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1.
Oecologia ; 204(4): 899-913, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38582800

RESUMO

Allelopathy has a profound impact on the germination and growth of plants, influencing the establishment of plant populations and shaping community ecological patterns. However, the allelopathic potential of many grassland species remains poorly understood. In this study, we prepared aqueous extracts from 17 herbaceous plants to investigate their allelopathic effects on the seed germination and seedling growth of Leymus chinensis, a dominant grassland species. Our results revealed that the response of L. chinensis to allelopathic compounds was dependent on the specific plant species, extract concentration, and target plant organ. Notably, Fabaceae plants exhibited a stronger allelopathic potential than Poaceae, Asteraceae, and other plant families. Moreover, we observed that root growth of L. chinensis was more sensitive to allelopathy than shoot growth, and seed germination was more affected than seedling growth. Generally, the germination of L. chinensis was strongly inhibited as the donor plant extract concentration increased. The leachate of Fabaceae plants inhibited the seedling growth of L. chinensis at concentrations ranging from 0.025 to 0.1 g mL-1. On the other hand, the leachate from other families' plants exhibited either inhibitory or hormetic effects on the early growth of L. chinensis, promoting growth at 0.025 g mL-1 and hindering it at concentrations between 0.05 and 0.1 g mL-1. These findings highlight the significant allelopathic potential of grassland plants, which plays a critical role in establishing plant populations and associated ecological processes. In addition, they shed light on the coexistence of other plants with dominant plants in the community.


Assuntos
Alelopatia , Germinação , Pradaria , Plântula , Plântula/crescimento & desenvolvimento , Sementes/crescimento & desenvolvimento , Poaceae/crescimento & desenvolvimento , Raízes de Plantas/crescimento & desenvolvimento
2.
Plants (Basel) ; 13(5)2024 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-38475512

RESUMO

Grassland management affects soil respiration (Rs, consists of heterotrophic respiration and autotrophic respiration) through soil micro-ecological processes, such as hydrothermal, plant root, organic carbon decomposition and microbial activity. Flooding, an irregular phenomenon in grasslands, may strongly regulate the response of soil respiration and its components to grassland management, but the regulatory mechanism remains unclear. We conducted a 3-year experiment by grassland management (fencing and grazing) and flooding conditions (no flooding (NF), short-term flooding (STF) and long-term flooding (LTF)) to study their effects on Rs and its components in a meadow steppe in the Hui River basin of Hulunbuir. We found differences in the patterns of Rs and its components under grassland management and flooding conditions. In 2021-2023, the temporal trends of Rs, heterotrophic respiration (Rh) and autotrophic respiration (Ra) were generally consistent, with peaks occurring on days 190-220, and the peaks of grazing were higher than that of fencing. In NF, Rs of grazed grassland was significantly higher than that of fenced grassland in 2021-2022 (p < 0.05). In STF and LTF, there was no significant difference in Rs between fenced and grazed grassland (p > 0.05). The dependence of Rs on soil temperature (ST) decreased with increasing flooding duration, and the dependence of Rs on ST of grazed grassland was higher than fenced grassland under NF and STF, but there was no difference between fenced grassland and grazed grassland under LTF. In addition, Rh was more sensitive to ST than Ra. This may be due to the different pathways of ST effects on Rs under grazing in different flooding conditions. Our study indicates that the effect of flooding on Rs is the key to the rational use of grassland under future climate change. To reduce regional carbon emissions, we recommend grazing on flooding grassland and fencing on no-flooding grassland.

3.
Sci Total Environ ; 912: 168791, 2024 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-38000742

RESUMO

Excessive nitrogen (N) inputs shift grassland productivity from nitrogen (N) to phosphorus (P) limitation. However, how plant nutrient concentrations and stoichiometric dynamics at community and species level responding to variable soil N and P availability, and their roles in regulating net primary productivity in meadow steppe remain unclear. To address this issue, we carried out an experiment with fifteen treatments consisting of factorial combinations of N (0, 1.55, 4.65,13.95, 27.9 g N m-2 yr-1) and P (0, 5.24,10.48 g P m-2 yr-1) for three years in a meadow steppe in Inner Mongolia. We examined concentrations and stoichiometry of C (carbon), N, P in plants and soils, and their associations with plant primary productivity. Results revealed mean community N:P ratios for shoots (12.89 ± 0.98) did not exceed 14 within the control treatment, indicating that plant growth was primarily N-limited in this ecosystem. Shoot N:P ratios were significantly increased by N addition (>16 when N application rate above 4.65 g N m-2 yr-1), shifting the community from N- to P-limited whereas significantly reduced by P addition (N:P ratios <14), further aggravating N limitation. N addition increased leaf-N concentrations whereas decreased leaf C:N ratios of all four species, but only the values for two graminoid species were significantly influenced by P addition. Leaf-P concentrations significantly increased for graminoids but significantly decreased for forbs with the application of N. VPA analysis revealed that aboveground components, especially in grass leaves, explained more variation in aboveground net primary productivity (ANPP) and belowground net primary productivity (BNPP) than root and soil components. For grasses, leaf-N concentrations showed high association with ANPP, while leaf-P concentrations were associated with BNPP. These results highlight that N and P depositions could affect the leaf-nutrient concentrations of dominant grasses, and thereby potentially alter net primary productivity in meadow steppe.


Assuntos
Ecossistema , Poaceae , Fósforo/análise , Pradaria , Nitrogênio/análise , Plantas , Solo , Biomassa
4.
J Oral Microbiol ; 15(1): 2264619, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37808891

RESUMO

Acute pancreatitis (AP) is a common abdomen clinical emergency. Most APs have mild clinical symptoms and a good prognosis. However, about 20% of patients develop severe acute pancreatitis (SAP), increasing morbidity and mortality. The microbiome's impact on AP pathophysiology has received increasing attention. Hence, to explore changes in oral microbial composition in acute pancreatitis, we collected clinical information and oral saliva samples from 136 adult participants: 47 healthy controls, 43 acute mild AP (MAP), 29 moderate AP (MSAP), and 17 severe AP (SAP). Using 16S rRNA gene sequencing, 663,175 high-quality sequences were identified. The relative abundance and diversity of oral microorganisms in AP patients increased, with decreased beneficial bacteria such as Streptococcus, Neisseria, and Gemella, and increased Prevotella, Veillonella, Granulicatella, Actinomyces, and Peptostreptococcus in the AP group. Further changes in microbial composition occurred with increasing disease severity, including a decreased abundance of beneficial bacteria such as Neisseria, Haemophilus, and Gemella in MSAP and SAP compared to MAP. Moreover, the Lefse analysis showed that Prevotella, Peptostreptococcus, Actinomyces, and Porphyromonas were better microbial markers for AP. Therefore, oral microbiome changes could distinguish AP from healthy individuals and serve as an early novel predictor of disease severity in AP patients.

5.
Plants (Basel) ; 12(6)2023 Mar 09.
Artigo em Inglês | MEDLINE | ID: mdl-36986927

RESUMO

Improving plant water use efficiency is a key strategy for the utilization of regional limited water resources as well as the sustainable development of agriculture industry. To investigate the effects of different land use types on plant water use efficiency and their mechanisms, a randomized block experiment was designed in the agro-pastoral ecotone of northern China during 2020-2021. The differences in dry matter accumulation, evapotranspiration, soil physical and chemical properties, soil water storage and water use efficiency and their relationships among cropland, natural grassland and artificial grassland were studied. The results show that: In 2020, the dry matter accumulation and water use efficiency of cropland were significantly higher than those of artificial and natural grassland. In 2021, dry matter accumulation and water use efficiency of artificial grassland increased significantly from 364.79 g·m-2 and 24.92 kg·ha-1·mm-1 to 1037.14 g·m-2 and 50.82 kg·ha-1·mm-1, respectively, which were significantly higher than cropland and natural grassland. The evapotranspiration of three land use types showed an increasing trend in two years. The main reason affecting the difference of water use efficiency was that land use type affected soil moisture and soil nutrients, and then changed the dry matter accumulation and evapotranspiration of plants. During the study period, the water use efficiency of artificial grassland was higher in years with less precipitation. Therefore, expanding the planted area of artificial grassland may be one of the effective ways to promote the full utilization of regional water resources.

6.
Cell Death Dis ; 12(10): 867, 2021 09 23.
Artigo em Inglês | MEDLINE | ID: mdl-34556631

RESUMO

Some individuals develop prediabetes and/or diabetes following acute pancreatitis (AP). AP-induced beta-cell injury and the limited regenerative capacity of beta cells might account for pancreatic endocrine insufficiency. Previously, we found that only a few pancreatic cytokeratin 5 positive (Krt5+) cells differentiated into beta cells in the murine AP model, which was insufficient to maintain glucose homeostasis. Notch signaling determines pancreatic progenitor differentiation in pancreas development. This study aimed to examine whether Notch signaling inhibition could promote pancreatic Krt5+ cell differentiation into beta cells and improve glucose homeostasis following AP. Pancreatic tissues from patients with acute necrotizing pancreatitis (ANP) were used to evaluate beta-cell injury, Krt5+ cell activation and differentiation, and Notch activity. The murine AP model was induced by cerulein, and the effect of Notch inhibition on Krt5+ cell differentiation was evaluated both in vivo and in vitro. The results demonstrated beta-cell loss in ANP patients and AP mice. Krt5+ cells were activated in ANP pancreases along with persistently elevated Notch activity, which resulted in the formation of massive duct-like structures. AP mice that received Notch inhibitor showed that impaired glucose tolerance was reversed 7 and 15 days following AP, and increased numbers of newborn small islets due to increased differentiation of Krt5+ cells to beta cells to some extent. In addition, Krt5+ cells isolated from AP mice showed increased differentiation to beta cells by Notch inhibition. Collectively, these findings suggest that beta-cell loss contributes to pancreatic endocrine insufficiency following AP, and inhibition of Notch activity promotes pancreatic Krt5+ cell differentiation to beta cells and improves glucose homeostasis. The findings from this study may shed light on the potential treatment of prediabetes/diabetes following AP.


Assuntos
Diferenciação Celular , Glucose/metabolismo , Homeostase , Células Secretoras de Insulina/patologia , Queratina-5/metabolismo , Pâncreas/patologia , Pancreatite Necrosante Aguda/patologia , Receptores Notch/antagonistas & inibidores , Animais , Estudos de Casos e Controles , Modelos Animais de Doenças , Humanos , Camundongos , Modelos Biológicos , Pâncreas/cirurgia , Pancreatite Necrosante Aguda/metabolismo , Pancreatite Necrosante Aguda/cirurgia , Receptores Notch/metabolismo
7.
PeerJ ; 9: e11136, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33850661

RESUMO

Tartary buckwheat is a nutritious pseudo-cereal crop that is resistant to abiotic stresses, such as drought. However, the buckwheat's mechanisms for responding to drought stress remains unknown. We investigated the changes in physiology and gene expression under drought stress, which was simulated by treatment with polyethylene glycol (PEG). Five physiological indexes, namely MDA content, H2O2 content, CAT activity, SOD activity, and POD activity, were measured over time after 20% PEG treatment. All indexes showed dramatic changes in response to drought stress. A total of 1,190 differentially expressed genes (DEGs) were identified using RNA-seq and the most predominant were related to a number of stress-response genes and late embryogenesis abundant (LEA) proteins. DEGs were gathered into six clusters and were found to be involved in the ABA biosynthesis and signal pathway based on hierarchical clustering and GO and KEGG pathway enrichment. Transcription factors, such as NAC and bZIP, also took part in the response to drought stress. We determined an ABA-dependent and ABA-independent pathway in the regulation of drought stress in Tartary buckwheat. To the best of our knowledge, this is the first transcriptome analysis of drought stress in Tartary buckwheat, and our results provide a comprehensive gene regulatory network of this crop in response to drought stress.

8.
Aging (Albany NY) ; 13(4): 5928-5945, 2021 02 17.
Artigo em Inglês | MEDLINE | ID: mdl-33612483

RESUMO

The purpose of this study was to investigate the differentiation trajectory of gastric cancer (GC) cells and its clinical relevance and generate a prognostic risk scoring (RS) signature based on GC differentiation-related genes (GDRGs) to predict overall survival (OS). Integrated single-cell RNA sequencing (scRNA-seq) and bulk RNA-seq data from GC samples were used for analysis. The cell differentiation trajectory analysis identified three subsets with distinct differentiation states, of which subsets I/II were involved in metabolic disorders, subset II were also associated with hypoxia tolerance, and subset III were related to immune-related pathways. GC samples were divided into three GDRG-based molecular subtypes, and it was found that molecular typing based on cell differentiation successfully predicted patient OS, clinicopathological features, immune infiltration status, and immune checkpoint gene expression. An eight-GDRG-based prognostic RS signature was generated, and the OS of the high-risk group was significantly worse than that of the low-risk group. By integrating the GDRG-based RS signature with prognostic clinicopathological characteristics, a clinicopathologic-genomic nomogram was constructed, and this nomogram yielded strong predictive performance and high accuracy. The study highlights the implication of GC cell differentiation for predicting patient clinical outcome and potential immunotherapy response and proposes a promising treatment direction for GC.


Assuntos
Diferenciação Celular/imunologia , Imunoterapia , Prognóstico , Neoplasias Gástricas/imunologia , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Nomogramas , Neoplasias Gástricas/terapia
9.
Oxid Med Cell Longev ; 2021: 8891544, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33628394

RESUMO

BACKGROUND: Resveratrol (RSV), one of the SIRT1 agonists, has the ability of alleviating severe acute pancreatitis (SAP); however, the concrete protective mechanism remains unknown. It is noteworthy that microcirculation disturbance plays a vital role in SAP, and the SIRT1/FOX1 axis can regulate microcirculation. Therefore, this study is aimed at ascertaining what is the underlying mechanism of the protective effect of RSV on SAP, and whether it is associated with alleviating microcirculation disturbance by regulating the SIRT1/FOX1 axis. METHOD: The model of SAP was induced by retrograde injection of sodium taurodeoxycholate into the bile duct of the rats. The pancreatic wet/dry weight, ET/NO, and TXB2/6-keto-PGF1α ratios; microcirculatory function; and SIRT1 activity were examined. ELISA was used to examine the serum level of lipase, amylase, hemorheology, ET, NO, TXB2, and 6-keto-PGF1α and the content of SIRT1, VEGF, Ang I, and Ang II in the pancreas. RT-PCR was used to examine the mRNA level of VEGF, Ang I, and Ang II. Western blotting was used to detect SIRT1, FOXO1, and acetyl-FOXO1. Immunoprecipitation was used to examine the interaction of SIRT1 and FOXO1. RESULTS: Resveratrol can significantly decrease the expression of lipase, amylase, acetyl-FOXO1, VEGF, Ang II, ET, NO, TXB2, and 6-keto-PGF1α and the ratio of wet/dry weight, ET/NO, and TXB2/6-keto-PGF1α by improving microcirculatory dysfunction and blood viscosity in SAP. Moreover, resveratrol can also promote the interaction of SIRT1 and FOXO1 and increase SIRT1 activity and the expression of SIRT1 and Ang I. The SIRT1 inhibitor, Sirtinol (EX527), obliviously reversed the effects of RSV on SAP. CONCLUSION: Resveratrol can protect rats against SAP, and its protective mechanism is associated with suppressing microcirculation disturbance through activating SIRT1-FOXO1 axis.


Assuntos
Microcirculação , Proteínas do Tecido Nervoso/metabolismo , Pancreatite/tratamento farmacológico , Pancreatite/fisiopatologia , Resveratrol/uso terapêutico , Sirtuína 1/metabolismo , Amilases/sangue , Animais , Células Endoteliais/efeitos dos fármacos , Células Endoteliais/metabolismo , Hemorreologia/efeitos dos fármacos , Lipase/sangue , Masculino , Microcirculação/efeitos dos fármacos , Tamanho do Órgão/efeitos dos fármacos , Pâncreas/patologia , Pancreatite/sangue , Pancreatite/enzimologia , Ligação Proteica/efeitos dos fármacos , Ratos Sprague-Dawley , Resveratrol/química , Resveratrol/farmacologia
10.
Am J Cancer Res ; 11(1): 123-137, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33520364

RESUMO

Increasing evidence indicates the dysregulations and pivotal roles of lncRNAs in the development and progression of various cancers, including pancreatic cancer. Enhanced glycolytic flux and epithelial-to-mesenchymal transition (EMT) have been considered as important factors in driving the malignance of pancreatic cancer. Here, we sought to evaluate the biological role and involved mechanism of lncRNA CASC9 (CASC9) in pancreatic cancer. Our present study showed that CASC9 was upregulated in various pancreatic cancer cell lines. Loss- and gain-of function of CASC9 demonstrated its critical roles in promoting the glycolysis and EMT phenotypes of pancreatic cancer. Moreover, knockdown of CASC9 inhibited the tumorigenicity and metastasis in vivo. Additionally, our findings showed that hypoxia induced the expression of CASC9 and enhanced the binding of HIF-1α to its promoter. We also demonstrated that the positive feedback loop of CASC9 and the AKT/HIF-1α signaling cascade partially mediated this biological process. Altogether, our results suggest that CASC9 promotes the glycolysis and EMT of pancreatic cancer by a positive feedback loop with AKT/HIF-1α signaling, which is synergistically enhanced by the tumor hypoxic niche. Our study will provide potential therapeutic targets for treating pancreatic cancer.

11.
Liver Int ; 41(5): 1033-1043, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33347692

RESUMO

BACKGROUND: While CAR-T therapy has successfully treated haematological malignancies, it has proved sub-optimal for solid tumours. The main limitation is the inability of CAR-T cells to infiltrate and then proliferate within tumours. METHOD: We co-expressed IL-7 and PH20, a type of hyaluronidase, with CAR targeting GPC3 (G3CAR-7 × 20). We test the anti-tumour ability in vitro and in vivo. Moreover the capacity of infiltration and proliferation of G3CAR-7 × 20 was measured. RESULT: We found (G3CAR-7 × 20) exhibited better proliferation in vivo and in vitro than G3CAR, reduced the level of apoptosis after stimulation by tumour cells, and maintained the memory phenotype of CAR-T cells. G3CAR-7 × 20 also increased the ability of CAR-T cells to infiltrate tumour tissue. CONCLUSION: co-expressed IL-7 and PH20 may significantly enhance the efficacy of targeted GPC3 CAR-T cells in solid tumours treatment.


Assuntos
Moléculas de Adesão Celular/metabolismo , Hialuronoglucosaminidase/metabolismo , Imunoterapia Adotiva , Interleucina-7/metabolismo , Neoplasias/terapia , Receptores de Antígenos Quiméricos , Animais , Linhagem Celular Tumoral , Glipicanas , Humanos , Masculino , Camundongos , Ensaios Antitumorais Modelo de Xenoenxerto
12.
Sci Total Environ ; 759: 143541, 2021 Mar 10.
Artigo em Inglês | MEDLINE | ID: mdl-33198996

RESUMO

Nitrogen (N) and phosphorus (P) availability in soils commonly limit belowground biological processes in terrestrial ecosystems. Soil extracellular enzyme activities (EEAs) and microbial functional groups play critical roles in soil biological processes and nutrient cycling, yet their response to nutrient addition are poorly understood. To address this issue, we applied six fertilization treatments composed of combinations of N (0, 1.55, 13.95 g N m-2 yr-1) and P (0, 5.24 g P m-2 yr-1) for two years in a meadow steppe of Inner Mongolia. Soils were collected from each plot in July and August and analyzed for abundances of N-cycling genes and EEAs, and their relationships with treatments. The addition of N significantly increased C-acquisition enzyme activity and enzyme C:N and C:P ratios. Enzymatic stoichiometry indicated that N addition alleviated microbial demand for N, while it increased microbial C limitation. Microbial C and N limitation were significantly correlated with NH4+-N in July, yet they were correlated with soil water content (SWC) in August. The abundance of amoA significantly increased with N addition and was positively related to mineral-N accumulation. The abundance of denitrifier genes and gaseous N loss potential were accelerated by N addition in July, while a neutral effect was observed in August. Nitrate leaching potential was significantly increased by N addition, yet it declined with P addition in July. P addition also suppressed amoA abundance of ammonia oxidizing bacteria. Partial least squares path modelling indicated that N addition positively affected microbial-C limitation, soil N-loss potential and negatively affected microbial-N limitation. P addition negatively affected soil N-loss potential. Ultimately, this study highlights the importance of soil N availability in regulating microbial metabolism and soil N-loss potential, and enhances our understanding of the mechanisms responsible for variation in microbial nutrient cycling in meadow steppe soils.


Assuntos
Nitrogênio , Solo , China , Ecossistema , Pradaria , Fósforo , Microbiologia do Solo
13.
PeerJ ; 8: e8866, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32292650

RESUMO

Allium tenuissimum L. is a widely distributed perennial herbaceous species in temperate and desert steppes. Relative to other wild Allium species, it produces unique sweet flavors, more biomass in arid and cold environments, and has generated greater interest for crop production. Successful crop establishment, however, will depend on rapid and uniform seed germination. Our study aimed to characterize seed germination of A. tenuissimum under various temperature regimes (11, 15, 20, 24 and 28 °C) and water potential levels (0, -0.2, -0.4 and -0.6 MPa), and model germination by hydrotime (HT) and hydrothermal time (HTT) analysis. Final germination percentage (FGP) increased within the range of 11 to 20 °C, yet it declined within the range of 24 to 28 °C and generally decreased as water potential became more negative within each temperature setting. Maximum FGP was observed at 20 °C at all water potential settings and ranged from 55.0 ± 5.3 to 94.8 ± 1.4%. According to HT and HTT models, the base (T b) and optimum temperatures (T o) for seed germination were 7.0 and 20.5 °C, respectively. In addition, base water potential for the fraction of germination within the seed lot (Ψb(g)) shifted to 0 MPa as temperature increased from T b to ceiling temperature (T c). For obtaining 50 % seed germination, Ψb(50) and T c(50) were estimated to be -0.67 MPa and 27.2 °C, respectively. These values for T b and Ψb(50) suggest seed germination of A. tenuissimum is both cold and drought tolerant and suitable for production in semi-arid regions. Our characterization of the ideal sowing conditions for A. tenuissimum, i.e., 20.5 °C and soil water potential less negative than -0.67 MPa offers information to forecast suitable settings to enhance crop production.

14.
Sci Total Environ ; 706: 136048, 2020 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-31864135

RESUMO

Methane (CH4) oxidation in well-aerated grassland soils is an important sink for atmospheric CH4, which can be largely modified by land-use changes. However, the impacts of land-use changes (i.e., from native grasslands to artificial grasslands (AG) and croplands (CL)) on soil CH4 uptake in China remain uncertain. Therefore, the 2-year CH4 flux was measured from 3 land-use types, including heavily grazed steppe (HG, control), AG, and CL, in the agro-pastoral ecotone of Northern China to elucidate this impact. Moreover, a meta-analysis was conducted to elucidate this effect across Chinese grasslands. The results showed that the land-use types could not change the seasonal patterns but significantly (p < 0.05) influenced the strength of soil CH4 uptake. The mean annual CH4 uptake followed the decreasing order of 14.7 ± 0.48 (mean ± 1 standard error) (CL), 3.28 ± 0.09 (AG), and 1.24 ± 0.07 kg CH4-C ha-1 yr-1 (HG) in 2012-2014. This spatial variation pattern was linear and negatively (n = 6, radj.2= 0.73, p < 0.05) associated with the annual mean soil water-filled pore space. Non-growing season CH4 uptake contributed 22-46% to the annual CH4 uptake across land-use types. The meta-analysis also confirmed that the land-use changes significantly (p < 0.05) promoted the annual soil CH4 uptake in temperate grasslands in China. This increased uptake is primarily related to the significant (p < 0.05) decrease in the soil water contents and the increase in the sand contents due to the land-use changes. Furthermore, nitrogen application not exceeding 100 kg N ha-1 yr-1 in these N-limited ecosystems significantly (p < 0.05) promoted soil CH4 uptake. Collectively, our study demonstrated that land-use changes combined with low N application promoted soil CH4 uptake in the temperate grasslands of China.

15.
J Exp Clin Cancer Res ; 37(1): 291, 2018 Nov 28.
Artigo em Inglês | MEDLINE | ID: mdl-30486896

RESUMO

BACKGROUND: Profound chemoresistance remains an intractable obstacle in pancreatic cancer treatment. Pancreatic cancer stem cells (CSCs) and the ubiquitous hypoxic niche have been proposed to account for drug resistance. However, the mechanism involved requires further exploration. This study investigated whether the hypoxic niche enhances gemcitabine-induced stemness and acquired resistance in pancreatic cancer cells by activating the AKT/Notch1 signaling cascade. The therapeutic effects of blockading this signaling cascade on gemcitabine-enriched CSCs were also investigated. METHODS: The expression levels of CSC-associated markers Bmi1 and Sox2 as well as those of proteins involved in AKT/Notch1 signaling were measured by Western blot analysis. The expression level of the pancreatic CSC marker CD24 was measured by flow cytometry. Change in gemcitabine sensitivity was evaluated by the MTT assay. The ability of sphere formation was tested by the sphere-forming assay in stem cell medium. The ability of migration and invasion was detected by the transwell migration/invasion assay. A mouse xenograft model of pancreatic cancer was established to determine the effect of Notch1 inhibition on the killing effect of gemcitabine in vivo. The ability of metastasis was investigated by an in vivo lung metastasis assay. RESULTS: Gemcitabine promoted pancreatic cancer cell stemness and associated malignant phenotypes such as enhanced migration, invasion, metastasis, and chemoresistance. The AKT/Notch1 signaling cascade was activated after gemcitabine treatment and mediated this process. Blockading this pathway enhanced the killing effect of gemcitabine in vivo. However, supplementation with hypoxia treatment synergistically enhanced the AKT/Notch1 signaling pathway and collaboratively promoted gemcitabine-induced stemness. CONCLUSIONS: These findings demonstrate a novel mechanism of acquired gemcitabine resistance in pancreatic cancer cells through induction of stemness, which was mediated by the activation of AKT/Notch1 signaling and synergistically aggravated by the ubiquitous hypoxic niche. Our results might provide new insights for identifying potential targets for reversing chemoresistance in patients with pancreatic cancer.


Assuntos
Hipóxia Celular/efeitos dos fármacos , Desoxicitidina/análogos & derivados , Células-Tronco Neoplásicas/efeitos dos fármacos , Neoplasias Pancreáticas/tratamento farmacológico , Proteínas Proto-Oncogênicas c-akt/metabolismo , Receptor Notch1/metabolismo , Animais , Antimetabólitos Antineoplásicos/farmacologia , Linhagem Celular Tumoral , Desoxicitidina/farmacologia , Humanos , Camundongos , Camundongos Nus , Células-Tronco Neoplásicas/metabolismo , Células-Tronco Neoplásicas/patologia , Neoplasias Pancreáticas/metabolismo , Neoplasias Pancreáticas/patologia , Transdução de Sinais/efeitos dos fármacos , Ensaios Antitumorais Modelo de Xenoenxerto , Gencitabina
16.
Zhonghua Fu Chan Ke Za Zhi ; 47(3): 185-90, 2012 Mar.
Artigo em Chinês | MEDLINE | ID: mdl-22781069

RESUMO

OBJECTIVE: To investigate prevalence HPV infections in cervix among HIV-infected Chinese women. METHODS: From September 2009 to May 2011, 293 women with positive HIV underwent cervical cancer screening as study group matched with 200 women with negative HIV as control group. Questionnaires including demographic information and HIV associated information were collected, Pap smear and 23 subtype of HPV were performed in those women. The women with positive HPV were followed up per 6 months, and the period of following up were more than 12 months. Binary logistic analysis was used for high risk factors of HPV persistent infection. RESULTS: Prevalent HPV infection was 44.4% (130/293) in study group and 20.0% (40/200) in control group, respectively, which reached statistical difference (P < 0.05). The most common genotype of HPV was HPV 16, which prevalence was 13.7% (40/293) in study group and 7.0% (14/200) in control group. The other HPV subtype prevalence was HPV-58, HPV-52, HPV-43 and HPV-18, which was 9.2% (27/293), 8.2% (24/293), 8.2% (24/293), 6.8% (20/293) in study group and 3.0% (6/200), 2.5% (5/200), 1.5% (3/200), 2.5% (5/200) in control group. At time point of 12 months following up, the persistent prevalence of HPV was 47.5% (48/101) in study group and 21.1% (8/38) in control group, which reached statistical difference (P < 0.05). Multiple HPV infections (OR = 6.4, 95%CI: 1.6 - 25.6), abnormal cytology (OR = 18.1, 95%CI: 4.5 - 76.9) and lower CD(4) T cell count (compared with CD(4) > 3.5 × 10(8)/L, if 2.0 × 10(8) ≤ CD(4) ≤ 3.5 × 10(8), OR = 8.1, 95%CI: 1.3 - 56.3; if CD(4) < 2.0 × 10(8)/L, OR = 9.1, 95%CI: 1.8 - 46.9) were independently associated with HPV persistence among HIV-positive subjects. CONCLUSIONS: Prevalence and persistence of HPV infections were more common among HIV-positive Chinese women than those in HIV-negative Chinese women. Improving immune function, decreasing multiple HPV infections, treating abnormal cervical cytology could decrease prevalence of HPV infection.


Assuntos
Colo do Útero/virologia , Soropositividade para HIV , Papillomaviridae , Infecções por Papillomavirus/epidemiologia , Adulto , Contagem de Linfócito CD4 , Estudos de Casos e Controles , Colo do Útero/patologia , Coinfecção/epidemiologia , Coinfecção/virologia , Feminino , HIV , Soropositividade para HIV/complicações , Soropositividade para HIV/epidemiologia , Humanos , Pessoa de Meia-Idade , Teste de Papanicolaou , Papillomaviridae/genética , Infecções por Papillomavirus/complicações , Infecções por Papillomavirus/virologia , Fatores de Risco , Inquéritos e Questionários , Neoplasias do Colo do Útero/epidemiologia , Neoplasias do Colo do Útero/virologia , Esfregaço Vaginal , Adulto Jovem
17.
Clin Res Hepatol Gastroenterol ; 36(6): 574-82, 2012 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-22481087

RESUMO

INTRODUCTION: Since the advent of combined antiretroviral therapy (cART), liver-related mortality has become the leading cause of non-AIDS-related deaths in human immunodeficiency virus (HIV) infected patients in Western countries. OBJECTIVE: To investigate the incidence, mortality and risk factors of end-stage liver disease (ESLD) in HIV and hepatitis C virus (HCV) coinfected former plasma donors (FPDs) and blood recipients (BRs). METHOD: A retrospective study was conducted. RESULTS: Of 321 HIV-HCV coinfected patients, 42 (13.1%) developed ESLD and 40 (12.5%) died. Factors that were independently associated with ESLD included older age at baseline (Odds ratios [OR]: 2.444, P=0.035), alanine aminotransferase (ALT) greater or equal to 2 (the upper limit of normal [ULN]) at the end of follow-up (OR: 16.460, P=0.000), hepatitis B virus (HBV) (OR: 2.525, P=0.043), CDC stage C (OR: 5.806, P=0.001), duration of cART greater than 5 years (OR: 3.256, P=0.010), and CD4 count greater or equal to 200 cells/mm(3) at the end of follow-up (OR: 0.383, P=0.016). The probability of developing ESLD in HIV-HCV coinfected BRs was significantly higher than in FPDs (P=0.008). Mortality was also significantly higher in HIV-HCV coinfected patients with ESLD than in those without ESLD (P=0.000). CONCLUSION: In the cART era, ESLD was common among HIV-HCV coinfected Han Chinese patients and was responsible for reducing patient survival time.


Assuntos
Coinfecção , Doença Hepática Terminal/complicações , Doença Hepática Terminal/epidemiologia , Infecções por HIV/complicações , Hepatite C Crônica/complicações , Adolescente , Adulto , Idoso , Povo Asiático , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência , Estudos Retrospectivos , Fatores de Risco , Adulto Jovem
18.
Jpn J Infect Dis ; 64(5): 411-6, 2011.
Artigo em Inglês | MEDLINE | ID: mdl-21937823

RESUMO

The aim of this study was to evaluate the prevalence and risk factors of human papillomavirus (HPV) infection among human immunodeficiency virus (HIV)-positive women in China. To this end, we enrolled 200 HIV-positive and 182 HIV-negative women in this cross-sectional cohort study. The following sampling methods were used: (i) structured interview, (ii) CD4 cell counts, and (iii) cervical specimens. HPV genotype (total 23 types) was analyzed using polymerase chain reaction assay. Logistic regression analysis was used to identify independent causative factors for HPV infection. The prevalence of HPV infection was 3-fold higher in the HIV-positive women than in the HIV-negative women. The overall prevalences of HPV infection, high risk (HR)-HPV infection, and multiple HPV infections in the HIV-positive women were 36.5%, 33.5%, and 13.0%, respectively, and the corresponding values in HIV-negative women were 12.1%, 10.4%, and 6.0%, respectively (P < 0.05). The types of HR-HPVs were similar in the HIV-positive and HIV-negative women (HPV-16, -52, -58, and -18), and the prevalences of infections by these viruses were 1.5- to 3-fold higher in the HIV-positive group than in the HIV-negative group. HR-HPV infection among the HIV-positive women was associated with three factors: low CD4 count (OR for 200 ≤ CD4 ≤ 350 and CD4 < 200/µL were 2.11 and 3.13, respectively), HIV infection through sexual contact (OR, 7.90; 95% CI, 2.38-14.60), and having HIV-positive sexual partners (OR, 2.02; 95% CI, 1.03-3.95). We found that the prevalence of HPV infection among the HIV-positive Chinese women was higher than that among the HIV-negative women; moreover, among the HIV-positive women, factors associated with HIV infection were risk factors for HR-HPV infection.


Assuntos
Coinfecção/epidemiologia , Infecções por HIV/complicações , Papillomaviridae/isolamento & purificação , Infecções por Papillomavirus/epidemiologia , Medição de Risco , Adulto , Povo Asiático , Contagem de Linfócito CD4 , China/epidemiologia , Estudos de Coortes , Coinfecção/virologia , Estudos Transversais , Feminino , Infecções por HIV/imunologia , Infecções por HIV/patologia , Humanos , Entrevistas como Assunto , Pessoa de Meia-Idade , Infecções por Papillomavirus/virologia , Prevalência , Fatores de Risco
19.
J Cancer Res Clin Oncol ; 137(4): 609-14, 2011 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-20532560

RESUMO

OBJECTIVE: To determine the incidence and survival time of acquired immunodeficiency syndrome-related malignancies among HIV-infected population. METHODS: A clinical database search, chart review and verification with health records were undertaken for all AIDS-defining cancers diagnosed in Zhongnan Hospital Wuhan University, Hubei Province, China. Kaplan-Meier method was used to evaluate survival time in HIV-infected patients with cancer. RESULTS: A total of 3,554 patients with 11,072 person-years of HIV follow-up care were reviewed from January 2004 to December 2008. Sixty-three cancer cases were identified. The median ages of HIV-positive cancer cases were 42.4 ± 8.8 years, CD4 count were 220.9 ± 142.3/µl. The common cancers were non-Hodgkin's lymphoma (NHL, 28.6%), cervical cancer (22.2%), liver cancer (17.5%). Statistically significantly elevated SIRs were observed in NHL (SIR in all = 34.5, 95% CI 11.7-89.9, SIR in males = 45.3, 95% CI 24.7-138.9, females = 12.2, 95% CI 3.9-38.2), invasive cervical cancer (SIR = 68.1, 95% CI 19.2-84.5), liver cancer (SIR = 6.0, 95% CI 2.6-12.2), nasopharyngeal cancer (SIR = 6.2, 95% CI 1.5-44.9), bladder cancer (SIR = 4.9, 95% CI 0.9-22.9), esophageal cancer (SIR = 3.1, 95% CI 0.7-14.3), and stomach cancer (SIR = 2.6, 95% CI 0.6-11.6). All cancers combined showed a statistically significantly elevated SIR of 4.1 (95% CI 2.5-4.6), SIR for all cancers was much higher in female (SIR = 4.8, 95% CI 3.2-7.3) than in male (SIR = 3.1, 95% CI 2.1-4.3). Among HIV-positive patients with cancer, the median survival time was 14.5 ± 3.8 months in NHL group, 28.9 ± 3.6 months in cervix group, 5.1 ± 1.1 months in liver group, and 26.7 ± 6.7 months in other groups. The median survival time in HIV-infected group (23.1 ± 3.5 months) was shorter than that in non-HIV-infected group (43.0 ± 5.1 months), (P < 0.05). CONCLUSIONS: NHL, cervical cancers and liver cancer are common cancers among HIV-infected individuals in Hubei, China. Most malignant diseases that arise in the setting of HIV infection tend to occur at a more advanced stage with shorter survival time.


Assuntos
Infecções por HIV/complicações , Neoplasias/epidemiologia , Adulto , Estudos de Coortes , Feminino , Humanos , Neoplasias Hepáticas/epidemiologia , Linfoma não Hodgkin/epidemiologia , Masculino , Pessoa de Meia-Idade , Neoplasias/tratamento farmacológico , Neoplasias/etiologia , Prevalência , Neoplasias do Colo do Útero/epidemiologia
20.
Zhonghua Gan Zang Bing Za Zhi ; 18(9): 689-93, 2010 Sep.
Artigo em Chinês | MEDLINE | ID: mdl-20943082

RESUMO

OBJECTIVE: To investigate the incidence of hepatotoxicity in acquired immunodeficiency syndrome (AIDS) patients on combined anti-retroviral therapy (cART) containing nevirapine (NVP) and to assess the risk factors and its impact on cART. METHODS: 330 AIDS patients from March 2003 to June 2008 at local county were enrolled and a retrospective study using Kaplan-meier survival and Multivariate logistic regression modeling was conducted. RESULTS: 267 out of 330 patients received NVP based cART and 63 cases received EFV-based cART. The deference of prevalences of hepatotoxicity between the two groups is statistically significant (Chi2 = 6.691, P = 0.01). 133 out of 267 (49.8%) patients on NVP based cART had at least one episode of ALT elevation during a median 21 months (interquartile ranges, IQR 6, 37) follow-up time, amounts for 28.5 cases per 100 person-years. Baseline ALT elevation (OR = 14.368, P = 0.017)and HCV co-infection (OR = 3.009, P = 0.000) were risk factors for cART related hepatotoxicity, while greatly increased CD4+ T(CD4) cell count was protective against hepatotoxicity development (OR = 0.996, P = 0.000). Patients co-infected with HCV received NVP-based cART had the higher probability of hepatotoxicity than those without HCV co-infection (Log rank: Chi2 = 16.764, P = 0.000). 23 out of the 133 subjects (17.3%) with NVP related hepatotoxicity discontinued cART temporarily or shifted NVP to efavirenz. CONCLUSION: NVP related hepatotoxicity was common among ARV naive HIV infected subjects in our cohort. Baseline ALT elevation and HCV co-infection were associated statistically with the development of hepatotoxicity. Hepatotoxicity led to discontinuing cART temporarily or switching to other regimens in some subjects. It suggested that NVP should be used with caution in patients co-infected with HCV among whom anti-HCV therapy before cART initiation may contribute to minimizing the probability of NVP associated hepatotoxicity.


Assuntos
Síndrome da Imunodeficiência Adquirida/metabolismo , Antirretrovirais/efeitos adversos , Doença Hepática Induzida por Substâncias e Drogas/epidemiologia , Fígado/efeitos dos fármacos , Nevirapina/efeitos adversos , Síndrome da Imunodeficiência Adquirida/tratamento farmacológico , Adolescente , Adulto , Povo Asiático , Doença Hepática Induzida por Substâncias e Drogas/virologia , Feminino , Humanos , Incidência , Fígado/metabolismo , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco , Adulto Jovem
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