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Carlos Antonio Amado,1 Cecilia Pérez-García,2 Begoña Tamayo Fernández,3 Juan Agüero-Calvo,3 Pedro Muñoz-Cacho,4 Rafael Golpe5 1Hospital Universitario Marqués de Valdecilla, Servicio de Neumología, Universidad de Cantabria, Santander, Spain; 2Universidad de Cantabria, Santander, Spain; 3Hospital Universitario Marqués de Valdecilla, Servicio de Neumología, Santander, Spain; 4Servicio Cántabro de Salud, Santander, Spain; 5Hospital Universitario Lucus Augusti, Servicio de Neumología, Grupo C039 Biodiscovery HULA-USC, Instituto de Investigación Sanitaria de Santiago de Compostela (IDIS), Santander, SpainCorrespondence: Carlos Antonio AmadoServicio de Neumología, Hospital Universitario Marqués de Valdecilla, Avenida Valdecilla SN, Santander 39001, Cantabria, SpainEmail carlosantonio.amado@scsalud.esIntroduction: Improving patients’ information needs (IN) may contribute to better control in COPD. This study analyses IN using Lung Information Needs Questionnaire (LINQ) following an educational intervention, evaluates how clinical characteristics modify IN, and studies high IN as a prognostic factor for COPD exacerbations and hospital admissions.Methods: Cohort of 143 patients with initial diagnosis of COPD included in a structured educational program. Two months after completing the program, IN was assessed using LINQ. Correlations between IN and clinical variables of COPD and distribution of IN in different clinical groups were analyzed. Univariate and multivariate analysis was performed to determine influence of IN on exacerbations and COPD admissions over the following year.Results: LINQ scored 6.3± 2.9. There were no differences in LINQ scoring between different clinical groups, but LINQ score positively correlated with age (r=0.184, p=0.029). High IN was a predictor of COPD hospitalizations (HR 2.3 [95% CI 1.1– 5.1] (p=0.029)) but not of less severe exacerbations (p=0.334).Conclusion: IN was not associated with any clinical variables, but it correlated with age. High IN proved to be an independent predictor of admissions.Keywords: COPD, education, COPD exacerbation

Summary: Store-operated Ca2+ entry (SOCE) mediated by stromal interacting molecule (STIM)-gated ORAI channels at endoplasmic reticulum (ER) and plasma membrane (PM) contact sites maintains adequate levels of Ca2+ within the ER lumen during Ca2+ signaling. Disruption of ER Ca2+ homeostasis activates the unfolded protein response (UPR) to restore proteostasis. Here, we report that the UPR transducer inositol-requiring enzyme 1 (IRE1) interacts with STIM1, promotes ER-PM contact sites, and enhances SOCE. IRE1 deficiency reduces T cell activation and human myoblast differentiation. In turn, STIM1 deficiency reduces IRE1 signaling after store depletion. Using a CaMPARI2-based Ca2+ genome-wide screen, we identify CAMKG2 and slc105a as SOCE enhancers during ER stress. Our findings unveil a direct crosstalk between SOCE and UPR via IRE1, acting as key regulator of ER Ca2+ and proteostasis in T cells and muscles. Under ER stress, this IRE1-STIM1 axis boosts SOCE to preserve immune cell functions, a pathway that could be targeted for cancer immunotherapy.

In this news and views, we discuss our recent publication where we described how ER-PM membrane contact sites (MCS) are modulated during store operated calcium entry (SOCE). We also examine why enforcing ER-PM MCS by tethering proteins does not not enhance, but rather inhibits SOCE.

IRE1α plays a key role in the unfolded protein response (UPR) by promoting the unconventional splicing of the XBP1 and the selective cleavage of RNAs. Here the authors report that IRE1α is activated upon the DNA damage response and selectively controls the stability of mRNAs to maintain genome integrity.

Efficient immune responses require Ca2+ fluxes across ORAI1 channels during engagement of T cell receptors (TCR) at the immune synapse (IS) between T cells and antigen presenting cells. Here, we show that ZDHHC20-mediated S-acylation of the ORAI1 channel at residue Cys143 promotes TCR recruitment and signaling at the IS. Cys143 mutations reduced ORAI1 currents and store-operated Ca2+ entry in HEK-293 cells and nearly abrogated long-lasting Ca2+ elevations, NFATC1 translocation, and IL-2 secretion evoked by TCR engagement in Jurkat T cells. The acylation-deficient channel remained in cholesterol-poor domains upon enforced ZDHHC20 expression and was recruited less efficiently to the IS along with actin and TCR. Our results establish S-acylation as a critical regulator of ORAI1 channel trafficking and function at the IS and reveal that ORAI1 S-acylation enhances TCR recruitment to the synapse.

In this work, the fretting wear behavior and adhesion of DLC coatings deposited by PACVD on nitrided and non-nitrided martensitic stainless steels were studied. Fretting wear tests were carried out with different duration and loads and pin-on-disk was also performed. The adhesion was evaluated by Rockwell C indentation and scratch test with constant and variable loads. The coating thickness was 2.5 μm and the nitrided layer, 11 μm. The coating hardness and Young's Modulus were about 16 and 110 GPa, respectively. The duplex samples resulted with better adhesion than the only coated samples in all test conditions. In the scratch test, the critical load in the duplex sample was 58 N and in the coated sample, 12 N, showing a brittle failure mode. In the Rockwell C indentation test, the adhesion was better in the duplex sample because the nitriding treatment changed the failure mode of the system. The wear resistance was also related to adhesion, since in the experiments with high loads and long durations adhesive failures could be detected when stresses reached the interface and the substrate. In the duplex sample, the nitrided case, with higher load bearing capacity than the substrate, resulted in a better wear behavior of the system. Keywords: DLC hard coatings, Fretting wear, Adhesion

Plasma nitriding has become a powerful tool to improve wear resistance of stainless steels and sustain or improve corrosion resistance with an adequate selection of process parameters. In this work, the short treatment route with temperatures above 400ºC was selected for AISI 420 stainless steel. After the nitriding process, a wide nitrided layer, with good wear and corrosion properties was simultaneously obtained with selected parameters. A 5 hours treatment at 420 ºC resulted in a 10 µm nitrided layer. XRD revealed an expanded Fe-α layer with Fe nitrides but no signal of CrN was found. Wear resistance was improved three and four times in erosion and sliding tests compared to the non-nitrided material. Corrosion resistance was tested in anodic polarization experiments in a NaCl solution. In this test, the samples treated in the short time process presented the best results.

Surface enhanced Raman spectroscopy (SERS) is considered a versatile and multifunctional technique with the ability to detect molecules of different species at very low molar concentration. In this work, hierarchical ZnO microspheres (ZnO MSs) and Ag/ZnO MSs were fabricated and decorated by hydrothermal and photodeposition methods, respectively. For Ag deposition, precursor molar concentration (1.9 and 9.8 mM) and UV irradiation time (5, 15, and 30 min) were evaluated by SEM, TEM, X-ray diffraction and Raman spectroscopy. X-ray diffraction showed a peak at 37.9° corresponding to the (111) plane of Ag, whose intensity increases as precursor concentration and UV irradiation time increases. SEM images confirmed the formation of ZnO MSs (from 2.5 to 4.5 µm) building by radially aligned two-dimensional ZnO nanosheets with thicknesses below 30 nm. The Raman spectra of Ag/ZnO MSs exhibited a vibration mode at 486 cm−1 which can be directly associated to Ag deposition on ZnO MSs surface. The performance of SERS substrate was evaluated using rhodamine 6G. The SERS substrate grown at 9.8 mM during 30 min showed the best SERS activity and the ability to detect methylene blue at 10−9 M.

In the forging industry, surface quality and surface treatments of dies are crucial parameters to extend their life. These components are usually machined by milling or by Electrical Discharge Machining (EDM), and the final surface roughness depends on the machining techniques and operational conditions used in its fabrication. After milling, a nitriding treatment is widely applied to extend its service life. Nevertheless, no scientific report that informs about nitriding after EDM has been found. Accordingly, this work focuses on the wear and friction behavior of pins made of brass and medium carbon steel sliding over AISI H13 discs, made by wire EDM in the conditions of finishing and roughing. The discs are plasma nitride, and their effect on the wear during pin-on-disc tests is evaluated. In this sense, the analysis of the surface damage for the different pins will help us to understand the service life and wear evolution of the forging dies. The results show that plasma nitride reduces the friction and prevents the degradation of the pin, independently of the material of the pin, when sliding over finishing and roughing EDM conditions.

Se presentan 2 casos clínicos de recién nacidas que, entre otros síntomas, presentaron cifras bajas de glucemia mantenidas (menores 2,2 mmol/L), por lo que fueron evaluadas en el Servicio de Endocrinología del Hospital Provincial Pediátrico Docente "Eduardo Agramonte Piña" de Camagüey, donde se les diagnosticó nesidioblastosis -- hipoglucemia neonatal persistente --. En una de las pacientes el tratamiento médico resultó favorable, pero en la otra fue necesario realizar la pancreatectomía subtotal. Actualmente ambas afectadas reciben esquemas terapéuticos adecuados a sus necesidades clínicas

Single nucleotide polymorphisms (SNPs) located in the chromosome region 17q12-q21 are risk factors for asthma. Particularly, there are cis-regulatory haplotypes within this region that regulate differentially the expression levels of ORMDL3, GSDMB and ZPBP2 genes. Remarkably, ORMDL3 has been shown to modulate lymphocyte activation parameters in a heterologous expression system. In this context, it has been shown that Th2 and Th17 cytokine production is affected by SNPs in this region. Therefore, we aim to assess the impact of hereditary components within region 17q12-q21 on the activation profile of human T lymphocytes, focusing on the haplotype formed by allelic variants of SNPs rs7216389 and rs12936231. We measured calcium influx and activation markers, as well as the proliferation rate upon T cell activation. Haplotype-dependent differences in mRNA expression levels of IL-2 and INF-γ were observed at early times after activation. In addition, the allelic variants of these SNPs impacted on the extent of calcium influx in resting lymphocytes and altered proliferation rates in a dose dependent manner. As a result, the asthma risk haplotype carriers showed a lower threshold of saturation during activation. Finally, we confirmed differences in activation marker expression by flow cytometry using phytohemagglutinin, a strong polyclonal stimulus. Altogether, our data suggest that the genetic component of pro-inflammatory pathologies present in this chromosome region could be explained by different T lymphocyte activation dynamics depending on individual allelic heredity.

A cross-sectional study was performed with the purpose of identifying psychological predictors of condom use behaviors in a sample of 381 women in reproductive age from Tunja, Colombia. An instrument that evaluates knowledge, motives, social situations, and biological states related to condom use behaviors in the first sexual encounter, and throughout active sexual life was administered. For data processing descriptive statistics were obtained. Additionally, Pearson’s x2 test and a multivariate logistic regression analysis were used. Pearson’s x2 test showed differences between women who used and did not use condom in their first sexual intercourse (x2 [1] = 25.000; p = 0.000), and also showed differences between those who consistently or inconsistently used it throughout their active sexual life (x2 [3] = 21.907; p = 0.000). A multivariate logistic regression analysis showed that condom use behavior throughout these women’s active sexual life was predicted by the motive “Because I didn’t know how to use it” (x2 [2] = 6.786; p = 0.034). A discussion is presented about the importance of designing prevention programs for VHI infection that pay special attention to the motives underlying the use of condom, as well as the need to educate women in developing skills both for negotiation and for a consistent and effective use of condom

Leaves of Piper ovatum are known in folk medicine as 'joao burandi' or 'anestésica' and in traditional Brazilian medicine are used to treat inflammatory disease. The hydroalcoholic extract, fractions, and a mixture of piperovatine (1) and piperlonguminine (2) in a proportion of 2:3 obtained from Piper ovatum were assayed for anti-inflammatory activity by means of carrageenan-induced pleurisy in rats and croton oil-induced ear edema in mice. The hydroalcoholic extract was analyzed by high-performance liquid chromatography. Fraction constituents were evaluated by phytochemical screening, and the mixture of amides (1 and 2) was identified by analyses of spectral data of (1)H and (13)C nuclear magnetic resonance. Acute toxicity of the extract also was evaluated. At 500mg/kg, the hydroalcoholic extract of Piper ovatum leaves did not reduce the volume of inflammatory pleural exudates compared with control animals. However, the hydroalcoholic extract and fractions F1-F3 at doses of 5.0mg/ear and a mixture of piperovatine (1) and piperlonguminine (2) at doses of 2.5, 1.25, and 0.625mg/ear significantly reduced the degree of ear edema. Taken together, the results indicate that the amide fractions piperovatine and piperlonguminine showed the greatest inhibitory activity of topical inflammation induced by croton oil. [ABSTRACT FROM AUTHOR]

Monocyte distribution width (MDW) has been associated with inflammation and poor prognosis in various acute diseases. Chronic obstructive pulmonary disease (COPD) exacerbations (ECOPD) are associated with mortality. The objective of this study was to evaluate the utility of the MDW as a predictor of ECOPD prognosis. This retrospective study included patient admissions for ECOPD. Demographic, clinical and biochemical information; intensive care unit (ICU) admissions; and mortality during admission were recorded. A total of 474 admissions were included. MDW was positively correlated with the DECAF score (r = 0.184, p < 0.001) and C-reactive protein (mg/dL) (r = 0.571, p < 0.001), and positively associated with C-RP (OR 1.115 95% CI 1.076-1.155, p < 0.001), death (OR 9.831 95% CI 2.981- 32.417, p < 0.001) and ICU admission (OR 11.204 95% CI 3.173-39.562, p < 0.001). High MDW values were independent risk factors for mortality (HR 3.647, CI 95% 1.313-10.136, p = 0.013), ICU admission (HR 2.550, CI 95% 1.131-5.753, p = 0.024), or either mortality or ICU admission (HR 3.084, CI 95% 1.624-5.858, p = 0.001). In ROC analysis, a combined MDW-DECAF score had better diagnostic power (AUC 0.777 95% IC 0.708-0.845, p < 0.001) than DECAF (p = 0.023), MDW (p = 0.026) or C-RP (p = 0.002) alone. MDW is associated with ECOPD severity and predicts mortality and ICU admission with a diagnostic accuracy similar to that of DECAF and C-RP. The MDW- DECAF score has better diagnostic accuracy than MDW or DECAF alone in identifying mortality or ICU admission., (© 2024. The Author(s).)

Objectives: Resveratrol has been studied as a potential agent for treating rheumatic conditions; however, this compound suppresses glucose synthesis and glycogen catabolism when infused in perfused livers of both arthritic and healthy rats. This study investigated the effects of oral administration of resveratrol on inflammation and liver metabolism in rats with arthritis induced by Freund's adjuvant, which serves as rheumatoid arthritis model., Methods: Holtzman rats, both healthy and exhibiting arthritic symptoms, were orally treated with resveratrol at doses varying from 25 to 500 mg/kg for a 5-day period preceding arthritis induction, followed by an additional 20-day period thereafter. Paw edema, arthritic score and hepatic myeloperoxidase activity were assessed to evaluate inflammation. Glycogen catabolism and gluconeogenesis from lactate were respectively evaluated in perfused livers from fed and fasted rats., Results: Resveratrol decreased the liver myeloperoxidase activity at doses above 100 mg/kg, and decreased the paw edema and delayed the arthritic score at doses above 250 mg/kg. The hepatic gluconeogenesis was decreased in arthritic rats and resveratrol did not improve it. However, resveratrol did not negatively modify the gluconeogenesis in livers of healthy and arthritic rats. Glycogen catabolism was in part and slightly modified by resveratrol in the liver of arthritic and healthy rats., Conclusions: It is improbable that resveratrol negatively affects the liver metabolism, especially considering that gluconeogenesis is highly fragile to changes in cellular architecture. The findings suggest that resveratrol could serve as alternative for treating rheumatoid arthritis. Nevertheless, prudence is advised regarding its transient effects on liver metabolism., (© 2024 Walter de Gruyter GmbH, Berlin/Boston.)

Toxoplasma gondii is the causative agent of toxoplasmosis, a common zoonotic disease affecting vertebrates with high global incidence. For the parasite to disseminate throughout the body, it crosses the intestinal barrier, triggering inflammatory reactions. This study aimed to assess the tissue response in the ileum and colon of mice following chronic infection with T. gondii. Fourteen mice were divided into two groups: the infected group received 1000 T. gondii oocysts via gavage, and after 60 days, the mice were euthanized. The ileum and colon were collected and processed for histological analysis, inflammatory marker measurement and myenteric neuron analysis. Chronic infection resulted in a significant increase in intraepithelial lymphocytes and mast cells, as well as morphometric changes such as increased total intestinal wall thickness of the ileum, crypt depth, collagen fiber area, and a decrease in myeloperoxidase activity, without altering nitric oxide levels. While the number of myenteric neurons remained unchanged, there was an increase in vasoactive intestinal peptide expression. These results suggest persistence intestinal inflammatory stimuli in chronic T. gondii infection., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

This study aimed to investigate the antioxidant and anti-inflammatory properties of quercetin on the cellular components of the Enteric Nervous System in the ileum of rats with arthritis. Rats were distributed into five groups: control (C), arthritic (AIA), arthritic treated with ibuprofen (AI), arthritic treated with quercetin (AQ) and arthritic treated with both ibuprofen and quercetin (AIQ). The ileum was processed for immunohistochemical techniques for HuC/D, calcitonin gene-related peptide, and vasoactive intestinal polypeptide. Measurements in histological sections, chemiluminescence assays, and total antioxidant capacity were also performed. Rheumatoid arthritis resulted in a decrease in neuronal density, yet neuroplasticity mechanisms were evident through observed changes in varicosities size and neuronal area compared to the control group. Reduced paw edema and neuroprotective effects were predominantly noted in both plexuses, as evidenced by the increased density preservation of HuC/D-IR neurons in the AIQ group. The increase of lipoperoxidation levels and paw edema volume in the AQ group was observed compared to the arthritic, whereas the AIQ group mainly showed similar results to those observed in the control. The enteropathy associated with arthritis proved to be significant in the field of gastroenterology, and the combination of quercetin and ibuprofen demonstrated promising anti-inflammatory and neuroprotective effects.

In this paper, we present the design and synthesis of a novel series of pyrido[2,3- d ]pyridazine-2,8-dione derivatives via the annulation of the 2-pyridone pattern. The synthesized derivatives were evaluated for in vivo anti-inflammatory activity using an ear edema model. Compound 7c, which showed a greater inhibition of ear edema (82%), was further tested for its in vitro COX-1/COX-2 inhibitory activity. Compound 7c showed similar inhibitory activities against COX-1 and COX-2 isoenzymes. The structural features that ensure the dual inhibition of COX-1 and COX-2 were elucidated using molecular docking studies. Overall, the ring closing of 2-pyridone pattern I transformed this highly selective COX-2 inhibitor into a dual COX inhibitor (7c), which could serve as a model for determining selectivity for COX-2., Competing Interests: The authors declare no conflict of interest., (This journal is © The Royal Society of Chemistry.)

The aim of this work was to compare the anti-inflammatory and antioxidant effects of three natural coumarins: 1,2-benzopyrone, umbelliferone and esculetin. The antioxidant capacity of coumarins was evaluated using both chemical and biological in vitro assays. Chemical assays included DPPH and ABTS ∙+ radical scavenging as well as ferric ion reducing ability power (FRAP) assay. Inhibition of mitochondrial ROS generation and lipid peroxidation in brain homogenates were used as biological in vitro assays. The experimental method of carrageenan-induced pleurisy in rats was used for the in vivo investigation of the anti-inflammatory activity. In silico molecular docking analysis was undertaken to predict the affinity of COX-2 to the coumarins. Considering the antioxidant capacity, esculetin was the most efficient one as revealed by all employed assays. Particularly, the mitochondrial ROS generation was totally abolished by the compound at low concentrations (IC 50  = 0.57 μM). As for the anti-inflammatory effects, the COX-2 enzyme presented good affinities to the three coumarins, as revealed by the molecular docking analyses. However, considering the in vivo anti-inflammatory effects, 1,2-benzopyrone was the most efficient one in counteracting pleural inflammation and it potentiated the anti-inflammatory actions of dexamethasone. Umbelliferone and esculetin treatments failed to reduce the volume of pleural exudate. Overall, therefore, our results support the notion that this class of plant secondary metabolites displays promising effects in the prevention and/or treatment of inflammation and other diseases associated with oxidative stress, although the singularities regarding the type of the inflammatory process and pharmacokinetics must be taken into account., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

The present study prepared, optimized, and characterized solid lipid microparticles that contained trans-anethole (SLMAN), evaluated their antiinflammatory activity in acute and chronic inflammation models, and investigated their effects on the gastric mucosa in arthritic rats. The microparticles were obtained by a hot homogenization process and characterized by physicochemical analyses. The acute inflammatory response was induced by an intradermal injection of 0.1 ml of carrageenan solution (200 μg) in the hind paw. The rats were treated orally with a single dose of SLMAN 1 h before induction of the inflammatory response. The chronic inflammatory response was induced by the subcutaneous application of 0.1 ml of complete Freund's adjuvant suspension (500 µg) in the hind paw. SLMAN was orally administered, starting on the day of arthritis induction, and continued for 21 days. The results showed that SLMAN was obtained with good encapsulation efficiency. Treatment with SLMAN at doses of 25 and 50 mg/kg was as effective as trans-anethole (AN) at a dose of 250 mg/kg on acute and chronic inflammatory responses. Histological analyses showed that treatment with SLMAN did not aggravate lesions in the gastric mucosa in arthritic rats. These results indicated that treatment with SLMAN at a dose that was 5-10 times lower than non-encapsulated AN exerted an inhibitory effect on acute and chronic inflammatory responses, suggesting the better bioavailability and efficacy of microencapsulated AN without aggravating lesions in the gastric mucosa in arthritic rats., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: MOTS-c and Romo1 are mitochondrial peptides that are modulated by oxidative stress. No previous studies have explored circulating levels of MOTS-c in patients with chronic obstructive pulmonary disease (COPD)., Methods: We enrolled 142 patients with stable COPD and 47 smokers with normal lung function in an observational cross-sectional study. We assessed serum levels of both MOTS-c and Romo1 and associated these findings with clinical characteristics of COPD., Results: Compared with smokers with normal lung function, patients with COPD had lower levels of MOTS-c ( p = 0.02) and higher levels of Romo1 ( p = 0.01). A multivariate logistic regression analysis revealed that above-median MOTS-c levels were positively associated with Romo1 levels (OR 1.075, 95% CI 1.005-1.150, p = 0.036), but no association was found with other COPD characteristics. Below-median levels of circulating MOTS-c were associated with oxygen desaturation (OR 3.25 95% CI 1.456-8.522, p = 0.005) and walking <350 meters (OR 3.246 95% CI 1.229-8.577, p = 0.018) in six-minute walk test. Above-median levels of Romo1 were positively associated with current smoking (OR 2.756, 95% CI 1.133-6.704, p = 0.025) and negatively associated with baseline oxygen saturation (OR 0.776 95% CI 0.641-0.939, p = 0.009)., Conclusions: Reduced levels of circulating MOTS-c and increased levels of Romo1 were detected in patients diagnosed with COPD. Low levels of MOTS-c were associated with oxygen desaturation and poorer exercise capacity using 6 min walk test. Romo1 was associated with current smoking and baseline oxygen saturation., Trial Registration: www.clinicaltrials.gov; No.: NCT04449419; URL: www.clinicaltrials.gov. Date of registration: June 26, 2020., Competing Interests: CA has received speaker or consulting fees from Boehringer Ingelheim, Pfizer, AstraZeneca, Novartis, Chiesi, Faes Farma, Esteve, and GSK. CC has received speaker or consulting fees from AstraZeneca, Bial, Boehringer Ingelheim, Chiesi, GSK, Menarini, Novartis, and research grants from GSK, Menarini, and AstraZeneca. DF-P has received speaker or consulting fees from Chiesi and GSK. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Amado, Martín-Audera, Agüero, Lavín, Guerra, Boucle, Ferrer-Pargada, Berja, Martín, Casanova and García-Unzueta.)

Background: Chronic obstructive pulmonary disease (COPD) exacerbation (ECOPD) alters the natural course of the disease. To date, only C-reactive protein has been used as a biomarker in ECOPD, but it has important limitations. The mitochondria release peptides (Humanin (HN), FGF-21, GDF-15, MOTS-c and Romo1) under certain metabolic conditions. Here, we aimed to evaluate the pathophysiologic, diagnostic and prognostic value of measuring serum mitochondrial peptides at hospital admission in patients with ECOPD., Methods: A total of 51 consecutive patients admitted to our hospital for ECOPD were included and followed for 1 year; in addition, 160 participants with stable COPD from our out-patient clinic were recruited as controls., Results: Serum FGF-21 ( p < .001), MOTS-c ( p < .001) and Romo1 ( p = .002) levels were lower, and GDF-15 ( p < .001) levels were higher, in patients with ECOPD than stable COPD, but no differences were found in HN. In receiver operating characteristic analysis, MOTS-c (AUC 0.744, 95% CI 0.679-0.802, p < .001) and GDF-15 (AUC 0.735, 95% CI 0.670-0.793, p < .001) had the best diagnostic power for ECOPD, with a diagnostic accuracy similar to that of C-RP (AUC 0.796 95% IC 0.735-0.848, p < .001). FGF-21 (AUC 0.700, 95% CI 0.633-0.761, p < .001) and Romo1 (AUC 0.645 95% CI 0.573-0.712, p = .001) had lower diagnostic accuracy. HN levels did not differentiate patients with ECOPD versus stable COPD ( p = .557). In Cox regression analysis, HN (HR 2.661, CI95% 1.009-7.016, p = .048) and MOTS-c (HR 3.441, CI95% 1.252-9.297, p = .016) levels exceeding mean levels were independent risk factors for re-admission., Conclusions: Most mitochondrial peptides are altered in ECOPD, as compared with stable COPD. MOTS-c and GDF15 levels have a diagnostic accuracy similar to C-RP for ECOPD. HN and MOTS-c independently predict future re-hospitalization., Competing Interests: Declaration of conflicting interestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: Partially funded by GSK. Carlos Amado has received speaker or consulting fees from Boehringer Ingelheim, Pfizer, AstraZeneca, Novartis, Chiesi, Faes Farma, Esteve and GSK. Diego Ferrer has received speaker or consulting fees from Chiesi and GSK. The rest of the authors do not have any conflict of interest.

Aims: to investigate the effects of resveratrol on glycogen catabolism and gluconeogenesis in perfused livers of healthy and arthritic rats. The actions of resveratrol-3-O-glucuronide (R3G) and the biotransformation of resveratrol into R3G was further evaluated in the livers., Main Methods: arthritis was induced with Freund's adjuvant. Resveratrol at concentrations of 10, 25, 50, 100 and 200 μM and 200 μM R3G were introduced in perfused livers. Resveratrol and metabolites were measured in the outflowing perfusate. Respiration of isolated mitochondria and activity of gluconeogenic enzymes were also evaluated in the livers., Key Findings: resveratrol inhibited glycogen catabolism when infused at concentrations above 50 μM and gluconeogenesis even at 10 μM in both healthy and arthritic rat livers, but more sensitive in these latter. Resveratrol above 100 μM inhibited ADP-stimulated respiration and the activities of NADH- and succinate-oxidases in mitochondria, which were partially responsible for gluconeogenesis inhibition. Pyruvate carboxylase activity was inhibited by 25 μM resveratrol and should inhibit gluconeogenesis already at low concentrations. Resveratrol was significantly metabolized to R3G in healthy rat livers, however, R3G formation was lower in arthritic rat livers. The latter must be in part a consequence of a lower glucose disposal for glucuronidation. When compared to resveratrol, R3G inhibited gluconeogenesis in a lower extension and glycogen catabolism in a higher extension., Significance: the effects of resveratrol and R3G tended to be transitory and existed only when the resveratrol is present in the organ, however, they should be considered because significant serum concentrations of both are found after oral ingestion of resveratrol., Competing Interests: Declaration of competing interest The authors declare that no competing interest exists and that all approved the final manuscript., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: Invasion of the intestinal mucosa by T. gondii elicits a local immune response of variable intensity. These reactions can be lethal in C57BL/6 mice. The tissue damage caused by inflammation and the functional effects depend on the host immunity, strain, and developmental form of the parasite. We investigated the effects of acute oral infection with T. gondii on histoarchitecture, enteric nervous system (ENS), and inflammatory markers in the jejunum and ileum of mice., Methods: Female C57BL/6 mice were divided into a control group and a group orally infected with 1000 sporulated T. gondii oocysts (ME-49 strain). After 5 days, jejunum and ileum were collected and processed for analyzes (e.g., histological and histopathological examinations, ENS, cytokine dosage, myeloperoxidase, nitric oxide activity)., Main Results: In infected mice, we observed a significant increase in serotonin-immunoreactive cells (5-HT IR) in the intestinal mucosa, as well as cellular infiltrates in the lamina propria, periganglionitis, and ganglionitis in the myenteric plexus. We also noted decreased neuron density in the jejunum, increased population of enteric glial cells in the ileum, histomorphometric changes in the intestinal wall, villi, and epithelial cells, remodeling of collagen fibers, and increased myeloperoxidase activity, cytokines, and nitric oxide in the intestine., Conclusions and Inferences: Acute infection of female mice with T. gondii oocysts resulted in changes in ENS and a marked increase in 5-HT. These changes are consistent with its modulatory role in the development of moderate acute inflammation. The use of this experimental model may lend itself to studies aimed at understanding the pathophysiological mechanisms of intestinal inflammation in humans involving ENS., Competing Interests: Conflicts of interest The authors declare that there are no conflicts of interest., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Mitokines (Humanin (HN), GDF15 and FGF21) are produced as a result of mitochondrial dysfunction and may have major roles in chronic inflammation, malnutrition and exercise capacity in people with COPD. Except for GDF15, studies on this subject are lacking. A total of 165 patients with stable COPD and 49 smokers without COPD were enrolled. We assessed their serum mitokine levels and clinical characteristics at baseline. We recorded moderate and severe exacerbation for the next 12 months. Baseline serum HN (p = 0.037) and GDF-15 (p = 0.013) levels were higher in the COPD group. High HN levels were independently associated with a high risk of exacerbation (HRE) (OR 2.798, 95% CI 1.266-6.187, p = 0.011), malnutrition (OR 6.645, 95% CI 1.859-23.749, p = 0.004), and 6MWD (OR 0.995, 95% CI 0.991-0.999, p = 0.008), and future moderate (HR 1.826, 95% CI 1.181-2.822, p = 0.007) and severe exacerbations (HR 3.445, 95% CI 1.357-8.740, p = 0.009). High GDF15 levels were associated with HRE (OR 3.028, 95% CI 1.134-8.083, p = 0.027), 6MWD (OR 0.995, 95% CI 0.990-0.999, p = 0.017) and predicted desaturation in 6MWT (OR 3.999, 95% CI 1.487-10.757, p = 0.006). High FGF21 levels were associated with HRE (OR 2.144, 95% CI 1.000-4.600, p = 0.05), and predicted future severe exacerbation (HR 4.217, 95% CI 1.459-12.193, p = 0.008). The mitokine levels were higher in patients with COPD than smokers without COPD, and were associated with important clinical outcomes such as exercise capacity and COPD exacerbation. Among the mitokines, HN showed the strongest association with COPD and may serve as a future risk biomarker in this disease.Trial registation NCT04449419., (© 2022. The Author(s).)

Background: In COPD, the bronchial epithelium shows a pathologically activated Wnt pathway. Sclerostin (SOST) is a secreted glycoprotein that is associated with bone metabolism and blocks the Wnt pathway. We hypothesized that low sclerostin levels might be associated with lung function and COPD exacerbations in patients., Methods: We studied 139 outpatients with stable COPD and normal kidney function. We assessed the serum levels of SOST and bone metabolism parameters, body composition, clinical characteristics and lung function at baseline. We followed the patients prospectively for 12 months after enrolment. Moderate exacerbations and hospital admissions were recorded during follow-up., Results: The serum SOST levels were 23.98±7.6 pmol/l (men: 25.5±7.7 pmol/l, women: 20.3±5.9 pmol/l (p < 0.001)). SOST showed correlations with age (r = 0.36), FFMI (r = 0.38), FEV1 (r = 0.27), DLCO (r = 0.39), 6MWD (r = 0.19) and CAT (r = -0.24). In multivariate linear regression analysis, only age (beta=0.264) and FFMI (beta=1.241) remained significant. SOST showed a significant negative correlation with serum phosphorus (r = -0.29). Cox proportional risk analysis indicated that patients in the lower tertile of SOST levels were at higher risk of moderate COPD exacerbation (HR 2.015, CI95% 1.136-3.577, p = 0.017) and hospital admission due to COPD (HR 5.142, CI95% 1.380-19.158, p = 0.015) than the rest of the patients., Conclusions: SOST levels are associated with body composition and lung function in patients with COPD. Furthermore, lower SOST levels predict a higher risk of exacerbations and hospitalization., Competing Interests: Declaration of interests None., (Copyright © 2022 Sociedade Portuguesa de Pneumologia. Published by Elsevier España, S.L.U. All rights reserved.)

Objective: In the present study, the hepatoprotective effects of β-myrcene (MYR) on acetaminophen-induced hepatotoxicity were investigated., Materials and Methods: A total of 40 Balb/c mice were randomly divided into five groups as follows: 1) Normal control group which received only carboxymethylcellulose (CMC), the vehicle used to dissolve acetaminophen (N-acetyl-p-aminophenol, APAP, paracetamol) and MYR; 2) APAP group which received a single dose of acetaminophen (250 mg/kg) orally on day 7; 3) Silymarin group which received 200 mg/kg/day of silymarin; and 4 and 5) pretreatment groups in which, mice were treated with 100 or 200 mg/kg/day of MYR. Liver and blood samples were collected to analyze serum aminotransferases, inflammatory response, oxidative stress markers, and histopathological insults., Results: Our results showed that MYR pretreatment attenuated liver damage and restored liver cells function and integrity as it decreased the leakage of serum aminotransferases (alanine and aspartate aminotransferases (ALT and AST, respectively)) into the blood (p<0.01). MYR treatment also reduced levels of myeloperoxidase (MPO) activity and nitric oxide (NO) (p<0.001). In addition, MYR pretreatment demonstrated significant antioxidant activity by decreasing malondialdehyde (MDA), reactive oxygen species (ROS), and reduced glutathione (GSH) levels (p<0.001). Furthermore, it restored the hepatic level of superoxide dismutase (SOD), catalase (CAT), and oxidized glutathione (GSSG) (p<0.001)., Conclusion: For the first time, our results showed that MYR treatment significantly improved liver function by reducing oxidative stress and the inflammatory response induced by APAP., Competing Interests: The authors have declared that there is no conflict of interest.

Background: The 2-dimensional, 4-quadrant 2017 Global Initiative for Chronic Obstructive Lung Disease (GOLD) COPD A-D assessment tool (GOLD 2017 ) does not include lung function variables to classify patients into different risk groups. The previous 2011 tool (GOLD 2011 ) classified cases in the upper-quadrants (higher risk groups) regardless of whether they had a history of exacerbations or worse lung function. We hypothesized that a modified, three-dimensional classification (GOLD 3D ) that separately includes assessment of lung function and exacerbations history would improve the ability to predict adverse events., Methods: A total of 1303 COPD patients were included in a historical cohort study. The ability of GOLD 3D to predict outcomes (all-cause death and hospitalizations due to severe exacerbation) was compared with GOLD 2017 and GOLD 2011 ., Results: Mean follow-up was 45.0 ± 28.0 months. Two hundred and twenty-eight patients (17.5%) died and 337 (25.9%) subjects suffered at least a severe exacerbation that required hospital admission. The area under the receiver-operating characteristics curve for mortality prediction was slightly but significantly higher for GOLD 3D than for GOLD 2011 . The area under the curve for prediction of severe exacerbations was significantly higher for GOLD 3D than for GOLD 2011 and GOLD 2017 . A worse ventilatory obstruction was associated in most cases with a higher mortality risk and a higher exacerbation risk for the GOLD2017 A-D groups., Conclusions: The proposed GOLD 3D classification system upgrades the previous ones, and is advantageous in predicting future adverse events., Competing Interests: Disclosure of interest The authors report no conflict of interest., (Copyright © 2021 SPLF and Elsevier Masson SAS. All rights reserved.)

Background and Aim: The present study investigated the effects of orally administered α-tocopherol-loaded polycaprolactone nanoparticles on the articular inflammation and systemic oxidative status of middle-aged Holtzman rats with Freund's adjuvant-induced polyarthritis, a model for rheumatoid arthritis. Intraperitoneally administered free α-tocopherol provided the reference for comparison., Experimental Procedure: Two protocols of treatment were followed: intraperitoneal administration of free α-tocopherol (100 mg/kg i.p.) or oral administration of free and nanoencapsulated α-tocopherol (100 mg/kg p.o.). Animals were treated during 18 days after arthritis induction., Results: Free (i.p.) and encapsulated α-tocopherol decreased the hind paws edema, the leukocytes infiltration into femorotibial joints and the mRNA expression of pro-inflammatory cytokines in the tibial anterior muscle of arthritic rats, but the encapsulated compound was more effective. Free (i.p.) and encapsulated α-tocopherol decreased the high levels of reactive oxygen species in the brain and liver, but only the encapsulated compound decreased the levels of protein carbonyl groups in these organs. Both free (i.p.) and encapsulated α-tocopherol increased the α-tocopherol levels and the ratio of reduced to oxidized glutathione in these organs., Conclusion: Both intraperitoneally administered free α-tocopherol and orally administered encapsulated α-tocopherol effectively improved inflammation and systemic oxidative stress in middle-aged arthritic rats. However, the encapsulated form should be preferred because the oral administration route does not be linked to the evident discomfort that is caused in general by injectable medicaments. Consequently, α-tocopherol-loaded polycaprolactone nanoparticles may be a promising adjuvant to the most current approaches aiming at rheumatoid arthritis therapy., Competing Interests: There are no conflicts of interest to declare., (© 2021 Center for Food and Biomolecules, National Taiwan University. Production and hosting by Elsevier Taiwan LLC.)

Palicourea species has been used in folk medicine in the treatment of some diseases including cancer and inflammatory disorders. This work aimed to evaluate the in vitro antiproliferative and in vivo topical anti-inflammatory activities of the methanolic extract, fractions and two major alkaloids isolated from Palicourea minutiflora . Methanolic extract, non-alkaloidal and alkaloidal fractions exhibited strong growth inhibition for ovarian cell lines (OVCAR-3, GI 50 = 3.8 at 16.3 µg mL -1 ) and the vincosamide alkaloid revealed selective effect on the growth of glioma cell lines (U251, GI 50 = 33.0 µg mL -1 ) compared with doxorubicin (DOX, GI 50 = 0.42 and 0.025 µg mL -1 , respectively) anticancer drug. Methanolic extract, fractions and strictosidinic acid showed significant inhibitory effect with 62.7% at 77.5% (p < 0.05) to ear edema induced by croton oil and 81% at 100% (p < 0.05) to myeloperoxidase assay compared with indomethacin (positive control) 68.4% and 91.3% (p < 0.05), respectively.

Ethnopharmacological Relevance: Miconia albicans (Sw.) Triana has been widely used in Brazilian popular medicine for the treatment of several diseases. Aerial parts are used as an infusion to treat arthrosis and arthritis, to relieve rheumatic and stomach pains, and intestinal disorders due to its anti-inflammatory, anti-mutagenic anti-nociceptive, digestive and hepatoprotective properties., Aim of the Study: This study aimed to characterize the of M. albicans (Sw.) Triana fruits extract (MAFRE) chemical profile and to evaluate its antioxidant, anti-inflammatory and antitumor activities, as well as its toxicity., Materials and Methods: Maceration with methanol as liquid extractor was used to prepare MAFRE. M. albicans (Sw.) Triana fruits chemical composition was characterized by UHPLC-QTOF-MS/MS and GC-FID (fatty acid methyl esters composition from lyophilized fruits). MAFRE antioxidant potential was evaluated in vitro using a combination of assays: Folin-Ciocalteu reducing capacity, DPPH • and ABTS radical scavenging ability and ferric reducing antioxidant power (FRAP). In vitro antiproliferative activity was investigated in four human tumor cell lines (U251, 786-0, HT29 and MDA-MB-231) while the effect on the non-tumor cell viability was assessed in the VERO cell line using the on-step MTT assay. In addition, in vivo anti-inflammatory effect was assessed by Croton oil-induced ear edema in mice followed by myeloperoxidase (MPO) activity evaluation., Results: Thirty-five compounds were identified by UHPLC-QTOF-MS/MS. Among it flavonoids derived from quercetin (8), myricetin (1), kaempferol (2), terpenoids (6) and other compounds (18). GC-FID analysis identified and quantified nine fatty acids: palmitic, stearic, arachidic, behenic, elaidic, oleic, eicosenoic, and linoleic acids. The most abundant fatty acids were polyunsaturated fatty acids (5.33 ± 0.17 mg g -1 ), followed by saturated fatty acids (2.38 ± 0.07 mg g -1 ) and monounsaturated fatty acids (1.74 ± 0.09 mg g -1 ). The extract revealed high content of phenolic compounds (43.68 ± 0.50 mg GAE/g of extract), potent antioxidant, and ferrous chelating capacities. Morever, it proved to be non-toxic to the VERO cells, not affecting cells viability (95% of viable cells). No antiproliferative effect against human tumor cell lines were found. Furthermore, MAFRE significantly (p<0.05) reduced ear edema (≈35%) and MPO activity (84.5%) having a statistical effect similar to traditional steroidal and non-steroidal anti-inflammatory drugs., Conclusions: Taken together, the results evidenced that M. albicans fruit extract has antioxidant properties, a higher concentration of phenolic compounds, flavonoids, fatty acids, and also topical anti-inflammatory activity with low toxicity of extract on VERO cells. Through the ethnomedicinal study, these findings supporting the popular use of M. albicans, but also highlight that not only aerial parts and leaves deserve attention, but the fruits also have anti-inflammatory proprieties and can be a source of phenolic compounds and other substances with potential health benefices., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Background: Hypovitaminosis D has been linked to deterioration in clinical parameters and lung function in COPD. As a response to low levels of vitamin D serum Parathyroid Hormone (iPTH) is increased in some, but not all, patients. The aim of this study was to determine whether COPD patients with elevated PTH levels are at higher risk of COPD exacerbations and hospitalizations., Methods: 166 COPD outpatients were randomly preselected. Clinical and analytical characteristics were assessed at baseline. After excluding patients with other conditions known to disturb calcium metabolism 141 patients were identified. Except one, all patients were prospectively followed for 12 months after obtaining the blood samples. Hypovitaminosis D was considered when serum 25(OH)D < 30 ng/mL. Secondary hyperparathyroidism was considered when serum iPTH was higher than normal (50 pg/mL) in patients with hypovitaminosis D. COPD exacerbations and hospital admissions were recorded during the follow-up., Results: Prevalence of hypovitaminosis D in COPD patients was 89.3%, prevalence of secondary hyperparathyroidism associated with hypovitaminosis D was 22,9%. Cox proportional risk analysis showed that patients belonging to the high iPTH-low 25(OH)D group were at a higher risk of moderate COPD exacerbations (HR 1.81 (CI95% 1.043-3.127), p = 0.035) and hospital admissions (HR 5.45 (CI95% 2.018-14.720), p = 0.002) as compared with those with normal iPTH-low 25(OH)D levels., Conclusions: COPD patients with hypovitaminosis D and elevated iPTH have higher risk of moderate exacerbations and hospitalizations than those with hypovitaminosis D and normal iPTH., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

The present study evaluated the anti-inflammatory effect of nanoencapsulated curcuminoid preparations of poly(vinyl pyrrolidone) (Nano-cur) and free curcuminoids (Cur) in an experimental model of croton oil-induced cutaneous inflammation. Male Swiss mice, weighing 25-30 g, received oral treatment by gavage 1 h before CO application or topical treatment immediately after CO application (200 μg diluted in 70% acetone) with a single dose of Cur and Nano-cur. After 6 h, the animals were anesthetized and euthanized. The ears were sectioned into disks (6.0 mm diameter) and used to determine edema, myeloperoxidase (MPO) activity, and oxidative stress. Photoacoustic spectroscopy (PAS) was used to evaluate the percutaneous penetration of Cur and Nano-cur. Topical treatment with both preparations had a similar inhibitory effect on the development of edema, MPO activity, and the oxidative response. The PAS technique showed that the percutaneous permeation of both topically applied preparations was similar. Oral Nano-cur administration exerted a higher anti-inflammatory effect than Cur. Topical Cur and Nano-cur application at the same dose similarly inhibited the inflammatory and oxidative responses. Oral Nano-cur administration inhibited such responses at doses that were eight times lower than Cur, suggesting the better bioavailability of Nano-cur compared with Cur.Graphical abstract.

Anethole (AN) is a natural compound that has attracted great scientific interest because of its numerous biological activities, including anti-inflammatory effects. However, these effects were obtained with high doses of AN, which may be one limitation of its therapeutic use. This study evaluated the effects of a low-dose AN and ibuprofen (IB) combination on inflammatory parameters in Freund's complete adjuvant-induced arthritis (AIA) and arthritis-induced hepatic metabolic changes. Holtzman rats were used and divided into groups: normal, AIA (control), arthritics treated with IB, arthritics treated with AN, and arthritics treated with AN + IB. The volume of the paws, the appearance of secondary lesions, and the number of synovial leukocytes were evaluated. Gluconeogenesis and ureagenesis from alanine were determined in the rat liver in isolated perfusion. The AN + IB (62.5 + 8.75 mg/kg) treatment exerted an inhibitory effect on inflammatory parameters and partially prevented hepatic metabolic changes that was similar to the effect of high-dose IB (35 mg/kg) and AN (250 mg/kg) treatment. This effect of the treatments on hepatic metabolism can be, partly at least, explained by the preservation of both the alanine aminotransferase (ALT) activity and the cytosolic NADH/NAD + redox potential in the liver. Taken together, the data obtained provided evidence that the AN + IB combination at lower doses than AN and IB treatment alone had beneficial inhibitory potential for the treatment of AIA and attenuated metabolic changes in the liver. Graphical Abstract.

This study investigated the effect of prostaglandin E1 (PGE-1) treatment on the biochemical and histopathological changes in a model of nephropathy that was induced using renal microembolism in rats. Wistar rats were assigned to three groups: a control group (C, normal), a renal microembolism (RM) group, and a renal microembolism treated with PGE-1 (RM + PGE-1) group. The renal microembolism was induced by an arterial injection of polymethylmethacrylate microbeads into the remaining kidney of nephrectomized rats. Intramuscular treatment with PGE-1 was initiated on the day of the induction of the renal microembolism and continued once weekly for up to 60 days. At the end of the treatment period, blood samples were taken to assess the serum creatinine and urea concentrations, and 24-h urine samples were collected to determine the total protein levels. The rats' kidneys were removed and processed for histopathological analysis using the hematoxylin and eosin, periodic acid-Schiff, Mallory-Azan, and Picro-Sirius techniques. An immunohistochemical assay with vascular endothelial growth factor receptor-2 (anti-VEGFR-2) was also performed. The results showed that the PGE-1 treatment prevented vascular, glomerular, tubular, and interstitial alterations and reduced the biochemical changes, thus improving the renal function in rats that were subjected to renal microembolism. These effects could be partially attributable to an increase in the PGE-1-induced angiogenesis, because we observed an increase in the tissue expression of VEGFR-2, a specific marker of angiogenesis., Competing Interests: None., (IJCEP Copyright © 2020.)

The inflammatory response is the reaction of living tissue to an injury of a foreign nature, such as infection and irritants, and occurs as part of the body's natural defence response. Compounds capable of inhibiting cyclooxygenase (COX) enzymes, especially COX-2, have great potential as anti-inflammatory agents. Herein we present the regioselective synthesis of 49 novel compounds based on the 2-pyridone nucleus. The topical anti-inflammatory activity of seventeen compounds was evaluated in mice by croton oil (CO) induced ear edema assay. Most of the compounds exhibited a high level of in vivo anti-inflammatory activity, reducing ear edema and myeloperoxidase (MPO) activity. The most active compounds (2a and 7a) were inhibitors of COX enzymes. Compound 2a selectively inhibited the COX-2, while 7a was nonselective. Further, the compound 2a showed effective binding at the active site of COX-2 co-crystal by docking molecular study., Competing Interests: Declaration of Competing Interest The authors declared that there is no conflict of interest., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

There are different varieties of mushrooms not yet studied spread all over the planet. The objective of this study was to evaluate biochemical properties and effects on mitochondrial respiration of eight Basidiomycete mushrooms: Flaviporus venustus EF30, Hydnopolyporus fimbriatus EF41 and EF44, Inonotus splitgerberi EF46, Oudemansiella canarii EF72, Perenniporia sp. EF79, Phellinus linteus EF81, and Pleurotus albidus EF84. Total phenols, ABTS, TEAC, FRAP, and ORAC were measured in order to determine the antioxidant capacity. Antimicrobial potential was studied by disc-diffusion and microdilution method. Cytotoxicity was determined in murine peritoneal macrophages. The bioenergetic aspects were evaluated by the uncoupling of the oxidative phosphorylation in mitochondrias. The H. fimbriatus mushroom was the one that presented the most significant results for the antioxidant assays. Three mushrooms presented antimicrobial activity, indicating a potential for formulation of drugs. The results suggest that I. spligerberi has an uncoupling activity, even at the lowest concentration tested, dissipating the mitochondrial electrochemical gradient. On the other hand, P. albidus has effect only on succinate-oxidase activity without influencing mitochondrial respiratory efficiency. Therefore, both interfere negatively in mitochondrial respiration. In relation with the cytotoxicity in peritoneal macrophages, O. canarii and F. venustus were cytotoxic in this type of cells.

(-)-α-Bisabolol (BISA) is an unsaturated monocyclic sesquiterpenes compound, mainly found in the essential oil of chamomile (Matricaria chamomilla). It has been reported that this compound has several biological activities, but there are few studies evaluating the activity of this compound in the systemic inflammatory response in infectious processes. The aim of this study was to evaluate the effect of BISA on the inflammatory response and survival rate in a systemic infection model, and in vitro neutrophils phagocytic activity. BISA at concentration of 3, 10, 30, and 90 μg/ml did not presented in vitro cytotoxicity in MTT assay, and at concentrations of 1 and 3 μg/ml the BISA treatment increased in vitro phagocytic neutrophil activity. For the inflammatory response study, we verified the BISA treatment effect in a cecal ligation and puncture (CLP)-induced systemic infection model in mice; in this model, we demonstrate that BISA at dose of 100 mg/kg reduced the leukocyte recruitment in peritoneal cavity; at dose of 200 mg/kg, the NO concentration was increased in the peritoneal cavity. The bacteria CFU number was reduced in mice blood in the BISA treatment, at doses of 100 and 200 mg/kg. The BISA treatment at doses of 50 and 100 mg/kg increased the myeloperoxidase activity and reduction NO production in lung tissue of mice in CLP model. At dose of 100 mg/kg, the BISA treatment was able to reduce the mortality rate of mice submitted to CLP-induced sepsis and observed for 7 days. The results suggest an effect of BISA on inflammatory response, with activity on leukocyte chemotactic and NO production, in addition to increasing the survival rate of animals submitted to CLP model.

Aims: The aim of our study was to study the pathological mechanisms induced by the rheumatoid arthritis (RA) on the Enteric Nervous System (ENS)., Main Methods: We evaluated the effect of the chronic arthritis and its treatment with 50 mg/kg quercetin alone (AQ) and combined with 17.5 mg/kg ibuprofen (AIQ) for 60 days on neurons, glial cells and intestinal wall. Other groups were used: control (C), arthritic (A) and arthritic treated with 17.5 mg/kg ibuprofen (AI). After 60 days, the jejunum was removed and processed for immunohistochemical techniques. Immunostainings were performed for HuC/D and S100 (myenteric and submucosal plexuses), and GFAP (only myenteric plexus), while immunolabeling for CD45 and CD20 lymphocytes was performed using cryosections. Western blot was performed for GDNF, S100 and GFAP., Key Findings: A group yielded a remarkable density decrease of the neurons and glial cells with morphometric changes in the myenteric and submucosal plexuses, reduction of the GDNF expression and GFAP-related parameters (GFAP expression, occupancy area and GFAP-expressing glial cells) and intestinal inflammation and atrophy of the mucosa and intestinal wall. AQ group substantially reversed most of these effects, except for intestinal atrophy of the jejunum. The AI and AIQ groups displayed lower beneficial results than AQ for parameters related to the neurons and glial cells, although AIQ did not prevent the inflammation of the mucosa., Significance: The severe chronic rheumatoid arthritis induced severe effects on ENS and mucosa, and quercetin treatment continues to be an important antioxidant supplement preventing the progression of the RA severity., (Copyright © 2019 Elsevier Inc. All rights reserved.)