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Dao-Chen Lin Chi-Yu Huang Wei-Hsin Ting Fu-Sung Lo Chiung-Ling Lin Horng-Woei Yang Tzu-Yang Chang Chao-Hsu Lin Yao-Wei Tzeng Wan-Syuan Yang Yue-Li Juang Yann-Jinn Lee 《生物化学与生物物理学报:疾病的分子基础》2019,1865(2):428-433
Monogenic diabetes is caused by mutations that reduce β-cell function. While Sanger sequencing is the standard method used to detect mutated genes. Next-generation sequencing techniques, such as whole exome sequencing (WES), can be used to find multiple gene mutations in one assay. We used WES to detect genetic mutations in both permanent neonatal (PND) and type 1B diabetes (T1BD).A total of five PND and nine T1BD patients were enrolled in this study. WES variants were assessed using VarioWatch, excluding those identified previously. Sanger sequencing was used to confirm the mutations, and their pathogenicity was established via the literature or bioinformatic/functional analysis. The PND and T1BD patients were diagnosed at 0.1–0.5 and 0.8–2.7?years of age, respectively. Diabetic ketoacidosis was present at diagnosis in 60% of PND patients and 44.4% of T1BD patients. We found five novel mutations in five different genes. Notably, patient 602 had a novel homozygous missense mutation c.1295C?>?A (T432?K) in the glucokinase (GCK) gene. Compared to the wild-type recombinant protein, the mutant protein had significantly lower enzymatic activity (2.5%, p?=?0.0002) and Vmax (1.23?±?0.019 vs. 0.33?±?0.016, respectively; p?=?0.005). WES is a robust technique that can be used to unravel the etiologies of genetically heterogeneous forms of diabetes. Homozygous inactivating mutations of the GCK gene may have a significant role in PND pathogenesis. 相似文献
3.
Rai-Hua Lai Yen-Hung Chow Nai-Hsiang Chung Tsan-Chi Chen Feng-Shiun Shie Jyh-Lyh Juang 《Cell death & disease》2022,13(4)
Brainstem encephalitis, a manifestation of severe enterovirus 71 (EV71) infection, is an acute excessive inflammatory response. The mechanisms underlying its development remain poorly understood. Usually neurotropic viruses trigger acute host immune response by engaging cell surface or intracellular receptors. Here, we show that EV71 engagement with intracellular receptor TLR9 elicits IL-12p40-iNOS signaling causing encephalitis in mice. We identified IL-12p40 to be the only prominent cytokine-induced at the early infection stage in the brainstem of mice subjected to a lethal dose of EV71. The upregulated IL-12p40 proteins were expressed in glial cells but not neuronal cells. To better understand the role of IL-12p40 in severe EV71 infection, we treated the EV71-infected mice with an antibody against IL-12p40 and found the mortality rate, brainstem inflammation, and gliosis to be markedly reduced, suggesting that the acute IL-12p40 response plays a critical role in the pathogenesis of brainstem encephalitis. Mechanistically, intracellular TLR9 was found essential to the activation of the IL-12p40 response. Blocking TLR9 signaling with CpG-ODN antagonist ameliorated IL-12p40 response, brainstem inflammation, and limb paralysis in mice with EV71-induced encephalitis. We further found the glial IL-12p40 response might damage neurons by inducing excess production of neurotoxic NO by iNOS. Overall, EV71 engagement with intracellular TLR9 was found to elicit a neurotoxic glial response via IL12p40-iNOS signaling contributing to the neurological manifestation of EV71 infection. This pathway could potentially be targeted for the treatment of brainstem encephalitis.Subject terms: Toll-like receptors, Viral infection 相似文献
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Fu-Chou Cheng Jon-Son Kuo Wen-Ho Chang Dong-Juiing Juang Ying Shih Jeng-Shiow Lai 《Journal of chromatography. B, Analytical technologies in the biomedical and life sciences》1993,617(2)
The simultaneous measurement of homovanillic acid, 3,4-dihydroxyphenylacetic acid, serotonin and 5-hydroxyindoleacetic acid in human plasma by an ultrafiltration and microbore high-performance liquid chromatography—electrochemical detection technique is established. Conventional preparation of blood is very tedious and time-consuming, but isocratic separation of the analytes in plasma ultrafiltrates using a microbore column could be achieved within 10 min. Hence, theoretically, over 140 analyses can be performed in a working day. The detection limit (signal-to-noise ratio = 3) of this method is about 0.1–0.5 pg per injection for all analytes. The required volume of plasma samples can be less than 100 μl. Hence, blood loss is minimal, especially in repeated blood sampling. This rapid, simple and sensitive method can, therefore, be used as a routine clinical tool in the simultaneous measurement of plasma homovanillic acid, 3,4-dihydroxyphenylacetic acid, serotonin and 5-hydroxyindoleacetic acid. 相似文献
6.
Trace elements and lipid peroxidation in 26 patients with chronic renal failure treated with hemodialysis and 25 healthy subjects
were observed. Both plasma and erythrocyte trace elements and plasma malon dialdehyde (MDA) were examined immediately before
and after hemodialysis. Increased levels of plasma Cu, MDA, and erythrocyte Pb, Mn, Zn, and a significantly decreased plasma
Se, Zn and erythrocyte Se were found in patients before hemodialysis. After a single hemodialysis, erythrocyte Mn, Cu, Zn,
and plasma Cu, Al, and MDA were significantly increased whereas both plasma and erythrocyte Se were lower in patients than
in healthy subjects. The level of MDA was not significantly changed during the single hemodialysis. Both plasma and erythrocyte
Zn levels and plasma Cu and Al were significantly higher after hemodialysis than before hemodialysis. In conclusion, levels
of trace elements are altered by hemodialysis, which may increase patient susceptibility to lipid peroxidation in uremia. 相似文献
7.
Wang LY Tseng WC Wu TS Kaneko K Takayama H Kimura M Yang WC Wu JB Juang SH Wong FF 《Bioorganic & medicinal chemistry letters》2011,21(18):5358-5362
An efficient 1,3-dipolar cycloaddition method was performed for the synthesis of a series of monofluoro- and trifluoromethane-3,5-disubstituted 1,2,4-triazoles. This efficient cycloaddition method was to react hydrazonoyl hydrochlorides with a series of aldehydes in the presence of NEt(3) as catalytic basic agent to provide the corresponding product in 28-94%. Their growth inhibitory results against cancer cells indicated that some of the fluorine- and trifluoromethane-containing compounds could effectively inhibit the growth of NCI-H226 and T-cell leukemia (Jurkat) cells. Among the compounds, trifluoromethane-containing 1,2,4-triazoles possessed the five-membered ring groups on the C-5 position of the triazolic ring, including cyclopentyl, 3-furyl, 3-thienyl, and 2-pyrrolyl, possessed the significant inhibitory activity for NCI-H226 cancer cells. 相似文献
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The inhibitory effects of capillarisin on cell proliferation and invasion of prostate carcinoma cells 下载免费PDF全文
Ke‐Hung Tsui Ying‐Ling Chang Pei‐Shan Yang Chen‐Pang Hou Yu‐Hsiang Lin Bing‐Wei Lin Tsui‐Hsia Feng Horng‐Heng Juang 《Cell proliferation》2018,51(2)
Objectives
Capillarisin (Cap), an active component of Artemisia capillaris root extracts, is characterized by its anti‐inflammatory, anti‐oxidant and anti‐cancer properties. Nevertheless, the functions of Cap in prostate cancer have not been fully explored. We evaluated the potential actions of Cap on the cell proliferation, migration and invasion of prostate carcinoma cells.Materials and methods
Cell proliferation and cell cycle distribution were measured by water‐soluble tetrazolium‐1 and flow cytometry assays. The expression of cyclins, p21, p27, survivin, matrix metallopeptidase (MMP2 and MMP9) were assessed by immunoblotting assays. Effects of Cap on invasion and migration were determined by wound closure and matrigel transmigration assays. The constitutive and interlukin‐6 (IL‐6)‐inducible STAT3 activation of prostate carcinoma cells were determined by immunoblotting and reporter assays.Results
Capillarisin inhibited androgen‐independent DU145 and androgen‐dependent LNCaP cell growth through the induction of cell cycle arrest at the G0/G1 phase by upregulating p21 and p27 while downregulating expression of cyclin D1, cyclin A and cyclin B. Cap decreased protein expression of survivin, MMP‐2, and MMP‐9 and therefore blocked the migration and invasion of DU145 cells. Cap suppressed constitutive and IL‐6‐inducible STAT3 activation in DU145 and LNCaP cells.Conclusions
Our data indicate that Cap blocked cell growth by modulation of p21, p27 and cyclins. The inhibitory effects of Cap on survivin, MMP‐2, MMP‐9 and STAT3 activation may account for the suppression of invasion in prostate carcinoma cells. Our data suggest that Cap might be a therapeutic agent in treating advanced prostate cancer with constitutive STAT3 or IL‐6‐inducible STAT3 activation.10.