Iron nanoparticles as food additives and food supplements, regulatory and legislative perspectives.

Recently, the use of nanotechnology in food has gained great interest. Iron nanoparticles with unique chemical, physical and structural properties allow their potential use mainly as iron fortifiers, colorants and antimicrobial agents. However, in the market we can find only supplements and food colorants based on iron nanoparticles. Their use in food fortification has so far been focused only on in vitro and in vivo experimental studies, since the toxicological evaluation of these studies has so far been the basis for the proposals of laws and regulations, which are still in an early stage of development. Therefore, the aim of this work was to summarize the use of the different forms of iron nanoparticles (oxides, oxyhydroxides, phosphates, pyrophosphates and sulfates) as food additives and supplements and to resume the perspectives of legislation regarding the use of these types of nanoparticles in the food industry.

Probiotics, as Adjuvant Therapy and Preventive Measure on Progression, and Complications of Head and Neck Cancer.

BACKGROUND: Preclinical and clinical evidence implies that destructive therapies in local and malignant tissue are frequently used on patients with head and neck cancer. Consequently, the microbiome of the treated and adjacent regions is affected. Disruption of the normal microbiome plays an important role not only in the disease progression but also in its emergence, therefore new therapies involving probiotics, prebiotics, and synbiotics have been developed to control or regulate this microbial disruption. OBJECTIVE: This review aims to describe the current and potential uses of probiotics at different stages of development of head and neck squamous cell carcinoma, as an adjuvant therapy to prevent common complications such as radiation-induced oral mucositis (RIOM) and its role in other areas. METHODS: Currently, there is no widely effective strategy to treat or prevent this kind of cancer. Surgery, radiation therapy, and chemotherapy are the three main treatments for head and neck cancer. Some therapies can also cause long-term health problems, or complications which might change the way you eat, talk, hear and breathe. RESULTS: The main uses for which probiotics have been studied are: Prevention and reduction of severity of RIOM, change in dental plaque to reduce dysbiosis, and reduction of complications in post-operated patients. Potential uses of probiotics include the reduction of disease initiation and progression by reducing local inflammation caused by bacteria and other organisms. CONCLUSION: The incidence and severity of RIOM may be lessened by probiotics. To establish its uses in additional clinical settings, though, more studies are necessary.

Nurses knowledge and attitude regarding pain: A systematic review and meta-analysis.

AIM: To determine through a systematic review and meta-analysis the level of knowledge about pain of nursing health professionals based on their scores on the Knowledge and Attitudes Survey Regarding Pain tool and its subdimensions in different settings. BACKGROUND: Adequate pain management is closely related to the degree of knowledge about pain of the healthcare personnel. Therefore, pedagogical programs on pain have been implemented in diverse health setting. However, several studies have found significant deficiencies in the knowledge of pain in health professionals, including nurses. DESIGN: Systematic review and meta-analysis. The study protocol was developed, registered and published in the international prospective register of systematic reviews (PROSPERO). DATA SOURCES: Scopus, PubMed, Embase, Web of Science, Cochrane Library and Google Scholar databases were searched up to June 2021. Studies from 2010 to 2021 were included in the analysis. METHODS: This study was conducted according to the Report Article for Systematic Reviews and Meta-analysis (PRISMA) guidelines and the quality evaluation was realized by the Mix Methods Appraisal Tool (MMAT). A random effects model analyzed the data, due on the heterogeneity among the studies. The I2 index and Cochran's Q test were employed to inspect the heterogeneity between the studies. For the Cochran's Q test, the P-value was set at 0.05. RESULTS: Eighteen studies with 7942 nurses were included in the systematic review and meta-analysis. The percentage of total pain knowledge was 52.9 % (95 % CI: 47.2-58.6). The highest and the lowest knowledge scores were for the spiritual/cultural dimension (69.9 %, 95 % CI: 63.4-76.0) and the intervention dimension (36.8 %, 95 % CI: 28.1-45.9), respectively. The score of total knowledge of the six domains in nurses in the area of oncology (58.6 %, 95 % CI: 45.3-71.2) was higher than that of nurses of the other areas. CONCLUSIONS: The knowledge of the nursing professionals about pain was lower that the suggested level of 80 %. Our study found that the pain knowledge is positively related to the prior pain training. Therefore, there is an urgent need to include continuing educational initiatives to improve the knowledge level about pain management in all the health personnel, including the nursing professionals.

Potential Mechanisms of the Improvement of Glucose Homeostasis in Type 2 Diabetes by Pomegranate Juice.

Pomegranate is a polyphenol-rich fruit. Studies have shown that extracts prepared from its juice or from different parts of the pomegranate plant have various biological activities including antioxidant, antimicrobial, anti-inflammatory, anticarcinogenic, cardioprotective, and antidiabetic. The therapeutic potential has been attributed to various phytochemicals, including ellagic acid, punicic acid, flavonoids, anthocyanidins, anthocyanins, flavonols, and flavones. This review focuses on the scientific evidence of pomegranate juice as hypoglycemic, emphasizing the chemical composition and the possible mechanisms of action associated with this effect. Studies were identified using the PubMed, Scopus, and ISI Web of Science databases to identify relevant articles focused on the hypoglycemic effect of pomegranate juice. The physiological responses to pomegranate juice are reported here, including a decrease of oxidative stress damage, an increase of insulin-dependent glucose uptake, maintenance of ß-cell integrity, inhibition of nonenzymatic protein glycation, an increase of insulin sensitivity, modulation of peroxisome proliferator-activated receptor-gamma, inhibition of α-amylase, inhibition of α-glucosidase and dipeptidyl peptidase-4, and decreases in inflammation. Overall, we found a significant hypoglycemic effect of pomegranate in in vitro and in vivo studies and we summarize the potential mechanisms of action.

Stevia eupatoria and Stevia pilosa Extracts Inhibit the Proliferation and Migration of Prostate Cancer Cells.

Background and Objectives: Prostate cancer is the second most harmful disease in men worldwide and the number of cases is increasing. Therefore, new natural agents with anticancer potential should be examined and the response of existing therapeutic drugs must be enhanced. Stevia pilosa and Stevia eupatoria are two species that have been widely used in traditional medicine, but their effectiveness on cancer cells and their interaction with antineoplastic drugs have not been studied. The aim of this study was to evaluate the anticancer activity of Stevia pilosa methanolic root extract (SPME) and Stevia eupatoria methanolic root extract (SEME) and their effect, combined with enzalutamide, on prostate cancer cells. Materials and Methods: The study was conducted on a human fibroblast cell line, and on androgen-dependent (LNCaP) and androgen-independent (PC-3) prostate cancer cell lines. The cell viability was evaluated using a Trypan Blue exclusion test for 48 h, and the migration by a wound-healing assay for 24, 48, and 72 h. Results: The results indicate that SPME and SEME were not cytotoxic at concentrations less than 1000 µg/mL in the human fibroblasts. SPME and SEME significantly reduced the viability and migration of prostate cancer cells in all concentrations evaluated. The antiproliferative effect of the Stevia extracts was higher in cancer cells than in normal cells. The enzalutamide decreased the cell viability in all concentrations tested (10-50 µM). The combination of the Stevia extracts and enzalutamide produced a greater effect on the inhibition of the proliferation and migration of cancer cells than the Stevia extracts alone, but not of the enzalutamide alone. Conclusion: The results indicate that SPME and SEME have an inhibitory effect on the viability and migration of prostate cancer cells and do not interfere with the enzalutamide anticancer effect. The data suggest that Stevia extracts may be a potential source of molecules for cancer treatment.

Beneficial and Deleterious Effects of Female Sex Hormones, Oral Contraceptives, and Phytoestrogens by Immunomodulation on the Liver.

The liver is considered the laboratory of the human body because of its many metabolic processes. It accomplishes diverse activities as a mixed gland and is in continuous cross-talk with the endocrine system. Not only do hormones from the gastrointestinal tract that participate in digestion regulate the liver functions, but the sex hormones also exert a strong influence on this sexually dimorphic organ, via their receptors expressed in liver, in both health and disease. Besides, the liver modifies the actions of sex hormones through their metabolism and transport proteins. Given the anatomical position and physiological importance of liver, this organ is evidenced as an immune vigilante that mediates the systemic immune response, and, in turn, the immune system regulates the hepatic functions. Such feedback is performed by cytokines. Pro-inflammatory and anti-inflammatory cytokines are strongly involved in hepatic homeostasis and in pathological states; indeed, female sex hormones, oral contraceptives, and phytoestrogens have immunomodulatory effects in the liver and the whole organism. To analyze the complex and interesting beneficial or deleterious effects of these drugs by their immunomodulatory actions in the liver can provide the basis for either their pharmacological use in therapeutic treatments or to avoid their intake in some diseases.

Dietary chia seeds (Salvia hispanica) improve acute dyslipidemia and steatohepatitis in rats.

Chia seeds (Salvia hispanica L.) are rich in omega fatty acids. Dyslipidemia and steatohepatitis are diseases that require effective treatments in obese and non-obese patients. The aim was to evaluate the effect of chia intake on acute tyloxapol (TI)-induced dyslipidemia, on acute carbon tetrachloride (TC)-induced steatohepatitis, and on mixed damage (TC+TI) in non-obese rats. Four experimental groups were fed for 4 weeks a diet with established rodent food (DE), and four groups were fed a diet with 15% added chia (DC). Plasma samples were analyzed for total cholesterol, triglycerides, glucose, biochemical liver damage markers, and tumor necrosis factor-α (TNF-α). Liver samples were used to quantify glycogen, catalase, lipid peroxidation, and TNF-α. A histopathological analysis was performed. DC intake partially or totally prevented steatohepatitis, and reduced lipids in the dyslipidemic groups. The hypolipidemic and hepatoprotective effects of chia may be correlated to its high content of α-linolenic acid (omega-3) and phenolics. PRACTICAL APPLICATIONS: Metabolic syndrome is associated with non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH), which are currently the most common causes of chronic liver disease, cirrhosis, and hepatocellular carcinoma (HCC) worldwide. Dyslipidemia is a significant risk factor for NAFLD and NASH. Non-obese patients may have NAFLD or NASH. Metabolic syndrome and dyslipidemia are more strongly associated with NAFLD in non-obese than in obese patients. This is the first study evaluating the hypolipidemic and hepatoprotective effects of chia seed intake on acute dyslipidemia and/or steatohepatitis caused by the individual or combined administration of the inducers tyloxapol and carbon tetrachloride, respectively, in non-obese rats. The pharmacological effects of dietary chia are correlated to its high content of omega-3 and omega-6 (1:1), protein, dietary fiber, and phenolics. The results suggest that inclusion of chia in diets of non-obese patients with dyslipidemia and/or NAFLD/NASH may improve their health state and preventing cirrhosis or HCC.

Phytosterols and Triterpenoids for Prevention and Treatment of Metabolic-related Liver Diseases and Hepatocellular Carcinoma.

BACKGROUND: Liver ailments are among the leading causes of death; they originate from viral infections, chronic alcoholism, and autoimmune illnesses, which may chronically be precursors of cirrhosis; furthermore, metabolic syndrome may worsen those hepatopathies or cause Non-alcoholic Fatty Liver Disease (NAFLD) that may advance to non-alcoholic steatohepatitis (NASH). Cirrhosis is the late-stage liver disease and can proceed to hepatocellular carcinoma (HCC). Pharmacological treatment options for liver diseases, cirrhosis, and HCC, are limited, expensive, and not wholly effective. The use of medicinal herbs and functional foods is growing around the world as natural resources of bioactive compounds that would set the basis for the development of new drugs. Review and Conclusion: Plant and food-derived sterols and triterpenoids (TTP) possess antioxidant, metabolic-regulating, immunomodulatory, and anti-inflammatory activities, as well as they are recognized as anticancer agents, suggesting their application strongly as an alternative therapy in some chronic diseases. Thus, it is interesting to review current reports about them as hepatoprotective agents, but also because they structurally resemble cholesterol, sexual hormones, corticosteroids and bile acids due to the presence of the steroid nucleus, so they all can share pharmacological properties through activating nuclear and membrane receptors. Therefore, sterols and TTP appear as a feasible option for the prevention and treatment of chronic metabolic-related liver diseases, cirrhosis, and HCC.

Colorectal Cancer: Causes and Evidence of Chemopreventive Treatments.

BACKGROUND: Colorectal cancer (CRC) is the second and third most frequent cancer in women and men, respectively; indeed, CRC is placed as the fourth world's most deadly cancer (after lung, liver, and stomach cancer). The incidence of CRC is strongly influenced by nutrition and the high fat/high carbohydrate Western-style diet. CRC is one of the most intensively studied cancer types, partly because of its high prevalence, but also because of the existence of its precursor lesions, tubular or villous adenomas, and more recently serrated adenomas. The morphological steps in the adenomacarcinoma sequence have been elucidated at a molecular level, which allow the identification of the genes responsible for CRC. Review and Conclusions: The main aim of this review is to provide data regarding the pathophysiological characteristics, molecular mechanisms as well as carcinogenic and chemopreventive agents for CRC, with emphasis on evidence supporting their efficacy. These compounds may modulate multiple signaling pathways involved in cell proliferation and apoptosis in transformed cells, they also enhance the host immune system and favor an effective treatment. Despite promising results from experimental studies, only a limited number of these compounds have been tested in clinical trials. The mechanistic spectrum and specificity of the action of phytochemicals represent a complex and evolving field of research.

Hepatoprotective Effects of Nonpolar Extracts from Inflorescences of Thistles Cirsium vulgare and Cirsium ehrenbergii on Acute Liver Damage in Rat.

BACKGROUND: Drugs for the treatment of liver diseases are scarce and not effective enough. Some species of the genus Cirsium possess hepatoprotective activity. There are no studies on the hepatoprotective effects of nonpolar extracts from inflorescences of thistles Cirsium vulgare and Cirsium ehrenbergii, and there are few reports on their chemical composition. OBJECTIVE: The aim is to obtain the hexane extract from inflorescences of both thistles and to identify preliminarily their main chemical component, and to evaluate the hepatoprotective properties of the extracts. MATERIALS AND METHODS: Hexane extracts were obtained using a Soxhlet apparatus. The chemical composition was analyzed using infrared spectra and gas chromatography-mass spectrometry. Two doses (250 and 500 mg/kg, p.o.) of both extracts were administered to assess their hepatoprotective effect on acute carbon tetrachloride (TC)-induced liver damage in rats using biochemical markers of necrosis, cholestasis, functionality, oxidative stress, and histological analysis. RESULTS: Extracts were shown to have a very similar chemical profile. Their major constituent seems to be lupeol acetate. The two doses of both extracts demonstrated comparable hepatoprotective properties because they significantly diminished all the liver injury indicators (P < 0.05) and were corroborated using histopathology. CONCLUSION: This is the first study on the hepatoprotective effects of nonpolar extracts from inflorescences of thistles C. vulgare and C. ehrenbergii. Hexane extracts administration totally prevented the acute TC-induced liver damage. The preliminary chemical analysis strongly suggests the lupeol acetate as their major constituent. Lupeol and its derivatives have been previously reported as antiinflammatory and hepatoprotective agents. SUMMARY: Hexane extracts of both thistles kept normal liver functionality and glycogen store in carbon tetrachloride-induced acute liver damageHexane extracts of both thistles showed anti-necrotic and anti-cholestatic effects, also diminished the lipid peroxidation and nitric oxide levels on the carbon tetrachloride-induced acute liver damageThe two doses of hexane extracts administered (250 and 500 mg/kg) prevented the liver injury in a very similar extentBoth nonpolar extracts are chemically very similar and their main compound seems to be lupeol acetate. Abbreviations used: TC: Carbon tetrachloride; FT-IR: Fourier transform Infrared spectroscopy; GC-MS: Gas chromatography - Mass spectrometry; V: Vehicle; E: Extract; Ecv: Extract of Cirsium vulgare; Ece: Extract of Cirsium ehrenbergii; AP: Alkaline phosphatase; GGTP: γ-Glutamyl transpeptidase; ALT: Alanine aminotransferase; DB: Direct bilirubin; TB: Total bilirubin; LP: Lipid peroxidation; MDA: Malondialdehyde; NO: Nitric oxide; TNF-α: Tumor necrosis factor-α.

In Vitro Bioaccessibility and Effect of Mangifera indica (Ataulfo) Leaf Extract on Induced Dyslipidemia.

Cardiovascular diseases (CVDs) are the leading causes of death in the world, and epidemiological evidence points to dietary habits, stress, and obesity as major risk factors promoting pathological conditions like atherosclerosis, hypertension, and thrombosis. Current therapeutic approaches for CVDs rely on lifestyle changes and/or the use of drug agents. However, since the efficacy of such interventions is often limited by poor compliance and/or significant side effects, continued research on new preventive and therapeutic approaches is much needed. Our study is aimed to determine the bioaccessibility, total content of phenolic compounds, and antioxidant capacity (DPPH·, ABTS·+) of a methanolic extract from Mangifera indica L. leaves (MEM), and its lipid-lowering effect on an induced dyslipidemia model in Wistar rats. Our results showed that mangiferin is the main component of MEM. The extract showed a total content of polyphenol compounds of 575.28 gallic acid equivalents per dry matter basis (GAE/g db), antioxidant activity 77.68 µmol Trolox equivalents per gram (TE/g) db as measured by DPPH· and 20,630 µmol TE/g db by ABTS·+, and 12% of phenolic compounds were bioaccessible, and 100 mg/kg of MEM reduced hyperlipidemia levels induced in Wistar rats. Further study on the potential use of MEM as a nutraceutical to prevent CVDs in high-fat diet consumers is required.

The European Eel NCCß Gene Encodes a Thiazide-resistant Na-Cl Cotransporter.

The thiazide-sensitive Na-Cl cotransporter (NCC) is the major pathway for salt reabsorption in the mammalian distal convoluted tubule. NCC plays a key role in the regulation of blood pressure. Its inhibition with thiazides constitutes the primary baseline therapy for arterial hypertension. However, the thiazide-binding site in NCC is unknown. Mammals have only one gene encoding for NCC. The eel, however, contains a duplicate gene. NCCα is an ortholog of mammalian NCC and is expressed in the kidney. NCCß is present in the apical membrane of the rectum. Here we cloned and functionally characterized NCCß from the European eel. The cRNA encodes a 1043-amino acid membrane protein that, when expressed in Xenopus oocytes, functions as an Na-Cl cotransporter with two major characteristics, making it different from other known NCCs. First, eel NCCß is resistant to thiazides. Single-point mutagenesis supports that the absence of thiazide inhibition is, at least in part, due to the substitution of a conserved serine for a cysteine at position 379. Second, NCCß is not activated by low-chloride hypotonic stress, although the unique Ste20-related proline alanine-rich kinase (SPAK) binding site in the amino-terminal domain is conserved. Thus, NCCß exhibits significant functional differences from NCCs that could be helpful in defining several aspects of the structure-function relationship of this important cotransporter.

Betalain, Acid ascorbic, phenolic contents and antioxidant properties of purple, red, yellow and white cactus pears.

Commercialization of cactus pears based on their antioxidant properties can generate competitive advantages, and these can turn into business opportunities and the development of new products and a high-value ingredient for the food industry. This work evaluated the antioxidant activities (1,1-diphenyl-2-picrylhydrazyl radical-scavenging, protection against oxidation of a ß-carotene-linoleic acid emulsion, and iron (II) chelation), the content of total phenolic compounds, ascorbic acid, betacyanin, betaxanthin and the stability of betacyanin pigments in presence of Cu (II)-dependent hydroxyl radicals (OH•), in 18 cultivars of purple, red, yellow and white cactus pear from six Mexican states. Our results indicated that the antiradical activities from yellow and white cactus pear cultivars were not significantly different (p < 0.05) and were lower than the average antiradical activities in red and purple cultivars. The red cactus pear from the state of Zacatecas showed the highest antioxidant activity. The free radical scavenging activity for red cactus pears was significantly correlated (p < 0.05) to the concentration of total phenolic compounds (R(2) = 0.90) and ascorbic acid (R(2) = 0.86). All 18 cultivars of cactus pears studied showed significant chelating activity of ferrous ions. The red and purple cactus pears showed a great stability when exposed to OH•.

A single residue in transmembrane domain 11 defines the different affinity for thiazides between the mammalian and flounder NaCl transporters.

Little is known about the residues that control the binding and affinity of thiazide-type diuretics for their protein target, the renal Na(+)-Cl(-) cotransporter (NCC). Previous studies from our group have shown that affinity for thiazides is higher in rat (rNCC) than in flounder (flNCC) and that the transmembrane region (TM) 8-12 contains the residues that produce this difference. Here, an alignment analysis of TM 8-12 revealed that there are only six nonconservative variations between flNCC and mammalian NCC. Two are located in TM9, three in TM11, and one in TM12. We used site-directed mutagenesis to generate rNCC containing flNCC residues, and thiazide affinity was assessed using Xenopus laevis oocytes. Wild-type or mutant NCC activity was measured using (22)Na(+) uptake in the presence of increasing concentrations of metolazone. Mutations in TM11 conferred rNCC an flNCC-like affinity, which was caused mostly by the substitution of a single residue, S575C. Supporting this observation, the substitution C576S conferred to flNCC an rNCC-like affinity. Interestingly, the S575C mutation also rendered rNCC more active. Substitution of S575 in rNCC for other residues, such as alanine, aspartate, and lysine, did not alter metolazone affinity, suggesting that reduced affinity in flNCC is due specifically to the presence of a cysteine. We conclude that the difference in metolazone affinity between rat and flounder NCC is caused mainly by a single residue and that this position in the protein is important for determining its functional properties.

Effect of naringin on the DNA damage induced by daunorubicin in mouse hepatocytes and cardiocytes.

Naringin (Nar) is a flavonoid that has shown antigenotoxic effect against the chromosome damage induced by various compounds. The aims of the present investigation on Nar were threefold: a) to determine its DNA breaking potential in mouse hepatocytes and cardiocytes, b) to evaluate its capacity to inhibit the DNA damage induced by daunorubicin (Dau) in the same tissues, and c) to determine its capacity to trap free radicals in vitro using the 1,1-diphenyl-2-picryl-hydrazyl (DPPH) method. For the two first purposes we applied the comet assay to three groups of animals administered with Nar by the oral route (50, 250, 500 mg/kg), and made the observations before the chemical administration and at 3, 12, and 21 h postadministration. Other three groups of mice were given equal doses of Nar, and 1 h later they were intraperitoneally injected with 1 mg/kg of Dau. The results showed that Nar did not induce DNA breakage in both types of studied cells, in contrast with the significant damage induced by Dau in hepatocytes and cardiocytes. Moreover, the administration of Nar protected the DNA damage produced by Dau, showing a maximum reduction of 71.3% and 51.1% in hepatocytes and cardiocytes, respectively. With respect to the antioxidant potential, 20 mM of Nar produced a free radical scavenging activity as high as 95%. Our study established a high DNA breaking potential of Dau, and a protective effect by Nar, probably related with its capacity to trap free radicals.