Comparison of demineralized bone matrix with different cycling crushing times in posterolateral fusion model of athymic rats.

Decalcified bone matrix (DBM) is a widely used alternative material for bone transplantation. In the DBM production process, an effective particle size and the highest utilization rate of raw materials can be achieved only through multiple high-speed circulating comminution. The rat posterolateral lumbar fusion model (PLF) is the most mature small animal model for the initial evaluation of the efficacy of graft materials for bone regeneration and spinal fusion. To evaluate the differences in the in vivo osteogenic effects of DBM pulverization through 1, 5, 9, and 14 high-speed cycles, sixty athymic rats were divided into six groups: single cycling crushing (CC1), 5 cycles of crushing (CC5), 9 cycles of crushing (CC9), 13 cycles of crushing (CC13), autogenous bone graft (ABG) and negative control (NC). Posterolateral lumbar fusion was performed. Six weeks after surgery, the bilateral lumbar fusion of athymic rats was evaluated through manual palpation, X-ray, micro-CT and histological sections. Rank data were tested by the rank-sum test, and nonparametric data were tested by the Kruskal‒Wallis H test. The manual palpation and X-ray results showed that the fusion rate did not significantly differ between the CC1, CC5, CC9, CC13 and ABG groups. However, cavities appeared in CC9 and CC13 on the micro-CT image. The bone mass (BV/TV) of CC1, CC5, CC9 and CC13 was better than that of the ABG group, while almost no osteogenesis was observed in the NC group. Histologically, there was no obvious difference between the four groups except that the CC9 group and CC13 group had more fibrous tissues in the new bone. In conclusion, DMB with different cycling crushing times has no obvious difference in fusion rate of PLF, but it is slightly better than the ABG group.

Thioparib inhibits homologous recombination repair, activates the type I IFN response, and overcomes olaparib resistance.

Poly-ADP-ribose polymerase (PARP) inhibitors (PARPi) have shown great promise for treating BRCA-deficient tumors. However, over 40% of BRCA-deficient patients fail to respond to PARPi. Here, we report that thioparib, a next-generation PARPi with high affinity against multiple PARPs, including PARP1, PARP2, and PARP7, displays high antitumor activities against PARPi-sensitive and -resistant cells with homologous recombination (HR) deficiency both in vitro and in vivo. Thioparib treatment elicited PARP1-dependent DNA damage and replication stress, causing S-phase arrest and apoptosis. Conversely, thioparib strongly inhibited HR-mediated DNA repair while increasing RAD51 foci formation. Notably, the on-target inhibition of PARP7 by thioparib-activated STING/TBK1-dependent phosphorylation of STAT1, triggered a strong induction of type I interferons (IFNs), and resulted in tumor growth retardation in an immunocompetent mouse model. However, the inhibitory effect of thioparib on tumor growth was more pronounced in PARP1 knockout mice, suggesting that a specific PARP7 inhibitor, rather than a pan inhibitor such as thioparib, would be more relevant for clinical applications. Finally, genome-scale CRISPR screening identified PARP1 and MCRS1 as genes capable of modulating thioparib sensitivity. Taken together, thioparib, a next-generation PARPi acting on both DNA damage response and antitumor immunity, serves as a therapeutic potential for treating hyperactive HR tumors, including those resistant to earlier-generation PARPi.

Repeated treatments of Capan-1 cells with PARP1 and Chk1 inhibitors promote drug resistance, migration and invasion.

PARP1 and Chk1 inhibitors have been shown to be synergistic in different cancer models in relatively short time treatment modes. However, the consequences of long-term/repeated treatments with the combinations in cancer models remain unclear. In this study, the synergistic cytotoxicity of their combinations in 8 tumor cell lines was confirmed in a 7-day exposure mode. Then, pancreatic Capan-1 cells were repeatedly treated with the PARP1 inhibitor olaparib, the Chk1 inhibitor rabusertib or their combination for 211-214 days, during which the changes in drug sensitivity were monitored at a 35-day interval. Unexpectedly, among the 3 treatment modes, the combination treatments resulted in the highest-grade resistance to Chk1 (~14.6 fold) and PARP1 (~420.2 fold) inhibitors, respectively. Consistently, G2/M arrest and apoptosis decreased significantly in the resulting resistant variants exposed to olaparib. All 3 resistant variants also unexpectedly obtained enhanced migratory and invasive capabilities. Moreover, the combination treatments resulted in increased migration and invasion than olaparib alone. The expression of 124 genes changed significantly in all the resistant variants. We further demonstrate that activating CXCL3-ERK1/2 signaling might contribute to the enhanced migratory capabilities rather than the acquired drug resistance. Our findings indicate that repeated treatments with the rabusertib/olaparib combination result in increased drug resistance and a more aggressive cell phenotype than those with either single agent, providing new clues for future clinical anticancer tests of PARP1 and Chk1 inhibitor combinations.

[Transurethral columnar balloon dilation of the prostate for benign prostatic hyperplasia].

OBJECTIVE: To study the clinical effect of transurethral columnar balloon dilation of the prostate (TUCBDP) in the treatment of BPH and introduce the experience with the surgical procedure. METHODS: We retrospectively analyzed the clinical data on 265 cases of BPH treated by TUCBDP from August 2016 to August 2019. RESULTS: Operations were successfully completed in all the cases, with the mean operation time of (24.67 ± 7.6) min and the average intraoperative blood loss of (26.5 ± 21.4) ml, and all the patients had urinary patency after removal of the catheter. Follow-up examinations every 3 months after surgery showed significant improvement over the baseline in IPSS, quality of life score (QOL), maximum urinary flow rate (Qmax), postvoid residual urine (PVR) and other indicators (P < 0.05). Forty-five of the patients with sexual life exhibited no significant difference from the baseline in IIEF-5 and erectile hardness scale (EHS) scores (P > 0.05). Postoperative complications were observed in 53 cases (20%), including 28 cases of transient urinary incontinence (10.56%), 3 cases of hemorrhage (1.13%), 11 cases of urinary tract infection (4.15%), 1 case of urethral stricture (0.37%), and 8 cases of acute urinary retention (3.01%), which were all improved after regular treatment, with no occurrence of true urinary incontinence. Retrograde ejaculation occurred in 2 (4.45%) of the 45 patients with sexual life. CONCLUSIONS: Transurethral columnar balloon dilation of the prostate, with the advantages of short operation time and less intraoperative bleeding, has a significant short-term clinical effect in the treatment of BPH, particularly suitable for the elderly and those who want to retain the sexual function. Intraoperative localization of the protrusion may significantly influence the outcome of surgery, which deserves strengthened studies. Special attention should be paid to the incidence of postoperative transient urinary incontinence.

Genome-Wide Identification and Evolutionary Analysis of Argonaute Genes in Hexaploid Bread Wheat.

Argonaute (AGO) proteins play a pivotal role in plant growth and development as the core components of RNA-induced silencing complex (RISC). However, no systematic characterization of AGO genes in wheat has been reported to date. In this study, a total number of 69 TaAGO genes in the hexaploid bread wheat (Triticum aestivum cv. Chinese Spring) genome, divided into 10 subfamilies, were identified. Compared to all wheat genes, TaAGOs showed a significantly lower evolutionary rate, which is consistent with their high conservation in eukaryotes. However, the homoeolog retention was remarkably higher than the average, implying the nonredundant biological importance of TaAGO genes in bread wheat. Further homoeologous gene expression bias analyses revealed that TaAGOs may have undergone neofunctionalization after polyploidization and duplication through the divergent expression of homoeologous gene copies, to provide new opportunities for the generation of adaptive traits. Moreover, quantitative real-time polymerase chain reaction (qRT-PCR) analyses indicated that TaAGO gene expression was involved in response to heat, drought, and salt stresses. Our results would provide a theoretical basis for future studies on the biological functions of TaAGO genes in wheat and other gramineous species.

ELK1-induced upregulation lncRNA LINC02381 accelerates the osteosarcoma tumorigenesis through targeting CDCA4 via sponging miR-503-5p.

Long noncoding RNAs (lncRNAs) have been identified as functional modulators in human tumors. The purpose of our study was to determine the expressing trend, clinical significance and functions of lncRNA LINC02381(LINC02381) in osteosarcoma. We observed that the expression of LINC02381 and cell division cycle-associated protein 4 (CDCA4) were distinctly increased in osteosarcoma specimens and cells, while miR-503-5p expression was decreased. Additionally, ETS transcription factor ELK1 (ELK1) could bind directly to the LINC02381 promoter region and activate its transcription. Clinical assays revealed that high LINC02381 was associated with advanced clinical progress and poor clinical outcome. Functionally, knockdown of LINC02381 suppressed the proliferation, migration and invasion of osteosarcoma cells. What's more, LINC02381 could down-regulate CDCA4 via sponging miR-503-5p, and there existed a negative correlation between LINC02381 expression and miR-503-5p expression in 92 osteosarcoma samples. Rescue experiments proved the carcinogenic role of LINC02381/miR-503-5p/CDCA4 axis in osteosarcoma progression. Overall, our data illustrated how LINC02381 played an oncogenic role in osteosarcoma and might offer a novel diagnostic and prognostic biomarker and potential therapeutic target for osteosarcoma.

Site-directed mutagenesis identified the key active site residues of alcohol acyltransferase PpAAT1 responsible for aroma biosynthesis in peach fruits.

The aroma of peach fruit is predominantly determined by the accumulation of γ-decalactone and ester compounds. A previous study showed that the biosynthesis of these aroma compounds in peach fruit is catalyzed by PpAAT1, an alcohol acyltransferase. In this work, we investigated the key active site residues responsible for γ-decalactone and ester biosynthesis. A total of 14 candidate amino acid residues possibly involved in internal esterification and 9 candidate amino acid residues possibly involved in esterification of PpAAT1 were assessed via site-directed mutagenesis. Analyses of the in vitro enzyme activities of PpAAT1 and its site-directed mutant proteins (PpAAT1-SMs) with different amino acid residue mutations as well as the contents of γ-decalactone in transgenic tobacco leaves and peach fruits transiently expressing PpAAT1 and PpAAT1-SMs revealed that site-directed mutation of H165 in the conserved HxxxD motif led to lost enzymatic activity of PpAAT1 in both internal esterification and its reactions, whereas mutation of the key amino acid residue D376 led to the total loss of γ-decalactone biosynthesis activity of PpAAT1. Mutations of 9 and 7 other amino acid residues also dramatically affected the enzymatic activity of PpAAT1 in the internal esterification and esterification reactions, respectively. Our findings provide a biochemical foundation for the mechanical biosynthesis of γ-decalactone and ester compounds catalyzed by PpAAT1 in peach fruits, which could be used to guide the molecular breeding of new peach species with more favorable aromas for consumers.

[Inhibitory effect of 3-bromopyruvate on the proliferation, migration and invasive ability of prostate cancer PC-3 cells].

OBJECTIVE: To observe the effects of the glycolysis inhibitor 3-bromopyruvate (3-BrPA) on the proliferation, migration and invasive ability of prostate cancer PC-3 cells in vitro and explore the underlying mechanisms. METHODS: We cultured prostate cancer PC-3 cells in vitro and treated them with 3-BrPA at different concentrations for 24, 48 and 72 hours. Then we observed the morphological changes of the PC-3 cells under the inverted microscope. We also detected the effects of different concentrations of 3-BrPA on the proliferation, migration and invasive ability of the cells by MTT, wound-scratch and Transwell assays and determined the protein expressions of glucose transporter-1 (GLUT1), matrix metalloproteinase-14 (MMP-14), MMP-9 and MMP-2 in the PC-3 cells by Western blot. RESULTS: More significant changes were observed in the morphology of the PC-3 cells with increased concentrations of 3-BrPA. MTT assay showed that the inhibition rate of the proliferation of the PC-3 cells was remarkably increased in a concentration- and time-dependent manner (P<0.01). Wound-scratch and Transwell assays exhibited significant decreases in the scratch healing rate and number of invasive cells after 24 hours of intervention with 3-BrPA at 25, 50 and 100 µmol/L, even more significant after treated for 48 hours at the concentrations of 50 and 100 µmol/L (P<0.01). The expressions of the GLUT1, MMP-14, MMP-9 and MMP-2 proteins were markedly down-regulated after 3-BrPA intervention in comparison with those in the control group (P<0.01). CONCLUSIONS: The glycolysis inhibitor 3-BrPA reduces the proliferation, migration and invasive ability of prostate cancer PC-3 cells by down-regulating the expressions of the related proteins GLUT1, MMP-14, MMP-9 and MMP-2.

Modified grade 4 osteotomy for the correction of post-traumatic thoracolumbar kyphosis: A retrospective study of 42 patients.

Many surgical procedures have been developed for the treatment of post-traumatic thoracolumbar kyphosis. But there is a significant controversy over the ideal management. The aim of this study was to illustrate the technique of modified grade 4 osteotomy for the treatment of post-traumatic thoracolumbar kyphosis and to evaluate clinical and radiographic results of patients treated with this technique.From May 2013 to May 2018, 42 consecutive patients experiencing post-traumatic thoracolumbar kyphosis underwent the technique of modified grade 4 osteotomy, and their medical records were retrospectively collected. Preoperative and postoperative sagittal Cobb angle, visual analog scale (VAS), Oswestry disability index (ODI), and American Spinal Injury Association (ASIA) were recorded. The average follow-up period was 29.7 ±â€Š14.2 months.The operation time was 185.5 ±â€Š26.8 minutes, the intraoperative blood loss was 545.2 ±â€Š150.1 mL. The Cobb angles decreased from 38.5 ±â€Š3.8 degree preoperatively to 4.2 ±â€Š2.6 degree 2 weeks after surgery (P < .001). The VAS reduced from 6.5 ±â€Š1.1 preoperatively to 1.5 ±â€Š0.9 at final follow-up (P < .001), and the ODI reduced from 59.5 ±â€Š15.7 preoperatively to 15.9 ±â€Š5.8 at final follow-up (P < .001). Kyphotic deformity was successfully corrected and bony fusion was achieved in all patients. Neurologic function of 7 cases was improved to various degrees.Modified grade 4 osteotomy, upper disc, and upper one-third to half of pedicle are resected, is an effective treatment option for post-traumatic thoracolumbar kyphosis. However, the long-term clinical effect still needs further studies.

Modified extrapedicular kyphoplasty for the treatment of lumbar compression fracture: Case report and technical note.

RATIONALE: Traditionally, transpedicular approach was used in the treatment of osteoporotic lumbar compression fracture. In order to avoid the risks of pedicle disruption and spinal canal intrusion, extrapedicular approache has been attempted. The aim of the article is to present the modified extrapedicular kyphoplasty technique for the treatment of osteoporotic lumbar compression fracture. PATIENT CONCERNS: A 62-year-old woman suffered from severe low back pain after an accidental fall 10 days ago. Low back pain was obvious when turning over and getting out of bed. It was not relieved after bed rest and conservative treatment. Visual analog scale (VAS) of low back pain was 8 points and Oswestry disability index score was 80%. DIAGNOSIS: Magnetic resonance imaging showed osteoporotic vertebral compression fracture of L2 and L3. INTERVENTIONS: We performed modified extrapedicular kyphoplasty for the patient. The technique has a standardized operating procedure. The puncture point of skin is determined according to preoperative computer tomography and X-ray. The puncture point of vertebral body is located at the outer upper edge of the pedicle. The puncture direction is from the upper edge of the pedicle to the lower edge of the contralateral pedicle. OUTCOMES: The operation time was 20 minutes. The intraoperative blood loss was 5 mL. The amount of bone cement was 4 mL in L2 and 5 mL in L3. VAS of low back pain was 2 points in 1 day after surgery. Preoperative symptoms were significantly improved. LESSONS: Modified extrapedicular kyphoplasty is a safe and effective technique for the treatment of osteoporotic lumbar compression fracture, which should be promoted and applied.

Knockdown of GAS5 Inhibits Atherosclerosis Progression via Reducing EZH2-Mediated ABCA1 Transcription in ApoE-/- Mice.

Atherosclerosis is a disorder occurring in the large arteries and the primary cause of heart diseases. Accumulating evidence has implicated long non-coding RNAs (lncRNAs) in atherosclerosis. This study aims to clarify the potential effects of lncRNA growth arrest-specific 5 (GAS5) on cholesterol reverse-transport and intracellular lipid accumulation in atherosclerosis. GAS5 was mainly localized in the nucleus and highly expressed in the human monocytic leukemia cell line (THP-1) macrophage-derived foam cells in coronary heart disease. Overexpressed GAS5 increased THP-1 macrophage lipid accumulation. Of note, GAS5 can inhibit the expression of ATP-binding cassette transporter A1 (ABCA1) by binding to enhancer of zeste homolog 2 (EZH2). Overexpression of EZH2 reduced cholesterol efflux and ABCA1 expression. EZH2 promoted triple methylation of lysine 27 (H3K27) in the ABCA1 promoter region. Subjected to overexpressed GAS5, overexpressed EZH2, or downregulated ABCA1, the Apolipoprotein E (ApoE)-/- mice with atherosclerosis showed increased total cholesterol (TC), free cholesterol (FC), cholesterol ester (CE), low-density lipoprotein (LDL) levels, aortic plaque, and lipid accumulation, accompanied by reduced high-density lipoprotein (HDL) level and cholesterol outflow. Altogether, knockdown of GAS5 can potentially promote reverse-transportation of cholesterol and inhibit intracellular lipid accumulation, ultimately preventing the progression of atherosclerosis via reducing EZH2-mediated transcriptional inhibition of ABCA1 by histone methylation.

Retraction Note: Decreased microRNA-452 expression and its prognostic significance in human osteosarcoma.

The Editor-in-Chief is retracting this article [1] due to overlap with previously published articles [2, 3]. Fig. 3D "miR-452 mimics" is very similar to Fig. 3D "si-BANCR" in article [2]. Fig. 3D "miRNC" is very similar to Fig. 3E "si-NC" in article [2] and to Fig. 3E "miR-224 mimics" in article [3].

Relations between the Structural α-Relaxation and the Johari-Goldstein ß-Relaxation in Two Monohydroxyl Alcohols: 1-Propanol and 5-Methyl-2-hexanol.

The hydrogen-bonded monohydroxyl alcohols form a large class of glass formers studied more than one hundred years, and still the structure and dynamics have continued to be a research problem. Recent advance suggests a hydrogen-bonded transient supramolecular structure, which is the origin of the Debye relaxation dominating the dielectric loss spectra of many monohydroxyl alcohols. Obscured by the slower Debye relaxation, the structural α-relaxation is either not resolved or showing up as a shoulder and the supposedly universal Johari-Goldstein (JG) ß-relaxation is not always observed. Thus, properties of the α-relaxation and the JG ß-relaxation as well as the strong connection between the two relaxations generally observed in other classes of glass formers are not commonly known in the monohydroxyl alcohols. Notwithstanding, extremely broadband dielectric relaxation and high-precision light scattering experiments published recently have resolved the α-relaxation and a secondary relaxation in two archetypal monohydroxyl alcohols, 1-propanol and 5-methyl-2-hexanol (5M2H) by Gabriel et al. We analyzed their experimental data and applied the Coupling Model to show that the secondary relaxations in 1-propanol and 5M2H are JG ß-relaxations with strong connection to the α-relaxation. The result is novel because it is not known before whether the secondary relaxations of these two monohydroxyl alcohols are JG ß-relaxation involving the entire molecule or are intramolecular relaxations. On the basis of this conclusion, we predict that the secondary relaxation is pressure-dependent and the ratio τß( T, P)/τα( T, P) is invariant to variations of P and T, whereas τα( T, P) is maintained constant and provided that the frequency dispersion of the α-relaxation is also constant. The prediction is compared with the dielectric data of 5M2H at elevated pressures. On the basis of the identification of monohydroxyl alcohols as short-chain polymeric liquids by others, an explanation of the stronger T and P dependences of τα( T, P) than the Debye relaxation time τD( T, P) is given.

Involvement of oxytocin and GABA in consolation behavior elicited by socially defeated individuals in mandarin voles.

Consolation, which entails comforting contact directed toward a distressed party, is a common empathetic response in humans and other species with advanced cognition. Here, using the social defeat paradigm, we provide empirical evidence that highly social and monogamous mandarin voles (Microtus mandarinus) increased grooming toward a socially defeated partner but not toward a partner who underwent only separation. This selective behavioral response existed in both males and females. Accompanied with these behavioral changes, c-Fos expression was elevated in many of the brain regions relevant for emotional processing, such as the anterior cingulate cortex (ACC), bed nucleus of the stria terminalis, paraventricular nucleus (PVN), basal/basolateral and central nucleus of the amygdala, and lateral habenular nucleus in both sexes; in the medial preoptic area, the increase in c-Fos expression was found only in females, whereas in the medial nucleus of the amygdala, this increase was found only in males. In particular, the GAD67/c-Fos and oxytocin (OT)/c-Fos colocalization rates were elevated in the ACC and PVN, indicating selective activation of GABA and OT neurons in these regions. The "stressed" pairs matched their anxiety-like behaviors in the open-field test, and their plasma corticosterone levels correlated well with each other, suggesting an empathy-based mechanism. This partner-directed grooming was blocked by pretreatment with an OT receptor antagonist or a GABAA receptor antagonist in the ACC but not by a V1a subtype vasopressin receptor antagonist. We conclude that consolation behavior can be elicited by the social defeat paradigm in mandarin voles, and this behavior may be involved in a coordinated network of emotion-related brain structures, which differs slightly between the sexes. We also found that the endogenous OT and the GABA systems within the ACC are essential for consolation behavior in mandarin voles.

Hyperin Enhances the Sensitivity of HCT8/VCR Colon Cancer Cell Line to Vincristine by Down-Regulating P-Glycoprotein.

BACKGROUND: Long-term chemotherapy reduces the sensitivity of colon cancer cells to chemotherapeutics like vincristine (VCR) and lead to drug resistance, which has become a major barrier for colon cancer treatment. Calcium antagonists are used as clinical tumor multidrug resistance reversal agents to regulate the P-glycoprotein (P-gp) level and block efflux pump function now, but they have significant side effects. Hyperin as active component with low toxicity in traditional Chinese medicine has calcium antagonistic effect. Thus, the purpose of this study was to evaluate the inhibitory effect of hyperin on the growth of HCT8/VCR colon cancer cell line (vincristine-resistant) and analyze the enhancing effect of hyperin on the sensitivity of cancer cells to VCR and its relationship to the expression and function of P-gp. METHODS: Using the MTT method, we investigated the influence of hyperin, VCR alone, and hyperin plus VCR on the growth of HCT8/VCR cells. Western blot analysis was employed to detect the expression of P-gp, and flow cytometry was used to evaluate P-gp function by detecting the fluorescence intensity of intracellular Rho123. RESULTS: The inhibitory effect of hyperin at the dose of 12.5 µM on HCT8/VCR cell growth was not enhanced as time progressed and no significant inhibitory effect was found for VCR-treated cells at the dose of 2 µM. But the inhibition of cell growth was observed after the combined treatment of hyperin (12.5 µM) and VCR (2 µM). P-gp expression levels in HCT8/VCR cells treated with hyperin plus VCR were markedly lower than the levels in control cells and those treated with VCR. In addition, the intensity of Rho123 fluorescence of HCT8/VCR cells treated with hyperin plus VCR or hyperin alone was significantly higher than intensity observed in control cells and those treated with VCR alone. CONCLUSIONS: Hyperin synergistically augments the growth inhibitory effect of vincristine. The underlying mechanism most probably involves down-regulation of P-gp expression and inhibiting the function of the P-gp pump in HCT8/VCR cells.

Inhibition of autophagy attenuated curcumol-induced apoptosis in MG-63 human osteosarcoma cells via Janus kinase signaling pathway.

The present study aimed to investigate whether autophagy was triggered by curcumol and to explore the association between autophagy and apoptosis of MG-63 cells and the underlying mechanism. MG-63 cells were cultured in vitro. An MTT assay was performed to evaluate the proliferation inhibition of the MG-63 osteosarcoma cell line by curcumol. Fluorescein isothiocyanate-Annexin V/propidium iodide staining flow cytometry was performed to analyze the apoptotic rate of cells. The morphological alterations of cell nuclei were evaluated by Hoechst 33258 viable cell staining. The effects of autophagy in cells was investigated by green fluorescent protein (GFP)-light chain 3 (LC3) transfection and using a fluorescence microscope. The expression levels of LC3II, LC3I and cleaved caspase-3 and Janus kinase (JNK) signaling pathway activation were determined by western blot analysis. Cell proliferation was inhibited by curcumol in a dose- and time-dependent manner. Curcumol induced apoptosis by the caspase-dependent signaling pathway in MG-63 cells. The present study demonstrated that curcumol could induce autophagy of MG-63 cells, which was evaluated by transmission electron microscopy. Compared with the curcumol treatment alone group, the GFP-LC3-transfected green fluorescence plasmids and the LC3II/LC3I levels in cells of the curcumol and chloroquine (CQ) treatment group were upregulated, and the apoptotic ratio was downregulated following pretreatment with autophagy inhibitor CQ for 1 h. Furthermore, curcumol treatment induced phosphorylation of the JNK signaling pathway. Of note, pretreatment with the JNK inhibitor, SP600125, decreased the rates of autophagy and apoptosis, suggesting a crucial role served by the JNK signaling pathway in the activation of autophagy by curcumol. Taken together, the results of the present study suggested that activation of the JNK signaling pathway was involved in curcumol-induced autophagy. Curcumol is a novel drug for chemotherapeutic combination therapy. Curcumol demonstrated potential antitumor activities in MG-63 cells and may be used as a novel effective reagent in the treatment of osteosarcoma.

Interaction effects among IFN-γ+874, IL-2-330, IL-10-1082, IL-10-592 and IL-4-589 polymorphisms on the clinical progression of subjects infected with hepatitis B virus and/or hepatitis C virus: a retrospective nested case-control study.

BACKGROUND: The natural outcomes of hepatitis B virus (HBV) and/or hepatitis C virus (HCV) infections vary considerably among individuals The infection may heal naturally, or patients may succumb to chronic liver diseases, including chronic hepatitis, liver cirrhosis and hepatocellular carcinoma. The mechanism is not fully understood. OBJECTIVES: To evaluate the interaction among four single nucleotide polymorphisms (SNPs) and their influence on different clinical outcomes. METHODS: 277 individuals infected with HBV and/or HCV, including 81 patients with chronic hepatitis B and C, 122 asymptomatic HBV and/or HCV carriers and 74 controls who cleared HBV and HCV spontaneously, were involved in this study. The SNPs of four genes (rs2069762/-330 G/T of IL-2, rs2430561/+874A>T of IFN-γ, rs1800896/-1082G>A and rs1800872/-592C>A of IL-10 and rs2243250/-589C>T of IL-4) were analysed using restriction fragment length polymorphism-polymerase chain reaction or sequence-specific primer PCR. The gene-gene interactions were assessed using the multifactor-dimensionality reduction method. RESULTS: Interleukin (IL)-10-592 AC and IL-4-589 CC/CT showed a synergistic effect on liver inflammatory injury (p<0.01), whereas interferon (IFN)-γ+874 AA and IL-2-330 TT had a synergistic impact (p<0.05). IFN-γ+874 AA and IL-10-1082 AA had an antagonistic effect (p<0.01) on the clinical progression, including asymptomatic HBV and HCV carriers and chronic hepatitis. IL-2-330 TT and IL-10-1082 AA synergistically influenced the clinical outcome (p<0.05). IFN-γ+874 AA, IL-2-330 TT and IL-10-1082 AA interactively affected the clinical outcome including asymptomatic HBV and HCV carriers and chronic hepatitis (p<0.05). CONCLUSIONS: Interactions among polymorphisms of IFN-γ+874 AA, IL-2-330 TT, IL-10-1082 AA, IL10--592 AC and IL-4-589 CC/CT significantly influenced the clinical progression of the subjects with HBV and/or HCV infection.

Gastrodia elata attenuates inflammatory response by inhibiting the NF-κB pathway in rheumatoid arthritis fibroblast-like synoviocytes.

Gastrodia elata (GE), which belongs to the Orchidaceae family, was found to possess anti-inflammatory activity. However, the effect of GE on inflammatory response in rheumatoid arthritis fibroblast-like synoviocytes (RA-FLS) remains largely unknown. Thus, the aim of this study was to investigate the effects of GE on tumor necrosis factor-α (TNF-α)-induced inflammatory response in RA-FLS and the underlying molecular mechanism was also explored. Our results demonstrated that GE significantly attenuated TNF-α-induced IL-6 and IL-8 production in RA-FLS. GE also inhibited TNF-α-induced MMP-3 and MMP-13 expression in RA-FLS. Furthermore, pretreatment with GE significantly attenuated TNF-α-induced the expression of p-p65 and IκBα degradation in RA-FLS. In conclusion, this study demonstrated for the first time that GE attenuated inflammatory response by inhibiting the NF-κB pathway signaling in RA-FLS. Thus, GE might have a therapeutic potential towards the treatment of RA.

Smoking and Its Relation to Metabolic Status among Chinese Adults: Analysis of a Nationwide Survey

OBJECTIVE: To update the estimated prevalence rates of smoking and examine major metabolic diseases associated with smoking status in Chinese adults. METHODS: Using a complex, multistage, probability sampling design, we recruited a nationally representative sample of 98,658 Chinese adults aged ⋝18 years in 2010. Information on current, former, never, and passive smoking status was obtained using a standard questionnaire. All estimates were weighted to represent the overall Chinese adult population. RESULTS: The estimated proportion of current smokers was 28.3% for Chinese adults aged ⋝18 years. The corresponding values of former and passive smokers were 5.1% and 21.4%, respectively. Additionally, former smokers were found to have a less favorable metabolic risk profile among all categories of smoking status in both men and women. The prevalence of metabolic diseases such as diabetes and hypertension also increased with a greater number of smoking pack-years in men. CONCLUSION: The prevalences of current smoking and passive smoking remain high in Chinese adults.

[Dynamic changes of TGF-α and TGF-ß1 in rats with liver cirrhosis induced by multiple pathogenic factors].

OBJECTIVE: To explore the dynamic changes of transforming growth factor-α (TGF-α) and transforming growth factor-ß1 (TGF-ß1) of liver cirrhosis induced by multiple pathogenic factors in rats. METHODS: Animals in the cirrhosis group were fed a mixture of maize flour, lard, cholesterol and alcohol plus subcutaneously injection with carbon tetrachloride (CCl4), the CCl4(0.5 ml/100 g · w) was injected at the first day of experiment and the 40% CCl4oil solution (0.3 ml /100 g · w) was injected at an interval of three days. The thirty-six male SD rats were randomly divided into liver cirrhosis group of the 4th, 6th and 8 th week, and normal control group of the 4th, 6th and 8th week. The contents of alanine transferase (ALT), endotoxin, tumor necrosis factor-α (TNF-α) and homocysteine (Hcy) in plasma were evaluated. Histopathological changes of the liver were observed under microscope with the staining of HE. The expressions of TGF-α and TGF-ß1 were analyzed by the method of immunohistochemistry. RESULTS: Compared with the corresponding normal control group, the levels of ALT, endotoxin, TNF-α and Hcy in plasma were gradually significantly increased in liver cirrhosis group of the 4th, 6th and 8th week (P < 0.05); the expression of TGF-α in the liver tissues was significantly increased at the 4th week (P < 0.05); the expression of TGF-ß1 in the liver tissues was gradually significantly increased in every model group (P < 0.05). CONCLUSION: In the formation process of cirrhosis, the expression of TGF-α was increased in liver of cirrhosis group at the 4th week, and later it was suppressed; the expression of TGF-ß1 was continuously increased. The characteristic dynamic changes of TGF-α and TGF-ß1 might be related to sustained endotoxemia, the high level of TNF-α and hyperhomocysteinemia.