•FLNa’s structure and function.•Substances that can interact with FLNa and their mechanisms.•FLNa is involved in signal transduction, cell proliferation and differentiation, cytoskeleton ...reorganization and cell migration, vesicle transport and angiogenesis.•FLNa plays a vital role in genetic disease, tumor progression and pathogenic microorganism infection.
Filamin A(FLNa) is an actin-binding protein, which participates in the formation of the cytoskeleton, anchors a variety of proteins in the cytoskeleton and regulates cell adhesion and migration. It is involved in signal transduction, cell proliferation and differentiation, pseudopodia formation, vesicle transport, tumor resistance and genetic diseases by binding with interacting proteins. In order to fully elucidate the structure, function and pathogenesis of FLNa, we summarized all substances which directly or indirectly act on FLNa so far, upstream and downstream targets which having effect on it, signaling pathways and their functions. It also recorded the expression and effect of FLNa in different diseases, including hereditary disease and tumors.
Cellular Antioxidant Activity of Common Fruits Wolfe, Kelly L; Kang, Xinmei; He, Xiangjiu ...
Journal of agricultural and food chemistry,
09/2008, Letnik:
56, Številka:
18
Journal Article
Recenzirano
Measurement of antioxidant activity using biologically relevant assays is important in the screening of fruits for potential health benefits. The cellular antioxidant activity (CAA) assay quantifies ...antioxidant activity in cell culture and was developed to meet the need for a more biologically representative method than the popular chemistry antioxidant capacity measures. The objective of the study was to determine the cellular antioxidant activity, total phenolic contents, and oxygen radical absorbance capacity (ORAC) values of 25 fruits commonly consumed in the United States. Pomegranate and berries (wild blueberry, blackberry, raspberry, and blueberry) had the highest CAA values, whereas banana and melons had the lowest. Apples were found to be the largest contributors of fruit phenolics to the American diet, and apple and strawberries were the biggest suppliers of cellular antioxidant activity. Increasing fruit consumption is a logical strategy to increase antioxidant intake and decrease oxidative stress and may lead to reduced risk of cancer.
Liver diseases with different pathogenesis share common pathways of immune-mediated injury. Chitinase-3-like protein 1 (CHI3L1) was induced in both acute and chronic liver injuries, and recent ...studies reported that it possesses an immunosuppressive ability. CHI3L1 was also expressed in mesenchymal stem cells (MSCs), thus we investigates the role of CHI3L1 in MSC-based therapy for immune-mediated liver injury here. We found that CHI3L1 was highly expressed in human umbilical cord MSCs (hUC-MSCs). Downregulating CHI3L1 mitigated the ability of hUC-MSCs to inhibit T cell activation, proliferation and inflammatory cytokine secretion in vitro. Using Concanavalin A (Con A)-induced liver injury mouse model, we found that silencing CHI3L1 significantly abrogated the hUC-MSCs-mediated alleviation of liver injury, accompanying by weakened suppressive effects on infiltration and activation of hepatic T cells, and secretion of pro-inflammatory cytokines. In addition, recombinant CHI3L1 (rCHI3L1) administration inhibited the proliferation and function of activated T cells, and alleviated the Con A-induced liver injury in mice. Mechanistically, gene set enrichment analysis showed that JAK/STAT signalling pathway was one of the most significantly enriched gene pathways in T cells co-cultured with hUC-MSCs with CHI3L1 knockdown, and further study revealed that CHI3L1 secreted by hUC-MSCs inhibited the STAT1/3 signalling in T cells by upregulating peroxisome proliferator-activated receptor δ (PPARδ). Collectively, our data showed that CHI3L1 was a novel MSC-secreted immunosuppressive factor and provided new insights into therapeutic treatment of immune-mediated liver injury.
The fatigue prevalence in breast cancer survivors is high during the endocrine treatment. However, there are few evidence-based interventions to manage this symptom. The aim of this study was to ...investigate the effectiveness of spore powder of Ganoderma lucidum for cancer-related fatigue in breast cancer patients undergoing endocrine therapy. Spore powder of Ganoderma lucidum is a kind of Basidiomycete which is a widely used traditional medicine in China. 48 breast cancer patients with cancer-related fatigue undergoing endocrine therapy were randomized into the experimental or control group. FACT-F, HADS, and EORTC QLQ-C30 questionnaires data were collected at baseline and 4 weeks after treatment. The concentrations of TNF-α, IL-6, and liver-kidney functions were measured before and after intervention. The experimental group showed statistically significant improvements in the domains of physical well-being and fatigue subscale after intervention. These patients also reported less anxiety and depression and better quality of life. Immune markers of CRF were significantly lower and no serious adverse effects occurred during the study. This pilot study suggests that spore powder of Ganoderma lucidum may have beneficial effects on cancer-related fatigue and quality of life in breast cancer patients undergoing endocrine therapy without any significant adverse effect.
Recurrent metastasis is a major fatal cause of breast cancer. Regretfully, the driving force and the molecular beneath have not been fully illustrated yet. In this study, a cohort of breast cancer ...patients with locoregional metastasis was recruited. For them, we collected the matched samples of the primary tumor and metastatic tumor, and then we determined the mutation profiles with whole-exome sequencing (WES). On basis of the profiles, we identified a list of deleterious variants in eight susceptible genes. Of them, filamin A (FLNA) was considered a potential driver gene of metastasis, and its low expression could enhance 5 years' relapse survival rate by 15%. To prove the finding, we constructed a stable FLNA knockout tumor cell line, which manifested that the cell abilities of proliferation, migration, and invasion were significantly weakened in response to the gene knockout. Subsequently, xenograft mouse experiments further proved that FLNA knockout could inhibit local or distal metastasis. Putting all the results together, we consolidated that FLNA could be a potential driver gene to metastasis of breast cancer, in particular triple-negative breast cancer. Additional experiments also suggested that FLNA might intervene in metastasis
the regulation of MMP-1 expression. In summary, this study demonstrates that FLNA may play as a positive regulator in cancer proliferation and recurrence. It provides new insight into breast cancer metastasis and suggests a potential new therapeutic target for breast cancer therapy.
Glycometabolism is a distinctive aspect of energy metabolism in breast cancer, and key glycometabolism enzymes/pathways (glycolysis, hexosamine biosynthetic pathway, and pentose phosphate pathway) ...may directly or indirectly affect the clinical features. In this study, we analyzed the particular correlation between the altered glycometabolism and clinical features of breast cancer to instruct research and clinical treatment. Tissue microarrays containing 189 hollow needle aspiration samples and 295 triple-negative breast cancer tissues were used to test the expression of M2 isoform of pyruvate kinase (PKM2), glutamine-fructose-6-phosphate transaminase 1 (GFPT1), glucose-6-phosphate dehydrogenase (G6PD), and p53 by immunohistochemistry and the intensity of these glycometabolism-related protein was evaluated. Chi-square test, Kaplan-Meier estimates, and Cox proportional hazards model were used to analyze the relationship between the expression of these factors and major clinical features. PKM2, GFPT1, and G6PD affect the pathologic complete response rate of neoadjuvant chemotherapy patients in different ways; pyruvate kinase muscle isozyme 2 (PKM2) and G6PD are closely associated with the molecular subtypes, whereas GFPT1 is correlated with cancer size. All these three factors as well as p53 have impacts on the progression-free survival and overall survival of triple-negative breast cancer patients. Cancer size shows significant association with PKM2 and GFPT1 expression, while the pN stage and grade are associated with PKM2 and G6PD expression. Our study support that clinical characteristics are reflections of specific glycometabolism pathways, so their relationships may shed light on the orientation of research or clinical treatment. The expression of PKM2, GFPT1, and G6PD are hazardous factors for prognosis: high expression of these proteins predict worse progression-free survival and overall survival in triple-negative breast cancer, as well as worse pathologic complete response rate in neoadjuvant chemotherapy breast cancer. However, p53 appears as a protective factor only in the patients receiving neoadjuvant chemotherapy. All the four proteins, PKM2, GFPT1, G6PD and p53, are prognostic markers of breast cancer. The correlation among them suggests that there may be crosstalk of the four proteins in breast cancer.
Due to their excellent mechanical and thermal properties and medium resistance, epoxy/carbon nanotubes and nanocomposites have been widely used in many fields. However, the conventional thermosetting ...process is not only time- and energy-consuming, but also causes the agglomeration of nanofillers, which leads to unsatisfactory properties of the obtained composites. In this study, multi-walled carbon nanotubes (MWCNTs)/epoxy nanocomposites were prepared using UV photoinduced frontal polymerization (PIFP) in a rapid fashion. The addition of MWCNTs modified by a surface carboxylation reaction was found to enhance the impact strength and heat resistance of the epoxy matrix effectively. The experimental results indicate that with 0.4 wt % loading of modified MWCNTs, increases of 462.23% in the impact strength and 57.3 °C in the glass transition temperature
were achieved. A high-performance nanocomposite was prepared in only a few minutes using the PIFP approach. Considering its fast, energy-saving, and environmentally friendly production, the PIFP approach displays considerable potential in the field of the fast preparation, repair, and deep curing of nanocomposites and coatings.
Abstract
Hepatic specification and functional maturation are tightly controlled throughout development. N6-methyladenosine (m
6
A) is the most abundant RNA modification of eukaryotic mRNAs and is ...involved in various physiological and pathological processes. However, the function of m
6
A in liver development remains elusive. Here we dissect the role of Mettl3-mediated m
6
A modification in postnatal liver development and homeostasis. Knocking out Mettl3 perinatally with
Alb-Cre
(
Mettl3
cKO) induces apoptosis and steatosis of hepatocytes, results in severe liver injury, and finally leads to postnatal lethality within 7 weeks. m
6
A-RIP sequencing and RNA-sequencing reveal that mRNAs of a series of crucial liver-enriched transcription factors are modified by m
6
A, including
Hnf4a
, a master regulator for hepatic parenchymal formation. Deleting Mettl3 reduces m
6
A modification on
Hnf4a
, decreases its transcript stability in an Igf2bp1-dependent manner, and down-regulates
Hnf4a
expression, while overexpressing Hnf4a with AAV8 alleviates the liver injury and prolongs the lifespan of
Mettl3
cKO mice. However, knocking out Mettl3 in adults using
Alb-Cre
ERT2
does not affect liver homeostasis. Our study identifies a dynamic role of Mettl3-mediated RNA m
6
A modification in liver development.
Cancer stem cells are enriched in triple-negative breast cancer (TNBC) tumor tissues, which present strong capacities of proliferation and tumorigenicity. The present study detected the distribution ...of cancer stem cell markers cluster of differentiation (CD)44/CD24 and analyzed the clinical outcomes of different CD44/CD24 phenotypes in patients with TNBC. Multivariate Cox regression analyses were performed with regard to the prognostic value of cancer stem cell markers CD44/CD24, aldehyde dehydrogenase 1 and other baseline clinical characteristics, including tumor size, lymph node involved, adjuvant chemotherapy, Ki-67, breast cancer susceptibility gene 1, cellular tumor antigen p53, vimentin and basal-like status. The multivariate analyses showed that three of these factors, CD44/CD24 phenotype, basal-like status and number of lymph nodes involved, had an impact on overall survival. Furthermore, patients with CD44+/CD24− phenotype, basal-like tumors and ≥4 lymph nodes involved had a significantly worse prognosis. The expression of CD44 and CD24 was detected by double-staining immunohistochemistry, which can locate cancer stem cells individually. Overall, the present results indicated that CD44/CD24 status evaluated by double-staining immunohistochemistry constitutes an independent prognostic factor for TNBC.
This paper proposes an empirical likelihood based diagnostic technique for heteroscedasticity for semiparametric varying-coefficient partially linear models with missing responses. Firstly, the ...authors complement the missing response variables by regression method. Then, the empirical likelihood method is introduced to study the heteroscedasticity of the semiparametric varying-coefficient partially linear models with complete-case data. Finally, the authors obtain the finite sample property by numerical simulation.
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