Identification and validation of a new target is one of the most important steps for new antituberculosis (TB) drug discovery. Researches have shown that Mycobacterium tuberculosis (Mtb) encodes 20 CYP450 enzymes which play important roles in the synthesis and metabolism of lipid, cholesterol utilization, and the electron transport of respiratory chain in Mtb. With the critical roles within the organism as well as the protein structures of six Mtb CYP450 enzymes being clarified, some of them have been highlighted as potential anti-tuberculosis targets. In this paper, the phylogenetic analysis, the structural features, and the enzymatic functions of Mtb CYPs, as well as the mechanism of interactions with selective inhibitors such as azole antifungal agents for the CYPs have been reviewed and summarized. The druggability of the CYPs has also been analyzed for their further utility as targets in high throughput screening and rational design of more selective inhibitors.
Antitubercular Agents ; chemistry ; pharmacology ; Azoles ; chemistry ; pharmacology ; Cytochrome P-450 Enzyme Inhibitors ; chemistry ; pharmacology ; Cytochrome P-450 Enzyme System ; genetics ; metabolism ; Drug Delivery Systems ; methods ; Drug Discovery ; Humans ; Mycobacterium tuberculosis ; drug effects ; enzymology ; genetics ; Phylogeny ; Tuberculosis ; drug therapy ; microbiology

OBJECTIVETo assess the clinical outcomes of balloon kyphoplasty assisted with calcium phosphate cement (CPC) in treating osteoporotic vertebral fractures (OVF).

METHODSFrom January 2009 to January 2011, 26 patients with osteoporotic vertebral fractures were treated with balloon kyphoplasty assisted with CPC, including 31 vertebrae. There were 15 males and 11 females with an average age of (71.67 +/- 4.36) years old (ranged from 60 to 89 years). Course of disease was from 0.5 to 7 days with an average of 3.2 days. Clinical outcomes were assessed by the visual analogue scale (VAS) and the oswestry disability index (ODI). Vertebral height loss and kyphotic angle were measured by X-rays.

RESULTSAll patients were followed up for 10 to 24 months with an average of 18 months. Before operation, 24 hours after operation and at final follow-up, VAS scores were 7.91 +/- 1.20, 3.22 +/- 1.12, 1.92 +/- 0.83, respectively; ODI scores were 40.00 +/- 1.15, 17.00 +/- 2.12, 13.00 +/- 1.42, respectivesly; vertebral heights were (18.21 +/- 3.21), (23.82 +/- 3.10), (21.85 +/- 3.24) mm, respectivesly; vertebral kyphosis angles were (18.21 +/- 3.21) degrees, (7.42 +/- 3.13) degrees, (10.01 +/- 3.11) degrees, respectivesly. There was significant difference between preoperation and 24 hours after operation, and between final follow-up and preoperation (P < 0.05). There was no significant difference between final follow-up and 24 hours after operation (P > 0.05).

CONCLUSIONBalloon kyphoplasty assisted with calcium phosphate cement (CPC) is effective for the treatment of osteoporotic vertebral fractures (OVF), which can expeditiously relieve pain and effectively rebuild height of vertebral body and kyphotic angle, and also has advantages of minimal trauma and good security.

Aged ; Aged, 80 and over ; Bone Cements ; Calcium Phosphates ; therapeutic use ; Female ; Humans ; Kyphoplasty ; methods ; Male ; Middle Aged ; Osteoporotic Fractures ; surgery ; Spinal Fractures ; surgery ; Visual Analog Scale

Objective To investigate the proliferation inhibition of chlorpromazine combined with taxol on Hep-2 cells (human laryngeal carcinoma cell line) and the effects on cell cycle progression. Methods Hep-2 cells at logarithmic growth phase were divided into taxol groups(3.0,6.0 and 12.0 mg?L-1),chlorpromazine(12.0 mg?L-1) comined with taxol (4 mg?L-1)group and control group (100 mL culture fluid).MTT and flow cytometry were used to detect the proliferation inhibition rates of Hep-2 cells in various groups.Flow cytometry was also used to analyze the cell cycle progression of Hep-2 cells and apoptotic rate after administration.Results The proliferation inhibition rates in 3.0,6.0 and 12.0 mg?L-1 taxol groups were 14.0%,23.9% and 36.7%,respectively,there were significant differences between three groups(P

The author uses the database technique to manage the impedance spectroscopy data.In design of impedance spectroscopy database frame,ActiveX Data Object(ADO)technique is adopted to improve the agility and efficiency.It also enhances the efficiency to use data binding technique to avoid complex data type transformation in appending and amending.

In the tissue impedance spectroscopy measurements ,four-electrode method are normally used. A measurement error caused by stray capacitance between lines of drive electrode and receive electrode is not a trivial problem. This paper studied this error and reached the results This stray capacitance introduces errors which increase with frequency and has more effect on the imaginary part than on the real part in the measurement frequency range.

Objective To explore the molecular mechanisms of primary amenorrhea by using arrayCGH technology. Methods Ten patients with primary amenorrhea and 10 female volunteers with regular menstrual cycles as healthy controls were selected. All patients and control samples were analyzed by conventional chromosome analysis (G-banding technology) and array-CGH technology, respectively. ArrayCGH was performed using Affymetrix Cytogenetic 2. 7M arrays following the manufacturer's standard protocol. Results Both the patient group and control group analyzed by conventional G-banding karyotype technology showed a negative result with a normal female karyotype: 46, XX. The result of array-CGH analysis demonstrated a microdeletion of approximately 110 000 bp located at the end of the short arm of X chromosome [46, X, del (X) (p22. 33 )] were identified in 5 patients, which was not detected in the control group. All healthy control samples by array-CGH analysis showed no pathological DNA copy number variation. Conclusions Array-CGH technology can improve the diagnosis rate of chromosomal disease at the DNA level. It is necessary to provide array-CGH for higher resolution genetic analysis of idiopathic primary amenorrhea patient who can not be identified by conventional technology.

Objective:To observe the clinical efficacy of Yi Jin Jing (Sinew-transforming Qigong Exercises) for primary osteoporosis in the elderly.Methods:Eighty old patients with primary osteoporosis were randomized into a Yi Jin Jing group and a medication group,40 cases in each group.The Yi Jin Jing group was intervened by Yi Jin Jing (Sinew-transforming Qigong Exercises) training,while the medication group was intervened by oral administration of alendronate sodium tablet.Prior to and after 6-month intervention,the bone mineral density (BMD) of the proximal femur,visual analog scale (VAS) and activities of daily living (ADL) were estimated.Results:There were no significant differences in the BMD of the proximal femur,and VAS and ADL scores between the two groups before the intervention (P＞0.05).After 6-month intervention,the above items all improved significantly in both groups (both P＜0.01);the improvements in VAS and ADL scores in Yi Jin Jing group were more significant than those in the medication group (P＜0.01),while the between-group difference in the BMD of the proximal femur was statistically insignificant (P＞0.05).Conclusion:Practice of Yi Jin Jing (Sinew-transforming Qigong Exercises) can effectively ameliorate the BMD in the elderly with primary osteoporosis,and it can reduce the pain and improve ADL,with a better general effect compared to oral administration of alendronate sodium tablet.

Objective To investigate the relationship between peripheral inflammatory cytokines and anxiety symptoms in patients with the first?episode generalized anxiety disorder. Methods 48 patients diagnosed with the first?episode generalized anxiety disorder according to ICD?10 criteria and 48 healthy sub?jects were recruited. Peripheral levels of IL?1, IL?2, IL?4, IL?5, IL?6, IL?8, IL?10, IL?12p70, GM?CSF and IFN?γ of both groups were evaluated by enzyme?linked immunosorbent assay ( ELISA) ,and CRP was evalua?ted by immunoturbidimetric method. Generalized Anxiety Disorder Scale( GAD?7) and State?Trait Anxiety Inventory ( STAI ) were used to assess the levels of overall anxiety, state anxiety and trait anxiety. Results The levels of CRP ( ( 1. 19 ± 0. 80 ) mg/L vs ( 0. 68 ± 0. 70 ) mg/L, t=3. 31 ) , IL?1α( ( 70. 34 ± 3.60)pg/ml vs (16.94±3.42)pg/ml, t=74.50),IL?2((7.25±3.42)pg/ml vs (4.95±2.31)pg/ml, t=3.85), IL?4((102.02±73.14)pg/ml vs (75.55±32.78)pg/ml, t=2.29),IL?6((12.55±2.37)pg/ml vs (2.71±1.35) pg/ml, t=14.79),IL?8((44.64±16.21)pg/ml vs (35.69±11.70)pg/ml, t=3.10),IL?12((18.16±24.17) pg/ml vs (10.82±4.72)pg/ml, t=2.06),IFN?γ((23.32±15.52)pg/ml vs (16.48±6.80)pg/ml, t=2.79), GM?CSF((19.07±11.12)pg/ml vs (13.40±8.54)pg/ml, t=2.80) in patients with the first?episode general?ized anxiety disorder were significantly higher than normal controls(P<0.05) . Both SAI and TAI had signifi? cantly positive correlation with the levels of IL?1α, IL?2, IL?6, IL?8, IL?12, IFN?γ and GM?CSF ( r=0.24?0.76, P<0.05) . Conclusion The levels of some peripheral inflammatory cytokines in patients with the first?episode generalized anxiety disorder are significantly increased,and they have positive correlation with gener?al anxiety,state anxiety and trait anxiety,which may suggest some immune system defects in the patients.

Adenocarcinoma ; pathology ; Adenocarcinoma, Papillary ; pathology ; Aged, 80 and over ; Carcinoma, Renal Cell ; pathology ; Duodenal Neoplasms ; pathology ; Humans ; Kidney Neoplasms ; pathology ; Lung Neoplasms ; pathology ; Male ; Neoplasms, Multiple Primary ; pathology ; Sarcoma ; pathology ; Stomach Neoplasms ; pathology

Aim We used bone marrow-derived macro-phages ( BMMs ) , to explore the mechanism of macro-phage activation and the effect of TGF-β activated ki-nase-1 ( TAK1 ) inhibitor 5 Z-7-oxozeaenol on it under AGEs conditions. Methods The BMMs were obtained from C57 mice, and purity of BMMs was detected by flow cytometry. Cell viability was tested after treatment with different concentrations of TAK1 inhibitors. Laser confocal microscopy was used to detect macrophage M1 subtype . Flow cytometry was used to analyse the macro-phage activated by AGEs. TNF-α and MCP-1 mRNA levels were evaluated by qRT-PCR. Western blot was used to detect the expression levels of TAK1 signal pathway protein. Results AGEs stimulation could in-crese the activity of M1 macrophages,and 5Z-7-oxoze-aenol could inhibit the differentiation of BMMs. Com-pared with control group, AGEs increased the expres-sion of MCP-1 and TNF-α mRNA(P<0. 01). p-TAK1, TAB1,p-JNK,p-p38MAPK and NF-κBp65 proteins ex-pression also increased significantly ( P <0. 05 ) . After treatment with inhibitor, transcription levels of MCP-1 and TNF-α decreased significantly ( P < 0. 05 , P <0. 01 ) . 5 Z-7-oxozeaenol treatment downregulated the expression of p-TAK1,TAB1,p-JNK,p-p38MAPK and
NF-κBp65 proteins ( P <0. 05 ) . Conclusions AGEs can induce BMMs to M1 phenotypic polarization. 5Z-7-oxozeaenol reduces the expression of inflammatory cyto-kine via inhibiting TAK1/MAPKs, MAPKs/NF-κB pathways.