Diagnostic Accuracy of Serum Matrix Metalloproteinase-7 for Biliary Atresia.

The diagnosis of biliary atresia (BA) remains a clinical challenge because affected infants have signs, symptoms, and serum liver biochemistry that are also seen in those with other causes of neonatal cholestasis (non-BA). However, an early diagnosis and prompt surgical treatment are required to improve clinical outcome. Recently, the relative abundance of serum matrix metalloproteinase-7 (MMP-7) was suggested to have discriminatory features for infants with BA. To test the hypothesis that elevated serum concentration of MMP-7 is highly diagnostic for BA, we determined the normal serum concentration of MMP-7 in healthy control infants, and then in 135 consecutive infants being evaluated for cholestasis. The median concentration for MMP-7 was 2.86 ng/mL (interquartile range, IQR: 1.32-5.32) in normal controls, 11.47 ng/mL (IQR: 8.54-24.55) for non-BA, and 121.1 ng/mL (IQR: 85.42-224.4) for BA (P < 0.0001). The area under the curve of MMP-7 for the diagnosis of BA was 0.9900 with a cutoff value of 52.85 ng/mL; the diagnostic sensitivity and specificity were 98.67% and 95.00%, respectively, with a negative predictive value of 98.28%. Conclusion: Serum MMP-7 assay has high sensitivity and specificity to differentiate BA from other neonatal cholestasis, and may be a reliable biomarker for BA.

Synthesis and anti-inflammatory evaluation of novel paclitaxel analogs.

A series of paclitaxel analogs modified at C-3'-N and C-7 positions were synthesized from baccatin III and their structures were confirmed by 1H-NMR, 13C-NMR, HR-MS. Compound 7e exhibited potent ability to decrease TNFα (tumor necrosis factor α) in the LPS-activated RAW264.7 murine macrophage-like cell line. The preliminary data indicated that the anti-inflammatory effects may be related to MD-2 and Toll-like receptor 4 (TLR4), rather than Toll-like receptor 2 (TLR2).

Survival of 48866 cancer patients: results from Nantong area, China.

Objective: This study aimed to provide a realistic observation of survival by major site for 48,866 cancer patients treated at a tertiary cancer hospital in a rural area of China. Methods: Patients with cancer registered between 2007 and 2017 in the Nantong rural area were followed up. The starting date for survival calculation was the date of the first diagnosis of cancer at the Nantong Tumor Hospital, and the closing date was December 31, 2020. Observed survival (OS) was analyzed according to ICD-10 site, sex, age, region, and hospitalization period using the life table method and compared using the Wilcoxon (Gehan) statistic. Results: The overall 5-year OS rate was 40.48% for all 48,866 patients, 30.19% for males, and 51.90% for females. The top five cancer sites, accounting for 60.51% of the total cases, were the esophagus, lung, stomach, liver, and cervix, with 5-year OS rates of 33.72%, 18.64%, 32.10%, 19.04%, and 71.51%, respectively. The highest 5-year OS was observed in the thyroid (87.52%) and the lowest was in the pancreas (6.37%). Survival was significantly higher in younger patients than in older patients, with 5-year OSs of 69.26% and 19.84% in those aged 20-29 and 90-99 years, respectively. Five-year OSs improved significantly from 39.35% in 2007-2011 to 41.26% in 2012-2017. Conclusion: Overall survival improved over the years, although the improvement at some sites was not significant. The observed survival varies from region to region, reflecting differences in the patterns of major sites, disparities in proportions of hospitalization, and demographic characteristics.

[Bioinformatics Analysis of Microarray Data in Myelodysplastic Syndrome Based on Gene Expression Omnibus Database].

OBJECTIVE: To identify the key genes and explore mechanisms in the development of myelodysplastic syndrome (MDS) by bioinformatics analysis. METHODS: Two cohorts profile datasets of MDS were downloaded from Gene Expression Omnibus (GEO) database. Differentially expressed gene (DEG) was screened by GEO2R, functional annotation of DEG was gained from GO database, gene ontology (GO) enrichment analysis was performed via Kyoto Encyclopedia of Genes and Genomes (KEGG) database, and key genes were screened by Matthews correlation coefficient (MCC) based on STRING database. RESULTS: There were 112 DEGs identified, including 85 up-regulated genes and 27 down-regulated genes. GO enrichment analysis showed that biological processes were mainly enriched in immune response, etc, cellular component in cell membrane, etc, and molecular function in protein binding, etc. KEGG signaling pathway analysis showed that main gene enrichment pathways were primary immunodeficiency, hematopoietic cell lineage, B cell receptor signaling pathway, Hippo signaling pathway, and asthma. Three significant modules were screened by Cytoscape software MCODE plug-in, while 10 key node genes (CD19, CD79A, CD79B, EBF1, VPREB1, IRF4, BLNK, RAG1, POU2AF1, IRF8) in protein-protein interaction (PPI) network were screened based on STRING database. CONCLUSION: These screened key genes and signaling pathways are helpful to better understand molecular mechanism of MDS, and provide theoretical basis for clinical targeted therapy.

Inhibition by rno-circRNA-013017 of the apoptosis of motor neurons in anterior horn and descending axonal degeneration in rats after traumatic spinal cord injury.

Introduction: Spinal cord injury (SCI) often causes continuous neurological damage to clinical patients. Circular RNAs (circRNAs) are related to a lot of diseases, including SCI. We previously found five candidate circRNAs which were likely to regulate the secondary pathophysiological changes in rat model after traumatic SCI. Methods: In this study, we first selected and overexpressed target circRNA in rats. We then explored its functional roles using various functional assays in a rat model after SCI. Results: We found that rno-circRNA-013017-the selected target circRNA-reduced neuron apoptosis, preserved the survival and activity of motor neurons, and regulated apoptosis-related proteins at 3 days post-SCI using western blot, immunofluorescence and polymerase chain reaction. Additionally, we found that rno-circRNA-013017 inhibited descending axonal degeneration and preserved motor neurons and descending axons at 6 weeks post-SCI using immunofluorescence, biotin dextran amine diffusion tensor imaging. Finally, the overexpression of rno-circRNA-013017 promoted the locomotor function of rats after SCI using open-field test and gait analysis. Conclusion: Focusing on the functions of rno-circRNA-013017, this study provides new options for future studies exploring therapeutic targets and molecular mechanisms for SCI.

Maternal regulation of biliary disease in neonates via gut microbial metabolites.

Maternal seeding of the microbiome in neonates promotes a long-lasting biological footprint, but how it impacts disease susceptibility in early life remains unknown. We hypothesized that feeding butyrate to pregnant mice influences the newborn's susceptibility to biliary atresia, a severe cholangiopathy of neonates. Here, we show that butyrate administration to mothers renders newborn mice resistant to inflammation and injury of bile ducts and improves survival. The prevention of hepatic immune cell activation and survival trait is linked to fecal signatures of Bacteroidetes and Clostridia and increases glutamate/glutamine and hypoxanthine in stool metabolites of newborn mice. In human neonates with biliary atresia, the fecal microbiome signature of these bacteria is under-represented, with suppression of glutamate/glutamine and increased hypoxanthine pathways. The direct administration of butyrate or glutamine to newborn mice attenuates the disease phenotype, but only glutamine renders bile duct epithelial cells resistant to cytotoxicity by natural killer cells. Thus, maternal intake of butyrate influences the fecal microbial population and metabolites in newborn mice and the phenotypic expression of experimental biliary atresia, with glutamine promoting survival of bile duct epithelial cells.

Nickel(II)-Catalyzed [3 + 2] Cycloaddition of Nitrones and Allenoates to Access N-Vinylindoles and N-Vinylpyrroles.

A variety of N-vinylindoles and N-vinylpyrroles were prepared in moderate to good yields through the nickel(II)-catalyzed [3 + 2] cycloaddition of α,ß-unsaturated nitrones with allenoates under mild reaction conditions. A rational mechanism for the formation of N-vinylindoles was proposed based on the 18O-labeled experiments and key intermediates detected by high-resolution mass spectrometry trace experiments. The present method highlights a nickel(II)-controlled cyclization, atom-economical reaction, broad substrate scope, good functional group tolerance, and high Z-stereoselectivity for the enamine bond.

Deletion of Fam172a accelerates advanced atherosclerosis and induces plaque instability.

BACKGROUND AND AIMS: Vascular smooth muscle cells (VSMCs) play a critical role in atherosclerosis. The family with sequence similarity 172, member A (FAM172A) is a novel protein and its role in atherosclerosis has not been explored so far. Therefore, our aim is to investigate whether FAM172A affects atheroprogression through VSMCs and its possible mechanism. METHODS: Fam172a-/- mice were generated using CRISPR/Cas9 technology. Fam172a-/- and Apoe-/- double knockout (Fam172a-/-/Apoe-/-) mice and their littermates (Fam172a+/+/Apoe-/-) were fed with a Western diet for 18 weeks to induce advanced atherosclerotic lesions. The role and mechanism of Fam172a in phenotypic switching, proliferation and migration of VSMCs were investigated through in vivo and in vitro experiments. RESULTS: Compared with Fam172a+/+/Apoe-/- mice, Fam172a-/-/Apoe-/- mice showed increased atherosclerotic lesion size and plaque instability such as increased necrotic core area and decreased fiber deposition. Additionally, knockout of Fam172a promoted expression of CD68 and KLF4 and decreased expression of α-SMA and SM22α in atherosclerotic lesions. Furthermore, overexpression of Fam172a promoted Movas cells proliferation and migration, increased expression of α-SMA and SM22α and decreased expression of KLF4. Meanwhile, knockdown of Fam172a in Movas cells and deletion of Fam172a in VSMCs from Fam172a-/-/Apoe-/- mice showed opposite phenotypes. Similar phenotypes were also observed in human aortic smooth muscle cells. CONCLUSIONS: Our results provide the first direct evidence that Fam172a has a protective role in advanced atherosclerosis by increasing atherosclerotic plaque stability and inhibiting transition of VSMCs from contractile to synthetic phenotype, which may be through KLF4-dependent pathway.

[Value of endobronchial ultrasound-guided transbronchial needle aspiration in hilar and mediastinal lesions].

OBJECTIVE: To evaluate the diagnostic yield of endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) in cases of undiagnosed intrapulmonary lesions. METHODS: A total of 89 patients with intrathoracic lesions underwent EBUS-TBNA, including 56 pulmonary lesions, 7 lymph node staging in lung cancer patients, 21 unknown hilar and/or mediastinal lymphadenopathies and 5 mediastinal tumors. All samples were evaluated for cytological and pathological examinations. RESULTS: No complication of EBUS-TBNA was observed. Among 89 cases, 76 had positive results, 5 negative and 5 cases excluded as unsatisfied samples. In 56 patients with pulmonary lesions, EBUS-TBNA demonstrated 45 malignant tumors, 5 benign diseases, 3 suspicious cancers, 1 negative and 2 unsatisfied samples. In 7 lung cancer patients staged by EBUS-TBNA, 5 showed metastasis and 2 showed no metastasis. In 21 cases with mediastinal and/or hilar lymphadenopathy, EBUS-TBNA demonstrated 3 malignant tumors, 13 benign diseases, 2 negative and 3 unsatisfied samples. All 5 mediastinal lesions were malignant. Three suspicious cancers were confirmed, 1 by CT-guided percutaneous transthoracic needle biopsy and 2 by clinical follow-ups. In 2 lung cancer patients EBUS-TBNA showed negative, 1 surgical sample showed metastasis and another no metastasis by PET-CT. Three negative cases were diagnosed as benign by clinical follow-ups. The diagnostic sensitivity, specificity, positive predictive value and negative predictive value of EBUS-TBNA were 95%, 100%, 100% and 20% respectively. CONCLUSION: EBUS-TBNA is both effective and safe in making a diagnosis of intrathoracic lesions.

Robot-assisted thoracoscopic plication for diaphragmatic eventration.

BACKGROUND: Though conventional thoracoscopic plication is a favorable option of diaphragmatic eventration (DE), ribs limited the movement of trocars, making it difficult to suturing, knot-tying and time-consuming. The purpose of this study was to evaluate delicate surgical maneuvers and suturing time for the management of DE in robot-assisted thoracoscopic plication (RATP). METHODS: From January 2015 to November 2019, 20 patients (14 males; mean age: 10.5 ±â€¯5.2 months; mean weight: 8.6 ±â€¯4.5 kg) who underwent diaphragmatic plication for DE were reviewed at our institution. There were 13 patients with congenital diaphragmatic eventration and 7 patients with acquired diaphragm eventration after congenital heart surgery. RATP was performed on 9 patients (3 on the left and 6 on the right), and conventional thoracoscopic plication (CTP) was applied to 11 patients (5 on the left and 6 on the right). Demographics, the suturing time and complications were respectively evaluated. RESULTS: There was no difference between 2 groups with respect to gender, age at surgery and weight (p > 0.05). No conversion to thoracotomy was needed. The suturing time in RATP group was shorter than CTP group (27.7 ±â€¯3.4 min vs 48.1 ±â€¯4.2 min, p < 0.001). One patient (9.09%) experienced recurrence in CTP group and none was found in RATP group. CONCLUSIONS: Diaphragmatic plication with robot-assisted thoracoscopy or conventional thoracoscopy in DE has minimally invasive and good effect on children. RATP overcome the intercostal limitations to complete delicate suturing and free knot-tying, and has better ergonomics. LEVEL OF EVIDENCE: Level III.

FAM172A promotes follicular thyroid carcinogenesis and may be a marker of FTC.

Our aims were to uncover the role of FAM172A (Family with sequence similarity 172 member A) in the pathogenesis of follicular thyroid carcinoma (FTC) and to evaluate its value in the differential diagnosis between malignant and benign thyroid follicular lesions. FAM172A expression was evaluated by q-PCR, immunoblotting and immunohistochemistry (IHC). The ability of proliferation, migration and invasion of cells were assessed by Cell Counting Kit-8 assay (CCK8), clone-formation and Transwell assays. Nude mouse tumorigenicity assays were used to investigate the role of FAM172A in the pathogenesis of FTC in vivo. The value of FAM172A in the differential diagnosis for FTC was assessed using 120 formalin-fixed paraffin-embedded (FFPE) tissues after the operation and 81 fine-needle aspiration biopsy (FNAB) samples before the operation. FAM172A was highly expressed in FTC tissues and FTC cell lines. Downregulation of FAM172A inhibited the proliferation, invasion and migration of FTC cells through Erk1/2 and JNK pathways. Subcutaneous tumorigenesis in nude mice showed that knockdown of FAM172A inhibited tumor growth and progression in vivo. The FAM172A IHC scores of 3.5 had 92% sensitivity and 63% specificity to separate FTC from benign/borderline thyroid follicular lesions, and 92% sensitivity and 80% specificity to discriminate FTC from benign thyroid follicular lesions in postoperative FFPE samples. The corresponding values were 75 and 78%, and 75 and 89% in preoperative FNA samples, respectively. FAM172A plays an important role in the pathogenesis of FTC through Erk1/2 and JNK pathways. FAM172A may be a potential marker for the preoperative diagnosis of FTC based on the IHC results of thyroid FNAB samples.

Pathological significance of tRNA-derived small RNAs in neurological disorders.

Non-coding RNAs (ncRNAs) are a type of RNA that is not translated into proteins. Transfer RNAs (tRNAs), a type of ncRNA, are the second most abundant type of RNA in cells. Recent studies have shown that tRNAs can be cleaved into a heterogeneous population of ncRNAs with lengths of 18-40 nucleotides, known as tRNA-derived small RNAs (tsRNAs). There are two main types of tsRNA, based on their length and the number of cleavage sites that they contain: tRNA-derived fragments and tRNA-derived stress-induced RNAs. These RNA species were first considered to be byproducts of tRNA random cleavage. However, mounting evidence has demonstrated their critical functional roles as regulatory factors in the pathophysiological processes of various diseases, including neurological diseases. However, the underlying mechanisms by which tsRNAs affect specific cellular processes are largely unknown. Therefore, this study comprehensively summarizes the following points: (1) The biogenetics of tsRNA, including their discovery, classification, formation, and the roles of key enzymes. (2) The main biological functions of tsRNA, including its miRNA-like roles in gene expression regulation, protein translation regulation, regulation of various cellular activities, immune mediation, and response to stress. (3) The potential mechanisms of pathophysiological changes in neurological diseases that are regulated by tsRNA, including neurodegeneration and neurotrauma. (4) The identification of the functional diversity of tsRNA may provide valuable information regarding the physiological and pathophysiological mechanisms of neurological disorders, thus providing a new reference for the clinical treatment of neurological diseases. Research into tsRNAs in neurological diseases also has the following challenges: potential function and mechanism studies, how to accurately quantify expression, and the exact relationship between tsRNA and miRNA. These challenges require future research efforts.

Transumbilical enterostomy for Hirschsprung's disease with a two-stage laparoscopy-assisted pull-through procedure.

BACKGROUND: A one-stage laparoscopic operation has recently been considered a favorable option for the management of patients with Hirschsprung's disease (HD) due to its superior cosmetic results. One-stage transanal endorectal pull-through for the treatment of rectosigmoid HD has been widely used in newborns without complications. However, enterostomy is required in some HD cases for enterocolitis and dilated colon. Our transumbilical enterostomy (TUE) and two-stage laparoscopy-assisted anorectoplasty were effective and achieved a similar cosmetic effect to one-stage laparoscopy on the abdominal wall in patients with anorectal malformation, but the effect in patients with HD is unclear. AIM: To evaluate the safety, efficacy and cosmetic results of TUE in two-stage laparoscopy-assisted pull-through for HD. METHODS: From June 2013 to June 2018, 53 patients (40 boys, 13 girls; mean age at enterostomy: 5.5 ± 2.2 mo) who underwent enterostomy and two-stage laparoscopy-assisted pull-through for HD with stoma closure were reviewed at our institution. Two enterostomy approaches were used: TUE in 24 patients, and conventional abdominal enterostomy (CAE) in 29 patients. Eleven patients with rectosigmoid HD had severe preoperative enterocolitis or a dilated colon. 26 patients had long-segment HD, and 16 patients had total colonic aganglionosis (TCA). The patients with left-sided HD underwent the two-stage laparoscopic Soave procedure, and the patients with right-sided HD and TCA underwent the laparoscopic Duhamel procedure. Demographics, enterostomy operative time, complications and cosmetic results were respectively evaluated. RESULTS: There were no differences between the groups with respect to gender, age at enterostomy, weight and clinical type (P > 0.05). No conversion to open technique was required. Two patients experienced episodes of stomal mucosal prolapse in the TUE group and 1 patient in the CAE group (8.33% vs 3.45%, P > 0.05). No parastomal hernia was observed in either of the two groups. Wound infection at the stoma was seen in 1 case in the TUE group, and 2 cases in the CAE group (4.17% vs 6.90%, P > 0.05). No obstruction was noted in any of the patients in the TUE group, whereas obstruction was found in 1 patient in the CAE group. Enterocolitis was observed in 3 and 5 patients in the TUE and CAE group, respectively (12.50% vs 17.24%, P > 0.05). There was no significant difference between the TUE group and CAE group in terms of the incidence of soiling and constipation (P > 0.05). The cosmetic result using the scar score in the TUE group was better than that in the CAE group (6.83 ± 0.96 vs 13.32 ± 1.57, P < 0.05). CONCLUSION: TUE is a safe and feasible method for the treatment of HD, and the staged enterostomy and two-stage laparoscopy-assisted pull-through achieved a similar cosmetic effect to the one-stage laparoscopic procedure.

Dairy Consumption and Associations with Nutritional Status of Chinese Children and Adolescents.

OBJECTIVE: This study aimed to describe frequency and quantity of total dairy consumption of Chinese children and adolescents and explore the associations between dairy consumption and nutrition status, including stunting, wasting, overweight, and obesity. METHODS: Participants included 28,250 children and adolescents aged 6-17 years old. A food frequency questionnaire (FFQ) including 100 kinds of food was used to collect information about frequency and quantity of dairy consumption. Determination of stunting was with a height cutoff value for age and gender, and determination for wasting, overweight, and obesity was with BMI for age and gender. RESULTS: Of the total sample, 36.1% of children aged 6-17 reported consuming dairy food more than once per day (⪖ 1/day). The average total dairy intake of all the participants was 126.7 g/day. For boys, dairy consumption had an inverse correlation with stunting and wasting after controlling for confounders. For girls, dairy consumption was negatively associated with stunting and obesity after controlling for confounders as above. CONCLUSION: Dairy consumption in Chinese children and adolescents was relatively lower than that in developed countries, and was negatively associated with stunting and wasting for boys and with stunting and obesity for girls.

[Effects of melatonin on nerve cell apoptosis and expression of Bcl-2 & cytochrome C genes in rat cerebrum with deltamethrin induction].

OBJECTIVE: To study the effects of melatonin (MT) on nerve cell apoptosis and the expression of bcl-2 and cytochrome C genes in rat cerebrum with deltamethrin induction. METHODS: 35 male Wistar rats were randomly divided into five groups (eight rats per group): olive oil control, deltamethrin-treated (12.5 mg/kg), deltamethrin plus melatonin (25.0 mg/kg, 50 mg/kg and 100 mg/kg respectively) group. Animal models were established by intraperitoneal injection deltamethrin in rats. Nerve cell apoptosis and the protein expression of bcl-2 and cytochrome C genes were detected by flow cytometry with PI staining and immunohistochemistry respectively. RESULTS: Compared with DM group (20.73 +/- 3.34), the positive expression gradation of the bcl-2 protein in nerve cell was increased significantly in MT groups (DM + MT(25) was 45.26 +/- 3.84, DM + MT(50) 39.4 +/- 4.04 and DM + MT(100) 34.4 +/- 4.52) (P < 0.05) but significantly lower than the control group (59.33 +/- 4.03). Compared with DM group (34.86 +/- 4.15), the cytochrome C protein in nerve cell was decreased significantly in MT groups (20.53 +/- 3.17, 28.73 +/- 2.61 and 28.66 +/- 4.82 respectively) (P < 0.05). Compared with DM group (23.06 +/- 3.63), the apoptotic rate in nerve cell was decreased significantly in MT groups [(15.0 +/- 1.77)%, (14.88 +/- 1.84)% and (11.75 +/- 1.93)% respectively] (P < 0.05). CONCLUSION: MT can protect nerve cell against deltamethrin induced brain injury by inhibiting nerve cell apoptosis, downregulate the protein expression of cytochrome C gene and upregulate the protein expression of bcl-2 gene.

[Protective effect of melatonin on oxidative damage by deltamethrin in rat brain].

OBJECTIVE: To study the potential protective effect of melatonin on the oxidative damage induced by deltamethrin in cerebral cortex, hippocampus and cerebellum of rats. METHODS: 35 male wistar rats were randomly divided into five groups(seven rats per group): olive oil control, deltamethrin-treated (12.5 mg/kg), melatonin(25.0 mg/kg) and deltamethrin plus melatonin (25.0 mg/kg , 2.5 mg/kg respectively) group. Levels of malondialdehyde (MDA) and the activity of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px), glutathione (GSH) in cerebral cortex, hippocampus and cerebellum were determined after 5 days of DM treatments. RESULTS: MDA content in cerebral cortex, hippocampus and cerebellum tissue of the DM-treated rats were significantly higher than those in control group, and compared with DM-treated group, MDA content in those tissue of MT + DM-treated group have significantly decreased after 5 days of DM exposure (P < 0.05). Activities of GSH-Px in DM-treated group were significantly lower than those in control group, and those in the MT + DM group were significantly higher than DM group(P < 0.05). CONCLUSION: DM can induce the oxidative damage in rat brain and melatonin has protective effects on deltamethrin-induced oxidative damage in hippocampus, cerebral cortex and cerebellum of rats.

Postoperative Pain Self-Management Behavior in Patients Who Underwent Total Knee or Hip Arthroplasty.

The self-management of acute postoperative pain is not well researched. This cross-sectional study investigates postoperative pain and pain self-management behavior. We recruited 127 patients who underwent total knee or total hip arthroplasty in an acute care hospital. We measured postoperative pain intensity and pain self-management behavior for three postoperative days. The results showed that the participants experienced mild and moderate pain intensity and perceived moderate to severe pain interference, which influenced their mood, sleep patterns, ability to walk, and performance of general activities and rehabilitation exercises. Female participants reported significantly higher pain intensity and lower pain self-management behavior; highly educated participants reported significantly lower pain intensity and higher self-management behavior. Pain intensity scores had a significant negative correlation with the total self-management behavior score (r = -0.719, P < .01). Health care professionals must consider patients' demographic characteristics when providing education and support regarding pain self-management for postoperative pain control.

Apoptotic Mechanism of Human Leukemia K562/A02 Cells Induced by Magnetic Ferroferric Oxide Nanoparticles Loaded with Wogonin.

BACKGROUND: Traditional Chinese medicine wogonin plays an important role in the treatment of leukemia. Recently, the application of drug-coated magnetic nanoparticles (MNPs) to increase water solubility of the drug and to enhance its chemotherapeutic efficiency has attracted much attention. Drugs coated with MNPs are becoming a promising way for better leukemia treatment. This study aimed to assess the possible molecular mechanisms of wogonin-coated MNP-Fe3O4 (Wog-MNPs-Fe3O4) as an antileukemia agent. METHODS: After incubated for 48 h, the antiproliferative effects of MNPs, wogonin, or Wog-MNPs-Fe3O4on K562/A02 cells were determined by methyl thiazolyl tetrazolium (MTT) assay. The apoptotic rates of K562/A02 cells treated with either wogonin or Wog-MNPs-Fe3O4were determined by flow cytometer (FCM) assay. The cell cycle arrest in K562/A02 cells was determined by FCM assay. The elementary molecular mechanisms of these phenomena were explored by Western blot and reverse transcriptase polymerase chain reaction (RT-PCR). RESULTS: With cell viabilities ranging from 98.76% to 101.43%, MNP-Fe3O4was nontoxic to the cell line. Meanwhile, the wogonin and Wog-MNPs-Fe3O4had little effects on normal human embryonic lung fibroblast cells. The cell viabilities of the Wog-MNPs-Fe3O4group (28.64-68.36%) were significantly lower than those of the wogonin group (35.53-97.28%) in a dose-dependent manner in 48 h (P < 0.001). The apoptotic rate of K562/A02 cells was significantly improved in 50 µmol/L Wog-MNPs-Fe3O4group (34.28%) compared with that in 50 µmol/L wogonin group (23.46%; P< 0.001). Compared with those of the 25 and 50 µmol/L wogonin groups, the ratios of G0/G1-phase K562/A02 cells were significantly higher in the 25 and 50 µmol/L Wog-MNPs-Fe3O4groups (all P< 0.001). The mRNA and protein expression levels of the p21 and p27 in the K562/A02 cells were also significantly higher in the Wog-MNPs-Fe3O4group compared with those of the wogonin group (all P< 0.001). CONCLUSIONS: This study demonstrated that MNPs were the effective drug delivery vehicles to deliver wogonin to the leukemia cells. Through increasing cells arrested at G0/G1-phase and inducing apoptosis of K562/A02 cells, MNPs could enhance the therapeutic effects of wogonin on leukemia cells. These findings indicated that MNPs loaded with wogonin could provide a promising way for better leukemia treatment.

Syntheses and biological evaluation of C-3'-N-acyl modified taxane analogues from 1-deoxybaccatin-VI.

A series of side-chain modified taxane analogues were synthesized and their in vitro anticancer activities against four human cancer cell lines: MDA-MB-231 (human breast cancer), PC-3 (human prostatic cancer), HepG2 and H460 (human hepatoma) were studied. The three hydroxyl groups at C-7, C-9 and C-10 enable the behavior of these compounds to be evidently distinct from other similar compounds. The strong cytotoxicity in the four cell lines showed by the newly synthesized taxane analogues 13a and 13d indicated them as potential lead compounds for anticancer drug design.