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Cellular senescence and aging result in a reduced ability to manage persistent types of inflammation. Thus, the chronic low-level inflammation associated with aging phenotype is called “inflammaging”. Inflammaging is not only related with age-associated chronic systemic diseases such as cardiovascular disease and diabetes, but also skin aging. As the largest organ of the body, skin is continuously exposed to external stressors such as UV radiation, air particulate matter, and human microbiome. In this review article, we present mechanisms for accumulation of senescence cells in different compartments of the skin based on cell types, and their association with skin resident immune cells to describe changes in cutaneous immunity during the aging process.

Host life is inextricably linked to commensal microbiota, which play a crucial role in maintaining homeostasis and immune activation. A diverse array of commensal microbiota on the skin interacts with the host, influencing the skin physiology in various ways. Early-life exposure to commensal microbiota has long-lasting effects, and disruption of the epidermal barrier or transient exposure to these microorganisms can lead to skin dysbiosis and inflammation. Several commensal skin microbiota have the potential to function as either commensals or pathogens, both influencing and being influenced by the pathogenesis of skin inflammatory diseases. Here we explore the impact of various commensal skin microbiota on the host and elucidate the interactions between skin microbiota and host systems. A deeper understanding of these interactions may open new avenues for developing effective strategies to address skin diseases. Commensal microbiota shape skin health and immune response The skin is our body’s largest organ and acts as a barrier against the outside world. It hosts a variety of tiny organisms, known as microbiota, which include bacteria, fungi and viruses. These microbiota help to keep our skin healthy. However, scientists are still learning how these organisms interact with our skin and immune system. Researchers have found that certain bacteria, such as Staphylococcus epidermidis , help to repair skin and maintain its health. They conducted studies using mice and human skin samples to understand these interactions better. The research showed that these bacteria can influence immune responses and even help in healing wounds. The study highlights that the balance of skin microbiota is crucial for preventing skin diseases such as atopic dermatitis and psoriasis. When this balance is disrupted, it can lead to inflammation and other skin issues. This summary was initially drafted using artificial intelligence, then revised and fact-checked by the author.

Blood-brain barrier (BBB) disintegration is a key contributor to neuroinflammation; however, the biological processes governing BBB permeability under physiological conditions remain unclear. Here, we investigate the role of NLRP3 inflammasome in BBB disruption following peripheral inflammatory challenges. Repeated intraperitoneal lipopolysaccharide administration causes NLRP3-dependent BBB permeabilization and myeloid cell infiltration into the brain. Using a mouse model with cell-specific hyperactivation of NLRP3, we identify microglial NLRP3 activation as essential for peripheral inflammation-induced BBB disruption. Conversely, NLRP3 and microglial gasdermin D (GSDMD) deficiency markedly attenuates lipopolysaccharide-induced BBB breakdown. Notably, IL-1β is not required for NLRP3-GSDMD-mediated BBB disruption. Instead, microglial NLRP3-GSDMD axis upregulates CXCL chemokines and matrix metalloproteinases around BBB via producing GDF-15, promoting the recruitment of CXCR2-containing neutrophils. Inhibition of neutrophil infiltration and matrix metalloproteinase activity significantly reduces NLRP3-mediated BBB impairment. Collectively, these findings reveal the important role of NLRP3-driven chemokine production in BBB disintegration, suggesting potential therapeutic targets to mitigate neuroinflammation. The biological mechanisms regulating blood-brain barrier integrity remain unclear. Here, the authors identify microglial NLRP3-gasdermin D signaling as a driver of blood-brain barrier disruption during peripheral inflammation in mice, mediated by CXCL-dependent neutrophil recruitment.

Unilateral maxillary sinusitis and maxillary fungal ball (FB) have diverse etiologies. Maxillary sinus diseases are predominantly associated with odontogenic origins. This study aimed to investigate and compare the clinical characteristics of odontogenic maxillary sinus diseases between implant-related and implant-non-related etiologies. This retrospective study enrolled 195 patients with odontogenic maxillary sinus diseases undergoing endoscopic sinus surgery. The patients were categorized into four groups: implant-related and -non-related odontogenic sinusitis and implant-related and -non-related odontogenic FB. The study analyzed sinonasal symptoms, SNOT-22 scores, comorbidities, social history, allergic status, and olfactory function. Computed tomography scans were performed to assess dental disease, implant numbers, implant protrusion depth, and sinus inflammation degree. Smoking and alcohol consumption were significant risk factors for odontogenic maxillary sinusitis development, whereas hypertension and older age were associated with an increased odontogenic FB risk. However, the four groups demonstrated no statistically significant differences in terms of Lund-Mackay scores, SNOT-22 scores, olfactory function tests, allergic status, or comorbidities. Periodontitis and the length of the intramaxillary implant protrusion were important contributing factors in odontogenic maxillary sinus diseases. Odontogenic maxillary sinusitis and odontogenic FB exhibit distinct pathophysiological and clinical characteristics; therefore, these conditions need to be thoroughly understood for effective patient management.

Dendritic cells (DCs) are heterogeneous groups of innate immune cells, which orchestrate immune responses by presenting antigens to cognate T cells and stimulating other types of immune cells. Although the term ‘DCs’ generally represent highly mixed subsets with functional heterogeneity, the classical definition of DCs usually denotes conventional DCs (cDCs). Skin contains a unique DC network mainly composed of embryo precursor-derived epidermal Langerhans cells (LCs) and bone marrow-derived dermal cDCs, which can be further classified into type 1 (cDC1) and type 2 (cDC2) subsets. Psoriasis is a chronic inflammatory skin disease, which is principally mediated by IL-23/IL-17 cytokine axis. In the psoriatic skins, DCs are prominent cellular sources for TNF-α and IL-23, and the use of blocking antibodies against TNF-α and IL-23 leads to a significant clinical improvement in psoriatic patients. Recent elegant human and mouse studies have shown that inflammation-induced inflammatory DCs, LCs, dermal cDC2, and monocyte-derived DCs are pivotal DC subsets in psoriatic inflammation. Thus, targeting specific pathogenic DC subsets would be a potential strategy for alleviating and preventing DC-derived IL-23-dependent psoriatic inflammation and other inflammatory dermatoses in the future.

Dendritic cells are antigen-presenting cells orchestrating innate and adaptive immunity. The crucial role of transcription factors and histone modifications in the transcriptional regulation of dendritic cells has been extensively studied. However, it is not been well understood whether and how three-dimensional chromatin folding controls gene expression in dendritic cells. Here we demonstrate that activation of bone marrow-derived dendritic cells induces extensive reprogramming of chromatin looping as well as enhancer activity, both of which are implicated in the dynamic changes in gene expression. Interestingly, depletion of CTCF attenuates GM-CSF-mediated JAK2/STAT5 signaling, resulting in defective NF-κB activation. Moreover, CTCF is necessary for establishing NF-κB-dependent chromatin interactions and maximal expression of pro-inflammatory cytokines, which prime Th1 and Th17 cell differentiation. Collectively, our study provides mechanistic insights into how three-dimensional enhancer networks control gene expression during bone marrow-derived dendritic cells activation, and offers an integrative view of the complex activities of CTCF in the inflammatory response of bone marrow-derived dendritic cells. The role of 3D genome organization is not well understood in the transcriptional regulation of dendritic cells. Here the authors show that activation of dendritic cells in vitro induces dynamic reprogramming of the chromatin looping and enhancer activity linked to changes in gene expression and implicates a role for the chromatin architecture protein CTCF in the inflammatory response of dendritic cells.

In this study, we prepared stabilized vitamin A and C nanoemulsions, and investigated their efficacy on milk-specific proteins in bovine mammary epithelial cells (MAC-T). Emulsions of vitamin A (vit-A) and C (vit-C) were prepared using Lipoid S 75 and microfluidization. The particle size and polydispersity index (PDI) of nanoemulsified vit-A and vit-C were studied. The cytotoxic effect of nanoemulsion-free and nanoemulsified vit-A and vit-C was determined by an MTT assay. In addition, the efficacy of nanoemulsified vit-A and vit-C on the in vitro expression pattern of milk-specific proteins in MAC-T cells was investigated by quantitative RT-PCR. The results showed that the efficacies of stabilized nanoemulsions of vit-A and vit-C were 100% and 92.7%, respectively. The particle sizes were around 475.7 and 225.4 nm, and the zeta potentials were around −33.5 and −21.3 mV, respectively. The expression changes of αs2-, β- and κ-casein were higher in the presence of a stabilized nanoemulsion of vit-A, compared with nanoemulsion-free vit-A. Furthermore, the expression changes of αs2- and β-casein were lower and that of κ-casein was higher in the presence of a stabilized nanoemulsion of vit-C, compared with nanoemulsion-free vit-C. Thus, our findings demonstrate the efficacy of nanoemulsified vit-A and vit-C in changing the expression of milk-specific proteins in MAC-T cells.

Objective: Pregnancy in cattle after embryo transfer (ET) is influenced by several factors, including embryo quality. Therefore, preparing high-quality embryos with the greatest developmental potential is essential for achieving a successful pregnancy after ET. Meanwhile, blastocysts produced by in vitro fertilization (IVF) procedure have different developmental speed during in vitro culture (IVC) and they exhibited different competence in the establishment of pregnancy.Methods: This study aimed to identify the comparative features of early-, mid-, and late-developing bovine IVF blastocysts, when they first appeared at Day 7, 8, and 9 during IVC, respectively. In addition, the correlations between their molecular features and pregnancy ability were analyzed.Results: The results showed no difference in the morphological characteristics, including total cell count and diameter, between the Day 7, 8, and 9 blastocysts. However, the pregnancy rate post-ET was significantly different between the groups at 51.7%, 36.7%, and 17.8% for Day 7, 8, and 9 blastocysts, respectively. During early embryo development, late-developing blastocysts demonstrated a reduced cell count in the inner cell mass and decreased expression of the early embryo developmental genes (Oct4 and Sox2) compared with the early- and mid-developing blastocysts. In addition, the number of apoptotic cells and apoptosis-related gene expression (increased Bax and decreased Bcl2) gradually elevated from the Day 7 to Day 9 blastocysts. However, there was no difference in mitochondrial activity and mitochondria-relevant gene expression (Tfam and Cox1) between the groups. Correlation analysis identified a significantly negative correlation between the pregnancy rate and the blastocysts’ degree of apoptosis, indicating that the low pregnancy ability of late-developing blastocysts was mainly caused by increased apoptosis.Conclusion: This study’s results may contribute to the field of animal biotechnology by assisting in establishing an improved strategy for bovine ET with IVF embryos.

Dendritic cells (DCs) are readily generated from the culture of mouse bone marrow (BM) treated with either granulocyte macrophage-colony stimulating factor (GM-CSF) or FMS-like tyrosine kinase 3 ligand (FLT3L). CD11c + MHCII + or CD11c + MHCII hi cells are routinely isolated from those BM cultures and generally used as in vitro -generated DCs for a variety of experiments and therapies. Here, we examined CD11c + cells in the BM culture with GM-CSF or FLT3L by staining with a monoclonal antibody 2A1 that is known to recognize mature or activated DCs. Most of the cells within the CD11c + MHCII hi DC gate were 2A1 + in the BM culture with GM-CSF (GM-BM culture). In the BM culture with FLT3L (FL-BM culture), almost of all the CD11c + MHCII hi cells were within the classical DC2 (cDC2) gate. The analysis of FL-BM culture revealed that a majority of cDC2-gated CD11c + MHCII hi cells exhibited a 2A1 - CD83 - CD115 + CX 3 CR1 + phenotype, and the others consisted of 2A1 + CD83 + CD115 - CX 3 CR1 - and 2A1 - CD83 - CD115 - CX 3 CR1 - cells. According to the antigen uptake and presentation, morphologies, and gene expression profiles, 2A1 - CD83 - CD115 - CX 3 CR1 - cells were immature cDC2s and 2A1 + CD83 + CD115 - CX 3 CR1 - cells were mature cDC2s. Unexpectedly, however, 2A1 - CD83 - CD115 + CX 3 CR1 + cells, the most abundant cDC2-gated MHCII hi cell subset in FL-BM culture, were non-DCs. Adoptive cell transfer experiments in the FL-BM culture confirmed that the cDC2-gated MHCII hi non-DCs were precursors to cDC2s, i.e., MHCII hi pre-cDC2s. MHCII hi pre-cDC2s also expressed the higher level of DC-specific transcription factor Zbtb46 as similarly as immature cDC2s. Besides, MHCII hi pre-cDC2s were generated only from pre-cDCs and common DC progenitor (CDP) cells but not from monocytes and common monocyte progenitor (cMoP) cells, verifying that MHCII hi pre-cDC2s are close lineage to cDCs. All in all, our study identified and characterized a new cDC precursor, exhibiting a CD11c + MHCII hi CD115 + CX 3 CR1 + phenotype, in FL-BM culture.

During August 2020, we carried out a serological survey among students and employees at the Okinawa Institute of Science and Technology Graduate University (OIST), Japan, testing for the presence of antibodies against SARS-CoV-2, the causative agent of COVID-19. We used a FDA-authorized 2-step ELISA protocol in combination with at-home self-collection of blood samples using a custom low-cost finger prick-based capillary blood collection kit. Although our survey did not find any COVID-19 seropositive individuals among the OIST cohort, it reliably detected all positive control samples obtained from a local hospital and excluded all negatives controls. We found that high serum antibody titers can persist for more than 9 months post infection. Among our controls, we found strong cross-reactivity of antibodies in samples from a serum pool from two MERS patients in the anti-SARS-CoV-2-S ELISA. Here we show that a centralized ELISA in combination with patient-based capillary blood collection using as little as one drop of blood can reliably assess the seroprevalence among communities. Anonymous sample tracking and an integrated website created a stream-lined procedure. Major parts of the workflow were automated on a liquid handler, demonstrating scalability. We anticipate this concept to serve as a prototype for reliable serological testing among larger populations.