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1.
Clin Transl Oncol ; 2024 Aug 17.
Artigo em Inglês | MEDLINE | ID: mdl-39153177

RESUMO

PURPOSE: This study aimed to evaluate the prognostic significance of changes in inflammatory markers in patients with Hepatitis B virus-related hepatocellular carcinoma (HBV-HCC) treated with first-line lenvatinib plus a programmed cell death protein 1 (PD-1) inhibitor. METHODS: This study retrospectively included 117 HBV-HCC patients treated with first-line lenvatinib in combination with a PD-1 inhibitor. Independent factors affecting progression-free survival (PFS) and overall survival (OS) were explored based on baseline indicators and inflammatory markers changes after one treatment cycle. RESULTS: Multivariate analysis revealed that an alpha-fetoprotein (AFP) level ⩾ 400 ng/mL [hazard ratio (HR), 1.69; 95% confidence interval (CI), 1.11-2.58; P = 0.01] was identified as an independent risk factor, platelet-to-neutrophil ratio (PNR) ⩽ 65.43 (HR 0.50; 95% CI 0.30-0.84; P < 0.01 ) and SII ⩽ 539.47 (HR 0.54; 95% CI 0.30-0.96; P = 0.03) were identified as independent protective factors for PFS. Additionally, multivariate analysis demonstrated that AFP ⩾ 400 ng/mL, HBV-HCC patients with diabetes mellitus (DM), and SII > 303.66 were independent risk factors of OS. The patients whose SII had increased after one cycle of treatment showed a poorer PFS (HR 1.61; 95 %CI 1.10-2.37; P = 0.015) and OS (HR 1.76; 95 % CI 1.15-2.70; P = 0.009) than patients whose SII had decreased. The objective response rate (ORR) was higher in the SII-decreased patients (47.5% vs 32.5%, P = 0.11). Mann-Whitney test found a significant difference in therapeutic response between the SII-increased patients and the SII-decreased patients (P = 0.04). CONCLUSION: SII can be associated with outcomes in patients with HBV-HCC treated with first-line lenvatinib plus PD-1 inhibitors.

2.
Braz J Med Biol Res ; 57: e13379, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38808888

RESUMO

Ulcerative colitis (UC) is a difficult intestinal disease characterized by inflammation, and its mechanism is complex and diverse. Angiopoietin-like protein 2 (ANGPT2) plays an important regulatory role in inflammatory diseases. However, the role of ANGPT2 in UC has not been reported so far. After exploring the expression level of ANGPT2 in serum of UC patients, the reaction mechanism of ANGPT2 was investigated in dextran sodium sulfate (DSS)-induced UC mice. After ANGPT2 expression was suppressed, the clinical symptoms and pathological changes of UC mice were detected. Colonic infiltration, oxidative stress, and colonic mucosal barrier in UC mice were evaluated utilizing immunohistochemistry, immunofluorescence, and related kits. Finally, western blot was applied for the estimation of mTOR signaling pathway and NLRP3 inflammasome-related proteins. ANGPT2 silencing improved clinical symptoms and pathological changes, alleviated colonic inflammatory infiltration and oxidative stress, and maintained the colonic mucosal barrier in DSS-induced UC mice. The regulatory effect of ANGPT2 on UC disease might occur by regulating the mTOR signaling pathway and thus affecting autophagy-mediated NLRP3 inflammasome inactivation. ANGPT2 silencing alleviated UC by regulating autophagy-mediated NLRP3 inflammasome inactivation via the mTOR signaling pathway.


Assuntos
Autofagia , Colite Ulcerativa , Modelos Animais de Doenças , Inflamassomos , Proteína 3 que Contém Domínio de Pirina da Família NLR , Transdução de Sinais , Serina-Treonina Quinases TOR , Animais , Feminino , Humanos , Masculino , Camundongos , Angiopoietina-2/metabolismo , Proteína 2 Semelhante a Angiopoietina , Autofagia/fisiologia , Western Blotting , Colite Ulcerativa/induzido quimicamente , Colite Ulcerativa/patologia , Colite Ulcerativa/metabolismo , Sulfato de Dextrana , Imuno-Histoquímica , Inflamassomos/metabolismo , Camundongos Endogâmicos C57BL , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Estresse Oxidativo , Serina-Treonina Quinases TOR/metabolismo
3.
Braz. j. med. biol. res ; 57: e13379, fev.2024. graf
Artigo em Inglês | LILACS-Express | LILACS | ID: biblio-1557310

RESUMO

Ulcerative colitis (UC) is a difficult intestinal disease characterized by inflammation, and its mechanism is complex and diverse. Angiopoietin-like protein 2 (ANGPT2) plays an important regulatory role in inflammatory diseases. However, the role of ANGPT2 in UC has not been reported so far. After exploring the expression level of ANGPT2 in serum of UC patients, the reaction mechanism of ANGPT2 was investigated in dextran sodium sulfate (DSS)-induced UC mice. After ANGPT2 expression was suppressed, the clinical symptoms and pathological changes of UC mice were detected. Colonic infiltration, oxidative stress, and colonic mucosal barrier in UC mice were evaluated utilizing immunohistochemistry, immunofluorescence, and related kits. Finally, western blot was applied for the estimation of mTOR signaling pathway and NLRP3 inflammasome-related proteins. ANGPT2 silencing improved clinical symptoms and pathological changes, alleviated colonic inflammatory infiltration and oxidative stress, and maintained the colonic mucosal barrier in DSS-induced UC mice. The regulatory effect of ANGPT2 on UC disease might occur by regulating the mTOR signaling pathway and thus affecting autophagy-mediated NLRP3 inflammasome inactivation. ANGPT2 silencing alleviated UC by regulating autophagy-mediated NLRP3 inflammasome inactivation via the mTOR signaling pathway.

4.
Appl Microbiol Biotechnol ; 100(24): 10531-10542, 2016 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-27660181

RESUMO

The equine infectious anemia virus (EIAV) capsid protein (p26) is one of the major immunogenic proteins during EIAV infection and is widely used for the detection of EIAV antibodies in horses. However, few reports have described the use of EIAV-specific monoclonal antibodies (MAbs) in etiological and immunological detection. Previously, we developed an antigen capture enzyme-linked immunosorbent assay (AC-ELISA) for the quantification of the EIAV p26 protein level. However, the epitopes recognized by the MAbs were not identified, and the utilization of the MAbs needs to be evaluated. In this study, we characterized two monoclonal antibodies (9H8 and 1G11 MAbs) against EIAV p26. Two B-cell epitopes are located in amino acid residues, 73NLDKIAEE81 (HE) and 199KNAMRHLRPEDTLEEKMYAC218 (GE) for the 9H8 and 1G11 MAbs, respectively. The 1G11 epitope (GE) varied among viruses isolated worldwide but can be recognized by anti-EIAV sera from different regions, including China, the USA, and Argentina. Meanwhile, 1G11 MAb could react with the mutants of almost all the EIAV strains. Furthermore, we found that the histidine at position 204 (H204), leucine at position 205 (L205), and aspartic acid at position 209 (D209) of EIAV p26 individually played pivotal roles in binding with the 1G11 MAb. Our results revealed that the GE peptide might be a common B-cell binding epitope of EIAV antibodies. This is also the first report to identify a broad-spectrum monoclonal antibody (1G11) against p26 of EIAV. These findings may provide a useful basis for the development of new diagnostic assays for EIAV.


Assuntos
Mapeamento de Epitopos , Epitopos de Linfócito B/imunologia , Vírus da Anemia Infecciosa Equina/imunologia , Proteínas do Core Viral/imunologia , Anticorpos Monoclonais/imunologia , Anticorpos Antivirais/imunologia , Argentina , China , Vírus da Anemia Infecciosa Equina/isolamento & purificação , Estados Unidos
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