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To study the cyclic fertilin peptide effects on preimplantation human embryogenesis. Cyclic fertilin peptide reproduces the structure of the binding site of the sperm Fertilin β (also named A Disintegrin and Metalloprotease 2: ADAM2) disintegrin domain. It binds to the oocyte membrane and increases sperm-oocyte fusion index in human and fertilization rate in mouse, providing healthy pups. It also improves human oocyte maturation and chromosome segregation in meiosis I and binds to human embryo blastomeres, suggesting that it has a membrane receptor.

Spinal muscular atrophy (SMA) is a devastating neurodegenerative disease caused by reduced amounts of the ubiquitously expressed Survival of Motor Neuron (SMN) protein. In agreement with its crucial role in the biogenesis of spliceosomal snRNPs, SMN-deficiency is correlated to numerous splicing alterations in patient cells and various tissues of SMA mouse models. Among the snRNPs whose assembly is impacted by SMN-deficiency, those involved in the minor spliceosome are particularly affected. Importantly, splicing of several, but not all U12-dependent introns has been shown to be affected in different SMA models. Here, we have investigated the molecular determinants of this differential splicing in spinal cords from SMA mice. We show that the branchpoint sequence (BPS) is a key element controlling splicing efficiency of minor introns. Unexpectedly, splicing of several minor introns with suboptimal BPS is not affected in SMA mice. Using in vitro splicing experiments and oligonucleotides targeting minor or major snRNAs, we show for the first time that splicing of these introns involves both the minor and major machineries. Our results strongly suggest that splicing of a subset of minor introns is not affected in SMA mice because components of the major spliceosome compensate for the loss of minor splicing activity.

Overweight and obesity in children and adolescents have become a major public health problem affecting most countries worldwide. The purpose of the study was to assess the prevalence and risk factors of overweight and obesity among public high school students in Eastern Morocco.

Medical plants play an important role in the management of diabetes mellitus especially in developing countries where resources are meager. This review presents the profiles of plants with hypoglycaemic properties, reported in the literature from 1990 to 2000. The profiles presented include information about the scientific name, family, methodology used, the degree of hypoglycaemic activity and the active agents. The large number of plants described in this review (176 species belonging to 84 families) clearly demonstrated the importance of herbal plants in the treatment of diabetes. It also shows the effort to isolate new potential antidiabetic agents. The plant families, including the species (sp), most studied for their confirmed hypoglycaemic effects include: Leguminoseae (11 sp), Lamiaceae (7 sp), Liliaceae (8 sp), Cucurbitaceae (7 sp), Asteraceae (6 sp), Moraceae (6 sp), Rosaceae (6 sp), Euphorbiaceae (5 sp) and Araliaceae (5 sp). The most studied species are: Citrullus colocynthis (Opuntia streptacantha Lem. (Cactaceae), Trigonella foenum greacum L. (Leguminosea), Momordica charantia L. (Cucurbitaceae), Ficus bengalensis L. (Moraceae), Polygala senega L. (Polygalaceae), and Gymnema sylvestre R. (Asclepiadaceae). Many studies have confirmed the benefits of medicinal plants with hypoglycaemic effects in the management of diabetes mellitus. The effects of these plants may delay the development of diabetic complications and correct the metabolic abnormalities. Moreover, during the past few years some of the new bioactive drugs isolated from hypoglycaemic plants showed antidiabetic activity with more efficacy than oral hypoglycaemic agents used in clinical therapy. (Int J Diabetes Metab 14: 1-25, 2006)

The present review shows a listing of medicinal plants used in phytotherapy of diabetes and those experimentally studied as hypoglycaemic in Morocco. The review is presented as 3 tables. The first one includes the taxonomic classification of the plant, the popular names in Morocco, the parts used, the mode of preparation and the other medicinal uses and toxicity. The second table summarises the experiments done by Moroccan researchers to confirm the hypoglycemic activity of the medicinal plants. It also describes the methodology used, and the magnitude of the hypoglycemic activity. The third table lists the toxicological studies carried out with plants reported to be toxic. The large number of plants described in this review (94 species belonging to 38 families) demonstrated the prevalence of phytotherapy in Morocco. The plant families which contained the most commonly used species for their antidiabetic effects are: Compositae (18 species), Lamiaceae (14 sp.), Leguminosae (8 sp.), Liliaceae (5 sp.), Apiaceae (5 sp.), and Graminae (4 sp.). Among these medicinal plants, 17 are toxic, the most known being: Daphne gnidium, Nerium oleander, Ferula communis, Peganum harmala and Citrullus colocynthis.

This study aims to evaluate the vasodilatory effect of Chenopodium ambrosioideson the isolated rat aorta, and to explore its mechanism of action.

In muscle, clathrin plaques form microdomains that anchor a three-dimensional desmin intermediate filament web. Depletion of clathrin plaques, dynamin 2, and branched actin cause accumulation of desmin tangles in the cytoplasm, while centronuclear myopathy–causing dynamin 2 mutations lead to desmin disorganization in mice and humans.

Recombinant adeno-associated viral (rAAV) vectors exhibit interesting properties as vaccine carriers for their ability to induce long-lasting antibody responses. However, rAAV-based vaccines have been suggested to trigger functionally impaired long-term memory CD8+T cell responses, in part due to poor dendritic cell (DC) transduction. Such results, albeit limited to intramuscular immunization, undermined the use of rAAV as vaccine vehicles against intracellular pathogens. We report here that intradermal immunization with a model rAAV2/1-based vaccine drives the development of bona fide long-term memory CD8+T cell responses. The intradermal route of immunization and the presence of potent major histocompatibility complex (MHC) class II responses showed synergistic effects on the overall quantity and quality of systemic long-term effector memory transgene-specific CD8+T cells being generated against the transgene. Of key interest, we found that the induction of memory cytotoxic T lymphocytes (CTLs) following intradermal immunization was solely dependent on the cross-presentation of skin-expressed transgene products, which appeared highly enhanced as compared to muscle-expressed transgene products. Overall our results highlight key tissue-specific differences in transgene presentation pathway requirements of importance for the design of rAAV-based T cell-inducing vaccines.

Diabetes mellitus is a prevalent metabolic disorder globally, affecting a significant portion of the world's population. Moroccan traditional medicine employs Lavandula stoechas(Lamiaceae), for anti-diabetic purposes. This study aims to evaluate the antihyperglycemic effect of the aqueous extract of L. stoechas(AqLs) experimentally, and investigate the mechanisms responsible for this effect. In this research, the glucose tolerance test (OGTT) was used to examine the antihyperglycemic effect of AqLs at a dose of 150 mg/kg in male and female normal and diabetic Wistar rats. The AqLs significantly reduced postprandial hyperglycemia (P < 0.001) resulting from glucose overload. The AqLs was also found to reduce (P < 0.001) intestinal glucose absorption in situ at a dose of 250 mg/kg. In vitro, AqLs inhibited pancreatic α-amylase enzyme, with an IC50 of 0.485 mg/mL, and intestinal α-glucosidase enzyme, with an IC50 of 168 μg/mL. The inhibitory effect of AqLs on these enzymes was confirmed in vivo. Oral intake of AqLs at a dose of 150 mg/kg decreased hyperglycemia caused by sucrose and starch overload in normal and alloxan-induced diabetic Wistar rats. Furthermore, the oral acute toxicity test showed that AqLs did not induce any adverse effects in Albino mice of both sexes at different doses. In summary, the results of this study indicate that L. stoechashas an antihyperglycemic effect, which is partly attributed to the inhibition of intestinal glucose absorption and enzymes involved in the digestion of monosaccharides, such as α-amylase and α-glucosidase.

•New pyrazole tetrazole compounds were synthesized•They were characterized by spectroscopic and spectrometric analysis•Antifungal and vasorelaxant activities of these compounds were examined•Docking study supports the vasorelaxant activity results

Fertility is a quantitative, complex character governed by a considerable number of genes. Despite clinical and scientific advances, several cases of human infertility remain unexplained. In the present study, using a positional cloning approach in a mouse model of interspecific recombinant lines, a candidate gene, ALPP,encoding the placental alkaline phosphatase, was identified as being potentially involved in recurrent spontaneous abortion. We then analyzed patients for detecting putative associations between ALPPpolymorphisms, in vitrofertilization failures, and miscarriages. ALPPwas sequenced in 100 controls and 100 patients affected by recurrent spontaneous abortion, from the same ethnic background. The frequency of several alleles and allelic combinations were different between recurrent spontaneous abortion and control women. One polymorphism induced a coding substitution (Ile89Leu) that was associated with a decreased risk of abortion and in vitrofertilization failure. Thereafter, the population was increased by the analysis of 92 additional controls and 612 additional patients for the coding polymorphism Ile89Leu. We finally show, by functional analysis, that the 89Leu placental alkaline phosphatase has an enhanced alkaline phosphatase activity. This study suggests that ALPPgenotyping could be a strong predictor of implantation success.

The objective of this research is to describe the current situation (frequencies) of obesity and diabetes mellitus (DM) and their relationship in Oujda capital of eastern Morocco and its regions, and to investigate the influences of milieu, sex and age. A sample of 1,628 individuals at least 40 years old was formed by voluntary participation using convenience sampling through 26 campaigns in urban and rural areas in late 2008. The proportion in the total sample was globally 10.2% for DM, 8.1% for impaired fasting glucose (IFG), 25.1% for obesity and 40.3% for overweight. The relative frequency of DM was slightly higher in women than in men (10.7% vs. 9.3%, not significant (NS)); for IFG it was respectively 8.7% versus 7.01% (NS). The relative frequency of DM was 1.34 times higher in urban (10.9%) than in rural areas (7.9%, P < 0.05). It was also more elevated in obese subjects (15.9%) than in normal ones (9.7%, P < 0.001). Obesity proportion was markedly greater in women (32.7%) than in men (11.5%, P < 0.001). Obesity and overweight were more frequent in urban populations than in rural ones. In conclusion, our results show an alarming increasing trend in the current situation and frequencies of DM, obesity and overweight in the capital of eastern Morocco and its regions, especially for women in urban area.

Abstract: The objective of this research is to describe the current situation (frequencies) of obesity and diabetes mellitus (DM) and their relationship in Oujda capital of eastern Morocco and its regions, and to investigate the influences of milieu, sex and age. A sample of 1,628 individuals at least 40 years old was formed by voluntary participation using convenience sampling through 26 campaigns in urban and rural areas in late 2008. The proportion in the total sample was globally 10.2% for DM, 8.1% for impaired fasting glucose (IFG), 25.1% for obesity and 40.3% for overweight. The relative frequency of DM was slightly higher in women than in men (10.7% vs. 9.3%, not significant (NS)); for IFG it was respectively 8.7% versus 7.01% (NS). The relative frequency of DM was 1.34 times higher in urban (10.9%) than in rural areas (7.9%, P < 0.05). It was also more elevated in obese subjects (15.9%) than in normal ones (9.7%, P < 0.001). Obesity proportion was markedly greater in women (32.7%) than in men (11.5%, P < 0.001). Obesity and overweight were more frequent in urban populations than in rural ones. In conclusion, our results show an alarming increasing trend in the current situation and frequencies of DM, obesity and overweight in the capital of eastern Morocco and its regions, especially for women in urban area.

The objective of this research is to describe the current situation (frequencies) of obesity and diabetes mellitus (DM) and their relationship in Oujda capital of eastern Morocco and its regions, and to investigate the influences of milieu, sex and age. A sample of 1,628 individuals at least 40 years old was formed by voluntary participation using convenience sampling through 26 campaigns in urban and rural areas in late 2008. The proportion in the total sample was globally 10.2% for DM, 8.1% for impaired fasting glucose (IFG), 25.1% for obesity and 40.3% for overweight. The relative frequency of DM was slightly higher in women than in men (10.7% vs. 9.3%, not significant (NS)); for IFG it was respectively 8.7% versus 7.01% (NS). The relative frequency of DM was 1.34 times higher in urban (10.9%) than in rural areas (7.9%, P < 0.05). It was also more elevated in obese subjects (15.9%) than in normal ones (9.7%, P < 0.001). Obesity proportion was markedly greater in women (32.7%) than in men (11.5%, P < 0.001). Obesity and overweight were more frequent in urban populations than in rural ones. In conclusion, our results show an alarming increasing trend in the current situation and frequencies of DM, obesity and overweight in the capital of eastern Morocco and its regions, especially for women in urban area.

Arbutus unedoL. (Ericaceae) is used in oriental Morocco to treat arterial hypertension. We studied its vasodilator effect and mechanisms of action in vitro. The root aqueous extract of Arbutus (0.25 mg/mL) produced a relaxation of noradrenaline‐precontracted ring preparations of rat aorta with intact endothelium. Relaxation by Arbutus did not occur in specimens without endothelium and was inhibited by pretreatment with 100 μMNG‐methyl‐L‐arginine (L‐NMA), 10 μMmethylene blue or 50 μM1H‐[1,2,4] oxadiazolo [4,3‐a] quinoxaline‐1‐one (ODQ) but not by 10 μMatropine. These results suggest that Arbutus produces an endothelium‐dependent relaxation of the isolated rat aorta which may be mediated mainly by a stimulation of the endothelial nitric oxide synthase by mechanisms other than activation of muscarinic receptors. Copyright © 2002 John Wiley & Sons, Ltd.

Urtica dioica L. or Nettle (Urticaceae) is widely used in oriental Morocco to treat hypertension. Aqueous extract of Nettle (AEN) also exerts a hypotensive action in the rat in vivo. The aim of this work was to characterize the specific cardiac and vascular effects of AEN. In the isolated Langendorffperfused rat heart, AEN (1 and 2 g/l) markedly decreased heart rate and increased left ventricular pressure. Higher concentration (5 g/l) even led to cardiac arrest. Although carbachol mimicked the bradycardiac effect of AEN, atropine (a muscarinic receptor antagonist, 1 µM) did not modify the response. Beside its action on myocardium, AEN also affected vascular contractility. Indeed, AEN (0.1–5 g/l) produced a dose‐dependent increase in basal tone of isolated rat aorta. This effect was endothelium independent and was abolished by 1 µM prazosin (an α1‐adrenergic antagonist). AEN had little additional effects when the aorta was precontracted by noradrenaline (1 µM) or KCl (40 mM). Our data indicate that AEN produces a vasoconstriction of the aorta which is due to activation of α1‐adrenergic receptors. However, AEN also induces a strong bradycardia through non‐cholinergic and non‐adrenergic pathways which might compensate for its vascular effect and account for the hypotensive action of Urtica dioica Ldescribed in vivo. Copyright © 2002 John Wiley & Sons, Ltd.

BACKGROUND: The use of immature male germ cells to fertilize human oocytes raises several questions. Spermatozoa are normally quiescent, but many genes are transcribed post-meiotically in round spermatids. This creates a novel situation for the oocyte. We have therefore explored the effects on early embryonic development of introducing a fully transcriptionally active round spermatid into the oocyte. METHODS AND RESULTS: Following the micro-injection of spermatozoa or spermatids into mouse oocytes we have analysed the expression, at various times, of six genes in the resulting embryo. Spermatozoa and spermatids produced similar fertilization rates. Hprt was expressed in all embryos at all stages tested. Hsp70.1 was found normally during the 2-cell stage and repressed by the 4-cell stage in embryos from both spermatozoa and round spermatids. However, the amplitude of the signal was greatly reduced in 2-cell embryos from round spermatids. Smcy also showed a disturbed pattern of expression in embryos from round spermatids. Protamine 2, which is normally restricted to the spermatid stage, was expressed following fertilization with round spermatids, but was already repressed at the two pronuclei stage. Ube1Y, which is normally expressed post-meiotically and not during the post-implantatory development, was expressed up to the 2-cell stage in embryos from round spermatids only, and then repressed. Ube1X was also expressed up to the 2-cell stage, but in both embryo types. CONCLUSIONS: We therefore suspect that in embryos fertilized with round spermatids, regulatory mechanisms for inhibiting the inappropriate transcription of male post-meiotically expressed genes are activated following fertilization, permitting the zygotic genome activation to occur, though with some disturbances.

The use of immature male germ cells to fertilize human oocytes raises several questions. Spermatozoa are normally quiescent, but many genes are transcribed post-meiotically in round spermatids. This creates a novel situation for the oocyte. We have therefore explored the effects on early embryonic development of introducing a fully transcriptionally active round spermatid into the oocyte.

The purpose of this study was to isolate pure populations of round spermatids from mouse testis by flow cytometry followed by cell sorting. Cell suspensions from mouse testis were enriched in germ cells by centrifugation on a discontinuous Percoll gradient, then analysed using a FACScalibur flow cytometer measuring the cell size and density. A large and well-delimited population of cells (R1) expected to contain round spermatids was observed on the dot plot diagram. Sorted R1 cells were very homogeneous in size (approximately 11 microns) and displayed the characteristic cytological aspect of round spermatids. Spermatid-specific gene expression was confirmed by reverse transcriptase-polymerase chain reaction (RT-PCR) analysis of R1 cells using primers for protamine 2 gene (PRM2) and SP-10. A positive signal for SP-10 was obtained with a single cell using nested primers. The 5.5 kb transcript of c-kit, which is not expressed in spermatids, was not detected by nested RT-PCR, excluding a contamination with spermatogonia. Our results clearly established that flow cytometry followed by cell sorting allows the isolation of a highly homogeneous population of round spermatids from the testis.

Flow cytometry coupled to cell sorting is proposed as a method to isolate round spermatids from testicular biopsies in obstructive azoospermic patients. The cells were separated on the basis of their size and density only. We obtained homogenous populations of alive round spermatids free of lymphocytes and diploid germ cells. The detection of protamine 1 gene (PRM1) and PRM2 expression in the sorted cells proves that these cells are round spermatids. On the contrary, neither the expression of CD3-delta, which is specific to lymphoid cells, nor that of MAGE1, which has been demonstrated in diploid germ cells, could be observed in the round spermatid population even after using a nested polymerase chain reaction (PCR) assay. The flow cytometry procedure failed to isolate round spermatids from ejaculates in non-obstructive azoospermic patients. In > 39 ejaculates tested by reverse transcriptase-PCR, only nine revealed the presence of some round spermatids, as demonstrated by the expression of PRM1. However, these round spermatids did not express PRM2.

In order to examine the effect of Arbutus unedo extract on the development of genetic hypertension, three groups of six male spontaneously hypertensive rats (SHR) from 4 to 10 weeks of age, received orally an aqueous extract of the root of this Ericaceae plant at doses of 5, 50 and 250 mg/kg/24 h. The fourth group (n = 6) received tap water only and served as a control. A significant (p &lt; 0.01) reduction of indirect systolic blood pressure (BP) was observed after 4 weeks of treatment with the two highest doses but this effect attenuated 2 weeks later. The continuous measurement of direct BP in conscious 10-week-old rats indicated that chronic treatment with Arbutus did not significantly alter the BP level, the heart rate (HR), the cardiac baroreflex sensitivity and the sympathetic nervous and renin– angiotensin system activities. In contrast, Arbutus (50 mg/kg/24 h) attenuated the pressor responses to phenylephrine and angiotensin I. Finally, a diuretic effect was evidenced in the group receiving the highest dose. It is concluded that chronic oral administration of Arbutus unedo slowly delayed the development of hypertension but did not alter the final level of BP and HR in the SHR. The vascular and renal effects of this plant, which may account for its use in folk medicine, require a more detailed analysis. © 1998 John Wiley & Sons, Ltd.

In order to examine the effect of Arbutus unedoextract on the development of genetic hypertension, three groups of six male spontaneously hypertensive rats (SHR) from 4 to 10 weeks of age, received orally an aqueous extract of the root of this Ericaceae plant at doses of 5, 50 and 250 mg/kg/24 h. The fourth group (n= 6) received tap water only and served as a control.

To analyze the effect of a fertilin-derived peptide (cFEE) on in vitro maturation of human oocytes.

Origanum genus is one of the most widely used herbs in folk medicine for its biological properties. The present investigation aims to characterize, for the first time, endemic Origanum grosii collected from the Taounate region, Morocco. This characterization was realized by determining the concentration of metals in different parts of the plant (flowers, leaves, and stems) by ICP-MS, and the results were studied statistically by Principal Component Analysis (PCA). Phytochemical screening with the dosage of polyphenols and flavonoids has been conducted. To know more about this species, antihyperglycemic tests have been performed to highlight the presence or absence of the antidiabetic effect for this plant. An Oral Glucose Tolerance Test (OGTT) has been performed on normal mice which were divided into two groups of six mice each. Group 1 (control group) was treated with distilled water, and group 2 was treated with an aqueous extract of O. grosii by gavage at 150 mg/kg. Digestive enzyme α-amylase inhibition assay has also been evaluated to study the inhibition effect of the studied extract using acarbose as a control. The results showed that the leaves exhibited a high concentration of trace elements (Ca, Mg, and K) and total absence of heavy metals, which were found in small quantities (Cr, Ni, and B) on the stems, and this makes the plant safe to use. On the other hand, tannins, flavonoids, triterpenes, and steroids were the major families strongly present in this species. The antidiabetic results showed that O. grosii have significantly reduced postprandial hyperglycemia after glucose loading in normal rats. It showed also that this species has a significant antihyperglycemic activity reflected by the inhibition of α-amylase. The one responsible for this property could be the synergy between the trace elements and the nature of the chemical families of O. grosii species, which can make this plant useful in the management of postprandial hyperglycemia.

The present study aims to evaluate the hepatoprotective activity of stem aqueous extract of Caralluma europaea (AECe) on carbon tetrachloride- (CCl4-) induced hepatic damage in Wistar rats. The animals were daily treated with the aqueous extract of C. europaea at a dose of 250 mg/kg body weight for 14 days. CCl4 was injected (1 ml/kg, i.p.) two times, on the 7th and 14th days. At the end of the experimental period, all rats were anesthetized to collect blood for the assessment of biochemical parameters and then sacrificed to collect the liver for weighing. Hepatotoxicity was evaluated by measuring the serum levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), bilirubin (total and direct), malondialdehyde (MDA), total protein (TP), triglycerides (TG), total cholesterol, very low-density lipoprotein (VLDL-c ), low-density lipoprotein (LDL-c), high-density lipoprotein (HDL-c), urea, creatinine, and uric acid. Based on the results obtained in this study, the administration of C. europaea before exposure to the administration of CCl4 conferred favorable hepatoprotective effect in rats. The treatment with AECe (250 mg/kg) exhibits a significant hepatoprotective effect by ameliorating CCl4-induced alterations of these biochemical parameters. Hence, C. europaea could be a potential medicinal herb that can be used in the future to prevent liver intoxication.

CaVβ1E boosts downstream growth differentiation factor 5 signaling to counteract muscle mass loss in denervated or aged mouse muscles.