Baroreflex activation in conscious rats modulates the joint inflammatory response via sympathetic function

The baroreflex is a critical physiological mechanism controlling cardiovascular function by modulating both the sympathetic and parasympathetic activities. Here, we report that electrical activation of the baroreflex attenuates joint inflammation in experimental arthritis induced by the administration of zymosan into the femorotibial cavity. Baroreflex activation combined with lumbar sympathectomy, adrenalectomy, celiac subdiaphragmatic vagotomy or splenectomy dissected the mechanisms involved in the inflammatory modulation, highlighting the role played by sympathetic inhibition in the attenuation of joint inflammation. From the immunological standpoint, baroreflex activation attenuates neutrophil migration and the synovial levels of inflammatory cytokines including TNF, IL-1β and IL-6, but does not affect the levels of the anti-inflammatory cytokine IL-10. The anti-inflammatory effects of the baroreflex system are not mediated by IL-10, the vagus nerve, adrenal glands or the spleen, but by the inhibition of the sympathetic drive to the knee. These results reveal a novel physiological neuronal network controlling peripheral local inflammation.     

Evodiamine-inspired dual inhibitors of histone deacetylase 1 (HDAC1) and topoisomerase 2 (TOP2) with potent antitumor activity

A great challenge in multi-targeting drug discovery is to identify drug-like lead compounds with therapeutic advantages over single target inhibitors and drug combinations. Inspired by our previous efforts in designing antitumor evodiamine derivatives, herein selective histone deacetylase 1 (HDAC1) and topoisomerase 2 (TOP2) dual inhibitors were successfully identified, which showed potent in vitro and in vivo antitumor potency. Particularly, compound 30a was orally active and possessed excellent in vivo antitumor activity in the HCT116 xenograft model (TGI = 75.2%, 150 mg/kg, p.o.) without significant toxicity, which was more potent than HDAC inhibitor vorinostat, TOP inhibitor evodiamine and their combination. Taken together, this study highlights the therapeutic advantages of evodiamine-based HDAC1/TOP2 dual inhibitors and provides valuable leads for the development of novel multi-targeting antitumor agents.     

Voluntary ambulation using voluntary upper limb muscle activity and Hybrid Assistive Limb® (HAL®) in a patient with complete paraplegia due to chronic spinal cord injury: A case report

Context: We sought to describe our experience with the Hybrid Assistive Limb® (HAL®) for active knee extension and voluntary ambulation with remaining muscle activity in a patient with complete paraplegia after spinal cord injury.

Findings: A 30-year-old man with complete paraplegia used the HAL® for 1 month (10 sessions) using his remaining muscle activity, including hip flexor and upper limb activity. Electromyography was used to evaluate muscle activity of the gluteus maximus, tensor fascia lata, quadriceps femoris, and hamstring muscles in synchronization with the Vicon motion capture system. A HAL® session included a knee extension session with the hip flexor and voluntary gait with upper limb activity. After using the HAL® for one month, the patient’s manual muscle hip flexor scores improved from 1/5 to 2/5 for the right and from 2/5 to 3/5 for the left knee, and from 0/5 to 1/5 for the extension of both knees.

Conclusion/clinical relevance: Knee extension sessions with HAL®, and hip flexor and upper-limb-triggered HAL® ambulation seem a safe and feasible option in a patient with complete paraplegia due to spinal cord injury.     

A cross-sectional examination of sociodemographic factors associated with meeting physical activity recommendations in overweight and obese US adults

ObjectiveObesity has reached epidemic proportions in the US. Physical activity is an important component of obesity reduction, but little is known about contemporary exercise levels among overweight/obese American adults. In this study, we compared current physical activity levels in overweight and obese US adults to those of normal weight individuals as well as ascertained which sociodemographic factors influence the meeting of physical activity recommendations in these three groups.MethodsWe used national data from 2015 and 2017 Behavioral Risk Factor Surveillance System surveys (n = 726,075). Bivariate analyses were conducted to determine unadjusted physical activity levels in normal weight, overweight, and obese adults. We fit multinomial logistic models to identify associations between sociodemographic factors and meeting physical activity recommendations in our study population.ResultsAround 45% of overweight and 57% of obese adults failed to meet physical activity guidelines compared to 41% of normal weight adults. Age, sex, and race were significantly associated with physical activity levels for both overweight and obese adults. In overweight and obese individuals, associations between sociodemographic factors and physical activity were more similar between the two comparisons of insufficiently active (IA) versus active (A)/highly active (HA) and A versus HA but quite different to those in the inactive (IN) versus IA/A/HA comparison.ConclusionsFuture physical activity interventions should be aimed at increasing the number of overweight and obese US adults who meet physical activity guidelines as well as targeted towards specific sociodemographic groups within the overweight/obese population with low exercise levels.     

Physical activity and atrial fibrillation: Data from wearable fitness trackers

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狼毒二萜类化学成分及其药理作用研究进展

狼毒Euphorbiae Ebracteolatae Radix为大戟科(Euphorbiaceae)植物狼毒大戟Euphorbia fischeriana或月腺大戟E.ebracteolata的干燥根,是一种广泛应用,具有广阔开发前景的中药材。狼毒含有多种生物活性成分,其中二萜类化合物是最为重要的一个部分,主要包括松香烷型、巴豆烷型、海松烷型、玫瑰烷型、西松烷型、巨大戟烷型、贝壳杉烷型、阿替斯烷型8种类型,此外还有少量二萜二聚体及其他类型的二萜类化合物。狼毒二萜类化学成分具有显著的抗肿瘤、抗炎、抗菌、抗病毒等药理作用。对狼毒二萜类化学成分及其药理作用进行综述,以期为更好地开发狼毒资源及其临床应用提供参考。     

Curcumin attenuates spatial memory impairment by anti-oxidative,anti-apoptosis,and anti-inflammatory mechanism against methamphetamine neurotoxicity in male Wistar rats: Histological and biochemical changes

ObjectiveMethamphetamine is used extensively around the world as a psychostimulant. The complications related to methamphetamine include methamphetamine-induced neurotoxicity, mainly involving intraneuronal processes, such as oxidative stress and excitotoxicity. Curcumin is effective against neuronal injury due to its antioxidant, anti-inflammatory effects. In this study, we examined the protective effects of curcumin against methamphetamine neurotoxicity.MethodsSixty male Wistar rats were divided into the following groups: control (n = 12), DMSO (n = 12), methamphetamine (n = 12), and methamphetamine + curcumin (100 and 200 mg/kg, respectively, intraperitoneal [IP]; n = 12). Neurotoxicity was induced by 40 mg/kg of methamphetamine administrated through 4 injections (4 × 10 mg/kg, q2h, IP). Curcumin (100 and 200 mg/kg) was administered at 7 days after the last methamphetamine injection. By using a Morris water maze task, the hippocampus-dependent memory and spatial learning were evaluated 1 day after the last curcumin injection. Then, the animal brains were isolated for biochemical measurements, as well as glial fibrillary acidic protein (GFAP), ionized calcium-binding adaptor protein-1(Iba-1) and caspase-3 immunohistochemical staining.ResultsThe current study demonstrated that administration of curcumin significantly attenuates spatial memory impairment (P < 0.01) following methamphetamine neurotoxicity. Curcumin caused a significant increase in the levels of superoxide dismutase and glutathione peroxidase (P < 0.05). However, it decreased tumor necrosis factor (TNF-α) (P < 0.05) and malondialdehyde (P < 0.01) levels as compared to the methamphetamine group. Also, curcumin significantly reduced Iba-1 (P < 0. 01), GFAP and caspase-3 positive cells in the hippocampus (P < 0.001).ConclusionCurcumin exerted neuroprotective effects on methamphetamine neurotoxicity because of its antioxidant and anti-inflammatory effect.     

八段锦对视神经脊髓炎谱系疾病恢复情况的研究

[目的]评估规律性八段锦运动对视神经脊髓炎谱系疾病患者残疾状态及日常生活能力恢复情况的影响。[方法]选取视神经脊髓炎谱系疾病患者58例,随机分成试验组和对照组,每组29例,分别给予常规药物治疗+基础训练+八段锦干预、常规药物治疗+基础训练,疗程12周。比较两组扩展残疾状态量表(EDSS)评分、Barthel指数、Ashworth评分和疲劳严重度量表(FSS)评分的变化情况。[结果]试验组中,患者的EDSS评分、Barthel指数、Ashworth评分和FSS评分较干预前明显改善,差异具有统计学意义(P0.05);与对照组比较,EDSS评分和Barthel指数改善具有统计学意义(P0.05)。对照组中,患者Barthel指数、Ashworth评分和FSS评分较干预前明显改善(P0.05)。两组这4项指标的改善程度比较中,与对照组比较,试验组在EDSS评分、Barthel指数、Ashworth评分和FSS评分的改善程度更明显(P0.05)。[结论]规律的八段锦干预能明显改善视神经脊髓炎谱系疾病患者残疾状态、日常生活能力、肢体痉挛程度和疲劳状态,适合临床推广应用。