Could nanotechnology improve exercise performance? Evidence from animal studies.

This review provides the current state of knowledge regarding the use of nutritional nanocompounds on exercise performance. The reviewed studies used the following nanocompounds: resveratrol-loaded lipid nanoparticles, folic acid into layered hydroxide nanoparticle, redox-active nanoparticles with nitroxide radicals, and iron into liposomes. Most of these nutritional nanocompounds seem to improve performance in endurance exercise compared to the active compound in the non-nanoencapsulated form and/or placebo. Nutritional nanocompounds also induced the following physiological and metabolic alterations: 1) improved antioxidant activity and reduced oxidative stress; 2) reduction in inflammation status; 3) maintenance of muscle integrity; 4) improvement in mitochondrial function and quality; 5) enhanced glucose levels during exercise; 6) higher muscle and hepatic glycogen levels; and 7) increased serum and liver iron content. However, all the reviewed studies were conducted in animals (mice and rats). In conclusion, nutritional nanocompounds are a promising approach to improving exercise performance. As the studies using nutritional nanocompounds were all conducted in animals, further studies in humans are necessary to better understand the application of nutritional nanocompounds in sport and exercise science.

Resveratrol Alleviates Osteoporosis by Promoting Osteogenic Differentiation of Bone Marrow Mesenchymal Stem Cells via SITR1/PI3K/AKT Pathway / El Resveratrol Alivia la Osteoporosis al Promover la Diferenciación Osteogénica de las Células Madre Mesenquimales de la Médula Ósea a Través de la Vía SITR1/PI3K/AKT

SUMMARY: Senile osteoporosis is mainly caused by reduced osteoblast differentiation and has become the leading cause of fractures in the elderly worldwide. Natural organics are emerging as a potential option for the prevention and treatment of osteoporosis. This study was designed to study the effect of resveratrol on osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) in osteoporosis mice. A mouse model of osteoporosis was established by subcutaneous injection of dexamethasone and treated with resveratrol administered by gavage. In vivo and in vitro, we used western blot to detect protein expression, and evaluated osteogenic differentiation of BMSCs by detecting the expression of osteogenic differentiation related proteins, calcium deposition, ALP activity and osteocalcin content. Resveratrol treatment significantly increased the body weight of mice, the level of serum Ca2+, 25(OH)D and osteocalcin, ration of bone weight, bone volume/total volume, trabecular thickness, trabecular number, trabecular spacing and cortical thickness in osteoporosis mice. In BMSCs of osteoporosis mice, resveratrol treatment significantly increased the expression of Runx2, osterix (OSX) and osteocalcin (OCN) protein, the level of calcium deposition, ALP activity and osteocalcin content. In addition, resveratrol treatment also significantly increased the expression of SIRT1, p-PI3K / PI3K and p-AKT / AKT in BMSCs of osteoporosis mice. In vitro, resveratrol increased the expression of SIRT1, p-PI3K / PI3K and p-AKT / AKT, Runx2, OSX and OCN protein, the level of calcium deposition, ALP activity and osteocalcin content in BMSCs in a concentration-dependent manner, while SIRT1 knockdown significantly reversed the effect of resveratrol. Resveratrol can attenuate osteoporosis by promoting osteogenic differentiation of bone marrow mesenchymal stem cells, and the mechanism may be related to the regulation of SIRT1/PI3K/AKT pathway.

La osteoporosis senil es causada principalmente por una diferenciación reducida de osteoblastos y se ha convertido en la principal causa de fracturas en las personas mayores en todo el mundo. Los productos orgánicos naturales están surgiendo como una opción potencial para la prevención y el tratamiento de la osteoporosis. Este estudio fue diseñado para estudiar el efecto del resveratrol en la diferenciación osteogénica de las células madre mesenquimales de la médula ósea (BMSC) en ratones con osteoporosis. Se estableció un modelo de osteoporosis en ratones mediante inyección subcutánea de dexametasona y se trató con resveratrol administrado por sonda. In vivo e in vitro, utilizamos Western blot para detectar la expresión de proteínas y evaluamos la diferenciación osteogénica de BMSC detectando la expresión de proteínas relacionadas con la diferenciación osteogénica, la deposición de calcio, la actividad de ALP y el contenido de osteocalcina. El tratamiento con resveratrol aumentó significativamente el peso corporal de los ratones, el nivel sérico de Ca2+, 25(OH)D y osteocalcina, la proporción de peso óseo, el volumen óseo/ volumen total, el espesor trabecular, el número trabecular, el espaciado trabecular y el espesor cortical en ratones con osteoporosis. En BMSC de ratones con osteoporosis, el tratamiento con resveratrol aumentó significativamente la expresión de las proteínas Runx2, osterix (OSX) y osteocalcina (OCN), el nivel de deposición de calcio, la actividad de ALP y el contenido de osteocalcina. Además, el tratamiento con resveratrol también aumentó significativamente la expresión de SIRT1, p-PI3K/PI3K y p-AKT/AKT en BMSC de ratones con osteoporosis. In vitro, el resveratrol aumentó la expresión de las proteínas SIRT1, p-PI3K/PI3K y p- AKT/AKT, Runx2, OSX y OCN, el nivel de deposición de calcio, la actividad de ALP y el contenido de osteocalcina en BMSC de manera dependiente de la concentración, mientras que La caída de SIRT1 revirtió significativamente el efecto del resveratrol. El resveratrol puede atenuar la osteoporosis al promover la diferenciación osteogénica de las células madre mesenquimales de la médula ósea, y el mecanismo puede estar relacionado con la regulación de la vía SIRT1/PI3K/AKT.

Resveratrol modulates the Nrf2/NF-kB pathway and inhibits TSLP-mediated atopic march

Background: Resveratrol has been found to have anti-inflammatory and anti-allergic proper-ties. The effects of resveratrol on thymic stromal lymphopoietin (TSLP)-mediated atopic march remain unclear. Purpose: To explore the potential role of resveratrol in TSLP-mediated atopic march.Methods: The atopic march mouse model was established by topical application of MC903 (a vitamin D3 analog). Following the treatment with resveratrol, airway resistance in mice was discovered by pulmonary function apparatus, and the number of total cells, neutrophils, and eosinophils in bronchoalveolar lavage fluid was counted. The histopathological features of pul-monary and ear skin tissues, inflammation, and cell infiltration were determined by hematoxy-lin and eosin staining. The messenger RNA (mRNA) levels of TSLP, immunoglobulin E, interleukin (IL)-4, IL-5, and IL-13 were measured by real-time quantitative polymerase chain reaction. The protein expression of nuclear factor kappa B (NF-κB)/nuclear factor erythroid 2-related factor 2 (Nrf2) signaling-associated molecules (p-p65, p65, p-I kappa B kinase alpha (IκBα), IκBα, Nrf2, and TSLP) in lung and ear skin tissues were assessed by Western blot analysis.Results: Resveratrol attenuated airway resistance and infiltration of total cells, eosinophils, and neutrophils in both lung and ear skin tissues. Resveratrol ameliorates serum inflammatory markers in allergic mice. Moreover, the phosphorylation levels of NF-κB pathway-related pro-teins were significantly reduced by administration of resveratrol in allergic lung and ear skin tissues. Similarly, the protein expression of TSLP in both lung and ear skin tissues was reduced by resveratrol, and Nrf2, a protector molecule, was increased with resveratrol treatment (AU)

Resveratrol ameliorates spermatogenesis by increasing protamine 1, 2 and HSPA2 expression in experimental varicocele rat model / El resveratrol mejora la espermatogénesis al aumentar la expresión de protamina 1, 2 y HSPA2 en un modelo experimental de ratas con varicocele

Objectives: Varicocele is a common cause of male infertility associated with an elevated testicular temperature that induces apoptosis, spermatogenesis dysfunction, and affects sperm parameters. In this study, we investigate the probable therapeutic effects of resveratrol (RES), a natural phytoalexin, against varicocele. Materials and methods: In this study, 48 male Wistar rats randomly divided into 8 groups: normal, sham, normal+RES (20 and 50mg/kg), varicocele, varicocele+ethanol and varicocele+RES (20 and 50mg/kg). Incomplete closure of the left renal vein was used for varicocele induction and two months later, RES was administrated orally for 60 days. Then, sperm parameters, DNA fragmentations, chromatin density, and testis histopathology were analyzed. In addition, HSPA2, protamine 1, and 2 expression levels were evaluated using real-time PCR. Results: According to our results, resveratrol treatment improved sperm parameters, testis histopathology, DNA fragmentation, and chromatin maturation which damaged follow varicocele (p≤0.05). Also, it increased HSPA2, protamine 1, and 2 expression levels significantly in both doses (p≤0.05). Conclusion: Resveratrol potentially attenuates varicocele-induced spermatogenic impairments by its antioxidant features and regulates spermatogenic gene expression undergoing DNA fragmentation, so leads histopathological properties of tissues to physiological parameters. (AU)

Objetivos: El varicocele es una causa común de infertilidad masculina asociada con una temperatura testicular elevada que induce apoptosis, disfunción de la espermatogénesis y afecta los parámetros espermáticos. En este estudio, investigamos los probables efectos terapéuticos del resveratrol (RES), una fitoalexina natural, contra el varicocele. Materiales y métodos: En este estudio, 48 ratas Wistar macho se dividieron aleatoriamente en 8 grupos: normal, simulado, normal+ RES (20 y 50mg/kg), varicocele, varicocele+ etanol y varicocele+ RES (20 y 50mg/kg). Se utilizó el cierre incompleto de la vena renal izquierda para la inducción del varicocele y dos meses después se administró RES por vía oral durante 60 días. Luego se analizaron los parámetros espermáticos, las fragmentaciones de ADN, la densidad de cromatina y la histopatología testicular. Además, los niveles de expresión de HSPA2, protamina 1 y 2 se evaluaron mediante PCR en tiempo real. Resultados: Según nuestros resultados, el tratamiento con resveratrol mejoró los parámetros espermáticos, la histopatología testicular, la fragmentación del ADN y la maduración de la cromatina que dañó el varicocele posterior (p≤0,05). Además, aumentó significativamente los niveles de expresión de HSPA2, protamina 1 y 2 en ambas dosis (p≤0,05). Conclusión: El resveratrol atenúa potencialmente las deficiencias espermatogénicas inducidas por varicocele por sus características antioxidantes y regula la expresión de genes espermatogénicos que sufren fragmentación del ADN, por lo que conduce las propiedades histopatológicas de los tejidos a parámetros fisiológicos. (AU)

Resveratrol-Loaded Attalea funifera Oil Organogel Nanoparticles: A Potential Nanocarrier against A375 Human Melanoma Cells.

This study aimed to evaluate Attalea funifera seed oil with or without resveratrol entrapped in organogel nanoparticles in vitro against A375 human melanoma tumor cells. Organogel nanoparticles with seed oil (SON) or with resveratrol entrapped in the seed oil (RSON) formed functional organogel nanoparticles that showed a particle size <100 nm, polydispersity index <0.3, negative zeta potential, and maintenance of electrical conductivity. The resveratrol entrapment efficiency in RSON was 99 ± 1%. The seed oil and SON showed no cytotoxicity against human non-tumor cells or tumor cells. Resveratrol at 50 µg/mL was cytotoxic for non-tumor cells, and was cytotoxic for tumor cells at 25 µg/mL. Resveratrol entrapped in RSON showed a decrease in cytotoxicity against non-tumor cells and cytotoxic against tumor cells at 50 µg/mL. Thus, SON is a potential new platform for the delivery of resveratrol with selective cytotoxic activity in the treatment of melanoma.

Quercetin and resveratrol are associated with the downregulation of TNFalpha/NF-kB/inos axis-mediated acute liver injury in rats induced by paracetamol poisoning / La quercetina y el resveratrol están asociados con la regulación decreciente de la lesión hepática aguda mediada por el eje TNF-alfa/NF-kB/inos en ratas inducida por envenenamiento con paracetamol

SUMMARY: Paracetamol (known as acetaminophen, or APAP) poisoning causes acute liver damage that can lead to organ failure and death. We sought to determine that APAP overdose can augment tumor necrosis factor-alpha (TNF-α)/ nuclear factor kappa B (NF-kB)/induced nitic oxide synthase (iNOS) axis-mediated hepatotoxicity in rats, and the anti-inflammatory polyphenolic compounds, quercetin (QUR) plus resveratrol (RES) can ameliorate these parameters. Therefore, we induced acute hepatotoxicity in rats using APAP overdose (2 g/kg, orally) and the protective group of rats were treated with 50 mg/kg QUR plus 30 mg/kg RES for one week before APAP ingestion. Animals were killed at day 8. APAP poisoning caused the induction of hepatic tissue levels of TNF-α, NF-kB, and iNOS, which were significantly (p<0.05) decreased by QUR+RES. QUR+RES, also inhibited liver injury biomarkers, alanine aminotransferase (ALT) and aspartate aminotransferase (AST). Additionally, a link between liver injury and TNF-α /NF-kB / iNOS axis mediated hepatotoxicity was observed. Thus, the presented data backing the conclusion that intoxication by paracetamol increases TNF-α / NF-kB / iNOS axis -mediated hepatotoxicity, and is protected by a combination of quercetin and resveratrol.

El envenenamiento por paracetamol (conocido como acetaminofeno o APAP) causa daño hepático agudo que puede provocar una insuficiencia orgánica y la muerte. El objetivo de este trabajo fue determinar si la sobredosis de APAP puede aumentar la hepatotoxicidad mediada por el eje del factor de necrosis tumoral alfa (TNF-α)/factor nuclear kappa B (NF-kB)/óxido nítico sintasa inducida (iNOS) en ratas, y si el polifenólico antiinflamatorio compuesto por quercetina (QUR) más resveratrol (RES) pueden mejorar estos parámetros. Por lo tanto, inducimos hepatotoxicidad aguda en ratas usando una sobredosis de APAP (2 g/kg, por vía oral). El grupo protector de ratas se trató con 50 mg/ kg de QUR más 30 mg/kg de RES durante una semana antes de la ingestión de APAP. Los animales se sacrificaron el día 8. El envenenamiento con APAP en el tejido hepático provocó la inducción de niveles de TNF-α, NF-kB e iNOS, que se redujeron significativamente (p<0,05) con QUR+RES. QUR+RES, también inhibió los biomarcadores de daño hepático, la alanina aminotransferasa (ALT) y el aspartato aminotransferasa (AST). Además, se observó una relación entre la lesión hepática y la hepatotoxicidad mediada por el eje TNF-α /NF-kB/iNOS. Por lo tanto, los datos presentados respaldan la conclusión de que la intoxicación por paracetamol aumenta la hepatotoxicidad mediada por el eje TNF-α /NF-kB / iNOS, y está protegida por una combinación de quercetina y resveratrol.

Long-term resveratrol administration improves diabetes-induced pancreatic oxidative stress, inflammatory status, and ß cell function in male rats

Abstract Diabetes is a metabolic disorder caused by insulin resistance or a defect in the pancreatic beta cells in insulin secretion. The aim of this study was to evaluate the possible effectiveness of long-term administration of resveratrol on inflammatory and oxidative stress markers in the pancreatic tissue of diabetic rats. Male Wistar rats (n = 24) were randomly divided into four groups of six animals, namely a healthy group, a healthy group receiving resveratrol, a diabetic control group, and a diabetic group receiving resveratrol. Diabetes was induced by single dose injection of streptozotocin (50 mg/kg; ip), 15 min after injection of nicotinamide (110 mg/kg; ip). Resveratrol was also administered by gavage (5 mg/kg/day) for 4 months. Administration of resveratrol alleviated hyperglycemia, weight loss and pancreatic ß cell function measured by HOMA-ß. Resveratrol improved oxidative stress (nitrate/nitrite, 8-isoprostane and glutathione) and proinflammatory markers (tumor necrosis factor α, cyclooxygenase 2, interleukin 6 and nuclear factor kappa B) in the pancreatic tissue of diabetic rats. Resveratrol administration had no significant effect on the activity of superoxide dismutase and catalase enzyme. These observations indicate that resveratrol administration may be effective as a beneficial factor in improving pancreatic function and reducing the complications of diabetes

Resveratrol Nanoparticles Suppresses Migration and Invasion of Renal Cell Carcinoma Cells by Inhibiting Matrix Metalloproteinase 2 Expression and Extracellular Signal-Regulated Kinase Pathway.

The aim of this study was to examine the impact of Resveratrol nanoparticles on migration/invasion capacity of renal cell carcinoma (RCC) cells and its mechanism. Human RCC cells were exposed to dimethyl sulfoxide or gradient concentrations of Resveratrol nanoparticles respectively, and U0126 were also added in some experiments. We examined renal cell viability by MTT assay, and wound healing test and Transwell assays were used detect invasion and migration capability of RCC cells. We used Western blotting assay to analyze the protein levels in extracellular signal-regulated kinase (ERK) signaling. We also detected the enzymatic capacity of matrix metalloproteinase 2 (MMP-2) in cells by gelatin enzymatic profiling. Resveratrol nanoparticles treatment significantly suppressed cell viability to migrate and invade RCC cells in a dose-dependent manner. Also, notably were reduced MMP-2 activity and expression, and elevated TIMP-2 level were observed in RCC cells exposed with Resveratrol nanoparticles. Further, Resveratrol nanoparticles treatment significantly decreased only the expression of p-ERK1/2, but not p-p38 and p-JNK. Moreover, U0126, which is the ERK inhibitor, exerted similar role as Resveratrol nanoparticles did. Of note was that, combined use of U0126 and Resveratrol nanoparticles displayed a more intense suppression of MMP-2 activity and expression, and also the viability to migrate and invade the RCC cells, compared with Resveratrol nanoparticles treatment alone. The Resveratrol nanoparticles inhibited RCC cells migration and invasion by regulating MMP2 expression and ERK pathways.

Metformin and resveratrol suppress type 2 diabetes mellitus-induced articular cartilage damage in rats associated with the inhibition of inflammation and augmentation of proteoglycans / La metformina y el resveratrol suprimen el daño del cartílago articular inducido por la diabetes mellitus tipo 2 en ratas asociado con la inhibición de la inflamación y el aumento de proteoglicanos

SUMMARY: Induction of osteoarthritis (OA) following diabetes is characterized by a sever inflammation of the joints that can lead to disability. The cartilage content of proteoglycans can substantially be reduced, following the induction of diabetes mellitus associated with inflammation as well as knee joint injury, and the antidiabetic drug metformin combined with the anti-inflammatory agent resveratrol can prevent these deleterious effects. Therefore, insulin-independent diabetes, type 2 diabetes mellitus (T2DM) was induced in Albino rats by streptozotocin (STZ) injection (50 mg/kg) after being fed on a high carbohydrate and fat diets for 2 weeks. The protective group of rats which also received a single injection of STZ was treated daily with metformin (Met; 200 mg/kg) and resveratrol (Res; 30 mg/kg) for 12 weeks. Harvested knee joint tissues were prepared for basic histology stain and for proteoglycans staining using light microscopy. Histology images showed in diabetic rats (T2DM) OA development as demonstrated by profound injury to the knee joint and severe decrease of articular cartilage proteoglycans content, which were substantialy protected by Met+Res. Met+Res also significantly (p< 0.0001) decreased diabetes induced glycemia, dyslipidemia, and the inflammatory biomarkers, tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), and high sensitivity C-reactive protein (hs-CRP). In addition, there was a significant correlation between OA and glycemia, dyslipidemia, and inflammation. Collectively, we demonstrate an association between knee joint damage and biomarkers of glycemia, dyslipidemia, and inflammation in diabetes-induced OA, with metformin plus resveratrol providing protective effects.

RESUMEN: La inducción de osteoartritis (OA) después de la diabetes se caracteriza por una inflamación severa de las articulaciones que puede conducir a la discapacidad. El contenido de cartílago de proteoglicanos se puede reducir sustancialmente, luego de la inducción de diabetes mellitus asociada con inflamación y lesión en la articulación de la rodilla sin embargo, el fármaco antidiabético metformina combinado con el agente antiinflamatorio resveratrol puede prevenir estos efectos nocivos. Por lo tanto, se indujo diabetes insulino dependiente, diabetes mellitus tipo 2 (T2DM) en ratas albinas mediante inyección de estreptozotocina (STZ) (50 mg/kg) después de haber sido alimentadas con dietas ricas en carbohidratos y grasas durante 2 semanas. El grupo protector de ratas que también recibió una inyección única de STZ fue tratado diariamente con metformina (Met; 200 mg/kg) y resveratrol (Res; 30 mg/kg) durante 12 semanas. Tejidos de la articulación de la rodilla fueon retirados y teñidos con histología básica y tinción de proteoglicanos usando microscopía óptica. Las imágenes histológicas en ratas diabéticas mostraban (T2DM) desarrollo de OA visualizadas por una lesión profunda en la articulación de la rodilla y una disminución severa del contenido de proteoglicanos del cartílago articular, los cuales estaban sustancialmente protegidos por Met+Res. Met+Res. También disminuyó significativamente (p< 0,0001) la glucemia inducida por la diabetes, la dislipidemia y los biomarcadores inflamatorios, el factor de necrosis tumoral alfa (TNF-α), la interleucina-6 (IL-6) y la proteína C reactiva de alta sensibilidad (PCR-hs). Además, hubo una correlación significativa entre la OA y la glucemia, la dislipidemia y la inflamación. En conjunto, demostramos una asociación entre el daño de la articulación de la rodilla y los biomarcadores de glucemia, dislipidemia e inflamación en la OA inducida por diabetes, con metformina más resveratrol que brindan efectos protectores.

GSH-responsive poly-resveratrol based nanoparticles for effective drug delivery and reversing multidrug resistance.

Cancer poses a serious threat to human health and is the most common cause of human death. Polymer-based nanomedicines are presently used to enhance the treatment effectiveness and decrease the systemic toxicity of chemotherapeutic agents. However, the disadvantage of currently polymeric carriers is without therapy procedure. Herein, for the first time, glutathione (GSH)-responsive polymer (PRES) with anti-cancer effect was synthesized following the condensation-polymerization method using resveratrol (RES) and 3,3'-dithiodipropionic acid. PRES can not only suppress the tumor cells growth but can also self-assemble into nanoparticles (∼93 nm) for delivering antitumor drugs, such as paclitaxel (PTX@PRES NPs). The system could achieve high drug loading (∼7%) and overcome multidrug resistance (MDR). The results from the in vitro studies revealed that the NPs formed of PRES were stable in the systemic circulation, while could be efficiently degraded in tumor cells high GSH environment. Results from cytotoxicity tests confirmed that PTX@PRES NPs could effectively suppress the growth of cancer cells (A549) and drug-resistant cells (A549/PTX). The NPs could also be used to significantly increase the therapeutic efficacy of the drugs in A549/PTX tumor-bearing mice. In vivo investigations also demonstrated that the PRES-based NPs exhibited tumor inhibition effects. In summary, we report that the GSH-responsive polymer synthesized by us exhibited multiple interesting functions and could be used for effective drug delivery. The polymer exhibited good therapeutic effects and could be used to overcome MDR. Thus, the synthesized system can be used to develop a new strategy for treating cancer.

Impact of calcium ions and degree of oxidation on the structural, physicochemical, and in-vitro release properties of resveratrol-loaded oxidized gellan gum hydrogel beads.

Oxidized gellan gum (OGG) hydrogel beads as delivery systems for resveratrol were fabricated by ionic cross-linking with calcium chloride (CaCl2). The degree of oxidation (DO) and CaCl2 concentration had significant influences on the formation and functional properties of hydrogel beads. The resveratrol encapsulation efficiency (66.43%-79.84%) and loading capacity (4.15%-5.05%) of OGG hydrogel beads were enhanced as DO increased. The hydrogel beads exhibited a uniform spherical shape as observed by scanning electron microscope. Fourier transform infrared spectroscopy analysis confirmed that hydrogen bonds and ionic interaction participated in the formation of hydrogel beads. X-ray diffraction analysis revealed that the physical state of resveratrol was changed from crystalline to amorphous form after encapsulation. Furthermore, the physical stability and antioxidant capacity evaluation demonstrated that the hydrogel bead fabricated with DO80 OGG and CaCl2 concentration of 1.0 M could provide high protection for resveratrol against degradation by environmental stresses and maintain its antioxidant capacity. The DO and CaCl2 concentrations could modulate the in-vitro release behaviors of hydrogel beads and obtain a good small intestinal-targeted release of resveratrol at high DO and medium CaCl2 concentration. These findings suggested that a promising delivery system for encapsulating bioactive ingredients can be fabricated by rational design.

Resveratrol regulates intestinal barrier function in cyclophosphamide-induced immunosuppressed mice.

BACKGROUND: Resveratrol, a kind of polyphenolic phytoalexin, can be obtained from numerous natural foods. Although resveratrol is demonstrated to have various bioactivities, little is known about the regulation of intestinal barrier function under immunosuppression. The present study is aimed at investigating the regulatory effect of resveratrol on intestinal barrier function in immunosuppression in mice induced by cyclophosphamide. RESULTS: The effects of resveratrol on intestinal biological barrier were evaluated by 16S rRNA and metagenome sequencing analysis. The results showed that resveratrol could improve diversity of the intestinal microbiota and intestinal flora structure by increasing the abundance of probiotics, and resveratrol regulated the function of gut microbiota to resist immunosuppression. Resveratrol could significantly upregulate the secretion of secretory immunoglobulin A and promote the transcriptional levels of test cytokines, including tumor necrosis factor α, interferon γ, interleukin 4 and interleukin 6 in jejunum and ileum mucosa, suggesting improved intestinal immune barrier by resveratrol. The mRNA and protein levels of tight junction proteins involved in intestinal physical barrier function, including zonula occludens 1 (ZO-1), claudin 1 and occludin, were increased after resveratrol treatment. The protein levels of toll-like receptor 4 (TLR4), phosphorylation nuclear factor kappa-B (NF-κB-p65) and inhibitor of nuclear factor kappa-B kinase α were decreased by resveratrol treatment when compared with the untreated group, indicating inhibition of the TLR4/NF-ĸB signaling pathway. CONCLUSION: These results provide new insights into regulation of the intestinal barrier function by resveratrol under immunosuppression and potential applications of resveratrol in recovering intestinal function. © 2021 Society of Chemical Industry.

Additive effects of resveratrol and doxorubicin on bladder cancer cells.

The treatment of bladder cancer remains a challenge in clinical practice. Different chemotherapeutic protocols can be used; however, it is common to observe tumor recurrence and secondary effects that result in toxicity. Doxorubicin (DOX), one of the most effective anticancer agents used to treat bladder cancer, can cause chronic cardiotoxicity, limiting its use in clinical practice. Resveratrol (RES), a natural product with potential antitumor activity against bladder cancer, is associated with rapid metabolism and low bioavailability and needs to be combined with chemotherapeutic drugs to improve its use. Our study aimed to assess the therapeutic effect of a low concentration of DOX (2 µM) in combination with RES (150, 200 and 250 µM) on two bladder cancer cell lines. We investigated the mechanism of interaction between the drugs by performing cytotoxicity, clonogenic, oxidative stress, cell migration, cell morphology and nuclear division index (NDI) assays. Cytotoxicity evaluation revealed an additive interaction between RES and DOX for both cell lines. Additionally, the results of cell colony formation, oxidative stress, cell migration, cell morphology and NDI assays showed that a combination of DOX and RES was more effective than RES or DOX alone. In conclusion, a low concentration of DOX combined with RES could potentiate the antitumor effects of the drugs on bladder cancer cells, thus overcoming the secondary effects caused by DOX and the low bioavailability of resveratrol.

Bare Metal Stents on Resveratrol-Coated Balloons in Porcine Coronary and Peripheral Arteries.

Balloon angioplasty and stent implantation are standard techniques to reopen stenotic vessels. Often, balloons or stents coated with cytostatic drugs are used to prevent re-occlusion of the arteries. Resveratrol, which is known for its numerous beneficial effects on cardiovascular health, is used as an antioxidant additive on paclitaxel-coated balloon catheters. What is still unclear is whether resveratrol-only balloon coating in combination with a bare metal stent (BMS) also has positive effects on vascular healing. Here, we analyzed neointimal thickening, fibrin deposition, inflammation, vasa vasorum density, and reendothelialization after implantation of BMS via a resveratrol coated balloon approach in a porcine model. In general, resveratrol treatment did not result in significantly altered responses compared to the control group in peripheral arteries. In coronary arteries, an increase in vasa vasorum density became evident three days after resveratrol treatment compared to the control group and abolished up to day 7. Significant effects of the resveratrol treatment on the fibrin score or intima-media area were transient and restricted to either peripheral or coronary arteries. In conclusion, local single-dose resveratrol treatment via a resveratrol-only coated balloon and BMS approach did not lead to adverse systemic or local effects, but also no significant beneficial effects on vascular healing were detected in the current study.

The effectiveness of resveratrol in treatment of PCOS on the basis of experimental model in rats.

PURPOSE OF THE STUDY: Polycystic ovary syndrome (PCOS) is a widespread endocrine disorder in women of reproductive age. Further research is required to justify new directions of effective targeted therapy of this condition. Resveratrol possesses anti-inflammatory, antioxidant and antidiabetic properties. The purpose of this study was to evaluate the potential effectiveness of resveratrol in PCOS based on the created model of this disease in Wistar rats. MATERIALS AND METHODS: The PCOS model was created by oral administration of letrozole to female Wistar rats.. The animals received resveratrol at a dosage of 20 mg/kg and 30 mg/kg for the next 30 days. Then ovariectomy was performed for histological confirmation of the effectiveness of resveratrol in the treatment of PCOS. Regularity of estrous cycle, animal's body mass and the level of soluble receptors for advanced glycation end products (sRAGE) in the blood of rats were also evaluated in dynamics. RESULTS: The study revealed that administration of resveratrol leads to dose-dependent restoration of normal morphology of ovarian tissue, normalizes regularity of estrous cycle and decreases body weight of rats with PCOS. CONCLUSION: The results obtained in rats suggest that resveratrol may be a promising agent for the treatment of PCOS in women.

Resveratrol loaded nanoparticles attenuate cognitive impairment and inflammatory markers in PTZ-induced kindled mice.

Resveratrol has been found to exert protective effects in neurological disorders, including epilepsy. However, its poor bioavailability and difficulty in reaching the brain's targeted location reduce resveratrol's efficacy substantially. The side effects due to the higher concentration of drugs are another matter of concern. The objective of the present study is to propose solutions to these issues by encapsulating resveratrol in glutathione-coated collagen nanoparticles' core. The collagen nanoparticles increase the resveratrol's bioavailability, and glutathione helps in the passage of the encapsulated resveratrol to the target location in the brain. The concentration also substantially reduces due to resveratrol's encapsulation in glutathione-coated collagen nanoparticles. The encapsulated resveratrol is termed nanoresveratrol. The effectiveness of nanoresveratrol on epilepsy seizures was evaluated through histopathological examinations, ELISA tests, and qRT-PCR tests on the hippocampus of the kindled mice. The novelty of the present study thus lies in (i) the synthesis of nanoresveratrol using glutathione-coated collagen nanoparticles and (ii) the application of synthesized nanoresveratrol in the treatment of epilepsy. The study's outcome shows that nanoresveratrol has a favorable impact in reducing cognitive impairment in kindled mice, and it is more effective in controlling epilepsy seizures than resveratrol. The p-values of all the nanoresveratrol-given groups of mice (compared with the diseased group) were substantially smaller (∼10-4 to 10-2) than the significance level (0.05), indicating that the nanoresveratrol-given groups are significantly different from the diseased group, i.e., the nanoresveratrol has a significant effect on the mice. The concentration of resveratrol also decreases substantially in the proposed nanoformulation. It was observed that even 0.4 mg/kg of nanoformulation of resveratrol is performing better than 40 mg/kg of resveratrol.

Resveratrol and Colorectal Cancer: A Molecular Approach to Clinical Researches.

Phytochemicals are the most valuable and comprehensive structures, which may have a broad range of protective benefits, from reducing inflammation and speeding healing to preventing infection and fighting cancer. Resveratrol (RSV) is a natural phenolic compound from the oligomeric stilbenoids group, which is usually found in daily human diet, such as grape, peanut, berries and grains. It exhibits anti-inflammatory, neuroprotective, antioxidant, and cancer prevention and treatment effects. RSV is thought to have an impressive outcome in colorectal cancer (CRC) treatment through the vital molecules and cancer signaling pathways, including SIRT1, P53, P21, AMPK, ROS, BMP7, COX-2, NO, caspases, Wnt, TNFs, NF-κB, EMT, and pentose phosphate pathway. Therefore, this paper reviews the current researches on the pharmacological effects and pharmacokinetics of resveratrol and its drug delivery system, as well as clinical studies involving CRC.

Construction of IL-13 Receptor α2-Targeting Resveratrol Nanoparticles against Glioblastoma Cells: Therapeutic Efficacy and Molecular Effects.

Glioblastoma multiforme (GBM) is the most common lethal primary brain malignancy without reliable therapeutic drugs. IL-13Rα2 is frequently expressed in GBMs as a molecular marker. Resveratrol (Res) effectively inhibits GBM cell growth but has not been applied in vivo because of its low brain bioavailability when administered systemically. A sustained-release and GBM-targeting resveratrol form may overcome this therapeutic dilemma. To achieve this goal, encapsulated Res 30 ± 4.8 nm IL-13Rα2-targeting nanoparticles (Pep-PP@Res) were constructed. Ultraviolet spectrophotometry revealed prolonged Res release (about 25%) from Pep-PP@Res in 48 h and fluorescent confocal microscopy showed the prolonged intracellular Res retention time of Pep-PP@Res (>24 h) in comparison with that of free Res (<4 h) and PP@Res (<4 h). MTT and EdU cell proliferation assays showed stronger suppressive effects of Pep-PP@Res on rat C6 GBM cells than that of PP@Res (p = 0.024) and Res (p = 0.009) when used twice for 4 h/day. Pep-PP@Res had little toxic effect on normal rat brain cells. The in vivo anti-glioblastoma effects of Res can be distinctly improved in the form of Pep-PP@Res nanoparticles via activating JNK signaling, upregulating proapoptosis gene expression and, finally, resulting in extensive apoptosis. Pep-PP@Res with sustained release and GBM-targeting properties would be suitable for in vivo management of GBMs.

Prevention of recurrent respiratory infections : Inter-society Consensus.

Recurrent respiratory infections (RRIs) are a common clinical condition in children, in fact about 25% of children under 1 year and 6% of children during the first 6 years of life have RRIs. In most cases, infections occur with mild clinical manifestations and the frequency of episodes tends to decrease over time with a complete resolution by 12 years of age. However, RRIs significantly reduce child and family quality of life and lead to significant medical and social costs.Despite the importance of this condition, there is currently no agreed definition of the term RRIs in the literature, especially concerning the frequency and type of infectious episodes to be considered. The aim of this consensus document is to propose an updated definition and provide recommendations with the intent of guiding the physician in the complex process of diagnosis, management and prevention of RRIs.

Rationalizing the Design of Hyaluronic Acid-Decorated Liposomes for Targeting Epidermal Layers: A Combination of Molecular Dynamics and Experimental Evidence.

This work provides information on the features of low molecular weight hyaluronic acid (HA)-decorated liposomes to target resveratrol (RSV) in the skin. Deformable liposomes were made of soy-phosphatidylcholine with Tween 80 as the fluidizing agent. For HA conjugation, three different phosphoethanolamines were tested: 1,2-dipalmitoyl-sn-glycero-3-phosphoethanolamine (DPPE), 1,2-dimyristoyl-sn-glycero-3-phosphoethanolamine (DMPE), and 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine (DOPE). The different phosphoethanolamine-HA conjugates were inserted into the liposome bilayer by hydration (HA on both faces of the bilayer) or by the postinsertion method (HA only on the external face of the bilayer). The effect of these variables on deformability was experimentally assessed by an in-house method (K value, the lower the value, the higher the deformability) and molecular dynamics (MD) simulations. The results showed that the K values of HA-liposomes obtained by hydration were higher than the K values of HA-liposomes prepared by postinsertion, and both were at least 10-fold higher than the K values of the corresponding plain liposomes. The nature of the lipid anchor played a key role in deformability (DMPE > DOPE > DPPE) with high variability in the case of DOPE formulations. These data were justified by the trends found in silico for the bilayer bending modulus and the HA end-to-end distance. In addition to liposome flexibility, the HA extent seems to be the key factor governing the skin penetration of RSV. When the extent is higher, the amount of the drug retained in the skin is larger. Regarding skin permeation, a parabolic trend was recorded, and the optimal amount to favor skin permeation was an approximately 30 HA/phospholipid (µg/mmol) ratio. This study reports the first piece of evidence that it is possible to control drug delivery in the skin by tuning the amount of HA on the vesicle surface.