Lead compound optimization strategy (7) —— modification strategies for peptides / 药学学报

Most peptides have high binding affinity and good selectivity for endogenous receptors and are good lead compounds to develop into drugs. Many approved drugs are derived from the structural optimization of peptide molecules, such as the antihypertensive drug captopril and the anti-hepatitis C drug telaprevir. At present, the main problems in the development of peptide drugs include poor stability, short half-life, and high plasma clearance rate; lack of oral availability and poor patient compliance, a complex production process, and high production cost. Therefore, rational modification of peptides can not only reduce the production cost, but also improve the druggability of the peptides. Here we review structural modification strategies for peptides from the perspective of improving their physicochemical properties. These modification strategies are divided into two parts: one is modification of the peptide backbone, including unnatural amino acid modification, pseudopeptide strategy, inverse-peptide strategy, cyclization strategy, and terminal structure modification. Another is modification of the side chains of peptides, including fatty acid conjugation, polyethylene glycol conjugation, protein fusion strategy, and cholesterol conjugation.

Bergapten attenuates D-galactose-induced immunosenescence in BALB/c mice / 中国药理学与毒理学杂志

OBJECTIVE Bergapten (BG), is a furanocoumarin derived from herbal and citrus extracts can act as antioxidant and selective anticancer agents.The current study aimed to investigate whether bergapten would attenuate immunosenescence and to exploreits immunomodulatory effects on immune responses in D-galactose-induced aging BALB/c mice.METHODS Firstly,mice were given D-galactose(180 mg·kg-1)subcutaneous injections for 30 d.To evaluate the establishment of the aging-related effect in mice, serum samples of BALB/c mice were collected from tail vein. Aging BALB/c mice were freely divided into three groups: negative control group received 1% Tween 80 solution only, named D-gal group. Positive groups were received BG administration at the dose of 20 and 100 mg·kg-1, named D-gal+BG(20)group and D-gal+BG(100)group,respectively.Effects of bergapten on T lympho-cyte proliferation and flow cytometry were assessed by using the splenic cell suspension. Enzyme linked immunospot kits were used to quantitatively determine interferon-γ(IFN-γ)and interleukin-4(IL-4) levels of the isolated serum. Immunophenotype was determined by using mixture of antibodies includ-ing anti-CD3,anti-CD4,and anti-CD8.RESULTS Bergapten(20 mg·kg-1)therapy can modulate immu-nity against viral epidemics and attenuate aging-induced immune deficiency(P<0.01),which was correlat-ed with the decline in the activation of the Th and Tc responses in D-galactose induced aging BALB/c mice.According to the in vivo results,bergapten exposure up-regulated the secretion of IFN-γ and IL-4 in T-helper 1(Th1)and T helper 2(Th2)cells(P<0.05,P<0.01).Additionally,BG(20 mg·kg-1)restored antigen-specific CD4+and CD8+T cells in aging models (P<0.05, P<0.01), which may help to curing chronic infections. CONCLUSION The beneficial effect of bergapten in D-galactose induced aging BALB/c mice may be due to the Th and Tc responses activation.

Research on XOD captured components in Lagotis brevituba based on UPLC-Q-TOF-MS and molecular docking technology / 中国中药杂志

Potential xanthine oxidase (XOD) inhibitors in Lagotis brevituba were captured by using affinity and ultrafiltration. The structures of the captured components were identified by ultra-performance liquid chromatography coupled with Q-TOF mass spectrometry (UPLC-Q-TOF-MS). The binding intensity and binding mechanism between the captured components and XOD were analyzed by using molecular docking software Autodock 4.2. A total of 17 compounds were identified, including 9 flavonoids, 5 phenolic acids and 3 triterpenes. Molecular docking results showed that all the captured components could be spontaneously bound with XOD mainly via hydrogen bond, Van der Waals' force and hydrophobic interaction. From the perspective of binding energy and scoring function, the collected fractions all had potential prospects for XOD inhibitors, and the flavonoid luteolin-3',7 glucuronide had the best effect. The results also showed that affinity and ultrafiltration, ultra-performance liquid chromatography-mass spectrometry (UPLC-MS) and molecular docking technology can provide a powerful tool for the analysis of XOD inhibitor components in natural products.

Emergency clinical laboratory system for civilian and military uses in actual military operations / 医疗卫生装备

Objective To develop an emergency clinical laboratory system for civilian and military uses to enhance medical support of filed medical unit for mass casualties.Methods The missions of field medical unit were analyzed in the actual confrontation,and an emergency clinical laboratory system for civilian and military uses was built to fulfill clinical laboratory support.The factors were explored for clinical laboratory examination,and some measures were taken accordingly.Results The requirements of field medical unit were met by the developed system.Conclusion The system can be applied in largescale military exercises to enhance clinical laboratory support ability of field medical unit.

Study of pro-angiogenesis effect of neuropilin-2 on pancreatic neuroendocrine tumors / 重庆医学

Objective To investigate the role and significance of neuropilin-2(NRP2)for regulating the angiogenesis of pancreatic neuroendocrine tumors(PNETs).Methods The NRP2 expression in pancreatic neuroendocrine tumer BON-1 cell line was intevened.The BON-1 cells cultural supernatants in the control group and interference group were used to treat human umbilical vein endothelial cells(HUVEC).CCK-8 was used to detect the cell proliferation,Transwell was used to detected the cell migration and the tubule formation test was used detect the pro-angiogenesis.Results The CCK-8 detection showed that there was no statistically significant difference in the supernatant treated HUVEC proliferations between the interference group and control group medium(P>0.05):the absorbancy in the control group was 0.35±0.04,while which in the interference group was 0.32±0.04.The Transwell test showed that the invasion ability of HUVEC treated with cultural supernatants in the interference group was weakened compared with the control group,the control group was(203±13)/hole,while the interference group was(100±10)/hole(P＜0.01);the tubule formation test showed that HUVEC tubular formation treated by cultural supernatant in the interference group was decreased,the control group was 40±5,while the interference group was 24±3(P＜0.01).Conclusion Interfering NRP2 expression of BON-1 cells can inhibit the vessel formation ability of co-cultured HUVEC,suggesting that NRP2 may have the pro-angiogenesis effect of PNETs,and may be a potential new target for the treatment of PNETs.

Fast identification of constituents of Lagotis brevituba by using UPLC-Q-TOF-MS/MS method / 中国中药杂志

The chemical constituents of Lagotis brevituba were rapidly determined and analyzed by using ultra performance liquid chromatography tandem quadrupole time of flight mass spectrometry (UPLC-Q-TOF-MS/MS) method, providing material basis for the clinical application of L. brevituba. The separation was performed on UPLC YMC-Triart C₁₈ (2.1 mm×100 mm, 1.9 μm) column, with acetonitrile-water containing 0.2% formic acid as mobile phase for gradient elution. The flow rate was 0.4 mL•min-1 gradient elution and column temperature was 40 ℃, the injection volume was 2 μL. ESI ion source was used to ensure the data collected in a negative ion mode. The chemical components of L. brevituba were identified through retention time, exact relative molecular mass, cleavage fragments of MS/MS and reported data. The results showed that a total of 22 compounds were identified, including 11 flavones, 6 phenylethanoid glycosides, 1 iridoid glucosides, and 4 organic acid. The UPLC-Q-TOF-MS/MS method could fast identify the chemical components of L. brevituba, providing valuable information about L. brevituba for its clinical application.

Cytokine responses after lobectomy for early non-small cell lung cancer: a prospective randomized comparison of video-assisted thoracic surgery and open thoracotomy / 中华外科杂志

<p><b>OBJECTIVE</b>To compare video-assisted thoracic surgery (VATS) and open thoracotomy (OT) on acute inflammatory responses and immunosuppression after lobectomy for early non-small cell lung cancer (NSCLC).</p><p><b>METHODS</b>Present prospective randomized study. OT or VATS lobectomy was performed in patients who met enter criteria and clinical data was collected. Plasma concentration of IL-6, IL-8 and IL-10 were measured before surgery and at postoperative day (POD) 1 and POD 3. There were 271 patients underwent lobectomy for early NSCLC, including of 133 patients in group VATS and 138 patients in group OT from January 2007 to June 2008. There were 132 males and 139 females, aging from 19 ∼ 70 years with a mean of (56 ± 8) years.</p><p><b>RESULTS</b>Compared with OT group, shorter postoperative hospital stay [(8.2 ± 2.5) d vs. (9.8 ± 6.2) d, P = 0.03], lower morbidity rate (11.3% vs. 21.7%, P = 0.02) and lower increase of plasma concentration of IL-6 at POD 1 [(35 ± 25)% vs. (65 ± 43)%, P = 0.00], IL-6 at POD 3 [(14 ± 22)% vs. (55 ± 44)%, P = 0.00] and IL-10 at POD 1 [(25 ± 20)% vs. (43 ± 35)%, P = 0.00] were observed in patients of VATS group.</p><p><b>CONCLUSION</b>VATS lobectomy for early NSCLC is associated with less acute inflammatory responses and less immunosuppression when compared with OT.</p>

The early outcome of video-assisted thoracic surgery lobectomy for primary lung carcinoma / 中华外科杂志

<p><b>OBJECTIVE</b>To evaluate the early outcome of patients who underwent video-assisted thoracic surgery (VATS) lobectomy for primary lung carcinoma.</p><p><b>METHODS</b>The records of 121 patients with lung cancer undergoing VATS lung resection from 1997 to 2004 were reviewed retrospectively, I stage: 101 cases, 34 cases underwent right upper lobectomy, 13 cases underwent right middle lobectomy, 17 cases underwent right down lobectomy, 21 cases underwent left upper lobectomy, 16 cases underwent left down lobectomy. Thirty-eight cases underwent VATS lobectomy without assisted mini-incision.</p><p><b>RESULTS</b>There were 18 cases of morbidities (15%) and no surgical mortality. The 1-year, 2-year and 3-year survival rates of primary non-small cell lung cancer with I stage is: 99% (76/77), 96% (49/51) and 79% (15/19), respectively. There are statistic difference (P < 0.01) between adenocarcinoma and the others. There are no statistic difference (P > 0.05) between the VATS lobectomy with assisted mini-incision (n = 38) and without (n = 63), also no statistic difference (P > 0.05) between the VATS lobectomy and the standard procedure.</p><p><b>CONCLUSION</b>Our findings suggest that VATS lobectomy is superior regarding its ability to achieve the same survival rates and little morbidities in comparison with the standard procedure.</p>

Surgical management for pulmonary metastasis / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To investigate the indications of resection for lung metastasis, the surgical procedure and factors affecting the survival based on our experience accumulated for 37 years.</p><p><b>METHODS</b>A total of 108 patients with pulmonary metastasis was treated by surgery. Pathology showed 93 carcinoma (86.1%) and 15 (13.9%) sarcoma. Totally 122 operations were performed: partial lung resection 51, segmental lobectomy 7, lobectomy 40, pneumonectomy 15.</p><p><b>RESULTS</b>After surgery, the cumulative 1-, 3-, 5-, 7- and 10-year post-thoracotomy survivals were 87.9%, 47.3%, 31.7%, 23.7% and 13.9%, with an overall median survival of 34.8 months. Solitary lesions, disease-free interval (DFI) > 36 months, absence of extrathoracic disease and "open" thoracotomy were predictors of a longer survival whereas age, gender, symptom and pathology of the primary tumor were found statistically insignificant prognostic factors.</p><p><b>CONCLUSION</b>Surgery should be undertaken for patients who do fulfill these criteria, and "open" thoracotomy is a better choice. Surgical treatment for patients with short DFI and multiple lesions should be attempted with prudence.</p>

Transplantation of rectus abdominis musculocutaneous flap after open-window thoracostomy to manage chronic refractory pleural empyema and fistula with 2 cases report / 中华胸心血管外科杂志

Objective To report the experience of using rectus abdominis musculocutaneous flap after open-window thoracosto- my in managing refractory chronic pleural empyema.Methods From Nov.2004 to Mar.2006,intrathoracic transplantation of the musculocutaneous flap was performed successfully in 4 patients with empyema and fistula after upper lobectomy.The myocutaneous flap was designed in such a way that epigastrica vessels were incorporated.Results The rectus abdominis myocutaneous flap has provided sufficient bulk for tract obliteration.Over a mean follow-up period of 10 months,patients are free from recurrent infections and skin nacrosis.Conclusion Vaseularized museulocutaneous flap may help in healing refractory empyema.

Improvement and Analysis in Over- siderophores Production Bacteria Filtrating and Detecting / 微生物学通报

A novel stable blue agar plate which is convenient to preparing and more effective than the universal chrome azurol sulfonate (CAS) assay established by Schwyn and Neilands was designed by replacing MM9 growth medium and pipes with certain concentrate of phosphorus buffer solution which pH could be stabled at 6.8. It is more suitable for screening over- siderophores production bacteria. Since OD_ 630 of the sample is usually out of the range of spectrophotometer with CAS assay solution when quantifying the siderophores and the outcome is not steady,the measuring wavelength had been changed to 680 nm corresponding to the middle of max absorbance and the correlation between siderophores concentrations and OD was unchanged. But the detecting sensitivity is elevated by enlarged the absorbance differences among samples with different productivity of siderophores at 680 nm .

High-sensitive Detection Method for Siderophores from Pseudomonas / 微生物学通报

CAS (Chrome azurol S) assay was a universal method for detecting the bacterial siderophores, and Sugar-Asn liquid medium has been applied to the studies on siderophores from Pieudomonas. In this paper, Asp has been substituted for Asn, and MSA-CAS agar plate was developed by integrating the MSA (sugar-Asp) medium and CAS bright blue dye, which has been used in the universal CAS assay. On the aspect of siderophores detection , 8 strains of 7 species from Pseudomonas had been screened on MSA-CAS agar plates and universal CAS assay respectively. The results showed that MSA-CAS agar was higher-sensitive and lower basic fluorescent than universal CAS assay.

ISOLATION AND IDENTIFICATION OF A HIGH-MELANIN-PRODUCING BACTERIUM / 微生物学通报

A bacterium strain BFHM2002 is isolated from Lake Donghu, Wuhan. BFHM2002 has advantages that it can produce melanin with a high rate and high yield in the absence of tyrosine. Induced by tyrosine, melanin yield can be dramatically increased. BFHM2002 may be identified as a new strain in Bacillus firmus, for melanin-production.

THE APPLICATION OF ATOMIC FORCE MICROSCOPY IN MICROBIOLOGY / 微生物学通报

Atomic force microscopy is a powerful new tool to investigate the structure and measure the relationship between structure of surfaces and functions in microorganisms. Comparing with conventional electron microscope, atomic force microscope has higher resolution and can image real-time structures from atomic to molecular scale in three-dimensional mode under physiological condition. Therefore, atomic force microscope is being used in almost every aspect of microbiology and has gotten many exciting findings.