TGFβ1 is very important in the synthesis and degradation of extracellular matrix, and also in the mediation of human lung fibroblasts proliferation, and miR-29 plays an important role in this process. To explore the interactions of miR-29 family members and TGFβ1, the effects of transforming growth factor TGFβ1 on the expression of miR-29 and whether miR-29 is involved in pro-survival signaling pathways mediated by TGFβ1 were examined in human lung fibroblasts. Treatment of the human embryonic lung fibroblast cell line IMR90 with TGFβ1 caused a decrease in expression of miR-29a/b/c by real-time PCR analysis. TGFβ1 stimulation increased cell proliferation, colony formation and up-regulated expression of COL1A1; transfecting with miR-29a/b/c mimics reverse TGFβ1-induced phenotype changes in IMR90 cells. Western blot analyses showed that TGFβ1 treatment unchanged total protein expression levels of PI3K or AKT, but the expression levels of p-PI3K, p-AKT, and COL1A1 were increased; and miR-19a/b/c mimics interfering blocked phosphorylation of PI3K or AKT and decreased expression of COL1A1 after TGFβ1 treatment. The results indicate that TGFβ1 beta uses the PI3k-Akt pathway in these embryonic fibroblasts and miR29 blocks this activation pathway. It indicates a novel biological function of the PI3K-Akt pathway in IMR90. Elevated expression of miR-29 may play an important role in the pathogenesis of diseases related to fibrogenic reactions in human lung fibroblasts.
Background. Repetitive transcranial magnetic stimulation (rTMS) is a promising therapeutic tool for Parkinson’s disease (PD), and many stimulation targets have been implicated. We aim to explore whether low-frequency rTMS over the right dorsolateral prefrontal cortex (DLPFC) improves motor and nonmotor symptoms of individuals with PD. Methods. We conducted a randomized, single-blind, sham-controlled parallel trial to compare the effect of 10 consecutive daily sessions of 1 Hz rTMS over right DLPFC on individuals with idiopathic PD between active and sham rTMS group. Primary outcomes were changes in Unified Parkinson’s Disease Rating Scale (UPDRS) part III and Nonmotor Symptom Questionnaire (NMSQ). Secondary outcomes were changes in UPDRS total score, Hamilton Rating Scale for Depression (HRSD), Pittsburgh Sleep Quality Index (PSQI), and Montreal Cognitive Assessment (MoCA). Assessments were completed at baseline, after treatment, and at 1 month, 3 months, and 6 months after treatment. Results. A total of 33 participants with PD were randomized. All participants completed the study and no severe adverse effect was noticed. Compared to baseline, active rTMS showed significant improvements in UPDRS part III and NMSQ at 1 month. Change of scores on UPDRS part III, HRSD, and PSQI persisted for 3 months after rTMS intervention. The beneficial effect on cognitive performance assessed by MoCA was maintained for at least 6 months in the follow-up. No significant changes were observed in the group with sham rTMS. Conclusions. Low-frequency rTMS of right DLPFC could be a potential selection in managing motor and nonmotor symptoms in PD.
Background Dyskinesia is a troublesome complication of long-term dopaminergic medications in Par-kinson’s disease (PD) patients. Many factors are reported to be associated with dyskinesia in PD. Objective To investigate the association between sleep quality and dyskinesia in patients with PD. Methods Four hundred twenty-five patients with PD were enrolled in this study. Demographic information was collected. Unified Parkinson’s Disease Rating Scale (UPDRS) and Hoehn and Yahr (H-Y) stage scale were also performed. Epworth Sleepiness Scale (ESS) and Pittsburgh Sleep Quality Index (PSQI) were applied to evaluate daytime sleepiness and overall nighttime sleep quality, respectively, in PD patients. Results Patients with dyskinesia tended to have a longer duration of disease, higher daily levodopa-equivalent dose (LED), H-Y stage, UPDRS II and PSQI score, and a higher percentage of levodopa treatment than those without dyskinesia. After adjusting for age, sex, age at onset of PD, disease duration, UPDRS I, UPDRS II, UPDRS III, cigarette smoking, use of different antiparkinsonian drugs, phenotype, daily LED, and restless leg syndrome (RLS), PSQI score was still associated with dyskinesia, with corresponding ORs 1.111 (95% CI, 1.004–1.229) as a continuous variable, and 2.469 (95% CI, 1.051–5.800) as a categorical variable, respectively. Further analysis of PSQI components showed that subjective sleep quality and sleep latency were associated with dyskinesia in PD patients. Conclusions Our data showed that poor nighttime sleep is positively associated with dyskinesia in PD patients. Attention to the management of nighttime sleep quality may be beneficial to dyskinesia in patients with PD.
ObjectiveTo investigate whether in utero exposure to the Great Chinese Famine in 1959 to 1961 was associated with risk of intracerebral hemorrhage (ICH) in adulthood.MethodsIn this cohort analysis, we included 97,399 participants of the Kailuan Study who were free of cardiovascular disease and cancer at baseline (2006). Cases of incident ICH were confirmed by medical record review. We used the Cox proportional hazards model to calculate the hazard ratio (HR) and 95% confidence interval (CI) for ICH according to in utero famine exposure status.ResultsAmong 97,399 participants in the current analyses, 6.3% (n = 6,160) had been prenatally exposed to the Great Chinese Famine. During a median 9.0 years of follow-up (2006–2015), we identified 724 cases of incident ICH. After adjustment for potential confounders, the HR of ICH was 1.99 (95% CI 1.39–2.85) for in utero famine-exposed individuals vs individuals who were not exposed to the famine. When exposure to famine and severity of famine were examined jointly, the adjusted HR was 2.99 (95% CI 1.21–7.39) for in utero exposure to severe famine and 1.94 (95% CI 1.32–2.84) for in utero exposure to less severe famine relative to those without exposure to famine.ConclusionsIndividuals with in utero exposure to famine, especially those exposed to severe famine, were more likely to have ICH in midlife, highlighting the role of nutritional factors in susceptibility to this severe cerebral condition.
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