keyword
https://read.qxmd.com/read/38537596/regulation-of-inflammatory-response-by-linc00346-via-mir-25-3p-mediated-modulation-of-the-pten-pi3k-akt-nf-%C3%AE%C2%BAb-pathway
#1
JOURNAL ARTICLE
Min-Ji Kim, Su-Geun Lim, Dong-Hyung Cho, Jun-Yeong Lee, Kyoungho Suk, Won-Ha Lee
Long intergenic non-coding RNA 346 (LINC00346) has been reported to be involved in the development of atherosclerosis and specific cancers by affecting signaling pathways. However, its function in inflammation has not been thoroughly studied. Therefore, its expression pattern and function were determined in the human macrophage-like cell line THP-1. Lipopolysaccharide (LPS) treatment induced the expression of LINC00346. LPS-induced NF-κB activation and proinflammatory cytokine expression were suppressed or enhanced by the overexpression or knockdown of LINC00346, respectively...
March 25, 2024: Biochemical and Biophysical Research Communications
https://read.qxmd.com/read/38515298/self-organization-of-pip3-waves-is-controlled-by-the-topology-and-curvature-of-cell-membranes
#2
JOURNAL ARTICLE
Sema Erisis, Marcel Hörning
PIP3 is a signaling lipid on the plasma membrane that plays a fundamental role in cell signaling with a strong impact on cell physiology and diseases. It is responsible for the protruding edge formation, cell polarization, macropinocytosis and other membrane remodeling dynamics in cells. It has been shown that the membrane confinement and curvature affects the wave formation of PIP3 and F-actin. But even in the absence of F-actin, a complex self-organization of the spatiotemporal PIP3 waves is observed. In recent findings, we have shown that these waves can be guided and pinned on strongly bended Dictyostelium membranes caused by molecular crowding and curvature limited diffusion...
March 21, 2024: Biophysical Journal
https://read.qxmd.com/read/38404940/evidence-that-inositol-1-4-5-trisphosphate-3-kinase-and-inositol-1-3-4-5-tetrakisphosphate-are-negative-regulators-of-platelet-function
#3
JOURNAL ARTICLE
Kalwant S Authi, Sabeeya Khan, Jonathan M Gibbins, Susan D Brain
BACKGROUND: Inositol 1,3,4,5-tetrakisphosphate (IP4 ) is formed from inositol 1,4,5-trisphosphate (IP3 ) by IP3 3-kinase (ITPK) in most cells. Its function is unknown but has been suggested to be involved in Ca2+ entry, IP3 regulation, and phosphoinositide 3-kinase antagonism. OBJECTIVES: To better elucidate a function for IP4 , we tested a specific inhibitor of ITPK (GNF362) on platelets, the effects of IP4 directly in permeabilized platelets and its effect on phosphatidylinositol 3,4,5-trisphosphate (PIP3 ) binding to pleckstrin-homology (PH) domain-containing proteins in platelets...
January 2024: Research and Practice in Thrombosis and Haemostasis
https://read.qxmd.com/read/38339058/the-potential-of-pip3-in-enhancing-wound-healing
#4
JOURNAL ARTICLE
Yossi Blitsman, Etili Hollander, Chen Benafsha, Ksenia M Yegodayev, Uzi Hadad, Riki Goldbart, Tamar Traitel, Assaf Rudich, Moshe Elkabets, Joseph Kost
Given the role of phosphatidylinositol 3,4,5-trisphosphate (PIP3) in modulating cellular processes such as proliferation, survival, and migration, we hypothesized its potential as a novel therapeutic agent for wound closure enhancement. In this study, PIP3 was examined in its free form or as a complex with cationic starch (Q-starch) as a carrier. The intracellular bioactivity and localization of free PIP3 and the Q-starch/PIP3 complexes were examined. Our results present the capability of Q-starch to form complexes with PIP3, facilitate its cellular membrane internalization, and activate intracellular paths leading to enhanced wound healing...
February 1, 2024: International Journal of Molecular Sciences
https://read.qxmd.com/read/38191266/high-fat-diet-promotes-liver-tumorigenesis-via-palmitoylation-and-activation-of-akt
#5
JOURNAL ARTICLE
Lang Bu, Zhengkun Zhang, Jianwen Chen, Yizeng Fan, Jinhe Guo, Yaqing Su, Huan Wang, Xiaomei Zhang, Xueji Wu, Qiwei Jiang, Bing Gao, Lei Wang, Kunpeng Hu, Xiang Zhang, Wei Xie, Wenyi Wei, Ming Kuang, Jianping Guo
OBJECTIVE: Whether and how the PI3K-AKT pathway, a central node of metabolic homeostasis, is responsible for high-fat-induced non-alcoholic steatohepatitis (NASH) and hepatocellular carcinoma (HCC) remain a mystery. Characterisation of AKT regulation in this setting will provide new strategies to combat HCC. DESIGN: Metabolite library screening disclosed that palmitic acid (PA) could activate AKT. In vivo and in vitro palmitoylation assay were employed to detect AKT palmitoylation...
January 18, 2024: Gut
https://read.qxmd.com/read/38159819/a-study-on-molecular-mechanism-of-xihuang-pill-in-the-treatment-of-glioblastoma-based-on-network-pharmacology-and-validation-in-vitro-and-in-vivo
#6
JOURNAL ARTICLE
Hong-Bin Xu, Xian-Zhen Chen, Su-Yan Zhu, Fei Xue, Yuan-Bin Zhang
ETHNOPHARMACOLOGICAL RELEVANCE: Xihuang pill has been utilized to treat cancer for more than three hundred years in China. The molecular mechanisms of Xihuang pill in treating glioblastoma remains unclear. AIM OF THE STUDY: This study aimed to explore the core molecular mechanisms of Xihuang pill in treating glioblastoma by an integrative pharmacology-based investigation. MATERIALS AND METHODS: The main active compounds of Xihuang pill were identified from TCMSP, BATMAN-TCM, TCMID and CNKI...
December 28, 2023: Journal of Ethnopharmacology
https://read.qxmd.com/read/38141758/the-p2y2-receptor-mediates-terminal-adipocyte-differentiation-and-insulin-resistance-evidence-for-a-dual-g-protein-coupling-mode
#7
JOURNAL ARTICLE
Shenqi Qian, Yi Shi, Jared Senfeld, Qianman Peng, Jianzhong Shen
Several P2Y nucleotide receptors have been shown to be involved in the early stage of adipocyte differentiation in vitro and insulin resistance in obese mice; however, the exact receptor subtype(s) and its underlying molecular mechanism in relevant human cells are unclear. Here, using human primary visceral preadipocytes as a model, we found that during preadipocyte-to-mature adipocyte differentiation, the P2Y2 nucleotide receptor (P2Y2R) was the most upregulated subtype among the eight known P2Y receptors and the only one further dramatically upregulated after inflammatory TNFα treatment...
December 21, 2023: Journal of Biological Chemistry
https://read.qxmd.com/read/38118073/a-rapid-and-simplified-method-to-isolate-specific-regulators-based-on-biotin-avidin-binding-affinities-in-crops
#8
JOURNAL ARTICLE
Xiaojian Qin, Yuntong Li, Cuiping Li, Xiaowei Li, Yuanyuan Wu, Qian Wu, Huan Wen, Dan Jiang, Shifeng Liu, Wenbin Nan, Yongshu Liang, Hanma Zhang
Transcription factors (TFs) are indispensable components of transcriptional regulatory pathways involved in crop growth and development. Herein, we developed a new method for the identification of upstream TFs specific to genes in crops based on the binding affinities of biotin and avidin. First, we constructed and verified the new biotin and avidin system (BAS) by a coprecipitation assay. Subsequently, the feasibility of DNA-based BAS (DBAS) was further proved by in vivo and in vitro assays. Furthermore, we cloned the promoter of rice OsNRT1...
December 20, 2023: Journal of Agricultural and Food Chemistry
https://read.qxmd.com/read/38114855/recapitulation-of-anti-aging-phenotypes-by-global-overexpression-of-pten-in-mice
#9
JOURNAL ARTICLE
Mary Hager, Peter Chang, Michael Lee, Calvin M Burns, S Joseph Endicott, Richard A Miller, Xinna Li
The PTEN gene negatively regulates the oncogenic PI3K-AKT pathway by encoding a lipid and protein phosphatase that dephosphorylates lipid phosphatidylinositol-3,4,5-triphosphate (PIP3 ) resulting in the inhibition of PI3K and downstream inhibition of AKT. Overexpression of PTEN in mice leads to a longer lifespan compared to control littermates, although the mechanism is unknown. Here, we provide evidence that young adult PTENOE mice exhibit many characteristics shared by other slow-aging mouse models, including those with mutations that affect GH/IGF1 pathways, calorie-restricted mice, and mice treated with anti-aging drugs...
December 19, 2023: GeroScience
https://read.qxmd.com/read/38098889/structural-dynamics-of-p-rex1-complexed-with-natural-leads-establishes-the-protein-as-an-attractive-target-for-therapeutics-to-suppress-cancer-metastasis
#10
JOURNAL ARTICLE
Alaa R Hameed, Sama Fakhri Ali, Sarah M S Alsallameh, Ziyad Tariq Muhseen, Nahlah Makki Almansour, Naif ALSuhaymi, Mahdi H Alsugoor, Khaled S Allemailem
Phosphatidylinositol 3,4,5-trisphosphate- (PIP3-) dependent Rac exchanger 1 (P-Rex1) functions as Rho guanine nucleotide exchange factor and is activated by synergistic activity of G βγ and PIP3 of the heterotrimeric G protein. P-Rex1 activates Rac GTPases for regulating cell invasion and migration and promotes metastasis in several human cancers including breast, prostate, and skin cancer. The protein is a promising therapeutic target because of its multifunction roles in human cancers. Herein, the present study attempts to identify selective P-Rex1 natural inhibitors by targeting PIP3-binding pocket using large-size multiple natural molecule libraries...
2023: BioMed Research International
https://read.qxmd.com/read/38069368/z-ligustilide-combined-with-cisplatin-reduces-plpp1-mediated-phospholipid-synthesis-to-impair-cisplatin-resistance-in-lung-cancer
#11
JOURNAL ARTICLE
Pengyu Geng, Jinhui Zhao, Qi Li, Xiaolin Wang, Wangshu Qin, Ting Wang, Xianzhe Shi, Xinyu Liu, Jia Chen, Hongdeng Qiu, Guowang Xu
Lung cancer is a malignant tumor with one of the highest morbidity and mortality rates in the world. Approximately 80-85% of lung cancer is diagnosed as non-small lung cancer (NSCLC), and its 5-year survival rate is only 21%. Cisplatin is a commonly used chemotherapy drug for the treatment of NSCLC. Its efficacy is often limited by the development of drug resistance after long-term treatment. Therefore, determining how to overcome cisplatin resistance, enhancing the sensitivity of cancer cells to cisplatin, and developing new therapeutic strategies are urgent clinical problems...
December 1, 2023: International Journal of Molecular Sciences
https://read.qxmd.com/read/37952106/tipe-proteins-control-directed-migration-of-human-t-cells-by-directing-gpcr-and-lipid-second-messenger-signaling
#12
JOURNAL ARTICLE
Jiyeon Yu, Ali Zamani, Jason R Goldsmith, Zienab Etwebi, Chin Nien Lee, Youhai H Chen, Honghong Sun
Tissue infiltration by circulating leukocytes via directed migration (also referred to as chemotaxis) is a common pathogenic mechanism of inflammatory diseases. G-protein coupled receptors (GPCRs) are essential for sensing chemokine gradients and directing the movement of leukocytes during immune responses. The TNF-α-induced protein 8-like (TIPE or TNFAIP8L) family of proteins are newly described pilot proteins that control directed migration of murine leukocytes. However, how leukocytes integrate site-specific directional cues, such as chemokine gradients, and utilize GPCR and TIPE proteins to make directional decisions are not well understood...
November 11, 2023: Journal of Leukocyte Biology
https://read.qxmd.com/read/37892266/comparison-of-bilevel-volume-guarantee-and-pressure-regulated-volume-control-modes-in-preterm-infants
#13
JOURNAL ARTICLE
Şehribanu Işık, Fuat Emre Canpolat, Gülsüm Kadıoğlu Şimşek, Ömer Ertekin, Hayriye Gözde Kanmaz Kutman
The present study aimed to compare the bilevel volume guarantee (VG) and pressure-regulated volume control (PRVC) modes of the GE® Carescape R860 model ventilator and test the safety and feasibility of these two modes in preterm neonates. Infants who were less than 30 weeks of gestational age were included. After randomization, initial ventilator settings were adjusted for each patient. After the first 2 h of ventilation, the patients were switched to the other ventilator mode for 2 h. The ventilator parameters, vital signs, and blood gas values were evaluated...
September 26, 2023: Children
https://read.qxmd.com/read/37892191/sf-1-induces-nuclear-pip2
#14
JOURNAL ARTICLE
Ethan S Chi, Elizabeth A Stivison, Raymond D Blind
Metazoan cell nuclei contain non-membrane pools of the phosphoinositide lipid PI(4,5)P2 (PIP2), but how this hydrophobic lipid exists within the aqueous nucleoplasm remains unclear. Steroidogenic Factor-1 (NR5A1, SF-1) is a nuclear receptor that binds PIP2 in vitro, and a co-crystal structure of the complex suggests the acyl chains of PIP2 are hidden in the hydrophobic core of the SF-1 protein while the PIP2 headgroup is solvent-exposed. This binding mode explains how SF-1 can solubilize nuclear PIP2; however, cellular evidence that SF-1 expression associates with nuclear PIP2 has been lacking...
October 12, 2023: Biomolecules
https://read.qxmd.com/read/37888239/effects-of-interaction-of-protein-hydrolysate-and-arbuscular-mycorrhizal-fungi-effects-on-citrus-growth-and-expressions-of-stress-responsive-genes-aquaporins-and-soss-under-salt-stress
#15
JOURNAL ARTICLE
Qi Lu, Longfei Jin, Peng Wang, Feng Liu, Bei Huang, Mingxia Wen, Shaohui Wu
Protein hydrolysates (PHs) and arbuscular mycorrhizal fungi (AMF) are environmentally friendly biostimulants that effectively promote crop growth and alleviate the damage from abiotic stress. However, the physiological and molecular regulatory mechanisms are still unclear. This study aimed to explore the effects of PHs and AMF on growth, mineral nutrient absorption, and expression of Aquaporins and SOSs in Goutoucheng ( Citrus aurantium ) under salt stress. Results showed that PH application and AMF inoculation significantly promoted plant growth and enhanced mineral element absorption and sodium effluxion in citrus under salt stress...
September 29, 2023: Journal of Fungi (Basel, Switzerland)
https://read.qxmd.com/read/37867255/actomyosin-activity-and-piezo1-activity-synergistically-drive-urinary-system-fibroblast-activation
#16
JOURNAL ARTICLE
Guo Chen, Xiaoshuai Gao, Jiawei Chen, Liao Peng, Shuang Chen, Cai Tang, Yi Dai, Qiang Wei, Deyi Luo
Mechanical cues play a crucial role in activating myofibroblasts from quiescent fibroblasts during fibrosis, and the stiffness of the extracellular matrix is of significant importance in this process. While intracellular force mediated by myosin II and calcium influx regulated by Piezo1 are the primary mechanisms by which cells sense and respond to mechanical forces, their intercellular mechanical interaction remains to be elucidated. Here, hydrogels with tunable substrate are used to systematically investigate the crosstalk of myosin II and Piezo1 in fibroblast to myofibroblast transition (FMT)...
November 2023: Advanced Science (Weinheim, Baden-Wurttemberg, Germany)
https://read.qxmd.com/read/37792325/the-choreography-of-protein-kinase-pdk1-and-its-diverse-substrate-dance-partners
#17
JOURNAL ARTICLE
Alejandro E Leroux, Ricardo M Biondi
The protein kinase PDK1 phosphorylates at least 24 distinct substrates, all of which belong to the AGC protein kinase group. Some substrates, such as conventional PKCs, undergo phosphorylation by PDK1 during their synthesis and subsequently get activated by DAG and Calcium. On the other hand, other substrates, including members of the Akt/PKB, S6K, SGK, and RSK families, undergo phosphorylation and activation downstream of PI3-kinase signaling. This review presents two accepted molecular mechanisms that determine the precise and timely phosphorylation of different substrates by PDK1...
October 11, 2023: Biochemical Journal
https://read.qxmd.com/read/37786675/conformational-heterogeneity-of-the-btk-phth-domain-drives-multiple-regulatory-states
#18
David Yin-Wei Lin, Lauren E Kueffer, Puneet Juneja, Thomas Wales, John R Engen, Amy H Andreotti
Full-length BTK has been refractory to structural analysis. The nearest full-length structure of BTK to date consists of the autoinhibited SH3-SH2-kinase core. Precisely how the BTK N-terminal domains (the Pleckstrin homology/Tec homology (PHTH) domain and proline-rich regions (PRR) contain linker) contribute to BTK regulation remains unclear. We have produced crystals of full-length BTK for the first time but despite efforts to stabilize the autoinhibited state, the diffraction data still reveals only the SH3-SH2-kinase core with no electron density visible for the PHTH-PRR segment...
September 19, 2023: bioRxiv
https://read.qxmd.com/read/37719670/-aggregatibacter-actinomycetemcomitans-cytolethal-distending-toxin-modulates-host-phagocytic-function
#19
JOURNAL ARTICLE
Taewan J Kim, Bruce J Shenker, Andrew S MacElory, Samuel Spradlin, Lisa P Walker, Kathleen Boesze-Battaglia
Cytolethal distending toxins (Cdt) are a family of toxins produced by several human pathogens which infect mucocutaneous tissue and induce inflammatory disease. Human macrophages exposed to Aggregatibacter actinomycetemcomitans ( Aa ) Cdt respond through canonical and non-canonical inflammasome activation to stimulate cytokine release. The inflammatory response is dependent on PI3K signaling blockade via the toxin's phosphatidylinositol-3,4,5-triphosphate (PIP3) phosphatase activity; converting PIP3 to phosphatidylinsoitol-3,4-diphosphate (PI3,4P2) thereby depleting PIP3 pools...
2023: Frontiers in Cellular and Infection Microbiology
https://read.qxmd.com/read/37676769/parp1-inhibition-protects-mice-against-japanese-encephalitis-virus-infection
#20
JOURNAL ARTICLE
Perumal Arumugam Desingu, Sneha Mishra, Lavanya Dindi, Shalini Srinivasan, Raju S Rajmani, Venkatraman Ravi, Ankit Kumar Tamta, Sukanya Raghu, Krishnega Murugasamy, Anwit Shriniwas Pandit, Nagalingam R Sundaresan
Japanese encephalitis (JE) is a vector-borne viral disease that causes acute encephalitis in children. Although vaccines have been developed against the JE virus (JEV), no effective antiviral therapy exists. Our study shows that inhibition of poly(ADP-ribose) polymerase 1 (PARP1), an NAD+ -dependent (poly-ADP) ribosyl transferase, protects against JEV infection. Interestingly, PARP1 is critical for JEV pathogenesis in Neuro-2a cells and mice. Small molecular inhibitors of PARP1, olaparib, and 3-aminobenzamide (3-AB) significantly reduce clinical signs and viral load in the serum and brains of mice and improve survival...
September 5, 2023: Cell Reports
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