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"Wu, Qin"
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Protein arginine methylation: from enigmatic functions to therapeutic targeting
Protein arginine methyltransferases (PRMTs) are emerging as attractive therapeutic targets. PRMTs regulate transcription, splicing, RNA biology, the DNA damage response and cell metabolism; these fundamental processes are altered in many diseases. Mechanistically understanding how these enzymes fuel and sustain cancer cells, especially in specific metabolic contexts or in the presence of certain mutations, has provided the rationale for targeting them in oncology. Ongoing inhibitor development, facilitated by structural biology, has generated tool compounds for the majority of PRMTs and enabled clinical programmes for the most advanced oncology targets, PRMT1 and PRMT5. In-depth mechanistic investigations using genetic and chemical tools continue to delineate the roles of PRMTs in regulating immune cells and cancer cells, and cardiovascular and neuronal function, and determine which pathways involving PRMTs could be synergistically targeted in combination therapies for cancer. This research is enhancing our knowledge of the complex functions of arginine methylation, will guide future clinical development and could identify new clinical indications.Protein arginine methyltransferases (PRMTs) regulate numerous biological processes, including transcription, splicing and the DNA damage response. In this article, Barsyte-Lovejoy and colleagues discuss the development of PRMT inhibitors, predominantly for cancer, and describe the challenges and potential new indications in which PRMT inhibition could be therapeutically relevant.
Journal Article
النبات
أصدرت مؤسسة بيت الحكمة للاستثمارات الثقافية، النسخة العربية من السلسلة الموسوعية الأولى من نوعها باللغة العربية \"ثقافة وفنون الخطوط الصينية\" والمترجمة عن اللغة الصينية من إصدار دار نشر هوبي التعليمية بالصين، وتعد سلسلة \"ثقافة وفنون الخطوط الصينية\" المحتوى المعرفي الأكثر شمولا، والأول من نوعه بالعربية عن ثقافة الخط الصيني، الذي هو أحد روافد الثقافة الصينية وأحد فنون الكتابة الممتدة لخمسة آلاف عام، وتشتمل السلسلة الموسوعية على دراسات حول تاريخ الخطوط القديمة وأنواعها وفنون كتابتها، كما تضم المعارف الخاصة بأنواع الخطوط وسماتها وتاريخها، بل وبأدوات الكتابة ومراحل تطورها، وتمثل الخطوط الصينية أحد أبرز عناصر الثقافة الصينية التقليدية، بل وأحد أهم الفنون الصينية التراثية التي كانت ولا تزال سمة أساسية لثقافة الكتابة الصينية على مر العصور، والتي هي جزء لا يتجزأ من تراث البشرية.
BOOK
AMPK agonist alleviate renal tubulointerstitial fibrosis via activating mitophagy in high fat and streptozotocin induced diabetic mice
Renal tubulointerstitial fibrosis was a crucial pathological feature of diabetic nephropathy (DN), and renal tubular injury might associate with abnormal mitophagy. In this study, we investigated the effects and molecular mechanisms of AMPK agonist metformin on mitophagy and cellular injury in renal tubular cell under diabetic condition. The high fat diet (HFD) and streptozotocin (STZ)-induced type 2 diabetic mice model and HK-2 cells were used in this study. Metformin was administered in the drinking water (200 mg/kg/d) for 24 weeks. Renal tubulointerstitial lesions, oxidative stress and some indicators of mitophagy (e.g., LC3II, Pink1, and Parkin) were examined both in renal tissue and HK-2 cells. Additionally, compound C (an AMPK inhibitor) and Pink1 siRNA were applied to explore the molecular regulation mechanism of metformin on mitophagy. We found that the expression of p-AMPK, Pink1, Parkin, LC3II, and Atg5 in renal tissue of diabetic mice was decreased obviously. Metformin reduced the levels of serum creatinine, urine protein, and attenuated renal oxidative injury and fibrosis in HFD/STZ induced diabetic mice. In addition, Metformin reversed mitophagy dysfunction and the over-expression of NLRP3. In vitro pretreatment of HK-2 cells with AMPK inhibitor compound C or Pink1 siRNA negated the beneficial effects of metformin. Furthermore, we noted that metformin activated p-AMPK and promoted the translocation of Pink1 from the cytoplasm to mitochondria, then promoted the occurrence of mitophagy in HK-2 cells under HG/HFA ambience. Our results suggested for the first time that AMPK agonist metformin ameliorated renal oxidative stress and tubulointerstitial fibrosis in HFD/STZ-induced diabetic mice via activating mitophagy through a p-AMPK-Pink1-Parkin pathway.
Journal Article
Exosome-mediated communication in the tumor microenvironment contributes to hepatocellular carcinoma development and progression
The tumor microenvironment (TME) is an essential intrinsic portion of hepatocellular carcinoma (HCC) for the regulation of its origination, development, invasion, and metastasis. As emerging components of the tumor-host interaction, exosomes are increasingly recognized as professional carriers of information in TME and as pivotal molecular entities involved in tumorigenic microenvironment setup. However, much remains unknown about the role of the exosome communication system within TME in the development and progression of HCC. In this review, we focus on the roles and probable mechanisms of TME in HCC and show the exosome-based immune regulation in TME to promote HCC. Multiple processes are involved in HCC, including tumor survival, growth, angiogenesis, invasion, and metastasis. We also discuss the specific roles of exosomes in HCC processes by molding hospitable TME for HCC, such as providing energy, transmitting protumor signals, and evading inhibitory signals. In addition, exosomes induce angiogenesis by changing the biological characteristics of endothelial cells and directly regulating proangiogenic and propermeability factors. Furthermore, exosomes may lead to HCC metastatic invasion by epithelial-mesenchymal transformation, extracellular matrix degradation, and vascular leakage. Finally, we summarize the therapeutic usage of exosomes in the HCC microenvironment and attempt to provide a theoretical reference for modern antitumor agents designed to target these mechanisms.
Journal Article
Mlkl knockout mice demonstrate the indispensable role of Mlkl in necroptosis
Mixed lineage kinase domain-like protein （Mlkl） was recently found to interact with receptor interacting protein 3 （Rip3） and to be essential for tumor necrosis factor （TNF）-induced programmed necrosis （necroptosis） in cultured cell lines. We have generated Mlkl-deficient mice by transcription activator-like effector nucleases （TALENs）-mediated gene disruption and found Mlkl to be dispensable for normal mouse development as well as immune cell develop- ment. Mlkl-deficient mouse embryonic fibroblasts （MEFs） and macrophages both showed resistance to necrotic but not apoptotic stimuli. Mlkl-deficient MEFs and macrophages were indistinguishable from wild-type cells in their abil- ity to activate NF-KB, ERK, JNK, and p38 in response to TNF and lipopolysaccharides （LPS）, respectively. Consis- tently, Mlkl-deficient macrophages and mice exhibited normal interleukin-lp （IL-1β）, IL-6, and TNF production after LPS treatment. Mlkl deficiency protects mice from cerulean-induced acute pancreatitis, a necrosis-related disease, but has no effect on polymicrobial septic shock-induced animal death. Our results provide genetic evidence for the role of Mlkl in necroptosis.
Journal Article
Volatile Organic Compounds of the Plant Growth-Promoting Rhizobacteria JZ-GX1 Enhanced the Tolerance of Robinia pseudoacacia to Salt Stress
Salt stress is one of the major abiotic stresses that affects plant growth and development. The use of plant growth-promoting rhizobacteria to mitigcate salt stress damage in plants is an important way to promote crop growth under salt stress conditions. Rahnella aquatilis JZ-GX1 is a plant growth-promoting rhizobacterial strain, but it is not clear whether it can improve the salt tolerance of plants, and in particular, the role of volatile substances in plant salt tolerance is unknown. We investigated the effects of volatile organic compounds (VOCs) from JZ-GX1 on the growth performance, osmotic substances, ionic balance and antioxidant enzyme activities of acacia seedlings treated with 0 and 100mm NaCl and explored the VOCs associated with the JZ-GX1 strain. The results showed that compared to untreated seedlings, seedlings exposed to plant growth-promoting rhizobacterium JZ-GX1 via direct contact with plant roots under salt stress conditions exhibited increases in fresh weight, lateral root number and primary root length equal to approximately 155.1, 95.4, and 71.3%, respectively. Robinia pseudoacacia seedlings exposed to VOCs of the JZ-GX1 strain showed increases in biomass, soil and plant analyser development values and lateral root numbers equal to 132.1, 101.6, and 166.7%, respectively. Additionally, decreases in malondialdehyde, superoxide anion (O 2 − ) and hydrogen peroxide (H 2 O 2 ) contents and increases in proline contents and superoxide dismutase, peroxidase and glutathione reductase activities were observed in acacia leaves. Importantly, the sodium-potassium ratios in the roots, stems, and leaves of acacia exposed to VOCs of the JZ-GX1 strain were significantly lower than those in the control samples, and this change in ion homeostasis was consistent with the upregulated expression of the (Na + , K + )/H + reverse cotransporter RpNHX1 in plant roots. Through GC-MS and creatine chromatography, we also found that 2,3-butanediol in the volatile gases of the JZ-GX1 strain was one of the important signaling substances for improving the salt tolerance of plants. The results showed that R. aquatilis JZ-GX1 can promote the growth and yield of R. pseudoacacia under normal and salt stress conditions. JZ-GX1 VOCs have good potential as protectants for improving the salt tolerance of plants, opening a window of opportunity for their application in salinized soils.
Journal Article
The Influence of Online Reviews on the Purchasing Decisions of Travel Consumers
In this study, we investigate the impact of online review characteristics on consumers’ purchasing decisions in the context of spatial distance. We consider the product experience of online travel routes, geographical location characteristics, and price adjustment factors, as well as the dynamics between consumers and businesses during the booking of travel routes. Through empirical research and large-scale data simulation experiments, we have found that the variability in attributes of tourist routes significantly influences the user recommendation rate, while the overall rating has a positive moderating effect. Furthermore, the number of reviews negatively moderates the relationship between them. Additionally, the product information and service quality of tourist routes also significantly affect the recommendation rate. Finally, we propose a management strategy for tourism route managers to enhance user recommendation rates and achieve greater benefits.
Journal Article
Isolation and characterization of two phosphate-solubilizing fungi from rhizosphere soil of moso bamboo and their functional capacities when exposed to different phosphorus sources and pH environments
Phosphate-solubilizing fungi (PSF) generally enhance available phosphorus (P) released from soil, which contributes to plants' P requirement, especially in P-limiting regions. In this study, two PSF, TalA-JX04 and AspN-JX16, were isolated from the rhizosphere soil of moso bamboo (Phyllostachys edulis) widely distributed in P-deficient areas in China and identified as Talaromyces aurantiacus and Aspergillus neoniger, respectively. The two PSF were cultured in potato dextrose liquid medium with six types of initial pH values ranging from 6.5 to 1.5 to assess acid resistance. Both PSF were incubated in Pikovskaya's liquid media with different pH values containing five recalcitrant P sources, including Ca3(PO4)2, FePO4, CaHPO4, AlPO4, and C6H6Ca6O24P6, to estimate their P-solubilizing capacity. No significant differences were found in the biomass of both fungi grown in media with different initial pH, indicating that these fungi could grow well under acid stress. The P-solubilizing capacity of TalA-JX04 was highest in medium containing CaHPO4, followed by Ca3(PO4)2, FePO4, C6H6Ca6O24P6, and AlPO4 in six types of initial pH treatments, while the recalcitrant P-solubilizing capacity of AspN-JX16 varied with initial pH. Meanwhile, the P-solubilizing capacity of AspN-JX16 was much higher than TalA-JX04. The pH of fermentation broth was negatively correlated with P-solubilizing capacity (p<0.01), suggesting that the fungi promote the dissolution of P sources by secreting organic acids. Our results showed that TalA-JX04 and AspN-JX16 could survive in acidic environments and both fungi had a considerable ability to release soluble P by decomposing recalcitrant P-bearing compounds. The two fungi had potential for application as environment-friendly biofertilizers in subtropical bamboo ecosystem.
Journal Article