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1.
Discov Med ; 36(183): 816-826, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38665029

RESUMO

BACKGROUND: Pneumonia is a prevalent respiratory ailment involving complex physiological and pathological mechanisms. The tripartite motif containing 27 (TRIM27) plays a crucial role in regulating inflammation mechanisms. Therefore, the purpose of this study is to further explore the therapeutic potential of TRIM27 in pneumonia, based on its regulatory mechanisms in inflammation and autophagy. METHODS: This study established a mouse pneumonia animal model through lipopolysaccharide (LPS) administration, designating it as the LPS model group. Subsequently, adenovirus-mediated TRIM27 overexpression was implemented in the animals of the LPS model group, creating the TRIM27 treatment group. After a 7-day treatment period, lung tissues from the mice were collected. Various techniques, including immunohistochemistry, quantitative reverse transcription PCR (RT-qPCR), western blot, enzyme-linked immunosorbent assay (ELISA), and electron microscopy were utilized to analyze the impact of TRIM27 overexpression on inflammatory factors, oxidative stress, autophagy, and inflammatory processes in pulmonary tissues. Finally, an in vitro LPS cell model was established, and the effects of TRIM27 overexpression and autophagy inhibition on inflammatory cytokines and autophagosomes in LPS-induced inflammatory cells were examined through RT-qPCR and immunofluorescence techniques. RESULTS: The research findings demonstrate a significant reduction in the elevated levels of interleukin-6 (IL-6), IL-1ß, and Tumor necrosis factor-alpha (TNF-α) induced by LPS with TRIM27 overexpression (p < 0.01). Conversely, the autophagy inhibitor 3-Methyladenine (3-MA) diminished the effects induced by TRIM27 overexpression. Moreover, TRIM27 overexpression enhanced the expression of Microtubule-associated protein 1A/1B light chain 3 (LC3) II/I and Beclin-1 proteins in mice subjected to LPS stimulation (p < 0.01), while reducing the expression of the p62 protein (p < 0.01). The addition of 3-MA, however, decreased Beclin-1 expression and inhibited autophagy (p < 0.01). Additionally, TRIM27 overexpression decreased the expression of NOD-like receptor thermal protein domain associated protein 3 (NLRP3), cleaved caspase-1, IL-1ß, and Gasdermin D N-terminal fragment (GSDMD-N) proteins in LPS-stimulated mice (p < 0.05). TRIM27 overexpression also decreased the levels of malondialdehyde (MDA), Activating Transcription Factor 6 (ATF6), and C/EBP-homologous protein (CHOP), while increasing the levels of superoxide dismutase (SOD) and glutathione (GSH) in mice exposed to LPS (p < 0.01). CONCLUSION: The induction of TRIM27 overexpression emerges as a potential and effective pneumonia treatment. The underlying mechanism may involve inducing protective autophagy, thereby reducing oxidative stress and cell pyroptosis.


Assuntos
Autofagia , Pneumonia , Proteínas com Motivo Tripartido , Ubiquitina-Proteína Ligases , Animais , Masculino , Camundongos , Adenina/análogos & derivados , Adenina/farmacologia , Autofagia/efeitos dos fármacos , Autofagia/genética , Proteína Beclina-1/metabolismo , Proteína Beclina-1/genética , Modelos Animais de Doenças , Proteínas de Ligação a DNA , Lipopolissacarídeos/toxicidade , Pulmão/patologia , Pulmão/metabolismo , Camundongos Endogâmicos C57BL , Estresse Oxidativo/efeitos dos fármacos , Pneumonia/patologia , Pneumonia/metabolismo
2.
J Inflamm Res ; 15: 6495-6504, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36474517

RESUMO

Objective: The individualized prediction of treatment regimens of macrolide-unresponsive Mycoplasma pneumoniae pneumonia (MUMPP) is scarce. The aim of this study was, therefore, to evaluate the relevant data of patients and construct a nomogram for identifying refractory Mycoplasma pneumoniae pneumonia (RMPP) among children continued to be treated with macrolide after the confirmation of MUMPP, providing a reference for the choice of treatment regimen. Methods: We performed a retrospective study involving 162 children who continued to be treated with macrolide (azithromycin) after the confirmation of MUMPP without antibiotic changes between January 2020 and January 2022. We collected data on clinical feature, hospitalization period, treatments, laboratory data, extrapulmonary symptoms, parapneumonic effusion, and connections with other respiratory pathogens. In addition, the independent risk factors for RMPP were determined through univariate and multivariate analyses, and then a nomogram was constructed and validated. Results: In this study, the multivariate logistic regression analysis showed that age, leukocyte count, neutrophil proportion, serum procalcitonin, and lactate dehydrogenase were independent risk factors for RMPP. Using the five independent associated factors, the nomogram for identification of RMPP was constructed. Moreover, the area under the ROC curve (AUC) was 0.925 (95% CI: 0.882-0.968) for the nomogram showing excellent discrimination. The calibration curve, close to the 45-degree line, exhibited good calibration of nomogram. Conclusion: We constructed and validated a visual and user-friendly nomogram for individualized prediction of RMPP risk in children who continued to be treated with macrolide after the confirmation of MUMPP based on five variables. According to the nomogram model, continuation of macrolide should be considered rather than second-line antibiotics including tetracyclines (doxycycline or minocycline) and fluoroquinolones for MUMPP children with low predictive values.

3.
Transl Androl Urol ; 9(5): 2235-2241, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-33209688

RESUMO

BACKGROUND: Primary nephrotic syndrome (NS) is a common disease of the urinary system with an unclear pathogenesis. We aimed to detect the levels of urinary exosomal miR-23b-3p, miR-30a-5p, and miR-151-3p in children with primary NS, and to explore their diagnostic value for NS. METHODS: A total of 115 patients with NS who were admitted to the hospital from June 2017 to June 2019 were selected as the observation group. According to the disease progression, they were divided into an active group (acute active phase, n=68) and remission group (remission phase, n=47). In all, 50 healthy children were selected as the control group. Levels of urinary exosomal miR-23b-3p, miR-30a-5p, and miR-151-3p of each group in different periods were detected. RESULTS: The 24-h urine protein, serum albumin (ALB), and serum total cholesterol (TC) levels were significantly higher in the observation group than in the control group (P<0.05), while those in the active group were significantly higher than those in the remission group (P<0.05). The levels of miR-23b-3p and miR-30a-5p were significantly higher in the observation group than in the control group, and significantly higher in the active group than in the remission group (P<0.05). No miR-151-3p was detected in the urinary exosomes of the two groups. After treatment, levels of exosomal miR-23b-3p and miR-30a-5p in the two groups both decreased significantly (P<0.05). Results of receiver operating curve (ROC) curve analysis showed that urinary exosomal miR-23b-3p and miR-30a-5p can be used to identify children with NS and healthy children. The area under the ROC curve (AUC) was 0.711 for miR-23b-3p and 0.844 for miR-30a-5p. CONCLUSIONS: The levels of miR-23b-3p and miR-30a-5p in urinary exosomes of children with NS were significantly higher than those in healthy children, and decreased significantly after treatment, indicating that miR-23b-3p and miR-30a-5p in urinary exosomes are potential indicators for diagnosing the progression of NS and monitoring the treatment effect.

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