Synergistic effect of glucocorticoids and IGF-1 on myogenic differentiation through the Akt/GSK-3ß pathway in C2C12 myoblasts.

Purpose: Glucocorticoids are the only therapeutics that can delay the progression of Duchenne musculardystrophy (DMD), the most prevalent type of inherited neuromuscular disorder in males. However, beyond theiranti-inflammatory effects, glucocorticoids have other underlying mechanisms that remain unclear. Moreover, muscleand circulating levels of insulin growth factor-1 (IGF-1) often decrease in response to glucocorticoids. Therefore, wehypothesized that glucocorticoids, either alone or in combination with IGF-1, can improve myogenic differentiation.Materials and methods: Established C2C12 myoblasts were employed as an in vitro model of myogenic differentiation,and myogenic differentiation markers, as assessed by Western blot (myogenin, MyoD, and MyHC protein expression),cellular morphology analysis (fusion index) and RT-PCR (MCK mRNA expression), were measured.Results: Myogenic differentiation markers were increased by glucocorticoid treatment. Furthermore, this effect was furtherenhanced by IGF-1, and these results suggest that glucocorticoids, either alone or together with IGF-1, can promotemyogenic differentiation. Akt and GSK-3ß play important roles in myogenic differentiation. Interestingly, the levels ofboth phosphorylated Ser473-Akt and phosphorylated Ser9-GSK-3ß were increased by glucocorticoid and IGF-1 cotreatment.Pharmacological manipulation with LY294002 and LiCl was employed to inhibit Akt and GSK-3ß, respectively.We found that cellular differentiability was inhibited by LY294002 and enhanced by LiCl, indicating that theAkt/GSK-3ß signaling pathway is activated by glucocorticoid and IGF-1 treatment to promote myogenic differentiation.Conclusions: Glucocorticoids together with IGF-1 promote myogenic differentiation through the Akt/GSK-3ßpathway. Thus, these results further our knowledge of myogenic differentiation and may offer a potential alternativestrategy for DMD treatment based on glucocorticoid and IGF-1.

Long-term treatment of blepharospasm with botulinum toxin A: a service-based study over a 16-year follow-up in southern China.

OBJECTIVE: To elucidate the effect of long-term treatment with botulinum toxin A (BTX-A) for blepharospasm. Prevalence data and clinical features in southern China and influencing factors for selecting BTX-A treatment were explored. METHODS: We collected data retrospectively from 338 consecutive patients diagnosed with blepharospasm over 16 years to assess prevalence data and clinical features. Thereafter, all patients were classified into BTX-A (n = 135) or non-BTX-A (n = 203) treatment groups according to the patients' requests in order to explore the factors influencing whether BTX-A treatment was chosen. Furthermore, dynamic follow-up data were analyzed to evaluate the long-term efficacy in the BTX-A group. RESULTS: The prevalence was 23.3 per million, with an onset age of 50.3 ± 12.3 years and a female:male ratio of 2.4:1; the most common symptom was excessive blinking (91.2%). The symptom severity and psychological assessment scores were significantly decreased by treatment with BTX-A (p < 0.01), and there was no significant difference in response duration with the prolongation of BTX-A injections. Adverse events occurred 52 times (5.0%) among 1038 injections. The symptom severity and psychological assessment scores and the occurrence of eye-opening difficulty were higher, and medical expenses and the symptom tolerability rate were lower in the BTX-A group than in the non-BTX-A group (p < 0.05). CONCLUSION: The onset age was earlier than that in Western countries. However, starting BTX-A treatment early is justified, even though a higher dosage was needed to maintain reliable long-term efficacy. Additionally, symptom severity and medical expenses are the primary factors affecting whether patients select BTX-A treatment.

Predictors of oedema type in reversible posterior leukoencephalopathy syndrome with preeclampsia or eclampsia.

OBJECTIVE: To explore the predictive factors of oedema types in reversible posterior leukoencephalopathy syndrome (RPLS) with preeclampsia (PE) and eclampsia, which is closely related to reversible lesions and clinical recovery. METHOD: We collected data from 44 consecutive patients diagnosed with RPLS in PE or eclampsia between 2013 and 2017. All patients were classified into vasogenic oedema (n = 31) or cytotoxic oedema (n = 13) groups according to magnetic resonance imaging (MRI) results. General information, clinical data, biochemical indicators and imaging features were collected retrospectively to explore the differences between the groups. Furthermore, we analysed potential predictive factors by logistic regression. RESULTS: The occurrence rates of immune disease and stillbirth, hospitalization time and the levels of serum albumin (ALB), lactate dehydrogenase (LDH), aspartate transaminase (AST) and alanine aminotransferase (ALT) were higher, while the values of systolic blood pressure (SBP), mean arterial pressure (MAP) and 24-h urine protein were lower in the cytotoxic oedema patients than those in the vasogenic oedema patients (p < .05). The ALB concentration was closely correlated with vasogenic oedema, while AST and ALT were closely correlated with cytotoxic oedema by logistic regression (p < .05). CONCLUSION: The levels of ALB, AST and ALT are potential predictors for the development of oedema in RPLS. ALB is related to vasogenic oedema by a possible mechanism of decreased colloid osmotic pressure, while AST and ALT are related to cytotoxic oedema by a possible mechanism of endothelial dysfunction.

[Heavy metal pollution characteristics and ecological risk analysis for soil in Phyllostachys praecox stands of Lin'an].

An investigation was carried out in an attempt to reveal the characteristics of heavy metals contamination in the soils of Phyllostachys praecox forest in Lin' an. Based on the concentrations of Hg, As, Cu, Pb, Zn, Cd, Cr, Ni, Co and Mn in 160 topsoil samples, the pollution status and ecological risks of heavy metals in the soils were assessed by single factor pollution index, Nemerow integrated pollution index and Hankanson potential ecological risk index. The spatial variability of heavy metal concentrations in the soils closely related to the distribution of traffic, industrial and livestock pollution sources. The average concentrations of Hg, As, Cu, Pb, Zn, Cd, Cr, Ni, Co and Mn in the soils were 0.16, 7.41, 34.36, 87.98, 103.98, 0.26, 59.12, 29.56, 11.44 and 350.26 mg · kg(-1), respectively. Pb, Cd, Zn and Cu concentrations were as 2.89, 1.70, 1.12 and 1.12 times as the background values of soil in Zhejiang Province, respectively. But their concentrations were all lower than the threshold values of the National Environmental Quality Standard for Soil (GB 15618-1995). The average single factor pollution index revealed that the level of heavy metal pollution in the soils was in order of Pb>Cd>Cu= Zn>Hg>As>Ni>Co>Cr>Mn. Pb pollution was of moderate level while Cd, Cu and Zn pollutions were slight. There was no soil pollution caused by the other heavy metals. However, the Nemerow integrated pollution index showed that all the 160 soil samples were contaminated by heavy metals to a certain extent. Among total 160 soil samples, slight pollution level, moderate pollution level and heavy pollution level accounted for 55.6%, 29.4% and 15.0%, respectively. The average single factor potential ecological risk index (Er(i)) implied that the potential ecological risk related to Cd reached moderate level, while the others were of slight level. Furthermore, Cd and Hg showed higher potential ecological risk indices which reached up to 256.82 and 187.33 respectively, indicating Cd and Hg had a strong ecological risk and therefore might pose the most serious ecological risk in the soils of P. praecox standsin Lin' an. In addition, the integrated factor potential ecological risk analysis suggested a slight risk to local ecosystem originated from heavy metal contamination in the soils of P. praecox stands in Lin'an.