Alzheimer’s disease improved through the activity of mitochondrial chain complexes and their gene expression in rats by boswellic acid

Metabolic Brain Disease - The foremost neurodegenerative disease is Alzheimer’s (AD), which is characterized as a gradual decrease in memory, cognitive function, and also personal changes...     

Reliability of the Mangled Extremity Severity Score in the Management of Peripheral Vascular Injuries in Children: A Retrospective Review

This study was aimed to evaluate different management modalities for peripheral vascular trauma in children, with the aid of the Mangled Extremity Severity Score (MESS). A single-center retrospective analysis took place between 2010 and 2017 at University Hospitals, having emergencies and critical care centers. Different types of vascular repair were adopted by skillful vascular experts and highly trained pediatric surgeons. Patients were divided into three different age groups. Group I included those children between 5 and 10 years; group II involved pediatrics between 11 and 15 years; while children between 16 and 21 years participated in group III. We recruited 183 children with peripheral vascular injuries. They were 87% males and 13% females, with the mean age of 14.72 ± 04. Arteriorrhaphy was performed in 32%; end-to-end anastomosis and natural vein graft were adopted in 18% and 29% respectively. On the other hand, 20% underwent bypass surgery. The age groups I and II are highly susceptible to penetrating trauma ( p  = 0.001), while patients with an extreme age (i.e., group III) are more susceptible to blunt injury ( p  = 0.001). The MESS has a significant correlation to both age groups I and II ( p  = 0.001). Vein patch angioplasty and end-to-end primary repair should be adopted as the main treatment options for the repair of extremity vascular injuries in children. Moreover, other treatment modalities, such as repair with autologous vein graft/bypass surgery, may be adopted whenever possible. They are cost-effective, reliable, and simple techniques with fewer postoperative complication, especially in poor/limited resources.     

B7h is required for T cell activation, differentiation, and effector function

T helper (Th) cell activation, differentiation, and immune function are regulated by costimulatory molecules. Inducible costimulator (ICOS) is a recently identified costimulatory receptor expressed on activated T cells. A ligand for ICOS, B7h, is expressed on B cells and other types of antigen-presenting cells (APC). Although ICOS has been shown to be essential in T cell activation and differentiation, the regulatory roles of B7h at different stages of T cell immune responses have not been examined genetically. In this study, we generated and analyzed B7h-deficient mice. We present evidence that B7h is the only ligand for ICOS, and ICOS, its only corresponding receptor. Th cells, when activated with B7h-deficient APC, exhibited reduced proliferation and IL-2 production. In addition, Th cells produced significantly reduced amounts of IL-4 and -13 after differentiation at the presence of B7h-/- APC. This cytokine defect was associated with a deficiency in c-Maf expression and could be rescued completely by c-Maf overexpression in T cells. Furthermore, we showed that effector T cells, when restimulated in the presence of B7h-deficient APC, exhibited reduced Th2 cytokine production. Therefore, B7h is required for proper Th cell activation, differentiation, and effector cytokine expression.     

Ultrasound detection of spontaneous hepato-cellular carcinomas in X/myc bitransgenic mice.

AIMS: To evaluate trans-abdominal ultrasound for the detection of Hepatocellular carcinoma (HCC) in a bitrasgenic murine (X/myc) model using a commercially available high-frequency ultrasound unit. METHODS: Sixty-one female animals were included in this study. These animals were submitted to a single ultrasound examination of the liver under general anesthesia (isoflurane), and then euthanized. Results of ultrasound were compared with necropsy and histopathology. RESULTS: The lesions demonstrated a fairly consistent aspect (oval- or round-shaped, well-defined hypoechoic homogeneous lesions), and lesions as small as 2 mm were identified. For detection of hepatic nodules per mouse the sensitivity was 75%, the specificity was 100% and the accuracy was 88.5%. For detection of hepatic focal lesions per lesions the overall sensitivity was 60%, the specificity was 97%, and the accuracy was 75.9%. Contrast-enhanced harmonic ultrasound imaging did not improve the identification of the lesions in our experimental conditions. CONCLUSION: High-frequency ultrasound appears to be an efficient tool allowing new possibilities to use this animal model and evaluate new therapies in longitudinal studies, which are much more powerful.     

Tdentification of a new target region on the long arm of chromosome 7 in gastric carcinoma by loss of heterozygosity

AIM: To define the common deleted region on the long arm of haman chromosome 7q linked to primary gastric carcinomas in Chinese by loss of heterozygosity (LOH)and its clinical significance.METHODS: Nine microsatellite markers distributed over chromosome 7q with an average marker density of 10cM were used to examine 70 primary gastric carcinomas for LOH by PCR amplification. The PCR products were separated by electrophoresis on polyacrylamide gel.Genescan and Genotyper soft-wares were used to analyze LOH.RESULTS: LOH with at least one marker on 7q occurred in 34.3% (12/50) of the tumors. Among them, LOH at D7S486 and D7S798 was higher in 24.0% (24/70) and 19.2% (5/26), respectively. By statistical analysis we also observed an obvious genotype-phenotype correlation on 7q (P＜0.05). The frequency of LOH at D7S486 in patients with lymph node metastasis was significantly higher than that in those without lymph node metastasis (P= 0.015).CONCLUSION: The high incidence of LOH at D7S486and its correlation with poorer prognosis suggest that there might be putative tumor suppressor genes in this region involved in the tumorigenesis and progression of gastric carcinoma.     

The Prevalence and Symptom Profile of Asthma–COPD Overlap: The HUNT Study

The concept of asthma and COPD as separate conditions has been questioned, and the term asthma–COPD overlap syndrome has been introduced. We assessed the prevalence, symptoms, and lifestyle factors of asthma–COPD overlap (ACO) in a large Norwegian population-based study.

From 2006 to 2008, a total of 50,777 residents of Nord-Trøndelag participated in the Nord-Trøndelag Health Study, Norway. They completed questionnaires regarding respiratory symptoms, disease status, and medication use. We estimated the prevalence and 95% confidence intervals of ACO. Additionally, spirometry was used to estimate the prevalence of ACO in a subgroup.

The prevalence of self-reported ACO was 1.9%, and in age groups <40, 40–60 and ≥60 years it was 0.7%, 1.4%, and 3.2%, respectively. Among those reporting COPD, the proportion of ACO was 0.56. In the spirometry subgroup when ACO was defined as doctor diagnosed asthma ever and FEV₁/FVC < 0.70, the prevalence of ACO was 2.0%. All respiratory symptoms, separately or in combination, as well as medication use were reported most frequently in those with ACO compared to the other groups. Strikingly, we observed a two-fold higher proportion of allergic rhinitis in ACO compared to COPD only.

In this Norwegian population, the prevalence of self-reported ACO was 1.9%, and the corresponding proportion of ACO among those with COPD was 0.56. Participants with ACO generally had the highest proportions of respiratory symptoms compared to asthma or COPD.     

Novel ACOX1 mutations in two siblings with peroxisomal acyl-CoA oxidase deficiency

Peroxisomal acyl-CoA oxidase (ACOX1) deficiency is a rare autosomal recessive single enzyme deficiency characterized by hypotonia, seizures, failure to thrive, developmental delay, and neurological regression starting from approximately 3 years of age.Here, we report two siblings with ACOX1 deficiency born to non-consanguineous Japanese parents. They showed mild global developmental delay from infancy and began to regress at 5 years 10 months and 5 years 6 months of age respectively. They gradually manifested with cerebellar ataxia, dysarthria, pyramidal signs, and dysphasia. Brain MRI revealed T2 high-intensity areas in the cerebellar white matter, bilateral middle cerebellar peduncle, and transverse tracts of the pons, followed by progressive atrophy of these areas.Intriguingly, the ratios of C24:0, C25:0, and C26:0 to C22:0 in plasma, which usually increase in ACOX1 deficiency were within normal ranges in both patients. On the other hand, whole exome sequencing revealed novel compound heterozygous variants in ACOX1: a frameshift variant (c.160delC:p.Leu54Serfs*18) and a missense variant (c.1259 T > C:p.Phe420Ser). The plasma concentration of individual very long chain fatty acids (C24:0, C25:0, and C26:0) was elevated, and we found that peroxisomes in fibroblasts of the patients were larger in size and fewer in number as previously reported in patients with ACOX1 deficiency. Furthermore, the C24:0 β-oxidation activity was dramatically reduced.Our findings suggest that the elevation of individual plasma very long chain fatty acids concentration, genetic analysis including whole exome analysis, and biochemical studies on the patient’s fibroblasts should be considered for the correct diagnosis of ACOX1 deficiency.