles. These findings highlight the use of MALDI-TOF MS for rapid grouping pathogens but emphasize differences when compared to RAPD.
{"title":"Comparative Analysis of MALDI-TOF MS and RAPD for grouping Streptococcus agalactiae isolated from Subclinical Mastitis Isolates.","authors":"Ligia Beatriz Rizzanti Pereira, Breno Luis Nery Garcia, Carlos Eduardo Fidelis, Kristian da Silva Barbosa, Stéfani Thais Alves Dantas, Vera Lúcia Mores Rall, Marcos Veiga Dos Santos","doi":"10.1016/j.micpath.2025.107538","DOIUrl":"https://doi.org/10.1016/j.micpath.2025.107538","url":null,"abstract":"<p><p>Streptococcus agalactiae is a primary pathogen associated with subclinical mastitis in dairy herds, requiring accurate identification and characterization for effective management due to its highly contagious nature. This study evaluated the use of Matrix Assisted Laser Desorption/Ionization Time-of-Flight Mass Spectrometry (MALDI-TOF MS) for grouping S. agalactiae isolates from subclinical mastitis in cattle and buffaloes associating the antimicrobial susceptibility profiles of the isolates with the grouping results. A total of 198 milk samples were collected from three farms (Farm A: 67 cow isolates, Farm B: 101 cow isolates, Farm C: 30 buffalo isolates). Antimicrobial susceptibility testing using the Minimum Inhibitory Concentration (MIC) method was performed for 10 antimicrobials. High sensitivity (>90%) was observed for ceftiofur, penicillin, oxacillin, amoxicillin, cefquinome, gentamicin, and cefoxitin, while low sensitivity (<15%) was detected for enrofloxacin and cephalexin. Clustering was conducted using Random Amplified Polymorphic DNA (RAPD) and grouped by MALDI-TOF MS. RAPD identified 33 clusters at an 80% similarity breakpoint, while MALDI-TOF MS identified 8 distinct groups. MALDI-TOF MS successfully grouped all isolates, whereas RAPD clustered only 100. Both methods grouped isolates from the same herd with similar susceptibility profiles. These findings highlight the use of MALDI-TOF MS for rapid grouping pathogens but emphasize differences when compared to RAPD.</p>","PeriodicalId":18599,"journal":{"name":"Microbial pathogenesis","volume":" ","pages":"107538"},"PeriodicalIF":3.3,"publicationDate":"2025-04-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143795783","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-04-04DOI: 10.1016/j.micpath.2025.107528
Yaqin Dong, Rabia Ramzan, Yuyu Zhang, Wenjing Tang, Song Li, Ana Chen
Streptomyces scabies is a pathogenic actinomycete that infects potato crops and commonly causes scab-like lesions on potato tubers. Screening of strains antagonistic towards S. scabies in the natural environment was performed in this study. This study focused on the extraction of antibacterial substances and changes in potato defense enzymes and the rhizosphere microbiota. Together, these factors constitute biological control mechanisms. Pot experiments showed that Bacillus atrophaeus CY1 reduced the infection of scabs caused by S. scabies from 92 % to 60 % and the disease index from 62 % to 25 %. Scanning electron microscopy analysis revealed that B. atrophaeus CY1 repressed the growth of S. scabies by disrupting the mycelium and affecting potato defense enzymes. Compared with the infected group, catalase, peroxidase, and polyphenol oxidase activities in potato tubers of the co-culture group increased by 21.98 %, 71.49 %, and 116.15 %, respectively, and SOD activity decreased by 4.9 %. Moreover, at different developmental stages, the microbiota counts in the CY1 cocultured groups were significantly higher, and the actinomycete count was considerably lower. At the budding stage, urease activity was 13.39 mg g−1 in the co-culture group, representing an increase of 37.37 % and 20.62 %, respectively, compared to the control group. Cellulase activity in the SC group was 0.675 mg−1, which represented increases of 39.18 % and 43.92 %, respectively. These results demonstrate that B. atrophaeus CY1 is a potential candidate for the biological control of S. scabies.
{"title":"Exploring the antagonistic mechanism of Bacillus atrophaeus CY1 for the biological control of potato common scab","authors":"Yaqin Dong, Rabia Ramzan, Yuyu Zhang, Wenjing Tang, Song Li, Ana Chen","doi":"10.1016/j.micpath.2025.107528","DOIUrl":"10.1016/j.micpath.2025.107528","url":null,"abstract":"<div><div><em>Streptomyces scabies</em> is a pathogenic actinomycete that infects potato crops and commonly causes scab-like lesions on potato tubers. Screening of strains antagonistic towards <em>S. scabies</em> in the natural environment was performed in this study. This study focused on the extraction of antibacterial substances and changes in potato defense enzymes and the rhizosphere microbiota. Together, these factors constitute biological control mechanisms. Pot experiments showed that <em>Bacillus atrophaeus</em> CY1 reduced the infection of scabs caused by <em>S. scabies</em> from 92 % to 60 % and the disease index from 62 % to 25 %. Scanning electron microscopy analysis revealed that <em>B</em>. <em>atrophaeus</em> CY1 repressed the growth of <em>S. scabies</em> by disrupting the mycelium and affecting potato defense enzymes. Compared with the infected group, catalase, peroxidase, and polyphenol oxidase activities in potato tubers of the co-culture group increased by 21.98 %, 71.49 %, and 116.15 %, respectively, and SOD activity decreased by 4.9 %. Moreover, at different developmental stages, the microbiota counts in the CY1 cocultured groups were significantly higher, and the actinomycete count was considerably lower. At the budding stage, urease activity was 13.39 mg g<sup>−1</sup> in the co-culture group, representing an increase of 37.37 % and 20.62 %, respectively, compared to the control group. Cellulase activity in the SC group was 0.675 mg<sup>−1</sup>, which represented increases of 39.18 % and 43.92 %, respectively. These results demonstrate that <em>B. atrophaeus</em> CY1 is a potential candidate for the biological control of <em>S. scabies</em>.</div></div>","PeriodicalId":18599,"journal":{"name":"Microbial pathogenesis","volume":"204 ","pages":"Article 107528"},"PeriodicalIF":3.3,"publicationDate":"2025-04-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143785179","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-04-04DOI: 10.1016/j.micpath.2025.107542
Gilcele de Campos Martin Berber, Kevin Matheus Lima de Sarges, Thais Campos Dias da Cruz, Eric Henrique Roma, Fábio Miyajima, Jorge Reis Almeida, Cíntia Fernandes de Souza, Andrea Alice da Silva, Izaura Maria Vieira Cayres Vallinoto, Antônio Carlos Rosário Vallinoto, Maria Alice Freitas Queiroz, Tatiana Gasperin Baccin, Andréa Cauduro de Castro, Angélica Thomaz Vieira, Francisco Kennedy Scoffoni de Azevedo, Alexandre da Costa Pereira, Luiz Fábio Magno Falcão, Juarez Antônio Simões Quaresma, Fernanda Kehdy, Eduardo Tarazona Santos, Marilda Mendonça Siqueira, Cristiana Couto Garcia, Eduardo José Melo Dos Santos, Renata Dezengrini Slhessarenko
Immunogenetic factors such as human leucocyte antigen (HLA) alleles, have yielded contrasting associations with protection or increased chances of hospitalization due to COVID-19 worldwide. This case-control study included834 patients with confirmed COVID-19 diagnosis from five Brazilian states: Ceará (n=110), Mato Grosso (n=192), Pará (n=209), Rio de Janeiro (n=211) and Rio Grande do Sul (n=112). Genotyping was performed using the Axiom™ Human Genotyping SARS-CoV-2 array, targeting single nucleotide polymorphisms in HLA class I and II genes, and HLA alleles were imputed for eight loci. Among the 15 preselected candidate alleles, only DQA1*05:01 (p=0.015) in the state of Ceará remained significantly associated with hospitalization. The meta-analysis of the most frequent alleles in all states revealed that HLA-DPA1*01:03 (p=0.0229, OR=0.76, 95% CI=0.60-0.96) and -DPB1*04:01 (p=0.0474, OR=0.78, 95% CI=0.611.00) were associated with protection against hospitalization, whereas HLA-DPA1*02:01 (p=0.0259, OR=1.37, 95% CI=1.04-1.80), -DQA1*05:01 (p=0.0133, OR=1.40, 95% CI=1.07-1.82), and -DRB1*03:01 (p=0.0276, OR: 1.59, 95% CI: 1.05-2.40) were associated with increased risk. HLA evolutionary divergence (HED) scores were significantly higher among the non-hospitalized group for the HLA-A locus, which has been shown to be a protective factor for the most severe forms and consequently hospitalization due to COVID-19.
{"title":"POLYMORPHISMS IN HLA GENES AMONG BRAZILIAN PATIENTS HOSPITALIZED WITH COVID-19: INSIGHTS FROM A MULTICENTRIC STUDY.","authors":"Gilcele de Campos Martin Berber, Kevin Matheus Lima de Sarges, Thais Campos Dias da Cruz, Eric Henrique Roma, Fábio Miyajima, Jorge Reis Almeida, Cíntia Fernandes de Souza, Andrea Alice da Silva, Izaura Maria Vieira Cayres Vallinoto, Antônio Carlos Rosário Vallinoto, Maria Alice Freitas Queiroz, Tatiana Gasperin Baccin, Andréa Cauduro de Castro, Angélica Thomaz Vieira, Francisco Kennedy Scoffoni de Azevedo, Alexandre da Costa Pereira, Luiz Fábio Magno Falcão, Juarez Antônio Simões Quaresma, Fernanda Kehdy, Eduardo Tarazona Santos, Marilda Mendonça Siqueira, Cristiana Couto Garcia, Eduardo José Melo Dos Santos, Renata Dezengrini Slhessarenko","doi":"10.1016/j.micpath.2025.107542","DOIUrl":"https://doi.org/10.1016/j.micpath.2025.107542","url":null,"abstract":"<p><p>Immunogenetic factors such as human leucocyte antigen (HLA) alleles, have yielded contrasting associations with protection or increased chances of hospitalization due to COVID-19 worldwide. This case-control study included834 patients with confirmed COVID-19 diagnosis from five Brazilian states: Ceará (n=110), Mato Grosso (n=192), Pará (n=209), Rio de Janeiro (n=211) and Rio Grande do Sul (n=112). Genotyping was performed using the Axiom™ Human Genotyping SARS-CoV-2 array, targeting single nucleotide polymorphisms in HLA class I and II genes, and HLA alleles were imputed for eight loci. Among the 15 preselected candidate alleles, only DQA1*05:01 (p=0.015) in the state of Ceará remained significantly associated with hospitalization. The meta-analysis of the most frequent alleles in all states revealed that HLA-DPA1*01:03 (p=0.0229, OR=0.76, 95% CI=0.60-0.96) and -DPB1*04:01 (p=0.0474, OR=0.78, 95% CI=0.611.00) were associated with protection against hospitalization, whereas HLA-DPA1*02:01 (p=0.0259, OR=1.37, 95% CI=1.04-1.80), -DQA1*05:01 (p=0.0133, OR=1.40, 95% CI=1.07-1.82), and -DRB1*03:01 (p=0.0276, OR: 1.59, 95% CI: 1.05-2.40) were associated with increased risk. HLA evolutionary divergence (HED) scores were significantly higher among the non-hospitalized group for the HLA-A locus, which has been shown to be a protective factor for the most severe forms and consequently hospitalization due to COVID-19.</p>","PeriodicalId":18599,"journal":{"name":"Microbial pathogenesis","volume":" ","pages":"107542"},"PeriodicalIF":3.3,"publicationDate":"2025-04-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143795785","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Mycoplasma gallisepticum (MG) can infect a wide range of birds, seriously jeopardizing the development of the poultry industry. A nested-PCR method was constructed based on mgc2 gene for evaluating the prevalence of MG in duck flocks. A total of 1002 samples were detected from Shandong and Inner Mongolia by this method. The total positive rate of MG was 22.75% (228/1002), with the highest prevalence in commercial laying ducks (34.83%), the lowest in dead duck embryos (6.67%), and a proportionate prevalence of 17.33% in commercial meat ducks. Genetic evolutionary analysis by mgc2 gene showed that the homology among the wild strains of duck derived MG was 73.3%-99.8%, which revealed genetic diversity, and the homology with the international chicken-derived MG reference strain was ranged 68.4%-98.4%, indicating that some duck-derived MG strains had an independent origin. Duck embryo pathogenicity tests showed only the mortality rate of duck embryos infected by strain 1-9 reached 60%. To clarify the genetic background of strain 1-9, the data of whole genome sequencing showed that the full length of 1-9 was 962,503 bp, and the GC content was 31%. Among the predicted 1576 genes, a total of 599 genes were functionally classified, and the virulence genes were distributed in 21 virulence factors. Phylogenetic tree based on 16S rRNA and single copy gene set were confirmed that there was a far genetic evolutionary distance between the isolate 1-9 and the chicken-derived reference strains. Our findings provided a scientific basis for the research on the pathogenicity and exploring functional genes of duck-derived MG.
{"title":"Molecular epidemiological investigation and identification of Mycoplasma Gallisepticum in large-scale duck farms.","authors":"Luyang Zhou, Xuesheng Chen, Fahui Song, Changxu Yu, Jikun Wu, Jianhua Wang, Aofei Wang, Shuo Yang, Shuqi Wei, Ruihua Zhang, Shijin Jiang, Yanli Zhu","doi":"10.1016/j.micpath.2025.107539","DOIUrl":"https://doi.org/10.1016/j.micpath.2025.107539","url":null,"abstract":"<p><p>Mycoplasma gallisepticum (MG) can infect a wide range of birds, seriously jeopardizing the development of the poultry industry. A nested-PCR method was constructed based on mgc2 gene for evaluating the prevalence of MG in duck flocks. A total of 1002 samples were detected from Shandong and Inner Mongolia by this method. The total positive rate of MG was 22.75% (228/1002), with the highest prevalence in commercial laying ducks (34.83%), the lowest in dead duck embryos (6.67%), and a proportionate prevalence of 17.33% in commercial meat ducks. Genetic evolutionary analysis by mgc2 gene showed that the homology among the wild strains of duck derived MG was 73.3%-99.8%, which revealed genetic diversity, and the homology with the international chicken-derived MG reference strain was ranged 68.4%-98.4%, indicating that some duck-derived MG strains had an independent origin. Duck embryo pathogenicity tests showed only the mortality rate of duck embryos infected by strain 1-9 reached 60%. To clarify the genetic background of strain 1-9, the data of whole genome sequencing showed that the full length of 1-9 was 962,503 bp, and the GC content was 31%. Among the predicted 1576 genes, a total of 599 genes were functionally classified, and the virulence genes were distributed in 21 virulence factors. Phylogenetic tree based on 16S rRNA and single copy gene set were confirmed that there was a far genetic evolutionary distance between the isolate 1-9 and the chicken-derived reference strains. Our findings provided a scientific basis for the research on the pathogenicity and exploring functional genes of duck-derived MG.</p>","PeriodicalId":18599,"journal":{"name":"Microbial pathogenesis","volume":" ","pages":"107539"},"PeriodicalIF":3.3,"publicationDate":"2025-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143788621","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-04-03DOI: 10.1016/j.micpath.2025.107540
Rafaela da Silva Rangel , Raquel Tusi Tamiosso , Rúbia Schallenberger da Silva , Laís Suarez da Silva de Oliveira , Maria Fernanda Biscarra Bortolotto Paz , Teodoro Trevisan De Paula Martins , Alice Mazaro , Alana Bianca de Moraes Chitolina , Marina Machado Maurente , Cinthia Melazzo de Andrade , Jandora Lima Ortiz , Isabela Maraschin Vieira , Marcelo Leite da Veiga , Matheus Dellaméa Baldissera
Oxidative stress plays a pivotal role in the pathophysiology of infectious diseases, contributing to pathogenesis and the appearance of clinical symptoms. However, the involvement of oxidative stress in renal cryptococcosis remains unknown, as do the potential protective effects of rutin. Cryptococcus neoformans is considered the main agent of cryptococcosis, a systemic life-threatening opportunistic fungal disease that affects internal organs. In 2022, the World Health Organization classified it as a critical-priority group on its Fungal Priority Pathogens List. Rutin, a flavonoid with potent antioxidant and antifungal properties, has been proposed as a protective agent. Thus, this study aimed to evaluate whether 50 mg rutin/kg body weight prevents or reduces C. neoformans var. grubii-induced renal oxidative stress. Renal fungal burden was significantly lower in rats that were treated with rutin and experimentally infected with C. neoformans, compared to those treated with saline solution and experimentally infected. Renal reactive oxygen species (ROS) and protein carbonylation levels were significantly higher in experimentally infected rats compared to uninfected controls, whereas catalase (CAT) and glutathione S-transferase (GST) activities were significantly lower. Treatment with rutin prevented the increase in renal ROS levels and the inhibition of CAT activity elicited by C. neoformans var. grubii. However, no significant differences were observed in lipid damage or superoxide dismutase activity. This study is the first to demonstrate that C. neoformans var. grubii infection induces renal oxidative damage in rats by promoting oxidative stress, increasing ROS levels, and impairing antioxidant defenses. Rutin treatment restored redox status in experimental rats through mechanisms involving oxidative stress. The protective effects of rutin against C. neoformans-induced kidney damage may result from its combined ability to scavenge ROS, inhibit protein damage, and enhance the antioxidant system.
氧化应激在感染性疾病的病理生理学中起着关键作用，是发病机制和临床症状出现的诱因。然而，氧化应激在肾脏隐球菌病中的参与程度以及芦丁的潜在保护作用仍然未知。新型隐球菌被认为是隐球菌病的主要病原体，隐球菌病是一种影响内脏器官、危及生命的全身性机会真菌疾病。2022 年，世界卫生组织将其列为真菌性优先病原体名单中的关键优先群体。芦丁是一种具有强效抗氧化和抗真菌特性的类黄酮，被认为是一种保护剂。因此，本研究旨在评估 50 毫克芦丁/千克体重是否能预防或减轻 C. neoformans var.与接受生理盐水治疗和实验性感染的大鼠相比，接受芦丁治疗和实验性感染的大鼠的肾脏真菌负担明显降低。与未感染的对照组相比，实验感染大鼠的肾脏活性氧（ROS）和蛋白质羰基化水平明显升高，而过氧化氢酶（CAT）和谷胱甘肽 S-转移酶（GST）的活性则明显降低。用芦丁治疗可防止新酵母菌变种 grubii 引起的肾脏 ROS 水平升高和 CAT 活性受抑制。然而，在脂质损伤或超氧化物歧化酶活性方面没有观察到明显差异。这项研究首次证明，C. neoformans var. grubii感染会通过促进氧化应激、增加ROS水平和损害抗氧化防御功能来诱导大鼠肾脏氧化损伤。芦丁治疗可通过氧化应激机制恢复实验鼠的氧化还原状态。芦丁对新变形杆菌诱发的肾损伤具有保护作用，这可能是由于芦丁具有清除 ROS、抑制蛋白质损伤和增强抗氧化系统的综合能力。
{"title":"Rutin attenuates oxidative damage-induced renal injury in rats experimentally infected with Cryptococcus neoformans by improving antioxidant capacity and reducing fungal burden","authors":"Rafaela da Silva Rangel , Raquel Tusi Tamiosso , Rúbia Schallenberger da Silva , Laís Suarez da Silva de Oliveira , Maria Fernanda Biscarra Bortolotto Paz , Teodoro Trevisan De Paula Martins , Alice Mazaro , Alana Bianca de Moraes Chitolina , Marina Machado Maurente , Cinthia Melazzo de Andrade , Jandora Lima Ortiz , Isabela Maraschin Vieira , Marcelo Leite da Veiga , Matheus Dellaméa Baldissera","doi":"10.1016/j.micpath.2025.107540","DOIUrl":"10.1016/j.micpath.2025.107540","url":null,"abstract":"<div><div>Oxidative stress plays a pivotal role in the pathophysiology of infectious diseases, contributing to pathogenesis and the appearance of clinical symptoms. However, the involvement of oxidative stress in renal cryptococcosis remains unknown, as do the potential protective effects of rutin. <em>Cryptococcus neoformans</em> is considered the main agent of cryptococcosis, a systemic life-threatening opportunistic fungal disease that affects internal organs. In 2022, the World Health Organization classified it as a critical-priority group on its Fungal Priority Pathogens List. Rutin, a flavonoid with potent antioxidant and antifungal properties, has been proposed as a protective agent. Thus, this study aimed to evaluate whether 50 mg rutin/kg body weight prevents or reduces <em>C. neoformans var. grubii-</em>induced renal oxidative stress. Renal fungal burden was significantly lower in rats that were treated with rutin and experimentally infected with <em>C. neoformans,</em> compared to those treated with saline solution and experimentally infected. Renal reactive oxygen species (ROS) and protein carbonylation levels were significantly higher in experimentally infected rats compared to uninfected controls, whereas catalase (CAT) and glutathione S-transferase (GST) activities were significantly lower. Treatment with rutin prevented the increase in renal ROS levels and the inhibition of CAT activity elicited by <em>C. neoformans var. grubii.</em> However, no significant differences were observed in lipid damage or superoxide dismutase activity. This study is the first to demonstrate that <em>C. neoformans var. grubii</em> infection induces renal oxidative damage in rats by promoting oxidative stress, increasing ROS levels, and impairing antioxidant defenses. Rutin treatment restored redox status in experimental rats through mechanisms involving oxidative stress. The protective effects of rutin against <em>C. neoformans</em>-induced kidney damage may result from its combined ability to scavenge ROS, inhibit protein damage, and enhance the antioxidant system.</div></div>","PeriodicalId":18599,"journal":{"name":"Microbial pathogenesis","volume":"204 ","pages":"Article 107540"},"PeriodicalIF":3.3,"publicationDate":"2025-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143783861","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Salmonella contamination of seafood and its environment is an important public health concern. In this study, Salmonella enterica isolated from seafood in Mumbai, India were seroptyped and further characterized with respect to the distribution of virulence genes associated with Salmonella Pathogenicity Islands (SPIs) and their antimicrobial susceptibilities. The study included 89 isolates which were screened for 11 genes associated with five pathogenicity islands (SPI-1 to SPI-5), two phage-encoded virulence genes, and an enterotoxin gene. The isolates were serotyped into 10 serovars namely S. Typhimurium, S. Bareilly, S. Weltevreden, S. Volta, S. Newport, S. Tennessee, S. Kentucky, S. Lindenburg, S. Paratyphi B and S. Alachua. S. Bareilly (33) was the predominant serovar, followed by S. Typhimurium (15), S. Newport (10), S. Kentucky (9), S. Paratyphi B (8), and S. Tennessee (7). Ten S. Typhimurium and one each of S. Kentucky and S. Paratyphi B isolates possessed all the virulence genes tested, while the remaining isolates lacked one or more virulence genes. The antibiotic susceptibility testing revealed that the isolates were resistant against third-generation cephalosporins, quinolones, fluoroquinolones and tetracycline antibiotics, but sensitive to ceftazidime, aztreonam, carbapenems, chloramphenicol, and aminoglycosides. The diverse serovars of Salmonella contaminating fresh seafood in this geographical region constitute a notable public health concern.
{"title":"Serovar distribution, virulence gene and antibiotic susceptibility profiling of Salmonella enterica isolated from seafood in Mumbai, India","authors":"Parmanand Prabhakar , Manjusha Lekshmi , Parvathi Ammini , Binaya Bhusan Nayak , Sanath Kumar","doi":"10.1016/j.micpath.2025.107530","DOIUrl":"10.1016/j.micpath.2025.107530","url":null,"abstract":"<div><div><em>Salmonella</em> contamination of seafood and its environment is an important public health concern. In this study, <em>Salmonella enterica</em> isolated from seafood in Mumbai, India were seroptyped and further characterized with respect to the distribution of virulence genes associated with <em>Salmonella</em> Pathogenicity Islands (SPIs) and their antimicrobial susceptibilities. The study included 89 isolates which were screened for 11 genes associated with five pathogenicity islands (SPI-1 to SPI-5), two phage-encoded virulence genes, and an enterotoxin gene. The isolates were serotyped into 10 serovars namely <em>S</em>. Typhimurium, <em>S</em>. Bareilly, <em>S</em>. Weltevreden, <em>S</em>. Volta, <em>S</em>. Newport, <em>S</em>. Tennessee, <em>S</em>. Kentucky, <em>S</em>. Lindenburg, <em>S</em>. Paratyphi B and <em>S</em>. Alachua. <em>S</em>. Bareilly (33) was the predominant serovar, followed by <em>S.</em> Typhimurium (15)<em>, S.</em> Newport (10)<em>, S.</em> Kentucky (9)<em>, S.</em> Paratyphi B (8)<em>,</em> and <em>S.</em> Tennessee (7). Ten <em>S</em>. Typhimurium and one each of <em>S</em>. Kentucky and <em>S</em>. Paratyphi B isolates possessed all the virulence genes tested, while the remaining isolates lacked one or more virulence genes. The antibiotic susceptibility testing revealed that the isolates were resistant against third-generation cephalosporins, quinolones, fluoroquinolones and tetracycline antibiotics, but sensitive to ceftazidime, aztreonam, carbapenems, chloramphenicol, and aminoglycosides. The diverse serovars of <em>Salmonella</em> contaminating fresh seafood in this geographical region constitute a notable public health concern.</div></div>","PeriodicalId":18599,"journal":{"name":"Microbial pathogenesis","volume":"204 ","pages":"Article 107530"},"PeriodicalIF":3.3,"publicationDate":"2025-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143788726","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-04-03DOI: 10.1016/j.micpath.2025.107537
Mahsa Niknam, Leila Sadeghi, Gholamreza Zarrini
The rise of antibiotic-resistant bacteria necessitates the development of novel antimicrobial agents. In this study, antimicrobial peptides (AMPs) were isolated from Lactobacillus sp., yielding Bioactive Peptide I (BAP I) and Bioactive Peptide III (BAP III). Purified via gel filtration chromatography (GFC), these peptides were characterized by MALDI-TOF MS and SDS-PAGE, which confirmed their molecular masses as 4168.14 Da and 8076.45 Da, respectively, and verified their high purity. Both peptides demonstrated potent antibacterial activity against Pseudomonas aeruginosa, Streptococcus sanguinis, Bacillus cereus, and Staphylococcus aureus, with BAP I exhibiting superior efficacy. This enhanced activity is likely due to its amphipathic structure and hydrophobic C-terminal region, which promote effective bacterial membrane disruption as evidenced by FE-SEM imaging. In addition to compromising membrane integrity, both BAP I and BAP III inhibited bacterial DNA polymerase activity, as shown by reduced PCR product formation. Complementary Circular Dichroism (CD) spectroscopy analysis indicated that peptide binding induced conformational changes in Taq polymerase, reducing its α-helical and β-sheet content while increasing the proportion of random coil structures—thus enhancing the enzyme's flexibility. Molecular docking and dynamics studies further revealed stable interactions between the peptides and the enzyme, suggesting a dual mechanism of action that targets both the bacterial membrane and DNA replication processes. Collectively, these findings highlight the significant potential of BAP I and BAP III as novel antimicrobial agents against multidrug-resistant infections. Future research should focus on evaluating their safety and clinical efficacy, as well as exploring their synergistic potential with existing antibiotics to advance these peptides as therapeutic alternatives.
{"title":"Isolation and characterization of antimicrobial peptides from Lactobacillus: Exploring mechanisms of action","authors":"Mahsa Niknam, Leila Sadeghi, Gholamreza Zarrini","doi":"10.1016/j.micpath.2025.107537","DOIUrl":"10.1016/j.micpath.2025.107537","url":null,"abstract":"<div><div>The rise of antibiotic-resistant bacteria necessitates the development of novel antimicrobial agents. In this study, antimicrobial peptides (AMPs) were isolated from <em>Lactobacillus</em> sp., yielding Bioactive Peptide I (BAP I) and Bioactive Peptide III (BAP III). Purified via gel filtration chromatography (GFC), these peptides were characterized by MALDI-TOF MS and SDS-PAGE, which confirmed their molecular masses as 4168.14 Da and 8076.45 Da, respectively, and verified their high purity. Both peptides demonstrated potent antibacterial activity against <em>Pseudomonas aeruginosa</em>, <em>Streptococcus sanguinis</em>, <em>Bacillus cereus</em>, and <em>Staphylococcus aureus</em>, with BAP I exhibiting superior efficacy. This enhanced activity is likely due to its amphipathic structure and hydrophobic C-terminal region, which promote effective bacterial membrane disruption as evidenced by FE-SEM imaging. In addition to compromising membrane integrity, both BAP I and BAP III inhibited bacterial DNA polymerase activity, as shown by reduced PCR product formation. Complementary Circular Dichroism (CD) spectroscopy analysis indicated that peptide binding induced conformational changes in Taq polymerase, reducing its α-helical and β-sheet content while increasing the proportion of random coil structures—thus enhancing the enzyme's flexibility. Molecular docking and dynamics studies further revealed stable interactions between the peptides and the enzyme, suggesting a dual mechanism of action that targets both the bacterial membrane and DNA replication processes. Collectively, these findings highlight the significant potential of BAP I and BAP III as novel antimicrobial agents against multidrug-resistant infections. Future research should focus on evaluating their safety and clinical efficacy, as well as exploring their synergistic potential with existing antibiotics to advance these peptides as therapeutic alternatives.</div></div>","PeriodicalId":18599,"journal":{"name":"Microbial pathogenesis","volume":"204 ","pages":"Article 107537"},"PeriodicalIF":3.3,"publicationDate":"2025-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143785180","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
The novel coronavirus, COVID-19, which was first identified in December 2019 rapidly spread worldwide and was declared a global pandemic. Beyond respiratory symptoms, COVID-19 often results in coagulation and vascular endothelium disorders, causing increased clotting and bleeding, which are closely linked to the acute phase of the infection. Factor VIII is a crucial protein in the blood coagulation cascade, and elevated FVIII levels have been linked to thrombotic events in COVID-19, highlighting the need to understand its behavior during treatment. Remdesivir is an antiviral drug that has shown promise in reducing recovery time and mortality rates in COVID-19 patients. This study aims to examine the changes in blood factors and the expression of the factor VIII gene in patients treated with Remdesivir. Blood samples were collected from 30 COVID-19 patients before and after Remdesivir treatment and from 20 healthy individuals. Patients with underlying diseases were excluded from the study. RNA was extracted from these samples, followed by cDNA synthesis. The expression of the factor VIII gene was analyzed using Real-Time PCR. The results indicated that blood factors such as Urea, ALK, AST, WBC, and CRP were elevated in the patient group compared to the control group. At the same time, FBS, Urea, ALK, AST, WBC, RDW, INR, and K levels increased in the Remdesivir treatment group (P<0.001). Conversely, MCHC, RBC, and Ca levels decreased in both patient and treatment groups compared to the control group (P<0.001). The expression of the FVIII gene was upregulated approaching 2 times in COVID-19 patients and 1.5-fold in the treatment group compared to the control group (P<0.001). However, no significant changes were observed in FVIII expression before and after Remdesivir treatment. However, a positive correlation between RBC, FBS, and Urea in the patient group and a negative correlation between RDW and FVIII expression levels was observed. In the treatment group, FVIII expression level correlated negatively with Urea, P, and RDW. These findings suggest that elevated FVIII levels are associated with disease severity and excessive coagulation in COVID-19 patients. Additionally, Remdesivir does not appear to exacerbate the coagulation process.
{"title":"Impact of Remdesivir Treatment on Factor VIII Gene Expression and Hematological Parameters in COVID-19 Patients.","authors":"Ghazal Kakavand, Somayeh Arabzadeh, Sohameh Mohebbi, Kayvan Saeedfar, Atefeh Abedini, Masoud Mardani","doi":"10.1016/j.micpath.2025.107536","DOIUrl":"https://doi.org/10.1016/j.micpath.2025.107536","url":null,"abstract":"<p><p>The novel coronavirus, COVID-19, which was first identified in December 2019 rapidly spread worldwide and was declared a global pandemic. Beyond respiratory symptoms, COVID-19 often results in coagulation and vascular endothelium disorders, causing increased clotting and bleeding, which are closely linked to the acute phase of the infection. Factor VIII is a crucial protein in the blood coagulation cascade, and elevated FVIII levels have been linked to thrombotic events in COVID-19, highlighting the need to understand its behavior during treatment. Remdesivir is an antiviral drug that has shown promise in reducing recovery time and mortality rates in COVID-19 patients. This study aims to examine the changes in blood factors and the expression of the factor VIII gene in patients treated with Remdesivir. Blood samples were collected from 30 COVID-19 patients before and after Remdesivir treatment and from 20 healthy individuals. Patients with underlying diseases were excluded from the study. RNA was extracted from these samples, followed by cDNA synthesis. The expression of the factor VIII gene was analyzed using Real-Time PCR. The results indicated that blood factors such as Urea, ALK, AST, WBC, and CRP were elevated in the patient group compared to the control group. At the same time, FBS, Urea, ALK, AST, WBC, RDW, INR, and K levels increased in the Remdesivir treatment group (P<0.001). Conversely, MCHC, RBC, and Ca levels decreased in both patient and treatment groups compared to the control group (P<0.001). The expression of the FVIII gene was upregulated approaching 2 times in COVID-19 patients and 1.5-fold in the treatment group compared to the control group (P<0.001). However, no significant changes were observed in FVIII expression before and after Remdesivir treatment. However, a positive correlation between RBC, FBS, and Urea in the patient group and a negative correlation between RDW and FVIII expression levels was observed. In the treatment group, FVIII expression level correlated negatively with Urea, P, and RDW. These findings suggest that elevated FVIII levels are associated with disease severity and excessive coagulation in COVID-19 patients. Additionally, Remdesivir does not appear to exacerbate the coagulation process.</p>","PeriodicalId":18599,"journal":{"name":"Microbial pathogenesis","volume":" ","pages":"107536"},"PeriodicalIF":3.3,"publicationDate":"2025-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143788612","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-04-03DOI: 10.1016/j.micpath.2025.107532
Hanan Y. Aati , Momen M. Lotfy , Areej Al-tweel , Basmah Al-enezi , Karim Abdelkader , Sameh F. AbouZid , Mostafa E. Rateb , Hossam M. Hassan , Rabab Mohammed , Dalia El Amir
Objective
This study aims to assess the antibacterial potential of kojic acid produced by Trichoderma harzianum, a fungus isolated from the River Nile, and its potential application as a natural food preservative against Listeria monocytogenes.
Methods
A comprehensive chemical analysis of the ethyl acetate extract of T. harzianum was conducted using chromatographic and spectroscopic techniques. The isolated compounds were subsequently evaluated for their antibacterial activity and cytotoxic effects.
Results
Three major secondary metabolites were identified and purified from T. harzianum: kojic acid, di-(2-ethylhexyl) phthalate, and phomaligol A. Among these, only kojic acid demonstrated moderate antibacterial activity against L. monocytogenes, with negligible cytotoxicity against liver and colorectal cancer cell lines (IC50: 41.34 ± 1.7 μM and 17.35 ± 0.8 μM, respectively). In situ studies revealed a dose-dependent antibacterial effect of kojic acid against L. monocytogenes in skimmed milk. Further evaluation across different dairy products indicated that its efficacy was influenced by fat content, leading to a bacterial count reduction of up to 4.17 log units. Additionally, kojic acid effectively inhibited bacterial growth under both low and high contamination levels. Notably, it preserved milk stored at room temperature by preventing bacterial overgrowth for up to four days.
Conclusion
These findings suggest that kojic acid possesses significant potential as a natural milk preservative due to its selective antibacterial activity against L. monocytogenes and favorable safety profile. As a result, kojic acid could serve as a viable alternative to synthetic chemical preservatives in dairy products.
{"title":"Kojic acid: A River Nile-derived fungal secondary metabolite with preservative potential against Listeria monocytogenes in milk","authors":"Hanan Y. Aati , Momen M. Lotfy , Areej Al-tweel , Basmah Al-enezi , Karim Abdelkader , Sameh F. AbouZid , Mostafa E. Rateb , Hossam M. Hassan , Rabab Mohammed , Dalia El Amir","doi":"10.1016/j.micpath.2025.107532","DOIUrl":"10.1016/j.micpath.2025.107532","url":null,"abstract":"<div><h3>Objective</h3><div>This study aims to assess the antibacterial potential of kojic acid produced by <em>Trichoderma harzianum</em>, a fungus isolated from the River Nile, and its potential application as a natural food preservative against <em>Listeria monocytogenes</em>.</div></div><div><h3>Methods</h3><div>A comprehensive chemical analysis of the ethyl acetate extract of <em>T. harzianum</em> was conducted using chromatographic and spectroscopic techniques. The isolated compounds were subsequently evaluated for their antibacterial activity and cytotoxic effects.</div></div><div><h3>Results</h3><div>Three major secondary metabolites were identified and purified from <em>T. harzianum</em>: kojic acid, di-(2-ethylhexyl) phthalate, and phomaligol A. Among these, only kojic acid demonstrated moderate antibacterial activity against <em>L. monocytogenes</em>, with negligible cytotoxicity against liver and colorectal cancer cell lines (IC<sub>50</sub>: 41.34 ± 1.7 μM and 17.35 ± 0.8 μM, respectively). In situ studies revealed a dose-dependent antibacterial effect of kojic acid against <em>L. monocytogenes</em> in skimmed milk. Further evaluation across different dairy products indicated that its efficacy was influenced by fat content, leading to a bacterial count reduction of up to 4.17 log units. Additionally, kojic acid effectively inhibited bacterial growth under both low and high contamination levels. Notably, it preserved milk stored at room temperature by preventing bacterial overgrowth for up to four days.</div></div><div><h3>Conclusion</h3><div>These findings suggest that kojic acid possesses significant potential as a natural milk preservative due to its selective antibacterial activity against <em>L. monocytogenes</em> and favorable safety profile. As a result, kojic acid could serve as a viable alternative to synthetic chemical preservatives in dairy products.</div></div>","PeriodicalId":18599,"journal":{"name":"Microbial pathogenesis","volume":"204 ","pages":"Article 107532"},"PeriodicalIF":3.3,"publicationDate":"2025-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143785181","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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