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Human infertility is a healthcare problem that has a worldwide impact. Genetic causes of human infertility include chromosomal aneuploidies and rearrangements and single-gene defects. The sex chromosomes (X and Y) are critical players in human fertility since they contain several genes essential for sex determination and reproductive traits for both men and women. This paper provides a review of the most common sex chromosomes-linked single-gene disorders involved in human infertility and their corresponding phenotypes. In addition to the Y-linked SRY gene, which mutations may cause XY gonadal dysgenesis and sex reversal, the deletions of genes present in AZF regions of the Y chromosome (DAZ, RBMY, DBY and USP9Y genes) are implicated in varying degrees of spermatogenic dysfunction. Furthermore, a list of X-linked genes (KAL1, NR0B1, AR, TEX11, FMR1, PGRMC1, BMP15 and POF1 and 2 regions genes (XPNPEP2, POF1B, DACH2, CHM and DIAPH2)) were reported to have critical roles in pubertal and reproductive deficiencies in humans, affecting only men, only women or both sexes. Mutations in these genes may be transmitted to the offspring by a dominant or a recessive inheritance. 相似文献
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Souhir Chaabane Meriam Messedi Rim Akrout Mariem Ben Hamad Mouna Turki Sameh Marzouk Leila Keskes Zouheir Bahloul Ahmed Rebai Fatma Ayedi Abdellatif Maalej 《Inflammation research》2018,67(8):703-710
Objectives
The study investigated the association between plasma homocysteine, folate and vitamin B12 with 5,10 methylenetetrahydrofolate reductase (MTHFR C677T and A1298C), thymidylate synthase (TYMS 2R → 3R) and methionine synthase (MTR A2756G) polymorphisms and methotrexate (MTX) treatment and toxicity in Tunisian Rheumatoid arthritis (RA) patients.Methods
A total of 185 patients with RA were included. Homocysteine (Hcy) was assessed by fluorescence polarization immunoassay, and folate and vitamin B12 were measured by chemiluminescence immunoassays. The genetic polymorphisms were analyzed by PCR or PCR-RFLP. Hyperhomocysteinemia (HHC) was considered for Hcy?>?15 µmol/L.Results
MTHFR C677T polymorphism was associated with HHC in RA patients (multi-adjusted OR, 95% CI 2.18, [1.07–4.57]; p?=?0.031). No association was detected with the remaining polymorphisms. Plasma Hcy, folate, and vitamin B12 did not differ according to each polymorphism, or with MTX treatment or toxicity. However, HHC was more prevalent in patients with than those without MTX toxicity (32.7 vs. 16.7%; p?=?0.035).Conclusions
The MTHFR 677TT genotype is an independent risk factor for HHC in Tunisians RA patients. HHC could be a useful marker of MTX toxicity in RA patients.6.
Medial prefrontal circuits have been reported to undergo a major reorganization over time and gradually take a more important role for remote emotional memories such as contextual fear memory or food aversion memory. The medial prefrontal cortex, and specifically its ventral subregion, the infralimbic cortex (IL), was also reported to be critical for recent memory extinction of contextual fear conditioning and conditioned odor aversion. However, its exact role in the extinction of remotely acquired information is still not clear. Using postretrieval blockade of protein synthesis or inactivation of the IL, we showed that the IL is similarly required for extinction consolidation of recent and remote fear memory. However, in odor aversion memory, the IL was only involved in extinction consolidation of recent, but not remote, memory. In contrast, only remote retrieval of aversion memory induced c-Fos activation in the IL and preretrieval inactivation of the IL with lidocaine impaired subsequent extinction of remote but not recent memory, indicating IL is necessary for extinction learning of remote aversion memory. In contrast to the effects in odor aversion, our data show that the involvement of the IL in the consolidation of fear extinction does not depend on the memory age. More importantly, our data indicate that the IL is implicated in the extinction of fear and nonfear-based associations and suggest dissociation in the engagement of the IL in the learning and consolidation of food aversion extinction over time. 相似文献
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Xiangmin Li Qingping Wu Yizhen Xie Yinrun Ding William W. Du Mouna Sdiri Burton B. Yang 《Oncotarget》2015,6(19):17832-17846
We have previously screened thirteen medicinal mushrooms for their potential anti-cancer activities in eleven different cell lines and found that the extract of Amauroderma rude exerted the highest capacity in inducing cancer cell death. The current study aimed to purify molecules mediating the anti-cancer cell activity. The extract of Amauroderma rude was subject to fractionation, silica gel chromatography, and HPLC. We purified a compound and identified it as ergosterol by EI-MS and NMR, which was expressed at the highest level in Amauroderma rude compared with other medicinal mushrooms tested. We found that ergosterol induced cancer cell death, which was time and concentration dependent. In the in vivo experiment, normal mice were injected with murine cancer cell line B16 that is very aggressive and caused mouse death severely. We found that treatment with ergosterol prolonged mouse survival. We found that ergosterol-mediated suppression of breast cancer cell viability occurred through apoptosis and that ergosterol up-regulated expression of the tumor suppressor Foxo3. In addition, the Foxo3 down-stream signaling molecules Fas, FasL, BimL, and BimS were up-regulated leading to apoptosis in human breast cancer cells MDA-MB-231. Our results suggest that ergosterol is the main anti-cancer ingredient in Amauroderma rude, which activated the apoptotic signal pathway. Ergosterol may serve as a potential lead for cancer therapy. 相似文献
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Hibiscus sabdariffa increases hydroxocobalamin oral bioavailability and clinical efficacy in vitamin B12 deficiency with neurological symptoms 下载免费PDF全文
Zouhayr Souirti Mouna Loukili Imar D. Soudy Kaies Rtibi Aslihan Özel Nicolas Limas‐Nzouzi Seloua El Ouezzani Bruno Eto 《Fundamental & clinical pharmacology》2016,30(6):568-576
The aim of the study was to evaluate the bioavailability and clinical benefits of oral new formulation (HB12) of hydroxocobalamin (Hdrx) with Hibiscus sabdariffa (HS). First, in an observational study, a cohort of 30 vitamin B12‐deficient patients (vit B12 < 200 pg/mL) with neurological symptoms received oral fixed dose of Hdrx containing 15 mg Hdrx daily for 10 days followed by 15 mg monthly. Clinical benefits were evaluated on haematological and biochemical parameters, and neurological improvement at days 10 and 90 compared to day 0. To understand the mechanism, intestinal mucosa from mice were mounted in vitro in Ussing chambers to measure Hdrx Fluxes. In the clinical study, serum vitamin B12 level increased from 55.1 ± 36.9 to 1330 ± 335.5 pg/mL at day 10 and 431.0 ± 24.27 pg/mL at day 90, without overt adverse effects. In mice ileum, (i) intestinal bioavailability of Hdrx increased in dose‐dependent manner with HB12. The apparent permeability of Hdrx was Papp = 34.9 ± 4.6 × 10?6 cm/s in the presence of 3 mg/mL (HB12B) compared to the control Papp = 6.2 ± 0.7 × 10?6 cm/s. (ii) Total transepithelial electrical conductance (Gt) increased in dose‐dependent manner with HB12, Gt = 161.5 ± 10.8 mS/cm² with HB12B (Hdrx 1 mg + HS 3 mg) compared to the control Hdrx, Gt = 28.7 ± 4.0 mS/cm². In conclusion, the clinical study suggests that injections are not required when Hdrx is given orally. Intestinal bioavailability of Hdrx increased in vitro when it was used concomitantly with HS. 相似文献
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Patricia Recordon-Pinson Cathia Soulié Philippe Flandre Diane Descamps Mouna Lazrek Charlotte Charpentier Brigitte Montes Mary-Anne Trabaud Jacqueline Cottalorda Véronique Schneider Laurence Morand-Joubert Catherine Tamalet Delphine Desbois Muriel Macé Virginie Ferré Astrid Vabret Annick Ruffault Coralie Pallier Stéphanie Raymond Jacques Izopet Jacques Reynes Anne-Geneviève Marcelin Bernard Masquelier and the ANRS AC Resistance Study Group 《Antimicrobial agents and chemotherapy》2010,54(8):3335-3340