Сopper nanoparticles supported on charcoal and betacellulin – Two novel stimulators of ovarian granulosa cell functions and their functional interrelationships

The present experiments are aimed to examine the effect of copper nanoparticles supported on charcoal (CuNPs/ C), growth factor betacellulin (BTC) and their interrelationships in the control of ovarian cell functions. Porcine ovarian granulosa cells were cultured in the presence of CuNPs/C (0, 1, 10 or 100 ng/ml), BTC (100 ng/ml) and the combination of both, CuNPs/C + BTC. Markers of cell proliferation (BrDU incorporation), of the S-phase (PCNA) and G-phase cyclin B1) of the cell cycle, markers of extrinsic (nuclear DNA fragmentation) and cytoplasmic/mitochondrial apoptosis (bax and caspase 3), and the release of progesterone and estradiol were assessed by BrDU test, TUNEL, quantitative immunocytochemistry and ELISA. Both CuNPs/C and BTC, when added alone, increased the expression of all the markers of cell proliferation, reduced the expression of all apoptosis markers and stimulated progesterone and estradiol release. Moreover, BTC was able to promote the CuNPs/C action on the accumulation of PCNA, cyclin B1, bax and estradiol output. These observations demonstrate the stimulatory action of both CuNPs/C and BTC on ovarian cell functions, as well as the ability of BTC to promote the action of CuNPs/C on ovarian cell functions.This research was financially supported by the Scientific Grant Agency of the Ministry of Education, Science, and Sport of the Slovak Republic (VEGA) (project no. VEGA 1/0680/22), by the King Saud University, Riyadh, Saudi Arabia (Researchers Supporting Project no. RSP2023R17) and by the Generalitat Valenciana, Spain (GV; grant no. CIAICO/2022/017)

PCOS and inositols: controversial results and necessary clarifications. Basic differences between D-chiro and myo-inositol

Myo-Inositol (myo-Ins) and its phosphate derivatives—including inositol phosphates (InsPs), inositol pyrophosphates (IPPs) and phosphatidyl-inositol phosphate (PtdIns)—are credited to act as second messengers, which accumulate rapidly and transiently in response to external or endocrine signals, a phenomenon that allows signaling to be discrete and regulated (1, 2). Noticeably, inositol is involved in the transduction of several endocrine signals, including insulin (3, 4), thyroid hormones (5), gonadotropins (6), lipids with hormone-like activity (as prostaglandins) (7), and many other endocrine systems (8). Namely, in the last decade, a growing body of clinical and experimental research provided robust evidence about the efficiency of inositol in reversing a few clinical, metabolic, and endocrine features of the Polycystic Ovary Syndrome (PCOS). Myo-inositol, alone or in combination with its isomer D-Chiro-Inositol (D-Chiro-Ins), showed to exert a variable—albeit significant—effect in improving both symptoms and outcome in PCOS patients (9). Experimental and pilot clinical studies pointed out that a combination of both isomers could provide a reliable rationale for establishing a proper treatment strategy, as first suggested by Beemster’s seminal study (10, 11). However, the proper formula—i.e., the respective percentage of myo-Ins and D-Chiro-Ins—is still a matter of debate. In several cases, no conclusive insights can be obtained from clinical trials based on unclear rational design, limited number of recruited patients and variable formula composition and dosage(s). First, it is improper to compare clinical results from studies in which commercial nutraceutical formulas involve a wide range of concentrations (Table 1), with the myo-Ins/D-Chiro-Ins ratio varying implausibly from 0.4:1 to 104:1. Current commercial preparations also contain D-Chiro-Ins alone at concentrations reaching 600 mg that can be administered once or twice a day. Therefore, the daily dose of D-chiro-Ins, alone or with myo-Ins, ranges from low (less than 300 mg/die), medium (300–600 mg/die) and high (600–1,200 mg/die)

High-fat diet-induced aggravation of cardiovascular impairment in permethrin-treated Wistar rats.

This study characterized the impact of post-weaning high-fat diet (HFD) and/or permethrin (PER) treatment on heart dysfunction and fibrosis, as well as atherogenic risk, in rats by investigating interactions between HFD and PER. Our results revealed that HFD and/or PER induced remarkable cardiotoxicity by promoting cardiac injury, biomarker leakage into the plasma and altering heart rate and electrocardiogram pattern, as well as plasma ion levels. HFD and/or PER increased plasma total cholesterol, triacylglycerols, and low-density lipoprotein (LDL) cholesterol levels but significantly reduced high-density lipoprotein (HDL) cholesterol. Cardiac content of peroxidation malonaldehyde, protein carbonyls, and reactive oxygen species were remarkably elevated, while glutathione levels and superoxide dismutase, catalase and glutathione peroxidase activities were inhibited in animals receiving a HFD and/or PER. Furthermore, cardiac DNA fragmentation and upregulation of Bax and caspase-3 gene expression supported the ability of HFD and/or PER to induce apoptosis and inflammation in rat hearts. High cardiac TGF-β1 expression explained the profibrotic effects of PER either with the standard diet or HFD. Masson's Trichrome staining clearly demonstrated that HFD and PER could cause cardiac fibrosis. Additionally, increased oxidized LDL and the presence of several lipid droplets in arterial tissues highlighted the atherogenic effects of HFD and/or PER in rats. Such PER-induced cardiac and vascular dysfunctions were aggravated by and associated with a HFD, implying that obese individuals may be more vulnerable to PER exposure. Collectively, post-weaning exposure to HFD and/or PER may promote heart failure and fibrosis, demonstrating the pleiotropic effects of exposure to environmental factors early in life

The small phytomolecule resveratrol: A promising role in boosting tumor cell chemosensitivity

Resveratrol (RES), chemically known as trans-3,5,4′-trihydroxystilbene, is a polyphenolic molecule that occurs naturally and is produced by a variety of plants in response to being stimulated by diverse stimuli. It possesses a wide range of biological activities and provides a multitude of health benefits, including anti-tumor, cardioprotective, anti-inflammatory, and antioxidant characteristics. According to the findings of research on the bioavailability of RES, oral administration results in a high level of absorption. However, research has demonstrated that the administration of RES through gavage or intravenous administration produces more favorable results than the administration of RES through oral administration. As a result, more research has been carried out to address the rapid metabolism of RES. This has been accomplished through the utilization of novel formulation methodologies, metabolic regulation, and the analysis of potential interactions with other dietary variables. Through the process of triggering apoptosis, RES has been proposed as a possible agent for reversing drug resistance and improving the therapeutic potential of chemotherapy. Additionally, RES exhibits promising antiproliferative properties when paired with chemotherapeutic medicines, which enhances the overall function of these treatments. It is vital to do additional research to shed light on the beneficial role that RES plays in the context of cancer therapy, even though there have been few clinical trials that combine RES with anticancer medications

Inositol induces mesenchymal-epithelial reversion in breast cancer cells through cytoskeleton rearrangement

Inositol displays multi-targeted effects on many biochemical pathways involved in epithelial-mesenchymal transition (EMT). As Akt activation is inhibited by inositol, we investigated if such effect could hamper EMT in MDA-MB-231 breast cancer cells. In cancer cells treated with pharmacological doses of inositol E-cadherin was increased, β-catenin was redistributed behind cell membrane, and metalloproteinase-9 was significantly reduced, while motility and invading capacity were severely inhibited. Those changes were associated with a significant down-regulation of PI3K/Akt activity, leading to a decrease in downstream signaling effectors: NF-kB, COX-2, and SNAI1. Inositol-mediated inhibition of PS1 leads to lowered Notch 1 release, thus contributing in decreasing SNAI1 levels. Overall, these data indicated that inositol inhibits the principal molecular pathway supporting EMT. Similar results were obtained in ZR-75, a highly metastatic breast cancer line. These findings are coupled with significant changes on cytoskeleton. Inositol slowed-down vimentin expression in cells placed behind the wound-healing edge and stabilized cortical F-actin. Moreover, lamellipodia and filopodia, two specific membrane extensions enabling cell migration and invasiveness, were no longer detectable after inositol addiction. Additionally, fascin and cofilin, two mandatory required components for F-actin assembling within cell protrusions, were highly reduced. These data suggest that inositol may induce an EMT reversion in breast cancer cells, suppressing motility and invasiveness through cytoskeleton modifications

Three dispersal routes out of Africa: A puzzling biogeographical history in freshwater planarians

Aim Freshwater planarians may have a wide geographical range despite their assumed low vagility. Found across four continents, Dugesia may have either an ancient origin on a large palaeo landmass, followed by colonisation in different regions before continental fragmentation, or a more recent origin and subsequent transoceanic dispersal. We seek to resolve between these two hypotheses. Location Africa, Eurasia and Australasia. Taxon Genus Dugesia (Platyhelminthes: Tricladida: Dugesiidae). Methods We used data from the sequencing of six gene fragments and comprehensive taxonomic sampling of Dugesia from across its distribution range to reconstruct the phylogeny of this genus using maximum likelihood and bayesian inference methods. We conducted two phylogenetic dating analyses using Platyhelminthes fossils and palaeogeological events. Basing on the time-calibrated molecular phylogenetic framework we evaluated the contribution of vicariance and dispersal to the biogeographical evolution of Dugesia. By reconstructing the ancestral areas and present-day potential distribution using BioGeoBEARS and niche modelling, we elucidated the biogeographical history of the genus. Results The present-day distribution of Dugesia is a result of different vicariance and dispersal events. However, we also found evidence of transoceanic dispersal. Consistent with previous hypotheses, Dugesia dates to the Upper Jurassic in the Afro-Malagasy Gondwana region. We unveiled a novel biogeographical scenario for the genus, involving multiple events of colonisation in Eurasia from continental Africa via at least three dispersal routes. Main conclusions Dugesia is an ancient genus having reached its present distribution through a complex history of dispersal and vicariant events following its origin in southern Gondwana. Despite the low vagility of Dugesia, we found evidence of their overseas dispersal

Morphological and molecular aspects of Ceratomyxa ghannouchensis n. sp. and C. pallida Thélohan 1894 infecting the bogueı Boops boops (l.)

Thabet, Aouatef, Abdel-Baki, Abdel-Azeem S., Harrath, Abdel Halim, Mansour, Lamjed (2019): Morphological and molecular aspects of Ceratomyxa ghannouchensis n. sp. and C. pallida Thélohan 1894 infecting the bogueı Boops boops (l.). Journal of Natural History 53 (9): 541-556, DOI: 10.1080/00222933.2019.159720

DIRECT INHIBITORY EFFECT OF FLAXSEED ON PORCINE OVARIAN GRANULOSA CELL FUNCTIONS

Flaxseed is useful as a functional food and alternative medicine owing to its beneficial health effects. Its action on ovarian cell functions and interrelationships with the upstream hormonal regulators remain unknown. Our aim was to examine the direct influence of flaxseed extract on basal porcine ovarian functions (proliferation, apoptosis), leptin release, and response to insulin-like growth factor I (IGF-I). First, we examined the effect of flaxseed extract on the accumulation of proliferation (PCNA) and apoptosis (bax) marker and on leptin release in cultured porcine ovarian granulosa cells. Next, granulosa cells were cultured with IGF-I with and without flaxseed extract and analyzed for PCNA and bax accumulation by quantitative immunocytochemistry, whereas leptin was analyzed by RIA. Flaxseeds decreased the accumulation of proliferation marker and increased that of the apoptosis marker at all doses and reduced leptin output at 100 Âľg/ml. On the contrary, IGF-I promoted PCNA and suppressed bax. Flaxseed did not modify IGF-I action on these parameters. Thus, we showed flaxseed action on porcine reproductive processes, with a direct effect on the ovary and flaxseed ability to affect ovarian cell proliferation, apoptosis, and leptin release. Furthermore, we confirmed the pro-proliferating and anti-apoptosis action of IGF-I, but indicated that flaxseed action on ovarian cell proliferation and apoptosis are not due to changes in their response to IGF-I. The potential direct anti-reproductive action of flaxseed needs to be confirmed properly in in-vivo experiments and thereafter considered during its application in nutrition, medicine, and animal production.The accepted manuscript in pdf format is listed with the files at the bottom of this page. The presentation of the authors' names and (or) special characters in the title of the manuscript may differ slightly between what is listed on this page and what is listed in the pdf file of the accepted manuscript; that in the pdf file of the accepted manuscript is what was submitted by the author

Expression of Glucose Transporters 1 and 3 in the Placenta of Pregnant Women with Gestational Diabetes Mellitus

Background: The annual prevalence of gestational diabetes mellitus—characterized by an increase in blood glucose in pregnant women—has been increasing worldwide. The goal of this study was to evaluate the expression of glucose transporter 1 (GLUT1) and glucose transporter 3 (GLUT3) in the placenta of women with gestational diabetes mellitus. Methods: Sixty-five placentas from women admitted to the King Saud University Medical City, Riyadh, Saudi Arabia, were analyzed; 34 and 31 placentas were from healthy pregnant women and women with gestational diabetes, respectively. The expressions of GLUT1 and GLUT3 were assessed using RT-PCR, Western blotting, and immunohistochemical methods. The degree of apoptosis in the placental villi was estimated via a TUNEL assay. Results: The results of the protein expression assays and immunohistochemical staining showed that the levels of GLUT1 and GLUT3 were significantly higher in the placentas of pregnant women with gestational diabetes than those in the placentas of healthy pregnant women. In addition, the findings showed an increase in apoptosis in the placenta of pregnant women with gestational diabetes compared to that in the placenta of healthy pregnant women. However, the results of gene expression assays showed no significant difference between the two groups. Conclusions: Based on these results, we conclude that gestational diabetes mellitus leads to an increased incidence of apoptosis in the placental villi and alters the level of GLUT1 and GLUT3 protein expressions in the placenta of women with gestational diabetes. Understanding the conditions in which the fetus develops in the womb of a pregnant woman with gestational diabetes may help researchers understand the underlying causes of the development of chronic diseases later in life