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1.
J Invertebr Pathol ; 203: 108059, 2024 Mar.
Article En | MEDLINE | ID: mdl-38199517

Beauveria bassiana, a well-known filamentous biocontrol fungus, is the main pathogen of numerous field and forest pests. To explore the potential factors involved in the fungal pathogenicity, Bbhox2, an important and conserved functional transcription factor containing homeodomain was carried out by functional analysis. Homologous recombination was used to disrupt the Bbhox2 gene in B.bassiana. The conidia yield of the deletant fungal strain was significantly reduced. The conidial germination was faster, and stress tolerance to Congo red and high osmotic agents were decreased compared with that in the wildtype. Additionally, ΔBbhox2 showed a dramatic reduction in virulence no matter in topical inoculations or in intra-hemolymph injections against Galleria mellonella larvae, which is likely due to the failure of appressorium formation and the defect in producing hyphal body. These results indicate that the Bbhox2 gene markedly contributes to conidiation and pathogenicity in B. bassiana.


Beauveria , Moths , Animals , Virulence , Beauveria/genetics , Moths/microbiology , Larva/microbiology , Spores, Fungal/genetics , Fungal Proteins/genetics
2.
Article En | MEDLINE | ID: mdl-36293796

There is increasing concern about the adverse impact of exposure to microplastic, as an emerging pollutant, on wild organisms, and particularly on organisms co-exposed to microplastic and other environmental contaminants. It has been widely reported that the combination of microplastics and heavy metals showed obvious toxicity to organisms in terms their growth and development. The present study was performed to determine the impact of binary metal mixtures of cadmium (Cd) and polystyrene microplastic (PS-microplastic) on Tigriopus japonicus, a typical marine model organism, using a titration design. Increasing concentrations of PS-microplastic (2 µg/L, 20 µg/L, and 200 µg/L) were titrated against a constant concentration of Cd (15.2 µg/L). The results showed no significant impact of exposure to this dose of Cd or co-exposure to Cd and the lowest dose of PS-microplastic examined (2 µg/L). However, the feeding rate, filtration rate, oxygen consumption rate, and hatching number declined significantly in T. japonicus co-exposed to Cd and higher concentrations of PS-microplastic (20 µg/L and 200 µg/L) (p < 0.05). Furthermore, the development of F1 larvae from nauplius stage (N) to adult stage (A) was markedly delayed when co-exposed to Cd and higher doses of PS-microplastic (20 and 200 µg/L), and the effects persisted to the F2 larval stage. Interestingly, the present titration design did not affect the sex ratio or number of oocysts in either the F1 or F2 generation. These results indicated that the current marine environmental concentrations of Cd and microplastic are safe for wild organisms. Further studies are required to address the knowledge gap regarding toxicological effects at the cellular and molecular levels.


Copepoda , Metals, Heavy , Water Pollutants, Chemical , Animals , Microplastics/toxicity , Cadmium/toxicity , Plastics/toxicity , Polystyrenes , Water Pollutants, Chemical/toxicity , Metals, Heavy/toxicity , Aquatic Organisms
3.
Genes (Basel) ; 13(5)2022 05 17.
Article En | MEDLINE | ID: mdl-35627280

Pomegranate (Punica granatum L.) is a kind of fruit with significant economic, ecological and health values. AP2/ERF transcription factors belong to a large group of factors mainly found in plants and play key roles in plant growth and development. However, AP2/ERF genes in pomegranate and their implication in development and postharvest preservation have been little described. In this study, 116 PgAP2/ERF genes in pomegranate were identified and renamed based on their chromosomal distributions. Phylogenetic relationship with genes from other species, structures, duplications, annotations, cis-elements in promoter sequences, and protein-protein interaction networks among PgAP2/ERF proteins were comprehensively explored. Expression analysis revealed several PgAP2/ERFs associated with the phenotypes of pomegranate seed hardness, including PgAP2/ERF5, PgAP2/ERF36, PgAP2/ERF58, and PgAP2/ERF86. Subsequent analysis indicated that many differentially expressed PgAP2/ERF genes are potentially important regulators of pomegranate fruit development. Furthermore, expression of more than one-half of PgAP2/ERFs was repressed in 'Tunisian soft seed' pomegranate fruit under low-temperature cold storage. The results showed that 1-MCP implicated in promoting postharvest preservation of 'Tunisian soft seed' pomegranate upregulated the PgAP2/ERF4, PgAP2/ERF15, PgAP2/ERF26, PgAP2/ERF30, PgAP2/ERF35 and PgAP2/ERF45 genes compared to those under low-temperature cold storage. This indicates that these genes are important candidate genes involved in pomegranate postharvest preservation. In summary, the findings of the present study provide an important basis for characterizing the PgAP2/ERF family genes and provide information on the candidate genes involved in pomegranate fruit development and postharvest preservation.


Fruit , Pomegranate , Fruit/genetics , Fruit/metabolism , Gene Expression Regulation, Plant , Genome, Plant , Phylogeny , Pomegranate/genetics
4.
Article En | MEDLINE | ID: mdl-34769760

Heavy metal pollution has become a great concern due to its adverse effects on the ecological system and human health. The present study investigated the concentrations of six common heavy metals (Cr, Cu, Zn, As, Cd, and Pb) in the Tianjin coastal area to understand their distribution, enrichment, sources, and potential ecological risk levels, focusing on the main contributors. The results showed that the concentration of Cu was high in the surface seawater (6.89 µg/L for the average), while Cd was the main contaminating metal in the sediments, with an average concentration of 0.77 mg/kg. The potential ecological risk index (RI) implied that the heavy metals in the sediments could cause considerable ecological risk, and Cd was the major contributor to ecological risk in this area. In particular, the field investigation showed that Cd contamination occurred as a result of anthropogenic activities, including port transportation, mariculture, and metal fabrication along the coastal area. Therefore, it is necessary to control Cd contamination in the future to improve the quality of the marine environment in Bohai Bay.


Metals, Heavy , Water Pollutants, Chemical , China , Environmental Monitoring , Geologic Sediments , Humans , Metals, Heavy/analysis , Risk Assessment , Seawater , Water Pollutants, Chemical/analysis
5.
J Invertebr Pathol ; 184: 107639, 2021 09.
Article En | MEDLINE | ID: mdl-34139258

Beauveria bassiana is an important entomopathogenic fungus used to control a variety of insect pests. Conidia are the infective propagules of the fungus. However, some important factors that influence conidiation are still to be investigated. In this study, a mutant with decreased conidial production and hyphal growth was identified from a random T-DNA insertional library of B. bassiana. The corresponding gene (Bbthi) for this mutation encodes a putative thiazole synthase. Thiazole and pyrimidine are structural components of thiamine (vitamin B1), which is an essential nutrient for all forms of life. Disruption of Bbthi, Bbpyr, a putative pyrimidine synthetic gene, or both in B. bassiana results in a significant decrease of thiamine content. Loss of Bbthi and Bbpyr function significantly decreased the conidial production and hyphal growth, as well as disrupted the integrity of conidial cell wall. However, the defect of Bbpyr and Bbthi does not decrease the virulence of B. bassiana. Our results indicate the importance of thiamine biosynthesis in conidiation of B. bassiana, and provide useful information to produce conidia of entomopathogenic fungi for biocontrol of insect pests.


Beauveria/genetics , Fungal Proteins/genetics , Genes, Fungal/physiology , Spores, Fungal/physiology , Thiamine/biosynthesis , Beauveria/metabolism , Cell Wall/physiology , Fungal Proteins/metabolism , Thiamine/genetics
6.
Cell Death Dis ; 11(11): 969, 2020 11 11.
Article En | MEDLINE | ID: mdl-33177491

N6-methyladenosine (m6A) modification can alter gene expression by regulating RNA splicing, stability, translocation, and translation. Emerging evidence shows that m6A modification plays an important role in cancer development and progression, including cell proliferation, migration and invasion, cell apoptosis, autophagy, and drug resistance. Until now, the role of m6A modification mediated autophagy in cancer drug resistance is still unclear. In this study, we found that m6A methyltransferase METTL3-mediated autophagy played an important role in reversing gefitinib resistance by ß-elemene in non-small cell lung cancer (NSCLC) cells. Mechanistically, in vitro and in vivo studies indicated that ß-elemene could reverse gefitinib resistance in NSCLC cells by inhibiting cell autophagy process in a manner of chloroquine. ß-elemene inhibited the autophagy flux by preventing autophagic lysosome acidification, resulting in increasing expression of SQSTM1 and LC3B-II. Moreover, both ß-elemene and gefitinib decreased the level of m6A methylation of gefitinib resistance cells. METTL3 was higher expressed in lung adenocarcinoma tissues than that of paired normal tissues, and was involved in the gefitinib resistance of NSCLC cells. Furthermore, METTL3 positively regulated autophagy by increasing the critical genes of autophagy pathway such as ATG5 and ATG7. In conclusion, our study unveiled the mechanism of METTL3-mediated autophagy in reversing gefitinib resistance of NSCLC cells by ß-elemene, which shed light on providing potential molecular-therapy target and clinical-treatment method in NSCLC patients with gefitinib resistance.


Antineoplastic Combined Chemotherapy Protocols/pharmacology , Carcinoma, Non-Small-Cell Lung/drug therapy , Gefitinib/pharmacology , Lung Neoplasms/drug therapy , Methyltransferases/metabolism , Sesquiterpenes/pharmacology , Animals , Autophagy/drug effects , Carcinoma, Non-Small-Cell Lung/metabolism , Carcinoma, Non-Small-Cell Lung/pathology , Cell Line, Tumor , Cell Proliferation/drug effects , Drug Resistance, Neoplasm , Drug Synergism , Female , Gefitinib/administration & dosage , Humans , Lung Neoplasms/metabolism , Lung Neoplasms/pathology , Methyltransferases/chemistry , Mice , Mice, Inbred BALB C , Mice, Nude , Models, Molecular , Random Allocation , Sesquiterpenes/administration & dosage , Xenograft Model Antitumor Assays
7.
Cancer Biol Med ; 17(3): 676-692, 2020 08 15.
Article En | MEDLINE | ID: mdl-32944399

Objective: In this study, we aimed to develop an amino-terminal fragment (ATF) peptide-targeted liposome carrying ß-elemene (ATF24-PEG-Lipo-ß-E) for targeted delivery into urokinase plasminogen activator receptor-overexpressing bladder cancer cells combined with cisplatin (DDP) for bladder cancer treatment. Methods: The liposomes were prepared by ethanol injection and high-pressure microjet homogenization. The liposomes were characterized, and the drug content, entrapment efficiency, and in vitro release were studied. The targeting efficiency was investigated using confocal microscopy, ultra-fast liquid chromatography, and an orthotopic bladder cancer model. The effects of ATF24-PEG-Lipo-ß-E combined with DDP on cell viability and proliferation were evaluated by a Cell Counting Kit-8 (CCK-8) assay, a colony formation assay, and cell apoptosis and cell cycle analyses. The anticancer effects were evaluated in a KU-19-19 bladder cancer xenograft model. Results: ATF24-PEG-Lipo-ß-E had small and uniform sizes (˜79 nm), high drug loading capacity (˜5.24 mg/mL), high entrapment efficiency (98.37 ± 0.95%), and exhibited sustained drug release behavior. ATF24-PEG-Lipo-ß-E had better targeting efficiency and higher cytotoxicity than polyethylene glycol (PEG)ylated ß-elemene liposomes (PEG-Lipo-ß-E). DDP, combined with ATF24-PEG-Lipo-ß-E, exerted a synergistic effect on cellular apoptosis and cell arrest at the G2/M phase, and these effects were dependent on the caspase-dependent pathway and Cdc25C/Cdc2/cyclin B1 pathways. Furthermore, the in vivo antitumor activity showed that the targeted liposomes effectively inhibited the growth of tumors, using the combined strategy. Conclusions: The present study provided an effective strategy for the targeted delivery of ß-elemene (ß-E) to bladder cancer, and a combined strategy for bladder cancer treatment.


Antineoplastic Agents, Phytogenic/pharmacology , Cisplatin/pharmacology , Sesquiterpenes/pharmacology , Urinary Bladder Neoplasms/drug therapy , Animals , Apoptosis/drug effects , CDC2 Protein Kinase , Cell Cycle/drug effects , Cell Line, Tumor , Cell Proliferation/drug effects , Cell Survival/drug effects , Cyclin B1/metabolism , Female , G2 Phase Cell Cycle Checkpoints/drug effects , Humans , Liposomes/metabolism , Mice , Mice, Nude , Urinary Bladder Neoplasms/metabolism , Urinary Bladder Neoplasms/pathology , Xenograft Model Antitumor Assays
8.
Medicine (Baltimore) ; 99(32): e20683, 2020 Aug 07.
Article En | MEDLINE | ID: mdl-32769861

BACKGROUND: In China, traditional Chinese medicine (TCM) is an increasingly important part of the treatment of non-small cell lung cancer (NSCLC), which usually includes a combination of prescription and syndrome differentiation. Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) have been proven to be the first-line drugs for the treatment of advanced EGFR mutation-positive NSCLC. In China, EGFR-TKIs are used in combination with traditional Chinese medicines to reduce side effects and/or enhance effectiveness. Nevertheless, the relationship between TCMs and EGFR-TKIs remain unclear. This meta-review aimed to explore the clinical evidence of TCMs combined with EGFR-TKIs in the treatment of NSCLC. METHODS: Related studies were found by searching the databases of EMBASE, PubMed, Web of Science, MEDLINE, Cochrane library database, China Academic Journals (CNKI), Wanfang and Weipu. This study included 57 randomized controlled trials, all of these were processed by Stata software (version 12.0). In the study, all the materials are published articles, patient anonymity and informed consent and ethics Approval/Institutional review board are not necessary. RESULTS: This study demonstrated that the objective response rate was higher in the group of TCMs plus EGFR-TKIs than in the group of EGFR-TKIs alone (risk ratios 1.39, 95% confidence intervals [1.29, 1.50]). Further research of specific herbal medicines showed that Huangqi, Baishu, Fuling, Gancao, Maidong, Baihuashecao, Shashen, Dangshen and Renshen, had significant higher contributions to results. CONCLUSION: TCMs may improve the efficacy of EGFR-TKIs in the treatment of NSCLC.


Carcinoma, Non-Small-Cell Lung/therapy , ErbB Receptors/antagonists & inhibitors , Lung Neoplasms/therapy , Medicine, Chinese Traditional , Protein Kinase Inhibitors/therapeutic use , Combined Modality Therapy , Humans
9.
Signal Transduct Target Ther ; 5(1): 51, 2020 05 08.
Article En | MEDLINE | ID: mdl-32382060

Ferroptosis, a novel form of programmed cell death, is characterized by iron-dependent lipid peroxidation and has been shown to be involved in multiple diseases, including cancer. Stimulating ferroptosis in cancer cells may be a potential strategy for cancer therapy. Therefore, ferroptosis-inducing drugs are attracting more attention for cancer treatment. Here, we showed that erianin, a natural product isolated from Dendrobium chrysotoxum Lindl, exerted its anticancer activity by inducing cell death and inhibiting cell migration in lung cancer cells. Subsequently, we demonstrated for the first time that erianin induced ferroptotic cell death in lung cancer cells, which was accompanied by ROS accumulation, lipid peroxidation, and GSH depletion. The ferroptosis inhibitors Fer-1 and Lip-1 but not Z-VAD-FMK, CQ, or necrostatin-1 rescued erianin-induced cell death, indicating that ferroptosis contributed to erianin-induced cell death. Furthermore, we demonstrated that Ca2+/CaM signaling was a critical mediator of erianin-induced ferroptosis and that blockade of this signaling significantly rescued cell death induced by erianin treatment by suppressing ferroptosis. Taken together, our data suggest that the natural product erianin exerts its anticancer effects by inducing Ca2+/CaM-dependent ferroptosis and inhibiting cell migration, and erianin will hopefully serve as a prospective compound for lung cancer treatment.


Bibenzyls/pharmacology , Calcium Signaling/drug effects , Calcium/metabolism , Calmodulin/metabolism , Cell Movement/drug effects , Cell Proliferation/drug effects , Dendrobium/chemistry , Ferroptosis/drug effects , Lung Neoplasms/metabolism , Neoplasm Proteins/metabolism , Phenol/pharmacology , Plant Extracts/chemistry , Animals , Bibenzyls/chemistry , Cell Line, Tumor , Female , Humans , Lung Neoplasms/drug therapy , Lung Neoplasms/pathology , Mice , Mice, Inbred BALB C , Mice, Nude , Phenol/chemistry
10.
Article En | MEDLINE | ID: mdl-32457882

OBJECTIVE: Colorectal cancer is a malignant tumor of the digestive system with high morbidity and mortality. 5-fluorouracil remains a widely used chemotherapeutic drug in the treatment of advanced colorectal cancer, but chemotherapy drugs are prone to develop drug resistance, p53 deletion or mutation is an important reason for the resistance of colorectal cancer cells to 5-fluorouracil. ß-elemene has been proved to have the potential of reverse chemotherapy drug resistance, but the mechanism is unknown. This study aimed to investigate the effect of ß-elemene to 5-fluorouracil in drug-resistant p53-deficient colorectal cancer cells HCT116p53-/-, and determine the possible molecular mechanism of ß-elemene to reverse 5-fluorouracil resistance. METHODS: The effect of ß-elemene on HCT116p53-/- cell activity was detected by Cell counting Kit-8. Cell proliferation was detected by monoclonal plate. The apoptosis was detected by flow cytometry and western blot. The autophagy was detected by western blot, immunofluorescence and transmission electron microscope. Determine the role of Cyclin-related protein Cyclin D3 in ß-elemene reversing the resistance of HCT116p53-/- to 5-fluorouracil was detected by overexpression of Cyclin D3. The effect of ß-elemene on the tumorigenic ability of p53-deficient colorectal cancer cells was detected establishing HCT116p53-/- all line xenograft model. RESULTS: For p53 wildtype colorectal cancer cells, ß-elemene could augment the sensitivity of 5-fluorouracil, for p53-deficient colorectal cancer cells, ß-elemene significantly inhibited cell proliferation in a concentration-dependent manner, and reversed the resistance of HCT116p53-/- to 5-fluorouracil by inducing pro-death autophagy and Cyclin D3-dependent cycle arrest. CONCLUSION: ß-elemene enhances the sensitivity of p53 wild-type cells to 5-fluorouracil, ß-elemene can reverse the resistance of HCT116p53-/- to 5-fluorouracil by inducing pro-death autophagy and Cyclin D3-dependent cycle arrest in p53-deficient colorectal cancer, which will provide a new method for the treatment of p53 deletion colorectal cancer patients.

11.
Cancer Biol Med ; 17(1): 60-75, 2020 02 15.
Article En | MEDLINE | ID: mdl-32296587

Objective: This study aimed to develop a new polyethylene glycol (PEG)ylated ß-elemene liposome (PEG-Lipo-ß-E) and evaluate its characterization, pharmacokinetics, antitumor effects and safety in vitro and in vivo. Methods: The liposomes were prepared by ethanol injection and high-pressure micro-jet homogenization. Characterization of the liposomes was conducted, and drug content, entrapment efficiency (EE), in vitro release and stability were studied by ultra-fast liquid chromatography (UFLC) and a liquid surface method. Blood was drawn from rats to establish the pharmacokinetic parameters. The anticancer effect was evaluated in a KU-19-19 bladder cancer xenograft model. Histological analyses were performed to evaluate safety. Results: The PEG-Lipo-ß-E showed good stability and was characterized as 83.31 ± 0.181 nm in size, 0.279 ± 0.004 in polydispersity index (PDI), -21.4 ± 1.06 mV in zeta potential, 6.65 ± 0.02 in pH, 5.024 ± 0.107 mg/mL in ß-elemene (ß-E) content, and 95.53 ± 1.712% in average EE. The Fourier transform infrared spectroscopy (FTIR) and differential scanning calorimetry (DSC) indicated the formation of PEG-Lipo-ß-E. Compared to elemene injection, PEG-Lipo-ß-E demonstrated a 1.75-fold decrease in clearance, a 1.62-fold increase in half-life, and a 1.76-fold increase in area under the concentration-time curves (AUCs) from 0 hour to 1.5 hours (P < 0.05). PEG-Lipo-ß-E also showed an enhanced anticancer effect in vivo. Histological analyses showed that there was no evidence of toxicity to the heart, kidney, liver, lung or spleen. Conclusions: The present study demonstrates PEG-Lipo-ß-E as a new formulation with ease of preparation, high EE, good stability, improved bioavailability and antitumor effects.


Antineoplastic Agents, Phytogenic/administration & dosage , Neoplasms/drug therapy , Sesquiterpenes/administration & dosage , Animals , Antineoplastic Agents, Phytogenic/chemistry , Antineoplastic Agents, Phytogenic/pharmacokinetics , Biological Availability , Cell Line, Tumor , Curcuma/chemistry , Female , Humans , Liposomes , Male , Mice , Neoplasms/pathology , Particle Size , Polyethylene Glycols/chemistry , Rats , Sesquiterpenes/chemistry , Sesquiterpenes/pharmacokinetics , Xenograft Model Antitumor Assays
12.
Front Mol Biosci ; 7: 602282, 2020.
Article En | MEDLINE | ID: mdl-33585556

Baicalin, as a natural active ingredient extracted and isolated from the traditional Chinese medicine Scutellaria baicalensis Georgi., has been potentially used in various areas for its antioxidative, antitumor, anti-inflammatory, and anti-proliferative activities. Although several studies have reported the antitumor effects of baicalin against various cancer types, its beneficial effects on lung cancer have not yet been elucidated. Therefore, the therapeutic effects and molecular mechanisms of baicalin on lung cancer cell lines H1299 and H1650 were investigated. Here, the results of its antitumor activity were shown. We found that Akt/mTOR pathway inhibition was the essential determinant in baicalin-induced cell cycle arrest. Furthermore, when the Akt Agonist SC79 or Akt plasmid transfection was performed, the antitumor effect of baicalin was significantly abrogated in both H1299 and H1650 cells. In conclusion, we found that baicalin exerted its antitumor activity mainly by inducing Akt-dependent cell cycle arrest and promoting apoptosis, which show great potential for developing a new drug for lung cancer treatment.

13.
Article En | MEDLINE | ID: mdl-31815010

5-Fluorouracil (5-FU) is known as a first-line chemotherapeutic agent against colorectal cancer (CRC), but drug resistance occurs frequently and significantly limits its clinical success. Our previous study showed that the protocadherin 17 (PCDH17) gene was frequently methylated and functioned as a tumor suppressor in CRC. However, the relationship between PCDH17 and 5-FU resistance in CRC remains unclear. Here, we revealed that PCDH17 was more highly expressed in 5-FU-sensitive CRC tissues than in 5-FU-resistant CRC tissues, and high expression of PCDH17 was correlated with high BECN1 expression. Moreover, this expression profile contributed to superior prognosis and increased survival in CRC patients. Restoring PCDH17 expression augmented the 5-FU sensitivity of CRC in vitro and in vivo by promoting apoptosis and autophagic cell death. Furthermore, autophagy played a dominant role in PCDH17-induced cell death, as an autophagy inhibitor blocked cell death to a greater extent than the pancaspase inhibitor Z-VAD-FMK. PCDH17 inhibition by siRNA decreased the autophagy response and 5-FU sensitivity. Mechanistically, we showed that c-Jun NH2-terminal kinase (JNK) activation was a key determinant in PCDH17-induced autophagy. The compound SP600125, an inhibitor of JNK, suppressed autophagy and 5-FU-induced cell death in PCDH17-reexpressing CRC cells. Taken together, our findings suggest for the first time that PCDH17 increases the sensitivity of CRC to 5-FU treatment by inducing apoptosis and JNK-dependent autophagic cell death. PCDH17 may be a potential prognostic marker for predicting 5-FU sensitivity in CRC patients.

14.
J Cancer ; 10(25): 6207-6216, 2019.
Article En | MEDLINE | ID: mdl-31772653

Purpose: To determine whether p53, PCDH17, Beclin-1 expression is associated with clinicopathological characteristics of bladder cancer. Materials and Methods: 75 patients with non-muscle-invasive and muscle-invasive bladder cancer were included. Immunohistochemical staining for p53, PCDH17 and Beclin-1 were carried out on the same paraffin-embedded blocks serial sections of these patients who underwent surgery between 2010 and 2015. In addition, p53 gene mutations in these tumors were screened by DNA sequencing. Results: Forty-nine (66.7%) of 75 tumors had p53 gene mutations detected by DNA sequencing method. Of these tumors, 43 (86.0%) exhibited p53 high expression. Furthermore, p53 mutation and low expression of PCDH17 were significantly associated with muscle-invasive bladder cancer. Beclin-1 was also strongly associated with T stage. The p53 mutation, the expression of p53 and PCDH17 were significantly associated with survival from bladder cancer. In addition, patients with p53 high-expression or p53 mutation, PCDH17 low-expression and Beclin-1 low-expression significantly had a poor prognosis. Conclusions: Use of a DNA sequencing method to detect p53 gene mutations was consistent with an immunohistochemical method to detect p53 alterations. In conjunction with levels of p53/PCDH17/Beclin-1, p53 and PCDH17 were independently associated with prognosis; Beclin-1 only had a tendency towards overall survival. p53/PCDH17/Beclin-1 phenotype seems to play a more important role than p53 expression in bladder cancer outcome. It is also identified that p53/PCDH17, p53/Beclin-1 or PCDH17/Beclin-1 all have a cooperative and synergistic effect, which may provide us the potential biomarker for bladder cancer patients.

15.
Biomed Pharmacother ; 114: 108812, 2019 Jun.
Article En | MEDLINE | ID: mdl-30965237

ß-Elemene is a sesquiterpene compound extracted from the herb Curcuma Rhizoma and is used in traditional Chinese medicine (TCM) to treat several types of cancer, with no reported severe adverse effects. Recent studies, using in vitro and in vivo studies combined with molecular methods, have shown that ß-elemene can inhibit cell proliferation, arrest the cell cycle, and induce cell apoptosis. Recent studies have identified the molecular targets of ß-elemene that may have a role in cancer therapy. This review aims to discuss the anticancer potential of ß-elemene through its actions on several molecular targets including kinase enzymes, transcription factors, growth factors and their receptors, and proteins. ß-Elemene also regulates the expression of several key molecules that are involved in tumor angiogenesis and metastasis including vascular endothelial growth factor (VEGF), matrix metalloproteinases (MMPs), E-cadherin, N-cadherin, and vimentin. Also, ß-elemene has been shown to have regulatory effects on the immune response and increases the sensitivity of cancer cells to chemoradiotherapy and has shown effects on multidrug resistance (MDR) in malignancy. Recent studies have shown that ß-elemene can induce autophagy, which prevents cancer cells from undergoing apoptosis. Therefore, the molecular mechanisms for the treatment effects on cancer of the herbal extract, ß-elemene, which has been used for centuries in traditional Chinese medicine, are now being studied and identified.


Drugs, Chinese Herbal/pharmacology , Drugs, Chinese Herbal/therapeutic use , Neoplasms/drug therapy , Plant Extracts/pharmacology , Plant Extracts/therapeutic use , Sesquiterpenes/pharmacology , Sesquiterpenes/therapeutic use , Animals , Antineoplastic Agents/pharmacology , Antineoplastic Agents/therapeutic use , Apoptosis/drug effects , Autophagy/drug effects , Cell Proliferation/drug effects , Humans , Medicine, Chinese Traditional/methods
16.
Front Pharmacol ; 9: 1371, 2018.
Article En | MEDLINE | ID: mdl-30524291

Ferroptosis is an iron-dependent, oxidative cell death, and is characterized by iron-dependent accumulation of reactive oxygen species (ROS) within the cell. It has been implicated in various human diseases, including cancer. Recently, ferroptosis, as a non-apoptotic form of cell death, is emerging in specific cancer types; however, its relevance in colorectal cancer (CRC) is unexplored and remains unclear. Here, we showed that ferroptosis inducer RSL3 initiated cell death and ROS accumulation in HCT116, LoVo, and HT29 CRC cells over a 24 h time course. Furthermore, we found that ROS levels and transferrin expression were elevated in CRC cells treated with RSL3 accompanied by a decrease in the expression of glutathione peroxidase 4 (GPX4), indicating an iron-dependent cell death, ferroptosis. Overexpression GPX4 resulted in decreased cell death after RSL3 treatment. Therefore, RSL3 was able to induce ferroptosis on three different CRC cell lines in vitro in a dose- and time-dependent manner, which was due to increased ROS and an increase in the cellular labile iron pool. Moreover, this effect was able to be reversed by overexpression of GPX4. Taken together, our results suggest that the induction of ferroptosis contributed to RSL3-induced cell death in CRC cells and ferroptosis may be a pervasive and dynamic form of cell death for cancer treatment.

17.
Nanomicro Lett ; 6(4): 365-371, 2014.
Article En | MEDLINE | ID: mdl-30464948

The CrO2 micro rod powder was synthesized by decomposing the CrO3 flakes at a specific temperature to yield precursor and annealing such a precursor in a sealed glass tube. The magneto-transport properties have been measured by a direct current four-probe method using a Cu/CrO2 rods/colloidal silver liquid electrode sandwich device. The largest magnetoresistance (MR) around ~72 % was observed at 77 K with applied current of 0.05 µA. The non-linear I-V curve indicates a tunneling type transport properties and the tunneling barrier height is around 2.2 ± 0.04 eV at 77 K, which is obtained with fitting the non-linear I-V curves using Simmons' equation. A mixing of Cr oxides on the surface of CrO2 rod observed by X-ray photoemission spectroscopy provides a tunneling barrier rather than a single phase of Cr2O3 insulating barrier. The MR shows strong bias voltage dependence and is ascribed to the two-step tunneling process.

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