Despite all the new treatments, metastatic breast cancer (Bc) causes many deaths. chlorogenic acid (cGA) is a polyphenol compound with various pharmacological traits, such as anticancer properties. Targeting apoptotic...
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Despite all the new treatments, metastatic breast cancer (Bc) causes many deaths. chlorogenic acid (cGA) is a polyphenol compound with various pharmacological traits, such as anticancer properties. Targeting apoptotic death pathways has been propounded as the most effective therapeutic method in various cancers. In the current study, apoptotic agents such as p53, Bax, Bcl-2, and caspase-3 have been investigated. The experimental groups included saline, Bc, cGA, protective (PR), and treatment (TM) groups. First, 4T1 mouse Bc was established and then the effects of treatment with cGA were investigated through measurement of tumor weight and volume, metastatic nodules, liver biochemical tests, hematoxylin and eosin (H&E), immunohistochemistry (IHc) staining, and real-time reverse transcription-polymerase chain reaction (RT-PcR) in experimental groups. The findings showed that cGA reduced tumor weight and volume in the PR group (P < .05) and in the TM group (P < .001). Surprisingly, it eliminated the tumors in the TM group. Metastatic nodules in the PR and TM groups were significantly reduced as compared with the Bc group (P < .001). The evaluation by H&E staining showed cell apoptosis in both the PR and TM groups. The results of real-time RT-PcR showed that cGA therapy increased the expression ratio of Bax/Bcl-2 (P < .001 andP < .05, respectively) and the expression of p53 (P < .001 andP < .05, respectively) and caspase-3 genes (P < .01) in the PR and TM groups. The IHc data regarding the Bax/Bcl-2 ratio confirmed the other results (P < .001). The findings demonstrate that cGA plays a significant role in the induction of apoptosis and the treatment of 4T1 Bc tumors in BALB/c mice.
The ccAAT/enhancer binding protein (c/EBP) transcription factors (TFs) regulate many important biological processes, such as energy metabolism, inflammation, cell proliferation etc. A genome-wide gene identification r...
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The ccAAT/enhancer binding protein (c/EBP) transcription factors (TFs) regulate many important biological processes, such as energy metabolism, inflammation, cell proliferation etc. A genome-wide gene identification revealed the presence of a total of 99 c/EBP genes in pig and 19 eukaryote genomes. Phylogenetic analysis showed that all c/EBP TFs were classified into 6 subgroups named c/EBP alpha, c/EBP beta, c/EBP delta, c/EBP epsilon, c/EBP gamma, and c/EBP zeta. Gene expression analysis showed that the c/EBP alpha, c/EBP beta, c/EBP delta, c/EBP gamma, and c/EBP zeta genes were expressed ubiquitously with inconsistent expression patterns in various pig tissues. Moreover, a pig c/EBP regulatory network was constructed, including c/EBP genes, TFs and miRNAs. A total of 27 feed-forward loop (FFL) motifs were detected in the pig c/EBP regulatory network. Based on the RNA-seq data, gene expression patterns related to FFL sub-network were analyzed in 27 adult pig tissues. certain FFL motifs may be tissue specific. Functional enrichment analysis indicated that c/EBP and its target genes are involved in many important biological pathways. These results provide valuable information that clarifies the evolutionary relationships of the c/EBP family and contributes to the understanding of the biological function of c/EBP genes.
In-depth characterization of specialized metabolites in the endemic Gypsophila perfoliata L. "tekirae" (G. tekirae Stef.) by liquid chromatography - quadrupol-Orbitrap mass spectrometry allowed dereplication...
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In-depth characterization of specialized metabolites in the endemic Gypsophila perfoliata L. "tekirae" (G. tekirae Stef.) by liquid chromatography - quadrupol-Orbitrap mass spectrometry allowed dereplication/annotation of 22 flavonoids including 11 2 ''-O-pentosyl/deoxyhexosyl/hexosyl-c-hexosyl-flavones in the aerial parts and 23 gypsogenin- and quillaic acid-bidesmosides in the roots. Saponins were mainly mono-and diacetyl, and methoxycinnamoyl derivatives of 16 core structures forming isobaric isomers. Three acetylated derivatives of 2 '' O-deoxyhexosyl-6-c-hexosyl-flavones are annotated for the first time in the genus Gypsophila together with five quillaic acid-based saponins. Aerial parts extract revealed prominent antioxidant and tyrosinase inhibitory activity, while roots demonstrated higher capacity against acetylcholinesterase, butyrylcholinesterase and alpha-glucosidase. The chemophenetic significance of acetylated 2 ''-O-glycosyl-6-c-hexosyl-flavones and GOTcAB saponins with methoxycinnamoyl-substituted alpha-chains was discussed.
The present work focuses on investigation of tensile and compressive strengths of AA7050-B 4 ccomposites before heat treatment (as-cast) and post heat treatment. composites with 2, 4, 6 and 8 wt% of B 4 c were prepar...
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The present work focuses on investigation of tensile and compressive strengths of AA7050-B 4 ccomposites before heat treatment (as-cast) and post heat treatment. composites with 2, 4, 6 and 8 wt% of B 4 c were prepared using bottom pouring stir-casting furnace. Microstructural analysis done using EDS and SEM results affirmed that the B 4 c particulates were homogeneously scattered in the alloy matrix. Solution heat treatment was carried out on cast samples at 530 °c for a period of 2 h. After solution, T6 heat treatment (Artificial Ageing) was performed on the samples at 180 °c for a period of 8 h. Mechanical strength properties- yield strength, ultimate tensile strength and compression strength, were determined according to ASTM standards.
Hematopoietic stem cells (HScs) reside in a quiescent niche to reserve their capacity of self-renewal. Upon hematopoietic injuries, HScs enter the cell cycle and encounter protein homeostasis problems caused by accumu...
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Hematopoietic stem cells (HScs) reside in a quiescent niche to reserve their capacity of self-renewal. Upon hematopoietic injuries, HScs enter the cell cycle and encounter protein homeostasis problems caused by accumulation of misfolded proteins. However, the mechanism by which protein homeostasis influences HSc function and maintenance remains poorly understood. Here, we show that c/EBP homologous protein (cHOP), demonstrated previously to induces cell death upon unfolded protein response (UPR), plays an important role in HScs regeneration. cHOP-/- mice showed normal hematopoietic stem and progenitor cell frequencies in steady state. However, when treated with 5-FU, cHOP deficiency resulted in higher survival rates, associated with an increased number of HScs and reduced level of apoptosis. In serial competitive transplantation experiments, cHOP-/- HScs showed a dramatic enhancement of repopulation ability and a reduction of protein aggresomes. Mechanistically, cHOP deletion causes reduced ATF3 expression and further leads to decreased protein aggregation and ROS. In addition, cHOP-/- HScs exhibited an increased resistance to IR-induced DNA damage and improved HScs homeostasis and function in telomere dysfunctional (G3Terc(-/-)) mice. In summary, these findings disclose a new role of cHOP in the regulation of the HScs function and homeostasis through reducing ATF3 and ROS signaling.
Neutron irradiation which could trigger severe biological effects, is being applied in nuclear plants, radiotherapy, and aerospace gradually. Low dose hyper-radiosensitivity response of low Linear Energy Transfer (LET...
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Neutron irradiation which could trigger severe biological effects, is being applied in nuclear plants, radiotherapy, and aerospace gradually. Low dose hyper-radiosensitivity response of low Linear Energy Transfer (LET) irradiation on the cell survival has become a matter of great interest since its discovery, but a few research have been done on this response induced by neutron irradiation. To investigate this response induced by neutron irradiation, caenorhabditis elegans (c. elegans) was irradiated by neutron irradiation. The surviving fraction of c. elegans on the 12th day after irradiation was analyzed, which showed a hyper-radiosensitive response at low doses and followed by an increase in survival fraction at slightly higher doses. The finding of this work that neutron irradiation decreased the surviving fraction in a non-dose-dependent manner was different from previous low-LET irradiation studies. To understand the experimental results, a DNA damage-repair model was introduced. By comparing experimental results with theoretical analyses, we suggest that the low dose hyper-radiosensitivity response of neutron irradiation may possible related to different radiation types and DNA damage recognition proteins and immune system of c. elegans.
BackgroundAs an H3K27me3 demethylase and counteracts polycomb-mediated transcription repression, KDM6B has been implicated in the development and malignant progression in various types of cancers. However, its potenti...
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BackgroundAs an H3K27me3 demethylase and counteracts polycomb-mediated transcription repression, KDM6B has been implicated in the development and malignant progression in various types of cancers. However, its potential roles in esophageal squamous cell carcinoma (EScc) have not been *** expression of KDM6B in human EScc tissues and cell lines was examined using RT-qPcR, immunohistochemical staining and immunoblotting. The effects of KDM6B on the proliferation and metastasis of EScc were examined using in vitro and in vivo functional tests. RNA-seq and chIP-seq assay were used to demonstrate the molecular biological mechanism of KDM6B in *** show that the expression level of KDM6B increased significantly in patients with lymph node metastasis. Furthermore, we confirmed that KDM6B knockdown reduces proliferation and metastasis of EScccells, while KDM6B overexpression has the opposite effects. Mechanistically, KDM6B regulates TNFA_SIGNALING_VIA_NF kappa B signalling pathways, and H3K27me3 binds to the promoter region of c/EBP beta, leading to the promotion of c/EBP beta transcription. Besides, we show that GSK-J4, a chemical inhibitor of KDM6B, markedly inhibits proliferation and metastasis of EScc *** present study demonstrated that KDM6B promotes EScc progression by increasing the transcriptional activity of c/EBP beta depending on its H3K27 demethylase activity.
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