Hybrid Fruits for Improving Health-A Comprehensive Review.

Several species of hybrid fruits, such as citrus, grapes, blueberries, apples, tomatoes, and lingonberries among others, have attracted scientific attention in recent years, especially due to their reported antioxidant and anti-inflammatory properties. The bagasse, leaves, bark, and seeds of these hybrid fruits have large amounts of polyphenols, such as flavonoids, which act as potent antioxidants. Several studies have been carried out in cellular models of neurotoxicity of the extract of these fruits, to document the beneficial effects for human health, as well as to prove its antiproliferative effect in cancer cells. In the present review, through a synthesis of existing information in the scientific literature, we demonstrate that hybrid fruits are a source of antioxidant and bioactive compounds, which act in the inhibition of diseases such as cancer, diabetes, and inflammatory and neurodegenerative diseases, and consequently improving human health.

Botanical, nutritional, phytochemical characteristics, and potential health benefits of murici (Byrsonima crassifolia) and taperebá (Spondias mombin): insights from animal and cell culture models.

Brazil has great biodiversity, and the Amazon biome stands out for a variety of native fruits with high economic and nutritional potential. Murici (Byrsonima crassifolia) and taperebá (Spondias mombin) are sources of vitamins, minerals, and phytochemicals with potential health benefits. Because of the bioactive potential of these Brazilian fruits, this review aims to gather the most current existing knowledge about their botanical, nutritional, and phytochemical properties, because the presence of several bioactive compounds may bring promising strategies to the prevention and treatment of several diseases. The search was conducted of the LILACS, MEDLINE, PubMed, and Science Direct databases, considering articles published between 2010 and 2023. The compiled results showed that these fruits, their leaves, and seeds have great antioxidant activity and are a good source of phytochemicals, especially phenolic compounds. In vitro and in vivo studies indicate that these bioactive compounds have several health benefits related to the prevention or treatment of diseases, including antioxidant effects; anti-inflammatory effects; and antidiabetic, antidepressant, neuroprotective, antiproliferative, anticancer, hypolipemic, cardioprotective, gastroprotective, hepatoprotective, and nephroprotective effects, and they are particularly related to the reduction of damage from oxidative stress. This review highlights the potential of these fruits as functional foods and for therapeutic purposes. However, it is recommended to conduct more studies on the identification and quantification of phytochemicals present in these fruits and studies in humans to better understand the mechanisms of action related to their effects and to understand the interaction of these compounds with the human body, as well as to prove the safety and efficacy of these compounds on health.

Probiotic fermented whey-milk beverages: Effect of different probiotic strains on the physicochemical characteristics, biological activity, and bioactive peptides.

The effect of probiotic strains (Lactobacillus acidophilus La-03 (La-03); Lactobacillus acidophilus La-05 (La-05); Bifidobacterium Bb-12 (Bb-12) or Lacticaseibacillus casei-01 (L. casei-01)) on the characteristics of fermented whey-milk beverages during storage (4 °C, 30 days) was evaluated. The products were assessed for biological and antioxidant activities, physicochemical characteristics, and bioactive peptides. Probiotic addition increased α-amylase and α-glucosidase inhibition and antioxidant activities, mainly at 15 days of storage. L. casei-01 showed higher metabolic activity (higher titratable acidity and lower pH values) and the presence of anti-hypertensive peptides, while La-5 and Bb-12 showed higher α-glucosidase inhibition, improvements in the high saturated hypercholesterolemic index, and peptides with ACE-inhibitory, antimicrobial, immunomodulatory, and antioxidant activities. Our findings suggest that probiotic fermented whey-milk beverages may exert antidiabetic and antioxidant properties, being suggested La-5 or Bb-12 as probiotics and 15 days of storage.

Lycopene induces bone marrow lymphopoiesis and differentiation of peritoneal IgA-producing cells.

Lycopene is a hydrocarbon-carotenoid commonly found in red fruits intake with major function correlated to antioxidative capacity in several pathological conditions, including cancer and cardiovascular diseases. Recently, lycopene has been associated with hematopoiesis, although the effects on B lymphocyte differentiation and antibody production are poorly understood. In this work, the principal aim was to investigate whether lycopene affects B lymphopoiesis and terminal differentiation into plasma cells. Distinct in vivo and in vitro strategies based on lycopene supplementation were used direct in Balb/c mice or in culture systems with cells derived of these mice. In the bone marrow, lycopene expanded B220+IgM- progenitor B cells and B220+IgM+ immature B lymphocytes. In the spleen, lycopene induced terminal CD138+ plasma cell generation. In the blood, we found prominent IgA and low IgM levels after lycopene administration. Interestingly, the pattern of peritoneal IgM+ and IgA+ B cells indicated a significant IgM-to-IgA class switching after lycopene injection. These data indicated that lycopene induces B cell differentiation into IgA-producing plasma cells. Thus, a new cellular function has been attributed to lycopene for B lymphocyte biology and possibly associated with humoral responses and mucosal immunity.

Bovine Lactoferrin Induces Cell Death in Human Prostate Cancer Cells.

Bovine lactoferrin (bLf) is a multifunctional protein widely associated with anticancer activity. Prostate cancer is the second most frequent type of cancer worldwide. This study was aimed at evaluating the influence of bLf on cell viability, cell cycle progression, reactive oxygen species (ROS) production, and rate of apoptosis in the human prostate cancer cell line (DU-145). MTT assay and trypan blue exclusion were used to analyze cell viability. Morphological changes were analyzed through optical microscopy after 24 h and 48 h of bLf treatment. FITC-bLf internalization and cellular damage were observed within 24 h by confocal fluorescence microscopy. Cell cycle analyses were performed by flow cytometry and propidium iodide. For caspases 3/7 activation and reactive oxygen species production evaluation, cells were live-imaged using the high-throughput system Operetta. The cell viability assays demonstrated that bLf induces cell death and morphological changes after 24 h and 48 h of treatment compared to control on DU-145 cells. The bLf internalization was detected in DU-145 cells, G1-phase arrest of the cell cycle, caspase 3/7 activation, and increased oxidative stress on bLf-treated cells. Our data support that bLf has an important anticancer activity, thus offering new perspectives in preventing and treating prostate cancer.

A Decade of Research on Coffee as an Anticarcinogenic Beverage.

Coffee consumption has been investigated as a protective factor against cancer. Coffee is a complex beverage that contains more than 1000 described phytochemicals, which are responsible for its pleasant taste, aroma, and health-promoting properties. Many of these compounds have a potential therapeutic effect due to their antioxidant, anti-inflammatory, antifibrotic, and anticancer properties. The roasting process affects the phytochemical content, and undesirable compounds may be formed. In recent years, there have been contradictory publications regarding the effect of coffee drinking and cancer. Therefore, this study is aimed at evaluating the association of coffee consumption with the development of cancer. In PubMed, until July 2021, the terms "Coffee and cancer" resulted in about 2150 publications, and almost 50% of them have been published in the last 10 years. In general, studies published in recent years have shown negative associations between coffee consumption and the risk or development of different types of cancer, including breast, prostate, oral, oral and pharyngeal, melanoma, skin and skin nonmelanoma, kidney, gastric, colorectal, endometrial, liver, leukemic and hepatocellular carcinoma, brain, and thyroid cancer, among others. In contrast, only a few publications demonstrated a double association between coffee consumption and bladder, pancreatic, and lung cancer. In this review, we summarize the in vitro and in vivo studies that accumulate epidemiological evidence showing a consistent inverse association between coffee consumption and cancer.

Antitumor Effects of Freeze-Dried Robusta Coffee (Coffea canephora) Extracts on Breast Cancer Cell Lines.

Coffee consumption is believed to have chemopreventive and chemotherapeutic effects and to contribute to preventing the development and progression of cancer. However, there is still controversy around these claims. As indicated in our previous works, diet can influence the risk of breast cancer. Intake of coffee is hypothesized to reduce this risk, but current scientific evidence is not conclusive. This work is aimed at studying the effects of Robusta coffee bean extract on cell viability, proliferation, and apoptosis of different human cancers, especially breast cancer cell lines. To this end, cell viability was evaluated by Alamar Blue in 2D and 3D models, the cell cycle by PI, apoptosis by annexin V, mitochondrial morphology, and functionality by mitoTracker, and colony formation capacity by the clonogenic assay. Green and dark coffee extract significantly reduced viability in human breast, colorectal, brain, and bone cancer cells. Coffee anticancer activity was clearly evidenced in MDA-MB-231 (ER-) and MCF-7 (ER+) breast cancer cells but not in the normal breast cell line. In addition, coffee extract induces an increase S phase and a decrease G2/M population in breast cancer cells, affected the mitochondrial morphology, and triggered apoptosis. MDA-MB-231 breast cancer cells lost their clonogenic capacity after treatment. The antitumor activity was demonstrated in both 2D and 3D culture cell models.

Antiproliferative and apoptotic effects of probiotic whey dairy beverages in human prostate cell lines.

The present study aimed to evaluate the antiproliferative and apoptotic effects of probiotic whey dairy beverages in human prostate cancer cell lines (PC-3 and DU-145). Five different whey beverages were manufactured: conventional whey beverage (without addition of probiotic strain, CTL); and whey beverages containing Lactobacillus acidophilus La-05, Lactobacillus acidophilus La-03, Lactobacillus casei-01, and Bifidobacterium animalis Bb-12. Cell viability was determined by MTT assay and cell cycle arrest, and apoptosis by flow cytometry. All the samples presented cytotoxic activities against both cell lines. A decrease in the percentage of PC-3 cells in G0/G1 and S, followed by an increase in G2/M phase were observed with L. casei-01, Bb-12 and La-05 beverages (50.0 and 100.0 µg/mL). The extracts of the whey beverages caused extensive apoptosis induction in both cells' lines, regardless of the probiotic strain. However, the whey beverage added with L. casei-01 might be a better candidate against prostate cancer cells.

Antiproliferative effect of guava fruit extracts in MDA-MB-435 and MCF-7 human breast cancer cell lines.

Breast cancer is the most frequent and lethal neoplastic disease among women worldwide. Psidium Guajava is a promising functional food against cancer, owing to a variety of bioactive compounds. This study aimed to evaluate the anticarcinogenic potential of Pedro Sato (PS), Hitigio (HI) and Tsumori (TS) guava cultivars fruit pulp extracts in MDA-MB-435 and MCF-7 human breast cancer cells. The antioxidant capacity of the extracts and their effect on cell viability, cell cycle and apoptosis were assessed. Additionally, the concentration of carotenoids, total phenolics, ascorbic acid and other physicochemical parameters were evaluated. PS pulp extract showed the highest in vitro antioxidative activity by all tested methods, as well as the highest content of lycopene and total phenolics, while TS pulp extract presented the highest concentration of ß-carotene. After 48 hours treatment, all guava cultivars' extracts caused reduction of MDA-MB-435 and MCF-7 cells viability, with PS and HI being the most effective extracts. All guava extracts caused MDA-MB-435 and MCF-7 cell count reduction in G0/G1 and G2/M phases and increased apoptosis. The present results strongly suggest that guava pulp exerts antiproliferative effect on breast adenocarcinoma cells.

Improvement of antioxidant status after Brazil nut intake in hypertensive and dyslipidemic subjects.

OBJECTIVES: To investigate the effect of partially defatted Granulated Brazil nut (GBN) on biomarkers of oxidative stress and antioxidant status of hypertensive and dyslipidemic patients on nutrition and drug approaches. METHODS: Ninety one hypertensive and dyslipidemic subjects of both genders (51.6 % men), mean age 62.1 ± 9.3 years, performed a randomized crossover trial, double-blind, placebo controlled. Subjects received a diet and partially defatted GBN 13 g per day (≈227.5 µg/day of selenium) or placebo for twelve weeks with four-week washout interval. Anthropometric, laboratory and clinic characteristics were investigated at baseline. Plasma selenium (Se), plasma glutathione peroxidase (GPx3) activity, total antioxidant capacity (TAC), 8-epi PGF2α and oxidized LDL were evaluated at the beginning and in the end of each intervention. RESULTS: GBN intake significantly increased plasma Se from 87.0 ± 16.8 to 180.6 ± 67.1 µg/L, increased GPx3 activity in 24,8% (from 112.66 ± 40.09 to 128.32 ± 38.31 nmol/min/mL, p < 0,05), and reduced 3.25% of oxidized-LDL levels (from 66.31 ± 23.59 to 60.68 ± 20.88 U/L, p < 0.05). An inverse association between GPx3 and oxidized LDL levels was observed after supplementation with GBN by simple model (ß -0.232, p = 0.032) and after adjustment for gender, age, diabetes and BMI (ß -0.298, p = 0.008). There wasn't association between GPx3 and 8-epi PGF2α (ß -0.209, p = 0.052) by simple model. CONCLUSION: The partially defatted GBN intake has a potential benefit to increase plasma selenium, increase enzymatic antioxidant activity of GPx3 and to reduction oxidation in LDL in hypertensive and dyslipidemic patients. TRIAL REGISTRATION: ClinicalTrials.gov Identifier NCT01990391; November 20, 2013.

Lycopene and beta-carotene induce growth inhibition and proapoptotic effects on ACTH-secreting pituitary adenoma cells.

Pituitary adenomas comprise approximately 10-15% of intracranial tumors and result in morbidity associated with altered hormonal patterns, therapy and compression of adjacent sella turcica structures. The use of functional foods containing carotenoids contributes to reduce the risk of chronic diseases such as cancer and vascular disorders. In this study, we evaluated the influence of different concentrations of beta-carotene and lycopene on cell viability, colony formation, cell cycle, apoptosis, hormone secretion, intercellular communication and expression of connexin 43, Skp2 and p27(kip1) in ACTH-secreting pituitary adenoma cells, the AtT20 cells, incubated for 48 and 96 h with these carotenoids. We observed a decrease in cell viability caused by the lycopene and beta-carotene treatments; in these conditions, the clonogenic ability of the cells was also significantly decreased. Cell cycle analysis revealed that beta-carotene induced an increase of the cells in S and G2/M phases; furthermore, lycopene increased the proportion of these cells in G0/G1 while decreasing the S and G2/M phases. Also, carotenoids induced apoptosis after 96 h. Lycopene and beta-carotene decreased the secretion of ACTH in AtT20 cells in a dose-dependent manner. Carotenoids blocked the gap junction intercellular communication. In addition, the treatments increased the expression of phosphorylated connexin43. Finally, we also demonstrate decreased expression of S-phase kinase-associated protein 2 (Skp2) and increased expression of p27(kip1) in carotenoid-treated cells. These results show that lycopene and beta-carotene were able to negatively modulate events related to the malignant phenotype of AtT-20 cells, through a mechanism that could involve changes in the expression of connexin 43, Skp2 and p27(kip1); and suggest that these compounds might provide a novel pharmacological approach to the treatment of Cushing's disease.

Interplay of cysteinyl leukotrienes and TGF-ß in the activation of hepatic stellate cells from Schistosoma mansoni granulomas.

Hepatic stellate cells (HSCs) have a critical role in liver physiology, and in the pathogenesis of liver inflammation and fibrosis. Here, we investigated the interplay between leukotrienes (LT) and TGF-ß in the activation mechanisms of HSCs from schistosomal granulomas (GR-HSCs). First, we demonstrated that GR-HSCs express 5-lipoxygenase (5-LO), as detected by immunolocalization in whole cells and confirmed in cell lysates through western blotting and by mRNA expression through RT-PCR. Moreover, mRNA expression of 5-LO activating protein (FLAP) and LTC(4)-synthase was also documented, indicating that GR-HSCs have the molecular machinery required for LT synthesis. Morphological analysis of osmium and Oil-Red O-stained HSC revealed large numbers of small lipid droplets (also known as lipid bodies). We observed co-localization of lipid droplet protein marker (ADRP) and 5-LO by immunofluorescence microscopy. We demonstrated that GR-HSCs were able to spontaneously release cysteinyl-LTs (CysLTs), but not LTB(4,) into culture supernatants. CysLT production was highly enhanced after TGF-ß-stimulation. Moreover, the 5-LO inhibitor zileuton and 5-LO gene deletion were able to inhibit the TGF-ß-stimulated proliferation of GR-HSCs, suggesting a role for LTs in HSC activation. Here, we extend the immunoregulatory function of HSC by demonstrating that HSC from liver granulomas of schistosome-infected mouse are able to release Cys-LTs in a TGF-ß-regulated manner, potentially impacting pathogenesis and liver fibrosis in schistosomiasis.

Lycopene isomerisation and storage in an in vitro model of murine hepatic stellate cells.

BACKGROUND: Lycopene is a carotenoid whose biological activities and protective effect on prostate and breast cancer have been described, but little is known on its extra-intestinal metabolism and storage. While most alimentary lycopene is in all-trans configuration, in animal and human tissues approximately half of the lycopene is in cis isoforms. AIM OF STUDY: Our object was to monitor the capacity of storage, isomerisation, and intracellular localization of all-trans and cis lycopene in hepatic stellate cells, which are the major sites of metabolism and storage of retinoids and carotenoids in the body. METHODS: We used the GRX cell line representative of murine hepatic stellate cells, incubated with 1-30 muM lycopene in culture medium. Analysis was done by high-performance liquid chromatography. RESULTS: Lycopene was able to induce expression of the lipocyte phenotype and it was internalized into GRX cells. Its cellular release only occurred in presence of albumin with a rapid initial decrease of intracellular lycopene. A corresponding increase in the culture medium was observed at 24 h. All-trans, 13-cis and 9-cis lycopene isoforms were identified in all the cell compartments. The membrane fraction contained the major part of lycopene, followed by the cytoplasmic fraction, lipid droplets and nuclei. The ratio between all-trans and cis isomers was approximately 2/1 in the majority parts of cell compartments. CONCLUSIONS: This study identified a novel hepatic cell type able to store and isomerise lycopene. Liver can contribute to the serum and tissue equilibrium of cis/trans isomers of lycopene, and to participate in storage of lycopene under high extracellular concentration such as observed after the alimentary input.