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Int J Biol Macromol ; 2019 Nov 19.
Artigo em Inglês | MEDLINE | ID: mdl-31756487


OBJECTIVE: Fas is a positive regulator of Th17 cells differentiation in experimental autoimmune encephalomyelitis (EAE). However, its upstream regulators are still not fully determined. This study was designed to explore the upstream regulators of Fas in regulating Th17 cells differentiation in EAE. METHODS: The mouse model of EAE was established by myelin oligodendrocyte glycoprotein injection. Th17 cells differentiation was induced by IL-23, IL-6 and TGF-ß. RESULTS: Down-regulated Hsp70 and miR-374c and up-regulated Fas were observed in the spleen and brain of EAE mice. Hsp70 overexpression evidently reduced Fas protein level, but not mRNA level. The luciferase reporter assay indicated that miR-374c targets Fas. Overexpression of miR-374c down-regulated the mRNA and protein level of Fas. The concentration of IL-17A in CD4+ T-cells was reduced by miR-374c or Hsp70 overexpression, and Fas overexpression altered this trend. Hsp70 did not regulate the expression of miR-374c, and likewise, miR-374c did not regulate the expression of Hsp70. Further results suggested that Hsp70 and miR-374c regulated Fas expression through different ways to affect Th17 cells differentiation in EAE. CONCLUSIONS: This study suggested that down-regulated miR-374c and Hsp70 promote Th17 cell differentiation by inducing Fas expression in EAE.

Medicine (Baltimore) ; 97(50): e13625, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-30558047


RATIONALE: Anti-N-methyl-D-aspartate receptor (anti-NMDAR) encephalitis is an auto-immune and paraneoplastic encephalitis with prominent neuropsychiatric manifestations. The N-methyl-D-aspartate receptor is located in the forebrain and hippocampus and plays a role in learning and memory. PATIENT CONCERNS: A 29-year-old female patient with anti-NMDAR encephalitis, was reported and we also reviewed the literature and summarised the characteristics of the cases. DIAGNOSES: In the present study, we reported 1 patient with anti-NMDAR encephalitis diagnosed by the detection of anti-NMDAR antibodies in serum and cerebrospinal fluid (CSF). INTERVENTIONS: The patient received glucocorticoids and anti-epilepsy treatment as well as human immunoglobulin treatment. OUTCOMES: After treatment, the patient gradually regained consciousness and was discharged after 3 months of rehabilitation. At the follow-up 2 months later, the patient had the sequelae of memory impairment and limb movement disorders. LESSONS: An accurate early diagnosis and active treatment are crucial to the improvement in the prognosis of patients with anti-NMDAR receptor encephalitis.

Encefalite Antirreceptor de N-Metil-D-Aspartato , Anticonvulsivantes/administração & dosagem , Glucocorticoides/administração & dosagem , Imunoglobulinas/administração & dosagem , Receptores de N-Metil-D-Aspartato/imunologia , Adulto , Encefalite Antirreceptor de N-Metil-D-Aspartato/complicações , Encefalite Antirreceptor de N-Metil-D-Aspartato/diagnóstico , Encefalite Antirreceptor de N-Metil-D-Aspartato/fisiopatologia , Encefalite Antirreceptor de N-Metil-D-Aspartato/psicologia , Anticorpos/sangue , Anticorpos/líquido cefalorraquidiano , Diagnóstico Precoce , Feminino , Humanos , Imunomodulação , Transtornos da Memória/etiologia , Transtornos dos Movimentos/etiologia , Prognóstico , Resultado do Tratamento
Front Pharmacol ; 9: 1411, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30568590


ORY-1001, an inhibitor of covalent lysine (K)-specific demethylase 1A (KDM1A), has been used as a therapy for the treatment of acute leukemia. However, the underlying mechanisms of anticancer are still not fully elucidated. Here, we report that KDM1A is highly expressed in lung cancers, where it appears to drive aggressive growth. Furthermore, lung cancer patients with higher KDM1A levels have worse survival outcomes than patients with lower KDM1A levels. Interestingly, ORY-1001significantly inhibited the cell proliferation, colony formation, cell cycle, and induced apoptosis, by regulating the Warburg effect through controlling Hexokinases 2 (HK2) expression. In summary, these results indicate that ORY-1001 could inhibit the growth of lung cancer cells via regulating the Warburg effect by controlling HK2.

Semin Arthritis Rheum ; 47(5): 727-731, 2018 04.
Artigo em Inglês | MEDLINE | ID: mdl-29110911


OBJECTIVES: Blau syndrome (BS), a rare auto-inflammatory granulomatous disease, is a progressive disorder. Usually the maintenance dose of glucocorticoid may not be tapered below 15 mg per day while immunosuppressives is used. There has been some experience with biologic agents in refractory BS patients. The objective of this study is to describe the case of a BS patient benefiting from Tocilizumab, a humanized monoclonal antibody against interleukin 6 receptor. METHODS: We report the first Chinese patient with BS who was resistant to currently available therapies but had rapid quiescence after using Tocilizumab. We also conducted a systematic literature review about the current treatments of BS. RESULTS: A 13-year-old Chinese boy with BS, whose uveitis got worsened when treated with Infliximab, was well-controlled after taking Tocilizumab and prednisone was tapered off to a dose of 8mg per day. We identified 29 manuscripts providing 45 BS cases. Among these patients, 24 underwent biological treatments and 22 of them recovered. In these 29 manuscripts, the biological agents used to treat refractory BS included Etanercept, Infliximab, Adalimumab, Canakinumab and Anakinra. CONCLUSIONS: Case reports on the use of biological agents have yielded mixed results. The diversity of the symptoms may be due to functional differences in NOD2 mutations. For BS patients with fever, lymphadenopathy and hepatosplenomegaly, Tocilizumab may be a better choice.

Anticorpos Monoclonais Humanizados/uso terapêutico , Artrite/tratamento farmacológico , Imunossupressores/uso terapêutico , Sinovite/tratamento farmacológico , Uveíte/tratamento farmacológico , Adolescente , China , Humanos , Masculino , Resultado do Tratamento
Front Pharmacol ; 8: 421, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28713273


Cisplatin (DDP) is currently one of the most commonly used chemotherapeutic drugs for treating ovarian and lung cancer. However, resistance to cisplatin is common and it often leads to therapy failure. In addition, the precise mechanism of cisplatin resistance is still in its infancy. In this study, we demonstrated that the oxidative pentose phosphate pathway enzyme 6-phosphogluconate dehydrogenase (6PGD) promotes cisplatin resistance. We showed that cisplatin-resistant cancer cells (C13∗ and A549DDP), had higher levels of 6PGD compared to their cisplatin-sensitive counterparts (OV2008 and A549). Furthermore, ovarian and lung cancer patients with higher 6PGD levels have worse survival outcomes relative to patients with lower 6PGD expression. Interestingly, we found that the upregulation of 6PGD in cisplatin-resistant cells was due to the decreased expression of miR-206 and miR-613, which we found to target this enzyme. We further demonstrate that suppressing 6PGD using shRNA, inhibitor or miR-206/miR-613, either as single agents or in combination, could sensitize cisplatin-resistant cancer cells to cisplatin treatment and thereby improving the therapeutic efficacy of cisplatin. Taken together, our results suggest that 6PGD serves as a novel potential target to overcome cisplatin resistance.

Zhonghua Bing Li Xue Za Zhi ; 45(2): 102-6, 2016 Feb.
Artigo em Chinês | MEDLINE | ID: mdl-26879431


OBJECTIVE: To study the clinicopathologic features of tuberous sclerosis complex (TSC). METHODS: The clinicopathologic data of the patients diagnosed as TSC with refractory epilepsy and resection of epileptic focus were retrospectively analyzed. RESULTS: Fourteen cases were included, the mean age was (15.8±12.9) years, with a male predominance (male to female ratio=10:4). Frontal lobe was the most common (13/14) site of involvement. MRI showed multiple patchy long T1 and long T2 signals. CT images showed multiple subependymal high density calcified nodules in nine cases. Histology showed mild to severe disruption of the cortical lamination, cortical and subcortical tubers with giant cells and/or dysmorphic neurons. The giant cells showed strong immunoreactivity for vimentin and nestin, while the dysmorphic neurons partially expressed MAP2 and NF. Vimentin also stained strongly the "reactive" astrocytes. Thirteen cases had follow-up information: Engel class I in six cases, Engel class II in six cases, and Engel class III in one case. CONCLUSIONS: Diagnosis of TSC relies on combined pathologic, clinical and neuroradiological features. Immunohistochemical staining can be helpful. Resection of epileptic focus is an effective method to treat refractory epilepsy in TSC.

Epilepsia/patologia , Esclerose Tuberosa/patologia , Adolescente , Astrócitos/química , Astrócitos/patologia , Criança , Epilepsia Resistente a Medicamentos/cirurgia , Epilepsia/complicações , Epilepsia/metabolismo , Epilepsia do Lobo Frontal/complicações , Epilepsia do Lobo Frontal/metabolismo , Epilepsia do Lobo Frontal/patologia , Feminino , Células Gigantes/química , Células Gigantes/patologia , Humanos , Imagem por Ressonância Magnética , Masculino , Nestina/análise , Neurônios/metabolismo , Neurônios/patologia , Estudos Retrospectivos , Esclerose Tuberosa/complicações , Esclerose Tuberosa/metabolismo , Vimentina/análise