The loss of muscle mass and function with age, termed sarcopenia, is an inevitable process, which has a significant impact on quality of life. During ageing we observe a progressive loss of total muscle fibres and a reduction in cross-sectional area of the remaining fibres, resulting in a significant reduction in force output. The mechanisms which underpin sarcopenia are complex and poorly understood, ranging from inflammation, dysregulation of protein metabolism and denervation. However, there is significant evidence to demonstrate that modified ROS generation, redox dis-homeostasis and mitochondrial dysfunction may have an important role to play. Based on this, significant interest and research has interrogated potential ROS-targeted therapies, ranging from nutritional-based interventions such as vitamin E/C, polyphenols (resveratrol) and targeted pharmacological compounds, using molecules such as SS-31 and MitoQ. MK-125 order In this review we evaluate these approaches to target aberrant age-related ROS generation and the impact on muscle mass and function.Background Introduction of pro-angiogenic cells into tissue-engineered (TE) constructs (prevascularisation) is a promising approach to overcome delayed neovascularisation of such constructs post-implantation. Accordingly, in this study, we examined the contribution of human dermal microvascular endothelial cells (HDMECs) and human dermal fibroblasts (HDFs) alone and in combination on the formation of new blood vessels in ex-ovo chick chorioallantoic membrane (CAM) assay. Methods Poly-3-hydroxybutyrate-co-3-hydroxyvalerate (PHBV) and polycaprolactone (PCL) were first examined in terms of their physical, mechanical, and biological performances. The effect of gelatin coating and co-culture conditions on enhancing endothelial cell viability and growth was then investigated. Finally, the angiogenic potential of HDMECs and HDFs were assessed macroscopically and histologically after seeding on simple electrospun PHBV scaffolds either in isolation or in indirect co-culture using an ex-ovo CAM assay. Results The results demonstrated that PHBV was slightly more favourable than PCL for HDMECs in terms of cell metabolic activity. The gelatin coating of PHBV scaffolds and co-culture of HDMECs with HDFs both showed a positive impact on HDMECs viability and growth. Both cell types induced angiogenesis over 7 days in the CAM assay either in isolation or in co-culture. The introduction of HDMECs to the scaffolds resulted in the production of more blood vessels in the area of implantation than the introduction of HDFs, but the co-culture of HDMECs and HDFs gave the most significant angiogenic activity. Conclusion Our findings showed that the in vitro prevascularisation of TE constructs with HDMECs and HDFs alone or in co-culture promotes angiogenesis in implantable TE constructs.Background Stroke stands among the most leading causes of mortality worldwide. Although modifiable risk factors for stroke have been identified, current risk factors do not sufficiently explain the risk in young patients. Previous studies have postulated an association between infection by Helicobacter pylori (HP) and stroke. Objective To investigate the association between HP infection and stroke by using a systematic review and meta-analysis approach. Methods Four electronic search engines/libraries were systematically searched for relevant observational studies. Studies were screened for eligibility and data were extracted. The odds ratio (OR) and 95% confidence interval (95% CI) were combined under the random-effect model. The protocol was registered in PROSPERO (CRD42019123689). Results Among the included studies, 25 studies were analyzed for anti-HP IgG, 9 studies were for anti-Cag A, and 6 studies were for the C-urea breath test. The results showed that positive anti-HP IgG was significantly associated with an increased risk of stroke [OR (95% CI) = 1.43 (1.25-1.46)]. Similarly, both antiCag A and C-urea breath test were significantly associated with an increased risk of stroke with [OR (95% CI) = 1.77 (1.25-2.49)], and [OR (95% CI) = 2.21 (1.33-3.66)], respectively. Furthermore, our results indicated that positive anti-HP IgG was associated with stroke caused by atherothrombosis and small artery disease. Conclusions This study suggests that HP infection is significantly associated with increased risk of stroke. However, more well-designed studies are required to investigate if early HP eradication might decrease the incidence of stroke.Amyotrophic lateral sclerosis (ALS) and hereditary spastic paraplegia (HSP) are motor neuron diseases sharing clinical, pathological, and genetic similarities. While biallelic SPG7 mutations are known to cause recessively inherited HSP, heterozygous SPG7 mutations have repeatedly been identified in HSP and recently also in ALS cases. However, the frequency and clinical impact of rare SPG7 variants have not been studied in a larger ALS cohort. Here, whole-exome (WES) or targeted SPG7 sequencing was done in a cohort of 214 European ALS patients. The consequences of a splice site variant were analyzed on the mRNA level. The resulting protein alterations were visualized in a crystal structure model. All patients were subjected to clinical, electrophysiological, and neuroradiological characterization. In 9 of 214 (4.2%) ALS cases, we identified five different rare heterozygous SPG7 variants, all of which were previously reported in patients with HSP or ALS. All detected SPG7 variants affect the AAA+ domain of the encoded mitochondrial metalloprotease paraplegin and impair its stability or function according to predictions from mRNA analysis or crystal structure modeling. ALS patients with SPG7 mutations more frequently presented with cerebellar symptoms, flail arm or leg syndrome compared to those without SPG7 mutations, and showed a partial clinical overlap with HSP. Brain MRI findings in SPG7 mutation carriers included cerebellar atrophy and patterns suggestive of frontotemporal dementia. Collectively, our findings suggest that SPG7 acts as a genetic risk factor for ALS. ALS patients carrying SPG7 mutations present with distinct features overlapping with HSP, particularly regarding cerebellar findings.