Search

Levels of 137Cs and 134Cs resulting from the Chernobyl nuclear accident were studied in 195 birds that winter in two regions of Spain. Only five of the 12 species examined were contaminated. The average values for 137Cs vary between 1.6 and 41 Bq kg-1 fresh. In particular, the contamination for song-thrushes (Turdus philomelos) are compared between the regions of Extremadura and Valencia, 350 km east of Extremadura at the same latitude. The results show that the contamination of birds wintering in Spain decreases from east to west. The whole-body dose commitment for humans consuming these contaminated birds was calculated. The values are well below the established ICRP guideline. [ABSTRACT FROM AUTHOR]

A short axis echocardiographic cut of the heart from the subcostal approach was used to study the atrioventricular junction in 47 infants and children with congenital heart disease and 20 with normal hearts. Examination of the diastolic openings of both atrioventricular valves was able to establish normal developments of the valves and annuli even when this was found in cases of complex congenital heart disease. In 30 patients with atrioventricular septal defects the technique distinguished between a partial defect (when the two atrioventricular valves were linked transseptally) and a complete defect (when there was only one atrioventricular valve). A range of atrioventricular attachments was seen in these patients. Short axis echocardiography from the subcostal approach reliably identifies different forms of atrioventricular septal defects by defining the anatomy of the atrioventricular valves during maximal diastolic expansion. [ABSTRACT FROM PUBLISHER]

Background: HER2 amplification is frequent in DCIS and is associated with poor prognosis features. This study aimed to determine the molecular effects in Ras/Raf/MAK and PI3K/AKT signaling pathway of the HER2 inhibitor lapatinib in patients with HER2 positive DCIS as well as correlation with radiological and pathological response. Patients and Methods: Patients (pts) with HER2 positive DCIS received 1500 mg daily of lapatinib for 4 consecutive weeks prior to surgical resection. Changes in tumor volume were evaluated by MRI. The molecular effects of lapatinib on apoptotic level (TUNEL), cell proliferation (Ki67) and HER2 signaling pathway were determined in pre and post-treatment tumor biopsies. Results: A total of 20 pts were included. Lapatinib was well tolerated with only minor and transient side effects reported. The agent effectively modulated HER2 signaling by affecting cell cycle kinetics through decreasing cytoplasm pERK1 in 11 pts with no change or slight increase activation in 5 pts. Of those 11 pts: eight had parallel inactivation of pHER2, two pts had paradoxical activation of pAkt and three pts had an increase in apoptotic level. In addition, seven pts also presented with decrease in MRI signal intensity and tumor size. Conclusions: Four weeks of lapatinib for patients with HER2-positive DCIS result in significant antiproliferative changes through RAS/MAPK signaling pathway together with a decrease in MRI signal. [ABSTRACT FROM AUTHOR]

Background: Thyroid Hormones (THs) critically impact human cancer. Although endowed with both tumor-promoting and inhibiting effects in different cancer types, excess of THs has been linked to enhanced tumor growth and progression. Breast cancer depends on the interaction between bulk tumor cells and the surrounding microenvironment in which mesenchymal stem cells (MSCs) exert powerful pro-tumorigenic activities., Methods: Primary human MSCs from healthy female donors were co-cultured with DIO2 knock out (D2KO) and wild type (WT) MCF7 breast cancer cells to assess cell growth, migration, invasion and the expression of known epithelial-mesenchymal transition (EMT)- and inflammation-related markers. Furthermore, a surgery-free intraductal delivery model, i.e., the Mouse-INtraDuctal (MIND) injection method, was used as a tool for in vivo characterization of breast tumor formation and progression., Results: In this study, we uncovered a novel role of THs in regulating the tumor-stroma crosstalk. MCF7 cells enhanced the intracellular activation of THs through the TH-activating enzyme, D2, fostering their EMT properties and the dialogue with MSCs. D2 inactivation reduced the invasiveness of MCF7 cells and their responsiveness to the pro-tumorigenic induction via MSCs, both in vivo and in vitro ., Conclusions: Thus, we argue that intracellular activation of THs via D2 is a critical requirement for invasive and metastatic conversion of breast cancer cells, advising the blocking of D2 as a potential therapeutic tool for cancer therapy., (© 2025 The Author(s). Published by IMR Press.)

Obesity exacerbates the risk and aggressiveness of many types of cancer. Adipose tissue (AT) represents a prevalent component of the tumor microenvironment (TME) and contributes to cancer development and progression. Reciprocal communication between cancer and adipose cells leads to the generation of cancer-associated adipocytes (CAAs), which in turn foster tumor invasiveness by producing paracrine metabolites, adipocytokines, and growth factors. Interfering with the crosstalk between CAAs and cancer cells is of key relevance in the prevention of tumor progression. The present study aimed to analyze the contribution of peritumoral AT in renal cell carcinoma (RCC) progression in lean versus overweight or obese patients. By isolating human adipose-derived stromal/stem cells from the three groups of patients and performing conditioned medium studies with RCC cells along with in vivo xenograft experiments, we found that peritumoral adipocytes from the three groups show a distinct expression profile of genes. In particular, ADAM metallopeptidase domain 12 (ADAM12) and cytochrome P450 family 1 subfamily B member 1 (CYP1B1) were found to be upregulated in obesity and their silencing reduced RCC cell invasiveness. In conclusion, high ADAM12 and CYP1B1 expressions in the peritumoral adipocytes boost tumor invasiveness and may serve as an indicator of poor prognosis in RCC., (© 2025 The Author(s). Molecular Oncology published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies.)

Muscle and adipose tissue (AT) are in mutual interaction through the integration of endocrine and biochemical signals, thus regulating whole-body function and physiology. Besides a traditional view of endocrine relationships that imply the release of cytokines and growth factors, it is becoming increasingly clear that a metabolic network involving metabolites as signal molecules also exists between the two tissues. By elevating the number and functionality of mitochondria, a key role in muscle metabolism is played by the master regulator of mitochondrial biogenesis peroxisome-proliferator-activated receptor-γ coactivator-1α (PGC-1α), that induces a fiber type shift from glycolytic to oxidative myofibers. As a consequence, the upregulation of muscle respiratory rate might affect metabolite production and consumption. However, the underlying mechanisms have not yet been fully elucidated. Here, we used a muscle-specific PGC-1α overexpressing mouse model (MCK-PGC-1α) to analyze the metabolite secretion profile of serum and culture medium recovered from MCK-PGC-1α muscle fibers by NMR. We revealed modified levels of different metabolites that might be ascribed to the metabolic activation of the skeletal muscle fibers. Notably, the dysregulated levels of these metabolites affected adipocyte differentiation, as well as the browning process in vitro and in vivo. Interestingly such effect was exacerbated in the subcutaneous WAT, while only barely present in the visceral WAT. Our data confirm a prominent role of PGC-1α as a trigger of mitochondrial function in skeletal muscle and propose a novel function of this master regulator gene in modulating the metabolite production in turn affecting the activation of WAT and its conversion toward the browning., (© 2024 The Author(s). Journal of Cellular Physiology published by Wiley Periodicals LLC.)

Adipose tissue, particularly white adipose tissue (WAT), plays a central role in energy storage and metabolic regulation. Excess WAT, especially visceral fat, is strongly linked to metabolic disorders such as obesity and type 2 diabetes. The browning of WAT, whereby white fat cells acquire characteristics of brown adipose tissue (BAT) with enhanced thermogenic capacity, represents a promising strategy to enhance metabolic health. In this study, we investigated the effects of chronic supplementation with an infusion based on lyophilized, thin nectarines rich in abscisic acid (ABA), named AbaComplex, on promoting browning of WAT and activating BAT in mice. Over 30 days, C57BL/6 mice were treated with the ABA-rich infusion, and various metabolic and molecular parameters were assessed. The results showed that the AbaComplex significantly increased the expression of browning markers, such as UCP1 and PGC1-α, in both visceral and subcutaneous WAT. Additionally, mitochondrial biogenesis and function were enhanced, evidenced by elevated mitochondrial DNA content and activity. The treatment also reduced the weight of WAT (both visceral and subcutaneous) and BAT and significantly improved glucose uptake in WAT via upregulation of GLUT4, suggesting enhanced insulin sensitivity. Overall, the pronounced browning effect in WAT underscores the potential of AbaComplex as a natural approach for combating obesity and improving metabolic health.

The search and development of effective sirtuin small molecule inhibitors (SIRTIs) continues to draw great attention due to their wide range of pharmacological applications. Based on SIRTs' involvement in different biological pathways, their ligands were investigated for many diseases, such as cancer, neurodegenerative disorders, diabetes, cardiovascular diseases and autoimmune diseases. The elucidation of a substantial number of SIRT2-ligand complexes is steering the identification of novel and more selective modulators. Among them, SIRT2 in the presence of the SirReal2 analog series was the most studied. On this basis, we recently reported structure-based analyses leading to the discovery of thiazole-based compounds acting as SIRT2 inhibitors ( T1 , SIRT2 IC 50 = 17.3 µM). Herein, ligand-based approaches followed by molecular docking simulations allowed us to evaluate in silico a novel small series of thiazoles ( 3a - 3d and 5a , 5d ) as putative SIRT2 inhibitors. Results from the computational studies revealed comparable molecular interaction fields (MIFs) and docking positionings of most of these compounds with respect to reference SIRT2Is. Biochemical and biological assays validated this study and pointed to compound 5a (SIRT2 IC 50 = 9.0 µM) as the most interesting SIRT2I that was worthy of further development as an anticancer agent.

Thyroid hormones (THs) are critical regulators of muscle metabolism in both healthy and unhealthy conditions. Acting concurrently as powerful anabolic and catabolic factors, THs are endowed with a vital role in muscle mass maintenance. As a result, thyroid dysfunctions are the leading cause of a wide range of muscle pathologies, globally identified as myopathies. Whether muscle wasting is a common feature in patients with hyperthyroidism and is mainly caused by THs-dependent stimulation of muscle proteolysis, also muscle growth is often associated with hyperthyroid conditions, linked to THs-dependent stimulation of muscle protein synthesis. Noteworthy, also hypothyroid status negatively impacts on muscle physiology, causing muscle weakness and fatigue. Most of these symptoms are due to altered balance between muscle protein synthesis and breakdown. Thus, a comprehensive understanding of THs-dependent skeletal muscle protein turnover might facilitate the management of physical discomfort or weakness in conditions of thyroid disease. Herein, we describe the molecular mechanisms underlying the THs-dependent alteration of skeletal muscle structure and function associated with muscle atrophy and hypertrophy, thus providing new insights for targeted modulation of skeletal muscle dynamics., (© 2024 the author(s), published by De Gruyter, Berlin/Boston.)

Antimicrobial resistance poses a major threat to global health and food security and is primarily driven by antimicrobial use in human and veterinary medicine. Understanding its epidemiology at farm level is crucial for effective control measures. Despite the significant reduction in antibiotic use in conventional livestock production, the swine sector traditionally has a higher level of antibiotic use in veterinary medicine. Consequently, multidrug resistance (MDR) among microbial isolates of swine origin has been relatively frequent. The aim of this study was to assess the presence of multidrug-resistant (MDR) bacteria, enteric pathogens and resistance genes to the main antibiotics used in clinical practice, both within the environment and in animals across pig farms characterized by varying degrees of sanitary status. A total of 274 samples were collected. Of these, 34 samples were collected from the environment (wall swabs, slat swabs and slurry pit), and 240 samples were collected from animals (sows' and piglets' rectal faeces). All samples were analysed for MDR bacteria and enteric pathogens. The study revealed a high frequency of extended-spectrum beta-lactamases (ESBL)-producing Enterobacterales and Campylobacter spp., with ESBL-producing Enterobacterales predominating in high health status farms (environment and animals) and Campylobacter spp. in both high health status and low health status environments. Additionally, a high percentage of methicillin-resistant Staphylococcus aureus (MRSA) was found, mainly in environmental samples from high health status farms, and Clostridioides difficile was distributed ubiquitously among farms and samples. Furthermore, though less frequently, vancomycin-resistant Enterococcus faecium (VRE) was isolated only in high health status farms, and Gram-negative bacilli resistant to carbapenems were isolated only in environmental samples of high health status and low health status farms. This study underscores the importance of surveillance for MDR bacteria in farm animals and their environment, including their waste. Such ecosystems serve as crucial reservoirs of bacteria, requiring national-level surveillance to promote responsible antibiotic use and pandemic control.

Peripheral nerve injuries lead to severe functional impairments and long recovery times, with limited effectiveness and accessibility of current treatments. This has increased interest in natural bioactive compounds, such as ursolic acid (UA). Our study evaluated the effect of an oleolyte rich in UA from white grape pomace (WGPO) on neuronal regeneration in mice with induced sciatic nerve resection, administered concurrently with the induced damage (the WGPO group) and 10 days prior (the PRE-WGPO group). The experiment was monitored at two-time points (4 and 10 days) after injury. After 10 days, the WGPO group demonstrated a reduction in muscle atrophy, evidenced by an increased number and diameter of muscle fibers and a decreased Atrogin-1 and Murf-1 expression relative to the denervated control. It was also observed that 85.7% of neuromuscular junctions (NMJs) were fully innervated, as indicated by the colocalization of α-bungarotoxin and synaptophysin, along with the significant modulation of Oct-6 and S-100. The PRE-WGPO group showed a more beneficial effect on nerve fiber reformation, with a significant increase in myelin protein zero and 95.2% fully innervated NMJs, and a pro-hypertrophic effect in resting non-denervated muscles. Our findings suggest WGPO as a potential treatment for various conditions that require the repair of nerve and muscle injuries.

Sirtuin 6 (SIRT6) has a critical role in cutaneous Squamous Cell Carcinoma (cSCC): SIRT6 silencing in skin SCC cells has pro-differentiating effects and SIRT6 deletion abrogated DMBA-TPA-induced skin tumorigenesis in mice. On the other hand, SIRT6 acts as tumor suppressor in SCC by enhancing glycolysis in tumor propagating cells. Herein, pharmacological modulation of SIRT6 deacetylase activity was investigated in cSCC, with S6 (inhibitor) or MDL-800 (activator). In cSCC cells, S6 recreated the pro-differentiating effects of SIRT6 silencing, as the levels of Keratin 1, Keratin 10 and Loricrin were upregulated compared to controls. Next, the effects of SIRT6 pharmacological modulation were evaluated in a DMBA-TPA-induced skin cancer mouse model. Mice treated with the inhibitor S6 in a preventive approach, i.e. at the beginning of the promotion stage, presented reduced number and size of papillomas, compared to the controls. The epidermal hyperproliferation marker Keratin 6 and the cSCC marker Keratin 8 were less abundant when SIRT6 was inhibited. In S6-treated lesions, the Epithelial-Mesenchymal Transition (EMT) markers Zeb1 and Vimentin were less expressed compared to untreated lesions. In a therapeutic approach, i.e. treatment starting after papilloma appearance, the S6 group presented reduced papillomas (number and size), whereas MDL-800-treated mice displayed an opposite trend. In S6-treated lesions, Keratin 6 and Keratin 8 were less expressed, EMT was less advanced, with a higher E-cadherin/Vimentin ratio, indicating a delayed carcinogenesis when SIRT6 was inhibited. Our results confirm that SIRT6 plays a role in skin carcinogenesis and suggest SIRT6 pharmacological inhibition as a promising strategy in cSCC., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

The global action against coronavirus disease 2019 (COVID-19), caused by SARS-CoV-2 infection, shed light on endothelial dysfunction. Although SARS-CoV-2 primarily affects the pulmonary system, multiple studies have documented pan-vascular involvement in COVID-19. The virus is able to penetrate the endothelial barrier, damaging it directly or indirectly and causing endotheliitis and multi-organ injury. Several mechanisms cooperate to development of endothelial dysfunction, including endothelial cell injury and pyroptosis, hyperinflammation and cytokine storm syndrome, oxidative stress and reduced nitric oxide bioavailability, glycocalyx disruption, hypercoagulability, and thrombosis. After acute-phase infection, some patients reported signs and symptoms of a systemic disorder known as long COVID, in which a broad range of cardiovascular (CV) disorders emerged. To date, the exact pathophysiology of long COVID remains unclear: in addition to the persistence of acute-phase infection mechanisms, specific pathways of CV damage have been postulated, such as persistent viral reservoirs in the heart or an autoimmune response to cardiac antigens through molecular mimicry. The aim of this review is to provide an overview of the main molecular patterns of enduring endothelial activation following SARS-CoV-2 infection and to offer the latest summary of CV complications in long COVID.

Skeletal muscle (SkM) lipid composition plays an essential role in physiological muscle maintenance and exercise performance. Thyroid hormones (THs) regulate muscle formation and fuel energy utilization by modulating carbohydrates and lipid and protein metabolism. The best-known effects of THs in SkM include the promotion of mitochondrial biogenesis, the fiber-type switch from oxidative to glycolytic fibers, and enhanced angiogenesis. To assess the role of THs on the lipidic composition of SkM fibers, we performed lipidomic analyses of SkM cells and tissues, glucose tolerance experiments, and exercise performance tests. Our data demonstrated that TH treatment induces remodeling of the lipid profile and changes the proportion of fatty acids in SkM. In brief, THs significantly reduced the ratio of stearic/oleic acid in the muscle similar to what is induced by physical activity. The increased proportion of unsaturated fatty acids was linked to an improvement in insulin sensitivity and endurance exercise. These findings point to THs as critical endocrine factors affecting exercise performance and indicate that homeostatic maintenance of TH signals, by improving cell permeability and receptor stability at the cell membrane, is crucial for muscle physiology.

The circadian rhythm is regulated by an intrinsic time-tracking system, composed both of a central and a peripheral clock, which influences the cycles of activities and sleep of an individual over 24 h. At the molecular level, the circadian rhythm begins when two basic helix-loop-helix/Per-ARNT-SIM (bHLH-PAS) proteins, BMAL-1 and CLOCK, interact with each other to produce BMAL-1/CLOCK heterodimers in the cytoplasm. The BMAL-1/CLOCK target genes encode for the repressor components of the clock, cryptochrome (Cry1 and Cry2) and the Period proteins (Per1, Per2 and Per3). It has been recently demonstrated that the disruption of circadian rhythm is associated with an increased risk of developing obesity and obesity-related diseases. In addition, it has been demonstrated that the disruption of the circadian rhythm plays a key role in tumorigenesis. Further, an association between the circadian rhythm disruptions and an increased incidence and progression of several types of cancer (e.g., breast, prostate, colorectal and thyroid cancer) has been found. As the perturbation of circadian rhythm has adverse metabolic consequences (e.g., obesity) and at the same time tumor promoter functions, this manuscript has the aim to report how the aberrant circadian rhythms affect the development and prognosis of different types of obesity-related cancers (breast, prostate, colon rectal and thyroid cancer) focusing on both human studies and on molecular aspects., Competing Interests: Conflict of interest statement The authors declare that there are no conflicts of interest., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

There is increasing evidence that thyroid hormones (THs) work in an integrative fashion with androgen receptors (ARs) to regulate gonadal differentiation and reproductive function. Studies reveal that THs have interactions with the AR promoter region and increase AR expression. THs also have a role in the regulation of enzymes involved in the biosynthesis of androgens, such as 5α-reductase, which is essential in the conversion of testosterone into its active form, 5α-dihydrotestosterone. Additionally, the presence of androgen response elements in the promoter regions of TH-related genes, such as deiodinases and TH receptor isoforms, has been identified in some vertebrates, indicating a mutual interaction between THs and ARs. Since the androgen signaling pathway, mediated by ARs, plays a key role in the formation and progression of prostate cancer (PCa), the existence of crosstalk between THs and ARs supports the epidemiologic and experimental evidence indicating a relationship between the high incidence of PCa and hyperthyroidism. This article aims to review the role of androgen-TH crosstalk in PCa and its implication in clinical management. As life expectancy is growing these days, it can increase the number of patients with PCa and the critical relevance of the disease. In order to gain better knowledge about PCa and to improve clinical management, it is essential to get better insight into the key factors related to the formation and progression of this cancer.