The recent discovery of cancer stem cells (CSCs) has played a pivotal role in changing our view of carcinogenesis and chemotherapy. Based on this concept, CSCs are responsible for the formation and ...growth of neoplastic tissue and are naturally resistant to chemotherapy, explaining why traditional chemotherapies can initially shrink a tumor but fails to eradicate it in full, allowing eventual recurrence. Recently, we identified a CSC population in hepatocellular carcinoma (HCC) characterized by their CD133 phenotype. However, the molecular mechanism by which it escapes conventional therapies remains unknown. Here, we examined the sensitivity of these cells to chemotherapeutic agents (doxorubicin and fluorouracil) and the possible mechanistic pathway by which resistance may be regulated. Purified CD133+ HCC cells isolated from human HCC cell line and xenograft mouse models survived chemotherapy in increased proportions relative to most tumor cells which lack the CD133 phenotype; the underlying mechanism of which required the preferential expression of survival proteins involved in the Akt/PKB and Bcl-2 pathway. Treatment of CD133+ HCC cells with an AKT1 inhibitor, specific to the Akt/PKB pathway, significantly reduced the expression of the survival proteins that was normally expressed endogenously. In addition, treatment of unsorted HCC cells with both anticancer drugs in vitro significantly enriched the CD133+ subpopulation. In conclusion, our results show that CD133+ HCC cells contribute to chemoresistance through preferential activation of Akt/PKB and Bcl-2 cell survival response. Targeting of this specific survival signaling pathway in CD133+ HCC CSCs may provide a novel therapeutic model for the disease.
Drylands are home to more than 38% of the world's population and are one of the most sensitive areas to climate change and human activities. This review describes recent progress in dryland climate ...change research. Recent findings indicate that the long‐term trend of the aridity index (AI) is mainly attributable to increased greenhouse gas emissions, while anthropogenic aerosols exert small effects but alter its attributions. Atmosphere‐land interactions determine the intensity of regional response. The largest warming during the last 100 years was observed over drylands and accounted for more than half of the continental warming. The global pattern and interdecadal variability of aridity changes are modulated by oceanic oscillations. The different phases of those oceanic oscillations induce significant changes in land‐sea and north‐south thermal contrasts, which affect the intensity of the westerlies and planetary waves and the blocking frequency, thereby altering global changes in temperature and precipitation. During 1948–2008, the drylands in the Americas became wetter due to enhanced westerlies, whereas the drylands in the Eastern Hemisphere became drier because of the weakened East Asian summer monsoon. Drylands as defined by the AI have expanded over the last 60 years and are projected to expand in the 21st century. The largest expansion of drylands has occurred in semiarid regions since the early 1960s. Dryland expansion will lead to reduced carbon sequestration and enhanced regional warming. The increasing aridity, enhanced warming, and rapidly growing population will exacerbate the risk of land degradation and desertification in the near future in developing countries.
Key Points
Drylands are one of the most sensitive areas to climate change and human activities
Attribution of major drivers and processes to dryland climate change has been summarized
Enhanced warming, increasing aridity, and expanding drylands pose a threat to developing countries
miR-145-5p has been identified as a tumor suppressor involved in a wide variety of human cancers. Herein, we aimed to further explore the functional role and molecular mechanism of miR-145-5p on ...breast cancer (BC) progression and chemoresistance. The expressions of miR-145-5p and sex determining region Y-box2 (SOX-2) mRNA were assessed by qRT-PCR assay. SOX2 protein expression was measured using western blot. CCK-8 assays were used to determine the IC50 values of paclitaxel (PTX) and cell proliferation. Transwell assays were performed to detect cell migration and invasion. The target of miR-145-5p was verified by dual-luciferase reporter assays. Xenograft model was used to observe the role of miR-145-5p in vivo. The results showed that miR-145-5p was downregulated in BC tissues and cells and associated with PTX resistance of BC cells. Overexpression of miR-145-5p or SOX2 knockdown repressed the proliferation, migration, invasion, and attenuated PTX resistance in PTX-resistant BC cells. Mechanistically, miR-145-5p negatively regulated SOX2 expression by targeting SOX2. The inhibitory effects of miR-145-5p on the proliferation, migration, invasion, and PTX resistance were antagonized by SOX2 level restoration in PTX-resistant BC cells. Additionally, miR-145-5p repressed tumor growth in vivo. In conclusion, our study suggested that miR-145-5p reduced PTX resistance and repressed the progression at least partly by targeting SOX2 in PTX-resistant BC cells, highlighting miR-145-5p as a promising biomarker for BC treatment.
Consumption of avocados has been suggested to be beneficial for weight control, however, limited research is available about the related food choices. Understanding the food choices associated with ...avocados at meal occasions may further aid behavioural strategies to lose weight. The present study used a systematic approach to develop an avocado-specific food database, with the aim to explore food choices related to avocados at meal occasions as reported by overweight and obese volunteers in weight loss clinical trials.
The avocado-specific database was based on AUSNUT 2011-13 food composition database structure and was developed via a systematic approach, which determined the avocado content of Australian foods and beverages. Baseline usual food intake data was retrospectively pooled from four food-based clinical trials (n = 758). The Apriori algorithm of association rules, a two-step descriptive method was used to identify food choices associated with avocados at different meal occasions using a nested hierarchical food group classification system.
The avocado database identified 34 avocados and avocado-containing foods and beverages. The proportion of avocado consumers in the pooled cohort was 51.3% (n = 389), with an average avocado intake of 21.57 ± 36.75 grams per day. Avocados were found to be closely related to other food groups at all of the food group levels at main meal occasions. A total of 68 food items containing avocados were identified for avocado consumers at the breakfast, lunch and dinner meals.
The avocado specific database provides a snapshot of the foods and beverages which contain avocados. Enumerating the full range of food choices in relation to avocado consumption should provide examples of food choices that people might consider in their efforts to increase their avocado consumption.
In semi‐arid areas of north‐west China, grain yields of wheat (Triticum aestivum L.) are higher in recently bred cultivars than those released six decades earlier. The gas exchange, chloroplast ...activity and yield of six spring wheat cultivars grown in the 1950s, Hst and Gs96 (early), in the 1970s, Gy602 and Dx24 (intermediate), and in the 1990s, Gc20 and Lc8275 (modern) were compared with adequate water (WET) and drought stress (DRY) to determine the effects of drought stress among the cultivars. The results showed that in the WET treatment, the modern cultivars had significantly higher rates of leaf gas exchange, photosystem 2 (PS2) maximal photochemical efficiency, actual quantum yield of PS2 (ФPS2), photochemical quenching of chlorophyll (qp) and lower non‐photochemical quenching (NPQ) than early cultivars, but had significantly lower gas exchange rates, intercellular CO₂ concentration, ФPS2, qp and NPQ in the DRY treatment. In the WET treatment, the grain yield of early cultivars was significantly lower (10 %) than intermediate cultivars, but was significantly higher (17 %) than intermediate cultivars in the DRY treatment. The modern and intermediate cultivars had more sensitive stomata to water shortage, but the decreased activity of the PS2 reaction centre helped avoid damage from photoinhibition in these cultivars.
Ghrelin, a stomach-derived orexigenic hormone, has stimulated great interest as a potential target for obesity control. Pharmacological evidence indicates that ghrelin’s effects on food intake are ...mediated by neuropeptide Y (NPY) and agouti-related protein (AgRP) in the central nervous system. These include intracerebroventricular application of antibodies to neutralize NPY and AgRP, and the application of an NPY Y1 receptor antagonist, which blocks some of the orexigenic effects of ghrelin. Here we describe treatment of Agrp−/−;Npy−/− and Mc3r−/−;Mc4r−/− double knockout mice as well as Npy−/− and Agrp−/− single knockout mice with either ghrelin or an orally active nonpeptide ghrelin agonist. The data demonstrate that NPY and AgRP are required for the orexigenic effects of ghrelin, as well as the involvement of the melanocortin pathway in ghrelin signaling. Our results outline a functional interaction between the NPY and AgRP pathways. Although deletion of either NPY or AgRP caused only a modest or nondetectable effect, ablation of both ligands completely abolished the orexigenic action of ghrelin. Our results establish an in vivo orexigenic function for NPY and AgRP, mediating the effect of ghrelin.
Summary
T helper type 9 (Th9) cells are a novel identified subset of CD4+ T helper cells, which could partly contribute to allergic inflammation, while the precise contribution of Th9 cells in atopic ...dermatitis (AD) remains unknown. We aimed to explore the possible role of Th9 cells in AD pathogenesis. The Th9 cell percentage, transcription factor PU.1 and cytokine interleukin (IL)‐9 mRNA levels, as well as IL‐9 serum concentration in peripheral circulation, were measured in AD patients, psoriasis patients and healthy controls. The Th9 cell percentage, PU.1 and IL‐9 expression levels of AD patients were all increased significantly compared with the other two control groups (P < 0·01), and correlated positively with SCORing Atopic Dermatitis index, serum immunoglobulin (Ig)E and thymus‐ and activation‐regulated chemokine (TARC) levels (P < 0·05). In simple AD patients and AD patients complicated by allergic rhinitis or asthma, there were no significant differences in the Th9 cell percentage, PU.1 and IL‐9 expression levels between them. At the same time, IL‐9 and vascular endothelial growth factor (VEGF) mRNA levels were detected in AD lesions and normal skin samples, which were both distinctly elevated in AD lesions, and there was a positive association between them (P < 0·01). Keratinocytes were cultured with IL‐9 stimulation and the secretion of VEGF was detected. IL‐9 can promote the secretion of VEGF by keratinocytes in a time‐ and dose‐dependent manner. In conclusion, the expansion of the Th9 cell subset, up‐regulation of the PU.1 transcription factor and increased secretion of the IL‐9 cytokine may contribute to the pathogenesis of AD, which may be supported by the increased release of VEGF by keratinocyes after IL‐9 stimulation.
The low-energy properties of the one-dimensional anyon gas with a delta-function interaction are discussed in the context of its Bethe ansatz solution. It is found that the anyonic statistical ...parameter and the dynamical coupling constant induce Haldane exclusion statistics interpolating between bosons and fermions. Moreover, the anyonic parameter may trigger statistics beyond Fermi statistics for which the exclusion parameter alpha is greater than one. The Tonks-Girardeau and the weak coupling limits are discussed in detail. The results support the universal role of alpha in the dispersion relations.
We have recently identified and characterized a novel oncogene, maelstrom (MAEL) from 1q24, in the pathogenesis of hepatocellular carcinoma. In this study, MAEL was investigated for its oncogenic ...role in urothelial carcinoma of the bladder (UCB) tumorigenesis/aggressiveness and underlying molecular mechanisms. Here, we report that overexpression of MAEL in UCB is important in the acquisition of an aggressive and/or poor prognostic phenotype. In UCB cell lines, knockdown of MAEL by short hairpin RNA is sufficient to inhibit cell growth, invasiveness/metastasis and suppressed epithelial-mesenchymal transition (EMT), whereas ectopic overexpression of MAEL promoted cell growth, invasive and/or metastatic capacity and enhanced EMT both in vitro and in vivo. We further demonstrate that MAEL could induce UCB cell EMT by downregulating a critical downstream target, the metastasis suppressor 1 (MTSS1) gene, ultimately leading to an increased invasiveness of cancer cells. Notably, overexpression of MAEL in UCB cells substantially enhanced the enrichment of DNA methyltrans-ferase (DNMT)3B and histone deacetylase (HDAC)1/2 on the promoter of the MTSS1, and thereby epigenetically suppressing the MTSS1 transcription. Downregulation of MTSS1 by MAEL in UCB cells is partially dependent on DNMT3B. Furthermore, we identify that beside the gene amplification of MAEL, miR-186 is a key negative regulator of MAEL and downregulation of miR-186 is another important mechanism for MAEL overexpression in UCBs. These data suggest that overexpression of MAEL, caused by gene amplification and/or decreased miR-186, has a critical oncogenic role in UCB pathogenesis by downregulation of MTSS1, and MAEL could be used as a novel prognostic marker and/or effective therapeutic target for human UCB.
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