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1.
FASEB J ; 38(6): e23552, 2024 Mar 31.
Artigo em Inglês | MEDLINE | ID: mdl-38498336

RESUMO

Sex and gender disparities in biomedical research have been emphasized to improve scientific knowledge applied for the health of both men and women. Despite sex differences in cancer incidence, prognosis, and responses to therapeutic agents, mechanistic explanations at molecular levels are far from enough. Recent studies suggested that cell sex is an important biological variable due to differences in sex chromosome gene expression and differences in events associated with developmental biology. The objective of this study was to analyze the reporting of sex of cells used in cancer research using articles published in Cancer Cell, Molecular Cancer, Journal of Hematology & Oncology, Journal for ImmunoTherapy of Cancer, and Cancer Research in 2020, and to examine whether there exists any sex bias. We found that the percentage of cells with sex notation in the article was 36.5%. Primary cells exhibited higher sex notation compared to cell lines. A higher percentage of female cells were used in cell cultures with sex notation. Also, sex-common cells omitted sex description more often compared to sex-specific cells. None of the cells isolated from embryo and esophagus reported the cell sex in the article. Our results indicate cell sex report in cancer research is limited to a small proportion of cells used in the study. These results call for acknowledging the sex of cells to increase the applicability of biomedical research discoveries.


Assuntos
Pesquisa Biomédica , Células Cultivadas , Neoplasias , Feminino , Humanos , Masculino , Publicações , Fatores Sexuais , Sexismo
2.
Immunity ; 44(4): 889-900, 2016 Apr 19.
Artigo em Inglês | MEDLINE | ID: mdl-27084119

RESUMO

Metagenomic studies show that diverse resident viruses inhabit the healthy gut; however, little is known about the role of these viruses in the maintenance of gut homeostasis. We found that mice treated with antiviral cocktail displayed more severe dextran sulfate sodium (DSS)-induced colitis compared with untreated mice. DSS-induced colitis was associated with altered enteric viral abundance and composition. When wild-type mice were reconstituted with Toll-like receptor 3 (TLR3) or TLR7 agonists or inactivated rotavirus, colitis symptoms were significantly ameliorated. Mice deficient in both TLR3 and TLR7 were more susceptible to DSS-induced experimental colitis. In humans, combined TLR3 and TLR7 genetic variations significantly influenced the severity of ulcerative colitis. Plasmacytoid dendritic cells isolated from inflamed mouse colon produced interferon-ß in a TLR3 and TLR7-dependent manner. These results imply that recognition of resident viruses by TLR3 and TLR7 is required for protective immunity during gut inflammation.


Assuntos
Colite/imunologia , Trato Gastrointestinal/virologia , Interferon beta/imunologia , Glicoproteínas de Membrana/imunologia , Rotavirus/imunologia , Receptor 3 Toll-Like/imunologia , Receptor 7 Toll-Like/imunologia , Animais , Antivirais/farmacologia , Colite/induzido quimicamente , Células Dendríticas/imunologia , Sulfato de Dextrana , Microbioma Gastrointestinal , Trato Gastrointestinal/imunologia , Humanos , Inflamação/imunologia , Interferon beta/biossíntese , Glicoproteínas de Membrana/genética , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Knockout , RNA Ribossômico 16S/genética , Receptor 3 Toll-Like/genética , Receptor 7 Toll-Like/genética
3.
Nucleic Acids Res ; 51(12): 6143-6155, 2023 07 07.
Artigo em Inglês | MEDLINE | ID: mdl-37158258

RESUMO

Somatic stem cells contribute to normal tissue homeostasis, and their epigenomic features play an important role in regulating tissue identities or developing disease states. Enhancers are one of the key players controlling chromatin context-specific gene expression in a spatial and temporal manner while maintaining tissue homeostasis, and their dysregulation leads to tumorigenesis. Here, epigenomic and transcriptomic analyses reveal that forkhead box protein D2 (FOXD2) is a hub for the gene regulatory network exclusive to large intestinal stem cells, and its overexpression plays a significant role in colon cancer regression. FOXD2 is positioned at the closed chromatin and facilitates mixed-lineage leukemia protein-4 (MLL4/KMT2D) binding to deposit H3K4 monomethylation. De novo FOXD2-mediated chromatin interactions rewire the regulation of p53-responsive genes and induction of apoptosis. Taken together, our findings illustrate the novel mechanistic details of FOXD2 in suppressing colorectal cancer growth and suggest its function as a chromatin-tuning factor and a potential therapeutic target for colorectal cancer.


Assuntos
Neoplasias Colorretais , Histonas , Humanos , Cromatina/genética , Neoplasias Colorretais/genética , Neoplasias Colorretais/metabolismo , Elementos Facilitadores Genéticos , Fatores de Transcrição Forkhead/genética , Fatores de Transcrição Forkhead/metabolismo , Histonas/genética , Histonas/metabolismo
4.
Cancer Immunol Immunother ; 73(6): 101, 2024 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-38630265

RESUMO

BACKGROUND: Adoptive transfer of in vitro expanded tumor-infiltrating lymphocytes (TILs) has been effective in regressing several types of malignant tumors. This study assessed the yield and factors influencing the successful expansion of tumor-infiltrating lymphocytes (TILs) from head and neck squamous cell carcinoma (HNSCC), along with their immune phenotypes. METHODS: TILs were expanded from 47 surgically resected HNSCC specimens and their metastasized lymph nodes. The cancer tissues were cut into small pieces (1-2 mm) and underwent initial expansion for 2 weeks. Tumor location, smoking history, stromal TIL percentage, human papillomavirus infection, and programmed death-ligand 1 score were examined for their impact on successful expansion of TILs. Expanded TILs were evaluated by flow cytometry using fluorescence-activated cell sorting. A second round of TIL expansion following the rapid expansion protocol was performed on a subset of samples with successful TIL expansion. RESULTS: TILs were successfully expanded from 36.2% samples. Failure was due to contamination (27.6%) or insufficient expansion (36.2%). Only the stromal TIL percentage was significantly associated with successful TIL expansion (p = 0.032). The stromal TIL percentage also displayed a correlation with the expanded TILs per fragment (r = 0.341, p = 0.048). On flow cytometry analysis using 13 samples with successful TIL expansion, CD4 + T cell dominancy was seen in 69.2% of cases. Effector memory T cells were the major phenotype of expanded CD4 + and CD8 + T cells in all cases. CONCLUSION: We could expand TILs from approximately one-third of HNSCC samples. TIL expansion could be applicable in HNSCC samples with diverse clinicopathological characteristics.


Assuntos
Neoplasias de Cabeça e Pescoço , Imunoterapia Adotiva , Humanos , Linfócitos do Interstício Tumoral , Carcinoma de Células Escamosas de Cabeça e Pescoço/terapia , Transferência Adotiva , Neoplasias de Cabeça e Pescoço/terapia
5.
J Autoimmun ; 145: 103206, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38554656

RESUMO

Crohn's disease (CD) is a chronic inflammatory disorder affecting the bowel wall. Tissue-resident memory T (Trm) cells are implicated in CD, yet their characteristics remain unclear. We aimed to investigate the transcriptional profiles and functional characteristics of Trm cells in the small bowel of CD and their interactions with immune cells. Seven patients with CD and four with ulcerative colitis as controls were included. Single-cell RNA sequencing and paired T cell receptor sequencing assessed T cell subsets and transcriptional signatures in lamina propria (LP) and submucosa/muscularis propria-enriched fractions (SM/MP) from small bowel tissue samples. We detected 58,123 T cells grouped into 16 populations, including the CD4+ Trm cells with a Th17 signature and CD8+ Trm clusters. In CD, CD4+ Trm cells with a Th17 signature, termed Th17 Trm, showed significantly increased proportions within both the LP and SM/MP areas. The Th17 Trm cluster demonstrated heightened expression of tissue-residency marker genes (ITGAE, ITGA1, and CXCR6) along with elevated levels of IL17A, IL22, CCR6, and CCL20. The clonal expansion of Th17 Trm cells in CD was accompanied by enhanced transmural dynamic potential, as indicated by significantly higher migration scores. CD-prominent Th17 Trm cells displayed an increased interferon gamma (IFNγ)-related signature possibly linked with STAT1 activation, inducing chemokines (i.e., CXCL10, CXCL8, and CXCL9) in myeloid cells. Our findings underscored the elevated Th17 Trm cells throughout the small bowel in CD, contributing to disease pathogenesis through IFNγ induction and subsequent chemokine production in myeloid cells.


Assuntos
Doença de Crohn , Memória Imunológica , Células T de Memória , Células Th17 , Humanos , Doença de Crohn/imunologia , Doença de Crohn/genética , Doença de Crohn/patologia , Células Th17/imunologia , Células Th17/metabolismo , Células T de Memória/imunologia , Células T de Memória/metabolismo , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Mucosa Intestinal/imunologia , Mucosa Intestinal/metabolismo , Mucosa Intestinal/patologia , Subpopulações de Linfócitos T/imunologia , Subpopulações de Linfócitos T/metabolismo , Biomarcadores , Perfilação da Expressão Gênica , Adulto Jovem
6.
Eur J Clin Microbiol Infect Dis ; 43(5): 841-851, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38411778

RESUMO

PURPOSE: Distinguishing between complicated and uncomplicated Staphylococcus aureus bacteraemia (SAB) is therapeutically essential. However, this distinction has limitations in reflecting the heterogeneity of SAB and encouraging targeted diagnostics. Recently, a new risk stratification system for SAB metastatic infection, involving stepwise approaches to diagnosis and treatment, has been suggested. We assessed its applicability in methicillin-resistant SAB (MRSAB) patients. METHODS: We retrospectively analysed data of a 3-year multicentre, prospective cohort of hospitalised patients with MRSAB. We classified the patients into three risk groups: low, indeterminate, and high, based on the new system and compared between-group management and outcomes. RESULTS: Of 380 patients with MRSAB, 6.3% were classified as low-, 7.6% as indeterminate-, and 86.1% as high-risk for metastatic infection. No metastatic infection occurred in the low-, 6.9% in the indeterminate-, and 19.6% in the high-risk groups (P < 0.001). After an in-depth diagnostic work-up, patients were finally diagnosed as 'without metastatic infection (6.3%)', 'with metastatic infection (17.4%)', and 'uncertain for metastatic infection (76.3%)'. 30-day mortality increased as the severity of diagnosis shifted from 'without metastatic infection' to 'uncertain for metastatic infection' and 'with metastatic infection' (P = 0.09). In multivariable analysis, independent factors associated with metastatic complications were suspicion of endocarditis in transthoracic echocardiography, clinical signs of metastatic infection, Pitt bacteraemia score ≥ 4, and persistent bacteraemia. CONCLUSIONS: The new risk stratification system shows promise in predicting metastatic complications and guiding work-up and management of MRSAB. However, reducing the number of cases labelled as 'high-risk' and 'uncertain for metastatic infection' remains an area for improvement.


Assuntos
Bacteriemia , Staphylococcus aureus Resistente à Meticilina , Infecções Estafilocócicas , Humanos , Bacteriemia/tratamento farmacológico , Bacteriemia/microbiologia , Bacteriemia/diagnóstico , Bacteriemia/mortalidade , Infecções Estafilocócicas/tratamento farmacológico , Infecções Estafilocócicas/diagnóstico , Infecções Estafilocócicas/microbiologia , Infecções Estafilocócicas/mortalidade , Staphylococcus aureus Resistente à Meticilina/isolamento & purificação , Masculino , Feminino , Idoso , Pessoa de Meia-Idade , Estudos Prospectivos , Medição de Risco , Estudos Retrospectivos , Antibacterianos/uso terapêutico , Idoso de 80 Anos ou mais , Adulto , Fatores de Risco
7.
Environ Sci Technol ; 2024 Feb 08.
Artigo em Inglês | MEDLINE | ID: mdl-38329941

RESUMO

Perfluoroalkyl substances (PFAS) are a class of persistent organic pollutants known as "forever chemicals". Currently, the hydrated electron-based advanced reduction process (ARP) holds promise for the elimination of PFAS. However, the efficiency of ARP is often challenged by an oxygen-rich environment, resulting in the consumption of hydrated electron source materials in exchange for the high PFAS decomposition efficiency. Herein, we developed a ternary system constructed by indole and isopropyl alcohol (IPA), and the addition of IPA significantly enhanced the PFOA degradation and defluorination efficiency in the presence of low-concentration indole (<0.4 mM). Meanwhile, opposite results were obtained with a higher amount of indole (>0.4 mM). Further exploring the molecular mechanism of the reaction system, the addition of IPA played two roles. On one hand, IPA built an anaerobic reaction atmosphere and improved the yield and utilization efficiency of hydrated electrons with a low concentration of indole. On the other hand, IPA suppressed the attraction between indole and PFOA, thus reducing the hydrated electron transfer efficiency, especially with more indole. In general, the indole/PFAS/IPA system significantly improved the PFAS destruction efficiency with a small amount of hydrated electron donors, which provided new insights for development of simple and efficient techniques for the treatment of PFAS-contaminated wastewater.

8.
J Periodontal Res ; 59(4): 771-782, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38616305

RESUMO

BACKGROUND: Periodontitis is a chronic inflammatory disease mediated by dysbiosis of the oral microflora, resulting in the destruction of periodontal tissue. Increasing evidence suggested that mesenchymal stem cell (MSCs) and exosomes derived from MSCs play a critical role in periodontal tissue regeneration. However, whether stem cells from exfoliated deciduous teeth (SHED)-secreted exosomes can improve the therapeutic potential of periodontitis is largely unknown. OBJECTIVE: Here, we aim to evaluate the effect of SHED-exosomes on inflammation, apoptosis and osteogenic differentiation in periodontitis. METHODS: The periodontitis cell model was constructed by stimulating periodontal ligament stem cells (PDLSCs) with lipopolysaccharide (LPS), and the periodontitis rats were established by ligation. RESULTS: First, we isolated exosomes from the SHED, and we figured out that exosomes secreted by SHED were enriched in miR-92a-3p and the exosomes enhanced proliferation and osteogenic differentiation and reduced apoptosis and inflammatory responses in PDLSCs. In addition, we found that SHED-exosomes alleviated inflammatory effect and elevated the expression of osteogenic-related genes in periodontitis rat model. Moreover, miR-92a-3p targeted downstream Krüppel-Like Transcription Factor 4 (KLF4) and regulated the PI3K/AKT pathway. Finally, our data indicated that upregulation of KLF4 or activation of PI3K/AKT by 740Y-P counteracted the inhibitory effect of SHED-exosomes on periodontitis progression. CONCLUSION: Taken together, our finding revealed that exosomal miR-92a-3p derived from SHED contributed to the alleviation of periodontitis development and progression through inactivating the KLF4/PI3K/AKT signaling pathway, which may provide a potential target for the treatment of periodontitis.


Assuntos
Exossomos , Fator 4 Semelhante a Kruppel , Fatores de Transcrição Kruppel-Like , MicroRNAs , Periodontite , Fosfatidilinositol 3-Quinases , Proteínas Proto-Oncogênicas c-akt , Transdução de Sinais , Dente Decíduo , Exossomos/metabolismo , Periodontite/metabolismo , Humanos , MicroRNAs/metabolismo , Animais , Proteínas Proto-Oncogênicas c-akt/metabolismo , Fatores de Transcrição Kruppel-Like/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Ratos , Progressão da Doença , Ligamento Periodontal/citologia , Ligamento Periodontal/patologia , Apoptose/genética , Diferenciação Celular , Ratos Sprague-Dawley , Osteogênese/genética , Masculino , Modelos Animais de Doenças , Células-Tronco Mesenquimais/metabolismo , Proliferação de Células
9.
J Gastroenterol Hepatol ; 39(6): 1155-1163, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38357836

RESUMO

BACKGROUND AND AIM: Lack of awareness disturbs proper care for hepatitis C virus (HCV) infections in patients undergoing surgery. We investigated the status of HCV screening, confirmation, and treatment in patients who underwent surgery. METHODS: Patients who underwent surgery at a tertiary academic center between 2019 and 2021 were eligible for this retrospective study. RESULTS: Between 2019 and 2021, 96 894 patients (40 121 males; 41.4%) who underwent surgery under general anesthesia were recruited. The median age of the participants was 55.0 years. Of the 83 920 (86.6%) patients who tested positive for anti-HCV antibodies, 576 (0.7%) showed positive results, with a higher proportion of patients with diabetes mellitus (32.6% vs 18.5%), hypertension (50.5% vs 28.6%), liver cirrhosis (13.2% vs 1.7%), and unfavorable laboratory test results when compared with those with negative results (all P < 0.05). HCV RNA was tested in 215 patients (37.3%), with a positivity rate of 20.5% (n = 44). Of the 44 patients, 42 (95.5%) were referred for antiviral treatment, and 29 (69.0%) were successfully treated with direct-acting antiviral therapy. HCV RNA confirmation rates were higher in the Department of Hepatobiliary and Transplant Surgery (76.6%) than in the other surgical departments (25.0-33.5%) (P < 0.001). CONCLUSIONS: The proportion of patients who were positive for anti-HCV antibodies and failed to receive proper management after surgery was not negligible. Increased awareness of HCV infection among surgeons through appropriate education may be required.


Assuntos
Antivirais , Hepatite C , Centros de Atenção Terciária , Humanos , Masculino , Pessoa de Meia-Idade , Feminino , Estudos Retrospectivos , Hepatite C/diagnóstico , Antivirais/uso terapêutico , Anticorpos Anti-Hepatite C/sangue , Adulto , Idoso , Hepacivirus/imunologia , Hepacivirus/genética , RNA Viral/sangue , Procedimentos Cirúrgicos Operatórios/efeitos adversos , Cirrose Hepática/cirurgia , Programas de Rastreamento/métodos
10.
Artigo em Inglês | MEDLINE | ID: mdl-39343427

RESUMO

BACKGROUND AND AIM: The prevalence of metabolic dysfunction-associated steatotic liver disease (MASLD) is increasing worldwide, coinciding with aging population. However, limited studies have evaluated its incidence and progression to advanced fibrosis in the elderly population. Therefore, our study aimed to investigate the incidence of MASLD and advanced fibrosis in this age group. METHODS: We included 878 686 individuals aged ≥60 years from the Korea National Health Insurance Service-Senior cohort. After excluding participants with preexisting MASLD, 329 388 individuals were finally analyzed. Participants were categorized into four groups based on the presence of overweight/obesity and additional risk factors (aRF) included in the cardiometabolic diagnostic criteria of MASLD. RESULTS: The overall incidence of MASLD was 1.94 per 100 person-years, and the incidence of advanced fibrosis in MASLD patients was 1.78 per 100 person-years. MASLD development was significantly higher in overweight/obese patients (2.65 per 100 person-years) compared to lean patients (1.09 per 100 person-years), and this trend persisted after stratification by the presence of aRF. Similarly, the incidence of advanced fibrosis among MASLD patients was higher in overweight/obese individuals (2.06 per 100 person-years) compared to lean counterparts (0.87 per 100 person-years), irrespective of aRF. CONCLUSIONS: The lower incidence of MASLD in the elderly population compared to the general population underscores the importance of identifying age-specific risk factors. Overweight/obesity emerged as a robust predictor of MASLD development and advanced fibrosis. Additionally, the presence of additional cardiometabolic risk factors further increased the risk of incident MASLD and advanced fibrosis among the elderly.

11.
Environ Res ; 255: 119132, 2024 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-38735380

RESUMO

The anaerobic digestion (AD) process has become significant for its capability to convert organic wastewater into biogas, a valuable energy source. Excessive acetic acid accumulation in the anaerobic digester can inhibit methanogens, ultimately leading to the deterioration of process performance. Herein, the effect of magnetite particles (MP) as an enhancer on the methanogenic degradation of highly-concentrated acetate (6 g COD/L) was examined through long-term sequential AD batch tests. Bioreactors with (AM) and without (AO) MP were compared. AO experienced inhibition and its methane production rate (qm) converged to 0.45 L CH4/g VSS/d after 10 sequential batches (AO10, the 10th batch in a series of the sequential batch tests conducted using bioreactors without MP addition). In contrast, AM achieved 3-425% higher qm through the sequential batches, indicating that MP could counteract the inhibition caused by the highly-concentrated acetate. MP addition to inhibited bioreactors (AO10) successfully restored them, achieving qm of 1.53 L CH4/g VSS/d, 3.4 times increase from AO10 after 8 days lag time, validating its potential as a recovery strategy for inhibited digesters with acetate accumulation. AM exhibited higher microbial populations (1.8-3.8 times) and intracellular activity (9.3 times) compared to AO. MP enriched Methanosaeta, Peptoclostridium, Paraclostridium, OPB41, and genes related to direct interspecies electron transfer and acetate oxidation, potentially driving the improvement of qm through MP-mediated methanogenesis. These findings demonstrated the potential of MP supplementation as an effective strategy to accelerate acetate-utilizing methanogenesis and restore an inhibited anaerobic digester with high acetate accumulation.


Assuntos
Ácido Acético , Reatores Biológicos , Metano , Anaerobiose , Metano/metabolismo , Reatores Biológicos/microbiologia , Ácido Acético/metabolismo , Óxido Ferroso-Férrico/metabolismo , Eliminação de Resíduos Líquidos/métodos
12.
Clin Lab ; 70(4)2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38623666

RESUMO

BACKGROUND: We evaluated the diagnostic performance of the FilmArray Blood Culture Identification Panel (BCID; bioMerieux) for the detection of bloodstream pathogens. METHODS: From May to August 2022, up to 67 samples from positive blood cultures previously processed with BACTEC FX (BD) were collected and submitted to the BCID panel. BCID panel results were compared with traditional culture results. RESULTS: We tested 67 positive blood culture samples; 13 samples were from pediatric bottles of BACTEC Peds Plus/F media (BD). The overall sensitivity of the BCID panel was 89.9% (62/69; 95% CI, 80.2 - 95.3%). For blood-stream pathogens targeted by the BCID panel, sensitivity was 98.4% (62/63; 95% CI, 90.7 - > 99.9%). Interestingly, Proteus species were additionally detected in 6 samples from pediatric blood culture bottles. CONCLUSIONS: BCID demonstrated high clinical sensitivity for target pathogens, but positive findings for unexpected multiple targets or Proteus species require cautious interpretation to avoid false positives.


Assuntos
Bacteriemia , Reação em Cadeia da Polimerase Multiplex , Humanos , Criança , Reação em Cadeia da Polimerase Multiplex/métodos , Bactérias/genética , Hemocultura/métodos , Bacteriemia/diagnóstico
13.
J Infect Chemother ; 30(4): 366-370, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-37935348

RESUMO

Though remdesivir benefits COVID-19 patients, its use in those with renal dysfunction is currently limited due to concerns about possible toxic effects of accumulated sulfobutylether-ß-cyclodextrin (SBECD) on liver and kidney. We examined renal and hepatic function for a month in renally-impaired COVID-19 patients who were treated or not treated with remdesivir to assess the safety of the drug. A retrospective study was performed in adult COVID-19 patients with glomerular filtration rates of <30 ml/min/1.73 m2 at admission to a tertiary care hospital between November 2020 and March 2022. Data on serum creatinine and liver chemistry were collected serially. A total of 101 patients with impaired renal function were analyzed, comprising 64 remdesivir-treated patients and 37 who did not receive any antiviral agent. Although remdesivir-treated patients were more likely to be infected with the Omicron variant (79.7% vs. 48.6%), baseline characteristics did not differ significantly between the two groups. Among patients who initially did not require dialysis, 18.4% (7/38) of remdesivir-treated patients developed acute kidney injury (AKI) at days 4-6, compared with 51.7% (15/29) of non-remdesivir-treated patients. Liver injury severity worsened in 3.1% (2/64) of remdesivir-treated patients and 5.4% (2/37) of non-remdesivir-treated patients at days 4-6. In addition, there was no significant increase in AKI and liver injury over time in remdesivir-treated patients, and there were no cases of discontinuation of remdesivir due to adverse reactions. Concerns regarding the safety of SBECD should not lead to hasty withholding of remdesivir treatment in renally-impaired COVID-19 patients.


Assuntos
Injúria Renal Aguda , Monofosfato de Adenosina/análogos & derivados , Alanina/análogos & derivados , COVID-19 , Adulto , Humanos , SARS-CoV-2 , Estudos Retrospectivos , Tratamento Farmacológico da COVID-19 , Injúria Renal Aguda/induzido quimicamente , Injúria Renal Aguda/epidemiologia
14.
Lung ; 202(2): 127-137, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38502305

RESUMO

PURPOSE: The respiratory syncytial virus (RSV) is a common respiratory virus that causes acute lower respiratory tract infectious diseases, particularly in young children and older individuals. Activated leukocyte cell adhesion molecule (ALCAM) is a membrane glycoprotein expressed in various cell types, including epithelial cells, and is associated with inflammatory responses and various cancers. However, the precise role of ALCAM in RSV-induced airway inflammation remains unclear, and our study aimed to explore this gap in the literature. METHODS: C57BL/6 wild-type, ALCAM knockout mice and airway epithelial cells were infected with RSV and the expression of ALCAM and inflammatory cytokines were measured. We also conducted further experiments using Anti-ALCAM antibody and recombinant ALCAM in airway epithelial cells. RESULTS: The expression levels of ALCAM and inflammatory cytokines increased in both RSV-infected mice and airway epithelial cells. Interestingly, IL-33 expression was significantly reduced in ALCAM-knockdown cells compared to control cells following RSV infection. Anti-ALCAM antibody treatment also reduced IL-33 expression following RSV infection. Furthermore, the phosphorylation of ERK1/2, p38, and JNK was diminished in ALCAM-knockdown cells compared to control cells following RSV infection. Notably, in the control cells, inhibition of these pathways significantly decreased the expression of IL-33. In vivo study also confirmed a reduction in inflammation induced by RSV infection in ALCAM deficient mice compared to wild-type mice. CONCLUSION: These findings demonstrate that ALCAM contributes to RSV-induced airway inflammation at least partly by influencing IL-33 expression through mitogen-activated protein kinase signaling pathways. These results suggest that targeting ALCAM could be a potential therapeutic strategy for alleviating IL-33-associated lung diseases.


Assuntos
Infecções por Vírus Respiratório Sincicial , Vírus Sincicial Respiratório Humano , Animais , Camundongos , Molécula de Adesão de Leucócito Ativado/metabolismo , Citocinas/metabolismo , Inflamação/metabolismo , Interleucina-33/genética , Interleucina-33/metabolismo , Pulmão/metabolismo , Sistema de Sinalização das MAP Quinases , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Infecções por Vírus Respiratório Sincicial/metabolismo , Vírus Sincicial Respiratório Humano/metabolismo , Transdução de Sinais
15.
J Korean Med Sci ; 39(15): e136, 2024 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-38651222

RESUMO

BACKGROUND: Haemophilus influenzae is a frequently encountered pathogen responsible for respiratory tract infections in children. Following the detection of ceftriaxone-resistant H. influenzae at our institution, we aimed to investigate the resistance mechanisms of ceftriaxone in H. influenzae, with a particular focus on alterations in penicillin-binding protein 3 (PBP3) and ß-lactamase production. METHODS: Among H. influenzae isolates collected at Asan Medical Center Children's Hospital from March 2014 to April 2019, ceftriaxone-resistant strains by the disk-diffusion test were included. Ceftriaxone minimum inhibitory concentrations (MICs) were determined using the E-test according to the European Committee on Antimicrobial Susceptibility Testing (EUCAST) guidelines. The presence of ß-lactamase was assessed through cefinase test and TEM-1/ROB-1 polymerase chain reaction (PCR). PBP3 alterations were explored via ftsI gene sequencing. RESULTS: Out of the 68 collected strains, 21 exhibited resistance to ceftriaxone in disk diffusion tests. Two strains were excluded due to failed subculture. Among 19 ceftriaxone-resistant H. influenzae isolates, eighteen were non-typeable H. influenzae, and twelve were positive for TEM-1 PCR. Isolates were classified into groups II (harboring only N526K, n = 3), III (N526K+S385T, n = 2), III+ (S385T+L389F+N526K, n = 11), and III-like+ (S385T+L389F+R517H, n = 3) according to the PBP3 alteration pattern. With a median ceftriaxone MIC of 0.190 mg/L (range, 0.008-0.750), the median ceftriaxone MIC was the highest in group III-like+ (0.250 mg/L), followed by groups III+ (0.190 mg/L), III (0.158 mg/L), and II (0.012 mg/L). All three strains belonging to group II, which did not harbor the S385T substitution, had ceftriaxone MICs of ≤ 0.125 mg/L. CONCLUSION: The emergence of ceftriaxone-resistant H. influenzae with ceftriaxone MIC values of up to 0.75 mg/L was observed even in children in South Korea, with most associated with S385T and L389F substitutions. The N526K mutation alone does not significantly impact ceftriaxone resistance. Further large-scale studies are essential to investigate changes in antibiotic resistance patterns and factors influencing antibiotic resistance in H. influenzae isolated from pediatric patients in Korea.


Assuntos
Antibacterianos , Ceftriaxona , Infecções por Haemophilus , Haemophilus influenzae , Testes de Sensibilidade Microbiana , beta-Lactamases , Ceftriaxona/farmacologia , Haemophilus influenzae/efeitos dos fármacos , Haemophilus influenzae/isolamento & purificação , Haemophilus influenzae/genética , Humanos , Antibacterianos/farmacologia , República da Coreia , beta-Lactamases/genética , beta-Lactamases/metabolismo , Criança , Infecções por Haemophilus/microbiologia , Infecções por Haemophilus/tratamento farmacológico , Proteínas de Ligação às Penicilinas/genética , Pré-Escolar , Farmacorresistência Bacteriana , Lactente , Feminino , Masculino , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo
16.
J Korean Med Sci ; 39(25): e208, 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38952349

RESUMO

A 30-year-old Korean man with myelodysplastic syndrome admitted hospital due to undifferentiated fever and recurrent skin lesions. He received combination therapy with high doses of meropenem, tigecycline and amikacin, yielding carbapenem resistant Klebsiella pneumoniae (CRKP) harboring K. pneumoniae carbapenemase (KPC)-2 from blood cultures on hospital day (HD) 23. Ceftazidime/avibactam was started at HD 37 and CRKP was eradicated from blood cultures after 5 days. However, ceftazidime/avibactam-resistant CRKP carrying KPC-44 emerged after 26 days of ceftazidime/avibactam treatment and then ceftazidime/avibactam-resistant, carbapenem-susceptible K. pneumoniae carrying KPC-135 was isolated on HD 65. The 3-D homology of KPC protein showed that hot spot changes in the omega loop could be attributed to ceftazidime/avibactam resistance and loss of carbapenem resistance. Whole genome sequencing of serial isolates supported that phenotypic variation was due to clonal evolution than clonal replacement. The treatment regimen was changed from CAZ/AVI to meropenem-based therapy (meropenem 1 g iv q 8 hours and amikacin 600 mg iv per day) starting with HD 72. CAZ/AVI-susceptible CRKP was presented again from blood cultures on HD 84, and the patient expired on HD 85. This is the first Korean report on the acquisition of ceftazidime/avibactam resistance through the emergence of blaKPC variants.


Assuntos
Antibacterianos , Compostos Azabicíclicos , Bacteriemia , Ceftazidima , Combinação de Medicamentos , Infecções por Klebsiella , Klebsiella pneumoniae , Testes de Sensibilidade Microbiana , beta-Lactamases , Humanos , Ceftazidima/uso terapêutico , Ceftazidima/farmacologia , Klebsiella pneumoniae/isolamento & purificação , Klebsiella pneumoniae/genética , Klebsiella pneumoniae/efeitos dos fármacos , Masculino , Compostos Azabicíclicos/uso terapêutico , Adulto , Antibacterianos/uso terapêutico , Antibacterianos/farmacologia , beta-Lactamases/genética , beta-Lactamases/metabolismo , Infecções por Klebsiella/tratamento farmacológico , Infecções por Klebsiella/microbiologia , Bacteriemia/tratamento farmacológico , Bacteriemia/microbiologia , Carbapenêmicos/uso terapêutico , Carbapenêmicos/farmacologia , Sequenciamento Completo do Genoma , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Meropeném/uso terapêutico , Meropeném/farmacologia , Farmacorresistência Bacteriana Múltipla/genética
17.
Chem Biodivers ; 21(6): e202400511, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38538539

RESUMO

Two undescribed germacrane-type sesquiterpenoids, salcasins A (1) and B (2), together with three known compounds (3-5) were isolated and identified from the whole plant of Salvia cavaleriei var. simplicifolia Stib. The structures of the undescribed compounds were elucidated on the basis of spectroscopic methods, such as HR-ESI-MS, 1D and 2D NMR data. The relative configurations of 1 and 2 were established by analyzing their NOESY spectra as well as by 13C NMR calculations with DP4+ probability analyses. The absolute configurations of 1 and 2 were determined by comparing experimental and calculated ECD spectra. Furthermore, the in vivo anti-Alzheimer's disease activities of 1-5 were evaluated using Caenorhabditis elegans AD pathological model. Among all isolated compounds, salcasin A (1) significantly delayed AD-like symptoms of worm paralysis, which may be a potential anti-AD candidate agent.


Assuntos
Doença de Alzheimer , Caenorhabditis elegans , Salvia , Sesquiterpenos de Germacrano , Doença de Alzheimer/tratamento farmacológico , Doença de Alzheimer/metabolismo , Doença de Alzheimer/patologia , Animais , Salvia/química , Caenorhabditis elegans/efeitos dos fármacos , Sesquiterpenos de Germacrano/farmacologia , Sesquiterpenos de Germacrano/química , Sesquiterpenos de Germacrano/isolamento & purificação , Estrutura Molecular , Conformação Molecular , Modelos Animais de Doenças
18.
Sensors (Basel) ; 24(3)2024 Feb 02.
Artigo em Inglês | MEDLINE | ID: mdl-38339704

RESUMO

This paper introduces an approach to the automated measurement and analysis of dairy cows using 3D point cloud technology. The integration of advanced sensing techniques enables the collection of non-intrusive, precise data, facilitating comprehensive monitoring of key parameters related to the health, well-being, and productivity of dairy cows. The proposed system employs 3D imaging sensors to capture detailed information about various parts of dairy cows, generating accurate, high-resolution point clouds. A robust automated algorithm has been developed to process these point clouds and extract relevant metrics such as dairy cow stature height, rump width, rump angle, and front teat length. Based on the measured data combined with expert assessments of dairy cows, the quality indices of dairy cows are automatically evaluated and extracted. By leveraging this technology, dairy farmers can gain real-time insights into the health status of individual cows and the overall herd. Additionally, the automated analysis facilitates efficient management practices and optimizes feeding strategies and resource allocation. The results of field trials and validation studies demonstrate the effectiveness and reliability of the automated 3D point cloud approach in dairy farm environments. The errors between manually measured values of dairy cow height, rump angle, and front teat length, and those calculated by the auto-measurement algorithm were within 0.7 cm, with no observed exceedance of errors in comparison to manual measurements. This research contributes to the burgeoning field of precision livestock farming, offering a technological solution that not only enhances productivity but also aligns with contemporary standards for sustainable and ethical animal husbandry practices.


Assuntos
Computação em Nuvem , Aprendizado Profundo , Feminino , Bovinos , Animais , Reprodutibilidade dos Testes , Indústria de Laticínios/métodos , Tecnologia
19.
Sensors (Basel) ; 24(2)2024 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-38257521

RESUMO

The rapid evolution of 3D technology in recent years has brought about significant change in the field of agriculture, including precision livestock management. From 3D geometry information, the weight and characteristics of body parts of Korean cattle can be analyzed to improve cow growth. In this paper, a system of cameras is built to synchronously capture 3D data and then reconstruct a 3D mesh representation. In general, to reconstruct non-rigid objects, a system of cameras is synchronized and calibrated, and then the data of each camera are transformed to global coordinates. However, when reconstructing cattle in a real environment, difficulties including fences and the vibration of cameras can lead to the failure of the process of reconstruction. A new scheme is proposed that automatically removes environmental fences and noise. An optimization method is proposed that interweaves camera pose updates, and the distances between the camera pose and the initial camera position are added as part of the objective function. The difference between the camera's point clouds to the mesh output is reduced from 7.5 mm to 5.5 mm. The experimental results showed that our scheme can automatically generate a high-quality mesh in a real environment. This scheme provides data that can be used for other research on Korean cattle.

20.
J Pediatr Nurs ; 77: 35-44, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38479061

RESUMO

PURPOSE: This study aimed to develop and evaluate the effectiveness of a healthy lifestyle program based on a mobile serious game (HLP-MSG) to enhance the lifestyles of childhood cancer survivors (CCSs). METHODS: This program proceeded in two stages: development and evaluation, using a non-synchronized design with a quasi-randomized trial. The participants were CCSs aged 6-13 years whose treatment was terminated at least 12 months prior. Data were collected at baseline, and post-intervention, with a follow-up after four weeks using the Child Healthy Lifestyle Profile (CHLP). The experimental (n = 26) and control groups (n = 25) were compared. Data were analyzed using descriptive statistics, chi-squared tests, t-tests, and repeated-measures ANOVA. RESULTS: The HLP-MSG promoted a healthy lifestyle by solving 26 quests, including seven sub-elements (nutrition, exercise, hygiene, interpersonal relationships, stress management, meaning of life, and health responsibility). This study revealed significant differences in the interaction between measurement time and group assignment in the CHLP (p = .006) and physical activity (p = .013), one of the seven sub-dimensions. CONCLUSIONS: A healthy lifestyle program based on a mobile serious game is a feasible health education modality to enhance the physical, psychological, social, and spiritual health of CCSs. IMPLICATIONS TO PRACTICE: The findings add to scientific evidence on a mobile serious game for health education among CCSs. The HLP-MSG provides an evolutionary educational modality that can be delivered non-face-to-face to promote CCSs' continuous healthy behavior maintenance. Moreover, the HLP-MSG is adolescent-friendly and can be utilized as a healthcare tool for parents and children to cooperate.


Assuntos
Sobreviventes de Câncer , Estilo de Vida Saudável , Humanos , Masculino , Feminino , Criança , Sobreviventes de Câncer/psicologia , Adolescente , Promoção da Saúde/métodos , Jogos de Vídeo , Avaliação de Programas e Projetos de Saúde , Neoplasias/terapia , Exercício Físico , Aplicativos Móveis , Qualidade de Vida
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