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

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Objective To evaluate the influence of aging on left ventricular systolic and diastolic function by quantitative tissue velocity image(QTVI) and B-type natriuretic peptide (BNP). Methods Sixty healthy participants aged from 36 to 82 years old were divided into age <60 years group (32 cases) and age≥60 years old group (28 cases). Compared traditional echocardiography,QTVI and BNP between the two groups, and analysised the correlation between age and the abovementioned measurements. Results Compared age ≥60 years group with age <60 years group, the ratio of early to late mitral annulus flow velocity(E/A) (0. 92 ±0. 18 vs. 1. 28 ± 0. 18), mean of systolic mitral annulus velocity (Sm) ([6. 04 ± 0.77] cm/s vs.[6. 89 ± 1. 03] cm/s) ,mean of early diastolic mitral annulus velocity (Em) ([5. 67 ±0.99]cm/s vs. [7.29 ± 1. 11]cm/s),the ratio of Em to Am(Em/Am) (0. 79 ± 0. 13 vs. 1.18 ± 0. 33) were significantly decreased (t =5. 396,2.478,4.075,3. 535, respectively, Ps < 0. 05), whereas mean of late diastolic mitral annulus velocity (Am) ([7. 67 ±0. 80]cm/s vs. [6. 80 ± 1. 16] cm/s),the ratio of E to Em(E/Em) (14. 83 ±4.43 vs. 10. 68 ±2. 85), BNP ([51. 25 ± 12. 21] ng/L vs. [14. 15 ± 6. 68] ng/L) were significantly increased (t =-2. 268,-2.995 and-3. 523, Ps < 0.05) . Age was negatively correlated with Sm, Em, Em/Am, E/A (r =-0.411,-0. 631,-0.622,-0. 614,Ps<0.05),and age was positively correlated with Am,E/Em and BNP (r = 0.481,0.614 and 0. 684,Ps <0. 05). Conclusion Left ventricular systolic and diastolic function decreased with aging. QTVI and BNP could evaluate left ventricular function sensitively and easily.

Objective To investigate the effects of transforming growth factorβ1(TGFβ1)and β3 (TGFβ3)gene transfer on MMP-2,MMP-9 and TIMP-1 expression in hepatic stellate cells(HSC-T6).Methods TGFβ1 and TGFβ3 expression plagmids were constructed.The recombinant expression plasmid pcDNA3.1(+)-=TGFβ1 and pcDNA3.1(+).TGFβ3 were transfected or cotransfected into HSC-T6.At 24,48 and 72 h after transfection,the expression of MMP-2,MMP-9 and TIMP-1 mRNA were detected by real-time quantitative PCR,and the expression of MMP-2,MMP-9 and TIMP-1 protein were detected by Western blot.The recombinant expression plasmid pcDNA3.1(+).TGFβ1 was transfected into HSC-T6,and positive clones were selected by G418.The positive clones were transfected by the recombinant expression plasmid pcDNA3.1(+).TGFβ1,and the expression of MMP-2,MMP-9 and TIMP-1 were detected at 48 h after transfection.Results After transfection with peDNA3.1-TGFβ1,MMP-2 and TIMP-1 increaged remarkably in HSC-T6 cells(P＜0.05),but MMP-9 remained at the sanle level;After transfection with pcDNA3.1-TGFβ3,expression levels of MMP-2,MMP-9 and TIMP-1 mRNA were not changed,but TIMP-1 protein increased remarkably(P＜0.05);in cotransfection group,the expression of MMP-2 was higher than that in the blank and the control groups(P＜0.05),but MMP-9 level was not changed and TIMP-1was decreased compared with that in the TGF-β1 transfection group(P＜0.05).After TGFβ3was transfected into positive clones,the change of MMP-2 wag not significant(P＞0.05).but MMP-9 increaged and TIMP-1 decreased significantly at 48 h after transfection(P＜0.05).Conclusions TGFB3 may inhibit liver fibrosis by increase the activity of MMP-2 and MMP-9,and decrease the activity of TIMP-1.

Objective Probe into different method safe and effective fixation method,clinical result and cliniical to indications of different treatments in intertrochanter fracture of femur in the old elderly.Methods Adopting the femur near end dissecting type to lock the stencil plate fixation 14 of 58 cases of old intertrochanter fracture of femur separately.the hip screw of motive force(DHS) fixation was used in 24,femur near end stencil plate fixation in 20,and the blood loss,operation time,ossicle split off situation and fracture heal time were compared among the three groups.Sanders grade results and complications were followed up.Results Postoperative follow up Was done in all patients,from 8 months to 3 years,averaged 1.5 years.three groups of skill type fine rate of the three groups being 92.9%,92%,90%respectively.Conclusions Different methods showed good clinical results in treating the old intertrochanter fracture of femur,each having its indications.Operation should be done should follow based on fracture type,age,physique factors and patient's osteoporosis intensity,choosing the best healing solution by characteristics of intermal flxation while each combining.The hook board(ALHP)is suitable for old patients with serious osteoporosis,DHS for Evans Ⅰ,Ⅱ types and some Evans Ⅲ type,and femur near end dissecting type stencil plate for Ⅳ and Ⅴ types fractures.

The tuberous sclerosis complex (TSC) in children is also named Bourneville disease,the 3 main symptoms namely epilepsy,mental retardation and facial angiofibromas.It is an autosomal dominant disease.It is an important cause of epilepsy,skin disease,and renal and pulmonary disease in children and adults.The appropriate therapy and prognosis for TSC patients are often different than that for individuals with epilepsy,renal tumors,or interstitial lung disease from other causes.In recent years,certain progress has been made in management of tuberous sclerosis,inhibitors of the mammalian target of rapamycin (mTOR) have demonstrated regression of astrocytomas,angiofibromas,and angiomyoliomas,as well as improved pulmonary function in persons with TSC.This article reviews the current therapeutic recommendations for medical and surgical management of neurologic,renal,and pulmonary manifestations of TSC.

Objective:To study the effects of Il 6?IL 1??TNF? on the growth and development of cultured human fetal cerebral neurons.Methods:Established the model of primary culture of human fetal cerbral neurons in SFFD,by morphological observation and MTT assay.Results:IL 6 and IL 1? both promote the survival of neurons and IL 6 also promote the outgrowth of neuritis and differentiation of neurons in culture.TNF ? continuously inhibit the survival of neurons.Conclusion:IL 6?IL 1??TNF? can effect the development of cultured neurons.IL 6 and IL 1? both may effect as neurotrophic factor in the survival?growth and development by indirect mechanism.TNF? directly show neurotoxin effect in culture.

Objective To investigte the inhibit effects of drug combination of Kanglaite injection(KLT) and TXT on human pulmonary epithelial cells(95D) in vitro,and to find the best time of combination.Method 95D cell growth inhibition was measured with MTT assay.Results Various concentration of KLT and TXT could inhibit the proliferation of 95D cell,and KLT could enchance the sensiti vity of 95D cell to TXT(P

Objective:To study the effects of IL 6、IL 1? and TNF? on the expression of c fos and c jun,which may provide the foundation for a further study in clinic.Methods:Used the a model of primary culture of human fetal cerebral neurons in serum free medium,by DNA RNA dot blot hybrdization.Results:The expression of c fos and c jun was increased between 15 min to 30 min after stimulation,reached a maximum at 1 h and declined over the subsequent 1 h.Conclusion:IL 6、IL 1? and TNF ? have induce the expression of c fos and c jun during development of human fetal cerebral neurons in vitro at the level of transcription.