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1.

Gliomas are histologically defined as low-grade gliomas (LGG) and high-grade gliomas (HGG). The most common type of HGG is the glioblastoma (GBM). We aimed to determine the immunological characteristics of CD3 T-cells, Vδ1 T-cells, and microglia/macrophages infiltrating brain gliomas. We collected 24 formalin-fixed paraffin-embedded samples issued from 19 cases of GBM and 5 cases of LGG. An immunohistochemical analysis was performed using anti-CD3, anti-Vδ1, and anti-iba-1 antibodies. Labelling indexes (LI) of CD3 and Vδ1 were evaluated quantitatively, and other CD3, Vδ1, and iba-1 staining characteristics were evaluated qualitatively. The median age of patients was 49 years in GBM and 52 years in LGG. The sex ratio was 1.4 and GBM predominated in males (p?=?0.05). In GBM, the medians of CD3-LI and Vδ1-LI were 30 and 3.5 respectively. CD3-LI inversely correlated with survival in GBM cases (r?=????0.543; p?=?0.016). CD3 staining intensity correlated with CD3-LI (p?<?0.0001) and with the survival in GBM cases (p?=?0.003). Compared to LGG, the CD3-LI, the intensity of intra-tumoral Vδ1 staining, and the amount of iba-1 were higher in GBM (p?=?0.042; p?=?0.014; and p?=?0.001 respectively). The iba-1 organization was more amoeboid in older patients and more branched in younger patients (p?=?0.028) and tended to be more amoeboid in cases with high iba-1 amount (p?=?0.09). Our results suggest that a high level of CD3-LI and a strong intra-tumoral infiltration of Vδ1 T-cells as well as a high involvement of TAM can be considered potential markers of poor prognosis of GBM. However, this requires further studies on more balanced GBM-LGG sample, including an expanded panel of biomarkers.

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PurposeRare genetic variants in CDK13 are responsible for CDK13-related disorder (CDK13-RD), with main clinical features being developmental delay or intellectual disability, facial features, behavioral problems, congenital heart defect, and seizures. In this paper, we report 18 novel individuals with CDK13-RD and provide characterization of genome-wide DNA methylation.MethodsWe obtained clinical phenotype and neuropsychological data for 18 and 10 individuals, respectively, and compared this series with the literature. We also compared peripheral blood DNA methylation profiles in individuals with CDK13-RD, controls, and other neurodevelopmental disorders episignatures. Finally, we developed a support vector machine–based classifier distinguishing CDK13-RD and non–CDK13-RD samples.ResultsWe reported health and developmental parameters, clinical data, and neuropsychological profile of individuals with CDK13-RD. Genome-wide differential methylation analysis revealed a global hypomethylated profile in individuals with CDK13-RD in a highly sensitive and specific model that could aid in reclassifying variants of uncertain significance.ConclusionWe describe the novel features such as anxiety disorder, cryptorchidism, and disrupted sleep in CDK13-RD. We define a CDK13-RD DNA methylation episignature as a diagnostic tool and a defining functional feature of the evolving clinical presentation of this disorder. We also show overlap of the CDK13 DNA methylation profile in an individual with a functionally and clinically related CCNK-related disorder.  相似文献   
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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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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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Context The present study deals with new biological properties of the wild edible Diplotaxis simplex (Viv.) Spreng (Brassicaceae).

Objectives The current study evaluates the antioxidant, the anti-inflammatory and the anti-cancer properties of ethyl acetate and ethanol extracts from D. simplex flowers.

Materials and methods The anti-proliferative activity of the extracts (10–70?μg/mL) was assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) against human colon cancer cell line Caco-2. The anti-inflammatory potential was evaluated by the inhibitory effect of the extracts (1.5–7.5?mg/mL) on phospholipase A2 activity as well as on carrageenan-induced paw oedema in mice. Extracts (200?mg/kg) or indomethacin (50?mg/kg) as positive control were injected intraperitoneally for albino mice prior to the induction of the oedema by carrageenan. Antioxidant activities were investigated using various complementary methods.

Results Flower extracts contained a high level of polyphenolics (17.10–52.70?mg GAE/g) and flavonoids (74.20–100.60?mg QE/g), which correlate with its appreciable antioxidant potential in β-carotene peroxidation (IC50 value: 12.50–27.10?μg/mL), DPPH? radical-scavenging (IC50 value: 0.20–0.40?mg/mL), Fe3+?reducing (EC50 value: 0.10–0.14?mg/mL) and Fe2+?chelating (IC50 value: 0.20–0.60?mg/mL) assays. These extracts were effective in inhibiting cancer cell growth (IC50 value: 62.0–63.25?μg/mL). Besides, the ethyl acetate extract inhibited phospholipase A2 activity (IC50 value: 2.97?mg/mL) and reduced the paw oedema in mice (from 0.38?±?0.01 to 0.24?±?0.01?cm), 4?h post-carrageenan challenge.

Conclusion These data suggest that D. simplex may be useful as a candidate in the treatment of inflammation and the colon cancer.  相似文献   
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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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