Mucosal TLR5 activation controls healthspan and longevity.

Addressing age-related immunological defects through therapeutic interventions is essential for healthy aging, as the immune system plays a crucial role in controlling infections, malignancies, and in supporting tissue homeostasis and repair. In our study, we show that stimulating toll-like receptor 5 (TLR5) via mucosal delivery of a flagellin-containing fusion protein effectively extends the lifespan and enhances the healthspan of mice of both sexes. This enhancement in healthspan is evidenced by diminished hair loss and ocular lens opacity, increased bone mineral density, improved stem cell activity, delayed thymic involution, heightened cognitive capacity, and the prevention of pulmonary lung fibrosis. Additionally, this fusion protein boosts intestinal mucosal integrity by augmenting the surface expression of TLR5 in a certain subset of dendritic cells and increasing interleukin-22 (IL-22) secretion. In this work, we present observations that underscore the benefits of TLR5-dependent stimulation in the mucosal compartment, suggesting a viable strategy for enhancing longevity and healthspan.

Comparative Analysis of Antibacterial and Wound Healing Activities of Chitosan and Povidone-Iodine-Based Hydrogels.

PURPOSE: This study aimed to compare the antibacterial and wound healing efficacies of chitosan hydrogel with povidone-iodine (PI) hydrogel. METHODS: The in vitro antibacterial activities of chitosan and PI hydrogels against Staphylococcus aureus and Escherichia coli were evaluated. Nine 6- to 8-week-old male Sprague-Dawley rats were divided into plain, PI, and chitosan hydrogel groups. Each rat received two 10-mm full-thickness dorsal wounds using an excisional splinting model. Each wound was treated with 0.2 mL of gel thrice over the course of 3 postoperative weeks. Weekly observations were conducted, and at the end of the third postoperative week, the rats were killed for histopathological and quantitative polymerase chain reaction evaluations. Data analysis included both 2- and 1-way analyses of variance. RESULTS: Chitosan hydrogel exhibited comparable in vitro antibacterial activity and a significantly enhanced in vivo wound closure rate compared with PI hydrogel. Three weeks after the surgery, the chitosan hydrogel group demonstrated marked differences in wound repair (P < 0.01). Histologically, increased collagen deposition was observed with chitosan hydrogel treatment. Immunohistochemistry for CD68 revealed a lower number of macrophages in the wounds treated with chitosan hydrogel. Quantitative polymerase chain reaction analysis indicated a superior collagen 1 to 3 ratio and reduced expression of proinflammatory cytokine mRNAs (interleukin 1b, interleukin 6, tumor necrosis factor α, and interferon γ) in the chitosan hydrogel group. CONCLUSION: Chitosan hydrogel demonstrates the potential to serve as an effective alternative to PI hydrogel, providing enhanced wound healing capabilities while maintaining comparable antimicrobial properties.

The Fatal Role of Enterohaemorrhagic Escherichia coli Shiga Toxin-associated Extracellular Vesicles in Host Cells.

Enterohemorrhagic Escherichia coli (EHEC) is a specific subset of Shiga toxin-producing Escherichia coli (STEC) strains that are characterized by their ability to cause bloody diarrhea (hemorrhagic colitis) and potentially life-threatening, extraintestinal complications such as hemolytic uremic syndrome (HUS), which is associated with acute renal failure., contributing to severe clinical outcomes. The Shiga toxins (Stxs), produced by EHEC, are primary virulence factors. These potent cytotoxins are composed of one enzymatically active A subunit (StxA) and five receptor-binding B subunits (StxB). Although the toxins are primarily associated with cytotoxic effects, they also elicit other pathogenic consequences due to their induction of a number of biological processes, including apoptosis through ER-stress, pro-inflammatory responses, autophagy, and post-translational modification (PTM). Moreover, several studies have reported the association between Stxs and extracellular vesicles (EVs), including microvesicles and exosomes, demonstrating that Stx-containing EVs secreted by intoxicated macrophages are taken up by recipient cells, such as toxin-sensitive renal proximal tubular epithelial cells. This mechanism likely contributes to the spreading of Stxs within the host, and may exacerbate gastrointestinal illnesses and kidney dysfunction. In this review, we summarize recent findings relating to the host responses, in different types of cells in vitro and in animal models, mediated by Stxs-containing exosomes. Due to their unique properties, EVs have been explored as therapeutic agents, drug delivery systems, and diagnostic tools. Thus, potential therapeutic applications of EVs in EHEC Stxs-mediated pathogenesis are also briefly reviewed.

Tumor lipid metabolism: a mechanistic link between diet and cancer progression.

The potential for 'anti-cancer' diets to markedly alter cancer risk and prognosis has captured the imagination of patients, physicians, and researchers alike, but many of these dietary recommendations come from correlative studies that attribute certain diets to altered cancer risk. While provocative, little is known about the molecular mechanisms behind how these dietary interventions impact cancer progression. Within this context, however, changes in tumor lipid metabolism are emerging as a key contributor. In this review, we examine the current understanding of lipid metabolism in the tumor microenvironment (TME), suggesting how diet-induced changes in lipid composition may regulate tumor progression and therapeutic efficacy. By dissecting various cellular pathways involved in lipid metabolism, we highlight how diet modulates the balance between saturated and unsaturated fatty acid (FA) species in tumors to impact cancer cell and stromal cell function. Finally, we describe how current cancer therapies may synergize with diet to improve therapeutic efficacy.

Multiple Injections of Adipose-Derived Stem Cells Improve Graft Survival in Human-to-Rat Skin Xenotransplantation through Immune Modulation.

BACKGROUND: Adipose-derived stem cells (ADSCs) exert immunomodulatory effects in the treatment of transplant rejection. This study aimed to evaluate the effects of ADSCs on the skin graft survival in a human-to-rat xenograft transplantation model and to compare single and multiple injections of ADSCs. METHODS: Full-thickness human skin xenografts were transplanted into the backs of Sprague-Dawley rats. The rats were injected subcutaneously on postoperative days 0, 3, and 5. The injections were as follows: triple injections of phosphate-buffered saline (PBS group), a single injection of ADSCs and double injections of PBS (ADSC × 1 group), and triple injections of ADSCs (ADSC × 3 group). The immunomodulatory effects of ADSCs on human skin xenografts were assessed. RESULTS: Triple injections of ADSCs considerably delayed cell-mediated xenograft rejection compared with the PBS and ADSC × 1 groups. The vascularization and collagen type 1-3 ratios in the ADSC × 3 group were significantly higher than those in the other groups. In addition, intragraft infiltration of CD3-, CD4-, CD8-, and CD68-positive cells was reduced in the ADSC × 3 group. Furthermore, in the ADSC × 3 group, the expression levels of proinflammatory cytokine interferon-gamma (IFN-γ) were decreased and immunosuppressive prostaglandin E synthase (PGES) was increased in the xenograft and lymph node samples. CONCLUSION: This study presented that triple injections of ADSCs appeared to be superior to a single injection in suppressing cell-mediated xenograft rejection. The immunomodulatory effects of ADSCs are associated with the downregulation of IFN-γ and upregulation of PGES in skin xenografts and lymph nodes.

Epidemiology, staging and management of mucosal melanoma of the head and neck: a narrative review.

BACKGROUND AND OBJECTIVE: Mucosal melanoma of the head and neck (MMHN) are rare, aggressive neoplasms of melanocyte origin that remain incompletely understood and have a poor prognosis, with high rates of locoregional recurrence and distant metastasis. Several recent studies having expanded understanding of MMHN, we undertook a review of the latest evidence pertaining to its epidemiology, staging, and management. METHODS: A literature search was conducted for peer-reviewed articles reporting and discussing the epidemiology, staging, and management of MMHN. PubMed, Medline, Embase and the Cochrane Library were searched to identify relevant publications. KEY CONTENT AND FINDINGS: MMHN remains an uncommon disease. The current TNM staging system for MMHN provides inadequate risk stratification, and consideration of an alternative staging model such as one based on a nomogram may be justifiable. Tumour resection with clear histological margins remains the cornerstone of optimal treatment. Adjuvant radiotherapy may improve locoregional control but does not appear to affect survival. Immune checkpoint inhibitors and c-KIT inhibitors demonstrate promising efficacy in patients with advanced or unresectable mucosal melanomas, and warrant further research exploring the utility of combination therapies. Their roles as adjuvant therapies have not been determined. The efficacy of neoadjuvant systemic therapy is also not yet clear, although early results suggest that it may improve outcomes. CONCLUSIONS: New insights into the epidemiology, staging and management of MMHN have transformed the standard of care for this rare malignancy. Nonetheless, the results of ongoing clinical trials and future prospective studies are required to better understand this aggressive disease and optimise its management.

Effects of Lactobacillus reuteri MG5346 on Receptor Activator of Nuclear Factor-Kappa B Ligand (RANKL)-Induced Osteoclastogenesis and Ligature-Induced Experimental Periodontitis Rats.

Effects of culture supernatants of Lactobacillus reuteri MG5346 (CS-MG5346) on receptor activator of nuclear factor-kappa B ligand (RANKL)-induced osteoclastogenesis were examined. CS-MG5346 treatment up to 400 µg/mL significantly reduced tartrate-resistant acid-phosphatase (TRAP) activity, the phenotype biomarker of osteoclast, without affecting cell viability. CS-MG5346 inhibited the expression of osteoclast specific transcriptional factors (c-fos and nuclear factor-activated T cells c1) and their target genes (TRAP, cathepsin, and matrix metallo-proteinase-9) in a dose-dependent manner (p<0.05). The administration of L. reuteri MG5346 (2×108 CFU/day) for 8 wks significantly improved furcation involvement, but no difference was observed in alveolar bone loss in ligature-induced experimental periodontitis rats. The elevated RANKL/ osteoprotegerin ratio, the biomarker of periodontitis, was significantly lowered in the gingival tissue by administration of L. reuteri MG5346 (p<0.05). L. reuteri MG5346 showed excellent stability in simulated stomach and intestinal fluids and did not have antibiotic resistance. Based on the results, L. reuteri MG5346 has the potential to be a promising probiotic strain for oral health.

Glyoxal-derived advanced glycation end-products, Nε-carboxymethyl-lysine, and glyoxal-derived lysine dimer induce apoptosis-related gene expression in hepatocytes.

BACKGROUND: Advanced glycation end-products (AGEs) are proteins or lipids that have been glycated nonenzymatically by reducing sugars and their derivatives such as methylglyoxal. AGEs are known to cause inflammation, oxidative stress, and diseases in the human body. The toxic effects of AGEs and their structures on the origin of the protein being modified have not been well studied. METHODS AND RESULTS: Five different types of AGEs: AGE1 (glucose-derived), AGE2 (glyceraldehyde-derived), AGE3 (glycolaldehyde-derived), AGE4 (methylglyoxal-derived), and AGE5 (glyoxal-derived); were used to examine the effect of AGEs on HepG2 cells. AGE2 through 5 increase the production of reactive oxygen species (ROS) in liver cells, an initiating factor for apoptosis. At the mRNA and protein levels, AGE5 treatment showed the greatest increase in expression of apoptosis-related factors such as Bax, p53, and Caspase 3. Quantitative analysis revealed that Nε-carboxymethyl-lysine (CML) and glyoxal-lysine dimer (GOLD) were the important types of AGE5. The ROS generation and the expression of apoptotic factors both increased when cells were treated with CML and GOLD. CONCLUSION: These findings suggest that AGE5 treatment activates the apoptosis-related gene expression in hapatocytes, with CML and GOLD as potential major AGE compounds.

Critical care nurses' perceptions and practices towards clinical alarms.

BACKGROUND: Muted or controlled alarms resulting from alarm fatigue have become a threat to patient safety and several institutions are aware of this risk. AIMS: This study aimed to investigate critical care nurses' perceptions of medical device alarms, alarm fatigue, and alarm management practices. METHODS: This descriptive study investigated 48 nurses working at two intensive care units (ICUs) within a single university hospital, in South Korea. They were asked to complete a self-administered questionnaire about their perception of the ICU medical device alarm, alarm fatigue, and related management practices. The response rate was 100%. RESULTS: Critical care nurses experienced a moderate or higher level of alarm fatigue, scoring 29.1 out of 40. Participants identified the items "Frequent false alarms, which lead to reduced attention or response to alarm when they occur," and "Inadequate staff" as the most important issues for alarm management. The most frequently involved item in alarm management practice was "I only use infusion pumps for drugs that require precise dose." Alarm management practices among the nurses differed significantly according to ICU clinical career and experience of patient safety accidents. CONCLUSIONS: This study highlights the need to develop a standardized medical device alarm management protocol that can help identify different alarms correctly and respond to them rapidly and appropriately. RELEVANCE TO CLINICAL PRACTICE: It is necessary to reduce alarm fatigue and promote safe and effective alarm management practices among critical care nurses through sufficient education and steady training. Alarm fatigue should also be mitigated by employment of sufficient nursing personnel in ICUs.

Pseudomonas stutzeri PM101005 inhaled with atmospheric particulate matter induces lung damage through inflammatory responses.

Atmospheric particulate matter (PM) contains a mixture of chemical and biological elements that pose threat to human health by increasing susceptibility to respiratory diseases. Although the identification of the microorganisms composing the PM has been assessed, their immunological impacts are still questionable. Here, we examined the mechanisms responsible for the pathogenicity of Pseudomonas stutzeri PM101005 (PMPS), a bacterium isolated from fine dust, in lung epithelial cells, alveolar cells, and macrophages. Relative to its comparative strain Pseudomonas stutzeri (PS), infections with PMPS induced higher production of inflammatory cytokines and chemokines, mediated by the activation of NF-κB and MAPK signaling pathways. Additionally, with three-dimensional (3D) airway spheroids which mimic the human bronchial epithelium, we confirmed that PMPS infections lead to relatively higher induction of pro-inflammatory cytokines than PM infections. Consistent results were observed in murine models as the infections with PMPS provoked greater inflammatory responses than the infections with PS. These PMPS-induced responses were mediated by the signaling pathways of the Toll-like receptors (TLRs), which regulated PMPS infection and played an important role in the expression of the antibiotic peptide ß-defensin 3 (BD3) that suppressed PMPS proliferation. Moreover, PM pretreatment enhanced inflammatory responses and tissue damage of PMPS, while reducing BD3 expression. Overall, these results indicate that PM-isolated PMPS induce TLR-mediated inflammatory responses in lung tissues, and contributes to the understanding of the etiology of PM-induced respiratory damage.

Suppressed prefrontal neuronal firing variability and impaired social representation in IRSp53-mutant mice.

Social deficit is a major feature of neuropsychiatric disorders, including autism spectrum disorders, schizophrenia, and attention-deficit/hyperactivity disorder, but its neural mechanisms remain unclear. Here, we examined neuronal discharge characteristics in the medial prefrontal cortex (mPFC) of IRSp53/Baiap2-mutant mice, which show social deficits, during social approach. We found a decrease in the proportion of IRSp53-mutant excitatory mPFC neurons encoding social information, but not that encoding non-social information. In addition, the firing activity of IRSp53-mutant neurons was less differential between social and non-social targets. IRSp53-mutant excitatory mPFC neurons displayed an increase in baseline neuronal firing, but decreases in the variability and dynamic range of firing as well as burst firing during social and non-social target approaches compared to wild-type controls. Treatment of memantine, an NMDA receptor antagonist that rescues social deficit in IRSp53-mutant mice, alleviates the reduced burst firing of IRSp53-mutant pyramidal mPFC neurons. These results suggest that suppressed neuronal activity dynamics and burst firing may underlie impaired cortical encoding of social information and social behaviors in IRSp53-mutant mice.

Combined effects of cadmium and ochratoxin A on intestinal barrier dysfunction in human Caco-2 cells and pig small intestinal epithelial cells.

Hazardous chemicals are commonly found in cereals and cereal-based products. However, most studies focus on the individual effects of these mycotoxins or metals, rather than their combined toxicity. The main objective of this study was to evaluate the combined effects of cadmium (Cd) and ochratoxin A (OTA) on intestinal barrier integrity using Caco-2 cells and pig small intestinal epithelial (PSI) cells as models of intestinal epithelial cells and to measure alterations in cell survival and barrier integrity. The combined effects on cell viability were assessed in terms of a combination of index values. These findings showed that co-exposure to Cd + OTA had synergistic effects on Caco-2 and PSI cells at 25%, 50%, and 75% inhibitory concentrations (IC25, IC50, and IC75, respectively) against cell viability. Individual Cd and OTA treatments had no effect, but combined Cd + OTA exposure resulted in synergistic down-regulation of paracellular apical junction complex proteins, such as claudin-1, occludin, and E-cadherin. The current findings indicate that the combined effects of OTA + Cd may have consequences at the gut level, which should not be underestimated when considering their risk to human health.

Poly(vinyl alcohol) nanofibrous membranes via green electrospinning and tannin coating for selective removal of Pb(II) ion.

The conventional adsorbent fabrication methods involve complicated processes and may cause secondary contaminations. Therefore, an effective eco-friendly method is required for the fabrication of heavy metal adsorbents using inexpensive and eco-friendly materials without secondary pollution during their process. In this study, nanofibrous membranes (NFMs) were fabricated via green electrospinning of poly(vinyl alcohol) (PVA), a hydrophilic polymer, and their water resistance was improved through simple heat treatment without using additional additives. Then, nanofibrous heavy metal adsorbents were prepared by dip-coating the NFMs in an aqueous solution of tannic acid (TA), a natural polyphenol. First, the adsorption/desorption behavior of TA on PVA NFMs during the TA coating process was investigated. In addition, the effects of TA coating on the mechanical properties and heavy metal adsorption characteristics of the PVA NFMs were analyzed. The TA coating significantly increased the mechanical strength, heat resistance, and heavy metal (Pb(II)) adsorption capacity of the PVA NFM. The Pb2+ adsorption amount of TA-coated PVA NFMs exhibited about 5-7 times higher than those of other heavy metal ions, indicating excellent selectivity for Pb2+. In addition, the TA-coated PVA NFMs retained >70% of its initial adsorption capacity even after four cycles of adsorption/desorption, indicating its reusability.

Extracellular nucleoprotein exacerbates influenza virus pathogenesis by activating Toll-like receptor 4 and the NLRP3 inflammasome.

Host immune responses, such as those initiated by pattern recognition receptor (PRR) activation, are important for viral clearance and pathogenesis. However, little is known about the interactions of viral proteins with surface PRRs or, more importantly, the association of innate immune activation with viral pathogenesis. In this study, we showed that internal influenza virus proteins were released from infected cells. Among these proteins, nucleoprotein (NP) played a critical role in viral pathogenesis by stimulating neighboring cells through toll-like receptor (TLR)2, TLR4, and the NLR family pyrin domain containing 3 (NLRP3) inflammasome. Through the activation of these PRRs, NP induced the production of interleukin (IL)-1ß and IL-6, which subsequently led to the induction of trypsin. Trypsin induced by NP increased the infectivity of influenza virus, leading to increases in viral replication and pathology upon subsequent viral infection. These results reveal the role of released NP in influenza pathogenesis and highlight the importance of the interactions of internal viral proteins with PRRs in the extracellular compartment during viral pathogenesis.

Association between oral health and thyroid disorders: A population-based cross-sectional study.

OBJECTIVES: In this study, we aimed to determine the relationship between oral health status and thyroid dysfunction. METHODS: A population-based cross-sectional analysis using data from the Korean National Health and Nutrition Examination Survey (KNHNES) was performed. We investigated the association between oral health-related parameters and the prevalence of thyroid diseases. In addition, the relationship between oral health status and thyroid function test (TFT) results was analyzed. One-way analysis of variances or chi-square test was used for comparisons between oral health-related parameters and presence of thyroid diseases. Univariable and multivariable logistic regression analyses were conducted to evaluate the associations between participants' characteristics including oral health-related parameters and the abnormal results of TFTs. RESULTS: A total of 18,034 adults were surveyed. Histories of thyroid diseases were found to be more common in people who brushed their teeth frequently or used oral hygiene products. However, histories of periodontitis and community periodontal index (CPI) did not show significant associations with histories of thyroid diseases. Among 14,860 participants without history of thyroid disorders, people having higher CPI values demonstrated higher probabilities of abnormal TFTs (OR 1.381, 95% CI 1.241-1.537, p < .0001); however, statistical significance was not found after adjusting for the other variables. CONCLUSIONS: Our study demonstrated that good oral health-related behavior was associated with more frequent thyroid disease history. High CPI showed a significant association with TFT abnormalities; however, the significance of this association became lower when other variables such as age and sex were adjusted. Further studies will be needed to determine how the control of oral health-related conditions actually has a causal relationship with thyroid disease/dysfunction through prospective cohort studies.

Homeostasis effects of fermented Maillard reaction products by Lactobacillus gasseri 4M13 in dextran sulfate sodium-induced colitis mice.

BACKGROUND: The incidence of inflammatory bowel disease (IBD) continues to increase worldwide. Multiple factors, including diet, loss of the intestinal barrier function, and imbalance of the immune system can cause IBD. A balanced diet is important for maintaining a healthy bowel and preventing IBD from occurring. The effects of probiotic Lactobacillus gasseri-fermented Maillard reaction products (MRPs) prepared by reacting whey protein with galactose on anti-inflammation and intestinal homeostasis were investigated in this study, which compared MPRs and probiotics separately. RESULTS: In an animal colitis model induced by 2% dextran sulfate sodium (DSS), FWG administration alleviated colon length loss and maintained intestinal immune system homeostasis as reflected by down-regulated interleukin (IL)-6, IL-10, tumor necrosis factor (TNF)-α output, and metallopeptidase-9, and epithelial barrier balance as reflected by up-regulated occludin, E-cadherin, and zonula occludens-1 production in the colon. Furthermore, the expression of splenic cytokines such as IL-6, TNF-α, and IL-10 was up-regulated in the FWG-treated mice in a comparable amount to the control group to ensure the balance of immune responses. CONCLUSION: This study showed that the use of FWG protects the intestines from colitis caused by DSS and maintains immune balance. FWG increased antioxidant enzyme activity, increased intestinal permeability, and regulated the balance of pro- and anti-inflammatory cytokines in the intestines and spleen. Continued intake of FWG can alleviate IBD symptoms through the preservation of mucosal immune responses, epithelial junction and homeostasis through the regulated splenic cytokines. © 2021 Society of Chemical Industry.

Escherichia coli Shiga Toxins and Gut Microbiota Interactions.

Escherichia coli (EHEC) and Shigella dysenteriae serotype 1 are enterohemorrhagic bacteria that induce hemorrhagic colitis. This, in turn, may result in potentially lethal complications, such as hemolytic uremic syndrome (HUS), which is characterized by thrombocytopenia, acute renal failure, and neurological abnormalities. Both species of bacteria produce Shiga toxins (Stxs), a phage-encoded exotoxin inhibiting protein synthesis in host cells that are primarily responsible for bacterial virulence. Although most studies have focused on the pathogenic roles of Stxs as harmful substances capable of inducing cell death and as proinflammatory factors that sensitize the host target organs to damage, less is known about the interface between the commensalism of bacterial communities and the pathogenicity of the toxins. The gut contains more species of bacteria than any other organ, providing pathogenic bacteria that colonize the gut with a greater number of opportunities to encounter other bacterial species. Notably, the presence in the intestines of pathogenic EHEC producing Stxs associated with severe illness may have compounding effects on the diversity of the indigenous bacteria and bacterial communities in the gut. The present review focuses on studies describing the roles of Stxs in the complex interactions between pathogenic Shiga toxin-producing E. coli, the resident microbiome, and host tissues. The determination of these interactions may provide insights into the unresolved issues regarding these pathogens.

Fermented Maillard Reaction Products by Lactobacillus gasseri 4M13 Alters the Intestinal Microbiota and Improves Dysfunction in Type 2 Diabetic Mice with Colitis.

Inflammatory bowel disease is a chronic relapsing disease. Multiple factors can cause inflammatory bowel disease (IBD), including diet, imbalance of the immune system, and impaired intestinal barrier function. Type 2 diabetes mellitus is a complex and chronic metabolic disease caused by a combination of insulin resistance and an ineffective insulin secretory response. The co-occurrence of these two diseases, demonstrating interrelated effects within the gut microbiota, has been frequently reported. This study evaluated the effects of a fermented glycated conjugate of whey protein and galactose with Lactobacillus gasseri 4M13 (FMRP) to prevent type 2 diabetes mellitus with inflammatory bowel disease. C57BLKS/J- db/db mice were orally administered FMRP for 14 consecutive days and 2% dextran sulfate sodium (DSS) in water ad libitum for 5 days to induce colitis. FMRP-fed mice showed improved insulin secretion and symptoms of colitis. Compared to the DSS group, the FMRP group showed a decreased abundance of six bacterial genera and increased abundance of Alistipes and Hungateiclostridium. In cecal contents, the levels of short-chain fatty acids increased in the FMRP group compared to those in the DSS group. Continuous administration of FMRP thus may improve the homeostasis of not only insulin secretion and inflammation, but also the intestinal environment in inflammatory bowel disease and type 2 diabetes mellitus.

Female nursing graduate students' stress and health: the mediating effects of sense of coherence and social support.

BACKGROUND: Ninety-five percent of nursing graduate students in South Korea are women, and most are often engaged in both academic coursework and work outside of the academic environment. Nursing graduate students often experience stress leading to physical and mental health problems that negatively affect their academic performance and persistence during graduate programs. The purpose of this study was to test multiple mediation effects of sense of coherence (SOC) and social support in the relationship between stress and health status of nursing graduate students. METHODS: The participants of this study were 231 female nursing graduate students from 14 universities. Data were collected using an online survey conducted between August and October 2019. Bootstrap techniques using the PROCESS macro for SPSS software were applied to assess the multi-mediating effects. RESULTS: The total effect (B = - 12.29, p < .001) and direct effect (B = - 7.07, p < .001) of perceived stress on health status were significant. Perceived stress had negative direct effects on social support (B = - 0.41, p < .001) and SOC (B = - 5.77, p < .001). SOC had a positive direct effect on health status (B = 0.59, p < .001). However, social support was not a significant predictor of health status (B = 1.24, p = .232). In addition, there was a positive direct effect of social support on SOC (B = 5.23, p < .001). Furthermore, the indirect effect of perceived stress on health status through SOC was significant (B = - 3.42, 95% CI = - 5.2616, - 1.8906). There was also a significant indirect effect of perceived stress on health status through social support and SOC (B = - 1.28, 95% CI = - 2.1663, - 0.5992). CONCLUSION: It is necessary to create strategies that enhance nursing graduate students' SOC and social support to reduce their perceived stress and to improve their health status.

TLR2 and the NLRP3 inflammasome mediate IL-1ß production in Prevotella nigrescens-infected dendritic cells.

Prevotella nigrescens is an oral pathogen that is frequently observed in the subgingival plaque of periodontitis patients. Interleukin-1ß (IL-1ß) is known to be involved in the immunopathology of periodontal diseases and has been implicated in the destruction of bone. In this study, we investigated the mechanism of IL-1ß production by P. nigrescens in murine bone marrow-derived dendritic cells (BMDCs). Our results showed that a host receptor, Toll-like receptor 2 (TLR2), but not TLR4 is required for pro-IL-1ß induction and nucleotide-binding oligomerization domain like receptor pyrin domain containing 3 (NLRP3) priming in BMDCs in response to P. nigrescens and activation of the NLRP3 inflammasome is necessary for processing of pro-IL-1ß into mature IL-1ß. In addition, an inhibitor assay revealed that production of reactive oxygen species, P2X7R activity, and release of cathepsin B are involved in IL-1ß production in BMDCs in response to P. nigrescens.