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1.
Autophagy ; 16(1): 154-166, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31007124

RESUMO

Damaged or redundant peroxisomes and their luminal cargoes are removed by pexophagy, a selective autophagy pathway. In yeasts, pexophagy depends mostly on the pexophagy receptors, such as Atg30 for Pichia pastoris and Atg36 for Saccharomyces cerevisiae, the autophagy scaffold proteins, Atg11 and Atg17, and the core autophagy machinery. In P. pastoris, the receptors for peroxisomal matrix proteins containing peroxisomal targeting signals (PTSs) include the PTS1 receptor, Pex5, and the PTS2 receptor and co-receptor, Pex7 and Pex20, respectively. These shuttling receptors are predominantly cytosolic and only partially peroxisomal. It remains unresolved as to whether, when and how the cytosolic pools of peroxisomal receptors, as well as the peroxisomal matrix proteins, are degraded under pexophagy conditions. These cytosolic pools exist both in normal and mutant cells impaired in peroxisome biogenesis. We report here that Pex5 and Pex7, but not Pex20, are degraded by an Atg30-independent, selective autophagy pathway. To enter this selective autophagy pathway, Pex7 required its major PTS2 cargo, Pot1. Similarly, the degradation of Pex5 was inhibited in cells missing abundant PTS1 cargoes, such as alcohol oxidases and Fox2 (hydratase-dehydrogenase-epimerase). Furthermore, in cells deficient in PTS receptors, the cytosolic pools of peroxisomal matrix proteins, such as Pot1 and Fox2, were also removed by Atg30-independent, selective autophagy, under pexophagy conditions. In summary, the cytosolic pools of PTS receptors and their cargoes are degraded via a pexophagy-independent, selective autophagy pathway under pexophagy conditions. These autophagy pathways likely protect cells from futile enzymatic reactions that could potentially cause the accumulation of toxic cytosolic products.Abbreviations: ATG: autophagy related; Cvt: cytoplasm to vacuole targeting; Fox2: hydratase-dehydrogenase-epimerase; PAGE: polyacrylamide gel electrophoresis; Pot1: thiolase; PMP: peroxisomal membrane protein; Pgk1: 3-phosphoglycerate kinase; PTS: peroxisomal targeting signal; RADAR: receptor accumulation and degradation in the absence of recycling; RING: really interesting new gene; SDS: sodium dodecyl sulphate; TCA, trichloroacetic acid; Ub: ubiquitin; UPS: ubiquitin-proteasome system Vid: vacuole import and degradation.

2.
Environ Sci Technol ; 54(2): 996-1004, 2020 Jan 21.
Artigo em Inglês | MEDLINE | ID: mdl-31829571

RESUMO

Short-chain chlorinated paraffins (SCCPs), a class of ubiquitous pollutants, are considered to be embryotoxic and teratogenic. However, little is known regarding the bioactivity and mechanisms at environmentally relevant concentrations at the embryonic period. Here, a concentration-dependent reduced transcriptomic approach was used to evaluate the environmental dose (<100 ppb) effects of nine SCCP congeners and eight commercial mixtures on zebrafish embryos at 8 hpf. After 24 h of exposure, the overall biological potency of all the SCCPs, in terms of interference with 20% of the differentially expressed genes (PODDEG20), in zebrafish embryos ranged from 0.83 to 67.61 ppb. C10H14Cl8 (PODGO20 = 3.80 ppb) and C10-13 51.5% Cl (PODGO20 = 3.31 ppb) exhibited the strongest interference with biological processes compared to other SCCP homologs and mixtures, respectively. The most sensitive early molecular responses induced by SCCPs were associated with pathways of genetic damage, energy metabolite interference, and metal ion binding. Furthermore, the carbon number was positively correlated with the transcriptomic potency (PODGO20) of SCCP congeners (with chlorine content > 60%) (p = 0.038), and the chlorine content of SCCP congeners affected the bioactivity associated with genotoxic pathways. The concentration-dependent reduced transcriptomic approach significantly improved the understanding of the ecological risk of environmental contaminants at early life stages.

3.
Sci Total Environ ; 702: 134767, 2020 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-31726335

RESUMO

The aim of the present study was to investigate the sorption of atrazine and nicosulfuron onto several experimentally produced biochars, as well as to understand the influence of biochar structure on sorption mechanisms. Nine biochars were generated by pyrolyzing peanut shell at 300, 450, or 600 °C and exposing samples to each of the several deashing treatments: none, water or HCl. The sorption of atrazine and nicosulfuron by the nine biochars were evaluated. Biochars were characterized via elemental analyzer, BET-N2 surface area, FTIR and XPS. Three kinetic models were used to fit the sorption kinetics data and both the Freundlich and dual-mode models described the sorption isotherms well. All the biochar samples exhibited high sorption affinity for both atrazine and nicosulfuron. The sorption mechanisms of the biochar included hydrophobic partition, π-π electron donor-acceptor interactions, H-bonding, and pore-filling mechanism, and these mechanisms were dependent on both the degree of biochar carbonization and the concentration of atrazine or nicosulfuron. Ash could bind to atrazine and nicosulfuron by specific interactions but played a negative role in the sorption, especially on high pyrolyzing temperature biochars. These results will facilitate the production of efficient and cheap adsorbents for reducing the risk of atrazine and nicosulfuron.


Assuntos
Carvão Vegetal/química , Piridinas/química , Compostos de Sulfonilureia/química , Poluentes Químicos da Água/química , Adsorção , Arachis , Atrazina
4.
BMC Bioinformatics ; 20(Suppl 25): 691, 2019 Dec 24.
Artigo em Inglês | MEDLINE | ID: mdl-31874619

RESUMO

BACKGROUND: The association between BIN1 rs744373 variant and Alzheimer's disease (AD) had been identified by genome-wide association studies (GWASs) as well as candidate gene studies in Caucasian populations. But in East Asian populations, both positive and negative results had been identified by association studies. Considering the smaller sample sizes of the studies in East Asian, we believe that the results did not have enough statistical power. RESULTS: We conducted a meta-analysis with 71,168 samples (22,395 AD cases and 48,773 controls, from 37 studies of 19 articles). Based on the additive model, we observed significant genetic heterogeneities in pooled populations as well as Caucasians and East Asians. We identified a significant association between rs744373 polymorphism with AD in pooled populations (P = 5 × 10- 07, odds ratio (OR) = 1.12, and 95% confidence interval (CI) 1.07-1.17) and in Caucasian populations (P = 3.38 × 10- 08, OR = 1.16, 95% CI 1.10-1.22). But in the East Asian populations, the association was not identified (P = 0.393, OR = 1.057, and 95% CI 0.95-1.15). Besides, the regression analysis suggested no significant publication bias. The results for sensitivity analysis as well as meta-analysis under the dominant model and recessive model remained consistent, which demonstrated the reliability of our finding. CONCLUSIONS: The large-scale meta-analysis highlighted the significant association between rs744373 polymorphism and AD risk in Caucasian populations but not in the East Asian populations.

5.
Chemosphere ; 245: 125632, 2019 Dec 12.
Artigo em Inglês | MEDLINE | ID: mdl-31864044

RESUMO

Mechanistic information is essential to screen and predict the adverse effects of a large number of chemicals during early-life exposure. Concentration-dependent omics can capture the extent of perturbations of biological pathways or processes and provide information on the mechanism of toxicity. However, the application of concentration-dependent transcriptome to assess the developmental toxicity of environmental chemicals is still limited. Here, twelve chemicals representing five different modes of action (MOAs) were tested by the concentration-dependent reduced zebrafish transcriptome approach (CRZT) in combination with a phenotype-based high content screen (PHCS). The responsiveness, sensitivity and mechanistic differentiation of CRZT were validated in comparison with PHCS. First, PHCS identified 10 chemicals with obvious embryotoxicity (LD50 range: 2.11-70.68 µM), while the potencies of the biological pathways perturbed by 12 chemicals (PODpath20 range: 0.002-2.1 µM) were demonstrated by CRZT. Second, although the potency of the transcriptome perturbations was positively correlated with lethality (LD50) (R2 = 0.64, P-value < 0.05) for most tested chemicals, BbF was non-embryotoxic but was the most potent on the perturbance of biological pathways. Finally, the profiles of the perturbed biological processes and the transcriptome potency (PODpath20) captured by CRZT could effectively classify most chemicals corresponding to their known MOAs. In summary, CRZT could significantly improve testing the developmental toxicity of environmental chemicals.

6.
Mol Ther Nucleic Acids ; 18: 590-604, 2019 Dec 06.
Artigo em Inglês | MEDLINE | ID: mdl-31678735

RESUMO

Although our knowledge of human diseases has increased dramatically, the molecular basis, phenotypic traits, and therapeutic targets of most diseases still remain unclear. An increasing number of studies have observed that similar diseases often are caused by similar molecules, can be diagnosed by similar markers or phenotypes, or can be cured by similar drugs. Thus, the identification of diseases similar to known ones has attracted considerable attention worldwide. To this end, the associations between diseases at the molecular, phenotypic, and taxonomic levels were used to measure the pairwise similarity in diseases. The corresponding performance assessment strategies for these methods involving the terms "category-based," "simulated-patient-based," and "benchmark-data-based" were thus further emphasized. Then, frequently used methods were evaluated using a benchmark-data-based strategy. To facilitate the assessment of disease similarity scores, researchers have designed dozens of tools that implement these methods for calculating disease similarity. Currently, disease similarity has been advantageous in predicting noncoding RNA (ncRNA) function and therapeutic drugs for diseases. In this article, we review disease similarity methods, evaluation strategies, tools, and their applications in the biomedical community. We further evaluate the performance of these methods and discuss the current limitations and future trends for calculating disease similarity.

7.
Front Immunol ; 10: 2218, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31620132

RESUMO

Accumulating studies have suggested that long non-coding RNAs (lncRNAs) have drawn more and more attention in rheumatoid arthritis (RA), which can function as competitive endogenous RNAs (ceRNAs) in inflammation and immune disorders. Previously, we have found that lncRNA HIX003209 is differentially expressed in RA. However, the precise mechanism of lncRNA HIX003209 in RA is still vague. We aim to elucidate the role and its targeted microRNA of lncRNA HIX003209 in RA as ceRNA. Significantly increased expression of lncRNA HIX003209 was observed in the peripheral blood mononuclear cells (PBMCs) from RA cases. It was positively associated with TLR2 and TLR4 in RA. Besides, peptidoglycan (PGN) and lipopolysaccharide (LPS) could enhance the expression of lncRNA HIX003209, which reversely promoted the proliferation and activation of macrophages through IκBα/NF-κB signaling pathway. Moreover, HIX003209 was involved in TLR4-mediated inflammation via targeting miR-6089 in macrophages. LncRNA HIX003209 functions as a ceRNA and exaggerates inflammation by sponging miR-6089 through TLR4/NF-κB pathway in macrophages, which offers promising therapeutic strategies for RA.

8.
Hypertens Res ; 42(12): 1894-1904, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31541223

RESUMO

Cerebrovascular spasm is a life-threatening event in salt-sensitive hypertension. The relationship between store-operated calcium entry (SOCE) and vasoconstriction in hypertension has not been fully clarified. This study investigated the changes in cerebrovascular contractile responses in high salt intake-induced hypertension and the functional roles of the main components of SOCE, namely, polycystin-2 (TRPP2), stromal interaction molecule 1 (STIM1), and Orai3. Polycystic kidney disease 2 (which encodes TRPP2) knockout mice displayed decreased cerebrovascular SOCE-induced contraction. The blood pressure of age-matched rats fed a normal or high-salt diet for 4 weeks was monitored weekly using noninvasive tail-cuff plethysmography. The systolic blood pressure of the rats fed a high-salt diet was significantly higher than that of controls. Western blotting and immunohistochemical results showed that these hypertensive rats expressed higher levels of cerebrovascular TRPP2, STIM1, and Orai3 than controls. Cerebrovascular tension measurements of the basilar artery indicated that SOCE-mediated contraction was significantly increased in hypertensive rats compared with control rats. In addition, SOCE-mediated contraction was decreased in the basilar arteries of rats pretreated with the SOCE inhibitor BTP-2 (10 µM) or transfected with TRPP2-specific or STIM1-specific small interfering RNA. Staining with 2,3,5-triphenyltetrazolium chloride (TTC) was used to quantify the infarcted brain area 24 h after middle cerebral artery occlusion, a model of ischemic stroke, in rodents. The infarcted brain area was significantly greater in hypertensive rats and significantly lower in BTP-2-treated rats than in controls. Taken together, these findings indicate that SOCE-induced contraction may be overactive in the basilar arteries of salt-sensitive hypertensive rats, suggesting the dysregulation of TRPP2 and SOCE and its other components.

9.
Front Psychol ; 10: 2015, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31551870

RESUMO

Background: Organizational climate refers to an individual's perception and experience of the climate of the work environment, and it is the most important environmental variable that affects individuals' work performance. This study aims to classify characteristics of transformational leadership among kindergarten principals and examine their relationship to organizational climate. Methods: Convenience sampling yielded 498 kindergarten principals who completed the "Questionnaire on the Principal's Transformational Leadership Behavior" and "Questionnaire on Organizational Climate." Ethics approval was obtained from the Academic Ethics Committee of the College of Psychology of Northeast Normal University prior to starting the study. Results: Three latent classes were identified, including the high-level (68.8%), care-virtues (35.7%), and virtues groups (5.3%). There were significant differences in support, directive, restrictive, colleague, intimate, and disengaged behavior scores between groups. In terms of support, colleague, and intimate behavior, the high-level group had the highest scores, followed by the care-virtues group and virtues group, respectively. Regarding restrictive and disengaged behaviors, the highest scores were received by the virtues group, followed by the care-virtues and high-level group, respectively. Conclusion: The study suggested that principals' transformational leadership could be classified into three latent classes that are related to organizational climate.

10.
Adv Mater ; 31(43): e1903378, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31523873

RESUMO

Water scarcity is one of the greatest challenges facing human society. Because of the abundant amount of water present in the atmosphere, there are significant efforts to harvest water from air. Particularly, solar-driven atmospheric water generators based on sequential adsorption-desorption processes are attracting much attention. However, incomplete daytime desorption is the limiting factor for final water production, as the rate of water desorption typically decreases very quickly with decreased water content in the sorbents. Hereby combining tailored interfacial solar absorbers with an ionic-liquid-based sorbent, an atmospheric water generator with a simultaneous adsorption-desorption process is generated. With enhanced desorption capability and stabilized water content in the sorbent, this interfacial solar-driven atmospheric water generator enables a high rate of water production (≈0.5 L m-2 h-1 ) and 2.8 L m-2 d-1 for the outdoor environment. It is expected that this interfacial solar-driven atmospheric water generator, based on the liquid sorbent with a simultaneous adsorption-desorption process opens up a promising pathway to effectively harvest water from air.

11.
Genes (Basel) ; 10(9)2019 09 05.
Artigo em Inglês | MEDLINE | ID: mdl-31492001

RESUMO

Gibberellin (GAs) plays the important role in the regulation of grape developmental and growth processes. The bioinformatics analysis confirmed the differential expression of GA2, GA3, and GA20 gibberellin oxidase genes (VvGA2oxs, VvGA3oxs, and VvGA20oxs) in the grape genome, and laid a theoretical basis for exploring its role in grape. Based on the Arabidopsis GA2oxs, GA3oxs, and GA20oxs genes already reported, the VvGA2oxs, VvGA3oxs, and VvGA20oxs genes in the grape genome were identified using the BLAST software in the grape genome database. Bioinformatics analysis was performed using software such as DNAMAN v.5.0, Clustalx, MapGene2Chrom, MEME, GSDS v.2.0, ExPASy, DNAsp v.5.0, and MEGA v.7.0. Chip expression profiles were generated using grape Affymetrix GeneChip 16K and Grape eFP Browser gene chip data in PLEXdb. The expression of VvGA2oxs, VvGA3oxs, and VvGA20oxs gene families in stress was examined by qRT-PCR (Quantitative real-time-PCR). There are 24 GAoxs genes identified with the grape genome that can be classified into seven subgroups based on a phylogenetic tree, gene structures, and conserved Motifs in our research. The gene family has higher codon preference, while selectivity is negative selection of codon bias and selective stress was analyzed. The expression profiles indicated that the most of VvGAox genes were highly expressed under different time lengths of ABA (Abscisic Acid) treatment, NaCl, PEG and 5 °C. Tissue expression analysis showed that the expression levels of VvGA2oxs and VvGA20oxs in different tissues at different developmental stages of grapes were relatively higher than that of VvGA3oxs. Last but not least, qRT-PCR (Real-time fluorescent quantitative PCR) was used to determine the relative expression of the GAoxs gene family under the treatment of GA3 (gibberellin 3) and uniconazole, which can find that some VvGA2oxs was upregulated under GA3 treatment. Simultaneously, some VvGA3oxs and VvGA20oxs were upregulated under uniconazole treatment. In a nutshell, the GA2ox gene mainly functions to inactivate biologically active GAs, while GA20ox mainly degrades C20 gibberellins, and GA3ox is mainly composed of biologically active GAs. The comprehensive analysis of the three classes of VvGAoxs would provide a basis for understanding the evolution and function of the VvGAox gene family in a grape plant.


Assuntos
Giberelinas/metabolismo , Oxigenases de Função Mista/genética , Proteínas de Plantas/genética , Vitis/genética , Códon/genética , Duplicação Gênica , Regulação da Expressão Gênica de Plantas , Oxigenases de Função Mista/metabolismo , Proteínas de Plantas/metabolismo , Seleção Genética , Estresse Fisiológico , Regulação para Cima , Vitis/enzimologia
12.
J Cell Biochem ; 120(12): 19415-19421, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31448453

RESUMO

Accumulating studies have implicated that long noncoding RNA (lncRNA) plays a vital role in lung cancer. However, little is known of the role of lncRNA highly upregulated in liver cancer (HULC) in the pathogenesis of lung squamous cell carcinoma (LSCC). In this study, we investigated the modifying effects and underlying mechanisms of lncRNA HULC in LSCC. Significantly decreased level of lncRNA HULC was observed in LSCC samples compared with adjacent tissues. Besides, the expression of lncRNA HULC was negatively associated with protein tyrosine phosphatase receptor type O (PTPRO) in LSCC. Moreover, lncRNA HULC could promote the proliferation of LSCC cells by downregulating the expression PTPRO dependent on the phosphorylation and activation of nuclear factor-κB (NF-κB). The present study firstly shows strong evidence supporting a critical role of lncRNA HULC in promoting LSCC by regulating PTPRO/NF-κB signaling pathway, which provides new promising biomarkers for LSCC.

13.
Dalton Trans ; 48(41): 15646-15656, 2019 Oct 22.
Artigo em Inglês | MEDLINE | ID: mdl-31465061

RESUMO

Two optically pure chiral binuclear copper(ii) complexes [Cu2(µ-Cl)2L2]·CH2Cl2 (1) and Cu2L4 (2) based on the natural product rosin derivative N-(5-dehydroabietyl-1,3,4-thiadiazole)-2-substituted pyridinecarboxamide (HL) were prepared, fully characterized and their biological activities were evaluated. The circular dichroism (CD), fluorescence spectroscopy, and DNA melting studies indicate that 1 and 2 interact with calf thymus DNA (CT DNA) via intercalation. It can be concluded that 1 and 2 have a strong affinity to bovine serum albumin (BSA) based on the fluorescence and CD spectral evidence. The MTT assay illustrates that the selective cytotoxic activity of 1 is better than that of HL, 2, cisplatin and oxaliplatin. The exposure of 1 to MCF-7 cells resulted in cell cycle arrest in the G1 phase, apoptosis, mitochondrial dysfunction and an elevated ROS level. The western blot analysis results indicate that 1 might induce apoptosis through intrinsic and extrinsic pathways, autophagy and DNA damage in MCF-7 cells. Furthermore, the down-regulated VEGFR2, MMP-2 and MMP-9 expression levels indicate that 1 should have the ability to resist metastasis and angiogenesis. Thus, based on the above described results 1 has high potential value for anticancer applications.

14.
Sci Rep ; 9(1): 12538, 2019 Aug 29.
Artigo em Inglês | MEDLINE | ID: mdl-31467340

RESUMO

Tuned gene expression is crucial to the proper growth and response to the environmental changes of an organism. To enable tunable gene expression as designed is desirable in both scientific research and industrial application. Here, we introduce a novel promoter switching method based on the DDI2 promoter (PDDI2) that can fine tune the expression of target genes. We constructed a recyclable cassette (PDDI2-URA3-PDDI2) and integrated it upstream of yeast target genes to replace the native promoters by DDI2 promoter without introducing any junk sequence. We found that the presence or absence of cyanamide as an inducer could turn on or off the expression of target genes. In addition, we showed that PDDI2 could act as a gene switch to linearly regulate the expression levels of target genes in vivo. We switched the original promoters of RAD18, TUP1, and CDC6 with PDDI2 as a proof-of-concept.

15.
Front Genet ; 10: 519, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31354783

RESUMO

Alzheimer's disease (AD) is a common neurodegenerative disease. APOE is the strong genetic risk factor of AD. The existing genome-wide association studies have identified many single nucleotide polymorphisms (SNPs) with minor effects on AD risk and the polygenic risk score (PRS) is presented to combine the effect of these SNPs. On the other hand, the volumes of various brain regions in AD patients have significant changes compared to that in normal individuals. Ch4 brain region containing at least 90% cholinergic neurons is the most extensive and conspicuous in the basal forebrain. Here, we investigated the relationship between the combined effect of AD-associated SNPs and Ch4 volume using the PRS approach. Our results showed that Ch4 volume in AD patients is significantly different from that in normal control subjects (p-value < 2.2 × 10-16). AD PRS, is not associated with the Ch4 volume in AD patients, excluding the APOE region (p-value = 0.264) and including the APOE region (p-value = 0.213). However, AD best-fit PRS, excluding the APOE region, is associated with Ch4 volume in normal control subjects (p-value = 0.015). AD PRS based on 8070 SNPs could explain 3.35% variance of Ch4 volume. In addition, the p-value of AD PRS model in normal control subjects, including the APOE region, is 0.006. AD PRS based on 8079 SNPs could explain 4.23% variance of Ch4 volume. In conclusion, PRS based on AD-associated SNPs is significantly related to Ch4 volume in normal subjects but not in patients.

16.
Food Funct ; 10(6): 3684-3695, 2019 Jun 19.
Artigo em Inglês | MEDLINE | ID: mdl-31168531

RESUMO

In this study, the structure characteristics and the hypoglycemic and antioxidant activities of mulberry fruit polysaccharides obtained by the commonly used hot water (MFPh)-, ultrasonic (MFPu)-, acid (MFPc)- and alkali (MFPa)-assisted extraction methods were investigated. NMR analysis indicated that the four polysaccharides had similar glycosidic linkage patterns. Scanning electron microscopy analyses showed that the surface morphology of the polysaccharides was greatly affected by the extraction methods. The results of the bioactivity assays indicated that MFPh exhibited stronger antioxidant and α-amylase inhibitory activities than the other polysaccharides. Moreover, all the polysaccharides showed good α-glucosidase inhibitory activities except for MFPu with the lowest molecular weight. These results suggested that acid, alkali, and ultrasonic-assisted extractions have different effects on the degradation of polysaccharides without changing the main structure compared with hot water extraction. In addition, the molecular weight of polysaccharides plays a key role in the bioactivity of the mulberry fruit polysaccharides.


Assuntos
Fracionamento Químico/métodos , Morus/química , Extratos Vegetais/química , Extratos Vegetais/isolamento & purificação , Polissacarídeos/química , Polissacarídeos/isolamento & purificação , Antioxidantes/química , Antioxidantes/isolamento & purificação , Inibidores Enzimáticos/química , Inibidores Enzimáticos/isolamento & purificação , Frutas/química , Glucose/química , Inibidores de Glicosídeo Hidrolases/química , Inibidores de Glicosídeo Hidrolases/isolamento & purificação , Peso Molecular , alfa-Amilases/antagonistas & inibidores , alfa-Amilases/química , alfa-Glucosidases/química
17.
Front Plant Sci ; 10: 705, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31214223

RESUMO

Peroxisomes play vital roles in plant growth, development, and environmental stress response. During plant development and in response to environmental stresses, the number and morphology of peroxisomes are dynamically regulated to maintain peroxisome homeostasis in cells. To execute their various functions in the cell, peroxisomes associate and communicate with other organelles. Under stress conditions, reactive oxygen species (ROS) produced in peroxisomes and other organelles activate signal transduction pathways, in a process known as retrograde signaling, to synergistically regulate defense systems. In this review, we focus on the recent advances in the plant peroxisome field to provide an overview of peroxisome biogenesis, degradation, crosstalk with other organelles, and their role in response to environmental stresses.

18.
PeerJ ; 7: e7037, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31218122

RESUMO

Background: Acetyl-CoA carboxylase (ACC) plays an important role in the metabolism of various cancer cells, but its role in head and neck squamous cell carcinoma (HNSCC) is uncertain. Therefore, in the present study, we explored the role of ACC2 in HNSCC. Methods: Western blot and immunohistochemistry assays were used to determine ACC2 protein expression levels in laryngocarcinoma and adjacent normal tissues derived from patients with laryngocarcinoma. ACC2 expression was knocked down in the hypopharyngeal cancer cell line FaDu to determine its effect on apoptosis. Lipid oil red staining was used to test the change of intracellular lipid. Results: The results showed that the ACC2 protein was highly expressed in laryngocarcinoma and that the ACC2 expression level was positively associated with the clinical cancer stage and negatively associated with the degree of laryngocarcinoma cell differentiation. Kaplan-Meier analyses indicated that compared with patients having low levels of ACC2, those with high ACC2 levels had a decreased 5-year survival rate. The results of western blot and terminal deoxynucleotidyl transferase dUTP nick-end labeling assays showed that knockdown of ACC2 accelerated apoptosis in FaDu cells. Furthermore, knockdown of ACC2 significantly reduced the intracellular lipid levels in FaDu cells. Conclusion: These findings suggest that ACC2 may be an important prognostic marker for patients with HNSCC and that ACC2 may be a potential target in the treatment of HNSCC.

19.
Eur J Med Chem ; 176: 175-186, 2019 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-31103898

RESUMO

The development of optically pure drugs is the trend of new drugs research. Searching for optically pure metallodrugs against cancer has not been taken seriously. [CuL4Cl]Cl·2CH2Cl2·H2O (1) and [CuL4Br]Br·2CH2Cl2 (2) (L = 2-amino-5-dehydroabietyl-1,3,4-thiadiazole), two rosin-derivative based optically pure chiral copper(II) complexes, are rationally synthesized as potential anticancer agents. 1 exhibits effective in vitro and in vivo anticancer activities and tolerable toxicities. 1 promotes MCF-7 cell death by combination of cell arrest at G1 phase, apoptosis (both extrinsic and intrinsic apoptotic pathways), anti-metastasis, anti-angiogenesis, damage of DNA, protein and lipid, and autophagy mediated by the oxidative stress which is confirmed by ROS generation and intracellular glutathione depletion assays. 1 can be identified as a lead anticancer molecule of therapeutic importance. This work may offer insights into the design and mechanism study of multifunctional optically pure metal-based anticancer candidates derived from natural products.


Assuntos
Inibidores da Angiogênese/uso terapêutico , Antineoplásicos/uso terapêutico , Complexos de Coordenação/uso terapêutico , Cobre/química , Inibidores da Angiogênese/síntese química , Inibidores da Angiogênese/química , Inibidores da Angiogênese/farmacologia , Animais , Antineoplásicos/síntese química , Antineoplásicos/química , Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Complexos de Coordenação/síntese química , Complexos de Coordenação/química , Complexos de Coordenação/farmacologia , DNA/metabolismo , Dano ao DNA/efeitos dos fármacos , Pontos de Checagem da Fase G1 do Ciclo Celular/efeitos dos fármacos , Humanos , Peroxidação de Lipídeos/efeitos dos fármacos , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Camundongos Endogâmicos BALB C , Carbonilação Proteica/efeitos dos fármacos , Espécies Reativas de Oxigênio/metabolismo , Estereoisomerismo , Ensaios Antitumorais Modelo de Xenoenxerto
20.
Molecules ; 24(11)2019 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-31141940

RESUMO

There is growing evidence that neuroinflammation is closely linked to depression. Honokiol, a biologically active substance extracted from Magnolia officinalis, which is widely used in traditional Chinese medicine, has been shown to exert significant anti-inflammatory effects and improve depression-like behavior caused by inflammation. However, the specific mechanism of action of this activity is still unclear. In this study, the lipopolysaccharide (LPS) mouse model was used to study the effect of honokiol on depression-like behavior induced by LPS in mice and its potential mechanism. A single administration of LPS (1 mg/kg, intraperitoneal injection) increased the immobility time in the forced swimming test (FST) and tail suspension test (TST), without affecting autonomous activity. Pretreatment with honokiol (10 mg/kg, oral administration) for 11 consecutive days significantly improved the immobility time of depressed mice in the FST and TST experiments. Moreover, honokiol ameliorated LPS-induced NF-κB activation in the hippocampus and significantly reduced the levels of the pro-inflammatory cytokines; tumor necrosis factor α (TNF-α), interleukin 1ß (IL-1ß), and interferon γ (IFN-γ). In addition, honokiol inhibited LPS-induced indoleamine 2,3-dioxygenase (IDO) activation and quinolinic acid (a toxic product) increase and reduced the level of free calcium in brain tissue, thereby inhibiting calcium overload. In summary, our results indicate that the anti-depressant-like effects of honokiol are mediated by its anti-inflammatory effects. Honokiol may inhibit the LPS-induced neuroinflammatory response through the NF-κB signaling pathway, reducing the levels of related pro-inflammatory cytokines, and furthermore, this may affect tryptophan metabolism and increase neuroprotective metabolites.


Assuntos
Antidepressivos/uso terapêutico , Compostos de Bifenilo/uso terapêutico , Depressão/tratamento farmacológico , Lignanas/uso terapêutico , Animais , Antidepressivos/farmacologia , Sistema Nervoso Autônomo/efeitos dos fármacos , Compostos de Bifenilo/farmacologia , Encéfalo/metabolismo , Cálcio/metabolismo , Citocinas/sangue , Depressão/fisiopatologia , Modelos Animais de Doenças , Elevação dos Membros Posteriores , Imobilização , Indolamina-Pirrol 2,3,-Dioxigenase/genética , Indolamina-Pirrol 2,3,-Dioxigenase/metabolismo , Mediadores da Inflamação/sangue , Cinurenina/metabolismo , Lignanas/farmacologia , Lipopolissacarídeos , Camundongos Endogâmicos ICR , NF-kappa B/genética , NF-kappa B/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Natação , Triptofano/metabolismo
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