Traditional medicine (herb medicine) began to prevail again over last two decades, and it is about 70% of the world population taking herb medicine as supplement or alternative medicine according to a recent survey. The consumption of herb medicine increased exponentially in Canada, Australia and Europe during last 10 years. Since concomitant administration of herbal and western medicine has become a trend, it requires paying close attention to the problem. Herb-drug interactions have been extensively investigated worldwide, and there is an increasing concern about the clinical herb-drug interaction. In this review we introduced the current progress in the herb-drug interactions including evidence-based clinical studies and establishment of levels of evidence for herb-drug interaction; and in the related mechanisms including the induction and inhibition of metabolic enzymes, inhibition and induction of transport and efflux proteins, alteration of gastrointestinal functions, and alteration in renal elimination. We also analyzed both the achievements and the challenges faced in the concomitant administration of traditional Chinese medicine and western medicine.
ATP-Binding Cassette, Sub-Family B, Member 1 ; metabolism ; Biological Transport ; drug effects ; Cytochrome P-450 Enzyme System ; metabolism ; Drugs, Chinese Herbal ; isolation & purification ; pharmacokinetics ; pharmacology ; Evidence-Based Medicine ; methods ; Gastrointestinal Tract ; drug effects ; Herb-Drug Interactions ; Humans ; Kidney ; drug effects ; Medicine, Chinese Traditional ; Pharmacokinetics ; Phytotherapy ; Plants, Medicinal ; chemistry

Understanding the research methods for drug protein targets is crucial for the development of new drugs, clinical applications of drugs, drug mechanisms, and the pathogenesis of diseases. Cellular thermal shift assay (CETSA), a target research method without modification, has been widely used since its development. Now, there are various CETSA-based technology combinations, such as mass spectrometry-based cellular thermal shift assay (MS-CETSA), isothermal dose response-cellular thermal shift assay (ITDR-CETSA), amplified luminescent proximity homogeneous assay-cellular thermal shift assay (Alpha-CETSA), etc., which combine their respective advantages and further expand the application scope of CETSA. These technologies are suitable for the entire drug development chain, from drug screening to monitoring the target binding and off-target toxicity of drugs in patients. Based on the author's research experience, this paper reviews the principles of CETSA and related binding technologies, their application in target discovery, and the progress of data processing and analysis in recent years, aiming to provide reference and reference for the further application of CETSA.

The study is to establish an HPLC method using fluorescence detector for the determination of doxazosin enantiomers and investigate their chiral inversion in vitro and in vivo. Ultron ES-OVM was taken as the chiral chromatographic column, and the column temperature was 30 degrees C. Isocratic elution using a mobile phase of phosphate buffer-acetonitrile (85 : 15, v/v) at a flow rate of 0.8 mL x min(-1) was done. The fluorescence detection was set at lambda(Ex) = 255 nm and lambda(Em) = 385 nm. Prazosin was used as the internal standard. (-) Doxazosin or (+) doxazosin added into rat plasma in vitro was determined after incubating in 37 degrees C water bath for 2, 5 and 10 days. (-) Doxazosin or (+) doxazosin was administered orally to the rats for one months. Plasma samples were taken at 8 h after the last administration. A good linear relationship was achieved when the concentration of doxazosin enantiomers was within the range of 4 - 2 000 ng x mL(-1). The average recovery for (-) doxazosin was 99.5% with RSD 3.6%, and for (+) doxazosin was 99.3% with RSD 4.3%. Chiral inversion was observed neither in vitro nor in vivo studies. The method is selective, accurate and reproducible, which is suitable for the detection of doxazosin enantiomers in rat plasma. The in vitro and in vivo studies indicate that chiral inversion occurs uneasily between (-) doxazosin and (+) doxazosin in the rat.
Animals ; Blood Chemical Analysis ; methods ; Doxazosin ; blood ; chemistry ; Male ; Rats ; Rats, Sprague-Dawley ; Reproducibility of Results ; Sensitivity and Specificity ; Stereoisomerism

OBJECTIVETo investigate the effect of Rongshi granule on osteopontin(OPN) expression.

METHODThe urlisthiasis rats were induced by ethylene glycol (EG) and ammonium chloride, the control group rats were non-treated, and the Rongshi granule groups (low-dose group, middle-dose group and high-dose group) were administered Rongshi granule in addition to EG and ammonium chloride in 21 days. Pooled 24 h urine samples from each group were collected weekly with the use of metabolic cages, the concentration of uric calcium and oxalic acid were respectively measured by EDTA and photoelectric colorimetric method. Eight animals from each group were killed at 0, 7, 14, and 21 days, kidneys were histologic examinaed and immunohistochemical staining.

RESULTThe expression of kidney osteopontin in model group was obviously higher than that of control group (P <0.01), and was up to the highest at 21 days with 1.4 times (0.281 3/0.201 8) of the control group. The expression of kidney osteopontin in all of the Rongshi granule groups were lower than those of model group (P < 0.05), with an obvious dose-dependent manner. The degree of the kidney calcium oxalate crystal of the rats in all the Rongshi granule groups was much lower than that of model group, and the uric calcium and oxalic acid were much lower than those of model group (P < 0.01).

CONCLUSIONThe Rongshi granule could inhibit the expression of osteopontin in rat urolithiasis model.

Ammonium Chloride ; Animals ; Calcium ; urine ; Calcium Oxalate ; metabolism ; Dose-Response Relationship, Drug ; Drug Combinations ; Drugs, Chinese Herbal ; administration & dosage ; isolation & purification ; pharmacology ; Ethylene Glycol ; Female ; Kidney ; metabolism ; Kidney Calculi ; chemically induced ; metabolism ; Male ; Osteopontin ; metabolism ; Oxalic Acid ; urine ; Plants, Medicinal ; chemistry ; Random Allocation ; Rats ; Rats, Sprague-Dawley

OBJECTIVETo evaluate the clinical efficacy of bladder gasification and stasis dispersion combined with antibiotic therapy in the treatment of III A chronic prostatitis.

METHODSWe conducted a randomized controlled clinical study on 120 III A prostatitis patients that all met the diagnostic criteria. We divided the patients into groups A, B and C of equal number to receive oral medication of sparfloxacin, sparfloxacin + tamsulosin, and sparfloxacin + herbal decoction, respectively, all for a course of 4 weeks. We evaluated the primary therapeutic indexes according to the total scores of the patients on traditional Chinese medicine (TCM) syndrome and NIH-CPSI and the secondary therapeutic indexes based on the count of white blood cells (WBC) in the expressed prostatic secretion (EPS).

RESULTSAfter treatment, the total scores on TCM syndrome and NIH-CPSI were significantly reduced in groups B (42.15 +/- 10.29 and 13.25 +/- 6.04) and C (41.26 +/- 11.25 and 12.38 +/- 7.19) than in A (49.43 +/- 11.09 and 17.62 +/- 5.84) ( P < 0.05), and so was the WBC count in EPS in group C (7.76 +/- 15.73) than in groups A (11.45 +/- 10.33) and B (12.28 +/- 13.81) (P < 0.05). The difference between pre- and post-treatment scores on TCM syndrome was more significant in group C (12.65 +/- 11.76) than in B (8.55 +/- 10.15) (P < 0.05).

CONCLUSIONBladder gasification and stasis dispersion combined with antibiotic therapy is effective for the treatment of III A chronic prostatitis, and therefore deserves wide clinical application.

Adult ; Anti-Bacterial Agents ; therapeutic use ; Chronic Disease ; Combined Modality Therapy ; Drugs, Chinese Herbal ; therapeutic use ; Humans ; Male ; Medicine, Chinese Traditional ; Phytotherapy ; Prostatitis ; classification ; drug therapy ; Treatment Outcome

Objective To develop a HPLC-MS/MS method for the determination of Pregabalin in epileptic patients.Methods Analysis was performed on a Diamonsil C18column (4.6 mm × 150 mm,5 μm)eluted with methanol and water (0.05％ formic acid) in a gradient program.The flow rate was 1 mL · min-1,the injection volume was 20 μL,and the column temperature was 30 ℃.The multiple-reaction monitoring scanning (MRM) was employed for the quantification with switching electrospray ion source polarity in negative mode.The ion spray voltage was set at 5500 V and the turbo spray temperature was maintained at 650 ℃.The specificity,calibration curve,limit of detection,precision,recovery and stability of the method were investigated.20 patients with epilepsy were selected,and the serum concentration of pregabalin was determined by HPLC-MS/MS after oral administration of 75 mg pregabalin for one hour.Results Pregabalin showed a good linearity in the ranges of 13.76-5270.00 ng · mL-1,the lower limit of quantification was 0.65 ng · mL-1.The average recoveries varied from 94.7％-106.2％.The inter and intra-day RSD were less than 15％.Pregabalin was proved to be stable under study station.The concentration of pregabalin in epileptic patients ranged from 1.76 to 2.78 μg · mL-1.Conclusion The method is simple,rapid,and sensitive,which could be used for the determination of pregabalin in epileptic patients.

Objective To investigate hepatocyte growth factor(HGF)gene expression and biological effect after gene transfection into penumbra tissue in rat cerebral ischemic model.Methods Human HGF cDNA was ligated to pIRES2-EGFP vector.The recombinant plasmid was transfected into the penumbra tissue with liposome.Brains of treated and control animals were analyzed 7 days later.Expression of HGF protein was determined by fluorescence microscopy and immunohistochemistry.Vessel numbers were quantified.Changes of cerebral blood flow(CBF)was detected by CT perfusion.Results Enzymatic digestion and electrophoresis confirmed that HGF fragment had been correctly cloned into BamH I and Sal I sites of pIRES2-EGFP.After HGF gene transfection,expression of HGF in transfected neurocytes was observed with fluorescence microscopy and immunohistochemistry.The number of vessels was significantly increased in penumbra tissue transfected with HGF vector as compared with control vector(46.71?7.11, 20.43?3.21,18.00?3.27,respective,F = 74.447;P

OBJECTIVESTo explore MICM classification and adverse prognostic factors in adolescents with acute lymphoblastic leukemia (ALL).

METHODSThe MICM classification, clinical characteristics of 80 adolescents with ALL admitted to our hospital from January 1998 to December 2002 were retrospectively analyzed. Survival data were estimated by the Kaplan-Meier method and the prognostic factors were analyzed with the COX regression model.

RESULTSIn the 80 patients, B-ALL and T-ALL accounted for 69.12% and 26.47%, respectively. The percentage of Ph(+)ALL was 18.37% (9/49), and that of hyperdiploidy was 4.08%. Patients at diagnosis with high leukocyte counts (> 50 x 10(9)/L) accounted for 27.94%. Among the 78 cases treated with VDP(L) or CODP(L) regimens, 73 (91.03%) obtained CR in 4 weeks. After a median follow-up of 24 months, the estimated 3-year disease-free survival (DFS) rates of patients receiving chemotherapy or allo-HSCT were (32.55 +/- 16.50)% and (69.58 +/- 8.72)%, respectively (P < 0.05). In COX analysis, high initial leukocyte counts (> 50 x 10(9)/L) and Philadelphia chromosome positivity were adverse prognostic factors for long-term survival.

CONCLUSIONSMICM classification has important clinical and prognostic significance in the risk-directed therapy of adolescents with ALL. The adverse prognostic features for these patients were high leukocyte counts, less incidence of chromosome hyperdiploidy and Ph chromosome positivity.

Adolescent ; Combined Modality Therapy ; Female ; Humans ; Kaplan-Meier Estimate ; Karyotyping ; Leukocyte Count ; Male ; Precursor Cell Lymphoblastic Leukemia-Lymphoma ; classification ; genetics ; therapy ; Prognosis ; Retrospective Studies ; Risk Factors

The aim of the study was to determine the expression of cytidine deaminase (CDD) gene in bone marrow cells from patients with acute leukemia (AL) and evaluate the relationship between CDD expression and clinical feature. Semi-quantitative reverse transcription polymerase chain reaction (RT-PCR) was used for detection of expression level of CDD mRNA in bone marrow cells from 83 patients with acute leukemia and from 15 healthy peoples as control. CDD/beta-actin ratio >or= 0.5 was considered to be positive. The results showed that expression levels of CDD of 31 previously untreated patients were higher than those of 23 cases of AL in complete remission and of normal controls. Expression levels of CDD of 29 relapse/refractory patients were also higher than those of 23 AL patients in complete remission and of normal subjects. The expression levels of CDD in relapse/refractory ALL were higher than those in AML while expression levels of CDD were not correlated with the outcome of therapy. It is concluded that the level of CDD mRNA expression varies at the different stage of acute leukemia. The expression level of CDD seems not to be a prognostic factor.
Adolescent ; Adult ; Aged ; Aged, 80 and over ; Bone Marrow Cells ; enzymology ; Cytidine Deaminase ; genetics ; Female ; Gene Expression Regulation, Enzymologic ; Gene Expression Regulation, Neoplastic ; Humans ; Leukemia, Myeloid, Acute ; drug therapy ; enzymology ; genetics ; Male ; Middle Aged ; Neoplasm Recurrence, Local ; Precursor Cell Lymphoblastic Leukemia-Lymphoma ; drug therapy ; enzymology ; genetics ; RNA, Messenger ; genetics ; metabolism ; Remission Induction ; Reverse Transcriptase Polymerase Chain Reaction

Objective To investigate the effect of CYP46A1 on the pathogenesis of Alzheimer's disease.Methods Recombinant lentiviral vectors which including anthropogenic CYP46A1 were injected into bilateral hippocampus of 3-monthold male 5XFAD transgenic mice,while empty vectors were injected into the corresponding position of the control group.After two months,the ability of learning and memory were tested by Morris water maze and T maze experiments,and amyloid plaque and inflammatory infiltration in the brain were detected by immunohistochemical staining and ELISA respectively.Results Compared with the control group,CYP46A1 virus injection significantly increased the CYP46A1 mRNA and protein expression in hippocampus.In addition,CYP46A1 overexpression significantly decreased the latency to find the platform in Morris water maze test and increased the correct rate to choose in T maze test.Aβ immunohistochemical staining and plaques area statistics demonstrated that the amyloid plaque area of hippocampus in CYP46A1 overexpression mice was significantly reduced,and there was a significantly decrease of hippocampal astrocytes expression by means of GFAP staining.Furthermore,hippocampal CYP46A1 overexpression significantly decreased the expression level of Aβ40,Aβ42,IL-1β and TNF-α,while compare with the control group.Conclusion CYP46A1 overexpression in hippocampus can promote the cognitive impairment,as well as ameliorate the brain inflammatory infiltration in 5XFAD transgenic mice,suggesting that CYP46A1 has anti-Alzheimer's disease like effects.