Ramirezstout1612

We report 17 cases of sinusoidal large B-cell lymphoma (SLBCL). Clinical, morphologic, immunophenotypic, and molecular features were detected and analyzed. All cases showed an obvious sinusoidal growth pattern, usually associated with residual atrophic lymphoid tissue. All tumors contained large pleomorphic lymphoid cells and one or more prominent nucleoli, with abundant amphophilic cytoplasms; 15/17 cases showed anaplastic morphologic features. The patient age ranged from 43 to 80 years (median 57 years), and 7 males and 10 females were included. Eleven of 15 (73.3%) patients had Ann Arbor stage III or IV disease, and 10/15 (66.6%) patients had an International Prognostic Index (IPI) score ≥3. Immunophenotypically, 16/17 (94.1%) cases displayed a nongerminal center B-cell (non-GCB) immunophenotype. Furthermore, 16/17 (94.1%) cases were positive for CD30, and p53 was expressed in 10/16 (62.5%) cases. In total, 12/14 (85.7%) cases expressed BCL2 and MYC simultaneously (double expression), and 11/14 (78.6%) casBCL) have many overlapping clinicopathological and molecular features.An infestation of cat fleas in a research center led to the detection of two genotypes of Ctenocephalides felis biting humans in New Jersey, USA. The rarer flea genotype had an 83% incidence of Rickettsia asembonensis, a recently described bacterium closely related to R. felis, a known human pathogen. A metagenomics analysis developed in under a week recovered the entire R. asembonensis genome at high coverage and matched it to identical or almost identical (> 99% similarity) strains reported worldwide. Our study exposes the potential of cat fleas as vectors of human pathogens in crowded northeastern U.S, cities and suburbs where free-ranging cats are abundant. Furthermore, it demonstrates the power of metagenomics to glean large amounts of comparative data regarding both emerging vectors and their pathogens.Propionate is a short-chain fatty acid (SCFA) mainly produced from carbohydrates by gut microbiota. Sodium propionate (SP) has shown to suppress the invasion in G protein-coupled receptor 41 (GPR41) and GPR43-overexpressing breast cancer cells. In this study we investigated the effects of SP on the proliferation, apoptosis, autophagy, and antioxidant production of breast cancer cells. We showed that SP (5-20 mM) dose-dependently inhibited proliferation and induced apoptosis in breast cancer cell lines JIMT-1 (ER-negative and HER2-expressing) and MCF7 (ER-positive type), and this effect was not affected by PTX, thus not mediated by the GPR41 or GPR43 SCFA receptors. Meanwhile, we demonstrated that SP treatment increased autophagic and antioxidant activity in JIMT-1 and MCF7 breast cancer cells, which might be a compensatory mechanism to overcome SP-induced apoptosis, but were not sufficient to overcome SP-mediated suppression of proliferation and induction of apoptosis. We revealed that the anticancer effect of SP was mediated by inhibiting JAK2/STAT3 signaling which led to cell-cycle arrest at G0/G1 phase, and increasing levels of ROS and phosphorylation of p38 MAPK which induced apoptosis. In nude mice bearing JIMT-1 and MCF7 cells xenograft, administration of SP (20 mg/mL in drinking water) significantly suppressed tumor growth by regulating STAT3 and p38 in tumor tissues. These results suggest that SP suppresses proliferation and induces apoptosis in breast cancer cells by inhibiting STAT3, increasing the ROS level and activating p38. Therefore, SP is a candidate therapeutic agent for breast cancer.Immunotherapies for cancers may cause severe and life-threatening cardiotoxicities. The underlying mechanisms are complex and largely elusive. Currently, there are several ongoing clinical trials based on the use of activated invariant natural killer T (iNKT) cells. The potential cardiotoxicity commonly associated with this particular immunotherapy has yet been carefully evaluated. The present study aims to determine the effect of activated iNKT cells on normal and β-adrenergic agonist (isoproterenol, ISO)-stimulated hearts. Mice were treated with iNKT stimulants, α-galactosylceramide (αGC) or its analog OCH, respectively, to determine their effect on ISO-induced cardiac injury. We showed that administration of αGC (activating both T helper type 1 (Th1)- and T helper type 2 (Th2)-liked iNKT cells) significantly accelerated the progressive cardiac injury, leading to enhanced cardiac hypertrophy and cardiac fibrosis with prominent increases in collagen deposition and TGF-β1, IL-6, and alpha smooth muscle actin expression. In contrast to αGC, OCH (mainly activating Th2-liked iNKT cells) significantly attenuated the progression of cardiac injury and cardiac inflammation induced by repeated infusion of ISO. Flow cytometry analysis revealed that αGC promoted inflammatory macrophage infiltration in the heart, while OCH was able to restrain the infiltration. In vitro coculture of αGC- or OCH-pretreated primary peritoneal macrophages with primary cardiac fibroblasts confirmed the profibrotic effect of αGC and the antifibrotic effect of OCH. Our results demonstrate that activating both Th1- and Th2-liked iNKT cells is cardiotoxic, while activating Th2-liked iNKT cells is likely cardiac protective, which has implied key differences among subpopulations of iNKT cells in their response to cardiac pathological stimulation.Mucosal surfaces are colonized by highly diverse commensal microbiota. Coating with secretory IgA (SIgA) promotes the survival of commensal bacteria while it inhibits the invasion by pathogens. Bacterial coating could be mediated by antigen-specific SIgA recognition, polyreactivity, and/or by the SIgA-associated glycans. In contrast to many in vitro studies, only a few reported the effect of SIgA glycans in vivo. Here, we used a germ-free antibody-free newborn piglets model to compare the protective effect of SIgA, SIgA with enzymatically removed N-glycans, Fab, and Fc containing the secretory component (Fc-SC) during oral necrotoxigenic E. coli O55 challenge. SIgA, Fab, and Fc-SC were protective, whereas removal of N-glycans from SIgA reduced SIgA-mediated protection as demonstrated by piglets' intestinal histology, clinical status, and survival. In vitro analyses indicated that deglycosylation of SIgA did not reduce agglutination of E. ZM 447439 mw coli O55. These findings highlight the role of SIgA-associated N-glycans in protection.