Search

Rapid and uniform seed germination improves mechanized oilseed rape production in modern agricultural cultivation practices. However, the molecular basis of seed germination is still unclear in Brassica napus. A population of recombined inbred lines of B. napus from a cross between the lower germination rate variety 'APL01' and the higher germination rate variety 'Holly' was used to study the genetics of seed germination using quantitative trait locus (QTL) mapping. A total of five QTLs for germination energy (GE) and six QTLs for germination percentage (GP) were detected across three seed lots, respectively. In addition, six epistatic interactions between the QTLs for GE and nine epistatic interactions between the QTLs for GP were detected. qGE.C3 for GE and qGP.C3 for GP were co-mapped to the 28.5–30.5 cM interval on C3, which was considered to be a novel major QTL regulating seed germination. Transcriptome analysis revealed that the differences in sugar, protein, lipid, amino acid, and DNA metabolism and the TCA cycle, electron transfer, and signal transduction potentially determined the higher germination rate of 'Holly' seeds. These results contribute to our knowledge about the molecular basis of seed germination in rapeseed. [ABSTRACT FROM AUTHOR]

The retinoic acid-inducible gene I (RIG-I)-like receptors (RLRs) play a crucial role as pattern-recognition receptors within the innate immune system. These receptors, present in various cell and tissue types, serve as essential sensors for viral infections, enhancing the immune system's capacity to combat infections through the induction of type I interferons (IFN-I) and inflammatory cytokines. RLRs are involved in a variety of physiological and pathological processes, including viral infections, autoimmune disorders, and cancer. An increasing body of research has examined the possibility of RLRs or microRNAs as therapeutic targets for antiviral infections and malignancies, despite the fact that few studies have focused on the regulatory function of microRNAs on RLR signaling. Consequently, our main emphasis in this review is on elucidating the role of microRNAs in modulating the signaling pathways of RLRs in the context of cancer and viral infections. The aim is to establish a robust knowledge base that can serve as a basis for future comprehensive investigations into the interplay between microRNAs and RIG-I, while also facilitating the advancement of therapeutic drug development. [ABSTRACT FROM AUTHOR]

The sperm-associated antigen 5 (SPAG5) is an important protein in mitosis and cell cycle checkpoint regulation, with more attention as a novel oncogene in various cancers. High level of SPAG5 expression has been detected in our clinical gastric cancer (GC) samples and The Cancer Genome Atlas GC data. However, the bio-function and potential mechanism of SPAG5 in GC remain unclear. In this study, we investigated the role of SPAG5 in GC development and the correlation between SPAG5 and 5-fluorouracil (5-FU) treatment. SPAG5 expression was increased in GC samples compared with that in normal tissues (80.8% vs. 22.0%), which was apparently associated with a worse outcome. Biological experiments showed that knockdown of SPAG5 induced apoptosis and suppressed proliferation in cells and animal models. Downregulation of SPAG5 enhanced the sensitivity of 5-FU in GC cells. Gene microarray chip identified 856 upregulated and 787 downregulated genes in SPAG5 silencing cells. Furthermore, 12 significant genes, including CDKN1A, CDKN1B, EIF4E, MAPK1, and HSP90B1, belonged to the PI3K/AKT signaling pathway using ingenuity pathway analysis. Meanwhile, real-time PCR and Western blotting results showed that knockdown of SPAG5 inhibited PI3K/AKT signaling pathway. Collectively, SPAG5 promotes the growth of GC cells by regulating PI3K/AKT signaling pathway, which could be the promising target gene in GC therapy. [ABSTRACT FROM AUTHOR]

Dendrobium nobile Lindl. (DNL) is a traditional Chinese ethnobotanical herb. Dendrobine (DNE) has been designated as a quality indicator for DNL in the Chinese Pharmacopoeia. DNE exhibits various pharmacological activities, including the reduction of blood lipids, regulation of blood sugar levels, as well as anti-inflammatory and antioxidant properties. The objective of this study is to explore the impact of DNE on lipid degeneration in nonalcoholic fatty liver disease (NAFLD) liver cells and elucidate its specific mechanism. The findings aim to offer theoretical support for the development of drugs related to DNL. We utilized male C57BL/6J mice, aged 6 weeks old, to establish a NAFLD model. This model allowed us to assess the impact of DNE on liver pathology and lipid levels in NAFLD mice. We investigated the mechanism of DNE's regulation of lipid metabolism through RNA-seq analysis. Furthermore, a NAFLD model was established using HepG2 cells to further evaluate the impact of DNE on the pathological changes of NAFLD liver cells. The potential mechanism of DNE's improvement was rapidly elucidated using HT-qPCR technology. These results were subsequently validated using mouse liver samples. Following the in vitro activation or inhibition of PPARα function, we observed changes in DNE's ability to ameliorate pathological changes in NAFLD hepatocytes. This mechanism was further verified through RT-qPCR and Western blot analysis. DNE demonstrated a capacity to enhance serum TC, TG, and liver TG levels in mice, concurrently mitigating liver lipid degeneration. RNA-seq analysis unveiled that DNE primarily modulates the expression of genes related to metabolic pathways in mouse liver. Utilizing HT-qPCR technology, it was observed that DNE markedly regulates the expression of genes associated with the PPAR signaling pathway in liver cells. Consistency was observed in the in vivo data, where DNE significantly up-regulated the expression of PPARα mRNA and its protein level in mouse liver. Additionally, the expression of fatty acid metabolism-related genes (ACOX1, CPT2, HMGCS2, LPL), regulated by PPARα, was significantly elevated following DNE treatment. In vitro experiments further demonstrated that DNE notably ameliorated lipid deposition, peroxidation, and inflammation levels in NAFLD hepatocytes, particularly when administered in conjunction with fenofibrate. Notably, the PPARα inhibitor GW6471 attenuated these effects of DNE. In summary, DNE exerts its influence on the expression of genes associated with downstream fat metabolism by regulating PPARα. This regulatory mechanism enhances liver lipid metabolism, mitigates lipid degeneration in hepatocytes, and ultimately ameliorates the pathological changes in NAFLD hepatocytes. [Display omitted] • Dendrobine has capable of improving hepatic pathological changes in mice with NAFLD. • Dendrobine ameliorates hepatocellular steatosis, lipid peroxidation and inflammation in NAFLD. • Dendrobine ameliorates hepatic steatosis by modulating PPARα-related signaling in NAFLD. [ABSTRACT FROM AUTHOR]

The Chinese medicine Daji (the aerial part of Cirsium japonicum DC.) and its charred product (Cirsii Japonici Herba Carbonisata) have been widely used as hemostatic agents or diuretic agents to prepare a variety of Chinese herbal formula. Pectolinarigenin (PEC), one of the most abundant constituents in both Daji and its charred product, has been considered as the key effective substance responsible for the major pharmacological activities of Daji, including hemostasis, hepatoprotective, anti-tumor and anti-osteoporosis effects. However, the major metabolic pathways of PEC in humans and the influence of PEC metabolism on its biological activities are poorly understood. To characterize the main metabolic pathway(s) and key enzymes of PEC in human biological systems, as well as to reveal the influence of PEC metabolism on its biological activities. The metabolic stability assays of PEC were investigated in human liver microsomes (HLM). The O -glucuronide of PEC was biosynthesized and characterized by nuclear magnetic resonance (NMR) spectroscopy. The key enzymes responsible for O- glucuronidation of PEC in humans were assigned by performing UGT reaction phenotyping, chemical inhibition and enzymatic kinetic assays. The agonist effects of PEC and its O -glucuronide on nuclear factor erythroid2-related factor 2 (Nrf2), Peroxisome proliferator activated receptors (PPARα and PPARβ) were tested at the cellular level. PEC could be readily metabolized to form a mono- O -glucuronide in both human liver microsome (HLM) and human intestinal microsome (HIM). The mono- O -glucuronide was bio-synthesized by mouse liver S9 and its structure was fully characterized as PEC-7- O -β-D-glucuronide (PEC- O -7-G). UGT1A1, UGT1A3 and UGT1A9 are key enzymes responsible for PEC-7- O -glucuronidation in HLM, while UGT1A1, UGT1A9 and 1A10 may play key roles in this reaction in HIM. Biological tests revealed that PEC displayed strong agonist effects on Nrf2, PPARα and PPARβ, whereas PEC-7- O -glucuronide showed relatively weak Nrf2 agonist effect and very weak PPAR agonist effects, indicating that PEC-7- O -glucuronidation strongly weaken its agonist effects on Nrf2 and PPAR. Our results demonstrate that 7- O -glucuronidation is the major metabolic pathway of PEC in human tissues, while UGT1A1, 1A3 and 1A9 are key contributing enzymes responsible for PEC-7- O -glucuronidation in human liver. It is also found that PEC 7- O -glucuronidation significantly weakens the Nrf2 and PPAR agonist effects. All these findings are very helpful for the pharmacologists to deep understand the metabolic rates of PEC in humans. [Display omitted] • PEC- O -glucuronidation is a major metabolic pathway of PEC in humans. • The glucuronide was biosynthesized and fully characterized as PEC-7- O -β-D-glucuronide. • UGT1A1, UGT1A3 and UGT1A7-10 catalyzed PEC-7- O -glucuronidation. • PEC-7- O -glucuronidation strongly reduced the Nrf2 and PPAR agonist effects of PEC. [ABSTRACT FROM AUTHOR]