Dexmedetomidine inhibits cerebral nerve cell apoptosis after cerebral hemorrhage in rats via the Nrf2/HO-1/NQO1 signaling pathway.

OBJECTIVE: To investigate the effect of dexmedetomidine on the apoptosis of cerebral nerve cells after cerebral hemorrhage (CH) in rats and its molecular mechanism. MATERIALS AND METHODS: The rat model of CH was established by autologous blood injection. A total of 60 specific pathogen-free (SPF)-grade rats were randomly divided into sham-operation group, model group and dexmedetomidine group, and each group involved 20 rats. Rat brain water content was compared among the three groups. Besides, rat neurological function of the three groups was evaluated at 3, 5 and 7 d after operation by neurological function scoring. Western blotting assay was adopted to detect protein levels of apoptosis-related genes [B-cell lymphoma-2 (Bcl-2) and Bcl-2-associated X protein (Bax)] in rat brain tissues in the three groups. Moreover, the apoptosis level in the brain tissues in the groups was measured through terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) assay. Biochemical tests were conducted to determine activities of reduced glutathione (GSH), superoxide dismutase (SOD) and malondialdehyde (MDA) in the brain tissues among the three groups. Furthermore, the activation of the nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1)/NAD(P)H quinone oxidoreductase 1 (NQO1) signaling pathway in the brain tissues of the three groups of rats was examined via Western blotting assay. An in vitro oxygen-glucose deprivation (OGD) model was prepared using SH-SY5Y cells. In addition, Nrf2 was intervened in SH-SY5Y cells by small hairpin ribonucleic acid (shRNA) transfection. Finally, flow cytometry and Annexin V/PI assay were performed to detect the response of cells to dexmedetomidine in OGD + dexmedetomidine + sh-Nrf2 group. RESULTS: The brain water content and the neurological function score at 3, 5 and 7 d after operation were remarkably reduced in dexmedetomidine group compared with those in model group. The results of Western blotting and TUNEL assays indicated that dexmedetomidine group had a notably lowered apoptosis level in the brain tissues. Additionally, the biochemical test results manifested that activities of GSH and SOD were enhanced and that of MDA decreased in the brain tissues of dexmedetomidine group. Protein levels of Nrf2, HO-1 and NQO1 in the brain tissues were distinctly higher in dexmedetomidine group than those in model group. According to the results of flow cytometry, the apoptosis rate in OGD + dexmedetomidine + sh-Nrf2 group rose prominently compared with that in OGD + dexmedetomidine group. CONCLUSIONS: Dexmedetomidine inhibits the nerve cell apoptosis in rat brain tissues by activating the Nrf2/HO-1/NQO1 signaling pathway in rat CH models.

[Clinical application of self-made drainage tubes in different layers of soft tissue for negative-pressure wound therapy in 33 patients].

From January 2014 to June 2018, 28 patients with different types of deep soft tissue injury or infection were admitted to the Affiliated Jiangyin Hospital of Medical College of Southeast University; 5 patients were admitted to the Zhengzhou First People's Hospital. There were 24 males and 9 females, aged 18-89 (40±20) years. Disposable suction tubes with holes cut on side walls were used as self-made drainage tubes. The authors placed the self-made drainage tubes on different deep soft tissue layers and wound surfaces after debridement. The effective drainage sections of the wound surface drainage tubes were wrapped with silver ion antimicrobial functional active dressings. Bio-permeable membrane was used to close the operative area. The drainage tubes in the deep layer of wound and wound surface were connected in parallel by a tee and connected to wall-hanging medical negative-pressure suction device to conduct negative-pressure wound treatment at -20.0 to -10.6 kPa. The deep drainage tubes were usually removed or changed 4 or 5 days after surgery.The drainage tubes in the wound surface were synchronously replaced when removing or replacing he drainage tubes in the deep layer of wound. On 4 to 15 days after surgery, the deep drainage tubes were removed. On 8 to 25 days after surgery, the wound surface drainage tubes were removed. Then the treatment was changed to a conventional dressing change until the wounds were completely healed or the wound bed was ready for skin grafts or tissue flaps. The indwelling time of deep drainage tubes in this group of patients was (6.2±2.8) days, and the indwelling time of wound surface drainage tubes was (12.0±3.0) days. The wound healing time was (22±5) days, the hospital stay time was (29±7) days, and wound bacteria were reduced from 6 species and 11 strains before treatment to 3 species and 4 strains after treatment. No adverse events such as wound bleeding, irritative pain, and chronic sinus occurred during treatment. Twenty-three patients were followed up for 13 to 28 months, no treatment-related complications were observed.

LncRNA GIHCG regulates microRNA-1281 and promotes malignant progression of breast cancer.

OBJECTIVE: This study aimed to investigate the expression characteristics of long non-coding RNA (lncRNA) GIHCG in breast cancer (BCa), and further investigate its role in BCa and its relationship with clinical characteristics and prognosis. PATIENTS AND METHODS: Quantitative Real Time-Polymerase Chain Reaction (qRT-PCR) was performed to examine GIHCG expression in 53 pairs of BCa tumor tissues and adjacent tissues. The interaction between the level of GIHCG and the clinical indicators of BCa and the prognosis of patients was then analyzed. Lentivirus was transfected into BCa cell lines to construct the GIHCG knockdown model. The cell counting kit-8 (CCK-8), cell cloning, and 5-Ethynyl-2'-deoxyuridine (EdU) assays were performed to analyze the influence of GIHCG on the biological function of BCa cells, as well as to explore whether it could play a role via modulating microRNA-1281. RESULTS: QRT-PCR results showed that the GIHCG level was remarkably higher in the BCa tumor tissue than in adjacent ones. Compared with patients with low expression of GIHCG, patients with high expression of GIHCG had higher pathological grades and a lower overall survival. Besides, the proliferation ability of BCa cells in GIHCG knockdown group was significantly decreased compared with NC group. QRT-PCR results indicated that silencing GIHCG increased the expression of miR-1281, thereby promoting the malignant progression of BCa. Also, the silence of miR-1281 reversed the effect of GIHCG on the proliferative capacity of BCa, thus increasing the cell anti-apoptotic ability. CONCLUSIONS: GIHCG levels were remarkably increased in both BCa tissues and cells, which was related to the pathological stage and poor prognosis of BCa patients. Besides, GIHCG might promote the malignant progression of BCa by inhibiting microRNA-1281.

Circular RNA TTBK2 promotes the development of human glioma cells via miR-520b/EZH2 axis.

OBJECTIVE: Glioma is a highly malignant human disease characterized by limited response to clinical therapy. Evidence indicated that circular RNA Tau tubulin kinase 2 circular RNAs (circ-TTBK2) participated in glioma pathogenesis. However, the precise effect of circ-TTBK2 on glioma progression is needed to be highlighted. MATERIALS AND METHODS: The levels of circ-TTBK2, microRNA-520b (miR-520b), and enhancer of zeste homologue 2 (EZH2) were detected via quantitative Real Time-Polymerase Chain Reaction (qRT-PCR) or Western blot. 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) assay was performed to determine cell proliferation in vitro. Besides, a flow cytometry assay was conducted to examine apoptosis of A172 and U251 cells. Cell invasion was identified using the transwell assay. Moreover, Dual-Luciferase reporter assay was used to confirm the interaction between miR-520b and circ-TTBK2 or EZH2. The role of circ-TTBK2 in glioma progression was exposed using xenograft tumor experiments. RESULTS: The levels of circ-TTBK2 and EZH2 were markedly augmented, whereas miR-520b expression level was notably reduced in glioma tissues and cell lines. Either circ-TTBK2 or EZH2 detection could clearly facilitate cell apoptosis and block proliferation and invasion in A172 and U251 cells, while the effect of circ-TTBK2 or EZH2 deficiency was reverted by co-transfecting with miR-520 inhibitor. Moreover, circ-TTBK2 exerted its roles via miR-520b/EZH2 axis in glioma cells, and the knockdown of circ-TTBK2 could hinder the progression of glioma. CONCLUSIONS: Circ-TTBK2/miR-520b/EZH2 axis modulated cell proliferation, apoptosis, and invasion in glioma cell lines, and might serve as potential targets for glioma diagnosis and therapy.

MicroRNA-15a inhibits inflammatory response and apoptosis after spinal cord injury via targeting STAT3.

OBJECTIVE: To clarify the function of microRNA-15a in the spinal cord injury (SCI) and its potential mechanism. PATIENTS AND METHODS: The plasma levels of microRNA-15a and signal transducer and activator of transcription 3 (STAT3) in SCI patients were determined by quantitative Real Time-Polymerase Chain Reaction (qRT-PCR). The correlation between the expressions of microRNA-15a and STAT3 was analyzed. The in vitro SCI model was established in H2O2-induced C8-D1A and C8B4 cells, and in vivo SCI model was established in mice by hitting T10. The mRNA and protein expressions of tumor necrosis factor-α (TNF-α) and interleukin 6 (IL-6) were detected in the SCI model. The apoptosis was examined by flow cytometry or TUNEL staining, respectively. The motor function of mouse hindlimb was evaluated using the Basso Beattie Bresnahan (BBB) standard scale. The target gene of microRNA-15a was predicted by bioinformatics and further verified by dual-luciferase reporter gene assay. The expression changes of target genes in C8-D1A and C8B4 cells with microRNA-15a overexpression or knockdown were examined by qRT-PCR and Western blot. Finally, rescue experiments were performed to evaluate the regulatory effects of microRNA-15a and STAT3 on cell apoptosis. RESULTS: MicroRNA-15a was lowly expressed in plasma of SCI patients, while STAT3 was highly expressed with a negative correlation to microRNA-15a. Identically, microRNA-15a was lowly expressed in H2O2-induced C8-D1A and C8B4 cells, and STAT3 was highly expressed. MicroRNA-15a overexpression downregulated mRNA and protein levels of TNF-α and IL-6 in C8-D1A and C8B4 cells. BBB score was markedly low in SCI mice relative to controls. SCI mice injected with microRNA-15a mimics had higher BBB score than those injected with negative control. Besides, SCI mice with microRNA-15a overexpression had downregulated expressions of STAT3, TNF-α, and IL-6 in the impaired spinal cord tissues, as well as lower apoptotic rate. Through bioinformatics, we found binding sites between STAT3 and microRNA-15a. Their binding conditions were further verified by dual-luciferase reporter gene assay. Moreover, STAT3 expression was negatively regulated by microRNA-15a. Finally, rescue experiments showed that STAT3 overexpression could reverse the regulatory effects of microRNA-15a on expressions of TNF-α and IL-6, as well as apoptosis. CONCLUSIONS: MicroRNA-15a expression decreases in the SCI model, which participates in the process of SCI by regulating inflammatory response and cell apoptosis via targeting STAT3.

MiR-15 suppressed the progression of bladder cancer by targeting BMI1 oncogene via PI3K/AKT signaling pathway.

OBJECTIVE: To investigate the role of microRNA-15 (miR-15) in the progression of bladder cancer (BC) cell and its underlying mechanism. PATIENTS AND METHODS: Human BC specimens were collected from BC patients during operations. BC cell lines (T24, BIU87, and HT1376) and normal uroepithelial cell lines SV-HUV-1 were cultured. The abilities of cell proliferation and invasion were detected by Methyl thiazolyl tetrazolium (MTT) and transwell assay, respectively. Additionally, the relevant mRNA and protein expressions were measured by quantitative Real Time-Polymerase Chain Reaction (qRT-PCR), Western blot and immunohistochemistry, respectively. Furthermore, the luciferase reporter assay was used to verify the target gene of miR-15. Besides, Xenograft tumor formation assay was performed to confirm the effect of miR-15 on tumor growth. RESULTS: A low expression of miR-15 was detected by qRT-PCR, whereas the high expression of B cell-specific Moloney murine leukemia virus integration site 1 (BMI1) was detected by immunocytochemical assay in BC tissues. Moreover, miR-15 expression and BMI1 expression were significantly associated with the overall survival of BC patients. MTT and transwell assay results stated that the up-regulation of miR-15 inhibited BC cell proliferation, migration, and invasion. BMI-1 was verified as a direct target of miR-15 in BC using Luciferase reporter assay. Besides, miR-15 regulated epithelial-mesenchymal transition (EMT)-related makers, protein kinase B (AKT), and the phosphorylation of AKT protein levels in BC using the Western blot assay. Xenograft tumor formation assay indicated that the over-expression of miR-15 inhibited the tumor growth. CONCLUSIONS: We stated that miR-15 suppressed BC cell progression by targeting BMI1 through the phosphatidylinositol 3-kinase (PI3K)/AKT signaling pathway, which provided a potential target for BC treatment.

[Epidemiological study of occupational diseases in Gansu province, China in 2010-2017].

Objective: To analyze the epidemiological characteristics of occupational diseases in Gansu Province, China in 2010-2017, and to provide a scientific basis for the prevention and control of occupational diseases. Methods: The cluster sampling method was adopted to make statistical analysis of 1339 cases of occupational disease reported by "occupational disease and occupational health information monitoring system" in Gansu province from 2010 to 2017, to investigate the diseases, regions and industries of occupational diseases in June 2018. Results: A total of 1339 cases of occupational diseases (39 types, 8 classes) were diagnosed and reposed in 2010-2017. The three most frequent diseases were pneumoconiosis (87.53%, 1172/1339), occupational poisonings (5.83%, 78/1339), and occupational ear, nose, and throat (ENT) diseases (3.14%, 42/1339). The cases of silicosis accounted for 54.61% (640/1172) of all cases of pneumoconiosis, the second was coalworker pneumoconiosis, which accounted for 38.57% (452/1172). In the cases of occupational poisonings, 32.05% (25/78) suffered from carbon monoxide poisoning. Patients with occupational diseases were reported in 14 districts of Gansu, mostly in Lanzhou (27.52%, 347/1261), Jinchang (16.57%, 209/1261), and Baiyin (14.20%, 179/1261). The reported cases are mainly concentrated in mining (71.56%, 468/654) and manufacturing (21.87%, 143/654), the types of state-owned economy (55.63%, 692/1244) and private economy (33.68%, 419/1244), large (43.41%, 540/1244) and small enterprises (35.21%, 438/1244) in 2010-2017 in Gansu. Conclusion: The pneumoconiosis caused by silicious and coal dust and the occupational poisonings caused by carbon monoxide seem to be the main occupational hazards in Gansu province. Occupational diseases occur in all districts of Guangzhou and in various industries. The state-owned economy and private sector, large and small enterprises should be the focuses of occupational health supervision.

CalliSpheres® drug-eluting beads (DEB) transarterial chemoembolization (TACE) is equally efficient and safe in liver cancer patients with different times of previous conventional TACE treatments: a result from CTILC study.

PURPOSE: To assess the efficacy and safety of drug-eluting beads transarterial chemoembolization (DEB-TACE) in liver cancer patients with different times of previous conventional transarterial chemoembolization (cTACE) treatments. METHODS: 367 liver cancer patients about to receive DEB-TACE treatment were enrolled in this prospective cohort study. All patients were divided into no previous cTACE group (NPC group), 1-2 times previous cTACE group (PC group) and triple or above previous cTACE group (TPC group) according to the times of previous cTACE treatments. RESULTS: There was no difference in complete response (CR) (P = 0.671) and objective response rate (ORR) (P = 0.062) among three groups. Additionally, no difference in overall survival (OS) among groups (P = 0.899) was found. As to liver function, most liver function indexes were deteriorative at 1 week after DEB-TACE operation, but returned to baseline at 1-3 months after DEB-TACE operation in all three groups, while percentage of abnormal total bile acid (TBA) patients was higher in TPC group than NPC and PC groups at 1-3 month post-DEB-TACE (P = 0.018). As for safety profiles, the incidence of pain during DEB-TACE operation was lower in TPC group compared to NPC and PC groups (P = 0.005), while no difference of other adverse events was found during and 1 month post-DEB-TACE treatment among three groups. CONCLUSION: DEB-TACE treatment was equally efficient and tolerated in liver cancer patients with different times of previous cTACE treatments.

[YAP regulates the proliferation and modifies the sensitivity to sorafenib in hepatocellular carcinoma cells].

Objective: To detect the expression level of YES-associated protein 1 (YAP) in hepatocellular carcinoma (HCC) cell lines and investigate its effects on the proliferation activity and the sensitivity to sorafenib in HCC cells. Methods: Western blot was used to detect the protein expression levels of YAP in SMMC-7721, SK-Hep-1, HepG-2, Huh7 and the normal liver cell line L-O2. YAP specific small interfering RNA (si-YAP) or YAP expression plasmid were transfected in SK-Hep-1 or Huh7 cells, respectively. Cell counting kit-8 (CCK-8) test was used to detect the cell proliferation activity and the cell cycle test was conducted by flow cytometry. SK-Hep-1 and SK-Hep-1 si-YAP cells were subcutaneously injected into the nude mice which were sequentially treated by intragastric administration of sorafenib, and the tumor growth in vivo were observed and compared. Results: The expression of YAP was upregulated in HCC cell lines. Deletion of YAP expression significantly decreased the survival rate of SK-Hep-1 cells [(78.5±0.3)% vs (92.3±0.2)%, P=0.025]. Knockdown of YAP significantly increased the percentage of G(0)/G(1)-phase cells [ (65.4±3.3) % vs (55.7±3.4) %, P=0.039]. On the contrary, upregulation of the YAP expression in Huh7 cells significantly increased the cell survival rate [(81.2±1.3)% vs (62.5±1.1)%, P=0.013] and reduced the percentage of G(0)/G(1)-phase cells [(38.2±3.8)% vs (48.8±2.9)%, P=0.019]. The survival rate of SK-Hep-1 cells treated by si-YAP combined with sorafenib was (31.13±1.79)%, significantly lower than (48.87±0.58) % of SK-Hep-1 cells treated by sorafenib alone (P=0.001), while overexpression of YAP attenuated the inhibitory effect of sorafenib on the survival of Huh7 cells [(69.98±2.94) % vs (53.53±1.93)%, P=0.001]. The tumor weights of SK-Hep-1 group, sorafenib alone group, SK-Hep-1 si-YAP group and SK-Hep-1 si-YAP combined with sorafenib group were (0.96±0.08) g, (0.62±0.08) g, (0.70±0.06) g and (0.27±0.02) g, respectively. The tumor weights of sorafenib alone group and SK-Hep-1 si-YAP group were significantly lower than that of SK-Hep-1 group (P=0.012 and P=0.031, respectively). The tumor weight of SK-Hep-1 si-YAP combined with sorafenib group was significantly lower than that of SK-Hep-1 si-YAP group (P=0.001). Conclusions: The expression of YAP is upregulated in HCC cell lines, which regulates the proliferation, cell cycle, and sensitivity to sorafenib of HCC cells. YAP is a potential molecular target for HCC treatment.

[Comparison of therapeutics effects of transcatheter arterial chemoembolization combined with iodine-125 seed implantation and sorafenib for the treatment of hepatocellular carcinoma with portal vein tumor thrombosis].

Objective: To explore the factors affecting the prognosis of patients with hepatocellular carcinoma (HCC) combined with portal vein tumor thrombosis (PVTT), and to analyze the clinical value of transcatheter arterial chemoembolization (TACE) combined with iodine-125 seed implantation in such patients. Methods: A retrospective analysis of 53 patients with HCC combined with PVTT was performed. In the study group, 32 cases were treated with TACE combined with iodine-125 seed implantation, and 21 cases in the control group were treated with TACE combined with sorafenib. Survival analysis was carried out on eight factors such as gender, age, Child-Pugh classification, alpha fetoprotein level, portal vein tumor thrombosis (PVTT) type, forms of liver tumor, extra-hepatic metastasis and treatment modalities. The efficacy of TACE combined with iodine-125 seed implantation and TACE combined with sorafenib was further compared. The χ (2) test was used to evaluate the efficacy of the two groups. A single factor survival analysis was calculated by Kaplan-Meier estimator and multifactor survival analysis by Cox proportional hazards model. Results: All 53 patients were successfully treated. The median tumor progression time (mTTP) and median overall survival (mOS) were 8 months and 11 months, respectively. The disease control rate (DCR) of the study group for PVTT was 93.8%, which was significantly higher than that of the control group (61.9%, χ (2) = 6.448, P = 0.011). The difference was statistically significant; the objective remission rate of the study group for PVTT was 75.0%. Significantly higher than 9.5% in the control group, P < 0.05, the difference was statistically significant; the DCR of the primary tumor in the study group was 50.0%, which was lower than the 70.0% of the PVTT in the control group, P = 0.231, the difference was not statistically significant. The progression of primary HCC lesions in patients with multivariate survival analysis: Child-Pugh grade A patients were compared to grade B [Hazard ratio (HR) = 0.236, P = 0.003]; no extra-hepatic metastasis (HR = 0.258, P = 0.002); and TACE combined with iodine-125 seed implantation group compared with TACE combined sorafenib group (HR = 0.372, P = 0.002), the differences were statistically significant. Multivariate survival analysis of patients with overall survival: AFP < 400 ng/mL vs. AFP≥400 ng/mL (HR = 0.389, P = 0.030); Child-Pugh grade A vs. B (HR = 0.263, P = 0.006); and no extra-hepatic metastasis (HR = 0.306, P = 0.006), the differences were statistically significant. Conclusion: TACE combined with iodine-125 seed implantation for the treatment of HCC with PVTT can effectively control the progression of PVTT and intrahepatic lesions and improve the prognosis of patients.

Effect of exosome biomarkers for diagnosis and prognosis of breast cancer patients.

PURPOSE: Exosomes are gradually detected as an indicator for diagnosis and prognosis of breast cancer in clinic and a systematic review was conducted. METHODS: A search for clinical studies published before July 1, 2017 was performed. Methods of exosome purification and identification from all studies were extracted. For diagnosis evaluation, the comparison of exosome biomarkers expression between breast cancer patients and healthy women was obtained; for prognosis prediction, the correlation between exosome biomarkers expression and chemotherapy resistance, overall survival (OS), disease-free survival (DFS), recurrence and metastasis of breast cancer was also extracted. RESULTS: A total of 11 studies with 921 breast cancer patients were included. Ultracentrifugation is the most frequent method to purify exosomes and transmission electron microscopy is commonly used to identify exosomes. Exosome biomarkers (such as HER2, CD47, Del-1, miR-1246 and miR-21) in breast cancer patients are significantly higher than those in healthy controls, exosomal GSTP1 and TRPC5 are related to chemotherapy resistance, exosome-carrying TRPC5, NANOG, NEUROD1, HTR7, KISS1R and HOXC are correlated to PFS, DFS or OS, and some exosomal proteins (HER2, KDR, CD49d, CXCR4 and CD44) as well as miRNAs (miR-340-5p, miR-17-5p, miR-130a-3p, miR-93-5p) are associated with tumor recurrence or distant organ metastasis. CONCLUSIONS: Exosome biomarkers can be used for early diagnosis and prognosis of breast cancer patients in clinic.

The cadmium and lead content of the grain produced by leading Chinese rice cultivars.

The cadmium (Cd) and lead (Pb) content in both white and wholemeal flour milled from 110 leading rice cultivars was assessed. The white flour Cd content ranged from <0.0025 to 0.2530mg/kg (geometric mean (GM)=0.0150mg/kg), while its Pb content ranged from <0.0250 to 0.3830mg/kg (GM=0.0210mg/kg). The indica types took up higher amounts of Cd and Pb than did the japonica types. Although the heavy metal content of wholemeal flour tended to higher than that of white flour, nevertheless 84.5% (Cd) and 95.4% (Pb) of the entries were compliant with the national maximum allowable concentration of 0.2000mg/kg of each contaminant. An analysis of the Cd content in the white flour of three indica type cultivars grown in two consecutive years at two locations indicated that Cd content may be significantly affected by the conditions prevailing in the growing season.

Protein arginine methyltransferase 5 functions as an epigenetic activator of the androgen receptor to promote prostate cancer cell growth.

Protein arginine methyltransferase 5 (PRMT5) is an emerging epigenetic enzyme that mainly represses transcription of target genes via symmetric dimethylation of arginine residues on histones H4R3, H3R8 and H2AR3. Accumulating evidence suggests that PRMT5 may function as an oncogene to drive cancer cell growth by epigenetic inactivation of several tumor suppressors. Here, we provide evidence that PRMT5 promotes prostate cancer cell growth by epigenetically activating transcription of the androgen receptor (AR) in prostate cancer cells. Knockdown of PRMT5 or inhibition of PRMT5 by a specific inhibitor reduces the expression of AR and suppresses the growth of multiple AR-positive, but not AR-negative, prostate cancer cells. Significantly, knockdown of PRMT5 in AR-positive LNCaP cells completely suppresses the growth of xenograft tumors in mice. Molecular analysis reveals that PRMT5 binds to the proximal promoter region of the AR gene and contributes mainly to the enriched symmetric dimethylation of H4R3 in the same region. Mechanistically, PRMT5 is recruited to the AR promoter by its interaction with Sp1, the major transcription factor responsible for AR transcription, and forms a complex with Brg1, an ATP-dependent chromatin remodeler, on the proximal promoter region of the AR gene. Furthermore, PRMT5 expression in prostate cancer tissues is significantly higher than that in benign prostatic hyperplasia tissues, and PRMT5 expression correlates positively with AR expression at both the protein and mRNA levels. Taken together, our results identify PRMT5 as a novel epigenetic activator of AR in prostate cancer. Given that inhibiting AR transcriptional activity or androgen synthesis remains the major mechanism of action for most existing anti-androgen agents, our findings also raise an interesting possibility that targeting PRMT5 may represent a novel approach for prostate cancer treatment by eliminating AR expression.

[Research advances in the role of the Hippo-YAP/TAZ signaling pathway in primary liver cancer].

The Hippo-YAP/TAZ signaling pathway is an evolutionarily conserved pathway, which has been confirmed to play an important role in organ volume control, stem cell function, tissue regeneration, and tumorigenesis. Recent research findings show that the Hippo-YAP/TAZ signaling pathway is closely associated with the development and progression of primary liver cancer, and inhibition of the activity of this pathway may be a new method for the treatment of liver cancer. This article reviews the research advances in the role of the Hippo-YAP/TAZ signaling pathway in primary liver cancer.

Anti-inflammatory effects of three kinds of traditional Mongolian medicine monomer and its combination on LPS-stimulated RAW264.7 macrophages.

OBJECTIVE: Traditional Mongolian Medicine (TMM) exhibits useful biological activities including antifungal, antibacterial, and anti-inflammatory actions. The mechanisms of TMM in anti-inflammation were still unclear. The aim of this study was to investigate the effects of the three main monomers (geniposide, gallate, berberine hydrochloride and a mixture of them) of a traditional Mongolian medicine on cell survival and the proinflammatory cytokines signaling pathways which are activated by bacterial lipopolysaccharides (LPS). MATERIALS AND METHODS: Mouse macrophage-like cell line RAW264.7 was used as a model of inflammation to investigate the anti-inflammatory effects of three TMM momomers and their combination. RT-PCR and Western blot was used to quantify the change of mRNA and protein levels of cytokines, Toll-like receptor-4 (TLR4) and Nuclear Factor-κB (NF-κB) and its inhibitor IκB. The non-radioactive electrophoresis mobility shift assay (EMSA) was used to evaluate the binding activity of NF-κB. RESULTS: The monomers and their combination exhibited a potent anti-inflammatory effect for suppressing the LPS-evoked secretion of proinflammatory cytokines IL-1ß, IL-6 and TNFα. Furthermore, the monomers and their combination attenuated activation of NF-κB and expression of TLR4 at both mRNA and protein levels, the upstream player of the LPS-TLR4-cytokines/ NF-κB signaling pathway. CONCLUSIONS: The Mongolia herbal compound exerts a potent anti-inflammatory effect and could potentially be developed as a useful agent for the chemo-prevention of inflammatory diseases.

Metabolomic approach for the identification of therapeutic targets of erythropoietin against sepsis in rat models.

OBJECTIVE: Owing to a lack of effective treatment approaches, sepsis is considered a life-threatening clinical syndrome worldwide. Many therapeutic interventions combating sepsis have been evaluated in animal models and clinical cases over the past few decades. Due to the pleiotropic characteristics of EPO, many studies have shown that erythropoietin (EPO) would be used to alleviate sepsis-induced tissue injury beyond the hemoglobin elevation effect. Nevertheless, the organ protective activity of EPO could not be supported by all of the results. In order to address the unanswered questions, a new methodical approach is necessary to be considered. The latest progress in metabolomics could be helpful to interpret the underlying mechanisms of EPO on sepsis, via metabolite profiling, to bring in some potent predictable fact for clinical application. MATERIALS AND METHODS: Twenty-one male Sprague-Dawley rats were divided into 3 groups of 7 rats each. Sepsis was induced by cecal ligation and puncture (CLP). Rats in the sepsis group were injected with equal volume of saline post-CLP. Rats from the EPO group were treated twice with EPO (immediately and 24 hours after CLP, 3750 IU/kg). The rats in the sham group were subjected to a sham surgery and injected with saline at the same time as the sepsis group. Serum samples were collected for biochemical and metabolomic analysis 72 hours post-CLP. RESULTS: Biochemistry analysis revealed that erythropoietin improved the condition of multiple organs damaged by sepsis. Fifty-eight serum metabolites, including amino acids and fatty acids, displayed significant differences between the sepsis and sham groups. EPO treatment was found to attenuate the metabolic imbalances induced by CLP. CONCLUSIONS: This study indicated that the metabolomic approach provided a comprehensive insight towards the metabolic targets of EPO treatment of sepsis.