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Background and Objectives: Selenium deficiency represents a risk factor for the occurrence of severe diseases, such as acute kidney injury (AKI). Recently, selenoprotein-p1 (SEPP1), a selenium transporter, mainly released by the liver, has emerged as a promising plasmatic biomarker of AKI as a consequence of cardio-surgery operations. The aim of the present study was to investigate, on an in vitro model of hypoxia induced in renal tubular cells, HK-2, the effects of sodium selenite (Na2SeO3) and to evaluate the expression of SEPP1 as a marker of injury. Materials and Methods: HK-2 cells were pre-incubated with 100 nM Na2SeO3 for 24 h, and then, treated for 24 h with CoCl2 (500 µM), a chemical hypoxia inducer. The results were derived from an ROS assay, MTT, and Western blot analysis. Results: The pre-treatment determined an increase in cells’ viability and a reduction in reactive oxygen species (ROS), as shown by MTT and the ROS assay. Moreover, by Western blot an increase in SEPP1 expression was observed after hypoxic injury as after adding sodium selenite. Conclusions: Our preliminary results shed light on the possible role of selenium supplementation as a means to prevent oxidative damage and to increase SEPP1 after acute kidney injury. In our in vitro model, SEPP1 emerges as a promising biomarker of kidney injury, although further studies in vivo are necessary to validate our findings.

Aberrant activation of the RET proto-oncogene is implicated in a plethora of cancers. RET gain-of-function point mutations are driver events in multiple endocrine neoplasia 2 (MEN2) syndrome and in sporadic medullary thyroid cancer, while RET rearrangements are driver events in several non-medullary thyroid cancers. Drugs able to inhibit RET have been used to treat RET-mutated cancers. Multikinase inhibitors were initially used, though they showed modest efficacy and significant toxicity. However, new RET selective inhibitors, such as selpercatinib and pralsetinib, have recently been tested and have shown good efficacy and tolerability, even if no direct comparison is yet available between multikinase and selective inhibitors. The advent of high-throughput technology has identified cancers with rare RET alterations beyond point mutations and fusions, including RET deletions, raising questions about whether these alterations have a functional effect and can be targeted by RET inhibitors. In this mini review, we focus on tumors with RET deletions, including deletions/insertions (indels), and their response to RET inhibitors.

This study presents a comparative life cycle assessment (LCA) of two manufacturing scenarios for a camera housing: Powder Bed Fusion (PBF) using polyamide 12 (PA-12) and Computer Numeric Control (CNC) machining using aluminum, for a cradle-to-gate boundary. The selected impact categories were cumulative energy demand (CED) and global warming potential (GWP). The key findings indicate that the PA-12 PBF part outperformed the aluminum CNC machining one in terms of environmental and energy performance, showing a significant reduction of approximately 90% in equivalent carbon emissions and 84% in cumulative energy demand. Sensitivity analyses revealed that the PBF process was highly sensitive to changes in the proportion of virgin/recycled material for the printing process, variations in the life cycle inventory (LCI) data sources for PA-12 powder production, and changes in the transportation system for imported materials, as is the case for the main input in the process (PA-12 powder). Sensitivity analysis also showed less impact for the PBF camera housing even considering a lifespan of one-fifth that of the aluminum for the impact categories considered. However, it should be noted that this analysis did not include considerations for the usage and end-of-life phases, which may have significant contributions to the overall environmental impact. [ABSTRACT FROM AUTHOR]

The manuscript describes the development of zein nanoparticles containing paclitaxel (PTX) and the bromo-and extra-terminal domain inhibitor (S)-tertbutyl2-(4-(4-chlorophenyl)-2,3,9-trimethyl-6H-thieno(3,2-f)(1,2,4)triazolo(4,3-a)(1,4)diazepin-6-yl)acetate (JQ1) together with their cytotoxicity on triple-negative breast cancer cells. The rationale of this association is that of exploiting different types of cancer cells as targets in order to obtain increased pharmacological activity with respect to that exerted by the single agents. Zein, a protein found in the endosperm of corn, was used as a biomaterial to obtain multidrug carriers characterized by mean sizes of ˂200 nm, a low polydispersity index (0.1–0.2) and a negative surface charge. An entrapment efficiency of ~35% of both the drugs was obtained when 0.3 mg/mL of the active compounds were used during the nanoprecipitation procedure. No adverse phenomena such as sedimentation, macro-aggregation or flocculation occurred when the nanosystems were heated to 37 °C. The multidrug nanoformulation demonstrated significant in vitro cytototoxic activity against MDA-MB-157 and MDA-MB-231 cancer cells by MTT-test and adhesion assay which was stronger than that of the compounds encapsulated as single agents. The results evidence the potential application of zein nanoparticles containing PTX and JQ1 as a novel nanomedicine.

The release of molecules in exosomal cargoes is involved in tumor development and progression. We compared the profiles of exosomal microRNAs released by two thyroid cancer cell lines (TPC-1 and K1) with that of non-tumorigenic thyroid cells (Nthy-ori-3-1), and we explored the network of miRNA–target interaction. After extraction and characterization of exosomes, expression levels of microRNAs were investigated using custom TaqMan Advanced array cards, and compared with those expressed in the total cell extracts. The functional enrichment and network-based analysis of the miRNAs’ targets was also performed. Five microRNAs (miR-21-5p, miR-31-5p, miR-221-3p, miR-222-3p, and let-7i-3p) were significantly deregulated in the exosomes of tumor cells vs. non-tumorigenic cells, and three of them (miR-31-5p, miR-222-3p, and let-7i-3p) in the more aggressive K1 compared to TPC-1 cells. The network analysis of the five miRNAs identified some genes as targets of more than one miRNAs. These findings permitted the identification of exosomal microRNAs secreted by aggressive PTC cells, and indicated that their main targets are regulators of the tumor microenvironment. A deeper analysis of the functional role of the targets of exosomal miRNAs will provide further information on novel targets of molecular treatments for these neoplasms.

The underlying thesis of this study is that the biomass for energy purposes, coming from farms, forestry, timber industry and Short Rotation Forestry (SRF) for energy, can provide various environmental and socio-economic benefits. First of all, the production of forest biomass for energy involves the reduction of CO2 emissions and the improvement of forest functions, such as hydrogeological and biodiversity conservation. Moreover, forest biomass consumption could contribute to the socio-economic development of rural areas, through the restoration of agro-forest activities and technological advances in the bio-energy field. In the last ten years in Italy several companies of the bioenergy industry, attracted by Government subsidies planned to build dedicated power that use biomass as their main fuel. The primary goal of this study is to analyse the local forest wood supply chain. Therefore, field surveys have been done in order to classify the management and the characteristics of the woodchips supply chain (wood sub-product availability, forest enterprises, working systems, forest woodchips quality).

Abstract Background Numerous studies have investigated the role of the dietary factors in the prevention of cognitive decline but the short-term effects of foods choice on cognitive performances in the elderly are poorly explored. Our aim was to investigate the choice of foods among elderly Italian individuals and the association with cognitive function. Methods In this longitudinal study, the participants were 214 individuals aged ≥65 years with a score >20 at the Mini Mental State Examination. The cognitive sub-test of ADAScale was used to detect cognitive decline progression over 12 months. Food choices was measured by a combination of a 24-h recall and a seven-day diet record and Principal Components Analysis. Results The Principal Components Analysis identified four food and four nutrient patterns. MMSE and ADAS-cog score after 1 year were found to be associated with legumes pattern (B = 0.25, p = 0.007; 95% CI 0.07/0.44; and B = −0.10, p = 0.006; CI −0.79/−0.30, respectively). A dietary pattern including plant proteins was independently associated with an improved ADAS-cog after 1 year (B = 0.584, p = 0.04; OR 1.79, CI 0.04–0.42). Conclusions The Principal Components Analysis is useful to investigate the choice of foods and nutrients in the elderly. We demonstrated an association between legumes pattern with cognitive performances.

Background. Obesity has been hypothesized to contribute to the aggressiveness of thyroid cancer through the production of abnormal levels of serum adipokines. Leptin receptor (OB-R) expression has also been documented in papillary thyroid cancer (PTC). Aim. In this translational study, we analyzed in vitro the effects of leptin on the growth and migration of thyroid cancer cells (TPC-1 and K1), the molecular mechanisms underlying leptin’s action, and the influence of prolonged leptin exposure on cell response to a protein kinase inhibitor lenvatinib. The expression levels of OB-R mRNA and protein were also investigated in vivo in a series of aggressive PTCs divided into two groups based on the presence of the BRAF mutation. Results. In TPC-1 and K1 cells, prolonged treatment with leptin (500 ng/ml for 96 h) resulted in a mild increase in the proliferation (about 20% over control only in K1 cells, p

Synonymous mutations continue to be filtered out from most large-scale cancer genome studies, but several lines of evidence suggest they can play driver roles in neoplastic disease. We investigated a case of an aggressive, apparently sporadic medullary thyroid carcinoma (MTC) harboring a somatic RET p.Cys634Arg mutation (a known MTC driver). A germ-line RET substitution (p.Cys630=) had also been found but was considered clinically irrelevant because of its synonymous nature. Next generation sequencing (NGS) of the tumor tissues revealed that the RET mutations were in cis. There was no evidence of gene amplification. Expression analysis found an increase of RET transcript in p.Cys630=;p.Cys634Arg patient compared with that found in 7 MTCs harboring p.Cys634 mutations. Minigene expression assays demonstrated that the presence of the synonymous RET mutation was sufficient to explain the increased RET mRNA level. In silico analyses and RNA immunoprecipitation experiments showed that the p.Cys630 = variant created new exonic splicing enhancer motifs that enhanced SRp55 recruitment to the mutant allele, leading to more efficient maturation of its pre-mRNA and an increased abundance of mature mRNA encoding a constitutively active RET receptor. These findings document a novel mechanism by which synonymous mutations can contribute to cancer progression.

Many reports indicate that the protective action of nutraceuticals in the Mediterranean diet, against metabolic and cardiovascular diseases, can be attributed to the action of polyphenolic components of extra-virgin olive oil (EVOO). Here, we evaluated the protective effects of oleacein, one of the most abundant secoiridoids in EVOO, on the damages/metabolic alterations caused by high-fat diet (HFD) in male C57BL/6JolaHsd mice. After 5 weeks of treatment with 20 mg/kg of oleacein, body weight, glycemia, insulinemia, serum lipids, and histologic examination of liver tissue indicated a protective action of oleacein against abdominal fat accumulation, weight gain, and liver steatosis, with improvement of insulin-dependent glucose and lipid metabolism. Both serum parameters and hepatic histologic examination were altered in mice fed with HFD. By contrast, in the animals that received oleacein, plasma glucose, cholesterol and triglyceride serum levels, and liver histology were similar to controls fed with normocaloric diet. In addition, protein levels of FAS, SREBP-1, and phospho-ERK in liver were positively modulated by oleacein, indicating an improvement in liver insulin sensitivity. In a group of obese mice, treatment with oleacein determined a light, but still significant reduction of the increase in body weight, mainly due to lesser liver steatosis enlargement, associated with reduced levels of SREBP-1 and phospho-ERK and lower levels of total serum cholesterol; in these animals, altered plasma glucose and triglyceride serum levels were not reverted by oleacein. These results indicate that HFD-related hepatic insulin resistance may be partially prevented by oral administration of oleacein, suggesting a protective role of this nutraceutical against diet-dependent metabolic alterations. Additional studies are necessary to check whether oleacein can be used as an adjuvant to improve insulin sensitivity in humans.

Optimal management of patients with thyroid cancer requires the use of sensitive and specific biomarkers. For early diagnosis and effective follow-up, the currently available cytological and serum biomarkers, thyroglobulin and calcitonin, present severe limitations. Research on microRNA expression in thyroid tumors is providing new insights for the development of novel biomarkers that can be used to diagnose thyroid cancer and optimize its management. In this review, we will examine some of the methods commonly used to detect and quantify microRNA in biospecimens from patients with thyroid tumor, as well as the potential applications of these techniques for developing microRNA-based biomarkers for the diagnosis and prognostic evaluation of thyroid cancers.

The ultrasonic inspection of thick-walled welded joint with austenitic weld metal has proven to be a challenge due to its anisotropic microstructure that can promote ultrasonic waves attenuation. This work aimed to optimize the phased array ultrasonic inspection of the thick-walled joint of a 9% Ni steel pipe welded with Ni-based superalloy 625. The development was carried out by CIVA numeric simulation to preview the beam behavior during the inspection of GTAW (Gas Tungsten Arc Welding)/SMAW (Shielded Metal Arc Welding) joint with anisotropic weld metal. To validate the simulation results, experimental tests were performed with a phased array transducer using longitudinal waves on a calibration block withdrawn from the joint. The configuration of low frequency (2.25 MHz), 16 active elements and a scanning angle of 48° ensured the inspection of the entire joint and the computational simulation proved to be essential for the success of the inspection.

PAX8 is a thyroid-specific transcription factor whose expression is dysregulated in thyroid cancer. A recent study using a conditional knock-out mouse model identified 58 putative PAX8 target genes. In the present study, we evaluated the expression of 11 of these genes in normal and tumoral thyroid tissues from patients with papillary thyroid cancer (PTC). ATP1B1, GPC3, KCNIP3, and PRLR transcript levels in tumor tissues were significantly lower in PTCs than in NT, whereas LCN2, LGALS1 and SCD1 expression was upregulated in PTC compared with NT. Principal component analysis of the expression of the most markedly dysregulated PAX8 target genes was able to discriminate between PTC and NT. Immunohistochemistry was used to assess levels of proteins encoded by the two most dyregulated PAX8 target genes, LCN2 and GPC3. Interestingly, GPC3 was detectable in all of the NT samples but none of the PTC samples. Collectively, these findings point to significant PTC-associated dysregulation of several PAX8 target genes, supporting the notion that PAX8-regulated molecular cascades play important roles during thyroid tumorigenesis.

Anaplastic thyroid carcinoma (ATC) is a very aggressive human malignancy, having a marked degree of invasiveness and no features of thyroid differentiation. It is known that either HDAC inhibitors or PARP inhibitors have antiproliferative effects on thyroid cancer cells. Therefore, in this study the possible synergy between the two types of compounds has been investigated. The ATC-derived cell line SW1736 has been treated with the HDAC inhibitor suberoylanilide hydroxamic acid (SAHA) and the PARP inhibitor PJ34, alone or in combination. In terms of cell viability, the combination index value was always lower than 1 at various tested dosages, indicating, therefore, synergy in a wide range of doses for both compounds. Synergy was also observed in induction of apoptosis. In terms of thyroid-specific gene expression, synergy was observed for TSHR mRNA levels but not for NIS, TTF1, TTF2, and PAX8 mRNA levels. Altogether, these data suggest that the combined use of HDAC and PARP inhibitors may be a useful strategy for treatment of ATC.

The high consumption of olive tree products in the Mediterranean diet has been associated with a lower incidence of metabolic disorders and cardiovascular diseases. In particular, the protective effects of olive oil have been attributed to the presence of polyphenols such as oleuropein (Ole) and its derivatives. We have synthesized a peracetylated derivative of Ole (Ac-Ole) which has shown in vitro antioxidant and growth-inhibitory activity higher than the natural molecule. In this study, male C57BL/6JOlaHsd mice were fed with a standard (std), cafeteria (caf) diet, and caf diet supplemented with Ole (0.037 mmol/kg/day) and Ac-Ole (0.025 mmol/kg/day) for 15 weeks. We observed a significant reduction in the caf diet-induced body weight gain and increase of abdominal adipose tissue. Also, Ole and Ac-Ole prevented the development of hepatic steatosis. Finally, Ole and Ac-Ole determined a lower increase of HDL and LDL-cholesterol levels and corrected caf diet-induced elevation of plasma glucose concentrations by improving insulin sensitivity. The observed beneficial properties of Ole and Ac-Ole make these compounds and in particular Ac-Ole promising candidates for a potential pharmaceutic use in metabolic disorders.

Novel therapeutic approaches are required for the less differentiated thyroid cancers which are non-responsive to the current treatment. In this study we tested an innovative formulation of nanoliposomes containing sildenafil citrate or tadalafil, phosphodiesterase-5 inhibitors, on two human thyroid cancer cell lines (TPC-1 and BCPAP). Nanoliposomes were prepared by the thin layer evaporation and extrusion methods, solubilizing the hydrophilic compound sildenafil citrate in the aqueous phase during the hydration step and dissolving the lipophilic tadalafil in the organic phase. Nanoliposomes, made up of 1,2-dipalmitoyl-sn-glycero-3-phosphatidylcholine monohydrate (DPPC), cholesterol, and N-(carbonyl-methoxypolyethylene glycol-2000)-1,2-distearoyl-sn-glycero-3-phosphoethanolamine (DSPE-mPEG2000) (6:3:1 molar ratio), were characterized by a mean diameter of ~100 nm, a very low polydispersity index (~0.1) and a negative surface charge. The drugs did not influence the physico-chemical properties of the systems and were efficiently retained in the colloidal structure. By using cell count and MTT assay, we found a significant reduction of the viability in both cell lines following 24 h treatment with both nanoliposomal-encapsulated drugs, notably greater than the effect of the free drugs. Our findings demonstrate that nanoliposomes increase the antiproliferative activity of phosphodiesterase-5 inhibitors, providing a useful novel formulation for the treatment of thyroid carcinoma.

An increasing body of evidence suggests that epigenetic changes (DNA methylation, remodeling and post-translational modification of chromatin) play important roles in thyroid tumorigenesis, as a result of their effects on tumor-cell differentiation and proliferation. Epigenetic silencing of various thyroid-specific genes has been detected in thyroid tumors. These changes can diminish the tumor's ability to concentrate radioiodine, which dramatically reduces treatment options. Epigenetic changes in tumor-promoting and tumor-suppressor genes also contribute to the dysregulation of thyrocyte growth and other aspects of tumorigenesis, such as apoptosis, motility and invasiveness. We provide a brief overview of the mechanisms underlying epigenetic regulation of gene expression and the current methods used to investigate it. This is followed by a review of the principal epigenetic alterations detected in thyroid cancer cells, epigenetic strategies for treating thyroid cancers and data from preclinical and clinical studies (some still underway) on the use in this setting of demethylating agents and histone deacetylase inhibitors. [ABSTRACT FROM AUTHOR]

Background:Prohibitin (PHB) is a multifunctional protein that is localized in different intracellular sites. PHB may exert different roles in tumorigenesis, having either a permissive action on tumor growth or an oncosuppressor role, depending on the cellular context. The objective of this study was to evaluate PHB expression in normal thyroid tissues, thyroid follicular adenomas (FAs), and papillary thyroid carcinomas (PTCs).Methods:PHB expression was analyzed by immunohistochemistry, Western blot, and quantitative reverse transcription polymerase chain reaction (RT-PCR). Transfections in the BCPAP and TPC-1 thyroid cancer cell lines were used to evaluate the PHB promoter activity.Results:In terms of protein and mRNA levels, normal tissues from patients with serum thyrotropin (TSH) values >0.8 mU/L had PHB levels that were significantly reduced compared to specimens from patients with serum TSH values <0.5 mU/L, suggesting that TSH exerts an inhibitory effect on PHB expression. Consistent with this was the finding that the presence of TSH was associated with low PHB levels in normal FRTL5 thyroid cells. Immunohistochemical analysis showed relatively low and high PHB expression in FAs and PTCs, respectively. PHB mRNA and protein overexpression, as assessed by quantitative RT-PCR and Western blot, was noted only in PTCs bearing the BRAFV600Emutation. Notably, cell transfection experiments suggested that presence of the BRAFV600Emutation may be associated to increase of the PHB promoter activity.Conclusions:PHB is overexpressed in PTCs bearing the BRAFV600Emutation. We postulate that the presence of the BRAFV600Emutation increases PHB promoter activity and therefore potentially mediates effects of this mutation on the behavior of BRAFV600Epositive PTCs. [ABSTRACT FROM AUTHOR]

Background:Thyrogobulin (Tg) assay of material from fine-needle aspiration of neck masses can help distinguish neck masses of thyroid origin from other masses. We describe its utility in a patient with an unusual constellation of findings, a neck lump identified as a lymph node metastasis from a contralateral occult papillary thyroid carcinoma (PTC).Summary:A 56-year-old woman was referred to our center for evaluation of a 15-mm right lateral cervical neck mass which was strongly hypoechoic, not homogenous and contained several microcalcifications. There was no family history of thyroid disease, the patient was euthyroid and was not taking medications for thyroid disorders. On physical examination the thyroid was slightly enlarged and was normal on ultrasound except for a 1 × 3 mm hypoechoic nodule in the middle of the left lobe. Ultrasound-guided fine-needle aspiration biopsy (FNAB) of the right lateral cervical mass was performed with the Tg concentration of the FNAB washout liquid being >300 ng/mL and the cytology showing lymphoid elements mixed with polymorphous epithelial cells with atypical nuclei, suggesting lymph node metastasis from a cancer of epithelial origin. A lymph node metastasis from a papillary thyroid microcarcinoma (micro-PTC) was the presumptive diagnosis with the preoperative staging being Tx N1b. The patient underwent total thyroidectomy and bilateral lymph node dissection. At pathology, the right cervical mass was confirmed as lymph node metastasis of a PTC, and a unifocal micro-PTC was found in the middle left lobe. The patient was readmitted for a therapeutic 131I dose (4810 MBq). At the time of 131I administration, the whole-body scan showed only minimal thyroid bed uptake and serum Tg was <1 ng/mL. She was maintained on l-thyroxine treatment (150 μg/d). Five year later she did not have evidence of recurrent or residual PTC.Conclusions:We describe the first case of contralateral lymph node metastasis from a unifocal micro-PTC identified by the detection of high Tg levels in the wash-out liquid of FNAB. [ABSTRACT FROM AUTHOR]

The ultrasonic inspection of thick-walled welded joint with austenitic weld metal has proven to be a challenge due to its anisotropic microstructure that can promote ultrasonic waves attenuation. This work aimed to optimize the phased array ultrasonic inspection of the thick-walled joint of a 9% Ni steel pipe welded with Ni-based superalloy 625. The development was carried out by CIVA numeric simulation to preview the beam behavior during the inspection of GTAW (Gas Tungsten Arc Welding)/SMAW (Shielded Metal Arc Welding) joint with anisotropic weld metal. To validate the simulation results, experimental tests were performed with a phased array transducer using longitudinal waves on a calibration block withdrawn from the joint. The configuration of low frequency (2.25 MHz), 16 active elements and a scanning angle of 48° ensured the inspection of the entire joint and the computational simulation proved to be essential for the success of the inspection. [ABSTRACT FROM AUTHOR]

Context: Radioiodine uptake is rarely observed in normal non-lactating breast tissue. Investigation of the in vivoregulation of iodide uptake in breast tissue may be useful for the induction of radioiodine uptake in breast cancer tissue for diagnostic and therapeutic purposes. Case reports: We report the cases of two post-menopausal women who underwent radioiodine therapy for papillary thyroid carcinoma and in whom breast uptake of radioiodine on post-therapy whole body scan (WBS) was observed. Methods and results: In both patients, elevated serum prolactin levels (123 ng/mL in patient 1 and 48 ng/mL in patient 2) were documented at the time when radioiodine uptake in the breast was observed. The hyperprolactinemia was due to prolonged treatment with the anti-dopaminergic neuroleptic risperidone in Case 1, and chronic renal failure in Case 2. When prolactin levels were normalized (by withdrawal of risperidone in Case 1 and with cabergoline in Case 2), breast tissue uptake was no longer evident on WBS. Conclusion: These cases provide the first documented correlation between serum levels of endogenous prolactin and radioiodine uptake by involuted breast tissue in humans. [ABSTRACT FROM AUTHOR]