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1.
Life Sci ; : 117818, 2020 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-32445757

RESUMO

Activation of hepatic stellate cells (HSCs) is a central event in the pathogenesis of liver fibrosis and is characterized by the disappearance of lipid droplets. Although the exogenous supplementation of lipid droplet content can effectively reverse the activation of HSCs, the underlying molecular mechanisms are largely unknown. In our current study, we sought to investigate the role of lncRNA-H19 in the process of lipid droplets disappearance and to further examine the underlying molecular mechanisms. We found that the lncRNA-H19 level was increased in CCl4-induced fibrotic liver, which activated HSCs. Further research showed that hypoxia inducible factor-1α (HIF-1α) significantly increased lncRNA-H19 expression by binding to the lncRNA-H19 promoter at two hypoxia response element (HRE) sites located at 492-499 and 515-522 bp. Importantly, lncRNA-H19 knockdown markedly inhibited HSC activation and alleviated liver fibrosis, indicating that lncRNA-H19 may be a potential target for anti-fibrosis therapeutic approaches. Moreover, lncRNA-H19 knockdown could reverse the lipid droplet phenotype of activated HSCs, inhibiting the phosphorylated AMPK-mediated lipid oxidation signaling pathway. The AMPK agonist AICAR promoted AMPK phosphorylation and abrogated lipid droplets restoration in HSCs transfected with the lncRNA-H19 knockdown plasmid. Experimental molecular analysis showed that lncRNA-H19 triggered AMPKα to interact with LKB1 and resulted in AMPKα phosphorylation, which accelerating lipid droplets degradation and lipid oxidation. Taken together, our results highlighted the role of lncRNA-H19 in the metabolism of lipid droplets in HSC, and revealed a new molecular target for alleviating liver fibrosis.

2.
Free Radic Biol Med ; 153: 89-102, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32289481

RESUMO

BACKGROUND: It is well acknowledged that alcoholic liver disease (ALD) is widely prevalent all over the world, characterized by aberrant lipid deposition and excessive oxidative stress in hepatocytes. Recently, pyroptosis, a new type of programmed cell death, has been found in ALD, which provides new ideas for the treatment of ALD. METHODS: Male ICR mice were treated with the Lieber-De-Carli diet (Dyets) or isocaloric liquid diet for 8 weeks, and binge alcohol model was also used for ALD. Blood and livers were taken to evaluate the efficacy of oroxylin A. The levels of factors related to hepatocyte pyroptosis were measured via western blot analyses, immunofluorescence analyses and quantitative reverse transcriptase in vitro. RESULT: Our study found that oroxylin A suppressed hepatocyte pyroptosis through a NLRP3 inflammasome dependent-canonical caspase-1 pathway. Results illuminated that oroxylin A inhibited NLRP3 inflammasome activation by reducing ROS accumulation. Furthermore, oroxylin A upregulated mitofusin 2 (Mfn2) to resist lipid deposition and mitochondria-derived ROS overproduction. As an upstream mediator of Mfn2, peroxisome proliferator-activated receptor gamma coactivator 1 alpha (PGC-1α), a major regulator of mitochondria, was found to promote transcription of Mfn2 under oroxylin A treatment. CONCLUSION: Our research revealed that oroxylin A could alleviate ALD via PGC-1α/Mfn2 signaling mediated canonical pyroptosis pathway resistance.

3.
Int Immunopharmacol ; 84: 106470, 2020 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-32304991

RESUMO

Activation of hepatic stellate cells (HSCs) is a pivotal event in liver fibrosis, characterized by enhanced retinoic acid signals. Although up-regulated retinoic acid signal responds further to maintain HSC activation, the underlying molecular mechanisms are largely unknown. In this study, we sought to investigate the role of lncRNA-H19 in regulation of retinoic acid signals, and to further examine the underlying mechanism in this molecular context. We found that lncRNA-H19 upregulation could enhance retinoic acid signals to induce HSC activation, whereas lncRNA-H19 knockdown completely disturbed retinoic acid signals. Moreover, the activation of retinoic acid signals impaired the lncRNA-H19 knockdown mediated HSC inactivation. Interestingly, we also found that enhanced retinoic acid signals by lncRNA-H19 was associated with a coordinate increase in retinol metabolism during HSC activation. Increased retinol metabolism contributed to obvious lipid droplet consumption. Importantly, we identified that alcohol dehydrogenase III (ADH3) was essential for lncRNA-H19 to enhance retinoic acid signals. The inhibition of ADH3 completely abrogated the lncRNA-H19 mediated retinoic acid signals and HSC activation. Of note, we identified dihydroartemisinin (DHA) as a natural inhibitor for lncRNA-H19. Treatment with DHA significantly decreased the expression of lncRNA-H19, reduced the expression of ADH3, blocked retinoic acid signals, and in turn, inhibited HSC activation. Overall, these results provided novel implications to reveal the molecular mechanism of increased retinoic acid signals during HSC activation, and identify lncRNA-H19/ADH3 pathway as a potential target for the treatment of liver fibrosis.

4.
Toxicology ; 440: 152475, 2020 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-32344006

RESUMO

OBJECTIVES: Curcumol, a guaiane-type sesquiterpenoid hemiketal extracted from the herb Rhizoma Curcumae, exhibits multiple-pharmacological activities. We previously reported that curcumol ameliorated hepatic fibrosis by inhibiting hepatic stellate cell (HSC) activation. In this study, we aimed to investigate the effect of curcumol on HSC migration and adhesion, and reveal its regulation mechanisms. MATERIALS AND METHODS: Cellular viability was determined by Cell Counting Kit-8. Cell migration was detected by boyden chamber and cell scratch experiment. Recombinant human periostin (rh POSTN) and adeno-associated viral (AAV)-GFP-periostin were used to achieve POSTN overexpression in vitro and in vivo, respectively. Nuclear factor kappa B (NF-κB)-p65 overexpression was achieved by using plasmid. ELISA was conducted to detect POSTN level. Immunohistochemistry, qRT-PCR, Western blotting, and immunofluorescence were performed to assess associated factor expression. RESULTS: Curcumol suppressed HSC migration and adhesion, and reduced the secretion and expression of POSTN. By gain of function POSTN in HSCs, using rh POSTN, we found that the inhibition of HSC migration and adhesion by curcumol depended on the decrease of POSTN. Besides, curcumol protection against chronic CCl4-caused hepatic fibrosis could be impaired by POSTN overexpression. Moreover, we showed that curcumol repressed NF-κB signaling and the production of pro-inflammatory factor. Importantly, curcumol down-regulation of POSTN was rescued by knock-in of NF-κB, as well as the inhibition of HSC migration and adhesion. CONCLUSION: These findings reveal the molecular mechanism of curcumol-reduced HSC migration and adhesion, by which points to the possibility of using curcumol based on NF-κB dependent POSTN for the treatment of fibrogenesis.

5.
J Cell Mol Med ; 24(9): 5304-5316, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32243714

RESUMO

A growing number of studies recognize that long non-coding RNAs (lncRNAs) are essential to mediate multiple tumorigenic processes, including hepatic tumorigenesis. However, the pathological mechanism of lncRNA-regulated liver cancer cell growth remains poorly understood. In this study, we identified a novel function lncRNA, named polo-like kinase 4 associated lncRNA (lncRNA PLK4, GenBank Accession No. RP11-50D9.3), whose expression was dramatically down-regulated in hepatocellular carcinoma (HCC) tissues and cells. Interestingly, talazoparib, a novel and highly potent poly-ADP-ribose polymerase 1/2 (PARP1/2) inhibitor, could increase lncRNA PLK4 expression in HepG2 cells. Importantly, we showed that talazoparib-induced lncRNA PLK4 could function as a tumour suppressor gene by Yes-associated protein (YAP) inactivation and induction of cellular senescence to inhibit liver cancer cell viability and growth. In summary, our findings reveal the molecular mechanism of talazoparib-induced anti-tumor effect, and suggest a potential clinical use of talazoparib-targeted lncRNA PLK4/YAP-dependent cellular senescence for the treatment of HCC.

6.
Glob Chang Biol ; 26(6): 3185-3187, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32219944

RESUMO

Coastal lagoon ecosystems are important natural carbon sinks but are threatened by both climate change and direct human disturbances. By reconstructing the environmental change and carbon dynamics of the past 400 years for a tropical mangrove-fringed lagoon system in Java, Indonesia, Hapsari et al. provide important insights into how climate change and human land use co-regulate the vegetation and carbon cycles of a tropical lagoon system and its catchment. This article is a commentary on Hapsari et al. 26, 1414-1431.

7.
Cell Prolif ; 53(3): e12762, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32119185

RESUMO

OBJECTIVE: Hepatic sinusoidal angiogenesis owing to dysfunctional liver sinusoidal endothelial cells (LSECs) accompanied by an abnormal angioarchitecture is a symbol related to liver fibrogenesis, which indicates a potential target for therapeutic interventions. However, there are few researches connecting angiogenesis with liver fibrosis, and the deeper mechanism remains to be explored. MATERIALS AND METHODS: Cell angiogenesis and angiogenic protein were examined in primary LSECs of rats, and multifarious cellular and molecular assays revealed the efficiency of curcumol intervention in fibrotic mice. RESULTS: We found that curcumol inhibited angiogenic properties through regulating their upstream mediator hypoxia-inducible factor-1α (HIF-1α). The transcription activation of HIF-1α was regulated by hedgehog signalling on the one hand, and the protein stabilization of HIF-1α was under the control of Prospero-related homeobox 1 (PROX1) on the other. A deubiquitinase called USP19 could be recruited by PROX1 and involved in ubiquitin-dependent degradation of HIF-1α. Furthermore, our researches revealed that hedgehog signalling participated in the activation of PROX1 transcription probably in vitro. Besides, curcumol was found to ameliorate liver fibrosis and sinusoid angiogenesis via hedgehog pathway in carbon tetrachloride (CCl4 ) induced liver fibrotic mice. The protein expression of key regulatory factors, PROX1 and HIF-1α, was consistent with the Smo, the marker protein of Hh signalling pathway. CONCLUSIONS: In this article, we evidenced that curcumol controlling LSEC-mediated angiogenesis could be a promising therapeutic approach for liver fibrosis.


Assuntos
Inibidores da Angiogênese/uso terapêutico , Cirrose Hepática/tratamento farmacológico , Neovascularização Patológica/tratamento farmacológico , Sesquiterpenos/uso terapêutico , Transdução de Sinais/efeitos dos fármacos , Animais , Células Cultivadas , Células Endoteliais/efeitos dos fármacos , Células Endoteliais/metabolismo , Células Endoteliais/patologia , Proteínas Hedgehog/metabolismo , Proteínas de Homeodomínio/metabolismo , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Cirrose Hepática/metabolismo , Cirrose Hepática/patologia , Masculino , Camundongos Endogâmicos ICR , Neovascularização Patológica/metabolismo , Neovascularização Patológica/patologia , Ratos Sprague-Dawley , Proteínas Supressoras de Tumor/metabolismo , Proteína GLI1 em Dedos de Zinco/metabolismo
8.
Sci Adv ; 6(1): eaax0255, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31922002

RESUMO

Earlier vegetation greening under climate change raises evapotranspiration and thus lowers spring soil moisture, yet the extent and magnitude of this water deficit persistence into the following summer remain elusive. We provide observational evidence that increased foliage cover over the Northern Hemisphere, during 1982-2011, triggers an additional soil moisture deficit that is further carried over into summer. Climate model simulations independently support this and attribute the driving process to be larger increases in evapotranspiration than in precipitation. This extra soil drying is projected to amplify the frequency and intensity of summer heatwaves. Most feedbacks operate locally, except for a notable teleconnection where extra moisture transpired over Europe is transported to central Siberia. Model results illustrate that this teleconnection offsets Siberian soil moisture losses from local spring greening. Our results highlight that climate change adaptation planning must account for the extra summer water and heatwave stress inherited from warming-induced earlier greening.

9.
Int J Biometeorol ; 64(1): 115-122, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31654197

RESUMO

Plateau zokor (Myospalax baileyi) and plateau pika (Ochotona curzoniae) are endemic fossorial vertebrates in the Qinghai-Tibetan Plateau alpine meadow ecosystem. Their different burrowing activities together transform soil structure and then significantly change the landscape of meadow ecosystem. However, how their burrowing activities impact greenhouse gas (GHG) emissions and the pattern of GHG emissions between different types of tunnel burrowing still remain obscure. In this study, we conducted in situ measurements quantitatively investigating the impacts of the different burrowing activities of zokors and pikas on three main GHG CO2, CH4, and N2O from an alpine meadow ecosystem in southeastern Qinghai-Tibetan Plateau. Our results showed that zokor hummocks and pika burrows were sources of CO2 and N2O and sinks of CH4. Zokors burrowing increased N2O in the atmosphere, decreased CO2, and enhanced CH4 absorbing, while pikas burrowing increased N2O in the atmosphere and enhanced CH4 absorbing. Considering the controversial role of fossorial vertebrates in Qinghai-Tibetan Plateau, this study also shed lights on effective management of animal activities with the aim of stabilizing or increasing ecosystem carbon sequestration.


Assuntos
Ecossistema , Gases de Efeito Estufa , Animais , Pradaria , Solo , Tibet
10.
Oncol Lett ; 18(6): 5871-5878, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31788060

RESUMO

Macrophages are a heterogeneous group of phagocytes that play critical roles in inflammation, infection and tumor growth. Macrophages respond to different environmental factors and are thereby polarized into specialized functional subsets. Although hypoxia is an important environmental factor, its impact on human macrophage polarization and subsequent modification of the inflammatory microenvironment have not been fully established. The present study aimed to elucidate the effect of hypoxia exposure on the ability of human macrophages to polarize into the classically activated (pro-inflammatory) M1, and the alternatively activated (anti-inflammatory) M2 phenotypes. The effect on the inflammatory microenvironment and the subsequent modification of A549 lung carcinoma cells was also investigated. The presented data show that hypoxia promoted macrophage polarization towards the M2 phenotype, and modified the inflammatory microenvironment by decreasing the release of proinflammatory cytokines. Modification of the microenvironment by proinflammatory M1 macrophages under hypoxia reversed the inhibition of malignant behaviors within the proinflammatory microenvironment. Furthermore, it was identified p38 signaling (a major contributor to the response to reactive oxygen species generated by hypoxic stress), but not hypoxia-induced factor, as a key regulator of macrophages under hypoxia. Taken together, the data suggest that hypoxia affects the inflammatory microenvironment by modifying the polarization of macrophages, and thus, reversing the inhibitory effects of a proinflammatory microenvironment on the malignant behaviors of several types of cancer cell.

11.
Autophagy ; : 1-24, 2019 Nov 11.
Artigo em Inglês | MEDLINE | ID: mdl-31679460

RESUMO

Ferroptosis is a recently discovered form of programmed cell death, but its regulatory mechanisms remain poorly understood. Here, we show that the RNA-binding protein ZFP36/TTP (ZFP36 ring finger protein) plays a crucial role in regulating ferroptosis in hepatic stellate cells (HSCs). Upon exposure to ferroptosis-inducing compounds, the ubiquitin ligase FBXW7/CDC4 (F-box and WD repeat domain containing 7) decreased ZFP36 protein expression by recognizing SFSGLPS motif. FBXW7 plasmid contributed to classical ferroptotic events, whereas ZFP36 plasmid impaired FBXW7 plasmid-induced HSC ferroptosis. Interestingly, ZFP36 plasmid inhibited macroautophagy/autophagy activation by destabilizing ATG16L1 (autophagy related 16 like 1) mRNA. ATG16L1 plasmid eliminated the inhibitory action of ZFP36 plasmid on ferroptosis, and FBXW7 plasmid enhanced the effect of ATG16L1 plasmid on autophagy. Importantly, ZFP36 plasmid promoted ATG16L1 mRNA decay via binding to the AU-rich elements (AREs) within the 3'-untranslated region. The internal mutation of the ARE region abrogated the ZFP36-mediated ATG16L1 mRNA instability, and prevented ZFP36 plasmid-mediated ferroptosis resistance. In mice, treatment with erastin and sorafenib alleviated murine liver fibrosis by inducing HSC ferroptosis. HSC-specific overexpression of Zfp36 impaired erastin- or sorafenib-induced HSC ferroptosis. Noteworthy, we analyzed the effect of sorafenib on HSC ferroptosis in fibrotic patients with hepatocellular carcinoma receiving sorafenib monotherapy. Attractively, sorafenib monotherapy led to ZFP36 downregulation, ferritinophagy activation, and ferroptosis induction in human HSCs. Overall, these results revealed novel molecular mechanisms and signaling pathways of ferroptosis, and also identified ZFP36-autophagy-dependent ferroptosis as a potential target for the treatment of liver fibrosis.Abbreviations: ARE: AU-rich elements; ATG: autophagy related; BECN1: beclin 1; CHX: cycloheximide; COL1A1: collagen type I alpha 1 chain; ELAVL1/HuR: ELAV like RNA binding protein 1; FBXW7/CDC4: F-box and WD repeat domain containing 7; FN1: fibronectin 1; FTH1: ferritin heavy chain 1; GPX4/PHGPx: glutathione peroxidase 4; GSH: glutathione; HCC: hepatocellular carcinoma; HSC: hepatic stellate cell; LSEC: liver sinusoidal endothelial cell; MAP1LC3A: microtubule associated protein 1 light chain 3 alpha; MDA: malondialdehyde; NCOA4: nuclear receptor coactivator 4; PTGS2/COX2: prostaglandin-endoperoxide synthase 2; RBP: RNA-binding protein; ROS: reactive oxygen species; SLC7A11/xCT: solute carrier family 7 member 11; SQSTM1/p62: sequestosome 1; TNF: tumor necrosis factor; TP53/p53: tumor protein p53; UTR: untranslated region; ZFP36/TTP: ZFP36 ring finger protein.

12.
Life Sci ; 238: 116934, 2019 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-31610205

RESUMO

Proliferation and differentiation of hepatic stellate cells (HSCs) are the most noticeable events in hepatic fibrosis, in which the loss of lipid droplets (LDs) is the most important feature. However, the complex mechanisms of LD disappearance have not been fully elucidated. In the current study, we investigated whether oroxylin A has the pharmacological activity of reversing LDs in activated HSCs, and further examined its potential molecular mechanisms. Using genetic, pharmacological, and molecular biological measure, we found that LD content significantly decreased during HSC activation, whereas oroxylin A markedly reversed LD content in activated HSCs. Interestingly, oroxylin A treatment observably decreased the expression of adipose triglyceride lipase (ATGL) without large differences in classical LD synthesis pathway, LD-related transcription factors, and autophagy pathway. ATGL overexpression could completely impair the effect of oroxylin A on reversing LD content. Importantly, reactive oxygen species (ROS) signaling pathway mediated oroxylin A-induced ATGL downregulation and LD revision in activated HSCs. ROS specific stimulant buthionine sulfoximine (BSO) could dramatically diminish the antioxidant effect of oroxylin A, and in turn, abolish reversal effect of oroxylin A on LD content. Conversely, ROS specific scavenger N-acetyl cystenine (NAC) can significantly enhance the pharmacological effect of oroxylin A on LD revision. Taken together, our study reveals the important molecular mechanism of anti-fibrosis effect of oroxylin A, and also suggests that ROS-ATGL pathway is a potential target for reversing LDs.


Assuntos
Flavonoides/farmacologia , Regulação Enzimológica da Expressão Gênica/efeitos dos fármacos , Células Estreladas do Fígado/efeitos dos fármacos , Lipase/antagonistas & inibidores , Gotículas Lipídicas/metabolismo , Cirrose Hepática/tratamento farmacológico , Animais , Autofagia , Células Cultivadas , Regulação para Baixo , Células Estreladas do Fígado/metabolismo , Células Estreladas do Fígado/patologia , Gotículas Lipídicas/efeitos dos fármacos , Cirrose Hepática/etiologia , Cirrose Hepática/metabolismo , Cirrose Hepática/patologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Transdução de Sinais
13.
Front Physiol ; 10: 1006, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31447696

RESUMO

NAD+-dependent SIRT4 has been reported to be a key regulator of metabolic enzymes and antioxidant defense mechanisms in mitochondria. It also plays an important role in regulation of mitochondrial metabolism in response to exercise. Recent studies have shown that SIRT4 is involved in a wide range of mitochondrial metabolic processes, including depressing insulin secretion in pancreatic beta cells, promoting lipid synthesis, regulating mitochondrial adenosine triphosphate (ATP) homeostasis, controlling apoptosis and regulating redox. SIRT4 also appears to have enzymatic functions involved in posttranslational modifications such as ADP-ribosylation, lysine deacetylation and lipoamidation. However, the effects on SIRT4 by metabolic diseases and changes in metabolic homeostasis such as during exercise, along with the roles of SIRT4 in the regulation of metabolism during disease, are not well understood. The main goal of this review is to critically analyse and summarise the current research evidence on the significance of the SIRT4 as a metabolic regulator and in mitochondrial function and its putative roles in relation to metabolic diseases and exercise.

14.
Nat Commun ; 10(1): 2970, 2019 07 05.
Artigo em Inglês | MEDLINE | ID: mdl-31278320

RESUMO

The reported progressive change of vegetation activity along elevational gradients has important aesthetic and conservation values. With climate change, cooler locations are suggested to warm faster than warmer ones, raising concerns of a more homogenized landscape along the elevation. Here, we use global satellite data to investigate the spatio-temporal dynamics of the elevational gradient (EG) in vegetation greenness (NDVImax3), spring (SOS) and autumn phenology (EOS) during 1982-2015. Although we find clear geographical patterns of the EG in NDVImax3 and SOS, there are no prevalent trends of vegetation homogenization or phenology synchronization along elevational gradients. Possible mechanisms, including spatially heterogeneous temperature lapse rate changes, different vegetation sensitivities to climate change, and human disturbances, may play diverse roles across different regions. Our finding of mixed EG trends and no general rules controlling EG dynamics poses challenges for mitigating possible adverse impacts of climate change on mountainous biological diversity and ecosystem services.


Assuntos
Biodiversidade , Desenvolvimento Vegetal , Dispersão Vegetal , Análise Espaço-Temporal , Mudança Climática , Imagens de Satélites , Estações do Ano , Temperatura
15.
Life Sci ; 226: 91-97, 2019 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-30978348

RESUMO

The liver is importantly metabolic and detoxifying organ in the body. When various pathogenic factors affect the liver, the normal physiological and biochemical functions are weakened, resulting in liver diseases. Liver fibrosis is a common pathological process of chronic liver disease. During hepatic fibrosis the changes in the components of the extracellular matrix (ECM) provide an environment that facilitates tissue remodeling. Among these ECM components, periostin, a glycoprotein that is predominantly secreted by osteoblasts and their precursors, playing an important role in bone formation, has attracted great attention. Periostin not only involves in bone metabolism, but also functions in modulating the cell fate determination, proliferation, inflammatory responses, even tumorigenesis of many other tissues and organs including liver. In different categories of liver disease patients, the serum and liver tissue levels of periostin were closely related to the decline of liver function, and the pathological stage. Numerous animal studies and experiments in vitro subsequently demonstrated that the abnormal expression of periostin resulted in metabolic disorders, liver inflammation, fibrosis and even tumorigenesis. Here we review the current progress on the role of periostin in pathologic pathways of liver system to explore whether periostin is a potential therapeutic target for the treatment of different liver diseases.


Assuntos
Moléculas de Adesão Celular/metabolismo , Moléculas de Adesão Celular/fisiologia , Hepatopatias/metabolismo , Animais , Diferenciação Celular , Doença Crônica , Matriz Extracelular , Células Estreladas do Fígado , Hepatite , Humanos , Fígado/metabolismo , Fígado/fisiologia , Cirrose Hepática , Hepatopatias/fisiopatologia , Transdução de Sinais
16.
Glob Chang Biol ; 25(6): 1922-1940, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-30884039

RESUMO

Plant phenology, the annually recurring sequence of plant developmental stages, is important for plant functioning and ecosystem services and their biophysical and biogeochemical feedbacks to the climate system. Plant phenology depends on temperature, and the current rapid climate change has revived interest in understanding and modeling the responses of plant phenology to the warming trend and the consequences thereof for ecosystems. Here, we review recent progresses in plant phenology and its interactions with climate change. Focusing on the start (leaf unfolding) and end (leaf coloring) of plant growing seasons, we show that the recent rapid expansion in ground- and remote sensing- based phenology data acquisition has been highly beneficial and has supported major advances in plant phenology research. Studies using multiple data sources and methods generally agree on the trends of advanced leaf unfolding and delayed leaf coloring due to climate change, yet these trends appear to have decelerated or even reversed in recent years. Our understanding of the mechanisms underlying the plant phenology responses to climate warming is still limited. The interactions between multiple drivers complicate the modeling and prediction of plant phenology changes. Furthermore, changes in plant phenology have important implications for ecosystem carbon cycles and ecosystem feedbacks to climate, yet the quantification of such impacts remains challenging. We suggest that future studies should primarily focus on using new observation tools to improve the understanding of tropical plant phenology, on improving process-based phenology modeling, and on the scaling of phenology from species to landscape-level.


Assuntos
Mudança Climática , Fenômenos Fisiológicos Vegetais , Ecossistema , Desenvolvimento Vegetal , Folhas de Planta/fisiologia , Estações do Ano , Temperatura
17.
Cell Commun Signal ; 17(1): 11, 2019 02 11.
Artigo em Inglês | MEDLINE | ID: mdl-30744642

RESUMO

BACKGROUND: Contraction of hepatic stellate cells (HSCs) plays an important role in the pathogenesis of liver fibrosis by regulating sinusoidal blood flow and extracellular matrix remodeling. Here, we investigated how HSC contraction was affected by the natural compound oroxylin A, and elucidated the underlying mechanism. METHODS: Cell contraction and glycolysis were examined in cultured human HSCs and mouse liver fibrosis model upon oroxylin A intervention using diversified cellular and molecular assays, as well as genetic approaches. RESULTS: Oroxylin A limited HSC contraction associated with inhibiting myosin light chain 2 phosphorylation. Oroxylin A blocked aerobic glycolysis in HSCs evidenced by reduction in glucose uptake and consumption and lactate production. Oroxylin A also decreased extracellular acidification rate and inhibited the expression and activity of glycolysis rate-limiting enzymes (hexose kinase 2, phosphofructokinase 1 and pyruvate kinas type M2) in HSCs. Then, we identified that oroxylin A blockade of aerobic glycolysis contributed to inhibition of HSC contraction. Furthermore, oroxylin A inhibited the expression and activity of lactate dehydrogenase-A (LDH-A) in HSCs, which was required for oroxylin A blockade of glycolysis and suppression of contraction. Oral administration of oroxylin A at 40 mg/kg reduced liver injury and fibrosis, and inhibited HSC glycolysis and contraction in mice with carbon tetrachloride-induced hepatic fibrosis. However, adenovirus-mediated overexpression of LDH-A significantly counteracted the oroxylin A's effects in fibrotic mice. CONCLUSIONS: Blockade of aerobic glycolysis by oroxylin A via inhibition of LDH-A reduced HSC contraction and attenuated liver fibrosis, suggesting LDH-A as a promising target for intervention of hepatic fibrosis.


Assuntos
Flavonoides/farmacologia , Glicólise/efeitos dos fármacos , Células Estreladas do Fígado/enzimologia , L-Lactato Desidrogenase/antagonistas & inibidores , Aerobiose , Linhagem Celular , Células Estreladas do Fígado/efeitos dos fármacos , Humanos , L-Lactato Desidrogenase/metabolismo , Fígado/lesões , Fígado/patologia , Cirrose Hepática/metabolismo , Cirrose Hepática/patologia
18.
Environ Res ; 172: 159-165, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30782535

RESUMO

BACKGROUND: Soil pH is important for controlling many soil properties. The variation in soil pH can be associated with changes in climate, soil buffering system, nitrogen deposition, and plants. However, there still lacks a comprehensive study exploring the effects of all these factors on soil pH simultaneously. Here we aimed to investigate the environmental controls on the spatial variation of soil pH in planted forests across Northern China and reveal its response to different-forms of nitrogen deposition for different species of tree plantations. METHODS: We sampled 1980 soil profiles from 660 planted forest plots (3 profiles in each plot) in Northern China. We used correlation analyses and structure equation models (SEM) to explore the impacts of multiple environmental factors on soil pH. RESULTS: Climate (water balance, temperature) and soil inorganic carbon accounted for most variations of soil pH. Specifically, the concentration of hydrogen ions ([H+]) varied almost isometrically with soil inorganic carbon, which was also the major buffering system in this region. Nitrogen deposition affected both soil pH values and soil buffering system. Results from structure equation model indicated that nitrate nitrogen directly decreased soil pH, while ammonium nitrogen mostly affected soil pH indirectly through its impacts on soil inorganic carbon. The responses of soil pH to nitrogen deposition were species-specific, and conifer stands tended to have higher soil acidification rate than stands of other tree species. CONCLUSIONS: Our study provides important information for understanding mechanisms controlling the spatial pattern of soil pH in planted forests and highlights the need to develop informed policies for soil resource management under increasing threats from anthropogenic nitrogen deposition.


Assuntos
Meio Ambiente , Florestas , Nitrogênio , Solo , Carbono/metabolismo , China , Concentração de Íons de Hidrogênio , Nitrogênio/metabolismo , Solo/química
19.
Glob Chang Biol ; 2019 Jan 25.
Artigo em Inglês | MEDLINE | ID: mdl-30681229

RESUMO

A widely used approach for estimating actual evapotranspiration (AET) in hydrological and earth system models is to constrain potential evapotranspiration (PET) with a single empirical stress factor (Ω = AET/PET). Ω represents the water availability and is fundamentally linked to canopy-atmosphere coupling. However, the mean and seasonal variability of Ω in the models have rarely been evaluated against observations, and the model performances for different climates and biomes remain unclear. In this study, we first derived the observed Ω from 28 FLUXNET sites over North America during 2000-2007, which was then used to evaluate Ω in six large-scale model-based datasets. Our results confirm the importance of incorporating canopy height in the formulation of aerodynamic conductance in the case of forests. Furthermore, leaf area index (LAI) is central to the prediction of Ω and can be quantitatively linked to the partitioning between transpiration and soil evaporation (R2  = 0.43). The substantial differences between observed and model-based Ω in forests (range: 0.2~0.9) are highly related to the way these models estimated PET and the way they represented the responses of Ω to the environmental drivers, especially wind speed and LAI. This is the first assessment of Ω in models based on in situ observations. Our findings demonstrate that the observed Ω is useful for evaluating, validating, and optimizing the modeling of AET and thus of water and energy balances.

20.
IUBMB Life ; 71(1): 45-56, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30321484

RESUMO

Ferroptosis is recently reported as a new mode of regulated cell death. Its essential characteristics are disturbed redox homeostasis, overloaded iron, and increased lipid peroxidation. However, the role of ferroptosis in liver fibrosis remains poorly understood. In this study, we attempted to investigate the effect of artemether (ART) on ferroptosis in hepatic fibrosis and to further clarify the possible mechanisms. Our data showed that ART treatment markedly attenuated liver injury and reduced fibrotic scar formation in the mouse model of liver fibrosis. Moreover, experiments in vitro also confirmed that ART treatment significantly decreased expression of hepatic stellate cell (HSC) activation markers. Interestingly, HSCs treated by ART presented morphological features of ferroptosis. Furthermore, ART remarkably triggered ferroptosis by promoting the accumulation of iron and lipid peroxides, whereas inhibition of ferroptosis by specific inhibitor ferrostatin-1 (Fer-1) completely abolished ART-induced antifibrosis effect. More importantly, our discovery determined that tumor suppressor P53 was an upstream molecule in the facilitation of ART-induced HSC ferroptosis. Conversely, knockdown of P53 by siRNA evidently blocked ART-induced HSC ferroptosis in turn exacerbated liver fibrosis. Overall, our findings revealed that P53-dependent induction of ferroptosis is necessary for ART to ameliorate CCl4 -induced hepatic fibrosis and inhibit HSC activation. © 2018 IUBMB Life, 71(1):45-56, 2019.


Assuntos
Artemeter/farmacologia , Cirrose Hepática/tratamento farmacológico , Proteína Supressora de Tumor p53/genética , Animais , Apoptose/efeitos dos fármacos , Tetracloreto de Carbono/toxicidade , Morte Celular/genética , Proliferação de Células/efeitos dos fármacos , Modelos Animais de Doenças , Células Estreladas do Fígado/efeitos dos fármacos , Células Estreladas do Fígado/patologia , Humanos , Sobrecarga de Ferro/genética , Sobrecarga de Ferro/patologia , Peroxidação de Lipídeos/efeitos dos fármacos , Cirrose Hepática/induzido quimicamente , Cirrose Hepática/genética , Cirrose Hepática/patologia , Camundongos , RNA Interferente Pequeno/genética , Transdução de Sinais/efeitos dos fármacos
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