Genome-Wide Identification, Characterization and Function Analysis of Lineage-Specific Genes in the Tea Plant Camellia sinensis

Genes that have no homologous sequences with other species are called lineage-specific genes (LSGs), are common in living organisms, and have an important role in the generation of new functions, adaptive evolution and phenotypic alteration of species. Camellia sinensis var. sinensis (CSS) is one of the most widely distributed cultivars for quality green tea production. The rich catechins in tea have antioxidant, free radical elimination, fat loss and cancer prevention potential. To further understand the evolution and utilize the function of LSGs in tea, we performed a comparative genomics approach to identify Camellia-specific genes (CSGs). Our result reveals that 1701 CSGs were identified specific to CSS, accounting for 3.37% of all protein-coding genes. The majority of CSGs (57.08%) were generated by gene duplication, and the time of duplication occurrence coincide with the time of two genome-wide replication (WGD) events that happened in CSS genome. Gene structure analysis revealed that CSGs have shorter gene lengths, fewer exons, higher GC content and higher isoelectric point. Gene expression analysis showed that CSG had more tissue-specific expression compared to evolutionary conserved genes (ECs). Weighted gene co-expression network analysis (WGCNA) showed that 18 CSGs are mainly associated with catechin synthesis-related pathways, including phenylalanine biosynthesis, biosynthesis of amino acids, pentose phosphate pathway, photosynthesis and carbon metabolism. Besides, we found that the expression of three CSGs (CSS0030246, CSS0002298, and CSS0030939) was significantly down-regulated in response to both types of stresses (salt and drought). Our study first systematically identified LSGs in CSS, and comprehensively analyzed the features and potential functions of CSGs. We also identified key candidate genes, which will provide valuable assistance for further studies on catechin synthesis and provide a molecular basis for the excavation of excellent germplasm resources.

Macrophage Plasticity and Polarization Are Altered in the Experimental Model of Multiple Sclerosis

Multiple sclerosis (MS) is an immune-mediated demyelinating disease of the central nervous system. MS is characterized by infiltrations of leukocytes such as T and B lymphocytes and macrophages. Macrophages have been identified as major effectors of inflammation and demyelination in both MS and its animal model, experimental autoimmune encephalomyelitis (EAE). However, the activation and heterogeneity of macrophages in MS has been poorly investigated. Thus, in this study, we evaluated M1 and M2 macrophages immunophenotype from EAE and control mice by analyzing over 30 surface and intracellular markers through polychromatic flow cytometry, qRT-PCR, and ELISA assay. We showed that M1 macrophages possessed a higher proinflammatory profile in EAE compared to control mice, since they expressed higher levels of activation/co-stimulatory markers (iNOS, CD40, and CD80) and cytokines/chemokines (IL-6, IL-12, CCL2, and CXCL10), whereas M2 lost their M2-like phenotype by showing a decreased expression of their signature markers CD206 and CCL22, as well as a concomitant upregulation of several M1 makers. Furthermore, immunization of M1 and M2 macrophages with MOG35-55 led to a significant hyperactivation of M1 and a concomitant shift of anti-inflammatory M2 to pro-inflammatory M1 macrophages. Overall, we provide evidence for a phenotypic alteration of M1/M2 balance during MS, which can be of crucial importance not only for a better understanding of the immunopathology of this neurodegenerative disease but also to potentially develop new macrophage-centered therapeutic strategies.

Phenotypic alteration of macrophages during osteoarthritis: a systematic review

Objective Osteoarthritis (OA) has long been regarded as a disease of cartilage degeneration, whereas mounting evidence implies that low-grade inflammation contributes to OA. Among inflammatory cells involved, macrophages play a crucial role and are mediated by the local microenvironment to exhibit different phenotypes and polarization states. Therefore, we conducted a systematic review to uncover the phenotypic alterations of macrophages during OA and summarized the potential therapeutic interventions via modulating macrophages. Methods A systematic review of multiple databases (PubMed, Web of Science, ScienceDirect, Medline) was performed up to February 29, 2020. Included articles were discussed and evaluated by two independent reviewers. Relevant information was analyzed with a standardized and well-designed template. Results A total of 28 studies were included. Results were subcategorized into two sections depending on sources from human tissue/cell-based studies (12 studies) and animal experiments (16 studies). The overall observation indicated that M1 macrophages elevated in both synovium and circulation during OA development, along with lower numbers of M2 macrophages. The detailed alterations of macrophages in both synovium and circulation were listed and analyzed. Furthermore, interventions against OA via regulating macrophages in animal models were highlighted. Conclusion This study emphasized the importance of the phenotypic alterations of macrophages in OA development. The classical phenotypic subcategory of M1 and M2 macrophages was questionable due to controversial and conflicting results. Therefore, further efforts are needed to categorize macrophages in an exhaustive manner and to use advanced technologies to identify the individual roles of each subtype of macrophages in OA.

Nutrigenomics and Life Style Facet- A Modulatory Molecular Evidence in Progression of Breast and Colon Cancer with Emerging Importance

: Legitimate nutrition assumes a significant role in preventing diseases and, in this way, nutritional interventions establish vital strategies in the area of public health. Nutrigenomics centres on the different genes and diet in an individual and how an individual’s genes influence the reaction to bioactive foodstuff. It targets considering the genetic and epigenetic interactions with nutrients to lead to a phenotypic alteration and consequently to metabolism, differentiation, or even apoptosis. Nutrigenomics and lifestyle factors play a vital role in health management and represent an exceptional prospect for the improvement of personalized diets to the individual at risk of developing diseases like cancer. Concerning cancer as a multifactorial genetic ailment, several aspects need to be investigated and analysed. Various perspectives should be researched and examined regarding the development and prognosis of breast and colon cancer. Malignant growth occurrence is anticipated to upsurge in the impending days, and an effective anticipatory strategy is required. The effect of dietary components, basically studied by nutrigenomics, looks at gene expression and molecular mechanisms. It also interrelates bioactive compounds and nutrients because of different 'omics' innovations. Several preclinical investigations demonstrate the pertinent role of nutrigenomics in breast and colon cancer, and change of dietary propensities is conceivably a successful methodology for reducing cancer risk. The connection between the genomic profile of patients with breast or colon cancer and their supplement intake, it is conceivable to imagine an idea of personalized medicine, including nutrition and medicinal services.

Absence of nuclear receptors LXRs impairs immune response to androgen deprivation and leads to prostate neoplasia

Chronic inflammation is now a well-known precursor for cancer development. Infectious prostatitis are the most common causes of prostate inflammation, but emerging evidence points the role of metabolic disorders as a potential source of cancer-related inflammation. Although the widely used treatment for prostate cancer based on androgen deprivation therapy (ADT) effectively decreases tumor size, it also causes profound alterations in immune tumor microenvironment within the prostate. Here, we demonstrate that prostates of a mouse model invalidated for nuclear receptors liver X receptors (LXRs), crucial lipid metabolism and inflammation integrators, respond in an unexpected way to androgen deprivation. Indeed, we observed profound alterations in immune cells composition, which was associated with chronic inflammation of the prostate. This was explained by the recruitment of phagocytosis-deficient macrophages leading to aberrant hyporesponse to castration. This phenotypic alteration was sufficient to allow prostatic neoplasia. Altogether, these data suggest that ADT and inflammation resulting from metabolic alterations interact to promote aberrant proliferation of epithelial prostate cells and development of neoplasia. This raises the question of the benefit of ADT for patients with metabolic disorders.

The Role of Paracrine Regulation of Mesenchymal Stem Cells in the Crosstalk With Macrophages in Musculoskeletal Diseases: A Systematic Review

The phenotypic change of macrophages (Mφs) plays a crucial role in the musculoskeletal homeostasis and repair process. Although mesenchymal stem cells (MSCs) have been shown as a novel approach in tissue regeneration, the therapeutic potential of MSCs mediated by the interaction between MSC-derived paracrine mediators and Mφs remains elusive. This review focused on the elucidation of paracrine crosstalk between MSCs and Mφs during musculoskeletal diseases and injury. The search method was based on the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) and Cochrane Guidelines. The search strategies included MeSH terms and other related terms of MSC-derived mediators and Mφs. Ten studies formed the basis of this review. The current finding suggested that MSC administration promoted proliferation and activation of CD163+ or CD206+ M2 Mφs in parallel with reduction of proinflammatory cytokines and increase in anti-inflammatory cytokines. During such period, Mφs also induced MSCs into a motile and active phenotype via the influence of proinflammatory cytokines. Such crosstalk between Mφs and MSCs further strengthens the effect of paracrine mediators from MSCs to regulate Mφs phenotypic alteration. In conclusion, MSCs in musculoskeletal system, mediated by the interaction between MSC paracrine and Mφs, have therapeutic potential in musculoskeletal diseases.

MicroRNAs in Skeletal Muscle and Hints on Their Potential Role in Muscle Wasting During Cancer Cachexia

Cancer-associated cachexia is a heterogeneous, multifactorial syndrome characterized by systemic inflammation, unintentional weight loss, and profound alteration in body composition. The main feature of cancer cachexia is represented by the loss of skeletal muscle tissue, which may or may not be accompanied by significant adipose tissue wasting. Such phenotypic alteration occurs as the result of concomitant increased myofibril breakdown and reduced muscle protein synthesis, actively contributing to fatigue, worsening of quality of life, and refractoriness to chemotherapy. According to the classical view, this condition is primarily triggered by interactions between specific tumor-induced pro-inflammatory cytokines and their cognate receptors expressed on the myocyte membrane. This causes a shift in gene expression of muscle cells, eventually leading to a pronounced catabolic condition and cell death. More recent studies, however, have shown the involvement of regulatory non-coding RNAs in the outbreak of cancer cachexia. In particular, the role exerted by microRNAs is being widely addressed, and several mechanistic studies are in progress. In this review, we discuss the most recent findings concerning the role of microRNAs in triggering or exacerbating muscle wasting in cancer cachexia, while mentioning about possible roles played by long non-coding RNAs and ADAR-mediated miRNA modifications.

Phenotypical and functional alteration of unconventional T cells in severe COVID-19 patients

COVID-19 includes lung infection ranging from mild pneumonia to life-threatening acute respiratory distress syndrome (ARDS). Dysregulated host immune response in the lung is a key feature in ARDS pathophysiology. However, cellular actors involved in COVID-19–driven ARDS are poorly understood. Here, in blood and airways of severe COVID-19 patients, we serially analyzed unconventional T cells, a heterogeneous class of T lymphocytes (MAIT, γδT, and iNKT cells) with potent antimicrobial and regulatory functions. Circulating unconventional T cells of COVID-19 patients presented with a profound and persistent phenotypic alteration. In the airways, highly activated unconventional T cells were detected, suggesting a potential contribution in the regulation of local inflammation. Finally, expression of the CD69 activation marker on blood iNKT and MAIT cells of COVID-19 patients on admission was predictive of clinical course and disease severity. Thus, COVID-19 patients present with an altered unconventional T cell biology, and further investigations will be required to precisely assess their functions during SARS–CoV-2–driven ARDS.