Strengthening the gut epithelial barrier is a potential strategy for management of gut microbiota-associated illnesses. Here, we demonstrate that dual-specificity phosphatase 6 (Dusp6) knockout ...enhances baseline colon barrier integrity and ameliorates dextran sulfate sodium (DSS)-induced colonic injury. DUSP6 mutation in Caco-2 cells enhances the epithelial feature and increases mitochondrial oxygen consumption, accompanied by altered glucose metabolism and decreased glycolysis. We find that Dusp6-knockout mice are more resistant to DSS-induced dysbiosis, and the cohousing and fecal microbiota transplantation experiments show that the gut/fecal microbiota derived from Dusp6-knockout mice also confers protection against colitis. Further culturomics and mono-colonialization experiments show that one gut microbiota member in the genus Duncaniella confers host protection from DSS-induced injury. We identify Dusp6 deficiency as beneficial for shaping the gut microbiota eubiosis necessary to protect against gut barrier-related diseases.
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•Dusp6 deficiency protects against DSS-induced colitis in mice•Dusp6 knockout induces tight junction- and microvilli-associated gene expression•Dusp6 knockout results in elevation of mitochondrial oxygen consumption•A potential anti-colitis bacterium, NHRI-C1-K-H-1-87, is found in Dusp6-knockout mice
Chang et al. report that Dusp6 deficiency strengthens the junctions and extends the microvilli, thereby enhancing colonic barrier integrity. Dusp6 deficiency also promotes glucose-to-lipid metabolic switch and elevates mitochondrial oxygen consumption, thereby maintaining the anaerobic state for preserving obligatory bacteria. An anti-colitis anaerobe, NHRI-C1-K-H-1-87, is identified in Dusp6-knockout mice.
Soft ionotronics are emerging materials as wearable sensors for monitoring physiological signals, sensing environmental hazards, and bridging the human–machine interface. However, the next generation ...of wearable sensors requires multiple sensing capabilities, mechanical toughness, and 3D printability. In this study, a metal–organic framework (MOF) and three-dimensional (3D) printing were integrated for the synthesis of a tough MOF-based ionogel (MIG) for colorimetric and mechanical sensing. The ink for 3D printing contained deep eutectic solvents (DESs), cellulose nanocrystals (CNCs), MOF crystals, and acrylamide. After printing, further photopolymerization resulted in a second covalently cross-linked poly(acrylamide) network and solidification of MIG. As a porphyrinic Zr-based MOF, MOF-525 served as a functional filler to provide sharp color changes when exposed to acidic compounds. Notably, MOF-525 crystals also provided another design space to tune the printability and mechanical strength of MIG. In addition, the printed MIG exhibited high stability in the air because of the low volatility of DESs. Thereafter, wearable auxetic materials comprising MIG with negative Poisson’s ratios were prepared by 3D printing for the detection of mechanical deformation. The resulting auxetic sensor exhibited high sensitivity via the change in resistance upon mechanical deformation and a conformal contact with skins to monitor various human body movements. These results demonstrate a facile strategy for the construction of multifunctional sensors and the shaping of MOF-based composite materials.
Intensive methotrexate (MTX) treatment for childhood malignancies decreases osteogenesis but increases adipogenesis from the bone marrow stromal cells (BMSCs), resulting in bone loss and bone marrow ...adiposity. However, the underlying mechanisms are unclear. While microRNAs (miRNAs) have emerged as bone homeostasis regulators and miR-542-3p was recently shown to regulate osteogenesis in a bone loss context, the role of miR-542-3p in regulating osteogenesis and adipogenesis balance is not clear. Herein, in a rat MTX treatment-induced bone loss model, miR-542-3p was found significantly downregulated during the period of bone loss and marrow adiposity. Following target prediction, network construction, and functional annotation/ enrichment analyses, luciferase assays confirmed sFRP-1 and Smurf2 as the direct targets of miR-542-3p. miRNA-542-3p overexpression suppressed sFRP-1 and Smurf2 expression post-transcriptionally. Using in vitro models, miR-542-3p treatment stimulated osteogenesis but attenuated adipogenesis following MTX treatment. Subsequent signalling analyses revealed that miR-542-3p influences Wnt/β-catenin and TGF-β signalling pathways in osteoblastic cells. Our findings suggest that MTX treatment-induced bone loss and marrow adiposity could be molecularly linked to miR-542-3p pathways. Our results also indicate that miR-542-3p might be a therapeutic target for preserving bone and attenuating marrow fat formation during/after MTX chemotherapy.
Background and Aim
Asian populations have relatively lower prevalence of gastroesophageal reflux disease and tend to exhibit symptoms of prolonged gastric retention. However, it remains unknown if ...slower gastric emptying influences its features in Asian countries. We prospectively assessed the potential implications of slower gastric emptying in an Asian‐Pacific cohort of gastroesophageal reflux disease by a hospital‐based survey.
Methods
One hundred fifty‐two patients of gastroesophageal reflux disease complete the scintigraphic measurement of solid phase of gastric emptying. Clinical symptoms and psychological stress are recorded by self‐report questionnaire. The status of Helicobacter pylori infection, blood level of pepsinogen I, and I/II ratio are assessed.
Results
Forty‐seven percent and 28% of the patients have slower gastric emptying rate, depending on the incremental defined cut‐off values of slower gastric emptying, respectively. Multiple logistic regression analysis indicates that older age and depression score are independently related to slower gastric emptying. Subgroup analysis discloses that patients with slower gastric emptying and higher depression score tend to present with non‐erosive esophagitis whereas higher body mass index level and male gender in patients with normal gastric emptying predict the presence of erosive reflux disease.
Conclusions
Our study cohort of Asian patients indicates distinctive clinical implications of slower gastric emptying in patients with gastroesophageal reflux disease.
BACKGROUND
Pooled human platelet lysate (HPL) can replace fetal bovine serum (FBS) as xeno‐free supplement for ex vivo expansion of mesenchymal stromal cells (MSCs). We evaluate here whether a ...double‐virally‐inactivated HPL (DVI‐HPL) prepared from expired Intercept‐treated platelet concentrates (PCs) and treated by solvent/detergent (S/D) can be used for MSC expansion.
STUDY DESIGN AND METHODS
Expired Intercept‐treated PCs in 65% platelet (PLT) additive solution were pooled and subjected to a 1% tri‐n‐butyl phosphate/1% Triton X‐45 treatment followed by soybean oil, hydrophobic interaction chromatography purification, and sterile filtration. Bone marrow–derived MSCs (BM‐MSCs) were expanded for four passages in growth medium containing 10% DVI‐HPL, I‐HPL (from Intercept‐PC only), untreated HPL, and FBS. MSC morphology, doubling time, immunophenotype, immunosuppressive activity, and differentiation capacity were compared.
RESULTS
Expanded cells had typical spindle morphology and showed higher viability in all HPL conditions than in FBS. The DVI‐HPL and FBS‐expanded cells were morphologically larger than in I‐HPL and HPL supplements. The cumulative population doubling was lower using DVI‐HPL than with HPL and I‐HPL, but significantly higher than using FBS. Immunophenotype was not affected by the supplements used. Immunosuppressive activity was maintained with all supplements. Differentiation capacity into chondrocytes and osteocytes was more effective in DVI‐HPL but less toward adipocytes compared to other supplements.
CONCLUSIONS
Human PLT lysate made from Intercept‐PCs subjected to S/D treatment may be an alternative to untreated HPL and to I‐HPL for BM‐MSC expansion. This finding reinforces the potential of HPL as a virally safe alternative to FBS for clinical grade MSC expansion protocols.
Chemotherapeutic agents are very well evident extrinsic stimuli for causing damage to endothelial cells. Methotrexate is an antimetabolite commonly used to treat solid tumours and paediatric cancers. ...However, studies on the effect(s) of methotrexate on bone marrow microvascular system are inadequate. In the current study, we observed a significant bone marrow microvascular dilation following methotrexate therapy in rats, accompanied by apoptosis induction in bone marrow sinusoidal endothelial cells, and followed by recovery of bone marrow sinusoids associated with increased proliferation of remaining bone marrow sinusoidal endothelial cells. Our in vitro studies revealed that methotrexate is cytotoxic for cultured sinusoidal endothelial cells and can also induce apoptosis which is associated with upregulation of expression ratio of Bax and
Bcl‐2 genes and
Bax/Bcl‐2 expression ratio. Furthermore, it was shown that methotrexate can negatively affect proliferation of cultured sinusoidal endothelial cells and also inhibit their abilities of migration and formation of microvessel like tubes. The data from this study indicates that methotrexate can cause significant bone marrow sinusoidal endothelium damage in vivo and induce apoptosis and inhibit proliferation, migration and tube‐forming abilities of sinusoidal endothelial cells in vitro.
Methotrexate chemotherapy causes a significant bone marrow microvascular dilation in rats, accompanied by apoptosis induction in bone marrow sinusoidal endothelial cells, and followed by recovery of bone marrow sinusoids associated with increased proliferation of remaining bone marrow sinusoidal endothelial cells. In vitro, methotrexate can induce apoptosis and inhibit proliferation, migration and tube‐forming abilities of sinusoidal endothelial cells
The residential electricity demand were studied using the panel dataset of 21 cities and counties in Taiwan from 1998 to 2018. Observations were grouped and estimated separately for the urban and ...rural regions. Using the equality tests in the corresponding effects between the urban and rural models, the urban-rural gap of the electricity consumption was examined. The estimated results indicate that the effect of urbanization annually increased 0.52% of residential electricity demand in the urban regions, and decreased 0.02% of that in the rural regions. Considering the high replacement costs of appliances, low-income households tend to use the old and energy-inefficient ones that consume more electricity given the same electrical services. From 2011 to 2018, the decrease of the percentage of low-income households had reduced the electricity consumption by 0.68% in the rural regions.
With the rapid aging of the population structure, and the suicide ideation rate also increasing year by year, the ratio of people over 65 to the total number of deaths is increasing yearly. The study ...provides a reference for researchers interested in older adults' care to explore SI further affecting older adults in the future and provide a reference for qualitative research methods or interventional measures.
The objective of this study is to explore the influence of mental health status, life satisfaction, and depression status on suicidal ideation (SI) among hospitalized older adults.
In a cross-sectional correlation study, taking inpatients over 65 years old in a regional teaching hospital in eastern Taiwan, and the BSRS-5 ≧ 5 points of the screening cases, a total of 228 older adults agree to conduct data analysis in this study. Mainly explore the influence of personal characteristics, mental health status, life satisfaction, and depressed mood on SI among the hospitalized older adults. The basic attributes of the cases used in the data, mental health status, cognitive function, quality of life, depression, and suicide ideation, the data obtained were statistically analyzed with SPSS 20/Windows, and the descriptive statistics were average, standard deviation, percentage, median, etc. In the part of inference statistics, independent sample t-test, single-factor analysis of variance, Pearson performance difference correlation, and logistic regression analysis were used to detect important predictors of SI.
Research results in (1) 89.5% of hospitalized older adults have a tendency to depression. 2.26.3% of the older adults had SI. (2) Here are significant differences in the scores of SI among hospitalized older adults in different economic status groups and marital status groups. (3) The age, marital status, and quality of life of the hospitalized older adults were negatively correlated with SI; economic status, self-conscious health, mental health, and depression were positively correlated with SI. (4) The results of the mental health status and SI is (r = .345, p < .001), higher the score on the BSRS-5 scale, the higher the SI. The correlation between the depression scale score (SDS-SF) and SI was (r = .150, p < .05), the higher the depression scale score, the higher the SI.
The results of the study found that there was a statistically significant correlation between SI in older adults and age, marital status, economic status, mental health, quality of life, and depression, and also showed that they might interact with each other; the older adults in BSRS-5, GDS-SF, quality of life scale scores have statistically significant differences as essential predictors of SI. The results of this study suggest that medical staff can use the BSRS-5 scale to quickly screen and evaluate the mental health status of older adults, hoping to detect early and provide preventive measures, thereby improving the quality of life of older adults.
Lipocalin‐2 (LCN2) has been implicated in promoting apoptosis and neuroinflammation in neurological disorders; however, its role in neural transplantation remains unknown. In this study, we cultured ...and differentiated Lund human mesencephalic (LUHMES) cells into human dopaminergic‐like neurons and found that LCN2 mRNA was progressively induced in mouse brain after the intrastriatal transplantation of human dopaminergic‐like neurons. The induction of LCN2 protein was detected in a subset of astrocytes and neutrophils infiltrating the core of the engrafted sites, but not in neurons and microglia. LCN2‐immunoreactive astrocytes within the engrafted sites expressed lower levels of A1 and A2 astrocytic markers. Recruitment of microglia, neutrophils, and monocytes after transplantation was attenuated in LCN2 deficiency mice. The expression of M2 microglial markers was significantly elevated and survival of engrafted neurons was markedly improved after transplantation in LCN2 deficiency mice. Brain type organic cation transporter (BOCT), the cell surface receptor for LCN2, was induced in dopaminergic‐like neurons after differentiation, and treatment with recombinant LCN2 protein directly induced apoptosis in dopaminergic‐like neurons in a dose‐dependent manner. Our results, therefore, suggested that LCN2 is a neurotoxic factor for the engrafted neurons and a modulator of neuroinflammation. LCN2 inhibition may be useful in reducing rejection after neural transplantation.
Vitamin D deficiency or insufficiency is prevalent in childhood cancer patients and survivors after chemotherapy; further studies are needed to investigate the underlying aetiology and effectiveness ...of vitamin D supplementation in preventing chemotherapy-induced bone loss. This study used a rat model of treatment with antimetabolite methotrexate to investigate whether methotrexate chemotherapy causes vitamin D deficiency and if vitamin D supplementation attenuates the resultant bone loss. Methotrexate treatment (five daily injections) decreased serum vitamin D levels (from 52 to <30 ng/mL), reduced body and bone lengthening and tibial trabecular bone volume, and altered intestinal vitamin D metabolism, which was associated with intestinal mucosal damage known to cause malabsorption of nutrients, including dietary vitamin D and calcium. During the early stage after chemotherapy, mRNA expression increased for vitamin D activation enzyme CYP27B1 and for calcium-binding protein TRPV6 in the intestine. During the intestinal healing stage, expression of vitamin D catabolism enzyme CYP24 increased, and that of TRPV6 was normalised. Furthermore, subcutaneous calcitriol supplementation diminished methotrexate-induced bone loss due to its effect suppressing methotrexate-induced increased bone resorption. Thus, in young rats, methotrexate chemotherapy causes vitamin D deficiency, growth impairments, bone loss, and altered intestinal vitamin D metabolism, which are associated with intestinal damage, and vitamin D supplementation inhibits methotrexate-induced bone loss.
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