The antitumor activities of NL-101,aHDACi/DNA damage dual-targeting drug,on human multiple myeloma in vitro and in vivo were studied.Furthermore,the primary mechanisms were revealed.We detected the anti-proliferative activity of NL-101 on 10 human multiple myeloma cell lines,and the combinational effect of NL-101 and bortezomib on RPMI 8226 cell line.The inducing effects of NL-101 on cell cycle arrest and apoptosis were detected by FACS.The effects of NL-101 on acetyled-Histone H3,total Histone H3,acetyled α-Tubulin,total α-Tubulin,phospho-Histone H2A.X and total Histone H2A.X were evaluated by Western blott.We also demonstrated the antitumor activity of NL-101 and the combinational effect of NL-101 and bortezomib on RPMI 8226 xenograft tumor model in vivo.Results showed that NL-101 possessed strong antitumor activities on human multiple myeloma cells in vitro and in vivo.NL-101exhibited significant HDAC inhibitory activity and DNA alkylating activity.NL-101not only inhibited histone deacetylation level,but also increased the DNA damage in multiple myeloma cells.Meanwhile,NL-101 induced cell cycle arrest and apoptosis.Also,the synergistic effect of NL-101 was discovered when combined with bortezomib in vitro and in vivo.These data demonstrated that NL-101 may be a potent agent for the treatment of human multiple myeloma in future.

In this study, we investigate the bioaccessibility of heavy metals (Cu, Pb, As, Cd and Hg) in wild Artemisia annua and use target hazard quotients (THQ) proposed by US Environmental Protection Agency to assess the health risk under the heavy metal exposure. The results showed that the bioaccessibility of Cu, Pb, As, Cd and Hg in A. annua are 0.77, 0.66, 0.46, 0.68 and 0, respectively, and that the value of THQ for adults and children were 0.030 and 0.025 calculated by risk assessment model. The results indicated that the heavy metals in A. annua were not able to be completely absorbed by human body and that their contents were in a safe range. In this study, by combining the bioavailability of heavy metal and health risk assessment, we assessed the security of heavy metals of wild A. annua, which will provide reference for the standard of heavy metals for medicinal materials.
Artemisia annua ; chemistry ; metabolism ; Consumer Product Safety ; Drug Contamination ; Humans ; Metals, Heavy ; analysis ; metabolism ; Risk Assessment ; Soil Pollutants ; analysis ; metabolism

Based on the ecological and economic problems in Good Agriculture Practice (GAP) of Chinese material medica, we introduced the origin, concept, features and operative technology of eco-agriculture worldwide, emphasizing its modes on different biological levels of landscape, ecosystem, community, population, individual and gene in China. And on this basis, we analyzed the background and current situation of eco-agriculture of Chinese materia medica, and proposed its development ideas and key tasks, including: (1) Analysis and planning of the production pattern of Chinese material medica national wide. (2) Typical features extraction of regional agriculture of Chinese materia medica. (3) Investigation of the interaction and its mechanism between typical Chinese materia medica in each region and the micro-ecology of rhizosphere soil. (4) Study on technology of eco-agriculture of Chinese materia medica. (5) Extraction and solidification of eco-agriculture modes of Chinese materia medica. (6) Study on the theory of eco-agriculture of Chinese materia medica. Also we pointed out that GAP and eco-agriculture of Chinese material medica are both different and relative, but they are not contradictory with their own features. It is an irresistible trend to promote eco-agriculture in the GAP of Chinese material medica and coordinate ecological and economic development.
Agriculture ; methods ; standards ; trends ; China ; Drugs, Chinese Herbal ; chemistry ; pharmacology ; standards ; Ecosystem ; Humans ; Materia Medica ; chemistry ; standards ; Plants, Medicinal ; chemistry ; growth & development

To set standards for histomorphological studies on Lysimachia fortunei, an efficacious and widely applied folk medicine in this study, in order to develop its resources. Its species were identified by observing plant morphology and herbs appearance characters, preparing slices with routine methods and defining structural characters. According to the results of morphologic observation, leaves, stamen and pistil of this plant were different from the descriptions in Flora of China. The whole herb can be used in medicines, mainly including rhizomes, stems and leaves. According to the findings in the first study on microscopic structures, its rhizomes, stems and leaves were characteristic and worth identifying. The transaction tissue structures of rhizomes and stems were under developed and contained endodermis, secretory structures; Stems had sclerenchymata of different shapes of sclereids; Leaves were bifacial and had vascular bundles under midribs, which were surrounded by parenchymal sheathes. On the surface of leaves, stomata, glandular hairs and keratin lines were morphologically different in upper and lower epidermis. The herbal power had glandular hairs, sclereids and vessels. In conclusion, herbs of L. fortunei can be identified by the above histomorphological characteristics, which lays a foundation for further development and application of L. fortunei.
Medicine, Traditional ; Plant Leaves ; anatomy & histology ; growth & development ; Plant Stems ; anatomy & histology ; growth & development ; Plants, Medicinal ; anatomy & histology ; growth & development ; Primulaceae ; anatomy & histology ; growth & development

Suspension cultures cell of Sorbus aucuparia (SASC) was used as materials, the changes of physiological and biochemical indexes of SASC after treatment with yeast extract (YE) were detected, and the synthetic mechanism of secondary metabolites in SASC treated with YE was preliminarily explored. The results were as follows: under the assay conditions, SASC was induced to synthesize five biphenyl compounds, and these compounds content changed differently with induction time prolonging; YE treatment inhibited cell growth, the culture medium pH was gradually reduced after treatment; water-soluble protein content showed a trend of slow decline, which was significantly increased in YE treatment group (YE group) compared with the control group (CK group), the maximum relative content was 147.76% in contrast with CK group; both YE group and CK group were extracellular Ca2+ flow influx, but the YE group flow was significantly slow than CK group. The results indicate that YE induced the cells in a stress state, which was not conducive to the growth of cells and forced the cells to synthesize biphenyl compounds against external stress; water-soluble protein may serve as intracellular enzymes involved in the synthesis of compounds regulation; Ca2+ may as signal molecule mediate cell signal transduction respond to YE stress.
Cell Culture Techniques ; instrumentation ; methods ; Culture Media ; chemistry ; metabolism ; Saccharomyces cerevisiae ; chemistry ; Secondary Metabolism ; Sorbus ; growth & development ; metabolism

Aim To investigate the protective effect of astragaloside IV (AS-Ⅳ) on human retinal pigment epithelium injury induced by methylglyoxal (MGO), and explore its molecular mechanism.Methods The injury of ARPE-19 cells was induced by MGO and the cell viability was measured by CCK-8 method.The morphology of cell nucleus was analyzed by Hoechst 33342 staining and the cell apoptosis was analyzed by flow cytometry to detect labbled Annexin V-FITC/PI.JC-1 staining and fluorescence probe DCFH-DA were employed to evaluate the change of mitochondrial membrane potential and reactive oxygen species (ROS).The levels of SOD, MDA, caspase-9 and caspase-3 were determined by respective kits.Western blot was used to analyse the expression of Bcl-2, Bax and PARP.Results AS-Ⅳ could significantly inhibit the decrease of cell viability induced by MGO, improve the morphology of cell nucleus, reduce the ARPE-19 cell apoptosis rate and the level of ROS and MDA, and increase the activity of SOD.Furthermore, AS-Ⅳ could enhance mitochondrial membrane potential, the ratio of Bcl-2/Bax and the expression of PARP, and inhibit the activation of caspase-9 and caspase-3.Conclusion AS-Ⅳ may protect ARPE-19 cells from the injury induced by MGO by increasing the antioxidant ability of ARPE-19 cells and inhibiting cell apoptosis.

Objective:To observe the effect of herbal cake-partitioned moxibustion on liver X receptor alpha (LXRα) in rabbits with atherosclerosis.Methods:Thirty-six male New Zealand rabbits were randomly divided into a normal group,a model group,a herbal cake-partitioned moxibustion group and a simvastatin group according to the random number table method,with 9 rabbits in each group.Rabbits in the model group,the herbal cake-partitioned moxibustion group and the simvastatin group were modeled by high fat feeding method which took 12 weeks.After verification of the successful model,rabbits in the normal group were not treated,in the model group were bundled,in the herbal cake-partitioned moxibustion group were treated with herbal cake-partitioned moxibustion,and those in the simvastatin group were treated with simvastatin,all for a total of 4 weeks.At the end of the experiment,the aorta and liver were observed for pathological changes;serum and liver were used to detect lipid levels;Western blot (WB) and real-time quantitative polymerase chain reaction (RT-qPCR) were used to detect LXRα protein and mRNA expression levels,respectively.Results:Compared with the normal group,the structure of aorta was disordered,the wall was rough and thick,the intima was unsmooth,and the vascular smooth muscle cells were arranged closely and disorderly in the model group,which was consistent with the characteristics of the rabbit model of aortic atherosclerosis.Compared with the model group,the aortic structure was clear,the degree of hepatocyte degeneration was reduced,the serum total cholesterol and low-density lipoprotein levels were significantly decreased (all P＜0.01),the high-density lipoprotein level was elevated (P＜0.01),and the total liver cholesterol was decreased significantly (P＜0.01) in the rabbits of the herbal cake-partitioned moxibustion group and the simvastatin group;compared with the model group,the protein (P＜0.01 or P＜0.05) and mRNA (P＜0.01) expressions of rabbit LXRα in the herbal cake-partitioned moxibustion group and the simvastatin group were increased.Conclusion:Herbal cake-partitioned moxibustion can improve the aortic and hepatic lesions,regulate blood lipid and liver lipid levels,increase the expression of liver cholesterol reverse transport nuclear receptor LXRα,promote reverse cholesterol transport in the rabbits with aortic atherosclerosis,therefore produces an antiatherogenic effect.

Objective To study the clinical significance of fecal smear examination on diagnosing intestinal flora imbalance in infantile diarrhea.Methods A sterile cotton swab was used to spread a layer of fresh feces quantum satis from a sterile container on a clean slide;the smear was fixed and stained with Gram′s methods after it was air-dried,then the specimen was observed with a microscopy(field lens 100 ? eye lens 10) and recorded.Results In the acute diarrhea group(40 cases),the distribution feature of 3 floras on the fecal smears:≥50% Gram-negative bacilli in 6 cases(15%),≥50% Gram-positive cocci in 30 cases(75%) and ≥68% Gram-positive bacilli in 4 cases(10%).In the delayed and chronic diarrhea group(62 cases),the distribution feature of 3 floras on the fecal smears:≥50% Gram-negative bacilli in 7 cases(11.29%),≥50% Gram-positive cocci in 44 cases(70.97%) and ≥68% Gram-positive bacilli in 6 cases(9.68%).In the normal control group(32 cases),the distribution feature of 3 floras on the fecal smears:≥50% Gram-negative bacilli in 1 case(3.13%),≥50% Gram-positive cocci in 1 case(3.13%),and ≥68% Gram-positive bacilli in 17 cases(53.13%).For the distribution of 3 floras in the 3 groups,chi-squared test was performed,and the results showed that the difference was significant in Gram-positive cocci(?~2=47.76 P0.05).Conclusions Acute,delayed or chronic diarrhea can lead to flora imbalance.In order to timely and rapidly know the flora imbalance in children with diarrhea,clinically the simple,easily operated and practical smear staining method shall be widely applied.

Background Cooking oil fumes are closely related to immune response, and adipose tissue also plays an important role in immune regulation. At present, the biological effect and mechanism of inflammation of adipose tissue induced by oil fume exposure are not clear yet. Objective To investigate the inflammatory effect of different exposure duration of cooking fumes on adipose tissue in mice and explore the role of Nod-like receptor pyrin domain 3 (NLRP3)/cysteinyl aspartate specific proteinase 1 (Caspase 1)/interleukin (IL)-1β signaling pathway. Methods Forty 8-week-old female C57BL/6J mice were randomly divided into 3-day control group (CON₃ group), 7-day control group (CON₇ group), 3-day oil fume exposure group (COF₃ group), and 7-day oil fume exposure group (COF₇ group), with 10 mice in each group. The mice were exposed to oil fumes in a cooking oil fume formation and exposure equipment (COFFEE) for 20 min, followed by a 10-min pause, 1 h a day for consecutive 3 d or 7 d. General condition of mice was observed and body weight was measured every day. After exposure, blood was sampled from the eyeball. Serum levels of IL-6, IL-27, and IL-1β were detected by enzyme-linked immunosorbent assay (ELISA). The adipose tissue of mice was collected and observed after hematoxylin-eosin (HE) staining. The percentages of CD4⁺ and CD8⁺T cells in adipose tissue were detected by flow cytometry. Real-time quantitative PCR (RT-qPCR) was used to detect the expression levels of nuclear factor-κB (NF-κB), NLRP3, Caspase 1, and IL-1β in adipose tissue. Western blot was used to detect the expression levels of NLRP3, Caspase 1, and IL-1β in adipose. Results Compared with the corresponding control group, serum IL-6, IL-27, and IL-1β contents in the COF₃ group and the COF₇ group were significantly increased (P<0.05) except IL-6 in the COF₃ group, and the levels in the COF₇ group were significantly higher than those in the COF₃ group (P<0.05). Vacuolar lipid droplets in adipocytes decreased, cytoplasm shrank, and inflammatory cells infiltrated in the COF₇ group after HE staining. The flow cytometry results showed that the proportions of CD4⁺ and CD8⁺T cells in adipocytes of the COF₃ group and the COF₇ group were increased compared to the corresponding control group, with a significant increase in the COF₇ group (P<0.05), and the CD4⁺/CD8⁺T ratio also significantly increased progressively in the two groups (P<0.05). The results of RT-qPCR showed that compared with the corresponding control group, the mRNA expression levels of NF-κB, NLRP3, Caspase 1, and IL-1β in adipose tissue of mice in the COF₃ group and the COF₇ group were significantly increased (P<0.05, P<0.01). The mRNA expression levels of mice in each exposure group gradually increased over time. The Western blot results showed that compared with the corresponding control group, the protein expressions of NLRP3 and Caspase 1 in the COF₃ group were significantly increased (P<0.01), and the expression of IL-1β protein also increased but without statistical significance. The protein expressions of NLRP3, Caspase 1, and IL-1β in the COF₇ group were significantly higher than those in the CON₇ group (P<0.05, P<0.01). Conclusion Acute exposure to cooking oil fumes can induce significant inflammatory response in adipose tissue, and the effect gradually increases with the extension of exposure time. The mechanism of action may be related to the activation of NLRP3 inflammasome signaling pathway.

OBJECTIVEThe beta-thalassemia major is a common hereditary hematology disease in southern China. The combination of blood transfusion and iron chelation is now the reference treatment. The allogeneic hematopoietic stem cell transplantation is the only curative therapy for beta-thalassemia major. In this study the investigators observed and evaluated the effects of umbilical cord blood transplantation (UCBT) for patients with beta-thalassemia major.

METHODSTwelve cases of beta-thalassemia major aged from 1.3 to 8.3 years (8 male and 4 female) received UCBT. Eleven of the twelve donors were siblings and one was unrelative. Eight patients received no antigen and four patients received two antigen disparate grafts. According to the Pesaro's classification for thalassemia, 10 patients were at grade I or II, and 2 were at grade III. The HLA-identical patients accepted the conditioning regimen consisting of busulfan, cyclophosphamide and antithymocyteglobulin. The HLA-mismatched patients accepted the conditioning regimen consisting of hypertransfusions, continuous iv desferrioxamine, hydroxyurea, fludarabine, busulfan, cyclophosphamide and antithymocyteglobulin. The harvest stem cells contained 3.63 - 16.0 x 10(7)/kg of nucleated cells, 0.11 - 1.03 x 10(6)/kg of CD(34)(+) cells and 0.17 - 1.18 x 10(5)/kg of colony-forming-unit-granulocyte macrophages. Cyclosporine alone or in combination with mycophenolate mofetil (MMF) was given for acute graft-versus-host disease (aGVHD) prophylaxis.

RESULTSOf the 12 patients, 10 were engrafted. Ten patients had neutrophil recovery (> 0.5 x 10(9)/L) and seven patients had platelet recovery (> 50 x 10(9)/L). The median time was 18.1 and 57.3 days, respectively. Seven patients had disease-free survival (DFS) at a median follow up of 23 months (range 4 - 63 months). Three patients had rejection and autologous hematopoitic reconstitution. Two patients were not engrafted. One patient acquired severe aplastic anemia, another patient died of severe infection. The incidences of grade I and grade II aGVHD were 60% (6/10) and 40% (4/10), respectively. There were no long-term complications in the disease free survivors.

CONCLUSIONSGrade I-II beta-thalassemia major patients receiving sibling UCBT had high DFS. UCBT is an effective way to treat beta-thalassemia major.

Child ; Child, Preschool ; Cord Blood Stem Cell Transplantation ; adverse effects ; Female ; Graft vs Host Disease ; epidemiology ; Hematopoiesis ; Humans ; Infant ; Male ; beta-Thalassemia ; mortality ; therapy