Exploring the role of exosomes in the pathogenesis and treatment of cardiomyopathies: A comprehensive literature review.

Exosomes, a subset of small extracellular vesicles that play a crucial role in intercellular communication, have garnered significant attention for their potential applications in the diagnosis and treatment of cardiomyopathies. Cardiomyopathies, which encompass a spectrum of heart muscle disorders, present complex challenges in diagnosis and management. Understanding the role of exosomes in the etiology of cardiomyopathies such as dilated cardiomyopathy (DCM), restrictive cardiomyopathy (RCM), arrhythmogenic cardiomyopathy (AC), and hypertrophic cardiomyopathy (HCM) may open new possibilities for therapeutic intervention and diagnosis. Exosomes have indeed demonstrated promise as diagnostic biomarkers, particularly in identifying cardiac conditions such as atrial fibrillation (AF) and in the timely classification of high-risk patients with different forms of cardiomyopathy. In DCM, exosomes have been implicated in mediating pathological responses in cardiomyocytes, potentially exacerbating disease progression. Moreover, in RCM, AC, and HCM, exosomes present significant potential as diagnostic biomarkers and therapeutic targets, offering insights into disease pathogenesis and potential avenues for intervention. Understanding the influence of exosomes on disease progression and identifying the specific molecular pathways involved in cardiomyopathy pathogenesis may significantly advance diagnostic and treatment strategies. While key findings highlight the multifaceted role of exosomes in cardiomyopathy, they also emphasize the need for further research to elucidate molecular mechanisms and translate findings into clinical practice. This review highlights the evolving landscape of exosome research in cardiomyopathies and underscores the importance of ongoing investigations to harness the full potential of exosomes in improving patient outcomes.

Citrus limon var. pompia Camarda var. nova: A Comprehensive Review of Its Botanical Characteristics, Traditional Uses, Phytochemical Profile, and Potential Health Benefits.

Citrus limon var. pompia Camarda var. nova, commonly known as pompia, is a distinctive citrus ecotype native to Sardinia, notable for its unique botanical, phytochemical, and potential health benefits. It holds cultural significance as a traditional food product of Sardinia, recognized by the Italian Ministry of Agricultural Food and Forestry Policies. This comprehensive review examines pompia's traditional uses, taxonomic classification, pomological characteristics, phytochemical profile, and potential health benefits. Pompia phytochemical analyses reveal a rich composition of flavonoids and terpenoids, with notable concentrations of limonene, myrcene, and various oxygenated monoterpenes. Pompia essential oils are primarily extracted from its peel and leaves. Peel essential oils exhibit a high concentration of the monoterpene limonene (82%) and significantly lower quantities of myrcene (1.8%), geranial (1.7%), geraniol (1.5%), and neral (1.4%). In its rind extract, flavanones such as naringin (23.77 µg/mg), neoeriocitrin (46.53 µg/mg), and neohesperidin (44.57 µg/mg) have been found, along with gallic acid (128.3 µg/mg) and quinic acid (219.67 µg/mg). The main compounds detected in the essential oils from pompia leaves are oxygenated monoterpenes (53.5%), with limonene (28.64%), α-terpineol (41.18%), geranial (24.44%), (E)-ß-ocimene (10.5%), linalool (0.56%), and neryl acetate (13.56%) being particularly prominent. In pompia juice, the presence of phenolic compounds has been discovered, with a composition more similar to lemon juice than orange juice. The primary flavonoid identified in pompia juice is chrysoeriol-6,8-di-C-glucoside (stellarin-2) (109.2 mg/L), which has not been found in other citrus juices. The compound rhoifolin-4-glucoside (17.5 mg/L) is unique to pompia juice, whereas its aglycone, rhoifolin, is found in lemon juice. Other flavonoids identified in pompia juice include diosmetin 6,8-C-diglucoside (54.5 mg/L) and isorhamnetin 3-O-rutinoside (79.4 mg/L). These findings support the potential of pompia in developing nutraceuticals and natural health products, further confirmed by its compounds' antioxidant, anti-inflammatory and antibacterial properties. Future research should focus on optimizing extraction methods, conducting clinical trials to evaluate efficacy and safety, and exploring sustainable cultivation practices. The potential applications of pompia extracts in food preservation, functional foods, and cosmetic formulations also warrant further investigation. Addressing these areas could significantly enhance pompia's contribution to natural medicine, food science, and biotechnology.

Enhanced vasorin signaling mitigates adverse cardiovascular remodeling.

Arterial stiffening is a critical risk factor contributing to the exponential rise in age-associated cardiovascular disease incidence. This process involves age-induced arterial proinflammation, collagen deposition, and calcification, which collectively contribute to arterial stiffening. The primary driver of proinflammatory processes leading to collagen deposition in the arterial wall is the transforming growth factor-beta1 (TGF-ß1) signaling. Activation of this signaling is pivotal in driving vascular extracellular remodeling, eventually leading to arterial fibrosis and calcification. Interestingly, the glycosylated protein vasorin (VASN) physically interacts with TGF-ß1, and functionally restraining its proinflammatory fibrotic signaling in arterial walls and vascular smooth muscle cells (VSMCs). Notably, as age advances, matrix metalloproteinase type II (MMP-2) is activated, which effectively cleaves VASN protein in both arterial walls and VSMCs. This age-associated/MMP-2-mediated decrease in VASN levels exacerbates TGF-ß1 activation, amplifying arterial fibrosis and calcification in the arterial wall. Importantly, TGF-ß1 is a downstream molecule of the angiotensin II (Ang II) signaling pathway in the arterial wall and VSMCs, which is modulated by VASN. Indeed, chronic administration of Ang II to young rats significantly activates MMP-2 and diminishes the VASN expression to levels comparable to untreated older control rats. This review highlights and discusses the role played by VASN in mitigating fibrosis and calcification by alleviating TGF-ß1 activation and signaling in arterial walls and VSMCs. Understanding these molecular physical and functional interactions may pave the way for establishing VASN-based therapeutic strategies to counteract adverse age-associated cardiovascular remodeling, eventually reducing the risk of cardiovascular diseases.

microRNA 21 and long non-coding RNAs interplays underlie cancer pathophysiology: A narrative review.

Non-coding RNAs (ncRNAs) are a diverse group of functional RNA molecules that lack the ability to code for proteins. Despite missing this traditional role, ncRNAs have emerged as crucial regulators of various biological processes and have been implicated in the development and progression of many diseases, including cancer. MicroRNAs (miRNAs) and long non-coding RNAs (lncRNAs) are two prominent classes of ncRNAs that have emerged as key players in cancer pathophysiology. In particular, miR-21 has been reported to exhibit oncogenic roles in various forms of human cancer, including prostate, breast, lung, and colorectal cancer. In this context, miR-21 overexpression is closely associated with tumor proliferation, growth, invasion, angiogenesis, and chemoresistance, whereas miR-21 inactivation is linked to the regression of most tumor-related processes. Accordingly, miR-21 is a crucial modulator of various canonical oncogenic pathways such as PTEN/PI3K/Akt, Wnt/ß-catenin, STAT, p53, MMP2, and MMP9. Moreover, interplays between lncRNA and miRNA further complicate the regulatory mechanisms underlying tumor development and progression. In this regard, several lncRNAs have been found to interact with miR-21 and, by functioning as competitive endogenous RNAs (ceRNAs) or miRNA sponges, can modulate cancer tumorigenesis. This work presents and discusses recent findings highlighting the roles and pathophysiological implications of the miR-21-lncRNA regulatory axis in cancer occurrence, development, and progression. The data collected indicate that specific lncRNAs, such as MEG3, CASC2, and GAS5, are strongly associated with miR-21 in various types of cancer, including gastric, cervical, lung, and glioma. Indeed, these lncRNAs are well-known tumor suppressors and are commonly downregulated in different types of tumors. Conversely, by modulating various mechanisms and oncogenic signaling pathways, their overexpression has been linked with preventing tumor formation and development. This review highlights the significance of these regulatory pathways in cancer and their potential for use in cancer therapy as diagnostic and prognostic markers.

Tracing vitamins on the long non-coding lane of the transcriptome: vitamin regulation of LncRNAs.

A major revelation of genome-scale biological studies in the post-genomic era has been that two-thirds of human genes do not encode proteins. The majority of non-coding RNA transcripts in humans are long non-coding RNA (lncRNA) molecules, non-protein-coding regulatory transcripts with sizes greater than 500 nucleotides. LncRNAs are involved in nearly every aspect of cellular physiology, playing fundamental regulatory roles both in normal cells and in disease. As result, they are functionally linked to multiple human diseases, from cancer to autoimmune, inflammatory, and neurological disorders. Numerous human conditions and diseases stem from gene-environment interactions; in this regard, a wealth of reports demonstrate that the intake of specific and essential nutrients, including vitamins, shapes our transcriptome, with corresponding impacts on health. Vitamins command a vast array of biological activities, acting as coenzymes, antioxidants, hormones, and regulating cellular proliferation and coagulation. Emerging evidence suggests that vitamins and lncRNAs are interconnected through several regulatory axes. This type of interaction is expected, since lncRNA has been implicated in sensing the environment in eukaryotes, conceptually similar to riboswitches and other RNAs that act as molecular sensors in prokaryotes. In this review, we summarize the peer-reviewed literature to date that has reported specific functional linkages between vitamins and lncRNAs, with an emphasis on mammalian models and humans, while providing a brief overview of the source, metabolism, and function of the vitamins most frequently investigated within the context of lncRNA molecular mechanisms, and discussing the published research findings that document specific connections between vitamins and lncRNAs.

Association between ischemia-modified albumin (IMA) and peripheral endothelial dysfunction in rheumatoid arthritis patients.

The identification of circulating biomarkers of endothelial dysfunction (ED), a precursor to atherosclerosis, in rheumatoid arthritis (RA) would facilitate early risk stratification and prevention strategies. Ischemia-modified albumin (IMA) has emerged as a potential biomarker of oxidative stress, ischemia, and ED. However, studies examining the relationship between IMA and ED in RA patients are lacking. We measured serum IMA concentrations by using an albumin cobalt binding test and peripheral vasodilatory capacity by EndoPAT in 113 RA patients without previous cardiovascular events enrolled in the EDRA study (ClinicalTrials.gov: NCT02341066). The mean peripheral vasodilatory capacity, expressed by the log of reactive hyperemia index (logRHI), was 0.82, corresponding to 27% RA patients having ED. The mean plasma concentrations of IMA were 0.478 absorbance units. We observed a significant and inverse association between peripheral vasodilatory capacity and serum IMA concentrations (rho = - 0.22, p = 0.02). In univariate logistic regression, ED was significantly associated with serum IMA concentrations [OR 1173 (95% CI 1.3568 to 101,364), p = 0.040) and higher disease activity. In multivariate logistic regression, the independent association between ED and IMA remained significant after correction for disease activity and other RA-confounders [OR 2252 (95% CI 1.0596 to 4,787,505), p = 0.048 in Model 1; OR 7221 (95% CI 4.1539 to 12,552,859), p = 0.02 in Model 2]. Conclusions: This study suggests that IMA is a promising biomarker of ED in RA. Further research is needed to confirm our findings and determine the clinical utility of IMA in detecting and managing early atherosclerosis in RA patients.

Protective Effect of Knee Postoperative Fluid on Oxidative-Induced Damage in Human Knee Articular Chondrocytes.

The oxidative-stress-elicited deterioration of chondrocyte function is the initial stage of changes leading to the disruption of cartilage homeostasis. These changes entail a series of catabolic damages mediated by proinflammatory cytokines, MMPs, and aggrecanases, which increase ROS generation. Such uncontrolled ROS production, inadequately balanced by the cellular antioxidant capacity, eventually contributes to the development and progression of chondropathies. Several pieces of evidence show that different growth factors, single or combined, as well as anti-inflammatory cytokines and chemokines, can stimulate chondrogenesis and improve cartilage repair and regeneration. In this view, hypothesizing a potential growth-factor-associated action, we investigate the possible protective effect of post-operation knee fluid from patients undergoing prosthesis replacement surgery against ROS-induced damage on normal human knee articular chondrocytes (HKACs). To this end, HKACs were pre-treated with post-operation knee fluid and then exposed to H2O2 to mimic oxidative stress. Intracellular ROS levels were measured by using the molecular probe H2DCFDA; cytosolic and mitochondrial oxidative status were assessed by using HKACs infected with lentiviral particles harboring the redox-sensing green fluorescent protein (roGFP); and cell proliferation was determined by measuring the rate of DNA synthesis with BrdU incorporation. Moreover, superoxide dismutase (SOD), catalase, and glutathione levels from the cell lysates of treated cells were also measured. Postoperative peripheral blood sera from the same patients were used as controls. Our study shows that post-operation knee fluid can counteract H2O2-elicited oxidative stress by decreasing the intracellular ROS levels, preserving the cytosolic and mitochondrial redox status, maintaining the proliferation of oxidatively stressed HKACs, and upregulating chondrocyte antioxidant defense. Overall, our results support and propose an important effect of post-operation knee fluid substances in maintaining HKAC function by mediating cell antioxidative system upregulation and protecting cells from oxidative stress.

Potential Therapeutic Targets of Resveratrol in the Prevention and Treatment of Pulmonary Fibrosis.

Pulmonary fibrosis (PF) is a feared component in over 200 interstitial pulmonary diseases, which are characterized by increased alveolar wall thickness, excessive scarring, and aberrant extracellular matrix restructuring that, ultimately, affect lung compliance and capacity. As a result of its broad range of biological activities, including antioxidant, anti-inflammatory, antiapoptotic, and many others, resveratrol has been shown to be an effective treatment for respiratory system diseases, including interstitial lung disease, infectious diseases, and lung cancer. This work reviews the known molecular therapeutic targets of resveratrol and its potential mechanisms of action in attenuating PF in respiratory diseases, including cancer, COVID-19, interstitial lung diseases (ILDs) of known etiologies, idiopathic interstitial pneumonia, and ILDs associated with systemic disorders, such as rheumatoid arthritis, systemic sclerosis, Schrödinger's syndrome, systemic lupus erythematosus, and pulmonary hypertension. The current issues and controversies related to the possible use of resveratrol as a pharmaceutical drug or supplement are also discussed.

Metformin-mediated epigenetic modifications in diabetes and associated conditions: Biological and clinical relevance.

An intricate interplay between genetic and environmental factors contributes to the development of type 2 diabetes (T2D) and its complications. Therefore, it is not surprising that the epigenome also plays a crucial role in the pathogenesis of T2D. Hyperglycemia can indeed trigger epigenetic modifications, thereby regulating different gene expression patterns. Such epigenetic changes can persist after normalizing serum glucose concentrations, suggesting the presence of a 'metabolic memory' of previous hyperglycemia which may also be epigenetically regulated. Metformin, a derivative of biguanide known to reduce serum glucose concentrations in patients with T2D, appears to exert additional pleiotropic effects that are mediated by multiple epigenetic modifications. Such modifications have been reported in various organs, tissues, and cellular compartments and appear to account for the effects of metformin on glycemic control as well as local and systemic inflammation, oxidant stress, and fibrosis. This review discusses the emerging evidence regarding the reported metformin-mediated epigenetic modifications, particularly on short and long non-coding RNAs, DNA methylation, and histone proteins post-translational modifications, their biological and clinical significance, potential therapeutic applications, and future research directions.

Medicinal and mechanistic overview of artemisinin in the treatment of human diseases.

Artemisinin (ART) is a bioactive compound isolated from the plant Artemisia annua and has been traditionally used to treat conditions such as malaria, cancer, viral infections, bacterial infections, and some cardiovascular diseases, especially in Asia, North America, Europe and other parts of the world. This comprehensive review aims to update the biomedical potential of ART and its derivatives for treating human diseases highlighting its pharmacokinetic and pharmacological properties based on the results of experimental pharmacological studies in vitro and in vivo. Cellular and molecular mechanisms of action, tested doses and toxic effects of artemisinin were also described. The analysis of data based on an up-to-date literature search showed that ART and its derivatives display anticancer effects along with a wide range of pharmacological activities such as antibacterial, antiviral, antimalarial, antioxidant and cardioprotective effects. These compounds have great potential for discovering new drugs used as adjunctive therapies in cancer and various other diseases. Detailed translational and experimental studies are however needed to fully understand the pharmacological effects of these compounds.

An updated overview of cyanidins for chemoprevention and cancer therapy.

Anthocyanins are colored polyphenolic compounds that belong to the flavonoids family and are largely present in many vegetables and fruits. They have been used in traditional medicine in many cultures for a long time. The most common and abundant anthocyanins are those presenting an O-glycosylation at C-3 (C ring) of the flavonoid skeleton to form -O-ß-glucoside derivatives. The present comprehensive review summarized recent data on the anticancer properties of cyanidings along with natural sources, phytochemical data, traditional medical applications, molecular mechanisms and recent nanostrategies to increase the bioavailability and anticancer effects of cyanidins. For this analysis, in vitro, in vivo and clinical studies published up to the year 2022 were sourced from scientific databases and search engines such as PubMed/Medline, Google scholar, Web of Science, Scopus, Wiley and TRIP database. Cyanidins' antitumor properties are exerted during different stages of carcinogenesis and are based on a wide variety of biological activities. The data gathered and discussed in this review allows for affirming that cyanidins have relevant anticancer activity in vitro, in vivo and clinical studies. Future research should focus on studies that bring new data on improving the bioavailability of anthocyanins and on conducting detailed translational pharmacological studies to accurately establish the effective anticancer dose in humans as well as the correct route of administration.

Effect of Resveratrol on Pregnancy, Prenatal Complications and Pregnancy-Associated Structure Alterations.

Adverse pregnancy outcomes are considered significant health risks for pregnant women and their offspring during pregnancy and throughout their lifespan. These outcomes lead to a perturbated in-utero environment that impacts critical phases of the fetus's life and correlates to an increased risk of chronic pathological conditions, such as diabetes, obesity, and cardiovascular diseases, in both the mother's and adult offspring's life. The dietary intake of naturally occurring antioxidants promotes health benefits and disease prevention. In this regard, maternal dietary intake of polyphenolic antioxidants is linked to a reduced risk of maternal obesity and cardio-metabolic disorders, positively affecting both the fetus and offspring. In this work, we will gather and critically appraise the current literature highlighting the effect/s of the naturally occurring polyphenol antioxidant resveratrol on oxidative stress, inflammation, and other molecular and physiological phenomena associated with pregnancy and pregnancy conditions, such as gestational diabetes, preeclampsia, and preterm labor. The resveratrol impact on prenatal complications and pregnancy-associated structures, such as the fetus and placenta, will also be discussed. Finally, we will draw conclusions from the current knowledge and provide future perspectives on potentially exploiting resveratrol as a therapeutic tool in pregnancy-associated conditions.

Implications and theragnostic potentials of circular RNAs in rheumatic diseases.

Circular RNAs (circRNAs), a class of non-coding RNAs (ncRNAs), are highly stable and ubiquitous molecules that exhibit tissue-specific expression. Accumulating evidence has shown that aberrant expression of circRNAs can play a role in the pathogenesis of several diseases. Rheumatic diseases are a varied group of autoimmune and inflammatory disorders affecting mainly the musculoskeletal system. Notably, circRNAs, which are essential immune system gene modulators, are strongly linked to the occurrence and progression of autoimmune disorders. Here, we present and discuss the current findings concerning the roles, implications and theragnostic potentials of circRNAs in common rheumatic diseases, including ankylosing spondylitis (AS), osteoarthritis (OA), osteoporosis (OP), rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), Crohn's disease (CD), and gout. This review aims to provide new insights to support the development of novel diagnostic and therapeutic strategies for these disabling diseases.

Non-coding RNAs as biomarkers of myocardial infarction.

Non-coding RNAs (ncRNAs) encompass a family of ubiquitous RNA molecules that lack protein-coding potential and have tissue-specific expression. A significant body of evidence indicates that ncRNA's aberrant expression plays a critical role in disease onset and development. NcRNAs' biochemical characteristics such as disease-associated concentration changes, structural stability, and high abundance in body fluids make them promising prognostic and diagnostic biomarkers. Myocardial infarction (MI) is a leading cause of mortality worldwide. Acute myocardial infarction (AMI), the term in use to describe MI's early phase, is generally diagnosed by physical examination, electrocardiogram (ECG), and the presence of specific biomarkers. In this regard, compared to standard MI biomarkers, such as the cardiac troponin isoforms (cTnT & cTnI) and the Creatinine Kinase (CK), ncRNAs appears to provide better sensitivity and specificity, ensuring a rapid and correct diagnosis, an earlier treatment, and consequently a good prognosis for the patients. This review aims to summarize and discuss the most promising and recent data on the potential clinical use of circulating ncRNAs as MI biomarkers. Specifically, we focused primarily on miRNAs and lncRNAs, highlighting their significant specificity and sensitivity, discussing their limitations, and suggesting possible overcoming approaches.

Cytoprotective, antioxidant, and anti-migratory activity of Pistacia lentiscus L. supercritical carbon dioxide extract on primary human endothelial cells.

Green chemistry is a useful tool for producing valuable chemicals from biomass. However, extracted compounds need to be tested for safety and efficacy before their use in humans. Here we investigate the chemical composition and biological effects of a leaves Pistacia lentiscus L. supercritical carbon dioxide (SCCO2) extract. Terpenes represented the main extract fraction, with Germacrene D (11.18%), delta-cadinene (10.54%), and alpha-pinene (8.7%) the most abundant molecules. Challenged with endothelial cells (ECs), increasing extract concentrations failed to affect cell proliferation or promote cell toxicity. ROS assessment in unstressed and H2O2-treated ECs revealed an extract dose-dependent antioxidant activity. Exposition of H2O2-treated ECs to increasing extract concentrations dose-dependently counteracted H2O2-induced cell impairments. The extract significantly counteracted fetal calf serum-induced ECs migration. For the first time, we report that a SCCO2 extract obtained from PL leaves is safe on ECs and may be a useful source of valuable compounds with vasculoprotective properties.

Resveratrol-Mediated Regulation of Mitochondria Biogenesis-associated Pathways in Neurodegenerative Diseases: Molecular Insights and Potential Therapeutic Applications.

Neurodegenerative disorders include different neurological conditions that affect nerve cells, causing the progressive loss of their functions and ultimately leading to loss of mobility, coordination, and mental functioning. The molecular mechanisms underpinning neurodegenerative disease pathogenesis are still unclear. Nonetheless, there is experimental evidence to demonstrate that the perturbation of mitochondrial function and dynamics play an essential role. In this context, mitochondrial biogenesis, the growth, and division of preexisting mitochondria, by controlling mitochondria number, plays a vital role in maintaining proper mitochondrial mass and function, thus ensuring efficient synaptic activity and brain function. Mitochondrial biogenesis is tightly associated with the control of cell division and variations in energy demand in response to extracellular stimuli; therefore, it may represent a promising therapeutic target for developing new curative approaches to prevent or counteract neurodegenerative disorders. Accordingly, several inducers of mitochondrial biogenesis have been proposed as pharmacological targets for treating diverse central nervous system conditions. The naturally occurring polyphenol resveratrol has been shown to promote mitochondrial biogenesis in various tissues, including the nervous tissue, and an ever-growing number of studies highlight its neurotherapeutic potential. Besides preventing cognitive impairment and neurodegeneration through its antioxidant and anti-inflammatory properties, resveratrol has been shown to be able to enhance mitochondria biogenesis by acting on its main effectors, including PGC-1α, SIRT1, AMPK, ERRs, TERT, TFAM, NRF-1 and NRF-2. This review aims to present and discuss the current findings concerning the impact of resveratrol on the machinery and main effectors modulating mitochondrial biogenesis in the context of neurodegenerative diseases.

Association between Paraoxonase/Arylesterase Activity of Serum PON-1 Enzyme and Rheumatoid Arthritis: A Systematic Review and Meta-Analysis.

Background: A decrease in serum paraoxonase (PON-1) and arylesterase (ARE) activity has been reported in rheumatoid arthritis (RA) patients and linked to chronic inflammation and impaired antioxidant defense. Methods: A systematic review and meta-analysis were performed to critically appraise the current evidence on plasma/serum concentrations of PON-1 and ARE activity in RA patients and healthy controls. The Web of Science, PubMed, Scopus, and Google Scholar databases were searched from inception to November 2021. We used random-effects meta-analysis. The risk of bias was estimated using the Joanna Briggs Institute Critical Appraisal Checklist tool. The certainty of the evidence was assessed with GRADE. The study complied with the PRISMA statements and was registered in PROSPERO (CRD42022345380). Results: Seventeen studies reported PON-1 activity (1144 RA patients, 797 controls) and ten reported ARE activity (1367 RA patients, 1037 controls). RA patients had significantly lower PON-1 (SMD = −1.32, 95% CI −1.94 to −0.70; p < 0.001) and ARE activity (SMD = −0.91, 95% CI −1.37 to −0.46; p < 0.001). There was substantial heterogeneity (PON, I2 97%; ARE, 95.7%, p < 0.001 for both). There was no publication bias. The pooled SMD values did not significantly change after sensitivity analysis. The certainty of the evidence was very low due to the observational nature of the studies and the large heterogeneity. Conclusion: Our meta-analysis has shown that both serum PON-1 and ARE activity are significantly lower in RA patients, suggesting a deficit in antioxidant defense mechanisms in this disease.

Effects of the Storage Conditions on the Stability of Natural and Synthetic Cannabis in Biological Matrices for Forensic Toxicology Analysis: An Update from the Literature.

The use and abuse of cannabis, be it for medicinal or recreational purposes, is widely spread among the population. Consequently, a market for more potent and consequently more toxic synthetic cannabinoids has flourished, and with it, the need for accurate testing of these substances in intoxicated people. In this regard, one of the critical factors in forensic toxicology is the stability of these drugs in different biological matrices due to different storage conditions. This review aims to present the most updated and relevant literature of studies performed on the effects of different storage conditions on the stability of cannabis compounds present in various biological matrices, such as blood and plasma, urine, and oral fluids, as well as in alternative matrices, such as breath, bile fluid, hair, sweat, cerumen, and dried blood spots.

Disease-Associated Regulation of Non-Coding RNAs by Resveratrol: Molecular Insights and Therapeutic Applications.

There have been significant advances, particularly over the last 20 years, in the identification of non-coding RNAs (ncRNAs) and their pathophysiological role in a wide range of disease states, particularly cancer and other chronic conditions characterized by excess inflammation and oxidative stress such as atherosclerosis, diabetes, obesity, multiple sclerosis, osteoporosis, liver and lung fibrosis. Such discoveries have potential therapeutic implications as a better understanding of the molecular mechanisms underpinning the effects of ncRNAs on critical homeostatic control mechanisms and biochemical pathways might lead to the identification of novel druggable targets. In this context, increasing evidence suggests that several natural compounds can target ncRNAs at different levels and, consequently, influence processes involved in the onset and progression of disease states. The natural phenol resveratrol has been extensively studied for therapeutic purposes in view of its established anti-inflammatory and antioxidant effects, particularly in disease states such as cancer and cardiovascular disease that are associated with human aging. However, increasing in vitro and in vivo evidence also suggests that resveratrol can directly target various ncRNAs and that this mediates, at least in part, its potential therapeutic effects. This review critically appraises the available evidence regarding the resveratrol-mediated modulation of different ncRNAs in a wide range of disease states characterized by a pro-inflammatory state and oxidative stress, the potential therapeutic applications, and future research directions.