Background: The pseudokinase Tribbles 3 (TRIB3) is involved in many cellular processes and various cancers. In recent years, the importance of metabolic transformation in the maintenance of malignant tumors has become increasingly prominent. Abnormal metabolism of cancer cells is considered a hallmark of cancer. However, the exact role and molecular mechanism of TRIB3 in lung adenocarcinoma (LUAD) cell reprogramming is largely unknown. Methods: The oxygen consumption rate (OCR) and extracellular acidification rate (ECAR) of cells were examined with a Seahorse XF Extracellular Flux Analyzer. In vitro and in vivo RT-qPCR, Western blotting, and functional assays were performed to explore the functional roles of TRIB3 in LUAD. Results: In the present study, we demonstrated that TRIB3 is remarkably upregulated in LUAD cell lines as well as tissues. TRIB3 knockdown significantly inhibited LUAD cell growth and suppressed LUAD cell invasion, while TRIB3 overexpression conferred the opposite effects. Moreover, silencing TRIB3 suppressed the tumorigenesis and metastatic ability of LUAD cells. Mechanistically, we demonstrated that silencing TRIB3 significantly impaired aerobic glycolysis ability in LUAD cells. Furthermore, our data indicated that TRIB3 knockdown decreased hypoxia-inducible factor (HIF)1α levels and targeted the glycolytic genes regulated by HIF1α. Conclusion: Together, our findings revealed a previously unappreciated function of TRIB3 in cancer cell metabolism and tumor progression, illustrating that TRIB3 could be considered a valuable therapeutic target for LUAD patients. Keywords: TRIB3, LUAD, aerobic glycolysis, HIF1α
Abstract Flavihumibacter solisilvae 3-3 T (= KACC 17917 T = JCM 19891 T ) represents a type strain of the genus Flavihumibacter within the family Chitinophagaceae . This strain can use various sole carbon sources, making it applicable in industry and bioremediation. In this study, the draft genomic information of F. solisilvae 3-3 T is described. F. solisilvae 3-3 T owns a genome size of 5.41 Mbp, 47 % GC content and a total of 4,698 genes, including 4,215 protein coding genes, 439 pseudo genes and 44 RNA encoding genes. Analysis of its genome reveals high correlation between the genotypes and the phenotypes.
Broccoli is a nutritious vegetable. It is high in protein, minerals, and vitamins. Also, it possesses antioxidant activities and is beneficial to the human body. Due to its active effect, broccoli is widely accepted by people in daily life. However, in terms of current utilization, only its florets are consumed as vegetables, while more than half of its stalks and leaves are not utilized. The stalks and leaves contain not only nutrients but also bioactive substances with physiologically regulating properties. Therefore research into the action and mechanism of its bioactive substances as well as its development and utilization technology will make contributions to the further promotion of its resource development and utilization. As a theoretical foundation for the resource utilization of broccoli stalks and leaves, this report will review the distribution and consumption of broccoli germplasm resources, the mechanism of action of bioactive substances, and innovative methods for their exploitation.
Additional file 12: Table S12. Comparation of starch content between accessions carrying heterozygous blocks with high frequency and accessions carrying homozygous blocks in cultivars.
Additional file 17: Table S17. Genomic regions and genes that exhibit a decrease in both heterozygosity and nucleotide diversity during domestication from wild progenitors to cultivars (Top 0.99).
Heat-shock transcription factors (HSFs) with a HSF domain are regulators of fungal heat-shock protein (HSP) genes and many others vectoring heat-shock elements, to which the domain binds in response to heat shock and other stress cues. The fungal insect pathogen Beauveria bassiana harbors three HSF domain-containing orthologous to Hsf1, Sfl1, and Skn7 in many fungi. Here, we show that the three proteins are interrelated at transcription level, play overlapping or opposite roles in activating different families of 28 HSP genes and mediate differential expression of some genes required for asexual developmental and intracellular Na+ homeostasis. Expression levels of skn7 and sfl1 largely increased in Δhsf1, which is evidently lethal in some other fungi. Hsf1 was distinct from Sfl1 and Skn7 in activating most HSP genes under normal and heat-shocked conditions. Sfl1 and Skn7 played overlapping roles in activating more than half of the HSP genes under heat shock. Each protein also activated a few HSP genes not targeted by two others under certain conditions. Deletion of sfl1 resulted in most severe growth defects on rich medium and several minimal media at optimal 25°C while such growth defects were less severe in Δhsf1 and minor in Δskn7. Conidiation level was lowered by 76% in Δskn7, 62% in Δsfl1, and 39% in Δhsf1. These deletion mutants also showed differential changes in cell wall integrity, antioxidant activity, virulence and cellular tolerance to osmotic salt, heat shock, and UV-B irradiation. These results provide a global insight into vital roles of Hsf1, Sfl1, and Skn7 in B. bassiana adaptation to environment and host.
Since telomeres and telomerase play crucial roles in maintaining cell immortalization and cancer progression, they may be targets for anticancer treatment. PinX1 is a potent telomerase inhibitor, and a putative tumor suppressor. The use of PinX1 to treat cancers has not been reported yet.In order to use PinX1 in gene therapy for gastric carcinoma, we transfected PinX1 gene into the gastric carcinoma line MKN28 using the eukaryotic expression vector pIRES2-EGFP. PinX1-expressing, drug-resistant clones were screened with G418 and used in the study.MKN28 cells transfected with PinX1 gene grew more slowly than the cells not transfected or transfected with void vectors (p<0.05). The IC50 value decreased markedly in cells transfected with PinX1 gene. PinX1 gene transfection enhanced the sensitivity of MKN28 cells to 5-fluorouracil (p<0.05).PinX1 may be used in gene therapy for gastric carcinoma.
This study investigated the effects and mechanisms of total saponins of Panax japonicus(TSPJ) against liver injury induced by acetaminophen(APAP). Male Kunming mice were randomly divided into a blank control group, TSPJ group(200 mg·kg~(-1), ig), model group, APAP+ TSPJ low-dose group(50 mg·kg~(-1), ig), APAP+ TSPJ medium-dose group(100 mg·kg~(-1), ig), APAP+ TSPJ high-dose group(200 mg·kg~(-1), ig), and APAP+ N-acetyl-L-cysteine group(200 mg·kg~(-1), ip). The administration group received the corresponding medications via ig or ip once a day for 14 consecutive days. After the last administration for one hour, except for the blank control group and TSPJ group, all groups of mice were given 500 mg·kg~(-1) APAP by gavage. After 24 hours, mouse serum and liver tissue were collected for serum alanine aminotransferase(ALT), aspartate aminotransferase(AST), reactive oxygen species(ROS), tumor necrosis factor alpha(TNF-α), interleukin-1 beta(IL-1β), cyclooxygenase-2(COX-2), IL-6, IL-4, IL-10, as well as lactate dehydrogenase(LDH), glutathione(GSH), superoxide dismutase(SOD), catalase(CAT), total antioxidant capacity(T-AOC), malondialdehyde(MDA), and myeloperoxidase(MPO) liver tissue. Hematoxylin-eosin staining was used to observe the morphological changes of liver tissue. The mRNA expression levels of lymphocyte antigen 6G(Ly6G), galectin 3(Mac-2), TNF-α, IL-1β, COX-2, IL-6, IL-4, and IL-10 in liver tissue were determined by quantitative real-time polymerase chain reaction(PCR). Western blot was utilized to detect the protein expression levels of Ly6G, Mac-2, extracellular regulated protein kinases(ERK), phosphorylated extracellular regulated protein kinases(p-ERK), COX-2, inhibitor of nuclear factor κB protein α(IκBα), phosphorylated inhibitor of nuclear factor κB protein α(p-IκBα), and nuclear factor-κB subunit p65(NF-κB p65) in cytosol and nucleus in liver tissue. The results manifested that TSPJ dramatically reduced liver coefficient, serum ALT, AST, ROS, TNF-α, IL-1β, IL-6, and COX-2 levels, LDH, MPO, and MDA contents in liver tissue, and mRNA expressions of TNF-α, IL-1β, and IL-6 in APAP-induced liver injury mice. It prominently elevated serum IL-4 and IL-10 levels, GSH, CAT, SOD, and T-AOC contents, and mRNA expressions of IL-4 and IL-10 in liver tissue, improved the degree of liver pathological damage, and suppressed neutrophil infiltration and macrophage recruitment in liver tissue. In addition, TSPJ lessened the mRNA and protein expressions of neutrophil marker Ly6G, macrophage marker Mac-2, and COX-2 in liver tissue, protein expressions of p-ERK, p-IκBα, and NF-κB p65 in nuclear, and p-ERK/ERK and p-IκBα/p-IκBα ratios and hoisted protein expression of NF-κB p65 in cytosol. These results suggest that TSPJ has a significant protective effect on APAP-induced liver injury in mice, and it can alleviate APAP-induced oxidative damage and inflammatory response. Its mechanism may be related to suppressing ERK/NF-κB/COX-2 signaling pathway activation, thus inhibiting inflammatory cell infiltration, cytokine production, and liver cell damage.
Abstract Background Heterozygous genomes are widespread in outcrossing and clonally propagated crops. However, the variation in heterozygosity underlying key agronomic traits and crop domestication remains largely unknown. Cassava is a staple crop in Africa and other tropical regions and has a highly heterozygous genome. Results We describe a genomic variation map from 388 resequenced genomes of cassava cultivars and wild accessions. We identify 52 loci for 23 agronomic traits through a genome-wide association study. Eighteen allelic variations in heterozygosity for nine candidate genes are significantly associated with seven key agronomic traits. We detect 81 selective sweeps with decreasing heterozygosity and nucleotide diversity, harboring 548 genes, which are enriched in multiple biological processes including growth, development, hormone metabolisms and responses, and immune-related processes. Artificial selection for decreased heterozygosity has contributed to the domestication of the large starchy storage root of cassava. Selection for homozygous GG allele in MeTIR1 during domestication contributes to increased starch content. Selection of homozygous AA allele in MeAHL17 is associated with increased storage root weight and cassava bacterial blight (CBB) susceptibility. We have verified the positive roles of MeTIR1 in increasing starch content and MeAHL17 in resistance to CBB by transient overexpression and silencing analysis. The allelic combinations in MeTIR1 and MeAHL17 may result in high starch content and resistance to CBB. Conclusions This study provides insights into allelic variation in heterozygosity associated with key agronomic traits and cassava domestication. It also offers valuable resources for the improvement of cassava and other highly heterozygous crops.
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