Macrophage fate: to kill or not to kill?

Macrophages are dynamic innate immune cells that either reside in tissue, serving as sentinels, or recruited as monocytes from bone marrow into inflamed and infected tissue. In response to cues in the tissue microenvironment (TME), macrophages polarize on a continuum toward M1 or M2 with diverse roles in progression and resolution of disease. M1-like macrophages exhibit proinflammatory functions with antimicrobial and anti-tumorigenic activities, while M2-like macrophages have anti-inflammatory functions that generally resolve inflammatory responses and orchestrate a tissue healing process. Given these opposite phenotypes, proper spatiotemporal coordination of macrophage polarization in response to cues within the TME is critical to effectively resolve infectious disease and regulate wound healing. However, if this spatiotemporal coordination becomes disrupted due to persistent infection or dysregulated coagulation, macrophages' inappropriate response to these cues will result in the development of diseases with clinically unfavorable outcomes. Since plasticity and heterogeneity are hallmarks of macrophages, they are attractive targets for therapies to reprogram toward specific phenotypes that could resolve disease and favor clinical prognosis. In this review, we discuss how basic science studies have elucidated macrophage polarization mechanisms in TMEs during infections and inflammation, particularly coagulation. Therefore, understanding the dynamics of macrophage polarization within TMEs in diseases is important in further development of targeted therapies.

The Detection of Thoracolumbar Spine Injuries in Horses with Chronic Laminitis Using a Novel Clinical-Assessment Protocol and Ultrasonographic Examination.

Postural adaptation is a prominent feature in horses affected by laminitis. Laminitis induces intense pain, especially in the forelimbs, prompting affected horses to assume a caudally displaced trunk posture, resulting in the hyperflexion of the thoracolumbar spine. This study assessed the nature and prevalence of thoracolumbar injuries in horses with chronic laminitis compared to horses without it. Sixty horses were used (thirty laminitic and thirty non-laminitic) of different athletic purposes and ages (2-20 years). The experimental protocol entailed a single assessment of horses' thoracolumbar spines, utilizing physical examination by MACCTORE, a scoring system developed specifically for this study. Additional evaluations included the Grimace Equine Pain Scale (HGS) and ultrasound exams. Statistical tests were used to compare values (Mann-Whitney or t-test) and lesions prevalences (Fisher) between groups (p < 0.05). The results showed a higher pain manifestation (HGS and heart rate, p < 0.0001) and thoracolumbar-spine-injury levels in chronic laminitis horses, both in MACCTORE clinical examinations (11.7 ± 4.8 vs. 4.2 ± 3.3, p < 0.0001) and general ultrasonographic indices (39.6 ± 12.0 vs. 20.7 ± 7.1, p < 0.0001), including specific examination approaches for various spinal elements. Horses with laminitis presented with a 14-fold higher prevalence of ultrasound-relevant lesions in the thoracolumbar spine (CI: 4.4 to 50.6, p < 0.0001) compared to controls. These findings constitute new evidence of an association between chronic laminitis and the presence of thoracolumbar spine injuries in horses, which may be confirmed by more sophisticated study designs.

Device-measured physical activity and cardiometabolic health: the Prospective Physical Activity, Sitting, and Sleep (ProPASS) consortium.

BACKGROUND AND AIMS: Physical inactivity, sedentary behaviour (SB), and inadequate sleep are key behavioural risk factors of cardiometabolic diseases. Each behaviour is mainly considered in isolation, despite clear behavioural and biological interdependencies. The aim of this study was to investigate associations of five-part movement compositions with adiposity and cardiometabolic biomarkers. METHODS: Cross-sectional data from six studies (n = 15 253 participants; five countries) from the Prospective Physical Activity, Sitting and Sleep consortium were analysed. Device-measured time spent in sleep, SB, standing, light-intensity physical activity (LIPA), and moderate-vigorous physical activity (MVPA) made up the composition. Outcomes included body mass index (BMI), waist circumference, HDL cholesterol, total:HDL cholesterol ratio, triglycerides, and glycated haemoglobin (HbA1c). Compositional linear regression examined associations between compositions and outcomes, including modelling time reallocation between behaviours. RESULTS: The average daily composition of the sample (age: 53.7 ± 9.7 years; 54.7% female) was 7.7 h sleeping, 10.4 h sedentary, 3.1 h standing, 1.5 h LIPA, and 1.3 h MVPA. A greater MVPA proportion and smaller SB proportion were associated with better outcomes. Reallocating time from SB, standing, LIPA, or sleep into MVPA resulted in better scores across all outcomes. For example, replacing 30 min of SB, sleep, standing, or LIPA with MVPA was associated with -0.63 (95% confidence interval -0.48, -0.79), -0.43 (-0.25, -0.59), -0.40 (-0.25, -0.56), and -0.15 (0.05, -0.34) kg/m2 lower BMI, respectively. Greater relative standing time was beneficial, whereas sleep had a detrimental association when replacing LIPA/MVPA and positive association when replacing SB. The minimal displacement of any behaviour into MVPA for improved cardiometabolic health ranged from 3.8 (HbA1c) to 12.7 (triglycerides) min/day. CONCLUSIONS: Compositional data analyses revealed a distinct hierarchy of behaviours. Moderate-vigorous physical activity demonstrated the strongest, most time-efficient protective associations with cardiometabolic outcomes. Theoretical benefits from reallocating SB into sleep, standing, or LIPA required substantial changes in daily activity.

Stilbenes, phenanthrenes and antiproliferative activity of Cattleya intermedia.

The phytochemical study of Cattleya intermedia (Orchidaceae) led to the isolation of two new stilbenoids and one new 9,10-dihydrophenanthrene, 4',5-dihydroxy-2',3-dimethoxy-dihydrostilbene (1), 3,6'-dihydroxy-4'-methoxy-dihydrostilbene (2) and 1,2,6-trihydroxy-3,8-dimethoxy-9,10-dihydrophenanthrene (3), named cattleymediol, cattleyol and phenanmediol, respectively, in addition to other five known compounds (4-8). The structural elucidations of the isolated compounds were carried out through the analyses of the one-dimensional 1H,1³C and NOE NMR spectra, and the 2D HSQC, HMBC, COSY and NOESY spectra, besides high-resolution mass spectrometry. In addition to this, the crude extract and its main fractions were analysed by ultra-high performance liquid chromatography coupled to high resolution mass spectrometry (UHPLC-QTOF-MS/MS), leading to the putative identification of several other compounds, including flavonoids and organic acids derivatives. Finally, the main fractions of the crude extract, and the pure compounds cattleymediol (1) and lusiantridine (7), had their antiproliferative activities evaluated against human cancerous HeLa and non-cancerous VERO cells.

Factors associated with mortality among hospitalized patients with COVID-19 disease treated with convalescent plasma.

The use of convalescent plasma (CP) for hospitalized patients with SARS-CoV-2 infection might be a useful option in certain settings. Soon after the outbreak of COVID-19, the National Ministry of Health of Argentina recommended the use of CP transfusion for hospitalized patients with COVID-19 disease. Between 1 June and 3 October 2020, 480 patients, excluding those on invasive mechanical ventilation (IMV), received at least one CP infusion in the province of Santa Fe. We aimed to find factors associated with mortality among this cohort of patients. The median age was 60 years (interquartile range: 49-69 years) and 320 (66.7%) were males. Most of these patients (93.75%) received a single CP infusion, 82.1% and 95.6% before day 4 and day 7 of hospitalization, respectively. Anti-SARS-CoV-2 titers were determined in the CP units administered using Elecsys Anti-SARS-CoV-2 S assay. At 28 days of follow-up, 250 patients were discharged (52.1%), 131 (27.3%) remained hospitalized without and 16 (3.3%) with oxygen requirement, 27 (5.6%) were on IMV, and 56 (11.7%) had died. In the multivariate logistic regression analysis, the factors significantly associated with 28-day mortality were (i) requirement of IMV, (ii) the administration of CP after the third day of hospitalization, (iii) age, and (iv) number of comorbidities. The qualitative and quantitative analyses of antibodies against SARS-CoV-2 in the infused CP were not associated with mortality. Our findings may imply a seemingly favorable effect of CP administration among patients with severe COVID-19 disease when infused sooner after hospitalization.IMPORTANCEThe use of convalescent plasma (CP) could be an option for patients with severe COVID-19, especially in poor-resource countries where direct antiviral drugs are not commercially available. Currently, the U.S. Food and Drug Administration limits the CP administration for outpatients and inpatients with COVID-19 who are immunocompromised and only if high levels of anti-SARS-CoV-2 antibodies are confirmed in the CP unit. Although most of the randomized clinical trials failed to show a clear-cut benefit of CP in hospitalized patients with severe COVID-19, other studies have shown that if given early in the course of the disease, it might be a useful therapeutic option. In this retrospective study, we demonstrated that early treatment (within 3 days of hospitalization) was significantly associated with reduced 28-day mortality compared with those patients treated beyond day 3. The results from our study add up to the scientific evidence on the use of CP as a relatively safe, cheap, and possibly effective therapy in certain patients suffering from severe SARS-CoV-2 infection.

Antifungal efficacy of imidazo[1,2-a]pyrazine-based thiosemicarbazones and thiazolidinediones against Sporothrix species.

Aim: To evaluate antifungal potential of 5,6,7,8-tetrahydroimidazo[1,2-a]pyrazine hybrids based on thiosemicarbazones and thiazolidinediones against pathogenic Sporothrix species. Methods: Antifungal activity of nine compounds were assessed by broth microdilution. Interactions between active compounds and itraconazole were evaluated by the checkerboard assay using non-wild-type isolates. Cytotoxicity of the compounds was determined. Results: Four C-3 substituted analogs showed antifungal activity, unrelated to thiosemicarbazone or thiazolidinedione functions. Synergistic interactions between the four compounds and itraconazole, and low toxicity on mouse fibroblast cells were observed. Activity of 5,6,7,8-tetrahydroimidazo[1,2-a]pyrazine hybrids against Sporothrix depended on the substitution on the imidazopyrazine ring. Conclusion: Antifungal potential, overcoming itraconazole resistance and low toxicity indicate the possible use of that series of compounds in a therapeutic alternative for treatment of sporotrichosis.

Functional fitness trends among older adults in Portugal between 2008 and 2018: Keeping up with a healthy aging process.

OBJECTIVES: Maintaining a healthy aging process is vital to combating and delaying the adverse health outcomes faced by the growing older adult population, where a key aspect to achieving healthy aging is the preservation of functional fitness. This study aims to present trends on the functional fitness of Portuguese older adults between 2008 and 2018 and build new normative reference standards for the Senior Fitness Battery Tests. DESIGN: Cross-sectional study. METHODS: Functional fitness was measured with the Senior Fitness Battery Tests in two national representative cohorts of the Portuguese older adult population (≥65 years) using the 2008 (n = 4712) and 2018 (n = 2717) surveys. Changes were assessed according to sex and age group. Sex and age-group normative fitness scores were developed. RESULTS: Overall findings suggested that older adults' point prevalence for arm-curl, 8-ft up-and-go, and 30-s chair sit-to-stand remained stable between 2008 and 2018, with declining trends being observed for the 6-min walk and back-scratch tests. However, results for trends varied when stratified by sex and age categories. CONCLUSIONS: Our results suggest a trend toward a stabilization of most of the functional fitness tests over the past decade, but with a critical decline in the 6-min walk test. Thus, this test should be targeted by future health-care policies. Moreover, this investigation provides new and updated normative reference standards for the Senior Fitness Battery Tests that should be used as a tool to promote a healthy aging process among Portuguese older adults.

Physical fitness trends in a nationally representative sample of Portuguese youth: What has changed from 2008 to 2018?

This investigation aimed to describe the current physical fitness (PF) status of Portuguese youth, compare secular trends from 2008 and 2018, and establish updated age- and sex-specific percentile values for distinct PF tests. In 2008 and 2018, 22 048 and 8960 children and adolescents (10-18 years) were included in two national cross-sectional investigations. PF was evaluated using the FITESCOLA® battery tests and the handgrip strength test. Independent sample t-tests and chi-squared tests were used to model the results. Weight smoothed percentile values were calculated using Cole's Lambda-Mu-Sigma (LMS) method. All analyses were weighted according to age, sex, and geographic region. In 2018, boys surpassed girls in the 20-m shuttle run, curl-ups, push-ups, standing long, and vertical jump tests, while girls performed better in the sit-and-reach (p < 0.05). The percentage of boys and girls meeting the healthy zone in the 20-min shuttle run test did not differ between 2008 and 2018 (p ≥ 0.05). In boys, a higher percentage fell in the healthy zone for the curl-up and push-up tests in 2018 compared to 2008 (85.8% vs. 83.4%, and 57.8% vs. 53.8%; p < 0.05). Girls improved their flexibility component (sit-and-reach test), with a higher percentage meeting the healthy zone in 2018 (32.6% vs. 36.9%; p < 0.05); an opposite trend was seen for boys (65.5% vs. 50.1%; p < 0.05). The present investigation provides new and updated PF percentile curves for Portuguese youth, which can be used as a general overview of the current PF state among the Portuguese young population.

Results from Portugal's 2022 report card on physical activity for children and youth.

Background: The purpose of this study is to update results of Portuguese's Report Card on Physical activity (PA) for Children and Adolescents. Methods: The grades were assigned by results derived from the PA and Fitness in Portugal 2021 Portuguese Report Card and corresponds to the third report for the Portuguese children and adolescents. It includes indicators of PA and sedentary behavior (SB) that are common to the GLOBAL matrix 4.0: Overall Physical Activity, Organized Sport and Physical Activity, Active Play, Active Transportation, Sedentary Behaviors, Family and Peers, School, Community and the Environment, Government and Physical Fitness. The search focused on published national evidence/data sources (academia, NGO, governmental) from end 2018 onwards excluding data obtained during the covid-19 pandemic. Results: The grades were assigned as follows: Overall PA (D-), Organized Sport Participation (C-), Active Play (D+), Active Transportation (D-), Sedentary behaviors (C+), Physical Fitness (C), Family and Peers (B), School (A), Community and Environment (B), and Government (B). Conclusion: In line with previous Portuguese Report Cards, a large proportion of Portuguese children and adolescents are not sufficiently active nor fit enough setting urgency for effective strategies. Particular attention should be given to Active play, Active transport and Organized Sports Participation has their grades have decreased. Some actions in selected indicators as Governmental and policy seems promising however results weren't seen yet. Despite the strong support of schools with mandatory curricula in PE no correspondent change is observed in fitness or PA, so more research is needed to find why.

You Dropped the Bomb on Me: A Case Series of Carbon Tetrachloride Toxicity.

Carbon tetrachloride (CCl4) is a halogenated hydrocarbon that is a colorless, clear liquid with a sweetish, ether-like, nonirritant odor. It was previously used in dry cleaning agents, refrigerants, and fire extinguishers. CCl4 toxicity is rarely observed. Two patients with acute hepatitis following exposure to a CCl4-containing antique fire extinguisher are presented. A son (patient 1) and father (patient 2) were admitted to the hospital with acute, unexplained elevated transaminases. After extensive questioning, they reported recent exposure to a large amount of CCl4 when an antique firebomb shattered in their home. Both patients cleaned the debris without personal protective equipment and slept in the contaminated area. The patients presented to the emergency department (ED) at varying times between 24 and 72 hours after CCl4 exposure. Both patients received intravenous N-acetylcysteine (NAC); patient 1 also received oral cimetidine. Both recovered uneventfully without sequelae. Extensive workup for other causes of elevated transaminases was unremarkable. Serum analyses for CCl4 were also unremarkable due to the delay between exposure and hospital presentation. CCl4 is a potent hepatotoxin. CCl4 metabolism via cytochrome CYP2E1 produces its toxic metabolite, the trichloromethyl radical. This radical covalently binds to hepatocyte macromolecules and causes lipid peroxidation and oxidative damage with ensuing centrilobular necrosis. Treatment is not well established, but NAC is likely beneficial via glutathione repletion and antioxidant effects. Cimetidine blocks cytochrome P450 and, thus, metabolite formation. Cimetidine may also promote the stimulation of regenerative processes acting on DNA synthesis. CCl4 toxicity is rare and infrequently reported in current literature but should be maintained in the differential of acute hepatitis. Two patients presenting nearly identically - at two different ages but from the same household - offered a clue to this enigmatic diagnosis.

Blocking PCNA interaction with NKp44 enhances primary natural killer cell-mediated lysis of triple-negative breast cancer cells.

Among the innate immune cells, natural killer cells (NK) serve its role in cytolytic targeting against infected and cancerous cells. NK function is regulated by an intricate balance of signals from interactions between activating and inhibitory NK receptors and ligands expressed on target cells. As an immune evasion strategy, cancer cells, particularly triple-negative breast cancer cells (TNBCs), express ligands that interact with NK receptors to inhibit NK cell cytolytic function. Our studies have revealed that Proliferating Cell Nuclear Antigen (PCNA), normally expressed in the nucleus with DNA replication and repair roles, was present on the cell surface of TNBC cell lines MDA-MB-231, -436, and -468. To elucidate the function of cell surface PCNA, we blocked PCNA on TNBCs with antibodies which both disrupted interaction with NKp44 and enhanced lysis by primary NK cells. Furthermore, a combinational antibody treatment of TNBCs with α-LLT1 and α-PCNA antibodies augments NK-mediated lysis. These results together suggest that cell surface PCNA on TNBCs enables evasion from cytolytic killing by NK cells. Blocking PCNA-NKp44 interaction with antibodies may potentially open an additional avenue in treatment of TNBCs.

Physical Activity and Sedentary Behavior in the Portuguese Population: What Has Changed from 2008 to 2018?

PURPOSE: Assessment of trends in physical activity (PA) and sedentary time (ST) is important for evaluating the effectiveness of national policies and setting goals to improve population PA. This study describes changes in measured PA and ST through motion sensors of the Portuguese population from 2008 to 2018. METHODS: PA and ST were measured with accelerometry from individuals (≥10 yr) participating in the 2008 ( n = 4 532) and 2018 ( n = 6 369) Portuguese PA Surveillance Systems. Changes were analyzed using generalized linear and logistic models adjusted for accelerometer wear time. A weight factor was applied to all analyses in order to achieve national representativeness of the present results. RESULTS: In 2018, 15.4%, 71.2%, and 30.6% of Portuguese youth, adults, and older adults met the PA recommendations. Compared with 2008, the percentage meeting the PA guidelines increased in youth females (4.7% vs 7.7%, P < 0.05) and adult males (72.2% vs 79.4%, P < 0.05). A decrease in ST was observed for adult males, whereas ST increased in all youth. Male youth decreased the number of breaks in ST (BST per hour), whereas a favorable increase was found for both adult and older adult males and females. CONCLUSIONS: PA has remained fairly stable between 2008 and 2018 for all groups, except for youth females and adult males. For ST, a favorable decrease was observed for adult males; however, an inverse trend was found in youth. These results are relevant for policy makers to develop health care policies aimed at promoting PA and reducing ST across all age-groups.

How Personalization Affects Motivation in Gamified Review Assessments.

Personalized gamification aims to address shortcomings of the one-size-fits-all (OSFA) approach in improving students' motivations throughout the learning process. However, studies still focus on personalizing to a single user dimension, ignoring multiple individual and contextual factors that affect user motivation. Unlike prior research, we address this issue by exploring multidimensional personalization compared to OSFA based on a multi-institution sample. Thus, we conducted a controlled experiment in three institutions, comparing gamification designs (OSFA and Personalized to the learning task and users' gaming habits/preferences and demographics) in terms of 58 students' motivations to complete assessments for learning. Our results suggest no significant differences among OSFA and Personalized designs, despite suggesting user motivation depended on fewer user characteristics when using personalization. Additionally, exploratory analyses suggest personalization was positive for females and those holding a technical degree, but negative for those who prefer adventure games and those who prefer single-playing. Our contribution benefits designers, suggesting how personalization works; practitioners, demonstrating to whom the personalization strategy was more or less suitable; and researchers, providing future research directions. Supplementary Information: The online version contains supplementary material available at 10.1007/s40593-022-00326-x.

Can Physical Activity Make Up for the Self-Care Disability Effects of Too Much Sitting? A Moderation Analysis in Octogenarians Residing in Living Care Facilities.

BACKGROUND AND PURPOSE: Physical activity can delay the progression of self-care disability in older adults residing in living care facilities. Nonetheless, older adults residing in living care facilities spend most of their time sedentary and do not meet the physical activity recommendation, which may result in increasing self-care disability in this population group. In this study, we aimed to determine whether the association between sedentary time and self-care disability was moderated by moderate-to-vigorous physical activity (MVPA) in older adults residing in living care facilities. METHODS: Sedentary time and MVPA were both measured with accelerometers. Self-care disability was assessed with the Barthel Index. A multivariate regression model was used to ascertain the effects of the interaction between sedentary time and MVPA on the self-care disability of participants. The Johnson-Neyman technique was then used to estimate the exact MVPA threshold at which the effect of sedentary time on self-care disability became nonsignificant. RESULTS: We found a significant effect of sedentary time on self-care disability (standardized ß=-1.66; 95% CI -1.77 to -1.54, P = .013). Results indicated that MVPA moderates the relationship between self-care disability status and sedentary time (standardized ß= 1.14; 95% CI 1.13 to 1.14, P = .032). The Johnson-Neyman technique determined that 51 min/day of MVPA would offset the negative effects of sedentary time on self-care disability. CONCLUSIONS: Our results suggest physical therapists should focus on reducing sedentary time alongside physical activity to prevent the progression to dependency in octogenarians residing in living care facilities.

Apoptosis in epithelial cells and its correlation with leukocyte accumulation in lamellar tissue from horses subjected to experimental sepsis-associated laminitis.

Inflammation and apoptosis in the hoof lamellar interface both contribute to the early stages of sepsis-associated laminitis, but it is not clear whether apoptosis is occurring before the onset of inflammation or is being provoked by inflammation. Apoptosis and inflammation were therefore measured in lamellar tissues obtained at different time points throughout the early stages of experimentally induced laminitis. Apoptotic cells and leukocyte were enumerated in archived paraffin embedded lamellar tissue samples from previous experiments in which acute laminitis was induced using Black Walnut Extract (BWE) or starch (CHO). BWE-derived samples from 20 horses were allocated into four groups: Control (CON = 5); Early Time Point (ETP, 1.5 h after induction, n = 5); Developmental Time Point (DTP, 3-4 h after induction, n = 5); Obel Grade 1 (OG1, Onset of Lameness, n = 5). CHO-derived samples from 25 horses were allocated into four groups: CON (n = 8); DTP (10-12 h after induction, n = 6); OG 1 (n = 6); Obel 3 (OG3, lameness progression, n = 5). Apoptotic cells were enumerated using a horse validated TUNEL technique. Compared to controls, significant increases in apoptotic cell counts were not detected in lamellar epithelial cells during the developmental phase or at the onset of lameness during laminitis induction. A negative correlation between apoptosis and leukocyte infiltration was detected in the BWE model (P < 0.05). In conclusion, apoptosis does not play an important role in the initial stages of sepsis-related laminitis.

COVID-19 outbreak and healthcare worker behavioural change toward hand hygiene practices.

BACKGROUND: The coronavirus disease (COVID-19) pandemic has affected healthcare workers (HCWs) in their clinical practice. HCWs were challenged with new guidelines and practices to protect themselves from occupational risks. AIM: To determine whether hand hygiene behaviour by real-time measurement was related to the dynamic of the epidemic, and the type of patient being cared for in France. METHODS: This study used an automated hand hygiene recording system to measure HCW hand hygiene on entry to and exit from patient rooms throughout the COVID-19 pandemic. The correlation between hand hygiene compliance and COVID-19 epidemiological data was analysed. Analysis of variance was performed to compare compliance rate during the different periods of the epidemic. FINDINGS: HCW hand hygiene rate on room entry decreased over time; on room exit, it increased by 13.73% during the first wave of COVID-19, decreased by 9.87% during the post-lockdown period, then rebounded by 2.82% during the second wave of the epidemic. Hand hygiene during patient care and hand hygiene on room exit had a positive relationship with the local COVID-19 epidemic; conversely, hand hygiene on room entry did not depend on the trend of the epidemic, nor on nursing of COVID-19 patients, and it decreased over time. CONCLUSION: HCWs modified their behaviours to face the risk propensity of the pandemic. However, to improve the poor compliance at room entry, reducing confusion between the hand hygiene recommendation and glove recommendation may be necessary; disinfection of gloving hands might solve this issue.

Chemical profile, antioxidant and anti-inflammatory properties of Miconia albicans (Sw.) Triana (Melastomataceae) fruits extract.

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.

Cytotoxicity and anti-inflammatory effects of the extract, fractions and alkaloids from Palicourea minutiflora (Rubiaceae).

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, GI50 = 3.8 at 16.3 µg mL-1) and the vincosamide alkaloid revealed selective effect on the growth of glioma cell lines (U251, GI50 = 33.0 µg mL-1) compared with doxorubicin (DOX, GI50 = 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.

Antiproliferative activity and chemical constituents of Lonchocarpus cultratus (Fabaceae).

The aerial parts of L. cultratus were submitted to a phytopharmacological investigation in order to isolate and identify the major secondary metabolites and evaluate its crude extract, fractions and isolated compounds for antiproliferative activity. Seven compounds were isolated and identified as the chalcones 2',4'-dihydroxy-5'-prenylchalcone (1) and isocordoin (2), the flavanone 8-prenylpinocembrin (3), the alkaloid 4-hydroxy-N-methylproline (4), the triterpenes lupeol and lupenone. These compounds were identified by nuclear magnetic resonance of 1H and 13C data in comparison with literature. Hexanic fraction and chalcone 2',4'-dihydroxy-5'-prenylchalcone showed potent results against human cancer cell lines tested.

Mechanical nociceptive assessment of the equine hoof following distal interphalangeal joint intra-articular anesthesia.

BACKGROUND: With the hypothesis that equine dorsal lamellar tissue can be desensitized by anesthesia injection into distal interphalangeal joint (DIPJ), the objective was to assess the mechanical nociceptive threshold of hoof dorsal lamellae following intra-articular (IA) administration of lidocaine into this joint. METHODS: The DIPJ of the forelimbs of six adult healthy horses were injected with either 5 mL of lidocaine, or 5 mL of lactated Ringer's solution. Treatments were randomly distributed, with each forelimb undergoing a single treatment. The hooves were evaluated pre- and post-injection at pre-selected times over 4 h, using a pressure algometry model. Mechanical nociceptive thresholds (MNTs) were recorded for the sole (dorsal, palmarolateral, and palmaromedial regions), coronary band (medial, lateral, and dorsal regions), heel bulbs (medial and lateral), and dorsal lamellar region (2 cm and 4 cm distal to the coronary band). The MNT means were compared over time using the Friedman test and between treatments using the Wilcoxon signed-rank test, with values of P < 0.05 considered statistically significant. RESULTS: There were no differences between treatments for any region of the hoof during the evaluation period. However, MNT values indicating analgesia were recorded in the dorsal lamellar region in 50% of hooves following adminstration of lidocaine into the DIPJ. CONCLUSION: The administration of 5 mL of lidocaine into the DIPJ does not significantly increase the mechanical nociceptive threshold of the equine hoof.