Berberine and lycopene as alternative or add-on therapy to metformin and statins, a review.

Nutraceuticals are principally extracted from natural products that are frequently safe and well-tolerated. Lycopene and berberine are natural plants with a wide range of beneficial effects including protective activities against metabolic disorders such as diabetes and cardiovascular diseases. These compounds might be considered technically more as a drug than a nutraceutical and could be prescribed as a product. However, further studies are needed to understand if these supplements could affect metabolic syndrome outcomes. Even if nutraceuticals exert a prophylactic activity within the body, their bioactivity and bioavailability have high interindividual variation, and precise assessment of biological function of these bioactive compounds in randomized clinical trials is critical. However, these reports must be interpreted with more considerations due to the low quality of the trials. The aim of this paper is to bring evidence about the management of cardiovascular diseases and diabetes through the use of nutraceuticals with particular attention to lycopene and berberine effectiveness.

Phosphatidylserine-containing liposomes: Therapeutic potentials against hypercholesterolemia and atherosclerosis.

Liposomes have been suggested as potential tools for cholesterol deposit mobilization from atherosclerotic lesions. Here, we explored the anti-atherosclerotic effects of phosphatidylserine (PS)-containing liposomes in vivo. High-fat diet-fed New Zealand white rabbits which were divided into groups receiving weekly intravenous injections of PS liposomes, atorvastatin-loaded PS (PSA) liposomes (100 µg phospholipid/kg), or control buffer for four weeks. The size and severity grade of atherosclerotic plaques as well as lipid profile were evaluated at the completion of study. In vitro, the expression and levels of anti/pro-inflammatory genes and proteins, respectively, and macrophage cholesterol efflux capacity (CEC) of nanoliposomes were evaluated. Both PS and PSA lowered serum LDL-C (P = 0.0034, P = 0.0041) and TC (P = 0.029, P = 0.0054) levels but did not alter TG and HDL-C levels. Plaque size and grade were reduced by PS (P = 0.0025, P = 0.0031) and PSA (P = 0.016, P = 0.027) versus control. Moreover, intima-media thickness was significantly reduced in the PS vs. control group (P = 0.01). In cultured cells, ICAM-1 expression in the PS (P = 0.022) and VCAM-1 expression in the PS and PSA groups (P = 0.037, P = 0.004) were suppressed while TGF-ß expression was induced by both PS and PSA (P = 0.048, P = 0.046). Moreover, CEC from macrophages to nanoliposomes was enhanced by PSA (P = 0.003). Administration of anionic PS-containing liposomes could improve lipid profile and promote plaque regression through mechanisms that may involve cholesterol efflux and modulation of adhesion molecules.

A meta-meta-analysis: Evaluation of meta-analyses published in the effectiveness of cardiovascular comorbidities on the severity of COVID-19.

On January 2020, WHO confirmed the epidemic outbreak of SARS-CoV-2 as a Health Emergency of International Concern. The aim of this meta-meta-analysis is quantifying meta-analytic findings on the association of cardiovascular disease (CVD) comorbidities and COVID-19 severity. Findings suggest that chances of getting severe COVID-19 disease in patients with CVD is greater than those without CVD. Also, prevalence of CVD in patents with COVID-19 is 0.08 (95% CI = 0.07-0.08). The OR as 3.44 indicates that the odds of getting severe COVID-19 is more than 3 times higher in those with CVD. Also, prevalence of hypertension in patient with COVID-19 is 0.27 (95%CI = 0.27-0.28) and the OR as 2.68 indicates that the odds of getting severe COVID-19 in cases with high blood pressure is more than 2.5 times higher than those without hypertension. It is rational to suppose that persons with coronary artery disease are prone to severe viral infection thereby, guideline-directed diagnosis and medical therapy is vital in CVD patients.

Assessment of tramadol pharmacokinetics in correlation with CYP2D6 and clinical symptoms.

Objectives Due to lack of adequate data on tramadol kinetic in relevance of CYP2D6 toxicity, this study was designed to investigate the effect of CYP2D6 phenotype in tramadol poisoning. The saliva, urine and blood samples were taken at the admission time. Consequently, concentration of tramadol and its major metabolites were measured. Methods A pharmacokinetic and metabolic study was developed in cases of tramadol poisoned (n=96). Cases of tramadol poisoned evidenced seizure, hypertension, dizziness, nausea and vomiting symptoms participated. Results Female cases showed higher N-desmethyltramadol (M2) tramadol concentrations than male cases: in urine (40.12 ± 124.53 vs. 7.3 ± 7.13), saliva (16.91 ± 26.03 vs. 5.89 ± 7.02), and blood (1.11 ± 1.56 vs. 0.3 ± 0.38) samples. Significant correlation between blood, saliva, and urine concentrations were found (r = 0.5). Based on the metabolic ratio of O-desmethyltramadol (M1) of male (0.53 ± 0.22) and female (0.43 ± 0.26), poisoning and severe symptoms like seizure in female occurs statistically fewer (13.04%) than in male (50.6%). Assessment of CYP2D6 phenotype showed all of the participants were extensive metabolizers (EM) and their phenotype was associated with clinical symptoms. Conclusions According to our results, M1 as a high potent metabolite has an important role in toxicity and the likelihood of poisoning in people with EM phenotype. Finally, tramadol metabolic ratio may justify the cause of various symptoms in human tramadol poisoning.

Assessment of tramadol pharmacokinetics in correlation with CYP2D6 and clinical symptoms.

Objectives Due to lack of adequate data on tramadol kinetic in relevance of CYP2D6 toxicity, this study was designed to investigate the effect of CYP2D6 phenotype in tramadol poisoning. The saliva, urine and blood samples were taken at the admission time. Consequently, concentration of tramadol and its major metabolites were measured. Methods A pharmacokinetic and metabolic study was developed in cases of tramadol poisoned (n=96). Cases of tramadol poisoned evidenced seizure, hypertension, dizziness, nausea and vomiting symptoms participated. Results Female cases showed higher N-desmethyltramadol (M2) tramadol concentrations than male cases: in urine (40.12 ± 124.53 vs. 7.3 ± 7.13), saliva (16.91 ± 26.03 vs. 5.89 ± 7.02), and blood (1.11 ± 1.56 vs. 0.3 ± 0.38) samples. Significant correlation between blood, saliva, and urine concentrations were found (r = 0.5). Based on the metabolic ratio of O-desmethyltramadol (M1) of male (0.53 ± 0.22) and female (0.43 ± 0.26), poisoning and severe symptoms like seizure in female occurs statistically fewer (13.04%) than in male (50.6%). Assessment of CYP2D6 phenotype showed all of the participants were extensive metabolizers (EM) and their phenotype was associated with clinical symptoms. Conclusions According to our results, M1 as a high potent metabolite has an important role in toxicity and the likelihood of poisoning in people with EM phenotype. Finally, tramadol metabolic ratio may justify the cause of various symptoms in human tramadol poisoning.

The role of phosphatidylserine recognition receptors in multiple biological functions.

Apoptotic cells are rapidly engulfed and degraded by phagocytes through efferocytosis. Efferocytosis is a highly regulated process. It is triggered upon the activation of caspase-dependent apoptosis, which in turn promotes the expression of "eat me" signals on the surface of dying cells and the release of soluble "find me" signals for the recruitment of phagocytes. To date, many "eat me" signals have been recognized, including phosphatidylserine (PS), intercellular adhesion molecule-3, carbohydrates (e.g., amino sugars, mannose) and calreticulin. Among them, PS is the most studied one. PS recognition receptors are different functionally active receptors expressed by phagocytes. Various PS recognition receptors with different structure, cell type expression, and ability to bind to PS have been recognized. Although PS recognition receptors do not fall into a single classification or family of proteins due to their structural differences, they all share the common ability to activate downstream signaling pathways leading to the production of anti-inflammatory mediators. In this review, available evidence regarding molecular mechanisms underlying PS recognition receptor-regulated clearance of apoptotic cells is discussed. In addition, some efferocytosis-independent biological functions of PS recognition receptors are reviewed.

Antitumor effects of curcumin: A lipid perspective.

Lipid metabolism plays an important role in cancer development due to the necessities of rapidly dividing cells to increase structural, energetic, and biosynthetic demands for cell proliferation. Basically, obesity, type 2 diabetes, and other related diseases, and cancer are associated with a common hyperactivated "lipogenic state." Recent evidence suggests that metabolic reprogramming and overproduction of enzymes involved in the synthesis of fatty acids are the new hallmarks of cancer, which occur in an early phase of tumorigenesis. As the first evidence to confirm dysregulated lipid metabolism in cancer cells, the overexpression of fatty acid synthase (FAS) was observed in breast cancer patients and demonstrated the role of FAS in cancer. Other enzymes of fatty acid synthesis have recently been found to be dysregulated in cancer, including ATP-dependent citrate lyase and acetyl-CoA carboxylase, which further underscores the connection of these metabolic pathways with cancer cell survival and proliferation. The degree of overexpression of lipogenic enzymes and elevated lipid utilization in tumors is closely associated with cancer progression. The question that arises is whether the progression of cancer can be suppressed, or at least decelerated, by modulating gene expression related to fatty acid metabolism. Curcumin, due to its effects on the regulation of lipogenic enzymes, might be able to suppress, or even cause regression of tumor growth. This review discusses recent evidence concerning the important role of lipogenic enzymes in the metabolism of cancer cells and whether the inhibitory effects of curcumin on lipogenic enzymes is therapeutically efficacious.

Protective effect of lycopene against chemical and natural toxins: A review.

People are exposed to a number of environmental, occupational, and therapeutic toxic agents which may be natural or man made. These hazardous substances may manifest as direct side effects on the function of organs or indirectly induced alteration of gene expression, cancer-associated metabolic pathways, and/or alter homeostasis. Lycopene, as a one of the most potent antioxidant, is found in fruits and vegetables. High-intake of lycopene has been shown to be effective in decreasing the risk of both natural toxins including mycotoxins, bacterial toxins, and chemical toxins including heavy metals, pesticides as well as herbicides. Recently, there is growing attention in understanding the mechanisms of the phytochemicals and carotenoids as antioxidative, antiapoptotic, radical scavenging, and chelating agents and their roles in the modulation of inflammatory pathways. This review summarizes available data from several recent studies about lycopene and its role against chemical and natural toxicants. © 2018 BioFactors, 45(1):5-23, 2019.