CD45 regulates retention, motility, and numbers of hematopoietic progenitors, and affects osteoclast remodeling of metaphyseal trabecules

The CD45 phosphatase is uniquely expressed by all leukocytes, but its role in regulating hematopoietic progenitors is poorly understood. We show that enhanced CD45 expression on bone marrow (BM) leukocytes correlates with increased cell motility in response to stress signals. Moreover, immature CD45 knockout (KO) cells showed defective motility, including reduced homing (both steady state and in response to stromal-derived factor 1) and reduced granulocyte colony-stimulating factor mobilization. These defects were associated with increased cell adhesion mediated by reduced matrix metalloproteinase 9 secretion and imbalanced Src kinase activity. Poor mobilization of CD45KO progenitors by the receptor activator of nuclear factor κB ligand, and impaired modulation of the endosteal components osteopontin and stem cell factor, suggested defective osteoclast function. Indeed, CD45KO osteoclasts exhibited impaired bone remodeling and abnormal morphology, which we attributed to defective cell fusion and Src function. This led to irregular distribution of metaphyseal bone trabecules, a region enriched with stem cell niches. Consequently, CD45KO mice had less primitive cells in the BM and increased numbers of these cells in the spleen, yet with reduced homing and repopulation potential. Uncoupling environmental and intrinsic defects in chimeric mice, we demonstrated that CD45 regulates progenitor movement and retention by influencing both the hematopoietic and nonhematopoietic compartments

Necator americanus and Helminth Co-Infections: Further Down-Modulation of Hookworm-Specific Type 1 Immune Responses

Parasitic infections in humans are common in tropical regions and under bad housing and sanitation conditions multiple parasitic infections are the rule rather than the exception. For helminth infections, which are thought to affect almost a quarter of the world's population, most common combinations include soil-transmitted helminths, such as hookworm, roundworm, and whipworm, as well as extra-intestinal infections by schistosomes. In order to develop and test a hookworm vaccine in endemic areas, the understanding of the impact of multiple helminth infections (co-infection) on the immune response against hookworm in infected individuals is crucial. The authors report in their article, that several parameters of the cellular (T cell markers, cytokines, chemokines) and humoral immune response (e.g. IgG4 and IgE antibodies) against hookworm are significantly affected or modulated in individuals co-infected with hookworm, roundworm and/or schistosomes. These results imply that the immune response against components of a hookworm vaccine might be altered by previous contact with other helminth species in endemic areas

Wide Spectrum Potent Antimicrobial Efficacy of Wound Dressings Impregnated with Cuprous Oxide Microparticles

Copper has intrinsic antimicrobial properties. Wound dressings impregnated with cuprous oxide microparticles (hereafter termed COD) have been cleared for the management of acute and chronic wounds by the FDA and other regulatory bodies. The COD reduced the viable microbial titers of a wide spectrum of microbes by more than 10,000-fold (4-logs) within 3 h of exposure at 37 °C (p < 0.001). Similar microbial titer reductions were achieved by 3-year naturally aged COD dressings, showing the stability of the biocidal efficacy over time. The potent biocidal efficacy of the COD was maintained even after 7 daily consecutive inoculations of the dressings with ~106 CFU. COD with an adhesive contour blocked the passage of bacteria from the exterior environment to the wound bed side of the dressing even after 7 daily consecutive inoculations of different bacteria on the outer surface of the dressings. Taken together, the study demonstrates the wide spectrum potent in vitro biocidal efficacy of the cuprous oxide impregnated dressings against a wide panel of microorganisms

Wide Spectrum Potent Antimicrobial Efficacy of Wound Dressings Impregnated with Cuprous Oxide Microparticles

Copper has intrinsic antimicrobial properties. Wound dressings impregnated with cuprous oxide microparticles (hereafter termed COD) have been cleared for the management of acute and chronic wounds by the FDA and other regulatory bodies. The COD reduced the viable microbial titers of a wide spectrum of microbes by more than 10,000-fold (4-logs) within 3 h of exposure at 37 °C (p 6 CFU. COD with an adhesive contour blocked the passage of bacteria from the exterior environment to the wound bed side of the dressing even after 7 daily consecutive inoculations of different bacteria on the outer surface of the dressings. Taken together, the study demonstrates the wide spectrum potent in vitro biocidal efficacy of the cuprous oxide impregnated dressings against a wide panel of microorganisms

Circulating Levels of Visceral Adipose Tissue-Derived Serine Protease Inhibitor (Vaspin) Appear as a Marker of Musculoskeletal Pain Disability

Musculoskeletal pain (MSP), specifically low back pain (LBP), is often associated with several adipose tissue-derived cytokines (adipokines) and body composition, but their correlations with the LBP-related disability/severity phenotypes remain poorly understood. In this cross-sectional study, two self-reported validated questionnaires were used to collect back pain and disability data in an ethnically homogeneous family-based population sample (N = 1078). Plasma levels of relatively new adipokines, vaspin and adipsin, were detected by ELISA. Body composition parameters, including fat, skeletal muscle mass, extracellular water (ECW), and others were assessed through bioelectrical impedance analysis (BIA) technology. Statistical analysis was conducted, accounting for the familial composition of the sample. The multiple regression analyses with four LBP-related phenotypes as dependent variables consistently showed, for the first time, the significant associations with vaspin levels, regardless of other covariates. The odds ratios (OR)/SD ranged between 1.24 (95%CI = 1.03–1.50) and 1.33 (95%CI = 1.07–1.64), depending on the LBP phenotype. Among the tested body composition covariates, only ECW levels displayed consistent and highly significant associations with all tested LBP phenotypes (OR from 1.43, 95%CI = 1.14–1.79 to 1.68, 95%CI = 1.26–2.24). The results clearly suggest that circulating concentrations of vaspin and ECW levels could serve as biomarkers of MSP/LBP severity and complications

Pro-Inflammatory Biomarkers Combined with Body Composition Display a Strong Association with Knee Osteoarthritis in a Community-Based Study

Knee osteoarthritis (KOA) is one of the most common progressive, age-dependent chronic degenerative joint diseases. KOA often develops as a result of a gradual articular cartilage loss caused by its wear and tear. Numerous studies suggest that the degradation of the knee joint involves inflammatory components. This process is also associated with body composition, particularly being overweight and muscle mass loss. The present study aimed to search for novel circulating KOA inflammatory biomarkers, taking into account body composition characteristics. To this aim, we recruited 98 patients diagnosed and radiologically confirmed with KOA and 519 healthy controls from the Arab community in Israel. A panel of soluble molecules, related to inflammatory, metabolic, and musculoskeletal disorders, was measured by ELISA in plasma samples, while several body composition parameters were assessed with bioimpedance analysis. Statistical analysis, including multivariable logistic regression, revealed a number of the factors significantly associated with KOA, independently of age and sex. The most significant independent associations [OR (95% CI)] were fat body mass/body weight index—1.56 (1.20–2.02), systemic immune-inflammation index—4.03 (2.23–7.27), circulating vaspin levels—1.39 (1.15–1.68), follistatin/FSTL1 ratio—1.32 (1.02–1.70), and activin A/FSTL1 ratio—1.33 (1.01–1.75). Further clinical studies are warranted to confirm the relevance of these KOA-associated biological factors. Hereafter, they could serve as reliable biomarkers for KOA in the general human population