The diverse actions of cytoskeletal vimentin in bacterial infection and host defense.

Bacterial infection is a major threat to human health, with infections resulting in considerable mortality, urging the need for a more profound understanding of bacteria-host interactions. During infection of cells, host cytoskeletal networks constantly interact with bacteria and are integral to their uptake. Vimentin, an intermediate filament protein, is one such cytoskeletal component that interacts with bacteria during infection. Although vimentin is predominantly present in the cytoplasm, it also appears in a secreted form or at the surface of multiple cell types, including epithelial cells, endothelial cells, macrophages and fibroblasts. As a cytoplasmic protein, vimentin participates in bacterial transportation and the consequential immune-inflammatory responses. When expressed on the cell surface, vimentin can be both pro- and anti-bacterial, favoring bacterial invasion in some contexts, but also limiting bacterial survival in others. Vimentin is also secreted and located extracellularly, where it is primarily involved in bacterial-induced inflammation regulation. Reciprocally, bacteria can also manipulate the fate of vimentin in host cells. Given that vimentin is not only involved in bacterial infection, but also the associated life-threatening inflammation, the use of vimentin-targeted drugs might offer a synergistic advantage. In this Review, we recapitulate the abundant evidence on vimentin and its dynamic changes in bacterial infection and speculate on its potential as an anti-bacterial therapeutic target.

Comparative analysis of peripheral blood immunoinflammatory landscapes in patients with acute cholangitis and its secondary septic shock using single-cell RNA sequencing.

BACKGROUND: Acute cholangitis (AC) is a key pathogeny of septic shock, which has a high mortality rate. AC has significant clinical heterogeneity, but no study has analyzed the discrepancies in immunoresponsiveness between AC and its secondary septic shock. The immune inflammatory responses play a critical role in the development of septic shock. METHODS: We performed single-cell RNA sequencing (scRNA-seq) to analyze the differences of immunocytes in immunoresponse and inflammation between the early stages of AC (A1, A2, and A3) and its secondary septic shock (B1, B2, and B3). RESULTS: This study has identified seven cell types, including T cells, B cells, plasma cells, neutrophils, monocytes, platelets and erythrocytes. We mainly focused on neutrophils, monocytes, and T cells. Neutrophil subpopulation analysis indicated that neutrophil progenitors (proNeus) were identified in neutrophil subsets. Compared with patients suffering from AC, the gene phenotypes of proNeus (ELANE, AZU1, MPO, and PRTN3) were significantly upregulated in septic shock. The differentiation direction of neutrophil subsets in peripheral blood mononuclear cells (PBMCs) was determined; Moreover, the proNeus in septic shock presented a state of "expansion", with upregulation of neutrophil degranulation and downregulation of monocyte and T cell proliferation. Neutrophils-7 (CCL5, RPL23A, RPL13, RPS19 and RPS18) were mainly involved in the regulation of cellular functions. The neutrophils-7 subpopulation in septic shock were in a state of "exhaustion", and its biological functions showed the characteristics of weakening neutrophil migration and phagocytosis, etc., which maked infection difficult to control and aggravated the development of septic shock. Analysis of monocyte and T cell subpopulations showed that the expression genes and biological functions of subpopulations were closely related to immunoinflammatory regulation. In addition, CCL3 - CCR1, CXCL1 - CXCR2 and other ligand-receptors were highly expressed in neutrophils and monocytes, enhancing interactions between immune cells. CONCLUSION: ScRNA-seq revealed significant differences in immune cells between AC and its secondary septic shock, which were primarily manifested in the cellular numbers, differentially expressed genes, functions of cellular subsets, differentiation trajectories, cell-cell interactions and so on. We identified many subsets of neutrophil, T cell and monocyte were associated with inflammation and immunosuppression induced by septic shock. These provided a reference for accurately evaluating the pathological severity of patients with AC and discovering the targets for therapy.

Identification of key biomarkers and immune infiltration in the thoracic acute aortic dissection by bioinformatics analysis.

BACKGROUND: Thoracic acute aortic dissection (TAAD), one of the most fatal cardiovascular diseases, leads to sudden death, however, its mechanism remains unclear. METHODS: Three Gene Expression Omnibus datasets were employed to detect differentially expressed genes (DEGs). A similar function and co-expression network was identified by weighted gene co-expression network analysis. The least absolute shrinkage and selection operator, random forest, and support vector machines-recursive feature elimination were utilized to filter diagnostic TAAD markers, and then screened markers were validated by quantitative real-time PCR and another independent dataset. CIBERSORT was deployed to analyze and evaluate immune cell infiltration in TAAD tissues. RESULTS: Twenty-five DEGs were identified and narrowed down to three after screening. Finally, two genes, SLC11A1 and FGL2, were verified by another dataset and qRT-PCR. Function analysis revealed that SLC11A1 and FGL2 play significant roles in immune-inflammatory responses. CONCLUSION: SLC11A1 and FGL2 are differently expressed in aortic dissection and may be involved in immune-inflammatory responses.

Taste receptor polymorphisms and longevity: a systematic review and meta-analysis.

Bitter taste receptors (TAS2R) are involved in a variety of non-tasting physiological processes, including immune-inflammatory ones. Therefore, their genetic variations might influence various traits. In particular, in different populations of South Italy (Calabria, Cilento, and Sardinia), polymorphisms of TAS2R16 and TAS238 have been analysed in association with longevity with inconsistent results. A meta-analytic approach to quantitatively synthesize the possible effect of the previous variants and, possibly, to reconcile the inconsistencies has been used in the present paper. TAS2R38 variants in the Cilento population were also analysed for their possible association with longevity and the obtained data have been included in the relative meta-analysis. In population from Cilento no association was found between TAS2R38 and longevity, and no association was observed as well, performing the meta-analysis with data of the other studies. Concerning TAS2R16 gene, instead, the genotype associated with longevity in the Calabria population maintained its significance in the meta-analysis with data from Cilento population, that, alone, were not significant in the previously published study. In conclusion, our results suggest that TAS2R16 genotype variant is associated with longevity in South Italy.

Identification of the transcriptome signatures and immune-inflammatory responses in postmenopausal osteoporosis.

Postmenopausal osteoporosis is the most common type of osteoporosis in women. To date, little is known about their transcriptome signatures, although biomarkers from peripheral blood mononuclear cells are attractive for postmenopausal osteoporosis diagnoses. Here, we performed bulk RNA sequencing of 206 samples (124 postmenopausal osteoporosis and 82 normal samples) and described the clinical phenotypic characteristics of postmenopausal women. We then highlighted the gene set enrichment analyses between the extreme T-score group and the heathy control group, revealing that some immune-inflammatory responses were enhanced in postmenopausal osteoporosis, with representative pathways including the mitogen-activated protein kinase (NES = 1.6, FDR <0.11) pathway and B_CELL_RECEPTOR (NES = 1.69, FDR <0.15) pathway. Finally, we developed a combined risk prediction model based on lasso-logistic regression to predict postmenopausal osteoporosis, which combined eleven genes (PTGS2, CXCL16, NECAP1, RPS23, SSR3, CD74, IL4R, BTBD2, PIGS, LILRA2, MAP3K11) and three pieces of clinical information (age, procollagen I N-terminal propeptide, ß isomer of C-terminal telopeptide of type I) and provided the best prediction ability (AUC = 0.97). Taken together, this study filled a gap in the large-scale transcriptome signature profiles and revealed the close relationship between immune-inflammatory responses and postmenopausal osteoporosis, providing a unique perspective for understanding the occurrence and development of postmenopausal osteoporosis.

Immune-Inflammatory Responses of an Acellular Cartilage Matrix Biomimetic Scaffold in a Xenotransplantation Goat Model for Cartilage Tissue Engineering.

The rapid development of tissue engineering and regenerative medicine has introduced a new strategy for ear reconstruction, successfully regenerating human-ear-shaped cartilage and achieving the first clinical breakthrough using a polyglycolic acid/polylactic acid (PGA/PLA) scaffold. However, its clinical repair varies greatly among individuals, and the quality of regenerated cartilage is unstable, which seriously limits further clinical application. Acellular cartilage matrix (ACM), with a cartilage-specific microenvironment, good biocompatibility, and potential to promote cell proliferation, has been used to regenerate homogeneous ear-shaped cartilage in immunocompromised nude mice. However, there is no evidence on whether ACM will regenerate homogeneous cartilage tissue in large animals or has the potential for clinical transformation. In this study, xenogeneic ACM assisted with gelatin (GT) with or without autologous chondrocytes was implanted subcutaneously into goats to establish a xenotransplantation model and compared with a PGA/PLA scaffold to evaluate the immune-inflammatory response and quality of regenerated cartilage. The results confirmed the superiority of the ACM/GT, which has the potential capacity to promote cell proliferation and cartilage formation. Although there is a slight immune-inflammatory response in large animals, it does not affect the quality of the regenerated cartilage and forms homogeneous and mature cartilage. The current study provides detailed insights into the immune-inflammatory response of the xenogeneic ACM/GT and also provides scientific evidence for future clinical application of ACM/GT in cartilage tissue engineering.

Genetic Signatures of Centenarians: Implications for Achieving Successful Aging.

The extraordinary rise in the old population in the Western world underscores the importance of studies on aging and longevity to decrease the medical, economic and social problems associated with the increased number of non-autonomous individuals affected by invalidating pathologies. Centenarians have reached the extreme limits of the human life span. They are the best example of extreme longevity, representing selected individuals in which the appearance of major age-related diseases has been consistently delayed or avoided. There is growing evidence that the genetic component of longevity becomes higher with survival at the age of over 90 years. For centenaries, it reaches up to 33% for women and 48% for men. Therefore, exceptional longevity is a complex, hereditable trait that runs across generations. Longevity should correlate either with the presence of protective alleles or the absence of detrimental alleles. The aim of this review is to discuss the possible attainment of successful aging in the context of the lessons learned from centenarian genetics.