Human umbilical cord blood mononuclear cells ameliorate ischemic brain injury via promoting microglia/macrophages M2 polarization in MCAO Rats.

Cerebral infarction is one of the most prevalent cerebrovascular disorders. Microglia and infiltrating macrophages play a key role in regulating the inflammatory response after ischemic stroke. Regulation of microglia/macrophages polarization contributes to the recovery of neurological function in cerebral infarction. In recent decades, human umbilical cord blood mononuclear cells (hUCBMNCs) have been considered a potential therapeutic alternative. However, the mechanism of action is yet unclear. Our study aimed to explore whether hUCBMNCs treatment for cerebral infarction is via regulation of microglia/macrophages polarization. Adult male Sprague-Dawley rats were subjected to middle cerebral artery occlusion (MCAO) and were treated by intravenous routine with or without hUCBMNCs at 24 h following MCAO. We evaluated the therapeutic effects of hUCBMNCs on cerebral infarction by measuring animal behavior and infarct volume, and further explored the possible mechanisms of hUCBMNCs for cerebral infarction by measuring inflammatory factors and microglia/macrophages markers using Elisa and immunofluorescence staining, respectively. We found that administration with hUCBMNCs improved behavioral functions and reduced infarct volume. Rats treated with hUCBMNCs showed a significant reduction in the level of IL-6, and TNF-α and increased the level of IL-4 and IL-10 compared to those treated without hUCBMNCs. Furthermore, hUCBMNCs inhibited M1 polarization and promoted M2 polarization of microglia/macrophages after MCAO. We conclude that hUCBMNCs could ameliorate cerebral brain injury by promoting microglia/macrophages M2 polarization in MCAO Rats. This experiment provides evidence that hUCBMNCs represent a promising therapeutic option for ischemic stroke.

Sensitivity of Sniffer Dogs for a Diagnosis of Parkinson's Disease: A Diagnostic Accuracy Study.

BACKGROUND: The diagnostic criteria for Parkinson's disease (PD) remain complex, which is especially problematic for nonmovement disorder experts. A test is required to establish a diagnosis of PD with improved accuracy and reproducibility. OBJECTIVE: The study aimed to investigate the sensitivity and specificity of tests using sniffer dogs to diagnose PD. METHODS: A prospective, diagnostic case-control study was conducted in four tertiary medical centers in China to evaluate the accuracy of sniffer dogs to distinguish between 109 clinically established medicated patients with PD, 654 subjects without PD, 37 drug-naïve patients with PD, and 185 non-PD controls. The primary outcomes were sensitivity and specificity of sniffer dog's identification. RESULTS: In the study with patients who were medicated, when two or all three sniffer dogs yielded positive detection results in a sample tested, the index test sensitivity, specificity, and positive and negative likelihood ratios were 91% (95% CI: 84%-96%), 95% (95% CI: 93%-97%), and 19.16 (95% CI: 13.52-27.16) and 0.10 (95% CI: 0.05-0.17), respectively. The corresponding sensitivity, specificity, and positive and negative likelihood ratios in patients who were drug-naïve were 89% (95% CI: 75%-96%), 86% (95% CI: 81%-91%), and 6.6 (95% CI: 4.51-9.66) and 0.13 (95% CI: 0.05-0.32), respectively. CONCLUSIONS: Tests using sniffer dogs may be a useful, noninvasive, fast, and cost-effective method to identify patients with PD in community screening and health prevention checkups as well as in neurological practice. © 2022 International Parkinson and Movement Disorder Society.

Mutation Analysis of the ATP7B Gene in Seven Chinese Families with Wilson's Disease.

BACKGROUND: Wilson's disease (WD) is an autosomal recessive disease, which is characterized by an excessive copper accumulation in the liver and brain, leading to subsequent hepatic and/or neurological disorders. The causative gene for WD has been identified as the ATPase Cu2+ transporting beta polypeptide gene (ATP7B), which encodes a protein called copper-transporting ATPase 2. ATP7B mutations may lead to reduced biliary excretion of excess copper and disrupted copper homeostasis, resulting in various clinical symptoms of WD. METHODS: Direct sequencing of the ATP7B gene was performed in 7 Han Chinese families with WD, and haplotype analysis was conducted in families having the same mutation. RESULTS: Nine ATP7B gene mutations were identified, including 7 missense mutations (p.Asp765Gly, p.Arg778Leu, p.Thr888Pro, p.Pro992Leu, p.Asp1047Val, p.Ile1148Thr and p.Ala1295Val), 1 duplication mutation (c.525dupA), and 1 nonsense mutation (p.Gly837*). Combined with our previous data, haplotype analysis revealed that the founder effect accounted for 48% of alleles in Han Chinese, constituted by high allele frequency mutations p.Arg778Leu, p.Pro992Leu and p.Ala1295Val. CONCLUSION: This study revealed genetic defects of 7 Han Chinese families with WD, and has implications for their genetic counseling and clinical management.

Identification of a GNE homozygous mutation in a Han-Chinese family with GNE myopathy.

GNE myopathy is a rare, recessively inherited, early adult-onset myopathy, characterized by distal and proximal muscle degeneration which often spares the quadriceps. It is caused by mutations in the UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase gene (GNE). This study aimed to identify the disease-causing mutation in a three-generation Han-Chinese family with members who have been diagnosed with myopathy. A homozygous missense mutation, c.1627G>A (p.V543M) in the GNE gene co-segregates with the myopathy present in this family. A GNE myopathy diagnosis is evidenced by characteristic clinical manifestations, rimmed vacuoles in muscle biopsies and the presence of biallelic GNE mutations. This finding broadens the GNE gene mutation spectrum and extends the GNE myopathy phenotype spectrum.

Copper excess in liver HepG2 cells interferes with apoptosis and lipid metabolic signaling at the protein level.

BACKGROUND/AIMS: Copper is an essential trace element that serves as an important catalytic cofactor for cuproenzymes, carrying out major biological functions in growth and development. Although Wilson's disease (WD) is unquestionably caused by mutations in the ATP7B gene and subsequent copper overload, the precise role of copper in inducing pathological changes remains poorly understood. MATERIALS AND METHODS: Our study aimed to explore, in HepG2 cells exposed to copper, the cell viability and apoptotic cells was tested by MTT and Hoechst 33342 stainning respectively, and the signaling pathways involved in oxidative stress response, apoptosis and lipid metabolism were determined by real time RT-PCR and Western blot analysis. RESULTS: The results demonstrate dose- and time-dependent cell viability and apoptosis in HepG2 cells following treatment with 10 µM, 200 µM and 500 µM of copper sulfate for 8 and 24 h. Copper overload significantly induced the expression of HSPA1A (heat shock 70 kDa protein 1A), an oxidative stress-responsive signal gene, and BAG3 (BCL2 associated athanogene3), an anti-apoptotic gene, while expression of HMGCR (3-hydroxy-3-methylglutaryl-CoA reductase), a lipid biosynthesis and lipid metabolism gene, was inhibited. CONCLUSION: These findings provide new insights into possible mechanisms accounting for the development of liver apoptosis and steatosis in the early stages of Wilson's disease.

[Effect of PD-WEBB training on balance impairment and falls in people with Parkinson's disease].

OBJECTIVE: To determine the effect of Parkinson's disease-weight bearing exercise for better balance (PD-WEBB) exercise on balance impairment and falls in people with Parkinson's disease (PD). METHODS: A single-blind, randomized controlled clinical trial was conducted. The falls efficacy scale score, unified Parkinson disease rating scale (UPDRS) score and Mini-BESTest score were measured and compared between a PD-WEBB group and a control group. RESULTS: The falls efficacy scale score, UPDRS-2 score, UPDRS-3 score and Mini-BESTest score were improved in the PD-WEBB group compared with the control group (P<0.05), with no significant change in UPDRS-1 score between the two groups. CONCLUSION: PD-WEBB training can significantly improve the balance impairment and quality of life to prevent falls. PD-WEBB training is suitable for PD patients in China, and is a reasonable, effective and sustainable training of family and community assessment model.

Novel ATPase Cu(2+) transporting beta polypeptide mutations in Chinese families with Wilson's disease.

Wilson's disease (WD) is an autosomal recessive inherited disorder caused by mutations in the ATPase Cu(2+) transporting beta polypeptide gene (ATP7B). The detailed metabolism of copper-induced pathology in WD is still unknown. Gene mutations as well as the possible pathways involved in the ATP7B deficiency were documented. The ATP7B gene was analyzed for mutations in 18 Chinese Han families with WD by direct sequencing. Cell viability and apoptosis analysis of ATP7B small interfering RNA (siRNA)-treated human liver carcinoma (HepG2) cells were measured by 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT) assay and Hoechst 33342 staining. Finally, the expression of B-cell CLL/lymphoma 2 (BCL2), BCL2-associated X protein (BAX), sterol regulatory element binding protein 1 (SREBP1), and minichromosome maintenance protein 7 (MCM7) of ATP7B siRNA-treated cells were tested by real-time polymerase chain reaction (real-time PCR) and Western blot analysis. Twenty different mutations including four novel mutations (p.Val145Phe, p.Glu388X, p.Thr498Ser and p.Gly837X) in the ATP7B gene were identified in our families. Haplotype analysis revealed that founder effects for four mutations (p.Arg778Leu, p.Pro992Leu, p.Ile1148Thr and p.Ala1295Val) existed in these families. Transfection of HepG2 cells with ATP7B siRNA resulted in decreased mRNA expression by 86.3%, 93.1% and 90.8%, and decreased protein levels by 58.5%, 85.5% and 82.1% at 24, 48 and 72 hours, respectively (All P<0.01). In vitro study revealed that the apoptotic, cell cycle and lipid metabolism pathway may be involved in the mechanism of WD. Our results revealed that the genetic cause of 18 Chinese families with WD and ATP7B deficiency-induce apoptosis may result from imbalance in cell cycle and lipid metabolism pathway.

EIF4G1 Ala502Val and Arg1205His variants in Chinese patients with Parkinson disease.

Growing evidences show that genetic abnormalities play an important role in the etiopathogenesis of Parkinson disease (PD). At least 18 genetic loci and 13 disease-related genes for parkinsonism have been identified. Recently, the p.Ala502Val and p.Arg1205His variants in the eukaryotic translation initiation factor 4-gamma 1 gene (EIF4G1) were found to be associated with PD. To evaluate whether the EIF4G1 p.Ala502Val and p.Arg1205His variants are related to PD in Chinese Han population, we conducted genetic examination of these two variants in 425 PD patients from Mainland China and none was found in our patients. We did identify a known non-pathogenic polymorphism c.3660C>T (p.Ala1220Ala, rs143852330) in a 73-year-old male patient. Our results, consistent with other recent reports, suggest that the EIF4G1 p.Ala502Val and p.Arg1205His variants are a rare cause of PD, at least in Chinese population.

Acute myelitis in a patient with vogt-koyanagi-harada disease: case report and review of the literature.

BACKGROUND: Vogt-Koyanagi-Harada (VKH) disease is characterized by bilateral granulomatous uveitis with neurologic, auditory, and dermatologic manifestations. However, acute myelitis complicating VKH disease has rarely been reported. CASE REPORT: A 50-year-old Chinese Han woman presented with difficulty walking, numbness on the left side of the body, and difficulty with urination. The patient was diagnosed with incomplete VKH disease and received corticosteroid treatment prior to the neurological presentation. Acute myelitis was diagnosed based on both clinical and spinal-cord MRI findings. CONCLUSIONS: Clinicians should consider acute myelitis as a rare possible neurological manifestation in VKH disease patients, and early systemic administration of corticosteroids will suppress the acute inflammatory process and prevent recurrences. This report raises the possibility that VKH disease and acute myelitis share common pathogenic pathways.