The Experiences of People Who Smoke With Type 2 Diabetes: A Qualitative Interview Study Using the Capability, Opportunity, Motivation, and Behavior Model.

ABSTRACT: Few interventions to support smoking cessation include content specifically about diabetes. This is problematic, as people with diabetes face unique challenges when they stop smoking. The purpose of this study was to understand patients' needs and challenges in relation to smoking with Type 2 diabetes and assess the acceptability of a text message intervention to support smoking cessation. People who smoke and have Type 2 diabetes in the United States and the United Kingdom were recruited to participate in semistructured interviews (n = 20), guided by the Capability, Opportunity, Motivation, and Behavior model. A combination of inductive and deductive approaches with framework analysis was used to analyze the data. Results indicated that the participants' experiences related to the constructs of the Capability, Opportunity, Motivation, and Behavior model and the categories of mental health and diabetes distress were also notable parts of their experiences. Results can be used to guide intervention development in this unique group.

Effectiveness of interventions for improving physical activity level in working-age people (aged 18-60 years) with type 2 diabetes: a systematic review and meta-analysis.

BACKGROUND: The increasing prevalence of type 2 diabetes in working-age people imposes a substantial societal burden. Although physical activity is crucial for diabetes management, limited evidence exists to inform optimal strategies for promoting physical activity in this population. We aimed to determine and compare the effectiveness of interventions for increasing physical activity level in working-age people with diabetes. METHODS: In this systematic review and meta-analysis, we searched Web of Science, the Cochrane Library, Medline, Embase, PsycINFO, ClinicalTrials.gov, and ICTRP for papers published between Jan 1, 1931, and June 30, 2022, in English. Search terms included "physical activity", "diabetes", and "randomised controlled trial". We included trials reporting the effects of interventions on physical activity level (objectively or subjectively measured) in people with type 2 diabetes aged 18-60 years. Two independent reviewers conducted summary data extraction and quality assessment. We used pairwise random-effects, frequentist network meta-analyses, and meta-regression to obtain pooled effects. Heterogeneity was evaluated using I2 statistic. The risk of bias and certainty of evidence were assessed using the Cochrane risk-of-bias 2 tool and the Grading of Recommendations Assessment, Development, and Evaluation. This study is registered with PROSPERO (CRD42022323165). FINDINGS: We identified 52 trials (6257 participants) from 21 countries (32 Asia, ten North America, eight Europe, one Australia, one Africa). The overall risk of bias was classified as "some concerns" for included studies. Four types of interventions (structured exercise training, physical activity education, psychological intervention, physical activity education plus psychological intervention) were identified. Compared with control groups, the interventions showed significant effects in objectively measured (standardised mean difference 0·77, 95% CI 0·27-1·27, low certainty), subjectively measured (0·88, 0·40-1·35, very low certainty), and overall physical activity (0·82, 0·48-1·16, moderate certainty). Physical activity education exerted large effect in overall physical activity compared with control groups. Psychological intervention exerted large effects in overall physical activity compared with other interventions. Heterogeneity was high (I2=96-97%). Intervention setting (p=0·04) and facilitator (p=0·03) showed effects on heterogeneity. INTERPRETATION: Psychologically modelled education might be the most beneficial way of promoting physical activity. Intervention setting and facilitator type should be considered when designing interventions for improving physical activity level in working-age people with type 2 diabetes. Limitations of this review include restriction to the English language and considerable heterogeneity between studies. FUNDING: King's-China Scholarship Council PhD Scholarship (202108440151).

RASSF tumor suppressor gene family: biological functions and regulation.

Genetic changes through allelic loss and nucleic acid or protein modifications are the main contributors to loss of function of tumor suppressor proteins. In particular, epigenetic silencing of genes by promoter hypermethylation is associated with increased tumor severity and poor survival. The RASSF (Ras association domain family) family of proteins consists of 10 members, many of which are tumor suppressor proteins that undergo loss of expression through promoter methylation in numerous types of cancers such as leukemia, melanoma, breast, prostate, neck, lung, brain, colorectal and kidney cancers. In addition to their tumor suppressor function, RASSF proteins act as scaffolding agents in microtubule stability, regulate mitotic cell division, modulate apoptosis, control cell migration and cell adhesion, and modulate NFκB activity and the duration of inflammation. The ubiquitous functions of these proteins highlight their importance in numerous physiological pathways. In this review, we will focus on the biological roles of the RASSF family members and their regulation.

The tumor suppressor gene, RASSF1A, is essential for protection against inflammation -induced injury.

Ras association domain family protein 1A (RASSF1A) is a tumor suppressor gene silenced in cancer. Here we report that RASSF1A is a novel regulator of intestinal inflammation as Rassf1a(+/-) , Rassf1a(-/-) and an intestinal epithelial cell specific knockout mouse (Rassf1a (IEC-KO) ) rapidly became sick following dextran sulphate sodium (DSS) administration, a chemical inducer of colitis. Rassf1a knockout mice displayed clinical symptoms of inflammatory bowel disease including: increased intestinal permeability, enhanced cytokine/chemokine production, elevated nuclear factor of kappa light polypeptide gene enhancer in B-cells (NFκB) activity, elevated colonic cell death and epithelial cell injury. Furthermore, epithelial restitution/repair was inhibited in DSS-treated Rassf1a(-/-) mice with reduction of several makers of proliferation including Yes associated protein (YAP)-driven proliferation. Surprisingly, tyrosine phosphorylation of YAP was detected which coincided with increased nuclear p73 association, Bax-driven epithelial cell death and p53 accumulation resulting in enhanced apoptosis and poor survival of DSS-treated Rassf1a knockout mice. We can inhibit these events and promote the survival of DSS-treated Rassf1a knockout mice with intraperitoneal injection of the c-Abl and c-Abl related protein tyrosine kinase inhibitor, imatinib/gleevec. However, p53 accumulation was not inhibited by imatinib/gleevec in the Rassf1a(-/-) background which revealed the importance of p53-dependent cell death during intestinal inflammation. These observations suggest that tyrosine phosphorylation of YAP (to drive p73 association and up-regulation of pro-apoptotic genes such as Bax) and accumulation of p53 are consequences of inflammation-induced injury in DSS-treated Rassf1a(-/-) mice. Mechanistically, we can detect robust associations of RASSF1A with membrane proximal Toll-like receptor (TLR) components to suggest that RASSF1A may function to interfere and restrict TLR-driven activation of NFκB. Failure to restrict NFκB resulted in the inflammation-induced DNA damage driven tyrosine phosphorylation of YAP, subsequent p53 accumulation and loss of intestinal epithelial homeostasis.

14-3-3 mediated regulation of the tumor suppressor protein, RASSF1A.

Death receptor-dependent apoptosis is an important mechanism of growth control. It has been demonstrated that Ras association domain family protein 1A (RASSF1A) is a tumor suppressor protein involved in death receptor-dependent apoptosis. However, it is unclear how RASSF1A-mediated cell death is initiated. We have now detailed 14-3-3 dependent regulation of RASSF1A-mediated cell death. We demonstrate that basal association of RASSF1A with 14-3-3 was lost following stimulation with tumor necrosis factor alpha (TNFalpha) or TNFalpha related apoptosis inducing ligand (TRAIL). Subsequent to the loss of 14-3-3 association, RASSF1A associated with modulator of apoptosis (MOAP-1) followed by death receptor association with either TNFalpha receptor 1 (TNF-R1) or TRAIL receptor 1 (TRAIL-R1). 14-3-3 association required basal phosphorylation by the serine/threonine kinase, glycogen synthase kinase 3beta (GSK-3beta), on serine 175, 178, and 179. Mutation of these critical serines resulted in the loss of 14-3-3 association and earlier recruitment of RASSF1A to MOAP-1, TNF-R1, and TRAIL-R1. Furthermore, stable cells containing a triple serine mutant of RASSF1A [serine (S) 175 to alanine (A) [S175A], S178A, and S179A] resulted in increased basal cell death, enhanced Annexin V staining and enhanced cleavage of poly (ADP-ribose) polymerase (PARP) following TNFalpha stimulation when compared to stable cells containing wild type RASSF1A. RASSF1A-mediated cell death is, therefore, tightly controlled by 14-3-3 association.