[Research Progress in Data Acquisition and Intelligent Sensing Methods for Lumbar Electromyographic Signals].

Population aging trend is taking place in our country, and low back pain is a symptom of neuromuscular diseases of concern in the elderly. Accurately analyzing the disease of low back pain is important for both timely intervention and rehabilitation of patients. As a kind of bioelectrical signal, the acquisition and analysis of lumbar electromyography (EMG) signal is an important direction for the study of low back pain. The study reviews the acquisition of lumbar EMG by different types of sensors, introduces the signal characteristics of needle electrodes, surface electromyography electrodes and array electrodes, describes the use of signal algorithms, points out that wireless sensors and the use of deep learning algorithms are the direction of development, and puts forward prospects for its further development.

Quantitative assessment of Bell's palsy-related facial thermal asymmetry using infrared thermography: A preliminary study.

The temperature distribution of normal human skin is symmetrical. Facial paralysis generally changes this thermal symmetry. The aim of this study is to analyze facial thermal asymmetry during the early onset of Bell's palsy, and to assess the feasibility of the diagnosis of early-onset Bell's palsy using infrared thermography (IRT). Fifteen subjects with Bell's palsy and 15 healthy volunteers were considered in this study. The infrared thermal images of the front, left, and right sides of all the subjects were collected and analyzed. Each group of facial thermograms was divided into 16 symmetrical regions of interest (ROIs) with respect to the left and right sides. Three different temperature difference calculation methods were used to express the degree of thermal symmetry between the left- and right-side ROIs, namely, the mean temperature difference (ΔTroi), maximum temperature difference (ΔTmax), and minimum temperature difference (ΔTmin). Among the facial ROIs, there were significant differences in the thermal symmetries of the frontal region, medial canthus region, and infraorbital region between subjects with and without Bell's palsy (p < 0.05). Based on the results, ΔTroi was more effective than the other two methods for the diagnosis of early-onset Bell's palsy. The area under the ROC curve (AUC) of ΔTroi in the infraorbital region was 0.818; and the sensitivity and specificity were 0.867 and 0.800, respectively. Subjects with early-onset Bell's palsy exhibited thermal asymmetry on the left and right sides of their faces. The diagnosis of early-onset Bell's palsy using IRT is therefore necessary. Nevertheless, more effective thermal symmetry analysis methods will be investigated further in future research.

The changes of nociception and the signal molecules expression in the dorsal root ganglia and the spinal cord after cold water swimming stress in mice.

Several studies have previously reported that exposure to stress provokes behavioral changes, including antinociception, in rodents. In the present study, we studied the effect of acute cold-water (4°C) swimming stress (CWSS) on nociception and the possible changes in several signal molecules in male ICR mice. Here, we show that 3 min of CWSS was sufficient to produce antinociception in tailflick, hot-plate, von-Frey, writhing, and formalin-induced pain models. Significantly, CWSS strongly reduced nociceptive behavior in the first phase, but not in the second phase, of the formalin-induced pain model. We further examined some signal molecules' expressions in the dorsal root ganglia (DRG) and spinal cord to delineate the possible molecular mechanism involved in the antinociceptive effect under CWSS. CWSS reduced p-ERK, p-AMPKα1, p-AMPKα2, p-Tyk2, and p-STAT3 expression both in the spinal cord and DRG. However, the phosphorylation of mTOR was activated after CWSS in the spinal cord and DRG. Moreover, p-JNK and p-CREB activation were significantly increased by CWSS in the spinal cord, whereas CWSS alleviated JNK and CREB phosphorylation levels in DRG. Our results suggest that the antinociception induced by CWSS may be mediated by several molecules, such as ERK, JNK, CREB, AMPKα1, AMPKα2, mTOR, Tyk2, and STAT3 located in the spinal cord and DRG.

2,3-Dihydroxybenzoic Acid Decarboxylase from Fusarium oxysporum: Crystal Structures and Substrate Recognition Mechanism.

A 2,3-dihydroxybenzoic acid decarboxylase from Fusarium oxysporum (2,3-DHBD_Fo) has a relatively high catalytic efficiency for the decarboxylation of 2,3-dihydroxybenzoic acid (DHBA) and carboxylation of catechol, thus it has a different substrate spectrum from other benzoic acid decarboxylases. We have determined the structures of 2,3-DHBD_Fo in its apo form and complexes with catechol or 2,5-dihydroxybenzoic acid at 1.55, 1.97, and 2.45 Šresolution, respectively. The crystal structures of 2,3-DHBD_Fo show that the enzyme exists as a homotetramer, and each active center has a Zn2+ ion coordinated by E8, H167, D291 and three water molecules. This is different from 2,6-DHBD from Rhizobium sporomusa, in which the Zn2+ ion is also coordinated with H10. Surprisingly, mutation of A10 of 2,3-DHBD_Fo to His resulted in almost complete loss of the enzyme activity. Enzyme-substrate docking and site-directed mutation studies indicate that residue R233Δ interacts with the 3-hydroxy group of 2,3-DHBA, and plays an important role in substrate recognition for this enzyme, thus revealing the molecular basis 2,3-dihydroxybenzoic acid decarboxylase.

Meta-analysis of the efficacy of postoperative adjuvant chemotherapy for stage IB non-small cell lung cancer.

BACKGROUND: Many clinical trials have shown that postoperative adjuvant chemotherapy can provide a survival benefit for patients with stage IB non-small cell lung cancer. However, whether adjuvant chemotherapy should be routinely given after surgery remains controversial. Therefore, we performed a meta-analysis to investigate the efficacy of adjuvant chemotherapy versus surgery alone for stage IB non-small cell lung cancer (NSCLC). METHODS: Relevant retrospective studies or randomized controlled trial comparing the efficacy of postoperative adjuvant chemotherapy versus observation on the survival outcomes of NSCLC patients up to October 30, 2023 were searched in PubMed, Web of Science, EMBASE, Cochrane Library, VIP database, Wanfang database, and China National Knowledge Internet database. Patient survival data, population characteristics, and other relevant information were extracted, and data were analyzed using Review Manager 5.4. The primary endpoints included overall survival, disease-free survival, and recurrence-free survival. RESULTS: A total of 13 randomized controlled trials or cohort studies including 19,442 patients were included. The results of the meta-analysis showed that postoperative adjuvant chemotherapy in patients with stage IB NSCLC had better overall survival (odds ratio [OR] = 1.25, 95% confidence interval [CI] 1.19-1.31, P < .00001) and disease-free survival or recurrence-free survival (OR = 1.57, 95% CI 1.3-1.9, P < .00001) compared with observation; and the 4-year survival rate of patients who received postoperative adjuvant chemotherapy was better than the observation group (OR = 1.52, 95% CI 1.05-2.18, P = .03); and the 8-year survival rate of patients receiving postoperative adjuvant chemotherapy (OR = 1.5, 95% CI 0.94-2.4, P = .09) was comparable to the observation group. CONCLUSION: Receiving postoperative adjuvant chemotherapy improved people's survival and prolonged disease-free survival and recurrence-free survival in patients with stage IB non-small cell lung cancer compared with surgery alone.

Combination of metformin/efavirenz/fluoxetine exhibits profound anticancer activity via a cancer cell-specific ROS amplification.

The possible anticancer activity of combination (M + E + F) of metformin (M), efavirenz (E), and fluoxetine (F) was investigated in normal HDF cells and HCT116 human colon cancer cells. Metformin increased cellular FOXO3a, p-FOXO3a, AMPK, p-AMPK, and MnSOD levels in HDFs but not in HCT116 cells. Cellular ATP level was decreased only in HDFs by metformin. Metformin increased ROS level only in HCT116 cells. Transfection of si-FOXO3a into HCT116 reversed the metformin-induced cellular ROS induction, indicating that FOXO3a/MnSOD is the key regulator for cellular ROS level. Viability readout with M, E, and F alone decreased slightly, but the combination of three drugs dramatically decreased cell survival in HCT116, A549, and SK-Hep-1 cancer cells but not in HDF cells. ROS levels in HCT116 cells were massively increased by M + E + F combination, but not in HDF cells. Cell cycle analysis showed that of M + E + F combination caused cell death only in HCT116 cells. The combination of M + E + F reduced synergistically mitochondrial membrane potential and mitochondrial electron transport chain complex I and III activities in HCT116 cells when compared with individual treatments. Western blot analysis indicated that DNA damage, apoptosis, autophagy, and necroptosis-realated factors increased in M + E + F-treated HCT116 cells. Oral administration with M + E + F combination for 3 weeks caused dramatic reductions in tumor volume and weight in HCT116 xenograft model of nude mice when compared with untreated ones. Our results suggest that M + E + F have profound anticancer activity both in vitro and in vivo via a cancer cell-specific ROS amplification (CASRA) through ROS-induced DNA damage, apoptosis, autophagy, and necroptosis.

Integrative Analysis for Elucidating Transcriptomics Landscapes of Systemic Lupus Erythematosus.

Systemic lupus erythematosus (SLE) is a complex and heterogeneous autoimmune disease that the immune system attacks healthy cells and tissues. SLE is difficult to get a correct and timely diagnosis, which makes its morbidity and mortality rate very high. The pathogenesis of SLE remains to be elucidated. To clarify the potential pathogenic mechanism of SLE, we performed an integrated analysis of two RNA-seq datasets of SLE. Differential expression analysis revealed that there were 4,713 and 2,473 differentially expressed genes, respectively, most of which were up-regulated. After integrating differentially expressed genes, we identified 790 common differentially expressed genes (DEGs). Gene functional enrichment analysis was performed and found that common differentially expressed genes were significantly enriched in some important immune-related biological processes and pathways. Our analysis provides new insights into a better understanding of the pathogenic mechanisms and potential candidate markers for systemic lupus erythematosus.

Effects of Salvia miltiorrhiza Bunge extract and its single components on monosodium urate-induced pain in vivo and lipopolysaccharide-induced inflammation in vitro.

OBJECTIVE: To investigate the possible antinociceptive effects of Salvia (S.) miltiorrhiza Bunge and its single components in monosodium urate (MSU)-induced pain model in mice and lipopolysaccharide (LPS)-induced inflammation model in RAW264.7 cells. METHODS: Pretreatment of S. miltiorrhiza Bunge extract (from 1 to 50 µg/mL) concentration-dependently attenuated LPS-induced nitric oxide (NO) release. The extract of S. miltiorrhiza Bunge (50 or 100 mg/kg) also caused reversals of decreased threshold for pain in the MSU-treated group as measured by Von-Frey test. Furthermore, we assessed the antinociceptive and anti-inflammatory properties of the active single components from S. miltiorrhiza Bunge such as 15, 16-dihydrotanshinone Ⅰ tanshinone Ⅱ cryptotanshinone, miltirone, tanshinone ⅡA, and salvianolic acid B. Some of them showed an anti-inflammatory effect in LPS-induced NO release model and an antinociceptive effect in MSU-treated pain model. RESULTS: Our results suggest that S. miltiorrhiza Bunge extract may exert anti-inflammatory effect by reducing LPS-induced NO release and an antinociceptive property in MSU-treated pain model. Especially, tanshinoneⅡA, miltirone, cryptotanshinone, and 15,16-dihydrotanshinone Ⅰ not only appear to be responsible for LPS-induced NO release induced by S. miltiorrhiza Bunge, but also in the production of S. miltiorrhiza Bunge extract-induced antinociception in MSU-treated pain model. CONCLUSION: Therefore, the analgesic and anti-inflammatory property of S. miltiorrhiza Bunge indicate it as a therapeutic potential candidate for the treatment of pain and inflammation.

Metformin-induced ROS upregulation as amplified by apigenin causes profound anticancer activity while sparing normal cells.

Metformin increased cellular ROS levels in AsPC-1 pancreatic cancer cells, with minimal effect in HDF, human primary dermal fibroblasts. Metformin reduced cellular ATP levels in HDF, but not in AsPC-1 cells. Metformin increased AMPK, p-AMPK (Thr172), FOXO3a, p-FOXO3a (Ser413), and MnSOD levels in HDF, but not in AsPC-1 cells. p-AMPK and p-FOXO3a also translocated from the cytosol to the nucleus by metformin in HDF, but not in AsPC-1 cells. Transfection of si-FOXO3a in HDF increased ROS levels, while wt-FOXO3a-transfected AsPC-1 cells decreased ROS levels. Metformin combined with apigenin increased ROS levels dramatically and decreased cell viability in various cancer cells including AsPC-1 cells, with each drug used singly having a minimal effect. Metformin/apigenin combination synergistically decreased mitochondrial membrane potential in AsPC-1 cells but to a lesser extent in HDF cells. Metformin/apigenin combination in AsPC-1 cells increased DNA damage-, apoptosis-, autophagy- and necroptosis-related factors, but not in HDF cells. Oral administration with metformin/apigenin caused dramatic blocks tumor size in AsPC-1-xenografted nude mice. Our results suggest that metformin in cancer cells differentially regulates cellular ROS levels via AMPK-FOXO3a-MnSOD pathway and combination of metformin/apigenin exerts anticancer activity through DNA damage-induced apoptosis, autophagy and necroptosis by cancer cell-specific ROS amplification.

The Anti-Inflammatory and the Antinociceptive Effects of Mixed Agrimonia pilosa Ledeb. and Salvia miltiorrhiza Bunge Extract.

Arthritis is a common condition that causes pain and inflammation in a joint. Previously, we reported that the mixture extract (ME) from Agrimonia pilosa Ledeb. (AP) and Salvia miltiorrhiza Bunge (SM) could ameliorate gout arthritis. In the present study, we aimed to investigate the potential anti-inflammatory and antinociceptive effects of ME and characterize the mechanism. We compared the anti-inflammatory and antinociceptive effects of a positive control, Perna canaliculus powder (PC). The results showed that one-off and one-week treatment of ME reduced the pain threshold in a dose-dependent manner (from 10 to 100 mg/kg) in the mono-iodoacetate (MIA)-induced osteoarthritis (OA) model. ME also reduced the plasma TNF-α, IL-6, and CRP levels. In LPS-stimulated RAW 264.7 cells, ME inhibited the release of NO, PGE2, LTB4, and IL-6, increased the phosphorylation of PPAR-γ protein, and downregulated TNF-α and MAPKs proteins expression in a concentration-dependent (from 1 to 100 µg/mL) manner. Furthermore, ME ameliorated the progression of ear edema in mice. In most of the experiments, ME-induced effects were almost equal to, or were higher than, PC-induced effects. Conclusions: The data presented here suggest that ME shows anti-inflammatory and antinociceptive activities, indicating ME may be a potential therapeutic for arthritis treatment.

Intra- and Interrater Reliability of Infrared Image Analysis of Facial Acupoints in Individuals with Facial Paralysis.

Infrared thermography (IRT), as a noncontact tool for temperature measurement, is widely applied in the study of acupuncture modernization. The aim of this study was to assess the intra- and interrater reliability of infrared image analysis of facial acupoints of subjects with facial paralysis and determine the factors influencing the variability of the measured values. A total of 26 patients with facial paralysis on one side, aged 26 to 53 years, participated voluntarily in the study. Facial infrared thermal images of all participants were analyzed by two trained raters at two different time points at a one-week interval. The intraclass correlation coefficient (ICC) was used to determine the intra- and interrater reliability of IRT measurements. The ICC values varied depending on the analyzed acupoints. The reliability of temperature measurement ranged from moderate to excellent (intrarater, ICC ranged from 0.669 to 0.990; interrater, ICC ranged from 0.661 to 0.987). The reliability of temperature difference measurement ranged from low to excellent (intrarater, ICC ranged from 0.412 to 0.882; interrater, ICC ranged from 0.334 to 0.828). The main influencing factor of reliability is the incomplete consistency in selecting acupoint positions when repeatedly positioning the same acupoint manually. Despite low reliability of temperature difference measurement at some acupoints, some auxiliary measures can be used to reduce the error of manual positioning. Thus, infrared thermal imaging still has the potential to assist in objective and quantitative research on acupuncture.

The role of spinally located dopamine D2 receptors in the regulation of the blood glucose level in mice.

BACKGROUND: The possible role of dopamine D2 receptors located in the spinal cord in the regulation of the blood glucose level have not been investigated before. METHODS: In the present study, the effect of D2 receptor agonist and antagonist administered intrathecal (it) injection on the blood glucose level were examined in the Institute of Cancer Research (ICR) mice. RESULTS: We found that it injection with carmoxirole (D2 receptor agonist) caused an elevation of the blood glucose level in a dose-dependent manner. Carmoxirole-induced increase of the blood glucose was significantly attenuated by L-741,626 (D2 receptor antagonist). Previously, we indicated that intrathecal (it) treatment with 0.1 µg/5 µl pertussis toxin (PTX, a Gi/Go inhibitor) produces a hypoglycemic effect in ICR in a long-term manner. In the present study, it pretreatment with PTX for 6 days almost abolished the hyperglycemic effect induced by carmoxirole. The plasma insulin level was elevated by carmoxirole, and L-741,626 or PTX pretreatment reduced carmoxirole-induced increment of the insulin level. In addition, the plasma corticosterone level was increased by carmoxirole but it pretreatment with L-741,626 or PTX did not affect carmoxirole-induced increment of the corticosterone level. CONCLUSION: Our results suggest that D2 receptors located in the spinal cord play an important role in the elevation of the blood glucose level. Spinally located inhibitory G-proteins appear to be involved in hyperglycemic effect induced by carmoxirole.

Identification and Analysis of Genes Underlying Bone Mineral Density by Integrating Microarray Data of Osteoporosis.

Osteoporosis is a kind of brittle bone disease, which is characterized by a reduction in bone mineral density (BMD). In recent years, a number of genes and pathophysiological mechanisms have been identified for osteoporosis. However, the genes associated with BMD remain to be explored. Toward this end, we integrated multiple osteoporosis microarray datasets to identify and systematically characterize BMD-related genes. By integrating the differentially expressed genes from three osteoporosis microarray datasets, 152 genes show differentially expressed between high and low BMD osteoporosis samples in at least two of the three datasets. Among them, 88 were up-regulated in high BMD samples and 64 were up-regulated in low BMD samples. The expression of ZFP36, JUNB and TMEM8A were increased at high BMD samples in all three datasets. Hub genes were further identified by co-expression network analysis. Functional enrichment analysis showed that the gene up-regulated in high BMD were enriched in immune-related functions, suggesting that the immune system plays an important role in osteoporosis. Our study explored BMD-related genes based on the integration of osteoporosis microarray data, providing guidance to other researchers from a new perspective.

Antinociceptive effect of chrysin in diabetic neuropathy and formalin-induced pain models.

Chrysin, a natural flavonoid, is the main ingredient of many medicinal plants, which shows potent pharmacological properties. In the present study, the antinociceptive effects of chrysin were examined in ICR mice. Chrysin orally administered at the doses of from 10 to 100 mg/kg exerted the reductions of formalin-induced pain behaviors observed during the second phase in the formalin test in a dose-dependent manner. In addition, the antinociceptive effect of chrysin was further characterized in streptozotocin-induced diabetic neuropathy model. Oral administration chrysin caused reversals of decreased pain threshold observed in diabetic-induced peripheral neuropathy model. Intraperitoneally (i.p.) pretreatment with naloxone (a classic opioid receptor antagonist), but not yohimbine (an antagonist of α2-adrenergic receptors) or methysergide (an antagonist of serotonergic receptors), effectively reversed chrysin-induced antinociceptive effect in the formalin test. Moreover, chrysin caused a reduction of formalin-induced up-regulated spinal p-CREB level, which was also reversed by i.t. pretreated naloxone. Finally, chrysin also suppressed the increase of the spinal p-CREB level induced by diabetic neuropathy. Our results suggest that chrysin shows an antinociceptive property in formalin-induced pain and diabetic neuropathy models. In addition, spinal opioid receptors and CREB protein appear to mediate chrysin-induced antinociception in the formalin-induced pain model.

Brain Proteomic Profiling in Intractable Epilepsy Caused by TSC1 Truncating Mutations: A Small Sample Study.

Tuberous sclerosis complex (TSC) is a genetic disease characterized by seizures, mental deficiency, and abnormalities of the skin, brain, kidney, heart, and lungs. TSC is inherited in an autosomal dominant manner and is caused by variations in either the TSC1 or TSC2 gene. TSC-related epilepsy (TRE) is the most prevalent and challenging clinical feature of TSC, and more than half of the patients have refractory epilepsy. In clinical practice, we found several patients of intractable epilepsy caused by TSC1 truncating mutations. To study the changes of protein expression in the brain, three cases of diseased brain tissue with TSC1 truncating mutation resected in intractable epilepsy operations and three cases of control brain tissue resected in craniocerebral trauma operations were collected to perform protein spectrum detection, and then the data-independent acquisition (DIA) workflow was used to analyze differentially expressed proteins. As a result, there were 55 up- and 55 down-regulated proteins found in the damaged brain tissue with TSC1 mutation compared to the control. Further bioinformatics analysis revealed that the differentially expressed proteins were mainly concentrated in the synaptic membrane between the patients with TSC and the control. Additionally, TSC1 truncating mutations may affect the pathway of amino acid metabolism. Our study provides a new idea to explore the brain damage mechanism caused by TSC1 mutations.

The Molecular Signatures of Acute-immobilization-induced Antinociception and Chronic-immobilization-induced Antinociceptive Tolerance.

In the present study, the productions of antinociception induced by acute and chronic immobilization stress were compared in several animal pain models. In the acute immobilization stress model (up to 1 hr immobilization), the antinociception was produced in writhing, tail-flick, and formalin- induced pain models. In chronic immobilization stress experiment, the mouse was enforced into immobilization for 1 hr/day for 3, 7, or 14 days, then analgesic tests were performed. The antinociceptive effect was gradually reduced after 3, 7 and 14 days of immobilization stress. To delineate the molecular mechanism involved in the antinociceptive tolerance development in the chronic stress model, the expressions of some signal molecules in dorsal root ganglia (DRG), spinal cord, hippocampus, and the hypothalamus were observed in acute and chronic immobilization models. The COX-2 in DRG, p-JNK, p-AMPKα1, and p-mTOR in the spinal cord, p-P38 in the hippocampus, and p-AMPKα1 in the hypothalamus were elevated in acute immobilization stress, but were reduced gradually after 3, 7 and 14 days of immobilization stress. Our results suggest that the chronic immobilization stress causes development of tolerance to the antinociception induced by acute immobilization stress. In addition, the COX-2 in DRG, p-JNK, p-AMPKα1, and p-mTOR in the spinal cord, p-P38 in the hippocampus, and p-AMPKα1 in the hypothalamus may play important roles in the regulation of antinociception induced by acute immobilization stress and the tolerance development induced by chronic immobilization stress.

The effect of apelin-13 on pancreatic islet beta cell mass and myocardial fatty acid and glucose metabolism of experimental type 2 diabetic rats.

Apelin, a new identified adipokine, and its G protein-coupled receptor named APJ are widely expressed in various tissues. Apelin has been found to play important roles in the physiopathology of multiple diseases. Our aim is to assess the effect of long-term apelin treatment on serum insulin level and pancreatic islet beta-cell mass in the late stage of type 2 diabetes without hyperinsulinemia and to investigate the role of apelin in myocardial fatty acid and glucose metabolism. In the present study, the high-fat diet fed-streptozotocin-induced experimental type 2 diabetic rats were given once daily intraperitoneal injection of apelin-13 (0.1 µmol/kg) for 10 weeks. We observed that apelin significantly improved serum insulin reduction and reduced hyperglycemia. Histologic analysis showed that long-term apelin treatment significantly increased pancreatic islet beta cell mass. Exogenous apelin failed to change dyslipidaemia of type 2 diabetic rats. Apelin treatment markedly decreased elevated myocardial FFA and glycogen content. Treatment of type 2 diabetic rats with apelin markedly reduced increased gene expressions of the cardiac fatty acid transporter CD36, CPT-1, and Peroxisome proliferator-activated receptor (PPAR)-α. Whereas the gene levels of citrate synthase and peroxisome proliferator-activated receptor γ coactivator 1-α (PGC1-α), a transcriptional coactivator, mediating mitochondrial biogenesis in heart were unaltered in response to exogenous apelin. Taken together, longer-term apelin treatment prevented pancreatic beta-cell loss or failure in experimental type 2 diabetic rats. Apelin can regulate myocardial metabolism. Apelin reduced myocadial fatty acid uptake and oxidation through inhibiting PPAR-α but did not affect myocardial mitochondrial biogenesis in type 2 diabetic rats.

Effects of resveratrol and oxyresveratrol on hippocampal cell death induced by kainic acid.

In the present study, we have examined the possible neuroprotective effects of resveratrol and oxyresveratrol against kainic-acid (KA)-induced hippocampal neuronal cell death. Either resveratrol or oxyresvertrol was orally administered 30 min prior to intracerebroventricular (i.c.v.) administration with KA (0.05 µg). Oral pretreatment with oxyresveratrol (50 mg/kg) significantly protected KA-induced hippocampal CA3 neuronal cell death. However, the same dose (50 mg/kg) or a higher dose (100 mg/kg) pretreatment with resveratrol did not affect KA-induced hippocampal neuronal cell death. Furthermore, the i.c.v. pretreatment with 30 µg of oxyresveratrol or resveratrol did not show the protective effect against KA-induced hippocampal neuronal cell death. In the immunohistochemical analysis, FoxO3a and pFoxO3a expressions in the hippocampal CA3 region were significantly increased 30 min after KA administration. Oral pretreatment with oxyresveratrol (50 mg/kg) significantly reduced KA-induced Forkhead homeobox type O3a (FoxO3a) and pFoxO3a expression in CA3 region of the hippocampus, suggesting that oxyresveratrol may exert a neuroprotective effect against KA-induced hippocampal neuronal cell death by reducing the levels of FoxO3a and pFoxO3a protein expression in the hippocampal CA3 region. Furthermore, it is suggested that the neuroprotective effect of orally administered oxyresveratrol against KA-induced neurotoxicity might be possibly mediated by some metabolites rather than direct action of oxyresveratrol on the central nervous system.

Antinociceptive effect of N-(9,13b-dihydro-1H-dibenzo[c, f]imidazo[1,5-a]azepin-3-yl)-2-hydroxybenzamide on different pain models in mice

Abstract N-(9,13b-dihydro-1H-dibenzo[c,f]imidazo[1,5-a]azepin-3-yl)-2-hydroxybenzamide (DDIAHB) is a new drug developed through molecular modelling and rational drug design by the molecular association of epinastine and salicylic acid. The present study was designed to assess the possible antinociceptive effects of DDIAHB on different pain models in male ICR mice. DDIAHB exerted the reductions of writhing numbers and pain behavior observed during the second phase in the formalin test in a dose-dependent manner. Moreover, DDIAHB increased the latency in the hot-plate test in a dose-dependent manner. Furthermore, intragastric administration DDIAHB caused reversals of decreased pain threshold observed in both streptozotocin-induced diabetic neuropathy and vincristine-induced peripheral neuropathy models. Additionally, intragastric pretreatment with DDIAHB also caused reversal of decreased pain threshold observed in monosodium urate-induced pain model. We also characterized the possible signaling molecular mechanism of the antinociceptive effect-induced by DDIAHB in the formalin model. DDIAHB caused reductions of spinal iNOS, p-STAT3, p-ERK and p-P38 levels induced by formalin injection. Our results suggest that DDIAHB shows an antinociceptive property in various pain models. Moreover, the antinociceptive effect of DDIAHB appear to be mediated by the reductions of the expression of iNOS, p-STAT3, p-ERK and p-P38 levels in the spinal cord in the formalin-induced pain model.

Hemodynamic effect of apelin in a canine model of acute pulmonary thromboembolism.

The peptide apelin is expressed in the pulmonary vasculature and is involved in the pathogenesis of many cardiovascular diseases. It has a biphasic role in the regulation of vasomotor tone related to the vascular endothelium. In this study, we induced acute pulmonary embolism (APE) in dogs with autologous blood clots to assess the effect of apelin on pulmonary and systemic circulation in the acute phase of APE. The expression of apelin mRNA was found to be upregulated in the lung tissue in the early several hours after APE induction and decreased at 24 h. The expression of apelin protein in the pulmonary arteries did not change within 24 h after APE, but significantly increased in the bronchial epithelial cells as early as 1h and decreased at 24 h. In normal anesthetized dogs, intravenous bolus administration of apelin significantly reduced the mean arterial pressure (MAP), but did not significantly affect the mean pulmonary arterial pressure (MPAP). In the dogs with APE, apelin decreased MPAP, whereas its impact on MAP was not significantly different from that in the control group. Taken together, the level of endogenous apelin did not change significantly in the pulmonary arterial wall, whereas its expression in the bronchial epithelium was upregulated in the early stage of APE. The effect of exogenous apelin on vasomotor tone was complicated: it resulted in differential changes in the pulmonary and systemic arterial pressures under different physiological and pathological conditions.