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In this study, B. coagulans ATCC 7050T was used as a probiotic supplement. Genome analysis showed that carbohydrate metabolism pathways related to lactose and galactose were determined in B. coagulans ATCC 7050T, which indicated this strain has adaptability to fermented milk. The sugar metabolism phenotype analysis of this strain was also studied. The results showed that the strain had application potential in the development of dairy industry. Subsequently, the quality of yogurt samples fermented by commercial starter culture and B. coagulans ATCC 7050T in three proportions (1:1, 1:5, 1:10) was evaluated. Compared to the control group, the addition of B. coagulans ATCC 7050T enhanced fermented milk acidification and proteolysis. However, the post-acidification differences were more obvious with prolonged storage and the use of a larger inoculum of B. coagulans ATCC 7050T. Next, the physical properties of yogurt samples, including water holding capacity, hardness, consistency, cohesiveness, viscosity, and volatile compound content, were determined during the storage period. Compared to other groups, the yogurt samples in the YO-MIX 300 + B. coagulans ATCC 7050T (1:1) group were the most similar to the control group, suggesting the recommended proportion between starter culture and B. coagulans ATCC 7050T was 1:1 (viable bacteria). • Genomic analysis showed B. coagulans ATCC 7050T had the ability to utilize lactose and galactose. • Sugar metabolism phenotype analysis suggested this strain has adaptability to fermented milk. • The addition of B. coagulans ATCC 7050T significantly changed the physical properties of yogurt. [ABSTRACT FROM AUTHOR]

Ischemic stroke is a common disease worldwide with high mortality and disability rates. Nevertheless, pathogenesis of ischemic stroke is still vague, and finding novel therapeutic target is urgently necessary. TMEM59 (also known as dendritic cell-derived factor 1, DCF1), a type I transmembrane protein, contains a minimal 19-amino-acid peptide in its intracellular domain, and has been involved in neurological pathology. However, its biological impacts on ischemic stroke are still unknown. In this study, we provided new evidence that TMEM59 expression was significantly down-regulated upon ischemia/reperfusion (I/R). The effect of stroke insult on TMEM59 expression change was only detected in microglial cells by in vitro studies. We observed that TMEM59 knockout markedly accelerated cerebral I/R in mice induced by middle cerebral artery occlusion (MCAO), as evidenced by the elevated infarction volume, neurological deficit scores, brain water contents and neuronal death, further contributing to the abnormal behaviors for mice. We then found that microglial activation reflected by the enhanced expression of Iba-1 was dramatically potentiated by TMEM59 knockout in MCAO-treated mice. Pyroptosis was highly triggered in mice with cerebral I/R, while being further aggravated in mice with TMEM59 deletion, as proved by the considerably increased expression of NLRP3, ASC, cleaved Caspase-1, GSDMD-N, mature-IL-1β and mature-IL-18. Additionally, TMEM59 knockout mice exhibited accelerated activation of NF-κB signaling pathway compared with the wild type group of mice after MCAO operation, indicating the anabatic neuroinflammation. The effects of TMEM59 suppression on ischemic stroke were confirmed in microglial cells with exposure to oxygen-glucose deprivation/reoxygenation (OGD/R). In contrast, the in vitro studies verified that improving TMEM59 expression effectively hindered pyroptosis and inflammation in microglial cells upon OGD/R treatment. Taken together, these findings illustrated protective effects of TMEM59 against ischemic stroke through restraining pyroptosis and inflammatory response. Image 1 • TMEM59 expression in microglial cells is down-regulated in ischemic stroke. • TMEM59 deficiency accelerates ischemic stroke of MCAO-treated mice. • TMEM59 knockout promotes microglial activation, pyroptosis and neuroinflammation. • TMEM59 protects against pyroptosis and neuroinflammation in vitro. [ABSTRACT FROM AUTHOR]

Donor-derived CD4 + T lymphocytes are the major effector cells directly involved in the development of graft-versus-host disease (GVHD). As a negative regulator of immune cell differentiation and development, microRNA-150 (miR-150) induces immunological tolerance in CD4 + T cells after transplantation. However, the specific mechanisms have not been fully elucidated. In this study, we demonstrated that miR-150 is capable of not only inhibiting proliferation and activation of CD4 + T cells but also promoting apoptosis. Mechanistically, miR-150 targets v-akt murine thymoma viral oncogene homolog 3 (AKT3), and subsequently downregulates B-cell lymphoma 2 (Bcl-2) interacting mediator of cell death (BIM). We have also demonstrated that re-expression of AKT3 reversed miR-150-mediated inhibition of CD4 + T lymphocyte development. Therefore, we conclude that miR-150 negatively regulates CD4 + T cell function by inhibiting the AKT3/BIM signaling pathway. These findings also suggest that manipulating the levels of miRNA-150 could be a valuable strategy in prevention and/or treatment of acute graft-versus-host disease. [ABSTRACT FROM AUTHOR]

Constitutive NF-κB activation is required for survival of activated B cell-like subtype of diffuse large B cell lymphoma (ABC-DLBCL). However, current NF-κB targeting strategies lack cancer cell specificity. Here, we identified a novel inhibitor, piperlongumine, features direct binding to NF-κB p65 subunit and suppression of p65 nuclear import. This was accompanied by NF-κB reporter activity suppression and NF-κB target gene downregulation. Moreover, mutation of Cys 38 to Ser in p65 abolished this effect of piperlongumine on inhibition of p65 nuclear import. Furthermore, we show that piperlongumine selectively inhibited proliferation and induced apoptosis of ABC-DLBCL cells. Most notably, it has been reported that piperlongumine did not affect normal cells even at high doses and was nontoxic to animals. Hence, our current study provides new insight into piperlongumine's mechanism of action and novel approach to ABC-DLBCL target therapy. [ABSTRACT FROM AUTHOR]

Abstract: Janus kinase 2 (JAK2) is an important mediator of cytokine receptor signaling and plays a key role in the hematopoietic and immune responses. The acquired JAK2 C618R somatic mutation is detected in a subset of myeloproliferative disorders (MPDs) patients and presumed to be a biomarker for MPDs. However, how JAK2 C618R mutation causes MPDs is still unclear. Our results indicate that the amino acid residue E543 in JAK2 C618R is indispensable for its constitutive activation. When the glutamic acid at this position was mutated to alanine (E543A) in the JAK2 C618R, its activity significantly decreased. However when the glutamic acid was mutated to the acidic amino acid, aspartic acid, JAK2 C618R activity changed little. These results suggest that there is an interaction between the amino acid residue R618 and E543, and that this interaction is crucial to sustain the constitutive activation of JAK2 C618R. More importantly, the E543 single mutation had no effects on the function of wild type JAK2 (WT JAK2). This study suggests that the amino acid residue E543 might be a potential target for specific inhibitors to treat MPDs caused by the JAK2 C618R mutation. [Copyright &y& Elsevier]