Effects of Anthraquinones on Immune Responses and Inflammatory Diseases.

The anthraquinones (AQs) and derivatives are widely distributed in nature, including plants, fungi, and insects, with effects of anti-inflammation and anti-oxidation, antibacterial and antiviral, anti-osteoporosis, anti-tumor, etc. Inflammation, including acute and chronic, is a comprehensive response to foreign pathogens under a variety of physiological and pathological processes. AQs could attenuate symptoms and tissue damages through anti-inflammatory or immuno-modulatory effects. The review aims to provide a scientific summary of AQs on immune responses under different pathological conditions, such as digestive diseases, respiratory diseases, central nervous system diseases, etc. It is hoped that the present paper will provide ideas for future studies of the immuno-regulatory effect of AQs and the therapeutic potential for drug development and clinical use of AQs and derivatives.

miR-146a-5p-mediated suppression on trophoblast cell progression and epithelial-mesenchymal transition in preeclampsia.

OBJECTIVE: This study aims to identify the effect of miR-146a-5p on trophoblast cell invasion as well as the mechanism in preeclampsia (PE). METHODS: Expression levels of miR-146a-5p and Wnt2 in preeclamptic and normal placentae were quantified. Trophoblast cells (HTR-8) were separately transfected with miR-146a-5p mimic, miR-146a-5p inhibitor, pcDNA3.1-Wnt2 or sh-Wnt2, and then the expression levels of miR-146a-5p, Wnt2, and epithelial-mesenchymal transition (EMT)-related proteins (Vimentin, N-cadherin and E-cadherin) were measured. Moreover, the proliferative, migratory and invasive capacities of trophoblast cells were detected, respectively. Dual luciferase reporter assay determined the binding of miR-146a-5p and Wnt2. RESULTS: Compared with normal placental tissues, the placentae from PE patients showed higher miR-146a-5p expression and lower Wnt2 expression. Transfection of miR-146a-5p inhibitor or pcDNA3.1-Wnt2 exerted pro-migratory and pro-invasive effects on HTR-8 cells and encouraged EMT in HTR-8 cells; transfection with miR-146a-5p mimic or sh-Wnt2 weakened the proliferative, migratory and invasive capacities as well as reduced EMT process of HTR-8 cells. Moreover, Wnt2 overexpression could partially counteract the suppressive effects of miR-146a-5p overexpression on the progression and EMT of HTR-8 cells. CONCLUSION: miR-146a-5p mediates trophoblast cell proliferation and invasion through regulating Wnt2 expression.

miR-146a-5p-mediated suppression on trophoblast cell progression and epithelial-mesenchymal transition in preeclampsia

OBJECTIVE: This study aims to identify the effect of miR-146a-5p on trophoblast cell invasion as well as the mechanism in preeclampsia (PE). METHODS: Expression levels of miR-146a-5p and Wnt2 in preeclamptic and normal placentae were quantified. Trophoblast cells (HTR-8) were separately transfected with miR-146a-5p mimic, miR-146a-5p inhibitor, pcDNA3.1-Wnt2 or sh-Wnt2, and then the expression levels of miR-146a-5p, Wnt2, and epithelial-mesenchymal transition (EMT)-related proteins (Vimentin, N-cadherin and E-cadherin) were measured. Moreover, the proliferative, migratory and invasive capacities of trophoblast cells were detected, respectively. Dual luciferase reporter assay determined the binding of miR-146a-5p and Wnt2. RESULTS: Compared with normal placental tissues, the placentae from PE patients showed higher miR-146a-5p expression and lower Wnt2 expression. Transfection of miR-146a-5p inhibitor or pcDNA3.1-Wnt2 exerted pro-migratory and pro-invasive effects on HTR-8 cells and encouraged EMT in HTR-8 cells; transfection with miR-146a-5p mimic or sh-Wnt2 weakened the proliferative, migratory and invasive capacities as well as reduced EMT process of HTR-8 cells. Moreover, Wnt2 overexpression could partially counteract the suppressive effects of miR-146a-5p overexpression on the progression and EMT of HTR-8 cells. CONCLUSION: miR-146a-5p mediates trophoblast cell proliferation and invasion through regulating Wnt2 expression.

Association of the Polymorphism of rs1799822 on Carnitine Palmitoyltransferase II Gene with Severe Enterovirus 71 Encephalitis in Chinese Children.

Mutations of the CPT2 gene cause CPT2 deficiency and affect the ß-oxidation of fatty acids. This study examined the consequence of a polymorphism of rs1799822 in the CPT2 gene with respect to EV71 encephalitis in Chinese children. The study included 406 cases of both mild and severe EV71 infection diagnosed by RT-PCR, together with controls (n = 348). We used an improved multiplex ligation detection reaction technique to detect the polymorphism of rs1799822 in the CPT2 gene. The frequency of the (AG+GG) genotype and G allele in the EV71 infection group and in the severe EV71 encephalitis group was significantly lower than in the control group (p = 0.012 vs. p = 0.005, and p = 0.022 vs. p = 0.006, respectively). The frequency of the (AG+GG) genotype and G allele in the severe EV71 encephalitis group was markedly lower than in the mild EV71 encephalitis group (p = 0.045, p = 0.033). The ATP levels in the blood of the (AG+GG) genotype were distinctly higher than in the AA genotype in mild and severe EV71 encephalitis patients (P = 0.037, P = 0.040). A polymorphism of rs1799822 in the CPT2 gene is associated with the severity of EV71 encephalitis and may be one of the protection factors of severe EV71 encephalitis.

A case of Pitt-hopkins Syndrome with de novo mutation in TCF4: Clinical features and treatment for epilepsy.

Pitt-Hopkins syndrome (PTHS), belonging to the group of 18q-syndromes, is a rare genetic disorder caused by mutations in TCF4. PTHS is characterized by distinctive facial appearance, intermittent hyperventilation, intellectual disability and developmental delay. Although patients with PTHS generally have various systemic symptoms, most of them with a TCF4 mutation manifest the central nervous system (CNS) disorders. We described the first Chinese case with Pitt-Hopkins syndrome based on clinical presentations and genetic findings. In addition to the typical features of PTHS, the girl also had paroxysms of tachypnea followed by cyanosis and recurrent seizures. Comprehensive medical examinations were performed including metabolic screening, hepatic and renal function evaluation, abdominal and cardiac ultrasounds. The presence of epileptic discharges in electroencephalography and abnormal brain magnetic resonance imaging were found. High-throughput sequencing was used to detect genetic mutations associated with CNS disorders. Sanger sequencing was used to confirm the mutations in the patient. The c.2182C＞T (p.Arg728Ter) mutation was a de novo nonsense mutation at exon 18 in the TCF4 gene of the patient. In conclusion, we have identified a de novo nonsense mutation of TCF4 carried by a Chinese girl with PTHS. The patient underwent anti-epileptic therapy (sodium valproate, levetiracetam, clonazepam), resulting in a reduction of the seizures.

[The expression and antibody preparation of S100A10 protein].

OBJECTIVE: To prepare S100A10 protein and its specific polyclonal antibody. METHODS: The full-length gene fragment of S100A10 was amplified by PCR, and then cloned into pET28a(+) prokaryotic expression vector. After transformation, the vector was induced to express the recombinant (S100A10)(2) protein by IPTG in E.coli BL21 (DE3). The recombinant (S100A10)(2) was then purified by Ni-NTA resin. (S100A10)(2)-specific polyclonal antibody was prepared using the purified recombinant (S100A10)(2) protein as antigen to inoculate rabbit intradermally. The title and specificity of the polyclonal antibody were determined by ELISA and Western blotting. RESULTS: The study successfully constructed the prokaryotic recombinant expression vector pET28a(+)-(S100A10)(2), and obtained the purified recombinant (S100A10)(2) protein and polyclonal antibody with high titer and specificity. CONCLUSION: The prokaryotic expression and purification system for S100A10 has been established and polyclonal antibody of (S100A10)(2) been prepared, which provides helpful fools for further researches on S100A10.

Association of CPT II gene with risk of acute encephalitis in Chinese children.

BACKGROUND: Mutations of the CPT II gene cause CPT II deficiency, an inborn metabolic error affecting mitochondrial fatty acid ß-oxidation. Associations and mechanisms of CPT II gene with acute encephalitis need to be elucidated. We aimed to investigate the associations of CPT II gene variants and CPT II activity with development of acute encephalitis. METHODS: A total of 440 blood-unrelated Chinese children with acute encephalitis and 229 healthy controls were enrolled in this case control study. Sequencing of 5 exons of the CPT II gene was carried out to look for the variants associated with acute encephalitis. CPT II activity and blood adenosine triphosphate concentration were examined during high fever and convalescent phase to confirm the hypothesis. RESULTS: Polymorphism of rs2229291 in CPT II gene was significantly associated with an increased risk of acute encephalitis (P = 0.031), where as rs1799821 displayed a decrease risk (P = 0.018). Positive association was found between rs2229291 and patients with fever at onset of seizure and degree of pathogenetic condition (P = 0.018 and P = 0.023), but not for rs1799821. CPT II activity of patients with rs2229291 reduced greatly during high fever compared with the convalescent phase. CONCLUSIONS: rs2229291 and rs1799821 variants in CPT II gene might be 1 of the predisposing factors of acute encephalitis.