Carboxypeptidase E conditional knockout mice exhibit learning and memory deficits and neurodegeneration.

Carboxypeptidase E (CPE) is a multifunctional protein with many nonenzymatic functions in various systems. Previous studies using CPE knock-out mice have shown that CPE has neuroprotective effects against stress and is involved in learning and memory. However, the functions of CPE in neurons are still largely unknown. Here we used a Camk2a-Cre system to conditionally knockout CPE in neurons. The wild-type, CPEflox/-, and CPEflox/flox mice were weaned, ear-tagged, and tail clipped for genotyping at 3 weeks old, and they underwent open field, object recognition, Y-maze, and fear conditioning tests at 8 weeks old. The CPEflox/flox mice had normal body weight and glucose metabolism. The behavioral tests showed that CPEflox/flox mice had impaired learning and memory compared with wild-type and CPEflox/- mice. Surprisingly, the subiculum (Sub) region of CPEflox/flox mice was completely degenerated, unlike the CPE full knockout mice, which exhibit CA3 region neurodegeneration. In addition, doublecortin immunostaining suggested that neurogenesis in the dentate gyrus of the hippocampus was significantly reduced in CPEflox/flox mice. Interestingly, TrkB phosphorylation in the hippocampus was downregulated in CPEflox/flox mice, but brain-derived neurotrophic factor levels were not. In both the hippocampus and dorsal medial prefrontal cortex, we observed reduced MAP2 and GFAP expression in CPEflox/flox mice. Taken together, the results of this study demonstrate that specific neuronal CPE knockout leads to central nervous system dysfunction in mice, including learning and memory deficits, hippocampal Sub degeneration and impaired neurogenesis.

Systematic review and meta-analysis on microRNAs in amyotrophic lateral sclerosis.

MicroRNAs (miRNAs) exhibit a crucial role in the pathogenesis and progress of neurodegenerative disorders. Recent studies have shown abnormal levels of miRNA expression in patients with amyotrophic lateral sclerosis (ALS). Clinical data also confirmed that miRNAs in these patients are inconsistent across studies. A comprehensive systematic review and meta-analysis of current studies can help recognize the important roles of miRNAs during ALS development. Therefore, we initially aimed to perform a systematic literature review on the muscle or serum miRNAs in patients with ALS and healthy individuals. Subsequently, we quantitatively summarized the clinical data of muscle or serum miRNA of patients with ALS and healthy individuals using a meta-analytical technique. 11 studies comprising 281 patients with ALS and 244 healthy control (HC) controls were identified from PubMed and Web of Science for meta-analysis. A systematic review revealed that miRNA levels are closely associated with the occurrence of ALS disease. The expression levels of the most relevant miRNAs were either increased or decreased. The random-effects meta-analysis indicated that the levels of miR-206, miR-133b, and miR-338-3p were significantly elevated in patients with ALS than in HC subjects. By contrast, there was no significant differences in the miR-133a levels between patients with ALS and HC subjects. Collectively, our outcomes demonstrated that serum miR-206, miR-133b, and miR-338-3p were significantly increased in patients with ALS. We speculated that the increased expression levels of miR-206, miR-133b and miR-338-3p are potential promising biomarkers for ALS.

The antifibrotic effects of the novel compound gorse isoflavone alkaloid on chemical liver injury in rats.

OBJECTIVE: Liver fibrosis is a frequently occurring liver injury which lacks of effective treatment clinically. Here, we investigated the protective effects of a novel compound Gorse isoflavone alkaloid (GIA) against liver fibrosis. METHODS: Totally forty rats were randomly divided into four groups. Then we established a model of liver fibrosis induced by the intragastric administration of carbon tetrachloride (CCl4). This treated group was followed by the intragastric administration of GIA and colchicine. Then the liver index and spleen index, and liver function indexes were detected by kit. Western blotting assay was performed to estimate the expression of Transforming Growth Factor-ß1 (TGF-ß1) and related proteins. Tissue fibrosis was observed by Masson staining. RESULTS: Our results suggested that GIA reduced the deposition of collagen fibres and the fibrosis index hydroxyproline (Hyp) of liver tissue. Furthermore, we found that GIA significantly decreased the expression of Transforming Growth Factor-ß1 (TGF-ß1) and the ratio of p-smad2/3 to smad2/3, enhanced the level of superoxide dismutase (SOD), and decreased the concentration of malonic dialdehyde (MDA) in the liver. CONCLUSIONS: Our findings revealed that GIA has a beneficial effect to resist the liver fibrosis, and could be ideal for potential use in antifibrotic drugs for the liver.

Prevalence and Genetic Analysis of Porcine Circovirus 3 in China From 2019 to 2020.

Porcine circovirus type 3 (PCV3), a virus belonging to the Circoviridae family, is considered to be associated with respiratory and neurological signs, cardiac and multisystemic inflammation, reproductive failure, and porcine dermatitis and nephropathy syndrome-like disease in pigs (Sus scrofa). In this study, epidemiological and serological investigations of PCV3 in clinically healthy pigs from different regions of China were performed. Overall, 42.87% (1,101/2,568) of pigs were positive for PCV3 Cap antibody via indirect enzyme-linked immunosorbent assay, with a higher prevalence of PCV3 in multiparous sows (62.22%, 881/1,416) and fattening pigs (28.96%, 159/549) than in suckling piglets (8.96%, 32/357) and nursery pigs (11.79%, 29/246). Of the 2,568 samples, 255 were further tested for PCV3 DNA using real-time polymerase chain reaction, and 63.14% of these were positive, with nearly half having <10 virus copies. The PCV3 DNA and antibody positivity rates were high in the pig serum samples; however, the virus titers and antibody levels were both low, indicating that the humoral immune response of PCV3-infected pigs was weak or lagging, and persistent or repeated infections could occur. Additionally, the complete genomes of 23 PCV3 strains were sequenced and analyzed, which showed nucleotide identities of 98.5~100.0%, 98.6~100.0%, and 99.2~100.0% in the complete genome, open reading frame (ORF)2, and ORF1 sequences, respectively, and amino acid identities of 96.7~100.0% and 99.3~100.0% in the capsid and replicase proteins, respectively. Phylogenetic analysis based on ORF2 nucleotide sequences indicated that the PCV3 strains obtained in the present study could be classified into three sub-clades, with most strains clustered into clade 3c, indicating that PCV3c is the dominant subtype in the regions of China investigated. In general, the present study revealed a high prevalence and high genetic divergence of PCV3 among Chinese pig herds, and indicated that the potential effect of PCV3 on the pig industry may be a concern.

Incidence of psychological illness after coronavirus outbreak: a meta-analysis study.

BACKGROUND: The COVID-19 has had an enormous impact worldwide and is still spreading. Globally confirmed infections have surpassed 41.1 million, of which more than 1 million resulted in deaths. Considering the relationship between public health disasters and emotional disorders, it is essential to examine psychological well-being related to this pandemic. METHOD: We performed a systematic search on psychological problems from PubMed to 10 October 2020, and conducted a meta-analysis using Comprehensive Meta-Analysis V.3 software. RESULTS: The results showed a 19.4% and 26.8% pooled incidence for depression and post-traumatic stress disorder (PTSD), respectively, during the SARS and Middle East Respiratory Syndrome (MERS)-related coronavirus outbreaks. However, overall prevalence of depression was somewhat higher at 27.0% during the COVID-19 period. The pooled incidence of PTSD during COVID-19 compared with SARS and MERS outbreaks, was lower, at 16.4%. CONCLUSION: The results suggest that there are shared and distinct psychological responses following SARS, MERS and COVID-19, and show pessimistic estimates of a wide range of potentially upcoming psychological problems.

Peripheral blood neurotrophic factor levels in children with autism spectrum disorder: a meta-analysis.

Increasing evidence suggests that abnormal regulation of neurotrophic factors is involved in the etiology and pathogenesis of Autism Spectrum Disorder (ASD). However, clinical data on neurotrophic factor levels in children with ASD were inconsistent. Therefore, we performed a systematic review of peripheral blood neurotrophic factors levels in children with ASD, and quantitatively summarized the clinical data of peripheral blood neurotrophic factors in ASD children and healthy controls. A systematic search of PubMed and Web of Science identified 31 studies with 2627 ASD children and 4418 healthy controls to be included in the meta-analysis. The results of random effect meta-analysis showed that the peripheral blood levels of brain-derived neurotrophic factor (Hedges' g = 0.302; 95% CI = 0.014 to 0.591; P = 0.040) , nerve growth factor (Hedges' g = 0.395; 95% CI = 0.104 to 0.686; P = 0.008) and vascular endothelial growth factor (VEGF) (Hedges' g = 0.097; 95% CI = 0.018 to 0.175; P = 0.016) in children with ASD were significantly higher than that of healthy controls, whereas blood neurotrophin-3 (Hedges' g = - 0.795; 95% CI = - 1.723 to 0.134; P = 0.093) and neurotrophin-4 (Hedges' g = 0.182; 95% CI = - 0.285 to 0.650; P = 0.445) levels did not show significant differences between cases and controls. Taken together, these results clarified circulating neurotrophic factor profile in children with ASD, strengthening clinical evidence of neurotrophic factor aberrations in children with ASD.

Traditional Chinese Medicine Decoction Combined With Antipsychotic for Chronic Schizophrenia Treatment: A Systematic Review and Meta-analysis.

Despite several studies suggesting the effectiveness of traditional Chinese medicine (TCM) in schizophrenia, there is still a lack of systematic summary and analysis on the role of TCM as adjuvant therapy in chronic schizophrenia. For this purpose, we conducted a meta-analysis to study the efficacy of TCM as an adjuvant combined with antipsychotics in the treatment of chronic schizophrenia. Until April 2020, based on the review of six electronic databases, eight articles were selected. The articles compared TCM decoction assisted antipsychotic therapies with an antipsychotic alone in the treatment of chronic schizophrenia by analyzing a total of 810 cases. The results showed that TCM combined with antipsychotics have beneficial effects on the Positive and Negative Syndrome Scale (PANSS), including the changes in total score, negative score, and the clinical effects evaluated by the PANSS scale. Subgroup analysis showed that the effects of auxiliary TCM with different efficacy on the positive and psychopathological scores were significantly different. It was found that adjuvant treatment with TCM can reduce some side effects and improve the patient's living conditions in the evaluation of the Schizophrenia Quality Of Life Scale (SQLS). Many studies have proved that TCM is safe and well-tolerated. Although the difficulties of using limited TCM remains to be generalized, it still has great potential in the adjuvant treatment of chronic schizophrenia.