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Diabetic retinopathy is a major eye complication in patients with diabetes mellitus, and it is the leading cause of blindness and visual impairment in the world. Chronic hyperglycemia induces endothelial damage with consequent vascular lesions, resulting in global vasculitis, which affects the small vessels of the retina. These vascular lesions cause ischemic conditions in certain areas of the retina, with a consequent increase in the release of pro-angiogenic mediators. In addition to pharmacological interventions for controlling the blood glycaemic level, the main strategies for treating diabetic retinopathy are the intravitreal injections of drugs, surgical treatments, and vitrectomies. The complexity of diabetic retinopathy is due to its close interactions with different cell types (endothelial cells, astrocytes, and Müller cells). The evaluation of the efficacy of novel pharmacological strategies is mainly performed through in vivo models. However, the use of different animal species leads to heterogenic results and ethical concerns. For these reasons, the development of new and reliable in vitro models, such as cell co-cultures and eye organoids, represents an urgent need in this area of research. This review features an overview of the in vitro models used to date and highlights the advances in technology used to study this pathology. [ABSTRACT FROM AUTHOR]

Background/Objectives: The incidence and prevalence of tricuspid regurgitation (TR) are increasing worldwide. "Traditional" drug therapy with diuretics is often ineffective and the identification of new strategies, including non-pharmacological ones, is an urgent need. The aim of this study was to summarize the results on the efficacy and safety of Cardioband, one of the few approved transcatheter tricuspid valve repair systems, in patients with TR. Methods: Three databases (Medline, Scopus, and CENTRAL) were searched to identify clinical trials and observational studies on the efficacy (primary outcome) and safety (secondary outcome) of Cardioband. A random-effects meta-analysis was performed with R software (version 4.3.3). Survival and freedom from heart failure (HF) hospitalization were estimated with the method of reconstructing individual patient data from Kaplan–Meier curves (IPDfromKM). Results: Eleven studies were included in this systematic review and meta-analysis. Cardioband significantly reduced annulus diameter (−9.31 mm [95% Confidence Interval, CI: −11.47; −7.15]), vena contracta (−6.41 mm [95% CI: −8.34; −4.49]), and effective regurgitant orifice area (EROA) (−0.50 cm2 [95% CI: −0.72; −0.28]) in patients with TR. Cardioband reduced the severity of TR and the extent of heart failure in 91% [95% CI: 85; 97] and 63% [95% CI: 52–75] of patients, respectively. Finally, Cardioband implantation was associated with prolonged survival and freedom from HF hospitalization (80.1% and 57.8% at 24 months, respectively). Conclusions: This study demonstrates that Cardioband implantation leads to cardiac remodeling and mechanical improvements, reduces the severity of TR, and improves quality of life. Therefore, Cardioband is an effective option for the non-pharmacological treatment of TR. [ABSTRACT FROM AUTHOR]

Recently, there has been significant exploration into the utilization of food by-products as natural reservoirs of bioactive substances, particularly in the creation of functional foods naturally enriched with antioxidants. Citrus peels represent a viable option for formulating enhanced olive oils that contribute to a healthier diet, due to their bioactive compound content. This study aimed to (i) ascertain the compositional characteristics of Citrus reticulata olive oil (CrOO) and (ii) assess its nutraceutical properties in rats with metabolic disorder induced by 3 weeks of feeding with a high-fat diet (HFD). The results showed a peculiar phytochemical composition, thanks to the contribution of citrus peels, which are excellent bio-products. In addition, it demonstrated HFD-induced weight gain (18 ± 2% for HFD vs. 13 ± 0.9% for CrOO) and showed protective effects on fasting blood glucose levels (90.2 ± 3.8 mg/dL for HFD vs. 72.3 ± 2.6 for CrOO). Furthermore, a reduction in cardiovascular risk (total cholesterol/HDL cholesterol = 5.0 ± 0.3 for HFD vs. 3.8 ± 0.3 for CrOO) and an improvement in myocardial tissue function were observed, as well as a significant reduction in inflammatory mediators such as iNOS, COX-2, and mPGES-1 in aortic vessel tissues, thus preserving endothelial function at the vascular level. [ABSTRACT FROM AUTHOR]

Intermittent fasting (IF) has been indicated as a valuable alternative to the classical caloric restriction dietary regimen for lowering body weight and preventing obesity-related complications, such as metabolic syndrome and type II diabetes. However, is it effective? In this review article, we analyzed over 50 clinical studies in which IF, conducted by alternate day fasting (ADF) or time-restricted feeding (TRF), was compared with the caloric restriction approach. We evaluated the different roles of IF in treating and preventing human disorders such as metabolic syndrome, type II diabetes, and some types of cancer, as well as the usefulness of IF in reducing body weight and cardiovascular risk factors such as hypertension. Furthermore, we explored the cellular pathways targeted by IF to exert their beneficial effects by activating effector proteins that modulate cell functions and resistance to oxidative stress. In contrast, we investigated concerns regarding human health related to the adoption of IF dietary regimens, highlighting the profound debate surrounding weight loss regimens. We examined and compared several clinical trials to formulate an updated concept regarding IF and its therapeutic potential. [ABSTRACT FROM AUTHOR]

The prevalence of overweight and obesity has progressively increased in the last few years, becoming a real threat to healthcare systems. To date, the clinical management of body weight gain is an unmet medical need, as there are few approved anti‐obesity drugs and most require an extensive monitoring and vigilance due to risk of adverse effects and poor patient adherence/persistence. Growing evidence has shown that the gasotransmitter hydrogen sulfide (H2S) and, therefore, H2S‐donors could have a central role in the prevention and treatment of overweight/obesity. The main natural sources of H2S‐donors are plants from the Alliaceae (garlic and onion), Brassicaceae (e.g., broccoli, cabbage, and wasabi), and Moringaceae botanical families. In particular, polysulfides and isothiocyanates, which slowly release H2S, derive from the hydrolysis of alliin from Alliaceae and glucosinolates from Brassicaceae/Moringaceae, respectively. In this review, we describe the emerging role of endogenous H2S in regulating adipose tissue function and the potential efficacy of natural H2S‐donors in animal models of overweight/obesity, with a final focus on the preliminary results from clinical trials. We conclude that organosulfur‐containing plants and their extracts could be used before or in combination with conventional anti‐obesity agents to improve treatment efficacy and reduce inflammation in obesogenic conditions. However, further high‐quality studies are needed to firmly establish their clinical efficacy. [ABSTRACT FROM AUTHOR]

Irisin is a myokine secreted under the influence of physical activity and exposure to low temperatures and through different exogenous stimuli by the cleavage of its precursor, fibronectin type III domain-containing protein 5 (FNDC5). It is mainly known for maintaining of metabolic homeostasis, promoting the browning of white adipose tissue, the thermogenesis process, and glucose homeostasis. Growing experimental evidence suggests the possible central role of irisin in the regulation of cardiometabolic pathophysiological processes. On the other side, hydrogen sulfide (H2S) is well recognized as a pleiotropic gasotransmitter that regulates several homeostatic balances and physiological functions and takes part in the pathogenesis of cardiometabolic diseases. Through the S-persulfidation of cysteine protein residues, H2S is capable of interacting with crucial signaling pathways, exerting beneficial effects in regulating glucose and lipid homeostasis as well. H2S and irisin seem to be intertwined; indeed, recently, H2S was found to regulate irisin secretion by activating the peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α)/FNDC5/irisin signaling pathway, and they share several mechanisms of action. Their involvement in metabolic diseases is confirmed by the detection of their lower circulating levels in obese and diabetic subjects. Along with the importance of metabolic disorders, these modulators exert favorable effects against cardiovascular diseases, preventing incidents of hypertension, atherosclerosis, heart failure, myocardial infarction, and ischemia–reperfusion injury. This review, for the first time, aims to explore the role of H2S and irisin and their possible crosstalk in cardiovascular diseases, pointing out the main effects exerted through the common molecular pathways involved. [ABSTRACT FROM AUTHOR]

The healthy properties of pomegranate fruit, a highly consumed food, have been known for a long time. However, the pomegranate supply chain is still rather inefficient, with the non-edible fraction, whose weight is roughly half the total and is endowed with plenty of valuable bioactive compounds, either disposed of or underutilized. A novel extract obtained from non-edible byproducts (called PPE), using hydrodynamic cavitation, a green, efficient, and scalable technique, was investigated for its cardiovascular effects in vivo. PPE showed efficacy in an acute phenylephrine (PE)-induced hypertensive rat model, similar to the extract of whole fruit (PFE) obtained using the same extractive technique, along with good intestinal bioaccessibility after oral administration. Finally, when chronically administered for 6 weeks to spontaneously hypertensive rats, PPE was shown to significantly contain the increase in systolic blood pressure, comparable to the reference drug Captopril, and at a dose remarkably lower than the reported effective dose of ellagic acid. The extract from the non-edible fraction of the pomegranate fruit also showed good anti-inflammation and anti-fibrotic effects. The findings of this study, along with the extraction technique, could contribute to enhancing the value of the pomegranate supply chain, relieve the related environmental burden, and potentially improve public health. [ABSTRACT FROM AUTHOR]