Association of depression and sleep quality with frailty: a cross-sectional study in China.

Background: With the rapid growth of global aging, frailty has become a serious public health burden, affecting the life quality of older adults. Depressive symptoms (depression hereafter) and sleep quality are associated with frailty, but the pathways in which sleep quality and depression affect frailty remain unclear. Method: This cross-sectional study included 1866 community-dwelling older adults. Demographic characteristics and health-related data of them was collected, and we also assessed frailty, depression, and sleep quality. Descriptive statistics were carried out and ordinal logistic regression analysis was used to identify the factors correlated with frailty. Spearman correlation analysis and mediation analysis were employed to assess associations between sleep quality, depression and frailty. Two-sided p < 0.05 was considered as significant. Results: The results showed that 4.1% older adults were frail and 31.0% were pre-frail. Ordinal logistic regression showed that age, consumptions of vegetables, exercise, sleep quality, depression, number of chronic diseases, chronic pain, and self-rated health were correlated with frailty. Spearman correlation analysis revealed that frailty was associated with depression and sleep quality. There was a mediation effect that sleep quality was a significant and positive predictor of frailty (total effect = 0.0545, 95% boot CI = 0.0449-0.0641), and depression was a mediator between sleep quality and frailty (mediation effect = 60.4%). Conclusion: Depression and poor sleep quality may be early indicators of frailty in older adults. Improving the sleep quality and psychological state of older adults can improve frailty, which is beneficial for healthy aging.

Narcolepsy and psychiatric disorders: A bidirectional Mendelian randomization study.

Since the introduction of the concept of narcolepsy, there has been a proliferation of discussions about its association with psychiatry. To elucidate the causal role of narcolepsy in the three psychiatric disorders [i.e., schizophrenia (SCZ), major depressive disorder (MDD), and attention-deficit hyperactivity disorder (ADHD)], we applied a bidirectional Mendelian randomization study using two stages (discovery stage and validation stage) and data from three different genome-wide association studies of narcolepsy. The estimates from different stages were combined using fixed-effects meta-analysis. Our findings suggest that narcolepsy is associated with an increased risk of SCZ. Conversely, MDD may be causally related to narcolepsy. A causal relationship between narcolepsy and ADHD was excluded.

The association between graded prognostic assessment and the prognosis of brain metastases after whole brain radiotherapy: a meta-analysis.

Introduction: This meta-analysis aims to provide evidence-based medical evidence for formulating rational treatment strategies and evaluating the prognosis of brain metastasis (BM) patients by assessing the effectiveness of the graded prognostic assessment (GPA) model in predicting the survival prognosis of patients with BM after whole-brain radiotherapy (WBRT). Methods: A comprehensive search was conducted in multiple databases, including the China Biomedical Literature Database (CBM), China National Knowledge Infrastructure (CNKI), PubMed, Wanfang database, Cochrane Library, Web of Science, and Embase. Cohort studies that met the inclusion and exclusion criteria were selected. The quality of the included literature was evaluated using the Newcastle-Ottawa Scale, and all statistical analyses were performed with R version 4.2.2. The effect size (ES) was measured by the hazard ratio (HR) of overall survival (OS). The OS rates at 3, 6, 12, and 24 months of patients with BM were compared between those with GPAs of 1.5-2.5, 3.0, and 3.5-4.0 and those with GPAs of 0-1 after WBRT. Results: A total of 1,797 participants who underwent WBRT were included in this study. The meta-analysis revealed a significant association between GPA and OS rates after WBRT: compared with BM patients with GPA of 0-1, 3-month OS rates after WBRT were significantly higher in BM patients with GPA of 1.5-2.5 (HR = 0.48; 95% CI: 0.40-0.59), GPA of 3 (HR = 0.38; 95% CI: 0.25-0.57), and GPA of 3.5-4 (HR = 0.28; 95% CI: 0.15-0.52); 6-month OS rates after WBRT were significantly higher in BM patients with GPA of 1.5-2.5 (HR = 0.48; 95% CI: 0.41-0.56), GPA of 3 (HR = 0.33; 95% CI: 0.24-0.45), and GPA of 3.5-4 (HR = 0.24; 95% CI: 0.16-0.35); 12-month OS rates after WBRT were significantly higher in BM patients with GPA of 1.5-2.5 (HR = 0.49; 95% CI: 0.41-0.58), GPA of 3 (HR = 0.48; 95% CI: 0.32-0.73), and GPA of 3.5-4 (HR = 0.31; 95% CI: 0.12-0.79); and 24-month OS rates after WBRT were significantly higher in BM patients with GPA of 1.5-2.5 (HR = 0.49; 95% CI: 0.42-0.58), GPA of 3 (HR = 0.49; 95% CI: 0.32-0.74), and GPA of 3.5-4 (HR = 0.38; 95% CI: 0.15-0.94). Conclusion: BM patients with higher GPAs generally exhibited better prognoses and survival outcomes after WBRT compared to those with lower GPAs. Systematic review registration: https://www.crd.york.ac.uk/prospero/, identifier CRD42023422914.

Expression profiles of miRNAs from bovine mammary glands in response to Streptococcus agalactiae-induced mastitis.

This study aimed to describe the expression profiles of microRNAs (miRNAs) from mammary gland tissues collected from dairy cows with Streptococcus agalactiae-induced mastitis and to identify differentially expressed miRNAs related to mastitis. The mammary glands of Chinese Holstein cows were challenged with Streptococcus agalactiae to induce mastitis. Small RNAs were isolated from the mammary tissues of the test and control groups and then sequenced using the Solexa sequencing technology to construct two small RNA libraries. Potential target genes of these differentially expressed miRNAs were predicted using the RNAhybrid software, and KEGG pathways associated with these genes were analysed. A total of 18 555 913 and 20 847 000 effective reads were obtained from the test and control groups, respectively. In total, 373 known and 399 novel miRNAs were detected in the test group, and 358 known and 232 novel miRNAs were uncovered in the control group. A total of 35 differentially expressed miRNAs were identified in the test group compared to the control group, including 10 up-regulated miRNAs and 25 down-regulated miRNAs. Of these miRNAs, miR-223 exhibited the highest degree of up-regulation with an approximately 3-fold increase in expression, whereas miR-26a exhibited the most decreased expression level (more than 2-fold). The RNAhybrid software predicted 18 801 genes as potential targets of these 35 miRNAs. Furthermore, several immune response and signal transduction pathways, including the RIG-I-like receptor signalling pathway, cytosolic DNA sensing pathway and Notch signal pathway, were enriched in these predicted targets. In summary, this study provided experimental evidence for the mechanism underlying the regulation of bovine mastitis by miRNAs and showed that miRNAs might be involved in signal pathways during S. agalactiae-induced mastitis.

Transcriptome microRNA profiling of bovine mammary glands infected with Staphylococcus aureus.

MicroRNAs are small non-coding RNA molecules that are important regulators of gene expression at the post-transcriptional level. miRNAs impact the processes of cell proliferation, differentiation and apoptosis. Thus, the regulation of miRNA expression profiles associated with mastitis will be conducive for its control. In this study, Staphylococcus aureus (S. aureus) was administered to the mammary gland of Chinese Holstein cows to construct a bacteria-type mastitis model. Total RNA was isolated from bovine mammary gland tissue samples from the S. aureus-induced mastitis group and controls. miRNAs were analyzed using Solexa sequencing and bioinformatics processing for the experimental group and control group. Two miRNA libraries were constructed respectively. A total of 370 known bovine miRNAs and 341 novel mi RNAs were detected for the S. aureus and 358 known bovine miRNAs and 232 novel miRNAs for control groups. A total of 77 miRNAs in the S. aureus group showed significant differences compared to the control group. GO (Gene Ontology) analysis showed these target genes were involved in the regulation of cells, binding, etc., while KEGG (Kyoto Encyclopedia of Genes and Genomes) analysis showed that these genes were enriched in endocytosis, and olfactory transduction pathways involved in cancer. These results provide an experimental basis to reveal the cause and regulatory mechanism of mastitis and also suggest the potential of miRNAs to serve as biomarkers for the diagnosis of mastitis in dairy cows.

Platelet activating factor induces transient blood-brain barrier opening to facilitate edaravone penetration into the brain.

The blood-brain barrier (BBB) greatly limits the efficacy of many neuroprotective drugs' delivery to the brain, so improving drug penetration through the BBB has been an important focus of research. Here we report that platelet activating factor (PAF) transiently opened BBB and facilitated neuroprotectant edaravone penetration into the brain. Intravenous infusion with PAF induced a transient BBB opening in rats, reflected by increased Evans blue leakage and mild edema formation, which ceased within 6 h. Furthermore, rat regional cerebral blood flow (rCBF) declined acutely during PAF infusion, but recovered slowly. More importantly, this transient BBB opening significantly increased the penetration of edaravone into the brain, evidenced by increased edaravone concentrations in tissue interstitial fluid collected by microdialysis and analyzed by Ultra-performance liquid chromatograph combined with a hybrid quadrupole time-of-flight mass spectrometer (UPLC-MS/MS). Similarly, incubation of rat brain microvessel endothelial cells monolayer with 1 µM PAF for 1 h significantly increased monolayer permeability to (125)I-albumin, which recovered 1 h after PAF elimination. However, PAF incubation with rat brain microvessel endothelial cells for 1 h did not cause detectable cytotoxicity, and did not regulate intercellular adhesion molecule-1, matrix-metalloproteinase-9 and P-glycoprotein expression. In conclusion, PAF could induce transient and reversible BBB opening through abrupt rCBF decline, which significantly improved edaravone penetration into the brain. Platelet activating factor (PAF) transiently induces BBB dysfunction and increases BBB permeability, which may be due to vessel contraction and a temporary decline of regional cerebral blood flow (rCBF) triggered by PAF. More importantly, the PAF induced transient BBB opening facilitates neuroprotectant edaravone penetration into brain. The results of this study may provide a new approach to improve drug delivery into the brain.

Penetration of verapamil across blood brain barrier following cerebral ischemia depending on both paracellular pathway and P-glycoprotein transportation.

BACKGROUND: Blood brain barrier (BBB) dysfunction is a common facet of cerebral ischemia, and the alteration of drug transporter, P-glycoprotein (P-gp), has been documented. AIMS: This study explores influence of damaged BBB and elevated P-gp on cerebral verapamil penetration after ischemia both in vivo and in vitro. METHODS: Middle cerebral artery occlusion (MCAO) induced ischemia/reperfusion (I/R) of rats, and Na(2)S(2)O(4) induced hypoxia/reoxygenation (H/R) damage of rat brain mirovessel endothelial cells (RBMECs) respectively, served as BBB breakdown model in vivo and in vitro. Evans-Blue (EB) extravagation and (125)I-albumin were used to quantify BBB dysfunction; UPLC-MS/MS analytical method was performed to determine accurately the concentration of verapamil in brain tissue and cell. Flow cytometry, immunohistochemistry and western blotting were applied to evaluate transport function and protein expression of P-gp. RESULTS: Overexpressed ICAM-1 and MMP-9 mediated BBB dysfunction after ischemia, which induced EB leakage and (125)I-albumin uptake increase. Enhanced accumulation of verapamil in brain tissue, but intracellular concentration reduced evidently after H/R injury. Transcellular transportation of verapamil elevated when P-gp function or expression was inhibited after H/R injury. CONCLUSION: These data indicated that BBB penetration of verapamil under ischemia condition was not only depending on BBB breakdown, but also regulated by P-gp.

Therapeutic neuroprotective effects of XQ-1H in a rat model of permanent focal cerebral ischemia.

Cerebral ischemia is one of the leading causes for death and severe disabilities in the world. XQ-1H exerts neuroprotective effects under various neurotoxic conditions in vitro. In vivo, it reduces brain damage after transient focal cerebral ischemia. The present study evaluated the dose effectiveness and therapeutic time window of neuroprotection of XQ-1H by behavioral and histological measures in rats subjected to permanent middle cerebral artery occlusion (pMCAO). Neurological deficits, TTC stain, brain water content, necrosis neuron counts, and Evans-Blue extravasation were used to quantify brain damage and blood-brain barrier dysfunction. Our results demonstrated that postischemic treatment with XQ-1H at a dose of 31.2 mg/kg produced a significant reduction in neurological scores when treatment was initiated within 2 h of pMCAO. A similar improvement was also observed in infarct volume, brain water content, Evans-Blue extravasation, and neuronal necrosis when treatment was initiated within 1 h of pMCAO. Treatment with XQ-1H at the dose of 15.6 mg/kg within 1 h also produced significant improvement in ischemia deficit. In conclusion, the therapeutic time window of XQ-1H extends for up to 1 h after pMCAO, and treatment with XQ-1H exhibits potent neuroprotection that may be of value for the design of stroke therapies.

Therapeutic neuroprotective effects of ginkgolide B on cortex and basal ganglia in a rat model of transient focal ischemia.

Cerebral ischemia and reperfusion is one of the leading causes for death and severe disabilities in the world and often lead to irreversible brain damage over later lifespan. The aim of this study was to investigate the evolution of pathological damage in cerebral cortex and basal ganglia following ischemia and to evaluate the therapeutic neuroprotective effect of ginkgolide B in a rat model of stroke induced by middle cerebral artery occlusion (MCAO). TTC stain, brain water content and Evans-Blue extravasation were used to quantify brain damage. Our results demonstrated that basal ganglia undergo progressive pathological damage earlier following MCAO, and injury was stable and irreversible after 5 h following ischemia. However, onset of ischemia injury in cerebral cortex appeared later than basal ganglia and became evident about 3 h following MCAO, and injury was stable and irreversible after 6 h following ischemia. Blood brain barrier opened progressively, and it seemed to be significantly destroyed after 4 h following MCAO comparing with 0 h. Post-ischemic treatment with ginkgolide B improved neurological function and reduced infarct size in basal ganglia within 3 h and cerebral cortex within 5 h following MCAO. The therapeutic effect of ginkgolide B on extenuate brain edema and decrease blood brain barrier permeability were extended for 5h after ischemia, and more evident reversal effect were observed when administrated at earlier time.

Platelet activating factor induces blood brain barrier permeability alteration in vitro.

The purposes of this article were to investigate whether blood brain barrier (BBB) permeability is altered after platelet activating factor (PAF) induced injury in vitro and elucidate the preliminary possible mechanisms of it. MTT method was used to observe cell damage after PAF incubation with rat brain microvessel endothelial cells (RBMECs). Intracellular concentrations of Nimodipine in normal and PAF injured RBMECs were estimated by LC-MS/MS analytical method to estimate BBB permeability. Accumulation of P-glycoprotein (P-gp) substrate rhodamine 123 in normal or PAF injured RBMECs was measured with Poly Immune Analysis System-1420 to evaluate the function of P-gp on RBMECs. Intercellular adhesion molecule-1 (ICAM-1) mRNA and protein expression levels in RBMECs were assayed by RT-PCR and flow cytometry respectively. Results showed that after RBMECs were incubated with 1 µM PAF for 24h, cell survival rate was decreased, and intracellular concentrations of Nimodipine were increased evidently. Rhodamine 123 accumulation between normal and PAF injured cells has no significant difference, but ICAM-1 mRNA and protein expression were increased remarkably in PAF injured cells, which could be inhibited by PAF antagonists. In conclusion, the present study demonstrated that BBB permeability was increased after PAF incubation, and which may be due to ICAM-1 up-regulating but not P-glycoprotein function alteration.