The human YTH domain family (YTHDF) proteins are RNA-binding proteins that recognize N6-methyladenosine (m6A), facilitating various biological processes via m6A RNA modification. How these molecules associate with non–small-cell lung cancer (NSCLC) molecular mechanisms remain unclear. The protein expression levels of YTHDF1 and YTHDF2 in 603 cases of resected NSCLC were evaluated using immunohistochemistry. We analyzed the associations of these attributes with patient characteristics and survival. We also assessed four subsets of lymphocytes (PD-1+, CD8+, Foxp3+, and CD45RO+) as tumor-infiltrating lymphocytes (TILs) in the tumor nest and in the surrounding stroma separately. In addition, we investigated differentially expressed genes and the expression of PD-L1 in YTHDF1– and YTHDF2-deprived lung cancer cells. The expressions of both YTHDF1 and YTHDF2 were less in the advanced-stage tumors than in the early-stage tumors. The expressions of both YTHDF1 and YTHDF2 were also independent favorable prognostic factors for recurrence-free survival (HR, 0.745; 95% CI, 0.562–0.984 for YTHDF1; HR, 0.683; 95% CI, 0.503–0.928 for YTHDF2). The TIL densities of almost all four lymphocyte subsets in the stroma were significantly higher in the tumors with high YTHDF1 and YTHDF2 expression. In vitro, YTHDF1 and YTHDF2 knockdown in cells upregulated tumor PD-L1 expression and altered multiple immune-related genes. High expressions of both YTHDF1 and YTHDF2 are associated with a favorable prognostic outcome of NSCLC patients, a greater amount of TILs, and downregulation of PD-L1. YTHDF1 and YTHDF2 could be novel prognostic and druggable targets related to the tumor-immune microenvironment in lung cancers.

Good results can be expected from placement of Gianturco stents except when CT shows the obstruction to be totally enveloped by tumor.

No abstract

Gonocytes are progenitor-type germ cells that arise from primordial germ cells and differentiate further into spermatogonia, thereby initiating spermatogenesis. In the present study, freshly isolated gonocytes were found to have either weak or no expression of pluripotency determining transcription factors, such as POU5F1, SOX2 and C-MYC. Interestingly, the expression of these transcription factors, as well as other vital transcription factors, such as NANOG, KLF4 and DAZL, were markedly upregulated in cultured cells. Cells in primary cultures expressed specific germ cell and pluripotency markers, such as lectin Dolichos biflorus agglutinin (DBA), KIT, ZBTB16, stage-specific embryonic antigen (SSEA-1), NANOG and POU5F1. Using a monoclonal antibody to specifically identify porcine germ cells, the stem cell potential of fresh and cultured cells was determined with a testis xenotransplantation assay. Colonised porcine germ cells were detected only in mouse testes that were either transplanted with fresh testicular cells or with cells from primary cultures. Interestingly, testes transplanted with cells from primary cultures showed colonisation of germ cells in the interstitial space, reflecting their tumourigenic nature. The formation of teratomas with tissues originating from the three germinal layers following the subcutaneous injection of cells into nude mice from primary cultures confirmed their multipotency. The results of the present study may provide useful information for the establishment of multipotent germ stem cell lines from neonatal pig testis.

CD206, a mannose receptor, is mainly expressed on the surface of alternatively activated macrophages where it acts as a pattern recognition receptor and plays a role in innate and adaptive immunity. This study investigated serum soluble CD206 (sCD206) levels in community-acquired pneumonia (CAP) and examined their clinical significance. sCD206 concentrations were measured in the sera of two independent cohorts with CAP (127 and 125 patients, respectively) and 42 controls. The expression of CD206 in the lung from autopsied cases was also examined. Patients with CAP showed significantly elevated sCD206 levels than did the controls (p < 0.0001). Notably, fatal CAP patients had more than two-fold higher sCD206 concentrations than survivors in both cohorts (p < 0.0001). Serum sCD206 concentrations were associated with Pneumonia Severity Index (PSI) and CURB-65 values. Importantly, even fatal CAP patients classified as PSI I-IV, CURB65 0–2 or age <75 years had comparatively higher levels of sCD206 than those classified as PSI V, CURB-65 3–5 or age ≥75 years. Immunohistochemically, the infiltration of CD206+ macrophages was found in the lungs of fatal cases. Elevated levels of sCD206 are associated with CAP prognosis, suggesting sCD206 might be a potential biomarker to predict severity for CAP.