Light-intensity exercise improves memory dysfunction with the restoration of hippocampal MCT2 and miRNAs in type 2 diabetic mice

Cognitive decline associated with type 2 diabetes mellitus (T2DM) is a risk factor to impair human health. Although light-intensity exercise prevents hippocampal memory dysfunction in pre-symptomatic T2DM animals by altering hippocampal lactate transport and neurotrophic factors, the effects of light-intensity exercise in an advanced stage of T2DM animals remain unclear. Here, ob/ob mice, an animal model of T2DM, were subjected to light-intensity exercise (5.0 m/min) for 30 min/day, five days/week for four weeks. The effects of light-intensity exercise on hippocampal complications, mRNA expressions of monocarboxylate transporter (MCT), and miRNA levels were assessed. The light-intensity exercise improved hippocampal memory retention in ob/ob mice. Downregulated hippocampal Mct2 mRNA levels in T2DM were improved with light-intensity exercise. Hippocampal mRNA levels of Mct1 and Mct4 were unchanged within groups. Based on miRNA sequencing, sedentary ob/ob mice exhibited that 71 miRNAs were upregulated, and 77 miRNAs were downregulated in the hippocampus. In addition, the exercise significantly increased 24 miRNAs and decreased 4 miRNAs in the T2DM hippocampus. The exercise reversed T2DM-induced alterations of hippocampal 9 miRNAs, including miR-200a-3p. Our findings imply that miR-200a-3p/Mct2 in the hippocampus would be a possible clinical target for treating T2DM-induced memory dysfunction.

     

Ocimum sanctum attenuates oxidative damage and neurological deficits following focal cerebral ischemia/reperfusion injury in rats

Stroke is an enormous public health problem with an imperative need for more effective therapy. Free radicals have been reported to play a role in the expansion of ischemic brain lesions, and the effect of free radical scavengers is still under debate. The present study investigated the neuroprotective effect of Ocimum sanctum (OS) to reduce brain injury after middle cerebral artery occlusion (MCAO). Male Wistar rats were subjected to MCAO for 2?h and reperfused for 22?h. The administration of OS (200?mg/kg bwt., orally) once daily for 15?days before MCAO showed marked reduction in infarct size, reduced the neurological deficits, and suppressed neuronal loss in MCAO rats. A significantly depleted activity of antioxidant enzymes and content of glutathione in MCAO group were protected significantly in MCAO group pretreated with OS. Conversely, the elevated level of thiobarbituric acid-reactive substances (TBARS) in MCAO group was attenuated significantly in OS-pretreated group when compared with MCAO group. Consequently, OS pretreatment may reduce the deterioration caused by free radicals, and thus may used to prevent subsequent behavioral, biochemical and histopathological changes that transpire during cerebral ischemia. This finding reflects that supplementation of OS intuitively by reasonable and understandable treatment effectively ameliorates the cerebral ischemia-induced oxidative damage.     

Comprehensive characterization of the peroxisome proliferator activated receptor-δ agonist GW501516 for horse doping control analysis

According to international sport institutions, the use of peroxisome proliferator activated receptor (PPAR)-δ agonists is forbidden at any time in athlete career due to their capabilities to increase physical and endurance performances. The (PPAR)-δ agonist GW501516 is prohibited for sale but is easily available on internet and can be used by cheaters. In the context of doping control, urine is the preferred matrix because of the non-invasive nature of sampling and providing broader exposure detection times to forbidden molecules but often not detected under its native form due to the organism's metabolism. Even if urinary metabolism of G501516 has been extensively studied in human subjects, knowledge on GW501516 metabolism in horses remains limited. To fight against doping practices in horses' races, GW501516 metabolism has to be studied in horse urine to identify and characterize the most relevant target metabolites to ensure an efficient doping control. In this article, in vitro and in vivo experiments have been conducted using horse S9 liver microsome fractions and horse oral administration route, respectively. These investigations determined that the detection of GW501516 must be performed in urine on its metabolites because the parent molecule was extremely metabolized. To maximize analytical method sensitivity, the extraction conditions have been optimized. In accordance with these results, a qualitative analytical method was validated to detect the abuse of GW501516 based on its most relevant metabolites in urine. This work enabled the Laboratoire des Courses Hippiques (LCH) to highlight two cases of illicit administration of this forbidden molecule in post-race samples.     

Intra-fractional patient setup error during fractionated intracranial stereotactic irradiation treatment of patients wearing medical masks: comparison with and without bite block during COVID-19 pandemic

The immobilization of patients with a bite block (BB) carries the risk of interpersonal infection, particularly in the context of pandemics such as COVID-19. Here, we compared the intra-fractional patient setup error (intra-SE) with and without a BB during fractionated intracranial stereotactic irradiation (STI). Fifteen patients with brain metastases were immobilized using a BB without a medical mask, while 15 patients were immobilized without using a BB and with a medical mask. The intra-SEs in six directions (anterior–posterior (AP), superior–inferior (SI), left–right (LR), pitch, roll, and yaw) were calculated by using cone-beam computed tomography images acquired before and after the treatments. We analyzed a total of 53 and 67 treatment sessions for the with- and without-BB groups, respectively. A comparable absolute mean translational and rotational intra-SE was observed (P > 0.05) in the AP (0.19 vs 0.23 mm with- and without-BB, respectively), SI (0.30 vs 0.29 mm), LR (0.20 vs 0.29 mm), pitch (0.18 vs 0.27°), roll (0.23 vs 0.23°) and yaw (0.27 vs 22°) directions. The resultant planning target volume (PTV) margin to compensate for intra-SE was <1 mm. No statistically significant correlation was observed between the intra-SE and treatment times. A PTV margin of <1 mm was achieved even when patients were immobilized without a BB during STI dose delivery.     

Azadirachta indica mitigates behavioral impairments, oxidative damage, histological alterations and apoptosis in focal cerebral ischemia–reperfusion model of rats

Azadirachta indica Linn. (Meliaceae) has been used from ancient times as a remedy for various ailments. The present study was designed to investigate the antioxidant and anti-apoptotic properties of A. indica seed extract (ASE) in transient middle cerebral artery occlusion (MCAO) rat model. Antioxidant potential of ASE was determined in vitro. Further, ASE was evaluated against neurological deficits, histological alterations (TTC, CV and H&E) and oxidative damage (TBARS, GSH and nitrite) in MCAO rats. Moreover, caspase-3 and -9 were analyzed to evaluate the anti-apoptotic activity of ASE. ASE has shown potent in vitro reducing power (126.2 mg AsAE/g extract) and free radical scavenging activities (DPPH 171.0 and NO 176.0 μg/ml). Furthermore, ASE inhibited oxidative stress and decreased the activities of caspase-3 (26.7 %, p < 0.05) and caspase-9 (31.2 %, p < 0.01) thus, reduced neuronal loss in MCAO rats. Our data revealed that ASE has potent antioxidant and anti-apoptotic properties, and may be explored for its active constituents against neurodegenerative diseases.     

Centella asiatica attenuates the neurobehavioral, neurochemical and histological changes in transient focal middle cerebral artery occlusion rats

Centella asiatica has been used as psychoactive and antioxidant herbal medicine since ancient time. The present study was design to evaluate the preventive role of ethanolic extract of C. asiatica in middle cerebral artery occlusion (MCAO) in rats. Male Wistar rats were gavaged orally with C. asiatica extract (100, 200 and 300 mg/kg body weight once daily) for 21 days and thereafter subjected to right MCAO for 2 h followed by 22-h reperfusion. Brain injury was evaluated by 2,3,5-triphenyltetrazolium chloride and hematoxylin and eosin staining. Behavioural outcomes as neurological deficit, rota rod test, and grip strength were assessed. In addition, lipid peroxidation, enzymatic and non enzymatic antioxidants were analyzed to assess the oxidative stress. Our results revealed that C. asiatica administration greatly improved neurobehavioral activity and diminished infarction volume along with the restored histological morphology of brain in MCAO rats. Furthermore, supplementation with this extract to MCAO group has reduced the level of thiobarbituric acid reactive species, restored glutathione content and augmented the activities of antioxidant enzymes—catalase, glutathione peroxidase, glutathione reductase, glutathione-S-transferase and superoxide dismutase in a dose-dependent manner in ischemic rats. The remarkable antioxidant activity of C. asiatica may be attributed to its bioactive triterpenes, asiatic acid, asiaticoside, madecassic acid and madecosside and may be translated to clinical level for prevention of ischemic stroke.     

Effect of Different Downward Loads on Canal Centering Ability,Vertical Force,and Torque Generation during Nickel–Titanium Rotary Instrumentation

This study aimed to examine how downward loads influence the torque/force and shaping outcome of ProTaper NEXT (PTN) rotary instrumentation. PTN X1, X2, and X3 were used to prepare J-shaped resin canals employing a load-controlled automated instrumentation and torque/force measuring device. Depending on the torque values, the handpiece was programmed to move as follows: up and down; downward at a preset downward load of 1 N, 2 N or 3 N (Group 1N, 2N, and 3N, respectively; each n = 10); or upward. The torque/force values and instrumentation time were recorded, and the canal centering ratio was calculated. The results were analyzed using a two-way or one-way analysis of variance and the Tukey test (α = 0.05). At the apex level, Group 3N exhibited the least canal deviation among the three groups (p < 0.05). The downward force was Group 3N > Group 2N > Group 1N (p < 0.05). The upward force, representing the screw-in force, was Group 3N > Group 1N (p < 0.05). The total instrumentation time was Group 1N > Group 3N (p < 0.05). In conclusion, increasing the downward load during PTN rotary instrumentation improved the canal centering ability, reduced the instrumentation time, and increased the upward force.     

S-allyl cysteine mitigates oxidative damage and improves neurologic deficit in a rat model of focal cerebral ischemia

Oxidative stress and inflammatory damage play an important role in cerebral ischemic pathogenesis and may represent a target for treatment. The present study examined the hypothesis that S-allyl cysteine (SAC), organosulfur compounds found in garlic extract, would reduce oxidative stress–associated brain injury after middle cerebral artery occlusion (MCAO). To test this hypothesis, male Wistar rats were subjected to MCAO for 2 hours and 22-hour reperfusion. S-allyl cysteine was administered (100 mg/kg, b.wt.) intraperitoneally 30 minutes before the onset of ischemia and after the ischemia at the interval of 0, 6, and 12 hours. After 24 hours of reperfusion, rats were tested for neurobehavioral activities and were killed for the infarct volume, estimation of lipid peroxidation, glutathione content, and activity of antioxidant enzymes (glutathione peroxidase, glutathione reductase, catalase, and superoxide dismutase). S-allyl cysteine treatment significantly reduced ischemic lesion volume, improved neurologic deficits, combated oxidative loads, and suppressed neuronal loss. Behavioral and biochemical alterations observed after MCAO were further associated with an increase in glial fibrillary acidic protein and inducible nitric oxide expression and were markedly inhibited by the treatment with SAC. The results suggest that SAC exhibits exuberant neuroprotective potential in rat ischemia/reperfusion model. Thus, this finding of SAC-induced adaptation to ischemic stress and inflammation could suggest a novel avenue for clinical intervention during ischemia and reperfusion.