Ingramwalker5993

Cancer cells generally recruit and influence non-malignant immune cells to support the tumor growth. Classical Hodgkin lymphoma (cHL) is a good example because the affected lymphoid tissue contains only a few malignant Hodgkin and Reed-Sternberg (H-RS) cells, which are supported by a massive infiltrate of lymphocytes, fibroblasts, and innate immune cells. The transmembrane receptor CD30, which is selectively expressed on the H-RS cells, plays an important role, not only in cell stimulation and intercellular communication but also in tumor diagnosis and targeted tumor therapy. Different protein processing pathways influence its functionality. Depending on the conditions, the receptor is internalized or released. The release of CD30 occurs either as an intact molecule, embedded in the membrane of extracellular vesicles (EVs), or as a cleaved soluble ectodomain (sCD30). CD30 cleavage is predominantly catalyzed by ADAM10. The enzyme is catalytically active in cells as well as in EVs and gradually releases sCD30. Because the circulation contains no CD30+ donor cells, this mechanism explains that the cleaved ectodomain represents the predominant form of CD30 in the plasma of cHL patients. CD30 processing might influence the impact of CD30 antibody-drug conjugates, such as Brentuximab Vedotin (BV). Whereas, ADAM10-degraded CD30 impedes the BV efficacy, tumor-derived EVs load bystander cells with CD30 and generate new targets among supporter cells. This crossfire effect might contribute to the enormous clinical impact of BV, whereas the ADAM10-dependent cleavage to the mild systemic off-target effects of the treatment with BV. Copyright © 2020 Hansen, Paes Leme and Hallek.We report on an observational, multicenter study of 345 adult CVID patients, designed to assess the diagnostic value and the clinical association of serum free light chain (sFLC) pattern in Common Variable Immunodeficiency disorders (CVID). Sixty CVID patients were tested twice in order to assess intraindividual variability of sFLC. As control groups we included 138 patients affected by undefined primary antibody defects (UAD), lymphoproliferative diseases (LPDs), and secondary antibody deficiencies not related to hematological malignancies (SID). CVID patients presented lower κ and λ chain concentration compared to controls, showing low intraindividual sFLC variability. On the basis of the sFLC pattern, patients were classified into four groups κ-λ+, κ+λ-, κ-λ-, κ+λ+. The most common pattern in CVID patients was κ-λ- (51%), followed by κ-λ+, (25%), κ+λ+ (22%), and κ+λ- (3%). In UAD, LPD, and SID groups κ+λ+ was the most common pattern observed. By analyzing the possible association between sFLC patterns and ttern seems to be related to disease phenotypes and clinical manifestations of CVID and after confirmation by further studies, sFLC assay might be considered a promising prognostic tool for identifying patients at higher risk of developing enteropathy and chronic lung damage or splenomegaly. This will allow designing a tailored follow-up for CVID patients. Copyright © 2020 Scarpa, Pulvirenti, Pecoraro, Vultaggio, Marasco, Ria, Altinier, Compagno, Firinu, Plebani, De Carli, Matucci, Vianello, Vacca, Spadaro, Quinti, Agostini, Milito and Cinetto.Functional equilibrium between vaginal microbiota and the host is important for maintaining gynecological and reproductive health. Apart from host genetics, infections, changes in diet, life-style and hygiene status are known to affect this delicate state of equilibrium. More importantly, the gonadal hormones strongly influence the overall structure and function of vaginal microbiota. Several studies have attempted to understand (a) the composition of vaginal microbiota in specific stages of women's reproductive cycle as well as in menopause (b) their association with gonadal hormones, and their potential role in manifestation of specific health conditions (from the perspective of cause/consequence). However, a single study that places, in context, the structural variations of the vaginal microbiome across the entire life-span of women's reproductive cycle and during various stages of menopause is currently lacking. With the objective to obtain a holistic overview of the community dynamics of vaginal micro-end post-reproductive phases. In addition to reinforcing the known influence/role of gonadal hormones in maintaining gynecological health, results indicate how hormonal level perturbations cause/contribute to imbalances in vaginal microbiota. The nature of resulting dysbiotic state and its influence on vaginal health is also analyzed and discussed. Results also suggest that elevated vaginal microbial diversity in pregnancy does not necessarily indicate a state of bacterial infection. The study puts forward a hormone-level driven microbiome diversity hypothesis for explaining temporal patterns in vaginal microbial diversity during various stages of women's reproductive cycle and at menopause. Copyright © 2020 Kaur, Merchant, Haque and Mande.Antimicrobial-resistant (AMR) bacterial infections, including those caused by Acinetobacter baumannii, have emerged as a clinical crisis worldwide. read more Immunization with AMR determinants has been suggested as a novel approach to combat AMR bacteria, but has not been validated. The present study targeted tigecycline (TGC) resistance determinants in A. baumannii to test the feasibility of this approach. Using bioinformatic tools, four candidates, AdeA, AdeI, AdeK, and TolC, belonging to the resistance-nodulation-division (RND) efflux pump were identified as highly conserved and exposed antigens from 15 A. baumannii genomes. Antisera generated from recombinant proteins showed the capability to reserve Hoechst 33342, a substrate of the efflux pump, in bacterial cells. The rTolC antisera had the highest complement-dependent killing and opsonophagocytosis effect compared to the sera from phosphate-buffered saline immunized mice. Among the antisera, anti-rAdeK-specific antisera decreased the minimal inhibitory concentration of TGC in 26.7% of the tested isolates. Immunization with rAdeK significantly potentiated TGC efficacy in treating TGC-resistant A. baumannii pneumonia in the murine model. The bacterial load (7.5 × 105 vs. 3.8 × 107, p less then 0.01) and neutrophil infiltration in the peri-bronchial vasculature region of immunized mice was significantly lower compared to the PBS-immunized mice when TGC was administrated concomitantly. Collectively, these results suggest that active immunization against resistance determinants might be a feasible approach to combat multidrug-resistant pathogens in high risk population. Copyright © 2020 Chiang, Yang, Sun, Wang, Kuo, Lee, Chuang and Chen.