International Journal of Immunopathology and Pharmacology最新文献

Objectives: Lymphocyte-activation gene 3 (LAG-3) represents a potential immune checkpoint target for cancer treatment. We investigated LAG-3 expression and its prognostic value in patients with surgically treated clear cell renal cell carcinoma (RCC) and correlated LAG-3 expression with programmed cell death ligand 1(PD-L1).

Methods: We evaluated LAG-3 and PD-L1 expression using immunohistochemistry on tissue microarrays incorporating 134 primary excision specimens of clear cell RCC (ccRCC). The patients were analyzed as two groups: the whole cohort and those with metastatic RCC (mRCC). The cancer genome atlas (TCGA) data analysis of LAG-3 was done through UALCAN web servers.

Results: Using the UALCAN cancer transcriptional data analysis, we found that LAG-3 was overexpressed in ccRCC. LAG-3 expression was significantly correlated with PD-L1 expression in the whole cohort and in the mRCC group (all, p < 0.05). Both LAG-3⁺ RCC and PD-L1⁺ RCC presented with a higher TNM stage and higher Fuhrman nuclear grade (all, p < 0.05). PD-L1⁺/LAG-3⁺ RCC and PD-L1⁻/LAG-3⁺ RCC showed poorer cancer-specific survival (CSS) than PD-L1⁻/LAG-3⁻ RCC (all, p = 0.01). Similarly, PD-L1⁺/LAG-3⁺ mRCC and PD-L1⁻/LAG-3⁺ mRCC showed poorer CSS than PD-L1⁻/LAG-3⁻ mRCC (all, p < 0.05). Multivariate analysis showed that PD-L1⁺/LAG-3⁺ mRCC (hazard ratio: 3.19; 95% CI: 0.77-13.67; p = 0.033) was a predictor of poor CSS.

Conclusion: Both LAG-3⁺ and PD-L1⁺ RCC have adverse pathological features, and their coexpression predicts worse clinical outcomes. Our findings suggest LAG-3 blockade in combination with programmed cell death 1/PD-L1 blockade as a potential therapeutic approach for RCC.

Objectives: Salidroside is used for treating inflammation-based diseases; however, its molecular mechanism is unclear. In this study, we determined the protective role of salidroside on the endotoxin-induced damage caused to the mouse alveolar epithelial type II (MLE-12) cells and its underlying mechanism.

Methods: An in vitro model for acute lung injury was constructed by inducing the MLE-12 cells using lipopolysaccharide (lipopolysaccharides, 1 mg/L). Then, The MTT assay was conducted to assess the survival rate of the MLE-12 cells in the different groups. After the treatment, apoptosis of MLE-12 cells was determined, and the mRNA and protein expression of miR-199a-5p, HMGB1, NF-kB65, TNFAIP8L2, p-IkB-α, and TLR4 was estimated by Western Blotting and RT-PCR. ELISA was also used to measure the concentration of inflammatory cytokine molecules IL-1β, IL-6, TNF-α, and IL-18 in the cell-free supernatant. Lastly, cell morphology was examined using the AO/EB technique.

Results: We showed that salidroside reduced the protein and gene expression of HMGB1, NF-kB65, miR-199a-5p, p-IkB-α, and TLR4, whereas it increased the gene and protein expression of TNFAIP8L2. Furthermore, it decreased the concentrations of cytokine molecules like IL-1β, IL-6, TNF-α, and IL-18 in the cell-free supernatant. MLE-12 also showed a lower apoptosis rate, higher survival rate, and better cell morphology.

Conclusion: Salidroside significantly inhibited the LPS-induced MLE-12 cell damage. Our results suggest that this could be by reducing miR-199a-5p and enhancing TNFAIP8L2 expression.

Introduction: The SARS-CoV-2 pandemic has had a considerable impact, causing millions of deaths worldwide, including many healthcare workers (HCWs). The pharmaceutical industry has been working diligently since the start of the pandemic to develop various vaccines to fight the spread of the virus and protect the population.

Objective: To study the seroprevalence of neutralizing anti-SARS-CoV-2 antibodies in vaccinated HCWs at the Mohamed VI University Hospital in Marrakech and to determine the parameters that can influence immune response.

Methods: A cross-sectional study of 138 HCWs was performed between October and December 2021 by measuring IgG antibodies directed against the spike antigen of SARS-CoV-2 using an Abbott Architect^® SARS-CoV-2 IgG II assay.

Results: The mean age was 31.42 years, the sex ratio was 2.94 women to each man, and the overall prevalence was 97%. We found 39.5% of the participants had experienced COVID-19 infections pre-vaccination, which decreased to 26.8% after vaccination. Neutralizing antibody titers were dependent on the type of vaccine: they were higher with the Pfizer-BioNTech vaccine, the number of doses (p < .001), and post-vaccine COVID-19 form. The post-vaccine COVID-19 infection rates were lower with the Sinopharm vaccine.

Conclusion: Heterologous vaccination with non-mRNA and mRNA vaccines and the consideration of post-vaccination COVID-19 infection as a booster could help optimize vaccine results while reducing potential side effects.

Up-regulation of tripartite motif-containing 27 (TRIM27) in varieties of tumors found that TRIM27 advanced tumor metastasis and invasion. Nevertheless, the relation of TRIM27 and immune infiltration in hepatocellular carcinoma (HCC) and the prognostic value of TRIM27 expression is unknown. We assessed TRIM27 association with immune infiltrates and the prognostic value of TRIM27 in HCC. From the Cancer Genome Atlas, we obtained TRIM27 transcriptional expression profiles of HCC and normal tissues. Using the Human Protein Atlas to evaluate the expression TRIM27, protein-protein interaction (PPI) networks were produced using the STRING database. Functional enrichment analysis was performed by using the clusterProfiler package. The tumor immune estimation resource was used to determine the relation of TRIM27 expression and immune infiltrates. We found that the expression of TRIM27 was up-regulated in HCC tissues compared with adjacent normal tissues. High TRIM27 expression correlated with high pathologic stage and high TNM stage. The receiver operating characteristic curve of TRIM27 area was 0.946. Kaplan-Meier analyses showed poor prognosis in HCC patients with high expression of TRIM27. Correlation analysis suggested that the expression of TRIM27 was related to immune infiltrates and tumor purity. This study indicated in HCC up-regulated the expression of TRIM27 is correlated to poor survival and immune infiltration. TRIM27 is an underlying target of immune therapy and is an underlying biomarker for poor prognosis in HCC.

Angiogenesis is the process of new vascular formation, which is derived from various factors. For suppressing cancer cell growth, targeting angiogenesis is one of the therapeutic approaches. Vascular endothelial growth factor family receptors, including Flt-1, Flk-1 and Flt-4, have been found to play an essential role in regulating angiogenesis. Rapamycin is a macrolide compound with anti-proliferative properties, while platelet factor-4 (PF-4) is an antiangiogenic ELR-negative chemokine. Rapamycin inhibits mTOR ligands activation, thus suppressing cell proliferation, while PF-4 inhibits cell proliferation through several mechanisms. In the present study, we evaluated the effects of rapamycin and platelet factor-4 toward breast carcinoma at the proteomic and genomic levels. A total of 60 N-Methyl-N-Nitrosourea-induced rat breast carcinomas were treated with rapamycin, platelet factor-4 and rapamycin+platelet factor-4. The tumours were subsequently subjected to immunohistochemical protein analysis and polymerase chain reaction gene analysis. Protein analysis was performed using a semiquantitative scoring method, while the mRNA expression levels were analysed based on the relative expression ratio. There was a significant difference in the protein and mRNA expression levels for the selected markers. In the rapamycin+platelet factor-4-treated group, the Flt-4 marker was downregulated, whereas there were no differences in the expression levels of other markers, such as Flt-1 and Flk-1. On the other hand, platelet factor-4 did not exhibit a superior angiogenic inhibiting ability in this study. Rapamycin is a potent antiangiogenic drug; however, platelet factor-4 proved to be a less effective drug of anti-angiogenesis on rat breast carcinoma model.

Objectives: To investigate the distinctive features of lymphocytes promoting inflammation in ulcerative colitis.

Methods: We performed flow cytometric analysis of peripheral blood mononuclear cells (PBMCs) and colorectal mucosa lymphocytes in ulcerative colitis patients (n = 13) and control patients (n = 5).

Results: CD62L⁺/CD3⁺CD4⁺ (35.7 ± 14.0% vs. 19.9 ± 6.4%) and CD62L⁺/CD3⁺CD4^- cells (17.1 ± 17.4% vs. 2.4 ± 3.9%) were higher in the rectum of ulcerative colitis patients than in control patients. Subpopulation analysis revealed that CD45RA^-CD62L⁺/CD3⁺CD4⁺, that is, central memory T cell fraction in CD4⁺ T cells, was significantly increased in the rectum of ulcerative colitis, compared to that in control patients (23.3 ± 10.5% vs. 8.2 ± 4.0%). Comparison of rectum and colon samples in ulcerative colitis patients indicated that CD56⁺/CD3⁺ was decreased in the rectum compared to that in the colon (11.3 ± 12.5% vs. 21.3 ± 16.5%). The ratio of CD56⁺/CD3⁺ was also decreased in the rectum of active ulcerative colitis patients compared to that in ulcerative colitis patients at the endoscopic remission stages (2.8 ± 1.7% vs. 18.5 ± 13.3%).

Conclusion: We demonstrated that CD62L⁺ T lymphocytes, particularly the CD45RA^-CD62L⁺ T cell subset that represents central memory T cells, were increased in the rectum of patients with ulcerative colitis. In addition, the CD56⁺/CD3⁺ subset (natural killer T cells) was decreased in the rectum compared to that of less inflamed colonic mucosa. These results suggest that the enrichment of central memory T lymphocytes and the reduction of natural killer T cells in the gut mucosa are involved in the pathogenesis of ulcerative colitis.