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Hepatocellular carcinoma (HCC) is a common malignant tumor worldwise. The incidence rate of HCC is high and is easy to metastasis and recurrence, which seriously affects human health. Traditional chemical drugs have some challenges such as toxicity, side effects, and multidrug resistance, thus it is urgent to find new drugs and effective targets. Here we synthesized a novel chemical, protonic bis-phenanthroline (H-BP), and the antitumor effect was investigated in the study. The results showed that H-BP could selectively inhibit the proliferation of tumor cells and cause HCC apoptosis. And also, in HCC tumor-bearing mice, H-BP could effectively prevent the growth of tumor mass, even completely eliminate the tumor at medium dose (5 mg·kg-1) and high dose (10 mg·kg-1), and meanwhile H-BP has no significant effect on the body weight of mice. The experimental protocol was approved by the Animal Ethics Committee of Southwest University, and the experimental operation was strictly carried out in accordance with the ethical principles of animal use and care. Mechanism studies showed that H-BP induced HCC apoptosis was related to down-regulation the expression of pleomorphic adenoma gene like-2 (PLAGL2), a oncogene transcription factor, resulting in the down-regulation of PLAGL2 downstream proteins hypoxia inducible factor and β-catenin. This study not only introduces the dimerization method to form novel compounds that will provide a new approach for drug design, but also suggests that PLAGL2 may be an effective target in tumor therapy.
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Objective To investigate the effect of Euryale ferox seeds ethanol extract on renal funtion of diabetic nephropathy (DN) induced by strepotozotocin (STZ) in rats and the antioxidant ability of ethanol extract, water extract supernatant and precipitation. Methods Ethanol extract of Euryale ferox seeds were prepared by ethanol extraction and followed by evaporation and freeze-dry. The seeds residue was further extracted with water and precipitated with ethanol to obtain water extract supernatant and precipitation. Sprague Dawley male rats were given intraperitoneal injection of STZ at a dose of 60 mg/kg to induce DN. STZ-induced DN rats were administrated by gavage with different dose of Euryale ferox seeds ethanol extract (75, 150, 300 and 600 mg/ kg body weight) once daily for 12 weeks. 24 h urine was collected for examining urinary protein and microalbumin every four weeks. Blood serum was also collected for examining of serum creatinine (Cr) and blood urea nitrogen (BUN) level after rats sacrificed at the end of 12 weeks after administration, and the pathological changes of kidney were observed. Antioxidant capacity of the three extracts were determined by Fe3z reduction, and radical scavenging rate to 1, 1-diphenyl-2-picrylhydrazyl radical 2,2-diphenyl-1-(2,4,6-trinitrophenyl)hydrazl (DPPH), 02" and OH" free radicals. Results Compared with model group, the content of 24 h urine protein and urine microalbumin of DN rats were reduced in all Euryale ferox seeds ethanol extract administration groups, and 24 h proteinuria were significantly reduced in the group of 150 and 600 mg/kg administration (P<0.05); BUN level was also reduced in all dose of Euayale ferox seeds ethanol extract administration, and more remarkably reduced in the group of 300mg/kg (P<0.01). 12 weeks after administration, kidney damage amelioration was observed in pathological sections of rats in Euryale ferox seeds ethanol
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The seed. coat, petiole and peduncle of Euryale feroxibelonging to Nymphaeaceae) are used as medicinal potions through solvent extraction, reflux extraction and ultrasonic extraction, and purification on macroporous resin. The quality controls are performed by near infra-red fingerprint spectrum. HPLC. X-ray diffraction Fourier spectrum, and ITS2 barcode. The nutrients of E. ferox contain large amount of amino acids, fatty acids and various microelements; medicinal ingredients are identified to be polyphenol, sesquineolignan. tocopherol, cerebroside, and cyclic dipeptide. The pharmacological effects of E. ferox extracts include antioxidant, free radical scavenging, hypoglycemic activity, decreasing urine protein, bacteriostasis and prevention of gastric mucosal injury. Treatment with E. ferox preparations for diabetes and chronic nephritis are performed in clinics. This review summarizes the study of E. ferox in recent years for further research and development.
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Background Mitomycin C (MMC) has an inhibitory effect on the growth and proliferation of human pterygium fibroblasts,however,there is little literature about its influence on plasma membrane. Objective This study was to investigate the influence of MMC on the physical and chemical features and ultrastructures of plasma membrane. Methods Human pterygium tissues were obtained during the surgery.Human pterygium fibroblasts were primarily cultured and passaged using explant cultured method and identified by Vimentin staining.The third generation of cells were incubated to 96 well plate at a density of 5 × 103 cells/well,and 0,50,100,200,300 and 400 mg/L MMC was added in the culture well respectively to act for 12 hours.Cell viability was assayed using cell counting kit-8 ( CCK-8 ),and cellular apoptosis was detected using annexin V-FICT/PI.The changes of cell membrane structure were examined under an atomic force microscope.Malondialdehyde( MDA ) content in cell supernatant and level of lactate dehydrogenase ( LDH ) in extracellular fluid were detected to assess the lipid peroxidation level and permeability of cell membrane.Intracellular Ca2+ changes and membrane surface topography were assessed by Fluo-3/AM mark and flow cytometry( FCM ).This study was approved by Ethic Commission of Affiliated First Hospital of Jinan University.Informed consent was obtained from each patient. Results A lot of cells grew with the shape of spindle 1-2 weeks after culture.Positive response was seen in cultured cells for Vimentin.Growth and proliferation of the cells reduced 12 hours after action of MMC with the increase of MMC concentrations.The apoptosis rate of human pterygium fibroblasts was 4.2％,4.2％,5.4％,19.3％ and 25.8％ in 0,50,100,200 and 300 mg/L MMC groups respectively.Different degrees of abnormalities of cells membrane were found in various concentrations of MMC groups.The elevated contents of LDH and MDA in extracellular fluid were detected in various concentrations of MMC groups compared with the control group,and the LDH and MDA levels were gradually ascended as the increase of MMC concentrations,with a significant difference between any two groups(P＜0.05).The disturbance of intracellular Ca2+ homeostasis was also been seen after MMC acted. Conclusions MMC leads to the changes of physical and chemical features in human pterygium fibroblasts at a dose-dependent manner.Cell membrane may be the acting target of MMC.
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BackgroundCorneal neovascularization (CNV) is a common eye disease.The researches on the pathogenesis and treatment of CNV are focus in Ophthalmology.ObjectiveThis study was to investigate the effects of culture supernatant from human amniotic epithelial cells (AECs) on CNV in vitro and its mechanism.MethodsHuman AECs were obtained from a placenta and cultured in serum-free medium for 48 hours,and the supernatant was collected.The levels of interleukin-1 receptor antagonist (IL-1 Ra) and pigment epithelium-derived factor (PEDF) in the human AECs culture supernatant were detected by enzyme-linked immunosorbent assay (ELISA).Rabbit corneal epithelial cells (CECs) were obtained and cultured in different concentrations of human AECs culture supernatant for 48 hours,serum-free medium was used as the control group.The expression of vascular endothelial growth factor (VEGF) mRNA and basic fibroblast growth factor (bFGF) mRNA in rabbit CECs were measured by quantitative real-time PCR (QRT-PCR).Human umbilical cord vein endothelial cells (UVECs) were cultured in the three mediums above,and the proliferation of human UVECs (absorbance value,A value) was tested by the cell counting kit 8 ( CCK8 ).Migration assay was performed by the wound healing method for the human UVECs.The membrane ultra-structure of human UVECs was examined under the atomic force microscope (AFM).ResultsCultured and passaged human AECs showed a positive response for keratin.The expression of VEGF mRNA (1.00±0.22) and bFGF mRNA (1.00±0.36) in rabbit CECs was suppressed by the human AECs culture supernatant,with a significant reduction in comparison with the serum-free DMEM group (2.98±0.46,2.55±0.48 )(P=0.001,0.002).The A value was significantly lowered in the human AECs culture group for 72 hours compared with the serum-free DMEM group ( 1.941 ± 0.036 versus 2.144 ± 0.059 ) ( P =0.000 ),and the bFGF-induced migration rate of human UVECs was strongly inhibited by the culture supernatant of human AECs in comparison with serum-free DMEM.The plasma membrane of human UVECs cultured with the human AECs culture supernatant was full of bumps,and decreased intercellular connection and cellular pseudopodia were found on the AFM image.The concentration of IL-1Ra was (153.56±0.36)ng/L and that of PEDF was (70.41 ±0.68 )μ,g/L in the human AECs culture supernatant.Nothing was deteched in serum-free DMEM group.Conclusions Human AECs culture supernatant suppressed the expression of VEGF and bFGF in CECs as well as the migration and proliferation of vascular endothelial cells.The effect may be associated with IL-1Ra and PEDF secreted by human AECs.These results suggest that human AECs may be a potential therapy for the inhibition of CNV.
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<p><b>OBJECTIVE</b>To evaluate the value of coronary CT angiography in assessment of bifurcation lesions.</p><p><b>METHODS</b>The original image of 79 established and suspected coronary artery disease patients who underwent both coronary CT angiography and conventional artery angiography (CAG) sequentially were included in this analysis. Bifurcation lesions were assessed on primary and secondary vessels with diameter ≥ 2.0 mm, bifurcation lesions were graded according to Chen's classification. CAG was used as golden standard. The sensitivity, specificity, positive predictive value and negative predictive value were calculated. Spearman's test and Kappa test were used to evaluate the correlation and classification identity of the two methods.</p><p><b>RESULTS</b>CAG evidenced 177 bifurcation lesions out of 445 bifurcation vessels and coronary CT detected 168 bifurcation lesions out of 404 bifurcation vessels with satisfactory imaging quality and 390 bifurcation vessels could be analyzed by both CAG and coronary CT. Sensitivity, specificity, positive predictive value and negative predictive value of coronary CT angiography were 94.2%, 94.6%, 90.7%, 96.1%, respectively. The results for the lesions at LM-LAD/LCX + LAD/Mid, LAD/Diag, RCA/PDA were more satisfactory and the sensitivity and specificity were as high as: 97.1% and 94.2%, 95.7% and 89.5%, 92.3% and 98.7%, respectively. There were significant correlations for evaluating the narrow degree of the opening of the bifurcation branch with these two methods (r = 0.799 58, P < 0.01) and for identifying I, II, III type bifurcation lesions (Kappa coefficient = 0.7959, P < 0.01) as well as for identifying the subtype bifurcation lesions (Kappa coefficient = 0.6328, P < 0.01) using the two methods.</p><p><b>CONCLUSION</b>Coronary CT angiography is efficient in identifying the bifurcation lesions and offers a reasonable indication for bifurcation lesion classification.</p>
Subject(s)
Adult , Aged , Aged, 80 and over , Female , Humans , Male , Middle Aged , Coronary Angiography , Methods , Coronary Artery Disease , Diagnostic Imaging , Retrospective Studies , Tomography, X-Ray ComputedABSTRACT
<p><b>OBJECTIVE</b>To observe the effect of acupoint Sanyinjiao (SP6) moxibustion (S-Mox) on the duration of the first labor stage and uterine contractive pain in primiparae.</p><p><b>METHODS</b>Sixty primipara women in labor were equally assigned according to their choice to three groups: women in the S-Mox group received bilateral S-Mox for 30 min, women in the non-acupoint group received moxibustion (Mox) applied on non-acupoints for 30 min, and those in the control group did not receive Mox intervention. The duration of the first labor stage was recorded and the degree of labor pain was estimated by a visual analogue scale (VAS) before and after Mox.</p><p><b>RESULTS</b>The duration of the first stage active phase in the S-Mox group was significantly shorter than that in the other two groups (P<0.05, P<0.01); the VAS score after Mox was lower in the S-Mox group, showing a statistical difference in comparison with the control group (P<0.05).</p><p><b>CONCLUSIONS</b>Applying S-Mox could markedly shorten the active phase of the first stage of labor and lower the VAS score of uterine contractive pain, which means alleviating the pain caused by vaginal delivery. Its mechanism is worthy of further study.</p>
Subject(s)
Adult , Female , Humans , Pregnancy , Young Adult , Acupuncture Points , Labor Pain , Therapeutics , Labor Stage, First , Physiology , Moxibustion , Pain Measurement , Parity , Uterine Contraction , PhysiologyABSTRACT
<p><b>OBJECTIVE</b>To observe the effect of needling "Housanli" (ST 36) with different retaining-needle time on the pain threshold of mice using the hot water tail-flick test, and investigate the relationship between the retaining-needle time and the therapeutic effect.</p><p><b>METHODS</b>Twenty-four healthy mice were randomly divided into four groups: no retaining-needle group (group A), retaining-needle 10 min group (group B), retaining-needle 20 min group (group C) and retaining-needle 30 min group (group D), with 6 mice for each group. After acupuncture "Housanli", the tail of mouse was put into the hot water at 50 degrees C, and the intervening time from the tail entered water to the tail flicked out of water was recorded and analyzed for each group.</p><p><b>RESULTS</b>After acupuncturing "Housanli", the pain threshold was significantly improved with the hot water tail-flick test in both group A and group C (both P<0.01), however, there was no significant difference in both group B and group D (both P>0.05). Within 30 min of retaining-needle, the effect curve of acupuncture analgesia was showed in a waved line. In contrast, the maximum value of latent period on the tail-flick was detected in the group C that was the biggest effect of acupuncture analgesia among the four groups.</p><p><b>CONCLUSION</b>The best retaining-needle time of hand-acupuncture for acupuncture analgesia is 20 min.</p>