Folic acid, a water soluble B vitamin, plays an important role in cellular metabolic activities, such as functioning as a cofactor in one‐carbon metabolism for DNA and RNA synthesis as well as ...nucleotide and amino acid biosynthesis in the body. A lack of dietary folic acid can lead to folic acid deficiency and result in several health problems, including macrocytic anemia, elevated plasma homocysteine, cardiovascular disease, birth defects, carcinogenesis, muscle weakness, and walking difficulty. However, the effect of folic acid deficiency on skeletal muscle development and its molecular mechanisms are unknown. We, therefore, investigated the effect of folic acid deficiency on myogenesis in skeletal muscle cells and found that folic acid deficiency induced proliferation inhibition and cell cycle breaking as well as cellular senescence in C2C12 myoblasts, implying that folic acid deficiency influences skeletal muscle development. Folic acid deficiency also inhibited differentiation of C2C12 myoblasts and induced deregulation of the cell cycle exit and many cell cycle regulatory genes. It inhibited expression of muscle‐specific marker MyHC as well as myogenic regulatory factor (myogenin). Moreover, immunocytochemistry and Western blot analyses revealed that DNA damage was more increased in folic acid‐deficient medium‐treated differentiating C2C12 cells. Furthermore, we found that folic acid resupplementation reverses the effect on the cell cycle and senescence in folic acid‐deficient C2C12 myoblasts but does not reverse the differentiation of C2C12 cells. Altogether, the study results suggest that folic acid is necessary for normal development of skeletal muscle cells.
Effect of folic acid resupplementation on the differentiation of C2C12 cells cultured in folic acid‐deficient conditions. We found that folic acid resupplementation reverses the effect on the cell cycle and senescence in folic acid‐deficient C2C12 myoblasts but does not reverse the differentiation of C2C12 cells.
Currently there is no neuroprotective or neurorestorative therapy for Parkinson's disease. Here we report that transient receptor potential vanilloid 1 (TRPV1) on astrocytes mediates endogenous ...production of ciliary neurotrophic factor (CNTF), which prevents the active degeneration of dopamine neurons and leads to behavioural recovery through CNTF receptor alpha (CNTFRα) on nigral dopamine neurons in both the MPP(+)-lesioned or adeno-associated virus α-synuclein rat models of Parkinson's disease. Western blot and immunohistochemical analysis of human post-mortem substantia nigra from Parkinson's disease suggests that this endogenous neuroprotective system (TRPV1 and CNTF on astrocytes, and CNTFRα on dopamine neurons) might have relevance to human Parkinson's disease. Our results suggest that activation of astrocytic TRPV1 activates endogenous neuroprotective machinery in vivo and that it is a novel therapeutic target for the treatment of Parkinson's disease.
Objectives
Recurrence in the late post‐treatment period is relatively common in salivary gland cancer (SGC), but risk factors and survival associated with late recurrence have been rarely studied. We ...investigated the incidence and risk factors of SGC recurrence >5 years after treatment and associated survival.
Design
A retrospective cohort study.
Setting
University hospital.
Participants
A total of 240 patients with previously untreated SGC who underwent definitive treatment.
Main outcome measures
Late recurrence was defined as recurrence at a time point >5 years after treatment. Univariate and multivariable analyses were used to identify the association of clinicopathologic factors with recurrence‐free survival (RFS), cancer‐specific survival (CSS) and late recurrence.
Results
Of the 240 patients, 124 (51.7%) patients developed recurrence during a median follow‐up of 160.0 months (range 121.5–282.2 months). Sixteen (6.7%) patients developed late recurrence; the median time to late recurrence was 92.5 months (range 60.2–138.3 months) after treatment. Multivariable analysis showed that primary site, histologic grade and N classification were independent variables of both RFS and CSS (P < 0.05 each). Extraparenchymal extension was also an independent variable of CSS (P = 0.022). In addition, a non‐parotid tumour location was a significant factor for late recurrence in multivariable analysis (P = 0.017). The median overall survival after the development of late recurrence was 79.7 months (range 0.2–163.4 months), significantly longer than that after early recurrence (19.7 months) (P = 0.043).
Conclusion
Late recurrence occurs in some SGC patients. Long‐term close surveillance may be required for patients with non‐parotid SGC.
Background:
The objective of this study was to determine the prevalence of electrocardiographic (ECG) findings suggestive of sudden cardiac death risk in apparently healthy young Korean men.
...Methods:
We administered questionnaires that elicited personal and family histories and performed ECGs on 10,867 male subjects (mean age, 20.9 years). The subjects with abnormal ECG findings underwent echocardiography, a treadmill test, Holter monitoring, a flecainide provocation test, or an electrophysiologic study (EPS) according to the ECG findings and histories.
Results:
Of the subjects, 5.95% had left ventricular hypertrophy on ECG, but no subjects had hypertrophic cardiomyopathy by echocardiography. The percentage of subjects with a Brugada ECG pattern was 0.90%. We identified one subject with a positive result on the flecainide provocation test. The percentage of subjects with a preexcitation ECG was 0.17%. In two of the subjects, supraventricular tachycardia was induced in the EPS. Of the subjects, 0.05% had epsilon waves, but there were no subjects with arrhythmogenic right ventricular dysplasia/cardiomyopathy by echocardiography. The percentage of subjects with long QT intervals was 0.02%, but there were no arrhythmias on the treadmill test or Holter monitoring.
Conclusions:
The prevalence of a Brugada ECG pattern in apparently healthy young men is higher in Korea than other countries. (PACE 2011; 717–723)
Chronic obstructive pulmonary disease (COPD) acute exacerbations are significant causes of morbidity and mortality. "Frequent exacerbator" phenotypes are considered a distinct subgroup and this ...phenotype has a negative effect on lung function, quality of life, activity, hospital admission, and mortality. We assess inhaler handling technique and adherence, and evaluate risk factors associated with frequent exacerbations in COPD patients.
This study was a cross-sectional, case-control study. We prospectively enrolled 189 COPD patients from Yeungnam University Hospital from January 2018 to November 2018. Subjects were tested regarding their inhaler technique in face-to-face interviews with an advanced practice nurse of inhaler upon study entry. Frequency of moderate to severe COPD exacerbations were reviewed via electronic medical records during 12 months prior to study entry. Frequent exacerbations were defined as ≥2 moderate to severe exacerbations in the prior 12 months. Multivariate logistic regression was performed to identify risk factors for frequent exacerbations.
Among 189 COPD patients, 50 (26.5%) were frequent exacerbators. Based on univariate analyses, body mass index (BMI) < 25 kg/m
, lower forced expiratory volume in 1 s (FEV
), higher mMRC, lower feeling of satisfaction with the inhaler, and any critical errors were potential risk factors for frequent exacerbations. Multivariate logistic regression analyses revealed that BMI < 25 kg/m
(OR, 2.855, 95% CI, 1.247-6.534; p=0.013), higher mMRC (OR, 1.625, 95% CI, 1.072-2.463; p=0.022), and any critical error (OR, 2.020, 95% CI, 1.021-3.999; p=0.044) were risk factors.
Any critical error, BMI < 25 kg/m
and high mMRC are independent risk factors for frequent exacerbations in COPD patients. Careful monitoring and education around inhaler devices, particularly in frequent exacerbators, are important components of COPD treatment.
This study investigated the PKA-dependent inhibitory effect of pycnogenol (Pyc) on lipolysis using ob/ob mice and primary mouse adipocytes. Supplementation of Pyc at 30 mg/kg significantly reduced ...body weight gain and visceral fat mass. The serum and hepatic triglyceride (TG) and total cholesterol (TC) levels were reduced by Pyc supplementation, and high density lipoprotein (HDL)-cholesterol level significantly increased. In addition, hormone sensitive lipase (HSL) and adipose triglyceride lipase (ATGL) mRNA levels increased with Pyc supplementation in adipose tissue of ob/ob mice. The treatment of primary cultured adipocytes with Pyc at 100 μg/mL significantly increased glycerol release, cAMP level by reduction of phosphodiestersae-3B (PDE3B), and HSL levels, but decreased protein levels of perilipin A and fatty acid synthetase (FAS). The PKA inhibitor (H89) clearly blocked the cellular levels of perilipin A and HSL, suggesting that Pyc promotes lipolysis of adipocytes through activation of cAMP-dependent PKA, resulting in induction of HSL and reduction of perilipin A. Therefore, this study may elucidate the possible mechanism of Pyc, which is a candidate for weight loss through stimulation of lipolysis.
The SPEAR (or "FIMS") instrumentation has been used to conduct the first large-scale spectral mapping of diffuse-cosmic far-ultraviolet (FUV; 900-1750 AA) emission, including important diagnostics of ...interstellar hot (10 super(4)-10 super(6) K) and photoionized plasmas, H sub(2), and dust-scattered starlight. The instrumentation's performance has allowed for the unprecedented detection of astrophysical diffuse FUV emission lines. A spectral resolution of l/ lambda 6550 and an imaging resolution of 5, is achieved on-orbit in the Short (900-1150 AA) and Long (1350-1750 AA) bandpass channels within their respective 4.0 x 4'.6 and 7.4 x 4'.3 fields of view. We describe the SPEAR imaging spectrographs, their performance, and the nature and handling of their data.
In this note, we address the problem of transforming a nonlinear system into nonlinear observer canonical form in the extended state-space with the aid of dynamic system extension and introduction of ...virtual outputs. As an intermediate step for the general problem, we consider a restricted structure of dynamic extension, which is obtained, roughly speaking, by adding the chains of integrators to the outputs of original system. We propose sufficient conditions which can be verified using the system dynamics expressed in their original coordinates. An illustrative example is included that demonstrates the advantage of the proposed method over the conventional method.
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