Correlations between oxidative DNA damage and formation of hepatic tumours in two flatfish species from contaminated environments.

Many species in aquatic environments face increased exposure to oncogenic pollution due to anthropogenic environmental change which can lead to higher cancer prevalence. The mechanistic relationship connecting environmental pollution and cancer is multi-factorial and poorly understood, and the specific mechanisms are so far still uncharacterized. One potential mediator between pollutant exposure and cancer is oxidative damage to DNA. We conducted a study in the field with two flatfish species, European flounder (Platichthys flesus L.) and common dab (Limanda limanda L.) with overlapping distribution and similar ecological niche, to investigate if the link between oncogenic pollutants and cancer described in ecotoxicological literature could be mediated by oxidative DNA damage. This was not the case for flounders as neither polycyclic aromatic hydrocarbon (PAH) bile metabolites nor metallic trace element concentrations were related to oxidative DNA damage measurements. However, dabs with higher PAH concentrations did exhibit increased oxidative damage. High oxidative DNA damage also did not predict neoplasm occurrence, rather, healthy individuals tended to have higher oxidative damage measurements compared to fishes with pre-neoplastic tumours. Our analyses showed that flounders had lower concentrations of PAH bile metabolites, suggesting that compared to dab this species is less exposed or better at eliminating these contaminants.

Hypercapnia in hospitalized children and adolescents with anorexia nervosa as a predictive marker for readmission: a prospective study.

PURPOSE: To determine whether hypercapnia is associated with risk of hospital readmission related to anorexia nervosa (AN) in children and adolescents. METHODS: We performed a prospective study of patients ≤ 18 years old admitted due to AN decompensation from November 2018 to October 2019. Both subtypes of AN, restricting subtype (AN-R) and binge-eating/purging subtype (AN-BP), were included. Study participants were evaluated upon admission, at discharge and six months after discharge. T-tests or Mann-Whitney U tests was used to compare means values. Pearson or Spearman correlations were used to measure the association between two variables. Logistic regression models were developed to evaluate the relationship between scoring methods and readmission. RESULTS: Of the 154 persons admitted during the study period, 131 met the inclusion criteria. Median age was 15.1 years. At admission, 71% of participants were malnourished and 33 (25%) had been previously admitted. We observed a marked decrease in venous pH and stable pCO2 elevation during follow-up period. Hypercapnia at discharge was associated with a twofold increased likelihood of readmission and the odds of readmission increased as discharge pCO2 rose. These findings did not depend on AN subtype or participant sex. Electrolytes persisted within the normal range. CONCLUSION: Hypercapnia and respiratory acidosis are common alterations in children and adolescents hospitalized due to AN decompensation. Hypercapnia persists for at least 6 months after discharge despite clinical improvement and is associated with higher odds of readmission. This is the first study to identify an abnormal laboratory finding as a potential predictor of readmission in AN. LEVEL OF EVIDENCE: IV: Multiple time series without intervention.

Temporal trends of mercury levels in fish (dab, Limanda limanda) and sediment from the German Bight (North Sea) in the period 1995-2020.

As a toxic and harmful global pollutant, mercury (Hg) enters the marine environment through natural sources, and human activities. It bioaccumulates through the food chain and therefore, Hg is of great importance for environmental monitoring. This study aims to answer the question if Hg contamination in fish and sediment from the German Bight follows temporal trends. Therefore, 496 individual female dab (Limanda limanda) were analyzed. The Hg concentrations in the muscle of dab from the German Bight showed significant increase in function of time with an annual percental change of 1.4%, leading to a 41% increase in Hg contamination level within 25 years of monitoring. At the same time, Hg concentrations in sediment-analyzed in 86 samples-significantly decreased in the nearby North Sea environment. This surprising contradiction is shown in the present study and possible causes are discussed. It could be clearly shown that contamination in sediment and biota can follow completely different time courses and therefore, different environmental matrices should be considered in future monitoring studies. Age of the fish turned out to be a biological factor of particular importance for temporal trend analysis.

Acral peeling as the sole skin manifestation of COVID-19 in children.

Skin lesions in children with proven COVID-19 are not frequent in the literature apart from those associated with multisystem inflammatory syndrome. Fortunately, microbiologic testing for SARS-CoV-2 has become widely available not only for admitted patients but also for mild cases. We present a series of 6 children with mild erythema and desquamation of the fingertips and/or toes as the only skin manifestation of COVID-19. As all children had asymptomatic to mildly symptomatic disease, it is reasonable to consider this a sign of benign disease and favorable outcome.

Swimming exercise changed the collagen synthesis and calcification in calcaneal tendons of mice.

Obesity is characterized by the excess of body fat and, therefore, may cause musculoskeletal alterations that can negatively influence the tendons. Such overweight-influenced alterations are exercise sensitive though. Morphological and biochemical alterations were reported in the calcaneal tendon of mice submitted to a lipid-rich diets along with practicing exercises, with the following groups: normal diet without exercise (ND), normal diet with exercise (NDex), lipid-rich diet without exercise (LD), lipid-rich diet without exercise (LDex). The calcaneal tendons were removed and subjected to histological and biochemical analysis. Layers of the tissue were stained with Hematoxylin and Eosin, Picrosirius Red and Von Kossa while a protein dosage was conduce by the Bradford method. The morphologicals analysis there was no statistical difference concerning the number of fibroblasts among the groups. Groups submitted to exercises showed higher amount of collagen and non-collagenous protein deposition. The lipid-rich diet without exercse group had a more disorganized collagen matrix with intense basophilia. The same group had areas of calcification confirmed by Von Kossa technique. Practicing physical activity, such as swimming, can improve the changes caused in the calcaneal tendon in mice submitted to a lipid-rich diets, having a better collagen organization and the synthesis.

CD1 is involved in diet-induced hypothalamic inflammation in obesity.

Obesity-associated hypothalamic inflammation plays an important role in the development of defective neuronal control of whole body energy balance. Because dietary fats are the main triggers of hypothalamic inflammation, we hypothesized that CD1, a lipid-presenting protein, may be involved in the hypothalamic inflammatory response in obesity. Here, we show that early after the introduction of a high-fat diet, CD1 expressing cells gradually appear in the mediobasal hypothalamus. The inhibition of hypothalamic CD1 reduces diet-induced hypothalamic inflammation and rescues the obese and glucose-intolerance phenotype of mice fed a high-fat diet. Conversely, the chemical activation of hypothalamic CD1 further increases diet-induced obesity and hypothalamic inflammation. A bioinformatics analysis revealed that hypothalamic CD1 correlates with transcripts encoding for proteins known to be involved in diet-induced hypothalamic abnormalities in obesity. Thus, CD1 is involved in at least part of the hypothalamic inflammatory response in diet-induced obesity and its modulation affects the body mass phenotype of mice.

A review of select minerals influencing the haematopoietic process.

Micronutrients are indispensable for adequate metabolism, such as biochemical function and cell production. The production of blood cells is named haematopoiesis and this process is highly consuming due to the rapid turnover of the haematopoietic system and consequent demand for nutrients. It is well established that micronutrients are relevant to blood cell production, although some of the mechanisms of how micronutrients modulate haematopoiesis remain unknown. The aim of the present review is to summarise the effect of Fe, Mn, Ca, Mg, Na, K, Co, iodine, P, Se, Cu, Li and Zn on haematopoiesis. This review deals specifically with the physiological requirements of selected micronutrients to haematopoiesis, showing various studies related to the physiological requirements, deficiency or excess of these minerals on haematopoiesis. The literature selected includes studies in animal models and human subjects. In circumstances where these minerals have not been studied for a given condition, no information was used. All the selected minerals have an important role in haematopoiesis by influencing the quality and quantity of blood cell production. In addition, it is highly recommended that the established nutrition recommendations for these minerals be followed, because cases of excess or deficient mineral intake can affect the haematopoiesis process.

A New Proposal for Three-Dimensional Positioning of the Chin Using a Single Computer-Aided Design/Computer-Aided Manufacturing Surgical Guide.

The workflow digital to aid the treatment of dentofacial deformities is a reality. Associated with the virtual planning, the creation of surgical guides assists the performance of osteotomies and bone positioning, increasing the accuracy of surgical outcomes. This study aims to present a new method of surgical guide for genioplasty based on the selected osteosynthesis plate.

Effects of glutamine, taurine and their association on inflammatory pathway markers in macrophages.

The immune system is essential for the control and elimination of infections, and macrophages are cells that act as important players in orchestrating the various parts of the inflammatory/immune response. Amino acids play important role in mediating functionality of the inflammatory response, especially mediating macrophages functions and cytokines production. We investigated the influence of glutamine, taurine and their association on the modulation of inflammatory pathway markers in macrophages. The RAW 264.7 macrophage cell line was cultivated in the presence of glutamine and taurine and proliferation rates, cell viability, cell cycle phases, IL-1α, IL-6, IL-10 and TNF-α as well as H2O2 production and the expression of the transcription factor, NFκB, and its inhibitor, IκBα, were evaluated. Our results showed an increase in viable cells and increased proliferation rates of cells treated with glutamine concentrations over 2 mM, as well as cells treated with both glutamine and taurine. The cell cycle showed a higher percentage of cells in the phases S, G2 and M when they were treated with 2 or 10 mM glutamine, or with glutamine and taurine in cells stimulated with lipopolysaccharide. The pNFκB/NFκB showed reduced ratio expression when cells were treated with 10 mM of glutamine or with glutamine in association with taurine. These conditions also resulted in reduced TNF-α, IL-1α and H2O2 production, and higher production of IL-10. These findings demonstrate that glutamine and taurine are able to modulate macrophages inflammatory pathways, and that taurine can potentiate the effects of glutamine, illustrating their immunomodulatory properties.

A Review of Commercial and Medical-Grade Physiological Monitoring Devices for Biofeedback-Assisted Quality of Life Improvement Studies.

With the rise in wearable technology and "health culture", we are seeing an increasing interest and affordances in studying how to not only prolong life expectancy but also in how to improve individuals' quality of life. On the one hand, this attempts to give meaning to the increasing life expectancy, as living above a certain threshold of pain and lack of autonomy or mobility is both degrading and unfair. On the other hand, it lowers the cost of continuous care, as individuals with high quality of life indexes tend to have lower hospital readmissions or secondary complications, not to mention higher physical and mental health. In this paper, we evaluate the current state of the art in physiological therapy (biofeedback) along with the existing medical grade and consumer grade hardware for physiological research. We provide a quick primer on the most commonly monitored physiologic metrics, as well as a brief discussion on the current state of the art in biofeedback-assisted medical applications. We then go on to present a comparative analysis between medical and consumer grade biofeedback devices and discuss the hardware specifications and potential practical applications of each consumer grade device in terms of functionality and adaptability for controlled (laboratory) and uncontrolled (field) studies. We end this article with some empirical observations based on our study so that readers might use take them into consideration when arranging a laboratory or real-world experience, thus avoiding costly time delays and material expenditures.

Effects of Sleep Deprivation on Mice Bone Marrow and Spleen B Lymphopoiesis.

B lymphocytes are immune cells crucial for the maintenance and viability of the humoral response. Sleep is an essential event for the maintenance and integrity of all systems, including the immune system (IS). Thus, sleep deprivation (SD) causes problems in metabolism and homeostasis in many cell systems, including the IS. In this study, our goal was to determine changes in B lymphocytes from the bone marrow (BM) and spleen after SD. Three-month-old male Swiss mice were used. These mice were sleep deprived through the modified multiple platform method for different periods (24, 48, and 72 h), whereas another group was allowed to sleep for 24 h after 72 h of SD (rebound group) and a third group was allowed to sleep normally during the entire experiment. After this, the spleen and BM were collected, and cell analyses were performed. The numbers of B lymphocytes in the BM and spleen were reduced by SD. Additionally, reductions in the percentage of lymphocyte progenitors and their ability to form colonies were observed. Moreover, an increase in the death of B lymphocytes from the BM and spleen was associated with an increase in oxidative stress indicators, such as DCFH-DA, CAT, and mitochondrial SOD. Rebound was not able to reverse most of the alterations elicited by SD. The reduction in B lymphocytes and their progenitors by cell death, with a concomitant increase in oxidative stress, showed that SD promoted a failure in B lymphopoiesis.

A puzzling case of contamination with 241Am.

Two people were exposed to and contaminated with 241Am. In vivo determinations of the incorporated 241Am were performed using a whole-body counter and two partial-body counters for the skull and lung, respectively. Additionally, urine samples were analysed to estimate the systemic activity removed from the body. To improve the geometry of the skull measurements, an optimised detector configuration was used, a calibration with three physical phantoms of the human head was conducted, and the morphological variability between the individuals was also considered. The results of the measurements indicate that activity is not deposited in the deep tissues, rather in the skin tissues close to the body surface. Unfortunately, the many open questions relating to the actual circumstances during and after the incident make the interpretation of this case difficult if at all possible.

Cryosurgery with refrigerant gas as a therapeutic option for the treatment of leukoplakia: a case report.

Leukoplakia is a nondetachable, potentially malignant, white lesion that is commonly found in smokers of advanced age. Leukoplakia occurs more frequently in men; however, there is a higher index of dysplastic changes and malignant transformation in women. The proposed treatments for this disease range from monitoring to surgical excision. Cryosurgery has been reported as an alternative to conventional surgery. Cryosurgery destroys the tissues of a potentially malignant lesion through the application of low temperatures. This technique offers a low rate of postsurgical infection, absence of hemorrhage, and ease of application, and it is widely accepted by patients. The most commonly used cryogenic agent, liquid nitrogen, is costly and difficult to use. The objective of this article is to suggest the use of a combination of refrigerant gases (propane and butane), commonly employed in pulp sensitivity tests, for cryosurgery of potentially malignant lesions of the oral cavity and to report a case of leukoplakia treated with this approach.

A synthetic fragment of leptin increase hematopoietic stem cell population and improve its engraftment ability.

Several studies have shown the important actions of cytokine leptin that regulates food intake and energy expenditure. Additionally, the ability to modulate hematopoiesis has also been demonstrated. Previous reports have shown that some synthetic sequences of leptin molecules can activate leptin receptor. Herein, decapeptides encompassing amino acids from positions 98 to 122 of the leptin molecule were constructed to evaluate their effects on hematopoiesis. Among them, the synthetic peptide Lep(110-119)-NH2 (LEP F) was the only peptide that possessed the ability to increase the percentage of hematopoietic stem cells (HSC). Moreover, LEP F also produced an increase of granulocyte/macrophage colony-forming units and activated leptin receptor. Furthermore, LEP F also improves the grafting of HSC in bone marrow, but did not accelerate the recovery of bone marrow after ablation with 5-fluorouracil. These results show that LEP F is a positive modulator of the in vivo expansion of HSC and could be useful in bone marrow transplantation.

Nitric oxide-induced murine hematopoietic stem cell fate involves multiple signaling proteins, gene expression, and redox modulation.

There are a growing number of reports showing the influence of redox modulation in cellular signaling. Although the regulation of hematopoiesis by reactive oxygen species (ROS) and reactive nitrogen species (RNS) has been described, their direct participation in the differentiation of hematopoietic stem cells (HSCs) remains unclear. In this work, the direct role of nitric oxide (NO(•)), a RNS, in the modulation of hematopoiesis was investigated using two sources of NO(•) , one produced by endothelial cells stimulated with carbachol in vitro and another using the NO(•)-donor S-nitroso-N-acetyl-D,L-penicillamine (SNAP) in vivo. Two main NO(•) effects were observed: proliferation of HSCs-especially of the short-term HSCs-and its commitment and terminal differentiation to the myeloid lineage. NO(•)-induced proliferation was characterized by the increase in the number of cycling HSCs and hematopoietic progenitor cells positive to BrdU and Ki-67, upregulation of Notch-1, Cx43, PECAM-1, CaR, ERK1/2, Akt, p38, PKC, and c-Myc. NO(•)-induced HSCs differentiation was characterized by the increase in granulocytic-macrophage progenitors, granulocyte-macrophage colony forming units, mature myeloid cells, upregulation of PU.1, and C/EBPα genes concomitantly to the downregulation of GATA-3 and Ikz-3 genes, activation of Stat5 and downregulation of the other analyzed proteins mentioned above. Also, redox status modulation differed between proliferation and differentiation responses, which is likely associated with the transition of the proliferative to differentiation status. Our findings provide evidence of the role of NO(•) in inducing HSCs proliferation and myeloid differentiation involving multiple signaling.

The impaired viability of prostate cancer cell lines by the recombinant plant kallikrein inhibitor.

BACKGROUND: Kallikreins play a pivotal role in establishing prostate cancer. RESULTS: In contrast to the classical Kunitz plant inhibitor SbTI, the recombinant kallikrein inhibitor (rBbKIm) led to prostate cancer cell death, whereas fibroblast viability was not affected. CONCLUSION: rBbKIm shows selective cytotoxic effect and angiogenesis inhibition against prostate cancer cells. SIGNIFICANCE: New actions of rBbKIm may contribute to understanding the mechanisms of prostate cancer. Prostate cancer is the most common type of cancer, and kallikreins play an important role in the establishment of this disease. rBbKIm is the recombinant Bauhinia bauhinioides kallikreins inhibitor that was modified to include the RGD/RGE motifs of the inhibitor BrTI from Bauhinia rufa. This work reports the effects of rBbKIm on DU145 and PC3 prostate cancer cell lines. rBbKIm inhibited the cell viability of DU145 and PC3 cells but did not affect the viability of fibroblasts. rBbKIm caused an arrest of the PC3 cell cycle at the G0/G1 and G2/M phases but did not affect the DU145 cell cycle, although rBbKIm triggers apoptosis and cytochrome c release into the cytosol of both cell types. The differences in caspase activation were observed because rBbKIm treatment promoted activation of caspase-3 in DU145 cells, whereas caspase-9 but not caspase-3 was activated in PC3 cells. Because angiogenesis is important to the development of a tumor, the effect of rBbKIm in this process was also analyzed, and an inhibition of 49% was observed in in vitro endothelial cell capillary-like tube network formation. In summary, we demonstrated that different properties of the protease inhibitor rBbKIm may be explored for investigating the androgen-independent prostate cancer cell lines PC3 and DU145.

Targeting of neuroblastoma cells through Kynurenine-AHR pathway inhibition.

Neuroblastoma poses significant challenges in clinical management. Despite its relatively low incidence, this malignancy contributes disproportionately to cancer-related childhood mortality. Tailoring treatments based on risk stratification, including MYCN oncogene amplification, remains crucial, yet high-risk cases often confront therapeutic resistance and relapse. Here, we explore the aryl hydrocarbon receptor (AHR), a versatile transcription factor implicated in diverse physiological functions such as xenobiotic response, immune modulation, and cell growth. Despite its varying roles in malignancies, AHR's involvement in neuroblastoma remains elusive. Our study investigates the interplay between AHR and its ligand kynurenine (Kyn) in neuroblastoma cells. Kyn is generated from tryptophan (Trp) by the activity of the enzymes indoleamine 2,3-dioxygenase 1 (IDO1) and tryptophan 2,3-dioxygenase (TDO2). We found that neuroblastoma cells displayed sensitivity to the TDO2 inhibitor 680C91, exposing potential vulnerabilities. Furthermore, combining TDO2 inhibition with retinoic acid or irinotecan (two chemotherapeutic agents used to treat neuroblastoma patients) revealed synergistic effects in select cell lines. Importantly, clinical correlation analysis using patient data established a link between elevated expression of Kyn-AHR pathway genes and adverse prognosis, particularly in older children. These findings underscore the significance of the Kyn-AHR pathway in neuroblastoma progression, emphasizing its potential role as a therapeutic target.

Tryptophan fuels MYC-dependent liver tumorigenesis through indole 3-pyruvate synthesis.

Cancer cells exhibit distinct metabolic activities and nutritional dependencies compared to normal cells. Thus, characterization of nutrient demands by individual tumor types may identify specific vulnerabilities that can be manipulated to target the destruction of cancer cells. We find that MYC-driven liver tumors rely on augmented tryptophan (Trp) uptake, yet Trp utilization to generate metabolites in the kynurenine (Kyn) pathway is reduced. Depriving MYC-driven tumors of Trp through a No-Trp diet not only prevents tumor growth but also restores the transcriptional profile of normal liver cells. Despite Trp starvation, protein synthesis remains unhindered in liver cancer cells. We define a crucial role for the Trp-derived metabolite indole 3-pyruvate (I3P) in liver tumor growth. I3P supplementation effectively restores the growth of liver cancer cells starved of Trp. These findings suggest that I3P is a potential therapeutic target in MYC-driven cancers. Developing methods to target this metabolite represents a potential avenue for liver cancer treatment.

Hydrogen peroxide (H2O2) induces leukemic but not normal hematopoietic cell death in a dose-dependent manner.

Over the last few years, studies have suggested that oxidative stress plays a role in the regulation of hematopoietic cell homeostasis. In particular, the effects of hydrogen peroxide (H2O2) range from hematopoietic cell proliferation to cell death, depending on its concentration in the intracellular milieu. In this work, we evaluated the effects of an oxidative environment on normal and leukemic hematopoietic cells by stimulating normal human (umbilical cord blood) and murine (bone marrow) hematopoietic cells, as well as human myeloid leukemic cells (HL-60 lineage), upon H2O2 stimulus. Total cell populations and primitive subsets were evaluated for each cell type. H2O2 stimulus induces HL-60 cell death, whereas the viability of human and murine normal cells was not affected. The effects of H2O2 stimulus on hematopoietic stem/progenitor cell subsets were examined and the normal primitive cells were found to be unaffected; however, the percentage of leukemic stem cells (LSC) increased in response to H2O2, while clonogenic ability of these cells to generate myeloid clones was inhibited. In addition, H2O2 stimulus caused a decrease in the levels of p-AKT in HL-60 cells, which most likely mediates the observed decrease of viability. In summary, we found that at low concentrations, H2O2 preferentially affects both the LSC subset and total HL-60 cells without damage normal cells.

Visual quantification and identification of shallow seafloor marine litter in the southernmost North and Baltic seas using an epibenthic video sledge (EVS) - A comparison to bottom trawl data.

The quantification of the marine litter at the seafloor is a challenging process. Currently the majority of the data of marine litter at the seafloor is a by-product of bottom trawl fish stocks assessment. In the search for a new, less invasive and universally usable method, an epibenthic video sledge was used to make video recordings of the seafloor. With these videos a visual estimation of the marine litter in the southernmost North and Baltic seas was done. The estimated mean litter abundances with 526.8 litter items (LI)·km-2 in the Baltic Sea and 305.1 LI·km-2 in the North Sea are significantly higher compared to bottom trawl studies. Using both results conversion factors for marine litter catch efficiency of two fishing gears were calculated for the first-time. These new factors now allow obtaining more realistic quantitative data of seafloor litter abundance.