The association between 5-HT1A binding and temporal lobe epilepsy: A meta-analysis of molecular imaging studies.

BACKGROUND: Studies have shown conflicting results in the correlation between serotonin-1A (5-HT1A) receptor binding levels in the brain and temporal lobe epilepsy (TLE). There is a need to systematically evaluate the correlation between the 5-HT1A binding level and TLE from the perspective of the brain using molecular imaging. METHODS: Chinese and English databases, such as the China National Knowledge Infrastructure (CNKI), the China Science and Technology Journal Database (VIP), WanFang, the Chinese Biomedical Literature Service System (SinoMed), PubMed and Web of Science, were searched. RESULTS: Two evaluators independently screened the literature, extracted data, and evaluated the risk of bias in the included studies according to the inclusion and exclusion criteria. RevMan 5.4.1 was used to analyze the data. A total of 196 participants were included; of these, 95 had TLE and 131 were healthy controls who had never had a seizure before participating in the study. Meta-analysis results suggested that 1) decreased 5-HT1A binding was found on the affected side of patients with TLE (standard mean difference (SMD) = -1.45, 95% confidence interval (CI) [-2.27, -0.64], Z = 3.48, P = 0.0005); 2) decreased 5-HT1A binding was found in the ipsilateral hippocampus of patients with TLE (SMD = -1.76, 95% CI [-2.51, -1.00], Z = 4.57, P＜0.00001); 3) decreased 5-HT1A binding was found in the ipsilateral temporal lobe cortex of patients with TLE (SMD = -0.46, 95% CI [-0.80, -0.12], Z = 2.66, P = 0.008); 4) decreased 5-HT1A binding was found in the ipsilateral amygdala in patients with TLE (SMD = -1.36, 95% CI [-2.48, -0.23], Z = 2.37, P = 0.02); and 5) decreased 5-HT1A binding was found in the frontal lobe of patients with TLE(SMD = -0.75, 95% CI [-1.29, -0.20], Z = 2.67, P = 0.008). CONCLUSION: A reduction in 5-HT1A binding in the hippocampus, temporal cortex, amygdala, and frontal lobe was observed on the affected side of patients with TLE. The decrease in 5-HT1A binding can be considered related to TLE. Potentially relevant factors should be considered in future molecular imaging studies.

Analysis of antiplatelet therapy adherence in patients with ischemic cerebral stroke.

BACKGROUND: The related factors affecting the adherence of ischemic cerebral stroke (ICS) patients to antiplatelet therapy have attracted much attention. METHODS: Patients with ICS (confirmed by CT or MRI) were enrolled from January 2020 to July 2021. The demographic data were retrospectively investigated and analyzed. The adherence calculation was as follows: Adherence = number of tablets taken/number of tablets needed to be taken. Adherence < 100% was defined as nonadherence. Severe nonadherence is defined as adherence ≤ 75%. RESULTS: A total of 229 patients with ICS were enrolled. We found no significant difference in the proportion of patients with nonadherence, while the proportion of severe nonadherence in the aspirin group was significantly higher (p < .001). Multivariable analysis indicated that medical insurance (odds ratio [OR] = 0.071, p < .001) and regular exercise (OR = 0.438, p = .015) were independent factors associated with adherence. In addition, only medical insurance (OR = 5.475, p < .001) and aspirin treatment (OR = 0.228, p < .001) were independent risk factors associated with severe nonadherence. We therefore constructed a nomogram plot and a model as follows: Adherence risk score = 3 × medical insurance + regular exercise. Patients were divided into low-risk and high-risk groups for adherence based on the median model score. A total of 13.3% of patients in the low-risk group were nonadherent patients compared with 53.4% in the high-risk group (p < .001). Similarly, 8.4% of patients in the low-risk group had severe nonadherence compared with 19.9% in the high-risk group (p = .022). Moreover, in low-risk patients, no significant difference was observed. In patients with high risk, aspirin-treated patients showed significantly decreased adherence compared with the other two groups. CONCLUSION: Medical insurance and regular exercise were independent factors for antiplatelet therapy adherence. For patients with high model scores, timely intervention is necessary.

Is depression in patients with temporal lobe epilepsy related to hippocampal sclerosis? A meta-analysis.

OBJECTIVE: To systematically evaluate the association between hippocampal sclerosis (HS) and depression in patients with temporal lobe epilepsy (TLE) through a meta-analysis. METHODS: Chinese and English databases, such as the China National Knowledge Infrastructure (CNKI), Chinese Scientific Journals (VIP), WanFang, the Chinese Biomedical Literature Service System (SinoMed), PubMed and the Web of Science, were searched. RESULTS: Two evaluators independently screened the literature, extracted data and evaluated the risk of bias in the included studies in accordance with the inclusion and exclusion criteria. RevMan 5.1 was used to analyze the data. A total of 786 patients with epilepsy were included in the study, including 82 depressive patients with HS and 64 depressive patients without HS. The results showed that the TLE patients with HS were more likely to develop depression than those without HS (odds ratio (OR)= 2.14, 95% confidence interval (CI) [1.45, 3.16], Z = 3.85, p = 0.0001). CONCLUSION: HS can be considered a high-risk factor for depression in patients with TLE, and the correlation is significant. However, the sample size included in the study was small; additional high-quality studies are needed in the future.

Notoginsenoside R2 reduces Aß25-35-induced neuronal apoptosis and inflammation via miR-27a/SOX8/ß-catenin axis.

Background: Alzheimer's disease (AD) has affected numerous elderly individuals worldwide. Panax notoginseng has been shown to ameliorate AD symptoms, and notoginsenoside R2 is a key saponin identified in this plant. Purpose: In the current study, we aimed to explore whether notoginsenoside R2 could improve the prognosis of AD. Methods: Herein, primary rat cortical neurons were isolated and they were treated with amyloid beta-peptide (Aß) 25-35 oligomers. Cellular apoptosis was examined via flow cytometry and Western blotting. miR-27a and SOX8 mRNA expression levels were quantified by quantitative reverse transcription-polymerase chain reaction. Furthermore, the interaction between miR-27a and SOX8 was investigated by utilizing a dual-luciferase reporter assay. Finally, an AD mouse model was established to validate the in vitro findings. Results: Notoginsenoside R2 alleviated Aß25-35-triggered neuronal apoptosis and inflammation. During this process, miR-27a expression was decreased by notoginsenoside R2, and miR-27a negatively modulated SOX8 expression. Furthermore, activation of SOX8 upregulated ß-catenin expression, thus suppressing apoptosis and neuroinflammation. Conclusions: Our animal experiments revealed that notoginsenoside R2 enhanced the cognitive function of AD mice and inhibited neuronal apoptosis. Notoginsenoside R2 ameliorated AD symptoms by reducing neuronal apoptosis and inflammation, thus suggesting a novel direction for AD pharmacotherapy.

LncRNA UCA1 alleviates aberrant hippocampal neurogenesis through regulating miR-375/SFRP1-mediated WNT/ß-catenin pathway in kainic acid-induced epilepsy.

Temporal lobe epilepsy (TLE) is a chronic disease of the nervous system, associated with increased proliferation in the hippocampus. Urothcarcinoma associated 1 (UCA1) is a long long non-coding RNA that was shown to regulate proliferation and differentiation of neural progenitors in vitro. We hypothesised that TLE-associated abnormal proliferation is a consequence of the downregulation of UCA1. This hypothesis was tested in mice with kainic acid (KA)-induced seizures, and then the potential mechanism was explored in vitro and in vivo. Result showed that the expression of UCA1 and Secreted Frizzled Related Protein 1 (SFRP1) were significantly reduced in hippocampal tissues of epileptic mice, while miR-375 was increased compared with the control group. Pearson correlation analysis showed that UCA1 was positively correlated with SFRP1, while miR-375 was negatively correlated with UCA1 and SFRP1. Besides, UCA1 was overexpressed in mice and the overexpression of UCA1 significantly reversed the abnormal proliferation of hippocampal neurons in epilepsy mice. In vitro Luciferase assay showed that UCA1 and Sfrp1 are both the targets of miR-375, and UCA1 promotes the expression of Sfrp1 by competitively adsorbing miR-375, thereby inhibiting the activation of the WNT/ß-catenin pathway. The inactivation of the WNT/ß-catenin pathway prevented the abnormal proliferation of neural progenitors in the epileptic hippocampus. In conclusion, our findings provide a theoretical basis for the clinical application of UCA1.

Efficacy and safety of modified Sini San for treating poststroke depression: A meta-analysis of randomized controlled trials.

OBJECTIVE: The aim of this meta-analysis was to evaluate the efficacy and safety of modified Sini San (MSS) for poststroke depression (PSD). METHODS: Randomized controlled trials of MSS for PSD were identified in the Web of science, PsycINFO, World Cat, CNKI, VIP, Wanfang, DuXiu, and Embase databases according to the inclusion and exclusion criteria. RESULTS: In total, 7 trials with 548 patients were included in the review. The meta-analysis showed that MSS had superior effects to fluoxetine hydrochloride in terms of response rate in patients with PSD (relative risk (RR): 1.19, 95% confidence interval (CI) [1.10, 1.28], Z = 4.31, P < 0.0001). MSS may be more effective at reducing Hamilton depression rating scale (HAMD) scores and modified Edinburgh-Scandinavia stroke scale (SSS) scores than fluoxetine hydrochloride after 4 and 8 weeks of treatment. CONCLUSIONS: Our meta-analysis demonstrated that MSS appears to have excellent therapeutic effects on PSD and no serious adverse effects. However, due to the small sample sizes and low quality of the literature, studies with higher methodological quality, larger sample sizes, and placebo controls are recommended in future research on MSS in patients with PSD to enhance the strength of the evidence. Therefore, clinicians should be cautious in using this evidence to make clinical decisions.

Altered amygdala resting-state functional connectivity following acupuncture stimulation at BaiHui (GV20) in first-episode drug-Naïve major depressive disorder.

Amygdala is an important locus of dysfunction implicated in major depressive disorder(MDD). Aberrant amygdala networks(AN) had been reported in resting-state functional magnetic resonance imaging (rs-fMRI) study. The safety and efficacy of acupuncture treatment for MDD have been verified in previous clinical studies. This study is aimed to investigate whether acupuncture at GV20 could modulate the abnormal AN of patients with the first-episode, drug-naïve MDD by using rs-fMRI combined with functional connectivity (FC) method. Thirty MDD patient underwent 6-min rs-fMRI scans respectively before and after 20-min electro-acupuncture stimulate(EAS) at GV20. Twenty-nine healthy subjects underwent only a 6-min rs-fMRI scan. Based on the amygdala as the seed region, FC method was adopted to examine abnormal AN in patients by comparing with healthy subjects and to evaluate the influence of EAS on intrinsic connectivity within the AN in patients with MDD. Compared to healthy subjects, MDD patients had aberrant intrinsic AN which mainly showed increased FC between amygdala and hippocampus, precuneus, precentral gyrus and angular gyrus, as well as decreased FC between amygdala and orbital frontal cortex(OFC). Moreover, our results indicated that EAS at GV20 induced increased/decreased FC between amygdala and certain regions in MDD patients. In addition, the intrinsic amygdala FC within other certain brain regions in MDD patients were regulated by EAS at GV20. The abnormal AN of MDD patients could be modulated by EAS at GV20. Our findings may further provide the potential imaging evidence to support the modulatory mechanisms of acupuncture on MDD.

Comorbidity of Pain and Depression in a Lumbar Disc Herniation Model: Biochemical Alterations and the Effects of Fluoxetine.

of Background Data: Depression is one of the most common comorbidities in patients with chronic low back pain. However, the mechanisms of depression in chronic low back pain patients and the effect of antidepressants on the comorbidity of pain and depression need to be further explored. The establishment of the appropriate animal models and of more effective therapies is critical for this comorbidity. Lumbar disc herniation (LDH) is the most common disease that causes low back pain. The current study examined whether an LDH model shows behavioral and biochemical alterations that are in accordance with the characteristics of the comorbidity of pain and depression and tested the effect of fluoxetine (FLX) on these measures. Objective: The current study examined whether an LDH model showed the behavioral and biochemical alterations that were in accordance with the characteristics of the comorbidity of pain and depression and tested the effect of FLX on these measures. Methods: The LDH animal model was generated by the implantation of the autologous nucleus pulposus on the left L5 nerve root just proximal to the dorsal root ganglion in Wistar rats. Pain intensity was evaluated by mechanical allodynia and thermal hyperalgesia, and changes in depressive behavior were examined by the taste preference and forced swim tests. Hippocampal serotonin (5-HT) levels were measured by liquid chromatography-mass spectrometry, and tumor necrosis factor-α (TNF-α) mRNA was quantified using real-time reverse transcriptase PCR. Results: LDH resulted in chronic pain, which further induced depressive behavior that persisted for 6 weeks after surgery. There were decreased 5-HT concentrations and upregulated TNF-α mRNA levels that were accompanied by behavioral changes. FLX treatment improved depressive behavior and moderately alleviated pain through increased 5-HT concentrations, and inhibited TNF-α mRNA expression. Conclusions: In summary, our studies provide initial evidence that the LDH chronic pain model might serve as a model of the comorbidity of low back pain and depression. The finding that FLX improved depressive behavior and pain through normalized 5-HT concentrations and TNF-α mRNA expression establishes the initial mechanism of the comorbidity of pain and depression.

Curcumin Reduces Neuronal Loss and Inhibits the NLRP3 Inflammasome Activation in an Epileptic Rat Model.

BACKGROUND: Epilepsy is a chronic neurological disorder affecting an estimated 50 million people worldwide. Emerging evidences have accumulated over the past decades supporting the role of inflammation in the pathogenesis of epilepsy. Curcumin is a nature-derived active molecule demonstrating anti-inflammation efficacy. However, its effects on epilepsy and corresponding mechanisms remain elusive. OBJECTIVE: To investigate the effects of curcumin on epilepsy and its underlying mechanism. METHOD: Forty Sprague Dawley rats were divided into four groups: (1) control group; (2) Kainic Acid (KA)-induced epilepsy group; (3) curcumin group; and (4) curcumin pretreatment before KA stimulation group. Morris water maze was utilized to assess the effect of curcumin on KA-induced epilepsy. The hippocampi were obtained from rats and subjected to western blot. Immunohistochemistry was conducted to investigate the underlying mechanisms. RESULTS: Rats received curcumin demonstrated improvement of recognition deficiency and epilepsy syndromes induced by KA. Western blot showed that KA stimulation increased the expression of IL-1ß and NLRP3, which were reduced by curcumin treatment. Further investigations revealed that curcumin inhibited the activation of NLPR3/inflammasome in epilepsy and reduced neuronal loss in hippocampus. CONCLUSION: Curcumin inhibits KA-induced epileptic syndromes via suppression of NLRP3 inflammasome activation; therefore, offers a potential therapy for epilepsy.

A meta-analysis of three identified single nucleotide polymorphisms at 1p13.3 and 1q41 and their associations with lipid levels and coronary artery disease.

The aim of this meta-analysis was to detect whether three identified single nucleotide polymorphisms (SNPs) (rs646776, rs599839, and rs17465637) at 1p13.3 and 1q41 are associated with lipid levels and the risk of coronary artery disease (CAD). Databases of MEDLINE, EMBASE, the Cochrane Library, and BIOSIS were systematically searched. The pooled effects were expressed as odds ratio or standardized mean difference or mean difference with 95% confidence intervals. A total of 14 studies with 57,916 patients were included in the meta-analysis. Pooled effects showed that the AA group of 1p13.3 rs599839 had higher total cholesterol (TC) and low-density lipoprotein cholesterol (LDLC), and lower high-density lipoprotein cholesterol (HDLC) levels than the GA/GG group, and the CAD group had higher AA genotype frequency than the control group. The TT group of 1p13.3 rs646776 had higher TC and LDLC levels and lower HDLC levels than the CT/CC group. The CAD group also had higher CC genotype frequency of 1q41 rs17465637 than the control group. The SNPs of 1p13 rs599839 and rs646776 were associated with serum lipid levels. The genetic variants of 1p13 rs599839 and 1q41 rs17465637 SNPs were prominently related to CAD, and the genetic variants of chromosome 1p13 promote the risk of CAD by increased TC and LDLC levels and decreased HDLC levels.

Modulation of the Default Mode Network in First-Episode, Drug-Naïve Major Depressive Disorder via Acupuncture at Baihui (GV20) Acupoint.

BACKGROUND: Previous neuroimaging studies have revealed that acupuncture modulates the default mode network (DMN) in healthy subjects and patients with certain disorder. However, few studies have been performed to investigate whether or not acupuncture might modulate the DMN in patients with major depressive disorder (MDD). Thereby, the aim of the present study was to assess alterations of the DMN induced by acupuncture stimulation in patients with first-episode, drug-naïve MDD. MATERIALS AND METHODS: Twenty nine patients with first-episode, drug-naïve MDD and 29 healthy subjects were enrolled in this study. All the healthy subjects underwent 6-min resting-state functional magnetic resonance imaging (R-fMRI) scan. While patients underwent acupuncture stimulation for 20-min electro-acupuncture stimulation (EAS) at Baihui acupoint (GV20) and two 6-min R-fMRI scans before and after EAS. Based on the precuneus/posterior cingulate cortex (PC/PCC) as the seed region, functional connectivity (FC) method was adopted to examine abnormal DMN in patients by comparing with healthy subjects and to evaluate the influence of EAS on intrinsic connectivity within the DMN in patients with MDD. RESULTS: Compared to healthy subjects, MDD patients had abnormal DMN. Moreover, results showed that EAS at GV20 induced increased FC between the PC/PCC and bilateral anterior cingulate cortex (ACC), and decreased FC between the PC/PCC and left middle prefrontal cortex, left angualr gyrus and bilateral hippocampus/parahippocampus (HIPP/paraHIPP) in patients with MDD, which were the main brain regions showing significant differences between the patients and healthy subjects. CONCLUSION: Our findings provide imaging evidence to support that GV20-related acupuncture stimulation may modulate the DMN in patients with first-episode, drug-naïve MDD. This study may partly interpret the neural mechanisms of acupuncture at GV20 which is used to treat patients with MDD in clinical.

Activation of brain indoleamine 2,3-dioxygenase contributes to epilepsy-associated depressive-like behavior in rats with chronic temporal lobe epilepsy.

BACKGROUND: Depression has most often been diagnosed in patients with temporal lobe epilepsy (TLE), but the mechanism underlying this association remains unclear. In this study, we report that indoleamine 2,3-dioxygenase 1 (IDO1), a rate-limiting enzyme in tryptophan metabolism, plays a key role in epilepsy-associated depressive-like behavior. METHODS: Rats which develop chronic epilepsy following pilocarpine status epilepticus exhibited a set of interictal disorders consistent with depressive-like behavior. Changes of depressive behavior were examined by taste preference test and forced swim test; brain IL-1ß, IL-6 and IDO1 expression were quantified using real-time reverse transcriptase PCR; brain kynurenine/tryptophan and serotonin/tryptophan ratios were analyzed by liquid chromatography-mass spectrometry. Oral gavage of minocycline or subcutaneous injection of 1-methyltryptophan (1-MT) were used to inhibite IDO1 expression. RESULTS: We observed the induction of IL-1ß and IL-6 expression in rats with chronic TLE, which further induced the upregulation of IDO1 expression in the hippocampus. The upregulation of IDO1 subsequently increased the kynurenine/tryptophan ratio and decreased the serotonin/tryptophan ratio in the hippocampus, which contributed to epilepsy-associated depressive-like behavior. The blockade of IDO1 activation prevented the development of depressive-like behavior but failed to influence spontaneous seizures. This effect was achieved either indirectly, through the anti-inflammatory tetracycline derivative minocycline, or directly, through the IDO antagonist 1-MT, which normalizes kynurenine/tryptophan and serotonin/tryptophan ratios. CONCLUSION: Brain IDO1 activity plays a key role in epileptic rats with epilepsy-associated depressive-like behavior.

Association between the CETP polymorphisms and the risk of Alzheimer's disease, carotid atherosclerosis, longevity, and the efficacy of statin therapy.

The purpose of this meta-analysis was to detect the association between the cholesteryl ester transfer protein gene polymorphisms and the risk of Alzheimer's disease (AD), carotid atherosclerosis, longevity, and the efficacy of statin therapy. Databases of MEDLINE, EMBASE, BIOSIS, the Cochrane Library, and the Chinese National Knowledge Infrastructure were systematically searched. Thirty-two studies were included in this meta-analysis. There was no difference in the I405V, C629A, and Taq1B polymorphisms between AD and control groups. However, stratified analysis showed that AD group had higher B2B2 genotype frequency than control group in Asian populations with APOE4+ in Taq1B. I405V and Taq1B polymorphisms were not associated with the risk of carotid atherosclerosis and longevity. The efficacy of statin therapy was not associated with Taq1B polymorphism. In conclusion, there was no association between cholesteryl ester transfer protein gene polymorphisms and the risk of AD, carotid atherosclerosis, longevity, and the efficacy of statin therapy in the pooled effects of overall population. However, the B2B2 genotype of Taq1B was associated with increased risk of AD in the Asian populations with APOE4+.