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1.
Article in English | MEDLINE | ID: mdl-36072411

ABSTRACT

Dynamic pulmonary hyperinflation and abnormal air exchange are the primary causes of the exercise limitation of chronic obstructive pulmonary disease (COPD) patients. During exercise, COPD sufferers' lungs are dynamically hyperinflated. Increased inefficient ventilation reduces ventilation efficiency and causes a mismatch between ventilation volume and blood flow. The ventilatory equivalent for CO2 (VeqCO2) is a physiological parameter that can be measured using cardiopulmonary exercise testing. Therefore, the aim of this exploratory study was to perform cardiopulmonary exercise testing on people with COPD, investigate the impact of static pulmonary function on ventilation efficiency under the exercise state, and screen the predictive indicators of ventilation efficiency. Subject. The aim of this study was to look at the factors that influence the exercise ventilation efficiency of people with COPD. Method. A total of 76 people with COPD were recruited during the stable period. Age, gender, body height, body mass, and other basic information were recorded. The body mass index (BMI) was determined, and forced vital capacity (FVC), forced expiratory volume in one second (FEV1), residual volume/total lung capacity (RV/TLC), diffusing capacity of the lung for carbon monoxide (DLCO), and DLCO divided by the alveolar volume (DLCO/VA) were measured. The ventilatory equivalent for carbon dioxide (VE/VCO2) under the rest state (EqCO2rest), anaerobic threshold (EqCO2at), and maximum exercise state (EqCO2 max) were calculated to investigate the influencing factors for ventilation efficiency of people with COPD. Results. FEV1% was negatively correlated with EqCO2rest (r = -0.277, P value <0.05); FEV1/FVC % was negatively correlated with EqCO2rest and EqCO2at (r = -0.311, -0.287, P value <0.05); DLCO% was negatively correlated with EqCO2rest, EqCO2at, and EqCO2max (r = -0.408, -0.462, and -0.285, P value <0.05); DLCO/VA% was negatively correlated with EqCO2rest, EqCO2at, and EqCO2max (r = -0.390, -0.392, and -0.245, P value <0.05); RV/TLC was positively correlated with EqCO2rest and EqCO2at (r = 0.289, 0.258, P-value <0.05). The prediction equation from the multivariable regression analysis equation was Y = 40.04-0.075X (Y = EqCO2, X = DLCO/VA%). Conclusions. As the degree of ventilatory obstruction increased, the ventilation efficiency of the stable people with COPD under the exercise state showed a progressive decrease; the ventilation efficiency of the people with COPD decreased significantly under the maximum exercise state, and the ventilation capacity and diffusion capacity were the significant factors that affected the exercise ventilation efficiency. The diffusion function may predict the maximum ventilation efficiency and enable primary hospitals without exercise test equipment in developing countries to predict and screen patients at risk for current exercise based on limited information.

2.
Cell Rep ; 35(12): 109281, 2021 06 22.
Article in English | MEDLINE | ID: mdl-34161765

ABSTRACT

Obesity has become a global pandemic. Identification of key factors in adipogenesis helps to tackle obesity and related metabolic diseases. Here, we show that DDB1 binds the histone reader BRWD3 to promote adipogenesis and diet-induced obesity. Although typically recognized as a component of the CUL4-RING E3 ubiquitin ligase complex, DDB1 stimulates adipogenesis independently of CUL4. A DDB1 mutant that does not bind CUL4A or CUL4B fully restores adipogenesis in DDB1-deficient cells. Ddb1+/- mice show delayed postnatal development of white adipose tissues and are protected from diet-induced obesity. Mechanistically, by interacting with BRWD3, DDB1 is recruited to acetylated histones in the proximal promoters of ELK1 downstream immediate early response genes and facilitates the release of paused RNA polymerase II, thereby activating the transcriptional cascade in adipogenesis. Our findings have uncovered a CUL4-independent function of DDB1 in promoting the transcriptional cascade of adipogenesis, development of adipose tissues, and onset of obesity.


Subject(s)
Adipogenesis , DNA-Binding Proteins , Histones , Obesity , Transcription Factors , Transcription, Genetic , Animals , Humans , Mice , 3T3-L1 Cells , Adipogenesis/genetics , Base Sequence , Diet, High-Fat , DNA-Binding Proteins/deficiency , DNA-Binding Proteins/metabolism , Genes, Immediate-Early , Histones/metabolism , Mice, Inbred C57BL , Obesity/genetics , Promoter Regions, Genetic/genetics , Protein Binding/genetics , RNA Polymerase II/metabolism , Transcription Factors/metabolism
4.
Article in English | MEDLINE | ID: mdl-32021143

ABSTRACT

Background: Glycopyrrolate/formoterol fumarate metered dose inhaler (GFF MDI) is a long-acting muscarinic antagonist/long-acting ß2-agonist fixed-dose combination therapy delivered by MDI, formulated using innovative co-suspension delivery technology. The PINNACLE-4 study evaluated the efficacy and safety of GFF MDI in patients with moderate-to-very severe chronic obstructive pulmonary disease (COPD) from Asia, Europe, and the USA. This article presents the results from the China subpopulation of PINNACLE-4. Methods: In this randomized, double-blind, placebo-controlled, parallel-group Phase III study (NCT02343458), patients received GFF MDI 18/9.6 µg, glycopyrrolate (GP) MDI 18 µg, formoterol fumarate (FF) MDI 9.6 µg, or placebo MDI (all twice daily) for 24 weeks. The primary endpoint was change from baseline in morning pre-dose trough forced expiratory volume in 1 second at Week 24. Secondary lung function endpoints and patient-reported outcome measures were also assessed. Safety was monitored throughout the study. Results: Overall, 466 patients from China were included in the intent-to-treat population (mean age 63.6 years, 95.7% male). Treatment with GFF MDI improved the primary endpoint compared to GP MDI, FF MDI, and placebo MDI (least squares mean differences: 98, 104, and 173 mL, respectively; all P≤0.0001). GFF MDI also improved daily total symptom scores and time to first clinically important deterioration versus monocomponents and placebo MDI, and Transition Dyspnea Index focal score versus placebo MDI. Rates of treatment-emergent adverse events were similar across the active treatment groups and slightly higher in the placebo MDI group. Conclusion: GFF MDI improved lung function and daily symptoms versus monocomponents and placebo MDI and improved dyspnea versus placebo MDI. All treatments were well tolerated with no unexpected safety findings. Efficacy and safety results were generally consistent with the global PINNACLE-4 population, supporting the use of GFF MDI in patients with COPD from China.


Subject(s)
Adrenergic beta-2 Receptor Agonists/therapeutic use , Formoterol Fumarate/therapeutic use , Glycopyrrolate/therapeutic use , Lung/drug effects , Metered Dose Inhalers , Muscarinic Antagonists/therapeutic use , Pulmonary Disease, Chronic Obstructive/drug therapy , Administration, Inhalation , Adrenergic beta-2 Receptor Agonists/administration & dosage , Adrenergic beta-2 Receptor Agonists/adverse effects , Aged , Bronchodilator Agents/administration & dosage , Bronchodilator Agents/adverse effects , China , Double-Blind Method , Drug Combinations , Female , Forced Expiratory Volume , Formoterol Fumarate/administration & dosage , Formoterol Fumarate/adverse effects , Glycopyrrolate/adverse effects , Humans , Lung/physiopathology , Male , Middle Aged , Muscarinic Antagonists/administration & dosage , Muscarinic Antagonists/adverse effects , Pulmonary Disease, Chronic Obstructive/diagnosis , Pulmonary Disease, Chronic Obstructive/physiopathology , Recovery of Function , Severity of Illness Index , Time Factors , Treatment Outcome
5.
Medicine (Baltimore) ; 98(35): e16885, 2019 Aug.
Article in English | MEDLINE | ID: mdl-31464917

ABSTRACT

BACKGROUND: This study aims to systematically assess the efficacy and safety of fasudil for the treatment of aneurysmal subarachnoid hemorrhage (ASH). METHODS: This study will include all of randomized controlled trials on the efficacy and safety of fasudil for the treatment of ASH. Ten electronic databases of PubMed, Embase, Cochrane Library, Google Scholar, Web of Science, Ovid, Cumulative Index to Nursing and Allied Health Literature, Allied and Complementary Medicine Database, Chinese Biomedical Literature Database, and China National Knowledge Infrastructure will be searched from inception to the May 1, 2019 without language restrictions. We will also search gray literatures to avoid missing any other potential studies. Two authors will independently perform study selection, data extraction and management, and methodologic quality assessment. The primary outcome is limbs function. The secondary outcomes comprise of muscle strength, muscle tone, quality of life, and adverse events. RESULTS: This study will provide a comprehensive literature search on the current evidence of fasudil for the treatment of ASH from primary and secondary outcomes. CONCLUSION: The results of this study will present evidence to determine whether fasudil is an effective and safety treatment for patients with ASH. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42019136215.


Subject(s)
1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine/analogs & derivatives , Intracranial Aneurysm/complications , Subarachnoid Hemorrhage/drug therapy , 1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine/adverse effects , 1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine/therapeutic use , Humans , Randomized Controlled Trials as Topic , Research Design/standards , Subarachnoid Hemorrhage/etiology , Treatment Outcome
6.
Medicine (Baltimore) ; 98(26): e16263, 2019 Jun.
Article in English | MEDLINE | ID: mdl-31261594

ABSTRACT

BACKGROUND: Pressure therapy (PST) has been reported for the treatment of hypertrophic scar (HS) effectively. However, no study has assessed its effect and safety systematically. Therefore, this study will investigate its effect and safety for patients with HS. METHODS: A comprehensive literature search will be performed from the electronic databases and grey literatures. The electronic databases include MEDILINE, EMBASE, Cochrane Library, Web of Science, Allied and Complementary Medicine Database, Chinese Biomedical Literature Database, and China National Knowledge Infrastructure. All of them will be searched from inception to the present without language restrictions. Any randomized controlled trials on assessing the effect and safety of PST on HS will be considered for inclusion. In addition, we will also search grey literature to avoid missing any potential studies. RevMan V.5.3 software will be utilized for statistical analysis. RESULTS: This study will provide the most recent evidence of PST on HS by evaluating primary outcomes of scar pruritus and improvement of scar; and secondary outcomes of scar blood flow, elasticity, volume, pain and burning. In addition, we will also evaluate adverse events. CONCLUSION: This study will provide up-to-date evidence of PST in patients with HS.Systematic review registration: PROSPERO CRD42019136627.


Subject(s)
Cicatrix, Hypertrophic/therapy , Physical Therapy Modalities , Pressure , Humans , Randomized Controlled Trials as Topic , Research Design , Systematic Reviews as Topic , Treatment Outcome
7.
Cell Rep ; 26(1): 209-221.e5, 2019 01 02.
Article in English | MEDLINE | ID: mdl-30605677

ABSTRACT

Fatty acid uptake is the first step in fatty acid utilization, but it remains unclear how the process is regulated. Protein palmitoylation is a fatty acyl modification that plays a key regulatory role in protein targeting and trafficking; however, its function in regulating fatty acid metabolism is unknown. Here, we show that two of the Asp-His-His-Cys (DHHC) motif-containing palmitoyl acyltransferases, DHHC4 and DHHC5, regulate fatty acid uptake. DHHC4 and DHHC5 function at different subcellular localizations to control the palmitoylation, plasma membrane localization, and fatty acid uptake activity of the scavenger receptor CD36. Depletion of either DHHC4 or DHHC5 in cells disrupts CD36-dependent fatty acid uptake. Furthermore, both Dhhc4-/- and adipose-specific Dhhc5 knockout mice show decreased fatty acid uptake activity in adipose tissues and develop severe hypothermia upon acute cold exposure. These findings demonstrate a critical role of DHHC4 and DHHC5 in regulating fatty acid uptake.


Subject(s)
Acyltransferases/metabolism , CD36 Antigens/metabolism , Fatty Acids/metabolism , Lipoylation , Membrane Proteins/metabolism , 3T3-L1 Cells , Adipose Tissue/metabolism , Amino Acid Sequence , Animals , Biological Transport , Cell Membrane/metabolism , HEK293 Cells , Humans , Male , Mice , Mice, Inbred C57BL , Mice, Knockout , Transfection
8.
Medicine (Baltimore) ; 97(31): e11625, 2018 Aug.
Article in English | MEDLINE | ID: mdl-30075540

ABSTRACT

BACKGROUND: This study assessed the effect transcutaneous vagus nerve stimulation (TVNS) for poststroke epilepsy (PSE). METHODS: Fifty-two patients with PSE were included in this study. Twenty-seven patients received TVNS, 30 minutes each session, once daily, twice weekly for a total of 4 weeks; and were assigned to the treatment group. Twenty-five patients were at waiting list and were assigned to the control group. The primary outcome included weekly seizure frequency. The secondary outcomes consisted of each seizure episode, and quality of life, measured by the Quality of Life in Epilepsy Inventory-31 (QOLIE-31), as well as the adverse events. All outcomes were measured before and after 4-week treatment. RESULTS: After treatment, TVNS failed to show better outcomes in weekly seizure frequency (treatment group, P = .12; control group, P = .56), seizure episode (treatment group, P = .65; control group, P = .92), and QOLIE-31 (treatment group, P = .73; control group, P = .84) compared with these before the treatment. Furthermore, TVNS also did not elaborate the promising effect in seizure frequency (P = .81), seizure episode (P = .75), and QOLIE-31 (P = .33), compared with these in the control group. In addition, minor and acceptable adverse events were recorded in this study. CONCLUSION: The results of this study showed that TVNS may be not effective for Chinese patients PSE after 4-week treatment.


Subject(s)
Epilepsy/therapy , Stroke/complications , Transcutaneous Electric Nerve Stimulation/methods , Vagus Nerve Stimulation/methods , Adult , Aged , Epilepsy/etiology , Female , Humans , Male , Middle Aged , Quality of Life , Retrospective Studies , Treatment Outcome , Young Adult
9.
Guang Pu Xue Yu Guang Pu Fen Xi ; 37(3): 723-7, 2017 Mar.
Article in Chinese, English | MEDLINE | ID: mdl-30148553

ABSTRACT

A series of SrBPO5∶Dy3+ phosphor used for UV excited white LEDs were synthesized with high temperature solid state method. The XRD patterns and luminescent properties were investigated. The results indicated that the sample was single SrBPO5 phase. The emission spectrum included two emission peaks locating at 485 and 575 nm excited by 388 nm UV light. The influence of Dy3+ ions concentration, Mg2+ ions dosage, sintering temperature and charge compensator on the luminescent properties was studied. The emission intensity reaches the maximum when the concentration of Dy3+ ions is 4 mol%; the ratio of B/Y increases with the amount of Mg2+ ions and Na+ is the optimal charge compensation. The results showed that this phosphor has a stronger yellow peak, which can raise the yellow emission and enhance the ability of penetrating haze of UV based high transmission white LED.


Subject(s)
Luminescent Agents , Ultraviolet Rays , Color , Luminescence , Sodium
10.
Respir Care ; 61(2): 220-4, 2016 Feb.
Article in English | MEDLINE | ID: mdl-26374906

ABSTRACT

BACKGROUND: Exercise testing is recommended before prescribing individualized exercise intensity. However, there are few data demonstrating how exercise test responses are translated into individualized training intensity using a simple method. We previously developed a simple method to rate dyspnea called the count scale, including the count scale number (CSN) and count scale time. The purpose of this study was to assess the CSN for translation of exercise test response to training intensity. METHODS: Twenty-eight subjects (22 men and 6 women) with COPD age 66.6 ± 8.22 y participated in 2 exercise sessions. During the first session, in which exercise was guided by the heart rate, the CSN and heart rate were obtained (ie, CSN1 and HR1) while the heart rate was increased by 20% compared with the resting heart rate. During the second session, exercise was guided by the CSN. When the CSN was close to the CSN1, the CSN and corresponding heart rate were recorded as CSN2 and HR2. Differences between CSN1 and CSN2 and between HR1 and HR2 were compared. The relationship between HR1 and HR2 was analyzed. Agreement between HR1 and HR2 was evaluated by Bland-Altman plots. RESULTS: No significant differences were seen between HR1 and HR2 (96 ± 11 and 97 ± 11, respectively; P = .14). A high correlation between HR1 and HR2 was found (r = 0.932, P < .001). The 95% CI for the difference between HR1 and HR2 was -1.2 to 8.5 beats/min. CONCLUSIONS: Exercise guided by the CSN alone could result in a given heart rate response, suggesting that the CSN is a simple and practical tool in translating exercise test results into individualized training intensity. With the CSN as the intensity indicator, patients can exercise safely and effectively.


Subject(s)
Exercise Test/methods , Exercise Tolerance/physiology , Pulmonary Disease, Chronic Obstructive/physiopathology , Aged , Exercise/physiology , Female , Heart Rate , Humans , Male , Middle Aged , Pulmonary Disease, Chronic Obstructive/therapy
11.
Spectrochim Acta A Mol Biomol Spectrosc ; 138: 247-51, 2015 Mar 05.
Article in English | MEDLINE | ID: mdl-25498821

ABSTRACT

A novel pyrazoline-based fluorescent probe, 2-[4-(3,5-diphenyl-4,5-dihydro-pyrazol-1-yl)-benzylidene]-malononitrile, with a simple structure and low detection limit (6.16×10(-6)M) for the detection of hydrazine is designed and synthesized. The probe responds selectively to hydrazine over other molecules with marked fluorescence enhancement. The probe can detect hydrazine effectively at pH 5.0-9.0 with a special emission wavelength at 520nm. Moreover, the probe can be used to detect hydrazine from variety of natural source water.


Subject(s)
Fluorescent Dyes/chemistry , Hydrazines/chemistry , Pyrazoles/chemistry , Water Pollutants, Chemical/analysis , Acetates/chemistry , Acetonitriles/chemistry , Hydrogen-Ion Concentration , Limit of Detection , Magnetic Resonance Spectroscopy , Molecular Structure , Solvents/chemistry , Spectrometry, Fluorescence , Water/chemistry , Water Purification
12.
BMC Pulm Med ; 14: 16, 2014 Feb 07.
Article in English | MEDLINE | ID: mdl-24507622

ABSTRACT

BACKGROUND: A higher slow vital capacity (VC) compared with forced vital capacity (FVC) indicates small airway collapse and air trapping. We hypothesized that a larger difference between VC and FVC (VC-FVC) would predict impaired exercise capacity in patients with chronic obstructive pulmonary disease (COPD). METHODS: Pulmonary function and incremental cardiopulmonary exercise responses were assessed in 97 COPD patients. Patients were then divided into two groups: one in which VC > FVC (n = 77) and the other in which VC ≤ FVC (n = 20). RESULTS: Patients with VC > FVC had lower FEV1 and peak oxygen uptake (VO2/kg) compared with patients with VC ≤ FVC. There was a significant inverse correlation for the entire group between VC-FVC and peak VO2/kg (r = -0.404; p < 0.001). There was also a direct correlation between FEV1% pred and peak VO2/kg (r = 0.418; p < 0.001). The results of the multivariate regression analysis with peak VO2/kg as the dependent variable showed that VC-FVC, FEV1(% pred) and age were all significant independent predictors of peak VO2/kg. The model explained 35.9% of the peak VO2/kg variance. CONCLUSIONS: The difference between VC and FVC, easily measured by spirometry, can be used not only as an index of severity of airflow limitation, but also to predict exercise performance in COPD patients.


Subject(s)
Exercise Tolerance , Pulmonary Disease, Chronic Obstructive/physiopathology , Vital Capacity , Female , Humans , Male , Middle Aged , Time Factors
13.
Biosens Bioelectron ; 55: 386-90, 2014 May 15.
Article in English | MEDLINE | ID: mdl-24434493

ABSTRACT

A novel compound, 2-(1,5-diphenyl-4,5-dihydro-1H-pyrazol-3-yl)phenyl acrylate (probe L), was designed and synthesized as a highly sensitive and selective fluorescent probe for recognizing and detecting glutathione among cysteine, homocysteine and other amino acids. The structures of related compounds were characterized using IR, NMR and HRMS spectroscopy analysis. The probe is a non-fluorescent compound. On being mixed with glutathione in buffered EtOH:PBS=3:7 solution at pH 7.4, the probe exhibited the blue emission of the pyrazoline at 474 nm and a 83-fold enhancement in fluorescence intensity. This probe is very sensitive and displayed a linear fluorescence off-on response to glutathione with fluorometric detection limit of 8.2 × 10(-8)M. The emission of the probe is pH independent in the physiological pH range. Live-cell imaging of HeLa cells confirmed the cell permeability of the probe and its ability to selectively discriminate GSH from Cys and Hcy in cells. The toxicity of the probe was low in cultured HeLa cells.


Subject(s)
Fluorescent Dyes/chemical synthesis , Glutathione/metabolism , Molecular Probe Techniques , Pyrazoles/chemical synthesis , Spectrometry, Fluorescence/methods , Subcellular Fractions/metabolism , Cell Survival/drug effects , Fluorescent Dyes/analysis , Fluorescent Dyes/toxicity , HeLa Cells , Humans , Pyrazoles/toxicity , Subcellular Fractions/drug effects
14.
J Fluoresc ; 24(3): 657-63, 2014 May.
Article in English | MEDLINE | ID: mdl-24337815

ABSTRACT

This paper presents the preparation of a pyrazoline compound and the properties of its UV-Vis absorption and fluorescence emission. Moreover, this compound can be used to determine Hg(2+) ion with selectivity and sensitivity in the EtOH:H2O =9:1 (v/v) solution. This sensor forms a 1:1 complex with Hg(2+) and shows a fluorescent enhancement with good tolerance of other metal ions. This sensor is very sensitive with fluorometric detection limit of 3.85 × 10(-10) M. In addition, the fluorescent probe has practical application in cells imaging.


Subject(s)
Biosensing Techniques , Fluorescent Dyes/chemistry , Mercury/analysis , Pyrazoles/chemistry , Molecular Structure , Spectrometry, Fluorescence
15.
Int J Mol Sci ; 14(12): 24029-45, 2013 Dec 10.
Article in English | MEDLINE | ID: mdl-24336063

ABSTRACT

The exact molecular mechanism that mediates hypoxia-induced pulmonary fibrosis needs to be further clarified. The aim of this study was to explore the effect and underlying mechanism of angiotensin II (Ang II) on collagen synthesis in hypoxic human lung fibroblast (HLF) cells. The HLF-1 cell line was used for in vitro studies. Angiotensinogen (AGT), angiotensin converting enzyme (ACE), angiotensin II type 1 receptor (AT1R) and angiotensin II type 2 receptor (AT2R) expression levels in human lung fibroblasts were analysed using real-time polymerase chain reaction (RT-PCR) after hypoxic treatment. Additionally, the collagen type I (Col-I), AT1R and nuclear factor κappaB (NF-κB) protein expression levels were detected using Western blot analysis, and NF-κB nuclear translocation was measured using immunofluorescence localization analysis. Ang II levels in HLF-1 cells were measured with an enzyme-linked immunosorbent assay (ELISA). We found that hypoxia increased Col-I mRNA and protein expression in HLF-1 cells, and this effect could be inhibited by an AT1R or AT2R inhibitor. The levels of NF-κB, RAS components and Ang II production in HLF-1 cells were significantly increased after the hypoxia exposure. Hypoxia or Ang II increased NF-κB-p50 protein expression in HLF-1 cells, and the special effect could be inhibited by telmisartan (TST), an AT1R inhibitor, and partially inhibited by PD123319, an AT2R inhibitor. Importantly, hypoxia-induced NF-κB nuclear translocation could be nearly completely inhibited by an AT1R or AT2R inhibitor. Furthermore pyrrolidine dithiocarbamate (PDTC), a NF-κB blocker, abolished the expression of hypoxia-induced AT1R and Col-I in HLF-1 cells. Our results indicate that Ang II-mediated NF-κB signalling via ATR is involved in hypoxia-induced collagen synthesis in human lung fibroblasts.


Subject(s)
Angiotensin II/metabolism , Cell Hypoxia , Collagen Type I/metabolism , Angiotensin II/analysis , Angiotensinogen/genetics , Angiotensinogen/metabolism , Benzimidazoles/pharmacology , Benzoates/pharmacology , Cell Line , Collagen Type I/genetics , Fibroblasts/cytology , Fibroblasts/metabolism , Gene Expression Regulation/drug effects , Humans , Imidazoles/pharmacology , Lung/cytology , Lung/metabolism , NF-kappa B/antagonists & inhibitors , NF-kappa B/metabolism , Peptidyl-Dipeptidase A/genetics , Peptidyl-Dipeptidase A/metabolism , Pyridines/pharmacology , Pyrrolidines/pharmacology , RNA, Messenger/metabolism , Receptor, Angiotensin, Type 1/chemistry , Receptor, Angiotensin, Type 1/genetics , Receptor, Angiotensin, Type 1/metabolism , Receptor, Angiotensin, Type 2/chemistry , Receptor, Angiotensin, Type 2/genetics , Receptor, Angiotensin, Type 2/metabolism , Telmisartan , Thiocarbamates/pharmacology
16.
Biomed Res Int ; 2013: 760904, 2013.
Article in English | MEDLINE | ID: mdl-24195079

ABSTRACT

During growth, C. botulinum is always exposed to different environmental changes, such as temperature increase, nutrient deprivation, and pH change; however, its corresponding global transcriptional profile is uncharacterized. This study is the first description of the genome-wide gene expression profile of C. botulinum in response to heat shock stress. Under heat stress (temperature shift from 37°C to 45°C over a period of 15 min), 176 C. botulinum ATCC 3502 genes were differentially expressed. The response included overexpression of heat shock protein genes (dnaK operon, groESL, hsp20, and htpG) and downregulation of aminoacyl-tRNA synthetase genes (valS, queA, tyrR, and gatAB) and ribosomal and cell division protein genes (ftsZ and ftsH). In parallel, several transcriptional regulators (marR, merR, and ompR families) were induced, suggesting their involvement in reshuffling of the gene expression profile. In addition, many ABC transporters (oligopeptide transport system), energy production and conversion related genes (glpA and hupL), cell wall and membrane biogenesis related genes (fabZ, fabF, and fabG), flagella-associated genes (flhA, flhM, flhJ, flhS, and motAB), and hypothetical genes also showed changed expression patterns, indicating that they may play important roles in survival under high temperatures.


Subject(s)
Bacterial Proteins/biosynthesis , Clostridium botulinum/metabolism , Gene Expression Regulation, Bacterial/physiology , Heat-Shock Response/physiology , Microbial Viability , Bacterial Proteins/genetics , Clostridium botulinum/genetics , Gene Expression Profiling , Genes, Bacterial/physiology , Hot Temperature
17.
Analyst ; 138(23): 7169-74, 2013 Dec 07.
Article in English | MEDLINE | ID: mdl-24106736

ABSTRACT

A new fluorescent probe, N-(4-(1,5-diphenyl-4,5-dihydro-1H-pyrazol-3-yl)phenyl)-2,4-dinitrobenzenesulfonamide (probe 3), was designed and synthesized as a highly sensitive and selective fluorescent probe for recognizing and detecting glutathione among biological thiols in aqueous media. Probe 3 is a nonfluorescent compound. On being mixed with biothiols under neutral aqueous conditions, the 2,4-dinitrobenzenesulfoyl moiety can be cleaved off by glutathione, and the blue emission of the pyrazoline at 464 nm is switched on, with a fluorescence enhancement of 488-fold for glutathione. Furthermore, probe 3 was highly selective for glutathione without interference from some biologically relevant analytes. The detection limit of glutathione was 4.11 × 10(-7) M. The emission of the probe is pH independent in the physiological pH range. Moreover, the probe can be used for fluorescent imaging of cellular glutathione and can be used for detecting glutathione in calf serum.


Subject(s)
Fluorescent Dyes/chemistry , Glutathione/analysis , Pyrazoles/chemistry , Hydrogen-Ion Concentration , Kinetics , Limit of Detection , Microscopy, Fluorescence
18.
Chin Med J (Engl) ; 126(19): 3616-20, 2013.
Article in English | MEDLINE | ID: mdl-24112151

ABSTRACT

BACKGROUND: The Borg scale is most commonly used to measure dyspnea in China. However, many patients that find it is difficult to distinguish the labeled numbers corresponding to different dyspnea scores. We developed a new method to rate dyspnea, which we call the count scale (CS). It includes the count scale number (CSN) and count scale time (CST). The aims of the present study were to determine the reproducibility and sensitivity of the CS during exercise in patients with chronic obstructive pulmonary disease (COPD). METHODS: Fourteen male patients with COPD (aged 58.00 ± 7.72 years) participated in this study. A progressive incremental exercise and a 6-minute constant work exercise test were performed every 2 to 3 days for a total of 3 times. The CS results were evaluated at rest and at 30% and 70% of maximal workload (Wmax) and Wmax. The Borg scales were obtained during exercise. RESULTS: No significant differences occurred across the three trials during exercise for the CS and Borg scores. The CSN and CST were more varied at Wmax (coefficient of variation (CV) = (22.28 ± 16.96)% for CSN, CV = (23.08 ± 19.11)% for CST) compared to 30% of Wmax (CV = (11.92 ± 8.78)% for CSN, CV = (11.16 ± 9.96)% for CST) and 70% of Wmax (CV = (9.08 ± 7.09)% for CSN, CV = (12.19 ± 12.32)% for CST). Dyspnea ratings with either CSN or CST tended to decrease at the higher workload compared to the lower workload. CSN and CST scores were highly correlated (r = 0.861, P < 0.001). CSN was negatively correlated with Borg scores (r = -0.363, P = 0.001). Similar results were obtained for the relationship between CST and Borg scores (r = -0.345, P = 0.003). CONCLUSION: We concluded that the CS is simple and reproducible when measuring dyspnea during exercise in patients with COPD.


Subject(s)
Dyspnea/diagnosis , Exercise , Pulmonary Disease, Chronic Obstructive/physiopathology , Aged , Humans , Male , Middle Aged , Reproducibility of Results
19.
CNS Neurosci Ther ; 19(12): 954-62, 2013 Dec.
Article in English | MEDLINE | ID: mdl-24164691

ABSTRACT

BACKGROUND: Baroreflex gain increase up closely to adult level during initial postnatal weeks, and any interruption within this period will increase the risk of cardiovascular problems in later of life span. We hypothesize that this short period after birth might be critical for postnatal development of vagal ganglion neurons (VGNs). METHODS: To evaluate neuroexcitability evidenced by discharge profiles and coordinate changes, ion currents were collected from identified A- and C-type VGNs at different developmental stages using whole-cell patch clamping. RESULTS: C-type VGNs underwent significant age-dependent transition from single action potential (AP) to repetitive discharge. The coordinate changes between TTX-S and TTX-R Na(+) currents were also confirmed and well simulated by computer modeling. Although 4-AP or iberiotoxin age dependently increased firing frequency, AP duration was prolonged in an opposite fashion, which paralleled well with postnatal changes in 4-AP- and iberiotoxin-sensitive K(+) current activity, whereas less developmental changes were verified in A-types. CONCLUSION: These data demonstrate for the first time that the neuroexcitability of C-type VGNs increases significantly compared with A-types within initial postnatal weeks evidenced by AP discharge profiles and coordinate ion channel changes, which explain, at least in part, that initial postnatal weeks may be crucial for ontogenesis in visceral afferent reflex function.


Subject(s)
Action Potentials/physiology , Neurons/physiology , Reflex/physiology , Vagus Nerve/physiology , Visceral Afferents/physiology , 4-Aminopyridine/pharmacology , Age Factors , Animals , Animals, Newborn , Nerve Fibers, Myelinated/physiology , Nerve Fibers, Unmyelinated/physiology , Patch-Clamp Techniques , Peptides/pharmacology , Potassium Channel Blockers/pharmacology , Rats , Rats, Sprague-Dawley , Sodium Channel Blockers/pharmacology , Tetrodotoxin/pharmacology
20.
Shock ; 39(3): 317-25, 2013 Mar.
Article in English | MEDLINE | ID: mdl-23364429

ABSTRACT

The aim of the present study was to examine the effect and possible mechanism of salvianolic acid B (SalB) on pulmonary microcirculation disturbance induced by lipopolysaccharide (LPS) in rat. Male Sprague-Dawley rats were subjected to thoracotomy under continuous anesthesia and mechanical ventilation. Albumin leakage from pulmonary capillary and the numbers of leukocytes adherent to the pulmonary capillary wall were determined for 60 min by an upright microscope upon LPS (2 mg · kg(-1) · h(-1)) infusion with or without administration of SalB (5 mg · kg(-1) · h(-1)). Pulmonary tissue wet-to-dry weight ratio, tumor necrosis factor α, and interleukin 8 in plasma and bronchoalveolar lavage fluid were measured. In addition, the expressions of E-selectin, intercellular adhesion molecule 1, and myeloperoxidase in pulmonary tissue were assessed by immunohistochemistry. The expressions of aquaporin 1 (AQP-1), AQP-5, metalloproteinase 2 (MMP-2), and MMP-9 were assessed by Western blot assay. Pretreatment with SalB significantly attenuated LPS-induced pulmonary microcirculatory disturbance, including the increase in leukocyte adhesion and albumin leakage. In addition, LPS increased pulmonary tissue wet-to-dry weight ratio and tumor necrosis factor α and interleukin 8 levels in plasma and bronchoalveolar lavage fluid enhanced the expression of E-selectin, intercellular adhesion molecule 1, myeloperoxidase, MMP-2, and MMP-9, whereas it decreased the expression of AQP-1 and AQP-5 in pulmonary tissue, all of which were attenuated by SalB pretreatment. Salvianolic acid B pretreatment improves pulmonary microcirculation disturbance and lung injury on LPS exposure. More studies are required to evaluate the potential of SalB as an option for protecting lung from endotoxemia.


Subject(s)
Acute Lung Injury/prevention & control , Benzofurans/therapeutic use , Pulmonary Circulation/drug effects , Acute Lung Injury/chemically induced , Acute Lung Injury/pathology , Acute Lung Injury/physiopathology , Animals , Bronchoalveolar Lavage Fluid/chemistry , Capillaries/metabolism , Capillaries/pathology , Capillary Permeability/drug effects , Cell Adhesion/drug effects , Drug Evaluation, Preclinical/methods , Drugs, Chinese Herbal/therapeutic use , E-Selectin/metabolism , Intercellular Adhesion Molecule-1/metabolism , Interleukin-8/metabolism , Leukocytes/physiology , Lipopolysaccharides , Lung/metabolism , Male , Matrix Metalloproteinase 2/metabolism , Matrix Metalloproteinase 9/metabolism , Microcirculation/drug effects , Peroxidase/metabolism , Rats , Rats, Sprague-Dawley , Tumor Necrosis Factor-alpha/metabolism
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