The erythrocytic membrane ATPase activity and intraerythrocytic cation levels have been measured in 20 noninsulin dependent diabetes mellitus(NIDDM)patients with retinopathy(DR group),20 NIDDM patients without retinopathy(DM group)and 20 normal subjects (C group)respectively.The activities of Na+- K+-ATPase and Ca2+-ATPase were significantly lower in both DR and DM groups than in C group.The levels of intraerythrocyte sodium and calcium were significantly higher,and of magnisium waws significantly lower in DR and DM groups than in C group.The above observed abnormalities especially decreased level of magnisium,were more significant in DR group than in DM group.
（Chin J Ocul Fundus Dis,1994,10:11-13）
ObjectiveTo summarize functions and mechanisms of poly ADP-ribose polymerase (PARP) inhibitors and its application in germline BRCA mutated breast cancer.MethodThe literatures about the PARP inhibitors and their applications in the treatment of germline BRCA mutated breast cancer at home and abroad in recent years were collected to make a review.ResultsAs a DNA repair enzyme, the PARP played an important role in the DNA repair pathway. Based on this mechanism, the PARP inhibitors had been developed and widely used in the clinic. On the other hand, the previous studies had shown that the PARP inhibitors marked the synthetic lethal effect in the cancers with homologous recombination deficiency mechanism. By inhibiting the PARP activity in the tumor cells with BRCA mutation, all the DNA damage repair pathways were blocked, which could induce the cell apoptosis or increase the sensitivity of tumor cells to chemoradiotherapy, resulting in the cell death.ConclusionIn patients with germline BRCA mutated breast cancer, PARP inhibitors can selectively kill breast cancer cells and show a high potential for individualized treatment.
Objective To investigate the effect of adiponectin on proliferation of airway smooth muscle cells( ASMCs) , and explore its possible mechanism. Methods ASMCs were derived fromrat airway tissue and were cultured in vitro. RT-PCR was used to verify the expression of adiponectin receptors on ASMCs. Then ASMCs were treated with adiponectin at different concentrations( 5, 10, 20, 40, 80 μg/mL) for different periods of time( 1, 12, 24, 48, 72 hours) , respectively. The absorbsence ratios of adiponectin at different concentrations were determined by MTT assay. The adenosine monophosphate-activated protein kinase( AMPK) and phosphorylated AMPK( pho-AMPK) in ASMCs were quantified by Western blot after being treated with adiponectin at different concentrations ( 5, 10, 20, 40 μg/mL) for 48 hours. ResultsThe inhibition of adiponectin on ASMCs was showed in dose-dependent manner( r = 0. 324, P lt; 0. 01) and time-dependent manner( r = 0. 607, P lt; 0. 05) . Western blot indicated that the expression of pho-AMPK increased with the increased concentrations of adiponectin( r =0. 607, P lt; 0. 01) . The ratio of pho-AMPK/AMPK were ( 27. 66 ±1. 03) % , ( 31. 91 ±0. 86 ) %, ( 75. 52 ±2. 67) % , and ( 84. 50 ±1. 05) % ,respectively, with significant differences between each concentrations of adiponectin( P lt; 0. 05) . There was no expression of pho-AMPK in the control group. Conclusion Adiponectin can significantly inhibit ASMCs’proliferation by activating AMPK.
Objective To investigate the changes and roles of myocardial adenosine triphosphate enzyme(ATPase) in the mechanism of cardiac dysfunction after blunt chest trauma（BCT）. Methods Thirtysix rabbits were divided into 6 groups with random number table, control group, 2 h group, 4 h group, 8 h group, 12 h group and 24 h group, 6 in each group. The models of BCT were established with BIMⅡ biological impact machine, catheterization technique was used through the right jugular artery into the left ventricle measure its pressure. The hemodynamics and the activities of ATPase in myocardial cell plasm, homogenate and mitochondria were measured at preinjury(control group), 2 h, 4 h, 8 h, 12 h and 24 h postinjury. Results Left ventricular endsystolic pressure(LVESP), the maximal ascending rate of left intraventricular pressure(+dp/dtmax), isovolemec pressure(IP) and the maximal physiological velocity(Vpm) decreased significantly at 2 h group after BCT(Plt;0.05）, and recovered to preinjury level in 4 h, 8 h and 12 h group during 4-12 h after BCT; isovolumic relaxation phase left ventricular pressure descending time constant (T). Left ventricular enddiastolic pressure(LVEDP) and the maximal descending rate of left intraventricular pressure(-dp/dtmax) were significantly higher （Plt;0.05, 0.01）. The activity of ATPase in homogenate, mitochondria and cell plasm decreased significantly at 2 h group and 4 h group after BCT（Plt;0.05, 001, respectively）, and 8 h group and 12 h group recovered after BCT. There was negative correlations between [CM(159mm]LVEDP and -dp/dtmax and the decrease of the activity of Na+-K+-ATPase in homogenate（r=-0.674, -0.691, Plt;0.05）, the Ca2+-ATPase in homogenate（r=-0.613,-0.642, Plt;0.05）, the Na+-K+-ATPase in mitochondria（r=-0.622,-0.616, Plt;0.05）,the Ca2+-ATPase in myocardial cell plasm（r=-0.672,-0.658, Plt;0.05）, the Na+-K+-ATPase in myocardial cell plasm（r=-0.627,-0.632,Plt;0.05）,and the Mg2+-ATPase in myocardial cell plasm（r=-0.677,-0.661, Plt;0.05）. Conclusion The left ventricular function is impaired obviously after BCT, especially in diastolic phase. The decrease of the activity of ATPase in myocardial cells may be one of the reasons of cardiac dysfunction after BCT.
The mortality rate of ovarian cancer is the highest among female reproductive tract malignancies. Although most patients have undergone recurrent treatments such as surgery, chemotherapy, and targeted therapy, the recurrence rate is still high. The exploration of scholars in this field has never stopped. In recent years, remarkable achievements have been made in the medical treatment of ovarian cancer. The research of poly adenosinediphosphate-ribose polymerase, immunotherapy (immunocheckpoint inhibitor monotherapy, immune checkpoint inhibitor combined with other drugs) and anti-angiogenic drugs have provided new methods for the treatment of this disease, and throughout the whole process of ovarian cancer treatment. This paper summarizes this, and aims to provide a reference for the clinical treatment of ovarian cancer.
The retina of SD rats was incubated in four types of the Eagle solution respectively. The results showed the cAMP level of retinas was the lowest in the hGnMg(high glucose with normal magnesium) solution but the cAMP level was significantly increased in the hGhMg(high glucose with high magnesium) and higher than that of normal control group. The cAMP level was the highest in the nGhMg(normal glucose with high magnesium). The results suggested that magnesium might play an important role in maintaining the normal metabolism of glucose of the retinal tissue.
（Chin J Ocul Fundus Dis,1992,8:138-140）
【Abstract】ObjectiveTo investigate the effects of endogenous photodynamic therapy (PDT) on intracellular cAMP and cGMP concentrations of human colon carcinoma cell lines SW480. MethodsSW480 cells were divided into control group, light group, δaminolevulinic acid （ALA） group (ALA group) and endogenous PDT group (ALAPDT group). Intracellular cAMP and cGMP concentrations of each group were detected by radioimmunoassay at 30, 60, 90 and 120 min after irradiation. ResultsThere was a significant increase in intracellular cAMP concentration of ALAPDT group at 30 min after irradiation (P＜0.001) and sequent decrease, but intracellular cAMP concentrations of ALAPDT group at 60, 90 and 120 min after irradiation had no statistical difference than the other groups (Pgt;0.05). Intracellular cGMP concentration of different time point of each group was not significantly different. ConclusionThese results indicate that the cytoprotection of SW480 cell are produced by an instantaneous increase in the intracellular cAMP concentration while endogenous PDT is killing SW480 cell.
Objective To investigate the mechanism of adenosine-tri phosphate (ATP) activated mammal ian target of rapamycin (mTOR)/signal transducer and activator of transcription 3 (STAT3) signal pathway in the physiology and pathology of spinal cord injury (SCI). Methods Ninety-six adult healthy female Sprague-Dawley rats were randomly divided into 4 groups (groups A, B, C and D, n=24). In groups A, B and C, the rats were made the SCI models at T8-10 levels by using a modified Allen’ s stall, and in group D, rats were given laminectomy without SCI. The rats were subjected to the administration of ATP (40 mg/kg) for 7 days in group A, to the administration of physiological sal ine (equal-volume) for 7 days in group B, to the administration of ATP (40 mg/kg) and rapamycin (3 mg/kg) for 7 days in group C, and to the administration of physiological sal ine (equal-volume) for 7 days in group D. Locomotor activity was evaluated using the Basso-Beattie-Bresnahan rating scale at the postoperative 1st, 2nd, 3rd, and 4th weeks. Then, the expressions of spinal cord cell marker [Nestin, neuron-specific enolase (NSE), gl ial fibrillary acidic protein (GFAP)] and the mTOR/STAT3 pathway factors (mTOR, STAT3) were detected at the postoperative 1st, 2nd, 3rd, and 4th weeks by immunohistochemistry analysis, Western blot assay, and real-time fluorescence PCR analysis. Results The BBB scores in group A showed a steady increase in the postoperative 1st-4th weeks and were significantly higher than those in groups B and C (P lt; 0.01), but were lower than that in group D (P lt; 0.01). Real-time fluorescence PCR results showed that the mRNA expressions of mTOR, STAT3, NSE of group A steadily increased, however, the Nestin mRNA expression gradually decreased in the postoperative 1st-4th weeks, which were all significantly higher than those of groups B, C, and D (P lt; 0.01). The mRNA expression of GFAP showed a steady increase in group A and was significantly less than those of groups B and C, but was higher than that of group D (P lt; 0.01). There were significant differences (Plt; 0.01) in all markers between groups B, C, and group D; there were significant differences in mTOR, P-mTOR, STAT3, and P-STAT3 mRNA between groups B and C at 1st-4th weeks (P lt; 0.05). The similar changes were found by Western blot assay. Conclusion ATP can activate the mTOR/STAT3 pathway to induce endogenic NSCs to prol iferate and differentiate into neurons in rats, it enhances the heal ing of SCI.
