A fast and non-invasive artificial intelligence olfactory-like system that aids diagnosis of Parkinson's disease.

BACKGROUND AND PURPOSE: Several previous studies have shown that skin sebum analysis can be used to diagnose Parkinson's disease (PD). The aim of this study was to develop a portable artificial intelligence olfactory-like (AIO) system based on gas chromatographic analysis of the volatile organic compounds (VOCs) in patient sebum and explore its application value in the diagnosis of PD. METHODS: The skin VOCs from 121 PD patients and 129 healthy controls were analyzed using the AIO system and three classic machine learning models were established, including the gradient boosting decision tree (GBDT), random forest and extreme gradient boosting, to assist the diagnosis of PD and predict its severity. RESULTS: A 20-s time series of AIO system data were collected from each participant. The VOC peaks at a large number of time points roughly concentrated around 5-12 s were significantly higher in PD subjects. The gradient boosting decision tree model showed the best ability to differentiate PD from healthy controls, yielding a sensitivity of 83.33% and a specificity of 84.00%. However, the system failed to predict PD progression scored by Hoehn-Yahr stage. CONCLUSIONS: This study provides a fast, low-cost and non-invasive method to distinguish PD patients from healthy controls. Furthermore, our study also indicates abnormal sebaceous gland secretion in PD patients, providing new evidence for exploring the pathogenesis of PD.

Hemichorea due to ipsilateral thalamic infarction: A case report.

BACKGROUND: Hemichorea usually results from vascular lesions of the basal ganglia. Most often, the lesion is contralateral to the affected limb but rarely, it may be ipsilateral. The pathophysiology of ipsilateral hemichorea is still poorly understood. We review the literature on hemichorea due to ipsilateral cerebral infarction and explore possible mechanisms for its occurrence. CASE SUMMARY: A 72-year-old woman presented with complaints of involuntary movements of the muscles of the left side of the face and mild weakness of the right limbs. Her symptoms had started suddenly 1 d earlier. After admission to the hospital, the involuntary movements spread to involve the left limbs also. Magnetic resonance imaging revealed a left thalamic infarction. The patient's hemichorea subsided after treatment with haloperidol (2 mg per time, 3 times/d) for 3 d; the hemiparesis resolved with rehabilitation physiotherapy. She is presently symptom free and on treatment for prevention of secondary stroke. We review the literature on the occurrence of ipsilateral hemichorea following thalamic infarction and discuss the possible pathomechanisms of this unusual presentation. CONCLUSION: Ipsilateral hemichorea following a thalamic stroke is rare but it can be explained by structure of the extrapyramidal system. The thalamus is a relay station that exerts a bilateral control of motor function.

Hyperglycemic hemianopia: A case report.

BACKGROUND: Nonketotic hyperglycemia (NKH) is characterized by hyperglycemia with little or no ketoacidosis. Diverse neurological symptoms have been described in NKH patients, including choreoathetosis, hemiballismus, seizures, and coma in severe cases. Homonymous hemianopia, with or without occipital seizures, caused by hyperglycemia is less readily recognized. CASE SUMMARY: We describe a 54-year-old man with NKH, who reported seeing round, colored flickering lights with right homonymous hemianopia. Cranial magnetic resonance imaging demonstrated abnormalities in the left occipital lobe, with decreased T2 signal of the white matter, restricted diffusion, and corresponding low signal intensity in the apparent diffusion coefficient map. He responded to rehydration and a low-dose insulin regimen, with improvements of his visual field defect. CONCLUSION: Patients with NKH may present focal neurologic signs. Hyperglycemia should be taken into consideration when making an etiologic diagnosis of homonymous hemianopia.

LUM is the hub gene of advanced fibrosis in nonalcoholic fatty liver disease patients.

INTRODUCTION: Advanced fibrosis in nonalcoholic fatty liver disease (NAFLD) is associated with a poor prognosis. The genetic factors contributing to fibrosis in NAFLD have been described. However, the genetic mechanism and hub genes of advanced fibrosis have not been elucidated to date. In this study, we performed a weighted gene coexpression network analysis (WGCNA) to identify the hub genes related to advanced fibrosis in NAFLD. MATERIALS AND METHODS: The datasets GSE89632 and GSE31803 of NAFLD patients were selected from the Gene Expression Omnibus (GEO) database of NCBI and analyzed by WGCNA. The hub genes were selected in the GSE31803 dataset and verified in the GSE31803 dataset. Gene Ontology (GO) term enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis of the dataset were also performed. RESULTS: The gene LUM was identified as the hub gene in the datasets GSE89632 and GSE31803 according to three different algorithms (gene significance and module membership, the pathways of the genes, and protein expressed by the genes). The functional enrichment analysis shows that the identified module is related to the extracellular matrix, regulation of cell proliferation, and the inflammatory response. The metabolic pathway analysis identified metabolic pathways and focal adhesion as the most important pathways. CONCLUSION: By a variety of methods, LUM was identified as the hub gene of advanced fibrosis in patients with NAFLD. Therefore, further research on the LUM gene is warranted.

How to estimate renal function in patients with liver disease: choosing the most suitable equation.

BACKGROUND: Hepatitis B virus (HBV) infection is a public health challenge, especially in China. In clinical practice, HBV infection is associated with nephropathy. Impaired renal function is frequently observed in compensated Chronic Hepatitis B (CHB) and cirrhosis (LC). Thus, renal function must be monitored to avoid nephrotoxic effects before and during nucleoside analog treatment. Investigating the predictive markers of early renal dysfunction is essential. New GFR-predicting equations, based on Pcr and/or CystC, have been recently recommended in the general population, but their performance in liver disease patients has been rarely studied. In this study, we will discuss how to detect renal dysfunction in patients with HBV infection. METHODS: A total of 16 LC patients and 23 CHB patients were enrolled in this study, and we collected and compared the clinical data of the two groups. The estimated glomerular filtration rates (eGFRs) were also calculated by several equations. All patients received 99mTc-DTPA dynamic radionuclide imaging examinations to obtain mGFRs as the reference standard. To evaluate the performance of any equation in the CHB and LC groups, paired t test, Pearson's correlation, Kappa analysis and Bland-Altman plots were utilized. Moreover, all 39 subjects were divided into two groups (according to GFR > 90 mL/min/1.73 m2). We compared the serum and urinary markers of kidney injury between the two groups and selected the indicators of renal injury by univariate analysis. RESULTS: The mGFR was 72.26 ± 20.69 mL/min/1.73 m2 in the LC group, and 87.49 ± 25.91 mL/min/1.73 m2 in the CHB group. The paired t test results of eGFR and mGFR showed no difference between eGFR (estimated by the CHINAcr-cys equation) and mGFR (p > 0.05) in the compensated LC and CHB groups. The difference between mGFR and eGFR estimated by other methods was obvious (p < 0.05). Comparing the eGFRs (estimated by 5 different equations) with mGFR in the compensated LC and CHB groups, Pearson's correlation showed that only eGFR (estimated by the CHINAcr-cys equation) had a significant correlation coefficient in CHB (r = 0.678, p = 0.000) and had the highest R2 (R2 = 0.459) among all other measures. The kappa consistency test showed that eGFR from CHINAscr-cys had poor consistency with mGFR in the compensated LC group but moderate consistency in the CHB group. Bland-Altman consistency analysis showed that in the CHB group, the CHINAcr-cys and CKD-EPIcr equations presented narrower acceptable limits than did the aMDRD, c-aMDRD, and CKD-EPIcr-cys equations (62.8, 56.1 vs .85.7, 102.9, 93.6 mL/min per 1.73 m2). In the compensated LC group, the CHINAcr-cys and CKD-EPIcr equations presented narrower acceptable limits than did the aMDRD, c-aMDRD, and CKD-EPIcr-cys equations (83.6, 81.3 vs. 98, 113.5, 106.3 mL/min per 1.73 m2). Serum or urinary markers were compared with renal function (GFR > 90 mL/min/1.73 m2) and showed International normalized ratio (INR) (p = 0.009), creatinine (p = 0.006), urine N-acetyl-ß-glucosaminidase (NAG) (p = 0.001) and serum cystatin C (CysC) (p = 0.044). CONCLUSION: The CHINAcr-cys equation may be more suitable for the estimation of GFR in Chinese patients with CHB or compensated cirrhosis. INR, creatinine, NAG, and CysC are proper biomarkers for screening renal dysfunction in Chinese patients with CHB or compensated LC.

Novel Zinc Finger Transcription Factor ZFP580 Facilitates All-Trans Retinoic Acid -Induced Vascular Smooth Muscle Cells Differentiation by Rarα-Mediated PI3K/Akt and ERK Signaling.

BACKGROUND/AIMS: Phenotypic switching of vascular smooth muscle cells (VSMC) plays a vital role in the development of vascular diseases. All-trans retinoic acid (ATRA) is known to regulate VSMC phenotypes. However, the underlying mechanisms remain completely unknown. Here, we have investigated the probable roles and underlying mechanisms of the novel C2H2 zinc finger transcription factor ZFP580 on ATRA-induced VSMC differentiation. METHODS: VSMCs were isolated, cultured, and identified. VSMCs were infected with an adenovirus encoding ZFP580 or Ad-siRNA to silence ZFP580. The expression levels of ZFP580, SMα-actin, SM22α, SMemb, RARα, RARß, and RARγ were assayed by Q-PCR and western blot. A rat carotid artery injury model and morphometric analysis of intimal thickening were also used in this study. RESULTS: ATRA caused a significant reduction of VSMC proliferation and migration in a doseand time-dependent manner. Moreover, it promoted VSMC differentiation by enhancing expression of differentiation markers and reducing expression of dedifferentiation markers. This ATRA activity was accompanied by up-regulation of ZFP580, with concomitant increases in RARα expression. In contrast, silencing of the RARα gene or inhibiting RARα with its antagonist Ro41-5253 abrogated the ATRA-induced ZFP580 expression. Furthermore, ATRA binding to RARα induced ZFP580 expression via the PI3K/Akt and ERK pathways. Adenovirusmediated overexpression of ZFP580 promoted VSMC differentiation by enhancing expression of SM22α and SMα-actin and reducing expression of SMemb. In contrast, silencing ZFP580 dramatically reduced the expression of differentiation markers and increased expression of dedifferentiation markers. The classic rat carotid artery balloon injury model demonstrated that ZFP580 inhibited proliferation and intimal hyperplasia in vivo. CONCLUSION: The novel zinc finger transcription factor ZFP580 facilitates ATRA-induced VSMC differentiation by the RARα-mediated PI3K/Akt and ERK signaling pathways. This might represent a novel mechanism of regulation of ZFP580 by ATRA and RARα, which is critical for understanding the biological functions of retinoids during VSMC phenotypic modulation.

Targeting of NT5E by miR-30b and miR-340 attenuates proliferation, invasion and migration of gallbladder carcinoma.

MicroRNAs (miRNAs) have been closely associated with the proliferation, invasion and migration of various cancers, including gallbladder carcinoma (GBC). Previous studies have revealed dysregulation of miR-30b and miR-340 in many types of cancer. However, the role of miR-30b and miR-340 in the development and progression of GBC remains unclear. Moreover, epithelial-to-mesenchymal transition (EMT) has been gradually viewed as a significant contributor to tumor metastasis. In this study, the cell line GBC-SD was used and we explored that EMT promoted GBC cells invasion and migration and inhibited the expression level of miR-30b and miR-340 compared with the control. We showed that overexpression of miR-30b and miR-340 suppressed GBC cells proliferation, invasion and migration, as well as the expression of EMT-associated genes. In addition, we identified ecto-5'-nucleotidase (NT5E) as a common target of miR-30b and miR-340 using bioinformatics analysis and a luciferase assay. Further experiments found that exogenous expression of NT5E in GBC cells could partially reverse the inhibitory effect of miR-30b and miR-340 on cell proliferation, invasion and migration. Our findings suggest that NT5E-targeting miRNAs (miR-30b and miR-340) function as tumor suppressors and may represent promising therapeutic targets for GBC.

The regulatory effect of oxymatrine on the TLR4/MyD88/NF-κB signaling pathway in lipopolysaccharide-induced MS1 cells.

BACKGROUND: Oxymatrine (OM), a major quinolizidine alkaloid extracted from the roots of Sophora flavescens, has been proved to regulate a variety of signaling pathways to produce a wide range of pharmacological effects. OBJECTIVES: The regulatory effects of OM on the TLR4/MyD88/NF-κB signaling pathway under the stimulation of lipopolysaccharide (LPS) in MS1 cells were explored to illuminate the potential anti-inflammatory mechanism of OM for pancreatitis treatment. METHODS: The signaling molecules related to the TLR4/MyD88/NF-κB pathway in MS1 cells were detected by Western blotting under different conditions, including OM pretreatment and LPS stimulation. The mRNA expression levels of TLR4, MyD88, NF-κB p65 and IκBα were detected by real-time PCR. The NF-κB p65 nuclear translocation in MS1 cells was measured by immunofluorescence, and the pro-inflammatory cytokine of IL-1ß was detected by ELISA. RESULTS: Increased levels of TLR4, MyD88 and NF-κB p65, induced by LPS stimulation, were significantly inhibited by OM pretreatment in MS1 cells. The decreased protein, but not mRNA, level of IκBα induced by LPS stimulation was increased by OM pretreatment. Meanwhile, LPS induced NF-κB p65 protein translocation to the nucleus as well as LPS increased expression of IL-1ß were also inhibited by OM pretreatment. CONCLUSION: Inhibitory effects of OM on molecules related to the TLR4/MyD88/NF-κB signaling pathway in pancreatic microvascular endothelial cells can alleviate inflammatory responses.

Bibliometric analysis of top 100 cited articles in nonalcoholic fatty liver disease research.

AIM: To identify and assess the research situation of top 100 cited articles in nonalcoholic fatty liver disease (NAFLD). METHODS: The global scientific research articles in the Science Citation Index-Expanded relevant to NAFLD were retrieved and listed according to their citation times from the most to the least. The 100 most frequently cited original articles were selected to systematically evaluate their bibliometric parameters including times cited, publication year, journals, subject categories, and the highly related concepts of NAFLD, which reflected the history and current situation, publication distribution of leading countries and institutes as well as the research hotspots of NAFLD. RESULTS: Top 100 cited articles in NAFLD were published from 1965 to 2015 with a citation ranging of 227 to 2151 times since publication, in which the United States was the most predominant country and Mayo Clin was the most productive institution. The majority of the top 100 cited articles were concentrated in SCI subject category of Gastroenterology and Hepatology. Hepatology and Gastroenterology is the top journal that published over half 100 top-cited articles. The significant peak of top cited articles present in the first half of the 2000s while the highest mean number of citation presents in first half of the 1980s. In addition, concepts related to pathology characteristics, epidemiology and medicalization, metabolic syndrome and its combination of symptoms including insulin resistance, biomarkers of lipid metabolism and obesity are listed as the highly related concepts. CONCLUSION: The 100 top-cited articles marked with the leading countries, institutions, journals, hotspots and development trend in NAFLD field that could provide the foundation for further investigations.

The 100 most cited articles in ectopic pregnancy: a bibliometric analysis.

Ectopic pregnancy (EP) remains a major gynecological emergency and is a cause of morbidity or even mortality in women. As a consequence, top citation analysis of EP research in database of the Science Citation Index Expanded is needed to assess the publication trends of leading countries/territories and institutes as well as the research hotspots of EP. A total of 4881 articles relevant to EP were retrieved in the database of the Science Citation Index Expanded from 1965 to present, in which the 100 top-cited articles were selected for further analysis. The number of citations ranged from 81 to 482 (131.57 ± 69.76), with a time span of 40 years between 1969 and 2009. These citation classics came from 14 countries, and 65 of the articles came from the United States. Yale University in Connecticut led the list of classics with six papers. The 100 top-cited articles were published in 32 journals, in which the journal of Fertility and Sterility published the most (23 papers). Stovall TG and Ling FW published the highest number of studies (6 papers each). Articles that originated in the United States and that were published in high-impact journals were most likely to be cited in the field of EP research. Bibliometric analysis was used to provide a historical perspective on the progress in EP research over the past 50 years. Citation analysis is a feasible tool to comprehensively recognize the advances of EP research in the past and future research.

Potential Signaling Pathways Involved in the Clinical Application of Oxymatrine.

Oxymatrine, an alkaloid component extracted from the roots of Sophora species, has been shown to have antiinflammatory, antifibrosis, and antitumor effects and the ability to protect against myocardial damage, etc. The potential signaling pathways involved in the clinical application of oxymatrine might include the TGF-ß/Smad, toll-like receptor 4/nuclear factor kappa-light-chain-enhancer of activated B cells, toll-like receptor9/TRAF6, Janus kinase/signal transduction and activator of transcription, phosphatidylinositol-3 kinase/Akt, delta-opioid receptor-arrestinl-Bcl-2, CD40, epidermal growth factor receptor, nuclear factor erythroid-2-related factor 2/heme oxygenase-1 signaling pathways, and dimethylarginine dimethylaminohydrolase/asymmetric dimethylarginine metabolism pathway. In this review, we summarize the recent investigations of the signaling pathways related to oxymatrine to provide clues and references for further studies on its clinical application. Copyright © 2016 John Wiley & Sons, Ltd.

Global publication trends and research hotspots of nonalcoholic fatty liver disease: a bibliometric analysis and systematic review.

With the globally increasing prevalence, nonalcoholic fatty liver disease (NAFLD) becomes the predominant cause of chronic liver disease. A global look at the publication trends and the research hotspots of NAFLD are urgently needed to assess the situation of NAFLD research. The global scientific research in the Science Citation Index-Expanded covered articles relevant to NAFLD was retrieved and its bibliometric parameters and research hotspots of NAFLD were systematically evaluated. To sum up, 6356 articles were published in 994 different journals covering 93 SCI subject categories during 1986-2013, in which English was the most predominant language used. Starting from the late 1980s, the publication on NAFLD grew slowly and entered into a highly developing period in the 21st century, especially in the last decade. Besides hepatic steatosis, metabolic syndrome and its combination of symptoms such as obesity, insulin resistance are listed as the top frequent keywords. Bibliometric results suggest that the obviously rapid growth of the articles in recent years appears to be associated with the accelerating incidence of NAFLD and its cofactors such as metabolic syndrome. In addition, epidemiology focusing on comparing different regions and population is attracting ever-growing attention. Meantime, pathology plays an important role in NAFLD research.

Genetic alteration regulated by microRNAs in biliary tract cancers.

Biliary tract cancers (BTCs) constitute a relatively rare but highly malignant class of tumors with poor prognosis including gallbladder cancer, intra- and extra-hepatic cholangiocarcinoma. Recently, accumulated evidences have demonstrated that deregulated expression of microRNAs (miRNAs) is closely associated with the development, invasion, metastasis and prognosis of different cancers including BTCs. MiRNAs comprise an endogenously expressed and highly evolutionarily conserved group of small, non-coding, single-stranded RNAs which negatively regulate target genes expression by means of combining with 3' untranslated region (UTR) of corresponding mRNAs at the post-transcriptional level with significant roles in various fundamental cellular procedures including cell proliferation, differentiation, migration, cell cycle control and apoptosis. Recent studies have indicated that miRNAs could function as novel tumor-promoting genes or tumor suppressor genes to act as potential therapeutic targets in anticancer treatment because the genetic alteration regulated by miRNAs could result in tumorigenesis and tumor inhibition. Anomalous miRNAs expression patterns, acting as phenotypic signatures of distinct cancers, are promising to be used as diagnostic, prognostic, predictive biomarkers. In this review, we summarize the current findings from the studies about potential genetic alteration regulated by miRNAs and their roles in BTCs.

Genomewide analysis of rat periaqueductal gray-dorsal horn reveals time-, region- and frequency-specific mRNA expression changes in response to electroacupuncture stimulation.

Electroacupuncture (EA) has been widely applied for illness prevention, treatment or rehabilitation in the clinic, especially for pain management. However, the molecular events that induce these changes remain largely uncharacterized. The periaqueductal gray (PAG) and the spinal dorsal horn (DH) have been verified as two critical regions in the response to EA stimulation in EA analgesia. In this study, a genetic screen was conducted to delineate the gene expression profile in the PAG-DH regions of rats to explore the molecular events of the analgesic effect induced by low-frequency (2-Hz) and high-frequency (100-Hz) EAs. Microarray analysis at two different time points after EA stimulation revealed time-, region- and frequency-specific gene expression changes. These expression differences suggested that modulation of neural-immune interaction in the central nervous system played an important role during EA analgesia. Furthermore, low-frequency EA could regulate gene expression to a greater degree than high-frequency EA. Altogether, the present study offers, for the first time, a characterized transcriptional response pattern in the PAG-DH regions followed by EA stimulation and, thus, provides a solid experimental framework for future in-depth analysis of the mechanisms underlying EA-induced effects.

Prevention effect of allopurinol on post-endoscopic retrograde cholangiopancreatography pancreatitis: a meta-analysis of prospective randomized controlled trials.

BACKGROUND: Pancreatitis is the most common complication of endoscopic retrograde cholangiopancreatography (ERCP) which can be severe and cause death in approximately 10% of cases. Up to now, six randomized controlled trials (RCTs) have been found relevant to the effect of allopurinol on prevention of Post-ERCP pancreatitis (PEP). However, these results remained controversial. OBJECTIVE: To conduct a meta-analysis with RCTs published in full text to determine the effectiveness of prophylactic allopurinol of different dosages and administration time in the incidence and severity of PEP. METHODS: Literature search was performed in PubMed, Embase, Web of Science and Cochrane Library from databases inception to May 2014. RCTs comparing the effect of allopurinol with placebo on prevention of PEP were included. Statistical heterogeneity was quantitatively evaluated byχ2 test with the significance set P<0.10 or I2>50%. RESULTS: Six RCTs consisting of 1974 participants were eventually included. The incidences of PEP in allopurinol group and placebo group were 8.4%(83/986) and 9.9%(98/988) respectively. Meta-analysis showed no evident prevention effect of allopurinol on the incidence of PEP (RR 0.75, 95%CI 0.39-1.42) with significant heterogeneity (I2 = 70.4%, P = 0.005). When studies were stratified according to the dosages and administration time of allopurinol they applied, there was still no evident prevention effect of allopurinol on mild, moderate or severe PEP. However, statistically substantial heterogeneity was presented in the subgroup of moderate PEP when the effect of high dose of allopurinol was analyzed (Imoderate2 = 82.3%, Pmoderate = 0.018). Statistically significant heterogeneity was also observed in subgroup of mild PEP, when the effect of long adminstration time of allopurinol was investigated (Imild2 = 62.8%, Pmild = 0.068). CONCLUSION: The prophylactic use of allopurinol in different dosages and administration time had no effect in preventing incidence and severity of PEP.

Potential role of NADPH oxidase in pathogenesis of pancreatitis.

Studies have demonstrated that reactive oxygen species (ROS) are closely related to inflammatory disorders. Nicotinamide adenine dinucleotide phosphate oxidase (NOX), originally found in phagocytes, is the main source of ROS in nonphagocytic cells. Besides directly producing the detrimental highly reactive ROS to act on biomolecules (lipids, proteins, and nucleic acids), NOX can also activate multiple signal transduction pathways, which regulate cell growth, proliferation, differentiation and apoptosis by producing ROS. Recently, research on pancreatic NOX is no longer limited to inflammatory cells, but extends to the aspect of pancreatic acinar cells and pancreatic stellate cells, which are considered to be potentially associated with pancreatitis. In this review, we summarize the literature on NOX protein structure, activation, function and its role in the pathogenesis of pancreatitis.

Low- and high-frequency transcutaneous electrical acupoint stimulation induces different effects on cerebral µ-opioid receptor availability in rhesus monkeys.

Although systematic studies have demonstrated that acupuncture or electroacupuncture (EA) analgesia is based on their accelerating endogenous opioid release to activate opioid receptors and that EA of different frequencies is mediated by different opioid receptors in specific areas of the central nervous system, there is little direct, real-time evidence to confirm this in vivo. The present study was designed to investigate the effects of transcutaneous electrical acupoint stimulation (TEAS), an analogue of EA, at low and high frequencies on µ-opioid receptor (MOR) availability in the brain of rhesus monkeys. Monkeys underwent 95-min positron emission tomography (PET) with (11) C-carfentanil three times randomly while receiving 0, 2, or 100 Hz TEAS, respectively. Each TEAS was administered in the middle 30 min during the 95-min PET scan, and each session of PET and TEAS was separated by at least 2 weeks. The results revealed that 2 Hz but not 100 Hz TEAS evoked a significant increase in MOR binding potential in the anterior cingulate cortex, the caudate nucleus, the putamen, the temporal lobe, the somatosensory cortex, and the amygdala compared with 0 Hz TEAS. The effect remained after the end of TEAS in the anterior cingulate cortex and the temporal lobe. The selective increase in MOR availability in multiple brain regions related to pain and sensory processes may play a role in mediating low-frequency TEAS efficacy.

Manipulation of and sustained effects on the human brain induced by different modalities of acupuncture: an fMRI study.

The javascript:void(0)manipulation and sustained effects of acupuncture have been investigated in multiple studies, but several findings are inconsistent with one another. One possible explanation for these discrepancies is that different modalities of acupuncture were utilized in these studies. In the present study, we investigated both the manipulation and sustained effects of acupuncture in different modalities, including manual acupuncture (MA), electroacupuncture (EA) and transcutaneous electrical acupoint stimulation (TEAS). MA, EA, TEAS and sensory control stimulation were applied to 18 healthy subjects, and combined block-designed and resting-state fMRI scans were performed. In analyzing these data, the block-designed datasets were used to assess the manipulation effect by employing a modified general linear model. The data from the resting states, before and after stimulation, were used to explore the brain networks involved in the sustained effect. The results showed that the two 1-min stimulation periods produced similar activation patterns in the sensory control with positive activation in the sensorimotor areas and negative activation in the default mode areas. Although similar patterns could be detected in the first stimulation period in MA, EA and TEAS, no positive activation result was observed in the second stimulation period, and EA showed a more extensive deactivation compared to MA and TEAS. Additionally, all three of the modalities of acupuncture stimulation could increase the instinct brain network in rest. A more secure and spatially extended connectivity of the default mode network was observed following MA and EA, and TEAS specifically increased the functional connectivity in the sensorimotor network. The present study suggested that different brain mechanisms might be recruited in different acupuncture modalities. In addition, the findings from our work could provide methodological information for further research into the mechanism of acupuncture.

Roles of BN52021 in platelet-activating factor pathway in inflammatory MS1 cells.

AIM: To determine the effects of BN52021 on platelet-activating factor receptor (PAFR) signaling molecules under lipopolysaccharide (LPS)-induced inflammatory conditions in MS1 cells. METHODS: MS1 cells (a mouse pancreatic islet endothelial cell line) were grown in Dulbecco's modified Eagle's medium supplemented with 10% fetal bovine serum, 2 mmol/L glutamine and 100 µg/mL penicillin/streptomycin in 5% CO2 at 37 °C. After growth to confluency in media, the cells were processed for subsequent studies. The MS1 cells received 0, 0.1, 1 and 10 µg/mL LPS in this experiment. The viability/proliferation of the cells induced by LPS was observed using a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide colorimetric assay. Apoptosis and necrosis of the cells under the inflammatory condition described previously were observed using Hoechst 33342-propidium iodide staining. Adenylate cyclase (AC), phospholipase A2 (PLA2), phospholipase Cß (PLCß), protein tyrosine kinase (PTK), G protein-coupled receptor kinases (GRK) and p38-mitogen-activated protein kinase (p38 MAPK) mRNA in the PAFR signaling pathway were measured by real-time polymerase chain reaction. The protein expression level of phosphorylated AC (p-AC), phosphorylated PLA2 (p-PLA2), phosphorylated PTK (p-PTK), phosphorylated p38 MAPK (p-p38 MAPK), PLCß and GRK was measured using Western blotting analysis. RESULTS: The activity of MS1 cells incubated with different concentrations of LPS for 6 h decreased significantly in the 1 µg/mL LPS group (0.49 ± 0.10 vs 0.67 ± 0.13, P < 0.05) and 10 µg/mL LPS group (0.44 ± 0.10 vs 0.67 ± 0.13, P < 0.001), but not in 0.1 µg/mL group. When the incubation time was extended to 12 h (0.33 ± 0.05, 0.32 ± 0.03 and 0.25 ± 0.03 vs 0.69 ± 0.01) and 24 h (0.31 ± 0.01, 0.29 ± 0.03 and 0.25 ± 0.01 vs 0.63 ± 0.01), MS1 cell activity decreased in all LPS concentration groups compared with the blank control (P < 0.001). BN52021 significantly improved the cell activity when its concentration reached 50 µmol/L compared with the group that received LPS treatment alone, which was consistent with the results obtained from fluorescence staining. The mRNAs levels of AC (4.02 ± 0.14 vs 1.00 ± 0.13), GRK (2.63 ± 0.03 vs 1.00 ± 0.12), p38 MAPK (3.87 ± 0.07 vs 1.00 ± 0.17), PLA2 (3.31 ± 0.12 vs 1.00 ± 0.12), PLCß (2.09 ± 0.08 vs 1.00 ± 0.06) and PTK (1.85 ± 0.07 vs 1.00 ± 0.11) were up-regulated after LPS stimulation as compared with the blank control (P < 0.05). The up-regulated mRNAs including AC (2.35 ± 0.13 vs 3.87 ± 0.08), GRK (1.17 ± 0.14 vs 2.65 ± 0.12), p38 MAPK (1.48 ± 0.18 vs 4.30 ± 0.07), PLCß (1.69 ± 0.10 vs 2.41 ± 0.13) and PLA2 (1.87 ± 0.11 vs 2.96 ± 0.08) were significantly suppressed by BN52021 except for that of PTK. The level of p-AC (1.11 ± 0.12 vs 0.65 ± 0.08), GRK (0.83 ± 0.07 vs 0.50 ± 0.03), PLCß (0.83 ± 0.16 vs 0.50 ± 0.10) and p-p38 MAPK (0.74 ± 0.10 vs 0.38 ± 0.05) was up-regulated after LPS stimulation as compared with the blank control (P < 0.05). The up-regulated proteins, including p-AC (0.65 ± 0.15 vs 1.06 ± 0.14), GRK (0.47 ± 0.10 vs 0.80 ± 0.06), PLCß (0.47 ± 0.04 vs 0.80 ± 0.19) and p-p38 MAPK (0.30 ± 0.10 vs 0.97 ± 0.05), was significantly suppressed by BN52021, but p-PLA2 and p-PTK protein level were not suppressed. CONCLUSION: BN52021 could effectively inhibit LPS-induced inflammation by down-regulating the mRNA and protein levels of AC, GRK, p38 MAPK, PLA2 and PLCß in the PAFR signaling pathway.

Differences in neural-immune gene expression response in rat spinal dorsal horn correlates with variations in electroacupuncture analgesia.

BACKGROUND: Electroacupuncture (EA) has been widely used to alleviate diverse pains. Accumulated clinical experiences and experimental observations indicated that significant differences exist in sensitivity to EA analgesia for individuals of patients and model animals. However, the molecular mechanism accounting for this difference remains obscure. METHODOLOGY/PRINCIPAL FINDINGS: We classified model male rats into high-responder (HR; TFL changes >150) and non-responder (NR; TFL changes ≤ 0) groups based on changes of their pain threshold detected by tail-flick latency (TFL) before and after 2 Hz or 100 Hz EA treatment. Gene expression analysis of spinal dorsal horn (DH) revealed divergent expression in HR and NR after 2 Hz/100 Hz EA. The expression of the neurotransmitter system related genes was significantly highly regulated in the HR animals while the proinflammation cytokines related genes were up-regulated more significantly in NR than that in HR after 2 Hz and 100 Hz EA stimulation, especially in the case of 2 Hz stimulation. CONCLUSIONS/SIGNIFICANCE: Our results suggested that differential regulation and coordination of neural-immune related genes might play an important role for individual variations in analgesic effects responding to EA in DH. It also provided new candidate genes related to EA responsiveness for future investigation.