Effect of valproic acid on miRNAs affecting histone deacetylase in a model of anaplastic thyroid cancer

Background

Thyroid cancer is the most common malignant tumor of the endocrine system seen in the thyroid gland. More than 90% of thyroid cancers comprise papillary thyroid cancer (PTC) and follicular thyroid cancer (FTC). Although anaplastic thyroid carcinoma (ATC) accounts for less than 2% of thyroid cancer. But patients’ lifespan after diagnosis is about 6 months. Surgical interventions, radioactive iodine use, and chemotherapy are not sufficient in the treatment of ATC, so alternative therapies are needed.

Methods and results

The WST-1 assay test was performed to evaluate the anti-proliferative effects of Valproic acid (VPA). Also, the effect of VPA on miRNAs affecting histone deacetylase was determined by Quantitative RT-PCR. In the SW1736 cell line, IC50 dose for VPA was found 1.6 mg/ml. In our study, the level of oncogenic genes expression in cells treated with VPA, including miR-184, miR-222-5p, miR-124-3p, and miR-328-3p, decreased. Also, the expression of tumor inhibitory genes including miR-323-5p, miR-182-5p, miR-138-5p, miR-217, miR-15a-5p, miR-29b-3p, miR-324-5p and miR-101-5p increased significantly.

Conclusions

VPA can ad-just countless gene expression patterns, including microRNAs (miRNAs), by targeting histone deacetylase (HDAC). However, further studies are required for more accurate results.

     

Riboregulators in kidney development and function

The discovery of microRNAs has brought in another level of intricacy in gene regulation. These microRNAs are small non-coding RNAs that have dual ability to act as repressors or inducers of gene activity. MicroRNAs have been implicated in a wide spectrum of biological processes and their expressions have been found to be dysregulated in several diseases. Recently, microRNAs have emerged as a new area of interest in renal development and pathology. MicroRNA profilings have revealed a number of microRNAs that are specific to the kidney or restricted to certain regions of the organ suggesting possible exclusive roles therein. Recently, knockout studies have shown that these riboregulators are critical for normal renal growth and functional renal system. Individual microRNAs have also been identified in renal disease models including kidney cancers, diabetic nephropathy and polycystic kidney disease. Several mechanisms of modulating microRNA activity have also been introduced in recent years. Further progress in the understanding of microRNA activity, identification of microRNA signatures in different states as well as advancement of microRNA manipulation techniques will be valuable for kidney research.     

Protein thiolation index (PTI) as a biomarker of oxidative stress

Several biomarkers of oxidative stress have been proposed and used in clinical research but so far unreliable or, at least, controversial results have been obtained. Given the high susceptibility of sulfhydryl groups to oxidation, we here suggest the use of a protein thiolation index (PTI), i.e., the molar ratio between the sum of all low molecular mass thiols bound to plasma proteins (forming, as a whole, S-thiolated proteins) and protein free cysteinyl residues, as a suitable biomarker of oxidative stress. While titration of free thiols can be performed by a simple spectrophotometric procedure, accurate quantification of S-thiolated proteins is problematic and current methods require, in most cases, application of time-consuming chromatographic techniques, making their application to large-scale clinical studies difficult. Here we report a new spectrophotometric method which relies on the specific determination of low molecular mass thiols released from S-thiolated proteins after dithiothreitol reduction. These amino acids can be titrated by conjugation with ninhydrin which, reacting with primary and secondary amine groups, yields a deep blue-purple color, which can be spectrophotometrically revealed. PTI showed an age dependency with a near linear increase during aging in humans. In addition, PTI was significantly higher in patients suffering from alkaptonuria with respect to healthy controls, suggesting that increased prooxidant conditions occur in the blood of these subjects.     

Epidemiology of soil transmitted helminths and risk analysis of hookworm infections in the community: Results from the DeWorm3 Trial in southern India

Since 2015, India has coordinated the largest school-based deworming program globally, targeting soil-transmitted helminths (STH) in ~250 million children aged 1 to 19 years twice yearly. Despite substantial progress in reduction of morbidity associated with STH, reinfection rates in endemic communities remain high. We conducted a community based parasitological survey in Tamil Nadu as part of the DeWorm3 Project—a cluster-randomised trial evaluating the feasibility of interrupting STH transmission at three geographically distinct sites in Africa and Asia—allowing the estimation of STH prevalence and analysis of associated factors. In India, following a comprehensive census, enumerating 140,932 individuals in 36,536 households along with geospatial mapping of households, an age-stratified sample of individuals was recruited into a longitudinal monitoring cohort (December 2017-February 2018) to be followed for five years. At enrolment, a total of 6089 consenting individuals across 40 study clusters provided a single adequate stool sample for analysis using the Kato-Katz method, as well as answering a questionnaire covering individual and household level factors. The unweighted STH prevalence was 17.0% (95% confidence interval [95%CI]: 16.0–17.9%), increasing to 21.4% when weighted by age and cluster size. Hookworm was the predominant species, with a weighted infection prevalence of 21.0%, the majority of which (92.9%) were light intensity infections. Factors associated with hookworm infection were modelled using mixed-effects multilevel logistic regression for presence of infection and mixed-effects negative binomial regression for intensity. The prevalence of both Ascaris lumbricoides and Trichuris trichiura infections were rare (<1%) and risk factors were therefore not assessed. Increasing age (multivariable odds ratio [mOR] 21.4, 95%CI: 12.3–37.2, p<0.001 for adult age-groups versus pre-school children) and higher vegetation were associated with an increased odds of hookworm infection, whereas recent deworming (mOR 0.3, 95%CI: 0.2–0.5, p<0.001) and belonging to households with higher socioeconomic status (mOR 0.3, 95%CI: 0.2–0.5, p<0.001) and higher education level of the household head (mOR 0.4, 95%CI: 0.3–0.6, p<0.001) were associated with lower odds of hookworm infection in the multilevel model. The same factors were associated with intensity of infection, with the use of improved sanitation facilities also correlated to lower infection intensities (multivariable infection intensity ratio [mIIR] 0.6, 95%CI: 0.4–0.9, p<0.016). Our findings suggest that a community-based approach is required to address the high hookworm burden in adults in this setting. Socioeconomic, education and sanitation improvements alongside mass drug administration would likely accelerate the drive to elimination in these communities.Trial Registration: {"type":"clinical-trial","attrs":{"text":"NCT03014167","term_id":"NCT03014167"}}NCT03014167.     

Anchusella, a new genus ofBoraginaceae from the Central-Eastern Mediterranean

The two closely related speciesLycopsis variegata andAnchusa cretica, formerly placed inAnchusa subg.Rivinia, were compared with the type species ofLycopsis andAnchusa, on the basis of a set of macro and microcharacters. The presence of only two fertile stamens as well as other peculiar characters in flower structure, androecium, gynoecium, pollen and fruit, supports the institution of the new genusAnchusella, consisting ofA. variegata andA. cretica. Karyological and eco-chorological aspects are consistent with morphological data in pointing to the autonomy of this genus, which appears characterized by autapomorphic, advanced traits.