Kunxian Capsule for Rheumatoid Arthritis: Inhibition of Inflammatory Network and Reducing Adverse Reactions Through Drug Matching DOI Creative Commons
Yujun Tang, Yi Zhang, Lin Li

et al.

Frontiers in Pharmacology, Journal Year: 2020, Volume and Issue: 11

Published: April 17, 2020

Tripterygium wilfordii Hook.f and hypoglaucum (H.Lév.) Hutch is effective herbs to prevent aggravation of Rheumatoid arthritis (RA). However, both them show severe side effects in the reproductive system other systems. Kunxian Capsule (KX), a Traditional Chinese Medicine (TCM) patent prescription, comprised 4 herbs, including H.Lév. Hutch, reported be an available prescription treating RA with fewer as compares tablets. To reveal pharmacological mechanism KX treatment effect alleviation, we collected related information from open-access databases performed various analyses. 1354 targets were identified KX. These enriched calcium signaling pathway, cAMP cGMP-PKG pathway PI3K-AKT forming biological functions such cofactor binding, coenzyme etc. pathways or mostly affect cell cycle, differentiation maturation Th17 cells, macrophage synovial fibroblast. also act on IL-17 TNF which inflammation response inhibition. Next, disease network was constructed, indicated IMPDH2, MTHFD1 are key genes answering for Hutch. The lead negative regulation nucleic acid, could restored by rest 3 through some positive amino acid metabolism. In conclusion, relatively safe alternative approach intervention.

Language: Английский

RAS Proteins and Their Regulators in Human Disease DOI Creative Commons
Dhirendra K. Simanshu, Dwight V. Nissley, Frank McCormick

et al.

Cell, Journal Year: 2017, Volume and Issue: 170(1), P. 17 - 33

Published: June 1, 2017

Language: Английский

Citations

1600
mTORC1 signaling and the metabolic control of cell growth DOI
Issam Ben‐Sahra, Brendan D. Manning

Current Opinion in Cell Biology, Journal Year: 2017, Volume and Issue: 45, P. 72 - 82

Published: April 1, 2017

Language: Английский

Citations

565
PI3K isoforms in cell signalling and vesicle trafficking DOI
Benoît Bilanges, York Posor, Bart Vanhaesebroeck

et al.

Nature Reviews Molecular Cell Biology, Journal Year: 2019, Volume and Issue: 20(9), P. 515 - 534

Published: May 20, 2019

Language: Английский

Citations

426
The ASD Living Biology: from cell proliferation to clinical phenotype DOI Creative Commons
Eric Courchesne, Tiziano Pramparo, Vahid Gazestani

et al.

Molecular Psychiatry, Journal Year: 2018, Volume and Issue: 24(1), P. 88 - 107

Published: June 19, 2018

Abstract Autism spectrum disorder (ASD) has captured the attention of scientists, clinicians and lay public because its uncertain origins striking unexplained clinical heterogeneity. Here we review genetic, genomic, cellular, postmortem, animal model, cell model evidence that shows ASD begins in womb. This leads to a new theory is multistage, progressive brain development, spanning nearly all prenatal life. can begin as early 1st 2nd trimester with disruption proliferation differentiation. It continues neural migration, laminar disorganization, altered neuron maturation neurite outgrowth, synaptogenesis reduced network functioning. Among most commonly reported high-confidence ( hcASD ) genes, 94% express during life affect these fetal processes neocortex, amygdala, hippocampus, striatum cerebellum. A majority genes are pleiotropic, proliferation/differentiation and/or synapse development. Proliferation subsequent stages also be disrupted by maternal immune activation trimester. Commonly implicated pathways, PI3K/AKT RAS/ERK, pleiotropic multiple from through functional In different individuals, variation how when pathways dysregulated, will lead different, even opposing effects, producing well later Thus, pathogenesis not set at one point time does reside process, but rather cascade pathogenic vast toddlers. Despite this knowledge biology womb, current research methods have provided individualized information: What early-age molecular cellular differences underlie each individual child? Without such knowledge, rapid advances biological-based diagnostic, prognostic, precision medicine treatments cannot occur. Missing, therefore, what call Living Biology. conceptual paradigm shift towards focus on abnormal underlying within living individual. The concept emphasizes specific need for foundational child’s development beginnings stages. Biology seeks linking genetic vitro molecular, measurements vivo post-natal presentation progression child. We first study, which confirms multistage nature provides fetal-stage explanation overgrowth. Within-child novel coin here advocates integration information generate group-level explanations, clinically useful prognoses, approaches truly beneficial infant toddler ASD.

Language: Английский

Citations

283
Attenuation of Lipopolysaccharide-Induced Acute Lung Injury by Hispolon in Mice, Through Regulating the TLR4/PI3K/Akt/mTOR and Keap1/Nrf2/HO-1 Pathways, and Suppressing Oxidative Stress-Mediated ER Stress-Induced Apoptosis and Autophagy DOI Open Access
Ching‐Ying Huang, Jeng‐Shyan Deng, Wen‐Chin Huang

et al.

Nutrients, Journal Year: 2020, Volume and Issue: 12(6), P. 1742 - 1742

Published: June 10, 2020

The anti-inflammatory effect of hispolon has identified it as one the most important compounds from Sanghuangporus sanghuang. research objectives were to study this compound using an animal model by lipopolysaccharide (LPS)-induced acute lung injury. Hispolon treatment reduced production pro-inflammatory mediator NO, TNF-α, IL-1β, and IL-6 induced LPS challenge in tissues, well decreasing their histological alterations protein content. Total cell number was also bronchoalveolar lavage fluid (BALF). Moreover, inhibited iNOS, COX-2 IκB-α phosphorylated IKK MAPK, while increasing catalase, SOD, GPx, TLR4, AKT, HO-1, Nrf-2, Keap1 PPARγ expression, after challenge. It regulated apoptosis, ER stress autophagy signal transduction pathway. results show that regulates LPS-induced (increasing CHOP, PERK, IRE1, ATF6 GRP78 expression), apoptosis (decreasing caspase-3 Bax Bcl-2 expression) (reducing LC3 I/II Beclin-1 expression). This vivo experimental suggests suppresses activation inflammatory pathways, oxidative injury, stress, potential be used therapeutically major anterior segment diseases.

Language: Английский

Citations

204
A review of mechanisms of disease across PIK3CA-related disorders with vascular manifestations DOI Creative Commons
Guillaume Canaud, Adrienne M. Hammill, Denise M. Adams

et al.

Orphanet Journal of Rare Diseases, Journal Year: 2021, Volume and Issue: 16(1)

Published: July 8, 2021

Abstract Background PIK3CA -related disorders include vascular malformations and overgrowth of various tissues that are caused by postzygotic, somatic variants in the gene encoding phosphatidylinositol-3-kinase (PI3K) catalytic subunit alpha. These mutations result activation PI3K/AKT/mTOR signaling pathway. The goals this review to provide education on underlying mechanism disease for group rare conditions summarize recent advancements understanding of, as well current emerging treatment options disorders. Main body spectrum (PROS), malformations, nonvascular lesions. Somatic activating (predominantly hotspots helical kinase domains PIK3CA, but also other domains), lead hyperactivation PI3K pathway, which results abnormal tissue growth. Diagnosis is complicated variability overlap phenotypes associated with should be performed clinicians required expertise along coordinated care from a multidisciplinary team. Although mosaicism presents challenges confirmation mutations, next-generation sequencing selection have improved detection. Clinical improvement, radiological response, patient-reported outcomes typically used assess response clinical studies patients disorders, objective assessment difficult using imaging (due heterogeneous nature these superimposed upon patient growth development). Despite their limitations, outcome tools may best suited gauge improvement. New therapeutic needed an alternative or supplement standard approaches such surgery sclerotherapy. Currently, there no systemic agents regulatory approval mTOR inhibitor sirolimus has been several years trials off label address symptoms. There under investigation act inhibitors target different components pathway including AKT (miransertib) alpha (alpelisib). Conclusion Management requires approach. Further ongoing targeting highly anticipated.

Language: Английский

Citations

108
PTEN mutations impair CSF dynamics and cortical networks by dysregulating periventricular neural progenitors DOI
Tyrone DeSpenza,

Emre Kiziltug,

Garrett Allington

et al.

Nature Neuroscience, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 24, 2025

Language: Английский

Citations

2
The Scribble Cell Polarity Module in the Regulation of Cell Signaling in Tissue Development and Tumorigenesis DOI

Rebecca Stephens,

Krystle Y.B. Lim, Marta Portela

et al.

Journal of Molecular Biology, Journal Year: 2018, Volume and Issue: 430(19), P. 3585 - 3612

Published: Feb. 8, 2018

Language: Английский

Citations

131
Exome sequencing implicates genetic disruption of prenatal neuro-gliogenesis in sporadic congenital hydrocephalus DOI
Sheng Chih Jin, Weilai Dong, Adam J. Kundishora

et al.

Nature Medicine, Journal Year: 2020, Volume and Issue: 26(11), P. 1754 - 1765

Published: Oct. 19, 2020

Language: Английский

Citations

125
Vascular Anomalies DOI
Denise M. Adams, Kiersten Ricci

Hematology/Oncology Clinics of North America, Journal Year: 2019, Volume and Issue: 33(3), P. 455 - 470

Published: April 25, 2019

Language: Английский

Citations

103