ABSTRACT
Enterococcus faecalis is an important contributor to the persistence of chronic apical periodontitis. However, the mechanism by which E. faecalis infection in the root canals and dentinal tubules affects periapical tissue remains unclear. Bacterial extracellular vesicles (EVs) act as natural carriers of microbe-associated molecular patterns (MAMPs) and have recently attracted considerable attention. In this study, we investigated the role of EVs derived from E. faecalis in the pathogenesis of apical periodontitis. We observed that E. faecalis EVs can induce inflammatory bone destruction in the periapical areas of mice. Double-labeling immunofluorescence indicated that M1 macrophage infiltration was increased by E. faecalis EVs in apical lesions. Moreover, in vitro experiments demonstrated the internalization of E. faecalis EVs into macrophages. Macrophages tended to polarize toward the M1 profile after treatment with E. faecalis EVs. Pattern recognition receptors (PRRs) can recognize MAMPs of bacterial EVs and, in turn, trigger inflammatory responses. Thus, we performed further mechanistic exploration, which showed that E. faecalis EVs considerably increased the expression of NOD2, a cytoplasmic PRR, and that inhibition of NOD2 markedly reduced macrophage M1 polarization induced by E. faecalis EVs. RIPK2 ubiquitination is a major downstream of NOD2. We also observed increased RIPK2 ubiquitination in macrophages treated with E. faecalis EVs, and E. faecalis EV-induced macrophage M1 polarization was notably alleviated by the RIPK2 ubiquitination inhibitor. Our study revealed the potential for EVs to be considered a virulence factor of E. faecalis and found that E. faecalis EVs can promote macrophage M1 polarization via NOD2/RIPK2 signaling. To our knowledge, this is the first report to investigate apical periodontitis development from the perspective of bacterial vesicles and demonstrate the role and mechanism of E. faecalis EVs in macrophage polarization. This study expands our understanding of the pathogenic mechanism of E. faecalis and provides novel insights into the pathogenesis of apical periodontitis.
Subject(s)
Enterococcus faecalis , Extracellular Vesicles , Macrophages , Periapical Periodontitis , Periapical Periodontitis/microbiology , Periapical Periodontitis/metabolism , Animals , Mice , Macrophages/microbiology , Nod2 Signaling Adaptor Protein/metabolism , Mice, Inbred C57BL , Disease Models, AnimalABSTRACT
Objective: To investigate the chronic respiratory symptoms and pulmonary function of adult residents in 3 towns of Hongtong County, Shanxi Province, and to explore their risk factors. Methods: The investigation of chronic respiratory symptoms and lung function status of adult residents in Hongdong County is based on the regional population of the entire county in Hongdong County. The project was initiated by the Science and Technology Department of Linfen City and coordinated by the Hongdong County Government. The investigation will be conducted in 3 townships in Hongdong County, Linfen City, Shanxi Province from April to November 2021: Demographic characteristics, respiratory symptoms, smoking dust exposure and other personal history were collected through questionnaires. Physical examination, routine blood tests and lung function tests were also performed on each individual. SPSS 22.0 software was used to conduct t test, χ2 test, ANOVA or Kruskal-Wallis test for statistical analysis of the collected information. Results: 10 945 subjects aged 18-102 years were included in the analysis, of whom 3 754 (34.3%) were male, 1 222 (11.2%) had a history of dust exposure, 7 164 (65.5%) had used straw and firewood as cooking fuel, and 3 296 (30.1%) had a history of smoking. Among the participants, 394 (3.6%), 339 (3.1%), and 1 543 (14.1%) had respiratory symptoms such as chronic cough, sputum, and dyspnea. Statistics showed that the population with chronic respiratory symptoms was more elderly and had a smoking history, and the incidence of chronic respiratory symptoms was higher in those who smoked more than 40 packs a year (all P<0.05). Men with a history of dust exposure were more likely to suffer from chronic cough and expectoration, while emaciation and biofuel use for more than 40 years were more likely to suffer from chronic expectoration and dyspnea (all P<0.05). The median values of forced expiratory volume in 1 second (FEV1), forced vital capacity (FVC) and FEV1/FVC in 1 second were 2.19 L/s, 3.24 L and 69.16%, respectively. Among them, the lung function of 5 801 (53.0%) respondents was lower than the expected value. The median FEV1/FVC decreased with the increase of age. The FEV1/FVC of people over 40 years old with smoking history was lower, the dust exposure history of people with decreased lung function was more than that of people with normal lung function, and the incidence of chronic expectoration and dyspnea was higher in people with decreased lung function (all P<0.05). The absolute value and ratio of eosinophils in patients with decreased ventilation function over 60 years old were significantly higher than those with normal ventilation function, but the level of body mass index (BMI) was lower (all P<0.05). Conclusion: In Hongdong County, Shanxi Province, grassroots residents have poor medical awareness, low lung function examination rate, chronic respiratory symptoms and lung function decline are associated with more risk factors. Primary medical institutions need to formulate prevention strategies and carry out lung function detection according to the actual situation, focusing on monitoring and follow-up of high-risk groups to achieve early and timely prevention, diagnosis and treatment of chronic obstructive pulmonary disease.
Subject(s)
Lung Diseases , Pulmonary Disease, Chronic Obstructive , Aged , Adult , Humans , Male , Middle Aged , Female , Cough/epidemiology , Lung , Pulmonary Disease, Chronic Obstructive/epidemiology , Chronic Disease , Vital Capacity , Dyspnea , Dust/analysis , Forced Expiratory VolumeABSTRACT
Objective: To develop a venous thromboembolism (VTE) risk assessment scale for adult burn patients and to test its reliability and validity. Methods: The scale research method and multi-center cross-sectional survey method were used. Based on the results of literature analysis method and brain-storming method, the letter questionnaire for experts was formulated. Then 27 experts (9 doctors of burn department, 9 vascular surgeons, and 9 nurses) were performed with two rounds of correspondences by Delphi method, and the reliability of the experts was analyzed. The weight of each item was determined by optimal sequence diagram method and expert importance evaluation to form the VTE Risk Assessment Scale for Adult Burn Patients. A total of 223 adult burn inpatients, who were admitted to 5 tier â ¢ grade A general hospitals including the Affiliated Hospital of Southwest Medical University, West China Hospital of Sichuan University, the Affiliated Hospital of North Sichuan Medical College, Nanchong Central Hospital, and the Second People's Hospital of Yibin City from October 1st 2019 to January 1st 2020, were selected as respondents by convenience sampling method. The first assessment was performed with the VTE Risk Assessment Scale for Adult Burn Patients within 24 hours of admission of patients, and real-time assessment was performed as the patients' condition and treatment changed. The highest value was taken as the result. Correlation coefficient method and critical ratio method were used for item analysis; Cronbach's α coefficient was used to test the internal consistency of scale; content validity index was used to analyze the content validity of the scale, and receiver's operating characteristic (ROC) curve was drawn to test the predictive validity of the scale. Data were statistically analyzed with chi-square test, Pearson correlation analysis, independent sample t test, and Z test. Results: As four questionnaires in the first round of correspondence were rejected as unqualified, and another 4 experts were selected for the 2 rounds of correspondence. Most of them were aged 41 to 50 years with postgraduate degrees, engaging in the current profession for 11 to 30 years, and all of them had professional titles of associate senior or above. The scale, constructed through literature analysis, group brainstorming, and two rounds of correspondence, includes 3 primary items and 50 secondary items. In the first round of correspondence, the recovery rate of valid questionnaires and the ratio with expert opinions were 85.2% (23/27) and 47.8% (11/23), respectively. In the second round of correspondence, the recovery rate of valid questionnaires and the ratio with expert opinions were 100% (27/27) and 11.1% (3/27), respectively. The average collective authority coefficients of experts were both 0.90 in the 2 rounds of correspondence. The mean values of importance assignment, full score rate, and selection rate above 4 were 4.21, 52.5%, and 77.2%, respectively, in the first round of correspondence, and 4.28, 45.2%, and 85.8%, respectively, in the second round of correspondence. The mean coefficients of variation and the mean value of Kendall's coefficient of harmony for each item were 0.21 and 0.30 in the first round of correspondence, respectively, and 0.16 and 0.36 in the second round of correspondence, respectively. In the first and second rounds of correspondence, the Kendall's coefficients of harmony of 3 primary items (age and underlying diseases, burn injury factors, and burn treatment factors) and total secondary items were statistically significant (with χ2 values of 121.46, 107.09, 116.00, 331.97, 169.97, 152.12, 141.54, and 471.70, P<0.01). The weights of primary items for age and underlying diseases, burn injury factors, and burn treatment factors were 0.04, 0.05, and 0.07, respectively. The weights of secondary items ranged from 0.71 to 0.99, with assigned values of 3 to 6. The total burn area of 223 patients ranged from 1% to 89% total body surface area, and the patients were aged from 19 to 96 years, with the risk assessment score from 0 to 98. Nine patients developed VTE, with a risk assessment score of 41 to 90. The scores of 37 items were significantly positively correlated with the total score of scale (with r values of 0.14 to 0.61, P<0.05 or P<0.01), and the items were retained. There were 36 secondary items with statistically significant differences between the patients in high-score group and low-score group (with Z values of -4.88 to -2.09, t values of -11.63 to -2.09, P<0.05 or P<0.01), and the items were retained. The total Cronbach's α coefficient of scale was 0.88. The total content validity index of scale was 0.95. The optimal threshold of the scale for the diagnosis of VTE was 40, at which the sensitivity was 88.9%, the specificity was 87.4%, the Youden index was 0.87, and the area under the ROC curve was 0.96 (with 95% confidence interval of 0.93 to 0.99, P<0.01). Conclusions: The age and underlying diseases, burn injury factors, and burn treatment factors are the risk factors for VTE in adult burn patients. The VTE risk assessment scale for adult burn patients developed based on these factors has good reliability and validity, and provide good reference value for clinical VTE risk assessment.
Subject(s)
Burns , Venous Thromboembolism , Adult , Burns/complications , Cross-Sectional Studies , Humans , Reproducibility of Results , Risk Assessment , Venous Thromboembolism/diagnosisABSTRACT
This article presents data related to the research article entitled "Diffusion of oxygen and nitrogen into titanium under laser irradiation in air" [1]. When irradiated with varying laser parameters under ambient air, titanium surfaces are observed to exhibit differing colors. To better understand this phenomenon, the dynamic reaction steps between titanium and air under laser irradiation were investigated with in-situ synchrotron X-ray diffraction method. With a programmed laser profile, a set of diffraction patterns were collected by a 2D detector and then analyzed with the program FIT2D. Based on the data, the detailed high-temperature reactions between titanium and air during laser irradiation were clearly revealed. The presented raw in-situ synchrotron X-ray diffraction data can be reused for the further insights of laser surface modification of titanium in air, or for discovering the optimal laser conditions for industrial decoration or medical applications of titanium.
ABSTRACT
OBJECTIVE: To analyze the related influencing factors of urinary tract infection in patients undergoing transurethral resection of the prostate (TURP). PATIENTS AND METHODS: A total of 343 patients with benign prostatic hyperplasia admitted to this hospital from January 2013 to December 2016, were selected and treated by TURP. Patients were divided into infection group and non-infection group according to the occurrence of urinary tract infection after operation. The possible influencing factors were collected to perform univariate and multivariate logistic regression analysis. RESULTS: There were 53 cases with urinary tract infection after operation among 343 patients with benign prostatic hyperplasia, accounting for 15.5%. The univariate analysis displayed that the occurrence of urinary tract infection in patients undergoing TURP was closely associated with patient's age ≥ 65 years old, complicated diabetes, catheterization for urinary retention before operation, no use of antibiotics before operation and postoperative indwelling catheter duration ≥ 5 d (p < 0.05). Multivariate logistic regression analysis revealed that age ≥ 65 years old, complicated diabetes, catheterization before operation, indwelling catheter duration ≥ 5 d and no use of antibiotics before operation were risk factors of urinary tract infection in patients receiving TURP (p < 0.05). CONCLUSIONS: The patient's age ≥ 65 years old, catheterization before operation, complicated diabetes and long-term indwelling catheter after operation, can increase the occurrence of urinary tract infection after TURP, while preoperative prophylactic utilization of anti-infective drugs can reduce the occurrence of postoperative urinary tract infection.
Subject(s)
Prostatic Hyperplasia/surgery , Transurethral Resection of Prostate/adverse effects , Urinary Tract Infections/etiology , Age Factors , Aged , Catheterization , Diabetes Complications/complications , Gram-Negative Bacteria/isolation & purification , Gram-Positive Bacteria/isolation & purification , Humans , Logistic Models , Male , Middle Aged , Postoperative Complications , Postoperative Period , Prostatic Hyperplasia/complications , Risk Factors , Urinary Tract Infections/microbiologyABSTRACT
OBJECTIVE: This study investigates the clinical value of monitoring blood levels of tumor necrosis factor-α (TNF-α), high mobility group protein Bl (HMGBl), and neuron-specific enolase (NSE), and examining an amplitude-integrated electroencephalogram (aEEG) for the diagnosis and short-term prognosis of brain damage caused by neonatal asphyxia. PATIENTS AND METHODS: Sixty full-term neonates born in Yidu Central Hospital from January to December 2015 were enrolled in the study. The neonates were classified into one of 3 groups: 23 neonates in the mild asphyxia group, 7 in a severe asphyxia group and 30 in a control group admitted to the NICU but without asphyxia. The neonates presenting asphyxia received standard neonatal resuscitation before they were transferred to the NICU. The dynamic changes of the umbilical artery/peripheral blood TNF-α, HMGBl, and NSE levels and aEEG results were monitored and compared among the groups. RESULTS: The umbilical artery and serum TNF-α, HMGBl, and NSE levels at day 1 were significantly higher in the two asphyxia groups than in the control group; and the values were higher in the severe asphyxia group (p <0.05). Furthermore, the correlation coefficients between TNF-α and HMGB1, TNF-α and NSE, and HMGB1 and NSE at all the monitoring time points were positive: 0.5516, 26.943 and 15.87, respectively (p <0.001). Additionally, the neonates with abnormal aEEG results at 6 hours postpartum had higher serum TNF-α, HMGBl and NSE levels than those with normal aEEG results (p <0.05). The patients with persistently abnormal or progressively deteriorating aEEG results usually had a poor evolution. CONCLUSIONS: The dynamic monitoring of TNF-α, HMGBl, and NSE levels combined with aEEG can provide useful evidence for the early diagnosis, the determination of severity and the short-term prognosis of brain damage caused by neonatal asphyxia.
Subject(s)
Asphyxia Neonatorum/physiopathology , Brain Injuries/etiology , Phosphopyruvate Hydratase/blood , Tumor Necrosis Factor-alpha/blood , Early Diagnosis , Electroencephalography/methods , Female , Fetal Blood , Humans , Infant, Newborn , Male , PrognosisABSTRACT
OBJECTIVE: Postoperative cognitive dysfunction is a clinical syndrome associated with cognitive decline in patients after anesthesia. This study aimed to investigate the effect of VB12 (Vitamin B12), a kind of necessary micronutrients promoting the growth and development of the nervous system, on cognitive dysfunction induced by isoflurane anesthesia. MATERIALS AND METHODS: Eighteen-month-old rats were exposed to or were not exposed to 1.4% isoflurane for 2 h. Two hours before isoflurane exposure, rats in groups with VB12 were injected intramuscularly with VB12 at 10 or 20 µg. Two weeks later, rats were subjected to Barnes maze and Morris water maze. RESULTS: Rats exposed to isoflurane had significant impairments in long-term spatial memory assessed by Barnes maze. There was no statistical significance in the percentage of swimming time and path length in the Morris water maze tests among five groups, suggesting that isoflurane may not impair the recall of learned information in rats. Isoflurane increased the expression of interleukin 1ß (IL-1ß) and activated caspase 3 in the hippocampus, but not cortex of the rats. The increase of IL-1ß and activated caspase 3 was attenuated by VB12. However, isoflurane did not change the amount of tumor necrosis factor-α (TNF-α) and ß-amyloid peptide in the hippocampus and cerebral cortex. CONCLUSIONS: VB12 can attenuate cognitive dysfunction induced by isoflurane anesthesia. At the same time, IL-1ß may play an important role in this isoflurane effect.
Subject(s)
Anesthetics, Inhalation/adverse effects , Cognitive Dysfunction/drug therapy , Isoflurane/adverse effects , Postoperative Complications/drug therapy , Vitamin B 12/therapeutic use , Animals , Caspase 3/physiology , Cognitive Dysfunction/etiology , Hippocampus/metabolism , Interleukin-1beta/physiology , Postoperative Complications/etiology , RatsABSTRACT
The aim of this study was to investigate the expression of T-cell immunoglobulin mucin domain molecule-3 (Tim-3) in osteosarcoma tissues, and analyze its effect on cell proliferation and metastasis in an osteosarcoma cell line. Tim-3 mRNA and protein expression in osteosarcoma tissue was detected by reverse transcriptase-polymerase chain reaction and immunohistochemistry, respectively. Additionally, the cell viability, apoptosis rate, and invasive ability of the osteosarcoma cell line MG-63 were tested using the methyl thiazolyl tetrazolium assay, Annexin V-propidium iodide flow cytometry, and a Transwell assay, respectively, following Tim-3 interference using small interfering RNA (siRNA). We also analyzed the expression of Snail, E-cadherin, vimentin, and nuclear factor (NF)-kB in the cells by western blot. We observed that Tim-3 mRNA and protein was significantly overexpressed in osteosarcoma tissues, compared to the adjacent normal tissue (P < 0.01). Moreover, MG-63 cells transfected with the Tim-3 siRNA presented lower cell viability, a greater number of apoptotic cells, and decreased invasive ability (P < 0.01), compared to control cells. Additionally, we observed a decrease in Snail and vimentin expression, an increase in the E-cadherin level, and an increase in NF-kB p65 phosphorylation (P < 0.01) in Tim-3 siRNA-transfected MG-63 cells. Based on these results, we concluded that Tim-3 is highly expressed in osteosarcoma tissue. Moreover, we speculated that interfering in Tim-3 expression could significantly suppress osteosarcoma cell (MG-63) proliferation and metastasis via the NF-kB/Snail signaling pathway and epithelial-mesenchymal transition.
Subject(s)
Bone Neoplasms/genetics , Epithelial-Mesenchymal Transition/genetics , Gene Expression Regulation, Neoplastic , Hepatitis A Virus Cellular Receptor 2/genetics , Osteosarcoma/genetics , Antigens, CD , Apoptosis , Bone Neoplasms/metabolism , Bone Neoplasms/pathology , Cadherins/genetics , Cadherins/metabolism , Cell Line, Tumor , Cell Movement , Cell Proliferation , Cell Survival , Collagen/chemistry , Diffusion Chambers, Culture , Drug Combinations , Hepatitis A Virus Cellular Receptor 2/antagonists & inhibitors , Hepatitis A Virus Cellular Receptor 2/metabolism , Humans , Laminin/chemistry , Lymphatic Metastasis , Neoplasm Invasiveness , Osteosarcoma/metabolism , Osteosarcoma/pathology , Phosphorylation , Proteoglycans/chemistry , RNA, Small Interfering/genetics , RNA, Small Interfering/metabolism , Signal Transduction , Snail Family Transcription Factors/genetics , Snail Family Transcription Factors/metabolism , Transcription Factor RelA/genetics , Transcription Factor RelA/metabolism , Vimentin/genetics , Vimentin/metabolismABSTRACT
Brain function emerges from hierarchical neuronal structure that spans orders of magnitude in length scale, from the nanometre-scale organization of synaptic proteins to the macroscopic wiring of neuronal circuits. Because the synaptic electrochemical signal transmission that drives brain function ultimately relies on the organization of neuronal circuits, understanding brain function requires an understanding of the principles that determine hierarchical neuronal structure in living or intact organisms. Recent advances in fluorescence imaging now enable quantitative characterization of neuronal structure across length scales, ranging from single-molecule localization using super-resolution imaging to whole-brain imaging using light-sheet microscopy on cleared samples. These tools, together with correlative electron microscopy and magnetic resonance imaging at the nanoscopic and macroscopic scales, respectively, now facilitate our ability to probe brain structure across its full range of length scales with cellular and molecular specificity. As these imaging datasets become increasingly accessible to researchers, novel statistical and computational frameworks will play an increasing role in efforts to relate hierarchical brain structure to its function. In this perspective, we discuss several prominent experimental advances that are ushering in a new era of quantitative fluorescence-based imaging in neuroscience along with novel computational and statistical strategies that are helping to distil our understanding of complex brain structure.
ABSTRACT
This data article is related to the research paper entitled "senary refractory high-entropy alloy Cr x MoNbTaVW [1]". In this data article, the pseudo-binary Cr-MoNbTaVW phase diagram is presented to show the impact of Cr content to the senary Cr-MoNbTaVW alloy system; the sub-lattice site fractions are presented to show the disordered property of the Cr-MoNbTaVW BCC structures; the equilibrium and Scheil solidification results with the actual sample elemental compositions are presented to show the thermodynamic information of the melted/solidified Cr x MoNbTaVW samples; and the raw EDS scan data of the arc-melted Cr x MoNbTaVW samples are also provided.
ABSTRACT
This study aims to explore the roles of somatic embryogenesis receptor-like kinase (SERK) in Malus hupehensis (Pingyi Tiancha). The full-length sequences of SERK1 in triploid Pingyi Tiancha (3n) and a tetraploid hybrid strain 33# (4n) were cloned, sequenced, and designated as MhSERK1 and MhdSERK1, respectively. Multiple alignments of amino acid sequences were conducted to identify similarity between MhSERK1 and MhdSERK1 and SERK sequences in other species, and a neighbor-joining phylogenetic tree was constructed to elucidate their phylogenetic relations. Expression levels of MhSERK1 and MhdSERK1 in different tissues and developmental stages were investigated using quantitative real-time PCR. The coding sequence lengths of MhSERK1 and MhdSERK1 were 1899 bp (encoding 632 amino acids) and 1881 bp (encoding 626 amino acids), respectively. Sequence analysis demonstrated that MhSERK1 and MhdSERK1 display high similarity to SERKs in other species, with a conserved intron/exon structure that is unique to members of the SERK family. Additionally, the phylogenetic tree showed that MhSERK1 and MhdSERK1 clustered with orange CitSERK (93%). Furthermore, MhSERK1 and MhdSERK1 were mainly expressed in the reproductive organs, in particular the ovary. Their expression levels were highest in young flowers and they differed among different tissues and organs. Our results suggest that MhSERK1 and MhdSERK1 are related to plant reproduction, and that MhSERK1 is related to apomixis in triploid Pingyi Tiancha.
Subject(s)
Flowers/genetics , Malus/genetics , Phylogeny , Amino Acid Sequence/genetics , Arabidopsis Proteins/genetics , Cloning, Molecular , Flowers/growth & development , Gene Expression Regulation, Plant , Malus/growth & development , Plant Proteins/biosynthesis , Plant Proteins/genetics , Protein Kinases/genetics , Sequence Alignment , Tetraploidy , TriploidyABSTRACT
Excessive production of reactive oxygen species (ROS) by an overactive nicotinamide adenine dinucleotide phosphate (NADPH) oxidase system in penile tissue is an important mechanism of erectile dysfunction (ED). S-allyl cysteine (SAC), a bioactive component derived from garlic, was recently reported to exert versatile antioxidant properties. We hypothesized that SAC would be able to resolve diabetes-related ED by reducing ROS generation, and designed this study to investigate this possibility as well as to determine the related underlying mechanisms. A streptozotocin-induced diabetes rat model was established and used for comparative analysis of 4-week treatment regimens with insulin or SAC. The ratio of maximal intracavernous pressure (ICP) to mean arterial blood pressure (MAP) was measured to determine erectile function. Differential levels of ROS, NADPH oxidase subunits, nitric oxide (NO)/cyclic guanosine monophosphate (cGMP) signalling pathway, and apoptosis were evaluated in cavernous tissues. Max ICP/MAP was found to be markedly decreased in untreated diabetic rats; SAC, but not insulin, treatment restored the ratio to baseline (in non-diabetic untreated controls). The corpus cavernosum of untreated diabetic rats showed increased p47(phox) and p67(phox) expression, ROS production and penile apoptotic index, and decreased phospho-endothelial nitric oxide synthase (phospho-eNOS, Ser1177) expression, cGMP concentration, B-cell lymphoma 2 (Bcl-2)/Bcl-2-associated X protein (Bax) ratio and smooth muscle cell number. SAC treatment normalized all the diabetes-induced effects, whereas insulin treatment partially normalized the alterations, but produced no effects on P47(phox) expression, penile ROS level, apoptotic index, Bcl-2/Bax ratio and smooth muscle cell number. Collectively, these data indicate that SAC treatment can restore erectile function in diabetic rats by preventing ROS formation through modulation of NADPH oxidase subunit expression. Furthermore, the poor efficacy of conventional insulin treatment for diabetic ED may be associated with an elevated level of ROS in penile tissue.
Subject(s)
Cysteine/analogs & derivatives , Diabetes Mellitus, Experimental/metabolism , Penile Erection/drug effects , Reactive Oxygen Species/metabolism , Animals , Cysteine/pharmacology , Insulin/metabolism , Male , Nitric Oxide Synthase Type III/metabolism , Rats , Rats, Sprague-Dawley , StreptozocinABSTRACT
Hepatitis B virus (HBV) covalently closed circular DNA (cccDNA) is responsible for viral persistence. This study aimed to investigate the serum surrogate markers for cccDNA and to evaluate the intrahepatic viral events associated with disease activity in HBeAg-negative chronic hepatitis B patients. Thirty-three treatment-naïve patients with a negative HBeAg who had a liver biopsy were studied. Active disease was defined as a serum alanine aminotransferase >40 IU/L and a serum HBV DNA >10,000 copies/ml. This study showed significant correlation between serum HBV DNA and both log cccDNA (r = 0.41, P = 0.018) and log total intrahepatic HBV DNA (r = 0.71, P < 0.0001). No significant correlation was observed between serum HBsAg and log cccDNA (P = 0.15) or log total intrahepatic HBV DNA (P = 0.97). Fourteen and 19 patients had inactive and active disease, respectively. The median log cccDNA and log total intrahepatic HBV DNA (copies/10(6) cells) were significantly higher in patients with active disease compared with those with inactive disease (4.11 vs. 3.53, P = 0.03 and 5.46 vs. 4.64, P < 0.001, respectively). The HBV replicative efficiency, defined as the ratio of serum HBV DNA to cccDNA, was approximately 20% higher in patients with active disease. No significant difference was observed in the HBsAg levels and the ratio of serum HBsAg to cccDNA between the two groups. In conclusion, serum HBV DNA, but not HBsAg, reflects the amount of cccDNA and the replication efficiency of HBV in patients with HBeAg-negative chronic hepatitis B.
Subject(s)
DNA, Circular/blood , DNA, Viral/blood , Hepatitis B Surface Antigens/blood , Hepatitis B e Antigens/blood , Hepatitis B virus/isolation & purification , Hepatitis B, Chronic/blood , Hepatitis B, Chronic/virology , Adult , Female , Hepatitis B virus/genetics , Hepatitis B virus/physiology , Humans , Liver/virology , Male , Middle Aged , Virus AssemblyABSTRACT
Current guidelines recommend antiviral therapy for chronic hepatitis B (CHB) patients with elevated alanine aminotransferase (ALT) and high viral load. Scant histological data exist for CHB patients with persistently normal ALT (PNALT) because disease progression is thought to be rare. To identify potential predictors of significant histology in the presence of PNALT, we compared the clinical characteristics and histology of Chinese CHB PNALT patients to those in patients with elevated ALT. Percutaneous liver biopsy was performed in 522 CHB patients with Chinese ethnicity who had not had antiviral treatment. Differences in age, ALT, viral load, hepatitis B e antigen (HBeAg) status and liver histology were compared between eligible PNALT (252) and elevated ALT (270) patients. Of the PNALT patients, 38.5% had normal liver histology, 25.4% had significant necroinflammation and/or fibrosis and 8.4% had established cirrhosis. Furthermore, histopathological differences between patients with high-normal ALT (0.5-1.0 x the upper limit of normal (ULN)) and low-normal ALT (≤ 0.5 x ULN) were evaluated. There was a significantly greater prevalence of histopathology in the high-normal group (40.0%) than in the low-normal group (16.6%) (P < 0.001). Multiple logistic regression identified that significant histopathology findings in PNALT patients correlated with age (P < 0.001) and ALT level (P < 0.001), with age >40 years and ALT >0.5 x ULN predicting significant histopathology. Our data indicate that liver biopsy is recommended in CHB patients >40 years of age, particularly when their ALT is 0.5-1.0 x ULN. The findings above provide evidence for indication of antiviral therapy in patients with PNALT and significant histopathological change.
Subject(s)
Alanine Transaminase/blood , Hepatitis B, Chronic/pathology , Liver/pathology , Adult , Asian People , Biopsy , Female , Hepatitis B e Antigens/blood , Histocytochemistry , Humans , Male , Middle Aged , Viral Load , Young AdultABSTRACT
The effects of doping with magnetic Mn ions or nonmagnetic Ga ions on the structural, electrical transport and magnetic properties of Na(0.75)CoO(2) have been investigated. It has been found that the lattice parameter c of the samples increases with Ga or Mn ion doping. Ga doping raises the electrical resistivity of Na(0.75)CoO(2), but the metallic conducting behaviour of the compound has not been influenced. In contrast, 5% Mn doping leads to a metal-insulator transition at low temperatures in Na(0.75)Co(1-y)Mn(y)O(2). The susceptibility of the Ga doped sample shows strong magnetic field dependence, while the susceptibility of the Mn doped samples is not very sensitive to the magnetic field. This work implies that magnetic interaction plays an important role in Na(x)CoO(2).
ABSTRACT
The heat transfer coefficient and adiabatic effectiveness of cylindrical, fan shaped holes and a slot are presented for the region zero to 50 diameters downstream of the holes. Narrow-band liquid crystals were used on a heated flat plate with heated air coolant. These parameters have been measured in a steady state, low speed facility at engine representative Reynolds number based on hole diameter and pressure difference ratio (ideal momentum flux ratio). The aerodynamic loss due to each of the film cooling geometries has been measured using a traverse of the boundary layer far downstream of the film cooling holes. Compared to the cylindrical holes, the fan shaped hole case showed an improvement in the uniformity of cooling downstream of the holes and in the level of laterally averaged film cooling effectiveness. The fan effectiveness approached the slot level and both the fan and cylindrical hole cases show lower heat transfer coefficients than the slot and non film cooled cases based on the laterally averaged results. The drawback to the fan shaped hole was that the aerodynamic loss was significantly higher than both the slot and cylindrical hole values due to inefficient diffusion in the hole exit expansion.
ABSTRACT
It has recently been shown that a Chinese traditional medicine, kurorinone, extracted from Sophora Flavescens Ait, possesses antiviral properties. We evaluated the efficacy and safety of kurorinone treatment in patients with chronic hepatitis B. Ninety-four patients with abnormal alanine transaminase (ALT) levels and hepatitis B e antigen (HBeAg) and/or hepatitis B virus (HBV) DNA-positivity were randomly assigned to receive either kurorinone 400 mg daily (45 patients) or 3 million units (MU) of interferon-alpha (IFN-alpha) (49 patients, daily for 1 month, every other day for 2 months) for 3 months. Patients were followed-up for 12 months. At baseline, both groups were comparable regarding age, gender and serological parameters. At the end of treatment, complete response (defined as ALT normalization and HBeAg and/or HBV DNA loss) occurred in 50% of the kurorinone group and in 61.3% of the IFN-alpha-treated group (P > NS). At the end of the 12-month follow-up period, a complete response (sustained response) occurred in 26.7-36.7% of kurorinone-treated patients with moderate or mild liver damage and in 44.4-46.7% of IFN-alpha-treated patients with similar liver injury. In kurorinone- as well as in IFN-alpha-treated patients, there was no statistical significant difference with respect to complete response rates between HBeAg-positive and hepatitis B e antibody-positive subgroups. Kurorinone had no untoward side-effects except for local pain at injection sites. The results of this trial suggest that kurorinone is able to inhibit HBV replication and improve disease remission in patients with chronic hepatitis B.
Subject(s)
Antiviral Agents/therapeutic use , Drugs, Chinese Herbal/therapeutic use , Hepatitis B, Chronic/drug therapy , Interferon-alpha/therapeutic use , Adolescent , Adult , Alanine Transaminase/blood , DNA, Viral/blood , Drug Therapy, Combination , Female , Follow-Up Studies , Hepatitis B Antibodies/blood , Hepatitis B e Antigens/blood , Hepatitis B virus/isolation & purification , Hepatitis B, Chronic/blood , Hepatitis B, Chronic/virology , Humans , Male , Middle AgedABSTRACT
AIM: To establish a sensitive and efficient reporter gene based screening model and use it to screen compounds for discovering new ligands of estrogen receptor alpha subtype. METHODS: A recombinant Epstein-Barr virus episomal vector (pMT/ERE-CAT) was constructed by inserting a synthetic sequence composed of five estrogen response elements upstream of promoter and a chloramphenicol acetyltransferase (CAT) gene downstream of promoter. pMT/ERE-CAT was transfected into HepG2 cells expressing estrogen receptor alpha subtype (ER +HepG2). Hygromycin (200 micrograms.mL-1) was added 48 h after transfection for selection. One stably transfected clone was isolated and used to screen compounds for activity of stimulating CAT gene expression using colorimetric CAT assay. RESULTS: In the ER +HepG2 cells, the expression of CAT gene was induced by estradiol. A dose-dependent expression of CAT gene with half-maximal induction at 0.07 nmol.L-1 was observed. The ER +HepG2 cell was used to screen compounds for activity of stimulating CAT gene expression. Resveratrol was found to produce a maximal level of induction (1.75 times of estradiol). In vitro radiation survival experiment showed that the radioprotection activity of resveratrol (D0 = 3.18 Gy) is stronger than that of estradiol (D0 = 2.59 Gy). CONCLUSION: Vector pMT/ERE-CAT was used to generate stably transfected ER +HepG2 cell lines. The cell lines can be used to screen compounds for estrogen activity by testing extracts of cells grown in microtiter wells directly using colorimetric CAT assay. This system should provide an efficient method for screening and analyzing the activity of large numbers of ligands of estrogen receptor.
Subject(s)
Chloramphenicol O-Acetyltransferase/genetics , Estrogens/pharmacology , Genes, Reporter , Receptors, Estrogen , Drug Evaluation, Preclinical/methods , Estrogen Receptor alpha , Humans , Ligands , Tumor Cells, CulturedABSTRACT
AIM: To study the effects of sex hormones, estradiol (Est), progesterone (Pro) and testosterone (Tes) on the action potential (AP) and contraction of guinea pig papillary muscle. METHODS: Using conventional glass microelectrode and mechanical recording of myocardial contraction. RESULTS: Est slowed down the maximal rate of rise of phase 0 (Vmax) of AP at low concentration (1 mumol.L-1). At 10 mumol.L-1 and above, Est also prolonged AP duration (APD50 and APD90), effective refractory period (ERP) and decreased the maximal isometric tension (Pmax) and velocity of tension development (dT/dt) of contraction. Tes (100 mumol.L-1 - 1 mmol.L-1) prolonged APD90 and ERP with decreased Pmax and dT/dt. But Pro (1 mumol.L-1 - 1 mmol.L-1) had no effects on both AP and contraction. CONCLUSION: Est prolonged AP and depressed contraction of guinea pig papillary muscle.
Subject(s)
Gonadal Steroid Hormones/pharmacology , Myocardial Contraction/drug effects , Papillary Muscles/physiology , Action Potentials/drug effects , Animals , Depression, Chemical , Estradiol/pharmacology , Guinea Pigs , Male , Progesterone/pharmacology , Refractory Period, Electrophysiological/drug effects , Testosterone/pharmacologyABSTRACT
AIM: To study the effects of sodium pentobarbital (SP) on the action potential (AP) and contraction of guinea pig papillary muscle. METHODS: Using conventional glass microelectrode and mechanical recording of myocardium contraction. RESULTS: SP (> or = 10 mumol.L-1) prolonged the AP duration (APD) and effective refractory period (ERP), while amplitude (APA) and Vmax of phase 0 showed no changes. The effects of SP were abolished by pretreatment with cromakalim, an agonist of ATP-sensitive K+ channel. The maximal isometric tension (Pmax) and velocity of tension development (dT/dt) were decreased to 51% and 48% of control, respectively. The first postrest beat (B1) and second postrest beat (B2) were also depressed. CONCLUSION: SP affected the action potential by reducing activities of the K+ channels and reduced the contraction of guinea pig myocardium.