Effect of Ni Sulfate Residue on Oxygen Evolution Reaction (OER) in Porous NiFe@NiFe Layered Double Hydroxide.

The development of cost-effective and high-performance oxygen evolution reaction (OER) catalysts is a significant challenge. This study presents the synthesis of binder-free NiFe@NiFe layered double hydroxide (NNF) via one-pot electrodeposition on carbon paper and Ni foam at high current densities. The presence of Ni sulfate residues on the prepared NNF is also investigated. The findings indicate that Ni sulfate significantly improves OER performance and durability. The sulfate content can be controlled by varying the method and duration of washing. NNF prepared through dipping (NNF-D) exhibits outstanding OER activity with a low overpotential of 241 mV, which is 25 mV lower than that of NNF washed for 60 s (NNF-W-60 s) at 10 mA cm-2 in 1 m KOH. Furthermore, density functional theory analyses indicate that the Ni sulfate residue helps modify the electronic structure, thereby optimizing the binding strength of *OOH. This synthetic strategy is expected to inspire the development of next-generation catalysts utilizing various adsorbates.

Review of Scoring Systems for Predicting 30-Day Mortality in Ruptured Abdominal Aortic Aneurysm.

BACKGROUND: Ruptured abdominal aortic aneurysms (rAAAs) are a serious disease that can lead to high mortality; thus, their early prediction can save patients' lives. The aim of this study was to compare the accuracies of various models for predicting rAAA mortality-including the Glasgow Aneurysm Score, Vancouver Scoring System, Dutch Aneurysm Score, Edinburgh Ruptured Aneurysm Score (ERAS), and Hardman index-based on rAAA treatment outcomes at our institution. METHODS: Between 2016 and 2022, we retrospectively analyzed the early outcome data-including 30-day mortality-of patients who underwent emergency surgery for rAAA at our institution. Receiver operating characteristic curve analysis was performed to compare the aneurysm scoring systems for mortality using the area under the receiver operating characteristic curve (AUC). RESULTS: The AUC was better for the ERAS (0.718; 95% confidence interval, 0.601-0.817) than for the other scoring systems. Significant differences were observed between ERAS and Hardman indices (difference: 0.179; P = 0.016). No significant differences were found among the Glasgow Aneurysm Score, Vancouver Scoring System, and Dutch Aneurysm Score predictive risk models. CONCLUSIONS: Among the models for predicting mortality in patients with rAAA, the ERAS model demonstrated the highest AUC value; however, significant differences were only observed between ERAS and Hardman indices. This study may help develop strategies for improving rAAA prediction.

Biochar-based materials as remediation strategy in petroleum hydrocarbon-contaminated soil and water: Performances, mechanisms, and environmental impact.

Petroleum contamination is considered as a major risk to the health of humans and environment. Biochars as low-cost and eco-friendly carbon materials, have been widely used for the removal of petroleum hydrocarbon in the environment. The purpose of this paper is to review the performance, mechanisms, and potential environmental toxicity of biochar, modified biochar and its integration use with other materials in petroleum contaminated soil and water. Specifically, the use of biochar in oil-contaminated water and soil as well as the factors that could influence the removal ability of biochar were systematically evaluated. In addition, the modification and integrated use of biochar for improving the removal efficiency were summarized from the aspects of sorption, biodegradation, chemical degradation, and reusability. Moreover, the functional impacts and associated ecotoxicity of pristine and modified biochars in various environments were demonstrated. Finally, some shortcoming of current approaches, and future research needs were provided for the future direction and challenges of modified biochar research. Overall, this paper gain insight into biochar application in petroleum remediation from the perspectives of performance enhancement and environmental sustainability.

Domain-specific Physical Activity and the Risk of All-cause Mortality Among Middle-aged and Older Adults in Taiwan: A Prospective Cohort Study.

BACKGROUND: The impact of meeting leisure-time physical activity (LTPA) recommendations and household physical activity (HPA) on all-cause mortality in the Taiwanese population is unclear. We aimed to investigate the relationship between sufficient LTPA and all-cause mortality in middle-aged and older Taiwanese adults and the role of HPA in those with insufficient LTPA. METHODS: This nationwide prospective cohort study included 4,960 participants aged ≥50 years from the Taiwan Longitudinal Study in Aging (TLSA) survey. Physical activity patterns were assessed in 2003 and then followed up until 2015 for mortality through the National Death Registration Record. Cox proportional hazards regression was conducted to evaluate hazard ratios (HRs) and 95% confidence intervals (CIs) for all-cause mortality. RESULTS: Of the 4,960 participants, 1,712 died of all-cause mortality. Compared to those who had insufficient LTPA, participants who engaged in sufficient LTPA showed a significantly lower risk of all-cause mortality (HR = 0.84, 95% CI, 0.73-0.97). For those with insufficient LTPA, HPA also had a significantly reduced risk of all-cause mortality (HR = 0.85, 95% CI, 0.75-0.96) among general population. Similar associations were observed in subsequent sensitivity analyses. The subgroup analysis showed that the relationship between HPA and reduced mortality risk was only found in the women with insufficient LTPA group. CONCLUSION: This study confirmed that sufficient LTPA is associated with a lower risk of all-cause mortality. If sufficient LTPA cannot be performed, additional HPA is related to lower mortality.

Non-invasive administration of AAV to target lung parenchymal cells and develop SARS-CoV-2-susceptible mice.

Adeno-associated virus (AAV)-mediated gene delivery holds great promise for gene therapy. However, the non-invasive delivery of AAV for lung tissues has not been adequately established. Here, we revealed that the intratracheal administration of an appropriate amount of AAV2/8 predominantly targets lung tissue. AAV-mediated gene delivery that we used in this study induced the expression of the desired protein in lung parenchymal cells, including alveolar type II cells. We harnessed the technique to develop severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-susceptible mice. Three kinds of immune function-relevant gene knockout (KO) mice were transduced with AAV encoding human angiotensin-converting enzyme 2 (hACE2) and then injected with SARS-CoV-2. Among these mice, type I interferon receptor (IFNAR) KO mice showed increased viral titer in the lungs compared to that in the other KO mice. Moreover, nucleocapsid protein of SARS-CoV-2 and multiple lesions in the trachea and lung were observed in AAV-hACE2-transduced, SARS-CoV-2-infected IFNAR KO mice, indicating the involvement of type I interferon signaling in the protection of SARS-CoV-2. In this study, we demonstrate the ease and rapidness of the intratracheal administration of AAV for targeting lung tissue in mice, and this can be used to study diverse pulmonary diseases.

WFDC2 Promotes Spasmolytic Polypeptide-Expressing Metaplasia Through the Up-Regulation of IL33 in Response to Injury.

BACKGROUND & AIMS: WAP 4-disulfide core domain protein 2 (WFDC2), also known as human epididymis protein 4, is a small secretory protein that is highly expressed in fibrosis and human cancers, particularly in the ovaries, lungs, and stomach. However, the role of WFDC2 in carcinogenesis is not fully understood. The present study aimed to investigate the role of WFDC2 in gastric carcinogenesis with the use of preneoplastic metaplasia models. METHODS: Three spasmolytic polypeptide-expressing metaplasia (SPEM) models were established in both wild-type and Wfdc2-knockout mice with DMP-777, L635, and high-dose tamoxifen, respectively. To reveal the functional role of WFDC2, we performed transcriptomic analysis with DMP-777-treated gastric corpus specimens. RESULTS: Wfdc2-knockout mice exhibited remarkable resistance against oxyntic atrophy, SPEM emergence, and accumulation of M2-type macrophages in all 3 SPEM models. Transcriptomic analysis revealed that Wfdc2-knockout prevented the up-regulation of interleukin-33 (IL33) expression in the injured mucosal region of SPEM models. Notably, supplementation of recombinant WFDC2 induced IL33 production and M2 macrophage polarization, and ultimately promoted SPEM development. Moreover, long-term treatment with recombinant WFDC2 was able to induce SPEM development. CONCLUSIONS: WFDC2 expressed in response to gastric injury promotes SPEM through the up-regulation of IL33 expression. These findings provide novel insights into the role of WFDC2 in gastric carcinogenesis.

Gasdermin D Deficiency Does Not Protect Mice from High-Fat Diet-Induced Glucose Intolerance and Adipose Tissue Inflammation.

The adipose tissue NLRP3 inflammasome has recently emerged as a contributor to obesity-related metabolic inflammation. Recent studies have demonstrated that the activation of the NLRP3 inflammasome cleaves gasdermin D (GSDMD) and induces pyroptosis, a proinflammatory programmed cell death. However, whether GSDMD is involved in the regulation of adipose tissue function and the development of obesity-induced metabolic disease remains unknown. The aim of the present study was to investigate the role of GSDMD in adipose tissue inflammation as well as whole-body metabolism using GSDMD-deficient mice fed a high-fat diet (HFD) for 30 weeks. The effects of GSDMD deficiency on adipose tissue, liver, and isolated macrophages from wild-type (WT) and GSDMD knockout (KO) mice were examined. In addition, 3T3-L1 cells were used to examine the expression of GSDMD during adipogenesis. The results demonstrate that although HFD-induced inflammation was partly ameliorated in isolated macrophages and liver, adipose tissue remained unaffected by GSDMD deficiency. Compared with the WT HFD mice, GSDMD KO HFD mice exhibited a mild increase in HFD-induced glucose intolerance with increased systemic and adipose tissue IL-1ß levels. Interestingly, GSDMD deficiency caused accumulation of fat mass when challenged with HFD, partly by suppressing the expression of peroxisome proliferator-activated receptor gamma (PPARγ). The expression of GSDMD mRNA and protein was dramatically suppressed during adipocyte differentiation and was inversely correlated with PPARγ expression. Together, these findings indicate that GSDMD is not a prerequisite for HFD-induced adipose tissue inflammation and suggest a noncanonical function of GSDMD in regulation of fat mass through PPARγ.

Protein arginine methyltransferase 1 contributes to the development of allergic rhinitis by promoting the production of epithelial-derived cytokines.

BACKGROUND: Arginine methylation is a posttranslational modification mediated by protein arginine methyltransferases (PRMTs). Although previous studies have shown that PRMT1 contributes to the severity of allergic airway inflammation or asthma, the underlying mechanism is poorly understood. OBJECTIVE: This study aimed to explore the role of PRMT1 and its relevant mechanism in the development of allergic rhinitis (AR). METHODS: The expression levels of PRMTs and cytokines were determined by RT-PCR, and the localization of PRMT1 was determined by immunohistochemistry and confocal microscopy. The levels of house dust mite (HDM)-specific immunoglobulins in serum and of cytokines in nasal lavage fluids were determined by ELISA. PRMT1 inhibition was achieved by siRNA and treatment with the pan PRMT inhibitor arginine N-methyltransferase inhibitor-1. RESULTS: PRMT1 expression was significantly increased in the nasal mucosa of patients and mice with AR. The degree of eosinophilic infiltration in the nasal mucosa was reduced in PRMT1+/- AR mice compared with wild-type mice. PRMT1 haploinsufficiency reduced the levels of HDM-specific immunoglobulins in serum and those of TH2 (IL-4, IL-5, and IL-13) and epithelial (thymic stromal lymphopoietin [TSLP], IL-25, and IL-33) cytokines in the nasal lavage fluids of AR mice. In nasal epithelial cells, HDM and IL-4 cooperate to enhance PRMT1 expression through a mitogen-activated protein kinase-dependent pathway. In addition, PRMT1 was essential for the production of TSLP, IL-25, and IL-33 in response to HDM and IL-4. Arginine N-methyltransferase inhibitor-1 treatment alleviated AR in the mouse model. CONCLUSIONS: PRMT1 plays an important role in AR development by regulating epithelial-derived cytokine production and might be a new therapeutic target for AR.

Hydroxy Pentacyclic Triterpene Acid, Kaempferol, Inhibits the Human 5-Hydroxytryptamine Type 3A Receptor Activity.

Monoamine serotonin is a major neurotransmitter that acts on a wide range of central nervous system and peripheral nervous system functions and is known to have a role in various processes. Recently, it has been found that 5-HT is involved in cognitive and memory functions through interaction with cholinergic pathways. The natural flavonoid kaempferol (KAE) extracted from Cudrania tricuspidata is a secondary metabolite of the plant. Recently studies have confirmed that KAE possesses a neuroprotective effect because of its strong antioxidant activity. It has been confirmed that KAE is involved in the serotonergic pathway through an in vivo test. However, these results need to be confirmed at the molecular level, because the exact mechanism that is involved in such effects of KAE has not yet been elucidated. Therefore, the objective of this study is to confirm the interaction of KAE with 5-HT3A through electrophysiological studies at the molecular level using KAE extracted from Cudrania tricuspidata. This study confirmed the interaction between 5-HT3A and KAE at the molecular level. KAE inhibited 5-HT3A receptors in a concentration-dependent and voltage-independent manner. Site-directed mutagenesis and molecular-docking studies confirmed that the binding sites D177 and F199 are the major binding sites of human 5-HT3A receptors of KAE.

Factors Affecting Postoperative Lung Functions in Patients Undergoing Lobectomy for Non-Small Cell Lung Cancer.

Background and Objectives: The estimation of lung function impairment after pulmonary lobectomy for primary non-small cell lung cancer (NSCLC) has been of great interest since the reduction of respiratory function might severely affect a patient's quality of life. The perioperative factors that may have an influence on widening the gap between the postoperative measured lung function and predicted postoperative lung function were our greatest concern. We aimed to analyze the perioperative patient factors that may influence postoperative lung function in patients undergoing pulmonary lobectomy. Materials and Methods: A retrospective study was conducted using the medical records of 199 patients who underwent lobectomy for lung cancer between July 2017 and May 2020. After comparing the achieved postoperative forced expiratory volume in 1 s (FEV1) and predicted postoperative (ppo) FEV1, patients were divided into two groups: group A (n = 127), who had preserved pulmonary lung function; and group B (n = 72), who had decreased pulmonary lung function. Primary endpoints included location of pulmonary resection, preoperative performance status, body mass index (BMI) on admission, total muscle area, and muscle index. Results In group A, the proportion of normal weighted patients was significantly higher than that in group B (67.7% vs. 47.2%, p = 0.003). Conversely, the proportion of overweight patients was significantly higher in group B than in group A (47.2% vs. 28.3%, p = 0.003). Group B had a significantly high incidence of upper lobe resection (p = 0.012). The mean total muscle area in group A was higher than that in group B, but the difference was not statistically significant. Conclusions: A greater decrease in postoperative lung function than in ppo FEV1 was associated with BMI and the location of pulmonary resection in patients who underwent lobectomy. Postoperative physiologic changes due to high BMI and the resection of upper lobes need to be discussed to prevent postoperative morbidities.

Germinal Center-Induced Immunity Is Correlated With Protection Against SARS-CoV-2 Reinfection But Not Lung Damage.

Germinal centers (GCs) elicit protective humoral immunity through a combination of antibody-secreting cells and memory B cells, following pathogen invasion or vaccination. However, the possibility of a GC response inducing protective immunity against reinfection following severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection remains unknown. We found GC activity was consistent with seroconversion observed in recovered macaques and humans. Rechallenge with a different clade of virus resulted in significant reduction in replicating virus titers in respiratory tracts in macaques with high GC activity. However, diffuse alveolar damage and increased fibrotic tissue were observed in lungs of reinfected macaques. Our study highlights the importance of GCs developed during natural SARS-CoV-2 infection in managing viral loads in subsequent infections. However, their ability to alleviate lung damage remains to be determined. These results may improve understanding of SARS-CoV-2-induced immune responses, resulting in better coronavirus disease 2019 (COVID-19) diagnosis, treatment, and vaccine development.

Molecular evolution of dengue virus types 1 and 4 in Korean travelers.

Dengue virus (DV) is a mosquito-borne virus that is endemic to many tropical and subtropical areas. Recently, the annual incidence of DV infection has increased worldwide, including in Korea, due to global warming and increased global travel. We therefore sought to characterize the molecular and evolutionary features of DV-1 and DV-4 isolated from Korean overseas travelers. We used phylogenetic analysis based on the full coding region to classify isolates of DV-1 in Korea into genotype I (43251, KP406802), genotype IV (KP406803), and genotype V (KP406801). In addition, we found that strains of DV-4 belonged to genotype I (KP406806) and genotype II (43257). Evidence of positive selection in DV-1 strains was identified in the C, prM, NS2A, and NS5 proteins, whereas DV-4 showed positive selection only in the non-structural proteins NS2A, NS3, and NS5. The substitution rates per site per year were 5.58 × 10-4 and 6.72 × 10-4 for DV-1 and DV-4, respectively, and the time of the most recent common ancestor was determined using the Bayesian skyline coalescent method. In this study, the molecular, phylogenetic, and evolutionary characteristics of Korean DV-1 and DV-4 isolates were evaluated for the first time.

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.

Removal of potentially toxic metal by biochar derived from rendered solid residue with high content of protein and bone tissue.

The purpose of this study was to produce rendering animal carcass residue char (RACR-C) by pyrolyzing the solid residues of low-recyclable rendered pig carcasses and to evaluate their cadmium (Cd) adsorption characteristics and mechanisms. As the pyrolysis temperature increased, the inorganic content of RACR-C increased, while the carbon content decreased. In particular, the surface structure and chemistry of RACR-Cs prepared at different pyrolysis temperatures were well described by SEM-EDS, XRD, XRF, TGA, and FTIR. The Cd adsorption characteristics of RACR-C were in good agreement with the Langmuir isotherm and pseudo-second-order models, and the Cd adsorption capacities of RACR-Cs prepared at various pyrolysis temperatures were in the order of RACR-C500 (73.5 mg/g)> RACR-C600 (53.8 mg/g)> RACR-C400 (41.5 mg/g) " RACR-C250 (15.9 mg/g). The intraparticle diffusion model suggested that the adsorption of Cd by RACR-C is greatly influenced by internal diffusion as well as external boundary. Since the Cd adsorption capacity of RACR-C is greatly influenced by the initial dosage, pH, and co-existing metals, it is necessary to manage these influencing factors when treating wastewater containing heavy metals. Our results suggest that Cd adsorption by RACR-C is a complex adsorption phenomenon by various mechanisms such as adsorption by functional group (CË­C and C-O), precipitation of Cd-P and ion exchange reaction by exchangeable cation occurring rather than by a single specific mechanism.

Molecular and evolutionary analysis of dengue virus serotype 2 isolates from Korean travelers in 2015.

In Korea, dengue infection has been frequently reported in travelers to tropical and subtropical countries. Global warming increases the probability of autochthonous dengue outbreaks in Korea. In this report, the molecular and evolutionary properties of four dengue virus (DENV) type 2 isolates from Korean overseas travelers were examined. Three of these isolates were classified as Cosmopolitan genotypes and further divided into sublineages 1 (43,253, 43,254) and 2 (43,248), while the other isolate (KBPV-VR29) was related to American genotypes. The variable amino acid motifs related to virulence and replication were identified in the structural and non-structural proteins. A negative selection mechanism was clearly verified in all of the DENV proteins. Potential recombination events were identified in the NS5 protein of the XSBN10 strain. The substitution rate (5.32 × 10-4 substitutions per site) and the time of the most recent common ancestor (TMRCA) for each evolutionary group were determined by the Bayesian skyline coalescent method. This study shows that DENV type 2 strains with distinct phylogenetic, evolutionary, and virulence characteristics have been introduced into Korea by overseas travelers and have the potential to trigger autochthonous dengue outbreaks.

Nitrogen Stimulates Microcystis-Dominated Blooms More than Phosphorus in River Conditions That Favor Non-Nitrogen-Fixing Genera.

Despite the implementation of intensive phosphorus reduction measures, periodic outbreaks of cyanobacterial blooms in large rivers remain a problem in Korea, raising the need for more effective solutions to reduce their occurrence. This study sought to evaluate whether phosphorus or nitrogen limitation is an effective approach to control cyanobacterial (Microcystis) blooms in river conditions that favor this non-nitrogen-fixing genus. These conditions include nutrient enrichment, high water temperature, and thermal stratification during summer. Mesocosm bioassays were conducted to investigate the limiting factors for cyanobacterial blooms in a river reach where severe Microcystis blooms occur annually. We evaluated the effect of five different nitrogen (3, 6, 9, 12, and 15 mg/L) and phosphorus (0.01, 0.02, 0.05, 0.1, and 0.2 mg/L) concentrations on algae growth. The results indicate that nitrogen treatments stimulated cyanobacteria (mostly Microcystis aeruginosa) more than phosphorus. Interestingly, phosphorus additions did not stimulate cyanobacteria, although it did stimulate Chlorophyceae and Bacillariophyceae. We conclude that phosphorus reduction might have suppressed the growth of Chlorophyceae and Bacillariophyceae more than that of cyanobacteria; therefore, nitrogen or at least both nitrogen and phosphorus control appears more effective than phosphorus reductions alone for reducing cyanobacteria in river conditions that are favorable for non-nitrogen-fixing genera.

Water extract of tendril of Cucurbita Moschata Duch. suppresses RANKL-induced osteoclastogenesis by down-regulating p38 and ERK signaling.

Background: Pumpkin (Curcubita sp.) is a natural product that is commonly used in folk medicine. However, the inhibitory effect and molecular mechanisms of tendril of Cucurbita Moschata Duch. (TCMD) on osteoclast differentiation have yet to be clearly elucidated. Thus, the present study aimed to investigate the effect and underlying mechanism of water extract of TCMD on osteoclast differentiation. Methods: Bone marrow-derived macrophages (BMDMs), osteoclast precursors, were cultured with macrophage colony stimulating factor (M-CSF) 30 ng/ml and receptor activator of nuclear factor-kappa B ligand (RANKL) 100 ng/ml for four days. We investigated the effect of TCMD on RANKL-induced osteoclast differentiation, tartrate-resistant acid phosphatase (TRAP) staining, F-actin ring formation, and bone resorption assay. RANKL signaling pathways were determined through Western blotting, and osteoclast differentiation marker genes were confirmed by Real-time PCR. Results: TCMD inhibited the RANKL-induced osteoclast differentiation in a dose-dependent manner without cytotoxicity. Further, F-actin ring formation and bone resorption were reduced by TCMD in RANKL-treated BMDMs. In addition, TCMD decreased the phosphorylation of p38 and ERK as well as the expression of osteoclast-related genes in BMDMs treated with RANKL. Conclusion: These findings suggest that TCMD may have preventive and therapeutic effects for destructive bone diseases.

Tendril extract of Cucurbita moschata suppresses NLRP3 inflammasome activation in murine macrophages and human trophoblast cells.

Inflammation is the root cause of many diseases that pose a serious threat to human health. Excessive inflammation can also result in preterm birth or miscarriage in pregnant women. Pumpkin (Cucurbita moschata Duchesne, CMD) is a well-known traditional health food and medicinal herb used in many countries to treat diabetes, obesity, osteoporosis, cancer and other diseases. In this study, we investigated the effects of hot water extract derived from the tendrils of C. moschata Duchesne (TCMD) on NLRP3 inflammasome activation in murine macrophages and human trophoblast cells. The TCMD treatment of LPS-primed bone marrow-derived macrophages (BMDMs) and human trophoblast cells attenuated NLRP3 inflammasome activation induced by inflammasome activators such as ATP, nigericin, and monosodium urate (MSU). TCMD treatment suppressed IL-1ß secretion in a dose-dependent manner, without affecting IL-6 secretion. In addition, TCMD inhibited NLRP3-dependent pyroptosis in BMDMs. TCMD also suppressed the release of mature IL-1ß and activation of cleaved-caspase-1 via limited ASC oligomerization. Furthermore, TCMD significantly inhibited IL-1ß secretion and pyroptotic cell death in human trophoblast cells. These results suggest that TCMD exhibits anti-inflammatory effects mediated via inhibition of NLRP3 inflammasome activation suggesting therapeutic potential against inflammatory diseases, preterm birth, and miscarriage.

New 8-C-p-Hydroxylbenzylflavonol Glycosides from Pumpkin (Cucurbita moschata Duch.) Tendril and Their Osteoclast Differentiation Inhibitory Activities.

Six new 8-C-p-hydroxybenzylflavonol glycosides were isolated from a hot water extract of pumpkin (Cucurbita moschata Duch.) tendril and elucidated as 8-C-p-hydroxybenzylquercetin 3-O-rutinoside, 8-C-p-hydroxybenzoylquercetin 3-O-ß-D-glucopyranoside, 8-C-p-hydroxybenzylkaempferol 3-O-(α-L-rhamnopyranosyl(1→6)-ß-D-galactopyranoside, 8-C-p-hydroxybenzoylkaempferol 3-O-rutinoside, 8-C-p-hydroxybenzylisorhamnetin 3-O-rutinoside, and 8-C-p-hydroxybenzylisorhamnetin 3-O-(α-L-rhamnopyranosyl(1→6)-ß-D-galactopyranoside. Their chemical structures were determined using nuclear magnetic resonance (NMR) and electrospray ionization-mass spectrometer (ESIMS) analyses. The 8-C-p-hydroxybenzylflavonol glycosides were found to inhibit the receptor activator of nuclear factor-κB (RANKL)-induced osteoclast differentiation of bone marrow derived macrophage (BMDM), an osteoclast progenitor. Additionally, 8-C-p-hydroxybenzylflavonol glycosides effectively reduced the expression of osteoclast-related genes, such as tartrate-resistant acid phosphatase, cathepsin K, nuclear factor activated T-cell cytoplasmic 1, and dendritic cell specific transmembrane protein in RANKL-treated BMDMs. These results indicate that the 8-C-p-hydroxybenzylflavonol glycosides may be the main components responsible for the osteoclast differentiation inhibitory effect of pumpkin tendril.

Recognition of the microbiota by Nod2 contributes to the oral adjuvant activity of cholera toxin through the induction of interleukin-1ß.

The role of symbiotic bacteria in the development of antigen-specific immunity remains poorly understood. Previous studies showed that sensing of symbiotic bacteria by nucleotide-binding oligomerization domain-containing protein 2 (Nod2) regulates antibody responses in response to nasal immunization with antigen and cholera toxin (CT). In this study, we examined the role of the microbiota in the adjuvant activity of CT induced after oral immunization with antigen. Germ-free (GF) mice showed impaired production of antibody responses and T-cell-specific cytokines after oral immunization when compared with that observed in conventionally raised mice. Similar to GF mice, Nod2-deficient mice showed reduced humoral responses upon oral immunization with antigen and CT. Treatment with CT enhanced the production of interleukin-1ß (IL-1ß), but not tumor necrosis factor-α or IL-12p40, induced by stimulation of dendritic cells with muramyl dipeptide, the Nod2 ligand. Mechanistically, the enhanced production of IL-1ß induced by muramyl dipeptide and CT stimulation required Nod2 and was mediated by both increased synthesis of pro-IL-1ß and caspase-1 activation. Furthermore, antigen-specific antibody and cytokine responses induced by CT were impaired in orally immunized IL-1ß-deficient mice. Collectively, our results indicate that Nod2 stimulation by symbiotic bacteria contributes to optimal CT-mediated antigen-specific oral vaccination through the induction of IL-1ß production.