Traumatic brain injury (TBI) is a principal cause of death and disability worldwide. Melatonin, a hormone made by the pineal gland, is known to have anti-inflammatory and antioxidant properties. In ...this study, using a weight-drop model of TBI, we investigated the protective effects of ramelteon, a melatonin MT1/MT2 receptor agonist, and its underlying mechanisms of action. Administration of ramelteon (10 mg/kg) daily at 10:00 a.m. alleviated TBI-induced early brain damage on day 3 and long-term neurobehavioral deficits on day 28 in C57BL/6 mice. Ramelteon also increased the protein levels of interleukin (IL)-10, IL-4, superoxide dismutase (SOD), glutathione, and glutathione peroxidase and reduced the protein levels of IL-1β, tumor necrosis factor, and malondialdehyde in brain tissue and serum on days 1, 3, and 7 post-TBI. Similarly, ramelteon attenuated microglial and astrocyte activation in the perilesional cortex on day 3. Furthermore, ramelteon decreased Keap 1 expression, promoted nuclear factor erythroid 2-related factor 2 (Nrf2) nuclear accumulation, and increased levels of downstream proteins, including SOD-1, heme oxygenase-1, and NQO1 on day 3 post-TBI. However, in Nrf2 knockout mice with TBI, ramelteon did not decrease the lesion volume, neuronal degeneration, or myelin loss on day 3; nor did it mitigate depression-like behavior or most motor behavior deficits on day 28. Thus, timed ramelteon treatment appears to prevent inflammation and oxidative stress via the Nrf2-antioxidant response element pathway and might represent a potential chronotherapeutic strategy for treating TBI.
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•Ramelteon provided marked neuroprotection after TBI.•Ramelteon activated the Nrf2-ARE pathway in the brain after TBI.•The protection by ramelteon was partially lost in Nrf2-/- mice with TBI.
Obesity is regarded as an abnormal or excessive buildup of fat that may be bad for health and is influenced by a combination of intestinal flora, genetic background, physical activity level and ...environment. Symbiotic supplementation may be a realistic and easy therapy for the reversal of obesity and associated metabolic problems. In this study, we chose two Bifidobacterium species, three Lactobacilli species and four prebiotics to make a new symbiotic formulation. High or low doses of the symbiotic were administered to rats, and biochemical indicators were recorded to assess the biological effects in a high-fat-diet-induced rat model. The underlying mechanisms were explored by integrating 16S rRNA sequencing with an extensively targeted metabolome. High-dose symbiotic supplementation was effective in reducing obesity and concomitant metabolic syndrome. The high-dose symbiotic also significantly increased the abundance of Blautia, which was negatively correlated with taurocholic acid and the main differential metabolites involved in amino acid and bile acid metabolism. While the low-dose symbiotic had some therapeutic effects, they were not as strong as those at the high dose, demonstrating that the effects were dose-dependent. Overall, our novel symbiotic combination improved plasma glucose and lipid levels, shrunk adipocyte size, restored liver function, increased the abundance of Blautia and adjusted bile acid and amino acid metabolism.
Pre‐eclampsia (PE) is a pregnancy‐specific disease characterized by the occurrence of hypertension and proteinuria after two weeks of gestation. Long noncoding RNAs (lncRNAs) are emerging as key ...regulators in PE development. This study aims to investigate the role of lncRNA, small nucleolar RNA host gene 5 (SNHG5), in the pathogenesis of PE. The expression of SNHG5 was significantly downregulated in placental tissues from patients with severe PE compared normal controls. Overexpression of SNHG5 promoted trophoblast (HTR‐8/SVneo) cell proliferation, invasion, and migration, and flow cytometry results showed that SNHG5 overexpression inhibited apoptosis and caused a decrease of cell population at the G
0/G
1 phase and an increase of cell population at the S phase, while knockdown of SNHG5 had the opposite effects. The interaction between SNHG5 and miR‐26a‐5p was predicted by bioinformatics analysis and confirmed by luciferase reporter assay and RNA immunoprecipitation, and miR‐26a‐5p was negatively regulated by SNHG5; miR‐26a‐5p expression was upregulated in PE placental tissues and was inversely correlated with SNHG5 expression. Furthermore, miR‐26a‐5p was predicted to target the 3′ untranslated region of N‐cadherin, which was confirmed by luciferase reporter assay, and miR‐26a‐5p overexpression suppressed N‐cadherin expression in HTR‐8/SVneo cells. N‐cadherin mRNA expression was downregulated in PE placental tissues and was positively correlated with SNHG5 expression. Both overexpression of miR‐26a‐5p and knockdown of N‐cadherin suppressed HTR‐8/SVneo cell invasion and migration, and also attenuated the effects of SNHG5 on the cellular functions of HTR‐8/SVneo cells. In conclusion, our study suggested that SNHG5 promotes trophoblast cell proliferation, invasion, and migration at least partly via regulating the miR‐26a‐5p/N‐cadherin axis.
Our data demonstrated the downregulation of small nucleolar RNA host gene 5 (SNHG5) in placental tissues from patients with pre‐eclampsia (PE). The results from our study suggested that SNHG5 promotes trophoblast cell proliferation, invasion, and migration at least partly via regulating the miR‐26a‐5p/N‐cadherin axis.
Although intracerebral hemorrhage (ICH) is a devastating disease worldwide, the pathologic changes in ultrastructure during the acute and chronic phases of ICH are poorly described. In this study, ...transmission electron microscopy was used to examine the ultrastructure of ICH-induced pathology. ICH was induced in mice by an intrastriatal injection of collagenase. Pathologic changes were observed in the acute (3 days), subacute (6 days), and chronic (28 days) phases. Compared with sham animals, we observed various types of cell death in the injured striatum during the acute phase of ICH, including necrosis, ferroptosis, and autophagy. Different degrees of axon degeneration in the striatum were seen in the acute phase, and axonal demyelination was observed in the ipsilateral striatum and corpus callosum at late time points. In addition, phagocytes, resident microglia, and infiltrating monocyte-macrophages were present around red blood cells and degenerating neurons and were observed to engulf red blood cells and other debris. Many synapses appeared abnormal or were lost. This systematic analysis of the pathologic changes in ultrastructure after ICH in mice provides information that will be valuable for future ICH pathology studies.
Atopic dermatitis is a chronic, relapsing form of inflammatory skin disorder that is affected by genetic and environmental factors. We performed a genome-wide association study of atopic dermatitis ...in a Chinese Han population using 1,012 affected individuals (cases) and 1,362 controls followed by a replication study in an additional 3,624 cases and 12,197 controls of Chinese Han ethnicity, as well as 1,806 cases and 3,256 controls from Germany. We identified previously undescribed susceptibility loci at 5q22.1 (TMEM232 and SLC25A46, rs7701890, Pcombined = 3.15 × 10−9, odds ratio (OR) = 1.24) and 20q13.33 (TNFRSF6B and ZGPAT, rs6010620, Pcombined = 3.0 × 10−8, OR = 1.17) and replicated another previously reported locus at 1q21.3 (FLG, rs3126085, Pcombined = 5.90 × 10−12, OR = 0.82) in the Chinese sample. The 20q13.33 locus also showed evidence for association in the German sample (rs6010620, P = 2.87 × 10−5, OR = 1.25). Our study identifies new genetic susceptibility factors and suggests previously unidentified biological pathways in atopic dermatitis.
•We evaluated outcomes of ICH that affect right-hemispheric structures in mice.•ICH was induced in ventricle, cortex, hippocampus, and striatum.•Motor, cognitive, and emotion-related behaviors were ...evaluated.•Brain damage and behavioral deficits after ICH differed by brain region affected.•This study will help to inform future preclinical studies of ICH outcomes.
Intracerebral hemorrhage (ICH) is a detrimental type of stroke. Mouse models of ICH, induced by collagenase or blood infusion, commonly target striatum, but not other brain sites such as ventricular system, cortex, and hippocampus. Few studies have systemically investigated brain damage and neurobehavioral deficits that develop in animal models of ICH in these areas of the right hemisphere. Therefore, we evaluated the brain damage and neurobehavioral dysfunction associated with right hemispheric ICH in ventricle, cortex, hippocampus, and striatum. The ICH model was induced by autologous whole blood or collagenase VII-S (0.075 units in 0.5 µl saline) injection. At different time points after ICH induction, mice were assessed for brain tissue damage and neurobehavioral deficits. Sham control mice were used for comparison. We found that ICH location influenced features of brain damage, microglia/macrophage activation, and behavioral deficits. Furthermore, the 24-point neurologic deficit scoring system was most sensitive for evaluating locomotor abnormalities in all four models, especially on days 1, 3, and 7 post-ICH. The wire-hanging test was useful for evaluating locomotor abnormalities in models of striatal, intraventricular, and cortical ICH. The cylinder test identified locomotor abnormalities only in the striatal ICH model. The novel object recognition test was effective for evaluating recognition memory dysfunction in all models except for striatal ICH. The tail suspension test, forced swim test, and sucrose preference test were effective for evaluating emotional abnormality in all four models but did not correlate with severity of brain damage. These results will help to inform future preclinical studies of ICH outcomes.
•A cost-effective method of producing succinic acid was created.•Corn steep liquor powder was used as nitrogen source to replace yeast extract.•Heme was added to the medium and the culture was ...agitated at a low speed.
In this study, corn steep liquor powder (CSL) was used as nitrogen source to replace the relatively costly yeast extract typically used for the production of succinic acid with Actinobacillus succinogenes NJ113. Moreover, when heme was added to the fermentation medium and the culture was agitated at a low speed, a maximum succinic acid concentration of 37.9g/l was obtained from a glucose concentration of 50g/l, and a productivity of 0.75g/l/h was achieved. These yields are almost as high as for fermentation with glucose and yeast extract. These results suggest that heme-supplemented CSL may be a suitable alternative nitrogen source for a cost-effective method of producing succinic acid with A. succinogenes NJ113 while consuming less energy than previous methods.
The proliferation of vascular smooth muscle cells may perform a crucial role in the pathogenesis of diabetic vascular disease. AMPK additionally exerts several salutary effects on vascular function ...and improves vascular abnormalities. The current study sought to determine whether sodium tanshinone IIA silate (STS) has an inhibitory effect on vascular smooth muscle cell (VSMC) proliferation and migration under high glucose conditions mimicking diabetes without dyslipidemia, and establish the underlying mechanism. In this study, STS promoted the phosphorylation of AMP-activated protein kinase (AMPK) at T172 in VSMCs. VSMC proliferation was enhanced under high glucose (25 mM glucose, HG) versus normal glucose conditions (5.5 mM glucose, NG), and this increase was inhibited significantly by STS treatment. We utilized western blotting analysis to evaluate the effects of STS on cell-cycle regulatory proteins and found that STS increased the expression of p53 and the Cdk inhibitor, p21, subsequent decreased the expression of cell cycle-associated protein, cyclin D1. We further observed that STS arrested cell cycle progression at the G0/G1 phase. Additionally, expression and enzymatic activity of MMP-2, translocation of NF-κB, as well as VSMC migration were suppressed in the presence of STS. Notably, Compound C (CC), a specific inhibitor of AMPK, as well as AMPK siRNA blocked STS-mediated inhibition of VSMC proliferation and migration. We further evaluated its potential for activating AMPK in aortas in animal models of type 2 diabetes and found that Oral administration of STS for 10 days resulted in activation of AMPK in aortas from ob/ob or db/db mice. In conclusion, STS inhibits high glucose-induced VSMC proliferation and migration, possibly through AMPK activation. The growth suppression effect may be attributable to activation of AMPK-p53-p21 signaling, and the inhibitory effect on migration to the AMPK/NF-κB signaling axis.
Background
Stigma toward mental disorders (STMD) is a significant barrier to mental health service delivery. To improve the provision of mental health services for community‐dwelling residents in ...China, this study investigated STMD and its associated factors in community mental health workers (CMHWs) in Wuhan, China.
Methods
In this cross‐sectional study, a total of 3869 CMHWs (22.9% men and 37.1 ± 8.4 years old) were randomly selected through multistage sampling and invited to participate in this survey. The perceived devaluation‐discrimination scale (PDD) and the National Mental Health Literacy Questionnaire (NMHLQ) were used to assess STMD and mental health knowledge, respectively. The presence of STMD was indicated by a mean item score of 3.0 or higher on the PDD. Multiple logistic regression was used to identify factors associated with STMD.
Results
Of the CMHWs, 41.9% had poor mental health knowledge (NMHLQ score < 80), and 18.5% exhibited STMD. In multiple regression analysis, factors significantly associated with STMD were social workers (vs. primary care physicians, OR = 1.44, p < .001), poor self‐rated capacity to handle common mental health problems (vs. good, OR = 1.57, p < .001), and poor mental health knowledge (vs. NMHLQ score ≥ 80, OR = 1.46, p < .001).
Conclusion
STMD is common among Chinese CMHWs. To reduce STMD among CMHWs, training programs in mental health care skills and mental health education may be necessary.
There is growing evidence that extracellular vesicles (EVs) play a functional role in tissue repair and anti-aging by transferring the contents of donor cells to recipient cells. We hypothesized that ...Dauer (
C. elegans
), known as “ageless” nematodes, can also secrete extracellular vesicles and influence the lifespan of
C. elegans
. Here, we isolated EVs of dauer larvae (dauer EVs). Dauer EVs were characterized using transmission electron microscopy, nanoparticle tracking analysis (NTA), and Western blot analysis. Wild-type
C. elegans
were fed in the presence or absence of dauer EVs and tested for a range of phenotypes, including longevity, mobility and reproductive capacity. Results showed that dauer EVs increased the average lifespan of nematodes by 15.74%, improved mobility, slowed age-related pigmentation as well as body length, and reduced the accumulation of reactive oxygen species and lipids, while not impairing nematode reproductive capacity. These findings suggest that dauer EVs can extend the lifespan of
C. elegans
as well as the healthy lifespan by reducing ROS accumulation, with potential anti-aging capacity.
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