Alpha-lipoic acid (alpha-LA) is an antioxidant used for the treatment of a variety of diseases, including liver cirrhosis, heavy metal poisoining, and diabetic polyneuropathy. In addition to its protective effect against oxidative stress, alpha-LA induces apoptosis in different cancer cells types. However, whether alpha-LA acid induces apoptosis of hepatoma cells is unknown. Herein, we investigated whether alpha-LA induces apoptosis in two different hepatoma cell lines FaO and HepG2. The results showed that alpha-LA inhibits the growth of both cell lines as indicated by the reduction in cell number, the reduced expression of cyclin A and the increased levels of the cyclin/CDKs inhibitors, p27(Kip1) and p21(Cip1). Cell cycle arrest was associated with cell loss, and DNA laddering indicative of apoptosis. Apoptosis was preceded by increased generation of reactive oxygen species, and associated with p53 activation, increased expression of Bax, release of cytochrome c from mitochondria, caspases activation, decreased levels of survivin, induction of pro-apoptotic signaling (i.e JNK) and inhibition of anti-apoptotic signaling (i.e. PKB/Akt) pathways. In conclusion, this study provides evidence that alpha-LA induces apoptosis in hepatoma cells, describes a possible sequence of molecular events underlying its lethal effect, and suggests that it may prove useful in liver cancer therapy.

Background: Evidence suggests that sedentary behaviour (SB) is associated with poor health outcomes. SB at any age may have significant consequences for health and well-being and interventions targeting SB are accumulating. Therefore, the need to review the effects of multicomponent, complex interventions that incorporate effective strategies to reduce SB are essential. Methods: A systematic review and meta-analysis were conducted investigating the impact of interventions targeting SB across the lifespan. Six databases were searched and two review authors independently screened studies for eligibility, completed data extraction and assessed the risk of bias and complexity of each of the included studies. Results: A total of 77 adult studies (n=62, RCTs) and 84 studies (n=62, RCTs) in children were included. The findings demonstrated that interventions in adults when compared to active controls resulted in non-significant reductions in SB, although when compared to inactive controls significant reductions were found in both the short (MD-56.86; 95%CI-74.10,-39.63; n=4632; I 2 83%) and medium-to-long term (MD-20.14; 95%CI-34.13,-6.16; n=4537; I 2 65%). The findings demonstrated that interventions in children when compared to active controls may lead to relevant reductions in daily sedentary time in the short-term (MD-59.90; 95%CI-102.16,-17.65; n=267; I 2 86%), while interventions in children when compared to inactive controls may lead to relevant reductions in the short-term (MD-25.86; 95%CI-40.77,-10.96; n=9480; I 2 98%) and medium-to-long term (MD-14.02; 95%CI-19.49,-8.55; n=41, 138; I 2 98%). The assessment of complexity suggested that interventions may need to be suitably complex to address the challenges of a complex behaviour such as SB, but demonstrated that a higher complexity score is not necessarily associated with better outcomes in terms of sustained long-term changes.

BackgroundOlder adults are the fastest growing segment of the world‘s population. Recent evidence indicates that excessive sitting time is harmful to health, independent of meeting the recommended moderate to vigorous physical activity (PA) guidelines. The SITLESS project aims to determine whether exercise referral schemes (ERS) can be enhanced by self-management strategies (SMSs) to reduce sedentary behaviour (SB), increase PA and improve health, quality of life and function in the long term, as well as psychosocial outcomes in community-dwelling older European citizens from four countries, within a three-armed pragmatic randomised controlled trial, compared with ERS alone and also with general recommendations about PA.MethodsA total of 1338 older adults will be included in this study, recruited from four European countries through different existing primary prevention pathways. Participants will be randomly allocated into an ERS of 16 weeks (32 sessions, 45–60 min per session), ERS enhanced by seven sessions of SMSs and four telephone prompts, or a control group. Outcomes will be assessed at baseline, month 4 (end of ERS intervention), month 16 (12 months post intervention) and month 22 (18 months post intervention). Primary outcomes will include measures of SB (time spent sedentary) and PA (counts per minute). Secondary outcomes will include muscle and physical function, health economics’ related outcomes, anthropometry, quality of life, social networks, anxiety and depressive symptoms, disability, fear of falling, executive function and fatigue. A process evaluation will be conducted throughout the trial. The full analysis set will follow an intention-to-treat principle and will include all randomised participants for whom a baseline assessment is conducted. The study hypothesis will be tested with mixed linear models with repeated measures, to assess changes in the main outcomes (SB and PA) over time (baseline to month 22) and between study arms.DiscussionThe findings of this study may help inform the design and implementation of more effective interventions to reduce SB and increase PA levels, and hence improve long-term health outcomes in the older adult population. SITLESS aims to support policy-makers in deciding how or whether ERS should be further implemented or restructured in order to increase its adherence, impact and cost-effectiveness.Trial registrationClinicalTrials.gov, NCT02629666. Registered 19 November 2015.Electronic supplementary materialThe online version of this article (doi:10.1186/s13063-017-1956-x) contains supplementary material, which is available to authorized users.

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This survey reviews theoretical and empirical evidence on the impact of insularity on regional economic development. Far from being a mere geographical condition, insularity can be regarded as a permanent phenomenon of economic and social peripheralization that prevents islands to reach the goals of sustainable development that are reached by the mainland. Even if the issue of the consequences of insularity on economic development is garnering greater interest in light of the growing recognition of the significant economic disadvantage faced by islands, both the theoretical and empirical literature in this regard are fragmented. More importantly, the effects of insularity on economic development are not disentangled from similar conditions such as remoteness, smallness and peripherality. The survey focus as well on the two-sided nature of insularity, since if it is true that islands suffer from permanent handicaps, adequate policy interventions may not only mitigate insularity effect, but also transform insularity into an asset leading a great potential for growth. Finally, some policy suggestions are drawn, highlighting the need for custom-tailored policy measures.