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OBJECTIVES: To investigate cases of five Campylobacter jejuni outbreaks and describe laboratory characteristics of these infections. METHODS: Whole-genome sequencing and conventional methods were combined to thoroughly investigate the outbreaks, and data of contemporaneous sporadic cases was included for comparison. RESULTS: Seven sequence types (STs) of C. jejuni caused 83 cases, including ST9079 which recurred across 2 years. Trace-back investigation could not identify any food items of infection but detected identical campylobacters from food contacts. Phylogenetic analysis unveiled genetic closeness between outbreak strains and some concurrent sporadic strains, indicating local campylobacteriosis may not be wholly sporadic but rather a series of linked cases. Virulence genes disclosed species/case-specific signatures to differentiate outbreaks from truly non-outbreak strains. Resistance to fluoroquinolones and/or macrolides was prevalent (90.8%, 108/119), with a noteworthy portion exhibiting multidrug resistance (31.1%, 37/119). Five types of plasmids were harbored among outbreak isolates, of which one plasmid harboring anti-stress and resistant genes was rarely found in C. jejuni. CONCLUSIONS: This is the first reported sequential outbreak of C. jejuni in China. Our observations help to define the genomic landscape and antimicrobial resistance patterns of Campylobacter, emphasizing the need for a broader 'One Health' perspective to combat the threats posed by campylobacteriosis.
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Antibacterianos , Infecciones por Campylobacter , Campylobacter jejuni , Brotes de Enfermedades , Filogenia , Secuenciación Completa del Genoma , Campylobacter jejuni/genética , Campylobacter jejuni/efectos de los fármacos , Campylobacter jejuni/aislamiento & purificación , Campylobacter jejuni/clasificación , Humanos , China/epidemiología , Infecciones por Campylobacter/epidemiología , Infecciones por Campylobacter/microbiología , Adulto , Niño , Masculino , Femenino , Antibacterianos/farmacología , Adolescente , Persona de Mediana Edad , Farmacorresistencia Bacteriana Múltiple/genética , Adulto Joven , Preescolar , Pruebas de Sensibilidad Microbiana , Plásmidos/genética , Genoma BacterianoRESUMEN
Increasing human salmonellosis caused by Salmonella enterica serovar Kentucky and London has raised serious concerns. To better understand possible health risks, insights were provided into specific genetic traits and antimicrobial resistance of 88 representative isolates from human and food sources in Zhejiang Province, China, during 2016-2021. Phylogenomic analysis revealed consistent clustering of isolates into the respective serovar or sequence types, and identified plausible interhost transmission via distinct routes. Each serovar exhibited remarkable diversity in host range and disease-causing potential by cgMLST analyses, and approximately half (48.6%, 17/35) of the food isolates were phylogenetically indistinguishable to those of clinical isolates in the same region. S. London and S. Kentucky harbored serovar-specific virulence genes contributing to their functions in pathogenesis. The overall resistance genotypes correlated with 97.7% sensitivity and 60.2% specificity to the identified phenotypes. Resistance to ciprofloxacin, cefazolin, tetracycline, ampicillin, azithromycin, chloramphenicol, as well as multidrug resistance, was common. High-level dual resistance to ciprofloxacin and cephalosporins in S. Kentucky ST198 isolates highlights evolving threats of antibiotic resistance. These findings underscored the necessity for the development of effective strategies to mitigate the risk of food contamination by Salmonella host-restricted serovars.
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Campylobacter is a zoonotic pathogen that causes foodborne diarrheal illness globally. To better understand health risks in Southeastern China, Campylobacter spp. were surveyed in humans and representative poultry products over 3 years. One hundred and ninety-five representative isolates (n = 148, Campylobacter jejuni; n = 45, Campylobacter coli; n = 2 Campylobacter hyointestinalis) were examined for genetic relatedness and antimicrobial susceptibility. Nearly all Campylobacter isolates (99.0%, 193/195) were resistant to at least one class of antimicrobials, and 45.6% (89/195) of the isolates exhibited multidrug resistance. Genotypic analysis revealed high diversity among tested strains. Multilocus sequence typing (MLST) displayed 120 sequence types (STs) including 42 novel STs being added to the PubMLST international database. Sixty-two STs belonged to 16 previously characterized clonal complexes (CCs), of which CC-21, CC-45, CC-464, CC-574, CC-353, and CC-828 were most frequently identified. In addition, pulsed-field gel electrophoresis (PFGE) fingerprinting resulted in 66 PFGE SmaI patterns among the 125 isolates, with eight patterns shared between human and poultry sources. Subtyping data did not correlate with antimicrobial resistance phenotypes. Taken together, this large-scale surveillance study highlights high antimicrobial resistance and molecular features of Campylobacter isolates in Southeastern China.
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The aim of the present study was to examine the potential role of human heparinbinding epidermal growth factor (HBEGF) secreted by M2 macrophages in the development of radioresistance in head and neck squamous cell carcinoma (HNSCC). Immunohistochemistry was used to detect radiosensitivity in human papilloma virus (HPV)positive and HPVnegative HNSCC tissues and immunohistochemical staining with specific antibodies for macrophage surface markers was used to assess the infiltration of M1 and M2 macrophages in HPVpositive and negative HNSCC tissues. The expression of HBEGF in HPVpositive and negative HNSCC tissues was determined by multicytokine detection in order to determine the relationship between HBEGF and radiosensitivity. M1 and M2 macrophages were cocultured with the HNSCC cell line CAL27 and treated with HBEGF and its neutralizing antibodies to assess radiation sensitivity. Finally, the major DNA doublestrand break repair pathways required for the activation of HBEGF and promotion of epidermal growth factor receptor (EGFR) were identified. The results revealed that radiosensitivity was higher in HPVpositive HNSCC compared with HPVnegative. There was a higher infiltration of M2 macrophages in HPVnegative HNSCC, which were revealed as the main source of HBEGF secretion. Furthermore, it was determined that overexpression of HBEGF induced radioresistance in HPVnegative HNSCC. HBEGF promoted the activation of the nonhomologous endjoining pathway by activating EGFR. To the best of our knowledge, this is the first study to demonstrate the association between HBEGF and radiosensitivity in HNSCC. These results indicated that the secretion of HBEGF by M2 macrophages could induce radioresistance of HPVnegative HNSCC.
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Neoplasias de Cabeza y Cuello/radioterapia , Factor de Crecimiento Similar a EGF de Unión a Heparina/metabolismo , Macrófagos/inmunología , Infecciones por Papillomavirus/radioterapia , Tolerancia a Radiación/inmunología , Carcinoma de Células Escamosas de Cabeza y Cuello/radioterapia , Línea Celular Tumoral , Técnicas de Cocultivo , Roturas del ADN de Doble Cadena/efectos de la radiación , Reparación del ADN por Unión de Extremidades , Receptores ErbB/metabolismo , Femenino , Neoplasias de Cabeza y Cuello/inmunología , Neoplasias de Cabeza y Cuello/patología , Neoplasias de Cabeza y Cuello/virología , Humanos , Macrófagos/metabolismo , Masculino , Persona de Mediana Edad , Papillomaviridae/aislamiento & purificación , Infecciones por Papillomavirus/inmunología , Infecciones por Papillomavirus/patología , Infecciones por Papillomavirus/virología , Carcinoma de Células Escamosas de Cabeza y Cuello/inmunología , Carcinoma de Células Escamosas de Cabeza y Cuello/patología , Carcinoma de Células Escamosas de Cabeza y Cuello/virologíaRESUMEN
Radiation is a crucial component of head and neck squamous cell carcinoma (HNSC) treatment. Human papillomavirus-positive (HPV+) HNSC is significantly more radiosensitive than HPV- HNSC, but the mechanism underlying this increased sensitivity is unknown. We investigated the possible involvement of macrophage subpopulations as key mediators of HNSC radiosensitivity linked to HPV status. We collected forty-one clinical HNSC specimens and determined HPV status and radiosensitivity of each sample. We investigated cytokine mediated induction of macrophage polarization by HPV+ and HPV- HNSC cells. Radiosensitive HNSC tissues exhibited greater numbers of infiltrating M1 macrophages than radioresistant tumor tissue samples. Moreover, M1 macrophage numbers were positively correlated with HNSC radiosensitivity. HPV+ and HPV- tumor cells induced macrophage polarization to M1 and M2 type, respectively. HPV+ HNSC cells secreted more IL-6 than HPV- cells. HPV promoted tumor cell secretion of IL-6, thereby increasing radiosensitivity through M1 polarization of macrophages. M1 macrophages represent an important tissue microenvironment factor with implications for HNSC treatment efficacy and may prove valuable as a biomarker of radiation sensitivity.
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Neoplasias de Cabeza y Cuello/radioterapia , Papillomavirus Humano 16/patogenicidad , Papillomavirus Humano 18/patogenicidad , Interleucina-6/metabolismo , Macrófagos/metabolismo , Tolerancia a Radiación , Carcinoma de Células Escamosas de Cabeza y Cuello/radioterapia , Adulto , Anciano , Técnicas de Cocultivo , Femenino , Neoplasias de Cabeza y Cuello/metabolismo , Neoplasias de Cabeza y Cuello/patología , Neoplasias de Cabeza y Cuello/virología , Interacciones Huésped-Patógeno , Humanos , Macrófagos/patología , Macrófagos/virología , Masculino , Persona de Mediana Edad , Comunicación Paracrina , Fenotipo , Transducción de Señal , Carcinoma de Células Escamosas de Cabeza y Cuello/metabolismo , Carcinoma de Células Escamosas de Cabeza y Cuello/patología , Carcinoma de Células Escamosas de Cabeza y Cuello/virología , Células THP-1 , Microambiente TumoralRESUMEN
BACKGROUND/AIMS: Human papillomavirus (HPV) is an etiological risk factor for a subset of head and neck squamous cell carcinomas. HPV has been proven to be a powerful prognostic biomarker for oropharyngeal cancer, but its role in the larynx has not been explored in depth. Here, we sought to evaluate the prevalence and genotype distribution of HPV in patients with laryngeal squamous cell carcinoma (LSCC) in northeast China. METHODS: HPV DNA in specimens from 211 patients diagnosed with LSCC was analyzed by the polymerase chain reaction and in situ hybridization, and p16 overexpression was evaluated by immunohistochemistry. p16 expression was scored positive if strong and diffuse nuclear and cytoplasmic staining was present in > 75% of tumor cells. RESULTS: In this study, infection with HPV and p16 expression were not absolutely consistent. Among all patients, 132 (62.6%) were positive for HPV DNA (HPV+), while 23 (10.9%) were inconsistent for HPV and p16. Multivariate analysis indicated that HPV, but not p16, is an independent prognostic factor for overall survival in LSCC. Overall survival was significantly improved in HPV+ LSCC patients compared with the HPV-negative group (hazard ratio, 0.395; 95% confidence interval, 0.185-0.843; p = 0.016). Among the 132 HPV+ patients, 28 (21.2%) were HPV-16 single infection. CONCLUSION: This study indicates that HPV DNA is a more reliable surrogate marker than p16 for the prediction of survival in patients with LSCC.
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Carcinoma de Células Escamosas/diagnóstico , Neoplasias Laríngeas/diagnóstico , Papillomaviridae/genética , Adulto , Anciano , Anciano de 80 o más Años , Carcinoma de Células Escamosas/epidemiología , Carcinoma de Células Escamosas/mortalidad , Carcinoma de Células Escamosas/virología , China/epidemiología , Inhibidor p16 de la Quinasa Dependiente de Ciclina/metabolismo , ADN Viral/metabolismo , Femenino , Humanos , Estimación de Kaplan-Meier , Neoplasias Laríngeas/epidemiología , Neoplasias Laríngeas/mortalidad , Neoplasias Laríngeas/virología , Masculino , Persona de Mediana Edad , Papillomaviridae/aislamiento & purificación , Prevalencia , Pronóstico , Modelos de Riesgos ProporcionalesRESUMEN
Human papillomavirus-positive (HPV+) head and neck squamous cell cancer (HNSCC) exhibits a better prognosis than HPV-negative (HPV-) HNSCC. This difference may in part be due to enhanced immune activation in the HPV+ HNSCC tumor microenvironment. To characterize differences in immune activation between HPV+ and HPV- HNSCC tumors, we identified and annotated differentially expressed genes based upon mRNA expression data from The Cancer Genome Atlas (TCGA). Immune network between immune cells and cytokines was constructed by using single sample Gene Set Enrichment Analysis and conditional mutual information. Multivariate Cox regression analysis was used to determine the prognostic value of immune microenvironment characterization. A total of 1673 differentially expressed genes were functionally annotated. We found that genes upregulated in HPV+ HNSCC are enriched in immune-associated processes. And the up-regulated gene sets were validated by Gene Set Enrichment Analysis. The microenvironment of HPV+ HNSCC exhibited greater numbers of infiltrating B and T cells and fewer neutrophils than HPV- HNSCC. These findings were validated by two independent datasets in the Gene Expression Omnibus (GEO) database. Further analyses of T cell subtypes revealed that cytotoxic T cell subtypes predominated in HPV+ HNSCC. In addition, the ratio of M1/M2 macrophages was much higher in HPV+ HNSCC. The infiltration of these immune cells was correlated with differentially expressed cytokine-associated genes. Enhanced infiltration of B cells and CD8+ T cells were identified as independent protective factors, while high neutrophil infiltration was a risk enhancing factor for HPV+ HNSCC patients. A schematic model of immunological network was established for HPV+ HNSCC to summarize our findings.
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Linfocitos Infiltrantes de Tumor/inmunología , Infecciones por Papillomavirus/inmunología , Carcinoma de Células Escamosas de Cabeza y Cuello/inmunología , Microambiente Tumoral/inmunología , Adulto , Anciano , Linfocitos B/inmunología , Femenino , Humanos , Macrófagos/inmunología , Masculino , Persona de Mediana Edad , Papillomaviridae/inmunología , Subgrupos de Linfocitos T/inmunología , TranscriptomaRESUMEN
Cell invasion is crucial for high mortality and recurrence rate in glioma. Epithelial-mesenchymal transition (EMT) is an important step in cancer invasion. Metadherin (MTDH) contributes to EMT in several cancers, but the role and mechanism of MTDH in EMT-like process of glioma remain unknown. Here we demonstrate that MTDH was overexpressed in glioma tissues and cells and induced EMT-like change and invasion of glioma cells. Interestingly, MTDH could modulate the expression of a group of glioma-related miRNAs. In particular, MTDH upregulated miR-130b transcription via acting as a coactivator of NF-kB. MiR-130b promoted EMT-like change and invasion of glioma cells through targeting multiple EMT-related genes, including PTEN, PPP2CA and SMAD7. In addition, PTEN acted as the competing endogenous RNA (ceRNA) to affect PPP2CA and SMAD7 expression, and inhibited EMT-like change in glioma cells. Furthermore, miR-130b mediated EMT-like change induced by MTDH, and MTDH inhibited the expression levels of PTEN, PPP2CA and SMAD7. Taken together, we reveal a novel mechanism that MTDH induces EMT-like change and invasion of glioma via the regulation of miR-130b-ceRNAs, providing the first direct link between MTDH and miRNAs in cancer cells.
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Moléculas de Adhesión Celular/metabolismo , Transición Epitelial-Mesenquimal/genética , Glioma/genética , Glioma/patología , MicroARNs/genética , Línea Celular Tumoral , Movimiento Celular/genética , Regulación Neoplásica de la Expresión Génica , Células HEK293 , Humanos , Proteínas de la Membrana , MicroARNs/biosíntesis , FN-kappa B/metabolismo , Invasividad Neoplásica/patología , Recurrencia Local de Neoplasia/genética , Fosfohidrolasa PTEN/genética , Proteína Fosfatasa 2/genética , Proteínas de Unión al ARN , Transducción de Señal , Proteína smad7/genéticaRESUMEN
Persistent infection with human papillomavirus (HPV), particularly type 16, is causally associated with cervical cancer and its precursors. The role of miRNAs in HPV16 persistence currently remains unclear. Preliminary analysis of miRNA profile demonstrated that HPV16 infection caused a striking downregulation of miR-34a. Through bioinformatics analysis and dual-luciferase assay with site-directed mutagenesis strategy, NLRC5, a negative regulator of NF-κB signaling, was identified to be a novel interactor of miR-34a. Transfection of miR-34a mimic strikingly downregulated NLRC5 in the HPV16-positive cervical cells, which might result in the nuclear accumulation of NF-κB p65. However, transfection of miR-34a inhibitor exhibited an opposite effect. The antagonistic expressions of NLRC5 and miR-34a were also observed in keratinocytes harboring HPV16 genome as well as in human cervical samples with persistent infection of HPV16. Our data uncover a previously unknown connection among HPV16 persistence, miR-34a and its interactor NLRC5.