Foxp3 is a novel member of forkhead and winged-helix transcription factor family.Foxp3 is specifically expressed in CD4+ CD25 + regulatory T cells,and Foxp3 is a critical regulator of CD4+ CD25 + regulatory T cell development and function maintain.With the development of molecular biology techniques,the understanding of Foxp3's structure and function is increasingly clear.Foxp3 plays an important role in the lung cancer's development,clinical treatment and prognosis.Thus to clarify the regulatory mechanism of Foxp3 expression is beneficial for the explanation of lung cancer's immunal environment and the establishment of a better immunal therapeutic regimen,so as to provide profound significance for lung cancer's prevention and treatment.
Key words:
Lung neoplasms; Foxp3 ; Regulatory T cells
Cinobufocini injection is a preparation containing water-soluble components of the toad skin. The aim of the present study was to investigate the apoptosis of human lung adenocarcinoma cell line A 549 induced by cinobufocini. A 549 or HLF-1(human lung fibroblast) cells were treated with cinobufocini at different concentrations for 24 and 48 h, respectively. The proliferation of cells was detected with the 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyl tetrazolium bromide (MTT) assay. Morphology of cells was carried out with scanning electronic microscopy (SEM) and Hoechst 33258 staining. The apoptosis rate was examined by flow cytometry. The expression of survivin was examined with RT-PCR and Western blot assay. The caspase-3 and caspase-7 activities were detected with caspase colorimetric protease assay. We found that cinobufocini significantly inhibited tumor growth of A 549 cells in a dose- and time-dependent manner without damaging non-cancerous cells (HLF-1) and induced granular apoptotic bodies of A 549 cells. Next, cinobufocini increased the percentage of cells in G1 phase and decreased the percentage of cells in S phase in A 549 cells. Furthermore, cinobufocini downregulated the expression of survivin mRNA and protein. Finally, cinobufocini upregulated caspase-3 activity. We concluded that cinobufocini induces apoptosis of A 549 cells, which is associated with the decreasing expression of survivin mRNA and protein, increasing caspase-3 activity of A 549 cells.
Selenium polysaccharides have attracted significant interest due to their superior function to that of individual polysaccharides. However, limited research has compared the protective effects of different selenium polysaccharides from different selenization methods on diabetes. This work aims to compare the preventive effects of natural selenium-enriched green tea polysaccharides (NSe-TPS), synthetic selenized green tea polysaccharides (PCSe-TPS), and a mixture of sodium selenite and green tea polysaccharides (ordinary tea polysaccharides (Ord-TPS)+Se) on the development of diabetes. While establishing a diabetes model induced by a high-sugar, high-fat diet combined with streptozotocin, different selenium polysaccharides were administered daily by gavage for nine weeks. Our findings indicate that PCSe-TPS exhibited superior preventive effects on developing type 2 diabetes compared to NSe-TPS and Ord-TPS+Se. PCSe-TPS effectively regulated glucose metabolism and insulin resistance by activating the PI3K/Akt pathway, thereby preventing elevated blood glucose levels. Additionally, PCSe-TPS mitigated oxidative damage and inflammatory responses in liver tissues. Notably, PCSe-TPS intervention reversed the decline in bacterial species richness and the abundance of unclassified_Oscillospiraceae during the development of diabetes in mice. These results provide valuable insights into the protective effects of PCSe-TPS against diabetes development, highlighting its advantages over NSe-TPS and Ord-TPS+Se.
Abstract Background Cancer-associated cachexia is a multifactorial syndrome defined by progressive weight loss with ongoing loss of adipose tissue and skeletal muscle. Adipose loss occurs in the early stage of cachexia and is associated with reduced quality of life and survival time. Although numerous lncRNAs are regarded as novel regulators in adipose metabolism, the role of lncRNAs that selectively modulate the development of adipose loss in cachexia remains limited. Methods In this study, we analyzed microarray data of lncRNAs in adipose loss and further explored the function and mechanism of MALAT1 in adipose loss. First, we explored the expression and function of MALAT1 in adipose cell by quantitative PCR and RNA knockdown. Subsequently, the mechanism of MALAT1 involvement in adipose loss was analyzed via RNA-seq, bioinformatics analysis and reporter gene assay. Finally, we explored the clinical significance of MALAT1 through correlation analysis. Results Cellular experiments revealed that knocking down MALAT1 significantly inhibited the process of adipogenesis. RNA-seq data showed that numerous adipogenic genes were downregulated upon MALAT1 knockdown. A protein–protein interaction network analysis identified PPAR-γ as the central node transcription factor, the inhibition of which explains the downregulation of numerous adipogenic genes. A reporter gene assay suggested that MALAT1 can regulate the gene expression of PPAR-γ at the transcriptional level. Moreover, MALAT1 was weakly expressed in the subcutaneous white adipose tissue of cancer-associated cachexia patients and was related to low fat mass index and poor prognosis in cancer patients. Conclusions This study indicated that MALAT1 is associated with adipose loss in cancer-associated cachexia by regulating adipogenesis through PPAR-γ, which may potentially be a novel target for the diagnosis and treatment of cancer-associated cachexia in the clinic.
Satellite cells are main muscle stem cells that could provide myonuclei for myofiber growth and synaptic-specific gene expression during the early postnatal development. Here, we observed that splicing factor SRSF1 is highly expressed in myoblasts and its expression is closely related with satellite cell activation and proliferation. By genetic deletion of SRSF1 in myogenic progenitors, we found that SRSF1 is critical for satellite cell proliferation in vitro and in vivo. Most notably we also observed that SRSF1 is required for the functional neuromuscular junction (NMJ) formation, as SRSF1-deficient mice fail to form mature pretzel-like NMJs, which leads to muscle weakness and premature death in mice. Finally, we demonstrated that SRSF1 contributes to muscle innervation and muscle development likely by regulating a restricted set of tissue-specific alternative splicing events. Thus, our data define a unique role for SRSF1 in postnatal skeletal muscle growth and function in mice.
Abstract Selenylation modification is an effective way to improve the nutritional and health effects of tea polysaccharide (TPS), but the effects of different selenylation methods on the structure and efficacy of polysaccharides remain unclear. In this study, a series of chemically selenized tea polysaccharides (CSe-TPS, selenium content of 129.98 ~ 1454.99 µg/g) were prepared by Na2SeO3-HNO3 method, which were promoted by heating (HCSe-TPS), ultrasound (UCSe-TPS) and pulse electric field (PCSe-TPS) treatment, respectively. These different CSe-TPSs were systematacially compared with ordinary tea polysaccharides (Ord-TPS) and naturally selenium-enriched tea polysaccharides (NSe-TPS) in aspect of molecular structure and biological functions. The results of molecular structure and apparent morphology showed that the particle size (p < 0.05) and the thermal stability of Ord-TPS were reduced after selenylation modification, while the absolute potential of polysaccharide was increased (p < 0.05), coupled with altered monosaccharide composition and changed apparent morphology. However, the main functional groups and the secondary structure of Ord-TPS did not change. The antioxidant activity of TPS after selenylation were improved as well as their inhibitory effects on carbohydrate digestive enzymes (p < 0.05). The total antioxidant capacity (T-AOC) of PCSe-TPS (selenium content of 240.66 µmol/g) was enhanced by 85.41% compared with Ord-TPS (selenium content of 129.80 µmol/g), while its IC50 values on inhibition of α-amylase and α-glucosidase were significantly lower than other TPS (p < 0.05), which suggested best antioxidant and hypoglycemic activity. Moreover, TPS with higher selenium content and smaller particle size showed better antioxidant and hypoglycemic activities. This research will provide new strategies for application of tea polysaccharides.
Using a large-scale culture technique, the hairy roots of Astragalus membranaceus were produced with a yield reaching 10 g/L. The results from RP-HPLC detection showed that the contents of crude saponin and astragaloside i.v. in the hairy roots were 5.81% and 0.14%, respectively. Six isoflavonoid compounds were also determined. Polysaccharide analysis showed that the total polysaccharide content in the hairy roots was 22.97%; of this content, acidic 8.29% and soluble 14.88%. In comparison with the dry roots, the hairy roots contained higher crude saponin and soluble polysaccharide contents, similar astragaloside i.v. content and lower contents of 6 isoflavonoids, total and acidic polysaccharides, showing that the quality of both types of roots was similar. Regaining the immunity function of rats with low immunity after feeding the aqueous extract of the hairy roots produced by large-scale culture showed that its capacity was similar to the dry roots of A. membranaceus in increasing the immunity function. The results in this paper give evidence that the hairy roots may be a new source of A. membranaceus.
To observe the effect of Feiyanning Granule (FYN) on tumor growth and cell cycle distribution in mice with Lewis lung cancer, as well as its influence on G1/S cell cycle checkpoint dominating signaling RB-E2F1 bio-axis.Modeled C57BL/6 mice were randomly divided into 6 groups: the model group (A), the DDP treated group (B) peritoneally injected with cisplatin 0.1 mg on d1, d3 and d5 after modeling, and the 4 FYN treated groups (C-F), administered via gastrogavage with FYN Decoction, and FYN Granule in small-, median- and high- dose respectively for 14 days. The tumour inhibiting rate, tumour weight, and body weight of mice were observed after treatment; cell cycle distribution was detected by flow cytometry (FCM), RB-E2F1mRNA expressions in tumour tissue were analyzed by RT-PCR, and their protein expressions by Western blot.Tumour weight in the 5 treated groups was lower than that in the model group (P < 0.05, P < 0.01). Body weight in group E was significantly higher than that in group A and B (P < 0.05, P < 0.01). FCM analysis showed the proportion of G0/G1 phase was higher in group E than in group A, B and C (P < 0.01), and cancer cell proliferation index (PI) in group E was lower than in group B (P < 0.05, P < 0.01). RT-PCR showed mRNA level of E2F1 was lower, but that of RB was significantly higher in group E than those in group A, B and C respectively (P < 0.01). Westem blot analysis showed the protein expression of E2F1 was lower in group E and B than that in group A (P < 0.05), while the protein expression of Rb in group E was higher than that in group A, B and C (P < 0.05).The effect of FYN in inhibiting Lewis lung cancer growth was related to its intervention on cancer cell cycle distribution which blocks most tumor cells in G0/G1 phase. Moreover, FYN can reduce MDM2 expression, enhance P53 expression to influence cell cycle G1/S checkpoint dominating signaling, so as to achieve the effect of antagonizing lung cancer cell proliferation.
Dysregulation of calcium homeostasis endoplasmic reticulum protein (CHERP) has been implicated in several cancers, but it remains elusive how CHERP contributes to cancer cell proliferation and cancer development. Here, we observed that CHERP and its binding partner SR140 are significantly upregulated in human clinical colorectal cancer tissues (CRC). CHERP and SR140 could form a protein complex to stabilize each other. Knockdown of CHERP or SR140 triggers double-stranded DNA breaks and cell death. Furthermore, UPF3A, the RNA surveillance factor, was identified as a splicing target of CHERP and SR140, which bind specifically to the regulated exon4 and modulate UPF3A splicing. UPF3A knockdown recapitulates CHERP/SR140 depletion both in vitro and in mice. Importantly, overexpression of UPF3A significantly rescues proliferation defect of CHERP/SR140-depleted cells. These results confirmed that the effect of CHERP/SR140 in promoting tumorigenesis was partially mediated by UPF3A. Extending these results, upregulation of CHERP/SR140 observed in CRC remarkably parallels increased inclusion of UPF3A exon4. Together, our study clarifies how CHERP/SR140 exert an oncogenic role in CRC development partially through regulating expression of UPF3A variants.
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