Peripheral Immune Cells Contribute to the Pathogenesis of Alzheimer's Disease.

Alzheimer's disease (AD) is the most common neurodegenerative disorder with progressive memory and cognitive loss. Neuroinflammation is a central mechanism involved in the progression of AD. With the disruption of the blood-brain barrier (BBB), peripheral immune cells and inflammatory molecules enter into AD brain. However, the exact relationship between peripheral immune cells and AD remains unknown due to various challenges. This study aimed to investigate the potential causal association between peripheral immune cells and AD by using a two-sample Mendelian randomization (TSMR) analysis. We conducted a TSMR to decipher the causal relationship between AD and 731 types of peripheral immune cell parameters from the TBNK, regulatory T cell (Treg), myeloid cell, monocyte, maturation stages of T cell, dendritic cell (DC), and B cell panels.  Various analytical methods were employed, including inverse variance weighting (IVW), MR Egger, and weighted median methods. The Cochran's Q statistic, MR-Egger intercept, and MR-PRESSO tests were used to verify the heterogeneity and horizontal pleiotropy of the results. To further verify our results, we also conducted a replication analysis. The analysis identified CD33 on CD14 + monocyte (OR = 1.03; 95% CI, 1.01-1.04; p = 1.14E-04; adjust-p = 0.042) had an increased risk association for AD, which was verified by the replication study. CD33 on CD33dim HLA DR + CD11b- cell (OR = 1.02; 95% CI, 1.01-1.04; p = 2.87E-04; adjust-p = 0.035) had an increased risk association for AD, while secreting CD4 regulatory T cell %CD4 regulatory T cell (OR = 0.97; 95% CI, 0.96-0.99; p = 1.90E-04; adjust-p = 0.046) and CD25 on switched memory B cell (OR = 0.95; 95% CI, 0.92-0.98; p = 2.87E-04; adjust-p = 0.042) were discovered to be related to a lower risk of AD. However, the causal effect of these three immune cells on AD was insufficiently validated in the replication analysis. The MR analysis suggests a potential causal relationship between peripheral immune cells and the risk of AD. Further extensive research is needed on the specific role of peripheral immune cells in AD.

Successful Treatment of a Patient with brain tissue edema associated with Olanzapine overdose.

Olanzapine is one of the atypical antipsychotic agents which is being increasingly used, and it is synthetic derivative of thienobenzodiazepine with antipsychotic, and antinausea, and antiemetic activities. Olanzapine overdose is mainly associated with the development of anticholinergic toxicity and is characterized by central nervous system (CNS) suppression, tachycardia, and delirium. As little is yet known about the effects of this agent in toxic doses, it is important to report the features of overdose. Herein, we reported a 28-year-old male with a history of mental illness and substance abuse, who was admitted in a comatose state with generalized tonic-clonic seizures. Head computed tomography (CT) and cerebrospinal fluid (CSF) analysis revealed significant cerebral edema and raised intracranial pressure, indicative of olanzapine-induced neurotoxicity. Management involved immediate cessation of olanzapine, administration of intravenous mannitol for cerebral edema, and supportive care. The patient's condition gradually improved with these interventions. Elevated olanzapine plasma concentration confirmed the diagnosis of overdose. Cranial pressure-lowering treatment has a certain effect on improving the condition of patients.

A case report of the treatment of carotid artery stenosis by staged angioplasty based on intraoperative TCD monitoring.

Objective: Cerebral hyperperfusion syndrome (CHS) is the most severe complication of carotid artery stenting (CAS) or endarterectomy (CEA). Staging treatment can effectively reduce the risk of CHS without increasing the risk of ischemic stroke. The first stage of balloon dilatation is critical for staged treatment. However, the successful criterion of the first stage balloon dilatation is still inconsistent. Method: In the current study presents a case of a 61-year-old male with bilateral internal carotid subtotal occlusion, transcranial doppler (TCD) was used to measure middle cerebral artery (MCA) flow rate on the narrow side of surgery and the results are promising. Result: Intraoperative TCD monitoring is expected to be an evaluation criterion for staged angioplasty for carotid artery stenosis. Conclusion: The approach of blood flow velocity in the brain based on intraoperative measurement of TCD during the treatment of this patient is a new idea for staging treatment in the future.

Genetic association between gut microbiota and the risk of Guillain-Barré syndrome.

BACKGROUND: Guillain-Barré Syndrome (GBS) is an autoimmune disease that typically develops after a previous gastrointestinal (GI) infection. However, the exact association between Gut Microbiota (GM) and GBS still remains unknown due to various challenges. This study aimed to investigate the potential causal association between GM and GBS by using a two-sample Mendelian Randomization (TSMR) analysis. METHODS: Utilizing the largest available genome-wide association study (GWAS) meta-analysis from the MiBioGen consortium (n = 13,266) as a foundation, we conducted a TSMR to decipher the causal relationship between GM and GBS. Various analytical methods were employed, including the inverse variance weighted (IVW), MR-PRESSO, MR-Egger, and weighted median. The heterogeneity of instrumental variables (IVs) was assessed using Cochran's Q statistics. RESULTS: The analysis identified three microbial taxa with a significantly increased risk association for GBS, including Ruminococcus gnavus group (OR = 1.40, 95 % CI: 1.07-1.83), Ruminococcus gauvreauii group (OR = 1.51, 95 % CI: 1.02-2.25), and Ruminococcaceae UCG009 (OR = 1.42, 95 % CI: 1.02-1.97), while Eubacterium brachy group (OR = 1.44, 95 % CI: 1.10-1.87) and Romboutsia (OR = 1.67, 95 % CI: 1.12-2.47) showed a suggestively causal association. On the other hand, Ruminococcaceae UCG004 (OR = 0.61, 95 % CI: 0.41-0.91) had a protective effect on GBS, while Bacilli (OR = 0.60, 95 % CI: 0.38-0.96), Gamma proteobacteria (OR = 0.63, 95 % CI: 0.41-0.98) and Lachnospiraceae UCG001 (OR = 0.69, 95 % CI: 0.49-0.96) showed a suggestively protective association for GBS. CONCLUSION: The MR analysis suggests a potential causal relationship between specific GM taxa and the risk of GBS. However, further extensive research involving diversified populations is imperative to validate these findings.

Peripheral Blood Th1/Th17 Immune Cell Shift is Associated with Disease Activity and Severity of AQP4 Antibody Sero-Positive Neuromyelitis Optica Spectrum Disorder.

Purpose: Neuromyelitis optica spectrum disorder (NMOSD) is a rare recurrent autoimmune disease of the central nervous system. However, to date, the peripheral blood profile of the T helper cell subsets in NMOSD remains controversial and poorly understood. This study aimed to compare the levels of helper T cell subsets in the peripheral blood from patients with NMOSD in different phases of the disease and studied their correlation with the clinical severity of the disease. Patients and methods: We used flow cytometry with cellular membrane surface staining to measure the levels of helper T cell subsets in 50 patients with NMOSD during the attack (n = 25) and remission (n = 25) phases and in 21 healthy controls. Results: Patients with NMOSD had higher levels of Th1 and Th17 cells in the attack phase compared to parallel populations in the remission phase and healthy controls. Th1/Th2 and Th17/Treg ratios were positively correlated with the severity of the disease in the attack phase of NMOSD. In contrast, Treg cell levels were negatively correlated with the severity of the disease in the attack phase in patients with NMOSD. Conclusion: The peripheral blood immune profile in NMOSD towards a Th1/Th17 cell-mediated pro-inflammatory immune response, which is associated with disease activity and severity of neuromyelitis optica spectrum disorder.

Curcumin Regulates Gut Microbiota and Exerts a Neuroprotective Effect in the MPTP Model of Parkinson's Disease.

Objectives: The experiment aimed to explore the effects of curcumin on motor impairment, dopamine neurons, and gut microbiota in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mice model. Methods: Mice were randomly assigned to six groups: normal control group, solvent control group, MPTP group, curcumin-low-dose group (40 mg/kg), curcumin-medium-dose group (80 mg/kg), and curcumin-high-dose group (160 mg/kg). After 14 days, each group of mice was subjected to the pole text, the hanging test, and the open-field test. Tyrosine hydroxylase (TH) immunohistochemistry was used to observe the survival of nigrostriatal dopamine neurons. Moreover, ultrastructural changes were observed with a transmission electron microscope in mice striatal tissue cells. Then, 16S rRNA was used to assess changes in the gut microbiota. Results: (1) Each dose of curcumin reduced pole climbing time and increased suspension score and total distance moved dose-dependently. (2) All curcumin groups improved cell wrinkling and vacuolar degeneration, increased the number of TH positives, improved cell survival, and the higher the dose of curcumin, the better the effect. (3) There were differences in microbiota composition and a relative abundance among the groups. The relative abundance of Patescibacteria, Proteobacteria, and Verrucomicrobia was higher in the MPTP group. The relative abundance of Patescibacteria, Enterobacteriaceae, Enterococcaceae all decreased in all curcumin groups. In addition, the Kyoto Encyclopedia of Genes and Genomes pathways showed a reduction in the superpathway of N-acetylneuraminate degradation after medium- and high-dose curcumin administration. Conclusions: Curcumin regulates gut microbiota and exerts a neuroprotective effect in the MPTP mice model. This preliminary study demonstrates the therapeutic potential of curcumin for Parkinson's disease, providing clues for microbially targeted therapies for Parkinson's disease.