Regulation of Baicalin on Growth of Extranodal NK/T Cell Lymphoma Cells through FOXO3/CCL22 Signaling Pathway / 中国实验血液学杂志

OBJECTIVE@#To investigate the effect of baicalin on the growth of extranodal NK/T cell lymphoma (ENKTCL) cells and its related mechanism.@*METHODS@#Normal NK cells and human ENKTCL cells lines SNK-6 and YTS were cultured, then SNK-6 and YTS cells were treated with 5, 10, 20 μmol/L baicalin and set control. Cell proliferation and apoptosis was detected by Edu method and FCM method, respectively, and expressions of BCL-2, Bax, FOXO3 and CCL22 proteins were detected by Western blot. Interference plasmids were designed and synthesized. FOXO3 siRNA interference plasmids and CCL22 pcDNA overexpression plasmids were transfected with PEI transfection reagent. Furthermore, animal models were established for validation.@*RESULTS@#In control group and 5, 10, 20 μmol/L baicalin group, the proliferation rate of SNK-6 cells was (56.17±2.96)%, (51.92±4.63)%, (36.42±1.58)%, and (14.60±2.81)%, respectively, while that of YTS cells was (58.85±2.98)%, (51.38±1.32)%, (34.75±1.09)%, and (15.45±1.10)%, respectively. In control group and 5, 10, 20 μmol/L baicalin group, the apoptosis rate of SNK-6 cells was (5.93±0.74)%, (11.78±0.34)%, (28.46±0.44)%, and (32.40±0.37)%, respectively, while that of YTS cells was (7.93±0.69)%, (16.29±1.35)%, (33.91±1.56)%, and (36.27±1.06)%, respectively. Compared with control group, the expression of BCL-2 protein both in SNK-6 and YTS cells decreased significantly (P<0.001), and the expression of Bax protein increased in SNK-6 cells only when the concentration of baicalin was 20 μmol/L (P<0.001), while that in YTS cells increased in all three concentrations(5, 10, 20 μmol/L) of baicalin (P<0.001). The expression of FOXO3 protein decreased while CCL22 protein increased in ENKTCL cell lines compared with human NK cells (P<0.001), but the expression of FOXO3 protein increased (P<0.01) and CCL22 protein decreased after baicalin treatment (P<0.001). Animal experiments showed that baicalin treatment could inhibit tumor growth. The expression of CCL22 protein in ENKTCL tissue of nude mice treated with baicalin decreased compared with control group (P<0.01), while the FOXO3 protein increased (P<0.05). In addition, FOXO3 silencing resulted in the decrease of FOXO3 protein expression and increase of CCL22 protein expression (P<0.01, P<0.001).@*CONCLUSION@#Baicalin can inhibit proliferation and promote apoptosis of ENKTCL cell lines SNK-6 and YTS, up-regulate the expression of Bax protein, down-regulate the expression of BCL-2 protein, and down-regulate the expression of CCL22 protein mediated by FOXO3. Animal experiment shown that the baicalin can inhibit tumor growth. Baicalin can inhibit the growth and induce apoptosis of ENKTCL cells through FOXO3/CCL22 signaling pathway.

Clinical features of long segmental myelopathy caused by nitrous oxide / 北京大学学报(医学版)

OBJECTIVE@#To analyze the clinical and imaging characteristics of the neurological damage caused by nitrous oxide (N2O).@*METHODS@#In the study, 10 patients in the Department of Neurology of China-Japan Friendship Hospital from October 2015 to February 2018 were retrospectively analyzed for the demographic data, the history of inhaled N2O, clinical features, blood examination, electrophysiological examination, spinal magnetic resonance imaging and therapeutic efficacy profiles.@*RESULTS@#The male-to-female ratio was 4:6 and it presented with an age-of-onset 17-26 years [the average age: (20.80±3.12) years]. The time from inhaled N2O to onset was 1 month to 1 year [the average time: (6.95±4.19) months]. Paralysis in all the patients and numbness in 9 patients were the main clinical features, while positive Lhermitte's sign in 3 patients, urinary and defecation disturbance in 4 patients were also found. Blood examination indicated anemia in 2 patients, giant cell anemia in 1 case and small cell hypochromic anemia in 1 case. 3 cases had been treated with vitamin B12 in an external hospital, and the other 7 cases had abnormal increase in homocysteine levels. Electrophysiological examinations showed sensory and motor nerve involvement in 9 patients, and motor nerve involvement in 1 patient. The severity of lower extremity lesion was significantly heavier than that of upper extremity. Spinal magnetic resonance imagings showed that long segmental lesions were present in the cervical spinal cord of all the patients, 3 cases with long segmental lesions of the thoracic cord and 2 cases with spinal cord swelling. In 6 cases, the horizontal axis had an "inverted V-type" T2 high signal, 1 case was classified as "crescent", and 3 cases were "eight-shaped". The symptoms in these 10 cases were alleviated in varying degrees after stopping the inhalation of nitrous oxide, actively supplementing high doses of vitamin B12 and doing early rehabilitation exercises.@*CONCLUSION@#Myelopathy with nitrous oxide presents as paralysis and numbness in limb extremities. In imaging, cervical spinal cord damage is common, accompanied by thoracic spinal cord damage. The horizontal axis is more common in the "inverted V-type". Treatment with high doses of vitamin B12 is effective.

MiR-30b Regulates the Cisplatin-Resistance of Human NK/T Cell Lypnphoma Cell Lines SNK-6 and YTS by Targeting the CCL22 / 中国实验血液学杂志

OBJECTIVE@#To explore the effect and mechanism of miR-30b on cisplatin-resistance of human NK/T cell lymphoma lines SNK-6 and YTS cells.@*METHODS@#Normal NK cells, SNK-6 and YTS cells were cultured, the expression levels of miR-30b and macrophage-derived chemokine (CCL22) were detected by real-time PCR assay, and the CCL22 expression was detected by Western blot. The SNK-6 and YTS cells were transfected with miR-30b mimics and inhibitor respectively, then the effect of cisplatin resistance in SNK-6 and YTS cells was measured by MTT assay, the activity of caspase-3 was detected by caspase-3 assay kit, and the cell apoptosis was analyzed by flow cytometry. Dual-luciferase reporter gene assay was used to determine the targeting relationship between miR-30b and CCL22. Furthermore, the effect of CCL22 on cisplatin-resistance and caspase-3 actirity was also evaluated.@*RESULTS@#Compared with the normal NK cells, the expression levels of miR-30b significantly decreased in both SNK-6 and YTS cells (P＜0.01), but CCL22 mRNA expression increase in both cells (P＜0.01). MiR-30b mimics decreased the cell activity (P＜0.05), down-regulated the cisplatin-resistance (P＜0.05), and increased cell apoptosis and caspase-3 activity (P＜0.05). The effects of miR-30b inhibitor were contrary to the mimics. Up-regulation of miR-30b expression significantly decreased the luciferase activity in CCL22 3'-UTR-transfected NK cells, but not in Mut-CCL22 3'UTR group, suggesting that CCL22 could act as a direct target of miR-30b. The expressions of CCL22 pathway proteins were down-regulated after SNK-6 cells transfected with miR-30b mimics (P＜0.05), while this effect was restored by overexpression of CCL22. Moreover, CCL22 overexpression also increased the cell activity and decreased caspase-3 activity when SNK-6 cells were transfected with miR-30b mimics.@*CONCLUSION@#MiR-30b inhibits cisplatin-resistance of human NK/TCL SNK-6 and YTS cells by targeting CCL22.

Three-dimensional structure of beads self-assembled by cyclodextrin using synchrotron radiation X-ray microcomputed tomography / 药学学报

Beads, a novel drug delivery system self-assembled by cyclodextrins (CDs) and oil, has potential applications in the solidification of oil drugs and improving the bioavailability of lipid-soluble drugs. However, very few researches were dedicated to the mechanism of beads formation. In this study, three-dimensional structures of beads were visualized and investigated using synchrotron radiation X-ray microcomputed tomography (SR-μCT). The structural changes of beads attributed by drying process were analyzed and confirmed via visualization results of SR-μCT. Productively, it was proposed that Pickering emulsion droplets obtained during beads formation process were spatially localized orderly. Moreover, the effects of loading lipid soluble drug, namely, vitamin K1, on the structural changes of beads were also analyzed. It is well known that the surface tension of oil phase could be changed by the addition of lipid soluble constituents. It was reasonable that the three-dimensional structure of beads might be altered during the drug loading of vitamin K1 into the beads. However, although the morphologies of beads were changed to some extent, the ordered Pickering emulsion droplets during the process of beads formation was successfully illustrated based on the SR-μCT results. Conclusively, according to the three-dimensional structural analysis of the beads, this study revealed the organized architecture for Pickering emulsion droplet assembly and beads formation in cyclodextrin semi-inclusion complex, which significantly complements the formation mechanism of beads, and provides a structural basis for the further study of beads.

Genetics and clinical study of Chinese kindreds with dentatorubral pallidoluysian atrophy / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To investigate genetics and clinical characteristics of dentatorubral-pallidoluysian atrophy (DRPLA) in Chinese kindreds.</p><p><b>METHODS</b>Fragment analysis with laser-induced fluorescence in capillary electrophoresis was performed for the cytosine-adenine-guanine (CAG) repeats of DRPLA gene in 708 probands of autosomal dominant ataxia pedigrees and 119 sporadic ataxia cases.</p><p><b>RESULTS</b>Expanded CAG repeats of DRPLA gene were detected in probands of three ataxia pedigrees, with the numbers of repeats being 16/58, 16/58 and 14/54, respectively. In addition to ataxia, patients with adult-onset disease also exhibited spasm and neck torsion.</p><p><b>CONCLUSION</b>Only three cases of DRPLA have been identified among 827 cases, which suggested that DRPLA is a relatively rare subtype of SCA in Chinese population. Clinical variation among the patients suggested DRPLA has a wide spectrum of phenotype.</p>