The Phytochemical Agathisflavone Modulates miR146a and miR155 in Activated Microglia Involving STAT3 Signaling.

MicroRNAs (miRs) act as important post-transcriptional regulators of gene expression in glial cells and have been shown to be involved in the pathogenesis of neurodegenerative diseases, including Alzheimer's disease (AD). Here, we investigated the effects of agathisflavone, a biflavonoid purified from the leaves of Cenostigma pyramidale (Tul.), on modulating the expression of miRs and inflammatory mediators in activated microglia. C20 human microglia were exposed to oligomers of the ß-amyloid peptide (Aß, 500 nM) for 4 h or to lipopolysaccharide (LPS, 1 µg/mL) for 24 h and then treated or not with agathisflavone (1 µM) for 24 h. We observed that ß-amyloid and LPS activated microglia to an inflammatory state, with increased expression of miR-146a, miR-155, IL1-ß, IL-6, and NOS2. Treatment with agathisflavone resulted in a significant reduction in miR146a and miR-155 induced by LPS or Aß, as well as inflammatory cytokines IL1-ß, IL-6, and NOS2. In cells stimulated with Aß, there was an increase in p-STAT3 expression that was reduced by agathisflavone treatment. These data identify a role for miRs in the anti-inflammatory effect of agathisflavone on microglia in models of neuroinflammation and AD.

Overexpression of miR-17-5p may negatively impact p300/CBP factor-associated inflammation in a hypercholesterolemic advanced prostate cancer model.

BACKGROUND: Previously, we demonstrated that cholesterol triggers the increase in p300/CBP-associated factor (PCAF), targeted by miR-17-5p. The p300, IL-6, PCAF, and miR-17-5p genes have important and contradictory roles in inflammation and prostate cancer (PCa). This study aimed to demonstrate the potential anti-inflammatory effect of miR-17-5 in an advanced PCa model with diet-induced hypercholesterolemia. METHODS AND RESULTS: In vitro, using the PC-3 cell line, we show that induction of miR-17-5p reduces p300 and PCAF expression, increases apoptosis, and decreases cell migration. Furthermore, we demonstrate that supplementing this same cell with cholesterol (2 µg/mL) triggers increased p300, IL-6, and PCAF. In vivo, after establishing the hypercholesterolemic (HCOL) model, xenografts were treated with miR-17-5p. Increased expression of this miR after intratumoral injections attenuated tumor growth in the control and HCOL animals and reduced cell proliferation. CONCLUSION: Our results demonstrate that inducing miR-17-5p expression suppresses tumor growth and inflammatory mediator expression. Further studies should be conducted to fully explore the role of miR-17-5p and the involvement of inflammatory mediators p300, PCAF, and IL-6.

Intratumoral Restoration of miR-137 Plus Cholesterol Favors Homeostasis of the miR-137/Coactivator p160/AR Axis and Negatively Modulates Tumor Progression in Advanced Prostate Cancer.

MicroRNAs (miRNAs) have gained a prominent role as biomarkers in prostate cancer (PCa). Our study aimed to evaluate the potential suppressive effect of miR-137 in a model of advanced PCa with and without diet-induced hypercholesterolemia. In vitro, PC-3 cells were treated with 50 pmol of mimic miR-137 for 24 h, and gene and protein expression levels of SRC-1, SRC-2, SRC-3, and AR were evaluated by qPCR and immunofluorescence. We also assessed migration rate, invasion, colony-forming ability, and flow cytometry assays (apoptosis and cell cycle) after 24 h of miRNA treatment. For in vivo experiments, 16 male NOD/SCID mice were used to evaluate the effect of restoring miR-137 expression together with cholesterol. The animals were fed a standard (SD) or hypercholesterolemic (HCOL) diet for 21 days. After this, we xenografted PC-3 LUC-MC6 cells into their subcutaneous tissue. Tumor volume and bioluminescence intensity were measured weekly. After the tumors reached 50 mm3, we started intratumor treatments with a miR-137 mimic, at a dose of 6 µg weekly for four weeks. Ultimately, the animals were killed, and the xenografts were resected and analyzed for gene and protein expression. The animals' serum was collected to evaluate the lipid profile. The in vitro results showed that miR-137 could inhibit the transcription and translation of the p160 family, SRC-1, SRC-2, and SRC-3, and indirectly reduce the expression of AR. After these analyses, it was determined that increased miR-137 inhibits cell migration and invasion and impacts reduced proliferation and increased apoptosis rates. The in vivo results demonstrated that tumor growth was arrested after the intratumoral restoration of miR-137, and proliferation levels were reduced in the SD and HCOL groups. Interestingly, the tumor growth retention response was more significant in the HCOL group. We conclude that miR-137 is a potential therapeutic miRNA that, in association with androgen precursors, can restore and reinstate the AR-mediated axis of transcription and transactivation of androgenic pathway homeostasis. Further studies involving the miR-137/coregulator/AR/cholesterol axis should be conducted to evaluate this miR in a clinical context.

Body image and association with BMI, and purgative behaviours for weight control in adolescents aged 11-14 years.

We aimed to evaluate the association of overweight/obesity based in BMI and purgative behaviours with body image (BI). Methods: Cross-sectional study, with probabilistic sample of 976 adolescents, aged 11-14 years, from the city of Florianópolis, Brazil. Multivariate analyses were performed. Overweight (including obesity) and four variables related to purgative methods for body weight control or eating behaviour were evaluated as outcomes, while BI satisfaction was the primary independent variable in each model. Models were controlled for age, sex, type of school (public or private), intake of fruit and vegetables, number of daily meals, and physical activity scores levels. A total of 31·4 % of adolescents wanted to enlarge their silhouette and 45·6 % wanted to reduce it. Among overweight/obese adolescents, 9·6 % were satisfied with their bodies, while 89·8 % wanted to reduce it, while among the not overweight/obese adolescents, 45·4 % wanted to enlarge their silhouette (P < 0·001). Multivariate analysis showed that the odds for overweight/obesity is higher among adolescents who wanted to reduce their silhouette (OR = 11·20; 95 % CI = 5·55, 22·58). Adolescents who want to reduce their silhouette are more likely to use diuretics (OR = 3·08; CI = 1·78, 5·32) and to use laxatives (OR = 2·10; CI = 1·20, 3·68). A significant association was also found between dissatisfaction with BI and overeating (among those who want to enlarge their silhouette: OR = 1·78; CI = 1·12, 2·85 and among those who want to reduce their silhouette: OR = 1·81; CI = 1·03, 3·19). Conclusion: BI dissatisfaction was associated with overweight/obesity, as well with overeating, and the use of purgative methods.

Reverted effect of mesenchymal stem cells in glioblastoma treated with agathisflavone and its selective antitumoral effect on cell viability, migration, and differentiation via STAT3.

Glioblastoma is the most lethal tumor of the central nervous system, presenting a very poor prognostic, with a survival around 16 months. The interaction of mesenchymal stem cells and tumor cells has been studied, showing a bias in their role favoring or going against aggressiveness. Natural products such as flavonoids have showed their anticancer properties and the synergic potential with the activation of microenvironment cells to inhibit tumor progression. Agathisflavone is a flavonoid studied in neurodegenerative diseases and cancer. The present study investigated the effect of flavonoid in the viability of heterogeneous glioblastoma (GBM) cells considering a coculture or conditioned medium of mesenchymal stem cells (MSCs) effect, as well as the dose-dependent effect of this flavonoid in tumor migration and differentiation via STAT3. Agathisflavone (3-10 µM) induced dose-dependent toxicity to GL-15 and U373 human GBM cells, since 24 h after treatments. It was not toxic to human MSC but modified the pattern of interaction with GBM cells. Agathisflavone also inhibited migration and increased differentiation of human GBM cells, associated with the reduction on the expression of STAT3. These results demonstrate that the flavonoid agathisflavone had a direct anti-glioma effect. However, could be observed its effect in MSCs response that may have an impact in controlling GBM growth and aggressiveness, an important factor to consider for new therapies.

The flavonoid rutin and its aglycone quercetin modulate the microglia inflammatory profile improving antiglioma activity.

Microglia cells are the immune effector in the Central Nervous System (CNS). However, studies have showed that they contribute more to glioma progression than to its elimination. Rutin and its aglycone quercetin are flavonoids present in many fruits as well as plants and have been demonstrated to bear anti-inflammatory, antioxidant and antitumor properties also to human glioblastoma cell lines. Previous studies also demonstrated that rutin, isolated from the Brazilian plant Dimorphandra mollis Bent., presents immunomodulatory effect on astrocytes and microglia. In this study, we investigate the antitumor and immunomodulatory properties of rutin and its aglycone quercetin on the viability of glioma cells alone and under direct and indirect interaction with microglia. Flavonoid treatment of rat C6 glioma cells induced inhibition of proliferation and migration, and also induced microglia chemotaxis that was associated to the up regulation of tumor necrosis factor (TNF) and the down regulation of Interleukin 10 (IL-10) at protein and mRNA expression levels, regulation of mRNA expression for chemokines CCL2, CCL5 and CX3CL1, and Heparin Binding Growth Factor (HDGF), Insulin-like growth factor (IGF) and Glial cell-derived neurotrophic factor (GDNF) growth factors. Treatment of human U251 and TG1 glioblastoma cells with both flavonoids also modulated negatively the expression of mRNA for IL-6 and IL-10 and positively the expression of mRNA for TNF characterizing changes to the immune regulatory profile. Treatment of microglia and C6 cells either in co-cultures or during indirect interaction, via conditioned media from glioma cells treated with flavonoids or via conditioned media from microglia treated with flavonoids reduced proliferation and migration of glioma cells. It also directed microglia towards an inflammatory profile with increased expression of mRNA for IL-1ß, IL-6, IL-18 and decreased expression of mRNA for nitric oxide synthase 2 (NOS2) and prostaglandin-endoperoxide synthase 2 (PTGS2), arginase and transforming growth factor beta (TGF-ß), as well as Insulin-like growth factor (IGF). Treatment of U251 cells with flavonoids also reduced tumorigenesis when the cells were xenotransplanted in rat brains, and directed microglia and also astrocytes in the microenvironment of tumor cell implantation as well as in the brain parenchyma to a not favorable molecular inflammatory profile to the glioma growth, as observed in cultures. Together these results demonstrate that the flavonoid rutin and its aglycone quercetin present antiglioma effects related to the property of modulating the microglial inflammatory profile and may be considered for molecular and preclinical studies as adjuvant molecules for treatment of gliomas.

Apigenin from Croton betulaster Müll restores the immune profile of microglia against glioma cells.

The flavonoid apigenin, extracted from the Brazilian plant Croton betulaster Müll. has demonstrated the ability to inhibit proliferation, induce differentiation, and modify the inflammatory profile of glioma cells. The aim of the present study was to evaluate the effect of apigenin on chemotaxis and regulation of inflammatory cytokines of microglia cells and these impacts on glioma cell growth. In cultures of isolated rat microglia, it was observed that apigenin induced changes in Iba1-positive cells to an ameboid phenotype, associated to an increase in the expression of the activated M1 profile marker OX-42 and iNOS and a reduction in the expression of the M2 profile marker CD206. Besides, apigenin modulated the tumor necrosis factor and IL-10 release by microglia. Treatment of C6 glioma cells with conditioned medium of microglia treated with apigenin-induced reduction of tumor migration and viability, associated with significant reduction in IL-6 levels. On the other hand, treatment of C6 cells with apigenin-induced microglia chemotaxis to glioma in vitro. Moreover, apigenin treatment of microglia/C6 co-cultures induced preferentially reduction in the viability of C6 cells and increased microglia-activated phenotype, associated with a change in the balance of TNF/IL-10 levels. Together, these results demonstrated that the flavonoid apigenin restores the immune profile of microglia against glioma cells.

Experimental type 2 diabetes induction reduces serum vaspin, but not serum omentin, in Wistar rats.

Vaspin and omentin are adipose tissue adipokines that have often been related to obesity and its comorbidities. The aim of this study was to investigate the behaviour of serum omentin and vaspin in models of type 2 diabetes. To do this, Wistar rats (~200 g) were randomly divided into two groups: a non-diabetic group (n = 6) and a diabetic group fed on a high-fat diet (n = 6) and a low dose of streptozotocin (Sigma® ). All procedures were approved by the Brazilian Ethics Committee. Body weight (BW) and food intake were recorded daily. Tail blood glucose levels were assessed at the end of the diabetes induction period. The insulin tolerance test (ITT) was performed after the diabetes induction period (7 weeks). The serum and tissues (liver, pancreas, and retroperitoneal (RET), epididymal (EPI) and visceral (VIS) white adipose tissues) were immediately removed and weighed. Analyses of levels of insulin, omentin, vaspin, adiponectin and inflammatory cytokines IL-6, IL-8 (CXCL8), TNF-α and C-reactive protein (CRP) in serum were performed using the enzyme-linked immunosorbent assay (ELISA). Our results showed that IL-8 and CRP serum levels in the diabetic group were significantly higher than in the non-diabetic group. Vaspin and adiponectin values were lower for the diabetic group than for the non-diabetic group. Omentin, IL-6 and TNF-α values did not differ between the groups. Our results showed that both the metabolism of the adipose tissue and the secretion of adipokines may be affected in diabetic rats. Omentin showed no difference between the groups, although the vaspin values decreased in the diabetic group.

Dementia in elderly inpatients admitted to medical wards in Brazil: diagnosis and comorbidity with other clinical diseases.

BACKGROUND: Specific comorbidities affect older patients with dementia admitted to general hospitals and may complicate the recognition of dementia. The aim of the present study was to estimate the prevalence of dementia among elderly inpatients admitted to hospital medical wards and to identify its distribution across clinical and sociodemographic conditions. METHODS: From June 2011 to May 2012, a sample of elderly inpatients (≥60 years old) were screened for dementia with the Mini-Mental State Examination and the Bayer Activities of Daily Living Scale to identify cognitive and functional impairment (CFI). Subjects with CFI underwent a diagnostic procedure for dementia using the Cambridge Mental Disorders of the Elderly Examination and the Diagnostic and Statistical Manual of Mental Disorders, 4th edition. The elderly inpatients also completed a standard questionnaire to investigate sociodemographic and clinical variables and a screening procedure for depression and delirium. The data obtained were submitted to univariate and multivariate analyses. RESULTS: The sample of 224 subjects had a mean age of 71.5 years and was mostly men (62.2%), poorly educated (≤4 years of schooling: 74.6%), and married (53.4%). CFI was observed in 84 subjects (prevalence: 37.4%; 95% confidence interval: 31.1-43.7), and dementia was observed in 31 subjects (prevalence: 17.2%; 95% confidence interval: 12.3-22.1). Dementia was related to older age and the presence of delirium, stroke, and pneumonia. CONCLUSIONS: The prevalence of CFI and dementia was high among the elderly inpatients examined. The identification of medical and sociodemographic conditions associated with a dementia diagnosis in a general hospital may be useful in the development of preventative actions.

Aerobic exercise and not a diet supplemented with jussara açaí (Euterpe edulis Martius) alters hepatic oxidative and inflammatory biomarkers in ApoE-deficient mice.

The pulp of jussara açaí (Euterpe edulis Martius) fruit is rich in anthocyanins that exert antioxidant and anti-inflammatory effects similar to those exerted by aerobic exercise. In the present study, we investigated the effects of jussara açaí fruit pulp consumption, either alone or in combination with aerobic exercise, on the hepatic oxidative and inflammatory status of ApoE-deficient (ApoE - / - ) mice. Male mice were divided into four groups (control (C), control plus açaí, exercise plus açaí (EXA) and exercise (EX)) and fed the AIN-93M diet or the AIN-93M diet formulated to contain 2 % freeze-dried açaí pulp. Mice in the EX and EXA groups were subjected to a progressive running programme (5 d/week, 60 min/d, 16 m/min) for 12 weeks. Mice that were made to exercise exhibited reduced (40·85 %; P< 0·05) hepatic superoxide dismutase activity when compared with the C mice, independent of the açaí diet. Mice in the EX group exhibited a lower (42 %; P< 0·05) mRNA expression of monocyte chemotactic protein-1 in the liver compared with the C mice. Mice in the EXA and EX groups had lower percentages of hepatic lipid droplets (70 % and 56 %, respectively; P< 0·05) when compared with the C mice. Mice in the EX group had smaller (58 %; P< 0·05) area of lesions in the aorta when compared with the C mice. Serum lipid profile was not affected (P>0·05). In conclusion, aerobic exercise training rather than açaí fruit pulp consumption or a combination of both enhances the hepatic oxidative and inflammatory status of ApoE - / - mice.

High Concentrations of Cannabidiol Induce Neurotoxicity in Neurosphere Culture System.

Recent studies have demonstrated that cannabinoids are potentially effective in the treatment of various neurological conditions, and cannabidiol (CBD), one of the most studied compounds, has been proposed as a non-toxic option. However, the adverse effects of CBD on neurodevelopmental processes have rarely been studied in cell culture systems. To better understand CBD's influence on neurodevelopment, we exposed neural progenitor cells (NPCs) to different concentrations of CBD (1 µM, 5 µM, and 10 µM). We assessed the morphology, migration, differentiation, cell death, and gene expression in 2D and 3D bioprinted models to stimulate physiological conditions more effectively. Our results showed that CBD was more toxic at higher concentrations (5 µM and 10 µM) and affected the viability of NPCs than at lower concentrations (1 µM), in both 2D and 3D models. Moreover, our study revealed that higher concentrations of CBD drastically reduced the size of neurospheres and the number of NPCs within neurospheres, impaired the morphology and mobility of neurons and astrocytes after differentiation, and reduced neurite sprouting. Interestingly, we also found that CBD alters cellular metabolism by influencing the expression of glycolytic and ß-oxidative enzymes in the early and late stages of metabolic pathways. Therefore, our study demonstrated that higher concentrations of CBD promote important changes in cellular functions that are crucial during CNS development.

Evaluation of AR, AR-V7, and p160 family as biomarkers for prostate cancer: insights into the clinical significance and disease progression.

PURPOSE: To assess the role of the p160 family, AR, and AR-V7 in different initial presentations of prostate cancer and their association with clinical endpoints related to tumor progression. METHODS: The study sample comprises 155 patients who underwent radical prostatectomy and 11 healthy peripheral zone biopsies as the control group. Gene expression was quantified by qPCR from the tissue specimens. The statistical analysis investigated correlations between gene expression levels, associations with disease presence, and clinicopathological features. Additionally, ROC curves were applied for distinct PCa presentations, and time-to-event analysis was used for clinical endpoints. RESULTS: The AR-V7 diagnostic performance for any PCa yielded an AUC of 0.77 (p < 0.05). For locally advanced PCa, the AR-V7 AUC was 0.65 (p < 0.05). Moreover, the metastasis group had a higher expression of SRC-1 than the non-metastatic group (p < 0.05), showing a shorter time to metastasis in the over-expressed group (p = 0.005). Patients with disease recurrence had super-expression of AR levels (p < 0.0005), with a shorter time-to-recurrence in the super-expression group (p < 0.0001). CONCLUSION: Upregulation of SRC-1 indicates a higher risk of progression to metastatic disease in a shorter period, which warrants further research to be applied as a clinical tool. Additionally, AR may be used as a predictor for PCa recurrence. Furthermore, AR-V7 may be helpful as a diagnostic tool for PCa and locally advanced cancer, comparable with other investigated tools.

Pulmonary expansion manoeuvres compared to usual care on ventilatory mechanics, oxygenation, length of mechanical ventilation and hospital stay, extubation, atelectasis, and mortality of patients in mechanical ventilation: A randomized clinical trial.

Pulmonary expansion manoeuvres are therapeutic techniques used to prevent and reverse atelectasis; however, no randomized controlled trials have provided evidence supporting the use of this intervention among individuals on mechanical ventilation. OBJECTIVE: To evaluate the effects of chest compression-decompression and chest block manoeuvres compared to usual care among patients on mechanical ventilation. METHODS: The current study was a randomized clinical trial of adult subjects on mechanical ventilation for 12 to 48 hours. The control group received usual care (passive or active mobilization, manoeuvres for airway clearance and tracheal aspiration). The intervention group received usual care plus two lung expansion manoeuvres, i.e., chest decompression and chest block, while remaining on mechanical ventilation. Assessments were performed before and after usual care, immediately after the intervention and 30 minutes after the intervention. The primary outcome was static compliance. The secondary outcomes were the incidence of atelectasis, dynamic compliance, airway resistance, driving pressure, oxygenation, duration of mechanical ventilation, extubation success, length of hospital and ICU stay, and mortality. RESULTS: Fifty-one participants (67±15 years old, 53% men, 26 in the control group and 25 in the intervention group) were evaluated. No differences in static compliance were observed between groups (intervention minus control) before and after expansion manoeuvres [3.64 ml/cmH2O (95% CI: -0.36-7.65, p = 0.074)]. Peripheral oxygen saturation differed between groups before and after expansion manoeuvres, with more favourable outcome observed in the control group [-1.04% (95% CI: -1.94 --0.14), p = 0.027]. No differences were found in other outcomes. CONCLUSION: Chest compression-decompression and chest block manoeuvres did not improve ventilatory mechanics, the incidence of atelectasis, oxygenation, the duration of mechanical ventilation, the length of stay in the ICU and hospital, or mortality in individuals on mechanical ventilation. The findings of this study can be valuable for guiding evidence-based clinical practice and developing a therapeutic approach that provides real benefits for this population.

Could Cratylia argentea replace Tifton 85 hay on growing and finishing lamb diets in tropical areas?

Legumes shrubs such as Cratylia argentea have an ability to thrive in environments with low water availability and poor soil. On the other hand, forage grasses such as Tifton 85 have a greater demand for inputs to be productive. The objective of this study was to evaluate the performance of growing and finishing Lacaune lambs fed Cratylia argentea hay as an alternative to Tifton 85 (Cynodon spp). Twenty-four Lacaune lambs aged between five and six months (average body weight [BW] 21.50 ± 3.38 kg) were arranged in a split-plot randomized block design. The plots consisted of different Cratylia to Tifton 85 hay proportions (0, 20%, 40%, or 100%, dry matter [DM] basis) as a roughage replacement in the total diet. The subplots represented two evaluation times, entitled "initial period" and "final period", which consisted of the early seven days of total feces and urine collection, and the last seven days of the experiment, respectively. The lambs were blocked by weight with six replicates per treatment. The results show that the level of Tifton 85 replacement for Cratylia hay in the roughage portion of the lamb diet did not influence (P > 0.05) weight gain (WG), dry matter intake or dry matter digestibility; feed conversion, feed efficiency; and the evaluated nitrogen balance variables. The digestibility coefficient of neutral detergent fiber decreased linearly as Tifton 85 replacement for Cratylia level was increased, which probably happened due to the presence of highly lignified material within the Cratylia hay. However, the alternative legume maintained animal performance of Tifton 85. In conclusion, Cratylia hay can be recommended as a potential substitute for Tifton 85 hay, which requires greater inputs for the production. Cratylia may be considered a feeding strategy for livestock production, especially for smallholder livestock systems and regions with unfavorable soil and climate.

Effects of Mimosa caesalpiniifolia pre-formulation on the intestinal barrier during sodium dextran sulfate-induced colitis in Wistar rats / Efectos de la preformulación de Mimosa caesalpiniifolia sobre la barrera intestinal durante la colitis inducida por sulfato de dextrano sódico en ratas Wistar

INTRODUCTION: Anti-inflammatories, immunosuppressants, and immunobiological are commonly used in the treatment of inflammatory bowel disease. However, some patients do not present an adequate response or lose effective response during the treatment. A recent study found a potential anti-inflammatory effect of the hydroalcoholic extract of Mimosa caesalpiniifolia on trinitrobenzene sulfonic acid-induced colitis in Wistar rats. OBJECTIVE: To evaluate the effects of M. caesalpiniifolia pre-formulation on the intestinal barrier using dextran sulfate sodium-induced colitis model. MATERIALS AND METHODS: Leaf extracts were prepared in 70% ethanol and dried with a Buchi B19 Mini-spray dryer using 20% Aerosil® solution. Thirty-two male Wistar rats were randomized into four groups: basal control, untreated colitis, pre-formulation control (125 mg/kg/day), and colitis treated with pre-formulation (125 mg/kg/day). Clinical activity index was recorded daily and all rats were euthanized on the ninth day. Colon fragments were fixed and processed for histological and ultrastructural analyses. Stool samples were collected and processed for analysis of the short-chain fatty acid. RESULTS: Treatment with the pre-formulation decreased the clinical activity (bloody diarrhea), inflammatory infiltrate, and the ulcers. Pre-formulation did not repair the epithelial barrier and there were no significant differences in the goblet cells index. There was a significant difference in butyrate levels in the rats treated with the pre-formulation. CONCLUSIONS: The pre-formulation minimized the clinical symptoms of colitis and intestinal inflammation, but did not minimize damage to the intestinal barrier.

Introducción: Los antiinflamatorios, inmunosupresores e inmunobiológicos se utilizan comúnmente para tratar la enfermedad intestinal inflamatoria. Sin embargo, algunos pacientes no presentan una respuesta adecuada o pierden respuesta efectiva durante el tratamiento. En un estudio reciente, se encontró un potencial efecto antiinflamatorio del extracto hidroalcohólico de Mimosa caesalpiniifolia en la colitis inducida por el ácido trinitrobenceno sulfónico utilizando ratas Wistar. Objetivo: Evaluar los efectos de la preformulación de M. caesalpiniifolia sobre la barrera intestinal durante la colitis inducida por sulfato de dextrano sódico. Materiales y métodos: Los extractos de hojas se prepararon con una solución que contenía 70 % de etanol y se secaron con un secador por aspersión Mini B19 de Buchi usando una solución con 20 % de Aerosil®. Treinta y dos ratas Wistar macho se aleatorizaron en cuatro grupos: control basal, colitis sin tratar, control con preformulación (125 mg/kg/día) y colitis tratada con preformulación (125 mg/kg/día). El índice de actividad clínica se registró diariamente y todas las ratas se sacrificaron el noveno día. Los fragmentos de colon se fijaron y se procesaron para análisis histológicos y ultraestructurales. Se recolectaron muestras de heces y se procesaron para el análisis de ácidos grasos de cadena corta. Resultados: El tratamiento con la preformulación disminuyó la actividad clínica (diarrea sanguinolenta), el infiltrado inflamatorio y las úlceras. La preformulación no reparó la barrera epitelial y no hubo diferencias significativas en el índice de células caliciformes. Se obtuvo una diferencia significativa en los niveles de butirato en las ratas tratadas con la preformulación. Conclusiones: La preformulación minimizó los síntomas clínicos de colitis e inflamación intestinal pero no minimizó el daño a la barrera intestinal.

Effects of kefir fermented milk beverage on sodium dextran sulfate (DSS)-induced colitis in rats.

Background and aim: The etiopathogenesis of inflammatory bowel disease (IBD) is associated with different factors such as genetic, infectious, immunological, and environmental, including modification of the gut microbiota. IBD's conventional pharmacological therapeutic approaches have become a challenge due to side effects, complications from prolonged use, and higher costs. Kefir fermented milk beverage is a functional food that has demonstrated multiple beneficial effects including anti-inflammatory and antioxidant activity. Alternative therapeutic strategies have been used for IBD as more natural products with low-cost and easy acquisition. The aim of this study is to evaluate the anti-inflammatory effects of kefir fermented milk beverage on sodium dextran sulfate (DSS)-induced colitis in rats. Methods: We used 4 groups to perform this study: baseline control (BC), kefir control (KC), 5% untreated DSS-induced colitis (DSS), and 5% DSS-induced colitis treated with kefir (DSSK). The animals received fermented kefir milk beverage ad libitum for six days and the disease activity index was recorded daily. Colon samples were processed for Transmission Electron Microscopy and histopathological evaluation. We analyzed short fatty chain acids through the fecal sample using gas chromatography. Results: Kefir supplementation was able to reduce the clinical activity index and inflammatory process evidenced by decreased neutrophil accumulation, decreased reticulum edema, and increased autophagosomes. Also, showed a trend to increase the levels of acetate and propionate. Conclusions: Our results suggest that kefir fermented milk beverage may have an anti-inflammatory effect minimizing the intestinal damage of DSS-induced colitis.

Volatile profile and micropropagation conditions of Bauhinia forficata Link.

Bauhinia forficata Link. is a native South American plant, which possesses volatile compounds with pharmaceutical and medicinal properties such as antidiabetic and anti-inflammatory effects. However, the conservation and propagation of this plant are complicated by its recalcitrant seeds and delayed flowering transition. Hence, tissue culture is employed for the safe and efficient propagation of B. forficata. However, the optimal conditions for the in vitro cultivation of B. forficata remain unknown. Thus, this study aimed to characterize the volatile profile of adult B. forficata field plants and evaluate the effects of different light intensities (43 and 70 µmol m-2 s-1), gas exchange rates (14 and 25 µL L-1 s-1), and exogenous sucrose concentrations (0, 20, and 30 g L-1) on their in vitro development. The results showed that ß-caryophyllene is the major volatile compound produced by B. forficata. Moreover, culturing in a medium containing 30 g L-1 of sucrose and flasks with membranes that allow CO2 exchange at the rate of 25 µL L-1 s-1 produced vigorous and hardened plants with high survival rates independent of irradiance. This study is the first to report the optimal in vitro culture conditions for B. forficata as a reference for future studies on micropropagation and secondary metabolite production using this species. Supplementary Information: The online version contains supplementary material available at 10.1007/s13205-023-03634-8.

The Flavonoid Agathisflavone Directs Brain Microglia/Macrophages to a Neuroprotective Anti-Inflammatory and Antioxidant State via Regulation of NLRP3 Inflammasome.

Agathisflavone, purified from Cenostigma pyramidale (Tul.) has been shown to be neuroprotective in in vitro models of glutamate-induced excitotoxicity and inflammatory damage. However, the potential role of microglial regulation by agathisflavone in these neuroprotective effects is unclear. Here we investigated the effects of agathisflavone in microglia submitted to inflammatory stimulus in view of elucidating mechanisms of neuroprotection. Microglia isolated from cortices of newborn Wistar rats were exposed to Escherichia coli lipopolysaccharide (LPS, 1 µg/mL) and treated or not with agathisflavone (1 µM). Neuronal PC12 cells were exposed to a conditioned medium from microglia (MCM) treated or not with agathisflavone. We observed that LPS induced microglia to assume an activated inflammatory state (increased CD68, more rounded/amoeboid phenotype). However, most microglia exposed to LPS and agathisflavone, presented an anti-inflammatory profile (increased CD206 and branched-phenotype), associated with the reduction in NO, GSH mRNA for NRLP3 inflammasome, IL1-ß, IL-6, IL-18, TNF, CCL5, and CCL2. Molecular docking also showed that agathisflavone bound at the NLRP3 NACTH inhibitory domain. Moreover, in PC12 cell cultures exposed to the MCM previously treated with the flavonoid most cells preserved neurites and increased expression of ß-tubulin III. Thus, these data reinforce the anti-inflammatory activity and the neuroprotective effect of agathisflavone, effects associated with the control of NLRP3 inflammasome, standing out it as a promising molecule for the treatment or prevention of neurodegenerative diseases.

Seroprevalence to Rabies Virus in Wildlife in Brazil.

Serum samples of 638 free-ranging wild mammals from São Paulo state, Brazil, were tested for neutralizing antibodies against rabies virus by the rapid fluorescent focus inhibition test. Overall seroprevalence was 1.7% among 24 species surveyed, with individuals of six species having positive results indicating exposure to rabies virus.

Neuroimmunomodulatory Properties of Flavonoids and Derivates: A Potential Action as Adjuvants for the Treatment of Glioblastoma.

Glioblastomas (GBMs) are tumors that have a high ability to migrate, invade and proliferate in the healthy tissue, what greatly impairs their treatment. These characteristics are associated with the complex microenvironment, formed by the perivascular niche, which is also composed of several stromal cells including astrocytes, microglia, fibroblasts, pericytes and endothelial cells, supporting tumor progression. Further microglia and macrophages associated with GBMs infiltrate the tumor. These innate immune cells are meant to participate in tumor surveillance and eradication, but they become compromised by GBM cells and exploited in the process. In this review we discuss the context of the GBM microenvironment together with the actions of flavonoids, which have attracted scientific attention due to their pharmacological properties as possible anti-tumor agents. Flavonoids act on a variety of signaling pathways, counteracting the invasion process. Luteolin and rutin inhibit NFκB activation, reducing IL-6 production. Fisetin promotes tumor apoptosis, while inhibiting ADAM expression, reducing invasion. Naringenin reduces tumor invasion by down-regulating metalloproteinases expression. Apigenin and rutin induce apoptosis in C6 cells increasing TNFα, while decreasing IL-10 production, denoting a shift from the immunosuppressive Th2 to the Th1 profile. Overall, flavonoids should be further exploited for glioma therapy.