Autophagy is a classical regulatory mechanism of energy metabolism and self-update system in the maintenance of the intracellular homeostasis and cell development. Autophagy has been recently found to play a role in tumor development. Autophagy regulates tumor formation, proliferation, metastasis, and metabolism. At the same time, the anticancer drugs formed with autophagic mediators have been used in the treatment, which suggested that improving autophagy activity to inhibit tumor has become a new way for cancer treatment of cancer patients. This article gives an overview of the regulatory mechanism of autophagy, the relationship between autophagy and tumor, and tumor therapy by targeting autophagy.
Antineoplastic Agents ; Autophagy ; Humans ; Neoplasms ; physiopathology

Epithelial-mesenchymal transition (EMT) refers to tne transition during which epithelial cells undergo the loss of apical-basal polarity, acquisition of migration capability and transformation into mesenchymal cells. EMT induces breast cancer in situ to developing into metastasis and associates with the drug resistence. The multiple elements including signal pathways, transcriptional factors and downstream genes orchestrate the transition. Among them, the transforming growth factor β (TGF-β) signaling pathway plays a key role in the regulation of EMT in breast cancer. And this paper reviews the development of TGF-β signaling pathway induced EMT in breast cancer.
Breast Neoplasms ; metabolism ; Epithelial Cells ; Epithelial-Mesenchymal Transition ; Humans ; Signal Transduction ; Transcription Factors ; Transforming Growth Factor beta ; physiology

Objective: To establish a method for the quality control of pharmaceutical cocrystal based on NIRS, using rhein-lysine (lysirein) cocrystal as a case study. Methods: Integrating sphere diffuse reflectance accessory combining partial least squares regression algorithm to establish an analytical method for the content of rhein-lysine cocrystal, and the model was used to study environmental factors, as well as wet mixing and granulating process eutectic degradation conditions. Results: The correlation coefficients (r), root mean square error of calibration (RMSEC), root mean square error of prediction (RMSEP), and root-mean-squares error of cross-validation (RMSECV) of the proposed models were 0.9995, 0.0093, 0.0110, and 0.0120; Under high temperature and light conditions, the content of rhein-lysine cocrystal remained roughly constant (content change < 1%). Under high humidity and wet granulation process, there were some changes in cocrystal concentration, content change < 3%, but it was not significant. Conclusion: The proposed method is fast, non-destructive, simple, and accurate; Rhein-lysine cocrystal in environmental factors and modeling granulation process remains stable.

Objective To investigate the expression of aquaporin-5(AQP5) in lipo-polysaccharide(LPS)-cigarette smoking inducible SD rats,and the effect of ambroxol chloride(AMB)on its expression. Methods Twenty-one SD rats were randomly divided into three groups: AMB intervention group,model group(LPS-cigarette smoking induction group) and control group.TNF-? was determined from lung homogenate supernatant,bronchial alveolar lavage fluid(BALF) and serum by ELISA.The semi-quantitation of AQP5 transcription and expression were measured by in situ hybridization and immunohistochemistry,respectively. Results TNF-? from lung homogenate supernatant and BALF in model group was more than AMB intervention group and control group(P

To evaluate the regulating effect of Buyang Huanwu decoction and its simple prescription (Naojian tablet) on CDK4/Cyclin D1 expression in hippocampus tissues of rats with cerebral ischemia, SD rats were divided into the sham-operation group, the model group, the Buyang Huanwu decoction group (ig, 3.15 g · kg⁻¹) and the simple prescription group (ig, 2.41 g · kg⁻¹). Each group was further divided into five subgroups based on time points after the administration, i. e. 1 d, 3 d, 7 d, 14 d and 28 d, respectively. CDK4/Cyclin D1 expressions of the group at different time points were examined by using immunohistochemistry and real-time qPCR. According to the results, the cerebral ischemia model group showed higher CDK4/Cyclin D1 expression than the sham-operation groups (P < 0.05), suggesting that the cell cycle signal pathway would be activated by the cerebral ischemic injury. Both Buyang Huanwu decoction and simple prescription groups showed significantly lower cyclin expression than the model group at 3 d, 7 d, 14 d, 28 d (P < 0.05), indicating both Buyang Huanwu decoction and its simple prescription could play the neuroprotective effect through the cell cycle signal pathway.
Animals ; Brain Ischemia ; drug therapy ; genetics ; metabolism ; physiopathology ; Cell Cycle ; drug effects ; Cyclin D1 ; genetics ; metabolism ; Cyclin-Dependent Kinase 4 ; genetics ; metabolism ; Drugs, Chinese Herbal ; administration & dosage ; Humans ; Male ; Rats ; Rats, Sprague-Dawley

Sphingosine kinase 1 (SphK1) plays critical roles in cell biological functions. Here we investigated the effects of SphK1 inhibitor SKI II on hepatoma HepG2 cell cycle progression and invasion. Cell survival was determined by SRB assay, cell cycle progression was assayed by flow cytometry, the ability of cell invasion was measured by Matrigel-Transwell assay and protein expression was detected by Western blotting. The results showed that SKI II markedly inhibited HepG2 cell survival in a dose-dependent manner, induced G1 phase arrest in HepG2 cell and inhibited cell invasion. SKI II markedly decreased the expressions of G1-phase-related proteins CDK2, CDK4 and Cdc2 and the levels of cell invasion-associated proteins MMP2 and MMP9. The results showed that SKI II inhibited cell cycle progression and cell invasion, implying SphK1 as a potential target for hepatoma treatment.
CDC2 Protein Kinase ; Cell Movement ; drug effects ; Cell Survival ; drug effects ; Cyclin-Dependent Kinase 2 ; metabolism ; Cyclin-Dependent Kinase 4 ; metabolism ; Cyclin-Dependent Kinases ; metabolism ; G1 Phase ; drug effects ; Hep G2 Cells ; Humans ; Matrix Metalloproteinase 2 ; metabolism ; Matrix Metalloproteinase 9 ; metabolism ; Phosphotransferases (Alcohol Group Acceptor) ; antagonists & inhibitors ; Thiazoles ; pharmacology

This article proposes the "Efficacy Theory" hypothesis of the traditional Chinese medicines (TCMs): TCMs take effects and weaken toxicities through the additive effects of numerous effective forms (including their constituents or/and metabolites) on a same target, the synergistic effects based on the overall action of the additive effects on individual targets and their toxicities scattering effects. A TCM may include approximately 1000 constituents and each constituent may produce about 100 metabolites in vivo after oral administration. Numerous effective forms of incalculable constituents and their metabolites could work like a "army group" together. When the quantity of a specific target molecule is larger than the pharmaceutical molecules, the molecules of different kinds of effective forms could combine with the target molecules successively, to exert the additive effects. When the target molecules are mostly occupied ("target most spaces occupied"), this TCM begins to work. The additive effects maybe exert not only in concentration but also in a time order way, which gives a sustained efficacy of TCM. The additive effects and the toxicities scattering effects are resulted from the same effective groups and not identical toxic groups among different effective form molecules. The "toxicities scattering effect" can be used to explain the non-toxic TCMs, but not fit for toxic TCMs. The efficacy theory showed that the variety of constituents and metabolites may participate in the process of pharmacodynamic actions, including the additive effects, synergy effects and toxicities scattering effects, which may be useful for explaining and developing the characteristic advantage of the TCMs. The questions we need to study or confirm are as follows: What are the TCMs' pharmacodynamic substance basis and mechanism made up of Why are toxicities of most TCMs' smaller How is the TCMs' "Efficacy Theory" which reflects characteristic advantage of TCMs applied in the research and development of new drugs.
Animals ; Drug Therapy ; Drugs, Chinese Herbal ; chemistry ; pharmacology ; Humans ; Medicine, Chinese Traditional ; Pharmaceutical Preparations ; chemistry

Objective:To clone and express the Staphylococcus aureus Efb(extracellular fibrinogen-binding protein) protein in Escherichia coli, to purify the expression product and prepare its functional antibody and to detect the functions of Efb protein for further studies on S.aureus infection.Methods: Efb gene was amplified by PCR using S.aureus NCTC-8325 genome DNA as template and cloned into the recombinant expression vectors pET28a. E.coli BL21(DE3) with the plasmid was induced with IPTG for protein production. The protein was purified by Ni~(2+) affinity chromatography. The function of Efb protein was determined by complement activity assay and inhibition ELISA.The polyclonal antibodies were prepared by immunizing the animals. Results: The purified recombinant Efb was obtained, which could inhibit the CH50 and AH50 effectively. The functional poly-antibodies of Efb were prepared.Conclusion:Efb could inhibit the classical pathway and alternative pathway of complement activation, and the antibodies against to Efb could block the inhibition of the classical pathway of complement activation induced by Efb.

Objective To explore the prognostic value of pediatric critical illness score(PCIS)and pediatric risk of mortality score(PRISMⅢ)and the accuracy for evaluating the state of children with acute respiratory distress syndrome(ARDS).Methods Seventy-one cases hospitalized children from 29 days to 14 years old of Hebei ARDS cooperation group were selected during the 13 months between 2005 and 2006.All cases were confirmed according to ARDS diagnostic standard.For prospective studies,the patients were scored simultaneously with PCIS and PRISMⅢ at different times:when the patients entered PICU,when the patients were in the worst situation in PICU,when the patients were diagnosed as ARDS and when ARDS was serious.The data were performed by using Logistic regression etc.Results Values of Logistic regression were P

OBJECTIVETo explore the functional brain localization with magnetic resonance imaging (MRI) after acupuncturing the Yuan-Source and He-Sea acupoints of Stomach Meridian of Foot-Yangming (ST).

METHODSThe study was performed in 30 healthy volunteers who underwent acupuncture at Yuan-Source acupoint (Chongyang, ST42) and He-Sea acupoint (Zusanli, ST36) (ST group). Ten of these were also underwent acupuncture at the non-acupoints as the control group. Blood oxygenation level dependent functional MRI was performed.

RESULTSIn the ST group, signal increasing areas were demonstrated in bilateral superior temporal gyri (Broadmann 22), bilateral supramarginal gyri (Broadmann 40), bilateral cerebellar hemispheres, bilateral cingulate gyri and isthmus of cingulate gyri (Broadmann 32, 30), bilateral superior parietal lobules (Broadmann 7); signal decreasing areas were shown in bilateral orbital gyri (Broadmann 11), bilateral temporal pole (Broadmann 38), right inferior frontal gyrus (Broadmann 47) and right medial occipitotemporal gyrus (Broadmann 36). In the control group, signal increases areas were demonstrated in superior temporal gyri, precentral gyri, cingulate gyri, thalamus, insula and cerebellum. The size, signal intensity and number of increasing areas in control group are less than in ST group.

CONCLUSIONCombined acupuncture of Yuan-Source and He-Sea acupoints of ST can activate and decrease the multiple brain regions of "splanchnic brain" and thus reach a new functional balance to relieve pain.

Acupuncture Points ; Adult ; Brain ; physiology ; Electroacupuncture ; Female ; Humans ; Magnetic Resonance Imaging ; Male ; Meridians ; Young Adult