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CYP27B1 mRNA expression was the highest in MFs and differed from that in SFs, whereas protein abundance was greater in MFs and SFs than in LFs. The expression of mRNA for CYP24A1 was higher in MFs than in SFs and LFs, while protein abundance did not differ between follicle classes. We have also described changes in the concentration of 1,25(OH)2D3 in the follicular fluid of antral follicles with its highest level in MFs. These findings show that the porcine antral follicle is a target tissue for direct VD action and is a local site of VD metabolism. Furthermore, we found that 1,25(OH)2D3 increased the secretion of progesterone and estradiol-17β by SFs and MFs in vitro, implying a crucial role of VD in the regulation of ovarian steroidogenesis in mature gilts. Therefore, VD appears to be an important intraovarian factor that could regulate follicular development and function in pigs.
Survivin is an inhibitor of apoptosis that is proposed as a target for anti-cancer therapy because of its high expression in cancer cells. It has potential as a prognostic and predictive biomarker of response to radiation and systemic therapies. We report its expression in head and neck squamous cell carcinoma (HNSCC) and its correlation with treatment response and survival.
We measured survivin protein expression in tumor specimens from 96 patients with HNSCC treated at Fox Chase Cancer Center, of whom 21 were p16+. Quantitative automated immunofluorescence was employed to score nuclear and cytoplasmic survivin in 5 tissue microarrays (TMAs) consisting of 316 H&N tumor cores and 107 control tissue cores. Survivin levels were then correlated to therapy response and survival outcomes.
Using the median score as the cutoff, overall survival (OS) was significantly shorter for the group expressing higher survivin in nuclear (p=0.013), cytoplasmic (p=0.018) and total compartments (p=0.006). No correlation was seen between survivin expression and patient sex or grade of tumor, T or N stage, or p16 status. Siponimod Survivin expression in metastases did not significantly differ from that in primary tumors. Levels of p53 expression showed a significant positive correlation with higher survivin expression in the cytoplasm (p=0.0264) and total compartments (p=0.0264), but not in the nucleus (p=0.0729).
Survivin expression above the median is associated with shorter overall survival in HNSCC, including for patients treated with chemotherapy or radiation. p16 expression did not correlate with survivin levels.
Survivin expression above the median is associated with shorter overall survival in HNSCC, including for patients treated with chemotherapy or radiation. p16 expression did not correlate with survivin levels.T-box 5 (TBX5) protein belongs to the T-box family whose members play a crucial role in cell-type specification, morphogenesis and organogenesis. TBX5 is a transcription factor important for cardiac development and upper limbs formation and its haploinsufficiency causes Holt-Oram syndrome (HOS). An increase in TBX5 dosage also leads to HOS, suggesting that TBX5 is a dose-sensitive transcription factor that needs to be tightly regulated but the molecular mechanisms involved remain unclear. In this work we report the cloning and functional analysis of human TBX5 promoter region 1 (upstream of exon 1) and promoter region 2 (upstream of exon 2), that probably regulate the transcription of the different transcript variants. In silico analysis showed several binding sites for cardiac and skeletal related transcription factors (TFs) and their functionality was assessed using promoter-luciferase constructions and TF-expressing vectors. MEF2A (Myocyte enhancer factor 2 A) was shown to positively regulate both TBX5 promoters, while EGR1 (early growth response 1) repressed both promoters. SOX9 (SRY (sex determining region Y)-box 9) repressed only the activity of promoter region 2. Interestingly, YY1 (Yin and yang 1) repressed promoter region 1 (that regulates the expression of variant 1 and 3), but activated promoter region 2 (that regulates the expression of variant 4). In conclusion, this work provides novel insights toward the better understanding of TBX5 transcriptional regulation by cardiac- and skeletal-related TFs.c/ebpα is a member of the C/EBP family of transcription factors, which are involved in cell growth and differentiation and have a conserved basic leucine zipper (bZIP) domain. However, little is known about its function in sex determination and differentiation. In the present study, c/ebpα was cloned from the gonads of Chinese tongue sole (Cynoglossus semilaevis). The full-length cDNA of c/ebpα was 1583 bp, with a 198-bp 5' UTR, a 446-bp 3' UTR, and a 939-bp open reading frame encoding a 312-amino acid peptide. qRT-PCR revealed that c/ebpα was predominantly expressed in undifferentiated gonads of male C. semilaevis at 30 dpf and 60 dpf and peaked at 60 dpf. Expression levels of c/ebpα in the testis were constantly higher than those in ovaries at all developmental stages. Moreover, a dual-luciferase assay revealed that c/ebpα could negatively regulate the male-determining gene dmrt1 in vitro. These results provide fundamental information indicating that C. semilaevis c/ebpa might be involved in early gonadal differentiation and functions as a negative regulator of dmrt1 by repressing its transcription.Balbaini body (Bb) plays a vital role in germ plasm (GP) assembly and dorsoventral pattern, which is of critical important in germline specification and development. Bucky ball (buc) is reported to be essential for boosting primordial germ cell (PGC) through Bb in previous research. In the present study, a buc homolog (Olbuc) was identified in medaka (Oryzias latipes), and the roles of Olbuc on PGC development were further elucidated. The full length of Olbuc was 2148 bp, which contains a 1724 bp CDS (Coding sequence), a 167 bp 5' UTR (Untranslated region), and a 257 bp 3' UTR. By RT-PCR, the Olbuc RNA expression was maternally provided during embryogenesis and was restricted in the ovary of adult tissues. By in situ hybridization, Olbuc RNA was abundant in oocyte of meiotic stage, but gradually decreased as the oogenesis proceeded. Surprisingly, Olbuc was not co-localized with dazl, the marker gene of Bb. Interestingly, GFP can be specifically and stably expressed through the induction of Olbuc 3'UTR in PGCs.
Homepage: https://www.selleckchem.com/products/baf312-siponimod.html
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