Relevance of Physical Fitness and Cardiovascular Disease Risk.

BACKGROUND: This study explored the relationship between fitness performance, in terms of muscular endurance and cardiorespiratory fitness (CRF), and cardiovascular disease (CVD) risk.Methods and Results:The study was performed on 51,500 eligible participants from the Republic of China Armed Forces. Participants were divided into 4 groups (obese or non-obese males and females). Correlations between the Framingham risk score of coronary artery disease (FRS-CAD) and physical fitness (evaluated using 2-min push-ups, 2-min sit-ups, and 3,000-m non-weight-bearing running tests) were calculated using univariate and multivariate linear regression, as well as an extended model that adjusted for covariates. In males, regardless of obesity status, there were significant negative correlations between quartiles of fitness performance and the FRS-CAD (P<0.001) in the unadjusted and adjusted models, except for the sit-up test in the model adjusted for age, serum uric acid, hemoglobin, creatinine, current drinking, betel nut chewing, and running test speed. FRS-CAD was lower for higher quartiles of physical fitness (P for trend <0.001) in male participants. However, no significant relationship between fitness performance and FRS-CAD was observed in females, regardless of obesity status. CONCLUSIONS: The findings highlighted a substantial association between fitness performance and FRS-CAD, especially in adult males. Muscular endurance and CRF may be a convenient risk evaluation tool for future CVD risk in the general, healthy, young to middle-aged male population in Taiwan.

Short-term auricular electrical stimulation rapidly elevated cortical blood flow and promoted the expression of nicotinic acetylcholine receptor α4 in the 2 vessel occlusion rats model.

BACKGROUND: Vascular dementia is the second dementing illness after Alzheimer's disease and caused by reduced blood flow to the brain, and affects cognitive abilities. Our previous study found that auricular electrical stimulation (ES) improved motor and learning impairment, and this phenomenon related with nicotinic acetylcholine receptor (nAChR) expressed cells. However, the underlying mechanism was not clear. In the present study, we investigated the effects of auricular ES on cortical blood flow (CBF) and acetylcholine (ACh) - nAChRs expressed cells. METHODS: Vascular dementia rat animal model was established by permanent occlusions of common carotid arteries with 6-0 nylon suture filament. At 21 day after surgery, motor impairment was confirmed by rotarod test. 15-Hz auricular ES were applied to the ears for 20 min and CBF was recorded at the mean time. The brains were immediately dissected for immunohistochemical stain and western blot analysis. RESULTS: Our results showed that 15-Hz auricular ES rapidly elevated CBF in the middle cerebral artery. The numbers of nAChR α4 immuno-positive cells and western blot levels were significally increased by 15-Hz auricular ES in the hippocampal CA2 output cortex. The numbers of choline acetyltransferase (ChAT) - a key enzyme for biosynthesis of ACh - immuno-positive cells and western blot levels had no significant differences. CONCLUSIONS: The present data suggested that the 15-Hz auricular ES for 20 min rapidly elevated cortical blood flow, promoted the expression of nAChR α4, and would be beneficial for the treatment of Alzheimer type and vascular type dementia.

Geopolymer technology for the solidification of simulated ion exchange resins with radionuclides.

In this study, geopolymer was applied to convert ion exchange resins contaminated with radionuclides into a solid waste form. Geopolymer has superior properties to enable the encapsulation of spent resins. The allowable limit of resin content in the converted waste form was analyzed to evaluate the solidification capability of geopolymer. The encapsulation of ion exchange resins into solid waste form was conducted using geopolymer prepared with ground granulated blast furnace slag and alkaline solution in an ambient atmosphere, with the addition of wollastonite powder to adjust its mechanical properties. The physical and mechanical properties of the converted solid wastes prepared using different resin content ratios and various SiO2/Na2O molar ratios were tested. The results indicate the wet ion exchange resin (the moisture content in the resin is 51%) content and the compressive strength of the solid resin waste were measured as 45 wt% and 8.5 MPa, respectively. The morphology and mineral phases of the formed solid wastes were characterized using SEM and EDS. The mechanical performance test results proved the formed solid wastes could comply with the fuel cycle and material administration standards ruled by the Atomic Energy Council of Taiwan. These results suggest that this blast furnace slag-based geopolymer is a promising matrix material for the solidification of radioactive wastes.

Epidemiologic characterization of 30 confirmed cases of human infection with avian influenza A(H7N9) virus in Hangzhou, China.

BACKGROUND: We examined the clinical and epidemiological characteristics of 30 cases of human infection with avian influenza A(H7N9) virus in Hangzhou and investigated their external environments to provide evidence for contact tracing and disease prevention and control. METHODS: The cases confirmed from April 1 through May 1, 2013 were studied. Field epidemiologic surveys were conducted to collect the clinical and epidemiologic data. Case-related and environmental specimens were collected for etiologic detection. RESULTS: Thirty cases of human infection with avian influenza A(H7N9) virus were confirmed in Hangzhou from April 1 through May 1, 2013, including one pregnant woman and three deaths. The median age of the patients was 62 years (range: 38-86 years). Twenty-three of the patients were men (76.67%). The median duration between disease onset and occurrence of respiratory failure and confirmed diagnosis was 5 and 6 days, respectively. Maximum medical observation of 666 close contacts of the patients revealed no irregularity. Of 314 external environmental specimens, the overall positive detection rate of H7N9 nucleic acid was 28.98%. Eight districts of Hangzhou city had positive detections in the external environments, the highest rate being in Yuhang District (78.13%). Statistical analysis of the specimen collection locations indicates a significant difference between the case-linked locations and the non-case locations (χ2 = 16.563, p < 0.05) in terms of H7N9 viral nucleic acid detection rate. No epidemiologic link has been found among the 30 cases. CONCLUSIONS: Most of the infected were retired individuals aged 60 years or older. Men made the majority. The cases are sporadic at present, with no evidence of human-to-human transmission. Exposures to poultry and live poultry markets may be important sources of infection.

Handelin alleviates cachexia- and aging-induced skeletal muscle atrophy by improving protein homeostasis and inhibiting inflammation.

BACKGROUND: Handelin is a bioactive compound from Chrysanthemum indicum L. that improves motor function and muscle integrity during aging in Caenorhabditis elegans. This study aimed to further evaluate the protective effects and molecular mechanisms of handelin in a mouse muscle atrophy model induced by cachexia and aging. METHODS: A tumour necrosis factor (TNF)-α-induced atrophy model was used to examine handelin activity in cultured C2C12 myotubes in vitro. Lipopolysaccharide (LPS)-treated 8-week-old model mice and 23-month-old (aged) mice were used to examine the therapeutic effects of handelin on cachexia- and aging-induced muscle atrophy, respectively, in vivo. Protein and mRNA expressions were analysed by Western blotting, ELISA and quantitative PCR, respectively. Skeletal muscle mass was measured by histological analysis. RESULTS: Handelin treatment resulted in an upregulation of protein levels of early (MyoD and myogenin) and late (myosin heavy chain, MyHC) differentiation markers in C2C12 myotubes (P < 0.05), and enhanced mitochondrial respiratory (P < 0.05). In TNF-α-induced myotube atrophy model, handelin maintained MyHC protein levels, increased insulin-like growth factor (Igf1) mRNA expression and phosphorylated protein kinase B protein levels (P < 0.05). Handelin also reduced atrogin-1 expression, inhibited nuclear factor-κB activation and reduced mRNA levels of interleukin (Il)6, Il1b and chemokine ligand 1 (Cxcl1) (P < 0.05). In LPS-treated mice, handelin increased body weight (P < 0.05), the weight (P < 0.01) and cross-sectional area (CSA) of the soleus muscle (P < 0.0001) and improved motor function (P < 0.05). In aged mice, handelin slightly increased the weight of the tibialis anterior muscle (P = 0.06) and CSA of the tibialis anterior and gastrocnemius muscles (P < 0.0001). In the tibialis anterior muscle of aged mice, handelin upregulated mRNA levels of Igf1 (P < 0.01), anti-inflammatory cytokine Il10 (P < 0.01), mitochondrial biogenesis genes (P < 0.05) and antioxidant-related enzymes (P < 0.05) and strengthened Sod and Cat enzyme activity (P < 0.05). Handelin also reduced lipid peroxidation and protein carbonylation, downregulated mRNA levels of Fbxo32, Mstn, Cxcl1, Il1b and Tnf (P < 0.05), and decreased IL-1ß levels in serum (P < 0.05). Knockdown of Hsp70 or using an Hsp70 inhibitor abolished the ameliorating effects of handelin on myotube atrophy. CONCLUSIONS: Handelin ameliorated cachexia- and aging-induced skeletal muscle atrophy in vitro and in vivo, by maintaining homeostasis of protein synthesis and degradation, possibly by inhibiting inflammation. Handelin is a potentially promising drug candidate for the treatment of muscle wasting.

Spatial distribution, source identification, and transportation paths of plutonium in the Beibu Gulf, South China Sea.

To investigate the spatial distribution and source of plutonium isotopes in the Beibu Gulf, surface sediments were collected and analyzed using sector field inductively coupled plasma mass spectrometry (SF-ICP-MS). The activities of 239+240Pu in surface sediments ranged from 0.012 to 0.451 mBq/g (mean: 0.171 ± 0.138 mBq/g, n = 36), indicating a decreasing trend in a counterclockwise direction from the southern bay mouth. The counterclockwise decreasing trend in the south of the bay mouth is similar to the current in the Beibu Gulf. The 240Pu/239Pu atom ratios in surface sediments ranged from 0.156 to 0.283 (mean: 0.236 ± 0.031, n = 36), slightly higher than that of the global fallout value of 0.18. This suggests that the Pu in the Beibu Gulf was a combination of global fallout and Pacific Proving Ground (PPG). The average contribution of the plutonium (Pu) derived from the PPG in the sediment was estimated to be 52 % ± 24 %.

Diosgenin, a Natural Steroidal Sapogenin, Alleviates the Progression of Diabetic Retinopathy in Diabetic Mice.

BACKGROUND/AIM: Diabetic retinopathy (DR) is the most common microvascular complication of diabetes and a major cause of blindness in working-age adults. Diosgenin (DG), a natural steroidal sapogenin extracted from fenugreek seeds and wild yam roots, has hypolipidemic, hypoglycemic, anticancer, and anti-inflammatory properties. Given its pharmacological effects, we speculated that DG may be a promising treatment for DR. Therefore, this study was aimed at evaluating the effectiveness of DG in preventing or slowing DR progression in a mouse model (+Leprdb/+Leprdb strain) of type 2 diabetes (T2D). MATERIALS AND METHODS: DG (5.0 mg/kg body weight) or phosphate-buffered saline (PBS) was administered to 8-week-old T2D mice via oral gavage daily for 24 weeks. Paraffin-embedded eye tissues from the mice were collected and stained with hematoxylin and eosin to evaluate retinal histopathology. Apoptosis-related proteins BCL2-associated X (Bax), B-cell lymphoma 2 (Bcl-2), and cleaved caspase-3 were evaluated by western blotting of mouse retinas. RESULTS: Body weight was slightly reduced in the DG-treated group; however, glucose levels were not markedly different between the DG- and PBS-treated groups. Total retinal thickness, thickness of the photoreceptor and outer nuclear layers, and loss of ganglion cells significantly improved in the retina of the DG-treated T2D mice compared with those in the PBS-treated T2D mice. Cleaved caspase-3 level significantly decreased in the retina of the DG-treated T2D mice. Conclusion: DG alleviates DR pathology and exerts a protective effect on the T2D mouse retina. The inhibitory effects of DG on DR may involve mechanisms of the anti-apoptotic pathway.

Electroacupuncture attenuates inflammatory pain via peripheral cannabinoid receptor type 1 signaling pathway in mice.

Pain is strongly associated with neuro-immune activation. Thus, the emerging role of the endocannabinoid system in neuro-inflammation is important. Acupuncture has been used for over 2500 years and is widely accepted for the management of pain. Our study aimed to investigate the effects of electroacupuncture on the regulation of cannabinoid receptor type 1 within the peripheral nervous system. Inflammatory pain was induced by injecting Complete Freund's adjuvant to induce mechanical and thermal hyperalgesia. Electroacupuncture significantly attenuated the mechanical and thermal sensitivities, and AM251, a cannabinoid receptor type 1 antagonist, eliminated these effects. Dual immunofluorescence staining demonstrated that electroacupuncture elevated expression of cannabinoid receptor type 1, co-localized with Nav 1.8. Furthermore, electroacupuncture significantly reduced levels of Nav 1.8 and COX-2 by western blot analysis, but not vice versa as AM251 treatment. Our data indicate that electroacupuncture mediates antinociceptive effects through peripheral endocannabinoid system signaling pathway and provide evidence that electroacupuncture is beneficial for pain treatment.

Naturally Occurring Bicoumarin Compound Daphnoretin Inhibits Growth and Induces Megakaryocytic Differentiation in Human Chronic Myeloid Leukemia Cells.

Daphnoretin extracted from the stem and roots of Wikstroemia indica (L.) C.A. Mey has been shown to possess antiviral and antitumor activities. Herein, we hypothesized that daphnoretin might induce megakaryocytic differentiation, thereby inhibiting the proliferation of cells and serving as a differentiation therapy agent for chronic myeloid leukemia (CML). Daphnoretin-treated K562 and HEL cells were examined for growth inhibition, cell morphology, and megakaryocyte-specific markers. Potential mechanisms of megakaryocytic differentiation of daphnoretin-treated K562 cells were evaluated. The results showed that daphnoretin inhibited the growth of K562 and HEL cells in a dose- and time-dependent manner. Flow cytometry analyses revealed that daphnoretin treatment slightly increased the proportion of sub-G1 and polyploid cells compared to that of dimethyl sulfoxide (DMSO)-treated control cells. Morphological examination showed that daphnoretin-treated K562 and HEL cells exhibited enlarged contours and multinucleation as megakaryocytic characteristics compared to DMSO-treated control cells. Daphnoretin treatment also dramatically enhanced the expression of megakaryocytic markers CD61 and CD41. Under optimal megakaryocytic differentiation conditions, daphnoretin increased the phosphorylation of STAT3 but not STAT5. In summary, daphnoretin inhibited cell growth and induced megakaryocytic differentiation in K562 and HEL cells. The efficacy of daphnoretin in vivo and in patients with CML may need further investigations for validation.

Application of acupuncture in the emergency department for patients with ileus: A pilot prospective cohort clinical study.

Acupuncture can be conveniently used for pain control in patients with a variety of conditions, and it has obvious effects on various acute pains. In 2018, we implemented a program for emergency treatment with Chinese medicine to promote the integration of Chinese and Western medicine at the Emergency Department (ED). Ileus is a common cause of abdominal pain among patients in the ED, and it is an indication for emergency treatment with Chinese medicine. This study investigated the efficacy of acupuncture as a traditional Chinese medicine (TCM)-based treatment method for the treatment of patients with ileus in the ED. We analyzed data of patients with ileus, who visited ED between January and December 2019, and compared the length of ED stay between the Western medicine group and the Western medicine plus acupuncture group. Furthermore, pain intensity was measured by a visual analogue scale before and after acupuncture. We found that the length of ED stay was 10.8 hours lesser in the Western medicine plus acupuncture group than in the Western medicine group (P = .04), and the visual analogue scale score decreased by 2.0 on average from before to after acupuncture treatment (P = .02). Acupuncture treatment was effective and rapid in relieving the symptoms and discomfort in patients with ileus and in reducing their length of stay in the ED.

Acid-sensing ion channel 3 mediates peripheral anti-hyperalgesia effects of acupuncture in mice inflammatory pain.

BACKGROUND: Peripheral tissue inflammation initiates hyperalgesia accompanied by tissue acidosis, nociceptor activation, and inflammation mediators. Recent studies have suggested a significantly increased expression of acid-sensing ion channel 3 (ASIC3) in both carrageenan- and complete Freund's adjuvant (CFA)-induced inflammation. This study tested the hypothesis that acupuncture is curative for mechanical hyperalgesia induced by peripheral inflammation. METHODS: Here we used mechanical stimuli to assess behavioral responses in paw and muscle inflammation induced by carrageenan or CFA. We also used immunohistochemistry staining and western blot methodology to evaluate the expression of ASIC3 in dorsal root ganglion (DRG) neurons. RESULTS: In comparison with the control, the inflammation group showed significant mechanical hyperalgesia with both intraplantar carrageenan and CFA-induced inflammation. Interestingly, both carrageenan- and CFA-induced hyperalgesia were accompanied by ASIC3 up-regulation in DRG neurons. Furthermore, electroacupuncture (EA) at the ST36 rescued mechanical hyperalgesia through down-regulation of ASIC3 overexpression in both carrageenan- and CFA-induced inflammation. CONCLUSIONS: In addition, electrical stimulation at the ST36 acupoint can relieve mechanical hyperalgesia by attenuating ASIC3 overexpression.

Case selection and implementation of tubeless percutaneous nephrolithotomy.

BACKGROUND: The tubeless percutaneous nephrolithotomy (PCNL) was proposed to eliminate the side effects of the nephrostomy tube in recent years, such as pain, channel infection, postoperative bleeding, and longer hospital stay. But there is neither clinical guidelines nor consensus about tubeless PCNL in clinical practice. The study is aimed to how to implement the tubeless PCNL step by step, including case selection preoperatively, improving the technique of the surgeon, making the correct decisions at the end of the procedure, which had not been previously examined. METHODS: From January 2017 to March 2018, 364 consecutive patients requiring PCNL were comprehensively analyzed preoperatively and patients were selected for scheduled tubeless PCNL based on four aspects. The selected patients were divided into two groups according to whether the nephrostomy tube was finally placed. The mean operative time, intraoperative blood loss, stone clearance rate, visual pain score, postoperative hospitalization days and perioperative complications were all evaluated. RESULTS: Based on the preoperative evaluation, 42 patients were selected for tubeless PCNL, among which there were finally 37 cases of completed tubeless PCNL. Compared with patients undergoing conventional PCNL, there were not statistical differences in the mean operative time (P=0.207) or intraoperative blood loss (P=0.450) in the tubeless group. Stone clearance rate was 100% in both groups. The visual pain scores in the tubeless PCNL group were lower on operation day (P=0.029), first postoperative day (P<0.001) and the day of discharge (P=0.025). The postoperative hospitalization for the tubeless PCNL group was shorter than that of the control group (P<0.001). No significant difference in grade 1 complications was seen (P=0.424), and no grade 2 or higher complications were observed in either group. CONCLUSIONS: Postoperative pain was significantly relieved and postoperative hospitalization was significantly shortened in the tubeless PCNL group. Tubeless PCNL is safe if patients are carefully selected using four criteria before operation, attention is paid to four key points and five confirmations are made during operation.

Mitochondrial Dysfunction as a Novel Target for Neuroprotective Nutraceuticals in Ocular Diseases.

The eyes require a rich oxygen and nutrient supply; hence, the high-energy demand of the visual system makes it sensitive to oxidative stress. Excessive free radicals result in mitochondrial dysfunction and lead to retinal neurodegeneration, as an early stage of retinal metabolic disorders. Retinal cells are vulnerable because of their coordinated interaction and intricate neural networks. Nutraceuticals are believed to target multiple pathways and have shown neuroprotective benefits by scavenging free radicals and promoting mitochondrial gene expression. Furthermore, encouraging results demonstrate that nutraceuticals improve the organization of retinal cells and visual functions. This review discusses the mitochondrial impairments of retinal cells and the mechanisms underlying the neuroprotective effects of nutraceuticals. However, some unsolved problems still exist between laboratory study and clinical therapy. Poor bioavailability and bioaccessibility strongly limit their development. A new delivery system and improved formulation may offer promise for health care applications.

Bibliometric analysis of obstructive sleep apnea research trends.

BACKGROUND: This study aimed to describe current trends and areas of future research using a bibliometric evaluation of the publication output associated with research on obstructive sleep apnea (OSA) during the 16-year period of 1991-2006. METHODS: Data encompassing the period from 1991 to 2006 were extracted from the Science Citation Index online version. We analyzed selected documents with "obstructive sleep apnea", "obstructive apnea", or "OSA" as a part of the title, abstract, or key words and reported the following parameters: trends of publication output, journal pattern, country of publication, authorship, author-generated key words, and KeyWords Plus. RESULTS: The annual number of articles on OSA grew at a faster rate than did the number of general scientific publications, from approximately 200 in 1991 to 650 in 2006. The main subject categories in which research on OSA was conducted were the respiratory system and clinical neurology, each of which accounted for > 10% of total articles. Most of the research was conducted in the major industrial countries, with most international collaborations involving the United States and Canada. Certain terms were identified by KeyWords Plus but not by author-generated key words, and some terms increased in frequency of use over time. CONCLUSION: This study provides a bibliometric analysis showing that the annual number of publications related to OSA has been increasing at a much faster rate than the overall scientific literature during the past 16 years in a growing number of specialized journals. Analysis of key words (KeyWords Plus) suggests research trends and areas for future research.

Electroacupuncture attenuates chronic fibromyalgia pain through the phosphorylated phosphoinositide 3-kinase signaling pathway in the mouse brain.

OBJECTIVES: Fibromyalgia (FM) is a central nervous system disorder characterized by widespread mechanical hyperalgesia due to unknown mechanisms. Several inflammatory mediators, such as interleukin-1 (IL-1), IL-6, IL-8, and tumor necrosis factor, are increased in the serum of FM patients. Although medications including pregabalin, duloxetine, and milnacipran are used to treat FM, the results are unsatisfying. In the present study we assessed whether electroacupuncture (EA) can reduce chronic FM pain and then proposed an underlying mechanism for this effect. MATERIALS AND METHODS: Chronic FM pain was induced in mice by dual acid saline injection lasting up to 4 weeks. RESULTS: Chronic FM pain was treated by EA manipulation, but not in the sham operated group. Phosphorylated phosphatidylinositol 3-kinase (pPI3K), protein kinase B, mechanistic target of rapamycin, and nuclear factor kappa-light-chain-enhancer of activated B cells were unaltered in the mouse dorsal root ganglion (DRG) and spinal cord (SC) after inducing FM and administering EA treatment. The pPI3K-associated nociceptive signaling pathway was increased in the thalamus of FM mice, but reversed by EA. Similar results were observed in the mouse somatosensory cortex. CONCLUSION: These data suggest that EA has a significant effect on a signaling pathway in brain areas of FM mice. These findings suggest the value of EA for clinical practice.

Electroacupuncture Relieves CCI-Induced Neuropathic Pain Involving Excitatory and Inhibitory Neurotransmitters.

Neuropathic pain caused by peripheral tissue injuries to the higher brain regions still has no satisfactory therapy. Disruption of the balance of excitatory and inhibitory neurotransmitters is one of the underlying mechanisms that results in chronic neuropathic pain. Targeting neurotransmitters and related receptors may constitute a novel approach for treating neuropathic pain. We investigated the effects of electroacupuncture (EA) on chronic constriction injury- (CCI-) induced neuropathic pain. The mechanical allodynia and thermal hyperalgesia pain behaviors were relieved by 15 Hz EA but not by 2 and 50 Hz. These phenomena were associated with increasing γ-amino-butyric acid (GABA) receptors in the hippocampus and periaqueductal gray (PAG) but not N-methyl-D-aspartate receptors. Furthermore, excitatory neurotransmitter glutamate was decreased in the hippocampus and inhibitory neurotransmitter GABA was increased in the PAG under treatment with EA. These data provide novel evidence that EA modulates neurotransmitters and related receptors to reduce neuropathic pain in the higher brain regions. This suggests that EA may be a useful therapy option for treating neuropathic pain.

Paeoniflorin has anti-inflammation and neurogenesis functions through nicotinic acetylcholine receptors in cerebral ischemia-reperfusion injury rats.

OBJECTIVES: Paeoniflorin (PF) has anti-oxidation, anti-inflammation, anti-apoptosis, and neuroprotection pharmacological effects against ischemic injury. The aim of the present study was to investigate the neuroprotection mechanisms of PF in cerebral ischemia-reperfusion injury rats. MATERIALS AND METHODS: We established an animal model of cerebral infarct by occlusion of the middle cerebral artery for 15 min, followed by reperfusion, and PF was administered 24 hr later (20 mg/kg, intraperitoneally for 6 days) after reperfusion. RESULTS: Treatment with PF reduced the neurological deficit score, improved motor function, decreased cell counts of nicotinic acetylcholine receptor (nAChR) α4ß2 immunoreactive cells, and increased cell counts of nAChR α7. Furthermore, PF administration suppressed neuronal apoptosis and promoted neurogenesis. CONCLUSION: PF rescued neurological deficit and underlying mechanisms were inhibition of neurological apoptosis and inflammation by nAChRs.

Electric Stimulation of Ear Reduces the Effect of Toll-Like Receptor 4 Signaling Pathway on Kainic Acid-Induced Epileptic Seizures in Rats.

Epilepsy is a common clinical syndrome with recurrent neuronal discharges in the temporal lobe, cerebral cortex, and hippocampus. Clinical antiepileptic medicines are often ineffective or of little benefit in 30% of epileptic patients and usually cause severe side effects. Emerging evidence indicates the crucial role of inflammatory mediators in epilepsy. The current study investigates the role of toll-like receptor 4 (TLR4) and its underlying mechanisms in kainic acid- (KA-) induced epileptic seizures in rats. Experimental KA injection successfully initiated an epileptic seizure accompanied by increased expression of TLR4 in the prefrontal cortex, hippocampus, and somatosensory cortex. In addition, calcium-sensitive phosphorylated Ca2+/calmodulin-dependent protein kinase II (pCaMKIIα) increased after the initiation of the epileptic seizure. Furthermore, downstream-phosphorylated signal-regulated kinase (ERK), c-Jun NH2-terminal protein kinase (JNK), and p38 kinase simultaneously increased in these brain areas. Moreover, the transcriptional factor phosphorylated nuclear factor-κB (pNF-κB) increased, suggesting that nucleus transcription was affected. Furthermore, the aforementioned molecules decreased by an electric stimulation (ES) of either 2 Hz or 15 Hz of the ear in the three brain areas. Accordingly, we suggest that ES of the ear can successfully control epileptic seizures by regulating the TLR4 signaling pathway and has a therapeutic benefit in reducing epileptic seizures.

Targeting TRPV1 to relieve motion sickness symptoms in mice by electroacupuncture and gene deletion.

Motion sickness (MS) is an acute disorder that occurs in healthy individuals worldwide regardless of gender, age, or ethnicity. Our study used a mouse model to rule out the effects of any psychological factors related to MS and EA. Subjects were randomly separated into four groups, namely the control group (Con), motion sickness inducing group (MS), mentioning sickness inducing with electroacupuncture treatment group (EA) and motion sickness inducing only in TRPV1 knockout mice group (TRPV1-/-). The consumption of kaolin, a non-nutrient substance, was measured as a behavior observed response of an emetic reflex in a murine model. This behavior is referred to as pica behavior. Our results showed that pica behavior was observed in the MS group. Moreover, kaolin consumption in the EA group decreased to the average baseline of the control group. A similar result was observed in TRPV1 null mice. We also observed an increase of TRPV1 and related molecules in the thalamus, hypothalamic and brain stem after MS stimulation and a significant decrease in the EA and TRPV1 null groups. This is the first study to demonstrate that TRPV1 pathways are possibly associated with mechanisms of MS, and can be attended through EA or TRPV1 genetic manipulation.

Electroacupuncture Attenuates CFA-induced Inflammatory Pain by suppressing Nav1.8 through S100B, TRPV1, Opioid, and Adenosine Pathways in Mice.

Pain is associated with several conditions, such as inflammation, that result from altered peripheral nerve properties. Electroacupuncture (EA) is a common Chinese clinical medical technology used for pain management. Using an inflammatory pain mouse model, we investigated the effects of EA on the regulation of neurons, microglia, and related molecules. Complete Freund's adjuvant (CFA) injections produced a significant mechanical and thermal hyperalgesia that was reversed by EA or a transient receptor potential V1 (TRPV1) gene deletion. The expression of the astrocytic marker glial fibrillary acidic protein (GFAP), the microglial marker Iba-1, S100B, receptor for advanced glycation end-products (RAGE), TRPV1, and other related molecules was dramatically increased in the dorsal root ganglion (DRG) and spinal cord dorsal horn (SCDH) of CFA-treated mice. This effect was reversed by EA and TRPV1 gene deletion. In addition, endomorphin (EM) and N6-cyclopentyladenosine (CPA) administration reliably reduced mechanical and thermal hyperalgesia, thereby suggesting the involvement of opioid and adenosine receptors. Furthermore, blocking of opioid and adenosine A1 receptors reversed the analgesic effects of EA. Our study illustrates the substantial therapeutic effects of EA against inflammatory pain and provides a novel and detailed mechanism underlying EA-mediated analgesia via neuronal and non-neuronal pathways.