Evaluation of the causal effects of immune cells on ischemic stroke: a Mendelian randomization study.

Background: Ischemic stroke (IS) is a cerebrovascular disease caused by various factors, and its etiology remains inadequately understood. The role of immune system dysfunction in IS has been increasingly recognized. Our objective was to evaluate whether circulating immune cells causally impact IS risk. Methods: We conducted two-sample Mendelian randomization analyses to evaluate the causal effects of 731 immune cell traits on IS, utilizing publicly available genome-wide association studies (GWAS) summary statistics for 731 immune cell traits as exposure data, and two GWAS statistics for IS as outcome data. A set of sensitivity analyses, including Cochran's Q test, I 2 statistics, MR-Egger intercept test, MR-PRESSO global test, and leave-one-out sensitivity analyses, were performed to assess the robustness of the results. Additionally, meta-analyses were conducted to combine the results from the two different IS datasets. Finally, we extracted instrumental variables of immune cell traits with causal effects on IS in both IS datasets for SNP annotation. Results: A total of 41 and 35 immune cell traits were identified to have significant causal effects on IS based on two different IS datasets, respectively. Among them, the immune cell trait CD62L- plasmacytoid Dendritic Cell AC and CD4+ CD8dim T cell%leukocyte respectively served as risk factor and protective element in both IS datasets. The robustness of the causal effects was confirmed through the sensitivity analyses. The results of the meta-analyses further support the causal effects of CD62L- plasmacytoid Dendritic Cell AC (pooled OR=1.030, 95%CI: 1.011-1.049, P=0.002) and CD4+ CD8dim T cell%leukocyte (pooled OR=0.959, 95%CI: 0.935-0.984, P=0.001). Based on these two immune cell traits, 33 genes that may be related to the causal effects were mapped. Conclusions: Our study demonstrated the potential causal effects of circulating immune cells on IS, providing valuable insights for future studies aimed at preventing IS.

A potentiation of REM sleep-active neurons in the lateral habenula may be responsible for the sleep disturbance in depression.

Psychiatric disorders with dysfunction of the lateral habenula (LHb) show sleep disturbance, especially a disinhibition of rapid eye movement (REM) sleep in major depression. However, the role of LHb in physiological sleep control and how LHb contributes to sleep disturbance in major depression remain elusive. Here, we found that functional manipulations of LHb glutamatergic neurons bidirectionally modulated both non-REM (NREM) sleep and REM sleep. Activity recording revealed heterogeneous activity patterns of LHb neurons across sleep/wakefulness cycles, but LHb neurons were preferentially active during REM sleep. Using an activity-dependent tagging method, we selectively labeled a population of REM sleep-active LHb neurons and demonstrated that these neurons specifically promoted REM sleep. Neural circuit studies showed that LHb neurons regulated REM sleep via projections to the ventral tegmental area but not to the rostromedial tegmental nucleus. Furthermore, we found that the increased REM sleep in a depression mouse model was associated with a potentiation of REM sleep-active LHb neurons, including an increased proportion, elevated spike firing, and altered activity mode. Importantly, inhibition of REM sleep-active LHb neurons not only attenuated the increased REM sleep but also alleviated depressive-like behaviors in a depression mouse model. Thus, our results demonstrated that REM sleep-active LHb neurons selectively promoted REM sleep, and a potentiation of these neurons contributed to depression-associated sleep disturbance.

Inactivated vaccines reduce the risk of liver function abnormality in NAFLD patients with COVID-19: a multi-center retrospective study.

BACKGROUND: Abnormal liver function was frequently observed in nonalcoholic fatty liver disease (NAFLD) patients infected with SARS-CoV-2. Our aim was to explore the effect of SARS-CoV-2 inactivated vaccines on liver function abnormality among NAFLD patients with COVID-19. METHODS: The multi-center retrospective cohort included 517 NAFLD patients with COVID-19 from 1 April to 30 June 2022. Participants who received 2 doses of the vaccine (n = 274) were propensity score matched (PSM) with 243 unvaccinated controls. The primary outcome was liver function abnormality and the secondary outcome was viral shedding duration. Logistic and Cox regression models were used to calculate the odds ratio (OR) and hazard ratio (HR) for the outcomes. Sensitivity analysis was conducted to assess robustness. FINDINGS: PSM identified 171 pairs of vaccinated and unvaccinated patients. Liver function abnormality was less frequent in the vaccinated group (adjusted OR, 0.556 [95% CI (confidence interval), 0.356-0.869], p = 0.010). Additionally, the vaccinated group demonstrated a lower incidence of abnormal bilirubin levels (total bilirubin: adjusted OR, 0.223 [95% CI, 0.072-0.690], p = 0.009; direct bilirubin: adjusted OR, 0.175 [95% CI, 0.080-0.384], p < 0.001) and shorter viral shedding duration (adjusted HR, 0.798 [95% CI, 0.641-0.994], p = 0.044) than the unvaccinated group. Further subgroup analysis revealed similar results, while the sensitivity analyses indicated consistent findings. INTERPRETATION: SARS-CoV-2 vaccination in patients with NAFLD may reduce the risk of liver dysfunction during COVID-19. Furthermore, vaccination demonstrated beneficial effects on viral shedding in the NAFLD population. FUNDING: 23XD1422700, Tszb2023-01, Zdzk2020-10, Zdxk2020-01, 2308085J27 and JLY20180124.

Research landscape and trends of cerebral amyloid angiopathy: a 25-year scientometric analysis.

Background: Cerebral amyloid angiopathy (CAA), a cerebral small vessel disease affecting leptomeningeal and cortical small blood vessels, is a common cause of spontaneous lobar intracerebral hemorrhage and cognitive impairment, particularly in elderly patients. This study aims to investigate the field of CAA research from a scientometric perspective. Methods: Publications related to CAA from January 1st, 1999 to September 29th, 2023 were retrieved from the Web of Science Core Collection database. The scientometric software VOSviewer and CiteSpace were used to analyze and visualize the publication trends, countries/regions, institutions, authors, journals, cited references, and keywords of CAA. Results: A total of 2,798 publications related to CAA from 73 countries/regions, led by the United States, were included. The number of publications showed an increasing trend over time. Massachusetts General Hospital was the most productive institution, and authors Greenberg and Charidimou published the most papers and were most frequently co-cited. Journal of Alzheimer's Disease was the most prolific journal in this field, and Neurology was the most co-cited journal. Apart from "cerebral amyloid angiopathy", the most frequently used keywords were "Alzheimer's disease", "amyloid beta", "intracerebral hemorrhage", and "dementia". The burst keywords in recent years included "cortical superficial siderosis" and "dysfunction". Conclusions: This scientometric analysis provides a comprehensive overview of CAA research over the past 25 years, and offers important insights for future research directions and scientific decision-making in this field.

Comparative efficacy and acceptability of selective serotonin reuptake inhibitor antidepressants for binge eating disorder: A network meta-analysis.

Background: There are several selective serotonin reuptake inhibitor (SSRI) antidepressants currently used to treat binge eating disorder (BED), but the efficacy and acceptability of these antidepressants are still controversial. Therefore, we designed a network meta-analysis (NMA) to compare the efficacy and acceptability of different SSRI antidepressants for the treatment of BED. Methods: Four databases including PubMed, Embase, the Cochrane Library, and Web of Science were systematically searched for the eligible randomized controlled trials (RCTs) for the treatment of patients with BED. The analysis was performed with Stata16 software. Results: 9 RCTs were included in this NMA. The results of the study showed that compared with placebo, sertraline and fluoxetine could significantly reduce the frequency of binge eating. Fluoxetine was shown to be the drug with the greatest reduction in Hamilton Rating Scale for Depression (HAMD) score. Besides, all SSRI antidepressants were ineffective in losing weight. In addition, all the investigated antidepressants were found to be well acceptable in regards to the acceptability reflected by the dropout rate. Conclusion: As far as both efficacy and acceptability were concerned, fluoxetine might be the best choice.

Higher levels of C-reactive protein in the acute phase of stroke indicate an increased risk for post-stroke depression: A systematic review and meta-analysis.

BACKGROUND: Investigations have revealed the association between inflammation and post-stroke depression (PSD). However, whether the C-reactive protein (CRP) level, a biomarker of inflammation, would affect the development of PSD is still controversial. METHODS: A systematic search of databases was performed for eligible studies. Standardized Mean Difference (SMD) with 95 % Confidence Interval (CI) was used to assess the association between the CRP level in the acute phase of stroke and the risk of PSD. RESULTS: 13 cohort studies that involved 3536 participants were included. Combined results showed that compared with non-PSD patients, the CRP level of PSD patients was significantly higher on admission (SMD = 0.19, 95 % CI: 0.12-0.27). A subgroup analysis by classifying the assessment time of depression showed obvious differences of the CRP levels between the PSD patients who were diagnosed more than 1 month after stroke and the non-PSD (1-3 months: SMD = 0.16, 95 % CI: 0.06-0.25; >3months: SMD = 0.34, 95 % CI: 0.18-0.51). CONCLUSION: A higher level of CRP in the acute phase of stroke suggests an increased risk for PSD.

RNF34 ablation promotes cerebrovascular remodeling and hypertension by increasing NADPH-derived ROS generation.

Cerebrovascular remodeling is the most common cause of hypertension and stroke. Ubiquitin E3 ligase RING finger protein 34 (RNF34) is suggested to be associated with the development of multiple neurological diseases. However, the importance of RNF34 in cerebrovascular remodeling and hypertension is poorly understood. Herein, we used mice with a global RNF34 knockout as well as RNF34 floxed mice to delete RNF34 in endothelial cells and smooth muscle cells (SMCs). Our results showed that global RNF34 knockout mice substantially promoted angiotensin II (AngII)-induced middle cerebral artery (MCA) remodeling, hypertension, and neurological dysfunction. Endothelial cell RNF34 did not regulate the development of hypertension. Rather, SMC RNF34 expression is a critical regulator of hypertension and MCA remodeling. Loss of RNF34 enhanced AngII-induced mouse brain vascular SMCs (MBVSMCs) proliferation, migration and invasion. Furthermore, MCA and MBVSMCs from SMC RNF34-deficient mice showed increased superoxide anion and reactive oxygen species (ROS) generation as well as nicotinamide adenine dinucleotide phosphate (NADPH) oxidase activity, but exhibited no marked effect on mitochondria-derived ROS. Knockout of RNF34 promoted p22phox expression, leading to increased binding of p22phox/p47phox and p22phox/NOX2, and eventually NADPH oxidase complex formation. Immunoprecipitation assay identified that RNF34 interacted with p22phox. RNF34 deletion increased p22phox protein stability by inhibiting ubiquitin-mediated degradation. Blockade of NADPH oxidase activity or knockdown of p22phox significantly abolished the effects of RNF34 deletion on cerebrovascular remodeling and hypertension. Collectively, our study demonstrates that SMC RNF34 deficiency promotes cerebrovascular SMC hyperplasia and remodeling by increased NADPH-derived ROS generation via reducing p22phox ubiquitin-dependent degradation.

HDAC3 protects against atherosclerosis through inhibition of inflammation via the microRNA-19b/PPARγ/NF-κB axis.

BACKGROUND AND AIMS: Atherosclerosis (AS) is one of the leading causes of cardiovascular diseases. Studies have revealed critical roles of microRNAs (miRNAs) in the progression of AS. This study was conducted to elucidate the role and mechanism by which miR-19b influences AS. METHODS: Human umbilical vein endothelial cells (HUVECs) were treated with oxidized-low-density lipoprotein (ox-LDL), and an AS mouse model was generated with the help of ApoE-/- mice using a high-fat diet regimen. The expression patterns of peroxisome proliferator-activated receptor γ (PPARγ), nuclear factor κB (NF-κB)/p65, miR-19b and histone deacetylase 3 (HDAC3) were then characterized by reverse transcription quantitative polymerase chain reaction and Western blot analysis. In addition, the relationship among PPARγ, NF-κB/p65, miR-19b and HDAC3 was evaluated by co-immunoprecipitation, chromatin immunoprecipitation and dual-luciferase reporter gene assays. Gain- and loss-of-function experiments were also performed to examine their functional significance on ox-LDL-induced inflammation in HUVECs. Enzyme-linked immunosorbent assay was applied to determine the expression patterns of inflammatory factors in AS mice. RESULTS: PPARγ and HDAC3 were poorly expressed, while miR-19b and NF-κB/p65 were highly expressed in ox-LDL-induced HUVECs and arterial tissues of AS mice. PPARγ inhibited ox-LDL-induced inflammation in HUVECs by ubiquitination and degradation of NF-κB/p65. miR-19b, downregulated by HDAC3, targeted PPARγ and negatively-regulated its expression. Upregulated PPARγ or HDAC3 or downregulated miR-19b or NF-κB/p65 reduced TNF-α and IL-1ß expression levels in ox-LDL-induced HUVECs and AS mice. CONCLUSIONS: Collectively, the results show that HDAC3 upregulation prevents inflammation to inhibit AS by inactivating NF-κB/p65 via upregulation of miR-19b-mediated PPARγ, providing a basic therapeutic consideration for AS treatment.

EGCG Regulates Cell Apoptosis of Human Umbilical Vein Endothelial Cells Grown on 316L Stainless Steel for Stent Implantation.

BACKGROUND: Nowadays, medical grade 316L stainless steel (316L SS) is being widely used for intravascular stents, and the drug-eluting stent (DES) system is able to significantly reduce the occurrences of in-stent restenosis. But the drugs and the polymer coating used in DES potentially induce the forming of late stent thrombosis. In order to reduce the occurrence of ISR after stent implantation, the development of novel drugs for DESs is urgently needed. METHODS: This study aimed to investigate the potential mechanisms of epigallocatechin-3-gallate (EGCG) on human umbilical vein endothelial cells (HUVEC) grown on 316L stainless steel (316L SS) using flow cytometry and Q-PCR methods. RESULTS: Our results showed that EGCG (12.5, 25, 50, 100 µmol/L) significantly inhibited HUVEC proliferation. Flow cytometry analysis indicated that EGCG (25, 50, 100 µmol/L) induced apoptosis. Moreover, qRT-PCRrevealed that genes associated with cell apoptosis (caspase-3, 8, 9, Fas) and autophagy (Atg 5, Atg 7, Atg 12) were up-regulated after EGCG treatment. CONCLUSION: These findings indicate that EGCG possesses chemo preventive potential in stent coating which may serve as a novel new drug for stent implantation.

Depression-like behavior is associated with lower Per2 mRNA expression in the lateral habenula of rats.

Circadian rhythm dysfunction is primary symptom of depression and is closely related to depression onset. The role of the lateral habenula (LHb) of the thalamus in the pathogenesis of depression has been a research topic of great interest. The neuronal activity of this structure has circadian characteristics, which are related to the regulation of circadian rhythms. However, in depression model of rats, the role of clock genes in the LHb has not been assessed. To address this gap, we used a clomipramine (CLI) injection-induced depression model in rats to assess the daily expression of rhythmic genes in the LHb and depression-like behavior in rats at multiple time points. In determining the role of the Per2 gene in the development of depression-like behavior in the LHb, we found that the expression of this clock gene differed in a circadian manner. Per2 expression was also significantly decreased in CLI-treated rats in late afternoon (17:00) and in the middle of the night (1:00). Furthermore, silencing Per2 in the LHb of normal rats induced depression-like behavior at night, suggesting that Per2 may play an important role in the pathogenesis of depression. Collectively, these results indicate that decreased Per2 expression in the LHb may be related to increased depression-like behavior at night in depression model of rats.

Supplementation of Diet With Different n-3/n-6 PUFA Ratios Ameliorates Autistic Behavior, Reduces Serotonin, and Improves Intestinal Barrier Impairments in a Valproic Acid Rat Model of Autism.

The implication of different dietary n-3/n-6 polyunsaturated fatty acids (PUFAs) ratios has been investigated in some neurodevelopmental disorders (including autism and depression). However, the mechanisms underlying the effects of different PUFAs ratios on the autism are still poorly understood. In the present study, a valproic acid (VPA) rat model of autism was used to study the effects of diet with different n-3/n-6 PUFA ratios on the autism, and the underlying mechanisms explored. Our results showed that rats with prenatal administration of VPA took less response time to sniff three odorants in the olfactory habituation/dishabituation tests, had lower frequency of pinning and following patterns, and had decreased hippocampal 5-hydroxytryptamine (5-HT), increased serum 5-HT and downregulated expression of tight junction protein (occludin and claudin-1) in the colon. However, supplementation of n-3/n-6 PUFAs (1:5) in the VPA treated rats ameliorated the autistic behaviors, increased hippocampal 5-HT and tight junction expression in the colon, and decreased serum 5-HT. In conclusion, dietary supplementation of n-3/n-6 PUFAs (1:5) significantly improves VPA-induced autism-like behaviors in rats, which may be, at least partially, related to the increased hippocampal 5-HT. Furthermore, this diet can increase the expression of tight junction proteins to improve intestinal barrier impairment.

A Case With IgG4-Related Spinal Pachymeningitis Causing Spinal Cord Compression.

Immunoglobulin G4 (IgG4)-related disease is a systemic disease characterized by sclerosing lesions and an increased serum IgG4 level. This condition can involve any organ, but IgG4-related spinal pachymeningitis is relatively rare. In the current study, we report a case of spinal cord compression caused by IgG4-related spinal pachymeningitis. A 39-year-old man presented to us with a 15-day history of back pain and a 3-day history of dysuresia, exacerbated by weakness in the lower extremities for 2 days. Cervical magnetic resonance imaging (MRI) showed strip-shaped abnormal signals along the anterior and posterior borders of the spinal cord at the C5-T4 levels. The IgG level in cerebrospinal fluid was 718.0 mg/L. Thoracic MRI revealed strip-shaped abnormal signals with remarkable enhancement along the anterior and posterior borders of the dural sac at the T1-T6 levels. Histopathological examination confirmed IgG4-related spinal pachymeningitis. The symptoms worsened rapidly, and surgical resection of the space-occupying lesion in the vertebral canal was performed for spinal decompression. Corticosteroid therapy was administered, and the patient's motor functions were mildly improved. IgG4-related disease can manifest as spinal pachymeningitis and cause spinal cord compression. Clinicians should be aware of this rare condition, and early diagnosis, timely surgical decompression, and appropriate corticosteroid therapy should be highlighted.

ClC-3 induction protects against cerebral ischemia/reperfusion injury through promoting Beclin1/Vps34-mediated autophagy.

Acute ischemic stroke is a devastating disease with very limited therapeutics. Growing appreciation of dysregulated autophagy contributes to the progression of brain ischemic injury, making it to be an appealing intervention target. In terms of its well-characterized consequences, the signal molecules required for autophagy activation are rather poorly defined. Here, we found the induction of chloride channel-3 (ClC-3) directly activated autophagy, which played an important role in limiting cerebral ischemia/reperfusion (I/R) injury. Further mechanism exploration discovered that the up-regulation of ClC-3 was critical for the interaction of Beclin1 and Vps34. After ClC-3 knockdown using adeno-associated virus vectors in vivo, the autophagy activation was partially inhibited through disrupting the formation of Beclin1 and Vps34 complex. Consistent with these observations, ClC-3 knockdown could also significantly aggravated cerebral I/R injury through suppressing autophagy in vivo, which further confirmed the neuroprotective roles of ClC-3. Collectively, we provided an novel evidence for ClC-3 serving as a crucial regulator of autophagy; and our results indicated that the induction of ClC-3 may serve as a self-protective mechanism against cerebral I/R injury.

MicroRNA-200a Inhibits Inflammation and Atherosclerotic Lesion Formation by Disrupting EZH2-Mediated Methylation of STAT3.

Endothelial inflammation and dysfunction are critical to the process of atherosclerosis. Emerging evidence demonstrates that upregulation of miR-200a reduces VCAM-1 expression and prevents monocytic cell adhesion onto the aortic endothelium. However, limited information is available about the role of microRNA-200a (miR-200a) in facilitating atherosclerotic lesion formation. We investigated the anti-inflammatory and anti-atherosclerotic actions of miR-200a. Human umbilical vein endothelial cells (HUVECs) were cultured in the presence of oxidized low-density lipoprotein (ox-LDL), and their viability and apoptosis were evaluated using CCK-8 assays and flow cytometric analysis. The enhancer of zeste homolog 2 (EZH2) promoter activity was evaluated in the presence of miR-200a by dual luciferase reporter gene assay. EZH2-mediated methylation of signal transducer and activator of transcription 3 (STAT3) was validated by ChIP and IP assays. ApoE-/- mice were given a 12-week high-fat diet and developed as in vivo atherosclerotic models. miR-200a was downregulated but EZH2 and HMGB1 were upregulated in ox-LDL-treated HUVECs and the aorta tissues of atherosclerotic mouse models. Elevated miR-200a was shown to protect HUVECs against ox-LDL-induced apoptosis and inflammation. EZH2 was verified as a target of miR-200a. The protective effects of miR-200a were abrogated upon an elevation of EZH2. EZH2 methylated STAT3 and enhanced STAT3 activity by increased tyrosine phosphorylation of STAT3, thereby increasing apoptosis and release of pro-inflammatory cytokines in ox-LDL-treated HUVECs. An anti-atherosclerotic role of miR-200a was also demonstrated in atherosclerotic mouse models. Our study demonstrates that miR-200a has anti-inflammatory and anti-atherosclerotic activities dependent on the EZH2/STAT3 signaling cascade.

Effects of Dietary Fat Profile on Gut Microbiota in Valproate Animal Model of Autism.

Autism spectrum disorder (ASD) is a developmental disability which may cause significant social, communication, and behavioral challenges. Besides certain essential symptoms, a lot of ASD individuals also suffer the comorbidity of gut microbiota dysbiosis, which possibly causes a variety of gastrointestinal (GI) difficulties. Interestingly, evidence has indicated that behavioral output may be modulated through the communication between the central nervous system and gut microbiota via the gut-brain axis. Polyunsaturated fatty acids (PUFAs) and n-3 fatty acids (n-3 PUFA) are structurally and functionally crucial components for the brain, and the state of n-3 PUFAs also affects the gut microbiota. However, how varying intake ratios of n-3/n6 PUFAs affect the gut microbiota composition in ASDs is not well-understood. Pregnant female Wistar rats with intraperitoneal administration of valproate acid (VPA) at embryonic day (E) 12.5 and their male offspring were grouped and fed three diets: a control chow (VPA group), omega-3 deficient (A group), and n-3/n6 (1:5) diet (B group). The diet of pregnant female Wistar rats with intraperitoneal administration of saline and their male offspring was a control chow (normal group). Microbial composition and species abundance were investigated accordingly by the 16S rRNA gene-based metagenomics analysis on the fecal samples. Results showed that fecal microbial abundance was decreased because of VPA administration in the period of pregnancy, and the changing pattern of gut microbiota was similar to that reported in ASD patients. Furthermore, the n-3/n6 (1:5) diet increased the fecal microbial abundance and decreased the elevated Firmicutes. In conclusion, n-3/n6 PUFAs (1:5) diet supplementation may alter gut microbiota composition in VPA-exposed rats. This study put forward a new strategy for the intervention and treatment of autism by n-3/n-6 PUFAs ratio supplementation intakes.

A tetraphenylethene-based Pd2L4 metallacage with aggregation-induced emission and stimuli-responsive behavior.

A tetraphenylethene-based Pd2L4 metallacage was self-assembled from four TPE-pyridine ligands with two Pd2+ ions. This metallacage with D4 symmetry exhibited a classical aggregation-induced emission property in different solvents and reversible stimuli-responsive behaviour with chloride ions and silver ions, successively.

LncRNA MIR4435-2HG potentiates the proliferation and invasion of glioblastoma cells via modulating miR-1224-5p/TGFBR2 axis.

Glioblastoma (GBM) belongs to the high-grade (IV) gliomas with extremely poor prognosis. Accumulating evidence uncovered the key roles of long non-coding RNAs (lncRNAs) in GBM development. This study aimed to determine the biological actions and the clinical relevance of lncRNA MIR4435-2 Host Gene (MIR4435-2HG) in GBM. Data from GEPIA database showed that MIR4435-2HG was up-regulated in GBM tissues and high expression of MIR4435-2HG correlated with shorter overall survival of GBM patients. Further experimental assays verified the up-regulation of MIR4435-2HG in GBM tissues and cell lines. In vitro cell studies and in vivo animal studies showed that knockdown of MIR4435-2HG resulted in the inhibition of GBM cell proliferation and invasion and in vivo tumour growth, while MIR4435-2HG overexpression driven GBM progression. Furthermore, MIR44435-2HG was found to sponge miR-1224-5p and suppress miR-1224-5p expression; overexpression of miR-1224-5p attenuated the enhancement in GBM cell proliferation and invasion induced by MIR4435-2HG overexpression. In a subsequent study, miR-1224-5p was found to target transforming growth factor-beta receptor type 2 (TGFBR2) and repressed TGFBR2 expression, and in vitro assays showed that miR-1224-5p exerted tumour-suppressive effects via targeting TGFBR2. More importantly, TGFRB2 knockdown antagonized hyper-proliferation and invasion of GBM cells with MIR4435-2HG overexpression. Clinically, the down-regulation of miR-1224-5p and up-regulation of TGFBR2 were verified in the GBM clinical samples. Taken together, the present study suggests the oncogenic role of MIR4435-2HG in GBM and underlies the key function of MIR4435-2HG-driven GBM progression via targeting miR-1224-5p/TGFBR2 axis.

Tetraphenylethene-Based Platinum(II) Bis-Triangular Dicycles with Tunable Emissions.

Tunable luminescent materials have attracted considerable interest for their wide applications in electronic optical devices, biological probes and sensors, tunable displays, and security technologies. Herein, we describe a strategy of coordination-driven self-assembly in order to prepare discrete tetraphenylethene-based platinum(II) bis-triangular dicycles 1 and 2 with aggregation-induced emission properties. The X-ray structure confirms that they possess two triangular cavities in which free rotation of the central TPE unit is restricted. As a kind of fluorescent material, the AIE-active dicycles have good emissions with wide tunability based on their aggregate states by changing different solvents, adjusting the temperature, or combining them with other dyes (e.g., perylene) via a co-assembly process.

Short-Term Efficacy and Tolerability of Paroxetine Versus Placebo for Panic Disorder: A Meta-Analysis of Randomized Controlled Trials.

OBJECTIVE: To explore the short-term efficacy and tolerability of paroxetine in the treatment of panic disorder in adults. METHODS: Multiple electronic databases were searched to find randomized controlled trials (RCTs) on paroxetine and panic disorder. The primary efficacy outcomes were: the mean change compared to the baseline in the total number of full panic attacks, Clinical Global Impression-Severity of Illness (CGI-S) score, and the proportion of participants with zero full panic attacks and with a 50% or greater reduction in the number of full panic attacks. The tolerability outcomes included withdrawal rate and the incidence of adverse events (AEs). RESULTS: 13RCTs were included. The pooled analyses showed patients who received paroxetine experienced greater improvements in the number of full panic attacks (total: MD=-1.96, 95%CI -3.45 to -0.47, P=0.010; ≥50% reduction: OR=1.66, 95%CI 1.08 to 2.55, P=0.02; zero full panic attacks: OR=1.70, 95%CI 1.42 to 2.03, P < 0.00001) and CGI-S (MD=-0.37, 95%CI -0.74 to -0.01, P=0.05) than placebo. There was no evident difference in the total withdrawal rate (OR=0.91, 95%CI 0.76 to 1.08, P=0.26) and withdrawal rate due to AEs (OR=1.29, 95%CI 0.97 to 1.72, P=0.07) between the two groups. Withdrawal rate due to lack of efficacy or relapse (OR=0.44, 95%CI 0.31 to 0.63, P < 0.00001) and the incidence of serious AEs (OR=0.42, 95%CI 0.23 to 0.79, P=0.007) in the paroxetine group was lower than the placebo group. Meanwhile, the incidence of any treatment-emergent adverse events (TEAEs) (OR=1.32, 95%CI 1.05 to 1.64, P=0.02) in the paroxetine group was higher in comparison with the placebo. CONCLUSIONS: Paroxetine is an effective and well-tolerated short-term treatment for adults with panic disorder.