Predicted deleterious variants in ABCA1, LPL, LPA and KIF6 are associated with statin response and adverse events in patients with familial hypercholesterolemia and disturb protein structure and stability.

OBJECTIVES: This study explored the association of deleterious variants in pharmacodynamics (PD) genes with statin response and adverse effects in patients with familial hypercholesterolemia (FH) and analyzed their potential effects on protein structure and stability. METHODS: Clinical and laboratory data were obtained from 144 adult FH patients treated with statins. A panel of 32 PD genes was analyzed by exon-targeted gene sequencing. Deleterious variants were identified using prediction algorithms and their structural effects were analyzed by molecular modeling studies. RESULTS: A total of 102 variants were predicted as deleterious (83 missense, 8 stop-gain, 4 frameshift, 1 indel, 6 splicing). The variants ABCA1 rs769705621 (indel), LPA rs41267807 (p.Tyr2023Cys) and KIF6 rs20455 (p.Trp719Arg) were associated with reduced low-density lipoprotein cholesterol (LDLc) response to statins, and the LPL rs1801177 (p.Asp36Asn) with increased LDLc response (P < 0.05). LPA rs3124784 (p.Arg2016Cys) was predicted to increase statin response (P = 0.022), and ABCA1 rs769705621 to increase the risk of statin-related adverse events (SRAE) (P = 0.027). LPA p.Arg2016Cys and LPL p.Asn36Asp maintained interactions with solvent, LPA p.Tyr2023Cys reduced intramolecular interaction with Gln1987, and KIF6 p.Trp719Arg did not affect intramolecular interactions. DDMut analysis showed that LPA p.Arg2016Cys and p.Tyr2023Cys and LPL p.Asp36Asn caused energetically favorable changes, and KIF6 p.Trp719Arg resulted in unfavorable energetic changes, affecting protein stability. CONCLUSION: Deleterious variants in ABCA1, LPA, LPL and KIF6 are associated with variability in LDLc response to statins, and ABCA1 rs769705621 is associated with SRAE risk in FH patients. Molecular modeling studies suggest that LPA p.Tyr2023Cys and KIF6 p.Trp719Arg disturb protein conformational structure and stability.

Ecotoxicological Consequences of Urbanization: A Multi-Biomarker Approach to Assessing Sewage Treatment Plant Effects on Free-Living Birds.

Birds are good bioindicators of disturbance in the environment. They are present in different habitats and trophic levels. In addition, rapid urbanization has led birds to use cities as shelter and for seeking food resources. Sewage treatment plants (STPs) are suitable locations for free-living birds within cities. However, few studies address the impacts of emerging pollutants from sewage treatment plants on wild birds. In this sense, the aim of this study was to analyze the genotoxic, mutagenic, and immunological impacts from metal and pollutant exposure on free-living birds collected at a STP. For comparison, birds were collected in a preserved environment, the Silvania National Forest (FLONA). To achieve this, we used non-destructive biomarkers sensitive to environmental changes. Birds were collected in both environments using mist nets. After collection, birds were weighed, measured, species-identified, and released. Blood was collected for comet assay, micronucleus test, and leukocyte profile, while feathers were collected for metal concentration analysis. Water physicochemical parameters were measured at both sites, and water samples were collected for metal analysis. Our results demonstrated that birds collected at the STP exhibit a higher frequency of genotoxic damage and erythrocyte abnormalities, and increased immune response compared to FLONA birds. Traces of potentially toxic metals, such as Hg and As, were found in the birds feathers from both environments, raising concerns about metal contamination in both environments. Trophic guilds appear to respond similarly to exposure. The parameters and metals found in the water reflect environmental characteristics and may be influencing pollutant availability. Finally, despite the advancement of our findings, studies linking these damages to detrimental effects on behavior and reproduction are encouraged.

LDLR and PCSK9 3´UTR variants and their putative effects on microRNA molecular interactions in familial hypercholesterolemia: a computational approach.

BACKGROUND: Familial hypercholesterolemia (FH) is caused by pathogenic variants in low-density lipoprotein (LDL) receptor (LDLR) or its associated genes, including apolipoprotein B (APOB), proprotein convertase subtilisin/kexin type 9 (PCSK9), and LDLR adaptor protein 1 (LDLRAP1). However, approximately 40% of the FH patients clinically diagnosed (based on FH phenotypes) may not carry a causal variant in a FH-related gene. Variants located at 3' untranslated region (UTR) of FH-related genes could elucidate mechanisms involved in FH pathogenesis. This study used a computational approach to assess the effects of 3'UTR variants in FH-related genes on miRNAs molecular interactions and to explore the association of these variants with molecular diagnosis of FH. METHODS AND RESULTS: Exons and regulatory regions of FH-related genes were sequenced in 83 FH patients using an exon-target gene sequencing strategy. In silico prediction tools were used to study the effects of 3´UTR variants on interactions between miRNAs and target mRNAs. Pathogenic variants in FH-related genes (molecular diagnosis) were detected in 44.6% FH patients. Among 59 3'UTR variants identified, LDLR rs5742911 and PCSK9 rs17111557 were associated with molecular diagnosis of FH, whereas LDLR rs7258146 and rs7254521 and LDLRAP1 rs397860393 had an opposite effect (p < 0.05). 3´UTR variants in LDLR (rs5742911, rs7258146, rs7254521) and PCSK9 (rs17111557) disrupt interactions with several miRNAs, and more stable bindings were found with LDLR (miR-4435, miR-509-3 and miR-502) and PCSK9 (miR-4796). CONCLUSION: LDLR and PCSK9 3´UTR variants disturb miRNA:mRNA interactions that could affect gene expression and are potentially associated with molecular diagnosis of FH.

Damage on DNA and hematological parameters of two bat species due to heavy metal exposure in a nickel-mining area in central Brazil.

Exposure to heavy metals in mining zones is a significant threat, which can affect ecosystem services and contribute to the decline of wild bat populations. The present study investigated the impacts caused by mining on two bat species in central Brazil, the nectarivorous Glossophaga soricina and the frugivorous Carollia perspicillata. The bats were collected from a nickel-mining zone (treatment) and a protected area (control). The leukocyte profile of each species was compiled and genotoxicity (comet assay) and mutagenicity (micronucleus test) were determined using the appropriate procedures. Glossophaga soricina presented significantly higher frequencies of eosinophils and monocytes in the mining zone in comparison with the protected area, whereas C. perspicillata presented higher frequencies of lymphocytes in the mining zone, but significantly lower frequencies of monocytes. Concomitantly, G. soricina also presented a higher frequency of DNA damage, although no variation was found in this parameter in C. perspicillata when comparing environments. We also found no significant differences between populations in terms of the frequency of micronuclei and other nuclear abnormalities. Overall, the results of the study indicate that bats are susceptible to immunological disorders and DNA damage in mining zones, with the nectarivorous G. soricina appearing to be relatively more susceptible and thus a potentially effective bioindicator of the impact of contamination in these environments.

ApoC-III is a novel inducer of calcification in human aortic valves.

Calcific aortic valve disease (CAVD) occurs when subpopulations of valve cells undergo specific differentiation pathways, promoting tissue fibrosis and calcification. Lipoprotein particles carry oxidized lipids that promote valvular disease, but low-density lipoprotein-lowering therapies have failed in clinical trials, and there are currently no pharmacological interventions available for this disease. Apolipoproteins are known promoters of atherosclerosis, but whether they possess pathogenic properties in CAVD is less clear. To search for a possible link, we assessed 12 apolipoproteins in nonfibrotic/noncalcific and fibrotic/calcific aortic valve tissues by proteomics and immunohistochemistry to understand if they were enriched in calcified areas. Eight apolipoproteins (apoA-I, apoA-II, apoA-IV, apoB, apoC-III, apoD, apoL-I, and apoM) were enriched in the calcific versus nonfibrotic/noncalcific tissues. Apo(a), apoB, apoC-III, apoE, and apoJ localized within the disease-prone fibrosa and colocalized with calcific regions as detected by immunohistochemistry. Circulating apoC-III on lipoprotein(a) is a potential biomarker of aortic stenosis incidence and progression, but whether apoC-III also induces aortic valve calcification is unknown. We found that apoC-III was increased in fibrotic and calcific tissues and observed within the calcification-prone fibrosa layer as well as around calcification. In addition, we showed that apoC-III induced calcification in primary human valvular cell cultures via a mitochondrial dysfunction/inflammation-mediated pathway. This study provides a first assessment of a broad array of apolipoproteins in CAVD tissues, demonstrates that specific apolipoproteins associate with valvular calcification, and implicates apoC-III as an active and modifiable driver of CAVD beyond its potential role as a biomarker.

Açaí (Euterpe oleracea Martius) Promotes Jejunal Tissue Regeneration by Enhancing Antioxidant Response in 5-Fluorouracil-Induced Mucositis.

Intestinal mucositis (IM) caused by antineoplastic chemotherapy is characterized by an important inflammatory process, which may compromise ongoing treatment. Our study aimed to investigate the effect of Açaí (Euterpe oleracea Martius) on the antioxidant response in BALB/c mice pretreated with Açaí pulp (200 g/kg) for 14 day. A group of animals receiving a single intraperitoneal injection of 5-FU (200 mg/kg) were euthanized on day three (D3) or seven (D7) after administration, the distal jejunum was isolated for the analyses of histology, superoxide dismutase (SOD) and catalase (CAT) enzyme activities, and concentration of total sulfhydryl groups (GSH). Seven days after induction, the intake of Açaí by the IM group almost completely regenerated tissue histology. Notably, SOD activity decreased in the MUC + Açaí group (D3). CAT activity reduced on D3 and D7 in the IM groups and Açaí treatment groups, respectively. No change was observed in the total GSH concentration at the tissue level. Our results demonstrated the protective effect of Açaí pulp components on intestinal damage induced by 5-FU, as well as the ability to control the response to oxidative stress, in order to mobilize defense pathways and promote tissue repair.

Prognostic factors in patients with advanced cancer and COVID-19: a cohort from the Palliative Care Unit of the Brazilian National Cancer Institute.

OBJECTIVE: To describe overall survival (OS) in 90 days and to evaluate the prognostic factors in patients with advanced cancer and COVID-19. METHODS: This is a retrospective cohort study carried out at the Palliative Care Unit of the Brazilian National Cancer Institute. Patients with advanced cancer and COVID-19 confirmed by Reverse Transcription Polymerase Chain Reaction were included. Kaplan-Meier's curves, log-rank test, and Cox regression were performed. RESULTS: Eighty-three inpatients were selected. The average age was 61.4 (±12.6) years, with a higher proportion of women (73.4%). The most prevalent tumor type was breast (36.7%), followed by gastrointestinal tract (20.3%). The OS was 32 [interquartile range (IQR): 6-70] days, and at the end of the follow-up period, 17 patients (20.5%) were alive and 66 (79.5%) had died. Patients with advanced cancer and COVID-19 and who were 60-74 years old [hazard ratio (HR): 2.03; 95% confidence interval (CI): 1.09-3.78], with lung tumors (HR: 17.50; 95% CI: 1.70-28.34), with lung metastasis (HR: 4.21; 95% CI: 2.17-8.15), and with chronic obstructive pulmonary disease (HR: 4.92; 95% CI: 1.01-24.69) had higher risk of death in 90 days. CONCLUSION: The age of 60-74 years old, lung tumors (primary or metastases), and the presence of chronic obstructive pulmonary disease were considered independent prognostic factors in patients with advanced cancer and COVID-19.

Açaí (Euterpe oleracea Martius) supplementation in the diet during gestation and lactation attenuates liver steatosis in dams and protects offspring.

PURPOSE: Maternal high-fat diet affects offspring and can induce metabolic disorders such as non-alcoholic fatty liver disease (NAFLD). New therapeutic strategies are being investigated as way to prevent or attenuate this condition. The objective of this study was to evaluate the effect of açaí supplementation in the maternal high-fat diet on dams and offspring lipid metabolism. METHODS: Female Fisher rats were divided in four groups and fed a control diet (C), a high-fat diet (HF), an açaí supplemented diet (CA) and a high-fat diet supplemented with açaí (HFA) 2 weeks before mating, during gestation and lactation. The effects of açaí were evaluated in the male offspring after birth (P1) and weaning (P21). RESULTS: HFA reduced relative liver weight, fat and cholesterol liver content in dams and improved liver steatosis as confirmed by histological analyses. HFA increased serum cholesterol and expression of Srebpf1 and Fasn genes. In offspring, HFA decreased relative liver weight, and serum cholesterol only in P21. An increase in the Sirt1, Srebpf1 and Fasn genes expression was observed in P21. CONCLUSIONS: These results suggest that açaí supplementation may attenuate NAFLD in dams and protect offspring from the detrimental effects of lipid excess from a maternal high-fat diet.

Hox D genes and the fin-to-limb transition: Insights from fish studies.

Genes in the 5' extremity of the HoxD cluster encode DNA-binding transcription factors essential for development of the autopod and digits, regulating primarily gene expression and, consequently, morphogenesis and skeletal differentiation. Comparative studies focused on their expression and regulation have led to the idea that evolution of a bimodal regulation of the HoxD cluster, mainly due to the activation of cis-regulatory units in the centromeric side of the cluster, was a fundamental mechanism that potentiated the fin-to-limb transition in vertebrates. In addition, functional assays demonstrated that increased levels of 5'HoxD genes stimulate the production of additional endochondral bone, while repressing the formation of dermal skeleton distally. Other data have come to light in recent years suggesting that these genes may interfere directly with the production of dermal skeleton components in fish and with the activity of cis-regulatory units involved in the formation of autopod and digits. Finally, increasing evidences suggest that the role of HoxD genes in fin evolution may relate to their ability to change the fate of distal mesenchymal cells conducting them to differentiate into endochondral bone rather than in dermal skeleton. Here, we trace the history of the research concerning the involvement of HoxD genes in the fin-to-limb transition in vertebrates. To this end, we discuss three interconnected topics that have benefited from profound advances in recent years due to comparative analyses and functional assays performed using fish species: (a) comparative HoxD genes expression; (b) comparative HoxD gene transcriptional regulation; and (c) functional characterization of 5'HoxD genes.

Exposure to deltamethrin induces oxidative stress and decreases of energy reserve in tissues of the Neotropical fruit-eating bat Artibeus lituratus.

Deltamethrin (DTM) is a synthetic pyrethroid insecticide highly used by farmers and home users. This pesticide has lipophilic properties that facilitate a high absorption and can cause toxicity in non-target organisms. During foraging, the fruit-eating bats Artibeus lituratus are exposed to pesticides. However, the knowledge of the toxicity of pesticides on the physiology of bats is relatively scarce. This study aimed to check the toxicity of short-term exposure to low concentration of DTM on fruit-eating bat A. lituratus. After seven days of exposure to two doses of DTM (0.02 and 0.04mg/kg of papaya), the fruit bats showed an increase in the enzyme aspartate aminotransferase, alanine aminotransferase, and hyperglycemia. The liver and pectoral muscle presented oxidative stress. In the liver, the hydrogen peroxide (H2O2) and nitric oxide (NO) were increased as well as the antioxidant glutathione (GSH), the activity of glutathione S-transferase (GST), superoxide dismutase (SOD) and catalase (CAT) but in a lesser extent. Yet, total lipids were increased while hepatic glycogen content is reduced. The pectoral muscle showed NO, SOD, CAT, malondialdehyde (MDA), and carbonyl increased protein levels in both concentrations of DTM. All these results show that low doses of DTM can cause hepatic and muscular toxicity and induce changes in carbohydrate metabolism. Physiological changes caused by exposure to DTM in bats may have direct consequences in flight capacity, reproduction, and metabolism of these animals.

Muscle development in the shark Scyliorhinus canicula: implications for the evolution of the gnathostome head and paired appendage musculature.

BACKGROUND: The origin of jawed vertebrates was marked by profound reconfigurations of the skeleton and muscles of the head and by the acquisition of two sets of paired appendages. Extant cartilaginous fish retained numerous plesiomorphic characters of jawed vertebrates, which include several aspects of their musculature. Therefore, myogenic studies on sharks are essential in yielding clues on the developmental processes involved in the origin of the muscular anatomy. RESULTS: Here we provide a detailed description of the development of specific muscular units integrating the cephalic and appendicular musculature of the shark model, Scyliorhinus canicula. In addition, we analyze the muscle development across gnathostomes by comparing the developmental onset of muscle groups in distinct taxa. Our data reveal that appendicular myogenesis occurs earlier in the pectoral than in the pelvic appendages. Additionally, the pectoral musculature includes muscles that have their primordial developmental origin in the head. This culminates in a tight muscular connection between the pectoral girdle and the cranium, which founds no parallel in the pelvic fins. Moreover, we identified a lateral to ventral pattern of formation of the cephalic muscles, that has been equally documented in osteichthyans but, in contrast with these gnathostomes, the hyoid muscles develop earlier than mandibular muscle in S. canicula. CONCLUSION: Our analyses reveal considerable differences in the formation of the pectoral and pelvic musculatures in S. canicula, reinforcing the idea that head tissues have contributed to the formation of the pectoral appendages in the common ancestor of extant gnathostomes. In addition, temporal differences in the formation of some cranial muscles between chondrichthyans and osteichthyans might support the hypothesis that the similarity between the musculature of the mandibular arch and of the other pharyngeal arches represents a derived feature of jawed vertebrates.

Clustered Cardiovascular Risk Factors Are Associated with Inflammatory Markers in Adolescents.

BACKGROUND: Clusters of cardiovascular risk (CVR) factors are associated with an increased risk of developing cardiovascular diseases (CVDs). This cross-sectional study assessed the associations between classic CVR factor clusters and inflammatory markers in Brazilian adolescents. METHODS: Measurements included anthropometric, clinical and biochemical parameters and selected inflammatory markers in 487 adolescents (236 boys/251 girls; 12.06 ± 1.41 years). RESULTS: After stratifying the population by gender and adjusting for potential confounding variables, principal component analysis was performed and it produced 5 independent components in both genders: adiposity, glucose metabolism, blood pressure, high-density lipoprotein (HDL)/triacylglycerols (TG), and cholesterol/low-density lipoprotein. Glucose metabolism was inversely associated with interleukin-1ß (IL-1ß) in both genders (r = -0.026; r = -0.021); blood pressure was inversely associated with tumor necrosis factor alpha (TNF-α) in girls (r = -0.046); HDL/TG was positively associated with interleukin-6 in girls (r = 0.012), with IL-1ß (r = 0.010) TNF-α (r = 0.045) in boys, and inversely associated with adiponectin in both genders (r = -0.015; r = -0.013). CONCLUSION: The results suggest that lipid metabolism alterations, as potential early events in the development of CVDs, have a strong link to the inflammatory process, in contrast to other clusters of risk factors.

Molecular characterization and population structure of the macaw palm, Acrocomia aculeata (Arecaceae), ex situ germplasm collection using microsatellites markers.

The Acrocomia aculeata is one of the most promising plants for sustainable production of renewable energy. In order to understand patterns of the distribution of the allelic diversity of A. aculeata ex situ germplasm collection, the present study investigated the hypothesis that the genetic variability of the accessions may match their geographical origin. A genotypic analysis of 77 A. aculeata accessions was conducted with 6 simple sequence repeat markers. A high degree of molecular diversity among the accessions was found, with an average of 9 alleles per locus and a polymorphic information content with a mean of 0.76. A total of 4 clusters was identified by the Bayesian analysis of population structure. The highest subpopulation diversity was identified in Pop1, mainly formed by accessions from State of Mato Grosso do Sul. The populations Pop2A, Pop2B, and Pop2C, all from the State of Minas Gerais, showed high genetic variability as determined by a higher F st, and a wide genetic variance, which were identified within and among the population by analysis of molecular variance. Based on our results and on Vavilov's theory on crop origins, one possible diversity center for A. aculeata is proposed to be in a region in southeast Brazil.

New frontiers in the evolution of fin development.

The locomotory appendages of vertebrates have undergone significant changes during evolution, which likely promoted a wide range of adaptive strategies. These appendages first evolved as unpaired finfolds in the dorsal midline of early chordates, more than 500 million years ago. Later on, during vertebrates' radiation, two sets of locomotory appendages emerged, developing from both sides of the latero-ventral body wall. The morphology of these paired fins in fishes at different phylogenetic positions suggests an evolutionary tendency for increasing elaboration of the endoskeleton and concomitant reduction of the distal dermoskeleton. This evolutionary process culminated with the origin of limbs in the lineages leading to tetrapods. The developmental programs responsible for the evolution of vertebrate appendages have been a major topic for evolutionary developmental biology recently. Gene expression comparisons performed in chordates explored how these mechanisms were transferred from a midline to latero-ventral position. On another front, gene function assays have begun to test classical hypotheses concerning the transition from fish fins to tetrapod limbs. In this review, we highlight these recent findings on the evolution of vertebrate fin development. First, we discuss new perspectives on the transition from midline to paired appendages focus on (i) origin and molecular regionalization of the lateral plate mesoderm and (ii) novel ectodermic competency zones for fin induction. Next, we review recent work exploring how tetrapod limbs evolved from fish fins, considering (i) molecular and structural changes in the distal ectoderm of fins and (ii) modulation of 5'HoxD transcription during fin endoskeleton development.

Physical activity is associated with malignant and benign breast diseases in low-income Brazilian women.

We compared the relationships among percentage of body fat (%BF) and physical activity with breast cancer (BC) and benign breast diseases (BBD) in low-income Brazilian women. A case-control study including 106 incident BC cases, 178 incident BBD cases, and 181 control women recruited from a public hospital-based screening center was conducted. Logistic regression models showed that sedentary women have a higher odds of developing BC in the age adjusted model [odds ratio (OR) = 2.39, 95% confidence interval (CI) 1.43-3.99]. After adjusting for hormonal-related risk factors and family history of breast cancer (OR = 2.94, 95% CI 1.50-5.79) and also for the % BF (OR = 2.71, 95% CI 1.36-5.37) the odds remained high. Independent of the adjustments made, %BF did not affect the odds for developing BC. When the same models were tested for women with BBD, we found a significant association with sedentary lifestyle in all models tested, with an OR = 3.03 (95% CI 1.69-5.42) in the fully adjusted model. In the same way, in the fully adjusted model %BF was significantly associated to risk for BBD (OR = 0.54, 95% CI 0.30-0.98). Similar to results found in other populations, our data suggest that physical activity is an important, independent protective factor for the risk of developing BC and BBD in low-income women from an admixed population.

Quality of life of women who underwent breast cancer treatment relative to sociodemographic, behavioral, and clinical factors.

OBJECTIVE: Patients with cancer often undergo multiple extended treatments that decrease their quality of life. However, the quality of life of women with breast cancer after they undergo treatment remains underexplored in Brazil. Therefore, this study determined sociodemographic, behavioral, and clinical factors related to the post-treatment quality of life of women with breast cancer. METHODS: This cross-sectional study involved 101 women diagnosed with breast cancer between 2014 and 2016 and treated at a Brazilian Oncology Reference Service. Data were collected from them using face-to-face surveys. Quality of life was evaluated using the European Organization for the Research and Treatment of Cancer Core Quality of Life questionnaire (EORTC QLQ-C30) and EORTC Breast Cancer-specific Quality of Life questionnaire (EORTC QLQ-BR23). The data collected were analyzed using Student's t-test and Mann-Whitney U test. RESULTS: The median score on the global health, functional, and symptom scales of the EORTC QLQ-C30 was 75.00 (Interquartile range=33.33), 75.99 (Standard deviation [SD]=19.26), and 19.67 (SD=16.91), respectively. The mean score on the functional and symptom scales of the EORTC QLQ-BR23 was 61.89 (SD=17.21) and 20.12 (SD=16.94), respectively. Furthermore, higher post-treatment quality of life was found to be associated with being aged 50 or more, being Black, having eight or more years of education, having a partner, having a paying job, receiving treatment from the private healthcare system, having a higher income, living in the municipality where healthcare services are availed, engaging in physical activity, not smoking, being more religious, having more social support, not being overweight, having no comorbidities, and undergoing lumpectomy. CONCLUSION: Sociodemographic, behavioral, and clinical factors significantly impact the quality of life of women who undergo breast cancer treatment. Implementing interventions that improve health and reducing inequalities in the access to healthcare services can improve the quality of life of these patients. BACKGROUND: Sociodemographic, clinical, and lifestyle factors impact the quality of life of breast cancer survivors. BACKGROUND: Breast cancer therapy may affect future perspectives and emotional, cognitive, and sexual function. BACKGROUND: Some aspects of quality of life still require attention from health professionals. BACKGROUND: Higher post-treatment quality of life of women with breast cancer is linked to being aged 50 or more, being Black, having 8 or more years of education, having a partner, having a paying job, receiving care from private healthcare, having a high per capita income, residing in the municipality where the service is availed, engaging in physical activity, not smoking, greater religiosity, having more social support, having a normal weight, having no comorbidities, and undergoing lumpectomy.

Gut bacterial markers involved in association of dietary inflammatory index with visceral adiposity.

OBJECTIVE: To deepen the understanding of the influence of diet on weight gain and metabolic disturbances, we examined associations between diet-related inflammation and body composition and fecal bacteria abundances in participants of the Nutritionists' Health Study. METHODS: Early-life, dietary and clinical data were obtained from 114 women aged ≤45 years. A validated food frequency questionnaire was used to calculate the energy-adjusted dietary inflammatory index (E-DII). Participants' data were compared by E-DII quartiles using ANOVA or Kruskal-Wallis. Associations of DXA-determined body composition with the E-DII were tested by multiple linear regression using DAG-oriented adjustments. Fecal microbiota was analyzed targeting the V4 region of the 16S rRNA gene. Spearman correlation coefficients were used to test linear associations; differential abundance of genera across the E-DII quartiles was assessed by pair-wise comparisons. RESULTS: E-DII score was associated with total fat (b=1.80, p<0.001), FMI (b=0.08, p<0.001) and visceral fat (b=1.19, p=0.02), independently of maternal BMI, birth type and breastfeeding. E-DII score was directly correlated to HOMA-IR (r=0.30; p=0.004), C-reactive protein (r=0.29; p=0.003) and to the abundance of Actinomyces, and inversely correlated to the abundance of Eubacterium.xylanophilum.group. Actinomyces were significantly more abundant in the highest (most proinflammatory) E-DII quartile. CONCLUSIONS: Association of E-DII with markers of insulin resistance, inflammation, body adiposity and certain gut bacteria are consistent with beneficial effects of anti-inflammatory diet on body composition and metabolic profile. Bacterial markers, such as Actinomyces, could be involved in the association between the dietary inflammation with visceral adiposity. Studies designed to explore how a pro-inflammatory diet affects both central fat deposition and gut microbiota are needed.

Tissue formation and host remodeling of an elastomeric biodegradable scaffold in an ovine pulmonary leaflet replacement model.

In pursuit of a suitable scaffold material for cardiac valve tissue engineering applications, an acellular, electrospun, biodegradable polyester carbonate urethane urea (PECUU) scaffold was evaluated as a pulmonary valve leaflet replacement in vivo. In sheep (n = 8), a single pulmonary valve leaflet was replaced with a PECUU leaflet and followed for 1, 6, and 12 weeks. Implanted leaflet function was assessed in vivo by echocardiography. Explanted samples were studied for gross pathology, microscopic changes in the extracellular matrix, host cellular re-population, and immune responses, and for biomechanical properties. PECUU leaflets showed normal leaflet motion at implant, but decreased leaflet motion and dimensions at 6 weeks. The leaflets accumulated α-SMA and CD45 positive cells, with surfaces covered with endothelial cells (CD31+). New collagen formation occurred (Picrosirius Red). Accumulated tissue thickness correlated with the decrease in leaflet motion. The PECUU scaffolds had histologic evidence of scaffold degradation and an accumulation of pro-inflammatory/M1 and anti-inflammatory/M2 macrophages over time in vivo. The extent of inflammatory cell accumulation correlated with tissue formation and polymer degradation but was also associated with leaflet thickening and decreased leaflet motion. Future studies should explore pre-implant seeding of polymer scaffolds, more advanced polymer fabrication methods able to more closely approximate native tissue structure and function, and other techniques to control and balance the degradation of biomaterials and new tissue formation by modulation of the host immune response.

IL-10 and IL-1ß Serum Levels, Genetic Variants, and Metabolic Syndrome: Insights into Older Adults' Clinical Characteristics.

Populational aging is marked by chronic noncommunicable diseases, such as metabolic syndrome (MetS). IL-10 and IL-1ß are pleiotropic cytokines with multiple biological effects linked to metabolic disorders. This cross-sectional study assessed 193 participants' IL-10 and IL-1ß serum levels regarding their role in developing MetS, clinical characteristics, and their IL1B rs1143627 and IL10 rs1800890 variants' genotype frequencies in a population over 60. IL-10 levels correlated weakly with HDL levels and fat mass and inversely with triglycerides, glucose, glycated hemoglobin, and estimated average blood glucose levels. IL-10 levels were also indirectly influenced by the patient's T2DM duration, lean mass amount, and bone mineral content. Participants with altered HDL, elevated serum glucose, raised HbA1c levels, or those over 80 had reduced serum IL-10 levels compared to those with normal levels or other age groups, respectively. Women also had higher serum IL-10 levels than men. Dissimilarly, IL-1ß levels correlated directly only with the number of total leukocytes and segmented neutrophils, showing only significant variations with self-reported alcohol consumption. Our study also found that those with the IL10 AA genotype (lower IL-10 levels) had a significantly higher risk of developing MetS. These findings may help direct future research and more targeted therapeutic approaches in older adults.

Can Salvinia auriculata bioremediate the toxic effects of Fipronil 800wg on the tadpoles of Dendropsophus minutus?

Worldwide, the indiscriminate and escalating application of pesticides has led to extensive impacts on both the environment and non-target organisms. Phytoremediation, which employs plants to decontaminate environments, is a potential strategy for the mitigation of this damage. The present study assessed the phytoremedial potential of Salvinia auriculata, an aquatic macrophyte known to be effective for the removal of environmental contaminants. In the laboratory, Dendropsophus minutus tadpoles were exposed to different concentrations (0.035, 0.1, 1.0, and 1.5 mg/l) of the commercial insecticide Fipronil 800wg in two treatments - (i) simple exposure for 96 h, and (ii) exposure for 168 h in aquariums containing S. auriculata. In the first experiment, a mortality rate of 33.3 % was recorded at the highest Fipronil concentration (1.5 mg/l), and genotoxic parameters increased at all concentrations except 0.035 mg/L, in comparison with the control. In the second experiment, phytoremediation occurred at all the concentrations tested, with lower frequencies of cells with micronuclei, and binucleated, anucleated, and pyknotic nuclei being observed, in comparison with the first experiment. These findings highlight the potential effectiveness of S. auriculata for the phytoremediation of environments contaminated by pesticides and contribute to the understanding of the benefits of this approach for the protection and preservation of aquatic biodiversity.