Integrating Lipidomics and Transcriptomics Reveals the Crosstalk Between Oxidative Stress and Neuroinflammation in Central Nervous System Demyelination.

Multiple sclerosis (MS) is an incurable and progressive neurodegenerative disease that affects more than 2.5 million people worldwide and brings tremendous economic pressures to society. However, the pathophysiology of MS is still not fully elucidated, and there is no effective treatment. Demyelination is thought to be the primary pathophysiological alteration in MS, and our previous study found abnormal lipid metabolism in the demyelinated corpus callosum. Growing evidence indicates that central nervous system (CNS) demyelinating diseases never result from one independent factor, and the simultaneous participation of abnormal lipid metabolism, oxidative stress, and neuroinflammation could potentiate each other in the pathogenesis of MS. Therefore, a single omics analysis cannot provide a full description of any neurodegenerative disease. It has been demonstrated that oxidative stress and neuroinflammation are two reciprocal causative reasons for the progression of MS disease. However, the potential crosstalk between oxidative stress and neuroinflammation remains elusive so far. With an integrated analysis of targeted lipidomics and transcriptomics, our research presents the potential interaction between abnormalities of lipid metabolism, mitochondrial dysfunction, oxidative stress, and neuroinflammation in CNS demyelinating diseases. The findings of this paper may be used to identify possible targets for the therapy of CNS demyelinating diseases.

High PYGL Expression Predicts Poor Prognosis in Human Gliomas.

Background: PYGL has been reported as a glycogen degradation-related gene, which is up-regulated in many tumors. This study was designed to investigate the predictive value of high PYGL expression in patients with gliomas through bioinformatics analysis of the gene transcriptome and the single-cell sequencing data. Methods: The gene transcriptome data of 595 glioma patients from the TCGA database and the single-cell RNA sequencing data of 7,930 GBM cells from the GEO database were included in the study. Differential analysis was used to find the distribution of expression of PYGL in different groups of glioma patients. OS analysis was used to assess the influence of the high expression of PYGL on the prognosis of patients. The reliability of its prediction was evaluated by the AUC of ROC and the C-index. The GSEA be used to reveal potential mechanisms. The single-cell analysis was used to observe the high expression of PYGL in different cell groups to further analyze the mechanism of its prediction. Results: Differential analysis identified the expression level of PYGL is positively associated with glioma malignancy. OS analysis and Cox regression analyses showed high expression of PYGL was an independent factor for poor prognosis of gliomas (p < 0.05). The AUC values were 0.838 (1-year ROC), 0.864 (3-year ROC) and 0.833 (5-year ROC). The C index was 0.81. The GSEA showed that gene sets related to MTORC1 signaling, glycolysis, hypoxia, PI3K/AKT/mTOR signaling, KRAS signaling up and angiogenesis were differentially enriched in the high PYGL expression phenotype. The single-cell sequencing data analysis showed TAMs and malignant cells in GBM tissues expressed a high level of PYGL. Conclusion: The high expression of PYGL is an independent predictor of poor prognosis in patients with glioma.

Case Report: Direct Visualization of the Nervus Intermedius During the Microvascular Decompression Procedure: Should We Take It Seriously?

Background: Nervus intermedius neuralgia (NIN), known as geniculate neuralgia (GN), is an uncommon cranial nerve disease caused by an offending vessel compressing the nervus intermedius (NI). Microvascular decompression (MVD) has now become a valued treatment approach for NIN because it can resolve neurovascular conflict (NVC) at the root entry zone of the NI. In the era of continuously optimizing and improving the surgical technique of MVD, further minimization of all possible postoperative complications is not only welcome but also necessary. Objective: The aim of this work is to assess the postoperative outcome of direct visualization of the NI during the MVD procedure. Methods: This study retrospectively reviewed the clinical records of a group of seven consecutive patients with NIN who underwent MVD in the period of 2013-2020 in our clinic and 16 studies reported NIN patients who underwent MVD in the period of 2007-2020. Results: In total, 91.3% of all patients experienced immediate and complete relief of cranial neuralgia after MVD. Six of 23 patients have experienced direct visualization of the NI intraoperatively, and 66.7% of those patients had complications such as facial paralysis, dysacousia, or a combination of these conditions postoperatively. Slight surgical approach-related complications such as complaints associated with excessive drainage of cerebrospinal fluid (CSF), nausea and vertigo, and delayed wound union were observed in 80% of the remaining 15 patients, and these symptoms are totally relieved in the telephone and outpatient follow-up after 6 months. Conclusion: Our case series shows that MVD produced immediate pain relief in the majority of NIN patients. MVD carries surgical risk, especially in patients who experience direct visualization of the NI after mechanical stretch and blunt dissection in surgical procedures. Attempts to avoid mechanical stretch and blunt dissection of the compressed nerve were important for intraoperative neuroprotection, especially facial nerve protection.

Integration of single-cell and bulk RNA sequencing data reveals key cell types and regulators in traumatic brain injury.

Traumatic brain injury (TBI) is a leading cause of disability and mortality worldwide, whose symptoms ranging from mild to severe, even life-threatening. However, specific cell types and key regulators involved in traumatic brain injury have not been well elucidated. In this study, utilizing single-cell RNA-seq (scRNA-seq) data from mice with TBI, we have successfully identified and characterized 13 cell populations including astrocytes, oligodendrocyte, newly formed oligodendrocytes, microglia, two types of endothelial cells, five types of excitatory and two types of inhibitory neurons. Differential expression analysis and gene set enrichment analysis (GSEA) revealed the upregulation of microglia and endothelial markers, along with the downregulation of markers of excitatory neurons in TBI. The cell-cell communication analysis revealed that microglia and endothelial cell might interact through the interaction of Icam1-Il2rg and C1qa-Cd93, and microglia might also communicate with each other via Icam1-Itagm. The autocrine ligand-receptor in microglia might result in activation of TYROBP causal network via Icam1-Itgam. The cell-cell contact between microglia and endothelial cell might activate integrin signaling pathways. Moreover, we also found that genes involved in microglia activation were highly downregulated in Tyrobp/Dap12-deficient microglia, indicating that the upregulation of Tyrobp and TYROBP causal network in microglia might be a candidate therapeutic target in TBI. In contrast, the excitatory neurons were involved in maintaining normal brain function, and their inactivation might cause dysfunction of nervous system in TBI patients. In conclusion, the present study has discerned major cell types such as microglia, endothelial cells and excitatory neurons, and revealed key regulator such as TYROBP, C1QA, and CD93 in TBI, which shall improve our understanding of the pathogenesis of TBI.

[Antihypertensive effect and pharmacokinetics of low molecular mass potassium alginate].

OBJECTIVE: To investigate the effect of low molecular weight potassium alginate (L-PA) on blood pressures in spontaneously hypertensive rats (SHRs) and its pharmacokinetics characteristics in mice. METHODS: The systolic blood pressure (SBP) was measured by tail-cuff method in conscious SHRs. Forty rats were randomly assigned to the following five groups: control, hydrochlorothiazide (HCT, 6.25 mg/kg), L-PA in low, middle or high dose groups (100, 250, 500 mg/kg). SHRs were intragastrically (i. g.) administrated once daily for 28 days. The SBP was measured once weekly during drug treatment, and 3 and 6 days after drug with drawal. KM mice were i. g. administered with 100 mg/kg (74 MBq/kg) of 3H-L-PA. Ten microl blood samples were obtained from the tail vein at 2, 5, 10, 20, 30 min and 1, 2, 4, 6, 12, 24, 48, 72, 96, 120 or 144 h after drug administration for measuring radioactivities. Pharmacokinetics parameters of the oral administration of L-PA were analysed with DAS 2.0 software. RESULTS: Twenty-one or 28 days after administration, the rats in the groups treated with HCT or L-PA at 100, 250 or 500 mg/kg had a significant decrease in SBP (P<0.01 vs control group). Three or 6 days after drug withdrawal, the antihypertensive effect of HCT disappeared (P>0.05), whereas the rats treated with 250 or 500 mg/kg L-PA still had lower SBP than the controls (P<0.01). The L-PA at a dose of 100 mg/kg also led to a significant decrease in SBP 3 days after drug withdrawal (P<0.05). The pharmacokinetics of L-PA (i. g.) was consistent with a two-compartment model, with 2.76 h of absorption half-life (t1/2, Ka), 42. 30 h of distributional half-life (t1/2alpha), 42. 31 h of elimination half-life (t1/2beta), and 36.28 h of terminal phase elimination half-life (t1/2z). CONCLUSION: Oral administration of L-PA has significant anti-hypertensive effect, which can be maintained to 6 days after drug withdrawal. The sustaining anti-hypertensive effect of L-PA is probably associated with its slow elimination in vivo.

Preventive effects of low molecular mass potassium alginate extracted from brown algae on DOCA salt-induced hypertension in rats.

Available evidence indicates that brown algae may be beneficial for the treatment of high blood pressure. Our recent study demonstrated that low molecular mass potassium alginate (L-PA), one of the major polysaccharides extracted from brown algae, decreased systolic blood pressure (SBP) in spontaneous hypertensive rats. The present study investigated the effects of L-PA on deoxycorticosterone acetate (DOCA) salt-induced hypertension in rats. Hypertension was induced by biweekly subcutaneous injections of 50mg/kg DOCA plus 1% NaCl in drinking water. The control group received saline injections. L-PA (250 or 500 mg/kg), KCl (239 mg/kg), or volume-matched solvent was administered orally once daily for 30 days. DOCA salt administration significantly increased SBP, sodium excretion, serum sodium content, circulating plasma volume (CPV), plasma atrial natriuretic peptide (ANP) content, heart and renal weight indices, and mortality and decreased plasma aldosterone (ALD) and serum potassium levels in the vehicle-treated DOCA salt group compared with the control group. However, L-PA dose-dependently normalized the above changes induced by DOCA salt, with the exception of further increasing sodium excretion, while KCl did not affect the changes caused by DOCA salt, with the exception of slightly ameliorating hypokalemia and mortality. These findings suggest that L-PA may offer a novel form of potassium supplementation with greater antihypertensive and sodium excretion actions than KCl and may likely be beneficial for the primary prevention and treatment of hypertension and its cardiovascular sequelae.