Variant of Associated with Increasing Risk in Chinese Patients with Relapsing-remitting Multiple Sclerosis / 中华医学杂志(英文版)

<p><b>Background</b>Multiple sclerosis (MS) is a common central nervous system autoimmune disorder. Increasing number of genome-wide association study (GWAS) analyses hint that MS is strongly associated with genetics. Unfortunately, almost all the GWAS analyses were Caucasian population based. Numbers of risk loci might not be replicated in Chinese MS patients. Hence, we performed a MassArray Assay to genotype the previously reported variants located in the transcription regulation genes in order to elucidate their role in the Chinese MS patients.</p><p><b>Methods</b>One hundred and forty-two relapsing-remitting MS (RRMS) patients and 301 healthy controls were consecutively collected from September 2, 2008, to June 7, 2013, as stage 1 subjects. Eight reported transcription regulation-related single-nucleotide polymorphisms (SNPs) were genotyped using the Sequenom MassArray system. In stage 2, another 44 RRMS patients and 200 healthy controls were consecutively collected and Sanger sequenced from April 7, 2015, to June 29, 2017, for the validation of positive results in stage 1. Differences in allele and genotype frequencies between patients and healthy controls, odds ratios, and 95% confidence intervals were calculated with the Chi-square test or Fisher's exact test. Hardy-Weinberg equilibrium was tested also using the Chi-square test.</p><p><b>Results</b>In stage 1 analysis, we confirmed only one previously reported risk variant, rs11129295 in EOMES gene. We found that the frequency of T/T genotype was much higher in MS group (χ = 10.251, P = 0.005) and the T allele of rs11129295 increased the risk of MS (χ = 10.022, P = 0.002). In stage 2 and combined analyses, the T allele of rs11129295 still increased the risk of MS (χ = 4.586, P = 0.030 and χ = 16.378, P = 5.19 × 10, respectively).</p><p><b>Conclusions</b>This study enhances the knowledge that the variant of EOMES is associated with increasing risk in Chinese RRMS patients and provides a potential therapeutic target in RRMS.</p>

Neuroprotective activity of two active chemical constituents from Tinospora hainanensis

Objective To determine the chemical structure of the new compound and investigate the protective effects of Tinosporaic acid A and B towards in-vitro neuro. Methods The structures of two new compounds were established by analyzing its 1D and 2D NMR spectra as well as HRESIMS. Their neuroprotective effects with respect to the antioxidant properties were evaluated by radical scavenging tests and hydrogen peroxide-injured oxidative stress model in PC12 cell lines. Cell morphology of treated PC12 cells was observed by phase contrast microscopy. In-vitro MTT assay, lactate dehydrogenase activity assay and oxidative stress markers (intracellular ROS production, MDA level, and caspase-3 activity) were used to evaluate the protective effects against hydrogen peroxide induced cytotoxicity in PC12 cells. Results The two new compounds, named Tinosporaic acid A and B, were isolated and identified from the stem bark of Tinospora hainanensis. Cell viability studies identified a representative concentration for each extract that was subsequently used to measure oxidative stress markers. Both extracts were able to reverse the oxidative damage caused by hydrogen peroxide, thus promoting PC12 cells survival. The concentration of Tinosporaic acid A and B were 86.34 μg/mL and 22.06 μg/mL respectively, which is neuroprotective for EC50. The results indicated that both of them significantly attenuated hydrogen peroxide-induced neurotoxicity. Conclusion The two new compounds isolated from ethanol extracts of Tinospora hainanensis are the promising natural ones with neuroprotective activity and needed for further research.

Neuroprotective activity of two active chemical constituents from Tinospora hainanensis

OBJECTIVE@#To determine the chemical structure of the new compound and investigate the protective effects of Tinosporaic acid A and B towards in-vitro neuro.@*METHODS@#The structures of two new compounds were established by analyzing its 1D and 2D NMR spectra as well as HRESIMS. Their neuroprotective effects with respect to the antioxidant properties were evaluated by radical scavenging tests and hydrogen peroxide-injured oxidative stress model in PC12 cell lines. Cell morphology of treated PC12 cells was observed by phase contrast microscopy. In-vitro MTT assay, lactate dehydrogenase activity assay and oxidative stress markers (intracellular ROS production, MDA level, and caspase-3 activity) were used to evaluate the protective effects against hydrogen peroxide induced cytotoxicity in PC12 cells.@*RESULTS@#The two new compounds, named Tinosporaic acid A and B, were isolated and identified from the stem bark of Tinospora hainanensis. Cell viability studies identified a representative concentration for each extract that was subsequently used to measure oxidative stress markers. Both extracts were able to reverse the oxidative damage caused by hydrogen peroxide, thus promoting PC12 cells survival. The concentration of Tinosporaic acid A and B were 86.34 μg/mL and 22.06 μg/mL respectively, which is neuroprotective for EC50. The results indicated that both of them significantly attenuated hydrogen peroxide-induced neurotoxicity.@*CONCLUSION@#The two new compounds isolated from ethanol extracts of Tinospora hainanensis are the promising natural ones with neuroprotective activity and needed for further research.

The protective effect and underlying mechanism of Hainan papaya water extract against neuronal apoptosis induced by Aβ40

Objective To investigate whether Hainan papayas has protective effects in an Aβ40-induced primary neuron injury model and elucidate the underlying molecular mechanism. Methods Cultured primary neurons from the dorsal root ganglia (DRG) of Sprague–Dawley (SD) rats were treated with 20 μM Aβ40 peptide, 100 μg/L Hainan papaya water extract, peptide plus extract, or culture medium for 24 h. Cell viability was measured by MTT assay, and neuronal apoptosis was evaluated by DAPI staining. ERK signaling pathway-associated molecule activation and changes in Bax expression were analyzed by Western blotting and immunofluorescence. Results A cell viability rate of (44.11 ± 6.59)% in the Aβ40 group was rescued to (79.13 ± 6.64)% by adding different concentrations of the extract. DAPI showed pyknotic nuclei in 39.5% of Aβ40-treated cells; the fraction dropped to 17.4% in the 100 μg/L extract group. ERK phosphorylation was observed in the Aβ40 group but was ameliorated by pretreatment with 100 μg/L extract. Hainan papaya water extract also prevented Aβ40-induced phosphorylation of MEK, RSK1 and CREB associated with ERK signaling and downregulated Bax expression in the neurons. Conclusion The results suggest that Hainan papaya water extract has protective effects on neurons; the mechanism may be related to suppression of ERK signaling activation.

The protective effect and underlying mechanism of Hainan papaya water extract against neuronal apoptosis induced by Aβ40

OBJECTIVE@#To investigate whether Hainan papayas has protective effects in an Aβ40-induced primary neuron injury model and elucidate the underlying molecular mechanism.@*METHODS@#Cultured primary neurons from the dorsal root ganglia (DRG) of Sprague-Dawley (SD) rats were treated with 20 μM Aβ40 peptide, 100 μg/L Hainan papaya water extract, peptide plus extract, or culture medium for 24 h. Cell viability was measured by MTT assay, and neuronal apoptosis was evaluated by DAPI staining. ERK signaling pathway-associated molecule activation and changes in Bax expression were analyzed by Western blotting and immunofluorescence.@*RESULTS@#A cell viability rate of (44.11 ± 6.59)% in the Aβ40 group was rescued to (79.13 ± 6.64)% by adding different concentrations of the extract. DAPI showed pyknotic nuclei in 39.5% of Aβ40-treated cells; the fraction dropped to 17.4% in the 100 μg/L extract group. ERK phosphorylation was observed in the Aβ40 group but was ameliorated by pretreatment with 100 μg/L extract. Hainan papaya water extract also prevented Aβ40-induced phosphorylation of MEK, RSK1 and CREB associated with ERK signaling and downregulated Bax expression in the neurons.@*CONCLUSION@#The results suggest that Hainan papaya water extract has protective effects on neurons; the mechanism may be related to suppression of ERK signaling activation.

Variants of Interferon Regulatory Factor 5 are Associated with Neither Neuromyelitis Optica Nor Multiple Sclerosis in the Southeastern Han Chinese Population / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Neuromyelitis optica (NMO) and multiple sclerosis (MS) are demyelinating disorders of the central nervous system. Interferon regulatory factor 5 (IRF5) is a common susceptibility gene to different autoimmune disorders. However, the association of IRF5 variants with NMO and MS patients has not been well studied. Therefore, we aimed to evaluate whether IRF5 variants were associated with NMO and MS in the Southeastern Han Chinese population.</p><p><b>METHODS</b>Four single nucleotide polymorphisms (SNPs) were selected and genotyped by matrix-assisted laser desorption/ionization time of flight mass spectrometry in 111 NMO patients, 145 MS patients and 300 controls from Southeastern China.</p><p><b>RESULTS</b>None of these 4 SNPs was associated with NMO or MS patients.</p><p><b>CONCLUSIONS</b>Our preliminary study indicates that genetic variants in IRF5 may affect neither NMO nor MS in the Southeastern Han Chinese population. Further studies with a large sample size and diverse ancestry populations are needed to clarify this issue.</p>

Variants of Interleukin-7/Interleukin-7 Receptor Alpha are Associated with Both Neuromyelitis Optica and Multiple Sclerosis Among Chinese Han Population in Southeastern China / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Neuromyelitis optica (NMO) and multiple sclerosis (MS) are autoimmune demyelinating diseases of the central nerve system. Interleukin-7 (IL-7) and interleukin-7 receptor alpha (IL-7Rα) were proved to be important in the pathogenesis of both diseases because of the roles they played in the differentiations of autoimmune lymphocytes. The variants of both genes had been identified to be associated with MS susceptibility in Caucasian, Japanese and Korean populations. However, the association of these variants with NMO and MS has not been well studied in Chinese Southeastern Han population. Here, we aimed to evaluate the association of six IL-7 variants (rs1520333, rs1545298, rs4739140, rs6993386, rs7816065, and rs2887502) and one variant of IL-7RA (rs6897932) with NMO and MS among Chinese Han population in southeastern China.</p><p><b>METHODS</b>Matrix-assisted laser desorption/ionization time of flight mass spectrometry (MassARRAY system) and Sanger sequencing were used to determine the variants of IL-7 and IL-7RA in 167 NMO patients, 159 MS patients and 479 healthy controls among Chinese Han population in southeastern China. Samples were excluded if the genotyping success rate <90%.</p><p><b>RESULTS</b>Statistical differences were observed in the genotypes of IL-7 rs1520333 in MS patients and IL-7RA rs6897932 in NMO patients, compared with healthy controls (P = 0.035 and 0.034, respectively). There was a statistically significant difference in the genotypes of IL-7 rs2887502 between MS and NMO patients (P = 0.014). And there were statistically significant differences in the rs6897932 genotypes (P = 0.004) and alleles (P = 0.042) between NMO-IgG positive patients and healthy controls.</p><p><b>CONCLUSIONS</b>The study suggested that among Chinese Han population in southeastern China, the variant of IL-7RA (rs6897932) was associated with NMO especially NMO-IgG positive patients while the variant of IL-7 (rs1520333) with MS patients. And the genotypic differences of IL-7 rs2887502 between MS and NMO indicated the different genetic backgrounds of these two diseases.</p>