High-intensity interval training mitigates the progression of periodontitis and improves behavioural aspects in rats.

AIM: To investigate the effects of high-intensity interval training (HIIT) on periodontitis (PD) progression and behavioural outcomes. MATERIALS AND METHODS: Forty-eight Wistar rats were divided into four groups: non-trained (NT); non-trained with PD; HIIT with PD; and HIIT. The HIIT protocol, involving daily treadmill sessions, spanned 8 weeks, with PD induced by ligature after the 6th week. Behavioural tests were conducted to assess anxiety and memory. Post euthanasia, we evaluated the systemic inflammatory profile and oxidative stress markers in the hippocampus and amygdala. A morphological evaluation and elemental composition analysis of the mandibular alveolar bone were performed. RESULTS: PD exacerbated alveolar bone level, bone surface damage and alterations in calcium and phosphorus percentages on the bone surface (p < .05), while HIIT attenuated these changes (p < .05). HIIT improved systemic inflammatory markers altered by PD (tumour necrosis factor [TNF]-α, interleukin [IL]-10, TNF-α/IL-10 and IL-1ß/IL-10 ratios, p < .05). PD animals exhibited lower total antioxidant capacity and levels of thiobarbituric acid reactive substances in the amygdala and hippocampus, respectively (p < .05). HIIT maintained these parameters at levels similar to those in NT animals. HIIT improved anxiety and memory outcomes altered by PD (p < .05). CONCLUSIONS: HIIT attenuates systemic inflammation, anxiety and memory outcomes promoted by PD.

Salivary cortisol and eye temperature changes during endurance competitions.

BACKGROUND: The purpose of this study was to investigate the usefulness of salivary cortisol (SC) and eye temperature measured by infrared thermography (IRTET) as biomarkers to manage competitions more effectively and monitor horse welfare in endurance competitions. Based on previous studies, it was hypothesised that pre-exercise baseline SC and IRTET would be higher in younger or less experienced horses, and that post-exercise variation from baseline would be higher in the top finishers. RESULTS: Salivary cortisol measured in 61 competing at qualifier 40 km and 80 km rides showed an abrupt variation (93-256% rise) of the baseline SC levels [median ± interquartile range (IQR) = 0.27 ng/dl ± 0.36] obtained at the Pre-Inspection (PI) into Vet Gate (VG)1 independently of the covered distance, but modest or even lower in the subsequent Vet Gates, e.g. VG2 or VG3. The IRTET measured concomitantly in 16 horses showed significant (p < 0.05) higher levels at the PI in less experienced horses participating in the 40 km ride (median ± IQR = 35.7 °C ± 1.4) than their counterparts in the 80 km ride (median ± IQR = 35.0 °C ± 1.5), but not SC. Baseline SC levels at the PI of horses classifying in the Top5 in the 40 km ride category were significantly (p < 0.05) higher median ± IQR = 0.90 ng/ml ±0.61) when compared to horses positioned from 10th position on (median ± IQR = 0.16 ng/ml ±0.40). A lower IRTET in the PI was correlated with better placement (p < 0.05) and those in the Top5 (median ± IQR = 33.9 °C ± 0.0) had a significantly (p < 0.5) higher variation (+ 10.65%) into the last VG. CONCLUSION: Pre-exercise baseline IRTET levels, but not SC, were higher in less experienced horses in the 40 compared to their counterparts in the 80 km ride competitions. SC and IRTET showed different indications according to the competition. In the40 km ride competition, higher baseline pre-exercise SC levels seemed to be linked to a better classification outcome. In contrast, in the 80 km ride horses, the higher IRTET variation from pre-exercise into final Vet Gate was the parameter associated with a better performance. A more controlled environment and a larger sample are needed to confirm these results and monitor horse welfare in competitions.

HA-g-CS Implant and Moderate-intensity Exercise Stimulate Subchondral Bone Remodeling and Promote Repair of Osteochondral Defects in Mice.

Background: Substantial evidence shows that crosstalk between cartilage and subchondral bone may play an important role in cartilage repair. Animal models have shown that hydroxyapatite-grafted-chitosan implant (HA-g-CS) and moderate-intensity exercise promote regeneration of osteochondral defects. However, no in vivo studies have demonstrated that these two factors may have a synergistic activity to facilitate subchondral bone remodeling in mice, thus supporting bone-cartilage repair. Questions: This study was to clarify whether HA-g-CS and moderate-intensity exercise might have a synergistic effect on facilitating (1) regeneration of osteochondral defects and (2) subchondral bone remodeling in a mouse model of osteochondral defects. Methods: Mouse models of osteochondral defects were created and divided into four groups. BC Group was subjected to no treatment, HC Group to HA-g-CS implantation into osteochondral defects, ME group to moderate-intensity treadmill running exercise, and HC+ME group to both HA-g-CS implantation and moderate-intensity exercise until sacrifice. Extent of subchondral bone remodeling at the injury site and subsequent cartilage repair were assessed at 4 weeks after surgery. Results: Compared with BC group, HC, ME and HC+ME groups showed more cartilage repair and thicker articular cartilage layers and HC+ME group acquired the best results. The extent of cartilage repair was correlated positively to bone formation activity at the injured site as verified by microCT and correlation analysis. Histology and immunofluorescence staining confirmed that bone remodeling activity was increased in HC and ME groups, and especially in HC+ME group. This bone formation process was accompanied by an increase in osteogenesis and chondrogenesis factors at the injury site which promoted cartilage repair. Conclusions: In a mouse model of osteochondral repair, HA-g-CS implant and moderate-intensity exercise may have a synergistic effect on improving osteochondral repair potentially through promotion of subchondral bone remodeling and generation of osteogenesis and chondrogenesis factors. Clinical Relevance: Combination of HA-g-CS implantation and moderate-intensity exercise may be considered potentially in clinic to promote osteochondral defect repair. Also, cartilage and subchondral bone forms a functional unit in an articular joint and subchondral bone may regulate cartilage repair by secreting growth factors in its remodeling process. However, a deeper insight into the exact role of HA-g-CS implantation and moderate-intensity exercise in promoting osteochondral repair in other animal models should be explored before they can be applied in clinic in the future.

Effect of dietary cellulose nanofiber and exercise on obesity and gut microbiota in mice fed a high-fat-diet.

Cellulose nanofiber (CN) consumption with exercise could be a potential strategy to control obesity. Here, we studied the effects of CN supplementation and voluntary exercise on obesity and gut microbiota in high-fat diet (HFD)-fed mice. Consumption of CN increased voluntary wheel running activity. CN intake and exercise together suppressed the increase in body weight and fat mass, and improved glucose tolerance. The fecal gut microbiota was analyzed by sequencing 16S ribosomal RNA genes. Principal component analysis revealed a shift in the microbiota composition resulting from exercise, but not from CN supplementation. Erysipelotrichaceae and Rikenellaceae decreased with exercise. Exercise also increased Ruminococcaceae, whereas exercise and CN intake together increased Eubacteriaceae. These two families are butyrate producers. Exercise increased the amount of acetate in the cecum. These results suggest that CN consumption improves exercise performance and exerts anti-obesity effects by modulating the balance of the gut microbiota.

Loss of homeoprotein Msx1 and Msx2 leading to athletic and kinematic impairment related to the increasing neural excitability of neurons in aberrant neocortex in mice.

Although homeoproteins Msx1 and Msx2, the cell-specific transcription regulators, have been proven to play multiple roles in the embryogenesis of bone, muscle and tooth, the functions and mechanisms of Msx1 and Msx2 in the development of the central nervous system of mice after birth are not clear because of the death of Msx1 and Msx1/2 germline-deleted embryo at late gestation of mouse. In current research, Nestin-Cre mice was introduced to generate the central nervous system-specific knockout mice (Nestin-Cre;Msx1,Msx2fl/fl). We found that besides the falling of the body mass and the brain volume, the cortical tissue sections and staining showed the decreasing thickness of layer II-IV and declining number of vertebral cells in layer V resulting from Msx1/2 deletion. In addition, electrophysiological tests revealed the aberrant action potential parameters of deep pyramidal neurons in Nestin-Cre;Msx1,2 fl/fl mice, which may be related with the ethology impairment displayed in further experiments. We discovered Nestin-Cre;Msx1,2 fl/fl mice had severe impairment in their athletic ability and kinematic learning ability in rotate test, and exhibited hyperactivity in open-field test. Above all, our results revealed that deletion of homeoproteins Msx1 and Msx2 could lead to behavioral disorders and suggested that Msx1 and Msx2 played a crucial role in regulating the development and function of the neocortex. In addition, our current research provided a new mouse model for understanding the pathogenesis of human central nervous system disease.

Chronic Embolic Pulmonary Hypertension Caused by Pulmonary Embolism and Vascular Endothelial Growth Factor Inhibition.

Our understanding of the pathophysiological basis of chronic thromboembolic pulmonary hypertension (CTEPH) will be accelerated by an animal model that replicates the phenotype of human CTEPH. Sprague-Dawley rats were administered a combination of a single dose each of plastic microspheres and vascular endothelial growth factor receptor antagonist in polystyrene microspheres (PE) + tyrosine kinase inhibitor SU5416 (SU) group. Shams received volume-matched saline; PE and SU groups received only microspheres or SU5416, respectively. PE + SU rats exhibited sustained pulmonary hypertension (62 ± 13 and 53 ± 14 mmHg at 3 and 6 weeks, respectively) with reduction of the ventriculoarterial coupling in vivo coincident with a large decrement in peak rate of oxygen consumption during aerobic exercise, respectively. PE + SU produced right ventricular hypokinesis, dilation, and hypertrophy observed on echocardiography, and 40% reduction in right ventricular contractile function in isolated perfused hearts. High-resolution computed tomographic pulmonary angiography and Ki-67 immunohistochemistry revealed abundant lung neovascularization and cellular proliferation in PE that was distinctly absent in the PE + SU group. We present a novel rodent model to reproduce much of the known phenotype of CTEPH, including the pivotal pathophysiological role of impaired vascular endothelial growth factor-dependent vascular remodeling. This model may reveal a better pathophysiological understanding of how PE transitions to CTEPH in human treatments.

Swimming and diving energetics in dolphins: a stroke-by-stroke analysis for predicting the cost of flight responses in wild odontocetes.

Exponential increases in hydrodynamic drag and physical exertion occur when swimmers move quickly through water, and underlie the preference for relatively slow routine speeds by marine mammals regardless of body size. Because of this and the need to balance limited oxygen stores when submerged, flight (escape) responses may be especially challenging for this group. To examine this, we used open-flow respirometry to measure the energetic cost of producing a swimming stroke during different levels of exercise in bottlenose dolphins (Tursiops truncatus). These data were then used to model the energetic cost of high-speed escape responses by other odontocetes ranging in mass from 42 to 2738 kg. The total cost per stroke during routine swimming by dolphins, 3.31±0.20 J kg-1 stroke-1, was doubled during maximal aerobic performance. A comparative analysis of locomotor costs (LC; in J kg-1 stroke-1), representing the cost of moving the flukes, revealed that LC during routine swimming increased with body mass (M) for odontocetes according to LC=1.46±0.0005M; a separate relationship described LC during high-speed stroking. Using these relationships, we found that continuous stroking coupled with reduced glide time in response to oceanic noise resulted in a 30.5% increase in metabolic rate in the beaked whale, a deep-diving odontocete considered especially sensitive to disturbance. By integrating energetics with swimming behavior and dive characteristics, this study demonstrates the physiological consequences of oceanic noise on diving mammals, and provides a powerful tool for predicting the biological significance of escape responses by cetaceans facing anthropogenic disturbances.

Exercise attenuates alveolar bone loss and anxiety-like behaviour in rats with periodontitis.

AIM: To evaluate the effects of physical training on inflammatory and behavioural parameters of Wistar rats with periodontal disease (PD). MATERIALS AND METHODS: Twenty four animals were distributed in a 2 × 2 factorial design (with and without exercise, with and without PD). Trained animals swimmed one hour daily during 8 weeks. PD was induced by ligature 14 days before the end of experiment, and in the last week, all animals were submitted to the Marble Burying Test. Histomorphometric analyses of the mandibles and expression of cytokines were conducted by Western blotting. We also evaluated the morphometry of hippocampal astrocytes using anti-glial fibrillary acidic protein antibody. RESULTS: Physical training attenuated bone loss and epithelial attachment loss levels of rats with PD. Trained animals with PD presented lower TNF-α expression in periodontal tissues while IL-10 was increased. TNF-α/IL-10 ratio was lower in trained animals with PD compared to those with induced periodontitis. PD increased anxiety-like behaviour, and physical training attenuated this parameter. Exercise increased the ramifications of hippocampal astrocytes in rats without PD. CONCLUSIONS: Exercise decreased anxiety behaviour, inflammatory proteins expression and bone loss in rats with PD.

Effect of temperament on cortisol response to a single exercise bout in Thoroughbred racehorses - short communication.

Temperament has not been taken into account in previous studies evaluating the stress response to exercise in horses. The aim of the present study was to investigate the cortisol response in Thoroughbred racehorses to a single exercise bout, and to analyse the results based on the basic personality of the horse examined. Twenty healthy Thoroughbred horses were selected for the study based on a 25-item rating questionnaire survey used for characterising equine temperament. Eight temperamental and twelve calm horses took part in the experiment. The horses trotted as a warm-up activity, and then galloped on a rounded sand track. Blood sampling was conducted four times for each horse. Horses with a more excitable temperament showed a higher cortisol response to the test (P = 0.036). In conclusion, cortisol levels in response to a mild intensive exercise can be affected by temperament in horses. Serum cortisol may be a relevant marker to quantify individual temperamental differences in racehorses.

Voluntary exercise increases IgA concentration and polymeric Ig receptor expression in the rat submandibular gland.

Salivary IgA-a primary factor in local immunity of the oral cavity-plays an important role in maintaining local immune function in the oral cavity and prevent upper respiratory tract infections. Oral IgA levels are known to fluctuate in an exercise-dependent manner; thus, we investigated the effects of voluntary exercise on salivary IgA secretion in rats to better understand the mechanism by which this occurs. Six-week-old male Wistar rats were placed in individual cages with or without access to exercise wheels for three weeks. Notably, animals who engaged in voluntary exercise demonstrated significant increases in IgA concentration in saliva and submandibular gland tissue, as well as a markedly higher salivary IgA flow rate. Moreover, active rats also exhibited elevated polymeric Ig receptor (pIgR) mRNA expression in submandibular gland tissue. Collectively, these results suggest that voluntary exercise may increase salivary IgA concentration and boost immune function in the oral cavity.

Functional recovery in spinal cord injured rats using polypyrrole/iodine implants and treadmill training.

Currently, there is no universally accepted treatment for traumatic spinal cord injury (TSCI), a pathology that can cause paraplegia or quadriplegia. Due to the complexity of TSCI, more than one therapeutic strategy may be necessary to regain lost functions. Therefore, the present study proposes the use of implants of mesoparticles (MPs) of polypyrrole/iodine (PPy/I) synthesized by plasma for neuroprotection promotion and functional recovery in combination with treadmill training (TT) for neuroplasticity promotion and maintenance of muscle tone. PPy/I films were synthesized by plasma and pulverized to obtain MPs. Rats with a TSCI produced by the NYU impactor were divided into four groups: Vehicle (saline solution); MPs (PPy/I implant); Vehicle-TT (saline solution + TT); and MPs-TT (PPy/I implant + TT). The vehicle or MPs (30 µL) were injected into the lesion site 48 h after a TSCI. Four days later, TT was carried out 5 days a week for 2 months. Functional recovery was evaluated weekly using the BBB motor scale for 9 weeks and tissue protection using histological and morphometric analysis thereafter. Although the MPs of PPy/I increased nerve tissue preservation (P = 0.03) and promoted functional recovery (P = 0.015), combination with TT did not produce better neuroprotection, but significantly improved functional results (P = 0.000) when comparing with the vehicle group. So, use these therapeutic strategies by separately could stimulate specific mechanisms of neuroprotection and neuroregeneration, but when using together they could mainly potentiate different mechanisms of neuronal plasticity in the preserved spinal cord tissue after a TSCI and produce a significant functional recovery. The implant of mesoparticles of polypyrrole/iodine into the injured spinal cord displayed good integration into the nervous tissue without a response of rejection, as well as an increased in the amount of preserved tissue and a better functional recovery than the group without transplant after a traumatic spinal cord injury by contusion in rats. The relevance of the present results is that polypyrrole/iodine implants were synthesized by plasma instead by conventional chemical or electrochemical methods. Synthesis by plasma modifies physicochemical properties of polypyrrole/iodine implants, which can be responsible of the histological response and functional results. Furthermore, no additional molecules or trophic factors or cells were added to the implant for obtain such results. Even more, when the implant was used together with physical rehabilitation, better functional recovery was obtained than that observed when these strategies were used by separately.

Signaling mechanisms in the restoration of impaired immune function due to diet-induced obesity.

Our previous data have linked obesity with immune dysfunction. It is known that physical exercise with dietary control has beneficial effects on immune function and the comorbidities of obesity. However, the mechanisms underlying the improvement of immune function in obesity after physical exercise with dietary control remain unknown. Here we show that moderate daily exercise with dietary control restores the impaired cytokine responses in diet-induced obese (DIO) mice and improves the resolution of Porphyromonas gingivalis-induced periodontitis. This restoration of immune responses is related to the reduction of circulating free fatty acids (FFAs) and TNF. Both FFAs and TNF induce an Akt inhibitor, carboxyl-terminal modulator protein (CTMP). The expression of CTMP is also observed increased in bone marrow-derived macrophages (BMMΦ) from DIO mice and restored after moderate daily exercise with dietary control. Toll-like receptor 2 (TLR2), which increases CTMP induction by FFAs, is inhibited in BMMΦ from DIO mice or after either FFA or TNF treatment, but unexpectedly is not restored by moderate daily exercise with dietary control. Furthermore, BMMΦ from DIO mice display reduced histone H3 (Lys-9) acetylation and NF-κB recruitment to TNF, IL-10, and TLR2 promoters after P. gingivalis infection. However, moderate daily exercise with dietary control restores these defects at promoters for TNF and IL-10, but not for TLR2. Thus, metabolizing FFAs and TNF by moderate daily exercise with dietary control improves innate immune responses to infection in DIO mice via restoration of CTMP and chromatin modification.

Thermal relations in sled dogs before and after exercise.

Regulation of internal body temperature (Tb), or thermoregulation, is an evolutionarily conserved trait that places demand on basal metabolic rate of endothermic animals. Across species, athletes generate increased quantities of heat in comparison to their nonathletic counterparts and, therefore, must mediate physiological unbalance by upregulating the effectiveness of their heat dissipation abilities. Canine athletes are no exception to this phenomenon, however, with literature denoting body temperatures lower than nonathletic canines, it is clear they must possess adaptations to mitigate this demand. With VO2 max measurements of more than 200 mL/kg/min in sled dogs with mild training to 300 mL/kg/min in highly trained animals, sled dogs are a prime example of athleticism in canines. Seeking to determine correlations between Tear and body mass, morphology, and age of canine athletes, core body temperature (Tb) was measured with an instant ear thermometer, using Tear as a correlate before and after a 2-mile run. In addition, we employed thermal imaging analysis to capture body-wide heat dissipation patterns in sled dogs, and focused on thermal variation of mouth (Tmouth), nose (Tnose), and eyes (Teye). Furthermore, we looked at correlations between thermal variability across these four tissues and head morphology of each dog. Tear was consistently the highest temperature across all tissues measured, with a 1.5°C increase between pre- to postexercise (p < 0.001). Thermal imaging revealed significant positive correlations between Tmouth and body mass 15 min postexercise (p = 0.0023) as well as significantly negative correlations between Tnose and body mass at before exercise (p = 0.0468), Teye and nose length after run (p = 0.0076), and Tmouth and nose length after run (p = 0.0110). As body temperature rises during exercise, it becomes increasingly important to regulate blood flow throughout the body to supply working tissues with oxygen. This demand is offset by the role of the snout in evaporative cooling through panting, functioning as a prime location for heat dissipation and therefore maintaining significant relationships with many other vascularized tissues.

Do tight nosebands have an effect on the upper airways of horses?

BACKGROUND/OBJECTIVES: The public perception relating to the welfare of horses involved with equestrian sports is associated with training methods used and the presentation of horses at events. In this context, very tight nosebands, which are intended to prevent the horse from opening its mouth, also attract a lot of attention. Various studies have evaluated the impact of tight nosebands on stress parameters, whereas the effect of tight nosebands on upper airway function is unknown. Therefore, the aim of the study was to use overground endoscopy to evaluate changes in pharyngeal and laryngeal function when a tight noseband is fitted. Moreover, the ridden horse pain ethogram (RHpE) was applied to investigate signs of discomfort (Dyson et al., 2018). STUDY DESIGN: A randomized, blinded, and prospective study was performed. METHODS: Sixteen warmblood horses consisting of twelve mares and four geldings with a mean age of 11.63 ± 3.53 years were ridden on 2 consecutive days with either loose or tight nosebands (two fingers or no space between bridge of the nose and noseband, respectively) and inserted endoscope in a random order. Videos were taken in a riding arena during a standardized exercise protocol involving beginner level tasks for 30 min in all gaits. For video analysis, freeze frames were prepared and analyzed at the beginning of the expiration phase. Pharyngeal diameter was measured using the pharynx-epiglottis ratio. Other findings (swallowing, pharyngeal collapse, soft palate movements, and secretion) were also evaluated. Moreover, the RHpE was applied. Descriptive statistics and generalized linear mixed effects models were used. Results with a p-value < 0.05 were considered statistically significant. RESULTS: While the pharynx-epiglottis ratio did not change significantly in horses ridden with loose versus tight nosebands, there was an increase in mean grade and total counts of parameters assessed in the pharyngeal region, for example, grade of secretion (1.5 [±SD 0.89] vs. 3.13 [±SD 0.96]; p = 0.0001), axial deviation of the aryepiglottic folds (0.29 [±SD 0.73] vs. 1.33 [±SD 1.44]; p = 0.01), and pharyngeal collapse (0.69 [±SD 0.87] vs. 1.88 [±SD 1.54]; p = 0.005) in horses ridden with tight nosebands. There was no RHpE score above 8 indicating musculoskeletal pain, but the RHpE scores were significantly higher in horses ridden with tight nosebands (p < 0.001). MAIN LIMITATIONS: Video quality was limited when horses showed large amounts of secretion. Another limitation was the small number of horses. CONCLUSIONS: Results add to the evidence obtained in other studies that tight nosebands do not only cause adverse reactions based on the RHpE score such as head behind the vertical or intense staring but also contribute to changes in the pharyngeal region, such as increased secretion and collapse of pharyngeal structures. This may provide further support for future decisions regarding regulations on nosebands.

Physical training mitigates alveolar bone and blood enzymatic antioxidants defense impairment induced by binge ethanol consumption in rats.

We aimed to investigate the effectiveness of physical training as a protective strategy to mitigate alveolar bone damage and blood antioxidant defense caused by ethanol (EtOH) consumption in a binge-drinking pattern. Male Wistar rats aged approximately 90 days were divided into four groups: control, training, EtOH, and training + EtOH. The physical training protocol was conducted on a treadmill for four consecutive weeks, while the animals in the EtOH group were administered EtOH via orogastric gavage for three consecutive days each week, following the binge drink pattern. After the training period, blood and mandibles were collected for plasma oxidative biochemistry analysis, and the alveolar bone was subjected to physicochemical composition analysis, tissue evaluation, and microtomography evaluation. Our results showed that EtOH induced oxidative stress and physical exercise promoted the recovery of antioxidant action. Physical training minimized the damage to the mineral/matrix composition of the alveolar bone due to EtOH consumption and increased the density of osteocytes in the trained group treated with EtOH than in those exposed only to EtOH. Furthermore, physical training reduced damage to the alveolar bone caused by EtOH consumption. Our findings suggest that physical training can serve as an effective strategy to reduce systemic enzymatic oxidative response damage and alleviate alveolar bone damage resulting from alcohol consumption. Further investigations are warranted to elucidate the underlying mechanisms and explore, in addition to physical training, the potential effects of other activities with varying intensities on managing alcohol-induced bone damage.

An examination of the effect of exercise and creatine monohydrate on oral tissues.

Although physical exercise is extremely important for health and a good lifestyle, it can trigger oxidative stress, inflammation, and muscle fatigue. The aim of this study was to determine changes in dental tissues and the mandible created by creatines monohydrate (CrM) supplementation together with low and high-intensity exercise (HIE). The study material comprised Balb/c male mices, which were separated into two groups for the application of low and HIE on a running band. CrM supplement was administered together with the exercise. At the end of the experiment period, dental tissue samples were surgically removed and examined histopathologically and immunohistochemically (TNF-α and lL-1ß).As a result of the histopathological examinations, in the pulp, oedema, vascular congestion, and capillary dilatation were seen to be statistically significantly increased in the Group 3 mices that performed HIE compared to the control group (p = 0.001, p = 0.003, p = 0.001, respectively). A statistically significant increase was observed in periodontal ligament (PDL) degeneration, and disruption of the continuity and separation of collagen fibers in Group 3 compared to the control group (p = 0.001). In the immunohistochemical examination, TNF-α and IL-1ß positivity was observed in Group 3, and this was significantly increased compared to the control group (p = 0.001, p = 0.000).Exposure of the mices to low and HIE caused histological and immunohistochemical changes in dental pulp and PDL, and it was determined that the use of CrM could have a protective effect against these changes. RESEARCH HIGHLIGHTS: The results of this study showed negative effects of HIE in the dental pulp and PDL, which play an important role in dental health. CrM was seen to be effective in preventing these negative effects.

Exercise Alleviates Fluoride-Induced Learning and Memory Impairment in Mice: Role of miR-206-3p and PREG.

Fluorosis decreases the learning and memory ability in humans and animals, while exercise can reduce the risk of cognitive decline. However, the effect of exercise on learning and memory in fluoride-exposed mice is unclear. For this purpose, in this study, mice were randomly allotted into four groups (16 mice per group, half male and half female): control group (group C), fluoride group (group F, 100 mg/L sodium fluoride (NaF)), exercise group (group E, treadmill exercise), and E plus F group (group EF, treadmill exercise, and 100 mg/L NaF). During 6 months of exposure, exercise alleviated the NaF-induced decline in memory and learning. In addition, NaF induced injuries in mitochondria and myelin sheath ultrastructure and reduced the neurons number, while exercise restored them. Metabolomics results showed that phosphatidylethanolamine, pregnenolone (PREG), and lysophosphatidic acid (LysoPA) were altered among groups C, F, and EF. Combined with previous studies, it can be suggested that PREG might be a biomarker in response to exercise-relieving fluorine neurotoxicity. The miRNA sequencing results indicated that in the differently expressed miRNAs (DEmiRNAs), miR-206-3p, miR-96-5p, and miR-144-3p were shared in groups C, F, and EF. After the QRT-PCR validation and in vitro experiments, it was proved that miR-206-3p could reduce cell death and regulate AP-1 transcription factor subunit (JunD) and histone deacetylase 4 (HDAC4) to alleviate fluoride neurotoxicity. To sum up, the current study reveals that exercise could alleviate NaF-induced neurotoxicity by targeting miR-206-3p or PREG, which will contribute to revealing the pathogenesis and therapeutic method of fluoride neurotoxicity.

Physical training minimizes immunological dysfunction, oxidative stress and tissue destruction on experimental periodontitis in rats.

The objective of this study is to investigate the effects of a moderate intensity physical training protocol, on alveolar bone morphology of rats submitted to ligature-induced periodontitis. Twenty-eight male Wistar rats were divided into four groups, considering the presence/absence of periodontitis and presence/absence of training. The training protocol was performed on a treadmill, 30 min/day, 5 days a week, for 4 weeks. In the experimental periodontal breakdown, with/without training, ligatures were placed on the lower first molars on the 14th day of the experiment, and were followed until the end of the protocol. At the end of the experiment, animals were euthanized and samples of plasma and mandibles were collected for immunoenzymatic evaluation of interleukins (IL)-1ß, IL-6, TNF-α and IL-10, evaluation of serum concentrations of C-reactive protein, analysis of lipid peroxidation (LPO) and reduced glutathione, histological and microtomographic analyses were performed. Physical training resulted in a reduced levels of IL-1ß, IL-6, TNF-α C-reactive protein and LPO and an increase in the levels of IL-10 in rats with periodontitis (p<0.05); a reduction in the inflammatory infiltrate and decreased fiber degradation was identified in histological analysis. Additionally, it was shown a decrease in vertical bone loss and an increase in the bone volume/trabecular volume ratio was identified in periodontitis+physical training group (p<0.05). Based on the results, the practice of frequent physical exercise, at moderate intensity, can contribute to the reduction of damage related to the disproportionate inflammatory response in periodontitis.

Exercise-induced enhancement of insulin sensitivity is associated with accumulation of M2-polarized macrophages in mouse skeletal muscle.

Exercise enhances insulin sensitivity in skeletal muscle, but the underlying mechanism remains obscure. Recent data suggest that alternatively activated M2 macrophages enhance insulin sensitivity in insulin target organs such as adipose tissue and liver. Therefore, the aim of this study was to determine the role of anti-inflammatory M2 macrophages in exercise-induced enhancement of insulin sensitivity in skeletal muscle. C57BL6J mice underwent a single bout of treadmill running (20 m/min, 90 min). Twenty-four hours later, ex vivo insulin-stimulated 2-deoxy glucose uptake was found to be increased in plantaris muscle. This change was associated with increased number of CD163-expressing macrophages (i.e. M2-polarized macrophages) in skeletal muscle. Systemic depletion of macrophages by pretreatment of mice with clodronate-containing liposome abrogated both CD163-positive macrophage accumulation in skeletal muscle as well as the enhancement of insulin sensitivity after exercise, without affecting insulin-induced phosphorylation of Akt and AS160 or exercise-induced GLUT4 expression. These results suggest that accumulation of M2-polarized macrophages is involved in exercise-induced enhancement of insulin sensitivity in mouse skeletal muscle, independently of the phosphorylation of Akt and AS160 and expression of GLUT4.

Exercise training-enhanced, endothelium-dependent dilation mediated by altered regulation of BK(Ca) channels in collateral-dependent porcine coronary arterioles.

OBJECTIVE: Test the hypothesis that exercise training increases the contribution of BK(Ca) channels to endothelium-mediated dilation in coronary arterioles from collateral-dependent myocardial regions of chronically occluded pig hearts and may function downstream of H2O2. METHODS: An ameroid constrictor was placed around the proximal left circumflex coronary artery to induce gradual occlusion in Yucatan miniature swine. Eight weeks postoperatively, pigs were randomly assigned to sedentary or exercise training (treadmill; 14 week) regimens. RESULTS: Exercise training significantly enhanced bradykinin-mediated dilation in collateral-dependent arterioles (~125 µm diameter) compared with sedentary pigs. The BK(Ca) -channel blocker, iberiotoxin alone or in combination with the H2O2 scavenger, polyethylene glycol catalase, reversed exercise training-enhanced dilation in collateral-dependent arterioles. Iberiotoxin-sensitive whole-cell K+ currents (i.e., BK(Ca)-channel currents) were not different between smooth muscle cells of nonoccluded and collateral-dependent arterioles of sedentary and exercise trained groups. CONCLUSIONS: These data provide evidence that BK(Ca)-channel activity contributes to exercise training-enhanced endothelium-dependent dilation in collateral-dependent coronary arterioles despite no change in smooth muscle BK(Ca)-channel current. Taken together, our findings suggest that a component of the bradykinin signaling pathway, which stimulates BK(Ca) channels, is enhanced by exercise training in collateral-dependent arterioles and suggest a potential role for H2O2 as the mediator.