RESUMEN
In this study, the impact of surfactants on the adsorption behavior of Pb(II) onto microplastics-sediment (MPs-S) complexes was investigated. Firstly, virgin polyamide (VPA) and polyethylene (VPE) were placed in Xiangjiang River sediment for six months to conduct in-situ aging. The results indicated that the biofilm-developed polyamide (BPA) and polyethylene (BPE) formed new oxygen-containing functional groups and different biofilm species. Furthermore, the adsorption capacity of Pb(II) in sediment (S) and MPs-S complexes was in the following order: S > BPA-S > VPE-S > VPA-S > BPE-S. The addition of sodium dodecyl benzenesulfonate (SDBS) promoted the adsorption of Pb(II), and the adsorption amount of Pb(II) increased with the higher concentration of SDBS, while adding cetyltrimethylammonium bromide (CTAB) showed the opposite result. The adsorption process of MPs-S complexes to Pb(II) was dominated by chemical adsorption, and the interaction between MPs-S complexes and Pb(II) was multilayer adsorption involving physical and chemical adsorption when the surfactants were added. Besides, the pH exerts a significant effect on Pb(II) adsorption in different MPs-S complexes, and the highest adsorption amount occurred at pH 6. Noteworthy, CTAB promoted the adsorption ability of Pb(II) when the exogenous FA was added. The binding characteristic of sediment endogenous DOM components and Pb(II) was influenced by the addition of MPs and surfactants. Finally, it confirmed that adsorption mechanisms mainly involve electrostatic and hydrophobic interaction. This study provides a new perspective to explore the environmental behaviors of Pb(II) by MPs and sediments with the addition of surfactants, which was conducive to evaluating the ecological risks of MPs and heavy metals in aquatic environments.
RESUMEN
PURPOSE: Organ fibrosis is a huge challenge in clinic. There are no drugs for fibrotic cataracts treatments in clinic. Nintedanib is approved by the FDA for pulmonary fibrosis treatments. This study aims to investigate the efficacy and mechanism of nintedanib on fibrotic cataracts. METHODS: Drug efficacy was validated through TGFß2-induced cell models and injury-induced anterior subcapsular cataract (ASC) mice. A slit lamp and the eosin staining technique were applied to access the degree of capsular fibrosis. The CCK-8 assay was used to evaluate the toxicity and anti-proliferation ability of the drug. The cell migration was determined by wound healing assay and transwell assay. The anti-epithelial mesenchymal transition (EMT) and anti-fibrosis efficacy were evaluated by qRT-PCR, immunoblot, and immunofluorescence. The inhibition of nintedanib to signaling pathways was certified by immunoblot. RESULTS: Nintedanib inhibited the migration and proliferation of TGFß2-induced cell models. Nintedanib can also repress the EMT and fibrosis of the lens epithelial cells. The intracameral injection of nintedanib can also allay the anterior subcapsular opacification in ASC mice. The TGFß2/ Smad and non-Smad signaling pathways can be blocked by nintedanib in vitro and in vivo. CONCLUSION: Nintedanib alleviates fibrotic cataracts by suppressing the TGFß2/ Smad and non-Smad signaling pathways. Nintedanib is a potential drug for lens fibrosis.
Asunto(s)
Movimiento Celular , Transición Epitelial-Mesenquimal , Fibrosis , Indoles , Cristalino , Factor de Crecimiento Transformador beta2 , Animales , Indoles/farmacología , Indoles/uso terapéutico , Cristalino/efectos de los fármacos , Cristalino/patología , Factor de Crecimiento Transformador beta2/metabolismo , Transición Epitelial-Mesenquimal/efectos de los fármacos , Ratones , Movimiento Celular/efectos de los fármacos , Fibrosis/tratamiento farmacológico , Humanos , Proliferación Celular/efectos de los fármacos , Línea Celular , Transducción de Señal/efectos de los fármacos , Catarata/tratamiento farmacológico , Ratones Endogámicos C57BL , Células Epiteliales/efectos de los fármacos , Modelos Animales de Enfermedad , Antifibróticos/farmacología , Antifibróticos/uso terapéutico , MasculinoRESUMEN
The coexistence of microplastics (MPs) and heavy metals in sediments has caused a potential threat to sediment biota. However, differences in the effects of MPs and heavy metals on microbes and plants in sediments under different sediment conditions remain unclear. Hence, we investigated the influence of polyethylene (PE) and polylactic acid (PLA) MPs on microbial community structure, Pb bioavailability, and wheatgrass traits under sequential incubation of sediments (i.e., flood, drainage, and planting stages). Results showed that the sediment enzyme activities presented a dose-dependent effect of MPs. Besides, 10 % PLA MPs significantly increased the F1 fractions in three stages by 11.13 %, 30.10 %, and 17.26 %, respectively, thus resulting in higher Pb mobility and biotoxicity. MPs altered sediment bacterial composition and structures, and bacterial community differences were evident in different incubation stages. Moreover, the co-exposure of PLA MPs and Pb significantly decreased the shoot length and total biomass of wheatgrass and correspondingly activated the antioxidant enzyme activity. Further correlation analysis demonstrated that community structure induced by MPs was mainly driven by sediment enzyme activity. This study contributes to elucidating the combined effects of MPs and heavy metals on sediment ecosystems under different sediment conditions.
Asunto(s)
Sedimentos Geológicos , Plomo , Microplásticos , Contaminantes Químicos del Agua , Sedimentos Geológicos/microbiología , Plomo/toxicidad , Microplásticos/toxicidad , Contaminantes Químicos del Agua/toxicidad , Microbiota/efectos de los fármacos , Poliésteres , Polietileno/toxicidad , Inundaciones , Bacterias/efectos de los fármacosRESUMEN
Microplastics (MPs) pollution is widely investigated owing to its potential threats to river ecosystems. However, it remains unclear whether hydraulic disturbance deepens or mitigates the effects of MPs-contaminated sediments on the river environment. Herein, we studied the impact of sediment aggregates, organic matter, and enzyme activity, with emphasis on microbial community structure and function in sediments exposed to MPs (1 %, 5 %, and 10 % w/w) in conjunction with hydraulic disturbance. The experimental results showed that the influence of MPs on the sediment under hydraulic disturbance is more significant than that of static culture, especially for various environmental factors (MWD, MBC, and sucrase activity etc.). The proportions of the >0.05 mm-fraction aggregates increased from 74-76 % to 82-88 % in the sediment throughout the entire disturbance process. It has been found that the disturbance generally promotes the interaction between MPs and sediments. FAPROTAX analysis demonstrated that the disturbance reduced the difference in effects on microbial functional genes between the control group and the MPs-added groups by up to 10 times, suggesting that the effects of disturbance on MPs-contaminated sediments are relatively complex. This work provides new insights into the effects of hydraulic disturbance on physicochemical properties and microbial communities of MPs-contaminated sediment.
Asunto(s)
Microbiota , Contaminantes Químicos del Agua , Microplásticos , Plásticos , Contaminación Ambiental , Ríos , Sedimentos Geológicos , Monitoreo del AmbienteRESUMEN
Pure gelatin film often exhibits high hydrophilicity and a lack of antibacterial activity, hindering its practical application in the field of food preservation. To address these issues, we incorporated 2,2,6,6-tetramethylpiperidine-1-oxyl radical (TEMPO)-oxidized bacterial cellulose (TOBC) nanofibers stabilized cinnamon essential oil (CEO) Pickering emulsions into the gelatin matrix to develop active food packaging films. The study revealed that the good distribution of emulsion droplets in the film matrix. While with increasing Pickering emulsion proportion, the microstructures of composite films were more heterogeneous, showing some pores or cavities. In addition, the insertion of TOBC-stabilized CEO emulsions could improve the elongation at break (EAB), water-resistance, UV blocking ability, and antibacterial activity of film, but reduced its tensile strength (TS) and water vapor barrier properties (WVP). Notably, the film prepared with 4 % TOBC-stabilized CEO Pickering emulsion demonstrated enhanced preservation of strawberries. Overall, the as-prepared gelatin-based active composite films have considerable potential for food packaging.
Asunto(s)
Celulosa Oxidada , Nanofibras , Aceites Volátiles , Celulosa Oxidada/química , Gelatina/química , Aceites Volátiles/farmacología , Aceites Volátiles/química , Cinnamomum zeylanicum/química , Emulsiones/química , AntibacterianosRESUMEN
Tomostethus sinofraxini Wang & Wei (a new name is proposed for Tomostethus fraxini Niu & Wei, 2022: Tomostethus sinofraxini Wang & Wei, nom. nov.), an emerging sawfly pest of the Chinese ash, Fraxinus chinensis, is now endemic to Beijing, Tianjin, Hebei, and Shandong provinces. Given the severity of its infestation and the speed of its range expansion, we studied the phylogenetic relationship of T. sinofraxini with other sawfly species and its life history to be better informed for the management strategies. The nearly complete T. sinofraxini mitogenome is 16,169 bp in length and encodes 2 ribosomal RNAs (rrnL and rrnS), 22 transfer RNAs (tRNAs), and 13 protein-coding genes. The nucleotide composition is biased toward adenine and thymine (Aâ +â Tâ =â 81.7%). In comparison to the architecture of the ancestral insect mitogenome, 2 transposition events occur on the IQM tRNA cluster, rearranging it from IQM to MQI. Our phylogenetic analysis suggests that T. sinofraxini belongs to a group composed of paraphyletic subfamilies Blennocampinae and Heterarthrinae. In addition, to document its life history, we observed T. sinofraxini development at 2 geographical locations in Beijing, China, with different altitudes. At Jiulong Mountain, with a higher altitude and a lower average temperature, the developmental time of egg, larval, and adult stages was 19%-31% longer than that observed at the Chinese Academy of Forestry. A basic understanding of biological traits and molecular signatures is the critical first step to develop an integrated pest management framework for this emerging pest of the Chinese ash.
Asunto(s)
Fraxinus , Genoma Mitocondrial , Himenópteros , Animales , Filogenia , ARN Ribosómico/genética , ARN de Transferencia/genéticaRESUMEN
Microplastics (MPs) accumulation in sediments has posed a huge threat to freshwater ecosystems. However, it is still unclear the effect of MPs on riparian sediment structures and contaminant adsorption under different hydrological processes. In this study, three concentrations of polyamide (PA) MPs-treated sediments (0.1%, 1%, and 10%, w/w) were subjected to natural (NA) exposure, dry-wet (DW) cycles, and freeze-thaw (FT) cycles. The results indicated that PA MPs-added sediment increased the micro-aggregates by 10.1%-18.6% after FT cycles, leading to a decrease in aggregate stability. The pH, OM, and DOC of sediments were significantly increased in DW and FT treatments. In addition, the increasing concentration of PA MPs showed an obvious decrease in aromaticity, humification, and molecular weight of sediment DOM in FT treatments. Also, high level of MPs was more likely to inhibit the formation of humic-like substances and tryptophan-like proteins. For DW and FT cycles, 0.1% and 1% PA MPs-treated sediments slightly increased the adsorption capacity of Cd(II), which may be ascribed to the aging of MPs. Further correlation analysis found that DW and FT altered the link between DOM indicators, and aggregate stability was directly related to the changes in sediment organic carbon. Our findings revealed the ecological risk of MPs accumulating in riparian sediments under typical hydrological processes.
RESUMEN
[This corrects the article DOI: 10.3389/fonc.2022.993243.].
RESUMEN
Subsequently to the publication of the above article, the authors alerted us to the fact that the data shown in Fig. 8I (for the 'ShCN / 0' panel) on p. 11 were mistakenly selected from those data belonging to the experiments shown in Fig. 7H (the 'ShCN / 0' panel) of this paper during the final assembly of the figures for review. Note that this error did not affect the conclusions reported in this paper, as both Fig. 7H ('ShCN / 0') and Fig. 8I ('ShCN / 0') show negative controls of the Comet assay, with no obvious trailing. The revised version of Fig. 8, showing the correct data for the 'ShCN / 0' panel in Fig. 8I, is shown on the next page. The authors are grateful to the Editor of International Journal of Oncology for allowing them this opportunity to publish a Corrigendum, and all the authors agree with its publication. Furthermore, the authors apologize to the readership for any inconvenience caused. [International Journal of Oncology 61: 106, 2022; DOI: 10.3892/ijo.2022.5396].
RESUMEN
The expression of O-GlcNAc transferase (OGT) and its catalytic product, O-GlcNAcylation (O-GlcNAc), are elevated in many types of cancers, including prostate cancer (PC). Inhibition of OGT serves as a potential strategy for PC treatment alone or combinational therapy. PC is the second common cancer type in male worldwide, for which chemotherapy is still the first-line treatment. However, the function of inhibition of OGT on chemotherapeutic response in PC cells is still unknown. In this study, we show that inhibition of OGT by genetic knockdown using shRNA or by chemical inhibition using OGT inhibitors sensitize PC cells to docetaxel, which is the most common chemotherapeutic agent in PC chemotherapy. Furthermore, we identified that microRNA-140 (miR-140) directly binds to OGT mRNA 3' untranslated region and inhibits OGT expression. Moreover, docetaxel treatment stimulates miR-140 expression, whereas represses OGT expression in PC cells. Overexpression of miR-140 enhanced the drug sensitivity of PC cells to docetaxel, which could be reversed by overexpression of OGT. Overall, this study demonstrates miR-140/OGT axis as therapeutic target in PC treatment and provides a promising adjuvant therapeutic strategy for PC therapy.
RESUMEN
BACKGROUND: To evaluate the global burden of cataracts by year, age, region, gender, and socioeconomic status using disability-adjusted life years (DALYs) and prevalence from the Global Burden of Disease (GBD) study 2019. METHODS: Global, regional, or national DALY numbers, crude DALY rates, and age-standardized DALY rates caused by cataracts, by year, age, and gender, were obtained from the Global Burden of Disease Study 2019. Socio-demographic Index (SDI) as a comprehensive indicator of the national or regional development status of GBD countries in 2019 was obtained from the GBD official website. Kruskal-Wallis test, linear regression, and Pearson correlation analysis were performed to explore the associations between the health burden with socioeconomic levels, Wilcoxon Signed-Rank Test was used to investigate the gender disparity. RESULTS: From 1990 to 2019, global DALY numbers caused by cataracts rose by 91.2%, crude rates increased by 32.2%, while age-standardized rates fell by 11.0%. Globally, age-standardized prevalence and DALYs rates of cataracts peaked in 2017 and 2000, with the prevalence rate of 1283.53 [95% uncertainty interval (UI) 1134.46-1442.93] and DALYs rate of 94.52 (95% UI 67.09-127.24) per 100,000 population, respectively. The burden was expected to decrease to 1232.33 (95% UI 942.33-1522.33) and 91.52 (95% UI 87.11-95.94) by 2050. Southeast Asia had the highest blindness rate caused by cataracts in terms of age-standardized DALY rates (99.87, 95% UI: 67.18-144.25) in 2019. Gender disparity has existed since 1990, with the female being more heavily impacted. This pattern remained with aging among different stages of vision impairments and varied through GBD super regions. Gender difference (females minus males) of age-standardized DALYs (equation: Y = -53.2*X + 50.0, P < 0.001) and prevalence rates (equation: Y = - 492.8*X + 521.6, P < 0.001) was negatively correlated with SDI in linear regression. CONCLUSION: The global health of cataracts is improving but the steady growth in crude DALY rates suggested that health progress does not mean fewer demands for cataracts. Globally, older age, females, and lower socioeconomic status are associated with higher cataract burden. The findings of this study highlight the importance to make gender-sensitive health policies to manage global vision loss caused by cataracts, especially in low SDI regions.
Asunto(s)
Catarata , Carga Global de Enfermedades , Masculino , Humanos , Femenino , Años de Vida Ajustados por Calidad de Vida , Salud Global , Prevalencia , Catarata/epidemiología , Ceguera/epidemiología , Ceguera/etiologíaRESUMEN
Colorectal cancer (CRC) is one of top five leading causes of cancerassociated mortalities worldwide. 5Fluorouracil (5FU) is the firstline chemotherapeutic drug in the treatment of CRC; however, its antineoplastic efficiency is limited due to acquired drug resistance. The regulatory mechanism underlying 5FU chemotherapeutic response and drug resistance in CRC remains largely unknown. The present study identified that silencing of methyltransferaselike 3 (METTL3) suppressed the proliferation and migration of CRC HCT8 cells. Using cell survival assays, flow cytometric and colony formation analyses, it was revealed that inhibition of METTL3 sensitized HCT8 cells to 5FU by enhancing DNA damage and inducing apoptosis in HCT8 cells under 5FU treatment. Furthermore, the expression of METTL3 was upregulated in 5FUresistant CRC cells (HCT8R), which contributed to drug resistance through regulation of RAD51 associated Protein 1 (RAD51AP1) expression. Western blotting, immunofluorescence staining and drug sensitivity assays demonstrated that knockdown of METTL3 augmented 5FUinduced DNA damage and overcame 5FUresistance in HCT8R cells, which could be mimicked by inhibition of RAD51AP1. The present study revealed that the METTL3/RAD51AP1 axis plays an important role in the acquisition of 5FU resistance in CRC, and targeting METTL3/RAD51AP1 may be a promising adjuvant therapeutic strategy for patients with CRC, particularly for those with 5FUresistant CRC.
Asunto(s)
Antineoplásicos , Neoplasias Colorrectales , Antineoplásicos/farmacología , Línea Celular Tumoral , Proliferación Celular , Neoplasias Colorrectales/tratamiento farmacológico , Neoplasias Colorrectales/genética , Neoplasias Colorrectales/patología , Resistencia a Antineoplásicos/genética , Fluorouracilo/farmacología , Fluorouracilo/uso terapéutico , Humanos , Metiltransferasas/genéticaRESUMEN
Methyltransferase-like 3 (METTL3) and N6-methyladenosine (m6A) are involved in many types of biological and pathological processes, including DNA repair. However, the function and mechanism of METTL3 in DNA repair and chemotherapeutic response remain largely unknown. In present study, we identified that METTL3 participates in the regulation of homologous recombination repair (HR), which further influences chemotherapeutic response in both MCF-7 and MDA-MB-231 breast cancer (BC) cells. Knockdown of METTL3 sensitized these BC cells to Adriamycin (ADR; also named as doxorubicin) treatment and increased accumulation of DNA damage. Mechanically, we demonstrated that inhibition of METTL3 impaired HR efficiency and increased ADR-induced DNA damage by regulating m6A modification of EGF/RAD51 axis. METTL3 promoted EGF expression through m6A modification, which further upregulated RAD51 expression, resulting in enhanced HR activity. We further demonstrated that the m6A 'reader,' YTHDC1, bound to the m6A modified EGF transcript and promoted EGF synthesis, which enhanced HR and cell survival during ADR treatment in BC. Our findings reveal a pivotal mechanism of METTL3-mediated HR and chemotherapeutic drug response, which may contribute to cancer therapy.
Asunto(s)
Neoplasias de la Mama , Factor de Crecimiento Epidérmico , Metiltransferasas , Recombinasa Rad51 , Reparación del ADN por Recombinación , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/genética , Femenino , Humanos , Metiltransferasas/genética , Metiltransferasas/metabolismo , Recombinasa Rad51/genética , Recombinasa Rad51/metabolismoRESUMEN
Chimeric antigen receptor T-cell (CAR-T) therapy has shown tremendous success in eradicating hematologic malignancies. However, this success has not yet been extrapolated to solid tumors due to the limited infiltration and persistence of CAR-T cells in the tumor microenvironment (TME). In this study, we screened a novel anti-CD70 scFv and generated CD70 CAR-T cells that showed effective antitumor functions against CD70+ renal carcinoma cells (RCCs) both in vitro and in vivo. We further evaluated the effect and explored the molecular mechanism of a PARP inhibitor (PARPi) in CAR-T cell immunotherapy by administering the PARPi to mouse xenografts model derived from human RCC cells. Treatment with the PARPi promoted CAR-T cell infiltration by stimulating a chemokine milieu that promoted CAR-T cell recruitment and the modulation of immunosuppression in the TME. Moreover, our data demonstrate that PARPi modulates the TME by activating the cGAS-STING pathway, thereby altering the balance of immunostimulatory signaling and enabling low-dose CAR-T cell treatment to induce effective tumor regression. These data demonstrate the application of CD70 CAR-T cell therapeutic strategies for RCC and the cross-talk between targeting DNA damage responses and antitumor CAR-T cell therapy. These findings provide insight into the mechanisms of PARPis in CAR-T cell therapy for RCC and suggest a promising adjuvant therapeutic strategy for CAR-T cell therapy in solid tumors.
Asunto(s)
Ligando CD27/antagonistas & inhibidores , Carcinoma de Células Renales/terapia , Inmunoterapia Adoptiva/métodos , Neoplasias Renales/terapia , Inhibidores de Poli(ADP-Ribosa) Polimerasas/uso terapéutico , Anticuerpos de Cadena Única/uso terapéutico , Animales , Ligando CD27/inmunología , Carcinoma de Células Renales/genética , Carcinoma de Células Renales/inmunología , Línea Celular Tumoral , Daño del ADN/efectos de los fármacos , Humanos , Neoplasias Renales/genética , Neoplasias Renales/inmunología , Proteínas de la Membrana/inmunología , Ratones , Nucleotidiltransferasas/inmunología , Transducción de SeñalRESUMEN
Apurinic/apyrimidinic endonuclease 1 (APE1) plays a critical role in the base excision repair (BER) pathway, which is responsible for the excision of apurinic sites (AP sites). In non-small cell lung cancer (NSCLC), APE1 is highly expressed and associated with poor patient prognosis. The suppression of APE1 could lead to the accumulation of unrepaired DNA damage in cells. Therefore, APE1 is viewed as an important marker of malignant tumors and could serve as a potent target for the development of antitumor drugs. In this study, we performed a high-throughput virtual screening of a small-molecule library using the three-dimensional structure of APE1 protein. Using the AP site cleavage assay and a cell survival assay, we identified a small molecular compound, NO.0449-0145, to act as an APE1 inhibitor. Treatment with NO.0449-0145 induced DNA damage, apoptosis, pyroptosis, and necroptosis in the NSCLC cell lines A549 and NCI-H460. This inhibitor was also able to impede cancer progression in an NCI-H460 mouse model. Moreover, NO.0449-0145 overcame both cisplatin- and erlotinib-resistance in NSCLC cell lines. These findings underscore the importance of APE1 as a therapeutic target in NSCLC and offer a paradigm for the development of small-molecule drugs that target key DNA repair proteins for the treatment of NSCLC and other cancers.
Asunto(s)
Apoptosis/inmunología , ADN-(Sitio Apurínico o Apirimidínico) Liasa/metabolismo , Necroptosis/inmunología , Piroptosis/inmunología , Animales , Carcinoma de Pulmón de Células no Pequeñas/patología , Humanos , Neoplasias Pulmonares/patología , Ratones , Ratones DesnudosRESUMEN
Studying animals in urban environments is especially challenging because much of the area is private property not easily accessible to professional scientists. In addition, collecting data on animals that are cryptic, secretive, or rare is also challenging due to the time and resources needed to amass an adequate dataset. Here, we show that community science can be a powerful tool to overcome these challenges. We used observations submitted to the community science platform iNaturalist to assess predation and parasitism across urbanization gradients in a secretive, 'hard-to-study' species, the Southern Alligator Lizard (Elgaria multicarinata). From photographs, we quantified predation risk by assessing tail injuries and quantified parasitism by counting tick loads on lizards. We found that tail injuries increased with age and with urbanization, suggesting that urban areas are risky habitats. Conversely, parasitism decreased with urbanization likely due to a loss of hosts and anti-tick medications used on human companion animals. This community science approach generated a large dataset on a secretive species rapidly and at an immense spatial scale that facilitated quantitative measures of urbanization (e.g. percent impervious surface cover) as opposed to qualitative measures (e.g. urban vs. rural). We therefore demonstrate that community science can help resolve ecological questions that otherwise would be difficult to address.
RESUMEN
DNA polymerase ß (Pol ß) plays a critical role in DNA base excision repair (BER), which is involved in maintaining genomic stability and in the modulation of DNA demethylation. Numerous studies implicated deficiency of Pol ß in the genomic instability and dysregulation of genes expression, leading to affecting initiation of cancer. However, the role of Pol ß in cancer progression is still unclear. Here, we show that Pol ß depresses migratory and invasive capabilities of both breast and lung carcinomas, which were evident in human breast and lung cancer cells, as well as in mouse xenograft tumors. On the molecular basis, overexpression of Pol ß enhanced expression of CDH13, which show function on cell adhesion and migration. Knockdown of CDH13 restores the migratory, invasive capabilities and angiogenesis in tumor, which gets impaired by Pol ß. According to the function of BER on modulation of DNA demethylation, our studies on CDH13 expression and the DNA methylation levels of CDH13 promoter suggested that Pol ß promotes expression of CDH13 by augmenting DNA demethylation of CDH13 promoter. Our findings elucidated a novel possibility that Pol ß impair cancer cell metastasis during cancer progression and shed light on the role of Pol ß in cancer therapy.
Asunto(s)
Neoplasias de la Mama/metabolismo , Cadherinas/metabolismo , Metilación de ADN , ADN Polimerasa beta/metabolismo , Neoplasias Pulmonares/metabolismo , Células A549 , Animales , Neoplasias de la Mama/genética , Neoplasias de la Mama/patología , Cadherinas/genética , ADN Polimerasa beta/genética , Modelos Animales de Enfermedad , Progresión de la Enfermedad , Femenino , Xenoinjertos , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patología , Células MCF-7 , Ratones , Ratones Desnudos , Ratones SCID , Regiones Promotoras GenéticasRESUMEN
Local community structure is shaped by processes acting at local and landscape scales. The relative importance of drivers operating across different spatial scales is difficult to test without observations across regional or latitudinal gradients. Cities exhibit strong but predictable environmental gradients overlaying a mosaic of highly variable but repeated habitat types within a constrained area. Thus, cities present a unique opportunity to explore how both local and landscape factors influence local biotic communities. We used insect communities to examine the interactions among local environmental variables (such as temperature and relative humidity), local habitat characteristics (such as plant community composition), and broad-scale patterns of urbanization (including biophysical, human-built, and socioeconomic variables) on local insect abundance, species richness, and species composition in Los Angeles, a hot, dry, near-desert city. After accounting for seasonal trends, insect species richness and abundance were highest in drier and hotter sites, but the magnitude of local environmental effects varied with the degree of urbanization. In contrast, insect species composition was best predicted by broad-scale urbanization trends, with the more native communities occurring in less urbanized sites and more cosmopolitan insects occurring in highly urbanized sites. However, insect species richness and abundance were >30% higher and insect composition was similar across sites that hosted either native or drought-tolerant plants, regardless of the degree of urbanization. These results demonstrate that urban insect biodiversity is a product of interacting mechanisms working at both local and landscape scales. However, local-scale changes to urban habitats, such as cultivating plants that are adapted to the natural environment nearest the city, can positively impact urban biodiversity regardless of location.
Asunto(s)
Biodiversidad , Insectos , Animales , Ciudades , Ecosistema , Humanos , UrbanizaciónRESUMEN
Obesity is associated with an increased risk of developing insulin resistance (IR) and type 2 diabetes (T2D). A diverse group of factors including miRNA has been implicated in the pathogenesis of these two metabolic conditions, although underlying molecular mechanisms involved are not well defined. Here, we provide evidence that hepatic miR-125a levels are diminished in both genetic as well as dietary mouse models of obesity. Overexpression of miR-125a enhanced insulin signaling and attenuated cellular lipid accumulation in HepG2 cells and Hepa1-6 cells. Likewise, treatment of mice with ago-miR-125a increased insulin sensitivity, similar to overexpression of miR-125a, whereas treatment of mice with antago-miR-125a blunted the insulin sensitivity. Furthermore, overexpression of miR-125a in mice previously fed a high-fat diet (HFD), significantly improved insulin sensitivity, and attenuated obesity-linked hepatic steatosis and hepatocyte lipid accumulation. In addition, we show that ELOVL fatty acid elongase 6 (Elovl6) is a direct target of miR-125a, and participates in miR-125a mediated regulation of insulin sensitivity and lipid metabolism. These data led us to conclude that dysregulated miR-125a expression augments the development of obesity-induced IR and that miR-125a might serve as a therapeutic target for the development of new drug(s) in the clinical management of metabolic diseases.