Glutathione S-transferase M1 and T1 null genotype frequency in chronic myeloid leukaemia.

Polymorphisms associated with genes coding for glutathione S-transferase enzymes are known to influence metabolism of different carcinogens and have been associated with incidence of various types of cancer. We have determined the GST M1 and GST T1 'null' genotype frequency in 81 patients with chronic myeloid leukaemia (CML) and 123 racially and geographically matched control individuals by multiplex polymerase chain reaction (PCR). GST M1 null genotype frequencies in CML and controls were 28.4% and 27.7%, respectively. GST T1 null genotype frequencies in CML and controls were 19.8% and 7.3%, respectively. The GST T1 null genotype frequency in CML patients is significantly different from that in controls (odds ratio (OR) 3.12, 95% confidence interval (CI) 1.3-7.45, P=0.008).     

Role of Vitamin D and Vitamin D Receptor in Oral Lichen Planus: A Systematic Review

BackgroundOral lichen planus (OLP) is known to be a chronic inflammatory disease associated with various other systemic disorders. Studies have shown that vitamin D deficiency can be involved in the pathogenesis of lichen planus. The aim of this study was to investigate the role of vitamin D and vitamin D receptor in OLPMethodsIn this review study, all English and Persian articles were searched by relevant keywords from the Google scholar, PubMed, science direct, Cochrane, Scopus and Sid databases until January 2020.ResultsFrom the 16 articles obtained after reviewing the abstracts, finally 14 appropriate articles were included in this study.ConclusionAccording to the results of the studies, vitamin D deficiency may be associated with an increased risk of OLP lesions.     

Cataract surgery in patients with ocular surface disease: An update in clinical diagnosis and treatment

In this article we review essentials of diagnosis and management of ocular surface disease in patients who undergo cataract surgery. It is clearly shown that dry eye disease worsens following the cataract surgery in patients with prior history of ocular surface disease, Also new cases of dry eye might appear. Current strategies for the timely diagnosis and proper management of dry eye syndrome in the face of cataract surgery patients are mainly emphasized. To achieve the best outcome in cataract surgery, a healthy ocular surface is crucial. While ocular surface preparation is indispensable in patients with established ocular surface disease, it is also helpful in those with minimal signs or symptoms of surface disease. The current approach begins with early diagnosis and drastic management of ocular surface disease before cataract surgery using a stepwise regimen customized to each patient and disease severity. These measures are continued throughout and after the surgery.     

COX-2 compensation in the uterus of COX-1 deficient mice during the pre-implantation period

Prostaglandins (PGs) produced by cyclooxygenase (COX) participate in many aspects of female reproduction. The two isoforms of cyclooxygenase, COX-1 and COX-2, have distinct expression patterns in the mouse uterus during the peri-implantation period and suggest their independent contribution to uterine PGs. Using wild type and COX-1(−/−) mice, we examined the role of COX-1-derived PGs on day 4 of pregnancy, when its expression is maximal. Uterine vascular permeability was measured by ¹²⁵I-labeled bovine serum albumin (BSA) uptake, and PG content was measured by gas chromatography–mass spectrometry. Vascular permeability and PG concentrations were reduced in COX-1(−/−) mice, but by less than the expected amount. After ovariectomy, uterine vascular permeability declined in both groups, but returned to baseline in wild type and was exaggerated in COX-1(−/−) females after treatment with ovarian steroids. Most importantly, COX-1(−/−) uteri displayed COX-2 expression on the morning of day 4, when COX-2 is normally absent. This hybridization pattern resembles the native expression of COX-1, and may partially offset the loss of COX-1-derived PGs. These data indicate that COX-1-derived PGs are important during uterine preparation for implantation, and that COX-2 compensation occurs in the absence of COX-1.     

Antisense c-myc effects on preimplantation mouse embryo development.

Antisense DNA inhibition of gene expression was explored as an approach toward elucidating mechanisms regulating development of preimplantation mammalian embryos. Specifically, a role for the c-myc protooncogene was examined. Detection of c-myc mRNA and immunoreactive nuclear c-myc protein in preimplantation mouse embryos at the eight-cell/morula and blastocyst stages suggested that this DNA-binding protein could be important during early embryo-genesis. The effects of c-myc oligodeoxyribonucleotides (oligos) on the in vitro development of two-cell mouse embryos were examined. Embryos cultured in medium containing an unmodified (phosphodiester) antisense c-myc oligo complementary to the translation initiation codon and spanning the first seven codons exhibited a dose-dependent arrest at the eight-cell/morula stage. At lower concentrations (7.5 microM) this inhibitory effect was specific to the antisense oligo and did not occur with the sense-strand complement or with duplexes of the antisense and sense oligos. However, at 4-fold higher concentrations of DNA (30 microM), all unmodified c-myc oligos were embryotoxic, causing embryos to arrest at the two-cell to four-cell stages. In contrast, almost all (98%) two-cell embryos cultured with a modified (chimeric phosphorothioate/phosphodiester) antisense c-myc oligo (7.5 microM) exhibited developmental arrest at the eight-cell/morula stage, whereas no developmental arrest occurred following incubation with high concentrations of the modified sense complement (30 microM). Culture of freshly recovered eight-cell embryos with antisense c-myc led to the absence of c-myc protein but no change in epidermal growth factor receptor in those embryos that developed a blastocoel. These effects on c-myc were specific for the antisense oligo. These results suggest that c-myc function becomes particularly critical for preimplantation mouse embryos at the eight-cell/morula stage of development and establish that antisense DNA can be successfully applied as an approach toward elucidating the roles of specific genes in preimplantation mammalian embryo development.     

Immunolocalization of estrogen receptor protein in the mouse blastocyst during normal and delayed implantation.

We previously showed that estrogen receptor (ER) mRNA is present in preimplantation mouse embryos. The apparent synthesis of ER mRNA by the blastocyst at the time of implantation when estrogen is required was of special interest. A demonstration of the presence of ER protein would support the idea that estrogen can act directly on the embryo. The mouse embryo at the blastocyst stage is differentiated into two cell types, the trophectoderm and the inner cell mass. To determine whether ER mRNA is translated into ER protein and its cell-specific distribution, immunocytochemical analyses were performed in mouse blastocysts. ER protein was detected in all cell types of the normal, dormant, or activated blastocyst. To trace the fate of ER in these cell types, immunocytochemistry was performed in implanting blastocysts and early egg cylinder stage embryos developed in culture. Again, ER was detected in all cells of the implanting blastocyst. At the early egg cylinder stage, continued expression of ER was observed in cells derived from the inner cell mass or the trophoblast. In trophoblast giant cells, ER was concentrated in small regions of the nucleus, possibly the nucleoli, which was similar to that observed in dormant and activated blastocysts. The embryonic expression of ER at such early stages in a broad array of cells suggests that ER may have a general role during early development.     

Estrogen is a critical determinant that specifies the duration of the window of uterine receptivity for implantation

Many underlying causes of human infertility have been overcome by using in vitro fertilization (IVF) and embryo transfer (ET) techniques. Nevertheless, implantation rates in IVF programs remain low despite the transfer of apparently healthy embryos. This suggests that there are problems with the differentiation of the uterus to the receptive state in response to the ovarian hormones estrogen and progesterone. The molecular basis of this receptive state when the uterine environment is conducive to blastocyst acceptance and implantation remains poorly understood. Normally, the "window" of uterine receptivity lasts for a limited time. Using ETs and the progesterone-treated delayed-implantation model in mice, we demonstrate here that levels of estrogen within a very narrow range determine the duration of the window of uterine receptivity. Although estrogen at different physiological concentrations can initiate implantation, we find that the window of uterine receptivity remains open for an extended period at lower estrogen levels but rapidly closes at higher levels. The uterine refractoriness that follows the receptive state at high estrogen levels is accompanied by aberrant uterine expression of implantation-related genes. These results suggest that careful regulation of estrogen levels is one of the important factors for improvement of female fertility in IVFET programs.     

Generation of stable ARE- driven reporter system for monitoring oxidative stress

Background

NF-E2-related factor2 (Nrf2)-antioxidant response element (ARE) signaling pathway is the major defensive mechanism against oxidative stress and is up regulated by specific antioxidants and oxidants to comprise the chemoptotective response. Detection of ARE-activating compounds helps to develop new drugs and identify/quantify the tension range of the oxidants.Important reasons promoting this work are high throughput, rapid and inexpensive experiments relative to the in vitro studies for ARE-Nrf2 pathway monitoring of chemicals and environmental samples.

Methods

In this study hepatoma Huh7 reporter cell line was generated which contains a luciferase gene under the control of an ARE. This is the first example of ARE construct containing one copy of extended consensus response element. The cells were treated with hydroquinone (HQ) and p-benzoquinone (BQ) (oxidative stress inducers) and the antioxidant, curcumin.

Results

The luciferase activity was induced in a concentration-dependent manner in a concentration range of 1–2 μM for BQ and HQ. Curcumin was also validated as an ARE inducer in concentration above 10 μM. In addition, this reporter cell line provides a rapid detection as early as 4 h to respond to the ARE inducers.

Conclusion

It is a powerful tool for the sensitive and selective screening of chemicals, drugs and environmental samples for their antioxidant and oxidant activities.