Female ; Humans ; Integrative Medicine ; Polycystic Ovary Syndrome ; therapy

Glomerular hypertrophy is the main pathological characteristic in the early stage of diabetic nephropathy (DN), and its regulatory mechanism is closely related to mammalian target of rapamycin (mTOR) signaling pathway activity. mTOR includes mTOR complex 1 (mTORC1) and mTOR complex 2(mTORC2), in which, the upstream pathway of mTORC1 is phosphatidylinositol-3-kinase (PI3K)/serine-threonine kinase(Akt)/adenosine monophosphate activated protein kinase(AMPK), and the representative signaling molecules in the downstream pathway of mTORC1 are 4E-binding proteins(4EBP) and phosphoprotein 70 S6Kinase(p70S6K). Some Chinese herbal extracts could improve cell proliferation via intervening the expressions of the key molecules in the upstream or downstream of PIK/Akt/mTOR signaling pathway in vivo. As for glomerular mesangial cells(MC) and podocyte, mTOR plays an important role in regulating glomerular inherent cells, including adjusting cell cycle, energy metabolism and matrix protein synthesis. Rapamycin, the inhibitor of mTOR, could suppress glomerular inherent cell hypertrophy, cell proliferation, glomerular basement membrane (GBM) thickening and mesangial matrix deposition in model rats with DN. Some Chinese herbal extracts could alleviate glomerular lesions by intervening mTOR signaling pathway activity in renal tissue of DN animal models or in renal inherent cells in vivo and in vitro.
Animals ; Diabetic Nephropathies ; drug therapy ; enzymology ; genetics ; pathology ; Drugs, Chinese Herbal ; administration & dosage ; Humans ; Hypertrophy ; drug therapy ; enzymology ; genetics ; pathology ; Kidney Glomerulus ; drug effects ; metabolism ; pathology ; Signal Transduction ; drug effects ; TOR Serine-Threonine Kinases ; genetics ; metabolism

In clinic, some urinary protein makers can dynamically and noninvasively reflect the degree of renal tubular injury in patients with diabetic nephropathy (DN). These urinary biomarkers of tubular damage are broadly divided into two categories. One is newfound, including kidney injury molecule-1 (Kim-1), neutrophil getatinase-associated lipocalin (NGAL), liver-type fatty acid-binding protein (L-FABP) and cystatin C (CysC); the other one is classical, including beta2 microglobulin (beta2-MG), retinal binding protein (RBP) and N-acetyl-beta-D-glucosaminidase (NAG). It is reported that, the increases in urinary protein markers are not only closely related to the damage of tubular epithelial cells in DN patients, but also can be ameliorated by the treatment with Chinese herbal compound preparations or Chinese herbal medicine. Recently, although urinary proteomics are used in the protein separation and identification, the traditional associated detection of urinary protein markers is more practical in clinic. At present, it is possible that the associated detection of urinary biomarkers of glomerular and tubular damages may be a feasible measure to reveal the clinical significance of urinary protein markers in DN patients and the interventional effects of Chinese herbal medicine.
Biomarkers ; urine ; Diabetic Nephropathies ; complications ; drug therapy ; urine ; Drugs, Chinese Herbal ; pharmacology ; therapeutic use ; Humans ; Medicine, Chinese Traditional ; methods ; Proteinuria ; complications

To analyze the characteristic of urinary protein spectrum in patients with stage III diabetic nephropathy (DN) and its compliance with traditional Chinese medicine (TCM)symptom, for the sake of providing a basis for clarifying the rules of TCM syndrome differentiation in DN. Adopting the traditional epidemiological retrospective method, thirty-eight TCM syndromes and urinary protein with medium or low molecular weight, as well as urinary enzyme, including 24 h urinary protein (Upro), urinary albumin( UAlb), urinary retinal binding protein( URBP), urinary cystatin C (UCysC), urinary N-acetyl-beta-D-glucosaminidase (UNAG), were collected from 108 patients with stage III DN, and a multiple factor regression analysis between them was conducted. As the results, the levels of Upro, UAlb, URBP, UCysC, and UNAG were increased in 108 patients with stage III DN. Qi-Yin deficiency type was the major type. The level of UAlb in patients with Qi-Yin deficiency type was significantly higher than those without Qi-Yin deficiency type (P < 0.05). The elevation of Upro with the factors as swift digestion with rapid hungering, lassitude and lack of strength, weakness of waist and knees was complied, the elevation of UA1b with the factors as dry mouth with desire to drink, the elevation of URBP with the factors as numbness of extremities, shortness of breath, the elevation of UCysC with the factors as clear urine in large amounts, and the elevation of UNAG with the factors as frequent micturition, were complied respectively. In conclusion, for 108 stage III DN patients. The increase in urinary protein spectrum including UAlb, URBP, UCysC, and UNAG is the major characteristic. Shen and Pi are the major organs related to the appearance of urinary protein; Pi-Shen deficiency is the basic pathogenesis. The level of UAlb is taken as one of the objective syndrome factors for Qi-Yin deficiency type. The levels of UNAG and UCysC are possibly the objective syndrome factors for Shen-Qi deficiency type.
Diabetic Nephropathies ; complications ; diagnosis ; urine ; Female ; Humans ; Male ; Medicine, Chinese Traditional ; methods ; Middle Aged ; Proteinuria ; complications ; urine ; Qi ; Regression Analysis ; Yin-Yang

Adolescent ; Adult ; Cardiac Catheterization ; economics ; methods ; Cardiac Surgical Procedures ; economics ; methods ; Cardiac Valve Annuloplasty ; Child ; China ; epidemiology ; Echocardiography ; Female ; Heart Septal Defects, Ventricular ; complications ; diagnostic imaging ; surgery ; Humans ; Length of Stay ; statistics & numerical data ; Male ; Operative Time ; Postoperative Complications ; epidemiology ; Septal Occluder Device ; Tricuspid Valve Insufficiency ; complications ; diagnostic imaging ; surgery ; Young Adult

AIMTo study the pharmacokinetics of fudosteine in healthy volunteers after the single and multiple dose administration.

METHODSThirty-six volunteers were divided into three groups randomly, each group included six men and six women. In the single dose design, the volunteers received either a single dose of 600 mg, 400 mg or 200 mg fudosteine. After a one-week wash out period, the volunteers of 400 mg group participated in the multiple dose design in which each volunteer received 400 mg fudosteine three times a day for five consecutive days. The plasma concentrations were determined by pre-column derivatization HPLC-FL method and the pharmacokinetic parameters of fudosteine were calculated.

RESULTSThe obtained pharmacokinetic parameters of fudosteine in single dose of 600 mg, 400 mg and 200 mg groups were as follows: T1/2 were (2.8 +/- 0.5), (2.7 +/- 0.5) and (3.2 +/- 0.6) h, respectively. T(max) were (0.51 +/- 0.22), (0.59 +/- 0.21) and (0.48 +/- 0.18) h, respectively. C(max) were (16 +/- 4), (11 +/- 3) and (6.1 +/- 1.5) microg x mL(-1), respectively. The AUC(0-10 h) and C(max) correlated linearly with doses, respectively (r > 0.99). The T(max), C(max) and AUC values of fudosteine in healthy male volunteers were smaller than those in female volunteers, and the T1/2 value was longer than that in female volunteers. The obtained multi-dose pharmacokinetic parameters of fudosteine were as follows: C(ss) was (4.1 +/- 0.8) microg x mL(-1); DF was 3.0 +/- 0.7; T1/2 was (2.5 +/- 0.4) h; T(max) was (0.6 +/- 0.3) h; C(max) was (13.2 +/- 1.3) microg x mL(-1).

CONCLUSIONThe values of pharmacokinetic parameters in healthy volunteers were linear in the range from 200 mg to 600 mg. Statistic analysis results showed that the differences of AUC and C(max) between men and women were not resulted from sexual differences, but from the weight differences. There was no significant difference in pharmacokinetic parameters between single dose and multi-dose.

Administration, Oral ; Adult ; Area Under Curve ; Body Weight ; Chromatography, High Pressure Liquid ; methods ; Cystine ; administration & dosage ; analogs & derivatives ; pharmacokinetics ; Dose-Response Relationship, Drug ; Female ; Humans ; Male ; Sex Factors

Objective To investigate the characteristics of radiation-induced optic neuropathy (RON) in patients with nasopharypgeal carcinoma after radiotherapy,and explore its risk factors.Methods A retrospective study was performed on the clinical data of 22 RON patients with nasopharyngeal carcinoma after radiotherapy,admitted to our hospital from January 1997 to January 2011.Their clinical manifestations,eye examinations and cranial MRI data were concluded.Results Visual deterioration,or even,blindness,was the most common manifestation.RON occurred after the initial radiotherapy in 18 cases,and during the initial radiotherapy in 2 cases.And 2 cases developed RON in re-irradiation for recurrences.Blindness developed in 8 eyes,and decreased vision occurred in 27 eyes; 14 patients displayed retinal optic nerve atrophy in the eye examinations.Typical radiological imaging of the skull showed optic nerve enlargement in 30 eyes,optic nerve atrophy in 5 eyes; and the incidence of optic neuropathy was high when radiation dose was over 70 Gy.Conclusion RON may occur in nasopharyngeal carcinoma patients following radiotherapy,having vision disorders,visual field changes,abnormal visual evoked potential and typical cranial imaging performances; the occurrence of RON may be correlated with radiation field and radiation dose; routine eye and imaging examination is of great significance.

OBJECTIVETo construct the eukaryotic expression vector of human microdystrophin gene and observe its expression in rat mesenchymal stem cells (rMSCs) in vitro.

METHODSThe plasmid PBSK-MICRO containing human microdystrophin cDNA was digested by restriction endonuclease, and the resultant microdystrophin fragment was inserted into the NotI site of pcDNA3.1(+) to prepare the eukaryotic expression vector-pcDNA3.1(+)/ microdystrophin, which was identified by endonuclease digestion and sequencing. The recombinant plasmid was transfected into rMSCs via lipofectamine, and after G418 selection, the expression of microdystrophin was detected by RT-PCR and indirect immunofluorescence assay.

RESULTSMicrodystrophin gene fragment was correctly inserted into the plasmid pcDNA3.1(+), as conformed by sequencing and digestion with Not I and Hind III. The total mRNA of the transfected rMSCs was extracted and microdystrophin mRNA expression was found in the cells by RT-PCR. Indirect immunofluorescence assay for the protein expression of microdystrophin showed bright red fluorescence in the transfected rMSCs.

CONCLUSIONEukaryotic expression plasmid pcDNA3.1(+)/microdystrophin has been constructed successfully and microdystrophin can be expressed in transfected rMSCs in vitro, which may facilitate further research of Duchenne muscular dystrophy treatment by genetically modified allogeneic stem cell transplantation.

Animals ; Base Sequence ; Cells, Cultured ; Dystrophin ; biosynthesis ; genetics ; Fluorescent Antibody Technique, Indirect ; Gene Expression ; Humans ; Mesenchymal Stromal Cells ; cytology ; metabolism ; Molecular Sequence Data ; Peptide Fragments ; biosynthesis ; genetics ; Plasmids ; genetics ; RNA, Messenger ; biosynthesis ; genetics ; metabolism ; Rats ; Rats, Sprague-Dawley ; Reverse Transcriptase Polymerase Chain Reaction ; Transfection

To investigate the effect of arsenic trioxide (As(2)O(3)) or all-trans retinoic acid (ATRA) on the mRNA and protein expression of tissue factor (TF) and thrombomodulin (TM) and procoagulant activity (PCA) in NB4 cells. The NB4 cells were cultured in vitro and treated with As(2)O(3) or ATRA, expression of TF and TM antigen, and PCA change of treated NB4 cells were detected with ELISA, TF and TM mRNA transcription on the NB4 cells was assayed with reversed transcription polymerase chain reaction (RT-PCR). The results showed that 1 micromol/L As(2)O(3) and 1 micromol/L ATRA both gradually downregulated the expression of TF antigen and mRNA on NB4 cells, a human promyelocytic leukemia cell line, in time-dependent manner, as compared with control. The levels of TF antigen expression in AS(2)O(3) group were 13.3 +/- 1.8, 8.6 +/- 1.9, 10.8 +/- 1.5, 2.0 +/- 0.6 and 2.6 +/- 0.9 ng/10(7) respectively; while the levels of TF antigen expression in ATRA group were 12.4 +/- 1.1, 11.3 +/- 1.8, 5.7 +/- 1.7, 2.8 +/- 0.8 and 2.0 +/- 0.6 ng/10(7) at 24, 48, 72, 96 and 120 hours respectively (P<0.05). The procoagulant activity (PCA) of NB4 cells was decreased, blood coagulation times were 123.5 +/- 10.5, 156.3 +/- 11.6, 179.3 +/- 15.3, 248.9 +/- 20.1, 312.0 +/- 29.8 seconds in As(2)O(3) groups, respectively; 76.4 +/- 5.6, 146.8 +/- 10.9, 198.2 +/- 15.6, 265.8 +/- 20.6 and 363.8 +/- 31.9 seconds in ATRA groups respectively at 24, 48, 72, 96 and 120 hours (P<0.05). ATRA upregulated TM antigen expression on NB4 cells. It is concluded that the As(2)O(3) and ATRA decrease mRNA transcription of TF, downregulate expression of TF and reduce procoagulant activity in NB4 cells. The TM transcription and expression upregulated by ATRA may alleviate dysfunction of coagulation in APL.
Antineoplastic Agents ; pharmacology ; Arsenicals ; pharmacology ; Humans ; Leukemia, Promyelocytic, Acute ; metabolism ; pathology ; Oxides ; pharmacology ; RNA, Messenger ; biosynthesis ; genetics ; Thrombomodulin ; biosynthesis ; genetics ; Thromboplastin ; biosynthesis ; genetics ; metabolism ; Tretinoin ; pharmacology ; Tumor Cells, Cultured

OBJECTIVETo observe the effect of intracoronary transfer of autologous HO-1 overexpressed MSCs in porcine model of myocardial ischemia (1 h)/reperfusion.

METHODSApoptosis was assayed and cytokine concentrations in supernatant were measured in cells exposed to hypoxia-reoxygen in vitro. In vivo, Chinese male mini-pigs were allocated to the following treatment groups: control group (saline), MSCs group (MSCs), MSCs transfected with pcDNA3.1-nHO-1 (HO-1-MSCs). 1 x 10(7) of autologous stem cells or identical volume of saline was injected intracoronary into porcine hearts 1 h after ischemia. MRI assay and postmortem analysis were assessed 3 months after stem cell transplantation.

RESULTSIn vitro, cell apoptosis rate post hypoxia-reoxygen was significantly reduced in HO-1-MSCs group (30.30% +/- 7.64%) compared with that in MSCs group (56.93% +/- 4.68%, P < 0.001) and LacZ-MSCs group (55.88% +/- 4.38%, P < 0.001), VEGF was also significantly upregulated in HO-1-MSCs group [(768.44 +/- 78.38) pg/ml] compared with that in MSCs group [(555.27 +/- 67.67) pg/ml, P < 0.001] and LacZ-MSCs group [(522.97 +/- 71.45) pg/ml, P < 0.001]. In vivo, cardiac function was significantly improved in both MSCs transplantation groups compared to saline group (all P < 0.05 vs.saline) and the left ventricular ejection fraction was significantly higher in HO-1-MSCs group compared with that in MSCs group at 3 months after transplantation (53.50% +/- 2.09% vs. 49.54% +/- 2.74%, P = 0.017), capillary density in the peri-infarct area was also significantly higher in HO-1-MSC group than that in MSCs group [(14.59 +/- 2.39)/HPF vs. (11.78 +/- 2.48)/HPF, P = 0.033].

CONCLUSIONSEfficacy of HO-1 overexpressed MSCs on improving cardiac function and promoting angiogenesis was greater than those by MSCs in this porcine ischemia/reperfusion model.

Animals ; Apoptosis ; Cells, Cultured ; Genetic Vectors ; Heme Oxygenase-1 ; genetics ; Male ; Mesenchymal Stem Cell Transplantation ; Myocardial Infarction ; therapy ; Myocardial Ischemia ; therapy ; Swine ; Swine, Miniature ; Transfection