Homozygous mutation of AURKC yields large-headed polyploid spermatozoa and causes male infertility.

The World Health Organization conservatively estimates that 80 million people suffer from infertility worldwide. Male factors are believed to be responsible for 20-50% of all infertility cases, but microdeletions of the Y chromosome are the only genetic defects altering human spermatogenesis that have been reported repeatedly. We focused our work on infertile men with a normal somatic karyotype but typical spermatozoa mainly characterized by large heads, a variable number of tails and an increased chromosomal content (OMIM 243060). We performed a genome-wide microsatellite scan on ten infertile men presenting this characteristic phenotype. In all of these men, we identified a common region of homozygosity harboring the aurora kinase C gene (AURKC) with a single nucleotide deletion in the AURKC coding sequence. In addition, we show that this founder mutation results in premature termination of translation, yielding a truncated protein that lacks the kinase domain. We conclude that the absence of AURKC causes male infertility owing to the production of large-headed multiflagellar polyploid spermatozoa.

State of knowledge on chemical, biological and nutritional properties of olive mill wastewater.

The Mediterranean olive oil industries are producing annually a massive quantity of olive mill wastewater (OMWW). Unfortunately, the OMWW is released arbitrarily in the nature without any pretreatment. Thus, it exhibits a high toxicity against the whole natural ecosystem including, microorganisms, plants and animals. In order to eliminate or reduce its pollution, OMWW must be properly treated prior to its release in the nature. In this regard, different treatment methods have been developed by researchers, but some of them were costly and others were inappropriate. Thus, more efforts should be made to save the nature from this pollutant. In the light of that, the current work summaries the state of knowledge regarding the OMWW from a chemical, biological, nutraceutical point of view, and the treatment methods that were used to eliminate its risk of pollution.

The Aurora Kinase C c.144delC mutation causes meiosis I arrest in men and is frequent in the North African population.

Infertility concerns a minimum of 70 million couples worldwide. An important proportion of cases is believed to have a genetic component, yet few causal genes have been identified so far. In a previous study, we demonstrated that a homozygous mutation (c.144delC) in the Aurora Kinase C (AURKC) gene led to the production of large-headed polyploid multi-flagellar spermatozoa, a primary infertility phenotype mainly observed in North Africans. We now want to estimate the prevalence of the defect, to improve our understanding of AURKC physiopathology in spermatogenesis and assess its implication in oogenesis. A carrier frequency of 1/50 was established from individuals from the Maghrebian general population, comparable to that of Y-microdeletions, thus far the only known recurrent genetic event altering spermatogenesis. A total of 62 patients were genotyped, all who had a typical phenotype with close to 100% large-headed spermatozoa were homozygously mutated (n = 32), whereas no AURKC mutations were detected in the others. Two homozygous females were identified; both were fertile indicating that AURKC is not indispensible in oogenesis. Previous FISH results had showed a great chromosomal heterogeneity in these patient's spermatozoa. We demonstrate here by flow cytometry that all spermatozoa have in fact a homogeneous 4C DNA content and are thus all blocked before the first meiotic division. Our data thus indicate that a functional AURKC protein is necessary for male meiotic cytokinesis while its absence does not impair oogenesis.

Early and Late Functional Outcomes of Anal Sphincter-Sparing Procedures With Total Mesorectal Excision for Anorectal Adenocarcinoma

BACKGROUND: The study aims to assess the functional outcome of anal sphincter sparing procedures (SSP) with TME for anorectal adenocarcinoma. METHODS: In a multicentric, prospective, single-group study in the period between December 2012 and November 2017, 93 patients presented with anorectal adenocarcinoma were included in the study. Sixty-nine patients underwent SSP with TME. SSP included the combined approach of transabdominal TME with intersphincteric resection (ISR) or transanal transabdominal TME (TATA). Using the Per Anal Examination Scoring System (PASS), postoperative anal function was assessed after one year. RESULTS: Bowel motility time was 50 (±19) hours. The time needed for narcotic analgesia was 54 (±18.8) hours. Mean hospital stay was 15.4 (±10.25) days. Incidence of evident fecal incontinence after ISR is 10.6% (7/67 cases). The Per Anal Examination Scoring System (PASS) findings of 69 cases are as follows: extremely hypotonic 8.6% (6 cases), slightly hypotonic 26.1% (18 cases), normal tone 58% (40 cases), slightly stenotic 3 cases (4.3%), or occluded 2.9% (2 cases). Urinary dysfunction occurred in one case (1.4%). Temporary diversion was performed in 61 patients (87.1%). CONCLUSION: Sphincter preservation with TME for anorectal adenocarcinoma helps avoid permanent stoma and provides a reasonable functional outcome. PASS is a new application for postoperative assessment of anal function.

Thioether-based 2-aminobenzamide derivatives: Novel HDAC inhibitors with potent in vitro and in vivo antitumor activity.

Previously, we focused on a series of 2-aminobenzamide-based histone deacetylase (HDAC) inhibitors, compound 9 of which displayed potent HDAC inhibitory activity against HDAC1 and HDAC2, and moderate anti-proliferative activity against several cancer cell lines. In the current study, we have designed and synthesized a series of novel HDAC inhibitors based on thioether moiety with 9 as a lead compound. Representative compounds12 g and 12 h showed apparently potent anti-proliferative activities against five solid cancer cell lines: A549, HCT116, Hela, A375 and SMMC7721, and low cytotoxicity against NIH 3T3 normal cells. Especially, 12 g and 12 h also revealed potent HDAC inhibitory activity against HDAC1, 2 and 3. In addition, the two compounds could arrest cell cycle in G2/M phase and promote cell apoptosis. Moreover, they showed extended inhibition of colony formation and effectively blocked cell migration towards A549 cancer cells. Furthermore, 12 g and 12 h possessed better pharmacokinetic properties than the lead compound 9. Benefiting from these results, we also explored 12 g and 12 h in the A549 xenografts model for in vivo antitumor activity. The in vivo experiment indicated that 12 g and 12 h could evidently augment antitumor activity (TGI = 56.9% and 62.7% respectively).

Preparation and antimicrobial activity of oregano essential oil Pickering emulsion stabilized by cellulose nanocrystals.

An effective antimicrobial system was developed by using oregano essential oil (OEO) Pickering emulsion. The Pickering emulsion was stabilized by cellulose nanocrystals (CNCs), which were from microcrystalline cellulose (MCC) by selective oxidization ammonium persulfate. Factors affecting the stability of OEO Pickering emulsions, such as oil/water ratio, CNCs concentration, ionic concentration and pH, were studied and analysed by the measurement of the droplet sizes and Zeta potential. The results showed that the emulsions had good stability at higher CNCs concentration and pH values, or at lower oil/water ratio and salt concentration. In addition, the antimicrobial efficacy of OEO Pickering emulsions against four food-related microorganisms was evaluated by determining the minimal inhibitory concentration (MIC). The results showed that prepared OEO Pickering emulsions could efficiently inhibit the growth of four tested microorganisms by destroying the integrity of the cells' membrane. The research would have a certain leading meaning on the design and use of OEO Pickering emulsions stabilized by CNCs for the delivery of antimicrobial essential oils in the food and other industries.

Enhancing the antimicrobial activity of d-limonene nanoemulsion with the inclusion of ε-polylysine.

The objective of this research was to investigate the synergism between ε-polylysine and d-limonene and develop a novel nanoemulsion system by merging the positive effect of these two antimicrobial agents. Results from the checkerboard method showed that ε-polylysine and d-limonene exhibit strong synergistic and useful additive effects against Escherichia coli, Staphylococcus aureus, Bacillus subtilis and Saccharomyces cerevisiae. In addition, d-limonene nanoemulsion with the inclusion of ε-polylysine was successfully prepared by high pressure homogenizer technology. Its antimicrobial efficiency was compared with pure d-limonene nanoemulsion by measuring the minimal inhibitory concentration, electronic microscope observation and the leakage of the intercellular constituents. The results demonstrated a wide improvement of the antimicrobial activity of d-limonene nanoemulsion following the inclusion of ε-polylysine. Overall, the current study may have a valuable contribution to make in developing a more efficient antimicrobial system in the food industry.

Organogel-nanoemulsion containing nisin and D-limonene and its antimicrobial activity.

The aim of this study was to investigate a novel delivery system containing D-limonene and nisin by food organogel-nanoemulsion and study its effect on the antimicrobial activity. Organogel-nanoemulsion containing with D-limonene and nisin or without nisin was prepared by a homogenization method. Factors that may affect the droplet size and stability of organogel-nanoemulsion such as pressure and surfactant to oil ratio (SOR) were studied. The average droplet size decreased with pressure, and the organogel-nanoemulsion could achieve good stability at low SOR. Positive effects and outstanding antimicrobial activities of organogel-nanoemulsion containing with D-limonene and nisin were confirmed by minimal inhibitory concentrations comparison, growth curves of bacteria, scanning electron microscopy and determination of cell constituents' release. Furthermore, the organogel-nanoemulsion applied as food preservative in milk also shown excellent antimicrobial performance. Overall, the research described in the current article show that organogel-nanoemulsion containing with D-limonene and nisin may be an effective antimicrobial system for the production and preservation of food.

Absolute polymorphic teratozoospermia in patients with oligo-asthenozoospermia is associated with an elevated sperm aneuploidy rate.

Infertile patients with abnormal sperm parameters have an increased sperm aneuploidy rate, despite a normal blood karyotype. The evaluation of sperm chromosome aberrations in patients with teratozoospermia only has shown a rate similar to that found in patients exhibiting oligo-astheno-teratozoospermia, which suggests that teratozoospermia is the critical parameter associated with aneuploidy. However, it is not known which alteration of the sperm morphology is associated with chromosome aberrations. The few cases reported so far have shown an association with the presence of abnormal head morphology and particularly with enlarged heads. We report the sperm aneuploidy rate of 3 patients with oligo-asthenozoospermia who have absolute teratozoospermia (100% abnormal forms) and a different percentage of sperm head abnormalities. Fourteen healthy men with normozoospermia served as control subjects. Sperm aneuploidy and diploidy rates were calculated by using triple-color fluorescence in situ hybridization (FISH) for chromosomes 12, X, and Y, and double-color FISH was used for chromosomes 8 and 18. Patient K53, who had the highest number of spermatozoa with enlarged heads (54.3%), also had the highest aneuploidy and diploidy rates. The other 2 patients, K56 and K61, had sperm aneuploidy and diploidy rates lower than those of patient K53 but still well above the range found in normal men. Sperm chromosome abnormalities were intermediate in patient K61 and lower in patient K56, who had the lowest rate of spermatozoa with enlarged heads (18.9%). These data add further evidence that patients with teratozoospermia have an increased sperm aneuploidy rate and that this is particularly high in presence of an elevated percentage of spermatozoa with enlarged heads. For this reason, germ cells exhibiting this abnormality should not be used in in vitro fertilization programs.

Formation and stability of D-limonene organogel-based nanoemulsion prepared by a high-pressure homogenizer.

D-limonene organogel-based nanoemulsion was prepared by high-pressure homogenization technology. The organogelator type had a major role on the formation of the formulations, in which stearic acid has given nanoemulsions with the smallest droplet size. The surfactant type and concentration also had an appreciable effect on droplet formation, with Tween 80 giving a mean droplet diameter (d ≈ 112 nm) among a range of non-ionic surfactants (Tween 20, 40, 60, 80, and 85). In addition, high-pressure homogenization conditions played a key role in the nanoemulsion preparation. The stability of d-limonene organogel-based nanoemulsion was also investigated under two different temperatures (4 and 28 °C) through 2 weeks of storage. Results showed a good stability of the formulations, which is maybe due to the incorporation of D-limonene into the organogel prior to homogenization. This study may have a valuable contribution for the design and use of organogel-based nanoemulsion as a delivery system in food.