[Correlation between Expression Patterns of CD117/CD200 in Plasma Cells and Molecular Genetic Prognostic Parameters in Multiple Myeloma].

OBJECTIVE: To investigate the correlation between the expression of CD117 and CD200 in plasma cells and molecular genetic abnormalities in patients with multiple myeloma (MM). METHODS: 100 newly diagnosed MM patients were selected, and fresh bone marrow fluid was collected from the patients. The immunophenotypes and chromosomal structural variations of plasma cells were detected by flow cytometry (FCM) and fluorescence in situ hybridization (FISH). RESULTS: The positive expression frequencies of CD117 and CD200 in abnormal plasma cells of all MM patients were 44.0% and 44.0%, respectively. At least one molecular genetic abnormality was detected in 53 of the 75 patients who underwent FISH testing, and the overall detection rate was 70.7% (53/75). The detection rates of 1q21 (CKS1B ) duplication, 1p32 (CDKN2C ) deletion, p53 deletion and IgH rearrangement were 48.6% (36/74), 10.6% (7/66), 11.1% (8/72) and 32.9% (24/73), respectively. The incidence of IgH rearrangement in CD117+ patients was significantly lower than that in CD117- patients (P<0.05), and the proportion of 1p32 (CDKN2C ) deletion in CD200- patients was significantly lower than that in CD200+ patients (P<0.05). According to the expressions of CD117 and CD200, the patients were divided into 4 groups: CD117+CD200+, CD117+CD200-, CD117-CD200+ and CD117-CD200-. Further analysis showed that the incidence of IgH rearrangement in the CD117+CD200- group was significantly lower than that in the CD117-CD200+ group (P<0.05), and the deletion rate of 1p32 (CDKN2C ) gene in CD117+CD200- group was significantly lower than that in CD117+CD200+ group and CD117-CD200+ group (P<0.05). CONCLUSION: The difference in the expression patterns of CD117 combined with CD200 shows important value in judging the prognosis of MM patients, and the MM patients with CD117-CD200+ expression patterns in abnormal plasma cells have a worse prognosis.

[Research progress on regulation of N6-adenylate methylation modification in lipid metabolism disorders].

Lipid metabolism is a complex physiological process, which is closely related to nutrient regulation, hormone balance and endocrine function. It involves the interactions of multiple factors and signal transduction pathways. Lipid metabolism disorder is one of the main mechanisms to induce a variety of diseases, such as obesity, diabetes, non-alcoholic fatty liver disease, hepatitis, hepatocellular carcinoma and their complications. At present, more and more studies have found that the "dynamic modification" of N6-adenylate methylation (m6A) on RNA represents a new "post-transcriptional" regulation mode. m6A methylation modification can occur in mRNA, tRNA, ncRNA, etc. Its abnormal modification can regulate gene expression changes and alternative splicing events. Many latest references have reported that m6A RNA modification is involved in the epigenetic regulation of lipid metabolism disorder. Based on the major diseases induced by lipid metabolism disorders, we reviewed the regulatory roles of m6A modification in the occurrence and development of those diseases. These overall findings inform further in-depth investigations of the underlying molecular mechanisms regarding the pathogenesis of lipid metabolism disorders from the perspective of epigenetics, and provide reference for health prevention, molecular diagnosis and treatment of related diseases.

Water-soluble chitosan and phytoremediation efficiency of two Brassica napus L. cultivars in cadmium-contaminated farmland soils.

Pot and field trials were conducted to investigate Cd uptake and phytoremediation efficiency of two Brassica napus cultivars (QY-1 and SYH) with applied water-soluble chitosan (WSC, Pot: 0, 2% and 4%; Field: 0 and 10 g·m-2) grown in Cd-contaminated soils. The results from the pot and field trials generally showed that WSC treatments significantly increased Cd concentrations in shoot and root tissues by 33.77-159.71% (except for SYH/JY) and 7.42-168.71% of two B. napus cultivars compared with the control (p < 0.05). The uptake of Cd by shoots of SYH was obviously higher than by shoots of QY-1 treated with WSC under pot and field conditions, which was 1.54-2.22 times than that of QY-1 (p < 0.05). The results indicated that 2% WSC treatment significantly increased the water-soluble and acid extractable Cd in rhizosphere soils of both B. napus cultivars. Furthermore, Cd concentrations in the oils of two B. napus cultivars with applied WSC (10 g·m-2) grown under field conditions were not significantly different from commercial rapeseed oils. Rapeseed oil of B. napus is not only an edible oil with high nutritional value, but it can also be converted into biomass diesel that can be used as a substitute for petroleum diesel.

[Tolerance Mechanism and Cadmium Enrichment Abilities in Two Brassica napus L. Cultivars].

A hydroponic experiment was conducted to explore the differences in growth status and Cd accumulation characteristics of two Brassica napus L. cultivars (QY-1 and SYH) under different concentrations of cadmium (Cd) stress (0, 2, and 5 mg·L-1). The Cd subcellular compartmentalization and antioxidant enzyme activities were determined to elucidate the intrinsic mechanism of the differences in the Cd accumulation capacity between the two cultivars of Brassica napus L. Furthermore, field trials were conducted to further verify the differences in phytoremediation of the two cultivars. Results show that neither of the cultivars exhibited obvious growth inhibition under Cd stress. Under the 2 mg·L-1 Cd condition, there were no significant differences in shoot Cd concentrations between the two cultivars. Under 5 mg·L-1 Cd condition, however, the Cd concentrations in both shoot and root of SYH were significantly higher than that of QY-1, which increased by 32.05% and 99.57%, respectively. In addition, the bioconcentration factor (BCF) of the root in SYH is significantly higher than that of QY-1. The subcellular Cd distribution in leaves of the two cultivars of Brassica napus L. showed that, with an increase of Cd stress, Cd concentrations of heat stable protein (HSP) and metal-rich granule (MRG) fractions in leaves significantly increased by 143.69% and 118.91% for QY-1, and by 63.34% and 118.91% for SYH. Thus, the segregation of Cd in HSP and MRG, which was reported to be biological detoxified metal fractions (BDM), might play an important role in the detoxification of Brassica napus L. at a subcellular level under Cd stress. Moreover, the distribution of Cd in the cellular debris fraction might be another important factor contributing to the differences in Cd accumulation of the two Brassica napus L. cultivars, which was 4.41 times higher in SYH than in QY-1 under Cd stress. The results of the antioxidant enzyme activities of two Brassica napus L. cultivars showed that, under the 5 mg·L-1 Cd condition, the antioxidant enzyme system may represent an important detoxification mechanism for QY-1 to cope with stress induced by high concentrations of Cd, while SYH is more effective in reducing the toxicity of Cd by separation of Cd into BDM fractions. The results of the field trial confirmed that the Cd concentrations in the above- and underground parts of SYH were 2.34 and 1.43 times higher than in QY-1, respectively. Therefore, SYH possess a higher Cd phytoextraction capacity than QY-1, and might be a good candidate for the remediation of moderate and mildly Cd-contaminated farmland.

Rh-Matched Transfusion through Molecular Typing for ß-Thalassemia Patients Is Required and Feasible in Chinese.

BACKGROUND: Molecular typing for RHCE blood group alleles has been established in many countries for patients and blood donors. In the Chinese literature nearly 80% of transfused patients with alloimmunization have antibodies specific for antigens of the Rh blood group system. We investigated if it is feasible to match packed red blood cells (RBCs) for Chinese ß-thalassemia patients by RHCE genotyping. METHODS: In this study, 481 patients with ß-thalassemia were enrolled. They were genotyped for RHCE alleles by a simple PCR method with sequence-specific primers (PCR-SSP). Among these patients, 203 continuously received RBCs of the identical Rh subgroups according to the genotyping results for at least 3 months. Subsequently, their phenotypes were tested through a micro-column gel card method. For validation purposes, 400 donors were serologically typed with the same technology, of which 164 were genotyped too. Finally, the C, c, E, and e frequencies and the feasibility of the simple genotyping method were analyzed. RESULTS: All patients showed mixed-field agglutination in the Rh subgroup gel cards before the same Rh subgroups in blood donors were selected for blood transfusion. The results, however, lacked mixed-field agglutination in all 203 cases after transfusion with RBC concentrates selected for the patient's C, c, E, and e antigens for at least 3 months. The genotyping results of 164 donors were all consistent with the serological results. Whole coding regions of RHCE were sequenced in 7 individuals with weak c, E, or e antigens. In only one sample we observed a 1059G>A nucleotide mutation coding for a truncated RhCE polypeptide (GenBank KT957625), in the other 6 samples no sequence variant was found. Both patients and donors were predominantly CcEe and CCee, with a prevalence of 55.3% and 24.9% for patients or 49.3% and 31.3% for donors, respectively. It revealed that about 80% of Chinese could receive Rh-matched RBCs easily. CONCLUSION: A simple RHCE genotyping technique is safe enough for Rh-matched transfusion of ß-thalassemia patients in Chinese Han.

C1q/TNF-Related Protein 9 Inhibits THP-1 Macrophage Foam Cell Formation by Enhancing Autophagy.

During the pathogenesis of early atherosclerosis, lipid-loaded macrophages are involved in plaque development and progression. As a novel adipokine, C1q/tumor necrosis factor-related protein-9 (CTRP9) has beneficial effects in cardiovascular disease. However, previous reports have not studied whether the formation of macrophage foam cell induced by oxidized low-density lipoprotein (ox-LDL) is affected by CTRP9. According to our study, in ox-LDL-induced THP-1 macrophages, CTRP9 could reduce the quantity of lipid droplets, lower the level of cholesteryl ester (CE), promote cholesterol efflux, as well as increase the expression level of the cholesterol transport receptors ATP-binding membrane cassette transporter A1 (ABCA1) and G1 (ABCG1). In addition, the protein of LC3 II is elevated and that of p62 is decreased in CTRP9-treated foam cells by enhancing autophagy. However, using 3-methyladenine (3-MA) abolished the role of CTRP9 by inhibiting autophagy. Mechanistically, the autophagy-promoting effects of CTRP9 on foam cells was reversed by an AMPK inhibitor, Compound C, which inhibited the signaling pathway of adenosine 5'-monophosphate (AMP)-activated protein kinase (AMPK)/mammalian target of rapamycin (mTOR). These results show that CTRP9 protects against atherosclerosis by promoting cholesterol efflux to reduce the formation of foam cell in virtue of inducing autophagy in an AMPK/mTOR signaling pathway-dependent manner.

In situ splitting after selective partial portal vein ligation or simultaneous hepatic artery ligation promotes liver regeneration.

This study seeks to compare the impact of selective partial portal vein ligation (PPVL) or the combination of simultaneous hepatic artery ligation (PPVAL) with in situ splitting (ISS) on liver regeneration and injury. Rats were randomized into three groups; namely: selective PVL, PPVL + ISS and PPVAL + ISS. The changes in hepatic hemodynamics, liver regeneration and hepatocytic injury were examined. Blood flow to the left portal branch and the microcirculation of the left median lobe after PPVL or PPVAL was significantly reduced. Liver regeneration of PPVAL + ISS group was more pronounced than that in the PPVL + ISS and PVL groups at 48 and 72 hours as well as 7 d postoperatively. The serum biochemical markers and histopathological examination demonstrated reduced levels of liver injury in the PPVL + ISS group. Injury to hepatocytes was more pronounced with PPVAL + ISS than PVL. HGF, TNF-α and IL-6 expression in the regenerated lobes in both PPVAL + ISS and PPVL + ISS groups increased significantly when compared to the PVL group. We demonstrated that both PPVL + ISS and PPVAL + ISS were effective and feasible means of inducing remnant liver hypertrophy and could serve as a rapid clinical application for qualified patients.

Sexual dimorphism of estrogen-sensitized synoviocytes contributes to gender difference in temporomandibular joint osteoarthritis.

OBJECTIVES: Temporomandibular joint osteoarthritis (TMJOA) is approximately twice as prevalent in women than in men. Synoviocytes are believed to play a critical role in joint inflammation. However, it is unknown whether synoviocytes from different genders possess sexual dimorphisms that contribute to female-predominant TMJOA. MATERIALS AND METHODS: Freund's complete adjuvant combined with monosodium iodoacetate was used to induce TMJOA in female and male rats. Histologic and radiographic features were used to evaluate TMJOA. The expression of CD68, MCP-1, iNOS, and IL-1ß was detected by immunohistochemistry and real-time PCR. Primary fibroblast-like synoviocytes (FLSs) isolated from the synovial membrane of female and male rats were used for in vitro experiments. RESULTS: Female rats showed aggravated TMJOA features as compared to male rats. Increased expression of iNOS and IL-1ß was detected in synovial membrane from female TMJOA rats as compared to male rats. Furthermore, greater amounts of CD68-positive macrophage infiltration and increased MCP-1 expression around the synovial membrane were detected in female TMJOA rats compared to males. Primary cultured FLSs from female rats showed higher sensitivity to TNF-α treatment and recruited increased macrophage migration than male FLSs. More important, ovariectomy (OVX) by ablation in female rats repressed the sensitivity of female FLSs to TNF-α treatment due to the loss of estrogen production. Blockage of the estrogen receptor repressed estrogen-potentiated TNF-α-induced pro-inflammatory cytokine expression in OVX-FLSs. Moreover, the injection of estrogen receptor antagonists relieved the cartilage destruction and bone deterioration of TMJOA in female rats. CONCLUSION: Estrogen-sensitized synoviocytes in female rats may contribute to gender differences in the incidence and progression of TMJOA.

Augmented reality technology for preoperative planning and intraoperative navigation during hepatobiliary surgery: A review of current methods.

BACKGROUND: Augmented reality (AR) technology is used to reconstruct three-dimensional (3D) images of hepatic and biliary structures from computed tomography and magnetic resonance imaging data, and to superimpose the virtual images onto a view of the surgical field. In liver surgery, these superimposed virtual images help the surgeon to visualize intrahepatic structures and therefore, to operate precisely and to improve clinical outcomes. DATA SOURCES: The keywords "augmented reality", "liver", "laparoscopic" and "hepatectomy" were used for searching publications in the PubMed database. The primary source of literatures was from peer-reviewed journals up to December 2016. Additional articles were identified by manual search of references found in the key articles. RESULTS: In general, AR technology mainly includes 3D reconstruction, display, registration as well as tracking techniques and has recently been adopted gradually for liver surgeries including laparoscopy and laparotomy with video-based AR assisted laparoscopic resection as the main technical application. By applying AR technology, blood vessels and tumor structures in the liver can be displayed during surgery, which permits precise navigation during complex surgical procedures. Liver transformation and registration errors during surgery were the main factors that limit the application of AR technology. CONCLUSIONS: With recent advances, AR technologies have the potential to improve hepatobiliary surgical procedures. However, additional clinical studies will be required to evaluate AR as a tool for reducing postoperative morbidity and mortality and for the improvement of long-term clinical outcomes. Future research is needed in the fusion of multiple imaging modalities, improving biomechanical liver modeling, and enhancing image data processing and tracking technologies to increase the accuracy of current AR methods.

Progesterone attenuates temporomandibular joint inflammation through inhibition of NF-κB pathway in ovariectomized rats.

Sex hormones may contribute to the symptomatology of female-predominant temporomandibular disorders (TMDs) inflammatory pain. Pregnant women show less symptoms of TMDs than that of non-pregnant women. Whether progesterone (P4), one of the dominant sex hormones that regulates multiple biological functions, is involved in symptoms of TMDs remains to be explored. Freund's complete adjuvant were used to induce joint inflammation. We evaluated the behavior-related and histologic effects of P4 and the expression of tumor necrosis factor (TNF)-α, interleukin (IL)-1ß, and IL-6 in the synovial membrane. Primary TMJ synoviocytes were treated with TNF-α or IL-1ß with the combination of P4. Progesterone receptor antagonist RU-486 were further applied. We found that P4 replacement attenuated TMJ inflammation and the nociceptive responses in a dose-dependent manner in the ovariectomized rats. Correspondingly, P4 diminished the DNA-binding activity of NF-κB and the transcription of its target genes in a dose-dependent manner in the synovial membrane of TMJ. Furthermore, P4 treatment showed decreased mRNA expression of proinflammatory cytokines, and partially reversed TNF-α and IL-1ß induced transcription of proinflammatory cytokines in the primary synoviocytes. Moreover, progesterone receptor antagonist RU-486 partially reversed the effects of P4 on NF-κB pathway. In conclusion, progesterone ameliorated TMJ inflammation through inhibition of NF-κB pathway.

Traditional surgical planning of liver surgery is modified by 3D interactive quantitative surgical planning approach: a single-center experience with 305 patients.

BACKGROUND: Decision making and surgical planning are to achieve the precise balance of maximal removal of target lesion, maximal sparing of functional liver remnant volume, and minimal surgical invasiveness and therefore, crucial in liver surgery. The aim of this prospective study was to validate the accuracy and predictability of 3D interactive quantitative surgical planning approach (IQSP), and to evaluate the impact of IQSP on traditional surgical plans based on 2D images. METHODS: A total of 305 consecutive patients undergoing hepatectomy were included in this study. Surgical plans were created by traditional 2D approach using picture archiving and communication system (PACS) and 3D approach using IQSP respectively by two groups of physicians who did not know the surgical plans of the other group. The two surgical plans were submitted to the chief surgeon for selection before operation. The specimens were weighed. The two surgical plans were compared and analyzed retrospectively based on the operation results. RESULTS: The two surgical plans were successfully developed in all 305 patients and all the 3D IQSP surgical plans were selected as the final decision. Total 278 patients successfully underwent surgery, including 147 uncomplex hepatectomy and 131 complex hepatectomy. Twenty-seven patients were withdrawn from hepatectomy. In the uncomplex group, the two surgical plans were the same in all 147 patients and no statistically significant difference was found among 2D calculated resection volume (2D-RV), 3D IQSP calculated resection volume (IQSP-RV) and the specimen volume. In the complex group, the two surgical plans were different in 49 patients (49/131, 37.4%). According to the significance of differences, the 49 different patients were classified into three grades. No statistically significant difference was found between IQSP-RV and specimen volume. The coincidence rate of territory analysis of IQSP with operation was 92.1% (93/101) for 101 patients of anatomic hepatectomy. CONCLUSIONS: The accuracy and predictability of 3D IQSP were validated. Compared with traditional surgical planning, 3D IQSP can provide more quantitative information of anatomic structure. With the assistance of 3D IQSP, traditional surgical plans were modified to be more radical and safe.

Estradiol upregulates voltage-gated sodium channel 1.7 in trigeminal ganglion contributing to hyperalgesia of inflamed TMJ.

BACKGROUND: Temporomandibular disorders (TMDs) have the highest prevalence in women of reproductive age. The role of estrogen in TMDs and especially in TMDs related pain is not fully elucidated. Voltage-gated sodium channel 1.7 (Nav1.7) plays a prominent role in pain perception and Nav1.7 in trigeminal ganglion (TG) is involved in the hyperalgesia of inflamed Temporomandibular joint (TMJ). Whether estrogen could upregulate trigeminal ganglionic Nav1.7 expression to enhance hyperalgesia of inflamed TMJ remains to be explored. METHODS: Estrous cycle and plasma levels of 17ß-estradiol in female rats were evaluated with vaginal smear and enzyme linked immunosorbent assay, respectively. Female rats were ovariectomized and treated with 17ß-estradiol at 0 µg, 20 µg and 80 µg, respectively, for 10 days. TMJ inflammation was induced using complete Freund's adjuvant. Head withdrawal thresholds and food intake were measured to evaluate the TMJ nociceptive responses. The expression of Nav1.7 in TG was examined using real-time PCR and western blot. The activity of Nav1.7 promoter was examined using luciferase reporter assay. The locations of estrogen receptors (ERα and ERß), the G protein coupled estrogen receptor (GPR30), and Nav1.7 in TG were examined using immunohistofluorescence. RESULTS: Upregulation of Nav1.7 in TG and decrease in head withdrawal threshold were observed with the highest plasma 17ß-estradiol in the proestrus of female rats. Ovariectomized rats treated with 80 µg 17ß-estradiol showed upregulation of Nav1.7 in TG and decrease in head withdrawal threshold as compared with that of the control or ovariectomized rats treated with 0 µg or 20 µg. Moreover, 17ß-estradiol dose-dependently potentiated TMJ inflammation-induced upregulation of Nav1.7 in TG and also enhanced TMJ inflammation-induced decrease of head withdrawal threshold in ovariectomized rats. In addition, the estrogen receptor antagonist, ICI 182,780, partially blocked the 17ß-estradiol effect on Nav1.7 expression and head withdrawal threshold in ovariectomized rats. ERα and ERß, but not GPR30, were mostly co-localized with Nav1.7 in neurons in TG. In the nerve growth factor-induced and ERα-transfected PC12 cells, 17ß-estradiol dose-dependently enhanced Nav1.7 promoter activity, whereas mutations of the estrogen response element at -1269/-1282 and -1214/-1227 in the promoter completely abolished its effect on the promoter activity. CONCLUSION: Estradiol could upregulate trigeminal ganglionic Nav1.7 expression to contribute to hyperalgesia of inflamed TMJ.

Protective Effect of Saccharomyces boulardii on Deoxynivalenol-Induced Injury of Porcine Macrophage via Attenuating p38 MAPK Signal Pathway.

The aims of our study were to evaluate the effects of Saccharomyces boulardii (S. boulardii) on deoxynivalenol (DON)-induced injury in porcine alveolar macrophage cells (PAMCs) and to explore the underlying mechanisms. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, flow cytometric analysis, ELISA, qRT-PCR, and western blot were performed to assess whether S. boulardii could prevent DON-induced injury by p38 mitogen-activated protein kinase (p38 MAPK) signal pathway. The results showed that pretreatment with 8 µM DON could decrease the viability of PAMC and significantly increase the apoptosis rate of PAMC, whereas S. boulardii could rescue apoptotic PAMC cells induced by DON. Further experiments revealed that S. boulardii effectively reversed DON-induced cytotoxicity via downregulating the expression of TNF-α, IL-6, and IL-lß. In addition, S. boulardii significantly alleviated DON-induced phosphorylation and mRNA expression of p38 and further increased the expression of apoptosis regulation genes Bcl-xl and Bcl-2 and inhibited the activation of Bax. Our results suggest that S. boulardii could suppress DON-induced p38 MAPK pathway activation and reduce the expression of downstream inflammatory cytokines, as well as promote the expression of anti-apoptotic genes to inhibit apoptosis induced by DON in PAMC.

Estradiol promotes M1-like macrophage activation through cadherin-11 to aggravate temporomandibular joint inflammation in rats.

Macrophages play a major role in joint inflammation. Estrogen is involved in rheumatoid arthritis and temporomandibular disorders. However, the underlying mechanism is still unclear. This study was done to verify and test how estrogen affects M1/M2-like macrophage polarization and then contributes to joint inflammation. Female rats were ovariectomized and treated with increasing doses of 17ß-estradiol for 10 d and then intra-articularly injected with CFA to induce temporomandibular joint (TMJ) inflammation. The polarization of macrophages and expression of cadherin-11 was evaluated at 24 h after the induction of TMJ inflammation and after blocking cadherin-11 or estrogen receptors. NR8383 macrophages were treated with estradiol and TNF-α, with or without blocking cadherin-11 or estrogen receptors, to evaluate the expression of the M1/M2-like macrophage-associated genes. We found that estradiol increased the infiltration of macrophages with a proinflammatory M1-like predominant profile in the synovium of inflamed TMJ. In addition, estradiol dose-dependently upregulated the expressions of the M1-associated proinflammatory factor inducible NO synthase (iNOS) but repressed the expressions of the M2-associated genes IL-10 and arginase in NR8383 macrophages. Furthermore, estradiol mainly promoted cadherin-11 expression in M1-like macrophages of inflamed TMJ. By contrast, blockage of cadherin-11 concurrently reversed estradiol-potentiated M1-like macrophage activation and TMJ inflammation, as well as reversed TNF-α-induced induction of inducible NO synthase and NO in NR8383 macrophages. The blocking of estrogen receptors reversed estradiol-potentiated M1-like macrophage activation and cadherin-11 expression. These results suggested that estradiol could promote M1-like macrophage activation through cadherin-11 to aggravate the acute inflammation of TMJs.

STAT3 regulates the migration and invasion of a stem­like subpopulation through microRNA­21 and multiple targets in hepatocellular carcinoma.

Despite advances in the detection and treatment of hepatocellular carcinoma (HCC), the prognosis remains poor partly due to recurrence or extra/intrahepatic metastasis. Stem­like cancer cells are considered the source of malignant phenotypes including metastasis in various types of cancer. HCC side population (SP), considered as stem­like cancer cells, plays an important role in the migration and invasion in HCC, while the mechanisms involved remain unknown. In the present study, high levels of STAT3 and phospho­STAT3 were observed in MHCC97H SP cells compared with the main population (MP) cells. Inhibition of phospho­STAT3 led to a reduction of miR­21 expression, an increase of PTEN, RECK, and programmed cell death 4 (PDCD4) expression as well as the migration and invasion of SP cells. A set of rescue experiments was performed using different combinations of STAT3 inhibitor, miR­21 mimics and siRNAs to observe the expression of miR­21 targets, cell migration and invasion alterations. Data indicated that the alterations induced by STAT3 inhibition were partly reversed by the upregulation of miR­21. Additionally, the cells migration and invasion when silencing the targets of miR­21 were also reversed by STAT3 inhibition. In conclusion, the present study revealed the aberrant expression of STAT3 and miR­21 in HCC SP cells. Targeting STAT3 may limit HCC migration and invasion, which is likely to involve the regulation of miR­21 and its targets PTEN, RECK and PDCD4. Strategies directed towards STAT3 may therefore be a novel approach for the treatment of HCC.

Estradiol-potentiated cadherin-11 in synovial membrane involves in temporomandibular joint inflammation in rats.

Estrogen is involved in inflammation/pain of temporomandibular joint (TMJ), but the underlying mechanisms are largely unknown. Cadherin-11 plays an essential role in synovial inflammation. This study examined whether estrogen could potentiate cadherin-11 in synoviocytes and contribute to TMJ inflammatory pain. Female rats were ovariectomized, treated with increasing doses of 17ß-estradiol for 10 days, and injected intra-articularly with complete Freund's adjuvant to induce TMJ inflammation. The expression of cadherin-11 in synovial membrane was evaluated. TMJ pain was blocked with intra-articular injection of anti-cadherin-11 antibody and evaluated by head withdrawal threshold. Primary TMJ synoviocytes were treated with estradiol and tumor necrosis factor (TNF)-α or blocked with anti-cadherin-11 antibody to assess the expression of cadherin-11, interleukin (IL)-6, cyclooxygenase 2 (COX-2), and inducible nitric oxide synthase (iNOS). We observed that estradiol potentiated the inflammation-induced expression of cadherin-11 in the synoviocytes of synovial membrane from inflamed TMJ. Estradiol induced cadherin-11 expression in a dose- and time-dependent manner in primary synoviocytes and further potentiated the induction of cadherin-11 by TNF-α in synoviocytes. Furthermore, an estrogen receptor antagonist or a NF-κB inhibitor partially blocked the effects of estradiol on cadherin-11 induction in the synovial membrane. Blocking cadherin-11 partially reversed the TMJ inflammatory pain and estradiol-potentiated proliferation of synovial lining cells accompanied with iNOS expression. In addition, blocking cadherin-11 reversed TNF-α-induced and estradiol-potentiated transcription of IL-6, COX-2, and iNOS in primary synoviocytes. These results suggest that estrogen aggravated TMJ inflammatory pain partially through cadherin-11-mediated release of proinflammatory cytokines and enzymes in the synoviocytes.

Survivin up-regulates the expression of breast cancer resistance protein (BCRP) through attenuating the suppression of p53 on NF-κB expression in MCF-7/5-FU cells.

Both breast cancer resistance protein (BCRP, ABCG2) and apoptosis-related molecules are involved in the development of multidrug resistance (MDR) in cancer cells. However, the association of BCRP with apoptosis-related molecules in the development of MDR is unknown. In this study, we investigated the changes in expression levels of BCRP, Survivin, p53, Bcl-2, Bcl-xL or Bax in cultured MCF-7 and MCF-7/5-FU cells, and explored whether these changes affected the expressions of BCRP. Our data showed that the protein and mRNA expression levels of BCRP, Survivin and Bcl-2 were significantly higher in MCF-7/5-FU cells than in MCF-7 cells, while p53 expression lower in MCF-7/5-FU cells than in MCF-7 cells. Knockdown of Survivin or Bcl-2 in MCF-7/5-FU cells and overexpression of Survivin in MCF-7 cells revealed that Survivin had significant association with BCRP expression. Luciferase reporter gene assays showed that Survivin up-regulated BCRP expression at transcriptional level and this response was mediated through NF-κB(p50) pathway. However, may be due to the physical interaction between p53 and Survivin, p53 directly affected Survivin-regulated BCRP expressions. Interestingly, we found that Survivin would suppress p53 expression. Furthermore, our data revealed that Survivin itself had no apparent effect on NF-κB(p50) and BCRP expression when knockdown of p53 in MCF-7 cells; whereas p53 exerted significant inhibitory action on these when knockdown of Survivin. In conclusion, through down regulation of p53 expression, Survivin attenuates the suppressing effect of p53 on NF-κB(p50) expression and then enhances BCRP expression. This may represent a novel strategy for reversal of BCRP drug transporter activity to modulate MDR in cancer cells.

Galectin-9 acts as a prognostic factor with antimetastatic potential in hepatocellular carcinoma.

Considerable research has been conducted concerning galectin-9 and carcinomas, but little information is available about any relation with the hepatocellular carcinoma. In this study, we employed a small interfering RNA (siRNA) targeting galectin-9 to down-regulate the expression in HepG2 cells. As a result, after galectin-9 expression was reduced, cell aggregation was suppressed, while other behaviour such as the proliferation, adhesion and invasion to ECM, cell-endothelial adhesion and transendothelial invasion of the cells were markedly enhanced. When tumors of 200 patients with hepatocellular carcinoma were tested for galectin-9 expression by immunohistochemistry, binding levels demonstrated intimate correlations with the histopathologic grade, lymph node metastasis, vascular invasion and intrahepatic metastasis (P<0.05). Moreover, survival analysis indicated that patients with galectin-9 expression had much longer survival time than those with negative lesions, and the Log-rank test indicated that this difference was statistical significant (P<0.0001). The Cox proportional hazards model suggested that negative galectin-9 expression in hepatocellular carcinoma represented a significant risk factor for patient survival. We propose that galectin-9 might be a new prognostic factor with antimetastatic potential in patients with hepatocellular carcinoma.

[A comparison of target controlled versus manually controlled infusion of propofol in elderly patients].

OBJECTIVE: To evaluate the impact of anesthesia via target-controlled infusion (TCI) on drug consumption, intraoperative hemodynamic stability and recovery compared with manual-controlled infusion (MCI) in elderly patients. METHODS: Under the approval of the hospital ethics committee, 60 elderly patients undergoing laparoscopic surgery were randomly allocated by random numbers to either the MCI group (n = 30) or the TCI group (n = 30). The patients in MCI group received an infusion of propofol at 200 ml/h while those in TCI group propofol at an initial plasma concentration of 2.0 µg/ml and titrated upwards by 0.5 µg/ml steps until loss of consciousness. Both groups received an infusion of remifentanil. After intubation, the infusion rate or the target concentration of propofol was titrated to maintain BIS (bispectral index) values between 40 and 60. The infusion of remifentanil was adapted to intraoperative hemodynamics. The doses of propofol and remifentanil were recorded, the hemodynamic parameters and the use of vasoactive drugs collected and the recovery times assessed. RESULTS: The time of loss of consciousness and the time to intubation, the doses of propofol and remifentanil during induction and maintenance were not significantly different between two groups. The times of pump adjustment were less in TCI group versus MCI group [(5.8 ± 2.1) vs (7.8 ± 3.7) times, P < 0.01]. Blood pressure and heart rates were not statistically different at any time point between two groups. There were no significant differences in BIS or the use of vasoactive drugs between two groups. The recovery times were similar for two groups. CONCLUSION: Although target infusion system is easy to use and requires less time of adjustment, it fails to show added benefit on propofol consumption, hemodynamic stability, anesthesia depth and recovery in elderly patients.

Oxygen vectors used for S-adenosylmethionine production in recombinant Pichia pastoris with sorbitol as supplemental carbon source.

In order to increase the yield of S-adenosylmethionine (SAM) in recombinant Pichia pastoris, a strategy of adding oxygen vectors and supplemental carbon sources was described. Three organic solutions were used as oxygen vectors for SAM accumulation at different concentrations and addition times. Firstly, n-hexane (0.5%) or n-heptane (1.0%) was added after 72 h of cultivation to improve SAM production. Carbon metabolism was scarce during the induction phase because of low methanol concentration. Secondly, sorbitol (1.2%), selected from three candidates (glycerol, lactic acid, and sorbitol), was used as the supplemental carbon source. The yield of SAM was improved significantly (53.26%) at 1.0%n-heptane added at 72 h (48 h induction), 1.2% sorbitol added at 72, 96, and 120 h of cultivation and 1.0% methanol added every 24 h during cultivation.