Acyl-Carnitines Exert Positive Effects on Mitochondrial Activity under Oxidative Stress in Mouse Oocytes: A Potential Mechanism Underlying Carnitine Efficacy on PCOS.

Carnitines play a key physiological role in oocyte metabolism and redox homeostasis. In clinical and animal studies, carnitine administration alleviated metabolic and reproductive dysfunction associated with polycystic ovarian syndrome (PCOS). Oxidative stress (OS) at systemic, intraovarian, and intrafollicular levels is one of the main factors involved in the pathogenesis of PCOS.

Polyhydroxybutyrate-producing cyanobacteria from lampenflora: The case study of the "Stiffe" caves in Italy.

This study aimed to estimate the green formation lampenflora of "Stiffe" caves in order to evaluate their suitability as an isolation source of cyanobacteria useful for the production of polyhydroxyalkanoates (PHAs). The cave system was chosen as the sampling site due to its touristic use and the presence of high-impact illuminations. The biofilms and the mats of the illuminated walls were sampled.

Phytochemistry and Biological Activity of Medicinal Plants in Wound Healing: An Overview of Current Research.

Wound healing is a complicated process, and the effective management of wounds is a major challenge. Natural herbal remedies have now become fundamental for the management of skin disorders and the treatment of skin infections due to the side effects of modern medicine and lower price for herbal products. The aim of the present study is to summarize the most recent in vitro, in vivo, and clinical studies on major herbal preparations, their phytochemical constituents, and new formulations for wound management.

Carnitines as Mitochondrial Modulators of Oocyte and Embryo Bioenergetics.

Recently, the importance of bioenergetics in the reproductive process has emerged. For its energetic demand, the oocyte relies on numerous mitochondria, whose activity increases during embryo development under a fine regulation to limit ROS production. Healthy oocyte mitochondria require a balance of pyruvate and fatty acid oxidation.

Mitochondrial Sirtuins in Reproduction.

Mitochondria act as hubs of numerous metabolic pathways. Mitochondrial dysfunctions contribute to altering the redox balance and predispose to aging and metabolic alterations. The sirtuin family is composed of seven members and three of them, SIRT3-5, are housed in mitochondria.

Crocetin Mitigates Irradiation Injury in an In Vitro Model of the Pubertal Testis: Focus on Biological Effects and Molecular Mechanisms.

Infertility is a potential side effect of radiotherapy and significantly affects the quality of life for adolescent cancer survivors. Very few studies have addressed in pubertal models the mechanistic events that could be targeted to provide protection from gonadotoxicity and data on potential radioprotective treatments in this peculiar period of life are elusive. In this study, we utilized an in vitro model of the mouse pubertal testis to investigate the efficacy of crocetin to counteract ionizing radiation (IR)-induced injury and potential underlying mechanisms.

Regulatory Functions of L-Carnitine, Acetyl, and Propionyl L-Carnitine in a PCOS Mouse Model: Focus on Antioxidant/Antiglycative Molecular Pathways in the Ovarian Microenvironment.

Polycystic ovary syndrome (PCOS) is a complex metabolic disorder associated with female infertility. Based on energy and antioxidant regulatory functions of carnitines, we investigated whether acyl-L-carnitines improve PCOS phenotype in a mouse model induced by dehydroepiandrosterone (DHEA). CD1 mice received DHEA for 20 days along with two different carnitine formulations: one containing L-carnitine (LC) and acetyl-L-carnitine (ALC), and the other one containing also propionyl-L-carnitine (PLC).

Methylglyoxal-Dependent Glycative Stress and Deregulation of SIRT1 Functional Network in the Ovary of PCOS Mice.

Advanced glycation end-products (AGEs) are involved in the pathogenesis and consequences of polycystic ovary syndrome (PCOS), a complex metabolic disorder associated with female infertility. The most powerful AGE precursor is methylglyoxal (MG), a byproduct of glycolysis, that is detoxified by the glyoxalase system. By using a PCOS mouse model induced by administration of dehydroepiandrosterone (DHEA), we investigated whether MG-dependent glycative stress contributes to ovarian PCOS phenotype and explored changes in the Sirtuin 1 (SIRT1) functional network regulating mitochondrial functions and cell survival.

SIRT1 participates in the response to methylglyoxal-dependent glycative stress in mouse oocytes and ovary.

Methylglyoxal (MG), a highly reactive dicarbonyl derived from metabolic processes, is the most powerful precursor of advanced glycation end products (AGEs). Glycative stress has been recently associated with ovarian dysfunctions in aging and PCOS syndrome. We have investigated the role of the NAD-dependent Class III deacetylase SIRT1 in the adaptive response to MG in mouse oocytes and ovary.

Crocetin and Crocin from Saffron in Cancer Chemotherapy and Chemoprevention.

Introduction: Cancer is a disorder which has a powerful impact on the quality life and life expectancy despite the increase in drugs and treatments available for cancer patients. Moreover, many new therapeutic options are known to have adverse reactions without any improvement in outcome than before. Nowadays, natural products or plant derivatives are used as chemoprevention drugs and chemotherapy is the new approach that uses specific cell premalignant transformation in the malignant form.

The Natural Carotenoid Crocetin and the Synthetic Tellurium Compound AS101 Protect the Ovary against Cyclophosphamide by Modulating SIRT1 and Mitochondrial Markers.

Cancer therapies are associated with increased infertility risk due to accelerated reproductive aging. Oxidative stress (OS) is a potential mechanism behind ovarian toxicity by cyclophosphamide (CPM), the most ovotoxic anticancer drug. An important sensor of OS is SIRT1, a NAD-dependent deacetylase which regulates cellular defence and cell fate.

Effects of Crocetin Esters and Crocetin from Crocus sativus L. on Aortic Contractility in Rat Genetic Hypertension.

Background: Endothelial dysfunction, characterized by an enhancement in vasoconstriction, is clearly associated with hypertension. Saffron (Crocus sativus L.) bioactive compounds have been recognized to have hypotensive properties.

Sirtuin Functions in Female Fertility: Possible Role in Oxidative Stress and Aging.

In search for strategies aimed at preventing oxidative threat to female fertility, a possible role of sirtuins has emerged. Sirtuins (silent information regulator 2 (Sir2) proteins), NAD(+) dependent enzymes with deacetylase and/or mono-ADP-ribosyltransferase activity, are emerging as key antiaging molecules and regulators in many diseases. Recently, a crucial role for SIRT1 and SIRT3, the main components of sirtuin family, as sensors and guardians of the redox state in oocytes, granulosa cells, and early embryos has emerged.

Crocetin, a carotenoid derived from saffron (Crocus sativus L.), improves acetylcholine-induced vascular relaxation in hypertension.

Background: Hypertension is associated with endothelial dysfunction characterized by decreased vasorelaxation. Crocetin, a bioactive compound of saffron, exhibits favorable cardiovascular properties. We analyze the vasomodulatory effects of crocetin in hypertension.

SIRT1 signalling protects mouse oocytes against oxidative stress and is deregulated during aging.

Study Question: Is SIRT1 involved in the oxidative stress (OS) response in mouse oocytes?

Summary Answer: SIRT1 plays a pivotal role in the adaptive response of mouse germinal vesicle (GV) oocytes to OS and promotes a signalling cascade leading to up-regulation of the MnSod gene.

What Is Known Already: OS is known to continuously threaten acquisition and maintenance of oocyte developmental potential during in vivo processes and in vitro manipulations. Previous studies in somatic cells have provided strong evidence for the role of SIRT1 as a sensor of the cell redox state and a protector against OS and aging.

Antitumor effects of saffron-derived carotenoids in prostate cancer cell models.

Crocus sativus L. extracts (saffron) are rich in carotenoids. Preclinical studies have shown that dietary intake of carotenoids has antitumor effects suggesting their potential preventive and/or therapeutic roles.

Crocus sativus stigma extract and its major constituent crocin possess significant antiproliferative properties against human prostate cancer.

In this study, we investigated the antiproliferative effects of saffron extract (SE) and its major constituent crocin on 5 different malignant and 2 nonmalignant prostate cancer cell lines. Using high performance liquid chromatography (HPLC), the purity and content of crocin were determined. All cells were incubated with different concentrations of SE or crocin for 48 h.

Increased levels of DNA methyltransferases are associated with the tumorigenic capacity of prostate cancer cells.

DNA methylation might be the earliest somatic genome changes in prostate cancer that also play an important role in the process of tumor invasion, growth and metastasis. In recent years, several inhibitors of DNA methyltransferases (DNMTis) have been developed and evaluated in pre-clinical models and in clinical trials. While these compounds are effective in the treatment of hematological conditions, clinical trials in solid tumors and in prostate cancer have shown limited or no efficacy.

Azacitidine improves antitumor effects of docetaxel and cisplatin in aggressive prostate cancer models.

One of the major obstacles in the treatment of hormone-refractory prostate cancer (HRPC) is the development of chemoresistant tumors. The aim of this study is to evaluate the role of azacitidine as chemosensitizing agent in association with docetaxel (DTX) and cisplatin using two models of aggressive prostate cancer, the 22rv1, and PC3 cell lines. Azacitidine shows antiproliferative effects associated with increased proportion of cells in G0/G1 and evident apoptosis in 22rv1 cells and increased proportion of cells in G2/M phase with the absence of acute cell killing in PC3 cells.

Downmodulation of dimethyl transferase activity enhances tumor necrosis factor-related apoptosis-inducing ligand-induced apoptosis in prostate cancer cells.

One of the major obstacles in curing prostate cancer is the development of drug resistance. It is not only imperative to discover the molecular basis of resistance but also to find therapeutic agents that can disrupt the resistant pathways. Tumor necrosis factor TNF-related apoptosis-inducing ligand TRAIL-like ligands or agonist TRAIL-receptor monoclonal antibodies have entered phase I and II clinical trials with a very limited cytotoxic profile when used systemically in a variety of cancers.

The farnesyltransferase inhibitor R115777 (ZARNESTRA) enhances the pro-apoptotic activity of interferon-alpha through the inhibition of multiple survival pathways.

Interferon alpha (IFNalpha) induces an EGF-Ras-->Raf-1-->Erk dependent survival pathway counteracting apoptosis induced by the cytokine. In this paper we have evaluated the effects of the combination between farnesyl-transferase inhibitor (FTI) R115777 and IFNalpha on the growth inhibition and apoptosis of cancer cells. Simultaneous exposure to R115777 and IFNalpha produced synergistic both antiproliferative and proapoptotic effects.

Pattern expression of glycan residues in AZT-treated K562 cells analyzed by lectin cytochemistry.

The present paper shows that human chronic myeloid (K562) cells exposed 3 h to 20 microM 3'-azido-3'-deoxythymidine (AZT) exhibit marked variations of the oligosaccharide moiety of glycoconjugates. These changes were analyzed by confocal fluorescence microscopy, upon incubation of control and AZT-treated cells with biotin-lectin conjugates to visualize cell surface glycans or total glycans after cells permeabilization. In addition, cell fluorescence distribution of the biotinylated lectins, localized with streptavidin conjugates labeled with Alexa Fluor 488, was analyzed by flow cytometry.

R115777 (Zarnestra)/Zoledronic acid (Zometa) cooperation on inhibition of prostate cancer proliferation is paralleled by Erk/Akt inactivation and reduced Bcl-2 and bad phosphorylation.

Zoledronic acid (ZOL) has proved activity in bone metastases from prostate cancer through inhibition of mevalonate pathway and of prenylation of intracellular proteins. We have reported that ZOL synergizes with R115777 farnesyltransferase inhibitor (FTI, Zarnestra) in inducing apoptosis and growth inhibition on epidermoid cancer cells. Here, we have studied the effects of the combination of these agents in prostate adenocarcinoma models and, specifically, on androgen-independent (PC3 and DU145) and -dependent (LNCaP) prostate cancer cell lines.

The farnesyl transferase inhibitor R115777 (Zarnestra) synergistically enhances growth inhibition and apoptosis induced on epidermoid cancer cells by Zoledronic acid (Zometa) and Pamidronate.

Pamidronate (PAM) and zoledronic acid (ZOL) are aminobisphosphonates (BPs) able to affect the isoprenylation of intracellular small G proteins. We have investigated the antitumor activity of BPs and R115777 farnesyl transferase inhibitor (FTI) against epidermoid cancer cells. In human epidermoid head and neck KB and lung H1355 cancer cells, 48 h exposure to PAM and ZOL induced growth inhibition (IC(50) 25 and 10 microM, respectively) and apoptosis and abolished the proliferative and antiapoptotic stimuli induced by epidermal growth factor (EGF).

Effects of AZT on cellular iron homeostasis.

3'-azido-3'-deoxythymidine (AZT), the first chemotherapeutic drug approved by FDA for treatment of HIV-infected patients and still used in combination therapy, has been shown to induce, upon prolonged exposure, severe bone marrow toxicity manifested as anemia, neutropenia and siderosis. These toxic effects are caused by inhibition of heme synthesis and, as a consequence, transferrin receptor (TfR) number appears increased and so iron taken up by cells. Since iron overload can promote the frequency and severity of many infections, siderosis is viewed as a further burden for AIDS patients.