共查询到20条相似文献,搜索用时 31 毫秒
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Photic responses of the circadian system are mediated through light-induced clock gene expression in the suprachiasmatic nucleus (SCN). In nocturnal rodents, depending on the timing of light exposure, Per1 and Per2 gene expression shows distinct compartmentalized patterns that correspond to the behavioral responses. Whether the gene- and region-specific induction patterns are unique to nocturnal animals, or are also present in diurnal species is unknown. We explored this question by examining the light-induced Per1 and Per2 gene expression in functionally distinct SCN subregions, using diurnal grass rats Arvicanthis niloticus. Light exposure during nighttime induced Per1 and Per2 expression in the SCN, showing unique spatiotemporal profiles depending on the phase of the light exposure. After a phase delaying light pulse (LP) in the early night, strong Per1 induction was observed in the retinorecipient core region of the SCN, while strong Per2 induction was observed throughout the entire SCN. After a phase advancing LP in the late night, Per1 was first induced in the core and then extended into the whole SCN, accompanied by a weak Per2 induction. This compartmentalized expression pattern is very similar to that observed in nocturnal rodents, suggesting that the same molecular and intercellular pathways underlying acute photic responses are present in both diurnal and nocturnal species. However, after an LP in early subjective day, which induces phase advances in diurnal grass rats, but not in nocturnal rodents, we did not observe any Per1 or Per2 induction in the SCN. This result suggests that in spite of remarkable similarities in the SCN of diurnal and nocturnal rodents, unique mechanisms are involved in mediating the phase shifts of diurnal animals during the subjective day. 相似文献
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S.G. Ferreira R.A. Peliciari-Garcia S.A. Takahashi-Hyodo A.C. Rodrigues F.G. Amaral C.M. Berra S. Bordin R. Curi J. Cipolla-Neto 《Brazilian journal of medical and biological research》2013,46(3):278-286
The antioxidant and free radical scavenger properties of melatonin have been well
described in the literature. In this study, our objective was to determine the
protective effect of the pineal gland hormone against the DNA damage induced by
cyclophosphamide (CP), an anti-tumor agent that is widely applied in clinical
practice. DNA damage was induced in rats by a single intraperitoneal injection
of CP (20 or 50 mg/kg). Animals received melatonin during the dark period for 15
days (1 mg/kg in the drinking water). Rat bone marrow cells were used for the
determination of chromosomal aberrations and of formamidopyrimidine DNA
glycosylase enzyme (Fpg)-sensitive sites by the comet technique and of
Xpf mRNA expression by qRT-PCR. The number (mean ± SE) of
chromosomal aberrations in pinealectomized (PINX) animals treated with melatonin
and CP (2.50 ± 0.50/100 cells) was lower than that obtained for PINX animals
injected with CP (12 ± 1.8/100 cells), thus showing a reduction of 85.8% in the
number of chromosomal aberrations. This melatonin-mediated protection was also
observed when oxidative lesions were analyzed by the Fpg-sensitive assay, both
24 and 48 h after CP administration. The expression of Xpf
mRNA, which is involved in the DNA nucleotide excision repair machinery, was
up-regulated by melatonin. The results indicate that melatonin is able to
protect bone marrow cells by completely blocking CP-induced chromosome
aberrations. Therefore, melatonin administration could be an alternative and
effective treatment during chemotherapy. 相似文献
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Nitat Sookrung Thanyathon Khetsuphan Urai Chaisri Nitaya Indrawattana Onrapak Reamtong Wanpen Chaicumpa Anchalee Tungtrongchitr 《Allergy, asthma & immunology research》2014,6(4):325-332
Purpose
Cockroach (CR) is a common source of indoor allergens, and Per a 1 is a major American CR (Periplaneta americana) allergen; however, several attributes of this protein remain unknown. This study identifies a novel specific B cell epitope and anatomical locations of Per a 1.0105.Methods
Recombinant Per a 1.0105 (rPer a 1.0105) was used as BALB/c mouse immunogen for the production of monoclonal antibodies (MAb). The MAb specific B cell epitope was identified by determining phage mimotopic peptides and pair-wise alignment of the peptides with the rPer a 1.0105 amino acid sequence. Locations of the Per a 1.0105 in P. americana were investigated by immunohistochemical staining.Results
The rPer a 1.0105 (~13 kDa) had 100%, 98% and ≥90% identity to Per a 1.0105, Per a 1.0101, and Cr-PII, respectively. The B-cell epitope of the Per a 1.0105 specific-MAb was located at residues99 QDLLLQLRDKGV110 contained in all 5 Per a 1.01 isoforms and Per a 1.02. The epitope was analogous to the Bla g 1.02 epitope; however, this B-cell epitope was not an IgE inducer. Per a 1.0105 was found in the midgut and intestinal content of American CR but not in the other organs. The amount of the Per a 1 was ~544 ℃g per gram of feces.Conclusions
The novel Per a 1 B-cell epitope described in this study is a useful target for allergen quantification in samples; however, the specific MAb can be used as an allergen detection reagent. The MAb based-affinity resin can be made for allergen purification, and the so-purified protein can serve as a standard and diagnostic allergen as well as a therapeutic vaccine component. The finding that the Per a 1 is contained in the midgut and feces is useful to increase yield and purity when preparing this allergen. 相似文献9.
Bmal1 is one of the central regulators of the clock machinery. Recently, we examined the expression profile of Bmal1 in total leukocytes for a 12h duration during the evening, overnight, and the morning, in subjects with Parkinson's disease (PD) and healthy controls. The results indicate that the expression of Bmal1 is significantly lower in PD patients versus control subjects. However, it is still unclear whether other key regulators of the clock machinery, especially Bmal2, the paralog of Bmal1, are also expressed differently in PD. To address this issue, the expression profiles of Bmal2, Clock, and Dec1 were examined in the same samples using real-time RT-PCR assay. The results show a difference in the expression pattern of Bmal2, but not Clock and Dec1. The expression of Bmal2 is significantly lower in PD at 21:00 h (p=0.005) and 00:00 h (p=0.025). These results together with our previous findings suggest that the molecular clock in total leukocytes is disturbed in PD patients. 相似文献
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In mammals, numerous physiological and behavioural functions are controlled by an endogenous circadian clock located in the suprachiasmatic nuclei (SCN). Within the SCN neurons, clock genes such as Per1 and Per2 interact in a molecular clockwork regulating the expression of hundreds of output genes. Through the timed release of humoral and neuronal signals, the rhythmicity of numerous biological processes, including reproductive behaviour, the oestrus cycle and endocrine parameters is controlled by the SCN. Mutations in Per genes in mice affect a wide array of physiological functions. Interestingly, most of these studies use only male animals, thus neglecting potential gender-specificities in clock function. In an attempt to broaden this perspective we have investigated the impact of Per1 and Per2 mutations on both glucocorticoid (GC) metabolite excretion and locomotor activity in relation to age and oestrus cycle stage of female mice. We show that the Per2 mutation dampens daily GC rhythms in young adult females. While locomotor activity does not vary along the different oestrus stages in Per2 mutant females, oestrus effects on GC excretion and locomotor activity are largely comparable between Per1 mutants and wild-type animals. 20 month-old, acyclic Per1 and wild-type females show reduced GC levels when compared to young adults while aged Per2 mutants retain their normal GC rhythmicity. Correlating with this, onsets of locomotor activity do not change with age in Per2 mutant females. Together, our data highlight specific roles for Per1 and Per2 in both the regulation of locomotor activity and endocrine functions in the female organism. 相似文献
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Tatjana Becker Makiyeh Tohidast-Akrad Susanne Humpeler Danielle M. Gerlag Hans-Peter Kiener Peter Zenz Günter Steiner Cem Ekmekcioglu 《Acta histochemica》2014
Patients with rheumatoid arthritis (RA) show modulated circadian rhythms of inflammatory cytokines and cortisol, which may be associated with a modified expression of clock genes. The expression of major clock genes was previously studied in synovial tissues and fibroblasts of patients with RA and osteoarthritis (OA). We therefore especially aimed to examine the localization of clock genes at the cellular level in synovial tissue. Furthermore we were interested in studying the expression of the D site of albumin promoter (albumin D-box) binding protein (DBP) at the immunohistochemical level in human samples. Methods used include the in situ expression of the clock genes Brain and muscle aryl hydrocarbon receptor nuclear translocator-like 1 (Bmal 1), Circadian Locomotor Output Cycles Kaput (Clock), Period 1 and 2 (Per 1 and Per 2), and DBP was examined by immunohistochemistry in synovial tissues of patients with RA or OA. Additionally, expression profiles of different clock genes were determined over 24 h by real time PCR in synovial fibroblasts (SFs) after a 2 h serum shock or TNF-α. Results show that all clock genes investigated were found to be expressed both in RA and OA synovial tissues. Double staining against cell specific markers revealed that clock proteins were especially seen in macrophages, SFs and B-lymphocytes. Cell counting showed that clock proteins were found in approximately 5–20% of cells. Additionally, preliminary cell culture experiments showed that TNF-α treatment resulted in differential 24 h expression profiles between RA and OA samples and also compared to the results obtained from the serum shock experiments. From our study we conclude that the major clock genes, including DBP, are expressed in samples from RA and OA patients, especially in macrophages and synovial fibroblasts, but also in B-lymphocytes. Preliminary experiments suggest that TNF-α seems to be able to modify clock gene expression in synovial fibroblasts. 相似文献
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Richard P Metz Xiaoyu Qu Brian Laffin David Earnest Weston W Porter 《Developmental dynamics》2006,235(1):263-271
Mouse mammary epithelial cells (HC-11) and mammary tissues were analyzed for developmental changes in circadian clock, cellular proliferation, and differentiation marker genes. Expression of the clock genes Per1 and Bmal1 were elevated in differentiated HC-11 cells, whereas Per2 mRNA levels were higher in undifferentiated cells. This differentiation-dependent profile of clock gene expression was consistent with that observed in mouse mammary glands, as Per1 and Bmal1 mRNA levels were elevated in late pregnant and lactating mammary tissues, whereas Per2 expression was higher in proliferating virgin and early pregnant glands. In both HC-11 cells and mammary glands, elevated Per2 expression was positively correlated with c-Myc and Cyclin D1 mRNA levels, whereas Per1 and Bmal1 expression changed in conjunction with beta-casein mRNA levels. Interestingly, developmental stage had differential effects on rhythms of clock gene expression in the mammary gland. These data suggest that circadian clock genes may play a role in mouse mammary gland development and differentiation. 相似文献
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Haijie Lu Qiqi Chu Guojiang Xie Hao Han Zheng Chen Benhua Xu Zhicao Yue 《International journal of clinical and experimental pathology》2015,8(9):10985-10994
Preoperative neoadjuvant chemoradiation therapy may be useful in patients with operable rectal cancer, but treatment responses are variable. We examined whether expression levels of circadian clock genes could be used as biomarkers to predict treatment response. We retrospectively analyzed clinical data from 250 patients with rectal cancer, treated with neoadjuvant chemoradiation therapy in a single institute between 2011 and 2013. Gene expression analysis (RT-PCR) was performed in tissue samples from 20 patients showing pathological complete regression (pCR) and 20 showing non-pCR. The genes analyzed included six core clock genes (Clock, Per1, Per2, Cry1, Cry2 and Bmal1) and three downstream target genes (Wee1, Chk2 and c-Myc). Patient responses were analyzed through contrast-enhanced pelvic MRI and endorectal ultrasound, and verified by histological assessment. pCR was defined histologically as an absence of tumor cells. Among the 250 included patients, 70.8% showed regression of tumor size, and 18% showed pCR. Clock, Cry2 and Per2 expressions were significantly higher in the pCR group than in the non-pCR group (P<0.05), whereas Per1, Cry1 and Bmal1 expressions did not differ significantly between groups. Among the downstream genes involved in cell cycle regulation, c-Myc showed significantly higher expression in the pCR group (P<0.05), whereas Wee1 and Chk2 expression did not differ significantly between groups. Circadian genes are potential biomarkers for predicting whether a patient with rectal cancer would benefit from neoadjuvant chemoradiation therapy. 相似文献
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Y.G. Tian M. Yue Y. Gu W.W. Gu Y.J. Wang 《Brazilian journal of medical and biological research》2014,47(9):753-758
Tibetan (TB) and Bama (BM) miniature pigs are two popular pig breeds that are used as
experimental animals in China due to their small body size. Here, we analyzed
single-nucleotide polymorphisms (SNPs) in gene fragments that are closely related to
growth traits [growth hormone (GH), growth hormone receptor
(GHR), and insulin-like growth factor
(IGF)-1)] in these pig breeds and a large white
(LW) control pig breed. On the basis of the analysis of 100 BMs, 108 TBs, and 50 LWs,
the polymorphic distribution levels of GH, GHR, and
IGF-1 were significantly different among these three pig breeds.
According to correlation analyses between SNPs and five growth traits - body weight
(BW), body length (BL), withers height (WH), chest circumference (CC), and abdomen
circumference (AC) - three SNP loci in BMs and four SNP loci in TBs significantly
affected growth traits. Three SNP sites in BMs and four SNP sites in TBs
significantly affected growth traits. SNPs located in the GH gene
fragment significantly affected BL and CC at locus 12 and BL at locus 45 in BMs, and
also BW, WH, CC, and AC at locus 45 and WH and CC at locus 93 in TBs. One SNP at
locus 85 in the BM GHR gene fragment significantly affected all
growth traits. All indices were significantly reduced with a mixture of alleles at
locus 85. These results provide more information regarding the genetic background of
these minipig species and indicate useful selection markers for pig breeding
programs. 相似文献
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J. Saturnino-Oliveira M.A. Tomaz T.F. Fonseca G.A. Gaban M. Monteiro-Machado M.A. Strauch B.L. Cons S. Calil-Elias A.M.B. Martinez P.A. Melo 《Brazilian journal of medical and biological research》2012,45(6):488-496
We studied the effect of pulsed ultrasound therapy (UST) and antibothropic polyvalent antivenom (PAV) on the regeneration of mouse extensor digitorum longus muscle following damage by Bothrops jararacussu venom. Animals (Swiss male and female mice weighing 25.0 ± 5.0 g; 5 animals per group) received a perimuscular injection of venom (1 mg/kg) and treatment with UST was started 1 h later (1 min/day, 3 MHz, 0.3 W/cm2, pulsed mode). Three and 28 days after injection, muscles were dissected and processed for light microscopy. The venom caused complete degeneration of muscle fibers. UST alone and combined with PAV (1.0 mL/kg) partially protected these fibers, whereas muscles receiving no treatment showed disorganized fascicules and fibers with reduced diameter. Treatment with UST and PAV decreased the effects of the venom on creatine kinase content and motor activity (approximately 75 and 48%, respectively). Sonication of the venom solution immediately before application decreased the in vivo and ex vivo myotoxic activities (approximately 60 and 50%, respectively). The present data show that UST counteracts some effects of B. jararacussu venom, causing structural and functional improvement of the regenerated muscle after venom injury. 相似文献
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Laurent Castéra Sophie Krieger Antoine Rousselin Angélina Legros Jean-Jacques Baumann Olivia Bruet Baptiste Brault Robin Fouillet Nicolas Goardon Olivier Letac Stéphanie Baert-Desurmont Julie Tinat Odile Bera Catherine Dugast Pascaline Berthet Florence Polycarpe Valérie Layet Agnes Hardouin Thierry Frébourg Dominique Vaur 《European journal of human genetics : EJHG》2014,22(11):1305-1313
To optimize the molecular diagnosis of hereditary breast and ovarian cancer (HBOC), we developed a next-generation sequencing (NGS)-based screening based on the capture of a panel of genes involved, or suspected to be involved in HBOC, on pooling of indexed DNA and on paired-end sequencing in an Illumina GAIIx platform, followed by confirmation by Sanger sequencing or MLPA/QMPSF. The bioinformatic pipeline included CASAVA, NextGENe, CNVseq and Alamut-HT. We validated this procedure by the analysis of 59 patients'' DNAs harbouring SNVs, indels or large genomic rearrangements of BRCA1 or BRCA2. We also conducted a blind study in 168 patients comparing NGS versus Sanger sequencing or MLPA analyses of BRCA1 and BRCA2. All mutations detected by conventional procedures were detected by NGS. We then screened, using three different versions of the capture set, a large series of 708 consecutive patients. We detected in these patients 69 germline deleterious alterations within BRCA1 and BRCA2, and 4 TP53 mutations in 468 patients also tested for this gene. We also found 36 variations inducing either a premature codon stop or a splicing defect among other genes: 5/708 in CHEK2, 3/708 in RAD51C, 1/708 in RAD50, 7/708 in PALB2, 3/708 in MRE11A, 5/708 in ATM, 3/708 in NBS1, 1/708 in CDH1, 3/468 in MSH2, 2/468 in PMS2, 1/708 in BARD1, 1/468 in PMS1 and 1/468 in MLH3. These results demonstrate the efficiency of NGS in performing molecular diagnosis of HBOC. Detection of mutations within other genes than BRCA1 and BRCA2 highlights the genetic heterogeneity of HBOC. 相似文献
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Sang-Jun Na Ji Hyun Lee So Won Kim Dae-Seong Kim Eun Hee Shon Hyung Jun Park Ha Young Shin Seung Min Kim Young-Chul Choi 《Yonsei medical journal》2014,55(3):660-668
Purpose
The underlying cause of myasthenia gravis (MG) is unknown, although it likely involves a genetic component. However, no common genetic variants have been unequivocally linked to autoimmune MG. We sought to identify the genetic variants associated with an increased or decreased risk of developing MG in samples from a Korean Multicenter MG Cohort.Materials and Methods
To determine new genetic targets related to autoimmune MG, a whole genome-based single nucleotide polymorphisms (SNP) analysis was conducted using an Axiom™ Genome-Wide ASI 1 Array, comprising 598375 SNPs and samples from 109 MG patients and 150 neurologically normal controls.Results
In total, 641 SNPs from five case-control associations showed p-values of less than 10-5. From regional analysis, we selected seven candidate genes (RYR3, CACNA1S, SLAMF1, SOX5, FHOD3, GABRB1, and SACS) for further analysis.Conclusion
The present study suggests that a few genetic polymorphisms, such as in RYR3, CACNA1S, and SLAMF1, might be related to autoimmune MG. Our findings also encourage further studies, particularly confirmatory studies with larger samples, to validate and analyze the association between these SNPs and autoimmune MG. 相似文献18.
Cristiane Oliveira Gustavo Jacob Louren?o Regina Aparecida Martinho Sagarra Sophie Fran?oise Mauricette Derchain José Getulio Segalla Carmen Silvia Passos Lima 《Disease markers》2012,33(3):155-159
Background: Exposure of ovarian cells to estrogen, which is detoxified by glutathione S-transferases (GSTs), has been associated with epithelial ovarian cancer (EOC) development.
Objectives: We tested in this study whether the GSTM1, GSTT1 and GSTP1 Ile105Val polymorphisms alter the risk of EOC.
Materials and methods: Genomic DNA from 132 EOC patients and 132 controls was analyzed by polymerase chain reaction and restriction fragment length polymorphism methods. The differences between groups were analyzed by χ2 or Fisher’s exact test.
Results: The frequencies of GSTP1 Ile/Ile (57.6% versus 45.5%, P = 0.03), GSTM1 null plus GSTP1 Ile/Ile (43.5% versus 25.8%; P = 0.03) and GSTM1 null plus GSTT1 null plus GSTP1 Ile/Ile (30.3% versus 7.7%; P = 0.007) genotypes were higher in patients than in controls. Individuals with the respective genotypes had a 1.80 (95% CI: 1.06–3.06), 2.38 (95% CI: 1.08–5.24) and 11.28 (95%CI: 1.95–65.30)-fold increased risks of EOC than those with the remaining genotypes.
Conclusions: Our data present preliminary evidence that GSTM1, GSTT1 and GSTP1 polymorphisms, particularly in combination, constitute important inherited EOC determinants in individuals from Southeastern Brazil. 相似文献
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J.O. Gon?alves A.C.A. Tannuri M.C.M. Coelho I. Bendit U. Tannuri 《Brazilian journal of medical and biological research》2014,47(10):850-857
We previously described a selective bile duct ligation model to elucidate the process
of hepatic fibrogenesis in children with biliary atresia or intrahepatic biliary
stenosis. Using this model, we identified changes in the expression of alpha
smooth muscle actin (α-SMA) both in the obstructed
parenchyma and in the hepatic parenchyma adjacent to the obstruction. However, the
expression profiles of desmin and TGF-β1, molecules
known to be involved in hepatic fibrogenesis, were unchanged when analyzed by
semiquantitative polymerase chain reaction (RT-PCR). Thus, the molecular mechanisms
involved in the modulation of liver fibrosis in this experimental model are not fully
understood. This study aimed to evaluate the molecular changes in an experimental
model of selective bile duct ligation and to compare the gene expression changes
observed in RT-PCR and in real-time quantitative PCR (qRT‐PCR). Twenty-eight Wistar
rats of both sexes and weaning age (21-23 days old) were used. The rats were
separated into groups that were assessed 7 or 60 days after selective biliary duct
ligation. The expression of desmin, α-SMA and
TGF-β1 was examined in tissue from hepatic parenchyma with
biliary obstruction (BO) and in hepatic parenchyma without biliary obstruction (WBO),
using RT-PCR and qRT‐PCR. The results obtained in this study using these two methods
were significantly different. The BO parenchyma had a more severe fibrogenic
reaction, with increased α-SMA and TGF-β1
expression after 7 days. The WBO parenchyma presented a later, fibrotic response,
with increased desmin expression 7 days after surgery and increased
α-SMA 60 days after surgery. The qRT‐PCR technique was more
sensitive to expression changes than the semiquantitative method. 相似文献