Transdermal characteristics and mechanism of asiaticoside nanoemulsions and asiaticoside nanoemulsions-based gels / 中国中药杂志

To prepare the asiaticoside nanoemulsions (ASI-NEs) and asiaticoside nanoemulsions-based gels (ASI-NBGs), compare them with the commercial cream of asiaticoside (ASI-C) in terms of transdermal characteristics, and investigate the transdermal mechanism of ASI-NEs and ASI-NBGs. Their transdermal characteristics were studied by using Franz diffusion cells. The effect of topical ASI-NEs and ASI-NBGs on ultrastructure of rabbit skin was evaluated by using HE staining method. The localization and the permeation pathway of asiaticoside were visually investigated by using laser scanning confocal microscope (CLSM). The transdermal studies in vitro showed that the cumulative amount of ASI permeated from ASI-NEs and ASI-NBGs at 12 h after application were (3 504.30±180.93), (1 187.40±128.88) μg·cm⁻² respectively, 6.57, 2.23 times of that in the control group of ASI-C; the drug deposition of ASI-NEs and ASI-NBGs in skin was (159.48±7.47), (120.53±5.71) μg·cm⁻² respectively, 5.93, 4.48 times of that of ASI-C. HE staining of the rabbit skin after application of ASI-NEs and ASI-NBGs showed that the epidermis structure was basically intact; stratum corneum was loosed and the keratin fragment was increased; at the same time, the gap of prickle cell was increased and the basal cells were arranged loosely. The study of CLSM showed that significant percutaneous enhancer effect was observed for ASI-NEs after the topical application of 6 h, as the fluorescent compound was penetrated in the dermis and diffused uniformly. The fluorescence area and the integral optical density (IOD) were 28.81, 32.51 times of that in the FITC aqueous solution group, respectively. The fluorescent preparations showed strong fluorescence in the epidermis, but weak in deeper layers; with the increase of treatment time, the fluorescence in deeper layer was increased and stronger in skin appendages. The prepared ASI-NEs and ASI-NBGs have good transdermal characteristics and the transdermal mechanism is related to breaking the ultrastructure of stratum corneum and penetrating by the path of skin adnexa.

ZM-66, a new podophyllotoxin derivative inhibits proliferation and induces apoptosis in K562/ADM cells / 中国医学科学杂志(英文版)

<p><b>OBJECTIVE</b>To investigate the anti-tumor effect of ZM-66 on multidrug-resistant leukemic cell line K562/ADM.</p><p><b>METHODS</b>The K562/ADM cells were treated with varying concentrations (0, 1, 2, 4 × 10⁻³ mmol/L) of ZM-66 or etoposide for 24 hours. The proliferation was detected by Sulforhodamine B Sodium Salt (SRB) assay and apoptosis was detected by flow cytometry analysis and fluorescent staining. In addition, the expression levels of p53 and bax genes in K562/ADM cells were detected by RT-PCR analysis. The level of P-glycoprotein (P-gp), P53 and Bax protein in K562/ADM cells were detected by Western blot assay.</p><p><b>RESULTS</b>SRB assay demonstrated that etoposide had little inhibitory effect on K562/ADM cells, whereas ZM-66 (1, 2, 4 × 10⁻³ mmol/L) had significantly inhibitory effect on K562/ADM cells (all P<0.01). The acridine orange/propidium iodide dual staining showed that there were typical condensation of chromatin and nuclear fragmentation nuclei with red color in ZM-66 treated cells. Flow cytometric analysis showed that there was a significantly increase of apoptotic cells in K562/ADM cells after treated with ZM-66. RT-PCR showed that the p53 and bax mRNA expression levels in K562/ADM cells treated with ZM-66 at 1, 2, 4 × 10⁻³ mmol/L were higher than those in the cell without treatment. Western blot showed that the P53 and Bax protein expression levels in K562/ADM cells treated with ZM-66 at 2, 4 × 10⁻³ mmol/L were higher than those in the cell without treatment. But the P-gp protein expression level in K562/ADM cells treated with ZM-66 at 2, 4 × 10⁻³ mmol/L was gradually lower than those in the cell without treatment.</p><p><b>CONCLUSION</b>ZM-66 is able to induce cell death by apoptosis in vitro, as a result of the reverse of the apoptosis resistance in drug-resistant K562/ADM cells by modulating expression of key factors associated with apoptosis induction.</p>

Novel mutations of cardiac troponin T in Chinese patients with hypertrophic cardiomyopathy / 中华心血管病杂志

<p><b>OBJECTIVE</b>To screen the cardiac troponin T (TNNT2) mutations in Chinese patients with hypertrophic cardiomyopathy (HCM) and to analyze the potential link between the genotype and the phenotype.</p><p><b>METHODS</b>Clinical features of 100 probands with HCM and some family members were evaluated, 200 unrelated normal subjects served as control. The exons and flanking introns of TNNT2 were amplified with PCR and direct sequencing was used to screen TNNT2 mutations/polymorphisms.</p><p><b>RESULTS</b>Two novel missense mutations were detected in 2 HCM patients: R92W and R286H. These 2 mutations were not found in 200 non-HCM controls. A five-basepair insertion/deletion polymorphism in intron 3 of TNNT2 was identified in this HCM cohort but was not related to the phenotype.</p><p><b>CONCLUSIONS</b>Two missense mutations, R92W and R286H, were found in 2/100 patients with HCM, TNNT 2 mutation is relatively low in Chinese patients with HCM.</p>

Characterization of atherosclerotic plaque in patients with unstable angina pectoris and stable angina pectoris by optical coherence tomography / 中华心血管病杂志

<p><b>OBJECTIVE</b>To compare the characterization of coronary atherosclerotic plaques in patients with unstable angina pectoris (UAP) and stable angina pectoris (SAP) by optical coherence tomography (OCT).</p><p><b>METHODS</b>OCT was performed in 47 patients (23 UAP and 24 SAP) undergoing coronary angiography. Lipid-rich plaque (defined by > or = 2 quadrants of the cross-section area), thin cap fibroatheroma (TCFA), thickness of fibrous cap, plaque rupture, calcification and thrombus visualized by OCT were compared between UAP and SAP patients.</p><p><b>RESULTS</b>OCT imaging was successfully in 44 out of 47 patients (22 UAP, 22 SAP). Proportion of lipid-rich plaques was similar between UAP and SAP groups [91% (20/22) vs. 73% (16/22), P = 0.741]. The minimum thickness of fibrous cap in the UAP group was significantly thinner than that in SAP group [(69.5 +/- 34.7) microm vs. (141.1 +/- 68.5) microm, P = 0.000] and the rate of fibrous cap erosion in the UAP group was significantly higher than that in the SAP group [59% (13/22) vs. 9% (2/22), P = 0.000]. Percents of TCFA [73% (16/22) vs. 14% (3/22), P = 0.000] and plaque rupture [50% (11/22) vs. 9% (2/22), P = 0.003] were significantly higher in UAP group compared those in SAP group. Incidence of thrombus and calcification were similar between two groups.</p><p><b>CONCLUSIONS</b>OCT imaging can clearly define plaque characterization of coronary atherosclerosis. UAP patients have thinner fibrous cap, higher incidences of fibrous cap erosion, plaque rupture and TCFA compared patients with SAP.</p>

Novel MYBPC3 mutations in Chinese patients with hypertrophic cardiomyopathy / 中华心血管病杂志

<p><b>OBJECTIVE</b>To screen the MYBPC3 gene mutations in Han Chinese patients with hypertrophic cardiomyopathy (HCM).</p><p><b>METHODS</b>Sixty-six patients with HCM were enrolled for the study. The exons in the functional regions of MYBPC3 were amplified with PCR and the products were sequenced.</p><p><b>RESULTS</b>Four novel mutations and four common polymorphisms were identified in this patient cohort. A Lys301fs mutation in exon10 was evidenced in a H30, and when he was 47 years old, he had the chest tightness, shortness of breath with septal hypertrophy of 18.7mm; a Asp463stop mutation in exon17 was detected in a H48, he was 24 years old 24-year-old when a medical examination showed ventricular septal hypertrophy of 15.4 mm; both Gly523Arg mutation in exon18 and Tyr847His mutation in exon26 were found in a H53 with onset age 36 years old, feeling chest tightness after excise and his ventricular septal hypertrophy was 27 mm that time. MYBPC3 mutations occurred in 4.5% patients in this cohort. These mutations were not found in 100 non-HCM control patients.</p><p><b>CONCLUSION</b>MYBPC3 mutation is presented in a small portion of Han Chinese patients with HCM.</p>

Coronary artery atherosclerotic plaque and stent visualizations by optical coherence tomography / 中华心血管病杂志

<p><b>OBJECTIVE</b>To evaluate coronary artery atherosclerotic plaque characteristics and changes post coronary stenting by optical coherence tomography (OCT).</p><p><b>METHODS</b>OCT images were obtained in 22 diseased coronary vessels after coronary angiography or percutaneous coronary interventions (PCI) in 20 patients and in 23 stents [7 sirolimus-eluting stents (SES) follow up at 4-29 months post stenting and 8 bare mental stents (BMS) at 4-35 months post stenting, 8 stents immediately after PCI].</p><p><b>RESULTS</b>All 22 vessels and 23 stents OCT images were successfully acquired. Two thromboses, 8 fibrous, 9 lipid-rich and 3 calcium plaques as well as 3 plaque ruptures were visualized by OCT. No significant neointimal proliferation and restenosis were found in SES stents and some struts were not covered with neointima even at 29 months post stenting. Significant neointimal proliferation on surfaces of stent struts were visualized in all 8 BMS stents and restenosis was detected in 3 BMS stents. OCT images obtained immediately after PCI showed that 3 stents were well positioned, tissue prolapse between coronary stent struts occurred in 4 stents and stent dissociation with vessel wall could be seen in 1 stent.</p><p><b>CONCLUSIONS</b>OCT imaging can clearly visualize different types of atherosclerotic plaques. By providing detailed information on plaque characteristics, this technique might help cardiologists in choosing suitable stents and guiding preventive therapy for patients with coronary heart disease.</p>

Analysis of MYH7, MYBPC3 and TNNT2 gene mutations in 10 Chinese pedigrees with familial hypertrophic cardiomyopathy and the correlation between genotype and phenotype / 中华心血管病杂志

<p><b>OBJECTIVE</b>The aim of this study was to screen the disease-causing gene mutations and investigate the genotype-phenotype correlation in 10 Chinese pedigrees with familial hypertrophic cardiomyopathy (HCM).</p><p><b>METHODS</b>There are 91 family members from these 10 pedigrees and 5 members were normal mutated carriers, 23 members were HCM patients (14 male) aged from 1.5 to 73 years old. The functional regions of myosin heavy chain gene (MYH7), cardiac myosin-binding protein C (MYBPC3) and cardiac troponin T gene (TNNT2) were screened with PCR and direct sequencing technique. Clinical information from all patients was also evaluated in regard to the genotype.</p><p><b>RESULTS</b>Mutations were found in 5 out of 10 pedigrees. Mutations in MYH7 (Arg663His, Glu924Lys and Ile736Thr) were found in 3 pedigrees and 3 patients from these pedigrees suffered sudden death at age 20-48 years old during sport. Mutations in MYBPC3 were found in 2 pedigrees, 1 with complex mutation (Arg502Trp and splicing mutation IVS27 + 12C > T) and 1 with novel frame shift mutation (Gly347fs) and the latter pedigree has sudden death history. No mutation was identified in TNNT2.</p><p><b>CONCLUSIONS</b>Although the Han Chinese is a relatively homogeneous ethnic group, different HCM gene mutations were responsible for familiar HCM suggesting the heterogeneity nature of the disease-causing genes and HCM MYH7 mutations are associated with a higher risk of sudden death in this cohort. Furthermore, identical mutation might result in different phenotypes suggesting that multiple factors might be involved in the pathogenesis of familiar HCM.</p>

Effect of geniposide on serum IL-1beta and TNF-alpha of rheumatoid arthritis rats / 中国中药杂志

<p><b>OBJECTIVE</b>To study the effect of geniposide on serum IL-1beta and TNF-alpha levels of rheumatoid arthritis rats, as well as the mechanism of this drug.</p><p><b>METHOD</b>To establish an experimental rat model of type II collagen-induced arthritic (CIA). The inhibitory effects on paw edema were observed, and serum IL-1beta and TNF-alpha levels were determined in experimental rats.</p><p><b>RESULT</b>Compared with the model, geniposide delayed the starting time of right paw edema significantly, and the levels of serum IL-1beta and TNF-alpha were significantly decreased by geniposide at high dose or medium dose (P < 0.01).</p><p><b>CONCLUSION</b>Geniposide can lower serum IL-1beta and TNF-alpha levels in rheumatoid arthritis rats. The effect may be close related to inhibitory development of rheumatoid arthritis by the agent.</p>