ABSTRACT
BACKGROUND: Inflammatory, immune, and nutritional status are key factors in obstructive colorectal cancer (OCRC). This study aims to investigate the value of modified Naples prognostic score (M-NPS) in evaluating OCRC prognosis. METHODS: A total of 196 OCRC patients were retrospectively analyzed to construct M-NPS based on serum albumin (ALB), total cholesterol (CHOL), neutrophil:lymphocyte ratio (NLR), and lymphocyte:monocyte ratio (LMR), and then they were divided into three groups. The Kaplan-Meier (KM) method and Cox proportional hazard regression analysis were performed for overall survival (OS) and disease-free survival (DFS) of OCRC patients. RESULTS: Patients with high M-NPS had worse OS and DFS (P = 0.0001, P = 0.0011). Multivariate COX analysis showed that M-NPS was an independent prognostic factor for OCRC patients. Patients in the M-NPS 2 group had significantly worse OS (hazard ratio [HR] = 4.930 (95% confidence interval [95% CI], 2.217-10.964), P < 0.001) and DFS (HR = 3.508 (95% CI, 1.691-7.277), P < 0.001) than those in the 0 group. CONCLUSION: M-NPS was an independent prognostic factor for OCRC patients; it might provide a potential reference for immunonutritional intervention in patients with obstruction.
Subject(s)
Colorectal Neoplasms , Lymphocytes , Humans , Prognosis , Retrospective Studies , Disease-Free SurvivalABSTRACT
Long non-coding RNAs (lncRNAs) are important players in cancer development. LncRNA FGD5-AS1 has been reported as a potential oncogene in ovarian cancer (OC). The present paper focused on the action mechanism of FGD5-AS1 in OC. Clinical OC samples were collected for expression analyses of FGD5-AS1, RBBP6, and miR-107. The expression of FGD5-AS1, RBBP6, and miR-107 in OC cells was altered by transfection. OC cell proliferation was assessed by MTT and colony formation assays, and angiogenesis of human umbilical vein endothelial cells (HUVECs) cultured with OC cell supernatants by matrigel angiogenesis assay. The interactions among FGD5-AS1, miR-107, and RBBP6 were detected by luciferase reporter assay. FGD5-AS1 and RBBP6 were strongly expressed and miR-107 was poorly expressed in clinical OC samples and OC cell lines. FGD5-AS1 or RBBP6 overexpression in Hey and SKOV3 cells could potentiate OC cell proliferation and HUVEC angiogenesis, while FGD5-AS1 or RBBP6 knockdown in OC cells inhibited the above cellular processes. FGD5-AS1 targeted miR-107 to positively regulate RBBP6 expression. Additionally, miR-107 overexpression or RBBP6 knockdown in SKOV3 cells partially reversed the FGD5-AS1-dependent stimulation of OC cell proliferation and HUVEC angiogenesis. FGD5-AS1 may act as a promoter of OC via miR-107/RBBP6 axis.
Subject(s)
MicroRNAs , Ovarian Neoplasms , RNA, Long Noncoding , Humans , Female , MicroRNAs/genetics , MicroRNAs/metabolism , RNA, Long Noncoding/genetics , RNA, Long Noncoding/metabolism , Endothelial Cells/metabolism , Gene Expression Regulation, Neoplastic , Cell Line, Tumor , Ovarian Neoplasms/genetics , Cell Proliferation , DNA-Binding Proteins/genetics , DNA-Binding Proteins/metabolism , Ubiquitin-Protein Ligases/genetics , Ubiquitin-Protein Ligases/metabolism , Guanine Nucleotide Exchange Factors/genetics , Guanine Nucleotide Exchange Factors/metabolismABSTRACT
Hyaluronidase (HAase) is implicated in inflammation, cancer development, and allergic reaction. The detection of HAase is significantly important in clinical diagnosis and medical treatment. Herein, we propose a new principle for the development of equipment-free and label-free paper-based flow sensors based on the enzymatic hydrolysis-induced viscosity change in a stimuli-responsive polymer solution, which increases the water flow distance on the pH indicator paper. The detection of HAase is demonstrated as an example. This facile and versatile method can overcome the potential drawbacks of traditional hydrogel-based sensors, including complex preparation steps, slow response time, or low sensitivity. Moreover, it can also avoid the use of specialized instruments, labeled molecules, or functionalized nanoparticles in the sensors developed using the polymer solutions. Using this strategy, the detection of HAase is achieved with a limit of detection as low as 0.2 U/mL. Also, it works well in human urine. Additionally, the detection of tannic acid, which is an inhibitor of HAase, is also fulfilled. Overall, a simple, efficient, high-throughput, and low-cost detection method is developed for the rapid and quantitative detection of HAase and its inhibitor without the use of labeled molecules, synthetic particles, and specialized instruments. As only minimal reagents of HAase, HA, and paper are used, it is very promising in the development of commercial kits for point-of-care testing.
Subject(s)
Hyaluronoglucosaminidase , Polymers , Humans , Hyaluronic Acid/chemistry , Hyaluronoglucosaminidase/urine , Hydrolysis , ViscosityABSTRACT
BACKGROUND: Limited access to genetic information has greatly hindered our understanding of the molecular evolution, phylogeny, and differentiation time of subg. Amygdalus. This study reported complete chloroplast (cp) genome sequences of subg. Amygdalus, which further enriched the available valuable resources of complete cp genomes of higher plants and deepened our understanding of the divergence time and phylogenetic relationships of subg. Amygdalus. RESULTS: The results showed that subg. Amygdalus species exhibited a tetrad structure with sizes ranging from 157,736 bp (P. kansuensis) to 158,971 bp (P. davidiana), a pair of inverted repeat regions (IRa/IRb) that ranged from 26,137-26,467 bp, a large single-copy region that ranged from 85,757-86,608 bp, and a small single-copy region that ranged from 19,020-19,133 bp. The average GC content of the complete cp genomes in the 12 species was 36.80%. We found that the structure of the subg. Amygdalus complete cp genomes was highly conserved, and the 12 subg. Amygdalus species had an rps19 pseudogene. There was not rearrangement of the complete cp genome in the 12 subg. Amygdalus species. All 12 subg. Amygdalus species clustered into one clade based on both Bayesian inference and maximum likelihood. The divergence time analyses based on the complete cp genome sequences showed that subg. Amygdalus species diverged approximately 15.65 Mya. CONCLUSION: Our results provide data on the genomic structure of subg. Amygdalus and elucidates their phylogenetic relationships and divergence time.
Subject(s)
Genome, Chloroplast , Rosaceae , Bayes Theorem , Evolution, Molecular , PhylogenyABSTRACT
An extremely sensitive multi-order mode refractive index (RI) sensor was fabricated by coupling titanium dioxide nanograss film coated FTO conductive glass with Kretschmann prism. Both calculation and experimental studies were carried out. Theoretical analysis by employing resonant waveguide modes indicated that the maximum sensitivity could be achieved when the mode worked at the weakly-bounded condition. The experimental results showed that for p-polarized and s-polarized light, the sensor exhibited a maximum RI sensitivity of 2938.21 nm/RI unit (RIU) and 1484.39 nm/RIU in the 1st order mode, respectively. Its maximum figure of merit was as high as 77.77. The proposed sensor is promising to be applied in environmental monitoring, immune analysis, nucleic acid test, etc.
ABSTRACT
Disrupted mitochondrial function and reactive oxygen species (ROS) generation cause cellular damage and oxidative stress-induced macrophage inflammatory cell death. It remains unclear how mitochondrial dysfunction relates to inflammasome activation and pyroptotic cell death. In this study, we demonstrated that tumor necrosis factor receptor-associated factor 3 (TRAF3) regulates mitochondrial ROS production and promotes TLR agonist LPS plus nigericin (LPS/Ng)-induced inflammasome and pyroptosis in mouse primary macrophages and human monocyte THP-1 cells. Co-IP assays confirmed that TRAF3 forms a complex with TRAF2 and cIAP1 and mediates ubiquitin and degradation of Unc-51 like autophagy activating kinase 1 (ULK1). Moreover, knockdown of ULK1 in THP-1 cells significantly promoted LPS/Ng-induced inflammasome by activating caspase 1 and mature IL-1ß. Apoptosis inducing factor (AIF) translocation from mitochondrial to nuclear was observed in ULK1-deficient THP-1 cells under LPS/Ng stimulation, which mediates LPS/Ng-induced cell death in ULK1 deficient macrophages. In conclusion, this study identified a novel role of TRAF3 in regulation of ULK1 ubiquitination and inflammasome signaling and provided molecular mechanisms by which ubiquitination of ULK1 controls mitochondrial ROS production, inflammasome activity, and AIF-dependent pyroptosis.
Subject(s)
Autophagy-Related Protein-1 Homolog/metabolism , Intracellular Signaling Peptides and Proteins/metabolism , Macrophages/metabolism , TNF Receptor-Associated Factor 3/metabolism , Animals , Autophagy-Related Protein-1 Homolog/deficiency , Autophagy-Related Protein-1 Homolog/genetics , Cells, Cultured , Gene Knockdown Techniques , Humans , Inflammasomes/metabolism , Inhibitor of Apoptosis Proteins/metabolism , Intracellular Signaling Peptides and Proteins/deficiency , Intracellular Signaling Peptides and Proteins/genetics , Lipopolysaccharides/pharmacology , Macrophages/cytology , Mice , Mice, Inbred C57BL , Mice, Knockout , Models, Biological , Monocytes/cytology , Monocytes/metabolism , Nigericin/pharmacology , Pyroptosis/drug effects , Reactive Oxygen Species/metabolism , THP-1 Cells , TNF Receptor-Associated Factor 3/deficiency , TNF Receptor-Associated Factor 3/genetics , Ubiquitination/drug effectsABSTRACT
OBJECTIVE: Previous studies have investigated the pretreatment prognostic nutritional index (PNI) as a prognostic factor in patients with nasopharyngeal carcinoma (NPC); however, the results remained inconsistent. We aimed to assess the prognostic value of PNI in patients with NPC through conducting meta-analysis. Methods: Pooled hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated for low PNI of overall survival (OS), progression-free survival (PFS), distant metastasis-free survival (DMFS), loco-regional recurrence-free survival (LRFS), and cancer-specific survival (CSS). Results: Totally, eight studies involving 4299 patients were included in this meta-analysis. A low pretreatment PNI was associated with poor OS (HR = 1.86, 95% CI = 1.55-2.33, P < 0.001), DMFS (HR = 2.03, 95% CI = 1.69-2.44, P < 0.001), PFS (HR = 1.57, 95% CI = 1.31-1.90, P < 0.001), and CSS (HR = 2.29, 95% CI = 1.54-3.42, P < 0.001). The subgroup analysis showed that low PNI remained a significant factor for poor OS, DMFS, and PFS irrespective of treatment, country, and cutoff value of PNI. In addition, low PNI was correlated to female gender (OR = 1.35, 95% CI = 1.12-1.62, P = 0.002), older age (OR = 1.75, 95% CI = 1.17-2.62, P = 0.007), and T3-T4 stage (OR = 1.27, 95% CI = 1.06-1.53, P = 0.011). Conclusions: A low PNI was associated with poor survival outcomes in patients with NPC. Moreover, PNI could serve as an index to help guide clinical management for older patients.
Subject(s)
Nasopharyngeal Neoplasms , Nutrition Assessment , Aged , Female , Humans , Nasopharyngeal Carcinoma , Prognosis , Proportional Hazards ModelsABSTRACT
Long-chain noncoding RNAs (lncRNAs) are involved in a wide range of biological and pathological processes in ovarian cancer. The purpose of this study was to investigate the effects of EZH2-mediated ABHD11-AS1 promoter on the pathogenesis of ovarian cancer. The expression levels of EZH2, ABHD11-AS1 and miR-133a-3p were examined in ovarian cancer tissues using reverse transcription-quantitative PCR. Cell proliferation was evaluated using cell counting kit 8 assay, and cell invasion/migration was determined using a Transwell assay. Cell apoptosis was evaluated using flow cytometry. Dual luciferase assay was performed to confirm the interaction between ABHD11-AS1 and miR-133a-3p. The binding site of H3K27me3 on ABHD11-AS1 promoter was confirmed by ChIP. The expression of ABHD11-AS1 was significantly upregulated in ovarian cancer samples, and its levels were closely associated with lymph node metastasis, tumor stage and 3-year survival rate. Furthermore, interference of ABHD11-AS1 suppressed the proliferation, migration and invasion of ovarian cancer cells, while cell apoptosis was promoted. Additionally, miR-133a-3p could be a novel target of ABHD11-AS1, and EZH2-mediated H3K27me3 protein might bind to ABHD11-AS1 promoter directly. Moreover, rescue experiments indicated that the effects caused by ABHD11-AS1 knockdown on the malignant characteristics of ovarian cancer cells were notably enhanced by miR-133a-3p mimics, whereas the influences on cell growth and metastasis induced by overexpressed ABHD11-AS1 were abrogated by the restoration of miR-133a-3p expression. In summary, EZH2-mediated enrichment of H3K27me3 on ABHD11-AS1 promoter could regulate the progression of ovarian cancer via miR-133a-3p. Therefore, EZH2/ABHD11-AS1/miR-133a-3p axis might be a putative candidate for targeted treatment of ovarian cancer.
Subject(s)
Enhancer of Zeste Homolog 2 Protein/metabolism , Ovarian Neoplasms/pathology , RNA, Long Noncoding/metabolism , Serine Proteases/metabolism , Adult , Aged , Apoptosis , Cell Line, Tumor , Cell Proliferation , Female , Humans , Lymphatic Metastasis/pathology , MicroRNAs , Middle Aged , Neoplasm Staging , Ovarian Neoplasms/mortalityABSTRACT
The wide application of xylose in the food, beverage, and pharmaceutical industries, as well as in the booming field of biorefinery, raises the demand for a rapid, accurate, and real-time xylose-sensing technique to rival the conventional methods based on chromatography, spectroscopy, and electrochemical analysis using non-specific enzymes or abiotic catalysts. Herein, a hybrid system comprising polyethylene glycerol swing-arm-tethered NAD+ and xylose dehydrogenase (XDH), coupled with platinum nanoparticles deposited on carbon nanotubes (PtNPs@MWCNTs), was constructed for the real-time sensing of xylose. The use of the PtNPs@MWCNTs composite enhanced the sensitivity of the electric response and reduced the oxidation potential of NADH significantly. Further, the NAD+ immobilization allowed an increase in its microenvironment concentration and facilitated cofactor regeneration. The screen-printed electrode cast with the hybrid system showed a wide xylose detection range of 0.5 to 10 mM or 3.33 to 66.61 mM, and a low detection limit of 0.01 mM or 3.33 mM (S/N = 3), when connected to a potentiostat or a homemade portable biosensor, respectively. The biosensor also exhibited excellent working stability as it retained 82% of its initial performance after 30 days. The analysis of various xylose-containing samples further revealed the merits of our portable xylose biosensor in real-time sensing, including its rapid response, inexpensive instrumentation, and high selectivity, suggesting its great potential in practical applications.
Subject(s)
Biosensing Techniques , Metal Nanoparticles , Nanotubes, Carbon , Electrochemical Techniques , Electrodes , NAD , Oxidoreductases , Platinum , XyloseABSTRACT
AIM: The aim of the present study was to evaluate the efficacy and safety of lurasidone for the treatment of Chinese schizophrenic patients. METHODS: Hospitalized schizophrenia patients aged 18-65 were randomized to 6 weeks of double-blind, double-dummy, flexible-dose treatment with lurasidone (40 or 80 mg/day) or risperidone (2, 4 or 6 mg/day). Efficacy was evaluated using a non-inferiority comparison of lurasidone relative to risperidone based on week 6 change in the Positive and Negative Syndrome Scale (PANSS) total score. Safety assessments included adverse events, clinical laboratory measures, and electrocardiograms. RESULTS: Four hundred and forty-four patients were screened to obtain an intent-to-treat sample of 384 patients, of whom 54 patients discontinued treatment prior to 6 weeks. Lurasidone met the criteria for non-inferiority versus risperidone on the PANSS total score. Adjusted mean (SE) change at week 6 on the PANSS total score was -31.2 (1.0) and -34.9 (1.0) in the lurasidone and risperidone group, respectively. The mean difference score was 3.7, and the upper boundary of the 95%-confidence interval (1.0-6.3) was less than the prespecified margin of 7.0. No clinically meaningful between-treatment group differences were evident on secondary efficacy measures, including PANSS positive, PANSS negative, Clinical Global Impression scale - Severity, and Calgary Depression Scale for Schizophrenia scales. The incidence of adverse events was lower for lurasidone vs risperidone for extrapyramidal symptoms (17.0% vs 38.2%), akathisia (7.2% vs 13.6%), prolactin increase (3.1% vs 14.1%), and weight increase (0.5% vs 5.2%). CONCLUSION: Lurasidone was found to be non-inferior to risperidone on the primary endpoint with minimal effects on weight, metabolic parameters, or prolactin levels.
Subject(s)
Antipsychotic Agents/pharmacology , Lurasidone Hydrochloride/pharmacology , Outcome Assessment, Health Care , Risperidone/pharmacology , Schizophrenia/drug therapy , Adult , Antipsychotic Agents/administration & dosage , Antipsychotic Agents/adverse effects , China , Double-Blind Method , Female , Humans , Lurasidone Hydrochloride/administration & dosage , Lurasidone Hydrochloride/adverse effects , Male , Middle Aged , Risperidone/administration & dosage , Risperidone/adverse effects , Young AdultABSTRACT
Low light is a type of abiotic stress that seriously affects plant growth and production efficiency. We investigated the response mechanisms of summer maize to low light by measuring the changes in endogenous hormones in the grains and during grain filling in summer maize at different light intensities to provide a theoretical basis for the production and management of summer maize under light stress. We applied different light treatments in a field experiment as follows: S, shading from tassel stage (VT) to maturity stage (R6); CK, natural lighting in the field; and L, increasing light from VT to R6. The shading level was 60%, and the maximum illumination intensity of the increasing light treatment on cloudy days was 1600-1800 µmol m-2 s-1. Compared with the control, shading significantly increased the grain abscisic acid (ABA) content at 5-20 days after pollination and decreased the indole acetic acid (IAA), zeatin riboside (ZR), and gibberellin (GA) contents (P < 0.05). The grain-filling rate decreased under shading conditions. Meanwhile, the grain volume, grain weight, and yield all decreased; the yields in 2013 and 2014 decreased by 61 and 60%, respectively. The grain IAA, ZR, and GA contents were increased by increasing light. The grain ABA content at 5-20 days after pollination did not significantly differ from that of CK (P < 0.05). After 20 days after pollination, the ABA content decreased, the grain-filling rate and the filling duration increased, and the yield increased. However, shading after anthesis increased the grain ABA content and reduced the IAA, ZR, and GA contents. Grain growth and development were inhibited, and the yield decreased. The grain ABA content decreased; the IAA, ZR, and GA contents increased; and the yield increased after increasing light. The results indicate that different light intensities regulated the levels of grains endogenous hormones, which influenced the grain-filling rate and duration, and consequently, regulated grain weight and yield.
Subject(s)
Edible Grain/radiation effects , Gibberellins/metabolism , Indoleacetic Acids/metabolism , Isopentenyladenosine/analogs & derivatives , Light , Plant Growth Regulators/metabolism , Zea mays/radiation effects , Edible Grain/growth & development , Edible Grain/metabolism , Isopentenyladenosine/metabolism , Seasons , Zea mays/growth & development , Zea mays/metabolismABSTRACT
OBJECTIVE: This study examined the pattern of adjunctive antidepressant use in schizophrenia patients and its demographic and clinical correlates in a nationwide survey in China. METHODS: Fourteen thousand and thirteen patients in 45 Chinese psychiatric hospitals or centers were interviewed (4,486 in 2002, 5,288 in 2006, and 4,239 in 2012). Patients' sociodemographic and clinical characteristics were recorded using a standardized protocol and data collection procedure. Chi-square test, independent-samples t test, Mann-Whitney U test, and multiple logistic regression analysis were used in data analyses. RESULTS: Antidepressant use was found in 5.2% of the study population with 4.6% in 2002, 4.3% in 2006, and 6.9% in 2012, respectively. A significant increase in use from 2006 to 2012 was found (p < .001). Multiple logistic regression analyses in the whole population revealed that patients receiving adjunctive antidepressants were more likely to be outpatients in tertiary referral centers (level-III hospitals) and who had an earlier age of onset, less severe global illness, but more depressive symptoms. They were less likely to receive first-generation antipsychotics but more likely to receive benzodiazepines (R2 = 0.255, p < .001). CONCLUSIONS: Despite an increasing trend, the frequency of antidepressant use in schizophrenia in China was considerably lower than in Western countries. The benefits and risks associated with concomitant use of antidepressants in schizophrenia need to be studied further.
Subject(s)
Antidepressive Agents/administration & dosage , Antipsychotic Agents/administration & dosage , Benzodiazepines/administration & dosage , Schizophrenia/drug therapy , Schizophrenia/epidemiology , Surveys and Questionnaires , Adult , China/epidemiology , Cross-Sectional Studies , Drug Therapy, Combination , Female , Humans , Male , Middle Aged , Young AdultABSTRACT
We propose a novel, highly sensitive refractive index (RI) sensor by means of combining the Kretschmann prism with a TiO2 nanowire array and do not use a metallic layer in the Kretschmann configuration. Its RI sensing performance was investigated through measuring different concentrations of sodium chloride solution. Experimental results showed that, with increasing RI of liquid, the resonant wavelength in the reflectance spectrum redshifted gradually in the visible light range. There was a very good linear relationship between resonant wavelength and RI in the range of 1.3330 to 1.3546. More importantly, in contrast to the surface plasmon resonance (SPR) sensor, the interferometric sensors showed higher sensitivity to the external RI. In the case of the transverse magnetic mode, the RI sensitivity is up to 320,700.93 a.u./RIU (refractive index unit) by expression of light intensity, which is 9.55 times that of the SPR sensor. As for the transverse electric mode, it achieves 4371.76 nm/RIU by expression of the resonant wavelength, which is increased by a factor of 1.4 in comparison with the SPR sensor. Moreover, the experimental results have favorable repeatability. A TiO2 nanowire array sensor has also other advantages, such as easy manufacturing, low cost, and in situ determination, etc. To our knowledge, this fact is reported for the first time. It has great potential applications in the field of biological and chemical sensing.
ABSTRACT
OBJECTIVE: Little is known about electroconvulsive therapy (ECT) use in the treatment of schizophrenia in China. This study examined the frequency of ECT use, its trend between 2006 and 2012, and its independent demographic and clinical correlates in a nationwide survey in China. METHODS: A total of 5162 inpatients in 45 Chinese psychiatric hospitals/centers were interviewed (2696 in 2006 and 2466 in 2012). Patients' sociodemographic and clinical characteristics were recorded using a standardized protocol and data collection procedure. RESULTS: Electroconvulsive therapy was used in 6.1% of the whole sample; 4.7% in 2006 and 7.7% in 2012 (P < 0.001) with wide interprovince variations. Multiple logistic regression analyses of the whole sample revealed that patients receiving ECT were more likely to be women, receive second-generation antipsychotics, treated in tertiary referral centers (level III hospitals), had a shorter illness duration, and more positive and depressive symptoms (R = 0.181; P < 0.001). CONCLUSIONS: Electroconvulsive therapy for schizophrenia has increased between 2006 and 2012 in China. Its percentage was higher than the figures reported in most other countries. Reasons for the substantial variations in the frequency of ECT across different provinces in China require further investigations.
Subject(s)
Electroconvulsive Therapy/statistics & numerical data , Schizophrenia/therapy , Adolescent , Adult , Aged , Aged, 80 and over , Antipsychotic Agents/therapeutic use , Asian People , China , Combined Modality Therapy , Cross-Sectional Studies , Depression/etiology , Depression/psychology , Depression/therapy , Female , Health Care Surveys , Hospitals, Psychiatric/statistics & numerical data , Humans , Inpatients , Male , Middle Aged , Schizophrenic Psychology , Sex Factors , Socioeconomic Factors , Young AdultABSTRACT
The aim of the study was to screen active components of Radix Bupleuri (a traditional Chinese herb) and discover novel anti-schizophrenic candidate drugs using human neuroblastoma SH-SY5Y cells. SH-SY5Y cells were used for preparation of the stationary phase in the cell membrane chromatography model. Retention components by the SH-SY5Y/CMC model were collected and then analyzed by GC/MS under the optimized conditions in offline conditions. After investigating the suitability and reliability of the SH-SY5Y/CMC method using amisulpride and haloperidol as standard compounds, this method was applied to screening active components from the extracts of Radix Bupleuri. Retention components of SH-SY5Y/CMC model were saikosaponin A, saikosaponin B1, saikosaponin B2, saikosaponin C and saikosaponin D, which were identified by the GC/MS method. In vitro pharmacological trials-MTT, saikosaponin B1, saikosaponin B2 and saikosaponin C could protect SY5Y cells. The protective effects of saikosaponin B1 and saikosaponin C were concentration dependent. Saikosaponin A and saikosaponin D inhibited cell viability at concentrations >30 µg/mL (p < 0.05). Via SH-SY5Y/CMC method and SH-SY5Y MTT trial, we rapidly detected target components from Radix Bupleuri, accurately identified them and determined their different effects on SH-SY5Y cells. Saikosaponin B1, saikosaponin B2 and saikosaponin C may be anti-schizophrenic candidate drugs.
Subject(s)
Chromatography, Liquid/methods , Drug Discovery/methods , Drugs, Chinese Herbal/analysis , Drugs, Chinese Herbal/pharmacokinetics , Neuroblastoma , Cell Line, Tumor , Cell Membrane/metabolism , Drugs, Chinese Herbal/chemistry , Drugs, Chinese Herbal/metabolism , Gas Chromatography-Mass Spectrometry , Humans , Medicine, Chinese Traditional , Oleanolic Acid/analogs & derivatives , Plants, Medicinal/chemistry , Plants, Medicinal/metabolism , Psychotropic Drugs , Reproducibility of Results , SaponinsABSTRACT
The response of a novel long-period fiber grating (LPFG) with a period of 180 µm to a surrounding refractive index (RI) was investigated. The results displayed that, with the increase in RI of the surrounding media of cladding glass in the grating region, the resonant peak located at 1336.4 nm in the transmission spectrum gradually shifts towards a shorter wavelength, while the resonant peak located at 1618 nm gradually shifted towards a longer wavelength. Moreover, the resonant peak at 1618 nm is much more sensitive to the surrounding RI than that of the one at 1336.4 nm. Compared with the conventional LPFG and other types of wavelength-interrogated RI sensors, such as ring resonators, surface plasmon resonance sensors, and Fabry-Perot interferometric sensors, this novel LPFG possesses a higher sensitivity, which achieved 10,792.45 nm/RIU (RI unit) over a RI range of 1.4436-1.4489.
ABSTRACT
Aberrant activation of Wnt signaling pathway is crucial for the onset and progression of human colorectal cancer (CRC). Owing to the persistent dependence on Wnt signaling for growth and survival, inhibition of this pathway is an attractive approach for new therapies. 11α, 12α-epoxyleukamenin E (EPLE) is a novel ent-kaurane diterpenoid that we previously isolated from Salvia cavaleriei, exhibiting antitumor activities in a variety of cancer cells. Herein, we found that whereas sparing normal human colon mucosal epithelial cells, EPLE selectively inhibited the proliferation of CRC cell lines as well as primary tumor cells. Mechanistically, we demonstrated EPLE exerted its function through suppressing Wnt signaling pathway, as evidenced by EPLE-mediated downregulation of Wnt target genes such as c-Myc, Axin2 and Survivin. Consistently, luciferase reporter assays showed that the EPLE directly blocked Wnt/ß-catenin-mediated transcriptional activation. In combination of co-immunoprecipitation and protein structure-based analyses, we determined that the EPLE entered the interface of ß-catenin/TCF4 complexes and blocked their interaction that is required for ß-catenin-mediated transcriptional activation. Moreover, overexpression of ß-catenin alleviated the cytotoxicity of EPLE in CRC cells, supporting Wnt signaling is a major and specific target of EPLE. Combined treatments of EPLE and 5-fluorouracil, the first-line chemotherapy for CRC patients, achieved a synergistic effect. More importantly, EPLE hampered tumor development in a CRC xenograft model. Our data thus establish EPLE as a novel inhibitor of Wnt signaling that holds great promise as a potential candidate for further preclinical evaluation for CRC treatments.
Subject(s)
Antineoplastic Agents, Phytogenic/pharmacology , Colorectal Neoplasms/drug therapy , Colorectal Neoplasms/metabolism , Diterpenes, Kaurane/pharmacology , Wnt Signaling Pathway/drug effects , beta Catenin/metabolism , Animals , Apoptosis/drug effects , Basic Helix-Loop-Helix Leucine Zipper Transcription Factors/metabolism , Cell Proliferation/drug effects , Colorectal Neoplasms/genetics , Colorectal Neoplasms/pathology , Diterpenes, Kaurane/chemistry , Drug Screening Assays, Antitumor , Gene Expression Regulation, Neoplastic/drug effects , HCT116 Cells/drug effects , Humans , Mice, Inbred BALB C , Molecular Docking Simulation , Molecular Targeted Therapy , Transcription Factor 4 , Transcription Factors/metabolism , Tumor Cells, Cultured , Xenograft Model Antitumor Assays , beta Catenin/antagonists & inhibitorsABSTRACT
OBJECTIVE: This study examined the use, demographic and clinical correlates of antipsychotic polypharmacy (APP) and its associations with treatment satisfaction and quality of life (QOL) in schizophrenia patients in China. METHOD: A total of 4239 patients in 45 nationwide Chinese psychiatric hospitals/centers were interviewed in 2012 in the third cross-sectional study, with the first two having been conducted in 2002 and 2006. Patients' socio-demographic and clinical characteristics, including psychopathology, side effects, satisfaction with treatment and QOL, were recorded using a standardized protocol and data collection procedure. RESULTS: The proportion of APP prescriptions in 2012 was 34.2%, which was significantly higher than the frequency of APP in 2002 (26.1%) and 2006 (26.4%) (p<0.001). Of patients on APP, 91.1% received two antipsychotics, 8.6% received three and 0.3% received four or more antipsychotics. Multiple logistic regression analyses revealed that compared to those on antipsychotic monotherapy, patients on APP and their families had lower satisfaction with treatment, had higher QOL in the mental domain, younger age of onset, more side effects, higher doses of antipsychotics and were more likely to receive first-generation antipsychotics and less likely to receive benzodiazepines (total R (2)=0.31, p<0.001). CONCLUSIONS: APP was found in about one in three schizophrenia patients. The prevalence of APP seems to have been increasing since 2002. Considering the increased frequency of drug-induced side effects and the patients' and their relatives' dissatisfaction with antipsychotic treatment, further examination of the rationale and appropriateness of APP and its alternatives is warranted.
Subject(s)
Antipsychotic Agents/therapeutic use , Patient Satisfaction/statistics & numerical data , Polypharmacy , Quality of Life/psychology , Schizophrenia/drug therapy , Adult , China/epidemiology , Female , Humans , Male , Middle Aged , Schizophrenia/epidemiologyABSTRACT
The tumor suppressor gene Smad4 has been localized to chromosome 18q21.1 and is a member of the Smad family that mediates the transforming growth factor ß signaling pathway suppressing epithelial cell growth. However, variable expression of Smad4 messenger RNA (mRNA) has been reported, with a loss in some cancers and increased expression in others. The aim of the present study was to investigate the Smad4 mRNA expression in prostate cancer tissues and adjacent noncancerous tissues and its potential relevance to clinicopathological variables and prognosis. The expression change of Smad4 mRNA was detected by using real-time quantitative reverse transcriptase-polymerase chain reaction analysis. The data showed that the Smad4 mRNA expression level in prostate cancer tissues was significantly lower than those in noncancerous tissues. The results indicated that the low expression of Smad4 mRNA in prostate cancer was associated with lymph node metastasis, preoperative prostate-specific antigen (PSA), and Gleason score. Kaplan-Meier survival analysis showed that patients with high Smad4 mRNA expression have longer biochemical recurrence-free survival time compared to patients with low Smad4 mRNA expression. Multivariate analysis revealed that Smad4 mRNA expression was an independent predictor of biochemical recurrence-free survival. Our results emphasize that Smad4 mRNA can be used as a predictive biomarker.
Subject(s)
Prostatic Neoplasms/genetics , RNA, Messenger/analysis , Smad4 Protein/genetics , Adult , Aged , Biomarkers, Tumor , Humans , Lymphatic Metastasis , Male , Middle Aged , Neoplasm Recurrence, Local , Prognosis , Prostatic Neoplasms/mortality , Prostatic Neoplasms/pathologyABSTRACT
The aim of this study was to evaluate reliability and psychiatric clinical value of quantum resonance spectrometer (QRS) in detection of affective disorders. We studied 1014 patients with schizophrenia and 248 patients with mood disorders (including 93 patients with major depression). Affective disorder symptoms of the same subjects obtained from the QRS test and psychiatrists' diagnoses were compared. In addition, three affective disorder symptoms of renumbered 93 patients with major depression were discriminated using QRS. Kappa values of affective disorder detection and diagnosis were more than 0.69 in all three symptoms of schizophrenia and more than 0.65 in six of seven symptoms of mood disorder. The same consistency could also be seen in receiver operating characteristic curve area under the curve. In the discriminated analysis, sensitivity, specificity, positive predictive value, and negative predictive value of hypothymia, anxiety, and irritability detected using QRS are more than 0.66 compared with psychiatrists' diagnoses. QRS could be an objective identification and diagnosis instrument and might promote psychiatric clinical diagnosis.