Neuronal control of microglia through the mitochondria.

The microbial toxin ß-N-methylamino-L-alanine (BMAA), which is derived from cyanobacteria, targets neuronal mitochondria, leading to the activation of neuronal innate immunity and, consequently, neurodegeneration. Although known to modulate brain inflammation, the precise role of aberrant microglial function in the neurodegenerative process remains elusive. To determine if neurons signal microglial cells, we treated primary cortical neurons with BMAA and then co-cultured them with the N9 microglial cell line. Our observations indicate that microglial cell activation requires initial neuronal priming. Contrary to what was observed in cortical neurons, BMAA was not able to activate inflammatory pathways in N9 cells. We observed that microglial activation is dependent on mitochondrial dysfunction signaled by BMAA-treated neurons. In this scenario, the NLRP3 pro-inflammatory pathway is activated due to mitochondrial impairment in N9 cells. These results demonstrate that microglia activation in the presence of BMAA is dependent on neuronal signaling. This study provides evidence that neurons may trigger microglia activation and subsequent neuroinflammation. In addition, we demonstrate that microglial activation may have a protective role in ameliorating neuronal innate immune activation, at least in the initial phase. This work challenges the current understanding of neuroinflammation by assigning the primary role to neurons.

Do Autistic and Depressed Rats Express the Same Type of Maternal Care?

Autism is a neurodevelopmental disorder that is more frequently diagnosed in men. Nevertheless, through current diagnostic tools, women have also been found to be affected by this disorder, but in different ways. Few studies have been conducted regarding unique periods of life, such as motherhood. Yet, extant literature has already described the existence of a comorbidity between autism and postpartum depression. Thus, this study aimed to compare the maternal care sphere between two animal models of these diseases. Lactating rats were subdivided into three groups (n = 8 animals/group): 1) control dams; 2) maternal separation (MS) dams, separated from their litter for 3 h daily from lactating day (LD) 2-12 for postpartum depression induction; and 3) valproic acid (VPA) dams, which were the pups of dams treated with 400 mg/kg of VPA (i.p.) on gestational day 12.5 for autism induction. Maternal care tests were performed during lactation and, after weaning, dams were euthanized for the analysis of dopaminergic system on the prefrontal cortex. The results showed an impairment of maternal care of MS dams and an improvement of VPA dams, as well as alterations on dopaminergic system that corroborates the behavior data. These findings indicate that VPA dams express better maternal care, even with cognitive and socialization difficulties. This is probably due to a hyper-focus, as opposed to MS dams, which mimic the maternal care dysfunction expressed by women with postpartum depression.

Bothrops jararacussu snake venom decreases CD1d, CD83, and CD86 expression on bone marrow-derived dendritic cells.

This study was designed to characterize mice bone marrow (BM) and bone marrow-derived dendritic cells (BMDC) and to compare the surface markers expression and inflammatory cytokine liberation in response to LPS and Bothrops jararacussu venom (BjV) stimulation. Typical morphology was observed in BM and BMDCs from the 4th up to the 8th day of culture using recombinant mouse GM-CSF and IL-4. A high basal level of MHC-II, CD1d, CD83, CD11c, CD80, and low CD86 was expressed by BM cells. After stimulation with GM-CSF/IL-4 for BMDCs differentiation, the BM cells differentiated into BMDCs presented MHC-II, CD1d, CD83, CD11c, CD86, and CD80 expression on the 4th - 8th day accompanied with high levels of TNF-α liberated. The difference between the surface markers' expression was observed in this time course in which CD1d, CD11c, and CD80 remained in high levels of expression, while MHC-II and CD83 showed moderate expression during the differentiation period. Also, cytokines liberation was monitored over the period of the BMDCs culture, and on the 6th day, low levels of IL-6 and IL-1ß were found, while high levels of TNF-α on the 4th and 8th days, both of which contributed to the maturity of the BMDCs. Maturation of DCs with LPS showed significant upregulation of surface markers (MHC-II, CD1d, CD83, CD86, CD80) and pro-inflammatory cytokines (IL-1ß, IL-6, TNF-α) liberation. On the other hand, BjV induced a decrease in CD1d, CD11c, CD83, and CD86 expression in mature BMDCs which was not observed when LPS was used to stimulate BMDCs which probably induces impairment in T-cell activation.

High-grade anal intraepithelial neoplasia treated with endoscopic submucosal dissection: a case report.

Anal intraepithelial neoplasia is a premalignant lesion for anal squamous cell carcinoma. Current treatment options, consisting of topical therapy and local ablative procedures with electrocautery or radiofrequency ablation, are effective although recurrence rates are high. Experience with endoscopic submucosal dissection for anal lesions is limited, with only a few cases of anal intraepithelial neoplasia and early anal squamous cell carcinoma. We present a 65-year-old woman with high-grade anal intraepithelial neoplasia successfully removed by endoscopic submucosal dissection with no complications or signs of recurrence after 5 months, suggesting that this technique could be a safe and effective approach for management of anal premalignant lesions.

A prospective study on the efficacy of oral estrogen in female patients with acromegaly.

PURPOSE: To evaluate the efficacy and safety of oral estrogen therapy in female patients of childbearing age with uncontrolled acromegaly and to verify the significance of the presence of estrogen receptor α (ER-α) in somatotropinomas. METHODS: Prospective study in which biochemical and radiological evaluations were performed at baseline and after six months of treatment with an oral formulation of ethinyl-estradiol 0.03 mg and levonorgestrel 0.15 mg. ER-α was assessed by immunohistochemistry and immunopositivity was considered when it was present in ≥ 1% of cells. RESULTS: Eight patients with uncontrolled acromegaly were selected. All patients underwent surgery. Four patients were on octreotide LAR 30 mg, two patients were on lanreotide autogel 120 mg, and two patients had active disease after surgery. At the end of follow-up, IGF-I normalized in 3/8 (37%), 2/8 (25%) patients presented with mean IGF-I reduction of 25% but without IGF-I normalization, and 2/8 (25%) did not respond-one had a 13% increase in IGF-I and IGF-I level remained unchanged after treatment in the other. In one patient, treatment was discontinued after 3 months due to side effects (headache), with an IGF-I reduction of 28% but without normalization. Tumor volume increase (41%) was observed in only one patient (the only tumor with positive ER-α expression). CONCLUSIONS: In uncontrolled patients with acromegaly, a trial with oral estrogen can be an option for young women. Oral estrogen was well tolerated, but the somatotropinoma that presented ER-α expression was the only somatotropinoma that presented growth during treatment.

On the generation of internal waves by river plumes in subcritical initial conditions.

Internal waves (IWs) in the ocean span across a wide range of time and spatial scales and are now acknowledged as important sources of turbulence and mixing, with the largest observations having 200 m in amplitude and vertical velocities close to 0.5 m s-1. Their origin is mostly tidal, but an increasing number of non-tidal generation mechanisms have also been observed. For instance, river plumes provide horizontally propagating density fronts, which were observed to generate IWs when transitioning from supercritical to subcritical flow. In this study, satellite imagery and autonomous underwater measurements are combined with numerical modeling to investigate IW generation from an initial subcritical density front originating at the Douro River plume (western Iberian coast). These unprecedented results may have important implications in near-shore dynamics since that suggest that rivers of moderate flow may play an important role in IW generation between fresh riverine and coastal waters.

Effectiveness of contact tracing and quarantine on reducing COVID-19 transmission: a retrospective cohort study.

OBJECTIVES: Contact tracing and quarantine are common measures used in the management of infectious disease outbreaks. However, few studies have measured their impact on the control of the COVID-19 pandemic. This study aimed to assess the effectiveness of those measures on reducing transmission of severe acute respiratory syndrome coronavirus 2 in a community setting. STUDY DESIGN: The study design is a retrospective cohort study. METHODS: A retrospective cohort study of COVID-19 cases notified in Eastern Porto from March 1st to April 30th, 2020 was performed. Intervention and control cohorts were defined based on whether cases were subjected to contact tracing and quarantine measures before the laboratory confirmation of disease. The number of secondary cases per index case and the proportion of cases with subsequent secondary cases were the primary outcomes. Secondary outcomes included the time from symptom onset to specimen collection and the number of close contacts. The analysis was stratified according to whether national lockdown measures had already been implemented. RESULTS: The intervention and control cohorts comprised 98 and 453 cases, respectively. No differences were observed concerning primary outcomes. The intervention group had a shorter time between symptom onset and specimen collection (median: 3 days, interquartile range [IQR]: 1-6, vs. median: 5 days, IQR: 2-7, P-value = 0.004) and fewer close contacts (median: 0, IQR: 0-2, vs. median: 2, IQR: 1-4, P-value<0.001). The stratified analysis returned similar results. CONCLUSION: Local public health measures were effective in reducing the time between symptom onset and laboratory diagnosis and the number of close contacts per case. No effect was apparent on secondary case figures, suggesting that further measures may be required.

Long lived second mode internal solitary waves in the Andaman Sea.

Internal waves are density oscillations propagating along the ocean's inner stratification, which are now acknowledged as a key constituent of the ocean's dynamics. They usually result from barotropic tides, which flow over bottom topography, causing density oscillations to propagate along the pycnocline with a tidal frequency (i.e. internal tides). These large-scale waves propagate away from their forcing bathymetry and frequently disintegrate into nonlinear short-scale (higher-frequency) internal wave packets. Typically, short-scale internal wave observations in the ocean are associated with vertical structures (in the water column) of the lowest fundamental mode. Higher vertical modes have recently been documented as well, but these are commonly short-lived (up to a few hours). However, unprecedented satellite images showing long-lived short-scale mode-2 internal waves have now been documented in the Andaman Sea, and we report here the companion results of a non-hydrostatic and fully nonlinear numerical model. The simulations reproduce the waves' main characteristics as observed in satellite imagery, and the results suggest a resonant coupling with a larger-scale mode-4 internal tide as an explanation for their long-lived character.

A field tool for the aerobic power evaluation of middle-aged female recreational runners.

This study used time to exhaustion (TTE) to predict V̇O2max in female recreational master runners. Forty-two middle-aged women (mean = 40.5 ± 5.9 years) who had trained for recreational running performed two Université de Montréal Track Tests in the facilities of the University of Barcelona (Spain). The first was performed on a treadmill (t), the second, on an athletics track (field: f). After measuring TTE and V̇O2max on the treadmill, a first-order equation was obtained to estimate fV̇O2max from fTTE. No significant difference was observed between the estimated fV̇O2max (46.5 ± 2.9 mL·kg-1·min-1) and the measured tV̇O2max (46.2 ± 5.3), with a mean value of the absolute differences of less than 8% of the tV̇O2max average. High agreement between the two V̇O2max values was also evident, as shown by the low bias of the differences and the Bland-Altman plot. The equation obtained is of interest to evaluate performance in middle-aged female recreational runners. It will allow coaches and runners to set running paces for training and could be used in training routines to determine improvements after a training program. Moreover, these tools could be used in the field to assess the physical fitness of middle-aged women, in efforts to preserve their health and physical function.

Novel strategies for genomic prediction of untested single-cross maize hybrids using unbalanced historical data.

KEY MESSAGE: Weighted outperformed unweighted genomic prediction using an unbalanced dataset representative of a commercial breeding program. Moreover, the use of the two cycles preceding predictions as training set achieved optimal prediction ability. Predicting the performance of untested single-cross hybrids through genomic prediction (GP) is highly desirable to increase genetic gain. Here, we evaluate the predictive ability (PA) of novel genomic strategies to predict single-cross maize hybrids using an unbalanced historical dataset of a tropical breeding program. Field data comprised 949 single-cross hybrids evaluated from 2006 to 2013, representing eight breeding cycles. Hybrid genotypes were inferred based on their parents' genotypes (inbred lines) using single-nucleotide polymorphism markers obtained via genotyping-by-sequencing. GP analyses were fitted using genomic best linear unbiased prediction via a stage-wise approach, considering two distinct cross-validation schemes. Results highlight the importance of taking into account the uncertainty regarding the adjusted means at each step of a stage-wise analysis, due to the highly unbalanced data structure and the expected heterogeneity of variances across years and locations of a commercial breeding program. Further, an increase in the size of the training set was not always advantageous even in the same breeding program. The use of the two cycles preceding predictions achieved optimal PA of untested single-cross hybrids in a forward prediction scenario, which could be used to replace the first step of field screening. Finally, in addition to the practical and theoretical results applied to maize hybrid breeding programs, the stage-wise analysis performed in this study may be applied to any crop historical unbalanced data.

Relação espacial entre o estojo córneo e a falange distal em éguas Campolina adultas com e sem obesidade / Spatial relationship between the hoof capsule and the distal phalanx in adult Campolina mares with and without obesity

A laminite endocrinopática tem acometido um número crescente de equinos com sinais de obesidade. Em um estudo recente com fêmeas jovens (até cinco anos) da raça Campolina, demonstraram-se indícios de alterações no dígito, ainda discretas, aparentemente associadas ao aumento da adiposidade. Com a hipótese de que essa associação é mais evidente em animais em faixa etária superior, o objetivo do presente estudo foi estudar éguas adultas (acima de cinco anos) da raça Campolina com e sem obesidade, avaliando-se radiograficamente a relação espacial entre estojo córneo e falange distal. Foram utilizadas 27 éguas entre seis e 14 anos de idade, sendo analisadas variáveis de adiposidade e medidas radiográficas dos cascos dos membros torácicos de equinos com escore corporal de 5 a 7/9 (grupo controle) e de 8 a 9 (grupo obeso). Foram feitas comparações entre os grupos e correlacionaram-se as variáveis de adiposidade com variáveis casco. A distância de afundamento da falange distal foi cerca de 20% superior nas éguas obesas (12,3±2,5 contra 10,2±2,2mm no grupo controle). Esse parâmetro também correlacionou (P<0,01) com vários parâmetros de adiposidade, com destaque para o escore de condição corporal (r=0,47) e a circunferência de pescoço a 75% (r=0,42). Os resultados corroboram estudos prévios que demonstraram associação entre obesidade e indícios de separação entre falange distal e estojo córneo em equinos de raças nacionais, comprovando, assim, a utilidade da avaliação radiográfica nesses animais. Em conclusão, éguas da raça Campolina com obesidade possuem alterações evidentes na relação espacial entre estojo córneo e falange distal, que se intensificam com o aumento da idade e da adiposidade.(AU)

In a recent study with young females (up to 5 years old) of the Campolina breed, there were discrete indications of alterations in the digit, apparently associated to the increase in adiposity. With the hypothesis that this association is more evident in horses in the upper age group, the objective was to study Campolina adult mares (above 5 years) with and without obesity, evaluating radiographically the spatial relationship between the horn and distal phalanx. Eighteen mares between six and fourteen years and with a body score of 5 to 7/9 (Control Group) and 8 to 9 (Obeso Group) were used. Adiposity and radiographic measurements from the forelimbs were analyzed. Comparisons were made between groups and adiposity variables were correlated with hoof variables. The sinking distance of the distal phalanx was about 20% higher in obese mares (12.3±2.5 versus 10.2±2.2mm). This parameter also correlated (P< 0.01) with several adiposity parameters, with emphasis on body score condition (r= 0.47) and neck circumference at 75% (r= 0.42). In conclusion, Campolina mares with obesity have obvious alterations in the spatial relation between the corneal and the distal phalanx, which get intense according to increases in age and adiposity.(AU)

Bowel preparation for small bowel capsule endoscopy - The later, the better!

BACKGROUND: In small bowel capsule endoscopy (SBCE), the presence of residue may compromise diagnostic accuracy. AIMS: To assess differences in quality of visualisation and diagnostic yield of SBCE using 3 different preparation protocols. METHODS: Prospective, randomized, blind, pilot study. Protocol A:Clear liquids diet the day before the examination with fasting from 8p.m.; Protocol B:Protocol A + 2 pouches of Moviprep®(polyethylene glycol electrolyte solution + sodium ascorbate) in 1 L of water from 8p.m. of the day before the examination; Protocol C: Protocol A + 2 pouches of Moviprep® in 1 L of water consumed after real-time confirmation of capsule arrival at small bowel. Small bowel preparation was classified by two experienced physicians, considering the percentage of the examination during which mucosal observation was adequate: Excellent(>90%); Good(90-75%); Fair(75-50%); Poor(<50%). RESULTS: 101 patients randomized to the 3 protocols (A 37, B 31, C 33 patients). Protocol C had an excellent/good small bowel preparation in a higher percentage of examinations for both readers(Reader 1-A:37.8% vs B:45.2% vs C:78.8%, p = 0.002 and Reader 2 -A:37.8% vs B:41.9% vs C:75.8%, p = 0.003). Also, protocol C had a higher detection of angioectasia (A:5.4% vs B:9.7% vs C:27.3%, p = 0.022). CONCLUSIONS: The administration of Moviprep® after the capsule had reached the small bowel was associated with a better small bowel preparation and a higher detection of angioectasia.

Acute lower gastrointestinal bleeding: are STRATE and BLEED scores valid in clinical practice?

AIM: Acute lower gastrointestinal bleeding (ALGIB) is a common gastroenterological emergency. Despite this, outcomes are difficult to predict. Only STRATE and BLEED scores are readily available. The aim of this study was to identify risk factors for severe ALGIB and access the validity of available scores. METHODS: Emergency consecutive admissions for ALGIB in the last 7 years were retrospectively reviewed. Severe ALGIB was defined as transfusion of ≥ 2 units of blood and/or a haematocrit decrease of ≥ 20% within the first 24 h and/or recurrent bleeding after 24 h of stability. STRATE and BLEED scores were calculated and concordance between score and respective severity outcome was accessed. RESULTS: A total of 132 patients were identified. Bleeding presented as haematochezia in 94.7% and was severe in 36.4% of cases. ALGIB was significantly more severe in patients with lower systolic (P = 0.02) and diastolic blood pressures on admission (P < 0.01), lower admission haemoglobin (P < 0.01), diverticular bleeding (P < 0.01), angioectasias (P = 0.02) and radiation colitis (P < 0.02). Severe ALGIB was associated with admission intermediate care units (P < 0.01), increased length of stay (P < 0.01) and volume of blood transfused (P < 0.01). We identified no significant association between outcomes with either the STRATE (P = 0.72) or BLEED scores (P = 0.05). CONCLUSIONS: Severe ALGIB is associated with greater length of stay, volume of blood transfusions and admission to greater level of care units. In our cohort, STRATE and BLEED scores were poor predictors of outcome.

The beneficial role of exercise in mitigating doxorubicin-induced Mitochondrionopathy.

Doxorubicin (DOX) is a widely used antineoplastic agent for a wide range of cancers, including hematological malignancies, soft tissue sarcomas and solid tumors. However, DOX exhibits a dose-related toxicity that results in life-threatening cardiomyopathy. In addition to the heart, there is evidence that DOX toxicity extends to other organs. This general toxicity seems to be related to mitochondrial network structural, molecular and functional impairments. Several countermeasures for these negative effects have been proposed, being physical exercise, not only one of the most effective non-pharmacologic strategy but also widely recommended as booster against cancer-related fatigue. It is widely accepted that mitochondria are critical sensors of tissue functionality, both modulated by DOX and exercise. Therefore, this review focuses on the current understanding of the mitochondrial-mediated mechanisms underlying the protective effect of exercise against DOX-induced toxicity, not only limited to the cardiac tissue, but also in other tissues such as skeletal muscle, liver and brain. We here analyze recent developments regarding the beneficial effects of exercise targeting mitochondrial responsive phenotypes against redox changes, mitochondrial bioenergetics, apoptotic, dynamics and quality control signalling affected by DOX treatment.

Detection of the antiviral activity of epicatechin isolated from Salacia crassifolia (Celastraceae) against Mayaro virus based on protein C homology modelling and virtual screening.

Mayaro fever, caused by Mayaro virus (MAYV) is a sub-lethal disease with symptoms that are easily confused with those of dengue fever, except for polyarthralgia, which may culminate in physical incapacitation. Recently, outbreaks of MAYV have been documented in metropolitan areas, and to date, there is no therapy or vaccine available. Moreover, there is no information regarding the three-dimensional structure of the viral proteins of MAYV, which is important in the search for antivirals. In this work, we constructed a three-dimensional model of protein C of MAYV by homology modelling, and this was employed in a manner similar to that of receptors in virtual screening studies to evaluate 590 molecules as prospective antiviral agents. In vitro bioassays were utilized to confirm the potential antiviral activity of the flavonoid epicatechin isolated from Salacia crassifolia (Celastraceae). The virtual screening showed that six flavonoids were promising ligands for protein C. The bioassays showed potent antiviral action of epicatechin, which protected the cells from almost all of the effects of viral infection. An effective concentration (EC50) of 0.247 µmol/mL was observed with a selectivity index (SI) of 7. The cytotoxicity assay showed that epicatechin has low toxicity, with a 50% cytotoxic concentration (CC50) greater than 1.723 µmol/mL. Epicatechin was found to be twice as potent as the reference antiviral ribavirin. Furthermore, a replication kinetics assay showed a strong inhibitory effect of epicatechin on MAYV growth, with a reduction of at least four logs in virus production. Our results indicate that epicatechin is a promising candidate for further testing as an antiviral agent against Mayaro virus and other alphaviruses.

Effects of ambroxol on the autophagy-lysosome pathway and mitochondria in primary cortical neurons.

Glucocerebrosidase (GBA1) mutations are the major genetic risk factor for Parkinson's Disease (PD). The pathogenic mechanism is still unclear, but alterations in lysosomal-autophagy processes are implicated due to reduction of mutated glucocerebrosidase (GCase) in lysosomes. Wild-type GCase activity is also decreased in sporadic PD brains. Small molecule chaperones that increase lysosomal GCase activity have potential to be disease-modifying therapies for GBA1-associated and sporadic PD. Therefore we have used mouse cortical neurons to explore the effects of the chaperone ambroxol. This chaperone increased wild-type GCase mRNA, protein levels and activity, as well as increasing other lysosomal enzymes and LIMP2, the GCase transporter. Transcription factor EB (TFEB), the master regulator of the CLEAR pathway involved in lysosomal biogenesis was also increased upon ambroxol treatment. Moreover, we found macroautophagy flux blocked and exocytosis increased in neurons treated with ambroxol. We suggest that ambroxol is blocking autophagy and driving cargo towards the secretory pathway. Mitochondria content was also found to be increased by ambroxol via peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC1-α). Our data suggest that ambroxol, besides being a GCase chaperone, also acts on other pathways, such as mitochondria, lysosomal biogenesis, and the secretory pathway.

Pollen Ingestion by Chrysoperla externa (Hagen) Adults in a Diversified Organic Agroecosystem.

Chrysoperla externa (Hagen) larvae prey on pest insects and mites in agroecosystems, and adults mainly feed on pollen, nectar, and honeydew. Therefore, preserving this lacewing in crop systems depends on having plants that provide these resources. The objectives of this research were to identify pollen grains ingested by Ch. externa adults collected in a diversified organic agroecosystem and to evaluate whether there is a difference in the amount of ingested pollen grains between males and females. The adults of Ch. externa were collected in four different crops during 13 months in Seropédica, state of Rio de Janeiro, Brazil, using a collecting net. The adults were killed and underwent acetolysis, in order to recover the pollen in the gut. A total of 37,441 pollen grains from 19 Angiospermae families were found, besides 16 Pteridophyte spores. Among the recognized pollen grains, those of Poaceae were the majority, both in frequency of occurrence (87.5%) and in quantity (33496), and were found and recovered in every month of collection. Females and males ingested, respectively, 71.9 and 28.1% of the total number of Angiospermae pollen grains consumed by both sexes. The highest number of Poaceae pollens was obtained from the females (72.1% of the total number of Poaceae pollen, recovered from females + males). Taken as a whole, this study showed that adults of Ch. externa find possibilities to maintain throughout the year, in different crops, but the main source of pollen to males and females was Poaceae plants.

Exercise and Doxorubicin Treatment Modulate Cardiac Mitochondrial Quality Control Signaling.

The cross-tolerance effect of exercise against heart mitochondrial-mediated quality control, remodeling and death-related mechanisms associated with sub-chronic Doxorubicin (DOX) treatment is yet unknown. We therefore analyzed the effects of two distinct chronic exercise models (endurance treadmill training-TM and voluntary free wheel activity-FW) performed during the course of the sub-chronic DOX treatment on mitochondrial susceptibility to permeability transition pore (mPTP), apoptotic and autophagic signaling and mitochondrial dynamics. Male Sprague-Dawley rats were divided into six groups (n = 6 per group): saline sedentary (SAL + SED), SAL + TM (12-weeks treadmill), SAL + FW (12-weeks voluntary free-wheel), DOX + SED [7-weeks sub-chronic DOX treatment (2 mg kg-1 week-1)], DOX + TM and DOX + FW. Apoptotic signaling and mPTP regulation were followed by measuring caspase 3, 8 and 9 activities, Bax, Bcl2, CypD, ANT, and cophilin expression. Mitochondrial dynamics (Mfn1, Mfn2, OPA1 and DRP1) and auto(mito)phagy (LC3, Beclin1, Pink1, Parkin and p62)-related proteins were semi-quantified. DOX treatment results in augmented mPTP susceptibility and apoptotic signaling (caspases 3, 8 and 9 and Bax/Bcl2 ratio). Moreover, DOX decreased the expression of fusion-related proteins (Mfn1, Mfn2, OPA1), increased DRP1 and the activation of auto(mito)phagy signaling. TM and FW prevented DOX-increased mPTP susceptibility and apoptotic signaling, alterations in mitochondrial dynamics and inhibits DOX-induced increases in auto(mito)phagy signaling. Collectively, our results suggest that both used chronic exercise models performed before and during the course of sub-chronic DOX treatment limit cardiac mitochondrial-driven apoptotic signaling and regulate alterations in mitochondrial dynamics and auto(mito)phagy in DOX-treated animals.

The influence of hyperbaric environment on the skeletal muscle mitochondrial energetic of rats after induced muscle contusion.

OBJECTIVE: Analyze the influence of the hyperbaric environment on skeletal muscle mitochondrial bioenergetic end-points of rats submitted to muscle contusion. METHODS: Twelve female Wistar rats were randomly assigned to three groups. All rats were submitted to muscle contusion in the right gastrocnemius through a standard protocol. The control group (C) remained under normobaric conditions without any treatment. The hyperbaric air (HB) and the hyperbaric oxygen (HBO2) groups had four sessions of HBO2 therapy 60 minutes, six, 12, 24 and 48 hours after the injury at 253.25 kPa (2.5 atmospheres absolute/ATA) with air or 100% oxygen, respectively. The animals were sacrificed 48 hours after muscle injury, and both muscles (injured and non-injured) were analyzed. Muscle mitochondrial bioenergetics and mitochondrial permeability transition pore (MPTP) susceptibility were evaluated. RESULTS: Significant differences were found in all parameters between the injured and the non-injured gastrocnemius in the C group. In the HB group, significantly better results concerning bioenergetics-related end points with complex I and II substrates where found in the right gastrocnemius, whereas in the HBO2 group the time to Vmax (time that elapsed until the faster swelling kinetics starts) was significantly higher and the swelling amplitude was significantly smaller than in other groups, which suggest a lower susceptibility to MPTP opening. CONCLUSION: The present data suggest that hyperbaric exposure, particularly with oxygen, positively modulates the efficiency of skeletal muscle mitochondria after muscle contusion.