Objective: To determine fatty acid synthase (FAS) expression in human multiple myeloma and verify its potential as a therapeutic target in multiple myeloma. Methods: FAS expression was determined by immunohistoche...Objective: To determine fatty acid synthase (FAS) expression in human multiple myeloma and verify its potential as a therapeutic target in multiple myeloma. Methods: FAS expression was determined by immunohistochemistry, reverse-transcription polymerase chain reaction (RT-PCR) and immunoblot analysis in bone marrow samples obtained from 27 patients with multiple myeloma (MM patients) and peripheral blood mononuclear cells (PBMCs) obtained from 12 healthy donors In parallel, additional analyses were performed on 2 human multiple myeloma cell lines, U266 and RPM18226. U266 cells were treated with cerulenin at various concentrations (5 to 320 μg/ml) for 24 h, and metabolic activity was measured by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assays. Apoptosis was evaluated by dual Annexin V/Pl (propidium iodide) labeling and flow cytometry (FCM) in U266 cells treated with 20 μg/ml cerulenin for 12 h or 24 h. Results: By immunohistochemistry, we found that 19 of 27 bone marrow samples obtained from MM patients expressed significantly high levels of FAS. Similarly, by RT-PCR, 22 of 27 bone marrow samples obtained from MM patients, U266 and RPM18226 showed FAS expression, whereas PBMC samples from 12 healthy donors did not express detectable level of FAS. FAS protein expression was confirmed by immunoblot analysis in 16 of 27 bone marrow samples obtained from MM patients, U266 and RPM18226 cell lines, and no FAS protein expression was detected in PBMC samples from 12 healthy donors. U266 cells were highly sensitive to cerulenin treatment, with a dosage-related effect on metabolic activity, as a measure for cell proliferation. U266 cells treated with 20 μg/ml cerulenin for 12 and 24 h also showed early sign of apoptosis with 56.9% and 69.3% Annexin V^+/Pl cells, and late apoptotic and necrotic cells with 3.2% and 17.6% Annexin V^+/Pl^+ cells. Conclusion: Increased FAS expression existed in multiple myeloma samples and human myeloma cell lines. Cerulenin greatly inhibited metabolic activity/cell proliferation of U266 cells and induced apoptosis, suggesting that FAS is an effective target for pharmacological therapy in human multiple myeloma.展开更多
Currently, pharmaceutical preparations are serious contributors to liver disease; hepatotoxicity ranking as the most frequent cause for acute liver failure and post-commercialization regulatory decisions. The diagnosi...Currently, pharmaceutical preparations are serious contributors to liver disease; hepatotoxicity ranking as the most frequent cause for acute liver failure and post-commercialization regulatory decisions. The diagnosis of hepatotoxicity remains a difficult task because of the lack of reliable markers for use in general clinical practice. To incriminate any given drug in an episode of liver dysfunction is a step-by-step process that requires a high degree of suspicion, compatible chronology, awareness of the drug’s hepatotoxic potential, the exclusion of alternative causes of liver damage and the ability to detect the presence of subtle data that favors a toxic etiology. This process is time-consuming and the final result is frequently inaccurate. Diagnostic algorithms may add consistency to the diagnostic process by translating the suspicion into a quantitative score. Such scales are useful since they provide a framework that emphasizes the features that merit attention in cases of suspected hepatic adverse reaction as well. Current efforts in collecting bona fide cases of drug-induced hepatotoxicity will make refinements of existing scales feasible. It is now relatively easy to accommodate relevant data within the scoring system and to delete low-impact items. Efforts should also be directed toward the development of an abridged instrument for use in evaluating suspected drug-induced hepatotoxicity at the very beginning of the diagnosis and treatment process when clinical decisions need to be made. The instrument chosen would enable a confident diagnosis to be made on admission of the patient and treatment to be fine-tuned as further information is collected.展开更多
AIM: To observe the therapeutic effects of dexamethasone on rats with severe acute pancreatitis (SAP) and investigate the influences of dexamethasone on the inflammatory mediators and NF-κB expression in multiple org...AIM: To observe the therapeutic effects of dexamethasone on rats with severe acute pancreatitis (SAP) and investigate the influences of dexamethasone on the inflammatory mediators and NF-κB expression in multiple organs of SAP rats as well as the mechanisms involved. METHODS: Ninety Sprague-Dawley (SD) rats with SAP were randomly divided into the model group (n = 45) and dexamethasone treatment group (n = 45), and another 45 rats were selected for the sham operation group. All groups were randomly subdivided into the 3 h, 6 h and 12 h groups, each group containing 15 rats. The survival of all groups and pathological changes of multiple organs (liver, kidney and lung) were observed at different time points after the operation. The pathologicalscore of multiple organs was carried out, followed by the determination of amylase, endotoxin and TNF-α contents in blood. The tissue microarray was used to detect the expression levels of NF-κB p65 protein in multiple organs. RESULTS: There was no marked difference between the model group and treatment group in the survival rate. The amylase content of the treatment group was significantly lower compared to the model group at 12 h (P < 0.01, 7791.00 vs 9195.00). Moreover, the endotoxin and TNF-α levels of the treatment group were significantly lower than that of the model group at 6 h and 12 h (P < 0.01, 0.040 vs 0.055, 0.042 vs 0.059 and P < 0.05, 58.30 vs 77.54, 38.70 vs 67.30, respectively). Regarding the changes in liver NF-κB expression, the model group significantly exceeded the sham operation group at 3 h (P < 0.01, 1.00 vs 0.00), and the treatment group significantly exceeded the sham operation group at 12 h (P < 0.01, 1.00 vs 0.00), whereas no marked difference was observed between the model group and treatment group at all time points. The kidney NF-κB expression level in the treatment group significantly exceeded the model group (P < 0.05, 2.00 vs 0.00) and the sham operation group (P < 0.01, 2.00 vs 0.00) at 12 h. No NF-κB expression in the lung was found in any group. CONCLUSION: Dexamethasone can lower the amylase, endotoxin and TNF-α levels as well as mortality of SAP rats. NF-κB plays an important role in multiple organ injury. Further studies should be conducted to determine whether dexamethasone can ameliorate the pathological changes of multiple organs by reducing the NF-κB expression in the liver and kidney. The advantages of tissue microarrays in pancreatitis pathological examination include time- and energy- saving, and are highly efficient and representative. The restriction of tissue microarrays on the representation of tissues to various extents due to small diameter may lead to the deviation of analysis.展开更多
AIM: To investigate the permeability characteristics of rebamipide across intestinal mucosa, and examine the effects of some absorption enhancers on the permeability across the colonic tissue. Another purpose is to de...AIM: To investigate the permeability characteristics of rebamipide across intestinal mucosa, and examine the effects of some absorption enhancers on the permeability across the colonic tissue. Another purpose is to demonstrate the colon-specific delivery of rebamipide with or without absorption enhancers using chitosan capsule as a carrier. METHODS: The permeability of rebamipide was evaluated using an in vitro diffusion chamber system, and the effects of some absorption enhancers on the permeability via colon were further investigated. The release of rebamipide from chitosan or gelatin capsule was studied by Japan Pharmacopoeia rotating basket method. The colonic and plasma concentrations were analyzed by high performance liquid chromatography (HPLC) to evaluate colon-targeting action after oral administration of various dosage forms, and rebamipide with absorption enhancers in chitosan dosage forms. RESULTS: The permeability of rebamipide across the jejunal or ileal membranes was higher than the colonic membranes. Both sodium laurate (C12) and labrasol signifi cantly increased permeability across the colon membranes. On the other hand, the release of rebamipide from chitosan capsule was less than 10%totally within 6 h. The area under concentration-time profile of drug in the colon mucosa using chitosan capsules (AUCLI, 1 6011.2 ng·h/g) was 2.5 times and 4.4 times greater than using gelatin capsules and CMC suspension, respectively. Meanwhile, the area under concentration-time profile of drug in the plasma (AUCPL) was 1016.0 ng·h/mL for chitosan capsule, 1887.9 ng·h/mL for CMC suspension p and 2163.5 ng·h/mL for gelatin capsule. Overall, both AUCLI and AUCPL were increased when C12 was co-administrated, but the increase of AUCLI was much greater; the drug delivery index (DDI) was more than 1 compared with simple chitosan capsule group. CONCLUSION: There was a regional difference in the permeability of Rabamipide across the jejunum, ileum and the colon, and passive diffusion seems to be one of the major transport mechanisms of rebamipide. Absorption enhancers can increase the permeability of rebamipide across the colon tissue signifi cantly. In addition, chitosan capsule may be a useful carrier to deliver rebamipide to the colon specifi cally and the co-administration of C12 with rebamipide may also be very useful in local treatment.展开更多
End stage liver disease (ESLD) is a health problem worldwide. Liver transplantation is currently the only effective therapy, but its many drawbacks include a shortage of donors, operative damage, risk of rejection and...End stage liver disease (ESLD) is a health problem worldwide. Liver transplantation is currently the only effective therapy, but its many drawbacks include a shortage of donors, operative damage, risk of rejection and in some cases recidivism of the pre-transplant disease. These factors account for the recent growing interest in regenerative medicine. Experiments have sought to identify an optimal source of stem cells, sufficient to generate large amounts of hepatocytes to be used in bioartificial livers or injected in vivo to repair the diseased organ. This update aims to give non-stem cell specialists an overview of the results obtained to date in this fascinating field of biomedical research.展开更多
Schizophrenia is a psychiatric disorder affecting approximately 1% of the population worldwide and is characterised by the presence of positive and negative symptoms and cognitive deficits. Whilst current therapeutics...Schizophrenia is a psychiatric disorder affecting approximately 1% of the population worldwide and is characterised by the presence of positive and negative symptoms and cognitive deficits. Whilst current therapeutics ameliorate positive symptoms, they are largely ineffective in improving negative symptoms and cognitive deficits. The cholinergic neurotransmitter system heavily influences cognitive function and there is evidence that implicates disruption of the central cholinergic system in schizophrenia. Historically, targeting the cholinergic system has been impeded by poor selectivity leading to intolerable side effects warranting the need to develop more targeted therapeutic compounds. In this review we will summarise evidence supporting the roles of the cholinergic system, particularly the muscarinic M1 receptor, in the pathophysiology of schizophrenia and discuss the potential of a promising new class of candidate compounds, allosteric ligands, for addressing the difficulties involved in targeting this system. The body of evidence presented here highlights the dysfunction of the cholinergic system in schizophrenia and that targeting this system by taking advantage of allosteric ligands is having clinically meaningful effect on cognitive deficits.展开更多
Ezetimibe is the f irst member of a new family of lipid- lowering drugs that inhibits uptake of dietary and bili- ary cholesterol. It was approved by the FDA in 2002 for hypercholesterolemia alone or in combination wi...Ezetimibe is the f irst member of a new family of lipid- lowering drugs that inhibits uptake of dietary and bili- ary cholesterol. It was approved by the FDA in 2002 for hypercholesterolemia alone or in combination with statins. Its use has been spreading over the last years. Ezetimibe was considered a safe drug. We report a case of a woman who developed a serious hepatocellular drug-induced liver disease after 4 mo therapy with 10 mg daily of ezetimibe. After withdrawal of the drug, the patient recovered slowly. Ezetimibe may produce seri- ous toxic hepatitis and prompt withdrawal is mandatory in case of a signif icant abnormality in liver testing after beginning or during treatment with ezetimibe.展开更多
Fibromyalgia(FM) has been described as a chronic clinical condition related to multisensory hypersensitivitypresenting with a complex of symptoms dominated by chronic widespread pain associated with the existence of a...Fibromyalgia(FM) has been described as a chronic clinical condition related to multisensory hypersensitivitypresenting with a complex of symptoms dominated by chronic widespread pain associated with the existence of a range of co-morbidities, such as fatigue, sleep disturbance, cognitive impairment, anxiety and depression. Current treatments include drugs that target serotonin and noradrenaline levels within the central nervous system, e.g., tricyclic antidepressants, serotonin noradrenaline reuptake inhibitors, and voltage-gated calcium channel subunit ligands, e.g., gabapentin and pregabalin. Investigation of a range of novel targets, such as melatoninergic, cannabinoid, dopamine, NMDA, angiotensin, orexin and opioid receptors, and ion channels, in addition revisiting bioamine modulation and subunits has provided efficacy outcomes that improve the health status of patients with FM. Nevertheless, modest and limited efficacy is often observed reflecting the heterogeneity of FM with existence of subpopulations of patients, the contribution of peripheral and central components to the pathophysiology, and the extensive range of accompanying co-morbidities. The complexity and multidimensional nature of FM is emphasized by the diversity of pharmacological targets gaining interest. Clues to underlying mechanisms which offer themselves as novel and potential targets for new medications are being provided by advances in the understanding of the pathophysiology of FM.展开更多
Retinal ischemia is a common clinical entity and, due to relatively ineffective treatment, remains a common cause of visual impairment and blindness. Generally, ischemic syndromes are initially characterized by low ho...Retinal ischemia is a common clinical entity and, due to relatively ineffective treatment, remains a common cause of visual impairment and blindness. Generally, ischemic syndromes are initially characterized by low homeostatic responses which, with time, induce injury to the tissue due to cell loss by apoptosis. In this re-spect, retinal ischemia is a primary cause of neuronal death. It can be considered as a sort of fnal common pathway in retinal diseases and results in irreversible morphological and functional changes. This review summarizes the recent knowledge on the effects of ischemia in retinal tissue and points out experimental strategies/models performed to gain better compre-hension of retinal ischemia diseases. In particular, the nature of the mechanisms leading to neuronal damage (i.e., excess of glutamate release, oxidative stress and infammation) will be outlined as well as the potential and most intriguing retinoprotective approaches and the possible therapeutic use of naturally occurring molecules such as neuropeptides. There is a general agreement that a better understanding of the funda-mental pathophysiology of retinal ischemia will lead tobetter management and improved clinical outcome. In this respect, to contrast this pathological state, spe-cifc pharmacological strategies need to be developed aimed at the many putative cascades generated during ischemia.展开更多
The spectrum of drug-induced liver injury (DILI) is both diverse and complex. The first step in diagnosis is a suspicion of DILl based on careful consideration of recent comprehensive reports on the disease. There a...The spectrum of drug-induced liver injury (DILI) is both diverse and complex. The first step in diagnosis is a suspicion of DILl based on careful consideration of recent comprehensive reports on the disease. There are some situations in which the suspicion of DILI is particularly strong. Exclusion of other possible etiologies according to the pattern of liver injury is essential for the diagnosis. In patients with suspected DILl, diagnostic scales, such as the Councils for International Organizations of Medical Sciences/ Roussel Uclaf Causality Assessment Method (CIOMS/RUCAM) scale, may be helpful for the final diagnosis. Early management of DILl involves prompt withdrawal of the drug suspected of being responsible, according to serum levels of alanine aminotransferase (ALT), alkaline phosphatase (ALP), and total bilirubin (T-Bil). However, as DILI patients may show resolution of liver injury without discontinuation of the drug, it should be carefully evaluated whether the suspected drug should be discontinued immediately with adequate consideration of the importance of the medication.展开更多
Irritable bowel syndrome (IBS) is a highly prevalent gastrointestinal disorder characterized by abdominal pain and discomfort in association with altered bowel habits. It is estimated tD affect 10%-15% of the Wester...Irritable bowel syndrome (IBS) is a highly prevalent gastrointestinal disorder characterized by abdominal pain and discomfort in association with altered bowel habits. It is estimated tD affect 10%-15% of the Western population, and has a large impact on quality of life and (in)direct healthcare costs. IBS is a multifactorial disorder involving dysregulation within the brain-gut axis, and it is frequently associated with gastrointestinal motor and sensory dysfunction, enteric and central nervous system irregularities, neuroimmune dysregulation, and postinfectious inflammation. As with other functional medical disorders, the treatment for IBS can be challenging. Conventional therapy for those with moderate to severe symptoms is largely unsatisfactory, and the development of new and effective drugs is made difficult by the complex pathogenesis, variety of symptoms, and lack of objective clinical findings that are the hallmark of this disorder. Fortunately, research advances over the past several decades have provided insight into potential mechanisms responsible for the pathogenesis of IBS, and have led to the development of several promising pharmaceutical agents. In recent years there has been much publicity over several of these new IBS medications (alosetron and tegaserod) because of their reported association with ischemic colitis and cardiovascular disease. While these agents remain available for use under restricted prescribing programs, this highlights the need for continued development of safe and effective medication for IBS. This article provides a physiologicallybased overview of recently developed and frequently employed pharmaceutical agents used to treat IBS, and discusses some non-pharmaceutical options that may be beneficial in this disorder.展开更多
AIM: To combine ultrasound-guided fine-needle aspiration (US-FNA) and Liu (Riu) stain to make a quick study on liver tumor lesions. METHODS: Two hundred and twenty-eight aspirations from 232 patients were comple...AIM: To combine ultrasound-guided fine-needle aspiration (US-FNA) and Liu (Riu) stain to make a quick study on liver tumor lesions. METHODS: Two hundred and twenty-eight aspirations from 232 patients were completely studied. The operator himself made the quick cytodiagnosis of US-FNA smear stained by Liu method within thirty minutes. The US-FNA specimen was also sent to the pathological department for cytological study and cellblock histology. The result of our Uu-stain quick cytodiagnosis in each patient was confirmed by the final cytopathological diagnosis from pathological report. RESULTS: Among 228 samples, the quick cytodiagnosis revealed 146 malignancies, 81 benign lesions and one inadequate specimen. Cytopathological diagnosis from the pathological department revealed 150 malignancies, and 78 benign lesions. Four well-differentiated hepatocellular carcinomas (HCCs) were under-diagnosed by quick cytodiagnosis as benign and 3 benign lesions were over-diagnosed as well-differentiated HCCs. Compared with cytopathological diagnosis, quick cytodiagnosis correctly diagnosed 143 malignancies and 77 benign lesions. Except for the one inadequate specimen in quick cytodiagnosis, the accuracy of quick cytodiagnosis was 96.9% (220/227), and its sensitivity, specificity and positive and negative predictive values were 97.9%, 95.1%, 97.3% and 96.3%, respectively. CONCLUSION: Liu-stain quick cytodiagnosis is a fast, convenient, safe and effective method for hepatologists in clinic practice to diagnose liver tumor. In few cases of well-differentiated HCC, Liu-stain quick cytodiagnosis has its limitation.展开更多
Kaposi’s sarcoma-associated herpesvirus (KSHV) was first identified as the etiologic agent of Kaposi’s sarcoma (KS) in 1994. KSHV infection is necessary,but not sufficient for the development of Kaposi sarcoma (KS),...Kaposi’s sarcoma-associated herpesvirus (KSHV) was first identified as the etiologic agent of Kaposi’s sarcoma (KS) in 1994. KSHV infection is necessary,but not sufficient for the development of Kaposi sarcoma (KS),primary effusion lymphoma (PEL),and multicentric Castleman disease (MCD). Advances in the prevention and treatment of KSHV-associated Diseases have been achieved,even though current treatment options are ineffective,or toxic to many affected persons. The identification of new targets for potential future therapies and the randomized trial to evaluate the efficacy of new antivirals are required.展开更多
Telomeres are non-coding tandem repeats of 1000-2000 TTAGGG nucleotide DNA sequences on the 3’ termini of human chromosomes where they serve as protective “caps” from degradation and loss of genes. The “cap” at t...Telomeres are non-coding tandem repeats of 1000-2000 TTAGGG nucleotide DNA sequences on the 3’ termini of human chromosomes where they serve as protective “caps” from degradation and loss of genes. The “cap” at the end of chromosome required to protect its integ-rity is a 150-200 nucleotide-long single stranded G-rich 3’ overhang that forms two higher order structures, a T-loop with Sheltering complex, or a G-quadruplex com-plex. Telomerase is a human ribonucleoprotein reverse transcriptase that continually added single stranded TTAGGG DNA sequences onto the single strand 3’ of telomere in the 5’ to 3’ direction. Telomerase activity is detected in male germ line cells, proliferative cells of renewal tissues, some adult pluripotent stem cells, embryonic cells, but in most somatic cells is not de-tected. Re-expression or up-regulation of telomerase in tumours cells is considered as a critical step in cell tumorigenesis and telomerase is widely considered as a tumour marker and a target for anticancer drugs. Dif-ferent approaches have been used in anticancer thera-peutics targeting telomerase. Telomerase inhibitors can block directly Human TElomerase Reverse Transcrip-tase (hTERT) or Human TElomerase RNA telomerase subunits activity, or G-quadruplex and Sheltering complex components, shortening telomeres and inhibiting cell proliferation. Telomerase can become an immune target and GV1001, Vx-001, I540 are the most wide-spread vaccines used with encouraging results. Another method is to use hTERT promoter to drive suicide gene expression or to control a lytic virus replication. Recently telomerase activity was used to activate pro-drugs such as Acycloguanosyl 5’-thymidyltriphosphate, a synthetic ACV-derived molecule when it is activated by telomer-ase it does not require any virus or host active immune response to induce suicide gene therapy. Advantage of all these therapies is that target only neoplastic cells without any effects in normal cells, avoiding toxicity and adverse effects of the current chemotherapy. However, as not all the approaches are equally effcient, further studies will be necessary.展开更多
Over the past three decades, concerns about the high prevalence of antipsychotic use in the nursing homes (NHs) for the management of behavioral and psychological symptoms of dementia continue to be emphasized and i...Over the past three decades, concerns about the high prevalence of antipsychotic use in the nursing homes (NHs) for the management of behavioral and psychological symptoms of dementia continue to be emphasized and intervened by many. However, despite the numerous side effects and the recent blackbox warning by the United States Food and Drug Administration about the increased risks for stroke and sudden death associated with the use of antipsychotics in dementia, the preva-lence of antipsychotic use in NHs remains high. While the use of antipsychotics appeared to have modest effcacy in reducing symptoms of aggression and psychosis in dementia, there is insuffcient evidence to routinely rec-ommend the use of alternative psychopharmacological treatments for these symptoms. Hence, clinicians have to balance the safety warnings against the need to treat these symptoms in order to prevent harm to the resident that may result from his/her dangerous behaviors. Although the use of antipsychotics may be warranted in some cases, organizational, resource and training support should be provided to encourage and equip NH staff to participate in interventions so as to minimize inappropriate use of these medicines in NHs. This review will discuss the place in therapy, the trend and appropriateness of antipsychotic use in NHs, as well as the effectiveness of current and future strategies for reducing antipsychotic use in the NHs.展开更多
Objective: To observe the clinical efficacy of oral traditional Chinese medicine (Jiaweitiaoqi decoction), electroacupuncture, biofeedback, and combined treatment on functional anorectal pain (FAP). Methods: A ...Objective: To observe the clinical efficacy of oral traditional Chinese medicine (Jiaweitiaoqi decoction), electroacupuncture, biofeedback, and combined treatment on functional anorectal pain (FAP). Methods: A total of 200 patients with FAP were randomly divided into 4 groups, with 50 patients in each group. Group 1 was given oral Jiaweitiaoqi decoction; group 2 was given electroacupuncture at the lumbosacral acupoints; group 3 was given biofeedback training; and group 4 was given combined treatment. The numeric rating scale (NRS), Short Form-36 (SF-36) quality of life scale, static pressure of the anal canal, and maximum systolic pressure were observed in the 4 groups. Results: The observation indices of the 4 groups were all improved after treatment compared with those before treatment, and the fourth group showed the most obvious improvement. Regarding NRS scores, the static pressure of the anal canal, and maximum systolic pressure, group 4 had lower values than the other 3 groups (P 〈 0.05 for all). In the SF-36 quality of life score, group 4 showed a higher value than the other 3 groups (P 〈 0.05). Conclusion: Non-drug therapy including acupuncture and physical exercise can enhance the clinical efficacy of single Chinese medicine in the treatment of FAP .展开更多
Chronic diarrhea can be divided into four types:retention of dampness leading to blockage of qi,invasion of the intestines by pathogenic wind,damp-retention due to deficiency of the spleen, andstagnation of the liver-...Chronic diarrhea can be divided into four types:retention of dampness leading to blockage of qi,invasion of the intestines by pathogenic wind,damp-retention due to deficiency of the spleen, andstagnation of the liver-qi with deficiency of thespleen.展开更多
To promote efficient screening of active angiogenic drugs from traditional medicines, we constructed a humanembryonic kidney-293 cell model using vascular endothelial growth factor (VEGF) gene promoter as the drug t...To promote efficient screening of active angiogenic drugs from traditional medicines, we constructed a humanembryonic kidney-293 cell model using vascular endothelial growth factor (VEGF) gene promoter as the drug target. Inthis model, VEGF gene promoter may regulate the expression of the luciferase reporter gene by responding to thestimulation of drug molecules. This cell model allows rapid and efficient screening of vascular-inducing activecomponents from several drug monomer molecules. Furthermore, we used rat bone marrow mesenchymal stem cells(rMSCs) to conduct a preliminary study on the activity of alantolactone. Using simvastatin as a positive control, weinvestigated the effects of alantolactone on the expression of vascular-related cell marker molecules such as VEGF andα-smooth muscle actin (α-SMA) in rMSCs. According to our results, 0.1, 1, 3 and 5 μM of alantolactone upregulated thetranscriptional luciferase gene activity of VEGF promoter, and a significant difference from that in the control group wasobserved. Among them, 3μM of alantolactone showed the better effect than that of 3 μM of simvastatin (P = 0.036) andother concentrations of alantolactone and simvastatin showed similar effects. Compared with that in the control group,rMSCs induced with 1μM alantolactone for 3 days showed a significant increase in the relative mRNA expressions ofVEGF and α-SMA genes. However, these effect of 5 μM alantolactone were weaker than those of 5 μM simvastatin (P 〈0.05); rMSCs treated with 1 μM alantolactone for 3 days showed brighter green fluorescence (FITC marker) of α-SMAand VEGF in situ expression than that observed in the control group and similar fluorescence intensity than that ofsimvastatin group in an immunoradiometric assay. The above results demonstrate the reliability of the highly efficientsystem for screening of active drug molecules and confirmed the vascular induction function of alantolactone at the geneand protein levels.展开更多
基金Project supported by the Medicine and Health Research Fund of Zhejiang Province(No.2007B091)the Office of Education of Zhejiang Province,China(No.20070104)
文摘Objective: To determine fatty acid synthase (FAS) expression in human multiple myeloma and verify its potential as a therapeutic target in multiple myeloma. Methods: FAS expression was determined by immunohistochemistry, reverse-transcription polymerase chain reaction (RT-PCR) and immunoblot analysis in bone marrow samples obtained from 27 patients with multiple myeloma (MM patients) and peripheral blood mononuclear cells (PBMCs) obtained from 12 healthy donors In parallel, additional analyses were performed on 2 human multiple myeloma cell lines, U266 and RPM18226. U266 cells were treated with cerulenin at various concentrations (5 to 320 μg/ml) for 24 h, and metabolic activity was measured by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assays. Apoptosis was evaluated by dual Annexin V/Pl (propidium iodide) labeling and flow cytometry (FCM) in U266 cells treated with 20 μg/ml cerulenin for 12 h or 24 h. Results: By immunohistochemistry, we found that 19 of 27 bone marrow samples obtained from MM patients expressed significantly high levels of FAS. Similarly, by RT-PCR, 22 of 27 bone marrow samples obtained from MM patients, U266 and RPM18226 showed FAS expression, whereas PBMC samples from 12 healthy donors did not express detectable level of FAS. FAS protein expression was confirmed by immunoblot analysis in 16 of 27 bone marrow samples obtained from MM patients, U266 and RPM18226 cell lines, and no FAS protein expression was detected in PBMC samples from 12 healthy donors. U266 cells were highly sensitive to cerulenin treatment, with a dosage-related effect on metabolic activity, as a measure for cell proliferation. U266 cells treated with 20 μg/ml cerulenin for 12 and 24 h also showed early sign of apoptosis with 56.9% and 69.3% Annexin V^+/Pl cells, and late apoptotic and necrotic cells with 3.2% and 17.6% Annexin V^+/Pl^+ cells. Conclusion: Increased FAS expression existed in multiple myeloma samples and human myeloma cell lines. Cerulenin greatly inhibited metabolic activity/cell proliferation of U266 cells and induced apoptosis, suggesting that FAS is an effective target for pharmacological therapy in human multiple myeloma.
基金Supported partly by research grants from the Agencia Espaoladel Medicamento from the Fondo de Investigación Sanitaria(FIS 04-1688 and FIS 04-1759)
文摘Currently, pharmaceutical preparations are serious contributors to liver disease; hepatotoxicity ranking as the most frequent cause for acute liver failure and post-commercialization regulatory decisions. The diagnosis of hepatotoxicity remains a difficult task because of the lack of reliable markers for use in general clinical practice. To incriminate any given drug in an episode of liver dysfunction is a step-by-step process that requires a high degree of suspicion, compatible chronology, awareness of the drug’s hepatotoxic potential, the exclusion of alternative causes of liver damage and the ability to detect the presence of subtle data that favors a toxic etiology. This process is time-consuming and the final result is frequently inaccurate. Diagnostic algorithms may add consistency to the diagnostic process by translating the suspicion into a quantitative score. Such scales are useful since they provide a framework that emphasizes the features that merit attention in cases of suspected hepatic adverse reaction as well. Current efforts in collecting bona fide cases of drug-induced hepatotoxicity will make refinements of existing scales feasible. It is now relatively easy to accommodate relevant data within the scoring system and to delete low-impact items. Efforts should also be directed toward the development of an abridged instrument for use in evaluating suspected drug-induced hepatotoxicity at the very beginning of the diagnosis and treatment process when clinical decisions need to be made. The instrument chosen would enable a confident diagnosis to be made on admission of the patient and treatment to be fine-tuned as further information is collected.
基金Technological Foundation Project of Traditional Chinese Medicine Science of Zhejiang Province, NO. 2003C130 and NO. 2004C142 Foundation Project for Medical Science and Technology of Zhejiang province, No. 2003B134+3 种基金 Grave Foundation Project for Technological and Development of Hangzhou, No. 2003123B19 Intensive Foundation Project for Technology of Hangzhou, NO. 2004Z006 Foundation Project for Medical Science and Technology of Hangzhou, No. 2003A004 and Foundation Project for Technology of Hangzhou, No. 2005224
文摘AIM: To observe the therapeutic effects of dexamethasone on rats with severe acute pancreatitis (SAP) and investigate the influences of dexamethasone on the inflammatory mediators and NF-κB expression in multiple organs of SAP rats as well as the mechanisms involved. METHODS: Ninety Sprague-Dawley (SD) rats with SAP were randomly divided into the model group (n = 45) and dexamethasone treatment group (n = 45), and another 45 rats were selected for the sham operation group. All groups were randomly subdivided into the 3 h, 6 h and 12 h groups, each group containing 15 rats. The survival of all groups and pathological changes of multiple organs (liver, kidney and lung) were observed at different time points after the operation. The pathologicalscore of multiple organs was carried out, followed by the determination of amylase, endotoxin and TNF-α contents in blood. The tissue microarray was used to detect the expression levels of NF-κB p65 protein in multiple organs. RESULTS: There was no marked difference between the model group and treatment group in the survival rate. The amylase content of the treatment group was significantly lower compared to the model group at 12 h (P < 0.01, 7791.00 vs 9195.00). Moreover, the endotoxin and TNF-α levels of the treatment group were significantly lower than that of the model group at 6 h and 12 h (P < 0.01, 0.040 vs 0.055, 0.042 vs 0.059 and P < 0.05, 58.30 vs 77.54, 38.70 vs 67.30, respectively). Regarding the changes in liver NF-κB expression, the model group significantly exceeded the sham operation group at 3 h (P < 0.01, 1.00 vs 0.00), and the treatment group significantly exceeded the sham operation group at 12 h (P < 0.01, 1.00 vs 0.00), whereas no marked difference was observed between the model group and treatment group at all time points. The kidney NF-κB expression level in the treatment group significantly exceeded the model group (P < 0.05, 2.00 vs 0.00) and the sham operation group (P < 0.01, 2.00 vs 0.00) at 12 h. No NF-κB expression in the lung was found in any group. CONCLUSION: Dexamethasone can lower the amylase, endotoxin and TNF-α levels as well as mortality of SAP rats. NF-κB plays an important role in multiple organ injury. Further studies should be conducted to determine whether dexamethasone can ameliorate the pathological changes of multiple organs by reducing the NF-κB expression in the liver and kidney. The advantages of tissue microarrays in pancreatitis pathological examination include time- and energy- saving, and are highly efficient and representative. The restriction of tissue microarrays on the representation of tissues to various extents due to small diameter may lead to the deviation of analysis.
基金Research Funding of Medical Association of Japanese-Chinese, Japan
文摘AIM: To investigate the permeability characteristics of rebamipide across intestinal mucosa, and examine the effects of some absorption enhancers on the permeability across the colonic tissue. Another purpose is to demonstrate the colon-specific delivery of rebamipide with or without absorption enhancers using chitosan capsule as a carrier. METHODS: The permeability of rebamipide was evaluated using an in vitro diffusion chamber system, and the effects of some absorption enhancers on the permeability via colon were further investigated. The release of rebamipide from chitosan or gelatin capsule was studied by Japan Pharmacopoeia rotating basket method. The colonic and plasma concentrations were analyzed by high performance liquid chromatography (HPLC) to evaluate colon-targeting action after oral administration of various dosage forms, and rebamipide with absorption enhancers in chitosan dosage forms. RESULTS: The permeability of rebamipide across the jejunal or ileal membranes was higher than the colonic membranes. Both sodium laurate (C12) and labrasol signifi cantly increased permeability across the colon membranes. On the other hand, the release of rebamipide from chitosan capsule was less than 10%totally within 6 h. The area under concentration-time profile of drug in the colon mucosa using chitosan capsules (AUCLI, 1 6011.2 ng·h/g) was 2.5 times and 4.4 times greater than using gelatin capsules and CMC suspension, respectively. Meanwhile, the area under concentration-time profile of drug in the plasma (AUCPL) was 1016.0 ng·h/mL for chitosan capsule, 1887.9 ng·h/mL for CMC suspension p and 2163.5 ng·h/mL for gelatin capsule. Overall, both AUCLI and AUCPL were increased when C12 was co-administrated, but the increase of AUCLI was much greater; the drug delivery index (DDI) was more than 1 compared with simple chitosan capsule group. CONCLUSION: There was a regional difference in the permeability of Rabamipide across the jejunum, ileum and the colon, and passive diffusion seems to be one of the major transport mechanisms of rebamipide. Absorption enhancers can increase the permeability of rebamipide across the colon tissue signifi cantly. In addition, chitosan capsule may be a useful carrier to deliver rebamipide to the colon specifi cally and the co-administration of C12 with rebamipide may also be very useful in local treatment.
基金The European Association for the Study of the Liver(EASL) Sheila Sherlock Post-Doc Fellowship and by"Ordine dei Medici Chirurghi ed Odontoiatri di Bologna"(SL)
文摘End stage liver disease (ESLD) is a health problem worldwide. Liver transplantation is currently the only effective therapy, but its many drawbacks include a shortage of donors, operative damage, risk of rejection and in some cases recidivism of the pre-transplant disease. These factors account for the recent growing interest in regenerative medicine. Experiments have sought to identify an optimal source of stem cells, sufficient to generate large amounts of hepatocytes to be used in bioartificial livers or injected in vivo to repair the diseased organ. This update aims to give non-stem cell specialists an overview of the results obtained to date in this fascinating field of biomedical research.
文摘Schizophrenia is a psychiatric disorder affecting approximately 1% of the population worldwide and is characterised by the presence of positive and negative symptoms and cognitive deficits. Whilst current therapeutics ameliorate positive symptoms, they are largely ineffective in improving negative symptoms and cognitive deficits. The cholinergic neurotransmitter system heavily influences cognitive function and there is evidence that implicates disruption of the central cholinergic system in schizophrenia. Historically, targeting the cholinergic system has been impeded by poor selectivity leading to intolerable side effects warranting the need to develop more targeted therapeutic compounds. In this review we will summarise evidence supporting the roles of the cholinergic system, particularly the muscarinic M1 receptor, in the pathophysiology of schizophrenia and discuss the potential of a promising new class of candidate compounds, allosteric ligands, for addressing the difficulties involved in targeting this system. The body of evidence presented here highlights the dysfunction of the cholinergic system in schizophrenia and that targeting this system by taking advantage of allosteric ligands is having clinically meaningful effect on cognitive deficits.
文摘Ezetimibe is the f irst member of a new family of lipid- lowering drugs that inhibits uptake of dietary and bili- ary cholesterol. It was approved by the FDA in 2002 for hypercholesterolemia alone or in combination with statins. Its use has been spreading over the last years. Ezetimibe was considered a safe drug. We report a case of a woman who developed a serious hepatocellular drug-induced liver disease after 4 mo therapy with 10 mg daily of ezetimibe. After withdrawal of the drug, the patient recovered slowly. Ezetimibe may produce seri- ous toxic hepatitis and prompt withdrawal is mandatory in case of a signif icant abnormality in liver testing after beginning or during treatment with ezetimibe.
文摘Fibromyalgia(FM) has been described as a chronic clinical condition related to multisensory hypersensitivitypresenting with a complex of symptoms dominated by chronic widespread pain associated with the existence of a range of co-morbidities, such as fatigue, sleep disturbance, cognitive impairment, anxiety and depression. Current treatments include drugs that target serotonin and noradrenaline levels within the central nervous system, e.g., tricyclic antidepressants, serotonin noradrenaline reuptake inhibitors, and voltage-gated calcium channel subunit ligands, e.g., gabapentin and pregabalin. Investigation of a range of novel targets, such as melatoninergic, cannabinoid, dopamine, NMDA, angiotensin, orexin and opioid receptors, and ion channels, in addition revisiting bioamine modulation and subunits has provided efficacy outcomes that improve the health status of patients with FM. Nevertheless, modest and limited efficacy is often observed reflecting the heterogeneity of FM with existence of subpopulations of patients, the contribution of peripheral and central components to the pathophysiology, and the extensive range of accompanying co-morbidities. The complexity and multidimensional nature of FM is emphasized by the diversity of pharmacological targets gaining interest. Clues to underlying mechanisms which offer themselves as novel and potential targets for new medications are being provided by advances in the understanding of the pathophysiology of FM.
基金Supported by Italian Ministry of Education,University and Research(PRIN2005,grant No.2005052312)and University of Tuscia
文摘Retinal ischemia is a common clinical entity and, due to relatively ineffective treatment, remains a common cause of visual impairment and blindness. Generally, ischemic syndromes are initially characterized by low homeostatic responses which, with time, induce injury to the tissue due to cell loss by apoptosis. In this re-spect, retinal ischemia is a primary cause of neuronal death. It can be considered as a sort of fnal common pathway in retinal diseases and results in irreversible morphological and functional changes. This review summarizes the recent knowledge on the effects of ischemia in retinal tissue and points out experimental strategies/models performed to gain better compre-hension of retinal ischemia diseases. In particular, the nature of the mechanisms leading to neuronal damage (i.e., excess of glutamate release, oxidative stress and infammation) will be outlined as well as the potential and most intriguing retinoprotective approaches and the possible therapeutic use of naturally occurring molecules such as neuropeptides. There is a general agreement that a better understanding of the funda-mental pathophysiology of retinal ischemia will lead tobetter management and improved clinical outcome. In this respect, to contrast this pathological state, spe-cifc pharmacological strategies need to be developed aimed at the many putative cascades generated during ischemia.
文摘The spectrum of drug-induced liver injury (DILI) is both diverse and complex. The first step in diagnosis is a suspicion of DILl based on careful consideration of recent comprehensive reports on the disease. There are some situations in which the suspicion of DILI is particularly strong. Exclusion of other possible etiologies according to the pattern of liver injury is essential for the diagnosis. In patients with suspected DILl, diagnostic scales, such as the Councils for International Organizations of Medical Sciences/ Roussel Uclaf Causality Assessment Method (CIOMS/RUCAM) scale, may be helpful for the final diagnosis. Early management of DILl involves prompt withdrawal of the drug suspected of being responsible, according to serum levels of alanine aminotransferase (ALT), alkaline phosphatase (ALP), and total bilirubin (T-Bil). However, as DILI patients may show resolution of liver injury without discontinuation of the drug, it should be carefully evaluated whether the suspected drug should be discontinued immediately with adequate consideration of the importance of the medication.
文摘Irritable bowel syndrome (IBS) is a highly prevalent gastrointestinal disorder characterized by abdominal pain and discomfort in association with altered bowel habits. It is estimated tD affect 10%-15% of the Western population, and has a large impact on quality of life and (in)direct healthcare costs. IBS is a multifactorial disorder involving dysregulation within the brain-gut axis, and it is frequently associated with gastrointestinal motor and sensory dysfunction, enteric and central nervous system irregularities, neuroimmune dysregulation, and postinfectious inflammation. As with other functional medical disorders, the treatment for IBS can be challenging. Conventional therapy for those with moderate to severe symptoms is largely unsatisfactory, and the development of new and effective drugs is made difficult by the complex pathogenesis, variety of symptoms, and lack of objective clinical findings that are the hallmark of this disorder. Fortunately, research advances over the past several decades have provided insight into potential mechanisms responsible for the pathogenesis of IBS, and have led to the development of several promising pharmaceutical agents. In recent years there has been much publicity over several of these new IBS medications (alosetron and tegaserod) because of their reported association with ischemic colitis and cardiovascular disease. While these agents remain available for use under restricted prescribing programs, this highlights the need for continued development of safe and effective medication for IBS. This article provides a physiologicallybased overview of recently developed and frequently employed pharmaceutical agents used to treat IBS, and discusses some non-pharmaceutical options that may be beneficial in this disorder.
文摘AIM: To combine ultrasound-guided fine-needle aspiration (US-FNA) and Liu (Riu) stain to make a quick study on liver tumor lesions. METHODS: Two hundred and twenty-eight aspirations from 232 patients were completely studied. The operator himself made the quick cytodiagnosis of US-FNA smear stained by Liu method within thirty minutes. The US-FNA specimen was also sent to the pathological department for cytological study and cellblock histology. The result of our Uu-stain quick cytodiagnosis in each patient was confirmed by the final cytopathological diagnosis from pathological report. RESULTS: Among 228 samples, the quick cytodiagnosis revealed 146 malignancies, 81 benign lesions and one inadequate specimen. Cytopathological diagnosis from the pathological department revealed 150 malignancies, and 78 benign lesions. Four well-differentiated hepatocellular carcinomas (HCCs) were under-diagnosed by quick cytodiagnosis as benign and 3 benign lesions were over-diagnosed as well-differentiated HCCs. Compared with cytopathological diagnosis, quick cytodiagnosis correctly diagnosed 143 malignancies and 77 benign lesions. Except for the one inadequate specimen in quick cytodiagnosis, the accuracy of quick cytodiagnosis was 96.9% (220/227), and its sensitivity, specificity and positive and negative predictive values were 97.9%, 95.1%, 97.3% and 96.3%, respectively. CONCLUSION: Liu-stain quick cytodiagnosis is a fast, convenient, safe and effective method for hepatologists in clinic practice to diagnose liver tumor. In few cases of well-differentiated HCC, Liu-stain quick cytodiagnosis has its limitation.
基金National Natural Science Foundation of China (30670093)
文摘Kaposi’s sarcoma-associated herpesvirus (KSHV) was first identified as the etiologic agent of Kaposi’s sarcoma (KS) in 1994. KSHV infection is necessary,but not sufficient for the development of Kaposi sarcoma (KS),primary effusion lymphoma (PEL),and multicentric Castleman disease (MCD). Advances in the prevention and treatment of KSHV-associated Diseases have been achieved,even though current treatment options are ineffective,or toxic to many affected persons. The identification of new targets for potential future therapies and the randomized trial to evaluate the efficacy of new antivirals are required.
文摘Telomeres are non-coding tandem repeats of 1000-2000 TTAGGG nucleotide DNA sequences on the 3’ termini of human chromosomes where they serve as protective “caps” from degradation and loss of genes. The “cap” at the end of chromosome required to protect its integ-rity is a 150-200 nucleotide-long single stranded G-rich 3’ overhang that forms two higher order structures, a T-loop with Sheltering complex, or a G-quadruplex com-plex. Telomerase is a human ribonucleoprotein reverse transcriptase that continually added single stranded TTAGGG DNA sequences onto the single strand 3’ of telomere in the 5’ to 3’ direction. Telomerase activity is detected in male germ line cells, proliferative cells of renewal tissues, some adult pluripotent stem cells, embryonic cells, but in most somatic cells is not de-tected. Re-expression or up-regulation of telomerase in tumours cells is considered as a critical step in cell tumorigenesis and telomerase is widely considered as a tumour marker and a target for anticancer drugs. Dif-ferent approaches have been used in anticancer thera-peutics targeting telomerase. Telomerase inhibitors can block directly Human TElomerase Reverse Transcrip-tase (hTERT) or Human TElomerase RNA telomerase subunits activity, or G-quadruplex and Sheltering complex components, shortening telomeres and inhibiting cell proliferation. Telomerase can become an immune target and GV1001, Vx-001, I540 are the most wide-spread vaccines used with encouraging results. Another method is to use hTERT promoter to drive suicide gene expression or to control a lytic virus replication. Recently telomerase activity was used to activate pro-drugs such as Acycloguanosyl 5’-thymidyltriphosphate, a synthetic ACV-derived molecule when it is activated by telomer-ase it does not require any virus or host active immune response to induce suicide gene therapy. Advantage of all these therapies is that target only neoplastic cells without any effects in normal cells, avoiding toxicity and adverse effects of the current chemotherapy. However, as not all the approaches are equally effcient, further studies will be necessary.
文摘Over the past three decades, concerns about the high prevalence of antipsychotic use in the nursing homes (NHs) for the management of behavioral and psychological symptoms of dementia continue to be emphasized and intervened by many. However, despite the numerous side effects and the recent blackbox warning by the United States Food and Drug Administration about the increased risks for stroke and sudden death associated with the use of antipsychotics in dementia, the preva-lence of antipsychotic use in NHs remains high. While the use of antipsychotics appeared to have modest effcacy in reducing symptoms of aggression and psychosis in dementia, there is insuffcient evidence to routinely rec-ommend the use of alternative psychopharmacological treatments for these symptoms. Hence, clinicians have to balance the safety warnings against the need to treat these symptoms in order to prevent harm to the resident that may result from his/her dangerous behaviors. Although the use of antipsychotics may be warranted in some cases, organizational, resource and training support should be provided to encourage and equip NH staff to participate in interventions so as to minimize inappropriate use of these medicines in NHs. This review will discuss the place in therapy, the trend and appropriateness of antipsychotic use in NHs, as well as the effectiveness of current and future strategies for reducing antipsychotic use in the NHs.
文摘Objective: To observe the clinical efficacy of oral traditional Chinese medicine (Jiaweitiaoqi decoction), electroacupuncture, biofeedback, and combined treatment on functional anorectal pain (FAP). Methods: A total of 200 patients with FAP were randomly divided into 4 groups, with 50 patients in each group. Group 1 was given oral Jiaweitiaoqi decoction; group 2 was given electroacupuncture at the lumbosacral acupoints; group 3 was given biofeedback training; and group 4 was given combined treatment. The numeric rating scale (NRS), Short Form-36 (SF-36) quality of life scale, static pressure of the anal canal, and maximum systolic pressure were observed in the 4 groups. Results: The observation indices of the 4 groups were all improved after treatment compared with those before treatment, and the fourth group showed the most obvious improvement. Regarding NRS scores, the static pressure of the anal canal, and maximum systolic pressure, group 4 had lower values than the other 3 groups (P 〈 0.05 for all). In the SF-36 quality of life score, group 4 showed a higher value than the other 3 groups (P 〈 0.05). Conclusion: Non-drug therapy including acupuncture and physical exercise can enhance the clinical efficacy of single Chinese medicine in the treatment of FAP .
文摘Chronic diarrhea can be divided into four types:retention of dampness leading to blockage of qi,invasion of the intestines by pathogenic wind,damp-retention due to deficiency of the spleen, andstagnation of the liver-qi with deficiency of thespleen.
文摘To promote efficient screening of active angiogenic drugs from traditional medicines, we constructed a humanembryonic kidney-293 cell model using vascular endothelial growth factor (VEGF) gene promoter as the drug target. Inthis model, VEGF gene promoter may regulate the expression of the luciferase reporter gene by responding to thestimulation of drug molecules. This cell model allows rapid and efficient screening of vascular-inducing activecomponents from several drug monomer molecules. Furthermore, we used rat bone marrow mesenchymal stem cells(rMSCs) to conduct a preliminary study on the activity of alantolactone. Using simvastatin as a positive control, weinvestigated the effects of alantolactone on the expression of vascular-related cell marker molecules such as VEGF andα-smooth muscle actin (α-SMA) in rMSCs. According to our results, 0.1, 1, 3 and 5 μM of alantolactone upregulated thetranscriptional luciferase gene activity of VEGF promoter, and a significant difference from that in the control group wasobserved. Among them, 3μM of alantolactone showed the better effect than that of 3 μM of simvastatin (P = 0.036) andother concentrations of alantolactone and simvastatin showed similar effects. Compared with that in the control group,rMSCs induced with 1μM alantolactone for 3 days showed a significant increase in the relative mRNA expressions ofVEGF and α-SMA genes. However, these effect of 5 μM alantolactone were weaker than those of 5 μM simvastatin (P 〈0.05); rMSCs treated with 1 μM alantolactone for 3 days showed brighter green fluorescence (FITC marker) of α-SMAand VEGF in situ expression than that observed in the control group and similar fluorescence intensity than that ofsimvastatin group in an immunoradiometric assay. The above results demonstrate the reliability of the highly efficientsystem for screening of active drug molecules and confirmed the vascular induction function of alantolactone at the geneand protein levels.