In recent years, biomarkers have been integrated into the diagnostic process and have become increasingly indispensable for obtaining knowledge of the neurodegenerative processes in Alzheimer’s disease (AD). Peripheral blood mononuclear cells (PBMCs) in human blood have been reported to participate in a variety of neurodegenerative activities. Here, a single-cell RNA sequencing analysis of PBMCs from 4 AD patients (2 in the early stage, 2 in the late stage) and 2 normal controls was performed to explore the differential cell subpopulations in PBMCs of AD patients. A significant decrease in B cells was detected in the blood of AD patients. Furthermore, we further examined PBMCs from 43 AD patients and 41 normal subjects by fluorescence activated cell sorting (FACS), and combined with correlation analysis, we found that the reduction in B cells was closely correlated with the patients’ Clinical Dementia Rating (CDR) scores. To confirm the role of B cells in AD progression, functional experiments were performed in early-stage AD mice in which fibrous plaques were beginning to appear; the results demonstrated that B cell depletion in the early stage of AD markedly accelerated and aggravated cognitive dysfunction and augmented the Aβ burden in AD mice. Importantly, the experiments revealed 18 genes that were specifically upregulated and 7 genes that were specifically downregulated in B cells as the disease progressed, and several of these genes exhibited close correlation with AD. These findings identified possible B cell-based AD severity, which are anticipated to be conducive to the clinical identification of AD progression.

Purpose: We aimed to retrospectively analyze the clinical features, laboratory and imaging results, and predictors of poor prognosis for patients with an initial diagnosis of autoimmune encephalitis (AE) at the Affiliated Hospital of Zunyi Medical University. Methods: Fifty patients with an initial diagnosis of AE who were admitted to our hospital from May 2014 to May 2018 were enrolled retrospectively. Clinical characteristics and experimental test data, including the neutrophil-to-lymphocyte ratio (NLR), were collected from medical records within 24 h of admission. Independent prognostic factors were determined by multivariate logistic regression analysis. A good or poor prognosis for patients was defined based on the modified Rankin Scale (mRS). The correlation between the immunotherapy latency and prognostic mRS score was determined using the Spearman rank correlation test. Results: Univariate analysis indicated that increased NLR (P = 0.001), decreased lymphocyte counts (P = 0.001), low serum albumin (P = 0.017), consciousness disorders (P = 0.001), epileptic seizures (P = 0.007), extrapyramidal symptoms (P = 0.042), abnormal electroencephalogram (EEG) findings (P = 0.001), abnormal brain magnetic resonance imaging (MRI) findings (P = 0.003), and pulmonary infection complications (P = 0.000) were associated with the poor prognosis of AE. Multivariate logistic regression analysis showed that NLR (odds ratio [OR] 2.169, 95% confidence interval [CI] 1.029–4.570; P < 0.05) was an independent risk factor for predicting the poor prognosis of AE. NLR > 4.45 was suggested as the cut-off threshold for predicting the adverse outcomes of AE. In addition, we revealed that there was a positive correlation between immunotherapy latency and mRS score (r_s = 0.535, P < 0.05). Conclusions: NLR may have predictive value for the poor outcomes of AE. Early initiation of immunotherapy is associated with a good prognosis.

TRAF-binding domain (Trabid), one of deubiquitination enzymes, was recently reported to activate Wnt/ β-catenin signaling pathway. However, the role of Trabid in tumors including hepatocellular carcinoma (HCC) and the underlying mechanisms controlling its activity remain poorly understood. Here, we report that Trabid is significantly downregulated in HCC tumor samples and cell lines compared with normal controls and that its expression level is negatively correlated with HCC pathological grading, recurrence, and metastasis. The reintroduction of Trabid expression in tumor cells significantly decreases HCC progression as well as pulmonary metastasis. The effect of Trabid on HCC development occurs at least partially through regulation of Twist1 activity. Mechanistically, Trabid forms a complex with Twist1 and specifically cleaves RNF8-induced K63-linked poly-ubiquitin chains from Twist1, which enhances the association of Twist1 with β-TrCP1 and allows for subsequent K48-linked ubiquitination of Twist1. Knockdown of Trabid increases K63-linked ubiquitination, but abrogates K48-linked ubiquitination and degradation of Twist1, thus enhancing HCC growth and metastasis. Interestingly, Twist1 negatively regulates the promoter activity of Trabid, indicating that a double-negative feedback loop exists. Our findings also identify an essential role for activation of Trabid by AKT-mediated phosphorylation at Ser78/Thr117 in negatively regulating Twist1 signaling, which further provides insights into the mechanisms by which Trabid regulates Twist1 ubiquitination. Our results reveal that Trabid is a previously unrecognized inhibitor of HCC progression and metastasis, which sheds light on new strategies for HCC treatment.

Recently, breakthroughs have been made in the use of mesenchymal stem cells (MSCs) to treat various diseases. Several stem cell types have been authorized as drugs by the European Medicines Agency and the U.S. Food and Drug Administration. The Chinese official document “Notification of the management of stem cell clinical research (trial)” was also published in August 2015. Currently, China has approved 106 official stem cell clinical research filing agencies and 62 clinical research projects, which are mostly focused on MSC therapy. Hence, the optimization and development of stem cell drugs is imperative. During this process, maximizing MSC expansion, minimizing cell loss during MSC transplantation, improving the homing rate, precisely regulating the differentiation of MSCs, and reducing MSC senescence and apoptosis are major issues in MSC preclinical research. Similar to artemisinin extracted from the stems and leaves of Artemisia annua, ginsenoside Rg1 (Rg1) is purified from the root or stem of ginseng. In the human body, Rg1 regulates organ function, which is inseparable from its regulation of adult stem cells. Rg1 treatment may effectively regulate the proliferation, differentiation, senescence, and apoptosis of MSCs in different microenvironments in vitro or in vivo. In this review, we discuss recent advances in understanding the effect of Rg1 on MSCs and describe the issues that must be addressed and prospects regarding Rg1 regulation of MSCs in preclinical or clinical studies.