A case of gaucher disease with a rare complication of gaucheroma and protein-losing enteropathy.

This case report describes a patient initially diagnosed with Gaucher disease (GD) with type I with homozygous mutation c.1448T > C p. (Leu483Pro) at age of 2, presenting with hepatosplenomegaly and cytopenia. Imiglucerase replacement therapy was initiated. At age 17, bilateral hearing loss developed, with subsequent Cranial MRI revealing thalamic damage, leading to a reclassification as type 3 GD. By age of 20, the patient presented with a range of symptoms, including abdominal pain, diarrhea, hypoproteinemia, multiple lymphadenopathy, edema, and Gaucher cell infiltration in the lymph nodes. Comprehensive diagnosis identifies Gaucher tumor and protein-losing enteropathy. Imiglucerase therapy at 90-120 U/kg every 2 weeks significantly improved clinical symptoms, emphasizing the importance of tailored interventions for managing GD manifestations.

Gigaxonin Suppresses Epithelial-to-Mesenchymal Transition of Human Cancer Through Downregulation of Snail.

Gigaxonin is an E3 ubiquitin ligase that plays a role in cytoskeletal stability. Its role in cancer is not yet clearly understood. Our previous studies of head and neck cancer had identified gigaxonin interacting with p16 for NFκB ubiquitination. To explore its role in cancer cell growth suppression, we analyzed normal and tumor DNA from cervical and head and neck cancers. There was a higher frequency of exon 8 SNP (c.1293 C>T, rs2608555) in the tumor (46% vs. 25% normal, P = 0.011) pointing to a relationship to cancer. Comparison of primary tumor with recurrence and metastasis did not reveal a statistical significance. Two cervical cancer cell lines, ME180 and HT3 harboring exon 8 SNP and showing T allele expression correlated with higher gigaxonin expression, reduced in vitro cell growth and enhanced cisplatin sensitivity in comparison with C allele expressing cancer cell lines. Loss of gigaxonin expression in ME180 cells through CRISPR-Cas9 or siRNA led to aggressive cancer cell growth including increased migration and Matrigel invasion. The in vitro cell growth phenotypes were reversed with re-expression of gigaxonin. Suppression of cell growth correlated with reduced Snail and increased e-cadherin expression. Mouse tail vein injection studies showed increased lung metastasis of cells with low gigaxonin expression and reduced metastasis with reexpression of gigaxonin. We have found an association between C allele expression and RNA instability and absence of multimeric protein formation. From our results, we conclude that gigaxonin expression is associated with suppression of epithelial-mesenchymal transition through inhibition of Snail. SIGNIFICANCE: Our results suggest that GAN gene exon 8 SNP T allele expression correlates with higher gigaxonin expression and suppression of aggressive cancer cell growth. There is downregulation of Snail and upregulation of e-cadherin through NFκB ubiquitination. We hypothesize that exon 8 T allele and gigaxonin expression could serve as diagnostic markers of suppression of aggressive growth of head and neck cancer.

An extranodal Richter's syndrome presenting with cardiac diffuse large B-cell lymphoma: a case report.

BACKGROUND: Richter's syndrome (RS) defines the transformation of chronic lymphocytic leukemia into high-grade lymphoma, which usually involves lymph nodes and bone marrow. Extranodal involvement of the heart is an extremely rare condition. Patients with heart involvement tended to have a low response to chemotherapy and relative poor prognosis. The transformation process of RS is often insidious and nonspecific making it challenging to diagnose. CASE PRESENTATION: A 64-year-old woman wih a history of chronic lymphocytic leukemia (CLL) presented with intermittent chest pain and was diagnosed with non-ST-elevation myocardial infarction (NSTEMI). However, the contrast enhanced echocardiography revealed a large irregular mass, measuring about 75.4 mm × 37.5 mm, located on the lateral and posterior wall of the right ventricle. Biopsy of the cardiac mass and the results revealed diffuse large B-cell lymphoma. CONCLUSIONS: We present a case of a 64-year-old woman with aggressive diffuse large B-cell lymphoma involving the heart. This case could provide some insights in the diagnosis of cardiac lymphoma.

Siberian Wildrye (Elymus sibiricus L.) Abscisic Acid-Insensitive 5 Gene Is Involved in Abscisic Acid-Dependent Salt Response.

Siberian wildrye (Elymus sibiricus L.) is a salt-tolerant, high-quality forage grass that plays an important role in forage production and ecological restoration. Abscisic acid (ABA)-insensitive 5 (ABI5) is essential for the normal functioning of the ABA signal pathway. However, the role of ABI5 from Siberian wildrye under salt stress remains unclear. Here, we evaluated the role of Elymus sibiricus L. abscisic acid-insensitive 5 (EsABI5) in the ABA-dependent regulation of the response of Siberian wildrye to salt stress. The open reading frame length of EsABI5 isolated from Siberian wildrye was 1170 bp, and it encoded a 389 amino acid protein, which was localized to the nucleus, with obvious coiled coil areas. EsABI5 had high homology, with ABI5 proteins from Hordeum vulgare, Triticum monococcum, Triticum aestivum, and Aegilops tauschii. The conserved domains of EsABI5 belonged to the basic leucine zipper domain superfamily. EsABI5 had 10 functional interaction proteins with credibility greater than 0.7. EsABI5 expression was upregulated in roots and leaves under NaCl stress and was upregulated in leaves and downregulated in roots under ABA treatment. Notably, tobacco plants overexpressing the EsABI5 were more sensitive to salt stress, as confirmed by the determining of related physiological indicators. EsABI5 expression affected the ABA and mitogen-activated protein kinase pathways. Therefore, EsABI5 is involved in antisalt responses in these pathways and plays a negative regulatory role during salt stress.

Ku86 alleviates human umbilical vein endothelial cellular apoptosis and senescence induced by a low dose of ionizing radiation.

OBJECTIVE: The aim of this study was to observe the effect of Ku86 on cellular senescence and apoptosis induced by various doses of ionizing radiation in human umbilical vein endothelial cells (HUVECs). METHODS: Senescence-associated ß-galactosidase activity was detected to evaluate cell senescence. Apoptosis was determined by flow cytometry and a caspase enzyme determination kit. p16Ink4a, Sirt1, superoxide dismutase 2 (SOD2), xanthine oxidase (XOD), and Bcl-2 protein expression levels were measured by western blotting. RESULTS: Low doses of ionizing radiation induced cellular senescence and apoptosis in a dose-dependent manner. The Ku86 protein was negatively correlated with ionization intensity. After transfection of Ku86 with a vector (pcDNA 3.1), or interference with siRNA (si-Ku86), apoptosis/senescence and related protein expression were observed. Western blot results revealed that this induction of senescence was associated with activated Sirt1 and SOD2, and downregulation of p16Ink4a and XOD in 0.2 Gy ionizing radiation. The expression levels of apoptosis-associated proteins, such as Bcl-2, cleaved caspase-3, caspase-8, and caspase-9, were significantly altered in both the presence and absence of Ku86 with ionizing radiation (0.2 Gy). CONCLUSIONS: Our study revealed that Ku86 overexpression inhibits HUVEC apoptosis and senescence induced by low doses of ionizing radiation.

Metabolic characterization of isocitrate dehydrogenase (IDH) mutant and IDH wildtype gliomaspheres uncovers cell type-specific vulnerabilities.

BACKGROUND: There is considerable interest in defining the metabolic abnormalities of IDH mutant tumors to exploit for therapy. While most studies have attempted to discern function by using cell lines transduced with exogenous IDH mutant enzyme, in this study, we perform unbiased metabolomics to discover metabolic differences between a cohort of patient-derived IDH1 mutant and IDH wildtype gliomaspheres. METHODS: Using both our own microarray and the TCGA datasets, we performed KEGG analysis to define pathways differentially enriched in IDH1 mutant and IDH wildtype cells and tumors. Liquid chromatography coupled to mass spectrometry analysis with labeled glucose and deoxycytidine tracers was used to determine differences in overall cellular metabolism and nucleotide synthesis. Radiation-induced DNA damage and repair capacity was assessed using a comet assay. Differences between endogenous IDH1 mutant metabolism and that of IDH wildtype cells transduced with the IDH1 (R132H) mutation were also investigated. RESULTS: Our KEGG analysis revealed that IDH wildtype cells were enriched for pathways involved in de novo nucleotide synthesis, while IDH1 mutant cells were enriched for pathways involved in DNA repair. LC-MS analysis with fully labeled 13C-glucose revealed distinct labeling patterns between IDH1 mutant and wildtype cells. Additional LC-MS tracing experiments confirmed increased de novo nucleotide synthesis in IDH wildtype cells relative to IDH1 mutant cells. Endogenous IDH1 mutant cultures incurred less DNA damage than IDH wildtype cultures and sustained better overall growth following X-ray radiation. Overexpression of mutant IDH1 in a wildtype line did not reproduce the range of metabolic differences observed in lines expressing endogenous mutations, but resulted in depletion of glutamine and TCA cycle intermediates, an increase in DNA damage following radiation, and a rise in intracellular ROS. CONCLUSIONS: These results demonstrate that IDH1 mutant and IDH wildtype cells are easily distinguishable metabolically by analyzing expression profiles and glucose consumption. Our results also highlight important differences in nucleotide synthesis utilization and DNA repair capacity that could be exploited for therapy. Altogether, this study demonstrates that IDH1 mutant gliomas are a distinct subclass of glioma with a less malignant, but also therapy-resistant, metabolic profile that will likely require distinct modes of therapy.

Asiatic acid enhances survival of human AC16 cardiomyocytes under hypoxia by upregulating miR-1290.

Asiatic acid (AA) could attenuate ischemia/reperfusion induced myocardial apoptosis through upregulating the Akt/GSK-3ß/HIF-1α pathway. HIF-3α is a negative regulator of HIF-1α, whose mRNA is a potential target of miR-1290. AA could upregulate miR-1290 in non-small-cell lung cancer A549 cells. This work aimed to investigate whether AA could inhibit hypoxia induced cardiomyocyte apoptosis through regulating the miR-1290/HIF3A/HIF-1α axis. The AC16 human myocardial cell line cultured under normoxic or hypoxic conditions was treated with various doses of AA for 24 h. Afterwards cell viability, apoptosis and the expression of miR-1290, HIF3A, and HIF1A were evaluated. Cells transfected with miR-1290 mimic or inhibitor were used to determine the role of miR-1290 in the anti-apoptosis effect of AA and the expression of HIF3A and HIF1A. Dual luciferase assay was performed to confirm miR-1290 targeting of HIF3A. HIF3A overexpression was achieved by transfection of HIF3A1 overexpressing lentivirus, and its effect on miR-1290 and AA-regulated survival of cardiomyocytes was evaluated. AA treatment protected cardiomyocytes from hypoxia-induced apoptosis and upregulated miR-1290 and HIF1A, but downregulated HIF3A under hypoxia. The protective effect of AA was abolished by miR-1290 knockdown, whereas enhanced by miR-1290 overexpression. In addition, miR-1290 knockdown increased HIF1A expression, but reduced HIF3A expression in cardiomyocytes. Dual luciferase assay confirmed miR-1290 direct targeting the 3' UTR of HIF3A. HIF3A overexpression counteracted the anti-apoptosis effect of AA or miR-1290. In conclusion, AA can protect cardiomyocytes against hypoxia-induced apoptosis through regulating the miR-1290/HIF3A/HIF-1α axis, and miR-1290 may be a potential target in the prevention of myocardial ischemia-reperfusion injury. © 2017 IUBMB Life, 69(9):660-667, 2017.

Umbilical Cord MSCs Reverse D-Galactose-Induced Hepatic Mitochondrial Dysfunction via Activation of Nrf2/HO-1 Pathway.

Mitochondria are the central hubs for cellular bioenergetics and are crucial to cell survival. It is well accepted that compromised mitochondrial function is linked with hepatocytes injury and contribute to progression of liver diseases. Despite the therapeutic potential of mesenchymal stem cells (MSCs) transplantation on hepatic disorders have been extensively investigated, the effects of MSCs on mitochondrial function in liver injury models remain unknown. Here we investigated the effects of treatment with umbilical cord (UC) MSC in a rat model of D-galactose (D-Gal) induced liver injury, characterized by organ damage, oxidative stress and mitochondrial dysfunction. Our results showed that UC-MSCs treatment significantly alleviated histological lesion and attenuated the elevation of liver biochemical markers, demonstrating its protective effects on D-Gal induced hepatic disorders. Mitochondria isolated from the liver of D-Gal models exhibited decreased antioxidant capacity as well as compromised bioenergetics functions, as shown by a loss of mitochondrial membrane potential, elevation of reactive oxygen species (ROS) production, reduction of mitochondrial respiration complexes and ATP decrement. Treatment of rats with UC-MSCs remarkably blunted these changes and rescued mitochondrial efficiency. Mechanistically, we found that the protective potential of UC-MSCs administration was mediated by nuclear factor-E2-related factor 2/heme oxygenase-1 (Nrf2/HO-1) pathway, but not FOXO3a pathway. In conclusion, the attenuating effects of UC-MSCs on hepatic damage partially rely on normalizing mitochondrial function and preventing a state of energetic deficit via activation of Nrf2/HO-1 pathway.

The effect of miR-146a on STAT1 expression and apoptosis in acute lymphoblastic leukemia Jurkat cells.

The effect of miR-146a-dependent regulation of STAT1 on apoptosis in acute lymphoblastic leukemia (ALL) Jurkat cells was investigated. The miR-146a mimic and miR-146a inhibitor vectors were constructed in vitro, and experimental grouping was as follows: Control group (untreated Jurkat cells), empty vector group (Jurkat cells transfected with empty vector), agonist group (Jurkat cells transfected with miR-146a mimic) and the inhibitor group (Jurkat cells transfected with miR-146a inhibitor). Western blot analysis was used to observe the expression, respectively, of STAT1, p-STAT1 and Bcl-xL, and flow cytometry was used to test apoptosis in Jurkat cells. STAT1 and p-STAT1 expression in the agonist group was higher than that in the control and empty vector groups, but lower in the inhibitor group, and differences were statistically significant (P<0.05). The rate of apoptosis in the agonist group was significantly higher than that of the control group and blank vector group, and it was significantly lower in the inhibitor group (P<0.05). As a tumor suppressor, miR-146a can regulate expression of apoptosis-promoting factor STAT1, and anti-apoptosis factor Bcl-xL, and is able to promote apoptosis of ALL Jurkat cells.

RNA-binding protein IGF2BP3 targeting of oncogenic transcripts promotes hematopoietic progenitor proliferation.

Posttranscriptional control of gene expression is important for defining both normal and pathological cellular phenotypes. In vitro, RNA-binding proteins (RBPs) have recently been shown to play important roles in posttranscriptional regulation; however, the contribution of RBPs to cell specification is not well understood. Here, we determined that the RBP insulin-like growth factor 2 mRNA-binding protein 3 (IGF2BP3) is specifically overexpressed in mixed lineage leukemia-rearranged (MLL-rearranged) B-acute lymphoblastic leukemia (B-ALL), which constitutes a subtype of this malignancy associated with poor prognosis and high risk of relapse. IGF2BP3 was required for the survival of B-ALL cell lines, as knockdown led to decreased proliferation and increased apoptosis. Enforced expression of IGF2BP3 provided murine BM cells with a strong survival advantage, led to proliferation of hematopoietic stem and progenitor cells, and skewed hematopoietic development to the B cell/myeloid lineage. Cross-link immunoprecipitation and high throughput sequencing uncovered the IGF2BP3-regulated transcriptome, which includes oncogenes MYC and CDK6 as direct targets. IGF2BP3 regulated transcripts via targeting elements within 3' untranslated regions (3'UTR), and enforced IGF2BP3 expression in mice resulted in enhanced expression of Myc and Cdk6 in BM. Together, our data suggest that IGF2BP3-mediated targeting of oncogenic transcripts may represent a critical pathogenetic mechanism in MLL-rearranged B-ALL and support IGF2BP3 and its cognate RNA-binding partners as potential therapeutic targets in this disease.

[Prostatic arterial embolization for benign prostatic hyperplasia in high-risk aged males].

OBJECTIVE: To explore the efficacy and safety of prostatic arterial embolization (PAE) in the treatment of benign prostatic hyperplasia ( BPH) in high-risk aged males. METHODS: We retrospectively analyzed the clinical data about 21 high-risk BPH patients aged 77-91 (mean 80) years treated by PAE. RESULTS: PAE was successfully performed in all the 21 patients, with the operation time of 90-120 min. At 2 weeks, 3 months, 6 months, and 12 months after surgery, the International Prostate Symptom Scores (IPSS) were 18.3 ± 3.1, 9.8 ± 2.7, 9.4 ± 2.5, and 10.1 ± 2.2, the quality of life scores ( QOL) were 4.6 ± 1.4, 4.3 ± 1.2, 4.6 ± 1.1, and 4.9 ± 0.6, the maximum urinary flow rates ( Qmax) were (12.5 ± 2.5), (15.8 ± 2.4), (16.6 ± 2.2), and (16.3 ± 1.8) ml/s, and the postvoid residual urine volumes (PVR) were (35.0 ± 3.4), (13.0 ± 3.3), (10.0 ± 3.0), and (8.0 ± 2.5) ml, respectively, markedly improved as compared with the baseline (IPSS: 24.5 ± 3.7, QOL: 5.7 ± 1.6, Qmax: [8.3 ± 2.1] ml/s, and PVR: [98.0 ± 11.0] ml), with statistically significant differences in IPSS, QOL, Qmax, and PVR (all P < 0.05). The maximal velocity of blood flow in the prostate was obviously decreased and the prostate volumes were (74.4 ± 4.8), (42.5 ± 4.4), (38.3 ± 4.0), and (36.7 ± 3.5) cm3 at 2 weeks, 3 months, 6 months, and 12 months, respectively, also significantly reduced in comparison with (84.3 ± 5.4) cm3 preoperatively (all P < 0.05). CONCLUSION: PAE is a safe and effective option for the treatment of BPH in high-risk aged males.

LncRNA Expression Discriminates Karyotype and Predicts Survival in B-Lymphoblastic Leukemia.

UNLABELLED: Long noncoding RNAs (lncRNA) have been found to play a role in gene regulation with dysregulated expression in various cancers. The precise role that lncRNA expression plays in the pathogenesis of B-acute lymphoblastic leukemia (B-ALL) is unknown. Therefore, unbiased microarray profiling was performed on human B-ALL specimens, and it was determined that lncRNA expression correlates with cytogenetic abnormalities, which was confirmed by qRT-PCR in a large set of B-ALL cases. Importantly, high expression of BALR-2 correlated with poor overall survival and diminished response to prednisone treatment. In line with a function for this lncRNA in regulating cell survival, BALR-2 knockdown led to reduced proliferation, increased apoptosis, and increased sensitivity to prednisolone treatment. Conversely, overexpression of BALR-2 led to increased cell growth and resistance to prednisone treatment. Interestingly, BALR-2 expression was repressed by prednisolone treatment and its knockdown led to upregulation of the glucocorticoid response pathway in both human and mouse B cells. Together, these findings indicate that BALR-2 plays a functional role in the pathogenesis and/or clinical responsiveness of B-ALL, and that altering the levels of particular lncRNAs may provide a future direction for therapeutic development. IMPLICATIONS: lncRNA expression has the potential to segregate the common subtypes of B-ALL, predict the cytogenetic subtype, and indicate prognosis.

Treatment of acute and closed Achilles tendon ruptures by minimally invasive tenocutaneous suturing.

Achilles tendon rupture is a common injury, and its complications can impair function. Numerous operations have been described for reconstructing the ruptured tendon, but these methods can compromise the microcirculation in the tendon and can seriously damage healing of the tendon. Suturing with a minimally invasive tenocutaneous technique soon after the rupture and systematic functional exercise can greatly reduce the possibility of complications. From June 1996 to February 2007, we treated 20 patients (14 males), who ranged in age from 21 to 66 years old, with this method. After follow-up period of 1 to 7 years, the mean American Orthopedic Foot and Ankle Society Ankle Hindfoot score was 95 (range 90 to 98), and the maximum length of postoperative scarring was 3 cm. One patient again ruptured his Achilles tendon 1 year after surgery in an accident; however, after 10 months, the repaired tendon was still intact. In another patient, the nervus suralis was damaged during surgery by piercing the tension suture at the near end, causing postoperative numbness and swelling. The tension suture was quickly removed, and the patient recovered well with conservative treatment. No large irregular scars, such as those sustained during immobilization, were present over the Achilles tendon. Minimally invasive percutaneous suturing can restore the original length and continuity of the Achilles tendon, is minimally invasive, and results in fewer postoperative complications than other methods.

Treatment of acute and closed Achilles tendon ruptures by minimally invasive tenocutaneous suturing.

BACKGROUND: Achilles tendon rupture is a common injury, and its complications can impair function. Numerous operations have been described for reconstructing the ruptured tendon, but these methods can compromise microcirculation in the tendon and can seriously impair its healing. Suturing with a minimally invasive tenocutaneous technique soon after the rupture and systematic functional exercise can greatly reduce the possibility of complications. METHODS: Between June 1996 and February 2009, we treated 88 patients (54 males; age range, 21-66 years) with this method. RESULTS: After follow-up ranging from 1-7 years, the mean American Orthopedic Foot and Ankle Society ankle-hind foot score was 95 (range, 90-98), and the maximum length of postoperative scarring was 3 cm. One patient re-ruptured his Achilles tendon one year after surgery in an accident, but after 10 months, the repaired tendon was still intact. In another patient, the nervus suralis was damaged during surgery by piercing the tension suture at the near end, causing postoperative numbness and swelling. The tension suture was quickly removed, and the patient recovered well with conservative treatment. No large irregular scars, such as those sustained during immobilization, were present over the Achilles tendon. CONCLUSION: Minimally invasive percutaneous suturing can restore the original length and continuity of the Achilles tendon, is minimally invasive, and has fewer postoperative complications than other methods.

Difference in intraosseous blood vessel volume and number in osteoporotic model mice induced by spinal cord injury and sciatic nerve resection.

In the present study, we examined intraosseous blood vessel parameters of the tibial metaphysis in mice using microcomputed tomography (µCT) to investigate the relationship between post-nerve-injury osteoporosis and local intraosseous blood vessel volume and number. Mice were randomly divided into groups receiving spinal cord injury (SCI), sciatic nerve resection group (NX), or intact controls (30 mice/group). Four weeks after surgery, mice were perfused with silicone and the distribution of intraosseous blood vessels analyzed by µCT. The bone density, µCT microstructure, biomechanical properties, and the immunohistochemical and biochemical indicators of angiogenesis were also measured. The SCI group showed significantly reduced tibial metaphysis bone density, µCT bone microstructure, tibial biomechanical properties, indicators of angiogenesis, and intraosseous blood vessel parameters compared to the NX group. Furthermore, the spinal cord-injured mice exhibited significantly decreased intraosseous blood vessel volume and number during the development of osteoporosis. In conclusion, these data suggest that decreased intraosseous blood vessel volume and number may play an important role in the development of post-nerve-injury osteoporosis.

[Analysis of long-time construct failure of spinal surgery in patients with Parkinson's disease].

OBJECTIVE: To assess the rate of complications of spine surgery and the therapeutic efficacy in the patients with Parkinson's disease (PD) and characterize the special needs of this unique population. METHODS: The data of 25 PD patients undergoing the spinal surgery from January 1998 to December 2006 were analyzed. The patients not followed on a regular basis by their spine surgeons were invited for a follow-up review. The points of analysis were complications, revisions and reasons of surgery failure. RESULTS: The mean follow-up period was 56.3 months. Of 25 patients, 20 (80%) required additional surgery for a total of 25 reoperations. Three patients in need of additional surgery underwent another operation at a remote spinal segment. And 17 patients had the reoperations because of segmental instability at the operated or adjacent levels. CONCLUSION: The PD patients undergoing spine surgery have a high reoperation rate associated with technical complications. They should be appropriately counseled regarding an increased risk of operative complications. A closely follow-up is essential.

Mass spectrometry (LC-MS/MS) site-mapping of N-glycosylated membrane proteins for breast cancer biomarkers.

Cancer cell membrane proteins are released into the plasma/serum by exterior protein cleavage, membrane sloughing, cellular secretion or cell lysis, and represent promising candidates for interrogation. Because many known disease biomarkers are both glycoproteins and membrane bound, we chose the hydrazide method to specifically target, enrich, and identify glycosylated proteins from breast cancer cell membrane fractions using the LTQ Orbitrap mass spectrometer. Our initial goal was to select membrane proteins from breast cancer cell lines and then to use the hydrazide method to identify the N-linked proteome as a prelude to evaluation of plasma/serum proteins from cancer patients. A combination of steps facilitated identification of the glycopeptides and also defined the glycosylation sites. In MCF-7, MDA-MB-453 and MDA-MB-468 cell membrane fractions, use of the hydrazide method facilitated an initial enrichment and site mapping of 27 N-linked glycosylation sites in 25 different proteins. However, only three N-linked glycosylated proteins, galectin-3 binding protein, lysosome associated membrane glycoprotein 1, and oxygen regulated protein, were identified in all three breast cancer cell lines. In addition, MCF-7 cells shared an additional 3 proteins with MDA-MB-453. Interestingly, the hydrazide method isolated a number of other N-linked glycoproteins also known to be involved in breast cancer, including epidermal growth factor receptor (EGFR), CD44, and the breast cancer 1, and early onset isoform 1 (BRCA1) biomarker. Analyzing the N-glycoproteins from membranes of breast cancer cell lines highlights the usefulness of the procedure for generating a practical set of potential biomarkers.

Inhibitory effect of aloe-emodin on metastasis potential in HO-8910PM cell line.

Aloe-emodin (AE) has been demonstrated to have antitumor activity in several tumor cells. However, no information is available on the effect of AE on metastasis in human carcinoma cells. This study was designed to investigate the inhibitory effect of AE on the metastasis potential of HO-8910PM cell line in vitro, and the role of AE in focal adhesion kinase (FAK) expression. Transwell chamber assay was performed to determine the effect of AE on the invasion and migration capacities of the cells. The effect of AE on the adhesion potential of HO-8910PM cells was determined by cell-Matrigel adhesion assay. We found that AE significantly inhibited invasion, migration, and adhesion capacities of HO-8910PM cells, and, furthermore, reduced the protein and mRNA expression of FAK. These findings suggest that the possible mechanistic explanation for the inhibitory effect of AE on metastasis potential in vitro is involved in FAK expression.

Effects of KGF on alveolar epithelial cell transdifferentiation are mediated by JNK signaling.

Rat alveolar epithelial cells (AEC) in primary culture transdifferentiate from a type II (AT2) toward a type I (AT1) cell-like phenotype, a process that can be both prevented and reversed by keratinocyte growth factor (KGF). Microarray analysis revealed that these effects of KGF are associated with up-regulation of key molecules in the mitogen-activated protein kinase (MAPK) pathway. To further explore the role of three key MAPK (i.e., extracellular signal-related kinase [ERK] 1/2, c-Jun N-terminal kinase [JNK] and p38) in mediating effects of KGF on AEC phenotype, primary rat AEC cultivated in minimal defined serum-free medium (MDSF) were treated with KGF (10 ng/ml) from Day 4 for intervals up to 48 hours. Exposure to KGF activated all three MAPK, JNK, ERK1/2, and p38. Inhibition of JNK, but not of ERK1/2 or p38, abrogated the ability of KGF to maintain the AT2 cell phenotype, as evidenced by loss of expression of lamellar membrane protein (p180) and increased reactivity with the AT1 cell-specific monoclonal antibody VIIIB2 by Day 6 in culture. Overexpression of JNKK2, upstream kinase of JNK, increased activation of endogenous c-Jun in association with increased expression of p180 and abrogation of AQP5, suggesting that activation of c-Jun promotes retention of the AT2 cell phenotype. These results indicate that retention of the AT2 cell phenotype by KGF involves c-Jun and suggest that activation of c-Jun kinase may be an important determinant of maintenance of AT2 cell phenotype.

[Study on the relationship between smoking behavior and other unhealthy behaviors among middle school students in 4 cities of China].

OBJECTIVE: To explore the situation of smoking behavior among the students of middle school in Beijing, Hangzhou, Wuhan and Urumchi and to analyze the relationship between smoking behavior and several unhealthy behaviors together with psychological troubles to provide evidence in developing an early intervention plan. METHODS: The National Health Education Institute (NHEI) of Chinese Center for Disease Control and Prevention (CDC) provided relevant data on all middle schools in the 4 cities and then U.S. CDC randomly sampled 100 common middle schools from them with a special sampling process. The core questionnaire developed by the experts from WHO and other countries was used in the survey among 9015 sampled students. RESULTS: Among all the sampled students, 29.4% of them had ever attempted cigarettes smoking while 6.6% of them tried tobacco in the 30 days before survey, 27.0% of the students with smoking behavior began smoking at the age of 9 or younger, 31.8% had learned how to refuse smoking from school education. The students with smoking behavior were more likely to drink alcohol, use drugs, bully others, be injured, miss classes, and have some psychological troubles than those without smoking behavior. CONCLUSION: There were increasing trends noticed on the incidence of attempt and smoking cigarettes. Smoking was closely related to other unhealthy behaviors and psychological troubles. Comprehensive education activities on "no-smoking" should be implemented as early as possible among adolescents, as well as to promote training on life skills.