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To modulate immunosuppressive tumor microenvironment and overcome the cancerous resistance to chemotherapy for effectively tumor killing, the novel nano-assemblies were developed for tumor chemo-immunotherapy. The broken of polydopamine (PDA) sensitized the tumor cells for reducing the tumor resistance against doxorubicin (DOX) and effectively induced immunogenic tumor cell death (ICD), respectively. The neo-antigen generated by the ICD effect in situ could be greatly presented by the simvastatin (SIM) activated dendritic cells (DCs) for specific T cells production. [Display omitted] • To modulate immunosuppressive tumor microenvironment and overcome the cancerous resistance to chemotherapy for effectively tumor killing, the SIM@NPs-PDA/DOX nano-assemblies, was developed to sequentially delivery doxorubicin (DOX), polydopamine (PDA) and simvastatin (SIM) for tumor chemo-immunotherapy. • The nano-assemblies were made of two kinds of lipopolymer, PDA-conjugated DSPE-PEG and DOX-absorbed DSPE-PEG. The SIM was subsequently loaded into the hydrophobic core during the self-assembling process. • The PDA was found the function of sensitizing the tumor cells for reducing the tumor resistance against DOX by deactivating AKT signaling pathway. • The neo-antigen generated by the immunogenic tumor cell death (ICD) effect in situ could be greatly presented by the SIM activated dendritic cells (DCs) for specific T cells production. The combination of chemotherapy and immunotherapy is the first line treatment for many cancers. However, resistance to chemotherapy is a common phenomenon, as well as the failure of antigen presentation and T cell infiltration are the fundamental obstacle for effective combined oncotherapy. Many studies have clarified the importance of increased reactive oxygen species (ROS) in reducing multidrug resistance (MDR) by disrupting oxidative balance and activating signaling pathways. Here, to modulate immunosuppressive tumor microenvironment (TME) and overcome the cancerous resistance to chemotherapy for effectively tumor killing, the SIM@NPs-PDA/DOX nano-assemblies, was developed to sequentially delivery doxorubicin (DOX), polydopamine (PDA) and simvastatin (SIM) for tumor chemo-immunotherapy. When the nano-assemblies penetrated into tumor TME, PDA and DOX were released by the hypoxia and low acid condition of TME, which sensitized the tumor cells for reducing the tumor resistance against DOX and effectively induced immunogenic tumor cell death (ICD), respectively. The neo-antigen generated by the ICD effect in situ could be greatly presented by the SIM activated dendritic cells (DCs) for specific T cells production. Simultaneously, the released DOX was also expected to kill tumor-associated macrophages (TAMs) for enhancing the specific T cell infiltration. In B16F10 and MCF-7 tumor cells with acquired drug resistance and relevant tumor models, the designed nano-assemblies showed powerful anti-tumor effects by reducing MDR, killing cancer cells and TAMs, promoting CD8+ T cells activation and infiltration. This study provides a novel nano-assemblies for effective onco-immuno-chemotherapy by overcoming cancer multidrug resistance and immuno-depletion. [ABSTRACT FROM AUTHOR]

Our previous studies have showed that sulfatide-reactive type II NKT (i.e. variant NKT, vNKT) cells inhibit the immunogenic maturation during the development of mature lung dendritic cells (LDCs), leading todeclined allergic airway inflammation in asthma. Nonetheless, the specific immunoregulatory roles of vNKT cells in LDC-mediated Th2 cell responses remain incompletely understood. Herein, we found that administration of sulfatide facilitated the generation of CD4+FoxP3+ regulatory T (Treg) cells in the lungs of wild-type mice, but not in CD1d−/− and Jα18−/− mice, after ovalbumin or house dust mite exposure. This finding implies that the enhancement of lung Treg cells by sulfatide requires vNKT cells, which dependent on invariant NKT (iNKT) cells. Furthermore, the CD4+FoxP3+ Treg cells induced by sulfatide-reactive vNKT cells were found to be associated with PD-L1 molecules expressed on LDCs, and this association was dependent on iNKT cells. Collectively, our findings suggest that in asthma-mimicking murine models, sulfatide-reactive vNKT cells facilitate the generation of lung Treg cells through inducing tolerogenic properties in LDCs, and this process is dependent on the presence of lung iNKT cells. These results may provide a potential therapeutic approach to treat allergic asthma. [ABSTRACT FROM AUTHOR]

• Cellular senescence-related biological processes may be involved in the pathogenesis of severe asthma. • The expression of ETS2, ETS1 and AURKA were increased in the severe asthma. • Two distinct senescence subtypes were identified in severe asthma with distinct immune microenvironment and molecular biological characteristics. • The random forest predictive model based on PEBP1 and MDH1 has good accuracy in predicting senescence subtypes of severe asthma. • Bezafibrate, EBPC and felodipine may be the potential therapeutical drugs for Cluster 1, while FK-888, trimethobenzamide and PD-0325901 may be the potential therapeutical drugs for Cluster 2. Recent studies have shown that cellular senescence is involved in the pathogenesis of severe asthma (SA). The objective of this study was to investigate the role of cellular senescence-related genes (CSGs) in the pathogenesis of SA. Here, 54 differentially expressed CSGs were identified in SA patients compared to healthy control individuals. Among the 54 differentially expressed CSGs, 3 CSGs (ETS2, ETS1 and AURKA) were screened using the LASSO regression analysis and logistic regression analysis to establish the CSG-based prediction model to predict severe asthma. Moreover, we found that the protein expression levels of ETS2, ETS1 and AURKA were increased in the severe asthma mouse model. Then, two distinct senescence subtypes of SA with distinct immune microenvironments and molecular biological characteristics were identified. Cluster 1 was characterized by increased infiltration of immature dendritic cells, regulatory T cells, and other cells. Cluster 2 was characterized by increased infiltration levels of eosinophils, neutrophils, and other cells. The molecular biological characteristics of Cluster 1 included aerobic respiration and oxidative phosphorylation, whereas the molecular biological characteristics of Cluster 2 included activation of the immune response and immune receptor activity. Then, we established an Random Forest model to predict the senescence subtypes of SA to guide treatment. Finally, potential drugs were searched for each senescence subgroup of SA patients via the Connectivity Map database. A peroxisome proliferator-activated receptor agonist may be a potential therapeutic drug for patients in Cluster 1, whereas a tachykinin antagonist may be a potential therapeutic drug for patients in Cluster 2. In summary, CSGs are likely involved in the pathogenesis of SA, which may lead to new therapeutic options for SA patients. [ABSTRACT FROM AUTHOR]

Abstract Porphyromonas gingivalis , a clinically important oral pathogen causing periodontal disease, is difficult to culture in routine conditions. Hence, it is necessary to establish a reliable technique to detect this pathogen. Previously, our laboratory developed a new isothermal detection method, called MB-LAMP (molecular beacon-Loop-mediated isothermal amplification), which combines the advantages of LAMP and qPCR through the accurate and quantitative detection of LAMP products. This approach offers significant potential for the point-of-care detection of P. gingivalis. Here, MB-LAMP was used to detect P. gingivalis targeting a specific fragment, and the sensitivity was as high as 1.4 × 10−1 pg μL–1. The method showed no cross-reaction with 14 other bacterial pathogens. For clinical samples, this assay showed a high diagnostic sensitivity (100%) and specificity (100%), equivalent to that of real-time quantitative polymerase chain reaction (real-time qPCR). Moreover, detection with MB-LAMP was significantly faster than that with real-time qPCR, reducing the time required for clinical diagnosis. Finally, we established an absolute quantification method with MB-LAMP for P. gingivalis using pilot samples. Thus, the highly specific, sensitive, and rapid assay developed in this study makes it feasible to diagnose P. gingivalis. Highlights • Establishing the MB-LAMP method to detect Porphyromonas gingivalis. • Enabling sensitive and specific assay of this bacterium by MB-LAMP detection. • Reducing the time required for clinical diagnosis of fastidious bacteria. [ABSTRACT FROM AUTHOR]

• Loop-mediated isothermal amplification assay for prevalent human respiratory adenoviruses. • Coupling with instrument-free DNA extraction device facilitating treating clinical samples. • A diagnostic platform enabling reliable screening test in resource-limited settings. Three human adenovirus (HAdV) genotypes, HAdV-7, HAdV-14, and HAdV-55, emerged as the most prevalent variants in China over the past decade and caused both sporadic, fatal cases and frequent, large outbreaks. Early diagnosis is essential to control infections and endemics. Here, we established a loop-mediated isothermal amplification (LAMP) assay coupled with an instrument-free nucleic acid extraction device recently developed by our group; the assay could detect all the 3 prevalent HAdV genotypes. Specificity analysis showed no cross-reactivity with other common respiratory pathogens and the analytical sensitivity was as low as 10 copies/μL. All detection steps could be completed within 1 hour. The assay's performance was evaluated using clinical samples and compared with the gold standard RT-PCR method, showing highly consistent results. The LAMP assay developed here could be readily used in basic laboratory facilities and with minimal DNA extraction equipment, and as a reliable screening test in a resource-limited setting. [ABSTRACT FROM AUTHOR]