BACKGROUND: Poststroke spasticity (PSS) is a common complication of stroke. Current PSS treatments have been linked to high costs, lack of long-term effectiveness, and undesirable side effects. Vibrational and heated stone-needle therapy (VHS) has not been utilized to treat PSS, and its safety and effectiveness have yet to be proven by high-quality clinical research. OBJECTIVE: The aim of this study was to determine the effectiveness of VHS combined with meridian dredging exercise (MDE) in patients with PSS. METHODS: One hundred participants with stroke were included and randomly assigned to a treatment group (VHS plus MDEs) and a control group (MDEs alone). Patients in both groups were treated for 4 weeks. The primary outcome measures were the Modified Ashworth Scale (MAS) and Fugl-Meyer Assessment (FMA), while the secondary outcome measures were the Activity of Daily Living (ADL) Scale and Stroke-Specific Quality of Life Scale (SS-QOL). The evaluations were at baseline (T0) at 4 weeks of treatment (T1) and at 12 weeks of follow-up without treatment (T2). RESULTS: At T1 and T2, there were significant differences in MAS between the two groups (p = 0.001). From the perspective of distribution, the VHS plus MDE group had significant changes, and the group-time interactions of upper and lower extremities in FMA, ADL, and SS-QOL were statistically significant (p < 0.001), indicating that patients' symptoms improved after treatment. But the overall effect size is small, especially the effect size of improvement in SS-QOL at T1. CONCLUSION: VHS in combination with MDE can consistently alleviate PSS, enhance limb function, and improve the quality of life of patients with PSS. But we need to optimize the device further and observe the improvement of patients for a more extended period.
Meridians , Quality of Life , Humans , Animals , Mice , Physical Therapy Modalities
The global coronavirus disease 2019 (COVID-19) has become one of the biggest threats to the world since 2019. The respiratory and gastrointestinal tracts are the main targets for severe acute respiratory syndrome coronavirus 2 infection for they highly express angiotensin-converting enzyme-2 and transmembrane protease serine 2. In patients suffering from COVID-19, gastrointestinal symptoms have ranged from 12% to 61%. Anorexia, nausea and/or vomiting, diarrhea, and abdominal pain are considered to be the main gastrointestinal symptoms of COVID-19. It has been reported that the direct damage of intestinal mucosal epithelial cells, malnutrition, and intestinal flora disorders are involved in COVID-19. However, the underlying mechanisms remain unclear. Thus, in this study, we reviewed and discussed the correlated mechanisms that cause gastrointestinal symptoms in order to help to develop the treatment strategy and build an appropriate guideline for medical workers.
COVID-19 , Gastrointestinal Diseases , Humans , COVID-19/complications , Gastrointestinal Diseases/therapy , Gastrointestinal Diseases/virology , Vomiting/therapy , Vomiting/virology
For the purpose of acquiring highly sensitive and differential spectra in in situ electrochemical nuclear magnetic resonance (EC-NMR) spectroscopy, uniform distributions of amplitudes and phases of radio frequency (RF) fields in the sample are needed for consistent flip angles of all nuclei under scrutiny. However, intrinsic electromagnetic incompatibility exists between such requirements with electric properties of the conductive material in an electrolytic cell, including metallic electrodes and ionic electrolytes. This proposed work presents the adverse repercussions of gradually varying electrolyte conductivity, which is strongly associated with the change of ion concentrations in a real-time electrochemical reaction, on spatial distributions of RF field amplitude and phase in the detective zone of an NMR probe coil. To compensate for such a non-linear trend of the spatial dependent distribution, we eliminate different excitation effects of the RF field on the build-in external standard and the electrolyte both situated in nearly the same detection area, as well as promote the greater accuracy of quantitative determination of reactant concentrations. The reliability and effectiveness of the improved in situ EC-qNMR (quantitative NMR) method are confirmed by the real-time monitoring of the electrochemical advanced oxidation process for phenol, in which instant concentrations of reactants and products are detected simultaneously to verify the degradation reaction scheme of phenol.
Magnetic Resonance Imaging , Radio Waves , Electrodes , Magnetic Resonance Spectroscopy , Reproducibility of Results
Catalpol is an iridoid glycoside extracted from the root of Rehmannia glutinosa. It has been reported to have antioxidant stress effects. Adenosine 5' monophosphate-activated protein kinase( AMPK) plays an important role in inhibiting oxidative stress. This study was designed to investigate the protective effects of catalpol on TNF-α-exposed human aorta epithelial cells( HAECs) via inhibit oxidative stress,and the relationship between catalpol and AMPK was detected by RNA interference technique. Levels of superoxide dismutase( SOD),malonaldehyde( MDA),glutathione( GSH) and lactate dehydrogenase( LDH) were measured with a colorimetric assay kit. The level of ROS was measured with FACS calibur. Western blot was employed to detect the protein expression of AMPK,phosphorylated-AMPK and NOX4. Finally,RNA interference technique was used to investigate the role of AMPK in catalpol-induced protective effects. TNF-α treatment decreased the expression of phosphorylated-AMPK protein level,however,catalpol could reverse the decreased phosphorylated-AMPK level. Catalpol could inhibit NOX4 protein expression and decrease ROS overproduction. After using AMPK siRNA that effects of catalpol on ROS overproduction and NOX4 protein expression inhibition were attenuated. The above results suggest that catalpol inhibits oxidative stress in TNF-α-exposed HAECs by activating AMPK.
Iridoid Glucosides/pharmacology , Humans , Iridoids , Oxidative Stress , Reactive Oxygen Species , Tumor Necrosis Factor-alpha
With the strength of liquid nuclear magnetic resonance (NMR) to noninvasively and specifically realize the structural elucidation and quantitative analysis of small organic molecules, in principle, liquid in situ electrochemical-NMR (EC-NMR) possesses great advantages for detecting dissolved species during the electrochemical process. However, the intrinsic incompatibilities between the coupling techniques as well as the sophisticated setups modification still limit the applications toward a wide range. To overcome these bottlenecks, herein we propose an easy-to-construct design with good compatibility and presenting improved electrochemical and NMR performances. As proof of concept, model experiments of alcohol electrooxidation were performed to confirm the capacity of this device for liquid in situ EC-NMR study. The temporal evolution of both the product and the current distributions can be reliably recorded to aid mechanistic and kinetic understanding of electrocatalysis. The depiction of the selective electrooxidation reveals the surface structure-catalytic functionality. This work demonstrates the universality and effectivity of the proposed platform to develop the liquid in situ EC-NMR technique as a useful tool for the dynamic analysis of electrochemical processes at a molecular level.
PURPOSE: To establish three-dimensional models of upper airway pre- and post-orthognathic surgery in patients with skeletal Class â ¢ malocclusion, and to compare the effects of different modes of orthognathic surgery on the cross-sectional areas and volumes of upper airway. METHODS: Twenty-eight patients with skeletal Class â ¢ malocclusion were divided into 2 groups. Group A (12 patients) underwent bilateral sagittal split ramus osteotomy(BSSRO) for mandibular setback, named single jaw surgery group; group B (16 patients) underwent BSSRO + Le Fort I osteotomy for mandibular setback and maxillary advancement, named bimaxillary surgery group. All patients received CT scanning before (T1) and 3 months after surgery (T2). The three-dimensional models of the upper airway containing velopharynx, glossopharynx and laryngopharynx were established by using Dolphin Imaging 11.7 software. The changes of sagittal diameters, coronal diameters, cross-sectional areas and volumes of the upper airway were measured and compared between the two groups pre- and post- surgery (T1, T2) using SPSS 16.0 software package, respectively. RESULTS: In velopharynx, the values of group A were decreased after surgery, while the other values of group B were increased except the value of coronal diameter. There was a significant difference between the two groups (P<0.05). In glossopharynx and laryngopharynx, the values of group A and group B were both decreased after surgery. The reduction of the cross-sectional areas and volumes in group A were more obvious than group B (P<0.05). CONCLUSIONS: The amount of narrowing of the upper airway is smaller in patients undergoing bimaxillary surgery than in patients undergoing mandibular setback surgery.
Malocclusion, Angle Class III , Orthognathic Surgery , Osteotomy, Le Fort , Cephalometry , Follow-Up Studies , Humans , Malocclusion, Angle Class III/surgery , Maxilla , Orthognathic Surgical Procedures , Osteotomy, Sagittal Split Ramus , Pharynx/surgery
We investigated the reversal effect of afatinib (AFT) on activity of adriamycin (ADR) in A549T cells and clarified the related molecular mechanisms. A549T cells overexpressing P-glycoprotein (P-gp) were resistant to anticancer drug ADR. AFT significantly increased the antitumor activity of ADR in A549T cells. AFT increased the intracellular concentration of ADR by inhibiting the function and expression of P-gp at mRNA and protein levels in A549T cells. Additionally, the reversal effect of AFT on P-gp mediated multidrug resistance (MDR) might be related to the inhibition of PI3K/Akt pathway. Cotreatment with AFT and ADR could enhance ADR-induced apoptosis and autophagy in A549T cells. Meanwhile, the co-treatment significantly induced cell apoptosis and autophagy accompanied by increased expression of cleaved caspase-3, PARP, LC3B-II, and beclin 1. Apoptosis inhibitors had no significant effect on cell activity, while autophagy inhibitors decreased cell viability, suggesting that autophagy may be a self protective mechanism of cell survival in the absence of chemotherapy drugs. Interestingly, when combined with AFT and ADR, inhibition of apoptosis and/or autophagy could enhance cell viability. These results indicated that in addition to inhibit P-gp, ADR-induced apoptosis, and autophagy promoted by AFT contributed to the antiproliferation effect of combined AFT and ADR on A549T cells. These findings provide evidence that AFT combined ADR may achieve a better therapeutic effect to lung cancer in clinic. J. Cell. Biochem. 119: 414-423, 2018. © 2017 Wiley Periodicals, Inc.
Doxorubicin/pharmacology , Gene Expression Regulation, Neoplastic/drug effects , Lung Neoplasms/drug therapy , Neoplasm Proteins/biosynthesis , Quinazolines/pharmacology , A549 Cells , ATP Binding Cassette Transporter, Subfamily B/biosynthesis , Afatinib , Humans , Lung Neoplasms/metabolism , Lung Neoplasms/pathology
Recently, accumulating evidence has indicated that glucocorticoid-induced osteoporosis (GIOP) is closely related to oxidative stress and apoptosis. Alpha-lipoic acid (LA), a naturally endogenous anti-oxidant, possesses anti-oxidative and anti-apoptosis activities, implicating LA as a therapeutic agent for the treatment of GIOP. In this study, the osteogenesis-promoting effects of LA against GIOP were investigated and the mechanisms were further probed. Here, the results showed that LA inhibited oxidative stress, suppressed apoptosis and improved osteopenia by promoting the expression of osteogenesis markers, including ALP, COL-I, OCN, BMP-2, RUNX2 and OSX. Further study revealed that the osteogenesis-promoting effects of LA likely occur via the regulation of the NOX4, NF-kappaB, JNK and PI3K/AKT pathways. The present study indicated that LA may prevent GIOP and promote osteogenesis and might be a candidate for the treatment of GIOP.
Antioxidants/pharmacology , Osteogenesis/drug effects , Osteoporosis/drug therapy , Signal Transduction , Thioctic Acid/pharmacology , Animals , Antioxidants/therapeutic use , Cell Line , Female , Glucocorticoids/toxicity , MAP Kinase Kinase 4/metabolism , NADPH Oxidase 4/metabolism , NF-kappa B/metabolism , Osteoporosis/etiology , Osteoporosis/metabolism , Phosphatidylinositol 3-Kinases/metabolism , Proto-Oncogene Proteins c-akt/metabolism , Rats , Rats, Sprague-Dawley , Thioctic Acid/therapeutic use
We report the design and the performance of a two-chamber thin-layer electrochemical device for in situ potential-dependent liquid NMR measurement. Liquid NMR spectra, simultaneously recorded with cyclic voltammetry (CV), have been obtained to reveal molecular changes with potentials scanning. As a proof of concept, redox properties of 1,4-benzoquinone based systems have been investigated, and a π dimerization has been identified by combining both in situ and ex situ NMR analyses. This work provides a new approach for spectroelectrochemistry, which will contribute to developing electrochemical NMR (EC-NMR) as an important tool for the analysis of electrochemical process at a molecular level.
Characterization of the forms of phosphorus (P) in four organic composts including compost of hulls and leaves of Castanea mollissima, edible fungi residues, corn stalks and chicken manure (BYZ), compost of edible fungi residues and chicken manure(ZF), composts of hulls and leaves of C. mollissima, edible fungi residues and chicken manure (BZ1 and BZ2) in Chinese chestnut producing area was conducted by sequential P fractionation developed by Dou et al. Field trial was conducted to study the effects of compost application on leaf phosphorus content of Castanea mollissima. The results showed that total phosphorus content(TP) of organic composts ranked as follows:BZ1(10.61 g·kg-1) > ZF(9.03 g·kg-1) > BYZ(8.56 g·kg-1) > BZ2(7.68 g·kg-1), and the inorganic phosphorus(Pi) accounted for 62.88%-73.62% of the total phosphorus in the organic composts. The content and proportion of HCl-P in the total fractionated phosphorus(Prt) was the highest among P forms in ZF, while that of H2O-P was the highest in BYZ, BZ1 and BZ2. The content of NaOH-P was very low in all the composts. Active H2O-Por NaHCO3-P had the highest inorganic phosphorus proportion(89.17%-96.00%) of all the P forms. The major Piforms in BZ2 were H2O- and HCl-extractable P fractions, while H2O-Pi, HCl-Pi and NaHCO3-Pi were major Pi forms in BYZ, BZ1 and ZF. Residual-P was the predominant organic phosphorus form, and BZ2 showed the highest Residual-P proportion of the total fractionated phosphorus(Prt) among all the composts. Leaf phosphorus contents per unit area of Castanea mollissima by field trial on the added phosphorus-equivalent basis were expressed as:BZ2>BZ1>BYZ>ZF>CK. Increment of leaf phosphorus content per unit area in Julyand per month on average showed positive relationship with the content and proportion of H2O-Pi in the total fractionated phosphorus of composts, which presumably played a key role in leaf phosphorus absorption of C. mollissima measured in the year of deep concentrated fertilization. The results suggested that composts of hulls and leaves of C. mollissima, edible fungi residues and chicken manure (BZ2) was a good choice in given area for aerobic composting raw material system in which organic wastes from Chinese chestnut industry accounted for 80% (hulls and leaves of Castanea mollissima and edible fungi residues accounted for 60% and 20% respectively), which had a high proportion of H2O-Pi and organic Residual-P pool and led to the highest leaf phosphorus content of C. mollissima.
Composting , Fagaceae/chemistry , Phosphorus/chemistry , Plant Leaves/chemistry , Soil/chemistry , Animals , Chickens , Fungi , Manure
Alisol B 23-acetate (AB23A) is a natural triterpenoid isolated from the traditional Chinese medicine rhizoma alismatis, which exhibits a number of pharmacological activities, including anti-hepatitis virus, anti-cancer and antibacterial effects. In this study we examined whether AB23A protected against non-alcoholic steatohepatitis (NASH) in mice, and the mechanisms underlying the protective effects. NASH was induced in mice fed a methionine and choline-deficient (MCD) diet for 4 weeks. The mice were simultaneously treated with AB23A (15, 30, and 60 mg·kg-1·d-1, ig) for 4 weeks. On the last day, blood samples and livers were collected. Serum liver functional enzymes, inflammatoru markers were assessed. The livers were histologically examined using H&E, Oil Red O, Masson's trichrome and Sirius Red staining. Mouse primary hepatocytes were used for in vitro experiments. The mechanisms underlying AB23A protection were analyzed using siRNA, qRT-PCR, and Western blot assays. AB23A treatment significantly and dose-dependently decreased the elevated levels of serum ALT and AST in MCD diet-fed mice. Furthermore, AB23A treatment significantly reduced hepatic triglyceride accumulation, inflammatory cell infiltration and hepatic fibrosis in the mice. AB23A-induced decreases in serum and hepatic lipids were related to decreased hepatic lipogenesis through decreasing hepatic levels of SREBP-1c, FAS, ACC1 and SCD1 and increased lipid metabolism via inducing PPARα, CPT1α, ACADS and LPL. The reduction in inflammatory cell infiltration corresponded to deceased serum levels of mKC and MCP-1 and decreased hepatic gene expression of MCP-1 and VCAM-1. The reduction in hepatic fibrosis was correlated with decreased hepatic gene expression of fibrosis markers. The protective effects of AB23A were FXR-dependent, because treatment with the FXR agonist CDCA mimicked AB23A-induced hepato-protection in the mice, whereas co-administration of FXR antagonist guggulsterone abrogated AB23A-induced hepato-protection. In mouse primary hepatocytes, FXR gene silencing abrogated AB23A-induced changes in gene expression of Apo C-II, CPT1α, ACADS and LPL. AB23A produces protective effects against NASH in mice via FXR activation.
Cholestenones/pharmacology , Non-alcoholic Fatty Liver Disease/prevention & control , Receptors, Cytoplasmic and Nuclear/agonists , Animals , Chenodeoxycholic Acid/pharmacology , Cholestenones/antagonists & inhibitors , Choline Deficiency , Dose-Response Relationship, Drug , Fibrosis/pathology , Gene Expression/drug effects , Hepatocytes/metabolism , Lipid Metabolism/drug effects , Lipogenesis/drug effects , Liver/enzymology , Liver/metabolism , Liver/pathology , Male , Methionine/deficiency , Mice , Pregnenediones/pharmacology , Primary Cell Culture , Protective Agents/pharmacology , Receptors, Cytoplasmic and Nuclear/antagonists & inhibitors
OBJECTIVE: To investigate the influences of mobile phone radiation on the quality and DNA methylation of human sperm in vitro. METHODS: According to the fifth edition of the WHO Laboratory Manual for the Examination and Processing of Human Semen, we randomly selected 97 male volunteers with normal semen parameters and divided each semen sample from the subjects into two equal parts, one exposed to mobile phone radiation at 1950 M Hz, SAR3. 0 W/kg for 3 hours while the other left untreated as the control. We obtained routine semen parameters as well as the acrosomal reaction ability, apoptosis and DNA methylation of sperm, and compared them between the two groups. RESULTS: Compared with the control, the radiation group showed significantly decreased progressive sperm motility ([36.64 ± 16.93] vs [27.56 ± 16.92]%, P < 0.01) and sperm viability ([63.72 ± 16.35] vs [54.31 ± 17.35]%, P < 0.01) and increased sperm head defects ([69.92 ± 4.46] vs [71.17 ± 4.89]%, P < 0.05), but no significant differences in sperm acrosomal reaction ([66.20 ± 6.75] vs [64.50 ± 3.47]%, P > 0.05). The early apoptosis rate of sperm cells was remarkably higher in the radiation group ([6.89 ± 9.84]%) than in the control ([4.44 ± 5.89]%) (P < 0.05). However, no statistically significant differences were found between the control and radiation groups in the DNA methylation patterns of the paternal imprinting gene H19 ICR ([0.60 ± 0.02] vs [1.40 ± 0.03]%, P > 0.05) or the maternal imprinting gene KvDMR1 ([0.00 ± 0.00] vs [1.80 ± 0.031%, P > 0.05). CONCLUSION: Mobile phone radiation reduces the progressive motility and viability of human sperm and increases sperm head defects and early apoptosis of sperm cells.
DNA Methylation/radiation effects , Spermatozoa/radiation effects , Cell Phone , Humans , In Vitro Techniques , Male , Semen/radiation effects , Semen Analysis , Sperm Head/radiation effects , Sperm Motility/radiation effects , Spermatozoa/cytology
Alpha-lipoic acid (ALA), a naturally occurring compound and dietary supplement, has been established as a potent antioxidant that is a strong scavenger of free radicals. Recently, accumulating evidences has indicated the relationship between oxidative stress and osteoporosis (OP). Some studies have investigated the possible beneficial effects of ALA on OP both in vivo and in vitro; however, the precise mechanism(s) underlying the bone-protective action of ALA remains unclear. Considering this, we focused on the anti-oxidative capacity of ALA to exert bone-protective effects in vitro and in vivo. In the present study, the effects of ALA on osteoblastic formation in H(2)O(2) -treated MC3T3-E1 pre-osteoblasts and ovariectomy (OVX)-induced bone loss in rats were investigated. The results showed that ALA promoted osteoblast differentiation, mineralization and maturation and inhibited osteoblast apoptosis, thus increasing the OPG/receptor activator of nuclear factor-κB (NF-κB) ligand (RANKL) ratio and leading to enhanced bone formation in vitro and inhibited bone loss in vivo. Further study revealed that ALA exerted its bone-protective effects by inhibiting reactive oxygen species (ROS) generation by down-regulating Nox4 gene expression and protein synthesis and attenuating the transcriptional activation of NF-κB. In addition, ALA might exert its bone-protective effects by activating the Wnt/Lrp5/ß-catenin signaling pathway. Taken together, the present study indicated that ALA promoted osteoblastic formation in H(2)O(2) -treated MC3T3-E1 cells and prevented OVX-induced bone loss in rats by regulating Nox4/ROS/NF-κB and Wnt/Lrp5/ß-catenin signaling pathways, which provided possible mechanisms of bone-protective effects in regulating osteoblastic formation and preventing bone loss. Taken together, the results suggest that ALA may be a candidate for clinical OP treatment.
Bone Resorption/drug therapy , Free Radical Scavengers/administration & dosage , Osteoporosis/drug therapy , Thioctic Acid/administration & dosage , Animals , Apoptosis/drug effects , Bone Resorption/pathology , Cell Differentiation/drug effects , Female , Humans , Hydrogen Peroxide/administration & dosage , Osteoblasts/drug effects , Osteogenesis/drug effects , Osteoporosis/pathology , Ovariectomy , RANK Ligand/biosynthesis , Rats , Wnt Signaling Pathway
Intrahepatic cholestasis is a clinical syndrome with systemic and intrahepatic accumulation of excessive toxic bile acids that ultimately cause hepatobiliary injury. Appropriate regulation of bile acids in hepatocytes is critically important for protection against liver injury. In the present study, we characterized the protective effect of alisol B 23-acetate (AB23A), a natural triterpenoid, on alpha-naphthylisothiocyanate (ANIT)-induced liver injury and intrahepatic cholestasis in mice and further elucidated the mechanisms in vivo and in vitro. AB23A treatment dose-dependently protected against liver injury induced by ANIT through reducing hepatic uptake and increasing efflux of bile acid via down-regulation of hepatic uptake transporters (Ntcp) and up-regulation of efflux transporter (Bsep, Mrp2 and Mdr2) expression. Furthermore, AB23A reduced bile acid synthesis through repressing Cyp7a1 and Cyp8b1, increased bile acid conjugation through inducing Bal, Baat and bile acid metabolism through an induction in gene expression of Sult2a1. We further demonstrate the involvement of farnesoid X receptor (FXR) in the hepatoprotective effect of AB23A. The changes in transporters and enzymes, as well as ameliorative liver histology in AB23A-treated mice were abrogated by FXR antagonist guggulsterone in vivo. In vitro evidences also directly demonstrated the effect of AB23A on FXR activation in a dose-dependent manner using luciferase reporter assay in HepG2 cells. In conclusion, AB23A produces protective effect against ANIT-induced hepatotoxity and cholestasis, due to FXR-mediated regulation of transporters and enzymes.
1-Naphthylisothiocyanate , Bile Acids and Salts/metabolism , Chemical and Drug Induced Liver Injury/prevention & control , Cholestasis, Intrahepatic/prevention & control , Cholestenones/pharmacology , Liver/drug effects , Membrane Transport Proteins/metabolism , Protective Agents/pharmacology , Receptors, Cytoplasmic and Nuclear/drug effects , Animals , Chemical and Drug Induced Liver Injury/genetics , Chemical and Drug Induced Liver Injury/metabolism , Chemical and Drug Induced Liver Injury/pathology , Cholestasis, Intrahepatic/genetics , Cholestasis, Intrahepatic/metabolism , Cholestasis, Intrahepatic/pathology , Cytoprotection , Disease Models, Animal , Dose-Response Relationship, Drug , Gene Expression Regulation, Enzymologic , Hep G2 Cells , Homeostasis , Humans , Liver/metabolism , Liver/pathology , Male , Mice, Inbred C57BL , Receptors, Cytoplasmic and Nuclear/genetics , Receptors, Cytoplasmic and Nuclear/metabolism , Signal Transduction/drug effects , Time Factors , Transfection
Icariin (ICA), a Traditional Chinese Medicine, has been demonstrated to be a promoting compound for extracellular matrix synthesis and gene expression of chondrocytes. However, whether ICA can act as a substitute for or cooperate with growth factors to directly promote stable chondrogenesis of bone marrow mesenchymal stem cells (BMSCs) remains unknown. In the present study, rat BMSCs were cultivated in monolayer cultures with a chondrogenic medium containing transforming growth factor-ß3 for 14 days; ICA was added to the same chondrogenic medium throughout the culture period at a concentration of 1×10-6 M. Cell morphology was observed using an inverted microscope, and chondrogenic differentiation markers, including collagen II, aggrecan and SRY (sex determining region Y)-box 9 (SOX9), were detected by immunofluorescence, reverse transcription-quantitative polymerase chain reaction and western blot analysis. Hypertrophic differentiation was also analyzed using collagen I gene expression and alkaline phosphatase (ALP) activity. The results revealed that ICA was effective at forming an increased number of and larger aggregates, and significantly upregulated the mRNA expression levels and protein synthesis of collagen II, aggrecan and SOX9. Furthermore, the chondrogenic medium alone caused hypertrophic differentiation through the upregulation of collagen I gene expression and ALP activity, which was not potentiated by the presence of ICA. Thus, ICA promoted directed chondrogenic differentiation of BMSCs, but had no effect on hypertrophic differentiation. The present results also suggested that ICA may be an effective accelerant of growth factors for cartilage tissue engineering by promoting their chondrogenic differentiating effects but reducing the effect of hypertrophic differentiation.
BACKGROUND: The pharmacokinetic (PK) studies of phosphocreatine (PCr) and its active metabolite creatine (Cr) are considerably lacking. This study is to comparatively investigate the PK profiles of PCr and Cr in mice plasma and myocardium as well as the ATP level. METHODS: After iv administration of equimolar PCr and preformed Cr to healthy and Pit-induced myocardial ischemic mice, plasma and myocardium samples were analyzed for exogenous PCr, Cr and related ATP concentrations using a specific ion-pair reversed-phase HPLC-UV assay. RESULTS: The plasma C-T data of iv PCr and Cr were well fitted to two-compartment model. Following iv PCr, Cr appeared in plasma as early as 1.0 min postdose with a longer t1/2 than PCr and had a fm of 72%. The mice dosed iv PCr preceded 5 min by ip Pit 30 U/kg showed longer t1/2ß PCr and t1/2 Cr in plasma and elevated Cmax, Cr and Cmax, ATP in myocardium compared with mice dosed iv PCr alone, and it was estimated that about 40% ATP produced by iv PCr was from Cr. CONCLUSION: The PCr in plasma is converted to Cr rapidly and mostly, and shows an elimination rate limited (ERL) metabolite disposition. Iv PCr caused a significantly elevated and long-lasing myocardial ATP and Cr levels. The Pit-induced myocardial ischemia brings slower elimination of PCr and Cr and higher peak concentrations of Cr and ATP in myocardium. The metabolite Cr at least partially mediates PCr-caused rise in myocardial ATP level and also possibly the cardio-protective effects of PCr.
Creatine/metabolism , Myocardial Ischemia/physiopathology , Myocardium/metabolism , Phosphocreatine/pharmacokinetics , Adenosine Triphosphate/metabolism , Animals , Chromatography, High Pressure Liquid , Disease Models, Animal , Half-Life , Male , Mice , Pituitary Hormones, Posterior/administration & dosage , Spectrophotometry, Ultraviolet
With the deepening of modernization of traditional Chinese medicine (TCM) and continuing emergence of new theories, methods and techniques, a very rapid and significant development has been achieved in the pharmacokinetics (PK) of TCM. This paper reviews the main research progresses of PK of TCM, including integrated PK of multiple effective components of TCM, fingerprint PK of TCM, novel dosage form PK of TCM, polysaccharide PK of TCM and drug interactions of TCM; and further sets up the prospects.
Drugs, Chinese Herbal/pharmacokinetics , Medicine, Chinese Traditional/methods , Animals , Drug Combinations , Drug Interactions , Drugs, Chinese Herbal/administration & dosage , Drugs, Chinese Herbal/analysis , Drugs, Chinese Herbal/chemistry , Drugs, Chinese Herbal/isolation & purification , Emulsions/pharmacokinetics , Humans , Liposomes/pharmacokinetics , Nanostructures , Plants, Medicinal/chemistry , Polysaccharides/pharmacokinetics
OBJECTIVE: To investigate the inhibitory effects of ursolic acid (UA) on the expression of C-reactive protein (CRP) induced by IL-6 in HepG2 cells and the protective effects on the CRP-induced injury to human umbilical vein endothelial cells (HUVECs). METHODS: HepG2 cells were treated with IL-6 or IL-6 and different concentrations of UA for 48 h, then the cells were collected. The total protein and RNA of the cells were extracted for western blotting and RT-PCR methods to detect CRP protein and mRNA expression. HUVECs were treated with CRP or CRP and different concentrations of UA for 24h. Cell proliferation in each group was assayed by MTT. Cells were collected for western blotting and RT-PCR methods to detect VCAM-1, LOX-1 protein or mRNA expression. RESULT: IL-6 can significantly increase CRP protein and mRNA expression in HepG2 cells, and this effect of IL-6 can be decreased by UA (6.25, 12.5, 25 µmol/L) markedly in a dose-dependent manner. UA can inhibit CRP-induced proliferation of HUVECs. CRP can obviously increase LOX-1/VCAM-1 expression in HUVECs, both on mRNA and protein levels and the effect of CRP can be inhibited by UA (5, 10, 20 µmol/L) in a dose-dependent manner. CONCLUSION: UA can reduce the over expression of CRP in HepG2 cells induced by IL-6 and inhibit the increased expression of VCAM-1 and LOX-1 in HUVECs caused by CRP. Our research suggests that UA can reduce CRP levels in plasma and prevent inflammatory cytokines from injuring endothelial cells by inhibiting the hepatic synthesis of CRP. So UA may have positive significance for prevention and treatment of atherosclerosis and other cardiovascular diseases.
Anti-Inflammatory Agents, Non-Steroidal/pharmacology , C-Reactive Protein/metabolism , Down-Regulation/drug effects , Endothelium, Vascular/drug effects , Hepatocytes/drug effects , Interleukin-6/metabolism , Triterpenes/pharmacology , Atherosclerosis/drug therapy , Atherosclerosis/prevention & control , C-Reactive Protein/antagonists & inhibitors , C-Reactive Protein/genetics , Cell Proliferation/drug effects , Cells, Cultured , Endothelium, Vascular/immunology , Endothelium, Vascular/metabolism , Hep G2 Cells , Hepatocytes/immunology , Hepatocytes/metabolism , Human Umbilical Vein Endothelial Cells/drug effects , Humans , Osmolar Concentration , RNA, Messenger/metabolism , Real-Time Polymerase Chain Reaction , Reverse Transcriptase Polymerase Chain Reaction , Scavenger Receptors, Class E/metabolism , Up-Regulation/drug effects , Vascular Cell Adhesion Molecule-1/genetics , Vascular Cell Adhesion Molecule-1/metabolism , Ursolic Acid
The present study investigated the effect and possible mechanisms of α-lipoic acid (LA) in preventing endothelial cell injury induced by oxidized low-density lipoprotein (oxLDL). A model of human umbilical vein endothelial cell (HUVEC) injury was established by incubating the HUVECs with 200 µg/ml oxLDL. HUVECs were pre-treated with 0.1, 0.2 or 0.5 mmol/l of LA in the presence of oxLDL for 24 h. Apoptosis and cellular surface ceramide content were investigated separately by flow cytometry and by LC-MS/MS. LOX-1, Bcl-2 and CRP protein expression levels were evaluated by western blotting. LOX-1 mRNA expression was evaluated by RT-PCR assay. The results showed that oxLDL induced cytotoxicity in both concentration-dependent and time-dependent manners. LA boosted the cell survival rate and significantly reduced the content of MDA and lactate dehydrogenase (LDH) leakage. Apoptotic rates were significantly reduced by the addition of LA compared to oxLDL group. LA might also have inhibited ceramide generation induced by oxLDL in a dose-dependent manner. Furthermore, LA down-regulated LOX-1 protein and mRNA expression and up-regulated Bcl-2 protein expression levels in a dose-dependent manner. Expression of CRP protein was weak and undetectable. These results suggested that LA exhibited cytoprotective effects against oxLDL by decreasing apoptotic rates and decreasing cellular surface ceramide content, two effects that are related to decreased LOX-1 expression, and also by stimulating the expression of Bcl-2 protein. The cytoprotective effects are not thought to be due to inhibited C-reactive protein (CRP) protein expression in HUVECs.
Endothelial Cells/drug effects , Lipoproteins, LDL/toxicity , Thioctic Acid/pharmacology , Apoptosis/drug effects , Cell Survival/drug effects , Cytoprotection/drug effects , Dose-Response Relationship, Drug , Endothelial Cells/pathology , Flow Cytometry , Gene Expression Regulation/drug effects , Human Umbilical Vein Endothelial Cells , Humans , Lipoproteins, LDL/administration & dosage , Proto-Oncogene Proteins c-bcl-2/genetics , Reverse Transcriptase Polymerase Chain Reaction , Scavenger Receptors, Class E/genetics , Thioctic Acid/administration & dosage , Time Factors
OBJECTIVE: To review tension-free repairing for the patients with inguinal hernia complicated with cirrhosis and ascites. METHODS: Tension-free herniorrhaphy was performed in 16 cases with inguinal hernia complicated with cirrhosis and ascites from November 1999 to November 2003. The laboratory data before and after the operation were compared and analyzed in this group. RESULTS: Of the patients, 13 cases were male and 3 were female, the mean age was (64 ± 12) years (range, 37 - 85 years). The liver function was classified as A degree in 4 case, B degree in 10 cases and C degree in 2 patients by using Child score. The operation was successfully carried out in all patients without complications and post-operative hepatoencephalopathy. There was no significant change in the plasma total protein, bilirubin, prothrombin activity and international normalized ratio (INR) after the operation. And the levels of albumin, globulin and white blood cell count changed remarkably after the operation (all P < 0.05). Plasma albumin level was obviously effected by the operation and treatment (P = 0.006). The mean follow-up time was 72.5 months (57 - 102 months). No recurrence occurred during the follow-up. There was no patient died in 30 days after the operation. Seven cases (43.8%) died in the later period of follow-up. CONCLUSIONS: The tension-free repairing is feasible for the inguinal hernia complicated with cirrhosis and ascites. More attention should be paid to the level of plasma albumin and it should be corrected in time. The liver cirrhosis and its complications will progress after the operation with a poor prognosis.
Ascites/complications , Hernia, Inguinal/surgery , Liver Cirrhosis/complications , Adult , Aged , Aged, 80 and over , Female , Follow-Up Studies , Hernia, Inguinal/complications , Humans , Male , Middle Aged , Prognosis , Retrospective Studies
