Poly(β-Amino Ester)-Nanoparticle Mediated Transfection of Retinal Pigment Epithelial Cells In Vitro and In Vivo

A variety of genetic diseases in the retina, including retinitis pigmentosa and leber congenital amaurosis, might be excellent targets for gene delivery as treatment. A major challenge in non-viral gene delivery remains finding a safe and effective delivery system. Poly(beta-amino ester)s (PBAEs) have shown great potential as gene delivery reagents because they are easily synthesized and they transfect a wide variety of cell types with high efficacy in vitro. We synthesized a combinatorial library of PBAEs and evaluated them for transfection efficacy and toxicity in retinal pigment epithelial (ARPE-19) cells to identify lead polymer structures and transfection formulations. Our optimal polymer (B5-S5-E7 at 60 w/w polymer∶DNA ratio) transfected ARPE-19 cells with 44±5% transfection efficacy, significantly higher than with optimized formulations of leading commercially available reagents Lipofectamine 2000 (26±7%) and X-tremeGENE HP DNA (22±6%); (p<0.001 for both). Ten formulations exceeded 30% transfection efficacy. This high non-viral efficacy was achieved with comparable cytotoxicity (23±6%) to controls; optimized formulations of Lipofectamine 2000 and X-tremeGENE HP DNA showed 15±3% and 32±9% toxicity respectively (p>0.05 for both). Our optimal polymer was also significantly better than a gold standard polymeric transfection reagent, branched 25 kDa polyethyleneimine (PEI), which achieved only 8±1% transfection efficacy with 25±6% cytotoxicity. Subretinal injections using lyophilized GFP-PBAE nanoparticles resulted in 1.1±1×103-fold and 1.5±0.7×103-fold increased GFP expression in the retinal pigment epithelium (RPE)/choroid and neural retina respectively, compared to injection of DNA alone (p = 0.003 for RPE/choroid, p<0.001 for neural retina). The successful transfection of the RPE in vivo suggests that these nanoparticles could be used to study a number of genetic diseases in the laboratory with the potential to treat debilitating eye diseases

The thrombotic potential of oral pathogens

In recent times the concept of infectious agents playing a role in cardiovascular disease has attracted much attention. Chronic oral disease such as periodontitis, provides a plausible route for entry of bacteria to the circulation. Upon entry to the circulation, the oral bacteria interact with platelets. It has been proposed that their ability to induce platelet aggregation and support platelet adhesion is a critical step in the pathogenesis of the infection process. Many published studies have demonstrated multiple mechanisms through which oral bacteria are able to bind to and activate platelets. This paper will review the various mechanisms oral bacteria use to interact with platelets

Enteropathy-associated T cell lymphoma subtypes are characterized by loss of function of SETD2

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Effect of walking on circadian rhythms and sleep quality of patients with lung cancer: A randomised controlled trial

Background:Sleep disturbances and poor rest-activity rhythms, which can reduce the quality of life, are highly prevalent among patients with lung cancer.Methods:This trial investigated the effects of a 12-week exercise intervention including home-based walking exercise training and weekly exercise counseling on 111 lung cancer patients. Participants were randomly allocated to receive the intervention or usual-care. Outcomes included objective sleep (total sleep time, TST; sleep efficiency, SE; sleep onset latency, SOL; and wake after sleep onset, WASO), subjective sleep (Pittsburgh Sleep Quality Index, PSQI), and rest-activity rhythms (r24 and I<O). Outcomes were assessed at baseline and 3 and 6 months after intervention.Results:The PSQI (Wald χ 2 =15.16, P=0.001) and TST (Wald χ 2 =7.59, P=0.023) of the patients in the exercise group significantly improved 3 and 6 months after intervention. The moderating effect of I<O on TST was significant (β of group × I<O=3.70, P=0.032).Conclusions:The walking program is an effective intervention for improving the subjective and objective sleep quality of lung cancer patients and can be considered an optional component of lung cancer rehabilitation.Link_to_subscribed_fulltex

Influence of periodontal disease on risk of dementia: a systematic literature review and a meta-analysis

This is an accepted manuscript of an article published by Springer in European Journal of Epidemiology on 12/06/2020, available online: https://doi.org/10.1007/s10654-020-00648-x The accepted version of the publication may differ from the final published version.Periodontal disease (PD) is common and increases cardiovascular diseases. However, it is unclear whether PD is associated with increased risk of dementia. We carried out a systematic review and meta-analysis to investigate the influence of PD on dementia. We projected the number of dementia cases to be saved by reducing PD prevalence in the world. We searched cohort and case–control studies reporting the association of PD with all dementia (or any specific type of dementia) through PubMed, MEDLINE, PsycINFO, SocINDEX, CINHAL, and CNKI until 7th November 2018. Five cohorts and seven case–control studies were identified for review. We pooled eligible data to calculate relative risk (RR) of dementia in relation to PD and computed the number of dementia cases saved through reducing PD prevalence. Of 12 studies, six were undertaken in Asia, four in Europe and two in America. Eleven studies showed a positive association between PD and the risk of dementia, of which 10 were significant, and one reported a non-significant inverse association. Overall their quality was good. Pooled RR of dementia in relation to PD from all high quality studies was 1.38 (95%CI 1.01–1.90); in the five cohorts was 1.18 (1.06–1.31) and in the two case–control studies 2.25 (1.48–3.42). A 50% reduction in the current prevalence of 20% of PD in the population could save 850,000 (630,000–1,420,000) patients with dementia in the world. PD could increase the risk of incident dementia. Preventing and treating PD could contribute to controlling the global epidemic of dementia.Professor Ruoling Chen and Dr Jie Tang thank an EU Grant from Horizon 2020 MSCA – DEMAIRPO #799247. Dr Kaarin Anstey is funded by NHMRC Fellowship #1102694. Dr Wu is the recipient of BBSRC [BB/P004695/1] and NIA [1R01AG049321-01A1] Grant for aging research. Dr Yuyou Yao, Associate Professor of Anhui Medical University, China is a visiting scholar at the Faculty of Education, Health and Wellbeing, University of Wolverhampton to support this study and has made valuable comments on the manuscript.Published versio

Are Chronic periodontitis and gingivitis associated with dementia? A nationwide, retrospective, matched-cohort study in Taiwan

[[abstract]]Background: Chronic periodontitis and gingivitis are associated with various diseases; however, their impact on dementia is yet to be elucidated. This study is aimed at investigating the association between chronic periodontitis and gingivitis, and the risk of developing dementia. Methods: A total of 2,207 patients, with newly diagnosed chronic periodontitis and gingivitis between January 1, 2000 and December 31, 2000, were selected from the National Health Insurance Research Database of Taiwan, along with 6,621 controls matched for sex and age. After adjusting for confounding factors, Cox proportional hazards analysis was used to compare the risk of developing dementia during the 10-year follow-up period. Results: Of the study subjects, 25 (1.13%) developed dementia compared to 61 (0.92%) in the control group. Cox proportional hazards regression analysis revealed that the study subjects were more likely to develop dementia (hazard ratio (HR) 2.085, 95% CI 1.552-4.156, p < 0.001). After adjusting for sex, age, monthly income, urbanization level, geographic region, and comorbidities, the HR for dementia was 2.54 (95% CI 1.297-3.352, p = 0.002). Conclusions: Patients with chronic periodontitis and gingivitis have a higher risk of developing dementia. However, further studies on other large or national data sets are required to support the current findings