Combining 2'-fucosyllactose and galactooligosaccharides exerts anti-inflammatory effects and promotes gut health.

This study investigated the potential of 2'-Fucosyllactose (2'-FL) and galactooligosaccharides (GOS) combinations as a novel and cost-effective substitute for human milk oligosaccharides (HMOs) in promoting gut health and reducing inflammation. In vitro studies using Caco-2 cells showed that 2'-FL and GOS combinations (H1: GOS:2'-FL ratio of 1.8:1; H2: ratio of 3.6:1) reduced lipopolysaccharide-induced inflammation by decreasing pro-inflammatory markers, while individual treatments had no significant effects. In a mouse model of dextran sulfate sodium (DSS)-induced colitis, combined 2'-FL and GOS supplementation alleviated symptoms, improved gut permeability, and enhanced intestinal structure, with the GH1 group (H1 combo with DSS) being the most effective. 2'-FL and GOS combinations also enhanced short-chain fatty acid production in infant fecal batch fermentation and mouse fecal analysis, with GH1 showing the most promising results. GH1 supplementation altered gut microbiota in mice with DSS-induced colitis, promoting microbial diversity and a more balanced Firmicutes to Bacteroidota ratio. Infant formula products (IFPs) containing 2'-FL and GOS combinations (IFP2: 174 mg GOS and 95 mg 2'-FL per 14 g serving, 1.8:1 ratio; IFP3: 174 mg GOS and 48 mg 2'-FL per 14 g serving, 3.6:1 ratio) demonstrated gastrointestinal protective and anti-inflammatory properties in a coculture model of Caco-2 and THP-1 cells. These findings suggest that 2'-FL and GOS combinations have potential applications in advanced infant formulas and supplements to promote gut health and reduce inflammation.

Epidemiologic characteristics and risk factors of Clostridioides difficile infection in patients with active tuberculosis in the Republic of Korea: A nationwide population-based study.

BACKGROUND: The relationship between anti-tuberculosis (TB) agents and Clostridioides difficile infection (CDI) remains unclear. This study aimed to investigate the epidemiological characteristics and risk factors for CDI in patients with TB. METHODS: This nationwide, population-based cohort study was conducted in the Republic of Korea (ROK) between January 2018 and December 2022. Data were extracted from the National Health Insurance Service (NHIS) National Health Information Database. The risk factors for CDI in patients with TB were identified through multivariate logistic regression analysis using a 1:4 greedy matching method based on age and sex. RESULTS: During the study period, CDI developed in 2,901 of the 131,950 patients with TB who were prescribed anti-TB agents. The incidence of CDI in patients with TB has increased annually in the ROK from 12.31/1000 in 2018 to 33.51/1000 in 2022. Oral metronidazole (81.94%) was the most common first-line treatment for CDI. The in-hospital mortality rate of patients with concomitant CDI and tuberculosis was 9.9% compared with 6.9% in those with TB alone (P<0.0001). Multivariate logistic regression analysis found intensive care unit admission, Charlson Comorbidity Index ≥3, antibiotics exposure, standard regimen, multidrug resistant TB, and extrapulmonary TB as significant risk factors for development of CDI in patients with TB. CONCLUSION: CDI is uncommon in patients with TB, but it results in a significantly increased mortality rate. Patients being treated for TB should be carefully monitored for the development of CDI. Further clinical research is warranted to identify effective interventions for preventing and controlling CDI during TB treatment.

Jaw in a day surgery: early experience with 19 patients at an Australian tertiary referral center.

BACKGROUND: The Jaw-in-a-Day (JIAD) procedure aims to achieve immediate functional occlusion via a single-stage approach to maxillofacial reconstruction. While JIAD has gained popularity since its inception by Levine and colleagues, efficacy and outcome data remain limited. In this report, we discuss our experience with the JIAD technique at an Australian tertiary referral centre. METHODS: A retrospective review of all JIAD procedures performed from April 2022 to December 2023 was conducted. Clinicopathologic data reviewed included demographic information, primary diagnosis, anatomical site of disease, and history of pre-operative radiotherapy. Outcome measures of interest included operative time, number of implants placed, post-operative complications and implant survival. RESULTS: Nineteen patients were identified for the study. Two maxillary and 17 mandibular JIAD procedures were performed. The most common indications were squamous cell carcinoma (n = 8) and ameloblastoma (n = 5). Surgical complications included recipient site wound infection (n = 3), flap dehiscence (n = 2), haematoma formation (n = 1), and neck abscess associated with partial flap failure (n = 1). No total flap failures were identified. Of the 55 total implants placed, one implant failure occurred 2-months post-operatively. No loss of irradiated implants (n = 21) was observed. The median time to adjuvant radiotherapy was 57 days (range, 32-61). Eighteen of 19 patients (95%) achieved immediate dental rehabilitation, and 15/19 patients (79%) retained a functional prosthesis by the end of the follow-up period. CONCLUSIONS: Our series supports the feasibility of single-stage reconstruction for both benign and malignant indications. Further research is required to understand the long-term functional, aesthetic, and health-related quality-of-life outcomes with the JIAD technique.

KL-Biome (Postbiotic Formulation of Lactiplantibacillus plantarum KM2) Improves Dexamethasone-Induced Muscle Atrophy in Mice.

Sarcopenia refers to an age-related decrease in muscle mass and strength. The gut-muscle axis has been proposed as a promising target to alleviate muscle atrophy. The effect of KL-Biome-a postbiotic preparation comprising heat-killed Lactiplantibacillus plantarum KM-2, its metabolites, and an excipient (soybean powder)-on muscle atrophy was evaluated using dexamethasone (DEX)-induced atrophic C2C12 myoblasts and C57BL/6J mice. KL-Biome significantly downregulated the expression of genes (Atrogin-1 and MuRF1) associated with skeletal muscle degradation but increased the anabolic phosphorylation of FoxO3a, Akt, and mTOR in C2C12 cells. Oral administration of KL-Biome (900 mg/kg) for 8 weeks significantly improved muscle mass, muscle function, and serum lactate dehydrogenase levels in DEX-treated mice. KL-Biome administration increased gut microbiome diversity and reversed DEX-mediated gut microbiota alterations. Furthermore, it significantly increased the relative abundances of the genera Subdologranulum, Alistipes, and Faecalibacterium prausnitzii, which are substantially involved in short-chain fatty acid production. These findings suggest that KL-Biome exerts beneficial effects on muscle atrophy by regulating gut microbiota.

Lactiplantibacillus plantarum LM1001 Improves Digestibility of Branched-Chain Amino Acids in Whey Proteins and Promotes Myogenesis in C2C12 Myotubes.

Lactiplantibacillus plantarum is a valuable potential probiotic species with various proven health-beneficial effects. L. plantarum LM1001 strain was selected among ten strains of L. plantarum based on proteolytic activity on whey proteins. L. plantarum LM1001 produced higher concentrations of total free amino acids and branched-chain amino acids (Ile, Leu, and Val) than other L. plantarum strains. Treatment of C2C12 myotubes with whey protein culture supernatant (1%, 2% and 3%, v/v) using L. plantarum LM1001 significantly increased the expression of myogenic regulatory factors, such as Myf-5, MyoD, and myogenin, reflecting the promotion of myotubes formation (p<0.05). L. plantarum LM1001 displayed ß-galactosidase activity but did not produce harmful ß-glucuronidase. Thus, the intake of whey protein together with L. plantarum LM1001 has the potential to aid protein digestion and utilization.

Presence and diversity of free-living amoebae and their potential application as water quality indicators.

Free-living amoebae (FLA) are found in diverse environments, such as soils, rivers, and seas. Hence, they can be used as bioindicators to assess the water quality based solely on their presence. In this study, we determined the presence of FLA in river water by filtering water samples collected from various sites and culturing the resulting filtrates. FLA were detected in all the water samples with varying quality grades (Grades Ι-V). The significant increase in the size of the amoebae population with the deterioration in the water quality. Monoxenic cultures of the amoebae were performed, and genomic DNAs were isolated, among which 18S rDNAs were sequenced to identify the amoeba species. Of the 12 species identified, 10 belonged to the Acanthamoeba genus; of the remaining 2 species, one was identified as Vannella croatica and the other as a species of Vermamoeba. Acanthamoeba was detected in samples with Grades Ι to VI quality, whereas the Vermamoeba species was present only in Grade Ι water. V. croatica was found exclusively in water with Grade ΙΙ quality. Following morphological observations, genomic DNA was sequenced using 16S rDNA to determine whether the species of Acanthamoeba harbored endosymbionts. Most of the isolated Acanthamoeba contained endosymbionts, among which 4 species of endogenous bacteria were identified and examined using transmission electron microscopy. This study provides evidence that the distribution of amoebae other than Acanthamoeba may be associated with water quality. However, further confirmation will be required based on accurate water quality ratings and assessments using a more diverse range of FLA.

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.

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.

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.

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.

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.