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Traumatic brain injury (TBI) is characterized by cellular damage and inflammation in lesioned brain tissue. Ferulic acid has been shown to have a melioration effect on neurological functions. However, the active pharmacological effects and the underlying mechanisms of ferulic acid against TBI remain unclear. On the basis of network pharmacology and molecular docking methodology, this study aimed to investigate the beneficial effects of ferulic acid in treating TBI, and characterized the detailed biotargets and mechanisms of these actions. The identified core targets were validated via in silico simulation. We identified 91 overlapping targets associated with ferulic acid and TBI. In-silico simulation analysis validated the putative core targets of tumor protein p53, mitogen-activated protein kinase (MAPK) 1, and estrogen receptor 1. The Gene Ontology-enriched annotations and findings were largely associated with cell proliferation, apoptosis, and inflammation in nerve cells. Additional Kyoto Encyclopedia of Genes and Genomes enrichment analysis unmasked the pharmacological pathways of ferulic acid in treating TBI, including the MAPK signaling pathway and hypoxia-inducible factor-1 signaling pathway. Bioinformatic analyses and findings provide a new preclinical strategy for revealing the core targets and network pathways of ferulic acid in treating TBI. Moreover, some bioinformatic findings were computationally validated in silico for exhibiting the neuroprotective action of ferulic acid against TBI.

Glioblastoma stem cells (GSC) express both radial glial cell and neural crest cell (NCC)-associated genes. We report that endothelin 3 (EDN3), an essential mitogen for NCC development and migration, is highly produced by GSCs. Serum-induced proliferative differentiation rapidly decreased EDN3 production and downregulated the expression of stemness-associated genes, and reciprocally, two glioblastoma markers, EDN1 and YKL-40 transcripts, were induced. Correspondingly, patient glioblastoma tissues express low levels of EDN3 mRNA and high levels of EDN1 and YKL-40 mRNA. Blocking EDN3/EDN receptor B (EDNRB) signaling by an EDNRB antagonist (BQ788), or EDN3 RNA interference (siRNA), leads to cell apoptosis and functional impairment of tumor sphere formation and cell spreading/migration in culture and loss of tumorigenic capacity in animals. Using exogenous EDN3 as the sole mitogen in culture does not support GSC propagation, but it can rescue GSCs from undergoing cell apoptosis. Molecular analysis by gene expression profiling revealed that most genes downregulated by EDN3/EDNRB blockade were those involved in cytoskeleton organization, pause of growth and differentiation, and DNA damage response, implicating the involvement of EDN3/EDNRB signaling in maintaining GSC migration, undifferentiation, and survival. These data suggest that autocrine EDN3/EDNRB signaling is essential for maintaining GSCs. Incorporating END3/EDNRB-targeted therapies into conventional cancer treatments may have clinical implication for the prevention of tumor recurrence. Mol Cancer Res; 9(12); 1668–85. ©2011 AACR.

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The current loop is the key to realizing high- precision permanent magnet synchronous motor (PMSM) drives. However,the performance of the current loop is deteriorated by the dc and ac disturbances. To deal with the problem,this paper proposes a discrete-time repetitive control-based active disturbance rejection control (DRC-ADRC) for the current loop. The DRC is embedded in the control law of the ADRC and operates in parallel with the discrete-time extended state observer (DESO),which is the core of the ADRC. The DRC is designed to compensate for the ac disturbance,while the DESO is designed to suppress the dc disturbance. The stability and anti-disturbance capability of the studied scheme are analyzed theoretically in the discrete-time domain,which can guide the tuning of control parameters. Compared with the existing ADRC-based PMSM control schemes,the proposed DRC-ADRC can suppress the dc and ac disturbances simultaneously,thereby improving dynamic- and steady-state performance of the current loop. Finally,the effectiveness of the studied DRC-ADRC is validated on a 4.4-kW PMSM drive platform.

Radiation-induced oral mucositis is a major adverse event of radiotherapy. Severe oral mucositis may cause unwanted interruption in radiotherapy and reduce long-term survival in cancer patients receiving radiotherapy, but until now, there have been no effective options for preventing radiation-induced oral mucositis. Quercetin is a flavonoid that is widely found in food species and has anti-inflammatory, antioxidant, and anticancer activities. In this study, we investigated a new role of quercetin in preventing radiation-induced oral mucositis. Quercetin exerted preventive effects against radiation-induced oral mucositis induced by single-dose (25 Gy) ionizing radiation or fractionated ionizing radiation ( 8 Gy × 3 ) in C57BL/6 mice and maintained the proliferation ability of basal epithelial cells. Quercetin pretreatment alleviated reactive oxygen species generation, NF-κB pathway activation, and downstream proinflammatory cytokine production and reduced DNA double-strand breaks and cellular senescence induced by ionizing radiation. Quercetin also upregulated BMI-1 expression in oral epithelial cells and promoted ulcer repair. In addition, quercetin exerted similar radioprotective effects in irradiated primary cultured normal human keratinocytes, reduced reactive oxygen species generation and proinflammatory cytokine release, and promoted DNA double-strand break repair and wound healing by upregulating the expression of BMI-1, which is a polycomb group protein. Thus, quercetin can block multiple pathological processes of radiation-induced oral mucositis by targeting BMI-1 and may be a potential treatment option for preventing radiation-induced oral mucositis.

Due to the advantages of strong robustness and fast convergence, the sliding-mode observer (SMO) is considered as an effective approach for sensorless surface-mounted permanent magnet synchronous motor (SPMSM) drives. However, the inherent chattering and none finite-time convergence are still challenging problems in SMO application. To address these problems, this article proposed a high-order terminal SMO (HOTSMO) for SPMSM position estimation. First, a terminal sliding-mode surface is designed to achieve finite-time convergence of state variables. Second, a high-order sliding-mode control law is presented to achieve chattering suppression. Compared with the conventional SMO, the studied HOTSMO can achieve high estimation accuracy without sacrificing strong robustness of SMO. The effectiveness of the studied scheme is experimentally verified on a 4.4-kW ARM-based SPMSM platform.

Activated hepatic stellate cells (aHSCs) are the major source of cancer-associated fibroblasts (CAFs) in the liver. Though the crosstalk between aHSCs and colorectal cancer (CRC) cells supports liver metastasis (LM), the mechanisms remain largely unknown. Here, we investigated BMI-1, a polycomb-group protein family member, which is high-expressed in LM, in hepatic stellate cells (HSCs) activation and interacting with CRC cells while promoting colorectal cancer liver metastasis (CRLM). We found the positivity of BMI-1 expression in the liver of CRLM patients was 77.8%, and the expression level of BMI-1 continued to increase during CRLM in mice. We overexpressed BMI-1 in HSCs (LX2) by lentivirus infection, and HSCs were activated, accompanied by increased expression levels of α-SMA, Fibronectin, TGF-β1, MMPs, and IL-6. CRC cells (HCT116 and DLD1) were cultured in HSCs-conditioned medium (LX2 NC CM or LX2 BMI-1 CM), and CRC cells cultured in BMI-1 CM exhibited enhanced proliferation and migration ability, and EMT phenotype with activation of TGF-β/SMAD pathway. Besides, a TFG-βR inhibitor SB-505124 largely diminished the effect of the BMI-1 CM on Smad2/3 phosphorylation in CRC cells. A mouse subcutaneous xenotransplantation tumor model was established by co-implantation of HSCs (LX2 NC or LX2 BMI-1) and CRC cells, andBMI-1 overexpressed LX2 HSCs promoted tumor growth and epithelial-mesenchymal transition (EMT) phenotype in vivo. In conclusion, BMI-1 activates HSCs to promote the EMT of CRC cells partially through the TGF-β/SMAD pathway. These findings demonstrate BMI-1 activated HSCs might be a new target in CRC therapy.

Colorectal liver metastasis (CRLM) is the leading cause of death in patients with colorectal cancer (CRC). MiR-30b-5p can function as an oncogene or tumor suppressor in cancers, but its role in CRLM is still unknown. Here, we found that miR-30b-5p overexpression suppressed the invasion, migration, adhesion, and motility of HCT116 and LoVo cells. The expression of EMT (Zeb1, Snail, and vimentin) and adhesion-related proteins (p-paxillin and p-Src) was decreased. We validated Rap1b, a Ras family small GTPase that regulates cell adhesion and mobility, as the direct and functional target of miR-30b-5p. Rap1b overexpression rescued the aggressive characteristics of CRC cells that were inhibited by miR-30b-5p. Rap1b knockdown suppressed invasion and migration and decreased CRC cell-matrix adhesion and spreading, which was consistent with the results of miR-30b-5p overexpression. Further in vivo experiments demonstrated that miR-30b-5p overexpression inhibited CRLM, but Rap1b rescue attenuated the inhibitory effect of miR-30b-5p. In addition, miR-30b-5p was downregulated in CRC specimens, and Rap1b showed a negative correlation with miR-30b-5p expression in primary CRC and LM tissues. These results indicate that miR-30b-5p functions as a metastasis suppressor by targeting Rap1b and may provide a new target for the treatment of CRLM.

Colorectal cancer (CRC) liver metastasis (CLM) is the leading death cause of CRC patients, but there is no satisfied approach to treat CLM. Gut microbiota plays a pivotal role in CRC initiation and development. Targeting dysbiosis of the gut microbiota might open up new opportunities for CLM treatment. Here, we investigated the efficacy of sodium butyrate (NaB), a major product of gut microbial fermentation, in modulating gut microbiota in CLM mice. NaB supplement decreased mouse colon cancer CT26 cell liver metastasis in intrasplenic tumor injection model of BALB/c mice. Using 16S rRNA gene sequencing, we found altered microbiota composition in CLM mice, characterized by increases of Firmicutes and Proteobacteria. NaB beneficially changed dysbiosis in CLM mice. Functional analysis of the KEGG pathways showed that NaB changed pathways related to immune system diseases and primary immunodeficiency in CLM mice. In addition, NaB decreased T regulatory cells and increased natural killer T cells and T helper 17 cells, accordingly decreased IL-10 and increased IL-17 secretion in CLM mice liver. In conclusion, NaB beneficially modulated gut microbiota and improved host immune response in CLM mice. These findings demonstrate the therapeutic potential of NaB in CLM treatment.

Brain injury is a major complication resulted from cardiopulmonary bypass (CPB). Dexmedetomidine (DEX) has potential brain-protective effects; however, the mechanism is unclear. The aim of this study is to investigate the effect of DEX on brain injury in CPB rats and its mechanism. The levels of interleukin-6 (IL-6), interleukin-10 (IL-10), S100β, and neuron-specific enolase (NSE) were measured by enzyme-linked immunosorbent assay. The hippocampus CA1 region in rats was observed by hematoxylin-eosin staining. Western blot and quantitative real-time polymerase chain reaction were performed to detect related proteins and mRNA expressions in the hippocampus tissues. We found that after CPB, the neuron cells in hippocampus CA1 region of rats were randomly arranged, and that the levels of IL-6, IL-10, S100β, NSE, Cleaved Caspase-3, and Bax were upregulated, while Bal-2 level was downregulated. However, after DEX treatment, the neuron cells arranged in an orderly manner, and the levels of IL-6, IL-10, S100β, NSE, Cleaved Caspase-3, and Bax were downregulated, but Bal-2 level was upregulated. DEX suppressed Janus kinase 2 (JAK2)/signal transducers and activators of transcription 3 (STAT3) pathway activated by CPB, ameliorated CPB-induced brain injury in rats by reducing inflammatory response, and inhibited neuronal apoptosis. The brain-protective effect of DEX may be related to the inhibition of the activation of JAK2/STAT3 pathway.

Background This review and meta-analysis aims to evaluate the analgesic efficacy of continuous transversus abdominis plane (TAP) block compared with epidural analgesia (EA) in adults after abdominal surgery. Methods The databases PubMed, Embase and Cochrane Central Register were searched from inception to June 2019 for all available randomized controlled trials (RCTs) that evaluated the analgesic efficacy of continuous TAP block compared with EA after abdominal surgery. The weighted mean differences (WMDs) were estimates for continuous variables with a 95% confidence interval (CI) and risk ratio (RR) for dichotomous data. The pre-specified primary outcome was the dynamic pain scores 24 h postoperatively. Results Eight trials including 453 patients (TAP block:224 patients; EA: 229 patients) ultimately met the inclusion criteria and seven trials were included in the meta-analysis. Dynamic pain scores after 24 h were equivalent between TAP block and EA groups (WMD:0.44; 95% CI: 0.1 to 0.99; I2 = 91%; p = 0.11). The analysis showed a significant difference between the subgroups according to regularly administering (4 trials; WMD:-0.11; 95% CI: − 0.32 to 0.09; I2 = 0%; p = 0.28) non-steroidal anti-inflammatory drugs (NSAIDs) or not (3 trials; WMD:1.02; 95% CI: 0.09 to 1.96; I2 = 94%; p = 0.03) for adjuvant analgesics postoperatively. The measured time of the urinary catheter removal in the TAP group was significantly shorter (3 trials, WMD:-18.95, 95% CI:-25.22 to − 12.71; I2 = 0%; p 2 = 67%; p Conclusion Continuous TAP block, combined with NSAIDs, can provide non-inferior dynamic analgesia efficacy compared with EA in postoperative pain management after abdominal surgery. In addition, continuous TAP block is associated with fewer postoperative side effects.

In the traditional overmodulation, the reference of voltage loop is selected as a constant. However, it keeps the motor working in the six-step mode regardless of torque demand, resulting in current and speed harmonics. To address this problem, an operation-area-selected (OAS) overmodulation strategy is proposed for flux-weakening control of surface-mounted permanent magnet synchronous motor. The compensation of the inscribed circle reference voltage is obtained by logical judgments of two designed reference voltages in an auxiliary closed-loop. The proposed scheme can adjust the reference of voltage loop dynamically according to different working conditions, leading to reduced current and speed ripples. The simulation results verify the effectiveness of the studied scheme.

The hybrid PWM with asynchronous space vector PWM (AS-SVPWM), synchronous space vector PWM (S-SVPWM), optimized synchronous PWM (OS-PWM), and square wave is an effective approach for traction PMSM drives at low switching frequency. However, the improper transition between different PWMs would cause severe current impact and torque fluctuation. This uncontrollable state would trigger the over-current protection of inverter, even motor structure damage. To address this problem, this paper proposed a smooth-transition hybrid PWM. For the transition of different carrier frequency ratios in the same modulation, a frequency regulation is designed to adjust the reference frequency by phase angle error. Then, the flux is estimated to make the flux vector consistent by compensating the missing voltage vector between S-SVPWM and selected harmonics elimination PWM (SHEPWM). The simulations are eventually conducted for validating the proposed method.

Liver is the most common metastatic site for colorectal cancer (CRC), there is no satisfied approach to treat CRC liver metastasis (CRCLM). Here, we investigated the role of a polycomb protein BMI-1 in CRCLM. Immunohistochemical analysis showed that BMI-1 expression in liver metastases was upregulated and associated with T4 stage, invasion depth and right-sided primary tumor. Knockdown BMI-1 in high metastatic HCT116 and LOVO cells repressed the migratory/invasive phenotype and reversed epithelial-mesenchymal transition (EMT), while BMI-1 overexpression in low metastatic Ls174T and DLD1 cells enhanced invasiveness and EMT. The effects of BMI-1 in CRC cells were related to upregulating snail via AKT/GSK-3β pathway. Furthermore, knockdown BMI-1 in HCT116 and LOVO cells reduced CRCLM using experimental liver metastasis mice model. Meanwhile, BMI-1 overexpression in Ls174T and DLD1 significantly increased CRCLM. Moreover, sodium butyrate, a histone deacetylase and BMI-1 inhibitor, reduced HCT116 and LOVO liver metastasis in immunodeficient mice. Our results suggest that BMI-1 is a major regulator of CRCLM and provide a potent molecular target for CRCLM treatment.

Artemis is a key protein of NHEJ (nonhomologous end joining), which is the major pathway for the repair of IR-induced DSBs in mammalian cells. However, the expression of Artemis in tumors and the influence of silencing Artemis on tumor sensitivity to radiation have not been investigated fully. In this study, we investigated how the expression levels of Artemis may affect the treatment outcome of radiotherapy and chemotherapy in colorectal cancer cells. First, we found that the expression of Artemis is strong in some human rectal cancer samples, being higher than in adjacent normal tissues using immunohistochemical staining. We then knocked down Artemis gene in a human colorectal cancer cell line (RKO) using lentivirus-mediated siRNAs. Compared to the control RKO cells, the Artemis knockdown cells showed significantly increased sensitivity to bleomycin, etoposide, camptothecin, and IR. Induced by DNA-damaging agents, delayed DNA repair kinetics was found by the γ-H2AX foci assay, and a significantly increased cell apoptosis occurred in the Artemis knockdown RKO cells through apoptosis detection methods and Western blot. We also found that the p53/p21 signaling pathway may be involved in the apoptosis process. Taken together, our study indicates that manipulating Artemis can enhance colorectal cancer cell sensitivity to DNA-damaging agents. Therefore, Artemis can serve as a therapeutic target in rectal cancer therapy.

The continuous reaching law is generally applied to reduce the chattering in sliding mode observer for position-sensorless permanent magnet synchronous motor (PMSM) drives. However, the robustness is accordingly reduced, and there exists output error problem. To address this problem, this paper proposed an integral sliding mode observer (ISMO). Compared with the conventional observer, it can compensate the estimated back-electromotive force (EMF) error by adding the presented integral term into continuous reaching law. The experimental results show the validity of the proposed ISMO.

Radiation-induced oral mucositis (RIOM) is one of the most common side effects of radiotherapy in cancer patients, especially in almost all head and neck cancer patients. It presents as severe pain and ulceration. The development of RIOM is composed of five stages: initiation, primary damage response, signal amplification, ulceration, and healing. However, the key regulators involved in the RIOM pathogenesis remain largely unknown. In this study, we reveal a novel role of miR-200c, a member of the miR-200 family, in modulating RIOM pathogenesis. Using a mouse model mimicking RIOM, we found that the miR-200 family numbers (miR-141, miR-200a, miR-200b, and miR-200c) except miR-429 were significantly induced during the RIOM formation. Besides, in RIOM mice, miR-200c expression level was also increased dramatically in the normal human keratinocytes (NHKs) after irradiation. Knockdown of miR-200c expression with miR-200c-3p-shRNA significantly reduced senescence phenotype and enhanced cell proliferation in NHKs after irradiation. The generation of reactive oxygen species (ROS) and p47 enzyme involved in ROS production was increased after irradiation but both were markedly reduced in NHKs by miR-200c inhibition. Knockdown of miR-200c expression in NHKs increased DNA double-strand break repair after irradiation compared with control NHKs. Furthermore, miR-200c inhibition repressed the production of proinflammatory cytokines (TGF-β, TNF-α, and IL-1α) via inhibiting NF-κB and Smad2 activation in NHKs exposed to IR. Additionally, miR-200c inhibition promoted NHK migration and increased the expression of molecules that regulate epithelial to mesenchymal transition, including Snail, Vimentin, Zeb1, and Bmi-1. These results not only identify the key role of miR-200c in the pathogenesis of RIOM but also provide a novel therapeutic target to treat RIOM.

It is known that higher torque capability and less torque ripple cannot be obtained at the same time for flux-weakening control of induction motor in voltage extension region (outside the inscribed circle but within the hexagon). Therefore, a tradeoff strategy for maximum toque and suppressed torque ripple is necessary. Meanwhile, in many previous research studies, VCFS (voltage closed-loop flux-weakening scheme) based voltage extension methods rely on the reconstructed voltage, which means the control performance is affected by the accuracy of reconstruction algorithm and the stability of DC-Link voltage. In this paper, an optimized flux-weakening controller is proposed with the following features: a proper balance between torque capability and torque ripple, an enhanced DC-Link overvoltage rejection and a better torque performance for load change conditions. Simulation and experiment results verify the validity of the proposed scheme.

Scope Short-chain fatty acid sodium butyrate (NaB) is the byproduct of bacterial anaerobic fermentation of dietary fiber in the colon, and has been shown to have an antitumor effect on colorectal cancer (CRC). The miR-200 family is a key regulator of the epithelial-mesenchymal transition (EMT). We investigate the role of miR-200s expression on cell migration in NaB-treated CRC cells. Methods and results HCT116 and LOVO CRC cells treated with NaB depicted reduced cell proliferation, enhanced apoptosis, and cell cycle arrest. NaB inhibited cell migration in the wound healing and transwell assays, and in spheriod cultures while regulating EMT-related protein expression. NaB reciprocally increased miR-200s but reduced expression of their target genes (Bmi-1, Zeb1, EZH2). Cells transfected with miR-200c shRNA displayed a significant blockade of NaB-induced anti-invasive activity. Upregulation of Bmi-1 expression partially reversed the effect of NaB. In addition to inhibition of tumor growth in vivo, qRT-PCR results showed that NaB increased miR-200c/200b/492 expression in the tumor tissues. Immunohistochemistry and Western blotting results demonstrated that NaB decreased Bmi-1 expression in vivo. Conclusion NaB inhibits CRC cell migration by enhancing miR-200c expression-mediated downregulation of Bmi-1. These findings support the utility of NaB in colorectal cancer therapy.

Speed-sensorless control is applied for induction motors in an electrical transportation system and some industry applications. In multi-motor drive system, the control becomes very complicated and has not been studied extensively. In this paper, a speed-sensorless vector control model of three induction motors, which is controlled by one inverter is established. Besides, the proposed control method analyzes and designs the feedback gains to ensure the stability of the estimate system in all the range and the robustness to parameters. The validity of the model is verified by the experiment results.

The expression profiles of global miRNAs in HCC and adjacent non-tumor tissues of HBV-positive and HBV-negative patients. A heatmap of global miRNAs in HCC and non-tumor tissues obtained from 12 people (6 tumor tissues and 6 adjacent non-tumor tissues from 6 HBV-positive HCC patients; 6 tumor tissues and 6 adjacent non-tumor tissues from 6 HBV-negative HCC patients). TN = tumors of HBV- negative patients, PN = adjacent non-tumor tissues of HBV-negative patient, TP = tumors of HBV-positive patients, PP = adjacent non-tumor tissues of HBV-positive patients. Figure S2. Expression of partial target genes predicted by differentially expressed miRNAs. (A) Expression of gene TP53, CDKN1A, ERK and PTEN in 32 pairs of HBV positive adjacent non-tumor and tumor tissues. (B) Expression of gene BIRC5, CCND1, PTK2 and BCL2 in 32 pairs of HBV positive adjacent non-tumor and tumor tissues. **P

Background and Purpose Doxorubicin-based chemotherapy induces cardiotoxicity, which limits its clinical application. We previously reported the protective effects of quercetin against doxorubicin-induced hepatotoxicity. In this study, we tested the effects of quercetin on the expression of Bmi-1, a protein regulating mitochondrial function and ROS generation, as a mechanism underlying quercetin-mediated protection against doxorubicin-induced cardiotoxicity. Experimental Approach Effects of quercetin on doxorubicin-induced cardiotoxicity was evaluated using H9c2 cardiomyocytes and C57BL/6 mice. Changes in apoptosis, mitochondrial function, oxidative stress and related signalling were evaluated in H9c2 cells. Cardiac function, serum enzyme activity and reactive oxygen species (ROS) generation were measured in mice after a single injection of doxorubicin with or without quercetin pre-treatment. Key Results In H9c2 cells, quercetin reduced doxorubicin-induced apoptosis, mitochondrial dysfunction, ROS generation and DNA double-strand breaks. The quercetin-mediated protection against doxorubicin toxicity was characterized by decreased expression of Bid, p53 and oxidase (p47 and Nox1) and by increased expression of Bcl-2 and Bmi-1. Bmi-1 siRNA abolished the protective effect of quercetin against doxorubicin-induced toxicity in H9c2 cells. Furthermore, quercetin protected mice from doxorubicin-induced cardiac dysfunction that was accompanied by reduced ROS levels and lipid peroxidation, but enhanced the expression of Bmi-1 and anti-oxidative superoxide dismutase. Conclusions and Implications Our results demonstrate that quercetin decreased doxorubicin-induced cardiotoxicity in vitro and in vivo by reducing oxidative stress by up-regulation of Bmi-1 expression. The findings presented in this study have potential applications in preventing doxorubicin-induced cardiomyopathy.

DNA markers are potentially useful for plant cultivar identification. However, its use is limited due to various drawbacks, especially how to use marker information to efficiently identify cultivars. In this study, we applied a very new approach, called the manual cultivar identification diagram (MCID), to use RAPD fingerprints in distinguishing 46 strawberry cultivars after the optimization of RAPD through choosing 11 nt primers and strict screening PCR annealing temperatures. The advantage of this MCID strategy includes use of few primers in the separation of the strawberry cultivars and the real utility of cultivar identification (CID) in practical strawberry cultivar identification by the corresponding primers marked on the diagram. The MCID approach can serve strawberry cultivar identification efficiently and provide information to separate the groups of cultivars studied. The reliability and efficiency of this method was checked and verified. To the best of our knowledge, this new approach is the most efficient and reliable strategy using the power of DNA markers in identification of existing plant cultivars, identification of new plant cultivars, protection of cultivar-rights and also beneficial for the nursery industry for early identification of seedlings.

Tumors treated with fractionated doses of ionizing radiation (IR) often acquire radioresistance. Although histone deacetylase inhibitors (HDIs) have been demonstrated to sensitize intrinsic radioresistant cancer cell lines to IR, little is known on the impact of HDIs on the effects of IR in acquired radioresistant cancer cells. This study evaluates the mechanisms by which HDIs sensitize acquired radioresistant esophageal squamous cell carcinoma cells to IR. The HDIs trichostatin A and sodium butyrate were tested for the irability to sensitize acquired radioresistant KYSE-150R and radiosensitive KYSE-150 parental cells to IR. Although the HDIs induced similar levels of cytotoxicity in the KYSE-150 and the KYSE-150R cells, HDIs increased the: (i) radiosensitivity, (ii) IR-induced ROS generation, and (iii) IR-induced G2/M arrest and apoptosis of KYSE-150R cells compared with those of KYSE-150 cells. These changes were accompanied by increased p21 expression and decreased mitochondrial membrane potential. When combined with IR, HDIs inhibited Bmi-1 expression in KYSE-150R cells and their ability to repair DNA damage. The results demonstrate the potential utility of HDIs in augmenting the efficacy of fractionated radiotherapy.

Although efavirenz (EFV) is efficacious as an anti-retroviral therapy when combined with other antiretroviral drugs, it may cause adverse clinical effects, including skin and mucosal eruptions, central nervous system complications, hepatotoxicity, renal failure and pulmonary complications. The present study investigated the phenotypic alterations caused by EFV in normal human keratinocytes (NHKs) and determined the cell death pathways leading to the lack of epithelial proliferation and regeneration. Replication kinetics, cellular morphology, and protein and mRNA levels of cell cycle regulatory genes and cell death markers were compared between the EFV-exposed cells and the untreated control. EFV treatment led to cell proliferation arrest and cell death of the NHKs by inducing autophagy mediated by proteasome-dependent degradation of p53. EFV also reduced the levels of mTOR and active ERK signaling in NHKs. Chemical inhibition of p53 degradation with a proteasome inhibitor led to reduced autophagic response of NHKs to EFV. In addition, EFV triggered terminal differentiation of NHKs by inducing the expression of involucrin, filaggrin, loricrin and genes involved in cornified envelope formation. Inhibition of autophagy in the EFV-treated NHKs with 3-methylalanine reduced the levels of involucrin and the extent of cell death. Our data indicate that EFV elicits cytotoxic effects on NHKs in part through induction of autophagy and aberrant differentiation of cells.