Cold atmospheric plasma (CAP) treatment has been proposed as a potentially innovative therapeutic tool in the biomedical field, notably for cancer due to its proposed toxic selectivity on cancer ...cells versus healthy cells. In the present study, we addressed the relevance of three-dimensional organoid technology to investigate the biological effects of CAP on normal epithelial stem cells and tumor cells isolated from mouse small intestine. CAP treatment exerted dose-dependent cytotoxicity on normal organoids and induced major transcriptomic changes associated with the global response to oxidative stress, fetal-like regeneration reprogramming, and apoptosis-mediated cell death. Moreover, we explored the potential selectivity of CAP on tumor-like Apc-deficient versus normal organoids in the same genetic background. Unexpectedly, tumor organoids exhibited higher resistance to CAP treatment, correlating with higher antioxidant activity at baseline as compared to normal organoids. This pilot study suggests that the ex vivo culture system could be a relevant alternative model to further investigate translational medical applications of CAP technology.
Background
Alcohol‐related liver disease (ALD) represents a major cause of death worldwide, and unfortunately, most patients are diagnosed at an advanced stage of the disease, which is related to ...poorer outcomes. Liver biopsy has historically been the gold standard for identifying advanced hepatic fibrosis, but this approach has several limitations, including invasiveness, low applicability, sampling variability, and cost.
Main Text
In order to detect earlier features of advanced liver fibrosis, surrogate biomarkers and techniques have been developed. While these were initially developed for chronic liver diseases such as viral hepatitis and nonalcoholic fatty liver disease (NAFLD), their performance in ALD has also been recently studied. Among the noninvasive surrogate markers and techniques used to detect liver fibrosis, the Enhanced Liver Fibrosis test, FibroTest, and Transient Elastography are the most accurate and validated techniques. In this review, we summarize the current status of the noninvasive assessment of liver disease in ALD and provide a synthesis of how these noninvasive tools can be used in clinical practice. Finally, we briefly outline novel biomarkers that are currently being investigated and discuss future directions and new opportunities in the noninvasive diagnosis of ALD.
Hypoxia depresses myocardial contractility in vitro but does not affect or may even improve indices of myocardial performance in vivo, possibly through associated changes in autonomic nervous system ...tone. The aim of this study was to explore the effects of hypoxic breathing on speckle-tracking echocardiographic indices of left ventricular function, with and without β1-adrenergic inhibition.
Speckle-tracking echocardiography was performed in 21 healthy volunteers in normoxia and after 30 min of hypoxic breathing (fraction of inspired oxygen, 0.12). Measurements were also obtained after the administration of atropine in normoxia (n = 21) and after bisoprolol intake in normoxia (n = 6) and in hypoxia (n = 10).
Hypoxia increased heart rate (from 68 ± 11 to 74 ± 9 beats/min, P = .001), without changing mean blood pressure (P = NS), and decreased total peripheral resistance (P = .003). Myocardial deformation magnitude increased (circumferential strain, -19.6 ± 1.9% vs -21.2 ± 2.5%; radial strain, 19.2 ± 3.7% vs 22.6 ± 4.1%, P < .05; longitudinal and circumferential strain rate, -0.88 ± 0.11 vs -0.99 ± 0.15 sec(-1) and -1.03 ± 0.16 vs -1.18 ± 0.18 sec(-1), respectively, P < .05 for both; peak twist, 8.98 ± 3.2° vs 11.1 ± 2.9°, P < .05). Except for peak twist, these deformation parameters were correlated with total peripheral resistance (P < .05). Atropine increased only longitudinal strain rate magnitude (-0.88 ± 0.11 vs -0.97 ± 0.14 sec(-1), P < .05). The increased magnitude of myocardial deformation persisted in hypoxia under bisoprolol (P < .05). In normoxia, bisoprolol decreased heart rate (73 ± 10 vs 54 ± 7 beats/min, P = .0005), mean blood pressure (88 ± 7 vs 81 ± 4 mm Hg, P = .0027), without altering deformation.
Hypoxic breathing increases left ventricular deformation magnitude in normal subjects, and this effect may not be attributed to hypoxia-induced tachycardia or β1-adrenergic pathway changes but to hypoxia-induced systemic vasodilation.
Abstract
Background and study aims
Nonalcoholic steatohepatitis (NASH) is a leading cause of chronic liver disease worldwide with limited treatment options. Duodenal mucosal resurfacing (DMR) has ...been associated with improvement in glycaemic parameters and liver function tests (LFTs) in type 2 diabetes. This study aimed to assess the effect of DMR in patients with NASH.
Patients and methods
This was a single-center, open-label pilot study. Patients with definite, biopsy-proven NASH (nonalcoholic fatty liver disease activity score NAS ≥ 4) underwent a single DMR procedure followed by a 2-week postprocedural diet, without lifestyle intervention. The primary outcome was either resolution of NASH with no worsening of fibrosis or improvement in fibrosis (≥ 1 stage) with no worsening of NASH at 12 months. Secondary outcomes were changes in key histological parameters of NASH, surrogate markers of fibrosis, LFTs, and metabolic factors at 12 months.
Results
From 2017 to 2019, 14 patients underwent successful DMR, of whom 11 were included in the analysis. After 12 months, no resolution of NASH was observed, while three patients (27 %) had marginal improvement in fibrosis with no worsening of NASH. Serious adverse events related to the procedure were reported in two patients out of 14 (14 %). Neither weight loss nor improvement in NAS score, or in the other secondary outcomes, were observed at 12 months.
Conclusions
In this small and heterogenous study population, we found that DMR, in the absence of lifestyle intervention, did not induce NASH resolution and marginally improved liver fibrosis at 12 months.
Lifestyle modification comprising calorie restriction (CR) and increased physical activity enabling weight loss is the first-line of treatment for non-alcoholic fatty liver disease (NAFLD). However, ...CR alone is not optimal and evidence suggests that dietary pattern and composition are also critical in NAFLD management. Accordingly, high consumption of red and processed meat, saturated fat, added sugar, and sweetened beverages are associated with an increased risk of developing NAFLD and hepatocellular carcinoma, while other foods and compounds such as fish, olive oil, and polyphenols are, in contrast, beneficial for metabolic disorders. Therefore, several dietary interventions have been studied in order to determine which strategy would be the most beneficial for NAFLD. The evidence regarding the effectiveness of different dietary interventions such as low carbohydrate/low-fat diet, time-restricted eating diet, CR, and the well-studied Mediterranean diet is summarized.
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