Crocetin, a naturally occurring carotenoid, possesses antioxidant and antiatherosclerotic properties, of which the underlying mechanism remains unclear. In the present study, we examined the effects of crocetin (0.1, 1, 10 μmol·L(-1)) on angiotensin II (Ang II, 0.1 μmol·L(-1)) induced expression of vascular cell adhesion molecule-1 (VCAM-1) in human umbilical vein endothelial cells (HUVECs) and monocyte-endothelial cell adhesion. The effects of crocetin on the activation of nuclear factor kappa B (NF-κB) and intracellular reactive oxygen species (ROS) were also observed. The results demonstrated that crocetin notably suppressed Ang II induced NF-κB activation (P<0.01) and VCAM-1 expression (P<0.05, P<0.01) in HUVECs, accompanied by a markedly reduced monocyte-endothelial cell adhesion (P<0.05, P<0.01). In addition, preincubation with crocetin resulted in a significant enhancement of cellular antioxidant capacity (P<0.05, P<0.01), while Ang II induced intracellular ROS decreased markedly (P<0.05, P<0.01). These results indicated that crocetin was capable of suppressing Ang II induced VCAM-1 expression and monocyte-endothelial cell adhesion by suppression of NF-κB activation, which might be derived from the enhancement of antioxidant capacity and subsequent reduction of intracellular ROS.
Angiotensin II ; metabolism ; Antioxidants ; pharmacology ; Carotenoids ; pharmacology ; Cell Adhesion ; drug effects ; Human Umbilical Vein Endothelial Cells ; cytology ; drug effects ; metabolism ; Humans ; Monocytes ; cytology ; NF-kappa B ; metabolism ; Reactive Oxygen Species ; metabolism ; Vascular Cell Adhesion Molecule-1 ; metabolism

Many tumors depend on glutamine for energy.Glutamine metabolism is recognized as a distinctive feature in addition to Warburg effect in tumors.Nuclear medicine molecular tracer techniques represented by positron emission tomography (PET) provide a good means for early diagnosis and prognosis of tumors.PET imaging can detect glutamine metabolism region in tumors noninvasively,which can provide new diagnosis and therapeutics for glutamine-addicted tumors.

Objective To study the prevalence and trend of tuberculosis for related policy development in Shandong.Methods The population under the current study was randomly sampled,using both stratified clustering sampling and proportional population sampling methods,following the national survey protocol.A total of 35 clusters including about 1500 subjects per cluster were established,representing a population of 9.31 million.Questionnaire interview and chest X-ray exam were applied to all inhabitants above 15 years of age.Sputum microscopy and culture were given to all suspected cases with cough longer than 2 weeks or having abnormal X-ray results.Results In total,54 279 subjects were interviewed and examined,accounting for 95.78％ of eligible population.Of them,183 active pulmonary tuberculosis cases were identified,with 60.11％ asymptomatic.Two of the 35 (5.71％) clusters had no active tuberculosis cases found,and 24(68.57％) did not show smear positive results.The standardized prevalence rates of active,smear positive and bacteriologic positive pulmonary tuberculosis cases were 270.87/105,17.45/105 and 29.57/105,with the estimated case numbers as 211 900 (170 100-253 600),13 600 (5800-21 500) and 23 100 (13 200-33 000)respectively.Compared to the survey in 2000,the rates on smear positive and bacteriologic positive tuberculosis had decreased significantly,at a rate of 81.63％,and 75.56％ respectively.The rates in urban areas and in women decreased quickly than those in rural areas and in men.People living in the rural areas,being elderly or males,had significantly higher prevalence rates of tuberculosis.Conclusion Remarkable reduction of tuberculosis prevalence had been achieved despite the fact that tuberculosis remained a major public health problem in Shandong province.Symptomatic patients should be under more serious concern in order to improve the detection of early cases.More efforts should be given to rural population,especially elderly,male population.

D-lactonohydrolase is useful in the procedure of resolution of racemic pantolactone to produce D-pantolactone, but the activity and stability under low pH of the wild type enzyme is not satisfactory enough to be applied to industrial production. The expected properties of wild type enzyme were enhanced by directed evolution. According to the formation of products and pH indicators, a screening system was designed. After three sequential error prone PCR and one round DNA shuffling followed by screening, Mut E-861, the best mutant with improved activity and stability under low pH situation was obtained. Gene analysis of the Mut E-861 mutant indicated that the mutant enzyme had A352C, G721A mutations and a silent mutation of position 1038. Moreover, the activity and stability of Mut E-861 were determined. The results showed that the activity of this mutant was 5.5-fold higher than that of wild type, and the stability under low pH was improved at no expense of D-lactonohydrolase activity. After incubated at pH 6.0 and pH 5.0 the activity of D-lactonohydrolase could be retained 75% to 50%, however, compared with 40% to 20% for wild type.
Carboxylic Ester Hydrolases ; biosynthesis ; genetics ; DNA Shuffling ; Directed Molecular Evolution ; Enzyme Stability ; Escherichia coli ; enzymology ; genetics ; Mutagenesis, Site-Directed ; Mutant Proteins ; genetics ; metabolism ; Polymerase Chain Reaction ; methods ; Protein Engineering ; Saccharomyces cerevisiae ; enzymology ; genetics

The safety of Chinese patent medicine has become a focus of social. It is necessary to carry out work on post-marketing clinical safety evaluation for Chinese patent medicine. However, there have no criterions to guide the related research, it is urgent to set up a model and method to guide the practice for related research. According to a series of clinical research, we put forward some views, which contained clear and definite the objective and content of clinical safety evaluation, the work flow should be determined, make a list of items for safety evaluation project, and put forward the three level classification of risk control. We set up a model of post-marketing clinical safety evaluation for Chinese patent medicine. Based this model, the list of items can be used for ranking medicine risks, and then take steps for different risks, aims to lower the app:ds:risksrisk level. At last, the medicine can be managed by five steps in sequence. The five steps are, collect risk signal, risk recognition, risk assessment, risk management, and aftereffect assessment. We hope to provide new ideas for the future research.
Clinical Trials as Topic ; Drug-Related Side Effects and Adverse Reactions ; epidemiology ; etiology ; Drugs, Chinese Herbal ; adverse effects ; chemistry ; economics ; therapeutic use ; Herbal Medicine ; economics ; legislation & jurisprudence ; Humans ; Patents as Topic ; Product Surveillance, Postmarketing ; Quality Control

BACKGROUNDWhether plasma can transfer the protective effect(s) of remote ischemic preconditioning (RIPC) between animals remains unresolved. We therefore investigated the effects of plasma collected 48 hours after transient limb ischemia on blood pressure recovery during myocardial ischemia reperfusion (IR) in homogenic rats.

METHODSPlasma was collected from Lewis rats, and the donor rats were randomly assigned to 2 groups: transient limb ischemia and control (n = 8 each). Transient limb ischemia was achieved by four cycles of 5-minute ischemia and 5-minute reperfusion by noninvasive ligation and deligation of the both legs using elastic rubber bands after anesthesia. In the control group, no ligation was performed. Forty-eight hours later, whole blood was collected, and the plasma spun off. Study Lewis rats underwent 30-minute left anterior descending coronary artery occlusion followed by 180-minute reperfusion, and were randomly assigned to 2 groups (group A and group B, n = 24 each), each further subdivided into 3 subgroups (n = 8 each). The subgroups of group A received normal saline (group A1) , plasma of control rats (group A2), plasma of transient limb ischemia rats (group A3) respectively at 1 hour before IR; the subgroups of group B received normal saline (group B1), plasma of control rats (group B2), plasma of transient limb ischemia rats (group B3) respectively at 24 hours before IR. BIOPAC systems were used to measure hemodynamics of rats during myocardial ischemiareperfusion.

RESULTSSystolic blood pressure (SBP) after IR in group B3 was different from that in groups B1 and B2 (B3 vs. B1, P = 0.007; B3 vs. B2, P = 0.039) at the beginning of reperfusion and 30 minutes after reperfusion. SBP was higher in group B3 than in groups B1 and B2 at the beginning of perfusion (B3 vs. B1, P = 0.010; B3 vs. B2, P = 0.002) and 30 minutes after reperfusion (B3 vs. B1, P = 0.001; B3 vs. B2, P = 0.001). SBP did not differ among subgroups A1, A2 and A3. Diastolic blood pressure and heart rate did not change in group A or group B.

CONCLUSIONSThe transfusion of plasma collected 48 hours after transient limb ischemia into homogenic rats 24 hours before IR can improve the SBP recovery during reperfusion. This may suggest that cardioprotective effect of late phase of RIPC is transferable via plasma.

Animals ; Blood Pressure ; physiology ; Extremities ; blood supply ; Ischemia ; Ischemic Preconditioning ; Male ; Plasma ; Rats ; Rats, Inbred Lew ; Time Factors

To explore novel histone deacetylase (HDACs) inhibitors with anti-tumor activity, MS-275, a HDACs inhibitor, was prepared and used as a lead compound to design new N-substituted benzamide derivatives. MS-275 and eleven target compounds were obtained, and their structures were confirmed by 1H NMR and HR-MS individually. The results showed that the activity of compound 9d was equal to MS-275 in HDACs inhibition tests in vitro and worthy of further investigation. Compound 5c, 5d and 9c displayed obvious dose-effect relationship, which possessed moderate HDACs inhibitory activities. Ten compounds except 9e had selective inhibitory activities on Hut78.
Antineoplastic Agents ; chemical synthesis ; chemistry ; pharmacology ; Benzamides ; chemical synthesis ; chemistry ; pharmacology ; Cell Line, Tumor ; Humans

OBJECTIVETo study different effects of Herba Lycopodii (HL) Alcohol Extracted Granule combined methylprednisolone on behavioral changes, brain derived neurotrophic factor (BDNF) expression levels, and N-methyl-D-aspartate (NMDA) receptor levels in rats with spinal cord injury (SCI).

METHODSMale adult SD rats were randomly divided into five groups, i.e., the sham-operation group, the model group, the HL treatment group, the methylprednisolone treatment group, the HL + methylprednisolone treatment group. Rats in the HL treatment group were intragastrically administered with HL at the daily dose of 50 mg/kg for 5 successive days. Rats in the methylprednisolone treatment group were intramuscularly injected with 50 mg/kg methylprednisolone within 8 h after spinal cord contusion, and then the dose of methylprednisolone was reduced for 10 mg/kg for 5 successive days. Rats in the HL + methylprednisolone treatment group received the two methods used for the aforesaid two groups. Basso Beattie and Bresnahan (BBB) score (for hindlimb motor functions) were assessed at day 0, 3, 7, and 28 after operation. At day 13 after SCI, injured spinal T8-10 was taken from 8 rats of each group and stored in liquid nitrogen. The N-methyl-D-aspartate (NMDA) receptor affinity (Kd) and the maximal binding capacity (Bmax) were determined using [3H]MK-801 radioactive ligand assay. Rats' injured spinal cords were taken for immunohistochemical assay at day 28 after SCI. Expression levels of BDNF in the ventral and dorsal horn of the spinal cord were observed.

RESULTSCompared with the sham-operation group, the number of BDNF positive neurons in the ventral and dorsal horn of the spinal cord increased in the model group, Bmax increased (470 ± 34), Kd decreased, and BBB scores decreased at day 3 -28 (all P <0. 05). Compared with the SCI model group, the number of BDNF positive neurons and Kd increased, BBB scores at day 3 -28 increased (P <0. 05) in each medicated group. Bmax was (660 ± 15) in the methylprednisolone treatment group, (646 ± 25) in the HL treatment group, and (510 ± 21) in the HL +methylprednisolone treatment group (P <0. 05). Compared with the methylprednisolone treatment group, the number of BDNF positive neurons and Kd increased, BBB scores at day 7 -28 increased, and Bmax decreased in the HL treatment group and the HL + methylprednisolone treatment group (all P <0. 05). Compard with the HL treatment group, the number of BDNF positive neurons and Kd increased, and Bmax decreased (all P < 0.05).

CONCLUSIONSHL could effectively improve motor functions of handlimbs, increase expression levels of BDNF in the spinal cord, and lessen secondary injury by affecting spinal levels of NMDA receptors. It showed certain therapeutic and protective roles in treating SCI. Its effect was better than that of methylprednisolone with synergism.

Animals ; Brain-Derived Neurotrophic Factor ; metabolism ; Drugs, Chinese Herbal ; pharmacology ; therapeutic use ; Ethanol ; Male ; Methylprednisolone ; pharmacology ; therapeutic use ; Models, Animal ; N-Methylaspartate ; metabolism ; Neurons ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Receptors, N-Methyl-D-Aspartate ; Spinal Cord Injuries ; drug therapy ; metabolism

OBJECTIVETo investigate the effect of sensory neuropeptide substance P (SP) on the differentiation of cultured epidermal stem cells (ESC) in vitro,with in vitro cultured ESC as the platform.

METHODSESC from newborn Wistar rats were isolated, purified by repeated passages in culture. SP was added for stimulation when ESC clone grew. Immunohistochemistry staining with K14 antibody, and flow cytometry (FCM) was performed at 0, 24th, 48th, 72nd, 96th, 144th, 192nd, 240th, 288th, 336th, 384th, 432nd post differentiation hours (PDH) to identify the cell groups and to detect if there were transient amplifying cells (TAC) among the cells.

RESULTSESC in culture formed large colonies after SP treatment with positive staining for K14, indicating that they were TACs. The results of FCM indicated that when ESC were stimulated by SP, TAC colony formation occurred and the cell number increased in a constant speed.

CONCLUSIONESC could differentiate into TAC by neuropeptide SP induction, and the number of ESC kept on a certain level during the process.

Animals ; Cell Differentiation ; drug effects ; Cells, Cultured ; Endothelial Cells ; cytology ; Female ; Flow Cytometry ; Male ; Rats ; Rats, Wistar ; Sensory Receptor Cells ; chemistry ; Stem Cells ; cytology ; Substance P ; pharmacology

Child ; China ; epidemiology ; Humans ; Monitoring, Immunologic ; statistics & numerical data ; Vaccination ; statistics & numerical data