Grape seed extract in combination with deferasirox ameliorates iron overload, oxidative stress, inflammation, and liver dysfunction in beta thalassemia children.

BACKGROUND AND PURPOSE: Iron overload in the body is associated with serious and irreversible tissue damage. This study aimed to investigate the iron-chelating, antioxidant, anti-inflammatory, and hepatoprotective activities of grape seed extract (GSE) supplement as well as its safety in ß-thalassemia major (ß-TM) pediatric patients receiving deferasirox as a standard iron-chelation therapy. MATERIALS AND METHODS: The children were randomly allocated to either GSE group (n = 30) or control group (n = 30) to receive GSE (100 mg/day) or placebo capsules, respectively, for 4 weeks. The serum levels of iron, ferritin, total iron-binding capacity (TIBC), alanine transaminase (ALT), aspartate aminotransferase (AST), tumor necrosis factor alpha (TNF-α), high-sensitivity C-reactive protein (hs-CRP), malondialdehyde (MDA), and glutathione (GSH) as well as superoxide dismutase (SOD) activity and hemoglobin (Hb) concentration were measured pre-and post-intervention. RESULTS: GSE supplement significantly attenuated the serum levels of iron (p = 0.030), ferritin (p = 0.017), ALT (p = 0.000), AST (p = 0.000), TNF-α (p = 0.000), and hs-CRP (p = 0.001). The TIBC level (p = 0.020) significantly enhanced in the GSE group compared with the placebo group. Moreover, GSE supplement remarkably improved the oxidative stress markers, MDA (p = 0.000) and GSH (p = 0.001). The changes in the SOD activity (p = 0.590) and Hb concentration (p = 0.670) were not statistically different between the groups. CONCLUSION: GSE supplement possesses several health beneficial influences on children with ß-TM by alleviating iron burden, oxidative stress, inflammation, and liver dysfunction.

A comprehensive insight into the antineoplastic activities and molecular mechanisms of deoxypodophyllotoxin: Recent trends, challenges, and future outlook.

Lignans constitute an important group of polyphenols, which have been demonstrated to potently suppress cancer cell proliferation. Numerous in vitro and in vivo studies indicate that deoxypodophyllotoxin as a natural lignan possesses potent anticancer activities against various types of human cancer. The purpose of current review is to provide the reader with the latest findings in understanding the anticancer effects and molecular mechanisms of deoxypodophyllotoxin. This review comprehensively describes the influence of deoxypodophyllotoxin on signaling cascades and molecular targets implicated in cancer cell proliferation and invasion. A number of various signaling molecules and pathways, including apoptosis, necroptosis, cell cycle, angiogenesis, vascular disruption, ROS, MMPs, glycolysis, and microtubules as well as NF-κB, PI3K/Akt/mTOR, and MAPK cascades have been reported to be responsible for the anticancer activities of deoxypodophyllotoxin. The results of present review suggest that the cyclolignan deoxypodophyllotoxin can be developed as a novel and potent anticancer agent, especially as an alternative option for treatment of resistant tumors to chemotherapy.

Natural Lignans Honokiol and Magnolol as Potential Anticarcinogenic and Anticancer Agents. A Comprehensive Mechanistic Review.

Plant lignans constitute an important group of polyphenols, which have been demonstrated to significantly induce cancer cell death and suppress cancer cell proliferation with minimal toxicity against non-transformed cells. Numerous epidemiological studies have shown that the intake of lignans is associated with lower risk of several cancers. These natural compounds have the potential to inhibit carcinogenesis, tumor growth, and metastasis by targeting various signaling molecules and pathways. Growing evidence indicates that honokiol and magnolol as natural lignans possess potent anticancer activities against various types of human cancer. The aim of present review is to provide the reader with the newest findings in understanding the cellular and molecular mechanisms mediating anticancer effects of honokiol and magnolol. This review comprehensively elucidates the effects of honokiol and magnolol on the molecular targets and signal transduction pathways implicated in cancer cell proliferation and metastasis. The findings of current review indicate that honokiol and magnolol can be considered as promising carcinopreventive and anticancer agents.

A comprehensive mechanistic insight into the dietary and estrogenic lignans, arctigenin and sesamin as potential anticarcinogenic and anticancer agents. Current status, challenges, and future perspectives.

A large body of evidence indicates that lignans as polyphenolic compounds are beneficial against life-threatening diseases such as cancer. Plant lignans have the potential to induce cancer cell death and interfere with carcinogenesis, tumor growth, and metastasis. Epidemiological studies have revealed that the intake of lignans is inversely associated with the risk of several cancers. Moreover, numerous experimental studies demonstrate that natural lignans significantly suppress cancer cell proliferation with minimal toxicity against non-transformed cells. Dietary lignans arctigenin and sesamin have been found to have potent antiproliferative activities against various types of human cancer. The purpose of this review is to provide the reader with a deeper understanding of the cellular and molecular mechanisms underlying anticancer effects of arctigenin and sesamin. Our review comprehensively describes the effects of arctigenin and sesamin on the signaling pathways and related molecules involved in cancer cell proliferation and invasion. The findings of present review show that the dietary lignans arctigenin and sesamin seem to be promising carcinopreventive and anticancer agents. These natural lignans can be used as dietary supplements and pharmaceuticals for prevention and treatment of cancer.

The anticarcinogenic and anticancer effects of the dietary flavonoid, morin: Current status, challenges, and future perspectives.

Flavonoids constitute one of the most important classes of polyphenols, which have been found to have a wide range of biological activities such as anticancer effects. A large body of evidence demonstrates that morin as a pleiotropic dietary flavonoid possesses potent anticarcinogenic and anticancer activities with minimal toxicity against normal cells. The present review comprehensively elaborates the molecular mechanisms underlying antitumorigenic and anticancer effects of morin. Morin exerts its anticarcinogenic effects through multiple cancer preventive mechanisms, including reduction of oxidative stress, activation of phase II enzymes, induction of apoptosis, attenuation of inflammatory mediators, and downregulation of p-Akt and NF-κB expression. A variety of molecular targets and signaling pathways such as apoptosis, cell cycle, reactive oxygen species (ROS), matrix metalloproteinases (MMPs), epithelial-mesenchymal transition (EMT), and microRNAs (miRNAs) as well as signal transducer and activator of transcription 3 (STAT3), NF-κB, phosphatidylinositol 3-kinase (PI3K)/Akt, mitogen-activated protein kinase (MAPK), and Hippo pathways have been found to be involved in the anticancer effects of morin. In the adjuvant therapy, morin has been shown to have synergistic anticancer effects with several chemotherapeutic drugs. The findings of this review indicate that morin can act as a promising chemopreventive and chemotherapeutic agent.

Effect of polyethylene glycol versus lactulose on abdominal pain in children occult constipation: a randomized controlled study: un estudio controlado aleatorio / Efecto del polietilenglicol versus lactulosa sobre el dolor abdominal en el estreñimiento oculto en niños

Introduction and aim: Functional abdominal pain (FAP) is one of the major gastrointestinal complaints in childhood. Studies have reported occult constipation (OC) as one of the leading causes of abdominal pain. Recent researches have proposed laxatives as potent therapeutic targets for abdominal pain in patients with OC. However, no study has compared effect of poly ethylene glycol (PEG) and lactulose on occult constipation. Materials and methods: 51 patients aged 4 to 18 years with abdominal pain who had OC (defined as fecal impaction in abdominal X ray) were studied. Demographic and clinical data including age, sex, body weight, height, abdominal pain duration, abdominal pain rate and fecal odor were registered. They were randomly assigned to receive PEG (1gr/kg) or Lactulose (1cc/kg) for at least two weeks. All patients were reevaluated by pain measurement scale after at least two weeks of treatment. Results: It is indicated that the efficacy of PEG for reducing abdominal pain in OC was 48% while it was 37% for Lactulose. This study indicated that this efficacy is not affected significantly by sex and fecal odor, however this efficacy is influenced by age, body weight, abdominal pain duration and abdominal pain rate for both PEG and Lactulose. Conclusion: It could be concluded that PEG is a more efficient drug for treating abdominal pain in occult constipation than Lactulose and its optimum effect can be achieved in elder patients with more severe abdominal pain.

Introducción y objetivo: El dolor abdominal funcional (FAP) es una de las principales molestias gastrointestinales en la infancia. Los estudios han informado que el estreñimiento oculto (OC) es una de las principales causas de dolor abdominal. Investigaciones recientes han propuesto laxantes como objetivos terapéuticos potentes para el dolor abdominal en pacientes con OC. Sin embargo, ningún estudio ha comparado el efecto del polietilenglicol (PEG) y la lactulosa sobre el estreñimiento oculto. Materiales y métodos: Se estudiaron 51 pacientes de 4 a 18 años con dolor abdominal que tenían OC (definida como impactación fecal en rayos X abdominales). Se registraron datos demográficos y clínicos que incluyen edad, sexo, peso corporal, altura, duración del dolor abdominal, tasa de dolor abdominal y olor fecal. Fueron asignados aleatoriamente para recibir PEG (1 gr/kg) o lactulosa (1 cc/kg) durante al menos dos semanas. Todos los pacientes fueron reevaluados por la escala de medición del dolor después de al menos dos semanas de tratamiento. Resultados: Se indica que la eficacia de PEG para reducir el dolor abdominal en OC fue del 48% mientras que fue del 37% para la lactulosa. Este estudio indicó que esta eficacia no se ve afectada significativamente por el sexo y el olor fecal, sin embargo, esta eficacia está influenciada por la edad, el peso corporal, la duración del dolor abdominal y la tasa de dolor abdominal tanto para PEG como para lactulosa. Conclusión: Se podría concluir que el PEG es un fármaco más eficaz para tratar el dolor abdominal en el estreñimiento oculto que la lactulosa y que su efecto óptimo se puede lograr en pacientes mayores con dolor abdominal más severo.Palabras clave: dolor abdominal, estreñimiento oculto, polietilenglicol, lactulosa.

A review of molecular mechanisms involved in anticancer and antiangiogenic effects of natural polyphenolic compounds.

The aim of this review is to obtain a further understanding of the reported inhibitory effects of polyphenols on cancer cell proliferation and angiogenesis process and the probable mechanisms by which these natural compounds inhibit proliferation of cancer cells and angiogenesis. Growing evidence indicates that polyphenols are beneficial against human fatal diseases such as cancer. Because angiogenesis has a critical role in tumor growth and metastasis, therefore, we decided to review the potential anticancer and antiangiogenic activities and molecular mechanisms of different groups of known polyphenolic compounds. As knowledge and data on anticancer and antiangiogenic effects of plant-derived phenols are on the rise, it may be possible in the near future to develop and discover specific polyphenolic compounds with potent anticancer and antiangiogenic activity for treatment of malignant tumors.

Effect of polyethylene glycol versus lactulose on abdominal pain in children occult constipation: a randomized controlled study.

INTRODUCTION AND AIM: Functional abdominal pain (FAP) is one of the major gastrointestinal complaints in childhood. Studies have reported occult constipation (OC) as one of the leading causes of abdominal pain. Recent researches have proposed laxatives as potent therapeutic targets for abdominal pain in patients with OC. However, no study has compared effect of poly ethylene glycol (PEG) and lactulose on occult constipation. MATERIALS AND METHODS: 51 patients aged 4 to 18 years with abdominal pain who had OC (defined as fecal impaction in abdominal X ray) were studied. Demographic and clinical data including age, sex, body weight, height, abdominal pain duration, abdominal pain rate and fecal odor were registered. They were randomly assigned to receive PEG (1gr/kg) or Lactulose (1cc/kg) for at least two weeks. All patients were reevaluated by pain measurement scale after at least two weeks of treatment. RESULTS: It is indicated that the efficacy of PEG for reducing abdominal pain in OC was 48% while it was 37% for Lactulose. This study indicated that this efficacy is not affected significantly by sex and fecal odor, however this efficacy is influenced by age, body weight, abdominal pain duration and abdominal pain rate for both PEG and Lactulose. CONCLUSION: It could be concluded that PEG is a more efficient drug for treating abdominal pain in occult constipation than Lactulose and its optimum effect can be achieved in elder patients with more severe abdominal pain.

Studying the correlation of renin-angiotensin-system (RAS) components and insulin resistance in polycystic ovary syndrome (PCOs).

OBJECTIVE: It is estimated that 5-7% of women of reproductive age have polycystic ovary syndrome (PCOS). Chronic anovulation, hyperandrogenism, and insulin resistance (IR) are the main characters of this complex syndrome. IR, diabetes and obesity are all strongly correlated with PCOS; moreover, the possibility of direct androgen mediated renin-angiotensin system (RAS) stimulation in women with PCOS is also reported. The aim of the present study was to investigate the correlation between RAS, IR and PCOS. STUDY DESIGN: Thirty one women with PCOS, diagnosed by the Rotterdam criteria, were compared with thirty six control subjects. Both case and control groups were evaluated regarding to their basal hormonal profile, fasting blood sugar, IR, angiotensin converting enzyme (ACE) activity, plasma renin activity (PRA) and angiotensin II (AngІІ) levels. RESULTS: Compared to controls both ACE activity (p = 0.04) and AngΙΙ levels (p = 0.01) were significantly higher in case group. No significant differences between patients and controls were found in PRA. The results demonstrated that IR (p = 0.02) and fasting insulin (p = 0.004) were higher in case group, there was also a positive correlation between ACE activity and IR in case group (p = 0.02, r = 0.2). CONCLUSION: These results may suggest that there is an important correlation between ACE activity and IR in patients with PCOS.

Atorvastatin: an efficient step forward in mesenchymal stem cell therapy of diabetic retinopathy.

Diabetic retinopathy (DR), a leading cause of vision loss and a significant source of morbidity, is the most common ocular complication of prolonged diabetes mellitus. Most therapeutic approaches address DR by preventing or destroying neovasculature; however, this fails to eliminate pathogenic causes. Mesenchymal stem cells (MSCs) are a promising candidate for cell therapy because they have unique regenerative potential and provide an option to manage retinal injuries. Transplantation of MSCs in rats with diabetes induced by streptozocin administration was shown to ameliorate DR. However, the poor viability and homing of MSCs after transplantation may reduce the efficacy of cell therapy. Intravitreal transplantation of MSCs was shown to augment vascular endothelial growth factor (VEGF). More recent studies have found a central role for VEGF in vascular lesion formation in DR and proposed blockage of VEGF as an effective approach to manage DR. Atorvastatin, a 3-hydroxy-3-methyl-glutaryl coenzyme A reductase inhibitor, has been proven to decrease VEGF production of MSCs under hypoxic conditions. It has also been demonstrated that atorvastatin increases the viability of MSCs through the adenosine monophosphate-activated protein kinase-endothelial nitric oxide synthase signaling pathway. There is also evidence that nitric oxide improves homing of MSCs by increasing chemokine-related receptor CXCR4 expression. It could be hypothesized that co-administration of MSCs with atorvastatin may be a significant step forward in development of an efficient MSC therapy of DR through preventing excess VEGF production by MSCs under hypoxic conditions as well as increasing the viability and homing of transplanted MSCs.

Finasteride as a potential tool to improve mesenchymal stem cell transplantation for myocardial infarction.

Mesenchymal stem cells (MSCs) therapy has emerged as a potent therapeutic strategy to improve myocardial infarction. However MSCs therapy encounters a few obstacles regarding the poor viability of the transplanted cells. Therefore, it is important to explore a strategy to enhance post-transplanted MSC viability. To overcome this problem, several protocols were suggested mainly by activating PI3K/Akt pathway. The PI3K/Akt cascade regulates several cellular processes such as proliferation and apoptosis. Finasteride is a specific inhibitor of type II 5α-reductase; the enzyme converts testosterone (T) to the more potent androgen receptor agonist dihydrotestosterone (DHT). Testosterone is found to stimulate rapid phosphorylation of Akt, and thereby activate the PI3K/Akt pathway. This pathway could lead to decreased apoptosis of the MSCs via increasing the expression of Bcl-2 and reducing Bax expression. It has been also reported that DHT would confine the differentiation capacity of MSCs so that a reduction in DHT levels caused by Finasteride would be accompanied by increased facilitation in differentiation of MSCs to cardiomyocyte by means of the signals originating from the injured cardiac tissue. These mechanisms could propose the potential role for Finasteride to improve the MSCs therapy for myocardial infarction.