Baccharis anomala DC. extract reduces inflammation and attenuates hepatic fibrosis in vivo by decreasing NF-kB and extracellular matrix compounds.

Baccharis anomala DC. (BA) is a plant species found in the tropical regions of South America and is widely used for its hepatoprotective effects, as well as for the treatment of gastrointestinal diseases. Studies have recently reported its antioxidant and anti-inflammatory potential. BA extract can reverse the activated phenotype of hepatic stellate cells (HSC), which plays a central role in extracellular matrix (ECM) deposition in the development of liver fibrosis. Thus, this study aimed to evaluate the effects of the treatment with BA extract on liver fibrosis in a CCl4-induced liver fibrosis model in BALB/c mice. Methanolic extract was obtained from BA leaves, a gas chromatography/mass spectrometry (GC/MS) to detect the compounds present was performed, and then administered by intraperitoneal injection in Balb/C mice at a concentration of 50 and 100 mg/kg together with the administration of CCl4 for inducing liver fibrosis. After 10 weeks, blood analysis, histopathology, oxidative stress, as well as protein and gene expression in the hepatic tissue were performed. Treatment with BA extract was able to reduce profibrotic markers by reducing the expression of α-SMA and Col-1 proteins, as well as reducing the formation of free radicals and lipid peroxidation. (BA extract showed anti-inflammatory effects in the liver by suppressing NF-kB activation and reducing gene expression of signaling targets (IL-6 and iNOS). The data obtained showed that BA extract has antifibrotic and anti-inflammatory effects.

Conventional Mirror Therapy versus Immersive Virtual Reality Mirror Therapy: The Perceived Usability after Stroke.

Background: Stroke is a widespread and complex health issue, with many survivors requiring long-term rehabilitation due to upper-limb impairment. This study is aimed at comparing the perceived usability of two feedback-based stroke therapies: conventional mirror therapy (MT) and immersive virtual reality mirror therapy (VR). Methods: The study involved 45 participants, divided into three groups: the stroke survivors (n = 15), stroke-free older adults (n = 15), and young controls (n = 15). Participants performed two tasks using both MT and VR in a semirandom sequence. Usability instruments (SUS and NASA-TLX) were applied at the end of the activities, along with two experience-related questions. Results: The results indicated that both MT and VR had similar levels of perceived usability, with MT being more adaptable and causing less overall discomfort. Conversely, VR increased the perception of task difficulty and prevented participants from diverting their attention from the mirror-based feedback. Conclusion: While VR was found to be less comfortable than MT, both systems exhibited similar perceived usability. The comfort levels of the goggles may play a crucial role in determining the usability of VR for upper limb rehabilitation after stroke.

Bezafibrate reduces the damage, activation and mechanical properties of lung fibroblast cells induced by hydrogen peroxide.

In pulmonary fibrosis, the proliferation of fibroblasts and their differentiation into myofibroblasts is often caused by tissue damage, such as oxidative damage caused by reactive oxygen species, which leads to progressive rupture and thus destruction of the alveolar architecture, resulting in cell proliferation and tissue remodeling. Bezafibrate (BZF) is an important member of the peroxisome proliferator-activated receptor (PPARs) family agonists, used in clinical practice as antihyperlipidemic. However, the antifibrotic effects of BZF are still poorly studied. The objective of this study was to evaluate the effects of BZF on pulmonary oxidative damage in lung fibroblast cells. MRC-5 cells were treated with hydrogen peroxide (H2O2) to induce oxidative stress activation and BZF treatment was administered at the same moment as H2O2 induction. The outcomes evaluated were cell proliferation and cell viability; oxidative stress markers such as reactive oxygen species (ROS), catalase (CAT) levels and thiobarbituric acid reactive substances (TBARS); col-1 and α-SMA mRNA expression and cellular elasticity through Young's modulus analysis evaluated by atomic force microscopy (AFM). The H2O2-induced oxidative damage decreased the cell viability and increased ROS levels and decreased CAT activity in MRC-5 cells. The expression of α-SMA and the cell stiffness increased in response to H2O2 treatment. Treatment with BZF decreased the MRC-5 cell proliferation, ROS levels, reestablished CAT levels, decreased the mRNA expression of type I collagen protein (col-1) and α-smooth muscle actin (α-SMA), and cellular elasticity even with H2O2 induction. Our results suggest that BZF has a potential protective effect on H2O2-induced oxidative stress. These results are based on an in vitro experiment, derived from a fetal lung cell line and may emerge as a possible new therapy for the treatment of pulmonary fibrosis.

Mars walking simulation: An electromyographic analysis.

CONTEXT: With a long duration return mission to Mars on the horizon, we must learn as much about the environment and its influence on the musculoskeletal system as possible to develop countermeasures and mitigate deleterious health effects and maladaptation. AIMS: To determine the influence of simulated Mars gravity on the activity of four locomotor muscles while walking, in comparison to 1 G, using lower body positive pressure (LBPP). MATERIAL AND METHODS: A total of 14 male subjects (mean age: 20.6 ± 2.4 years) performed bouts of walking in both simulated Mars gravity (0.38 G) and Earth gravity (1 G) using an LBPP device. The dependent variables were the muscle activity evoked in the tibialis anterior, vastus lateralis, gluteus maximus and lateral portion of the gastrocnemius, measured using electromyography and expressed as percentages of maximum voluntary isometric contractions, and heart rate (HR). For statistical analysis, a paired t-test was performed. Statistical significance was defined as P < 0.05. RESULTS: No significant differences in muscle activity were found across conditions for any of the investigated muscles. A significant mean difference in the HR was identified between Earth (105.15 ± 8.1 bpm) and Mars (98.15 ± 10.44 bpm) conditions (P = 0.027), wherein the HR was lower during the Mars trial. CONCLUSIONS: The Mars environment may not result in any deteriorative implications for the musculoskeletal system. However, if future research should report that stride frequency and thus activation frequency is decreased in the simulated Mars gravity, negative implications may be posed for muscle retention and reconditioning efforts on the Red Planet.

Fructose-1,6-Bisphosphate Prevents Bleomycin-Induced Pulmonary Fibrosis in Mice and Inhibits the Proliferation of Lung Fibroblasts.

Pulmonary fibrosis is a specific form of interstitial pneumonia. In addition to the idiopathic cause, it may be caused by drugs such as bleomycin (BLM)-used in the treatment of tumors. Fructose-1,6-bisphosphate (FBP) is a high-energy endogenous glycolytic compound that has antifibrotic, anti-inflammatory, and immunomodulatory effects. The aim of this study was to investigate the effects of FBP on both BLM-induced pulmonary fibrosis in mice and in a human embryonic lung fibroblast (MRC-5) culture system. C57BL/6 mice were divided into four groups: control, FBP, BLM, and BLM plus FBP. A single dose of bleomycin (7.5 U/kg) was administered intratracheally, and survival, body weight, Ashcroft score, and histological analysis were evaluated. Pulmonary function and bronchoalveolar lavage fluid (BALF) were also evaluated after a single dose of bleomycin (1.2 U/kg-intratracheally). Treatment with FBP (500 mg/kg) was given on day 0 intraperitoneally. Fibroblasts (MRC-5 cells) were used to access the effect of FBP in vitro. In vivo, FBP increased the survival rate and reduced body weight loss (BLM vs. BLM plus FBP-p < 0.05). FBP also prevented BLM-induced loss of pulmonary function and decreased BALF inflammatory cells, level of fibrosis, and superficial collagen density (p < 0.05). In vitro, FBP (0.62 and 1.25 mM) had inhibitory activity on MRC-5 cells and was able to induce senescence in fibroblasts. These results showed that FBP has the potential of reducing the toxic effects of BLM and may provide supportive therapy for conventional methods used for the treatment of cancer.

Postural assessment in class III patients before and after orthognathic surgery.

PURPOSE: This study aimed to assess body posture before and after bimaxillary orthognathic surgery by photogrammetry in skeletal class III patients. METHODS: Thirty-one patients with skeletal class III dentofacial deformities (14 men, 17 women) who underwent orthodontic preparation for surgery were included in this non-randomized controlled trial. Of these, 15 who did not undergo orthognathic surgery during the period of this study served as controls. Postural assessment was performed by photogrammetry using SAPO® (Postural Assessment Software) based on anterior-, posterior-, and lateral-view images taken 1 month before and 4 months after bimaxillary orthognathic surgery with internal rigid fixation (or 4 months after the initial assessment, for the control group). The study was approved by PUCRS Research Ethics Committee, and written informed consent was obtained from all individual participants prior to their inclusion in the study. RESULTS: There was no significant difference between groups for age, gender, and GAP. In the intervention group, the right leg/hindfoot angle, which initially indicated a valgus deformity, normalized after intervention (P < 0.048). Posterior displacement of the head (P < 0.005) and trunk (P < 0.004) were observed after intervention. CONCLUSIONS: These results suggest that correction of class III dentofacial deformities by bimaxillary orthognathic surgery can produce systemic postural adjustments, especially posterior displacement of the head and trunk and knee and ankle valgus.

Gallic acid reduces the effect of LPS on apoptosis and inhibits the formation of neutrophil extracellular traps.

Apoptosis and NETosis of neutrophils are two major mechanisms of programmed cell death that differ in their morphological characteristics and effects on the immune system. Apoptosis can be delayed by the presence of pathogens or chemical components such as lipopolysaccharide (LPS). Neutrophils have other antimicrobial strategy, called neutrophil extracellular traps (NETs), which contributes to the elimination and control of the pathogen. NETosis is induced by infection, inflammation or trauma and represents an innate immune activation mechanism. The objective of this study was to evaluate the effect of gallic acid (GA) in the modulation of apoptosis and NETs release. The results show that GA decreased the anti-apoptotic effect of LPS, blocked the induction of NETs and prevented the formation of free radicals induced by LPS. These findings demonstrate that the GA is a novel therapeutic agent for decreasing the exacerbated response of the body against an infectious agent.

Effect of N-acetylcysteine and fructose-1,6-bisphosphate in the treatment of experimental sepsis.

Sepsis is a syndrome caused by uncontrolled systemic inflammatory response of the individual, which represents a serious epidemiological problem worldwide. The aim of this study was to investigate the effect of N-acetylcysteine (NAC) and fructose-1,6-bisphosphate (FBP) in the treatment of experimental sepsis. We used rats that were divided into five experimental groups: normal control (not induced), septic control (induced using a capsule with non sterile fecal content and Escherichia coli), treated with FBP (500 mg/kg i.p.), treated with NAC (150 mg/kg i.p.), and treated with the combination of FBP with NAC. In the group treated with NAC, 16.68% of the mice survived, the FBP reduced the mortality of mice during the acute stage of the disease and increased the animals' survival time in 33.34%, and the combination of drugs had no effect. Our results show that NAC prevented the mortality of animals after septic induction. These data confirm the validity of the use of NAC in the treatment of sepsis. Our data also show that the synergistic action with FBP does not improve the picture.

Anti-inflammatory and immunomodulatory effects of RDV-8 [C18H22N2O2S (ethyl 1-butyl-6-methyl-2-phenyl-4-thioxo-1,4-dihydropyrimidine-5-carboxylate)] in a rat model of induced pleurisy and in vitro lymphoproliferation.

RDV-8 [C(18)H(22)N(2)O(2)S (ethyl 1-butyl-6-methyl-2-phenyl-4-thioxo-1,4-dihydropyrimidine-5-carboxylate)] is derived from the 4-thioxopyrimidine, and presents important clinical effects. The present study explored the RDV-8 effects in the proliferation of human peripheral blood mononuclear cells (PBMCs), as well as in a pleurisy-induced rat model. PBMCs were directly plated in four different RDV-8 concentrations (0.0125, 0.025, 0.05 and 0.1 mg/mL). RDV-8 decreased cell proliferation and monocyte chemotactic protein 1 synthesis. The interleukin 1 levels and the cytotoxic effect were not significantly affected by RDV-8 treatment. In the carrageenan-induced pleurisy model, the RDV-8 (3 mg/kg) treatment induced a significant reduction in the exudate volume, in the polymorphonuclear leukocyte migration and in the pleural exudate NO levels. The results indicate that RDV-8 may have an immunomodulatory effect, as well as anti-inflammatory actions suggesting that it could represent a new strategy in the inflammatory response modulation.

Antioxidant effect of cysteamine in brain cortex of young rats.

Cysteamine is a cystine-depleting drug used in the treatment of cystinosis, a metabolic disorder caused by deficiency of the lysosomal cystine carrier. As a result, cystine accumulates within lysosomes in many tissues and organs, including the nervous system. Studies with cystine dimethyl ester loaded cells suggest that cystine might induce apoptosis through oxidative stress. Our objective was to investigate the effects of co-administration of cysteamine with the oxidant cystine dimethyl ester on several parameters of oxidative stress in the brain cortex of rats. Animals were injected with 1.6 micromol/g cystine dimethyl ester and/or 0.26 micromol/g body weight cysteamine. Cystine dimethyl ester induced lipoperoxidation, protein carbonylation, and stimulated superoxide dismutase, glutathione peroxidase and catalase activities, probably through the formation of free radicals. Cysteamine prevented those effects, possibly increasing cellular thiol pool and acting as a scavenger of free radicals. These results suggest that the antioxidant effect of cysteamine may be important in the treatment of cystinosis.

Evaluation of renal enzymuria and cellular excretion as an marker of acute nephrotoxicity due to an overdose of paracetamol in Wistar rats.

INTRODUCTION: The present study was conducted to determine whether the urinary levels of excreted enzymes, gamma-glutamyltransferase (GGT), alkaline phosphatase (ALP), lactate dehydrogenase (LDH), aspartate (AST) and alanine aminotransferases (ALT), can efficiently indicate, within 24 h, an acute nephrotoxicity due to an overdose of paracetamol (PAR). METHODS: A baseline urine was collected from the experimental group. Thereafter, blood collected from the orbital sinus (1.0 ml) and paracetamol (650 mg/kg of body weight) was administered by gavage. After the drug administration, animals were returned to the metabolic cages and then urine was collected in the next 22 h. Blood and urine collection was performed at time 0+24 h (T(24)), as well as at times 48 and 72 h (T(48) and T(72)). After the last urine and blood collection, the rats were killed and the kidneys removed and prepared for histological examination. Plasma creatinine and urinary levels of creatinine (to determinate glomerular filtration rate-GFR), GGT, ALP, LDH, ALT and AST were measured. Kidney tissues were stained with hematoxylin and eosin stain for histological assessment. RESULTS: Urinary levels of GGT, ALP and LDH enzymes were significantly higher (P<0.05) at T(24) when compared to the levels at T(0) and returned to basal levels at T(48) and T(72). The number of urinary epithelial cells at T(24) was significantly higher when compared to the control time (T(0)) (P<0.001). The GFR was significantly reduced 24, 48 and 72 h after the drug administration. CONCLUSION: The number of urinary epithelial cells and urinary enzymes levels are a simple and low cost procedure that is available and can help in the detection of renal acute lesions.