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1.
Heliyon ; 10(5): e27417, 2024 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-38486755

RESUMO

Klebsiella pneumoniae (K. pneumoniae) is a common bacterium that can cause iatrogenic infection. Recently, the rise of antibiotic resistance among K. pneumoniae strains is one key factor associated with antibiotic treatment failure. Hencefore, there is an urgent need for effective K. pneumoniae vaccines. This study aimed to design a multi-epitope vaccine (MEV) candidate against K. pneumonia by utilizing an immunoinformatics method. In this study, we obtained 15 cytotoxic T lymphocyte epitopes, 10 helper T lymphocyte epitopes, 6 linear B-cell epitopes, and 2 conformational B-cell epitopes for further research. Then, we designed a multi-epitope vaccine composed of a total of 743 amino acids, containing the epitopes linked by GPGPG flexible links and an EAAAK linker to the Cholera Toxin Subunit B coadjuvant. The observed properties of the MEV, including non-allergenicity, high antigenicity, and hydrophilicity, are noteworthy. The improvements in the tertiary structure through structural refinement and disulfide bonding, coupled with promising molecular interactions revealed by molecular dynamics simulations with TLR4, position the MEV as a strong candidate for further investigation against K. pneumoniae.

2.
Braz J Med Biol Res ; 57: e12989, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38265340

RESUMO

Peri-implant disease (PID) is a general term for inflammatory diseases of soft and hard tissues that occur around implants, including peri-implant mucositis and peri-implantitis. Cytokines are a class of small molecule proteins, which have various functions such as regulating innate immunity, adaptive immunity, and repairing damaged tissues. In order to explore the characteristics and clinical significance of tumor necrosis factor (TNF)-α, interleukin (IL)-6, IL-10, and tumor growth factor (TGF)-ß1 expression levels in serum of patients with peri-implant disease, 31 patients with PID and 31 patients without PID were enrolled. The modified plaque index (mPLI), modified sulcus bleeding index (mSBI), and peri-implant probing depth (PD) were recorded. The levels of serum TNF-α, IL-6, IL-10, and TGF-ß1 were detected by ELISA. TNF-α, mPLI, mSBI, and PD levels were significantly higher in the PID group. TGF-ß1 levels were significantly higher in the control group. There was a significant positive correlation between TNF-α and mPLI, mSBI, and PD. TGF-ß1 was negatively associated with TNF-α, mPLI, mSBI, and PD. Multiple logistic regression analysis showed that TNF-α and PD were risk factors for the severity of PID. The receiver operating curve analysis showed that high TNF-α levels (cut-off value of 140 pg/mL) and greater PD values (cut-off value of 4 mm) were good predictors of PID severity with an area under the curve of 0.922. These results indicated that TNF-α and PD can be used as a biological indicator for diagnosing the occurrence and progression of PID.


Assuntos
Peri-Implantite , Fator de Necrose Tumoral alfa , Humanos , Interleucina-10 , Fator de Crescimento Transformador beta1 , Citocinas , Interleucina-6
3.
Braz J Med Biol Res ; 56: e12997, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38126537

RESUMO

Early and accurate diagnosis of acute graft-versus-host disease (aGVHD) after allogeneic hematopoietic stem cell transplantation is crucial for the prognosis of patients. This study identified a potential biomarker for the severity of aGVHD after human leukocyte antigen (HLA)-haploidentical peripheral blood hematopoietic stem cell transplantation (haplo-PBSCT). We included 20 healthy subjects and 57 patients who underwent haplo-PBSCT. Of these patients, 22 developed aGVHD after haplo-PBSCT. The results showed that patients with aGVHD had significantly increased levels of Tim-3+/Perforin+/Granzyme B+CD8+ T cells, but significantly decreased Galectin-9. The differences in Galectin-9 and Tim-3+/Granzyme B+CD8+ T cells between grade I-II aGVHD and III-IV aGVHD were also significant. In vitro, the apoptosis of CD8+ T cells from aGVHD patients was significantly increased after Tim-3/Galectin-9 pathway activation, which decreased Granzyme B secretion. As revealed by univariate analysis, the level of Tim-3+CD8+ T cells was a risk factor for severe aGVHD. ROC analysis demonstrated that high levels of Tim-3+CD8+ T cells had a significant diagnostic value for severe aGVHD, with an area under the curve of 0.854 and cut-off value of 14.155%. In conclusion, the binding of Tim-3 with exogenous Galectin-9 can promote apoptosis of CD8+ T cells and affect the secretion of Granzyme B. Tim-3+CD8+ T cells have the potential to serve as immunological markers for assessing the severity of aGVHD after haplo-PBSCT and identifying patients at a higher risk for severe aGVHD.


Assuntos
Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Humanos , Granzimas , Receptor Celular 2 do Vírus da Hepatite A , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Linfócitos T CD8-Positivos , Doença Enxerto-Hospedeiro/diagnóstico , Doença Enxerto-Hospedeiro/etiologia , Galectinas , Doença Aguda
4.
Braz. j. med. biol. res ; 57: e12989, 2024. tab, graf
Artigo em Inglês | LILACS-Express | LILACS | ID: biblio-1528107

RESUMO

Peri-implant disease (PID) is a general term for inflammatory diseases of soft and hard tissues that occur around implants, including peri-implant mucositis and peri-implantitis. Cytokines are a class of small molecule proteins, which have various functions such as regulating innate immunity, adaptive immunity, and repairing damaged tissues. In order to explore the characteristics and clinical significance of tumor necrosis factor (TNF)-α, interleukin (IL)-6, IL-10, and tumor growth factor (TGF)-β1 expression levels in serum of patients with peri-implant disease, 31 patients with PID and 31 patients without PID were enrolled. The modified plaque index (mPLI), modified sulcus bleeding index (mSBI), and peri-implant probing depth (PD) were recorded. The levels of serum TNF-α, IL-6, IL-10, and TGF-β1 were detected by ELISA. TNF-α, mPLI, mSBI, and PD levels were significantly higher in the PID group. TGF-β1 levels were significantly higher in the control group. There was a significant positive correlation between TNF-α and mPLI, mSBI, and PD. TGF-β1 was negatively associated with TNF-α, mPLI, mSBI, and PD. Multiple logistic regression analysis showed that TNF-α and PD were risk factors for the severity of PID. The receiver operating curve analysis showed that high TNF-α levels (cut-off value of 140 pg/mL) and greater PD values (cut-off value of 4 mm) were good predictors of PID severity with an area under the curve of 0.922. These results indicated that TNF-α and PD can be used as a biological indicator for diagnosing the occurrence and progression of PID.

5.
Braz. j. med. biol. res ; 56: e12997, 2023. tab, graf
Artigo em Inglês | LILACS-Express | LILACS | ID: biblio-1528096

RESUMO

Early and accurate diagnosis of acute graft-versus-host disease (aGVHD) after allogeneic hematopoietic stem cell transplantation is crucial for the prognosis of patients. This study identified a potential biomarker for the severity of aGVHD after human leukocyte antigen (HLA)-haploidentical peripheral blood hematopoietic stem cell transplantation (haplo-PBSCT). We included 20 healthy subjects and 57 patients who underwent haplo-PBSCT. Of these patients, 22 developed aGVHD after haplo-PBSCT. The results showed that patients with aGVHD had significantly increased levels of Tim-3+/Perforin+/Granzyme B+CD8+ T cells, but significantly decreased Galectin-9. The differences in Galectin-9 and Tim-3+/Granzyme B+CD8+ T cells between grade I-II aGVHD and III-IV aGVHD were also significant. In vitro, the apoptosis of CD8+ T cells from aGVHD patients was significantly increased after Tim-3/Galectin-9 pathway activation, which decreased Granzyme B secretion. As revealed by univariate analysis, the level of Tim-3+CD8+ T cells was a risk factor for severe aGVHD. ROC analysis demonstrated that high levels of Tim-3+CD8+ T cells had a significant diagnostic value for severe aGVHD, with an area under the curve of 0.854 and cut-off value of 14.155%. In conclusion, the binding of Tim-3 with exogenous Galectin-9 can promote apoptosis of CD8+ T cells and affect the secretion of Granzyme B. Tim-3+CD8+ T cells have the potential to serve as immunological markers for assessing the severity of aGVHD after haplo-PBSCT and identifying patients at a higher risk for severe aGVHD.

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