Effective strategies for improving the stability of peptides in vivo / 药学学报

Peptides have been extensively used in the fields of gene/drug delivery and disease targeting therapy. However, natural peptides are sensitive to protease digestion with short circulatory half-lives in vivo. Many studies on structural modifications of peptides have been reported to improve the delivery or therapeutic effect. In this review we focus on the recent literature on peptide stability in accordance with different structural modifications and summarize the methods and influential factors that are involved in the improvement of stability and half-life in vivo. This review will provide the scientific basis and theoretical references for further investigations and applications in vivo.

Mechanism and application of acid-sensitive peptides in drug delivery / 药学学报

As a part of novel drug delivery carriers, peptides have diverse biological activities, low immunogenicity and good biocompatibility. In recent years, studies on the delivery carriers modified by peptides have attracted much attention. Among them, the peptides with acid sensitivity can change their secondary structures under slightly acidic microenvironment of the tumor or in lysosome. Therefore, the carriers made or modified by acid-sensitive peptides can specifically release the loaded drug in the tumor tissue, enhance the cell internalization of drugs and improve its therapeutic effects. In accordance with acid-sensitive peptides studied, the side chains, number of polar residues, sequence and secondary structure of the peptides might be involved in the acid sensitivity. In this review, we summarize the acid-sensitive peptides from recent literatures, analyze the connection between the structure and the acid sensitivity, and focus on the mechanism and application of acid-sensitive peptides in drug delivery. This provides the basis for further development and utilization for acid-sensitive peptides for efficient drug delivery.

Research progress on medicinal values of scorpion venom components / 中国中药杂志

For thousands of years, scorpions and their venoms have been applied in traditional medicine in China to treat a variety of difficult miscellaneous diseases. The venom is a complex mixture of bioactive molecules, such as peptides and proteins (e.g. neurotoxins). Among them, neurotoxins (named scorpion toxins) are the most important bioactive components. Up to now, more and more characterized venom components have been isolated from different scorpions, providing numerous candidate molecules for drug design and development. Many investigations have shown the potent effects of venom or its components against the nervous, immune, infection, cardiovascular and neoplastic diseases. Moreover, the scorpion toxins could be used as molecular backbone to develop new specific drugs based on their unique structures and functions. In this review, we focus on the medicinal values and the possible mechanisms of scorpion toxins with promising medicinal prospect against the relative diseases, providing the data basis for further development of relative drugs.

Relationship between expression of EGFR in gastric cancer tissue and clinicopathological features

OBJECTIVE@#To investigate the relationship between the expression of epidermal growth factor receptor (EGFR) in gastric cancer and the clinicopathological features and prognosis.@*METHODS@#A total of 78 paraffin specimens of gastric cancer operation were collected. The immunohistochemical method was used to detect the expression of EGFR in 78 cases of gastric cancer and 20 cases of adjacent normal tissue. The relationship between the high expression of EGFR and clinicopathological features was analyzed.@*RESULTS@#EGFR positive expression rate in the 78 cases of gastric cancer tissue was 57.7 % (45/78), while EGFR was not expressed in 20 cases of adjacent normal tissue. The high EGFR expression was positively correlated with the position of gastric cancer, tumor size, cell differentiation, invasive depth, lymph node metastasis and TNM staging, yet having no obvious relation with gender or age.@*CONCLUSIONS@#EGFR expression level in gastric cancer is closely related to the incidence and development of gastric cancer, which can provide a theoretical basis for the targeted therapy for gastric cancer with EGFR as the target.

ABCG2-overexpressing S1-M1-80 cell xenografts in nude mice keep original biochemistry and cell biological properties / 癌症

S1-M1-80 cells, derived from human colon carcinoma S1 cells, are mitoxantrone-selected ABCG2-overexpressing cells and are widely used in in vitro studies of multidrug resistance(MDR). In this study, S1-M1-80 cell xenografts were established to investigate whether the MDR phenotype and cell biological properties were maintained in vivo. Our results showed that the proliferation, cell cycle, and ABCG2 expression level in S1-M1-80 cells were similar to those in cells isolated from S1-M1-80 cell xenografts (named xS1-M1-80 cells). Consistently, xS1-M1-80 cells exhibited high levels of resistance to ABCG2 substrates such as mitoxantrone and topotecan, but remained sensitive to the non-ABCG2 substrate cisplatin. Furthermore, the specific ABCG2 inhibitor Ko143 potently sensitized xS1-M1-80 cells to mitoxantrone and topotecan. These results suggest that S1-M1-80 cell xenografts in nude mice retain their original cytological characteristics at 9 weeks. Thus, this model could serve as a good system for further investigation of ABCG2-mediated MDR.

Risk factors analysis of hyperthyroidism complicated hyperthyroid heart disease / 中国地方病学杂志

Objective To study the risk factors of hyperthyroid heart diseases(HHD) by analyzing clinical features of patients in order to provide a scientific basis for prevention and treatment of HHD. Methods Nine hundred and eighty two cases were selected as objective from in-patient data of Thyroid Disease Treatment Centre of Shandong Province. The cases were divided into hyperthyroidism group and HHD group. The variables of etiology,sex, age, duration of disease, TSH, FT3, FT4 and TRAb were analyzed by comparative analysis. The risk factors were analyzed by logistic regression. Results The prevalence of hyperthyroidism complicated hyperthyroid heart disease was 7.7%(76/982), age, duration of diseases, FT3, TRAb in the HHD group were [(51.4 ± 11.5), (6.3 ±2.1) years, 21.6 pmol/L, 71.6 U/L], in hyperthyroidism group were [(37.9 ± 9.8), (2.6 ± 1.3) years, 14.9pmol/L, 49.6 U/L]. The differences were statistically significant(u = 9.93,15.23, T = 44954,48792.5, P ＜ 0.05)between the two groups. The factors of the older, higher FT3 and TRAb, longer duration, Graves disease (OR =1.751,1.470,1.483,1.445,1.234) increased the risk of HHD. Conclusions Graves disease, longer duration, old age, higher FT3 and TRAb are the risk factors of HHD. Timely prevention and control of risk factors is necessary to reduce the incidence of HHD.

A cell-based screen for anticancer activity of 13 pyrazolone derivatives / 癌症

<p><b>BACKGROUND AND OBJECTIVE</b>Pyrazolone derivatives were reported to have a potent cytotoxicity against some tumor cells. In the present study, we evaluated the cytotoxic activity of a series of pyrazolone derivatives against four human tumor cell lines including HepG2, OVCAR3, KB, and multidrug resistance (MDR) KBv200 cell lines in vitro and in vivo. Additionally, the structure-activity relationships of these compounds were discussed.</p><p><b>METHODS</b>To analyze the antiproliferative potential of the synthesized compounds against several human tumor cell lines, the 50% inhibitory concentration (IC50) values were determined by MTT assay. Besides, the KBv200 cell xenograft experimental model was established and the sensitivity to the pyrazolone compounds was compared between drug-sensitive parental KB cells and MDR KBv200 cells.</p><p><b>RESULTS</b>Of 13 compounds screened, compound 9 presented remarkable anticancer effects, of which IC50 values were (3.24 ± 0.28), (2.58 ± 0.61), (3.81 ± 0.02), and (3.45 ± 0.03) μg/mL in HepG2, OVCAR3, KB and MDR KBv200 cells, respectively (P > 0.05). Furthermore, compound 9 effectively inhibited tumor growth of KBv200 cell xenografts in vivo, the inhibition ratio was 25.37%, 38.43%, and 47.50% for 1.5 mg/kg, 3 mg/kg, and 6 mg/kg of compound 9 groups, respectively.</p><p><b>CONCLUSION</b>Compound 9 was the most promising antitumor agent in this study.</p>

Induction of apoptosis of tumor multidrug resistance cell by uvarigrin and its mechanism / 药学学报

<p><b>AIM</b>To study the effect of uvarigrin on mitochondrial dependent pathway during the apoptosis induced by it in MDR KBv200 cells and their parental sensitive KB cells.</p><p><b>METHODS</b>MTT assay was used to detect the cytotoxic effect of uvarigrin on KBv200 and KB cells. Annexin V FITC staining identified uvarigrin-induced apoptosis in KBv200 and KB cells. These cells underwent incubation with DCFH-DA, or DiOC6, followed by flowcytometry for the measurement of reactive oxygen species (ROS) and mitochondrial membrane potential (deltapsim), respectively. The Western blotting analysis was performed on Caspase-9 activation.</p><p><b>RESULTS</b>Uvarigrin inhibited the growth of KBv200 cells and KB cells in vitro. Most of the uvarigrin-induced cells death was found to be due to apoptosis, as determined by Annexin V FITC staining. During the apoptosis, the level of ROS increased while the level of deltapsim decreased in a time-dependent manner. Uvarigrin triggered Caspase-9 activation.</p><p><b>CONCLUSION</b>Uvarigrin induced apoptosis in KBv200 cells and KB cells probably through a mitochondria-dependent pathway.</p>

Effects of Chansu injection on transplanting-tumor models S180 in mice and human colon cancer HT-29 in nude mice / 中华胃肠外科杂志

<p><b>OBJECTIVE</b>To study the antitumor effects of Chansu injection on transplanting- tumor of S(180 ) in mice and human colon cancer HT-29 in nude mice.</p><p><b>METHODS</b>Using transplanting- tumor models of S(180 ) in mice and human colon cancer HT-29 in nude mice,the tumor inhibitive ratio(IR) of Chansu injection was determined and apoptosis was microscopically observed.</p><p><b>RESULTS</b>Compared with tumor-negative control groups, IR at different dosage of Chansu in models of S(180) and HT-29 was 19.1% - 38.2% and 9.5% - 15.8% respectively,there was a dose-dependent relationship in models of S ( 180) (P< 0.05) and HT- 29 (P> 0.05). The tumor growth was markedly inhibited by cyclophosphamide (CTX) in model of S( 180) with IR of 70.7% and in model of HT-29 with IR of 67.1%, compared with control groups, both P< 0.01; apoptosis induced by CTX was markedly observed by in microscope examination. No significant side effects were shown in the study group.</p><p><b>CONCLUSIONS</b>Chansu injection can significantly inhibit tumor growth in model of S(180), but not in model of HT- 29. Different type of tumor has different drug-sensitivity.</p>

Psychological rehabilitation on 57 schizophrenic patients / 中国康复理论与实践

@#ObjectiveTo standardize the service for mental disability in community, and evaluate scientifically the effect of rehabilitation measures and social factors on the prognosis of disease.MethodsIn the communities selected by cluster sampling method, family-social rehabilitation service was established. The observe groups or specified observers were selected by the community committee, and the maintenance treatment and rehabilitation evaluation were made by psychiatrists.ResultsAfter community rehabilitation treatment, schizophrenia could be compliant with maintenance treatment, which led to satisfactory social function evaluation and rehabilitation result.Conclusion Community rehabilitation treatment could increase the compliance with medical treatment and decrease the occurrence of relapse.

Experimental chemotherapy against xenografts derived from multidrug resistant KBv200 cells and parental drug-sensitive KB cells in nude mice by annonaceous acetogenin 89-2 / 药学学报

<p><b>AIM</b>Annonaceous acetogenin 89-2 was obtained from atemoya plant. To investigate the effect of 89-2 on experimental chemotherapy against xenografts derived from multidrug resistant KBv200 cells and parental drug-sensitive KB cells.</p><p><b>METHODS</b>Cytotoxicity was determined by tetrazolium (MTT) assay. The models of KB and KBv200 xenografts in nude mice were established to investigate the effect of 89-2 on experimental chemotherapy against cancer in vivo. Mechanistic experiments were conducted to examine the function of P-gp by Fura 2-AM assay.</p><p><b>RESULTS</b>The compound 89-2 showed potent cytotoxicity in KBv200 and KB cells, and the mean IC50 of 89-2 to KBv200 and KB cells was 48.7 and 64.6 nmol.L-1, respectively. The IC50 of 89-2 to multidrug resistant (MDR) cells was similar to that to the parental drug-sensitive cells (P < 0.05). In the models of KBv200 and KB cell xenografts in nude mice, 89-2 (0.90 mg.kg-1, q2d x 6) exhibited 52.3% and 56.5% in inhibiting the growth of xenografts, respectively. The toxicity was endurable. The intracellular accumulation of Fura-2 in KBv200 cells increased to 1.66, 2.03, and 2.74-fold, respectively, by addition of 12.8, 64 and 320 nmol.L-1 of 89-2.</p><p><b>CONCLUSION</b>Both MDR KBv200 cells and parental drug-sensitive KB cells were sensitive to the treatment of 89-2 in vitro and in vivo. The mechanism of overcoming MDR was associated with the decrease of P-gp function MDR cells.</p>