The recent movement toward returning individual research results to study subjects/participants generates ethical and legal challenges for laboratories performing research on human biospecimens. The concept of an individual's interest in knowing the results of testing on their tissue is pitted against individual and systemic risks and an established legal framework regulating the performance of laboratory testing for medical care purposes. This article discusses the rationale for returning individual research results to subjects, the potential risks associated with returning these results, and the legal framework in the United States that governs testing of identifiable human biospecimens. On the basis of these considerations, this article provides recommendations for investigators to consider when planning and executing human biospecimen research, with the objective of appropriately balancing the interests of research subjects, the need for ensuring integrity of the research process, and compliance with US laws and regulations. Intratracheal instillation of apoptotic cells enhances resolution of experimental lung inflammation by incompletely understood mechanisms. We report that this intervention induces functional regulatory T lymphocytes (Tregs) in mouse lung experimentally inflamed by intratracheal administration of lipopolysaccharide (LPS). Selective depletion demonstrated that Tregs were necessary for maximal apoptotic cell-directed enhancement of resolution and adoptive transfer of additional Tregs was sufficient to promote resolution without administering apoptotic cells. After intratracheal instillation labelled apoptotic cells were observed in the majority of CD11c+CD103+ myeloid dendritic cells (DCs) migrating to mediastinal draining lymph nodes and bearing migratory and immunoregulatory markers including increased CCR7 and β8 integrin (ITGB8) expression. In mice deleted for αv integrin in the myeloid line so as to reduce phagocytosis of dying cells by CD103+DCs, exogenous apoptotic cells failed to induce TGF-β1 expression or Treg accumulation and also failed to enhance resolution of LPS-induced lung inflammation. We conclude that in murine lung, myeloid phagocytes encountering apoptotic cells can deploy αv integrin-mediated mechanisms to induce Tregs and enhance resolution of acute inflammation. Hyaluronidase-2 (HYAL2) is a weak, acid-active hyaluronan-degrading enzyme that is broadly expressed in somatic tissues. Aberrant HYAL2 expression is implicated in diverse pathology. However, a significant proportion of HYAL2 is enzymatically inactive, thus the mechanisms through which HYAL2 dysregulation influences pathobiology is unclear. Recently, non-enzymatic HYAL2 functions have been described and our group has shown that nuclear HYAL2 can influence mRNA splicing to prevent myofibroblast differentiation. Myofibroblasts drive fibrosis, thereby promoting progressive tissue damage and leading to multimorbidity. This study identifies a novel HYAL2 cytoplasmic function in myofibroblasts that is unrelated to its enzymatic activity. In fibroblasts and myofibroblasts HYAL2 interacts with the small GTPase signaling molecule, RhoA. Transforming Growth Factor (TGF)-β1-driven fibroblast-to-myofibroblast differentiation promotes HYAL2 cytoplasmic re-localization to bind to the actin cytoskeleton. Cytoskeletal-bound HYAL2 functions as a key regulator of downstream RhoA signaling and influences pro-fibrotic myofibroblast functions including myosin light-chain kinase (MLCK) mediated myofibroblast contractility, myofibroblast migration, myofibroblast collagen/fibronectin deposition, as well as connective tissue growth factor (CTGF/CCN2) and matrix metalloproteinase-2 (MMP2) expression. These data demonstrate that in certain biological contexts the non-enzymatic effects of HYAL2 are critical in orchestrating RhoA signaling and downstream pathways that are important for full pro-fibrotic myofibroblast functionality. In conjunction with previous data demonstrating the influence of HYAL2 on RNA splicing, these findings begin to explain the broad biological effects of HYAL2. Gastric cancer is associated with chronic inflammation (gastritis) triggered by infection with the Helicobacter pylori (H. pylori) bacterium. Elevated tyrosine phosphorylation (pY) of the latent transcription factor STAT3 is a feature of gastric cancer, including H. pylori-infected tissues, and is aligned to nuclear transcriptional activity. By contrast, the transcriptional role of STAT3 serine phosphorylation (pS), which promotes STAT3-driven mitochondrial activities, is unclear. Here, by coupling pS-STAT3-deficient Stat3SA/SA mice with chronic H. felis infection, we reveal a key role for pS-STAT3 in promoting Helicobacter-induced gastric pathology. Immunohistochemical staining for infiltrating immune cells, and expression analyses of inflammatory genes, revealed that chronic gastritis was markedly suppressed in infected Stat3SA/SA mice compared to wild-type (WT) mice. Stomach weight and gastric mucosal thickness were also reduced in infected Stat3SA/SA (compared to WT) mice, which was associated with reduced proliferative potential of infected Stat3SA/SA gastric mucosa. The suppressed H. felis-induced gastric phenotype of Stat3SA/SA mice was phenocopied upon genetic ablation of signaling by the cytokine IL-11, which promotes gastric tumourigenesis via STAT3. pS-STAT3 dependency by Helicobacter coincided with transcriptional activity on STAT3-regulated genes, rather than its effect on mitochondrial and metabolic gene networks. In gastric mucosa of mice and gastritis patients, pS-STAT3 was constitutively expressed irrespective of Helicobacter infection. Collectively, these findings suggest an obligate requirement for IL-11 signaling via constitutive pS-STAT3 in Helicobacter-induced gastric carcinogenesis. Amyloid β-proteins (Aβs) Aβ1-42 and Aβ1-43 are converted via two product lines of γ-secretase to Aβ1-38 and Aβ1-40. This parallel stepwise processing model of γ-secretase predicts that Aβ1-42 and Aβ1-43, and Aβ1-38 and Aβ1-40 are proportional to each other, respectively. To obtain further insight into the mechanisms of parenchymal Aβ deposition, these four Aβ species were quantified in insoluble fractions of human brains (Brodmann areas 9-11) at various Braak senile plaque (SP) stages, using specific enzyme-linked immunosorbent assays.  https://www.selleckchem.com/products/reparixin-repertaxin.html  With advancing SP stages, the amounts of deposited Aβ1-43 in the brain increased proportionally to those of Aβ1-42. Similarly, the amounts of deposited Aβ1-38 correlated with those of Aβ1-40. Surprisingly, the ratios of deposited Aβ1-38/Aβ1-42 and Aβ1-40/Aβ1-43 were proportional and discriminated the Braak SP stages accurately. This result indicates that the generation of Aβ1-38 and Aβ1-40 decreased and the generation of Aβ1-42 and Aβ1-43 increased with advancing SP stages. Thus, Aβs deposition might depend on γ-secretase activity, as it does in the cerebrospinal fluid (CSF).