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Cancer treatment has been deeply changed by immunotherapy, achieving unprecedented improvement in overall and progression-free survival in several advanced and metastatic cancers. Currently, immune checkpoint inhibitor (ICI) antibodies against cytotoxic T-lymphocyte antigen (CTLA-4) and programmed death/ligand 1 (PD-1/PD-L1) are being tested and approved for different tumors, ranging from melanoma to lung carcinoma. However, only a subgroup of patients can reach treatment benefits and long-term responses, and reliable biomarkers that can accurately predict clinical responses to immunotherapy are still unidentified. In the last decade, accumulating evidence seems to suggest the gut microbiota as one of the modulators that can alter the efficacy and toxicity of immunotherapy drugs (as well as chemotherapeutics), mainly acting through the local and systemic immune system. Herein, we reviewed the highly dynamic and complex microbiome-immune system interface, its bidirectional relationship with cancer immunotherapies, and explored the future possibilities and risks in manipulating the gut microbiome.Fatty acid esters of hydroxy fatty acids (FAHFAs) represent a complex lipid class that contains both signaling mediators and structural components of lipid biofilms in humans. The majority of endogenous FAHFAs share a common chemical architecture, characterized by an estolide bond that links the hydroxy fatty acid (HFA) backbone and the fatty acid (FA). Two structurally and functionally distinct FAHFA superfamilies are recognized based on the position of the estolide bond omega-FAHFAs and in-chain branched FAHFAs. The existing variety of possible HFAs and FAs combined with the position of the estolide bond generates a vast quantity of unique structures identified in FAHFA families. In this review, we discuss the anti-diabetic and anti-inflammatory effects of branched FAHFAs and the role of omega-FAHFA-derived lipids as surfactants in the tear film lipid layer and dry eye disease. To emphasize potential pharmacological targets, we recapitulate the biosynthesis of the HFA backbone within the superfamilies together with the degradation pathways and the FAHFA regioisomer distribution in human and mouse adipose tissue. We propose a theoretical involvement of cytochrome P450 enzymes in the generation and degradation of saturated HFA backbones and present an overview of small-molecule inhibitors used in FAHFA research. The FAHFA lipid class is huge and largely unexplored. Besides the unknown biological effects of individual FAHFAs, also the enigmatic enzymatic machinery behind their synthesis could provide new therapeutic approaches for inflammatory metabolic or eye diseases. Therefore, understanding the mechanisms of (FA)HFA synthesis at the molecular level should be the next step in FAHFA research.
To evaluate the relationship between the accessibility of automatic external defibrillators (AEDs) and the survival rate of patients who have out-of-hospital cardiac arrest (OHCA).
The systematic review was conducted according to the Cochrane Handbook of Systematic Reviews. We searched the Chinese and English literature databases from 2009 to 2019. Study selection and data collection were conducted by three reviewers. One-month survival rates of OHCA with different AEDs accessibility were estimated using meta-analysis.
Overall 16 studies with 55,537 participants were included. The overall one-month survival rate for OHCA was 27.4%. The one-month survival rate was 35.2% for people receiving AEDs within 5min, 36.6% between 5min to 10min, and 28.4% for longer than 10min. By distance between the location of the AEDs and the location of the cardiac arrest, the one-month survival rate was 37.1% for those≤100m, 22.0% for 100m-200m, and 12.8% for>200m, respectively. The one-month survival rate was 39.3% in schools, sports venues and airports compared with 23.5% in other sites. The number of AEDs allocation was positively correlated, while the time and distance were negatively correlated with the one-month survival rate adjusted for other factors, but they were all non-significant correlations.
The improvement of accessibility of AEDs may increase the survival rate of OHCA and the survival rate may be higher in playgrounds, airports, and schools equipped with AEDs. However, the strength of evidence was limited by the considerably heterogeneity of included studies. Verification of these findings in further studies is warranted.
The improvement of accessibility of AEDs may increase the survival rate of OHCA and the survival rate may be higher in playgrounds, airports, and schools equipped with AEDs. However, the strength of evidence was limited by the considerably heterogeneity of included studies. Verification of these findings in further studies is warranted.Front-of-package (FOP) nutrition labels are placed on products to help consumers make healthy food choices. A lab-in-field experiment was conducted to test the effectiveness of two FOP labels in promoting healthy food choices among Dutch consumers, and to examine whether dieters and health conscious shoppers are more likely to use the FOP labels. In addition, it was examined whether the placement of relatively "good" FOP label scores on products might inadvertently lead to increases in serving sizes. Participants (N = 300) consisted of Dutch consumers shopping for groceries in a local supermarket. They were randomly assigned to one of three conditions (Nutri-score, Multiple Traffic Light (MTL) label, or no label control condition), presented with six different (labeled) cereals, and asked to make a choice. Next, participants were shown a product with a relatively good label score and selected their desired serving size. The results show that the Nutri-score promotes choice of the healthiest cereal. Dieting behaviour and health conscious shopping did not moderate this effect, and the labels did not affect serving size selection. Overall, the study provides evidence for the Nutri-score to promote healthy food choices among Dutch consumers.Growing evidence demonstrates that invertebrates display adaptive-like immune abilities, commonly known as "immune priming". Immune priming is a process by which a host improves its immune defences following an initial pathogenic exposure, leading to better protection after a subsequent infection with the same - or different - pathogens. Nevertheless, beneficial symbionts can enhance similar immune priming processes in hosts, such as when they face repeated infections with pathogens. This "symbiotic immune priming" protects the host against pathogenic viruses, bacteria, fungi, or eukaryotic parasites. In this review, we explore the extent to which protective symbionts interfere and impact immune priming against pathogens from both a mechanical (proximal) and an evolutionary (ultimate) point of view. We highlight that the immune priming of invertebrates is the cornerstone of the tripartite interaction of hosts/symbionts/pathogens. The main shared mechanism of immune priming (induced by symbionts or pathogens) is the sustained immune response at the beginning of host-microbial interactions. However, the evolutionary outcome of immune priming leads to a specific discrimination, which provides enhanced tolerance or resistance depending on the type of microbe. Based on several studies testing immune priming against pathogens in the presence or absence of protective symbionts, we observed that both types of immune priming could overlap and affect each other inside the same hosts. As protective symbionts could be an evolutionary force that influences immune priming, they may help us to better understand the heterogeneity of pathogenic immune priming across invertebrate populations and species.Until recently, it was assumed that insects lack immune memory since they do not have vertebrate-like specialized memory cells. Therefore, their most well studied evolutionary response against pathogens was increased basal immunity. However, growing evidence suggests that many insects also exhibit a form of immune memory (immune priming), where prior exposure to a low dose of infection confers protection against subsequent infection by the same pathogen that acts both within and across generations. Most strikingly, they can rapidly evolve as a highly parallel and mutually exclusive strategy from basal immunity, under different selective conditions and with divergent evolutionary trade-offs. However, the relative importance of priming as an optimal immune strategy also has contradictions, primarily because supporting mechanisms are still unclear. In this review, we adopt a comparative approach to highlight several emerging evolutionary, ecological and mechanistic features of priming vs basal immune responses that warrant immediate attention for future research.Arsenite induces many critical effects associated with the formation of reactive oxygen species (ROS) through different mechanisms. We focused on Ca2+-dependent mitochondrial superoxide (mitoO2-.) formation and addressed questions on the effects of low concentrations of arsenite on the mobilization of the cation from the endoplasmic reticulum and the resulting mitochondrial accumulation. Using various differentiated and undifferentiated cell types uniquely expressing the inositol-1, 4, 5-triphosphate receptor (IP3R), or both the IP3R and the ryanodine receptor (RyR), we determined that expression of this second Ca2+ channel is an absolute requirement for mitoO2-. formation and for the ensuing mitochondrial dysfunction and downstream apoptosis. In arsenite-treated cells, RyR was recruited after IP3R stimulation and agonist studies provided an indirect indication for a close apposition between RyR and mitochondria. It was also interesting to observe that arsenite fails to promote mitochondrial Ca2+ accumulation, mitoO2-. formation and mitochondrial toxicity in RyR-devoid cells, in which the IP3R is in close contact with the mitochondria. We therefore conclude that low dose arsenite-induced mitoO2- formation, and the resulting mitochondrial dysfunction and toxicity, are prerequisite of cell types expressing the RyR in close apposition with mitochondria.Dwarf bunt of wheat caused by Tilletia controversa Kühn has been identified an international quarantine disease, which replace the grain material into millions of teliospores. Agrobacterium tumefaciens-mediated transformation (ATMT) system is a powerful tool for fungi transformation with significant advantages of simple operation, high efficiency, and genetic stability of transformants. In this study, we constructed ATMT system for T. controversa. All the transformants were tested using Acetosyringone (AS) concentration at 150 μmol/l, hygromycin B at 25 μg/ml, 1 × 106 T. GSK 3 inhibitor controversa hypha cells/ml, A. tumefaciens with OD600 of 0.5 co-cultivation at 16 °C for 48 h and culture was incubated at 16 °C for 20 days. Using the ATMT method, we cultivated 8 generations of transformants on complete medium (CM) containing hygromycin B antibiotic and validated by PCR, which indicate that T-DNA had been successfully inserted into each of T. controversa transformants. In addition, thermal asymmetric interlaced PCR (TAIL-PCR) evaluated the Ti element inserts were at random sites in the fungal genome.
Website: https://www.selleckchem.com/GSK-3.html
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