Cancer cells remodeling and quality control are inextricably linked to autophagy

Autophagy is a normal cellular physiological process. As one of the cell degradation systems, it participates in the lysosomal pathway process of degrading damaged proteins and subcellular organelles to maintain cell metabolism and energy states. Moreover, autophagy is essential for regulating organelle quality control and cell homeostasis. In recent decades, a large number of studies have demonstrated that autophagy abnormalities are present in a variety of human malignancies and that autophagy plays a crucial role in all stages of tumor development. Multiple tumors interfere with autophagy's normal regulation and use autophagy's essential properties to restructure their proteome, reprogram their metabolism, and adapt to stress. This article primarily discusses how autophagy either promotes or inhibits cancer development, the significance of autophagy in maintaining cell genome stability, and the role of selective autophagy in the reshaping and quality control of tumor cells

Four sulfur mustard exposure cases: Overall analysis of four types of biomarkers in clinical samples provides positive implication for early diagnosis and treatment monitoring

AbstractIn one event, Chinese male individuals accidentally exposed to unknown chemicals and emerged erythema or blisters on contacted organism derma, then hospitalized. To identify the causative agents, blood, urine and exudate samples were collected from the patients during the therapeutic course. Five established liquid chromatography–mass spectrometry (LC–MS) and gas chromatography (GC)–MS methods were employed to analyze the samples. Here, an overall analysis of four types of sulfur mustard biomarkers, including the hydrolysis/oxidation products, β-lyase metabolites, DNA adducts and hemoglobin adducts, was conducted toward the samples from exposed individuals. The results of all the four types of biomarkers in different biomedical matrices showed high relevance, and verified that this exposure is indeed originated from sulfur mustard. The concentrations of the biomarkers in specimens revealed a good correlation with the severity of the patient's symptom. The concentration-time profile demonstrated that most of the biomarkers quickly achieved maximum at the beginning of the course, and then decreased and kept a detectable level until the 7th day after exposure. The DNA adducts in urine samples still appeared on the 30th day, and the N-terminal valine adducts in hemoglobin could be monitored for over 90 days, which was meaningful for the concurrent study of clinical samples. To the best of our knowledge, this work provides the total analysis and profile of four categories of biomarkers in human specimens for the first time, and the good accordance between concentration and level of burns, between time course and biomarkers will be of great importance for early diagnosis and medical treatment monitoring of sulfur mustard exposure

MAPK-activated transcription factor PxJun suppresses PxABCB1 expression and confers resistance to Bacillus thuringiensis Cry1Ac toxin in Plutella xylostella (L.)

Deciphering the molecular mechanisms underlying insect resistance to Cry toxins produced by Bacillus thuringiensis (Bt) is pivotal for the sustainable utilization of Bt biopesticides and transgenic Bt crops. Previously, we identified that MAPK-mediated reduced expression of the PxABCB1 gene is associated with Bt Cry1Ac resistance in the diamondback moth, Plutella xylostella (L.). However, the underlying transcriptional regulation mechanism remains enigmatic. Herein, the PxABCB1 promoter in Cry1Ac-susceptible and Cry1Ac-resistant P. xylostella strains was cloned and analyzed and found to contain a putative Jun binding site (JBS). A dual-luciferase reporter assay and yeast one-hybrid assay (Y1H) demonstrated that the transcription factor PxJun repressed PxABCB1 expression by interacting with this JBS. The expression levels of PxJun were increased in the midguts of all resistant strains compared to the susceptible strain. Silencing of PxJun expression significantly elevated PxABCB1 expression and Cry1Ac susceptibility in the resistant NIL-R strain, and silencing of PxMAP4K4 expression decreased PxJun expression and also increased PxABCB1 expression. These results indicate that MAPK-activated PxJun suppresses PxABCB1 expression to confer Cry1Ac resistance in P. xylostella, deepening our understanding of the transcriptional regulation of midgut Cry receptor genes and the molecular basis of insect resistance to Bt Cry toxins.ImportanceThe transcriptional regulation mechanisms underlying reduced expression of Bt toxin receptor genes in Bt-resistant insects remain elusive. This study unveils that a transcription factor PxJun activated by the MAPK signaling pathway represses PxABCB1 expression and confers Cry1Ac resistance in P. xylostella Our results provide new insights into the transcriptional regulation mechanisms of midgut Cry receptor genes and deepen our understanding of the molecular basis of insect resistance to Bt Cry toxins. To our knowledge, this study identified the first transcription factor that can be involved in the transcriptional regulation mechanisms of midgut Cry receptor genes in Bt-resistant insects

Synthesis of a Dual Functional Anti-MDR Tumor Agent PH II-7 with Elucidations of Anti-Tumor Effects and Mechanisms

Multidrug resistance mediated by P-glycoprotein in cancer cells has been a major issue that cripples the efficacy of chemotherapy agents. Aimed for improved efficacy against resistant cancer cells, we designed and synthesized 25 oxindole derivatives based on indirubin by structure-activity relationship analysis. The most potent one was named PH II-7, which was effective against 18 cancer cell lines and 5 resistant cell lines in MTT assay. It also significantly inhibited the resistant xenograft tumor growth in mouse model. In cell cycle assay and apoptosis assay conducted with flow cytometry, PH II-7 induced S phase cell cycle arrest and apoptosis even in resistant cells. Consistently revealed by real-time PCR, it modulates the expression of genes related to the cell cycle and apoptosis in these cells, which may contributes to its efficacy against them. By side-chain modification and FITC-labeling of PH II-7, we were able to show with confocal microscopy that not only it was not pumped by P-glycoprotein, it also attenuated the efflux of Adriamycin by P-glycoprotein in MDR tumor cells. Real-time PCR and western blot analysis showed that PH II-7 down-regulated MDR1 gene via protein kinase C alpha (PKCA) pathway, with c-FOS and c-JUN as possible mediators. Taken together, PH II-7 is a dual-functional compound that features both the cytotoxicity against cancer cells and the inhibitory effect on P-gp mediated drug efflux

The complete mitochondrial genome of Indo-Pacific soft coral Sinularia acuta Manuputty and van Ofwegen, 2007 (Octocorallia: Alcyonacea)

The complete mitochondrial genome (mitogenome) of the soft coral Sinularia acuta Manuputty and van Ofwegen, 2007 was sequenced and annotated using Illumina next-generation sequencing (NGS). The mitogenome of S. acuta was 18,730 bp in length and consisted of 14 protein-coding genes (PCGs), two ribosomal RNA genes (rRNA), and only one transfer RNA gene (tRNA-Met). The base composition was 30.18% A, 16.46% C, 19.35% G, and 34.00% T, with a total A + T content of 64.19%. The phylogenetic analysis demonstrated a close evolutionary relationship among Sinularia acuta, Sinularia penghuensis, and Sinularia maxima

Expression of ezrin in human lung carcinoma and its clinicopathologic significance

Background and objective Metastasis is the main cause of cancer related mortality, and identification of genes involved in tumor metastasis is important for effective therapies. The membrane cytoskeletal crosslinker participated in several functions including cell adhersion, motility and cell survival, and there is increasing evidence that it regulates tumor progression. However, the role played by ezrin in lung cancer metastasis has not been clearly delineated. The aims of this study are to investigate the ezrin expression pattern in human lung carcinomaand the correlation with clinicopathologic characteristics. Methods Ezrin expression was detected by two- step immunohistochemical staining technique in tumor tissues from 75 lung cancer cases and in normal lung tissues from16 cases with benign disease and analyzed by the lung cancer clinicopathologic characteristics.The gene and protein level expression of Ezrin in lung cancer cell lines was also detected by Confocal Laser Scanning Microscope"CLSM" and RT-PCR. Results The positive incidence of ezrin expression (77.3%) was significantly lower in lung cancer tissues than that in normal tissues (100%) (P<0.05) and the down-regulated of ezrin expression was significantly correlated with lymph node metastasis and distant metastasis (P<0.05) and was not correlated with gender,age, tumor size, pathological type, the degree of differentiation of tissue and clinical stage. Otherwise, the subcellular redistribution of ezrin from cell membrane to cell plasma was significantly correlated with lymph node metastasis (P<0.05), in consistance with in vitro experimental result. High metastasis cell line BE1 had the lowest expression of ezrin under CLSM, similar to RT-PCR, and ezrin was mainly located in cell plasma under CLSM. Conclusion Ezrin expression is down-regulated in lung cancer tissue and lung cancer cell line and the locational change from cell membrane to cell plasma may be associated with the oncogenesis and development of lung cancer

Effect of sodium concentration on the synthesis of faujasite by two-step synthesis procedure

International audienceThe relationship between concentration of sodium cations and the properties of faujasite (FAU) zeolite using a two-step synthesis procedure including (1) formation of amorphous aluminosilicate precursors and separation of amorphous nanoparticles, and (2) transformation of these amorphous particles into zeolite crystals by treatment with alkali solutions (NaOH) were studied. Three representative samples including two nano-sized zeolites and one micron-sized zeolite were prepared using different concentration of sodium hydroxide. The crystallization process of these zeolites was studied in details by FTIR, NMR, XRD, SEM, TEM, N 2 adsorption. The results indicated that minor changes in the concertation of inorganic cations can significantly shorten the induction period and crystallization time and thus affect the morphology, size and chemical composition of the zeolite crystals

Dual Regulation of Graphene Oxide Membrane by Crosslinker and Hydrophilic Promoter for Dye Separation

Graphene oxide (GO)-based membranes have shown considerable promise in the field of water treatment. However, the structural swelling of GO membranes in water has hindered their further development. A single regulatory approach seems difficult to simultaneously improve permeability, selectivity, and stability. In this study, we present a dual regulation strategy for GO membranes employing the 1,4-Diaminobutane crosslinker to prevent swelling and maintain an interlayer spacing of 1.34 nm, resulting in effective dye rejection, and employing the hydrophilic EMT-type zeolite promoter to improve the membrane's water permeability. The obtained NH 2-GO/10EMT composite membrane exhibited enhanced pure water flux (from 9.0 to 20.8 L/m 2 •h•bar) and anionic dye rejection (from 87.2% to 97.6%) with promising structure stability (at least 20 h), while greatly improving the membrane's fouling resistance (the water recovery ratio increased from 46.5% to 86.2%). Our findings provide a straightforward and efficient approach to the development of high-performance GO membranes for selective water separation

A Label-Free Fluorescent AND Logic Gate Aptasensor for Sensitive ATP Detection

In this study, a label-free fluorescent, enzyme-free, simple, highly sensitive AND logic gate aptasensor was developed for the detection of adenosine triphosphate (ATP). Double-stranded deoxyribonucleic acid (DNA) with cohesive ends was attached to graphene oxide (GO) to form an aptasensor probe. ATP and single-stranded DNA were used as input signals. Fluorescence intensity of PicoGreen dye was used as an output signal. The biosensor-related performances, including the logic gate construction, reaction time, linearity, sensitivity, and specificity, were investigated and the results showed that an AND logic gate was successfully constructed. The ATP detection range was found to be 20 to 400 nM (R2 = 0.9943) with limit of detection (LOD) of 142.6 pM, and the sensitivity range was 1.846 &times; 106 to 2.988 &times; 106 M&minus;1. This method for the detection of ATP has the characteristics of being simple, low cost, and highly sensitive

Effects of combined therapy of Phosphatidylinositol 3p-Kinase and Paclitaxel in human lung cancer nude mice model

Background and objective Increasing evidence suggests that aberrant activation of PI3K/Akt is involved in many human cancers, and that inhibition of the PI3K/Akt pathway might be a promising strategy for cancer therapy. The aims of this study is to evaluate the effects of combined therapy of Phosphatidylinositol 3-Kinase inhibitor(LY294002 ) and Paclitaxel in athymic mice xenogeneic transplant model of lung cancer and to reveal the possible mechanisms involved．Methods Eighteen athymic mice were randomly divided into 3 groups (control, paclitaxel alone and paclitaxel plus LY294002), and were treated respectively. Athymic mice xenogeneic transplant model was establishedby inoculation (sc) with A549 lung cancer cells. Body mass (BM) and diameter of tumor mass were measured. Furthermore,the protein expressions of CyclinD1，bcl-2 and bax in tumor tissues were analyzed with immunohistochemistry. Results The tumor-inhibiting rate of paclitaxel plus LY294002 (92.47%) was significantly higher than the paclitaxel alone (65.59%)（P<0.05).The protein expression of bcl-2 in paclitaxel plus LY294002 group were significantly higher, while bax wassignificantly lower than that in the other two groups (P <0.05). The protein expression of CyclinD1 was significantly lower than the control group (P <0.05). Conclusion LY294002 can enhance the effects of paclitaxel in the treatment of lung cancer and CyclinD1, bcl-2 and bax may be involved in its inhibitory effects