Astragalus membranaceus-Polysaccharides Ameliorates Obesity, Hepatic Steatosis, Neuroinflammation and Cognition Impairment without Affecting Amyloid Deposition in Metabolically Stressed APPswe/PS1dE9 Mice.

Astragalus membranaceus is commonly used in traditional Chinese medicine for strengthening the host defense system. Astragalus membranaceus-polysaccharides is an effective component with various important bioactivities, such as immunomodulation, antioxidant, anti-diabetes, anti-inflammation and neuroprotection. In the present study, we determine the effects of Astragalus membranaceus-polysaccharides on metabolically stressed transgenic mice in order to develop this macromolecules for treatment of sporadic Alzheimer's disease, a neurodegenerative disease with metabolic risk factors. Transgenic mice, at 10 weeks old prior to the appearance of senile plaques, were treated in combination of administrating high-fat diet and injecting low-dose streptozotocin to create the metabolically stressed mice model. Astragalus membranaceus-polysaccharides was administrated starting at 14 weeks for 7 weeks. We found that Astragalus membranaceus-polysaccharides reduced metabolic stress-induced increase of body weight, insulin and insulin and leptin level, insulin resistance, and hepatic triglyceride. Astragalus membranaceus-polysaccharides also ameliorated metabolic stress-exacerbated oral glucose intolerance, although the fasting blood glucose was only temporally reduced. In brain, metabolic stress-elicited astrogliosis and microglia activation in the vicinity of plaques was also diminished by Astragalus membranaceus-polysaccharides administration. The plaque deposition, however, was not significantly affected by Astragalus membranaceus-polysaccharides administration. These findings suggest that Astragalus membranaceus-polysaccharides may be used to ameliorate metabolic stress-induced diabesity and the subsequent neuroinflammation, which improved the behavior performance in metabolically stressed transgenic mice.

Toxic Metals Increase Serum Tumor Necrosis Factor-α Levels, Modified by Essential Elements and Different Types of Tumor Necrosis Factor-α Promoter Single-nucleotide Polymorphisms.

BACKGROUND: Lead (Pb), cadmium (Cd), and arsenic (As) could cause health issues through oxidative stress that is indicated in the elevated tumor necrosis factor-alpha (TNF-α). However, some of the essential elements-selenium (Se), zinc (Zn), cobalt (Co), and copper (Cu)-are cofactors or structural components of antioxidant enzymes. It is suggested that single-nucleotide polymorphisms (SNPs) in the TNF-α gene have different TNF-α responses. This study aims to evaluate the effect of serum TNF-α levels through the interactions between toxic metals and essential elements and how the interactions between the toxic metals and TNF-α SNPs (-1031 T > C, -863 C > A, -857 C > T, -308 G > A, -238 G > A) influence serum TNF-α levels. METHODS: Blood samples were collected from 455 workers who carried out annual health examinations and multielements determined by inductively coupled plasma mass spectrometry (ICP-MS). TNF-α levels were detected by enzyme-linked immunosorbent assay (ELISA). TNF-α promoter SNPs were analyzed by specific primer probes using real-time polymerase chain reaction (PCR) methods. RESULTS: Increasing blood Pb, Cd, and As levels were associated with elevated TNF-α levels. The interaction between Pb and Cu decreased TNF-α levels and so did the interaction between Cd and Se. In the interaction between Pb and SNPs, individuals with AA/AG (-308 G > A) and AA/AG (-238 G > A) had higher serum TNF-α levels. However, lower TNF-α levels were noted in those individuals with AA/CA (-863 C > A). In the interaction between As and SNPs, workers with AA/AG (-238 G > A) had synergic effect with As and induced higher serum TNF-α levels. CONCLUSIONS: Blood Cu and Se were antagonists of toxic metals (Pb, As, and Cd) through lower serum TNF-α levels. Variant types of TNF-α SNPs (-308 G > A, -238 G > A) and wild type of -863 CC would be more susceptible to toxic metals.

Xuefu Zhuyu decoction ameliorates obesity, hepatic steatosis, neuroinflammation, amyloid deposition and cognition impairment in metabolically stressed APPswe/PS1dE9 mice.

ETHNOPHARMACOLOGICAL RELEVANCE: Metabolic syndrome and vascular dysfunction was suggested to be the risk factors for Alzheimer's disease (AD). Xuefu Zhuyu decoction (XZD) is a traditional Chinese medicine used to treat metabolic syndrome and cardiac-cerebral vascular disease. The effects of XZD on ameliorating metabolic syndrome, amyloid-related pathologies and cognitive impairment in an animal model of AD with metabolic stress was investigated. MATERIALS AND METHOD: The animal model of AD with metabolic stress was created by administrating high-fat diet and a low-dose injection of streptozotocin prior to the appearance of senile plaques in APP/PS1 transgenic mice. The diabesity-associated metabolic changes and AD-related pathological alterations were examined. RESULTS: We found that XZD reduced body weight, insulin and leptin level, HOMA-IR, hepatic triglyceride, serum Aß42 in the metabolic stressed AD animal. XZD also ameliorated oral glucose tolerant, Aß deposition, astrocyte and microglia activation in the vicinity of plaques, and nesting behavior in the metabolic stressed AD animal. CONCLUSION: The results of this study suggest that XZD is able to reduce the peripheral metabolic stress-mediated vascular hypoperfusion, neuroinflammation and AD-related pathology in APP/PS1 mice.

Effects of Therapeutic Physical Agents on Achilles Tendon Microcirculation.

STUDY DESIGN: Controlled laboratory study. OBJECTIVES: To measure Achilles tendon microcirculation (total hemoglobin [THb] and oxygen saturation [StO2]) before and after the application of a physical agent in asymptomatic participants, and to compare differences between application location and physical agent dosage. BACKGROUND: Tendon microcirculation can be altered by superficial heating or cryotherapy. METHODS: Fifty-one healthy adults (median age, 22 years; range, 20-34 years) were recruited and randomly assigned into 1 of 4 groups. Participants in each group received an intervention consisting of 1 of the following 4 physical agents: ultrasound (n = 12), interferential current (n = 14), low-level laser (n = 11), or vibration massage (n = 14). In each group, the selected intervention was applied at 2 different doses (ultrasound, 0.8 or 1.2 W/cm(2); laser, 5.4 or 18 J) or target locations (vibration and electrostimulation, calf muscle or Achilles tendon). For each participant, each dose or target location was randomly applied to 1 randomly selected lower leg (each leg receiving only 1 of the 2 options). RESULTS: The StO2 values significantly increased after ultrasound at both doses (P<.008), and the THb value significantly increased for the higher dose only (P<.008). Both THb and StO2 values also significantly increased in response to vibration massage targeting the Achilles tendon (P<.008), and these values were greater than those resulting from the vibration massage applied to the calf muscle (P = .003 and .002, respectively). No significant THb and StO2 differences were found after the application of interferential current or low-level laser. CONCLUSION: Tendon microcirculation increases after ultrasound and vibration massage intervention concentrated on the Achilles tendon. These modalities may be considered for the purpose of temporarily increasing microcirculation in the tendon.

Evoked spinal reflexes and force development in elite athletes with middle-portion Achilles tendinopathy.

STUDY DESIGN: Controlled laboratory study. OBJECTIVES: To compare the neuromuscular function of the triceps surae muscle bilaterally in elite athletes with unilateral chronic Achilles tendinopathy. BACKGROUND: Previous studies suggest that tendinopathies or chronic pain may lead to a spinal/supraspinal level modulation of the excitability or voluntary activation of ipsilateral motor units. However, this has not been studied in Achilles tendinopathy. METHODS: Fourteen college athletes (mean ± SD age, 24.2 ± 1.7 years) who had unilateral chronic middle-portion tendinopathy in their Achilles tendons were recruited. Bilateral measurements of soleus reflex tests, including H-reflex and V wave, and rate of force development (RFD), as well as corresponding electromyography of the tibialis anterior and triceps surae muscles, were performed. Statistical within-subject and between-leg comparisons were made. RESULTS: In the leg with tendinopathy, the V wave of the soleus muscle was significantly increased (P<.001). The side with tendinopathy also had a reduced normalized RFD (0-30, 0-50, and 0-100 ms) in plantar flexion, and concomitant higher electromyography ratios between the tibialis anterior and soleus (0-30 and 0-50 milliseconds) during the early stage of explosive contractions (P<.05). No significant differences were found for H-reflex, maximal plantar flexion and dorsiflexion torque, and absolute RFD. CONCLUSIONS: Higher volitional supraspinal reflexes and lower maximal-strength independent force development occur in the triceps surae of elite athletes with unilateral middle-portion Achilles tendinopathy. These changes potentially indicate an acquired compensatory mechanism for maximal force production and deficits in explosive strength. The RFD is also suggested as a sensitive parameter to depict neuromuscular changes during treatment of chronic tendinopathies.

The changes in brain metabolism in people with activated brown adipose tissue: a PET study.

Brown adipose tissue (BAT) is a highly specialized thermogenic tissue and has profound effects on body weight, energy balance, and glucose metabolism. Body temperature regulation depends on the integrated activities of the autonomic nervous system, which is centered predominantly in the hypothalamus. The purpose of this study was to explore the interaction of brain and the activation of BAT by analyzing differences in brain metabolism between patients with and without activated BAT. Fluorodeoxyglucose (FDG) with positron emission tomography/computer tomography (PET/CT) was used to determine the activation of BAT and brain metabolism. After reviewing FDG PET/CT scans, we retrospectively collected 42 patients, 21 with activated BAT and 21 matched controls without activated BAT. We used the method of defining regions of interest (ROI) to examine differences in metabolism between their hypothalami and voxel (volumetric pixel)-based statistical parametric mapping to analyze the whole brain. Compared with controls, patients with activated BAT had a significant hypermetabolic area in the right inferior parietal lobule (Brodmann area 40) and significant hypometabolic areas in the left insula (Brodmann area 13) and right cerebellum; however, there were no metabolic differences in the hypothalamic regions. Our findings illustrate the close relationship of cold temperature exposure-triggered hypermetabolism in the right inferior parietal lobule and activated BAT. They also support the hypotheses that the insula and cerebellum regulate autonomic functions, which are important for controlling BAT thermogenesis within the central pathways.