Aim: To investigate the effect of desipramine (DES) on apoptosis and endoplasmic reticulum stress(ERS) in atherosclerotic model of rabbits. Methods: The rabbit model of atherosclerosis (AS) was established through abdominal aorta balloon injury and high fat diets for 12 weeks. They were divided into high-fat diet(HFD) group and HFD + DES group randomly. The same numbers of healthy rabbits with chow diet were divided randomly into normal control (NC) group and DES group. All interventions were given for the last 4 weeks. At the end of week 12, serum lipid was tested by conventional method. Plasma ox-LDL was measured by ELISA. Plasma and arterial acid sphingomyelinase(ASM) activity and ceramide levels were detected by UPLC analysis. Cell apoptosis in abdominal aorta was measured by TUNEL staining. Expression of GRP78 and CHOP proteins were detected by Western blot. Results: On the one hand, DES had no effect on serum lipid profiles including TG, TC, HDL-C.LDL-C and ox-LDL levels compared with either healthy or atherosclerosis rabbits. On the other hand, DES inhibited ASM and ceramide levels both in plasma and aorta, and decreased apoptotic cells and proteins of GRP78 and CHOP expression in abdominal aorta. Conclusions: DES attenuates AS via inhibition of ASM, down-regulating ceramide, attenuating ERS and thus reducing the apoptosis of AS plaques.

Intracranial Rosai-Dorfman disease (RDD) is a rare clinical histiocytosis proliferative disease. A 12-year-old boy with dizziness and headache for 1 month was admitted into Pediatric Neurosurgery of Xiangya Hospital, Central South University. The patient underwent total tumor resection and postoperative application of hormones and chemotherapy. During follow-up of 8 months, patient's condition was stable and no tumor recurrence was observed. For patient with a trend of tumor progression, stereotactic biopsy can help to confirm the diagnosis and determine the surgical strategy such as disposal of bone flaps. The treatment is mainly based on surgical intervention, supplemented by radiotherapy, chemotherapy and hormone therapy. Without affecting the nerve function, the surgeon should try to completely resect the tumor.
Biopsy ; Child ; Histiocytosis, Sinus ; Humans ; Male ; Neurosurgical Procedures ; Postoperative Period

To construct a plasmid expressing MDR1 short hairpin RNA (shRNA) mediated by pEGFP-C1/U6 vector, two coding sequences of 19 nucleotides were selected from MDR. Two pairs of oligonucleotides were designed for these two fragments. After annealing the formed double-stranded DNAs were ligated with plasmid pEGFP-C1/U6 (pEGFP-C1 vector with U6 promoter). The plasmids producing MDR1 shRNA were constructed from the inverted motif containing 9 spacers and four Ts. The results showed that the constructed plasmids were named pEGFP-C1/U6/A and pEGFP-C1/U6/B, and the constructs were identified by restriction and sequence analysis, no any base mutation was observed. It is concluded that plasmids of pEGFP-C1/U6/A and pEGFP-C1/U6/B expressing MDR1 shRNA were successfully constructed, providing a highly effective method for reversing the multidrug resistance in clinic.
ATP-Binding Cassette, Sub-Family B, Member 1 ; biosynthesis ; genetics ; DNA-Binding Proteins ; Drug Resistance, Multiple ; genetics ; Drug Resistance, Neoplasm ; genetics ; Genetic Vectors ; genetics ; Green Fluorescent Proteins ; genetics ; Humans ; Plasmids ; genetics ; RNA, Messenger ; biosynthesis ; genetics ; RNA, Small Interfering ; biosynthesis ; genetics ; RNA, Small Nuclear ; genetics

Objective To investigate the effect and mechanism of soluble epoxide hydrolase inhibitor (sEHI) for NF-κB pathway and cell circle arrest of tubular epithelial cell in unilateral ureteral obstruction (UUO) mice model.Methods Thirty-two healthy C57BL/6 male mice performed UUO surgery to induce renal interstitial fibrosis.Animals were randomly divided into 4 groups:sham group (n=8),sEHI (1 mg· kg-1·d-1) group (n=8),UUO group (n=8) and UUO+sEHI (1 mg· kg-1· d-1) group (n=8).Daily sEHI [1-(1-methylsulfonyl-piperidin-4-yl)-3-(4-trifluoromethoxy-phenyl)-urea,TUPS] or 2％ DMSO was applied to mice by oral gavage from day 1 to day 14 after surgery.All mice were sacrificed at day 14 and kidneys were harvested for further analysis.The changes of renal tissue morphology and pathology were observed by Hematoxylin and eosin (HE) and sirius red staining.The expressions of sEH,nuclear factor κB p65 (NF-κB p65) and IκB were measured by Western blotting.The expressions of TNF-α,IL-1β,MCP-1,IL-6,TGF-β,CTGF,collagen-Ⅳ and α-SMA were analyzed by real-time PCR.Immunofluorescence staining of phospho-histone H3 (p-HH3) and Ki67 was performed to determine the stage of cell cycle G2/M arrest.Results The expression and activity of sEH increased in UUO group (P ＜ 0.05).Administration of sEHI inhibited activity of sEH and infiltration of inflammatory cell in tubular interstitial,as well as attenuated tubular damage and tubular interstitial fibrosis.Western blotting analysis revealed administration of sEHI inhibited up-regulated NF-κB p65 and down-regulated IκB in UUO group (P ＜ 0.05).Real-time PCR demonstrated that administration of sEHI obviously decreased the mRNA expression of cytokines and fibrosis markers,including of TNF-α,IL-1 β,MCP-1,IL-6,TGF-β,CTGF,Collagen-Ⅳ,α-SMA (P ＜ 0.05).Immunofluorescence staining showed that there were much more p-HH3 and Ki67 double positive nuclear tubular epithelial cells and interstitial cells in UUO group,compared with Sham group (P ＜ 0.05).Administration of sEHI reduced the number of double positive nuclear cell only in tubular epithelial cells (P ＜ 0.05),but not in interstitial cells.Conclusions In UUO tubular interstitial fibrosis model,sEHI inhibits the activation of NF-κB pathway by down-regulating p65 and up-regulating IκB and ameliorates the infiltration of inflammatory cells.In addition,sEHI plays anti-fibrosis effect by moderating cell cycle G2/M arrest and reducing the excrete of pro-fibrosis factors of tubular epithelial cells.

OBJECTIVE: To determine the serum level of the growth differentiation factor 15 (GDF15) in multiple myeloma (MM) patients and analyze its level with other clinical parameters, and to investigate its significance in the formation, development and prognosis assessment of MM. METHODS: We used enzyme-linked immunosorbent assay (ELISA) to measure the serum level of GDF15 in an MM group (24 pre-treatment patients) and in 20 healthy controls. All patients' clinical data were collected. RESULTS: The serum GDF15 level was significantly higher in the MM group [(1.37±0.64) ng/mL] than in the normal control group [(0.14±0.06) ng/mL, P<0.01]. The mean serum GDF15 level in the MM patients in ISS stage III was (1.57±0.48) ng/mL, significantly higher than that of ISS stage (I+II) [(0.77±0.34) ng/mL, P<0.05]. There was no significant positive correlation between the serum GDF15 level and serum monoclonal proteins (M protein) level, β2-microglobulin and creatinemia (P<0.05), but significant inverse correlation was found between the GDF15 level with hemoglobin concentration and platelet count respectively (P<0.05). Serum GDF15 level was not associated with patients' age, albumin, lactic dehydrogenase (LDH), C-reactive protein (CRP), calcemia or leukocyte count (P>0.05). After 3 cycles of chemotherapy, patients with a>50% reduction of M protein had a significant reduction of GDF15, while for the patients whose M protein did not decrease obviously, their corresponding serum GDF15 level increased. CONCLUSION The serum GDF15 level may reflect the tumor burden in the MM patients, which increases obviously, is related with ISS, positively correlated with serum M protein level, β2- microglobulin level, serum creatinine and negatively with hemoglobin concentration and platelet count. The change of serum GDF15 level has some relation with the extent of M protein reduction, suggesting it may be used as a marker for therapy response.
Biomarkers, Tumor ; blood ; C-Reactive Protein ; Creatinine ; blood ; Enzyme-Linked Immunosorbent Assay ; Growth Differentiation Factor 15 ; blood ; Humans ; Multiple Myeloma ; blood ; Myeloma Proteins ; metabolism ; Prognosis ; beta 2-Microglobulin ; blood

Chemotherapy plays an important role in cancer treatment. With deeply understanding the mechanism of tumorigenesis, different chemotherapeutic drugs have been emerged as initial choices for cancer treatment. However, most patients gradually develop to chemotherapeutic resistance, resulting in failure to initial standard therapy. The mechanisms of chemoresistance are extensively explored. Recent studies indicated intrinsic or acquired alteration of DNA damage repair ability is the key determinant of chemoresistance. In this review, we present deregulation of DNA damage repair pathway in cancers and its involvement contributing to chemoresistance. Furthermore, we discuss strategies to sensitize chemotherapy by targeting at a parallel DNA repair pathway, which become promising approaches to overcome chemotherapeutic resistance.

Objective: To investigate the expressions of actin filament-associated protein 1 antisense RNA 1 (AFAP1-AS1), a long non-coding RNA (IncRNA) in four common human digestive system cancers including esophageal cancer, gastric cancer, liver cancer and colorectal cancer, and their clinical significance. Methods: The expression of AFAP1-AS1 was preliminarily detected in several digestive system tumor tissues and their corresponding adjacent normal tissues from 82 cases by multi-tumor tissue microarrays. These 82 patients included 11 with esophageal cancer, 11 with gastric cancer, 26 with liver cancer, and 34 with colorectal cancer. The expression of AFAP1-AS1 which had significant difference in liver tumor tissues was further tested by in situ hybridization (additional 70 cases) and real-time fluorescence quantitative PCR (additional 30 cases). The relationship between the expression of AFAP1-AS1 and the clinicopathological features was analyzed. The role of AFAP1-AS1 in tumor lymph node metastasis was assessed. Results: The expression of AFAP1-AS1 in liver cancer was significantly lower than that in its corresponding adjacent normal liver tissue (P < 0.05), but this expression was higher in esophageal cancer that in its corresponding adjacent normal esophageal tissue (P < 0.05). The expressions of AFAP1-AS1 in gastric cancer and colorectal cancer were not significantly different from those in their corresponding adjacent normal tissues (P > 0.05). Further test also revealed that the expression of AFAP1-AS1 was significantly down-regulated in liver cancer, and this effect was associated with clinical stage and lymph node metastasis (P < 0.05). The sensitivity, specificity, coincidence rate, positive predictive value and negative predictive value of AFAP1-AS1 serving as a molecular marker of metastasis were 68.75%, 65.00%, 65.63%, 28.21% and 91.23%, respectively. Conclusion: The expression of AFAP1-AS1 may play a role in the pathogenesis and progression of liver cancer and esophageal cancer, but this effect is different between these two cancer types. It is suggested that AFAP1-AS1 may become a noval molecular marker for clinical diagnosis of liver cancer. Copyright© 2014 by TUMOR.

Objective To investigate the relationship of tumor necrosis factor-α (TNF-α) and interferon-γ (IFN-γ) to interleukin-37 (IL-37) in the serum and peritoneal fluid, and investigate the pathogenesis of IL-37 in endometriosis (EMT) patients. Methods Thirty-six EMT patients, admitted in the Department of Obstetrics and Gynecology, the Third Xiangya Hospital of Central South University from Jul, 2018 to Jan. 2019, and confirmed by laparoscopic operation and pathology, were selected as the EMT group, of which 13 cases were in stage I and II, and 23 cases in stage III and IV. The other 28 women with simple ovarian cyst, teratoma or hysteromyoma were selected as the control group. ELISA was performed to detect the levels of IL-37, TNF-α and IFN-γ in serum and abdominal fluid of the two groups. And then the levels of IL-37, TNF-α and IFN-γ were compared between the two groups and their relationship was analyzed. Results The serum levels of IL-37 and TNF-α were significantly higher in EMT group than those in control group [(101.78±31.58) pg/ml vs. (63.50±14.48) pg/ml and (30.68±16.22) pg/ml vs. (18.09±1.27) pg/ml, respectively]. The levels of IL-37 and TNF-α in peritoneal fluid were significantly higher in EMT group than those in control group [(133.94±47.07) pg/ml vs. (68.43±12.60) pg/ml and (24.23±6.12) pg/ml vs. (16.63±3.13) pg/ml, respectively]. The levels of IFN-γ in serum and peritoneal fluid were significantly lower in EMT group than that in control group [(18.81±3.20) pg/ml vs. (20.52±1.38) pg/ml and (15.93±2.58) pg/ml vs. (20.32±7.03) pg/ml, respectively]. The differences were statistically significant (P<0.05). In EMT group, the expressive levels of IL-37 and TNF-α increased, and of IFN-γ decreased in serum and peritoneal fluid with the aggravation of the disease. In EMT group, the IL-37 levels in serum and peritoneal fluid were positively correlated with the TNF-α levels (r=0.338 and 0.518 respectively, P<0.05), while negatively correlated with the IFN-γ levels (r=–0.332 and –0.370 respectively, P<0.05). In control group, no significant correlation existed in IL-37 to TNF-α or to IFN-γ in serum and peritoneal fluid (P>0.05). Conclusion The levels of IL-37 in serum and peritoneal fluid are increased significantly in EMT patients, implying that IL-37 may play a certain role in occurrence and progression of EMT by promoting secretion of TNF-α and inhibiting secretion of IFN-γ.

AIM: To investigate the mechanism of apoptosis induced by (-)-epigallocatechin-3-gallate (EGCG) and the intervenient effect of EGCG on apoptosis inducted by Epstein-Barr (EB) virus latent membrane protein 1 (LMP1). METHODS: The established doxycycline regulated nasopharyngeal carcinoma cell line pTet-on-LMP1 HNE2 were exposed to 0.6 mg·L-1 Dox and 100 mg·L-1 EGCG for 24 h. Total RNAs were extracted from cells hybridized with the Atlas apoptosis cDNA expression array membrane containing mainly apoptosis related genes. RESULT: EGCG regulated several apoptosis related genes, they were either up- or down-regulated. CONCLUSION: EGCG induced apoptosis might be mediated through some specific genes and signal transduction pathways, and the presence U of EGCG showed some intervenient effect on LMP1 induced cell apoptosis.

Atherosclerosis/prevention & control* ; Cardiovascular Diseases/prevention & control* ; Humans ; Lipids ; Risk Factors