ABSTRACT
This study aims at the critical role of P-glycoprotein (P-gp) in tumor drug resistance, taking advantage of the adenosine triphosphate (ATP) dependence of P-gp mediated drug transport and efflux across the cell membrane. Mitochondrial targeted calcium arsenite/doxorubicin (DOX) lipid nanoparticles were constructed via hydrothermal method and thin-film dispersion method for reversing tumor drug resistance. The results showed that the lipid nanoparticles were uniform in size and well dispersed with a mean particle size of (261 ± 7) nm, zeta potential of (-9.6 ± 1.3) mV. The DOX loading efficiency and encapsulation efficiency were 22.6% and 84.0%. The in vitro drug release profile was pH-dependent; the drug accumulation at mitochondria was significantly increased, which then caused overload of calcium and inhibition of P-gp and ATP, thereby reversing tumor drug resistance. The simultaneously released arsenite ion and DOX could synergistically kill the tumor cells. In summary, the lipid nanoparticles prepared in this study have uniform particle size, high drug loading efficiency and encapsulation efficiency, excellent colloidal stability, pH responsiveness, and impressive ability to reverse tumor drug resistance, which may hold great potential in further clinical applications.
ABSTRACT
Background: Poor ovarian response phenomenon has been observed in some of the in vitro fertilization-embryo transfer patients. Some investigations found that follicle stimulating hormone receptor [FSHR] gene plays a role in the process, but no direct evidence shows the correlation between genotypes of FSHR and ovarian response
Objective: Exploring the molecular mechanism behind the mutation of FSHR promoter association with ovarian granulosa cells and poor ovarian response
Materials and Methods: This cross sectional study was performed using 158 women undergoing the controlled short program ovarian stimulation for IVF treatment. The 263 bp DNA fragments before the follicle stimulating hormone [FSH] receptor 5' initiation site were sequenced in the patients under IVF cycle, 70 of which had poor ovarian response and 88 showed normal ovarian responses
Results: With a mutation rate of 40%, 63 in 158 cases showed a 29[th] site G-A point mutation; among the mutated cases, the mutation rate of the poor ovarian responders was significantly higher than the normal group [60% versus 23.9%; [chi]2=21.450, p<0.001]. Besides, the variability was also obvious in antral follicle count, and ovum pick-ups. The estradiol peak values and the number of mature eggs between the two groups had significant difference. However, there was no obvious variability [t=0.457, p=0.324] in the basic FSH values between the two groups [normal group, 7.2 +/- 2.3 U/L; mutation group, 7.1 +/- 2.0 U/L]
Conclusion: The activity of FSHR promoter is significantly affected by the 29[th] site G-A mutation that will weaken promoter activity and result in poor response to FSH
ABSTRACT
This study examined the potential antilithic effects of a traditional Chinese medicine Urtica dentata Hand (UDH) in experimental rats and screened the optimal extract of UDH as a possible therapeutic agent for kidney stones.The rat model of urinary calcium oxalate stones was induced by intragastric (i.g.) administration of 2 mL of 1.25％ ethylene glycol (EG) and 1％ ammonium chloride (AC) for 28 days and was confirmed by Color Doppler ultrasound imaging.The rats in different experimental groups were then intragastrically given petroleum ether extract (PEE),N-butanol extract (NBE),aqueous extract (AqE) of UDH,Jieshitong (positive control drug),and saline,respectively.Treatment with NBE significantly reduced the elevated levels of urinary calcium,uric acid,phosphate,as well as increased urinary output.Accordingly,the increased calcium,oxalate levels and the number of calcium oxalate crystals deposits were remarkably reverted in the renal tissue of NBE-treated rats.In addition,NBE also prevented the impairment of renal function to decrease the contents of blood urea nitrogen (BUN) and creatinine.Taken together,these data suggest that NBE of UDH has a beneficial effect on calcium oxalate urinary stones in rats by flushing the stones out and protecting renal function.
ABSTRACT
<p><b>OBJECTIVE</b>To investigate the association between the anti-atherosclerotic effects of amlodipine and angiotensin converting enzyme (ACE) gene insertion/deletion (I/D) polymorphism in elderly essential hypertensive (EH) patients.</p><p><b>METHODS</b>A total of 220 EH patients were treated with amlodipine (2.5 - 10 mg, once daily) for twelve months and complete data were obtained from 208 patients with genotypes of II (n = 90), ID (n = 91) and DD (n = 27). The indices of carotid arterial were compared before and post amlodipine treatment in patients with identical genotype and among different ACE genotypes and each genotype post therapy.</p><p><b>RESULTS</b>The carotid mean intimal-medial thickness (MIMT) was slightly decreased in EH patients with ID and DD genotypes and significantly decreased in EH patients with II genotype (0.96 +/- 0.12 vs. 0.92 +/- 0.13, P < 0.01) compared to pre-treatment values. The decreased degree of MIMT (DeltaMIMT) in II genotype was significantly higher in II genotype than those in ID or DD genotype (0.05 +/- 0.03 vs. 0.01 +/- 0.02, 0.01 +/- 0.03 respectively, P < 0.01). The post treatment plaque score (PS) in patients with II genotype was significantly reduced (4.85 +/- 2.51 vs. 3.90 +/- 2.36, P < 0.05). Multivariate linear regression analysis showed the baseline SBP, the decreased degree of SBP (DeltaSBP) and the II genotype were the major factors affecting the DeltaMIMT.</p><p><b>CONCLUSION</b>Hypertensive patients carrying II genotype ACE genotype are the best responders for the anti-atherosclerotic effects of amlodipine.</p>
Subject(s)
Aged , Aged, 80 and over , Female , Humans , Male , Amlodipine , Therapeutic Uses , Carotid Artery Diseases , Pathology , Gene Frequency , Genotype , Hypertension , Drug Therapy , Genetics , Pathology , Peptidyl-Dipeptidase A , Genetics , Polymorphism, Genetic , Treatment OutcomeABSTRACT
Objective To study the relation between phlegm-damp retention type of metabolism syndrome and microcosmic indices in order to find out the objective evidence for TCM syndrome differentiation.Methods Totally 49 cases of metabolism syndrome were observed,25 of them were phlegm-damp retention type in differentiation and 24 were non-phlegm-damp retention type.The height, body weight,waistline and blood pressure of two groups were measured,the serum leptin,insulin and blood lipid were determined, and the insulin resistance index(IRI)and body mass index(BMI)were calculated.Results The leptin,BMI,systolic pressure,FINS and IRI of the phlegm-damp retention group were all higher than those of the non-phlegm-damp retention group.Conclusion BMI, leptin,insulin,and IRI may be taken as the the index of syndrome differentiation in metabolism syndrome.