A multi-omics approach to understand the influence of polyphenols in ovarian cancer for precision nutrition: a mini-review.

The impact of polyphenols in ovarian cancer is widely studied observing gene expression, epigenetic alterations, and molecular mechanisms based on new 'omics' technologies. Therefore, the combination of omics technologies with the use of phenolic compounds may represent a promising approach to precision nutrition in cancer. This article provides an updated review involving the current applications of high-throughput technologies in ovarian cancer, the role of dietary polyphenols and their mechanistic effects in ovarian cancer, and the current status and challenges of precision nutrition and their relationship with big data. High-throughput technologies in different omics science can provide relevant information from different facets for identifying biomarkers for diagnosis, prognosis, and selection of specific therapies for personalized treatment. Furthermore, the field of omics sciences can provide a better understanding of the role of polyphenols and their function as signaling molecules in the prevention and treatment of ovarian cancer. Although we observed an increase in the number of investigations, there are several approaches to data acquisition, analysis, and integration that still need to be improved, and the standardization of these practices still needs to be implemented in clinical trials.

Mitochondrial Reactive Oxygen Species Participate in Signaling Triggered by Heme in Macrophages and upon Hemolysis.

Hemolysis causes an increase of intravascular heme, oxidative damage, and inflammation in which macrophages play a critical role. In these cells, heme can act as a prototypical damage-associated molecular pattern, inducing TLR4-dependent cytokine production through the MyD88 pathway, independently of TRIF. Heme promotes reactive oxygen species (ROS) generation independently of TLR4. ROS and TNF production contribute to heme-induced necroptosis and inflammasome activation; however, the role of ROS in proinflammatory signaling and cytokine production remains unknown. In this study, we demonstrate that heme activates at least three signaling pathways that contribute to a robust MAPK phosphorylation and cytokine expression in mouse macrophages. Although heme did not induce a detectable Myddosome formation, the TLR4/MyD88 axis was important for phosphorylation of p38 and secretion of cytokines. ROS generation and spleen tyrosine kinase (Syk) activation induced by heme were critical for most proinflammatory signaling pathways, as the antioxidant N-acetyl-l-cysteine and a Syk inhibitor differentially blocked heme-induced ROS, MAPK phosphorylation, and cytokine production in macrophages. Early generated mitochondrial ROS induced by heme was Syk dependent, selectively promoted the phosphorylation of ERK1/2 without affecting JNK or p38, and contributed to CXCL1 and TNF production. Finally, lethality caused by sterile hemolysis in mice required TLR4, TNFR1, and mitochondrial ROS, supporting the rationale to target these pathways to mitigate tissue damage of hemolytic disorders.

According to Revised EWGSOP Sarcopenia Consensus Cut-Off Points, Low Physical Function Is Associated With Nutritional Status and Quality of Life in Maintenance Hemodialysis Patients.

OBJECTIVE: The aim of this study is to assess the association of nutritional status and quality of life with low physical function, according to the revised European Working Group on Sarcopenia in Older People (EWGSOP) - sarcopenia consensus cut-offs in maintenance hemodialysis patients. DESIGN AND METHODS: This is a cross-sectional study including patients on maintenance hemodialysis. Participants were submitted to a single evaluation of physical function, nutritional status, and quality of life. Handgrip strength, Short Physical Performance Battery (SPPB), sit-to-stand test, and gait speed were performed to evaluate physical function. Cut-offs proposed by the revised EWGSOP consensus were considered. Malnutrition Inflammation Score was used to assess nutritional status. Quality of life was assessed by the 36-Item Short Form Health Survey. RESULTS: Seventy-seven patients were enrolled, 64.9% male, mean age 55 ± 14 years. According to the cut-offs proposed by the most recent EWGSOP consensus, 55.8% of patients presented SPPB <8, 48.1% gait speed test ≤0.8 m/seconds, sit-to-stand test >15 seconds, and 39.0% handgrip strength <27 kg and <16 kg for men and women, respectively. Malnutrition Inflammation Score was significantly associated with all physical function parameters, except gait speed, in receiver operating characteristic curve and logistic regression. The 36-Item Short Form Health Survey domains or component summary were associated with SSPB, gait speed, and handgrip strength in logistic regression. CONCLUSION: Poor nutritional status and quality of life are associated with low physical function (according to the cut-offs proposed by EWGSOP) in hemodialysis patients.

Inflammatory, synaptic, motor, and behavioral alterations induced by gestational sepsis on the offspring at different stages of life.

BACKGROUND: The term sepsis is used to designate a systemic condition of infection and inflammation associated with hemodynamic changes that result in organic dysfunction. Gestational sepsis can impair the development of the central nervous system and may promote permanent behavior alterations in the offspring. The aim of our work was to evaluate the effects of maternal sepsis on inflammatory cytokine levels and synaptic proteins in the hippocampus, neocortex, frontal cortex, and cerebellum of neonatal, young, and adult mice. Additionally, we analyzed the motor development, behavioral features, and cognitive impairments in neonatal, young and adult offspring. METHODS: Pregnant mice at the 14th embryonic day (E14) were intratracheally instilled with saline 0.9% solution (control group) or Klebsiella spp. (3 × 108 CFU) (sepsis group) and started on meropenem after 5 h. The offspring was sacrificed at postnatal day (P) 2, P8, P30, and P60 and samples of liver, lung, and brain were collected for TNF-α, IL-1ß, and IL-6 measurements by ELISA. Synaptophysin, PSD95, and ß-tubulin levels were analyzed by Western blot. Motor tests were performed at all analyzed ages and behavioral assessments were performed in offspring at P30 and P60. RESULTS: Gestational sepsis induces a systemic pro-inflammatory response in neonates at P2 and P8 characterized by an increase in cytokine levels. Maternal sepsis induced systemic downregulation of pro-inflammatory cytokines, while in the hippocampus, neocortex, frontal cortex, and cerebellum an inflammatory response was detected. These changes in the brain immunity were accompanied by a reduction of synaptophysin and PSD95 levels in the hippocampus, neocortex, frontal cortex, and cerebellum, in all ages. Behavioral tests demonstrated motor impairment in neonates, and depressive-like behavior, fear-conditioned memory, and learning impairments in animals at P30 and P60, while spatial memory abilities were affected only at P60, indicating that gestational sepsis not only induces an inflammatory response in neonatal mouse brains, but also affects neurodevelopment, and leads to a plethora of behavioral alterations and cognitive impairments in the offspring. CONCLUSION: These data suggest that maternal sepsis may be causatively related to the development of depression, learning, and memory impairments in the litter.

Pharmacokinetic properties of tramadol and M1 metabolite in Northeast Brazilian donkeys (Equus asinus).

There is currently little information available on the pharmacokinetics and pharmacodynamics of the analgesic opioid tramadol when used in the veterinary medicine of domestic species. In this study, we aimed to determine the pharmacokinetics of tramadol and its active metabolite M1 following intravenous administration of 2 (T2) and 4 (T4) mg/kg to Northeast Brazilian donkeys. Tramadol and M1 plasma levels were quantified using a validated liquid chromatography-tandem mass spectrometry method. We found that plasma levels of tramadol and M1 were higher than those reported as clinically meaningful in humans for at least 3 hr. However, the pharmacokinetic parameter calculation corrected by dose analysis identified no proportional increase with dose for the AUC of tramadol (T2: 2,663 ± 1,827 vs. T4: 2,964 ± 1,038 ng*h/ml) and M1 (T2: 378 ± 237 vs. T4: 345 ± 142 ng*h/ml). This finding appears to be attributable to a significant increase in clearance and a reduction in the terminal half-life of tramadol. The frequency of adverse effects observed at the higher dose indicates that 2 mg/kg administered intravenously would be suitable for donkeys. Clinical studies are required to determine the implications of these observations regarding the pharmacodynamic response to tramadol in Northeast Brazilian donkeys.

Antiangiogenic therapy with Nintedanib affects hypoxia, angiogenesis and apoptosis in the ventral prostate of TRAMP animals.

The antiangiogenic therapy for prostate cancer with Nintedanib, a potent inhibitor of important growth factor receptors, has been proven to delay tumor progression and arrest tumor growth; thus, the aim herein is to evaluate Nintedanib effects on tumor cells, besides angiogenesis and apoptosis processes, metalloproteinases and hypoxia factor in an animal model. Nintedanib promoted growth inhibition and cell death in a dose-dependent manner, showing no tumor selectivity. Transgenic Adenocarcinoma of the Mouse Prostate (TRAMP) were treated with Nintedanib (10 mg/kg/day) in different stages of tumor development and the ventral prostate was examined for protein levels by means of immunohistochemistry and Western blotting and apoptosis evaluation. In vitro antiproliferative activity of Nintedanib was also assessed in nine human tumor cell lines. Early Nintedanib treatment has shown decreased levels of FGF-2, VEGFR-1, MMP-9 and HIF-1α and a significantly increased apoptosis of epithelial cells. Furthermore, late Nintedanib treatment decreased FGF-2, VEGFR-1 and FGFR-3 levels. Importantly, even after treatment discontinuation, treated animals displayed a significant decrease in VEGFR-1 as well as MMP-9. Although Nintedanib treatment in late stages of tumor growth has shown some good results, it is noteworthy that the drug presents the best tissue response when administered in the early stages of disease development. Nintedanib treatment has shown to be a promising approach for prostate cancer therapy, especially in the early stages of the disease, interfering in different carcinogenesis progression pathways.

Mechanisms of cadmium-stress avoidance by selenium in tomato plants.

Cadmium (Cd) is probably the most damaging metal to plant species; with a long biological half-life, it can be taken up by plants, disrupting the cell homeostasis and triggering several metabolic pathways. Selenium (Se) improves plant defence systems against stressful conditions, but the biochemical antioxidant responses to Cd stress in tomato plants is poorly understood. To further address the relationship of Cd-stress responses with Se mineral uptake, Cd and Se concentration, proline content, MDA and H2O2 production, and the activity of SOD, APX, CAT and GR enzymes were analyzed in Micro-Tom (MT) plants submitted to 0.5 mM Cd. The results revealed different responses according to Se combination and Cd application. For instance, roots and leaves of MT plants treated with Se exhibited an increase in dry mass and nutritional status, exhibited lower proline content and higher APX and GR activities when compared with plants with no Se application. Plants submitted to 0.5 mM Cd, irrespective of Se exposure, exhibited lower proline, MDA and H2O2 content and higher SOD, CAT and GR activities. Selenium may improve tolerance against Cd, which allowed MT plants exhibited less oxidative damage to the cell, even under elevated Cd accumulation in their tissues. The results suggest that Se application is an efficient management technique to alleviate the deleterious effects of Cd-stress, enhancing the nutritional value and activity of ROS-scavenging enzymes in tomato plants.

Impacts of warming and water deficit on antioxidant responses in Panicum maximum Jacq.

Agricultural activities are affected by many biotic and abiotic stresses associated with global climate change. Predicting the response of plants to abiotic stress under future climate scenarios requires an understanding of plant biochemical performance in simulated stress conditions. In this study, the antioxidant response of Panicum maximum Jacq. cv. Mombaça exposed to warming (+2°C above ambient temperature) (eT), water deficit (wS) and the combination eT + wS was analysed under field conditions using a temperature free-air-controlled enhancement facility. Warming was applied during the entire growth period. Data were collected at 13, 19 and 37 days after the start of the water deficit treatment (DAT) and at two sampling times (6:00 and 12:00 h). A significant decrease in chlorophyll was observed under the wS treatment, but an increment in total chlorophyll was observed in eT + wS, particularly at 19 DAT. Significant increase in H2 O2 content, malondialdehyde and protein oxidation was observed in the wS treatment at noon of the third sampling. In the combined wS + eT stress treatment, the activity of the enzymatic antioxidant system increased, particularly of superoxide dismutase (SOD; EC 1.15.1.1) and ascorbate peroxidase (APX; EC 1.11.1.11). The chlorophyll fluorescence images showed that the photochemical performance was not significantly affected by the treatments. In conclusion, under simulated future warming and water stress conditions, the photosystem II (PSII) activity of P. maximum acclimated to moderate warming and a water-stressed environment associated with a relatively favourable antioxidant response, particularly in the activity of APX and SOD.

New insights into cadmium stressful-conditions: Role of ethylene on selenium-mediated antioxidant enzymes.

Cadmium (Cd) contamination has generated an environmental problem worldwide, leading to harmful effects on human health and damages to plant metabolism. Selenium (Se) is non essential for plants, however it can improve plant growth and reduce the adverse effects of abiotic stress. In addition, ethylene may interplay the positive effects of Se in plants. In order to investigate the role of ethylene in Se-modulation of antioxidant defence system in response to Cd-stress, we tested the hormonal mutant Epinastic (epi) with a subset of constitutive activation of the ethylene response and Micro-Tom (MT) plants. For this purpose, Se mineral uptake, Cd and Se concentrations, pigments, malondialdeyde (MDA) and hydrogen peroxide (H2O2) contents, ethylene production, glutathione (GSH) compound, and superoxide dismutase (SOD), ascorbate peroxidase (APX), catalase (CAT), glutathione reductase (GR) and glutathione peroxidase (GSH-Px) activities were analysed in MT and epi plants submitted to 0.5 mM CdCl2 and 1 µM of selenate or selenite. MT plants treated with both Se forms increased growth in the presence or not of 0.5 mM CdCl2, but not change epi growth. Both Se forms reduced Cd uptake in MT plants and cause reverse effect in epi plants. P, Mg, S, K and Zn uptake increased in epi plants with Se application, irrespective to Cd exposure. Chlorophylls and carotenoids contents decreased in both genotypes under Cd exposure, in contrast to what was observed in epi leaves in the presence of Se. When antioxidant enzymes activities were concerned, Se application increased Mn-SOD, Fe-SOD and APX activities. In the presence of Cd, MT and epi plants exhibited decreased SOD activity and increased CAT, APX and GR activities. MT and epi plants with Se supply exhibited increased APX and GR activities in the presence of Cd. Overall, these results suggest that ethylene may be involved in Se induced-defence responses, that triggers a positive response of the antioxidant system and improve growth under Cd stress. These results showed integrative roles of ethylene and Se in regulating the cell responses to stressful-conditions and, the cross-tolerance to stress could be used to manipulate ethylene regulated gene expression to induce heavy metal tolerance.

Effects of egg exposure to atrazine and/or glyphosate on bone development in Podocnemis unifilis (Testudines, Podocnemididae).

This study was designed to investigate skeletal changes in Podocnemis unifilis embryos derived from artificially incubated eggs exposed to different concentrations of atrazine, glyphosate or atrazine and glyphosate mixture. Forty-two eggs were randomly allocated to one of seven trays containing vermiculite treated distilled water (control group) or the following solutions: 2 or 200 µg L-1 of atrazine (groups A1 and A2 respectively); 65 or 6500 µg L-1 of glyphosate (groups G1 and G2 respectively); 2 µg L-1 and 65 µg L-1 or 200 µg L-1 and 6500 µg L-1 of atrazine and glyphosate mixture (groups AG1 and AG2 respectively). Three eggs per tray were randomly collected on days 30 and 50 of the incubation period. Embryos were submitted to soft tissue diaphanization and stained with Alizarin red S or Alcian blue for morphological analysis of bone and cartilage tissues; histological analysis was performed to confirm ossification changes. Findings were compared between groups. Morphological changes were limited to sclerotic ring features and number of ribs. Malformations rates differed significantly (p < 0.05) between embryos in the control and treated groups A2, AG1 and AG2. Concurrent exposure to atrazine and glyphosate did not affect the presence or severity of embryonic malformations and was not associated with appendicular skeleton changes in P. unifilis embryos. However, further studies focusing on the axial skeleton with particular emphasis on rib abnormalities are warranted.

Hemolysis-induced lethality involves inflammasome activation by heme.

The increase of extracellular heme is a hallmark of hemolysis or extensive cell damage. Heme has prooxidant, cytotoxic, and inflammatory effects, playing a central role in the pathogenesis of malaria, sepsis, and sickle cell disease. However, the mechanisms by which heme is sensed by innate immune cells contributing to these diseases are not fully characterized. We found that heme, but not porphyrins without iron, activated LPS-primed macrophages promoting the processing of IL-1ß dependent on nucleotide-binding domain and leucine rich repeat containing family, pyrin domain containing 3 (NLRP3). The activation of NLRP3 by heme required spleen tyrosine kinase, NADPH oxidase-2, mitochondrial reactive oxygen species, and K(+) efflux, whereas it was independent of heme internalization, lysosomal damage, ATP release, the purinergic receptor P2X7, and cell death. Importantly, our results indicated the participation of macrophages, NLRP3 inflammasome components, and IL-1R in the lethality caused by sterile hemolysis. Thus, understanding the molecular pathways affected by heme in innate immune cells might prove useful to identify new therapeutic targets for diseases that have heme release.

Macrophages as target cells for Mayaro virus infection: involvement of reactive oxygen species in the inflammatory response during virus replication.

Alphaviruses among the viruses that cause arthritis, consisting in a public health problem worldwide by causing localized outbreaks, as well as large epidemics in humans. Interestingly, while the Old World alphaviruses are arthritogenic, the New World alphaviruses cause encephalitis. One exception is Mayaro virus (MAYV), which circulates exclusively in South America but causes arthralgia and is phylogenetically related to the Old World alphaviruses. Although MAYV-induced arthritis in humans is well documented, the molecular and cellular factors that contribute to its pathogenesis are completely unknown. In this study, we demonstrated for the first time that macrophages, key players in arthritis development, are target cells for MAYV infection, which leads to cell death through apoptosis. We showed that MAYV replication in macrophage induced the expression of TNF, a cytokine that would contribute to pathogenesis of MAYV fever, since TNF promotes an inflammatory profile characteristic of arthritis. We also found a significant increase in the production of reactive oxygen species (ROS) at early times of infection, which coincides with the peak of virus replication and precedes TNF secretion. Treatment of the cells with antioxidant agents just after infection completely abolished TNF secretion, indicating an involvement of ROS in inflammation induced during MAYV infection.

Cadmium stress antioxidant responses and root-to-shoot communication in grafted tomato plants.

Many aspects related to ROS modulation of signaling networks and biological processes that control stress responses still remain unanswered. For this purpose, the grafting technique may be a powerful tool to investigate stress signaling and specific responses between plant organs during stress. In order to gain new insights on the modulation of antioxidant stress responses mechanisms, gas-exchange measurements, lipid peroxidation, H2O2 content, proline, superoxide dismutase (SOD), catalase (CAT), glutathione reductase (GR), ascorbate peroxidase (APX) and guaiacol peroxidase (GPOX) were analyzed in Micro-Tom grafted plants submitted to cadmium (Cd). The results observed revealed that higher amounts of Cd accumulated mainly in the roots and rootstocks when compared to leaves and scions. Macronutrients uptake (Ca, S, P and Mg) decreased in non-grafted plants, but differed among plant parts in all grafted plants. The results showed that the accumulation of proline observed in scions of grafted plants could be associated to the lower MDA contents in the scions of grafted plants. In the presence of Cd, non-grafted plants displayed increased CAT, GR, GPOX and APX activities for both tissues, whilst grafted plants revealed distinct trends that clearly indicate signaling responses from the rootstocks, allowing sufficient time to activate defense mechanisms in shoot. The information available concerning plants subjected to grafting can provide a better understanding of the mechanisms of Cd detoxification involving root-to-shoot signaling, opening new possibilities on strategies which can be used to manipulate heavy metal tolerance, since antioxidant systems are directly involved in such mechanism.

Heme induces programmed necrosis on macrophages through autocrine TNF and ROS production.

Diseases that cause hemolysis or myonecrosis lead to the leakage of large amounts of heme proteins. Free heme has proinflammatory and cytotoxic effects. Heme induces TLR4-dependent production of tumor necrosis factor (TNF), whereas heme cytotoxicity has been attributed to its ability to intercalate into cell membranes and cause oxidative stress. We show that heme caused early macrophage death characterized by the loss of plasma membrane integrity and morphologic features resembling necrosis. Heme-induced cell death required TNFR1 and TLR4/MyD88-dependent TNF production. Addition of TNF to Tlr4(-/-) or to Myd88(-/-) macrophages restored heme-induced cell death. The use of necrostatin-1, a selective inhibitor of receptor-interacting protein 1 (RIP1, also known as RIPK1), or cells deficient in Rip1 or Rip3 revealed a critical role for RIP proteins in heme-induced cell death. Serum, antioxidants, iron chelation, or inhibition of c-Jun N-terminal kinase (JNK) ameliorated heme-induced oxidative burst and blocked macrophage cell death. Macrophages from heme oxygenase-1 deficient mice (Hmox1(-/-)) had increased oxidative stress and were more sensitive to heme. Taken together, these results revealed that heme induces macrophage necrosis through 2 synergistic mechanisms: TLR4/Myd88-dependent expression of TNF and TLR4-independent generation of ROS.

Epigenetic Regulation of DLK1-DIO3 Region in Thyroid Carcinoma.

Non-coding RNAs (ncRNAs) have emerged as pivotal regulators in cellular biology, dispelling their former perception as 'junk transcripts'. Notably, the DLK1-DIO3 region harbors numerous ncRNAs, including long non-coding RNAs (lncRNAs) and over 50 microRNA genes. While papillary thyroid cancer showcases a pervasive decrease in DLK1-DIO3-derived ncRNA expression, the precise mechanisms driving this alteration remain elusive. We hypothesized that epigenetic alterations underlie shifts in ncRNA expression during thyroid cancer initiation and progression. This study aimed to elucidate the epigenetic mechanisms governing DLK1-DIO3 region expression in this malignancy. We have combined the analysis of DNA methylation by bisulfite sequencing together with that of histone modifications through ChIP-qPCR to gain insights into the epigenetic contribution to thyroid cancer in cell lines representing malignancies with different genetic backgrounds. Our findings characterize the region's epigenetic signature in thyroid cancer, uncovering distinctive DNA methylation patterns, particularly within CpG islands on the lncRNA MEG3-DMR, which potentially account for its downregulation in tumors. Pharmacological intervention targeting DNA methylation combined with histone deacetylation restored ncRNA expression. These results contribute to the understanding of the epigenetic mechanisms controlling the DLK1-DIO3 region in thyroid cancer, highlighting the combined role of DNA methylation and histone marks in regulating the locus' expression.

DLK1-DIO3 region as a source of tumor suppressor miRNAs in papillary thyroid carcinoma.

BACKGROUND: In previous studies, we demonstrated the downregulation of several miRNAs from the DLK1-DIO3 genomic region in papillary thyroid carcinoma (PTC). Due to the large number of miRNAs within this region, the individual contribution of these molecules to PTC development and progression remains unclear. OBJECTIVE: In this study, we aimed to clarify the contribution of DLK1-DIO3-derived miRNAs to PTC. METHODS: We used different computational approaches and in vitro resources to assess the biological processes and signaling pathways potentially modulated by these miRNAs. RESULTS: Our analysis suggests that, out of more than 100 mature miRNAs originated from the DLK1-DIO3 region, a set of 12 miRNAs accounts for most of the impact on PTC development and progression, cooperating to modulate distinct cancer-relevant biological processes, such as cell migration, extracellular matrix remodeling, and signal transduction. The restoration of the expression of one of these miRNAs (miR-485-5p) in a BRAFT199A-positive PTC cell line impaired proliferation and migration, suppressing the expression of GAB2 and RAC1, validated miR-485-5p targets. CONCLUSIONS: Overall, our results shed light on the role of the DLK1-DIO3 region, which harbors promising tumor suppressor miRNAs in thyroid cancer, and open prospects for the functional exploration of these miRNAs as therapeutic targets for PTC.

Bacterial genomes recovered from litter's metagenomes in Amazonian Dark Earths.

Here, we report 27 metagenome-assembled bacterial genomes (MAGs) from litter samples of a secondary forest located in Brazil over an Amazonian Dark Earth pool. The data set includes members from the phyla Pseudomonadata (14 MAGs), Actinomycetota (7 MAGs), Bacteroidota (4 MAGs), Bacillota (1 MAG), and Bdellovibrionota (1 MAG).

MiR-495-3p regulates cell migration and invasion in papillary thyroid carcinoma.

Background: Papillary thyroid carcinoma (PTC) is the most prevalent histotype of thyroid cancer and the presence of BRAFV600E mutation in these tumors is related to the malignancy and prognosis of the disease. In recent years attention has been focused on the role of microRNAs in the biology of PTC cells, especially in their role in the modulation of pathways related to tumorigenesis. DLK1-DIO3-derived miRNAs have been shown to play important roles in tumor context and are globally downregulated in PTC. Methods: Based on a previous in silico target prediction and gene enrichment analysis, we identified miR-495-3p as the candidate with the highest tumor suppressor potential role in PTC among DLK1-DIO3-derived miRNAs. We used bioinformatics and an in vitro model of miR-495-3p overexpression to further understand the influence of this molecule on the tumorigenic processes of PTC. Results: Overexpression of miR-495-3p impaired cell migration and invasion of PTC cells harboring the BRAFV600E mutation and affected the expression of targets predicted in the bioinformatic analysis, such as TGFB2, EREG and CCND1. Conclusion: Overall, our results indicate that the loss of miR-495-3p expression during PTC development might play an important role in its progression.

Prescribing errors in a Brazilian teaching hospital: Causes and underlying factors from the perspective of junior doctors.

INTRODUCTION: In university hospital settings most prescriptions are written by junior doctors, who are more likely to make prescribing errors than experienced doctors. Prescribing errors can cause serious harm to patients and drug harm differs among low, middle and high-income countries. In Brazil, few studies have investigated the causes of these errors. Our aim was to explore medication prescribing errors in a teaching hospital, their causes, and underlying factors from the perspective of junior doctors. METHOD: Qualitative, descriptive and exploratory study that used a semi-structured individual interview with questions related to the planning and execution of prescriptions. It was conducted with 34 junior doctors who graduated from twelve different universities located in six Brazilian states. The data were analyzed according to the Reason's Accident Causation model. RESULTS: Among the 105 errors reported, medication omission stood out. Most errors resulted from unsafe acts during execution, followed by mistakes and violations. Many errors reached the patients; unsafe acts of rule violations and slips accounted for the majority. Work overload and time pressure were the most frequently reported causes. Difficulties faced by the National Health System and organizational problems were identified as latent conditions. CONCLUSION: The results reaffirm international findings about the severity of prescribing errors and the multifactorial aspect of their causes. Unlike other studies, we found a large number of violations, which, from the interviewees' perspectives, are related to socioeconomic and cultural patterns. The violations were not seen or mentioned by the interviewees as violations, but as difficulties in accomplishing their tasks on time. Knowing these patterns and perspectives is important for implementing strategies to improve the safety of both patients and professionals involved in the medication process. It is suggested that the exploitation culture of junior doctors' work be discouraged and that their training be improved and prioritized.

Variation of modulation and expression of biomarkers associated with inflammation in bariatric surgery patients: A systematic review and meta-analysis.

BACKGROUND: Bariatric surgery is an effective intervention that causes a series of metabolic changes related to inflammatory processes; however, the variation of biomarkers related to these processes is not entirely understood. Our objective was to investigate the variation of modulation and expression of biomarkers associated with inflammation in patients who underwent bariatric surgery. METHODS: We searched the MEDLINE (via PubMed), EMBASE (via Elsevier), Cochrane Central Register of Controlled Trials, Latin American and Caribbean Literature on Health Sciences (via virtual health library), Cumulative Index to Nursing and Allied Health Literature (via EBSCO), Web of Science core collection, and Scopus (via Elsevier) databases, and the gray literature was examined from inception to January 2022. Three pairs of reviewers performed data screening, extraction, and quality assessment independently. Meta-analysis with random effects models was used for general, subgroup, and sensitivity analyses. The I2 statistic was used to assess heterogeneity between studies. RESULTS: In total, 96 articles were included in this systematic review; of these, 87 studies met the criteria for the meta-analysis, involving 3,533 participants. Five biomarkers were included in the meta-analysis (tumor necrosis factor alpha; interleukin 6; leptin; interleukin 1 beta, and lipopolysaccharides). Only leptin showed a significant decrease in the first month after surgery (mean difference -20.71; [95% confidence interval: -28.10 to -13.32, P < .0001; I2 = 66.7%), with moderate heterogeneity. The 12 months after surgery showed a significant decrease in tumor necrosis factor alpha (mean difference -0.89; [95% confidence interval: -1.37 to -0.42], P = .0002; I2 = 94.7%), interleukin 6 (mean difference -1.62; [95% confidence interval: -1.95 to -1.29], P < .0001; I2 = 94.9%), leptin (mean difference -28.63; [95% confidence interval: -34.02 to -23.25], P < .0001; I2 = 92.7%), and interleukin 1 beta (mean difference -2.46; [95% confidence interval: -4.23 to -0.68], P = .006; I2 = 98.3%), all with high heterogeneity. The type of surgery did not show significant differences for the biomarkers at the first month and 12 months, and the results have not changed with high-quality studies. In the 12-month measurement, variations in tumor necrosis factor alpha and leptin were associated with body mass index. CONCLUSION: The findings of this meta-analysis suggest that Roux-en-Y gastric bypass and sleeve gastrectomy bariatric surgeries are associated with a significant reduction in leptin at 1 month after bariatric surgical intervention and tumor necrosis factor alpha, leptin, and interleukin 1 beta after 12 months.