miRNA regulation of cytotoxic effects in mouse Sertoli cells exposed to nonylphenol

Background: It is known that some environmental chemicals affect the human endocrine system. The harmful effects of endocrine disrupting chemical (EDC) nonylphenol (NP) have been studied since the 1980s. It is known that NP adversely affects physiological functions by mimicking the natural hormone 17 beta-estradiol. In the present study, we analyzed the expression of miRNAs and their target genes in mouse Sertoli TM4 cells to better understand the regulatory roles of miRNAs on Sertoli cells after NP exposure. Methods: Mouse TM4 Sertoli cells were treated with NP for 3 or 24 h, and global gene and miRNA expression were analyzed using Agilent mouse whole genome and mouse miRNA v13 arrays. Results: We identified genes that were > 2-fold differentially expressed in NP-treated cells and control cells (P < 0.05) and analyzed their functions through Gene Ontology analysis. We also identified miRNAs that were differentially expressed in NP-treated and control cells. Of the 186 miRNAs the expression of which differed between NP-treated and control cells, 59 and 147 miRNAs exhibited 1.3-fold increased or decreased expression at 3 and 24 h, respectively. Network analysis of deregulated miRNAs suggested that Ppara may regulate the expression of certain miRNAs, including miR-378, miR-125a-3p miR-20a, miR-203, and miR-101a, after exposure to NP. Additionally, comprehensive analysis of predicted target genes for miRNAs showed that the expression of genes with roles in cell proliferation, the cell cycle, and cell death were regulated by miRNA in NP-treated TM4 cells. Levels of expression of the miRNAs miR-135a* and miR-199a-5p were validated by qRT-PCR. Finally, miR-135a* target gene analysis suggests that the generation of reactive oxygen species (ROS) following exposure to NP exposure may be mediated by miR-135a* through regulation of the Wnt/beta-catenin signaling pathway. Conclusions: Collectively, these data help to determine NP's actions on mouse TM4 Sertoli cells and increase our understanding of the molecular mechanisms underlying the adverse effects of xenoestrogens on the reproductive system.This work was supported an Eco-Technopia 21 project grant from the Ministry of Environment (Development of Decision Method of Chromosomal Abnormality in Reproductive System by Toxic Substances at the Korea Institute of Toxicology)

A Study on the Flora of 15 Islands in the Western Sea of Jeollanamdo Province, Korea

AbstractThis study aims to investigate the flora of 15 islands in Yeonggwang, Shinan, and Mokpo of the Jeollanamdo province and the distribution of major plants in order to use the results as fundamental data for studies on plants in islands. Field surveys were performed 25 times from 2004 to 2010 to investigate the flora in these regions. A total of 793 taxa including 123 families, 421 genera, 695 species, 2 subspeices, 88 varieties, and 8 forms was found. Korean endemic plants including Hepatica insularis and Galium koreanum were 6 taxa. 25 taxa of rare plants including Trachomitum lancifolium, Daphne kiusiana, and Centranthera cochinchinensis var. lutea were confirmed 120 taxa floristic special plant species were confirmed; 11 taxa of the fifth class, four taxa of the fourth class, 28 taxa of the third class. 78 taxa of naturalized plants were confirmed

Biochemical characterization of a recombinant Japanese encephalitis virus RNA-dependent RNA polymerase

<p>Abstract</p> <p>Background</p> <p>Japanese encephalitis virus (JEV) NS5 is a viral nonstructural protein that carries both methyltransferase and RNA-dependent RNA polymerase (RdRp) domains. It is a key component of the viral RNA replicase complex that presumably includes other viral nonstructural and cellular proteins. The biochemical properties of JEV NS5 have not been characterized due to the lack of a robust <it>in vitro </it>RdRp assay system, and the molecular mechanisms for the initiation of RNA synthesis by JEV NS5 remain to be elucidated.</p> <p>Results</p> <p>To characterize the biochemical properties of JEV RdRp, we expressed in <it>Escherichia coli </it>and purified an enzymatically active full-length recombinant JEV NS5 protein with a hexahistidine tag at the N-terminus. The purified NS5 protein, but not the mutant NS5 protein with an Ala substitution at the first Asp of the RdRp-conserved GDD motif, exhibited template- and primer-dependent RNA synthesis activity using a poly(A) RNA template. The NS5 protein was able to use both plus- and minus-strand 3'-untranslated regions of the JEV genome as templates in the absence of a primer, with the latter RNA being a better template. Analysis of the RNA synthesis initiation site using the 3'-end 83 nucleotides of the JEV genome as a minimal RNA template revealed that the NS5 protein specifically initiates RNA synthesis from an internal site, U₈₁, at the two nucleotides upstream of the 3'-end of the template.</p> <p>Conclusion</p> <p>As a first step toward the understanding of the molecular mechanisms for JEV RNA replication and ultimately for the <it>in vitro </it>reconstitution of viral RNA replicase complex, we for the first time established an <it>in vitro </it>JEV RdRp assay system with a functional full-length recombinant JEV NS5 protein and characterized the mechanisms of RNA synthesis from nonviral and viral RNA templates. The full-length recombinant JEV NS5 will be useful for the elucidation of the structure-function relationship of this enzyme and for the development of anti-JEV agents.</p

Clonal and genetic structure of Iris odaesanensis and Iris rossii (Iridaceae): insights of the Baekdudaegan Mountains as a glacial refugium for boreal and temperate plants

The main Korean mountain range that stretches from north to south (the Baekdudaegan) has been suggested to harbor an important glacial refugium for boreal and temperate plant species. Under this scenario, we expect high levels of within-population genetic variation and low or moderate degree of among-population differentiation within these species. To test this hypothesis, we examined clonal diversity and levels of allozyme diversity in the boreal Iris odaesanensis and in its temperate congener Iris rossii. In addition, we compiled data on boreal and temperate species whose distribution in the Korean Peninsula is mostly centered in the Baekdudaegan to determine if there is a common pattern. We found lower clonal diversity in I. odaesanensis compared to I. rossii. Both studied species maintained high levels of genetic variation as well as a moderate genetic differentiation (%P = 52.5 and 47.5, A = 1.70 and 1.58, H e = 0.158 and 0.150, and F ST = 0.196 and 0.189 for I. odaesanensis and I. rossii, respectively), in line with what occurs for the species distributed on the Baekdudaegan (n = 14, %P = 46.7, A = 1.73, H e = 0.161, and F ST = 0.190). This study strongly suggests that the Baekdudaegan may have acted as a refugium for boreal and temperate species, in a similar way to the southern Appalachians in the eastern United States

Nitric oxide overcomes Cd and Cu toxicity in in vitro-grown tobacco plants through increasing contents and activities of rubisco and rubisco activase

AbstractToxic heavy metals such as cadmium (Cd) and copper (Cu) are global problems that are a growing threat to the environment. Despite some heavy metals are required for plant growth and development, others are considered toxic elements and do not play any known physiological role in plant cells. Elevated doses of Cd or Cu cause toxicity in plants and generate damages due to the stress condition and eventually cause a significant reduction in quantity and quality of crop plants. The nitric oxide (NO) donor sodium nitroprusside (SNP) is reported to alleviate the toxicity of some heavy metals like Cd and Cu. In the current study, the role of NO in alleviating stresses of Cd and Cu was investigated in in vitro-grown tobacco (Nicotiana tabacum) Based on plant growth, total chlorophyll contents, contents and activities of rubisco and rubisco activase. According to the results of this study, the growth and total chlorophyll contents of Cd/Cu stressed plants were hugely decreased in the absence of SNP, while the supplementation of SNP resulted in a significant increase of both fresh weight and total chlorophyll contents. Remarkable reductions of Rubisco and rubisco activase contents and activities were observed in Cd and Cu-induced plants. SNP supplementation showed the highest contents and activities of rubisco and rubisco activase compared to the control and Cu/Cd-stressed plants. Taken together, our findings suggest that SNP could play a protective role in regulation of plant responses to abiotic stresses such as Cd and Cu by enhancing Rubisco and Rubisco activase

A Neonate Diagnosed with Megalencephaly-Capillary Malformation-Polymicrogyria Syndrome with Mutation

Megalencephaly-capillary malformation-polymicrogyria syndrome (MCAP) is a rare genetic disorder characterized by megalencephaly, polymicrogyria, body overgrowth, and cutaneous capillary malformations. It has been reported recently that MCAP is related to a somatic mosaic mutation in the phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA) gene. We report a case of hemimegalencephaly with polymicrogyria and cutaneous capillary malformations diagnosed by genetic evaluation of MCAP in the neonatal period. The PIK3CA mutation [c.1635G>T (p. Glu545Asp)] was determined by Sanger sequencing. The patient was treated with a ventriculoperitoneal shunt for progressive hydrocephalus. Because of the dynamic, progressive clinical manifestations and tumor-prone traits of MCAP, early diagnosis is important. Moreover, since the phosphoinositide 3-kinase (PI3K)-specific inhibitor, a targeted therapy for the PI3K/AKT/mTOR signaling pathway is emerging as a new therapy, early genetic diagnosis is becoming increasingly important

Good Glycemic Control Is Associated with Better Survival in Diabetic Patients on Peritoneal Dialysis: A Prospective Observational Study

BACKGROUND: The effect of glycemic control after starting peritoneal dialysis (PD) on the survival of diabetic PD patients has largely been unexplored, especially in Asian population. METHODS: We conducted a prospective observational study, in which 140 incident PD patients with diabetes were recruited. Patients were divided into tertiles according to the means of quarterly HbA1C levels measured during the first year after starting PD. We examined the association between HbA1C and all-cause mortality using Cox proportional hazards models. RESULTS: The mean age was 58.7 years, 59.3% were male, and the mean follow-up duration was 3.5 years (range 0.4-9.5 years). The mean HbA1C levels were 6.3%, 7.1%, and 8.5% in the 1(st), 2(nd), and 3(rd) tertiles, respectively. Compared to the 1(st) tertile, the all-cause mortality rates were higher in the 2(nd) [hazard ratio (HR), 4.16; 95% confidence interval (CI), 0.91-18.94; p = 0.065] and significantly higher in the 3(rd) (HR, 13.16; 95% CI, 2.67-64.92; p = 0.002) tertiles (p for trend = 0.005), after adjusting for confounding factors. Cardiovascular mortality, however, did not differ significantly among the tertiles (p for trend = 0.682). In contrast, non-cardiovascular deaths, most of which were caused by infection, were more frequent in the 2(nd) (HR, 7.67; 95% CI, 0.68-86.37; p = 0.099) and the 3(rd) (HR, 51.24; 95% CI, 3.85-681.35; p = 0.003) tertiles than the 1(st) tertile (p for trend = 0.007). CONCLUSIONS: Poor glycemic control is associated with high mortality rates in diabetic PD patients, suggesting that better glycemic control may improve the outcomes of these patients

Dilated Cardiomyopathy in a 2 Month-Old Infant: A Severe Form of Hypocalcemia With Vitamin D Deficient Rickets

Dilated cardiomyopathy, which mostly has an idiopathic etiology or is caused by genetic inheritance or infection, can cause irreversible congestive heart failure. Hypocalcemia is a rare etiology of reversible dilated cardiomyopathy. Here we report the case of a two-month-old girl with congestive heart failure who was diagnosed as having dilated cardiomyopathy secondary to hypocalcemia. After calcium and vitamin D replacement therapy, the patient showed a rapid reduction in hypocalcemic tetany and a rapid recovery of left ventricular function. The cause of the hypocalcemia was vitamin D deficient rickets. She was exclusively breast-fed as an infant, and her mother had a vitamin D deficiency and was diagnosed with osteomalacia

Enhancement of angiogenic and vasculogenic potential of endothelial progenitor cells by haptoglobin

AbstractEndothelial progenitor cells (EPCs) were transfected with the haptoglobin (Hp) gene to investigate the effect of Hp on cell function. Hp potentiated the gene expression of various pro-angiogenic factors in the EPCs. The Hp-modified EPCs also increased in vitro tube formation on Matrigel compared with control cells. In hindlimb ischaemia models, Hp–EPCs showed a greater ability for improving blood perfusion and recovery from ischaemic injury. These results indicate that Hp improves EPC function in neovasculogenesis, which suggests that ex vivo modification of EPCs with the Hp gene can be applied to the treatment of vascular damage

Long-term cardiovascular outcomes of gestational diabetes mellitus: a prospective UK Biobank study

Background Previous studies showed that gestational diabetes mellitus (GDM) can be a risk factor for subsequent atherosclerotic cardiovascular disease. However, there is a paucity of information regarding diverse cardiovascular outcomes in elderly women after GDM. In the current study, we examined whether women with a history of GDM have an increased risk for long-term overall cardiovascular outcomes. Methods Among the UK participants, we included 219,330 women aged 40 to 69 years who reported at least one live birth. The new incidence of diverse cardiovascular outcomes was compared according to GDM history by multivariable Cox proportional hazard models. In addition, causal mediation analysis was performed to examine the contribution of well-known risk factors to observed risk. Results After enrollment, 13,094 women (6.0%) developed new overall cardiovascular outcomes. Women with GDM history had an increased risk for overall cardiovascular outcomes [adjusted HR (aHR) 1.36 (95% CI 1.18–1.55)], including coronary artery disease [aHR 1.31 (1.08–1.59)], myocardial infarction [aHR 1.65 (1.27–2.15)], ischemic stroke [aHR 1.68 (1.18–2.39)], peripheral artery disease [aHR 1.69 (1.14–2.51)], heart failure [aHR 1.41 (1.06–1.87)], mitral regurgitation [aHR 2.25 (1.51–3.34)], and atrial fibrillation/flutter [aHR 1.47 (1.18–1.84)], after adjustment for age, race, BMI, smoking, early menopause, hysterectomy, prevalent disease, and medication. In mediation analysis, overt diabetes explained 23%, hypertension explained 11%, and dyslipidemia explained 10% of the association between GDM and overall cardiovascular outcome. Conclusions GDM was associated with more diverse cardiovascular outcomes than previously considered, and conventional risk factors such as diabetes, hypertension, and dyslipidemia partially contributed to this relationship.This work was supported by NIGMS R01 GM138597 and by National Research Foundation of Korea (NRF) grant funded by the Korea government (MSIT) (No.NRF-2021R1F1A1046707, NRF-2022R1F1A1072279)