Autophagy is an important homeostatic cellular recycling mechanism responsible for degrading injured or dysfunctional cellular organelles and proteins in all living cells. Aging is a universal phenomenon characterized by progressive deterioration of cells and organs due to accumulation of macromolecular and organelle damage. Growing evidences indicate that the rate of autophagosome formation and maturation and the efficiency of autophagosome/lysosome fusion decline with age. Dysfunctional autophagy has also been observed in age-related diseases. Autophagy disruption resulted accumulation of mutated or misfolded proteins is the essential feature of neurodegenerative disorders. However, in cancers, fibroproliferative diseases or cardiovascular diseases, autophagy can play either a protective or destructive role in different types of disease, and even in different stages of the same disease. The review will discuss the cellular and molecular mechanisms of autophagy and its important role in the pathogenesis of aging and age-related diseases, and the ongoing drug discovery strategies for therapeutic intervention.
Aging ; Autophagy ; Drug Discovery ; Humans ; Lysosomes ; metabolism ; Neurodegenerative Diseases ; Phagosomes ; metabolism ; Protein Folding

Objective To evaluate the Diagnostic value of pulmonary tuberculosis to detecting the anti Mycobacterium tuberculosis antibody with serum samples by the mycobacterium tuberculosis protein Chip and the M.tuberculosis Antibody Colloidal Gold Diagnostic Kit.Methods Application of mycobacterium tuberculosis protein Chip and the M.tuberculosis Antibody Colloidal Gold Diagnostic Kit to detecting the anti Mycobacterium tuberculosis antibody with serum samples,These serum samples are from 110 cases of tuberculosis patients,60 cases of lung disease and 60 cases of healthy people.Results Mycobacterium tuberculosis protein chip sensitivity was 73.6％ (81/110),the specificity was 93.3％ (112/120),the diagnostic kit for detection of Mycobacterium tuberculosis antibody colloidal gold assay sensitivity was 64.5％ (71/110)and a specificity of 91.7％ (110/120),both the sensitivity and specificity compared to no significant difference (P ＞ 0.05).Conclusions The Tuberculosis protein chip and the M.tuberculosis Antibody Colloidal Gold Diagnostic Kit to detect serum Mycobacterium tuberculosis antibodies for diagnosis of TB has a high sensitivity and specificity.Both can be used for the auxiliary diagnosis of tuberculosis.

Objective:To examine the relation between the alteration of condylar endochondral in response to mandibular protrusion and the action time length by establishing a model of mandibular protrusion on young adult rats. Methods: 75 female Sprague-Dawley rats aged 9 weeks were divided into two experimental groups and one control group. In two experimental groups, bite jumping appliances created forward positioning of the condyle for twelve hours and whole day, respectively. The experimental rats, together with the control rats, were sacrificed on days 3, 7, 14, 21 and 30, respectively. Tissue sections were cut in the sagittal plane through the mandibular condyle and were processed for in situ hybridization and immunostaining of type X collagen. Results: The peak of type X collagen protein expression in 24-hour experimental groups appeared on day 21 which was on the top of all experimental groups, while in 12-hour experimental groups it was found on day 30. The results of in situ hybridization were basically in agreement with the results of immunostaining. Conclusion: Both intermittent and continuous mandibular advancement can provoke endochondral ossification in young adult rat condylar, while 24-hour ones can produce more obvious and quicker effect.

AIM:To investigate the effects of insulin on drug sensitivity of Etoposide(Vp-16) to MBA-MD-543(human breast cancer cell line) in vitro.METHODS:Insulin was applied directly to the MBA-MD-543 cultured in vitro.The effects of insulin and Vp-16 on the number of viable cell,the total number of cells were assayed by MTT method and cell count.RESULTS: Insulin could induce the cell growth and promote the cell metabolism at the concentration(4.0)-(32.0)(mU?ml~(-1))(8-18 hours).At the condition of same density of cells,the administration of insulin((7.5)(mU?ml~(-1))) before adding Vp-16 in 9-15 h,enhanced the chemocytotoxity of Vp-16((70.09)(?g?ml~(-1))) on human breast cancer cells as indicated by MTT colorimetry.CONCLUSION: Proliferation of human breast cancer cell line can be induced by insulin,and insulin can sensitize MBA-MD-543 to the anticancer activity of Vp-16 in vitro. The key of improving the chemotherapeutic effect is the selection of revulsant occasion and concentration.It is possible to increase the growth and metabolism of cancer cells first so as to enhance the chemosensibility,and then administer chemotherapeutic agents,thus improving their theraeutic effects.

Objective To observe the effect of Xiaotan Hezhong Recipe on pancreatic fibrosis forming and the expression of related proteins in model rats of chronic pancreatitis. Methods Twenty-four Wistar rats were randomly divided into normal group, model group, pancreatin group and Chinese medicine group (n=6). Rats model were made by DDC solution intraperitoneal injection. Pancreatin group and Chinese medicine group were treated by intragastric administration with pancreatin and Xiaotan Hezhong Recipe, respectively. Body weight of rats was measured regularly. The rats were killed after 4 weeks, with pancreatic pathological detection and laminin, matrix metalloproteinase-1 detection. Results After intraperitoneal injection of DDC solution, pancreatic tissue fibrosis in different degree and inflammatory cell infiltration were found. Chinese medicine group was better than the model group in general conditions, body weight change, pancreatic pathological score and expression of laminin, matrix metalloproteinase-1, the differences were statistically significant (P<0.05). Conclusion Xiaotan Hezhong Recipe can improve chronic pancreatitis rats generally and inhibit pancreatic fibrosis, its mechanism may be related with decreasing laminin expression and increasing the expression of matrix metalloproteinase-1.

Objective:To examine the relation between the alteration of condylar endochondral in response to mandibular protrusion and the action time length by establishing a model of mandibular protrusion on young adult rats.Methods:75 female Sprague-Dawley rats aged 9 weeks were divided into two experimental groups and one control group.In two experimental groups,bite jumping appliances created forward positioning of the condyle for twelve hours and whole day,respectively.The experimental rats,together with the control rats,were sacrificed on days 3,7,14,21 and 30,respectively.Tissue sections were cut in the sagittal plane through the mandibular condyle and were processed for in situ hybridization and immunostaining of type X collagen.Results:The peak of type X collagen protein expression in 24-hour experimental groups appeared on day 21 which was on the top of all experimental groups,while in 12-hour experimental groups it was found on day 30.The results of in situ hybridization were basically in agreement with the results of immunostaining.Conclusion:Both intermittent and continuous mandibular advancement can provoke endochondral ossification in young adult rat condylar,while 24-hour ones can produce more obvious and quicker effect.

Acupuncture Therapy ; Adult ; Aged ; Female ; Hiccup ; physiopathology ; therapy ; Humans ; Intestines ; physiopathology ; Male ; Middle Aged ; Qi ; Stomach ; physiopathology ; Young Adult

Background: Previous studies have demonstrated that ultrasonography is the recommended imaging modality for preoperative staging of papillary thyroid carcinomas (PTCs). However, only a few studies have kept watch on preoperative evaluation of capsular invasion (CI) or extracapsular extension (ECE) and cervical lymph node metastasis using preoperative ultrasonography. This study aimed to investigate the relationship between the CI or ECE and the cervical lymph node metastasis in PTCs using preoperative ultrasonography and postoperative pathology in Chinese patients. Methods: The data of preoperative ultrasonography and postoperative pathology of 166 patients who had a definitive diagnosis of PTCs from October 2011 to July 2014 at Xuanwu Hospital, Beijing were collected and reviewed. Preoperative ultrasonic parameters of thyroid nodules were compared with those of postoperative pathological diagnoses. All the patients were divided into bilateral PTCs group (n = 42, 78 nodules) and unilateral PTCs group (n = 124, 124 nodules), and the data of the nodule sizes, CI or ECE, and cervical lymph node metastasis by preoperative ultrasonography were compared between two groups. Results:Atotal of 202 nodules of 166 patients which were confirmed by preoperative ultrasonography and postoperative pathology were analyzed. Hypoechogenicity (n = 201, 99.5%) and irregular margins (n = 167, 82.7%) were the main ultrasonic characteristics of PTCs. A significant moderate agreement between preoperative ultrasonic examination and postoperative pathology for CI or ECE(κ=0.622,P<0.001)was observed. The diagnostic sensitivity was 92.0%, and specificity was 71.1%. In bilateral PTCs group, 81.0% had CI or ECE, and 61.9% had cervical lymph node metastasis. In unilateral PTCs group, 76.6% had CI or ECE, and 58.1% had cervical lymph node metastasis. There were no significant differences in the incidence of CI or ECE and cervical lymph node metastasis between two groups (all P > 0.05). Conclusions: Ultrasonography was proved to be a valuable method for preoperative diagnosis of PTCs. Hypoechogenicity and irregular margins were strongly associated with PTCs. CI or ECE in unilateral PTCs strongly implied the cervical lymph node metastasis. Therefore, the cervical lymph nodes should be carefully examined by ultrasonography in patients with PTCs.

Background Hypertension,ischemia and hypoxia induce the increase of glutamate level in eye tissue and furthermore produce excitatory damage and apoptosis of retinal ganglion cells(RGCs).At present,the study on the protection of traditional Chinese medicine on glutamate-induced retinal excitatory damage is lack.objective Present study was to explore the protective effects of Huoxue huayu decoction,a Chinese herbal recipe,on RGCs in acute ocular hypertension model. Methods Fony-five healthy clean Wistar rats were divided into three groups randomly.The acute ocular hypertension models were established in 40 Wistar rats by injecting the normal saline solution into the anterior chamber to elevate the intraocular pressure for 60 minutes.Huoxue huayu decoction of 4 ml was administered intragastrically once per day in 20 model rats.Other matched 5 normal Wistar rats served as normal control group.The rats were sacrificed on 1,3,7 and 14 days after modeling and the retinas were isolated for the histopathologieal and uhrastructure examination.Expression of glutamate transporter in the retina of acute ocular hypertension and normal rat retina were detected using quantitative real-time polymerase chain reaction.The utilization of animals followed the Association for Research in vision and Ophthalmology. Results After acute ocular hypertension.the retina thickness attenuated and the numbers of RGCs decreased under the light microscope in 1,3,7 and 14 days after modeling in comparison with normal control rats.The degradation of the organelle and edema as well as changes of cell nuclei were seen in model rats under the transmission electron microscopy.The expression of glutamate transporter mRNA in model group and glutamate transporter group was rapidly elevated in the first day (P<0.05),descended at the third days(P<0.01)and returned to the normal level 7 days later(P>0.05).Conclusion Huoxue huayu decoction can protect the retina against RGCs damage in the acute ocular hypertension by elevating the expression of glutamate transporters in retina.