Search

Metabolic dysfunction-associated steatotic liver disease (MASLD) is defined as morphofunctional changes in the liver. Studies have shown that Westernized eating patterns and environmental pollutants can directly induce the development of MASLD. This study evaluates the effect of co-exposure to interesterified palm oil (IPO) and 3,3',4,4',5-pentachlorobiphenyl (PCB-126) on the progression of MASLD in an animal model. C57BL/6 mice were fed IPO and co-exposed to PCB-126 for ten weeks. The co-exposure led to an imbalance in carbohydrate metabolism, increased systemic inflammation markers, and morphofunctional changes in the liver. These liver changes included the presence of inflammatory cells, fibrosis, alterations in aspartate transaminase (AST) and alanine transaminase (ALT) enzymes, and imbalance in gene expression related to fatty acid β-oxidation, de novo lipogenesis, mitochondrial dynamics, and endoplasmic reticulum stress. Separate exposures to IPO and PCB-126 affected metabolism and MASLD progression. Nutritional and lifestyle factors may potentiate the onset and severity of MASLD., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Aim: This study sought to evaluate the effects of LDT409, a pan-PPAR partial agonist obtained from the main industrial waste from cashew nut processing, on hepatic remodeling, highlighting energy metabolism and endoplasmic reticulum (ER) stress in high-fructose-fed mice., Methods: Male C57BL/6 mice received a control diet (C) or a high-fructose diet (HFRU) for ten weeks. Then, a five-week treatment started: C, C-LDT409, HFRU, and HFRU-LDT409. The LDT409 (40 mg/kg of body weight) was mixed with the diets., Results: The HFRU diet caused insulin resistance and endoplasmic reticulum (ER) stress. High Pparg and decreased Ppara expression increased steatosis and pro-fibrogenic gene expression in livers of HFRU-fed mice. Suppressed lipogenic factors, orchestrated by PPAR-gamma, and mitigated ER stress concomitant with the increase in beta-oxidation driven by PPAR-alpha mediated the LDT409 beneficial effects., Conclusions: LDT409 may represent a potential low-cost approach to treat metabolic dysfunction-associated steatotic liver disease, which does not currently have a specific treatment., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

The coordination of the Lewis superacid tris(pentafluorophenyl)alane (AlCF) to phosphine-supported, group 6 bis(dinitrogen) complexes [ML 2 (N 2 ) 2 ] is explored, with M = Cr, Mo or W and L = dppe (1,2-bis(diphenylphosphino)ethane), depe (1,2-bis(diethylphosphino)ethane), dmpe (1,2-bis(dimethylphosphino)ethane) or 2 × PMe 2 Ph. Akin to tris(pentafluorophenyl)borane (BCF), AlCF can form 1 : 1 adducts by coordination to one distal nitrogen of general formula trans -[ML 2 (N 2 ){(μ-η 1 :η 1 -N 2 )Al(C 6 F 5 ) 3 }]. The boron and aluminium adducts are structurally similar, showing a comparable level of N 2 push-pull activation. A notable exception is a bent (BCF adducts) vs. linear (AlCF adducts) M-N-N-LA motif (LA = Lewis acid), explained computationally as the result of steric repulsion. A striking difference arose when the formation of two-fold adducts was conducted. While in the case of BCF the 2 : 1 Lewis pairs could be observed in equilibrium with the 1 : 1 adduct and free borane but resisted isolation, AlCF forms robust 2 : 1 adducts trans -[ML 2 {(μ-η 1 :η 1 -N 2 )Al(C 6 F 5 ) 3 } 2 ] that isomerise into a more stable cis configuration. These compounds could be isolated and structurally characterized, and represent the first examples of trinuclear heterometallic complexes formed by Lewis acid-base interaction exhibiting p and d elements. Calculations also demonstrate that from the bare complex to the two-fold aluminium adduct, substantial decrease of the HOMO-LUMO gap is observed, and, unlike the trans adducts (1 : 1 and 1 : 2) for which the HOMO was computed to be a pure d orbital, the one of the cis -trinuclear compounds mixes a d orbital with a π* one of each N 2 ligands. This may translate into a more favourable electrophilic attack on the N 2 ligands instead of the metal centre, while a stabilized N 2 -centered LUMO should ease electron transfer, suggesting Lewis acids could be co-activators for electro-catalysed N 2 reduction. Experimental UV-vis spectra for the tungsten family of compounds were compared with TD-DFT calculations (CAM-B3LYP/def2-TZVP), allowing to assign the low extinction bands found in the visible spectrum to unusual low-lying MLCT involving N 2 -centered orbitals. As significant red-shifts are observed upon LA coordination, this could have important implications for the development of visible light-driven nitrogen fixation., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Growing obesity is linked to shifts in dietary patterns, particularly the increased intake of ultra-processed high-fat foods. This study aimed to evaluate the effects of interesterified palm oil consumption on glucose homeostasis, adipose tissue remodeling, and hepatic lipogenesis in C57BL/6 mice fed a high-fat diet. Sixty C57BL/6 mice were divided into four groups (n = 15): the control group (C) fed a standard diet (4% soybean oil), the high-fat group (HF) (23.8% lard), the high palm oil fat group (HFP) (23.8% palm oil), and the high interesterified palm fat group (HFI) (23.8% interesterified palm oil) for 8 weeks (all groups received 50% energy from lipids). The HFI group exhibited higher body mass than the HF group (+ 11%, P < 0.05), which was attributed to an increased percentage of fat mass. Plasma concentrations of IL-6, insulin, and HOMA-IR were also elevated in the HFI group. Both the HFP and HFI groups showed hypertrophied adipocytes and pancreatic islets, increased alpha and beta cell masses, hepatic steatosis, low expression of genes related to beta-oxidation, and upregulated lipogenesis. In conclusion, the consumption of interesterified palm oil alters inflammatory and glucose profiles., (© 2024. The Author(s).)

Two new spin crossover (SCO) Fe(III) compounds were prepared, their structures were analysed and their magnetic properties were investigated. An exhaustive analysis of the effects of halogen substitution and aromatic ring functionalisation on the magnetic properties of non-solvated Fe(III) perchlorate complexes has been performed. Through comparative analysis, different magnetic profiles were found for the compounds studied, namely F (1), Cl (2), H (3), Br (4a, 4b), and I (5). Using tools like Hirshfeld analysis, the study revealed patterns in octahedral distortions and deviations from the ideal octahedral geometry. The SCO phenomenon as the conducting wire in this study, emphasises the influence of intermolecular interactions on the low spin (LS) to high spin (HS) transitions in these halogen-substituted complexes. The prevalence of H⋯H contributions has been demonstrated, albeit being the weakest and an inverse strength relationship in H⋯X interactions ranging from F to I. The findings not only interpret the intricate balance between halogen substitution, functionalisation, and intermolecular interactions in modulating magnetic properties but also direct future works in designing similar molecular systems.

The discovery of metabolically active brown adipose tissue (BAT) in human adults and the worldwide increase in obesity and obesity-related chronic noncommunicable diseases (NCDs) has made BAT a therapeutic target in the last two decades. The potential of BAT to oxidize fatty acids rapidly and increase energy expenditure inversely correlates with adiposity, insulin and glucose resistance, and cardiovascular and metabolic diseases. Currently, BAT is recognized by a new molecular signature; several BAT-derived molecules that act positively on target tissues have been identified and collectively called batokines. Bioactive compounds present in foods are endowed with thermogenic properties that increase BAT activation signaling. Understanding the mechanisms that lead to BAT activation and the batokines secreted by it within the thermogenic state is fundamental for its recruitment and management of obesity and NCDs. This review contributes to recent updates on the morphophysiology of BAT, its endocrine role in obesity, and the main bioactive compounds present in foods involved in classical and nonclassical thermogenic pathways activation., (© 2024 Wiley‐VCH GmbH.)

The rising fructose intake in sugar-sweetened beverages and ultra-processed foods relates to the high incidence of nonalcoholic fatty liver disease. This study aimed to examine the effects of long-term high-fructose diet intake (for 16 or 20 weeks) on progressive hepatic damage, focusing on the endoplasmic reticulum stress markers and fibrogenesis as possible triggers of liver fibrosis. Forty 3-month-old male C57BL/6J mice were randomly divided into four nutritional groups: C16 (control diet for 16 weeks), C20 (control diet for 20 weeks), HFRU16 (high-fructose diet for 16 weeks), and HFRU20 (high-fructose diet for 20 weeks). Both HFRU groups showed oral glucose intolerance and insulin resistance, but only the HFRU20 group exhibited increased inflammation. The increased lipogenic and endoplasmic reticulum stress markers triggered hepatic fibrogenesis. Hence, time-dependent perivascular fibrosis with positive immunostaining for alpha-smooth muscle actin and reelin in HFRU mice was observed, ensuring fibrosis development in this mouse model. Our study showed time-dependent and progressive damage on hepatic cytoarchitecture, with maximization of hepatic steatosis without overweight in HFRU20 mice. ER stress and liver inflammation could mediate hepatic stellate cell activation and fibrogenesis, emerging as targets to prevent NAFLD progression and fibrosis onset in this dietary model.

Background: Oral isotretinoin (ISO) is the drug of choice for the treatment of severe acne. For photoaging treatment, ISO has been proved to be effective in some controlled and noncontrolled trials and is an alternative to topical retinoic acid (RA) therapy, which causes an expected skin irritation., Objective: To evaluate and compare the skin remodeling in patients taking ISO 20 mg 3 times a week for 12 weeks and 12 weeks after the end of the treatment to quantify collagen I and collagen III augmentation., Material and Methods: Immunohistochemical studies were performed to evaluate the expression of collagen I and collagen III, metalloproteinases (MMPs) -1, -3, -7, -9, -12, and the tissue inhibitor of MMP type-1 (TIMP-1) of the skin of 20 45 to 50-year-old women through morphometry in a semiquantitative method. The inclusion criteria were facial aging 2 and 3 of Glogau's classification, with phototypes between II and V who had not entered menopause. Biopsies of the skin of the left preauricular region were performed at three different times: pre-treatment (T0), end of 12-week treatment (T1), and 12 weeks posttreatment (T2)., Results: Collagen fibers I and III increased with statistical significance in T1 (50.7%; P = 0.012) but not in T2 (49.7%), which in turn was higher than in T0 (47.2%) for collagen I and T1 (33.3%; P = 0.002) but not in T2 (32.7%), and also was higher than T0 (32.0%) for collagen III. MMP-9 presented a decreased activity with statistical significance in T1 (P = 0.047) and T2 (P = 0.058). MMP-1 showed a reduction in T2 only (P = 0.015). MMPs -3, -7, -12, and TIMP-1 did not present significant modification in their expressions during or after the treatment., Conclusions: Low-dose ISO is effective in remodeling the extracellular matrix (ECM). This study found that the increase of collagen occurs through the augmentation of both collagen I and collagen III fibers. With originality, it was possible to verify the durability of these fibers for at least 12 weeks. This may be related to the decrease in MMP-9 expression verified at the end of the treatment and 12 weeks posttreatment., (© 2023 the International Society of Dermatology.)

Pd(II) catalysts, particularly the acetate salt in acetic acid, tended to favor regioselective C-H activation of quinoline N-oxides (QOs) at the C2 position. However, Pd(II)Cl 2 was shown to catalyze their C-H activation at C8 and, in the presence of water, C8-H activation was accompanied by the formation of 2-quinolinones. The aim of the DFT study described in this work was to shed light on the complete mechanism of these competing catalytic reactions, when PdCl 2 reacts with QO and benzaldehyde in dichloroethane. C-H activation of QO was the first step of the reaction and involved either a metallacycle, with a C QO -Pd(II) σ-bond and a C(8)-H-Pd(II) agostic bond, or an η 3 -QO complex, with three carbon atoms of the heteroring of QO binding PdCl 2 . The first situation led to the unusual C8 activation and the second to C2 activation. The σ-metallacycle undergoes C8-H activation and the energy of the TOF determining the transition state to form the product is ∼17 kcal mol -1 , while for the reaction through the π-metallacycle (C2-H activation) the corresponding energy is higher (∼29 kcal mol -1 ) and thus is not competitive under the same conditions. The reaction proceeding through the σ-complex, activating the C8 position, is preferred, in agreement with experimental results. Both reactions involve oxidation of Pd(II) to Pd(IV) and the catalyst is regenerated. When small amounts of water are added to the reaction mixture, C8-H activation (acylation) results from the same σ-metallacycle with the same barrier, but the simultaneous formation of 2-quinolinones is more complicated. It starts with OH - attack at the C2 position, and is followed by the migration of two hydrogen atoms, and the final reductive elimination step ends with Pd(0). The higher barriers for the migration and reoxidation of Pd(0) are associated with the more demanding reaction conditions. The different reactivity of Pd(II)(OAc) 2 under analogous conditions is clarified, as it is only capable of forming the above mentioned π-complex and thus of activating the C2 position of QO. This catalyst can preferentially activate the C8-H bond under rather different conditions, including in particular acetic acid medium, as shown by other authors.

Objective: This study aimed to evaluate the differential role of a high-fat diet (HF) or high-fructose diet (HFRU) on white adipose tissue and brown adipose tissue remodeling in C57BL/6 mice. Methods: The animals were randomly assigned to receive HF (50% of energy as lipids), HFRU (50% of energy as fructose), or a control diet (C, 10% of energy as lipids) for 12 weeks. Results: The HF group became overweight from the 7th week onwards, but both HF and HFRU groups showed hyperinsulinemia, oral glucose intolerance, and adverse adipose tissue remodeling. HF and HFRU groups showed interscapular brown adipose tissue whitening, tough the reduced Q A [nuclei] suggested maximized brown adipocyte dysfunction due to the HFRU diet. In contrast, HF and HFRU diets exerted similar effects upon subcutaneous white adipocytes, with a similar average cross-sectional area. Immunohistochemistry confirmed the whitening enhancement with reduced UCP1 immunodensity in the HFRU group. Conclusion: In conclusion, HF and HFRU diets had indistinguishable effects upon white adipocyte morphology, but the HFRU diet provoked a more pronounced whitening than the HF diet after a 12-week protocol. These results point to the silent and harmful impact that excessive fructose has upon the metabolism of lean mice.

This study aimed to evaluate the preventive and therapeutic effects of coffee consumption on molecular changes and adipose tissue remodeling in a murine model of high-fat diet-induced obesity. Three-month-old C57BL/6 mice were initially divided into three groups, namely, control (C), high-fat (HF), and coffee prevention (HF-CP) groups, and the HF group was subdivided at the end of the 10th week into two subgroups, an HF group and a coffee treatment (HF-CT) group; thus, a total of four groups were investigated at the 14th week of the experiment. The HF-CP group had lower body mass than the HF group (-7%, P < .05) and a better distribution of adipose tissue. Both groups that received coffee (HF-CP and HF-CT) showed improved glucose metabolism compared with the HF group. Coffee consumption also attenuated adipose tissue inflammation and showed decreased macrophage infiltration and lower IL-6 levels compared with the HF group (HF-CP: -337% %, P < .05; HF-CT: -275%, P < .05). Hepatic steatosis and inflammation were attenuated in the HF-CP and HF-CT groups. The HF-CP group showed more pronounced expression of genes involved in adaptive thermogenesis and mitochondrial biogenesis (PPARγ, Prdm16, Pcg1α, β3-adrenergic receptor, Ucp-1, and Opa-1) than the other experimental groups. Preventive coffee consumption associated with a high-fat diet ameliorates the metabolic profile related to the development of obesity and its comorbidities., Competing Interests: Declaration of competing interests The authors declare that there are no conflicts of interest., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Aims: The extracellular matrix (ECM) is fundamental for the normal endocrine functions of pancreatic islet cells and plays key roles in the pathophysiology of type 2 diabetes. Here we investigated the turnover of islet ECM components, including islet amyloid polypeptide (IAPP), in an obese mouse model treated with semaglutide, a glucagon-like peptide type 1 receptor agonist., Main Methods: Male one-month-old C57BL/6 mice were fed a control diet (C) or a high-fat diet (HF) for 16 weeks, then treated with semaglutide (subcutaneous 40 μg/kg every three days) for an additional four weeks (HFS). The islets were immunostained and gene expressions were assessed., Key Findings: Comparisons refer to HFS vs HF. Thus, IAPP immunolabeling and beta-cell-enriched beta-amyloid precursor protein cleaving enzyme (Bace2, -40 %) and heparanase immunolabeling and gene (Hpse, -40 %) were mitigated by semaglutide. In contrast, perlecan (Hspg2, +900 %) and vascular endothelial growth factor A (Vegfa, +420 %) were enhanced by semaglutide. Also, semaglutide lessened syndecan 4 (Sdc4, -65 %) and hyaluronan synthases (Has1, -45 %; Has2, -65 %) as well as chondroitin sulfate immunolabeling, and collagen type 1 (Col1a1, -60 %) and type 6 (Col6a3, -15 %), lysyl oxidase (Lox, -30 %) and metalloproteinases (Mmp2, -45 %; Mmp9, -60 %)., Significance: Semaglutide improved the turnover of islet heparan sulfate proteoglycans, hyaluronan, chondroitin sulfate proteoglycans, and collagens in the islet ECM. Such changes should contribute to restoring a healthy islet functional milieu and should reduce the formation of cell-damaging amyloid deposits. Our findings also provide additional evidence for the involvement of islet proteoglycans in the pathophysiology of type 2 diabetes., Competing Interests: Declaration of competing interest The authors declare no competing interests., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Aim: To evaluate the effects of single PPARα or PPARγ activation, and their synergism (combined PPARα/γ activation) upon the gut-adipose tissue axis, focusing on the endotoxemia and upstream interscapular brown adipose tissue (iBAT) function in high-saturated fat-fed mice., Methods: Male C57BL/6 mice received a control diet (C, 10% lipids) or a high-fat diet (HF, 50% lipids) for 12 weeks. Then, the HF group was divided to receive the treatments for four weeks: HFγ (pioglitazone, 10 mg/kg), HFα (WY-14643, 3.5 mg/kg), and HFα/γ (tesaglitazar, 4 mg/kg)., Results: The HF group exhibited overweight, oral glucose intolerance, gut dysbiosis, altered gut permeability, and endotoxemia, culminating in iBAT whitening. The downregulation of LPS-Tlr4 signaling underpinned reduced inflammation and improved lipid metabolism in iBAT in the HFα/γ group, the unique to show normalized body mass and increased energy expenditure., Conclusion: PPARα/γ synergism treated obesity by ameliorating the gut-adipose tissue axis, where restored gut microbiota and permeability controlled endotoxemia and rescued iBAT whitening through favored thermogenesis., Competing Interests: Declaration of competing interest The authors declare that there are no conflicts of interest., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Competing Interests: Declaration of competing interest The authors declare no conflict of interest.

Semaglutide (GLP-1 agonist) was approved for treating obesity. Although the effects on weight loss and metabolism are known, the responses of adipocytes to semaglutide are yet limited. C57BL/6 male mice (n = 20/group) were fed a control diet (C) or a high-fat (HF) diet for 16 weeks and then separated into four groups (n = 10/group) for an additional four weeks: C, C diet and semaglutide, HF, and HF diet and semaglutide. Epididymal white adipose tissue (eWAT) and subcutaneous white adipose tissue (sWAT) fat pads were studied with biochemistry, immunohistochemistry/fluorescence, stereology, and reverse transcription-quantitative polymerase chain reaction. In obese mice, semaglutide reduced the fat pad masses (eWAT, -55%; sWAT, -40%), plasmatic cytokines, and proinflammatory gene expressions: tumor necrosis factor-alpha (-60%); interleukin (IL)-6 (-55%); IL-1 beta (-40%); monocyte chemoattractant protein-1 (-90%); and leptin (-80%). Semaglutide also lessened endoplasmic reticulum (ER) stress genes of activating transcription factor-4 (-85%), CCAAT enhancer-binding protein homologous protein (-55%), and growth arrest and DNA damage-inducible gene 45 (-45%). The obese mice's adipocyte hypertrophy and macrophage infiltration were equally reduced by semaglutide. Semaglutide enhanced multiloculation and uncoupled protein 1 (UCP1) labeling in obese mice: peroxisome proliferator-activated receptor-alpha (+560%) and gamma (+150%), fibronectin type III domain-containing protein 5 (+215%), peroxisome proliferator-activated receptor-alpha coactivator (+110%), nuclear respiratory factor 1 (+260%), and mitochondrial transcription factor A (+120%). Semaglutide also increased thermogenetic gene expressions for the browning phenotype maintenance: beta-3 adrenergic receptor (+520%), PR domain containing 16 (+90%), and Ucp1 (+110%). In conclusion, semaglutide showed significant beneficial effects beyond weight loss, directly on fat pads and adipocytes of obese mice, remarkably anti-inflammatory, and reduced adipocyte size and ER stress. Besides, semaglutide activated adipocyte browning, improving UCP1, mitochondrial biogenesis, and thermogenic marker expressions help weight loss., (© 2022 John Wiley & Sons Ltd.)

Brown adipose tissue (BAT) remains active in adults, oxidizing fatty acids or glucose and releasing energy in the form of heat. Brown adipocytes and enhanced thermogenesis are targets for treating obesity and its comorbidities. BAT shows high synthesis activity and secretes several signaling molecules. The brown adipokines, or batokines, take action in an autocrine, paracrine, and endocrine manner. Batokines have a role in the homeostasis of the cardiovascular system, central nervous system, white adipose tissue, liver, and skeletal muscle and exert beneficial effects on BAT. The systemic function of batokines gives BAT an endocrine organ profile. Besides, the batokines Fibroblast Growth Factor-21, Vascular Endothelial Growth Factor A, Bone Morphogenetic Protein 8, Neuregulin 4, Myostatin, and Interleukin-6 emerge as targets to treat obesity and its comorbidities, deserving attention. This review outlines the role of six emerging batokines on BAT and their cross-talk with other organs, focusing on their physiological significance and diet-induced changes., (© 2022 Walter de Gruyter GmbH, Berlin/Boston.)

Chronic obesity damages the cytoarchitecture of brown adipose tissue (BAT), leading to whitening of brown adipocytes and impaired thermogenesis, characterizing BAT dysfunction. Understanding the pathways of whitening progression can bring new targets to counter obesity. This study aimed to evaluate the chronic effect (12, 16, and 20 weeks) of a high-fat diet (50% energy as fat) upon energy expenditure, thermogenic markers, and pathways involved in BAT whitening in C57BL/6J mice. Sixty adult male mice comprised six nutritional groups, where the letters refer to the diet type (control, C or high-fat, HF), and the numbers refer to the period (in weeks) of diet administration: C12, HF12, C16, HF16, C20, and HF20. After sacrifice, biochemical, molecular, and stereological analyses addressed the outcomes. The HF groups had overweight, oral glucose intolerance, and hyperleptinemia, resulting in progressive whitening of BAT and decreased numerical density of nuclei per area of tissue compared to age-matched control groups. In addition, the whitening maximization was related to altered batokines gene expression, decreased nonshivering thermogenesis, and body temperature, resulting in low energy expenditure. The HF20 group showed enlarged adipocytes with stable and dysfunctional lipid droplets, followed by inflammation and ER stress. In conclusion, chronic HF diet intake caused time-dependent maximization of whitening with defective nonshivering thermogenesis. Long-term BAT dysfunction includes down-regulated vascularization markers, upregulated inflammasome activation, and ER stress markers., (Copyright © 2022. Published by Elsevier Inc.)

Background: Obesity and comorbidities onset encompass gut dysbiosis, altered intestinal permeability, and endotoxemia. Treatments that target gut dysbiosis can cope with obesity and nonalcoholic fatty liver disease (NAFLD) management. Peroxisome proliferator-activated receptor (PPAR)-alpha activation and dipeptidyl-peptidase-4 (DPP-4) inhibition alleviate NAFLD, but the mechanism may involve gut microbiota modulation and merits further investigation., Aim: To address the effects of PPAR-alpha activation and DPP-4 inhibition (isolated or combined) upon the gut-liver axis, emphasizing inflammatory pathways in NAFLD management in high-fat-fed C57BL/6J mice., Methods: Male C57BL/6J mice were fed a control diet (C, 10% of energy as lipids) or a high-fat diet (HFD, 50% of energy as lipids) for 12 wk, when treatments started, forming the groups: C, HF, HFA (HFD + PPAR-alpha agonist WY14643, 2.5 mg/kg body mass), HFL (HFD + DPP-4 inhibitor linagliptin, 15 mg/kg body mass), and HFC (HFD + the combination of WY14643 and linagliptin)., Results: The HFD was obesogenic compared to the C diet. All treatments elicited significant body mass loss, and the HFC group showed similar body mass to the C group. All treatments tackled oral glucose intolerance and raised plasma glucagon-like peptide-1 concentrations. These metabolic benefits restored Bacteroidetes / Firmicutes ratio, resulting in increased goblet cells per area of the large intestine and reduced lipopolysaccharides concentrations in treated groups. At the gene level, treated groups showed higher intestinal Mucin 2 , Occludin , and Zo-1 expression than the HFD group. The reduced endotoxemia suppressed inflammasome and macrophage gene expression in the liver of treated animals. These observations complied with the mitigation of liver steatosis and reduced hepatic triacylglycerol, reassuring the role of the proposed treatments on NAFLD mitigation., Conclusion: PPAR alpha activation and DPP-4 inhibition (isolated or combined) tackled NAFLD in diet-induced obese mice by restoration of gut-liver axis. The reestablishment of the intestinal barrier and the rescued phylogenetic gut bacteria distribution mitigated liver steatosis through anti-inflammatory signals. These results can cope with NAFLD management by providing pre-clinical evidence that drugs used to treat obesity comorbidities can help to alleviate this silent and harmful liver disease., Competing Interests: Conflict-of-interest statement: The authors have no conflict of interest to declare., (©The Author(s) 2022. Published by Baishideng Publishing Group Inc. All rights reserved.)

Obesity causes white and brown adipocyte dysfunction, reducing browning and stimulating whitening. Drugs that tackle adipocyte dysfunction through thermogenesis stimulation could be used to treat obesity. This study sought to address whether a combination of the PPAR-alpha agonist (WY14643) and DPP4i (linagliptin) potentiates browning and mitigates adipose tissue dysfunction, emphasizing the pathways related to browning induction and the underlying thermogenesis in high-fat-fed mice. Adult male C57BL/6 mice were randomly assigned to receive a control diet (C, 10% lipids) or a high-fat diet (HF, 50% lipids) for 12 weeks. Experiment 1 aimed to evaluate whether 5 weeks of combined therapy was able to potentiate browning using a five-group design: C, HF, HFW (monotherapy with WY14643, 2.5 mg/kg body mass), HFL (monotherapy with linagliptin, 15 mg/kg body mass), and HFC (a combination of both drugs). Experiment 2 further addressed the pathways involved in browning maximization using a four-group study design: C, CC (C diet plus the drug combination), HF, and HFC (HF diet plus the drug combination). The HF group showed overweight, oral glucose intolerance, sWAT adipocyte hypertrophy, and reduced numerical density of nuclei per area of BAT confirming whitening. Only the combined treatment normalized these parameters in addition to body temperature increase, browning induction, and whitening rescue. The high expression of thermogenic marker genes parallel to reduced expression of inflammatory and endoplasmic reticulum stress genes mediated the beneficial findings. Hence, the PPAR-alpha agonist and DPP-4i combination is a promising target for obesity control by inducing functional brown adipocytes, browning of sWAT, and enhanced adaptive thermogenesis.

Accumulating evidence indicates that dietary phenolic compounds can prevent obesity-related disorders. We investigated whether the consumption of polyphenol-rich jabuticaba peel and seed powder (JPSP) could ameliorate the progression of diet-induced obesity in mice. Male mice were fed a control diet or a high-fat (HF) diet for 9 weeks. After this period, mice were fed control, HF or HF diets supplemented with 5 % (HF-J5), 10 % (HF-J10) or 15 % (HF-J15) of JPSP, for 4 additional weeks. Supplementation with JPSP not only attenuated HF-induced weight gain and fat accumulation but also ameliorated the pro-inflammatory response associated with obesity, as evidenced by the absence of mast cells in the visceral depot accompanied by lower IL-6 and TNF-α at the tissue and circulating levels. JPSP-supplemented mice also exhibited smaller-sized adipocytes, reduced levels of leptin and higher levels of adiponectin, concomitant with improved glucose metabolism and insulin sensitivity. The magnitude of the observed effects was dependent on JPSP concentration with HF-J10- and HF-J15-fed mice showing metabolic profiles similar to control. This study reveals that the consumption of JPSP protects against the dysfunction of the adipose tissue and metabolic disturbances in obese mice. Thus, these findings indicate the therapeutic potential of the phenolic-rich JPSP in preventing obesity-related disorders.

There are significant injuries of pancreatic islets due to obesity and insulin resistance. Therefore, GLP-1 receptor agonists like Semaglutide might benefit the islet structural remodeling and its endocrine function in diet-induced obese mice. One-month-old male C57BL/6 mice were allotted into two dietary groups (n = 60/group) and fed for 16 weeks a control diet (C) or a high‒fat diet (HF). Then, for an additional four weeks, the main groups were resampled to include treatment (Semaglutide, S, 40 μg/kg), or paired feed with the treated group (PF), totaling six groups (n = 20/group): C, CS, CPF, HF, HFS, HFPF. Biochemistry, stereology, immunohistochemistry/immunofluorescence, confocal microscopy, and RT-qPCR were used in the study. The mouse model reproduced metabolism and bodily changes due to diet-induced obesity. Pancreatic islet hypertrophy was observed with alpha- and beta-cell remodeling, cell disarray, and apoptosis. Semaglutide increased islet cell proliferation and recovered islet size and alpha- and beta-cell masses. The changes include recovery of glucose and hormone levels, reduction of pro-inflammatory markers, improvement of pancreatic duodenal homeobox 1 (PDX-1), glucose transporter 2 (GLUT-2), v-maf musculoaponeurotic fibrosarcoma oncogene homolog A (MAF-A), and peroxisome proliferator-activated receptors (PPAR) -gamma. In conclusion, damage to the pancreatic islet caused by insulin resistance and the attempt to adapt the islet of obese mice involved different pathways, especially the pro-inflammatory pathway, PDX1, and PPAR-alpha and gamma. Semaglutide showed beneficial effects on these pathways, reducing the lesion on the islet. However, the weight loss influence of Semaglutide was of little relevance in the pancreatic islet., (Copyright © 2022 Elsevier B.V. and Société Française de Biochimie et Biologie Moléculaire (SFBBM). All rights reserved.)

The consumption of a high-fat diet can cause metabolic syndrome and induces host gut microbial dysbiosis and non-alcoholic fatty liver disease (NAFLD). We evaluated the effect of polyphenol-rich jaboticaba peel and seed powder (JPSP) on the gut microbial community composition and liver health in a mouse model of NAFLD. Three-month-old C57BL/6 J male mice, received either a control (C, 10% of lipids as energy, n = 16) or high-fat (HF, 50% of lipids as energy, n = 64) diet for nine weeks. The HF mice were randomly subdivided into four groups (n = 16 in each group), three of which (HF-J5, HF-J10, and HF-J15) were supplemented with dietary JPSP for four weeks (5%, 10%, and 15%, respectively). In addition to attenuating weight gain, JPSP consumption improved dyslipidemia and insulin resistance. In a dose-dependent manner, JPSP consumption ameliorated the expression of hepatic lipogenesis genes (AMPK, SREBP-1, HGMCoA, and ABCG8). The effects on the microbial community structure were determined in all JPSP-supplemented groups; however, the HF-J10 and HF-J15 diets led to a drastic depletion in the species of numerous bacterial families (Bifidobacteriaceae, Mogibacteriaceae, Christensenellaceae, Clostridiaceae, Dehalobacteriaceae, Peptococcaceae, Peptostreptococcaceae, and Ruminococcaceae) compared to the HF diet, some of which represented a reversal of increases associated with HF. The Lachnospiraceae and Enterobacteriaceae families and the Parabacteroides, Sutterella, Allobaculum, and Akkermansia genera were enriched more in the HF-J10 and HF-J15 groups than in the HF group. In conclusion, JPSP consumption improved obesity-related metabolic profiles and had a strong impact on the microbial community structure, thereby reversing NAFLD and decreasing its severity., (Copyright © 2021 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Antiphospholipid syndrome (APS) is a systemic autoimmune disease characterized by arterial and venous thrombotic manifestations and/or pregnancy-related complications in patients with persistent antiphospholipid (aPL) antibodies. The introduction of Sapporo's classification criteria allowed uniformity in the classification of this pathology, representing a considerable advance in its diagnosis. However, currently some doubts about the application of these criteria still persist. The aim of this study was to contribute to the better understanding of APS by the assessment of aPL prevalence, the association between clinical and laboratory tests, and evaluation of the aPL confirmatory profile. In this study, 1,179 samples from patients with suspected APS of both genders, without age restrictions, who were advised to test for complete aPL's profile were analyzed. The samples were tested for lupus anticoagulant (LAC), anticardiolipin immunoglobulin (Ig) G/IgM and anti-β-2-glycoprotein I IgG/IgM antibodies. Patient samples with isolated test requests for analysis and samples from patients under the influence of anticoagulants or in an infectious process were excluded. The overall positivity found was 17.9% and the most frequent aPL was LAC. The antibodies were determined in isolation and in association. The prevalence of triple positivity was 0.8% and double positivity was 1.8%. Positivity was higher in inpatient/emergency services compared with outpatient services. There was a higher positivity in individuals over 41 years, males, patients with systemic lupus erythematosus, kidney complications, and deep vein thrombosis/thrombophlebitis. The positivity confirmation with second sample was 39.5% and the confirmation profile shows that 50.6% of samples confirmed with same positivity profile; 17.3% with a different profile and regarding to these, 2.5% of the samples confirmed positivity with a different antibody from the previously detected. This study suggests that the aPL's positivity tends to increase with age, showing that the aPL's testing should be avoided during an acute event and reinforces the need for complete aPL laboratory profile in the second sample and subsequent determinations., Competing Interests: Conflict of Interest None declared., (The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution License, permitting unrestricted use, distribution, and reproduction so long as the original work is properly cited. ( https://creativecommons.org/licenses/by/4.0/ ).)

Objective: Evaluate the association of late treatment with acetaminophen vs. immediate surgical ligation with death or neurodevelopmental impairment (NDI) among extremely low gestational age neonates (ELGANs) with persistent patent ductus arteriosus (pPDA)., Study Design: Retrospective comparative epoch study of ELGANs with pPDA being considered for surgical ligation. ELGANs in epoch 1 (2009-2012) were referred for ligation, while infants in epoch 2 (2012-2015) were treated with oral acetaminophen and referred for ligation in the absence of improvement. The primary outcome was a composite of death/NDI at 18-24 months., Results: Ninety-two ELGANs with median[IQR] GA 25.2 weeks [24.4, 26.3] had pPDA (43 in epoch 1, 49 in -epoch 2) with acetaminophen-exposed neonates receiving 7 days [7, 7] of treatment. ELGANs in epoch 2 had reduced ligation (aOR 0.30; 95%CI: [0.11, 0.87]), but there was no difference in death/NDI (aOR 1.03; 95%CI: [0.30, 3.56])., Conclusions: Late treatment with acetaminophen to avoid surgery for pPDA is associated with reduced ligation but no difference in death/NDI, supporting the safety and effectiveness of this approach., (© 2021. The Author(s), under exclusive licence to Springer Nature America, Inc.)

Obesity challenges lipid and carbohydrate metabolism. The resulting glucolipotoxicity  causes endoplasmic reticulum (ER) dysfunction, provoking the accumulation of immature proteins, which triggers the unfolded protein reaction (UPR) as an attempt to reestablish ER homeostasis. When the three branches of UPR fail to correct the unfolded/misfolded proteins, ER stress happens. Excessive dietary saturated fatty acids or fructose exhibit the same impact on the ER stress, induced by excessive ectopic fat accumulation or rising blood glucose levels, and meta-inflammation. These metabolic abnormalities can alleviate through dietary interventions. Many pathways are disrupted in adipose tissue, liver, and pancreas during ER stress, compromising browning and thermogenesis, favoring hepatic lipogenesis, and impairing glucose-stimulated insulin secretion within pancreatic beta cells. As a result, ER stress takes part in obesity, hepatic steatosis, and diabetes pathogenesis, arising as a potential target to treat or even prevent metabolic diseases. The scientific community seeks strategies to alleviate ER stress by avoiding inflammation, apoptosis, lipogenesis suppression, and insulin sensitivity augmentation through pharmacological and non-pharmacological interventions. This comprehensive review aimed to describe the contribution of excessive dietary fat or sugar to ER stress and the impact of this adverse cellular environment on adipose tissue, liver, and pancreas function., (© 2021. Springer-Verlag GmbH Germany, part of Springer Nature.)

This work provides new insights from our team regarding advances in targeting canonical and non-canonical nucleic acid structures. This modality of medical treatment is used as a form of molecular medicine specifically against the growth of cancer cells. Nevertheless, because of increasing concerns about bacterial antibiotic resistance, this medical strategy is also being explored in this field. Up to three strategies for the use of DNA as target have been studied in our research lines during the last few years: (1) the intercalation of phenanthroline derivatives with duplex DNA; (2) the interaction of metal complexes containing phenanthroline with G-quadruplexes; and (3) the activity of Mo polyoxometalates and other Mo-oxo species as artificial phosphoesterases to catalyze the hydrolysis of phosphoester bonds in DNA. We demonstrate some promising computational results concerning the favorable interaction of these small molecules with DNA that could correspond to cytotoxic effects against tumoral cells and microorganisms. Therefore, our results open the door for the pharmaceutical and medical applications of the compounds we propose.

Objectives: To characterize the relationship of echocardiographic markers of left heart overload and flow in peripheral major end-organ vessels (eg, celiac artery) with the presence of reversed holodiastolic flow in the descending aorta, considered a surrogate marker of an increased transductal shunt volume, in preterm patients with a patent ductus arteriosus (PDA)., Methods: This work was a retrospective study of data from echocardiography performed to investigate the hemodynamic significance of a PDA in preterm patients. We studied differences in echocardiographic markers of the PDA shunt volume according to patterns of flow in the postductal descending aorta (no PDA, PDA with antegrade diastolic flow, and PDA with reversed diastolic flow). The strength of the association between each echocardiographic marker and the presence of aortic holodiastolic flow reversal was investigated., Results: We studied 137 patients with a median (interquartile range) birth weight of 850 (694-1030) g and a median gestational age of 25 (24-27) weeks. Among patients with a PDA (113), those with diastolic flow reversal in the descending aorta (44) presented had increased echocardiographic markers representative of the shunt volume (increased left ventricular output, left atrial-to-aortic ratio, pulmonary vein D wave, and shorter isovolumic relaxation time) compared to those with aortic antegrade diastolic flow. A positive, albeit weak, correlation between diastolic flow reversal and shunt volume echocardiographic markers was found. Abnormal diastolic flow in the celiac artery had the strongest correlation (R 2  = 0.24)., Conclusions: In preterm patients with a PDA, echocardiographic markers of the shunt volume were more abnormal in patients with reversed diastolic flow in the descending aorta. These data support the assumption that variance in these markers are related to the shunt volume, which needs consideration when adjudicating hemodynamic significance., (© 2020 American Institute of Ultrasound in Medicine.)

Phosphoester hydrolysis is an important chemical step in DNA repair. One archetypal molecular model of phosphoesters is para-nitrophenylphosphate (pNPP). It has been shown previously that the presence of molecular metal oxide [Mo 7 O 24 ] 6- may catalyse the hydrolysis of pNPP through the partial decomposition of polyoxomolybdate framework resulting in a [(PO 4 ) 2 Mo 5 O 15 ] 6- product. Real-time monitoring of the catalytic system using electrospray ionisation mass spectrometry (ESI-MS) provided a glance into the species present in the reaction mixture and identification of potential catalytic candidates. Following up on the obtained spectrometric data, Density Functional Theory (DFT) calculations were carried out to characterise the hypothetical intermediate [Mo 5 O 15 (pNPP) 2 (H 2 O) 6 ] 6- that would be required to form under the hypothesised transformation. Surprisingly, our results point to the dimeric [Mo 2 O 8 ] 4- anion resulting from the decomposition of [Mo 7 O 24 ] 6- as the active catalytic species involved in the hydrolysis of pNPP rather than the originally assumed {Mo 5 O 15 } species. A similar study was carried out involving the same species but substituting Mo by W. The mechanism involving W species showed a higher barrier and less stable products in agreement with the non-catalytic effect found in experimental results., (© 2021 Wiley-VCH GmbH.)

Background: High-volume systemic-to-pulmonary ductus arteriosus shunts in premature infants are associated with adverse neonatal outcomes. The role of an atrial communication (AC) in modulating the effects of a presumed hemodynamically significant patent ductus arteriosus (PDA) is poorly studied. The objective of this study was to characterize the relationship between early AC and echocardiographic indices of PDA shunt volume and clinical neonatal outcomes., Methods: A retrospective review of preterm infants (born at <32 weeks' gestation) who underwent echocardiography in the first postnatal week was performed. The cohort was divided into four groups on the basis of presence of a presumed hemodynamically significant PDA (≥1.5 vs <1.5 mm) and AC size (≤1 vs >1 mm), and echocardiographic measures of PDA shunt volume were then compared. Clinical outcomes, including chronic lung disease and intraventricular hemorrhage, were also compared among all four groups., Results: A total of 199 preterm infants (mean birth weight, 928 ± 632 g; mean gestational age, 26.6 ± 1.5 weeks) were identified; 159 infants had PDAs ≥ 1.5 mm, of whom 52 had ACs ≤ 1 mm and 107 had ACs > 1 mm. The remaining 40 infants had PDAs < 1.5 mm, of whom 23 had ACs ≤ 1 mm and 17 had ACs > 1 mm. Infants with PDAs ≥ 1.5 mm and ACs > 1 mm had higher pulmonary vein D-wave velocities (P < .05), higher left ventricular output (P < .005), higher PDA scores (P < .001), and increased rates of reversed diastolic flow in the descending aorta (P < .001), celiac artery (P < .001), and middle cerebral artery (P < .001) than infants with either PDAs < 1.5 mm or PDAs ≥ 1.5 mm and ACs ≤ 1 mm. There was no difference in the incidence of intraventricular hemorrhage, but infants with PDAs ≥ 1.5 mm and ACs > 1 mm had a higher risk for a composite outcome of chronic lung disease or death before hospital discharge (P < .05)., Conclusions: Echocardiographic evidence of ACs > 1 mm in patients with PDAs ≥ 1.5 mm during the first postnatal week may be a marker of a more pathologic hemodynamically significant PDA in premature infants. Future investigations should evaluate if early identification and treatment of patients with both high-volume PDAs and larger atrial-level communications may help mitigate adverse outcomes, such as chronic lung disease or death, in this high-risk patient population., (Copyright © 2020 American Society of Echocardiography. Published by Elsevier Inc. All rights reserved.)

Objectives: To examine the effects of a selective peroxisome proliferator-activated receptor (PPAR-α) agonist treatment on interscapular brown adipose tissue (iBAT) whitening, focusing on thermogenic, lipolysis, and lipid oxidation markers in mice fed a high-fat or high-fructose diet., Methods: Fifty animals were randomly assigned to receive a control diet (C, 10% lipids as energy), high-fat diet (HF, 50% lipids as energy), or high-fructose diet (HFRU, 50% fructose as energy) for 12 wk. Each group was redivided to begin the 5-wk treatment, totaling five experimental groups: C, HF, HF-a, HFRU, and HFRU-a. The drug was mixed with diet at the dose of 3.5 mg/kg body mass., Results: HF group was the heaviest group, and the HF and HFRU groups had glucose intolerance. PPAR-α activation alleviated these metabolic constraints. HF and HFRU groups had negative vascular endothelial growth factor A (VEGF-A) immunostaining, but only the HF group had a pattern of lipid droplet accumulation that resembled the white adipose tissue, characterizing the whitening phenomenon. Whitening in the HF group was accompanied by decreased expression of genes related to thermogenesis, β-oxidation, and antiinflammatory effects. All of them were augmented by the PPAR-α activation in HF-a and HFRU-a groups, countering the whitening in the HF-a group. Treated groups also had a lower respiratory exchange ratio than untreated groups, suggesting that lipids were used as fuel for the enhanced thermogenesis., Conclusions: The PPAR-α agonist countered iBAT whitening by inducing the thermogenic pathway and reducing the lipid droplet size, in addition to enhanced VEGF-A expression, adrenergic stimulus, and lipolysis in HF-fed mice., Competing Interests: Declaration of interests The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Fructose dietary intake affects the composition of the intestinal microbiota and influences the development of hepatic steatosis. Endotoxins produced by gram-negative bacteria alter intestinal permeability and cause bacterial translocation. This study evaluated the effects of gut microbiota modulation by a purified PPAR-alpha agonist (WY14643), a DPP-4 inhibitor (linagliptin), or their association on intestinal barrier integrity, endotoxemia, and hepatic energy metabolism in high-fructose-fed C57BL/6 mice. Fifty mice were divided to receive the control diet (C group) or the high-fructose diet (HFRU) for 12 weeks. Subsequently, the HFRU group was divided to initiate the treatment with PPAR-alpha agonist (3.5 mg/kg/BM) and DPP-4 inhibitor (15 mg/kg/BM). The HFRU group had glucose intolerance, endotoxemia, and dysbiosis (with increased Proteobacteria) without changes in body mass in comparison with the C group. HFRU group showed damaged intestinal ultrastructure, which led to liver inflammation and marked hepatic steatosis in the HFRU group when compared to the C group. PPAR-alpha activation and DPP-4 inhibition countered glucose intolerance, endotoxemia, and dysbiosis, ameliorating the ultrastructure of the intestinal barrier and reducing Tlr4 expression in the liver of treated animals. These beneficial effects suppressed lipogenesis and mitigated hepatic steatosis. In conclusion, the results herein propose a role for PPAR-alpha activation, DPP-4 inhibition, and their association in attenuating hepatic steatosis by gut-liver axis modulation in high-fructose mice model. These observations suggest these treatments as potential targets to treat hepatic steatosis and avoid its progression.

The intermittent fasting (IF) might have benefits on metabolism and food intake. Twelve-week old C57BL/6 J mice were fed a control diet (C, 10% kcal fat), a high-fat diet (HF, 50% kcal fat) or a high-fructose diet (HFru, 50% kcal fructose) for 8 weeks, then half of the animals in each group underwent IF (24 h fed, 24 h fasting) for an additional 4 weeks. Although food intake on the fed day remained the same for all groups, all fasting groups showed a reduction in body mass compared to their counterparts. IF reduced total cholesterol, triacylglycerol, fasting glucose, fasting insulin resistance index, and plasma leptin, but increased plasma adiponectin. IF reduced Leptin gene expression in the HF-IF group, but increased proinflammatory markers in the hypothalamus, also in the C-IF group. Both groups HFru-IF and C-IF, showed alterations in the leptin signaling pathway (Leptin, OBRb, and SOCS3), mainly in the HFru-IF group, suggesting leptin resistance. NPY and POMC neuropeptides labeled the neurons of the hypothalamus by immunofluorescence, corroborating qualitatively other quantitative findings of the study. In conclusion, current results are convincing in demonstrating the IF effect on central regulation of food intake control, as shown by NPY and POMC neuropeptide expressions, resulting in a lower weight gain. Besides, IF improves glycemia, lipid metabolism, and consequently insulin and leptin resistance. However, there is increased expression of inflammatory markers in mouse hypothalamus challenged by the HF and HFru diets, which in the long term may induce adverse effects., (Copyright © 2020 Elsevier Inc. All rights reserved.)

During the 2016 Zika pandemic in Brazil, women's perceptions of infection risk, ability to adhere to Zika prevention strategies, or access to services following exposure were not emphasized in the public health response. Women in Fortaleza, Brazil, responded to a questionnaire on social factors related to perceived Zika risk and access to health care in June 2016. Data were coded using prespecified categories, and response frequency was reported. Of 37 respondents, most reported a lack of public services to support mosquito control ( n = 19) or delayed access to reproductive health care ( n = 14). Only 22% described specific maternal risks or fetal outcomes as a consequence of Zika infection. Respondents indicated an overall disconnect between public health efforts and women's perceptions of their reproductive control, including limited support concerning microcephaly in infants. Interventions targeting Zika may require a greater emphasis on strengthening health systems and infrastructure to realistically prevent transmission.

Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) have benefits in the metabolism of adipose tissue. However, its contribution to the adipogenesis is not entirely elucidated. The study aimed to evaluate the effects of EPA and DHA on adipogenesis, especially in the PPARγ (peroxisome proliferator-activated receptor-gamma) and Cidec (cell death-inducing DFFA-like effector c) pathway. Twenty-four hours after confluence, 3T3-L1 adipocytes were treated with EPA (100 μM), DHA (50μM) and EPA (100μM) + DHA (50μM) and at the end of differentiation (day 11) the cells were collected for analysis. Cell viability analysis indicated that the concentrations used for EPA and DHA did not cause cytotoxicity in cultured 3T3l1 adipocytes. The treatments have lessened the triacylglycerol accumulation in the adipocyte cytoplasm that, compared to the control group, were EPA-32%, DHA-38%, EPA + DHA -24%. The double-labeling immunofluorescence showed a signal attenuation of protein expressions of PPARγ, CIDEC, and SREBP-1c (sterol regulatory element-binding protein). EPA and DHA had a significant impact on the expression of cleaved CASPASE 3, which increases cell apoptosis and gene expressions of Pparγ and Cidec in the treated groups. Also, there was a reduction of C/ebpα (CCAAT/enhancer-binding protein alpha), Cd36 (cluster differentiation 36), and Foxo1 (forkhead box O). In conclusion, the study determined the ability of both EPA and DHA, alone or combined, in the adipogenesis modulation in cultured 3T3-L1 adipocytes, affecting the cell differentiation, maturation, and consequently, reducing adipogenesis via PPARγ-CIDEC suppression., Competing Interests: Declaration of Competing Interest The authors declare no conflict of interest., (Copyright © 2020 Elsevier GmbH. All rights reserved.)

Purpose: To verify whether the treatment with linagliptin induces the browning of the subcutaneous WAT (sWAT) and thermogenesis in murine diet-induced obesity (DIO) model., Methods: Forty animals were randomly assigned to receive a control diet (C, 10% lipids as energy) or a high-fat diet (HF, 50% lipids as energy) for 10 weeks. Each group was re-divided to begin the 5-week treatment, totalizing four experimental groups: C, C-L (C plus linagliptin, 30 mg/kg body mass; BM), HF, and HF-L (HF plus linagliptin, 30 mg/kg BM). The drug was mixed with diet., Results: HF animals showed overweight, glucose intolerance, and a greater cross-sectional area of adipocytes. The treatment with linagliptin was able to normalize the BM, restore the glucose tolerance and the cross-sectional area of adipocytes. These observations comply with the observation of UCP1-positive multilocular adipocytes in the sWAT of treated animals. Both treated groups (C-L and HF-L) showed high expression of thermogenic and type 2 cytokines genes, which agree with the enhanced body temperature and the lower respiratory exchange ratio, implying enhanced thermogenesis with the use of lipids as fuel., Conclusions: The reduced BM, the enhanced body temperature, and the presence of positive UCP1 beige cells in the sWAT point to the activation of the browning cascade on the sWAT of linagliptin-treated mice, and hence, linagliptin could induce the thermogenic pathway as a pleiotropic effect that can have translational potential.

Background & Aims: Cancer is a complex disease, with poor prognosis when associated with malnutrition. This condition can lead to Cancer Cachexia (CC), a syndrome characterized by loss of muscle mass with or without fat loss, often associated with higher risk of death. Although there are recommended screening tools to assess nutritional status in cancer patients, such as Patient-Generated Subjective Global Assessment (PG-SGA), little is known about CC prediction. The aim was to investigate the association between nutritional status of patients with head, neck and abdominal cancer, assessed by PG-SGA at the day of hospitalization, with CC, hospitalization time and death., Methods: This is a retrospective longitudinal study, where we collected data of 97 patients about PG-SGA nutritional classification, anthropometry, gender, age, cachexia diagnosis and death., Results: PG-SGA classification was strongly associated with all the anthropometric measures (p < 0.0001). According to PG-SGA classification, 30.61% (n = 15) of patients in group A developed pre-cachexia; 38.24% in group B developed CC (n = 13); and 60% (n = 9) in group C developed refractory cachexia (p < 0.0001). Death rate was 24.49% (n = 12), 54.55% (n = 18) and 80% (n = 12) in groups A, B and C, respectively (p < 0.0001). PG-SGA had good sensibility (89.5%) and accuracy (72%) for CC, and also good specificity (75.51%) and accuracy (69%) for death., Conclusions: PG-SGA demonstrated a significative association with the variables measured and was able to predict CC and death. This, in addition to its simple applicability, suggests that PG-SGA can be a useful tool to screen cancer patients for CC establishment and death risk., (Copyright © 2019 European Society for Clinical Nutrition and Metabolism. Published by Elsevier Ltd. All rights reserved.)

A new species of the Neotropical grasshopper genus Aptoceras Bruner, 1908 is described from individuals collected in the Iguaçu National Park, Paraná State, Brazil. Aptoceras iguassuensis n. sp. inhabits in shrubs in the Atlantic Forest. The species belongs to the genus group Nicarchae Brunner von Wattenwyl, 1893. Descriptions, photographs, and illustrations of the male and female, as well as photographs of the male phallic sclerites are presented. An identification key for the five species of Aptoceras from Brazil and a distribution map are also given.

The role of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) in browning and thermogenesis has not been fully elucidated. Thus, we meant to evaluate the effect of EPA and DHA, administered alone or combined, with the activation of browning markers in subcutaneous white adipose tissue (sWAT), and thermogenic markers in brown adipose tissue (BAT). C57BL/6 adult male mice received a control diet or a high-fructose diet (HFru) for eight weeks, but after the first three weeks, HFru was divided into new groups: HFru, HFru + EPA, HFru + DHA, and HFru-EPA + DHA. EPA and DHA diminished adipocyte hypertrophy, recovered markers of browning in sWAT and thermogenic factors in the BAT, and improved gene expressions linked with mitochondrial biogenesis and lipid metabolism. Importantly, EPA and DHA administrated alone showed stronger results than the combination of EPA + DHA. The results suggest that EPA and DHA might be useful as adjuvant strategies to treat metabolic-associated disorders., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Objective: The study objective was to evaluate the association of oral acetaminophen therapy versus immediate surgical ligation with neonatal outcomes in infants with persistent patent ductus arteriosus., Methods: We performed a retrospective cohort study of preterm infants born 28 +6  weeks or less gestational age with persistent large patent ductus arteriosus being considered for surgical ligation after unsuccessful medical therapy. Infants in epoch 1 (July 2009 to June 2012) were immediately referred for ligation, and infants in epoch 2 (July 2012 to June 2015) were treated with oral acetaminophen and referred for ligation in the absence of improvement. The primary outcome was a composite of death or chronic lung disease., Results: A total of 92 infants with median (interquartile range) gestational age 25.2 weeks (24.4-26.3) had persistent large patent ductus arteriosus (43 in epoch 1, 49 in epoch 2). Infants in epoch 2 had decreased surgical ligation (26 [53%] vs 31 [72%]; adjusted odds ratio [aOR], 0.32; 95% confidence interval [CI], 0.12-0.89) but increased chronic lung disease (36 [73%] vs 25 [58%]; aOR, 3.34; 95% CI, 1.05-10.58) and increased death/chronic lung disease of borderline significance (39 [80%] vs 29 [67%]; aOR, 3.09; 95% CI, 0.99-9.63). Infants in epoch 2 took longer to wean off of positive pressure ventilation (28.5 vs 24 days after enrollment; aOR, 0.52; 95% CI, 0.31-0.85)., Conclusions: Late oral acetaminophen therapy for infants with persistent patent ductus arteriosus is associated with reduced surgical ligation but increased chronic lung disease. In light of a lack of improvement in clinical outcomes, the individual contributory effects of acetaminophen, surgical ligation, and prolonged exposure to patent ductus arteriosus require further study to define the optimal approach., (Copyright © 2018 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.)

In this study, we describe a new species of the genus Poecilocloeus from Renascença municipality, Paraná State, Brazil. Poecilocloeus renascensis n. sp. inhabits the Atlantic Semideciduous Forest edges of Renascença and adjacent areas, and our study is the first record of this genus from southern Brazil. The species belongs to the group bullatus (Rehn, 1908), and the descriptions are based on morphological characters, mainly from male genitalia. Morphological descriptions are provided together with illustrations emphasizing the most significant diagnostic features of external morphology and male genitalia. Information is given about type specimens, examined material and geographic distribution.

The obesity and its comorbidities, including resistance to leptin, impacts the reproductive function. Testes express leptin receptors in the germ cells and Leydig cells. Then, leptin-deficient animals are obese and infertile. We aimed to evaluate the structure and steroidogenic pathway of the testis of deficient leptin mice. Three months old male C57BL/6 mice (wild-type, WT) and deficient leptin (ob/ob) mice had their testes dissected and prepared for analyses. Compared to the WT group, the ob/ob group showed a greater body mass with smaller testes, and alterations in the germinative epithelium: fewer spermatogonia, spermatocytes, and spermatids. The Sertoli cells and the germ cells showed condensed nuclei and nuclear fragmentation indicating cell death, in agreement with a low expression of the proliferating cell nuclear antigen and a high expression of Caspase3. In the ob/ob group, the sperm was absent in the seminiferous tubules, and the steroidogenic pathway was compromised (low 3Beta hydroxysteroid dehydrogenase and steroidogenic acute regulatory protein). Further, all hormone receptors involved in the testicular function were down expressed (androgen, estrogen, follicle-stimulating, luteinizing, aromatase, and nicotinamide adenine dinucleotide phosphate). In conclusion, the findings indicate significant morphological, hormonal and enzymatic changes in the testis of the ob/ob mice. The shifts in the enzymatic steroidogenic pathway and the enzymes related to spermatic activity support the insights about the failures in the fertility of these animals. The study provides new evidence and contributes to the understanding of how the lack of leptin and obesity might negatively modulate the testicular function leading to infertility., (Copyright © 2017 Elsevier GmbH. All rights reserved.)

Brown adipose tissue (BAT) is specialized in heat production, but its metabolism in ob/ob mice is still a matter of debate. We aimed to verify ob/ob mice BAT using C57Bl/6 male mice (as the wild-type, WT) and leptin-deficient ob/ob mice (on the C57Bl/6 background strain), at three months of age (n=10/group). At euthanasia, animals had their interscapular BAT weighed, and prepared for analysis (Western blot, and RT-qPCR). In comparison with the WT group, the ob/ob group showed reduced thermogenic signaling markers (gene expression of beta 3-adrenergic receptor, beta3-AR; PPARgamma coactivator 1 alpha, PGC1alpha, and uncoupling protein 1, UCP1). The ob/ob group also showed impaired gene expression for lipid utilization (perilipin was increased, while other markers were diminished: carnitine palmitoyltransferase-1b, CPT-1b; cluster of differentiation 36, CD36; fatty acid binding protein 4, FABP4; fatty acid synthase, FAS, and sterol regulatory element-binding protein 1c, SREBP1c), and altered protein expression of insulin signaling (diminished pAKT, TC10, and GLUT-4). Lastly, the ob/ob group showed increased gene expression of markers of inflammation (interleukin 1 beta, IL-1beta; IL-6, tumor necrosis factor alpha, TNFalpha; and monocyte chemotactic protein-1, MCP-1). In conclusion, the ob/ob mice have decreased thermogenic markers associated with reduced gene expression related to fatty acid synthesis, mobilization, and oxidation. There were also alterations in insulin signaling and protein and gene expressions of inflammation. The findings suggest that the lack of substrate for thermogenesis and the local inflammation negatively regulated thermogenic signaling in the ob/ob mice., (Copyright © 2016 Elsevier GmbH. All rights reserved.)

Objective: The objective of this study was to evaluate the effectiveness of rescue oral acetaminophen in improving echocardiography (echo) indices of patent ductus arteriosus (PDA) shunt volume and avoiding surgical ligation in extremely low gestational age (GA) neonates (ELGANs, <28 weeks) with persistent PDA., Study Design: Retrospective cohort study of ELGANs with moderate or severe PDA at risk for ligation after a practice change introducing oral acetaminophen (60 mg kg(-1) day(-1) for 3 to 7 days) to facilitate ductal constriction after indomethacin failure., Results: Twenty-six infants (median GA 24.4 weeks at birth) with persistent PDA under consideration for surgical ligation were treated with oral acetaminophen at a mean of 27 days of life. Echo indices of shunt volume improved in 12 (46%) infants (3 closed and 9 reduced to mild shunt), all of whom avoided ligation. There was no echo improvement in 14 (54%) infants, of which 8/14 underwent ligation, and ligation was deferred in 6/14 infants, mostly owing to improvement in respiratory stability. Fewer responders than non-responders underwent ligation (0% vs 57%, P<0.01), though there were no differences in other neonatal outcomes., Conclusions: In ELGANs with persistent significant PDA, rescue therapy with oral acetaminophen was associated with improvement in echo indices of shunt volume and avoidance of ligation in nearly half of infants.

The male reproductive accessory glands (RAGs) are important organs that contribute to the secretion of different substances that composed the ejaculate. Despite this important function, their composition, anatomy and function vary widely between species. Thus, the RAGs of three species of phyllostomid bats were morphologically and ultrastructurally characterized and compared in this study. The RAGs of the three analyzed species are composed of a prostate and a pair of bulbourethral glands (BG). In all species, the prostate is composed of three well-defined regions (ventral, dorsolateral and dorsal regions). The ventral region showed an atypical epithelium (undefined) with no obvious cellular limits and a holocrine PAS-positive secretion. The dorsolateral region of Carollia perspicillata and Phyllostomus discolor showed a pseudostratified cubic morphology, and that from Glossophaga soricina had a columnar morphology endowed with cytoplasmic projections and stereocilia. The dorsal region of the three analyzed species is composed of a pseudostratified columnar epithelium endowed with stereocilia; however, G. soricina also presented cytoplasmic projections in the apical portions of the secretory cells similar to those in the dorsolateral region. The BG of the three analyzed species are composed of a pseudostratified columnar epithelium including basal and PAS-positive secretory cells. In conclusion, this study morphologically and ultrastructurally characterized the RAGs of three species of phyllostomid bats, demonstrating the presence of a novel third prostatic region in species of this family. The results also showed the absence of seminal vesicles and ampullary glands, and better characterized the holocrine pattern of the prostatic ventral region, which is unique to bats., (Copyright © 2016 Elsevier GmbH. All rights reserved.)

Objective: The objective of the present study was to evaluate adverse perinatal outcome in a group of high order pregnancies pared with singletons by BW and GA at birth., Methods: Data was reviewed for all admissions of triplets and quadruplets in a 7 year period. For each study neonate we selected two singleton infants to constitute a control group. Variables analyzed included: respiratory distress syndrome, patent ductus arteriosus, intraventricular hemorrhage, necrotizing enterocolitis (NEC), bronchopulmonary dysplasia, retinopathy of prematurity and periventricular leukomalacia., Results: We studied a total of 128 multiple and 260 singleton infants. Mean gestational age and birth weight were similar in both groups (31.3 ± 2,5 wks e 31.5 ± 2,8 wks; 1470 ± 461 g vs 1495 ± 540 g). There was no significant difference between the groups in the majority of main morbidities. The incidence of NEC was higher in triplets (6.3 vs 0.8%, p value <0.01). Mortality was higher in singletons (9.6 vs 3.1%, p value <0.037)., Conclusions: Results show that major neonatal outcomes are very similar between multiples and singletons births when paired by gestational age and birth weight. NEC remained a significant morbidity in infants born from multiple gestations after adjustment for maternal and neonatal risk factors.

This study aimed to morphologically characterize and compare the male reproductive accessory glands (RAGs) of bats belonging to the five Brazilian subfamilies of the family Phyllostomidae (Carollia perspicillata-Carollinae; Desmodus rotundus-Desmodontinae; Glossophaga soricina-Glossophaginae; Phyllostomus discolor-Phyllostominae and Platyrrhinus lineatus-Stenodermatinae). The study demonstrated that the RAGs of phyllostomid bats were comprised of a pair of extra-abdominal bulbourethral glands and an intra-abdominal complex, composed of paraurethral glands and a prostate with two (Desmodontinae and Stenodermatinae) or three (Carollinae, Glossophaginae and Phyllostominae) different regions, with the absence of the seminal vesicles; this pattern possibly evolved from a process of compaction of the prostatic regions from an ancestor with three regions., (© 2014 Wiley Periodicals, Inc.)

Gastrin-releasing peptide is a neuroendocrine homolog of bombesin that demonstrated important growth-stimulatory effects in various types of cancer. High levels of expression of gastrin-releasing peptide receptors (GRPR) has been found in different malignancies, and the studies exploring the therapeutic use of GRPR antagonists have shown promising results. Our aim was to determine the GRPR expression in epidermoid carcinoma of the anal canal and discuss its potential clinical applications. We performed immunohistochemical analysis for GRPR on formalin-fixed and paraffin-embedded tumor samples obtained from 35 patients with anal cancer. As a control group, we analyzed 24 samples of nonmalignant anal tissues (hemorrhoidectomy specimens). GRPR expression was evaluated using a semiquantitative approach according to the intensity and distribution of staining. All analyzed tissues, except 1 control sample, showed positive GRPR immunoexpression. GRPR was strongly expressed in 54% of cancer specimens as compared with only 12% of the control specimens (P<0.003). In tumors, the receptor showed a diffuse and homogenous pattern of distribution within the specimens. In contrast, control specimens showed a focal pattern of staining restricted to the basal half of the epithelium. In conclusion, we demonstrated that GRPR is highly expressed in epidermoid carcinoma of the anal canal, suggesting this receptor might have a role in anal carcinogenesis. Our results provide a basis for exploiting GRPR as a target for diagnostic and therapeutic purposes in the anal cancer.