Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 626
Filtrar
1.
Artigo em Inglês | MEDLINE | ID: mdl-33655847

RESUMO

BACKGROUND: Ovarian cancer is a disease with the highest mortality in gynecologic malignancies. Activation of STAT3 pathway is well known to be associated with tumor progression and metastasis in a number of cancers including ovarian cancer. Therefore, STAT3 may be an ideal target for ovarian cancer treatment. OBJECTIVE: The present study aims to determine the antitumor activity of STAT3 inhibitor Napabucasin as a single agent or in combination with proteasome inhibitor MG-132 in ovarian cancer cells. METHODS: MTT was performed to determine the anti-proliferative effect of Napabucasin on ovarian cancer SKOV-3 cells. The involved anti-tumor mechanism was explored by flow cytometry, qRT-PCR and western blot. MDC staining and tandem mRFP-GFP-LC3 fluorescence microscopy were used to analyze the autophagy inducing capability of Napabucasin with or without MG-132. The combinational anticancer effect of Napabucasin and MG-132 was evaluated according to Chou and Talalay's method (1984). RESULTS: Napabucasin showed obvious tumor-inhibitory effects against SKOV-3 cells. Treatment by Napabucasin arrested cell cycle progression in G2/M phase. Mechanistically, elevated expression of p21 may contribute to the blockade of cell cycle. Moreover, we demonstrated that Napabucasin induced autophagy in SKOV-3 cells by using various assays including MDC staining, autophagic flux examination, and detection of the autophagy markers. In addition, combination of Napabucaisin with MG-132 exhibited significant synergistic anti-proliferative effect, probably by inducing apoptosis through a mitochondria-dependent pathway. The two compounds induced pro-survival autophagies, and co-treated with autophagy inhibiter might further enhance their antitumor effects. CONCLUSION: Napabucasin alone or in combination with MG-132 might be promising treatment strategies for ovarian cancer patients.

2.
Gut Microbes ; 13(1): 1-18, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33645438

RESUMO

Intestinal epithelial cell endoplasmic reticulum (ER) stress has been implicated in intestinal inflammation. It remains unclear whether ER stress is an initiator of or a response to inflammation. Winnie mice, carrying a Muc2 gene mutation resulting in intestinal goblet cell ER stress, develop spontaneous colitis with a depleted mucus barrier and increased bacterial translocation. This study aims to determine whether the microbiota was required for the development of Winnie colitis, and whether protein misfolding itself can initiate inflammation directly in absence of the microbiota. To assess the role of microbiota in driving Winnie colitis, WT and Winnie mice on the same background were rederived into the germ-free facility and housed in the Trexler-type soft-sided isolators. The colitis phenotype of these mice was assessed and compared to WT and Winnie mice housed within a specific pathogen-free facility. We found that Winnie colitis was substantially reduced but not abolished under germ-free conditions. Expression of inflammatory cytokine genes was reduced but several chemokines remained elevated in absence of microbiota. Concomitantly, ER stress was also diminished, although mucin misfolding persisted. RNA-Seq revealed that Winnie differentiated colon organoids have decreased expression of the negative regulators of the inflammatory response compared to WT. This data along with the increase in Mip2a chemokine expression, suggests that the epithelial cells in the Winnie mice are more responsive to stimuli. Moreover, the data demonstrate that intestinal epithelial intrinsic protein misfolding can prime an inflammatory response without initiating the unfolded protein response in the absence of the microbiota. However, the microbiota is necessary for the amplification of colitis in Winnie mice. Genetic predisposition to mucin misfolding in secretory cells initiates mild inflammatory signals. However, the inflammatory signal sets a forward-feeding cycle establishing progressive inflammation in the presence of microbiota.Abbreviations: Endoplasmic Reticulum: ER; Mucin-2: Muc-2; GF: Germ-Free; Inflammatory Bowel Disease: IBD.

3.
Analyst ; 2021 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-33565552

RESUMO

4-Mercaptobenzoic acid (MBA) is introduced as a matrix for laser desorption/ionization time-of-flight mass spectrometry (MS) analysis of metals, exhibiting matrix-interference-free background, greatly enhanced MS signal intensity, and excellent reproducibility. The developed method was successfully extended for the rapid screening and sensitive determination of ultratrace metals in fine particulate matter (PM2.5).

4.
Int J Nanomedicine ; 16: 881-893, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33574668

RESUMO

Purpose: Mesoporous silica (MSNs) have attracted considerable attention for its application in the field of drug delivery and biomedicine due to its high surface area, large pore volume, and low toxicity. Recently, numerous studies revealed that gut microbiota is of critical relevance to host health. However, the toxicological studies of MSNs were mainly based on the degradation, biodistribution, and excretion in mammalian after oral administration for now. Here in this study, we explored the impacts of oral administration of three kinds of MSNs on gut microbiota in rats to assess its potential toxicity. Methods: Forty rats were divided into four groups: control group; Mobil Composition of Matter No. 41 type mesoporous silica (MCM-41) group; Santa Barbara Amorphous-15 type mesoporous silica (SBA-15) group, and biodegradable dendritic center-radial mesoporous silica nanoparticle (DMSN) group. Fecal samples were collected 3 days and 7 days after the intake of MSNs and analyzed with high throughput sequencing. Gastric tissues in rats were obtained after dissection for the histological study. Results: Three different MSNs (MCM-41, SBA-15, and DMSN) were successfully prepared in this study. The pore size of three MSNs was calculated similarly as (3.54 ± 0.15) nm, (3.48 ± 0.21) nm, and (3.45 ± 0.17) nm according to the BET & BJH model, respectively, while the particle size of MCM-41, SBA-15 and DMSN was around 209.2 nm, 1349.56 nm, and 244.4 nm, respectively. In the gene analysis of 16S rRNA, no significant changes in the diversity and richness were found between groups, while Verrucomicrobia decreased and Candidatus Saccharibacteria increased in MCM-41 treated groups. Meanwhile, no inflammatory and erosion symptoms were observed in the morphological analysis of the colons, except the MCM-41 treated group. Conclusion: Three different MSNs, MCM-41, SBA-15, and DMSN were successfully prepared, and this study firstly suggested the impact of MSNs on the gut microbiota, and further revealing the potential pro-inflammatory effects of oral administration of MCM-41 was possibly through the changing of gut microbiota.

5.
Sci China Life Sci ; 2021 Feb 09.
Artigo em Inglês | MEDLINE | ID: mdl-33580429

RESUMO

After antigen stimulation, T cells preferentially increase aerobic glycolysis to meet the bioenergetic and biosynthetic demands of T cell activation, proliferation, and effector functions. Lactate, a by-product of glycolysis, has been reported to function as an important energy source and signaling molecule. Here, we found that lactate anions are involved in cytokine production in T cells after TCR activation. During ex vivo T cell activation, the addition of excess sodium lactate (NaL) increased the production of cytokines (such as IFNγ/IL-2/TNFα) more than the addition of sodium chloride (NaCl). This enhanced cytokine production was dependent on TCR/CD3 activation but not CD28 activation. In vivo, NaL treatment inhibited tumour growth in subcutaneously transplanted tumour models in a T cell-dependent manner, which was consistent with increased T cell cytokine production in the NaL treatment group compared to the NaCl treatment group. Furthermore, a mechanistic experiment showed that this enhanced cytokine production was regulated by GAPDH-mediated post-transcriptional regulation. Taken together, our findings indicate a new regulatory mechanism involved in glycolysis that promotes T cell function.

6.
Cell Res ; 2021 Feb 19.
Artigo em Inglês | MEDLINE | ID: mdl-33608671

RESUMO

The pluripotency of mammalian early and late epiblast could be recapitulated by naïve embryonic stem cells (ESCs) and primed epiblast stem cells (EpiSCs), respectively. However, these two states of pluripotency may not be sufficient to reflect the full complexity and developmental potency of the epiblast during mammalian early development. Here we report the establishment of self-renewing formative pluripotent stem cells (fPSCs) which manifest features of epiblast cells poised for gastrulation. fPSCs can be established from different mouse ESCs, pre-/early-gastrula epiblasts and induced PSCs. Similar to pre-/early-gastrula epiblasts, fPSCs show the transcriptomic features of formative pluripotency, which are distinct from naïve ESCs and primed EpiSCs. fPSCs show the unique epigenetic states of E6.5 epiblast, including the super-bivalency of a large set of developmental genes. Just like epiblast cells immediately before gastrulation, fPSCs can efficiently differentiate into three germ layers and primordial germ cells (PGCs) in vitro. Thus, fPSCs highlight the feasibility of using PSCs to explore the development of mammalian epiblast.

7.
J Agric Food Chem ; 69(8): 2485-2492, 2021 Mar 03.
Artigo em Inglês | MEDLINE | ID: mdl-33555192

RESUMO

To systematically study the multiple effects of nanoparticles (NPs) on the stability, interfacial activity, and digestive properties of Pickering emulsions (PEs), various oil-in-water PEs were prepared by NPs based on the self-assembled α-lactalbumin-derived peptides with a variety of morphologies, stiffnesses, and sizes. We discovered that PEs stabilized by small-sized and soft nanospheres (NSs) exhibited the highest stability compared with other nanoparticles observed by Turbiscan during storage. Dilational interfacial rheological analysis demonstrated that a highly elastic interfacial film of the NSs had been formed by orderly packing at oil/water interfaces. Meanwhile, the most stable Pickering emulsion stabilized by NSs possessed the lowest lipid digestion rate. The tubular NPs distributed unevenly at the oil-water interfaces therefore showed lower interfacial activity. Harder NPs with lower flexibility showed a lower emulsion stability. Curcumin was loaded in PEs to further study the effect of bioavailability. Moreover, in vivo pharmacokinetic results revealed that Pickering emulsion stabilized by NSs showed the highest curcumin bioavailability, which was 5.37 times higher than unencapsulated curcumin. This study suggested that Pickering emulsion stabilized by NSs with the optimum stability was the most promising delivery system for hydrophobic bioactive ingredients.

9.
World J Gastroenterol ; 27(4): 321-335, 2021 Jan 28.
Artigo em Inglês | MEDLINE | ID: mdl-33584065

RESUMO

BACKGROUND: Preoperative pulmonary function plays an important role in selecting surgical candidates and assessing postoperative complications. Reduced pulmonary function is associated with poor survival in several cancers, but the prognostic value of preoperative pulmonary function in esophageal squamous cell carcinoma (ESCC) is unclear. Nutritional and systemic inflammation parameters are vital to cancer survival, and the combination of these parameters improves the prognostic value. The hemoglobin, albumin, lymphocytes and platelets (HALP) score is a novel prognostic indicator to reflect the nutritional and inflammation status, but the clinical effects of the HALP score combined with maximal voluntary ventilation (MVV), an important parameter of pulmonary function, have not been well studied in ESCC. AIM: To investigate the prognostic value of MVV and HALP score for assessing postoperative survival of ESCC patients. METHODS: Data from 834 ESCC patients who underwent radical esophagectomy with R0 resection were collected and retrospectively analyzed. Preoperative MVV and HALP data were retrieved from medical archives. The HALP score was calculated by the formula: Hemoglobin (g/L) × albumin (g/L) × lymphocytes (/L)/platelets (/L). The optimal cut-off values of MVV and HALP score were calculated by the receiver operating characteristic curve analysis. The Kaplan-Meier method with log-rank test was used to draw the survival curves for the variables tested. Multivariate Cox proportional hazard regression models were used to analyze the independent prognostic factors for overall survival. RESULTS: MVV was significantly associated with gender (P < 0.001), age at diagnosis (P < 0.001), smoking history (P < 0.001), drinking history (P < 0.001), tumor length (P = 0.013), tumor location (P = 0.037) and treatment type (P = 0.001). The HALP score was notably associated with gender (P < 0.001), age at diagnosis (P = 0.035), tumor length (P < 0.001) and invasion depth (P = 0.001). Univariate Cox regression analysis showed that low MVV and low HALP score were associated with worse overall survival (all P < 0.001). Multivariate analysis showed that low MVV and the HALP score were both independent risk factors for overall survival (all P < 0.001). The combination of MVV and HALP score improved the prediction performance for overall survival than tumor-node-metastasis. Also, low combination of MVV and HALP score was an independent risk factor for poor overall survival (P < 0.001). CONCLUSION: MVV, HALP score and their combination are simple and promising clinical markers to predict overall survival of ESCC patients.

10.
Pest Manag Sci ; 2021 Feb 23.
Artigo em Inglês | MEDLINE | ID: mdl-33619804

RESUMO

BACKGROUND: Bemisia tabaci (Gennadius) is a major damaging agricultural pest and exhibits high resistance to pyrethroid insecticides. L925I (TTA to ATA) and T929V (ACT to GTT) mutations in para-type voltage-gated sodium channel (VGSC) are associated with resistance of B. tabaci to pyrethroids. Amplicon sequencing is a reliable and high-efficient method to detect the frequency of mutation linked with insecticide resistance. RESULTS: Similar frequencies of L925I and T929V mutations were obtained by amplicon sequencing and Sanger sequencing (L925I: 0.3548 vs 0.3619; T929V: 0.6140 vs 0.6434) with overlap of 95% confidence interval in SX population of B. tabaci. In five populations of B. tabaci from China, the maximum and minimum frequencies of the two mutations were found in LN (L925I: 0.1126; T929V: 0.8834) and JS population (L925I: 0.8776; T929V: 0.1166) by amplicon sequencing. However, there was no significant difference in frequencies between L925I and T929V mutation. The sum frequency of L925I and T929V exceeded 0.9688 in all populations. In addition, a combining mutation, L925 + T929V (L925I and T929V located in same allele), was found in five populations by amplicon sequencing even though its highest frequency was only 0.0157. CONCLUSION: We established an efficient approach for detecting frequency of mutation by amplicon sequencing. The frequencies of L925I and T929V in VGSC associated with pyrethroids resistance were detected in this study, which could provide foundational data for resistance management of B. tabaci.

11.
Stem Cell Reports ; 2021 Feb 11.
Artigo em Inglês | MEDLINE | ID: mdl-33577795

RESUMO

Direct neuronal reprogramming potentially provides valuable sources for cell-based therapies. Proneural gene Ascl1 converts astrocytes into induced neuronal (iN) cells efficiently both in vitro and in vivo. However, the underlying mechanisms are largely unknown. By combining RNA sequencing and chromatin immunoprecipitation followed by high-throughput sequencing, we found that the expression of 1,501 genes was markedly changed during the early stages of Ascl1-induced astrocyte-to-neuron conversion and that the regulatory regions of 107 differentially expressed genes were directly bound by ASCL1. Among Ascl1's direct targets, Klf10 regulates the neuritogenesis of iN cells at the early stage, Myt1 and Myt1l are critical for the electrophysiological maturation of iN cells, and Neurod4 and Chd7 are required for the efficient conversion of astrocytes into neurons. Together, this study provides more insights into understanding the molecular mechanisms underlying Ascl1-mediated astrocyte-to-neuron conversion and will be of value for the application of direct neuronal reprogramming.

12.
Pest Manag Sci ; 2021 Feb 24.
Artigo em Inglês | MEDLINE | ID: mdl-33624368

RESUMO

BACKGROUND: Over the past decades, many efficacious insecticides have been applied for control of Bemisia tabaci, one of the most notorious insect pests worldwide. Field-evolved insecticide resistance in B. tabaci has developed globally, however, this remains poorly 5understood in China. RESULTS: In this study, a total of 30 field samples from 8 provinces of China were collected in 2015 to 2018. Twenty-four of the populations were identified as MED, three were mixtures of MED/MEAM1, and three were MEAM1. After identifying whether they belong to MED or MEAM1, the selected individuals were used in bioassays assessing insecticide resistance to abamectin, thiamethoxam, spirotetramat, cyantraniliprole, and pyriproxyfen. Our results showed that all populations in the eight regions had little or no resistance to abamectin; abamectin resistance was highest in the Hunan (Changsha) and Hubei (Wuhan) regions and was lowest in the island region of Hainan (Sanya). The resistance of B. tabaci to spirotetramat, cyantraniliprole, and pyriproxyfen increased each year. The resistance to thiamethoxam remained low because of the high LC50 value for the laboratory strain. CONCLUSION: These findings suggest that a rotation system using efficacious B. tabaci insecticides with differing mode of actions ought to be implemented for sustainable control to reduce the potential of resistance development. This study provides important data to support the integrated pest management and insecticide resistance management of B. tabaci in China. This article is protected by copyright. All rights reserved.

13.
Nat Commun ; 12(1): 46, 2021 01 04.
Artigo em Inglês | MEDLINE | ID: mdl-33397902

RESUMO

The exploration of highly efficient processes to convert renewable biomass to fuels and value-added chemicals is stimulated by the energy and environment problems. Herein, we describe an innovative route for the production of methylcyclopentadiene (MCPD) with cellulose, involving the transformation of cellulose into 3-methylcyclopent-2-enone (MCP) and subsequent selective hydrodeoxygenation to MCPD over a zinc-molybdenum oxide catalyst. The excellent performance of the zinc-molybdenum oxide catalyst is attributed to the formation of ZnMoO3 species during the reduction of ZnMoO4. Experiments reveal that preferential interaction of ZnMoO3 sites with the C=O bond instead of C=C bond in vapor-phase hydrodeoxygenation of MCP leads to highly selective formations of MCPD (with a carbon yield of 70%).


Assuntos
Celulose/química , Ciclopentanos/química , Óxidos/química , Oxigênio/química , Adsorção , Catálise , Relação Estrutura-Atividade , Difração de Raios X
14.
Nat Commun ; 12(1): 76, 2021 01 04.
Artigo em Inglês | MEDLINE | ID: mdl-33397953

RESUMO

Full development of IL-17 producing CD4+ T helper cells (TH17 cells) requires the transcriptional activity of both orphan nuclear receptors RORα and RORγt. However, RORα is considered functionally redundant to RORγt; therefore, the function and therapeutic value of RORα in TH17 cells is unclear. Here, using mouse models of autoimmune and chronic inflammation, we show that expression of RORα is required for TH17 cell pathogenicity. T-cell-specific deletion of RORα reduces the development of experimental autoimmune encephalomyelitis (EAE) and colitis. Reduced inflammation is associated with decreased TH17 cell development, lower expression of tissue-homing chemokine receptors and integrins, and increased frequencies of Foxp3+ T regulatory cells. Importantly, inhibition of RORα with a selective small molecule antagonist mostly phenocopies our genetic data, showing potent suppression of the in vivo development of both chronic/progressive and relapsing/remitting EAE, but with no effect on overall thymic cellularity. Furthermore, use of the RORα antagonist effectively inhibits human TH17 cell differentiation and memory cytokine secretion. Together, these data suggest that RORα functions independent of RORγt in programming TH17 pathogenicity and identifies RORα as a safer and more selective therapeutic target for the treatment of TH17-mediated autoimmunity.


Assuntos
Inflamação/imunologia , Membro 1 do Grupo F da Subfamília 1 de Receptores Nucleares/antagonistas & inibidores , Células Th17/imunologia , Animais , Autoimunidade/efeitos dos fármacos , Peso Corporal/efeitos dos fármacos , Doença Crônica , Colo/patologia , Modelos Animais de Doenças , Encefalomielite Autoimune Experimental , Células HEK293 , Humanos , Inflamação/genética , Camundongos Endogâmicos C57BL , Membro 1 do Grupo F da Subfamília 1 de Receptores Nucleares/genética , Tamanho do Órgão/efeitos dos fármacos , Índice de Gravidade de Doença , Bibliotecas de Moléculas Pequenas/química , Bibliotecas de Moléculas Pequenas/farmacologia , Sulfonamidas/química , Sulfonamidas/farmacologia , Tiofenos/química , Tiofenos/farmacologia
15.
Artigo em Inglês | MEDLINE | ID: mdl-33478210

RESUMO

Great efforts have been made to design high-performing Si/C composite anodes for Li-ion batteries to improve their energy density and cycling life. However, challenges remain in achieving fast electrical conductivity while accommodating significant electrode volumetric changes. Here, we report a unique Si/C-based anode architecture, a Si-SiOx-CNx composite, which is simultaneously constructed via the pyrolysis of a polyaminosiloxane precursor. The obtained structure features high-purity Si nanocrystals embedded in an amorphous silica matrix and then embraced by N-doped carbon layers. Notably, in this structure, all three components derived from the polyaminosiloxane precursor are linked by chemical bonding, forming a compact Si-SiOx-CNx triple heterostructure. Because of the improvement in the volumetric efficiency for accommodating Si active materials and electrical properties, this anode design enables promising electrochemical performance, including excellent cycle performance (830 mAh g-1 after 100 cycles at 0.1 A g-1) and outstanding rate performance (400 mAh g-1 at 5 A g-1). Moreover, this composite anode demonstrates great potential for high-energy Li-ion batteries, where a Si-SiOx-CNx//LiNi0.9Co0.1O2 full-cell shows a high capacity of 180 mAh g-1 as well as stable cycle performance (150 mAh g-1 after 200 cycles at 0.19 A g-1).

16.
Artigo em Inglês | MEDLINE | ID: mdl-33461473

RESUMO

BACKGROUND: Bone metastasis is one of the most common complications of Prostate cancer (PCa). The detection of distal bone metastasis at the time of initial PCa diagnosis is valuable for the determination of therapeutic methods and for the prognosis of PCa. Many current therapeutic methods target PCa bone metastasis, but no uniform evaluation standard for therapeutic efficacy has been established; in addition, traditional therapeutic evaluation standards that rely on changes in the measured tumor volume are quite controversial. In clinical practice, the volumes of some tumors often change nonsignificantly at the early stage of therapy (especially targeted therapy),while the volumes of other tumors, such as metastatic bone lesions, are difficult to measure. Diffusion-weighted imaging (DWI) not only reflects the diffusion characteristics of tissues but can also allow the analysis of microstructural and functional changes in tissues. Therefore, DWI is suitable for evaluations of early responses to tumor therapy. OBJECTIVE: This study mainly reviews the principle of DWI and its progress in the detection and therapy evaluation of PCa bone metastasis. METHODS: PubMed was searched to identify eligible articles up to December 26, 2020. The keywords of the analysis included DWI, PCa, bone metastasis, therapeutic response, targeted therapy, bone scintigraphy (BS), positron emission tomography/computed tomography (PET/CT) and metastatic castration-resistant prostate cancer (mCRPC). RESULTS: This review based on collected articles achieved an imaging biomarker for detection and therapy evaluation of PCa bone metastasis. CONCLUSION: DWI is a promising imaging method for the detection and therapeutic evaluation of PCa bone metastases.

17.
BMC Plant Biol ; 21(1): 32, 2021 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-33413114

RESUMO

BACKGROUND: Carotenoids play important roles in photosynthesis, hormone signaling, and secondary metabolism. Phytoene synthase (PSY) catalyzes the first step of the carotenoid biosynthetic pathway. In this study, we aimed to characterize the PSY genes in tobacco and analyze their function. RESULTS: In this study, we identified three groups of PSY genes, namely PSY1, PSY2, and PSY3, in four Nicotiana species; phylogenetic analysis indicated that these genes shared a high similarity with those in tomato but not with those in monocots such as rice and maize. The expression levels of PSY1 and PSY2 were observed to be highest in leaves compared to other tissues, and they could be elevated by treatment with certain phytohormones and exposure to strong light. No PSY3 expression was detected under these conditions. We constructed virus-induced PSY1 and PSY2 silencing in tobacco and found that the newly emerged leaves in these plants were characterized by severe bleaching and markedly decreased carotenoid and chlorophyll content. Thylakoid membrane protein complex levels in the gene-silenced plants were also less than those in the control plants. The chlorophyll fluorescence parameters such as Fv/Fm, ΦPSII, qP, and NPQ, which reflect photosynthetic system activities, of the gene-silenced plants were also significantly decreased. We further performed RNA-Seq and metabonomics analysis between gene-silenced tobacco and control plants. RNA-Seq results showed that abiotic stress, isoprenoid compounds, and amino acid catabolic processes were upregulated, whereas the biosynthesis of cell wall components was downregulated. Metabolic analysis results were consistent with the RNA-Seq. We also found the downstream genes in carotenoid biosynthesis pathways were upregulated, and putative transcription factors that regulate carotenoid biosynthesis were identified. CONCLUSIONS: Our results suggest that PSY can regulate carotenoid contents not only by controlling the first biosynthesis step but also by exerting effects on the expression of downstream genes, which would thereby affect photosynthetic activity. Meanwhile, PSY may affect other processes such as amino acid catabolism and cell wall organization. The information we report here may aid further research on PSY genes and carotenoid biosynthesis.

18.
Cell Death Dis ; 12(1): 38, 2021 Jan 04.
Artigo em Inglês | MEDLINE | ID: mdl-33414420

RESUMO

Cancer cells secrete abundant exosomes, and the secretion can be promoted by an increase of intracellular Ca2+. Stromal interaction molecule 1 (STIM1) plays a key role in shaping Ca2+ signals. MicroRNAs (miRNAs) have been reported to be potential therapeutic targets for many diseases, including breast cancer. Recently, we investigated the effect of exosomes from STIM1-knockout breast cancer MDA-MB-231 cells (Exo-STIM1-KO), and from SKF96365-treated MDA-MB-231 cells (Exo-SKF) on angiogenesis in human umbilical vein endothelial cells (HUVECs) and nude mice. The exosomes Exo-STIM1-KO and Exo-SKF inhibited tube formation by HUVECs remarkably. The miR-145 was increased in SKF96365 treated or STIM1-knockout MDA-MB-231 cells, Exo-SKF and Exo-STIM1-KO, and HUVECs treated with Exo-SKF or Exo-STIM1-KO. Moreover, the expressions of insulin receptor substrate 1 (IRS1), which is the target of miR-145, and the downstream proteins such as Akt/mammalian target of rapamycin (mTOR), Raf/extracellular signal regulated-protein kinase (ERK), and p38 were markedly inhibited in HUVECs treated with Exo-SKF or Exo-STIM1-KO. Matrigel plug assay in vivo showed that tumor angiogenesis was suppressed in Exo-STIM1-KO, but promoted when miR-145 antagomir was added. Taken together, our findings suggest that STIM1 promotes angiogenesis by reducing exosomal miR-145 in breast cancer MDA-MB-231 cells.

19.
Environ Sci Technol ; 55(3): 1604-1614, 2021 Feb 02.
Artigo em Inglês | MEDLINE | ID: mdl-33427447

RESUMO

The occurrence of high-level tigecycline resistance tet(X) variant genes represents a new transferable resistance crisis to food safety and human health. Here, we investigated the abundance of tet(X)-variant genes [tet(X), tet(X1) to tet(X6)] in 33 samples collected from layer manures, manured/un-manured soils, and corresponding lettuce from three provinces in China. The results showed the occurrence of tet(X)/(X2), tet(X3), and tet(X4) in 24 samples. The detection rate of tet(X)/(X2) (23/24) is higher than that of tet(X3) (7/24) and tet(X4) (2/24), and tet(X)/tet(X2) and tet(X3) were found to be enriched and more abundant in most manured soil and several lettuce samples from manured soils than that from manure samples. Twenty six tigecycline-resistant bacteria were isolated, and tet(X)-variant genes were found to be disseminated not only by bacterial clone spreading but also via multidrug resistance plasmids. The total concentrations of tet(X)-variant genes showed significantly positive correlations (R = 0.683, p < 0.001) with ISCR2. Two veterinary tetracyclines (tetracycline and oxytetracycline) and other classes of antimicrobials (enrofloxacin, azithromycin, thiamphenicol, and florfenicol) showed significant correlations with the total concentrations of tet(X)-variant genes (R = 0.35-0.516, p < 0.05). The findings indicate the transmission of tet(X)-variant genes from layer manures to their receiving environmental soils and lettuce and highlight the contribution of veterinary antimicrobials to the spread of tet(X)-variant genes.

20.
J Mol Histol ; 2021 Jan 29.
Artigo em Inglês | MEDLINE | ID: mdl-33515112

RESUMO

Rhomboid domain containing 1 (RHBDD1) gene, which was reported to be upregulated in human several cancer, was associated with carcinogenesis. However, the potential biological function of RHBDD1 in non-small cell lung cancer (NSCLC) carcinogenesis remains still not known. In this study, we aimed to investigate the role of RHBDD1 and its underlying molecular mechanism in NSCLC. The gene RHBDD1 expression was detected in NSCLC tissues and matched nontumor adjacent tissues. In vitro experiments, NSCLC cell lines (A549, H1650, H358 and H1299) were performed to investigate the biological function of RHBDD1 and its molecular mechanism. Our findings showed that the mRNA and protein expression levels of RHBDD1 were notably increased in human NSCLC tissues and cell lines, especially in A549 and H1650 cells. Moreover, silencing of RHBDD1 by RNAi notably inhibited NSCLC cell proliferation and increased cell apoptosis. Caspase-3/7 activity was remarkably increased in cells treated with RHBDD1 siRNA. RHBDD1 silencing notably reduced the number of invading cells. Furthermore, our findings showed that silencing of RHBDD1 notably inhibited the mRNA and protein expression levels of ZEB1 in A549 and H1650 cells. The phosphorylation of PI3K and AKT was also remarkably decreased by RHBDD1 silencing. ZEB1/AKT overexpression reversed the effect of RHBDD1 silencing on NSCLC cell growth and invasion. Taken together, our findings indicated that RHBDD1 silencing inhibited cell growth and invasion of non-small cell lung cancer by mediating ZEB1/PI3K/AKT signaling pathway, implying that RHBDD1 was possibly a potential diagnostic and therapeutic target for NSCLC treatment.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...