Role of inflammatory cytokine in mediating the effect of plasma lipidome on epilepsy: a mediation Mendelian randomization study.

Background: Epilepsy is one of the most prevalent serious brain disorders globally, impacting over 70 million individuals. Observational studies have increasingly recognized the impact of plasma lipidome on epilepsy. However, establishing a direct causal link between plasma lipidome and epilepsy remains elusive due to inherent confounders and the complexities of reverse causality. This study aims to investigate the causal relationship between specific plasma lipidome and epilepsy, along with their intermediary mediators. Methods: We conducted a two-sample Mendelian randomization (MR) and mediation MR analysis to evaluate the causal effects of 179 plasma lipidomes and epilepsy, with a focus on the inflammatory cytokine as a potential mediator based on the genome-wide association study. The primary methodological approach utilized inverse variance weighting, complemented by a range of other estimators. 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 was performed to assess the robustness, heterogeneity and horizontal pleiotropy of results. Results: Our findings revealed a positive correlation between Phosphatidylcholine (18:1_18:1) levels with epilepsy risk (OR = 1.105, 95% CI: 1.036-1.178, p = 0.002). Notably, our mediation MR results propose Tumor necrosis factor ligand superfamily member 12 levels (TNFSF12) as a mediator of the relationship between Phosphatidylcholine (18,1_18:1) levels and epilepsy risk, explaining a mediation proportion of 4.58% [mediation effect: (b = 0.00455, 95% CI: -0.00120-0.01030), Z = 1.552]. Conclusion: Our research confirms a genetic causal relationship between Phosphatidylcholine (18:1_18:1) levels and epilepsy, emphasizing the potential mediating role of TNFSF12 and provide valuable insights for future clinical investigations into epilepsy.

[Development and optimization of a cell screening system for farnesoid X receptor agonist].

This study aims to develop an improved cell screening system for farnesoid X receptor (FXR) agonists based on a dual luciferase reporter gene system. FXR response element (FXRE) fragments from FXR target genes were cloned and inserted into upstream of firefly luciferase (Luc) gene in the plasmid pGL4-luc2P-Hygro. In combination with the internal reference plasmid containing renilla luciferase, a dual luciferase reporter gene system was developed and used for high throughput screening of FXR agonists. After studying the effects of over-expression of RXR, mouse or human FXR, various FXRE fragments, and different ratio of FXR plasmid amount to reporter gene plasmid, induction efficiency of the screening system was optimized by the known FXR agonist GW4064, and Z factor for the system reached 0.83 under optimized conditions. In summary, an improved cell screening system based on double luciferase reporter gene detection system was developed to facilitate the discovery of FXR agonists, where a new enhanced FXRE element was formed by a superposition of multiple FXRE fragments from FXR target genes, instead of a superposition of traditional IR-1 (inverted repeats-1) fragments.

Cognitive Function and White Matter Lesions in Medication-Overuse Headache.

PURPOSE: This study was designed to investigate the cognitive function and the white matter lesions (WMLs) and the relationship between them in medication-overuse headache (MOH) patients. METHODS: Subjects were enrolled and performed Montreal Cognitive Assessment (MoCA, Chinese-Beijing Version), Hamilton Anxiety Rating Scale (HAMA), Hamilton Depression Rating Scale (HAMD-24), and Pittsburgh Sleep Quality Index (PSQI) to evaluate the general cognitive function, anxiety, depression and sleep quality, and they were divided into three groups according to the MoCA scores: healthy controls, MOH with normal cognition group and MOH with cognitive impairment group. All the participants underwent MRI scans and images were obtained for WML evaluation with Fazekas scale. RESULTS: One hundred thirty-four participants were enrolled into this study, 46 of them for healthy controls, and 88 for MOH patients, 40 of the MOH patients for MOH with cognitive impairment group, and 48 for MOH with normal cognition group. MOH patients had significantly lower MoCA scores, including the scores of visuospatial and executive function, attention, and orientation, while they had significantly greater HAMA scores, HAMD-24 scores, PSQI scores, and deep white matter hyperintensity scores compared to healthy controls. And in MOH patients, the age, disease duration, monthly headache days, and periventricular white matter hyperintensity scores in patients with cognitive impairment were greater than those in patients with normal cognition. Moreover, the MoCA scores were negatively related to age, disease duration, monthly headache days, and Fazekas scale scores, and disease duration and monthly headache days were significant predictors of cognitive impairment in MOH patients. CONCLUSION: MOH patients showed cognitive impairment and increased WML burden. And in MOH patients, cognitive function was negatively related to WML burden, and disease duration and monthly headache days were potential predictors of cognitive impairment. Prompt and effective treatment to stop the progression of the disease may alleviate cognitive impairment in MOH patients.

1H NMR spectroscopy-based metabolic profiling of Ophiocordyceps sinensis and Cordyceps militaris in water-boiled and 50% ethanol-soaked extracts.

Ophiocordyceps sinensis, a well-known Chinese complementary herb, is a rare and valuable therapeutic resource. Cordyceps militaris (C. militaris) is a commonly used substitute for O. sinensis. A metabolomic-based approach for exploring the similarities and differences in the metabolites of O. sinensis and C. militaris in water-boiled and 50% ethanol-soaked extracts is of great significance. To distinguish between the global metabolite profiles of O. sinensis and C. militaris extracts obtained from either the water-boiled or 50% ethanol-soaked methods, we investigated the herb samples using 1HNMR-based metabolic fingerprints combined with multivariate statistical analysis. This study revealed that a total of 52 primary metabolites were identified and quantified from O. sinensis and C. militaris samples. Forty-three (83% of 52) metabolites were detectable in both O. sinensis and C. militaris. According to the variable importance in projection (VIP) value and p-value from the Mann-Whitney test, 7 metabolites (alanine, aspartate, glutamate, mannitol, ornithine, serine, and trehalose) differed between O. sinensis and C. militaris. Arginine, glucose, putrescine, pyroglutamate, betaine, O-phosphocholine, and xylose differed significantly between the water-boiled and 50% ethanol-soaked methods used to prepare the herb extracts. This study demonstrated that water-boiled extraction was a much faster method (30 min. vs 360 days) that resulted in a 30% higher number of extracted metabolites (compared to 50% for the ethanol-soaked method) for both O. sinensis and C. militaris.

Wilson's disease patient with iron metabolism discharge barriers: A case report.

Wilson's disease (WD) is an autosomal genetic disease. In the present study, the patient was a 35-year-old woman who exhibited drinking bucking (bulbar paralysis) and dysphagia for a period of nine years. Genetic analysis of the patient identified the Thr935Met and Pro992Leu mutations, which lead to copper metabolism discharge barriers. Moreover, magnetic resonance imaging revealed a susceptibility-weighted imaging (SWI) hyperintense area in the bilateral substantia nigra and lenticular nuclei. These SWI observations indicated that 'mineral deposits' were present. The present case demonstrates that the SWI hyperintense area in the bilateral lenticular nuclei, substantia nigra and red nucleus combined with the patient's symptoms indicated that there is a possibility to diagnose WD when it is not detected by genetic analysis. In addition, it demonstrates that systemic mineral removal treatment (including manganese, iron and copper) may be successful for the initial treatment of WD.

Anti-hyperglycemic and hypolipidemic effects of Cistanche tubulosa in type 2 diabetic db/db mice.

ETHNOPHARMACOLOGICAL RELEVANCE: The dried succulent stem of Cistanche tubulosa (Schenk) R. Wight is one component of traditional Chinese medicine prescriptions for diabetes. However, there have been no modern scientific reports to confirm this traditional claim for the Cistanche species until now. Thus, we investigated the effects of Cistanche tubulosa on glucose homeostasis and serum lipids in male BKS.Cg-Dock7(m) +/+ Lepr(db)/J (db/db) mice, a model of type 2 diabetes. MATERIALS AND METHODS: The verbascoside and echinacoside contents of Cistanche tubulosa powder were evaluated using HPLC. The total phenolic content, polysaccharide content and antioxidant activity of Cistanche tubulosa powder were also evaluated. Then, different doses of Cistanche tubulosa (equivalent to 120.9, 72.6 or 24.2mg verbascoside/kg) were administered orally once daily for 45 days to male db/db mice. Age matched db/+ mice were used as normal controls. Body weight, fasting blood glucose, postprandial blood glucose and insulin tolerance test were measured during the experiment. At the time of sacrifice, blood was collected for measurement of insulin level, the homeostatic model assessment of insulin resistance (HOMA-IR), and total cholesterol, triglyceride, HDL-c, LDL-c and VLDL-c levels; liver and muscle were harvested for measurement of glycogen levels. RESULTS: Cistanche tubulosa significantly suppressed the elevated fasting blood glucose and postprandial blood glucose levels, improved insulin resistance and dyslipidemia, and suppressed body weight loss in db/db mice. However, Cistanche tubulosa did not significantly affect serum insulin levels or hepatic and muscle glycogen levels. CONCLUSION: This study provides scientific evidence for the traditional use of Cistanche tubulosa to treat diabetes, suggesting that Cistanche tubulosa has the potential for development into a functional food ingredient or drug to prevent hyperglycemia and treat hyperlipidemia.

Cistanche deserticola decoction alleviates the testicular toxicity induced by hydroxyurea in male mice.

This study aimed to evaluate testicular toxicity induced by hydroxyurea (HU) and the possible counteracting effect of an aqueous extract of Cistanche deserticola (CD). HU is an antineoplastic drug that has potential reproductive toxicity, and Herba Cistanche has been used as a tonic for the reproductive system for thousands of years. Sixty mice were randomly divided into five groups. Except mice in normal group, the rest received HU (400 mg kg(-1) body weight) intragastrically. Meanwhile, mice in normal and HU control groups received purified water, and the rest received intragastrically three doses of CD decoctions (1.5, 3.0 and 6.0 g crude drug kg(-1) body weight, respectively) daily for 4 weeks. Severe testes lesions were observed, testes weight (P<0.01) and serum luteinising hormone levels (P<0.01) were also decreased significantly, in the HU groups. Three doses of CD decoctions alleviated the spermatogenetic cell degeneration induced by HU and modulated the serum sex hormones levels to some extent.

A neurofibromatosis type 1 patient with thoracic encapsulated fluid and intracranial hypotension syndrome: a case report.

INTRODUCTION: Spinal meningoceles are uncommon entities, mostly associated with neurofibromatosis type 1 (NF-1). Their intrusion into the thoracic cavity, which compresses lung tissue, is quite often mistaken as a "pleural effusion." The withdrawal of a large amount of "pleural effusion" can lead to the intracranial hypotension syndrome (IHS), herniation, or even death. CASE REPORT: A 43-year-old woman, with NF-1 and a large "pleural effusion" which compressed lung tissue, was admitted to the Thoracic Department due to the patient's shortness of breath during her physical activities. The patient complained of headache shortly after withdrawal of about 250 mL of "pleural effusion." She was diagnosed with IHS according to the typical symptoms of postural headache, low cerebrospinal fluid (CSF) pressure and magnetic resonance imaging findings of diffuse pachymeningeal gadolinium enhancement. The "pleural effusion" was examined and found to be CSF. CONCLUSION: The reported case is the first 1 in the literature in which the intrusion of the NF-1 patient's spinal meningoceles into the thoracic cavity was diagnosed as a "pleural effusion" and large CSF withdrawal led to IHS. We highlight the possibility that thoracic meningoceles can coexist with a thoracic spinal deformity and the caution that needs to be taken when cases with similar symptoms are subjected to withdrawal of fluid.