Major histocompatibility complex (MHC) class I chain-related gene A (MICA) is located 46 kb centromeric to HLA-B and encodes a stress-inducible protein. MICA allelic variation is thought to be associated with disease susceptibility and immune response to transplants. This study was aimed to investigate the haplotypic diversity and linkage disequilibrium between human leukocyte antigen (HLA)-B and (GCT)(n) short tandem repeat in exon 5 of MICA gene (MICA-STR) in a southern Chinese Han population. Fifty-eight randomly selected nuclear families with 183 members including 85 unrelated parental samples were collected in Hunan province, southern China. HLA-B generic typing was performed by polymerase chain reaction-sequence-specific priming (PCR-SSP), and samples showing novel HLA-B-MICA-STR linkage were further typed for HLA-B allelic variation by high-resolution PCR-SSP. MICA-STR allelic variation and MICA gene deletion (MICA*Del) were detected by fluorescent PCR-size sequencing and PCR-SSP. Haplotype was determined through family segregation analysis. Statistical analysis was applied to the data of the 85 unrelated parental samples. Nineteen HLA-B specificities and seven MICA-STR allelic variants were observed in 85 unrelated parental samples, the most predominant of which were HLA-B*46, -B60, -B*13, and -B*15, and MICA*A5, MICA*A5.1 and MICA*A4, respectively. Genotype distributions of HLA-B, MICA-STR loci were consistent with Hardy-Weinberg proportions. The HLA-B-MICA-STR haplotypic phases of all 85 unrelated parental samples were unambiguously assigned, which contained 30 kinds of HLA-B, MICA-STR haplotypic combinations, nine of them have not been reported in the literature. Significant positive linkage disequilibria between certain HLA-B and MICA-STR alleles, including HLA-B*13 and MICA*A4, HLA-B*38 and MICA*A9, HLA-B*58 and MICA*A9, HLA-B*46 and MICA*A5, HLA-B*51 and MICA*A6, HLA-B*52 and MICA*A6, and HLA-B60 and MICA*A5.1, were observed. HLA-B*48 was linked to MICA*A5, MICA*A5.1 and MICA*Del. HLA-B*5801-MICA*A10 linkage was found in a family. Our data indicated a high degree of haplotypic diversity and strong linkage disequilibrium between MICA-STR and HLA-B in a southern Chinese Han population, the data will inform future studies on anthropology, donor-recipient HLA matching in clinical transplantation and HLA-linked disease association.
ABSTRACT. We investigated azoospermia region microdeletions in male infertility patients with Klinefelter syndrome (KFS), as well as the association between azoospermia symptoms in patients with KFS and Y chromosome microdeletion polymorphisms. A total of 111 cases with male infertility confirmed to have KFS (47, XXY) and 94 fertile men were included in this study. Peripheral blood was drawn and DNA was extracted from these samples. Multiplex polymerase chain reaction was performed to screen the partial deletions of 25 sequence-tagged sites on the Y chromosome. In 111 cases with KFS, 1 case contained the AZFb+d+c deletion. The Gr/Gr deletion was identified in 12 KFS cases and 5 control cases. In addition, the b2/b3 deletion was identified in 13 KFS cases and 6 control cases. There were no significant differences in phenotype and genotype of the 2 partial AZFc deletions between patients and controls (P > 0.05). Our results suggest that patients with KFS may also have Y chromosome microdeletions to varying degrees 15141 AZF microdeletions in patients with Klinefelter syndrome ©FUNPEC-RP www.funpecrp.com.br Genetics and Molecular Research 14 (4): 15140-15147 (2015) and that the gr/gr deletion and b2/b3 deletion may not play a role in the susceptible genetic background of azoospermia in patients with KFS in the Sichuan population.
During spermatogenesis, developing germ cells that lack the cellular ultrastructures of filopodia and lamellipodia generally found in migrating cells, such as macrophages and fibroblasts, rely on Sertoli cells to support their transport across the seminiferous epithelium. These include the transport of preleptotene spermatocytes across the blood-testis barrier (BTB), but also the transport of germ cells, in particular developing haploid spermatids, across the seminiferous epithelium, that is to and away from the tubule lumen, depending on the stages of the epithelial cycle. On the other hand, cell junctions at the Sertoli cell–cell and Sertoli–germ cell interface also undergo rapid remodeling, involving disassembly and reassembly of cell junctions, which, in turn, are supported by actin- and microtubule-based cytoskeletal remodeling. Interestingly, the underlying mechanism(s) and the involving biomolecule(s) that regulate or support cytoskeletal remodeling remain largely unknown. Herein, we used an in vitro model of primary Sertoli cell cultures that mimicked the Sertoli BTB in vivo overexpressed with the ribosomal protein S6 (rpS6, the downstream signaling protein of mammalian target of rapamycin complex 1 [mTORC1]) cloned into the mammalian expression vector pCI-neo, namely, quadruple phosphomimetic and constitutively active mutant of rpS6 (pCI-neo/p-rpS6-MT) versus pCI-neo/rpS6-WT (wild-type) and empty vector (pCI-neo/Ctrl) for studies. These findings provide compelling evidence that the mTORC1/rpS6 signal pathway exerted its effects to promote Sertoli cell BTB remodeling. This was mediated through changes in the organization of actin- and microtubule-based cytoskeletons, involving changes in the distribution and/or spatial expression of actin- and microtubule-regulatory proteins.
Why estrogen hyperstimulation can lead to endometrial carcinogenesis has not been fully clear yet. Non-nuclear action of estrogen has arised much attention of many experts. Signal transducer and activator of transcription 3 is a very important signal molecule, which plays vital role in endometrial canver. The present study is oriented to the problem whether estrogen can activate STAT3 by non-nuclear action in endometrial cancer cells. So, the levels of phosphorylated STAT3 (P-STAT3) and total STAT3 were examined by western blot in endometrial cancer cells including Ishikawa with rich-expressed estrogen receptor (ER) and HEC-1A with poor-expressed ER after stimulation with 1μM estradiol (E2) at different time points and at varied doses of E2 for optimal time. Inhibitory role of AG490 on activation of STAT3 induced by E2 was also tested. P-STAT3/ STAT3 was used as a measure of activation of STAT3. We found that maximum P-STAT3/STAT3 took place at 15min in both Ishikawa cells and HEC-1A cells. The activation of STAT3 elicited gradually with increasing doses of E2. AG490 stopped the activating STAT3 in the same dose-dependent manner in both endometrial cancer cells. The results demonstrate that E2 is able to activate STAT3 in both Ishikawa with rich-expressed ER and HEC-1A with poor-expressed ER endometrial cancer cells by non-nuclear action, which provides the preliminary laboratory basis for the probability of endometrial adenocarcinoma treatment with blockage of STAT3 signaling, especially for ER-poor endometrial adenocarcinoma. Key words: endometrial cancer, signal transducer and activator of transcription 3, estrogen, non-nuclear action, carcinogenesis, estrogen receptorEndometrial carcinoma is one of the most common female genital tract malignancies. It is well-known that risk for endometrial adenocarcinoma increases in patients with high estrogen levels that are unopposed by progestins. Estrogen has been shown to exhibit growth-promoting properties in endometrial cancer cell [1]. The mechanism responsible for this promoting growth effect of estrogen involves 'classical' or 'genomic' mechanism, estrogen molecules penetrate into the cell and bind to the ER, which are members of the nuclear hormone receptors, and interact with the estrogen response element located in the regulatory region of target genes. The resulting fluctuations in mRNAs and the proteins they encode underlie series of responses that take place within hours following estrogen exposure. But the 'genomic' mechanism can't explain the truth that why some ER-positive endometrial carcinomas have no responses to endocrinal therapy while some ER-negative ones have responses. There must be other mechanisms involved. Indeed, there are rapid biochemical and physiological responses to estrogen occurring more rapidly (within seconds to minutes) than gene transcription events attributed to the ER (over the course of several hours) that cannot be accounted for by changes in gene expression mediated by nuclear ER. Our former data demonstrated that 17β-estradi...
CPT-loaded NPs with polyethylene glycol shells can increase its solubility in water and remain in circulation for a long time. This experiment has evaluated cytotoxicity and immune and subacute toxicity of CPT NPs. Camptothecin (CPT) was incorporated into biotin-F127-PLA or F127-PLA polymeric nanoparticles; a dialysis method was used for non-targeted CPT NPs and anti-CA125 antibodies for targeted CPT NPs. A cytotoxicity test was also conducted based on the growth inhibition of the mouse fibroblast-like L-929 cell line. The effects of the two CPT-loaded NPs on immunity were also determined through a carbon particle clearance rate assay. Each mouse was intraperitoneally injected with 0.4 ml/20 g.bw nanoparticles for 28 consecutive days in the subacute toxicity test. Results have showed that CPT NPs have reduced the toxicity of free CPT on the L-919 cells. The CPT NPs did not induce phagocytosis in the normal mice. At the end of subacute toxicity study no difference was found between the CPT NP and control groups in blood parameter analysis and main organ weight visceral coefficients. These results suggested that the new CPT NPs might elicit low toxic effects at cellular and organism levels.
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