Endothelial Drp1 Couples VEGF-induced Redox Signaling with Glycolysis Through Cysteine Oxidation to Drive Angiogenesis.

Angiogenesis plays a vital role for postnatal development and tissue repair following ischemia. Reactive oxygen species (ROS) generated by NADPH oxidases (NOXes) and mitochondria act as signaling molecules that promote angiogenesis in endothelial cells (ECs) which mainly relies on aerobic glycolysis for ATP production. However, the connections linking redox signaling with glycolysis are not well understood. The GTPase Drp1 is a member of the dynamin superfamily that moves from cytosol to mitochondria through posttranslational modifications to induce mitochondrial fission. The role of Drp1 in ROS-dependent VEGF signaling and angiogenesis in ECs has not been previously described. Here, we identify an unexpected function of endothelial Drp1 as a redox sensor, transmitting VEGF-induced H 2 O 2 signals to enhance glycolysis and angiogenesis. Loss of Drp1 expression in ECs inhibited VEGF-induced angiogenic responses. Mechanistically, VEGF rapidly induced the NOX4-dependent sulfenylation (CysOH) of Drp1 on Cys 644 , promoting disulfide bond formation with the metabolic kinase AMPK and subsequent sulfenylation of AMPK at Cys 299 / 304 via the mitochondrial fission-mitoROS axis. This cysteine oxidation of AMPK, in turn, enhanced glycolysis and angiogenesis. In vivo , mice with EC-specific Drp1 deficiency or CRISPR/Cas9-engineered "redox-dead" (Cys to Ala) Drp1 knock-in mutations exhibited impaired retinal angiogenesis and post-ischemic neovascularization. Our findings uncover a novel role for endothelial Drp1 in linking VEGF-induced mitochondrial redox signaling to glycolysis through a cysteine oxidation-mediated Drp1-AMPK redox relay, driving both developmental and reparative angiogenesis.

Working hours, social engagement, and depressive symptoms: an extended work-life balance for older adults.

BACKGROUND: In recent years, researchers have been examining the impact of work-life balance (WLB) on mental health, considering it as a potential risk factor. However, it remains unclear whether the traditional understanding of WLB applies to older adults who worked for fewer hours before full retirement and whose children are likely to be independent adults. Therefore, this study aims to propose a modified form of WLB specifically for older adults. Within this context, we hypothesize that an optimum balance between working hours and social engagement protects against depressive symptoms among older adults. METHOD: We conducted an analysis using data on 5,751 Korean adults older than 55 years from the Korean Longitudinal Study of Aging 2016. Multivariate logistic regression analysis was used to evaluate the relationships among working hours, social engagement, and depressive symptoms. RESULTS: Older adults who worked fewer than 35 h per week were less likely to experience depressive symptoms than were non-working older adults and those working 35 h or more per week. Additionally, older adults with a high level of informal social participation, thus occurring almost every day or two to three times per week, were less likely to experience depressive symptoms than were those with a low level of such participation (once a month or less). Furthermore, depressive symptoms were less frequent among those who worked fewer than 35 h per week and engaged in a high level of informal social participation compared to non-working older individuals and those with a low level of informal social participation. CONCLUSIONS: Maintaining an optimal number of working hours and degree of social engagement are necessary to minimize the risk of depressive symptoms in older adults. Based on these findings, we suggest that fulfillment for work and life and their balance are important for older adults and propose work-life fulfillment balance.

Complement C1q essential for aeroallergen sensitization via CSF1R+ conventional dendritic cells type 2.

BACKGROUND: Dendritic cells (DCs) are heterogeneous, comprising multiple subsets with unique functional specifications. Our previous work has demonstrated that the specific conventional type 2 DC subset, CSF1R+cDC2s, plays a critical role in sensing aeroallergens. OBJECTIVE: It remains to be understood how CSF1R+cDC2s recognize inhaled allergens. We sought to elucidate the transcriptomic programs and receptor-ligand interactions essential for function of this subset in allergen sensitization. METHODS: We applied single-cell RNA sequencing to mouse lung DCs. Conventional DC-selective knockout mouse models were employed, and mice were subjected to inhaled allergen sensitization with multiple readouts of asthma pathology. Under the clinical arm of this work, human lung transcriptomic data were integrated with mouse data, and bronchoalveolar lavage (BAL) specimens were collected from subjects undergoing allergen provocation, with samples assayed for C1q. RESULTS: We found that C1q is selectively enriched in lung CSF1R+cDC2s, but not in other lung cDC2 or cDC1 subsets. Depletion of C1q in conventional DCs significantly attenuates allergen sensing and features of asthma. Additionally, we found that C1q binds directly to human dust mite allergen, and the C1q receptor CD91 (LRP1) is required for lung CSF1R+cDC2s to recognize the C1q-allergen complex and induce allergic lung inflammation. Lastly, C1q is enriched in human BAL samples following subsegmental allergen challenge, and human RNA sequencing data demonstrate close homology between lung IGSF21+DCs and mouse CSF1R+cDC2s. CONCLUSIONS: C1q is secreted from the CSF1R+cDC2 subset among conventional DCs. Our data indicate that the C1q-LRP1 axis represents a candidate for translational therapeutics in the prevention and suppression of allergic lung inflammation.

CX3CR1+ Macrophage Facilitates the Resolution of Allergic Lung Inflammation via Interacting CCL26.

Rationale: The resolution of inflammation is an active process coordinated by mediators and immune cells to restore tissue homeostasis. However, the mechanisms for resolving eosinophilic allergic lung inflammation triggered by inhaled allergens have not been fully elucidated. Objectives: Our objectives were to investigate the cellular mechanism of tissue-resident macrophages involved in the resolution process of eosinophilic lung inflammation. Methods: For the study, we used the institutional review board-approved protocol for human subsegmental bronchoprovocation with allergen, mouse models for allergic lung inflammation, and novel transgenic mice, including a conditional CCL26 knockout. The samples were analyzed using mass cytometry, single-cell RNA sequencing, and biophysical and immunological analyses. Measurements and Main Results: We compared alveolar macrophage (AM) subsets in the BAL before and after allergen provocation. In response to provocation with inhaled allergens, the subsets of AMs are dynamically changed in humans and mice. In the steady state, the AM subset expressing CX3CR1 is a relatively small fraction in bronchoalveolar space and lung tissue but drastically increases after allergen challenges. This subset presents unique patterns of gene expression compared with classical AMs, expressing high C1q family genes. CX3CR1+ macrophages are activated by airway epithelial cell-derived CCL26 via a receptor-ligand interaction. The binding of CCL26 to the CX3CR1+ receptor induces CX3CR1+ macrophages to secrete C1q, subsequently facilitating the clearance of eosinophils. Furthermore, the depletion of CX3CR1 macrophages or CCL26 in airway epithelial cells delays the resolution of allergic lung inflammation displaying prolonged tissue eosinophilia. Conclusions: These findings indicate that the CCL26-CX3CR1 pathway is pivotal in resolving eosinophilic allergic lung inflammation.

Protein disulfide isomerase A1 as a novel redox sensor in VEGFR2 signaling and angiogenesis.

VEGFR2 signaling in endothelial cells (ECs) is regulated by reactive oxygen species (ROS) derived from NADPH oxidases (NOXs) and mitochondria, which plays an important role in postnatal angiogenesis. However, it remains unclear how highly diffusible ROS signal enhances VEGFR2 signaling and reparative angiogenesis. Protein disulfide isomerase A1 (PDIA1) functions as an oxidoreductase depending on the redox environment. We hypothesized that PDIA1 functions as a redox sensor to enhance angiogenesis. Here we showed that PDIA1 co-immunoprecipitated with VEGFR2 or colocalized with either VEGFR2 or an early endosome marker Rab5 at the perinuclear region upon stimulation of human ECs with VEGF. PDIA1 silencing significantly reduced VEGF-induced EC migration, proliferation and spheroid sprouting via inhibiting VEGFR2 signaling. Mechanistically, VEGF stimulation rapidly increased Cys-OH formation of PDIA1 via the NOX4-mitochondrial ROS axis. Overexpression of "redox-dead" mutant PDIA1 with replacement of the active four Cys residues with Ser significantly inhibited VEGF-induced PDIA1-CysOH formation and angiogenic responses via reducing VEGFR2 phosphorylation. Pdia1+/- mice showed impaired angiogenesis in developmental retina and Matrigel plug models as well as ex vivo aortic ring sprouting model. Study using hindlimb ischemia model revealed that PDIA1 expression was markedly increased in angiogenic ECs of ischemic muscles, and that ischemia-induced limb perfusion recovery and neovascularization were impaired in EC-specific Pdia1 conditional knockout mice. These results suggest that PDIA1 can sense VEGF-induced H2O2 signal via CysOH formation to promote VEGFR2 signaling and angiogenesis in ECs, thereby enhancing postnatal angiogenesis. The oxidized PDIA1 is a potential therapeutic target for treatment of ischemic vascular diseases.

Increased Type I interferon signaling and brain endothelial barrier dysfunction in an experimental model of Alzheimer's disease.

Blood-brain barrier (BBB) dysfunction is emerging as a key pathogenic factor in the progression of Alzheimer's disease (AD), where increased microvascular endothelial permeability has been proposed to play an important role. However, the molecular mechanisms leading to increased brain microvascular permeability in AD are not fully understood. We studied brain endothelial permeability in female APPswe/PS1∆E9 (APP/PS1) mice which constitute a transgenic mouse model of amyloid-beta (Aß) amyloidosis and found that permeability increases with aging in the areas showing the greatest amyloid plaque deposition. We performed an unbiased bulk RNA-sequencing analysis of brain endothelial cells (BECs) in female APP/PS1 transgenic mice. We observed that upregulation of interferon signaling gene expression pathways in BECs was among the most prominent transcriptomic signatures in the brain endothelium. Immunofluorescence analysis of isolated BECs from female APP/PS1 mice demonstrated higher levels of the Type I interferon-stimulated gene IFIT2. Immunoblotting of APP/PS1 BECs showed downregulation of the adherens junction protein VE-cadherin. Stimulation of human brain endothelial cells with interferon-ß decreased the levels of the adherens junction protein VE-cadherin as well as tight junction proteins Occludin and Claudin-5 and increased barrier leakiness. Depletion of the Type I interferon receptor in human brain endothelial cells prevented interferon-ß-induced VE-cadherin downregulation and restored endothelial barrier integrity. Our study suggests that Type I interferon signaling contributes to brain endothelial dysfunction in AD.

Caveolin-1 controls mitochondrial damage and ROS production by regulating fission - fusion dynamics and mitophagy.

As essential regulators of mitochondrial quality control, mitochondrial dynamics and mitophagy play key roles in maintenance of metabolic health and cellular homeostasis. Here we show that knockdown of the membrane-inserted scaffolding and structural protein caveolin-1 (Cav-1) and expression of tyrosine 14 phospho-defective Cav-1 mutant (Y14F), as opposed to phospho-mimicking Y14D, altered mitochondrial morphology, and increased mitochondrial matrix mixing, mitochondrial fusion and fission dynamics as well as mitophagy in MDA-MB-231 triple negative breast cancer cells. Further, we found that interaction of Cav-1 with mitochondrial fusion/fission machinery Mitofusin 2 (Mfn2) and Dynamin related protein 1 (Drp1) was enhanced by Y14D mutant indicating Cav-1 Y14 phosphorylation prevented Mfn2 and Drp1 translocation to mitochondria. Moreover, limiting mitochondrial recruitment of Mfn2 diminished formation of the PINK1/Mfn2/Parkin complex required for initiation of mitophagy resulting in accumulation of damaged mitochondria and ROS (mtROS). Thus, these studies indicate that phospho-Cav-1 may be an important switch mechanism in cancer cell survival which could lead to novel strategies for complementing cancer therapies.

Cysteine oxidation of copper transporter CTR1 drives VEGFR2 signalling and angiogenesis.

Vascular endothelial growth factor receptor type 2 (VEGFR2, also known as KDR and FLK1) signalling in endothelial cells (ECs) is essential for developmental and reparative angiogenesis. Reactive oxygen species and copper (Cu) are also involved in these processes. However, their inter-relationship is poorly understood. Evidence of the role of the endothelial Cu importer CTR1 (also known as SLC31A1) in VEGFR2 signalling and angiogenesis in vivo is lacking. Here, we show that CTR1 functions as a redox sensor to promote angiogenesis in ECs. CTR1-depleted ECs showed reduced VEGF-induced VEGFR2 signalling and angiogenic responses. Mechanistically, CTR1 was rapidly sulfenylated at Cys189 at its cytosolic C terminus after stimulation with VEGF, which induced CTR1-VEGFR2 disulfide bond formation and their co-internalization to early endosomes, driving sustained VEGFR2 signalling. In vivo, EC-specific Ctr1-deficient mice or CRISPR-Cas9-generated redox-dead Ctr1(C187A)-knockin mutant mice had impaired developmental and reparative angiogenesis. Thus, oxidation of CTR1 at Cys189 promotes VEGFR2 internalization and signalling to enhance angiogenesis. Our study uncovers an important mechanism for sensing reactive oxygen species through CTR1 to drive neovascularization.

Effects of ß-glucan, probiotics, and synbiotics on obesity-associated colitis and hepatic manifestations in C57BL/6J mice.

PURPOSE: Probiotics and prebiotics are commonly used to improve the gut microbiota. Since prebiotics can support the growth of probiotics, co-administration of these is called synbiotics. It has been demonstrated that obesity-induced gut dysbiosis can worsen inflammatory bowel disease symptoms. This study evaluated how modulation of gut microbiota with Schizophyllum commune-derived ß-glucan (BG), probiotics (PRO), and synbiotics containing both BG and PRO (SYN) could improve the symptoms of obesity-associated colitis and hepatic manifestation. METHODS: Mice were fed a normal diet (ND), high-fat diet (HFD), and HFD with different additives (BG, PRO, and SYN) for 12 weeks, followed by 5 days of colitis induction. Mice were sacrificed before and after colitis induction. During the experiment, body weight, food and water consumption, and rectal bleeding were monitored. Proteins from the colon were subjected to western blotting, and serum biomarkers such as alanine transaminase, alkaline phosphatase, triglycerides, and total cholesterol were analyzed. Colon and liver samples were sectioned for histological analysis. The fecal microbiota was analyzed based on partial 16S rRNA gene sequences. RESULTS: Although BG and PRO secured intestinal tight junctions, these two treatments did not modulate inflammatory cell infiltration and inflammatory markers (i.e., IL-6 and TNF-α). In contrast, SYN demonstrated stronger and broader effects in reducing colonic inflammation. While BG treatment increased the abundance of indigenous Lactobacillus, PRO treatment decreased bacterial diversity by suppressing the growth of several species of bacteria. SYN treatment groups, however, supported the growth of both indigenous and supplemented bacteria while maintaining bacterial diversity. CONCLUSION: Obesity-associated colitis can be improved by modulating gut bacteria with ß-glucan and probiotics. The co-administration of both outperformed ß-glucan and probiotic treatment alone by fostering both indigenous and supplemented probiotic strains.

Pathogenic NOTCH3 Variants Are Frequent Among the Korean General Population.

OBJECTIVE: This study aimed to determine the frequency of pathogenic NOTCH3 variants among Koreans. METHODS: In this cross-sectional study, we queried for pathogenic NOTCH3 variants in 2 Korean public genome databases: the Korean Reference Genome Database (KRGDB) and the Korean Genome Project (Korea1K). In addition, we screened the 3 most common pathogenic NOTCH3 variants (p.Arg75Pro, p.Arg544Cys, and p.Arg578Cys) for 1,000 individuals on Jeju Island, where the largest number of patients with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) have been reported in Korea. RESULTS: The pathogenic NOTCH3 variant (p.Arg544Cys) was found in 0.12% of sequences in the KRGDB, and 3 pathogenic variants (p.Arg75Pro, p.Arg182Cys, and p.Arg544Cys) were present in 0.44% of the Korea1K database. Of the 1,000 individuals on Jeju Island, we found 2 cysteine-altering NOTCH3 variants (p.Arg544Cys variant in 9 and p.Arg578Cys in 1 individual) in 1.00% of the participants (95% confidence interval: 0.48%-1.83%). The presence of cysteine-altering NOTCH3 variants was significantly associated with a history of stroke (p < 0.001). DISCUSSION: Pathogenic NOTCH3 variants are frequently found in the general Korean population. Such a high prevalence of pathogenic variants could threaten the brain health of tens of thousands to hundreds of thousands of older adults in Korea.

Mitophagy mediates metabolic reprogramming of induced pluripotent stem cells undergoing endothelial differentiation.

Pluripotent stem cells are known to shift their mitochondrial metabolism upon differentiation, but the mechanisms underlying such metabolic rewiring are not fully understood. We hypothesized that during differentiation of human induced pluripotent stem cells (hiPSCs), mitochondria undergo mitophagy and are then replenished by the biogenesis of new mitochondria adapted to the metabolic needs of the differentiated cell. To evaluate mitophagy during iPSC differentiation, we performed live cell imaging of mitochondria and lysosomes in hiPSCs differentiating into vascular endothelial cells using confocal microscopy. We observed a burst of mitophagy during the initial phases of hiPSC differentiation into the endothelial lineage, followed by subsequent mitochondrial biogenesis as assessed by the mitochondrial biogenesis biosensor MitoTimer. Furthermore, hiPSCs undergoing differentiation showed greater mitochondrial oxidation of fatty acids and an increase in ATP levels as assessed by an ATP biosensor. We also found that during mitophagy, the mitochondrial phosphatase PGAM5 is cleaved in hiPSC-derived endothelial progenitor cells and in turn activates ß-catenin-mediated transcription of the transcriptional coactivator PGC-1α, which upregulates mitochondrial biogenesis. These data suggest that mitophagy itself initiates the increase in mitochondrial biogenesis and oxidative metabolism through transcriptional changes during endothelial cell differentiation. In summary, these findings reveal a mitophagy-mediated mechanism for metabolic rewiring and maturation of differentiating cells via the ß-catenin signaling pathway. We propose that such mitochondrial-nuclear cross talk during hiPSC differentiation could be leveraged to enhance the metabolic maturation of differentiated cells.

Mitofusin-2 stabilizes adherens junctions and suppresses endothelial inflammation via modulation of ß-catenin signaling.

Endothelial barrier integrity is ensured by the stability of the adherens junction (AJ) complexes comprised of vascular endothelial (VE)-cadherin as well as accessory proteins such as ß-catenin and p120-catenin. Disruption of the endothelial barrier due to disassembly of AJs results in tissue edema and the influx of inflammatory cells. Using three-dimensional structured illumination microscopy, we observe that the mitochondrial protein Mitofusin-2 (Mfn2) co-localizes at the plasma membrane with VE-cadherin and ß-catenin in endothelial cells during homeostasis. Upon inflammatory stimulation, Mfn2 is sulfenylated, the Mfn2/ß-catenin complex disassociates from the AJs and Mfn2 accumulates in the nucleus where Mfn2 negatively regulates the transcriptional activity of ß-catenin. Endothelial-specific deletion of Mfn2 results in inflammatory activation, indicating an anti-inflammatory role of Mfn2 in vivo. Our results suggest that Mfn2 acts in a non-canonical manner to suppress the inflammatory response by stabilizing cell-cell adherens junctions and by binding to the transcriptional activator ß-catenin.

Regular Exercise and Depressive Symptoms in Korean Older Adults.

Prior studies have found that exercise has a positive effect on depressive symptoms in the general population. For older individuals, however, the association between exercise and depressive symptoms is conclusive. We examined whether regular exercise is related to depressive symptoms in 5379 Korean adults aged ≥ 55 years using data from a 2016 survey administered in the Korean Longitudinal Study of Aging. We used the 10-item Center for Epidemiological Studies-Depression scale to assess depressive symptoms. We performed a multivariate logistic regression analysis to investigate the relationship between regular exercise and depressive symptoms, adjusting for sociodemographic characteristics, self-rated health, number of chronic diseases, body mass index, hand-grip strength, physical disability, cognitive impairment, and health behavior. Interaction terms, including regular exercise and health-related factors, were also added. We found that a lack of regular exercise was significantly related to an increased frequency of depressive symptoms (OR = 1.18, 95% CI = 1.03-1.35). Moreover, hand-grip strength may increase the effect of regular exercise on depressive symptoms in individuals 65 years and older (OR = 1.01 vs. 1.70, 95% CI = 1.05-1.96). Our results suggest that it is important to encourage older individuals to exercise regularly as a means of relieving depressive symptoms.

Redox Regulation of NOX Isoforms on FAK(Y397)/SRC(Y416) Phosphorylation Driven Epithelial-to-Mesenchymal Transition in Malignant Cervical Epithelial Cells.

Epithelial-to-mesenchymal transition (EMT) promulgates epithelial cell associated disease-defining characteristics in tumorigenesis and organ fibrosis. Growth factors such as epidermal growth factor and fibroblast growth factor in addition to cytokines such as transforming growth factor-ß1 (TGF-ß1) is said to play a prominent role in remodeling related pathological events of cancer progression such as invasion, metastasis, apoptosis, EMT, etc. through redox related cellular secondary messengers, in particular the reactive oxygen species (ROS). However, the signaling cascade underlying the redox mechanism and thereby the progression of EMT remains largely unknown. In this study, upon TGF-ß1 treatment, we observed an induction in NOX isoforms-NOX2 and NOX4-that have time (early and late) and cellular localization (nucleus and autophagosome co-localized) dependent effects in mediating EMT associated cell proliferation and migration through activation of the focal adhesion kinase (FAK)/SRC pathway in HeLa, human cervical cancer cells. Upon silencing NOX2/4 gene expression and using the SRC inhibitor (AZD0530), progression of TGF-ß1 induced EMT related cellular remodeling, extra cellular matrix (ECM) production, cell migration and invasion, got significantly reverted. Together, these results indicate that NOX2 and NOX4 play important, albeit distinct, roles in the activation of cytokine mediated EMT and its associated processes via tyrosine phosphorylation of the FAK/SRC pathway.

Cytoplasm-localized SIRT1 downregulation attenuates apoptosis and cell cycle arrest in cisplatin-resistant lung cancer A549 cells.

Objective: We propose that sirtuin (SIRT) may induce a pro-apoptotic effect by deacetylating transcription factors in A549 cells: depletion of sirtuin-1 (SIRT1) induced cell cycle arrest in cisplatin-resistant A549 (A549/CADD) cells. Methods: Protein and mRNA levels of SIRT1 were investigated using western blot and RT-PCR. In A549 and A549/CADD cells, the cytotoxicity of cisplatin administration was evaluated by MTT assay, proliferation was measured by ECIS, and the cell cycle distribution was analyzed using FACS. Cells were transfected with pcDNA3.1-Myc-SIRT1 or pcDNA3.1-Myc-Control vectors to analyze the impact of SIRT-1 on cisplatin induced drug resistance. SIRT1 localization was studied using immunofluorescence analysis. In addition, immunoprecipitation and 20S proteasome activity assay were performed to examine the relationship of SIRT1 with the proteasome complex. Results: A549/CADD cells exhibited a mesenchymal-like cell characteristic. SIRT1 expression was markedly decreased in A549/CADD cells. We observed that cisplatin regulates p53 stability through the depletion of ubiquitination following SIRT1 downregulation. Furthermore, cisplatin treatment increased proteasomal activity and significantly decreased cytoplasmic SIRT1 protein levels in A549/CADD cells. Conclusion: In this study, we found SIRT1 to be depleted in A549/CADD cells and also determined the underlying resistance mechanism which may act as novel therapeutic targets in overcoming drug resistance.

Socioeconomic status, work-life conflict, and mental health.

BACKGROUND: Work-life conflict (WLC) has a critical effect on employee mental health. However, research on occupational health has neglected the family domain. Furthermore, although it is reasonable to assume that the effect of WLC on health may differ according to socioeconomic circumstances, there is little empirical evidence for differences in the impact of WLC by socioeconomic status (SES). The purpose of this study was to assess the role of SES as an effect modifier, while examining whether the SES level affects the relationship between WLC and mental health. METHOD: We analyzed data from the nationally representative South Korean Working Conditions Survey of 2014, including 49 401 workers. Logistic regression analyses, stratified by sexes, were performed to identify sex differences, and interaction terms including WLC and SES were also incorporated. RESULTS: WLC (men: OR = 1.24; women: OR = 1.18) and domestic demands (men: OR = 1.16; women: OR = 1.22) were significantly associated with mental health. WLC exhibited a stronger association with mental health for individuals with high SES, both in terms of education (men: OR = 1.61 vs 1.51; women: OR = 1.52 vs 1.24) and income (men: OR = 1.44 vs 1.10; women: OR = 1.48 vs 1.20). CONCLUSIONS: Our data suggest that future efforts for health promotion should consider workers' family demands and SES as important modifying factors of psychological health in the workplace.

Dietary intervention using (1,3)/(1,6)-ß-glucan, a fungus-derived soluble prebiotic ameliorates high-fat diet-induced metabolic distress and alters beneficially the gut microbiota in mice model.

PURPOSE: Western diet, rich in carbohydrates and fat, is said to be a major factor underlying metabolic syndrome. Interventions with prebiotics, the key modulators of the gut microbiota, have paramount impact on host-associated metabolic disorders. Herein, we investigated the effect of fungus-derived (1,3)/(1,6)-ß-glucan, a highly soluble dietary fiber, on high-fat diet (HFD)-induced metabolic distress. METHODS: Male C57BL/6 J mice were fed with different diet groups (n = 11): control diet, HFD, 3 g/kg or 5 g/kg of ß-glucan-incorporated HFD. At the end of experimental study period (12th week), body weight, feces weight and fecal moisture content were observed. Further, colonic motility was measured using activated charcoal meal study. Proteins extracted from liver and intestine tissues were subjected to western blot technique. Paraffin-embedded intestinal tissues were sectioned for histochemical [Periodic acid-Schiff (PAS) and Alcian blue (AB) staining] analysis. Fecal microbiota analysis was performed using MOTHUR bioinformatic software. RESULTS: ß-glucan consumption exhibited anti-obesity property in mice groups fed with HFD. In addition, ß-glucan ameliorated HFD-induced hepatic stress, colonic motility and intestinal atrophy (reduction in colon length, goblet cells, and mucosal layer thickness). Further, ß-glucan incorporation shifted bacterial community by increasing butyrate-producing bacteria such as Anaerostipes, Coprobacillus, and Roseburia and decreasing reportedly obesity-associated bacteria such as Parabacteroides and Lactococcus. CONCLUSION: Altogether, the outcomes of this present pre-clinical animal study show ß-glucan to be a promising therapeutic candidate in the treatment of HFD-induced metabolic distress. Further comprehensive research has to be conducted to brace its clinical relevance, reproducibility and efficacy for aiding human health.

ß-Glucan-Based Wet Dressing for Cutaneous Wound Healing.

Objective: Recognized as pathogen-associated molecular patterns (PAMPs), ß-glucans, a naturally occurring heterogeneous group of polysaccharides, were investigated for their ability to accelerate wound healing in the form of high water-retaining hydrogel dressing. Approach: Full-thickness wounds on the dorsal side of mice created using a 5-mm biopsy punch were treated with ß-glucan-based hydrogel for 2 weeks. Standardized photographs of the wound site were taken at regular time intervals to calculate the percentage of wound closure. Tissues isolated from the wound area were subjected to histological examination and immunoblot analysis. Results: ß-Glucan-based hydrogel significantly accelerated the duration of wound healing and enhanced the development of skin appendages in the regenerated skin tissue. Increased expression of transforming growth factor-ß3 in the skin tissue isolated from the healed wound site indicated that skin regeneration rather than skin repair occurred, thereby minimizing cutaneous scarring. The expression level of cytokeratin 10 and cytokeratin 14 in the isolated skin tissue revealed that the wounds treated with hydrogel showed proper differentiation and proliferation of keratinocytes in the epidermal layer. Innovation: Immunomodulating ß-glucan (responsible for fighting infections at the wound site, and enhancing the migration and proliferation of keratinocytes and fibroblasts) in the form of a three-dimensional hydrogel membrane that retains a high water content (responsible for cooling and soothing effect around the wound site, thereby reducing pain) was prepared and analyzed for its effects on the cutaneous wound healing mechanism. Conclusion: ß-Glucan-based hydrogels are promising as wet wound dressings in the health care industry.

Structural empowerment and nurses' patient identification behaviors: a cross-sectional study.

PURPOSE: The purpose of this paper is to identify the relationships between structural empowerment and patient identification behaviors of nurses. DESIGN/METHODOLOGY/APPROACH: The present study was a descriptive survey using a self-reported questionnaire, following a quality improvement project at a hospital in South Korea. The participants included 984 registered nurses, who administer medication and transfusions to patients in the hospital. Data were analyzed using the t-test, ANOVA, Scheffé's test, Pearson correlation coefficients and multiple regression analysis. FINDINGS: The patient identification behaviors of nurses were significantly correlated with opportunity, support, information, resources, formal power and informal power of structural empowerment. The support, information and informal power of structural empowerment, as well as the age and gender of the participants explained 10.7 percent of the variance in the patient identification behaviors of nurses. RESEARCH LIMITATIONS/IMPLICATIONS: The present study has some limitations. Although the data collected by the cross-sectional survey were analyzed, causal analysis could not have been conducted. Nursing managers can promote safety by creating a work environment that facilitates access to the support, information and resources needed for nurses to perform their duties effectively; providing opportunities for nurses to learn and develop professionally; acknowledging the achievements of nurses; and expanding their duties, so that nurses can demonstrate greater work flexibility. Future studies should investigate structural empowerment in multiple nursing organizations, and particularly the organizational characteristics that affect structural empowerment. ORIGINALITY/VALUE: The present study confirms that structural empowerment influences the patient identification behaviors of nurses.