Adult neurogenesis plays a vital role in maintaining cognitive functions in mammals and human beings. Mobilization of hippocampal neurogenesis has been regarded as a promising therapeutic approach to ...restore injured neurons in neurodegenerative diseases including Alzheimer's disease (AD). Icarisid II (ICS II), an active ingredient derived from Epimedii Folium, has been reported to exhibit multiple neuroprotective effects. In the present study, we investigated the effects of ICS II on the proliferation and differentiation of neural stem cells (NSCs) and amyloid precusor protein (APP)‐overexpressing NSCs (APP‐NSCs) in vitro. Our results demonstrated that ICS II dose‐dependently suppressed apoptosis and elevated viability of APP‐NSCs. ICS II (1 μM) potently promoted proliferation and neuronal differentiation of NSCs and APP‐NSCs. ICS II (1 μM) significantly upregulated Wnt‐3a expression, increased the phosphorylation of glycogen synthase kinase‐3β and enhanced the nuclear transfer of β‐catenin. Moreover, ICS II also promoted astrocytes to secrete Wnt‐3a, which positively modulates Wnt/β‐catenin signaling pathway. These findings demonstrate that ICS II promotes NSCs proliferation and neuronal differentiation partly by activating the Wnt/β‐catenin signaling pathway.
Infectious endophthalmitis (IE) poses a significant threat to vision. This study aimed to explore the impact of microRNA (miR)-27a-3p on inflammation in IE. A rat model was developed through ...intravitreal injection of lipopolysaccharide. Clinical and demographic data were collected for 54 participants: 31 diagnosed with IE and 23 non-infectious patients with idiopathic macular holes. Expression levels of miR-27a-3p and inflammatory genes were quantified via reverse transcription quantitative polymerase chain reaction. Concentrations of inflammatory cytokines in human vitreous samples were measured using enzyme-linked immunosorbent assay. In vitro studies were conducted to explore the target gene of miR-27a-3p. The final animal experiments further verified the role of miR-27a-3p and tuberous sclerosis complex (TSC)1 in inflammatory responses. Results showed that miR-27a-3p was elevated in LPS-treated rats and IE patients. Thirty-one IE patients were divided into the High (n = 15) and Low (n = 16) groups according to the expression of miR-27a-3p. No significant differences were observed in baseline clinical and demographic characteristics between the control and IE patient groups. Pro-inflammatory cytokine mRNA levels and concentrations were notably increased in both LPS-treated rats and the High group of patients. Besides, results showed that TSC1 is a target gene of miR-27a-3p. Moreover, TSC1 inhibition promoted inflammation in rat vitreous samples. In summary, our findings suggested that miR-27a-3p exacerbated inflammatory responses in IE though targeting TSC1, offering novel insights for potential therapeutic strategies targeting miR-27a-3p in the clinical management of IE.
Chemotaxis is crucial for bacterial adherence and colonization of the host gastrointestinal tract. Previous studies have demonstrated that chemotaxis affects the virulence of causative pathogens and ...the infection in the host. However, the chemotactic abilities of non‐pathogenic and commensal gut bacteria have rarely been explored. We observed that Roseburia rectibacter NSJ‐69 exhibited flagella‐dependent motility and chemotaxis to a variety of molecules, including mucin and propionate. A genome‐wide analysis revealed that NSJ‐69 has 28 putative chemoreceptors, 15 of which have periplasmic ligand‐binding domains (LBDs). These LBD‐coding genes were chemically synthesized and expressed heterologously in Escherichia coli. Intensive screening of ligands revealed four chemoreceptors bound to mucin and two bound to propionate. When expressed in Comamonas testosteroni or E. coli, these chemoreceptors elicited chemotaxis toward mucin and propionate. Hybrid chemoreceptors were constructed, and results showed that the chemotactic responses to mucin and propionate were dependent on the LBDs of R. rectibacter chemoreceptors. Our study identified and characterized R. rectibacter chemoreceptors. These results will facilitate further investigations on the involvement of microbial chemotaxis in host colonization.
The phenotypic transformation of microglia in the ischemic penumbra determines the outcomes of ischemic stroke. Our previous study has shown that chemokine-like-factor 1 (CKLF1) promotes M1-type ...polarization of microglia. In this study, we investigated the cellular source and transcriptional regulation of CKLF1, as well as the biological function of CKLF1 in ischemic penumbra of rat brain. We showed that CKLF1 was significantly up-regulated in cultured rat cortical neurons subjected to oxygen-glucose deprivation/reoxygenation (ODG/R) injury, but not in cultured rat microglia, astrocytes and oligodendrocytes. In a rat model of middle cerebral artery occlusion, we found that CKLF1 was up-regulated and co-localized with neurons in ischemic penumbra. Furthermore, the up-regulated CKLF1 was accompanied by the enhanced nuclear accumulation of NF-κB. The transcriptional activity of CKLF1 was improved by overexpression of NF-κB in HEK293T cells, whereas application of NF-κB inhibitor Bay 11-7082 (1 μM) abolished it, caused by OGD/R. By using chromatin-immunoprecipitation (ChIP) assay we demonstrated that NF-κB directly bound to the promoter of CKLF1 (at a binding site located at -249 bp to -239 bp of CKLF1 promoter region), and regulated the transcription of human CKLF1. Moreover, neuronal conditional medium collected after OGD/R injury or CKLF1-C27 (a peptide obtained from secreted CKLF1) induced the M1-type polarization of microglia, whereas the CKLF1-neutralizing antibody (αCKLF1) or NF-κB inhibitor Bay 11-7082 abolished the M1-type polarization of microglia. Specific knockout of neuronal CKLF1 in ischemic penumbra attenuated neuronal impairments and M1-type polarization of microglia caused by ischemic/reperfusion injury, evidenced by inhibited levels of M1 marker CD16/32 and increased expression of M2 marker CD206. Application of CKLF1-C27 (200 nM) promoted the phosphorylation of p38 and JNK in microglia, whereas specific depletion of neuronal CKLF1 in ischemic penumbra abolished ischemic/reperfusion-induced p38 and JNK phosphorylation. In summary, CKLF1 up-regulation in neurons regulated by NF-κB is one of the crucial mechanisms to promote M1-type polarization of microglia in ischemic penumbra.
Aim
The aim of this work is to examine the effectiveness of a psychoeducational intervention on self‐efficacy (primary outcome), anxiety, depression, treatment adherence, and health‐related quality ...of life (HRQoL) of patients undergoing haemodialysis.
Methods
A two‐group randomized controlled trial of 124 patients (65 and 59 patients in the intervention and control groups, respectively) recruited from a tertiary hospital in Singapore was conducted. Data were collected from January 2015 to June 2016. Outcomes were measured at baseline and 1, 3, and 6 months after the intervention. General linear model was used to analyse data.
Results
Our findings showed significant group effect on HRQoL (effects of kidney disease on daily life; p = 0.041), time effect on all outcomes (p < 0.05; except for treatment adherence behaviours and HRQoL burden of kidney disease), and group * time interaction effect on anxiety (p = 0.040) and depression (p = 0.003), with the intervention group reporting better outcomes.
Conclusions
The positive effects of our intervention on patients' self‐efficacy, psychological well‐being, treatment adherence attitudes, and HRQoL implied its potential use in dialysis/renal centres to improve patients' self‐care and health outcomes.
Summary statement
What is already known about this topic?
Patients undergoing haemodialysis commonly encounter physical and psychological health challenges due to the complexity of the disease and long‐term treatment regimens.
Improving self‐efficacy in self‐care could improve patients' psychological well‐being, treatment adherence, and health‐related quality of life among these patients.
Limited literature is available on how psychoeducational intervention can improve health outcomes of patients undergoing haemodialysis.
What this paper adds?
The psychoeducational intervention positively reduced haemodialysis patients' anxiety and depression and improved treatment adherence attitude and health‐related quality of life.
The implications of this paper:
The psychoeducational programme could be integrated into routine care in renal or dialysis centres to enhance the health outcomes of patients undergoing haemodialysis.
Future studies should incorporate technology in the delivery of psychoeducational interventions to improve their accessibility and sustainability.
Abstract
Background
Exoskeleton-assisted walking (EAW) is expected to improve the gait of spinal cord injury (SCI) individuals. However, few studies reported the changes of pulmonary function (PF) ...parameters after EAW trainings. Hence, we aimed to explore the effect of EAW on PF parameters, 6-min walk test (6MWT) and lower extremity motor score (LEMS) in individuals with SCI and to compare those with conventional trainings.
Methods
In this prospective, single-center, single-blinded randomized controlled pilot study, 18 SCI participants were randomized into the EAW group (n = 9) and conventional group (n = 9) and received 16 sessions of 50–60 min training (4 days/week, 4 weeks). Pulmonary function parameters consisting of the forced vital capacity (FVC), forced expiratory volume in 1 s (FEV
1
), forced expiratory flow (FEF), peak expiratory flow, and maximal voluntary ventilation, 6MWT with assisted devices and LEMS were reported pre- and post-training.
Results
Values of FVC (p = 0.041), predicted FVC% (p = 0.012) and FEV
1
(p = 0.013) were significantly greater in EAW group (FVC: 3.8 ± 1.1 L; FVC%
pred
= 94.1 ± 24.5%; FEV
1
: 3.5 ± 1.0 L) compared with conventional group (FVC: 2.8 ± 0.8 L; FVC%
pred
= 65.4 ± 17.6%; FEV
1
: 2.4 ± 0.6 L) after training. Participants in EAW group completed 6MWT with median 17.3 m while wearing the exoskeleton. There was no difference in LEMS and no adverse event.
Conclusions
The current results suggest that EAW has potential benefits to facilitate PF parameters among individuals with lower thoracic neurological level of SCI compared with conventional trainings. Additionally, robotic exoskeleton helped walking.
Trial registration
: Registered on 22 May 2020 at Chinese Clinical Trial Registry (ChiCTR2000033166).
http://www.chictr.org.cn/edit.aspx?pid=53920&htm=4
.
As there is no consensus on the optimal surgery strategy for multiple primary lung cancer (MPLC), we conducted this study to address this issue by comparing the prognosis of MPLC patients underwent ...different surgical strategies including sublobar resection and the standard resection through a systemic review and meta-analysis.
Relevant literature was obtained from three databases including PubMed, Embase and Web of Science. Inclusion and exclusion criteria were set for the screening of articles to be selected for further conduction of systemic review and meta-analysis. The HRs of OS of the sublobar group compared with standard resection group were extracted directly or calculated indirectly from included researches.
Ten researches published from 2000 to 2017 were included in this study, with 468 and 445 MPLC cases for the standard resection group and sublobar resection group respectively. The result suggested that OS of MPLC patients underwent sublobar resection (segmentectomy or wedge resection for at least one lesion) was comparable with those underwent standard resection approach (lobectomy or pneumonectomy for all lesions), with HR 1.07, 95% CI 0.67-1.71, p = 0.784. Further analysis found no difference in subgroups of synchronous and metachronous (from second metachronous lesion), different population region and dominant sex type.
This study may reveal that sublobar resection is acceptable for patients with MPLC at an early stage, because of the equivalent prognosis to the standard resection and better pulmonary function preservation. Further research is needed to validate these findings.
•Compound sophorae decoction can alleviate the clinical manifestations and pathological damage of UC.•Compound sophorae decoction abates intestinal inflammation and restores colonic barrier ...function.•Compound sophorae decoction can regulate Notch signaling pathway in DSS-induced colitis mice.
Compound sophorae decoction (CSD), a Chinese Herbal decoction, is frequently clinically prescribed for patients suffered from ulcerative colitis (UC) characterized by bloody diarrhea. Yet, the underlying mechanism about how this formulae works is remain elusive.
In the present study, the experimental colitis in C57BL/6 J mice was induced by oral administration of standard diets containing 3% dextran sodium sulfate (DSS), and CSD was given orally for treatment at the same time. The clinical symptoms including stool and body weight were recorded each day, and colon length and its histopathological changes were observed. Apoptosis of colonic epithelium was studied by detecting protein expression of cleaved caspase-3, and cell proliferation by Ki-67 immunohistochemistry. Tight junction complex like ZO-1 and occludin were also determined by transmission electron microscope and immunofluorescence. The concentration of FITC-dextran 4000 was measured to evaluate intestinal barrier permeability and possible signaling pathway was investigated. Mucin2 (MUC2) and notch pathway were tested through western blot. The M1/M2 ratio in spleen and mesenteric lymph nodes were detected by flow cytometry. And the mRNA levels of iNOS and Arg1 were examined by qRT-PCR.
CSD could significantly alleviate the clinical manifestations and pathological damage. Body weight loss and DAI score of mice with colitis were improved and shortening of colon was inhibited. The administration of CSD was able to reduce apoptotic epithelial cells and facilitate epithelial cell regeneration. Increased intestinal permeability was reduced in DSS-induced colitis mice. In addition, CSD treatment obviously up-regulated the expression of ZO-1 and occludin and the secretion of MUC2, regulated notch signaling, and decreased the ratio of M1/M2.
These data together suggest that CSD can effectively mitigate intestinal inflammation, promote phenotypic change in macrophage phenotype and enhance colonic mucosal barrier function by, at least in part, regulating notch signaling in mice affected by DSS-induced colitis.
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