The regulation of miRNAs by reconstituted high-density lipoproteins in diabetes-impaired angiogenesis

Diabetic vascular complications are associated with impaired ischaemia-driven angiogenesis. We recently found that reconstituted high-density lipoproteins (rHDL) rescue diabetes-impaired angiogenesis. microRNAs (miRNAs) regulate angiogenesis and are transported within HDL to sites of injury/repair. The role of miRNAs in the rescue of diabetes-impaired angiogenesis by rHDL is unknown. Using a miRNA array, we found that rHDL inhibits hsa-miR-181c-5p expression in vitro and using a hsa-miR-181c-5p mimic and antimiR identify a novel anti-angiogenic role for miR-181c-5p. miRNA expression was tracked over time post-hindlimb ischaemic induction in diabetic mice. Early post-ischaemia when angiogenesis is important, rHDL suppressed hindlimb mmu-miR-181c-5p. mmu-miR-181c-5p was not detected in the plasma or within HDL, suggesting rHDL specifically targets mmu-miR-181c-5p at the ischaemic site. Three known angiogenic miRNAs (mmu-miR-223-3p, mmu-miR-27b-3p, mmu-miR-92a-3p) were elevated in the HDL fraction of diabetic rHDL-infused mice early post-ischaemia. This was accompanied by a decrease in plasma levels. Only mmu-miR-223-3p levels were elevated in the hindlimb 3 days post-ischaemia, indicating that rHDL regulates mmu-miR-223-3p in a time-dependent and site-specific manner. The early regulation of miRNAs, particularly miR-181c-5p, may underpin the rescue of diabetes-impaired angiogenesis by rHDL and has implications for the treatment of diabetes-related vascular complications

Early Life Exposure to Fructose and Offspring Phenotype: Implications for Long Term Metabolic Homeostasis

The consumption of artificially sweetened processed foods, particularly high in fructose or high fructose corn syrup, has increased significantly in the past few decades. As such, interest into the long term outcomes of consuming high levels of fructose has increased significantly, particularly when the exposure is early in life. Epidemiological and experimental evidence has linked fructose consumption to the metabolic syndrome and associated comorbidities—implicating fructose as a potential factor in the obesity epidemic. Yet, despite the widespread consumption of fructose-containing foods and beverages and the rising incidence of maternal obesity, little attention has been paid to the possible adverse effects of maternal fructose consumption on the developing fetus and long term effects on offspring. In this paper we review studies investigating the effects of fructose intake on metabolic outcomes in both mother and offspring using human and experimental studies

Effects of antiplatelet therapy on stroke risk by brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases: subgroup analyses of the RESTART randomised, open-label trial

Background Findings from the RESTART trial suggest that starting antiplatelet therapy might reduce the risk of recurrent symptomatic intracerebral haemorrhage compared with avoiding antiplatelet therapy. Brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases (such as cerebral microbleeds) are associated with greater risks of recurrent intracerebral haemorrhage. We did subgroup analyses of the RESTART trial to explore whether these brain imaging features modify the effects of antiplatelet therapy

Proceedings of Patient Reported Outcome Measure’s (PROMs) Conference Oxford 2017: Advances in Patient Reported Outcomes Research

A33-Effects of Out-of-Pocket (OOP) Payments and Financial Distress on Quality of Life (QoL) of People with Parkinson’s (PwP) and their Carer

PANC Study (Pancreatitis: A National Cohort Study): national cohort study examining the first 30 days from presentation of acute pancreatitis in the UK

Abstract Background Acute pancreatitis is a common, yet complex, emergency surgical presentation. Multiple guidelines exist and management can vary significantly. The aim of this first UK, multicentre, prospective cohort study was to assess the variation in management of acute pancreatitis to guide resource planning and optimize treatment. Methods All patients aged greater than or equal to 18 years presenting with acute pancreatitis, as per the Atlanta criteria, from March to April 2021 were eligible for inclusion and followed up for 30 days. Anonymized data were uploaded to a secure electronic database in line with local governance approvals. Results A total of 113 hospitals contributed data on 2580 patients, with an equal sex distribution and a mean age of 57 years. The aetiology was gallstones in 50.6 per cent, with idiopathic the next most common (22.4 per cent). In addition to the 7.6 per cent with a diagnosis of chronic pancreatitis, 20.1 per cent of patients had a previous episode of acute pancreatitis. One in 20 patients were classed as having severe pancreatitis, as per the Atlanta criteria. The overall mortality rate was 2.3 per cent at 30 days, but rose to one in three in the severe group. Predictors of death included male sex, increased age, and frailty; previous acute pancreatitis and gallstones as aetiologies were protective. Smoking status and body mass index did not affect death. Conclusion Most patients presenting with acute pancreatitis have a mild, self-limiting disease. Rates of patients with idiopathic pancreatitis are high. Recurrent attacks of pancreatitis are common, but are likely to have reduced risk of death on subsequent admissions. </jats:sec

Primer Sequences and Qiagen QuantiTect Primer Assays™.

<p><b>Abbreviations:</b> HPRT, Hypoxanthine-guanine phosphoribosyltransferase; BMAL1, brain and muscle arnt-like protein 1; Clock, circadian locomotor output cycles kaput; Cry1 and Cry2, cryptochrome 1 & 2; XBP1s/ XBP1t, x-box binding protein spliced & total; GRP78, 78 kDa glucose-regulated protein or Binding immunoglobulin protein(BiP); SREBP1c, Sterol Regulatory Element-Binding Protein 1c; PER1 and PER2, period 1 & 2 genes; SIRT1, sirtuin 1; <i>NFκB (RelA)</i>, nuclear factor kappa-light-chain-enhancer of activated B cells; IL-1β, interleukin 1-beta; NLRP3, NLR family, pyrin domain containing 3, NFKBIA, nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor alpha; GLUT5, facilitated glucose/fructose transporter member 5.</p><p>Primer Sequences and Qiagen QuantiTect Primer Assays™.</p

Prenatal fructose intake induces maternal hepatic endoplasmic reticulum (ER) stress.

<p>Maternal GRP78 and XBP1 mRNA levels at 2 timepoints. XBP1 is expressed as a ratio of spliced to total mRNA levels. Data are presented as means ± S.E.M. All mRNA levels are relative to the geometric mean of housekeeping genes. * p < 0.05 compared to control fed mothers; n = 10 CON, n = 9 FR. CON: Control fed mothers, FR: Fructose fed mothers. E21: embryonic day 21, P10: postnatal day 10. GRP78: 78 kDa glucose-regulated protein, XBP1: X-box binding protein 1.</p

Offspring blood biochemistry.

<p>Data are presented as mean ± SEM. Values with different letters indicates significant differences. NS: not significant; inter’n: interaction; NEFA: non-esterified fatty acid; ALP: Alkaline phosphatase; AST: Aspartate aminotransferase; ALT: alanine aminotransferase, protein: total protein.</p><p>Offspring blood biochemistry.</p