scholarly journals Local Anesthetic Lidocaine and Cancer: Insight Into Tumor Progression and Recurrence

2021 ◽  
Vol 11 ◽  
Author(s):  
Caihui Zhang ◽  
Cuiyu Xie ◽  
Yao Lu
Keyword(s):  
Pain Relief ◽  
Signaling Pathways ◽  
Local Anesthetic ◽  
Immune Regulation ◽  
Molecular Mechanisms ◽  
Primary Treatment ◽  
Akt Signaling ◽  
Clinical Benefits ◽  
Insight Into ◽  
Anti Inflammation

Cancer is a leading contributor to deaths worldwide. Surgery is the primary treatment for resectable cancers. Nonetheless, it also results in inflammatory response, angiogenesis, and stimulated metastasis. Local anesthetic lidocaine can directly and indirectly effect different cancers. The direct mechanisms are inhibiting proliferation and inducing apoptosis via regulating PI3K/AKT/mTOR and caspase-dependent Bax/Bcl2 signaling pathways or repressing cytoskeleton formation. Repression invasion, migration, and angiogenesis through influencing the activation of TNFα-dependent, Src-induced AKT/NO/ICAM and VEGF/PI3K/AKT signaling pathways. Moreover, the indirect influences are immune regulation, anti-inflammation, and postoperative pain relief. This review summarizes the latest evidence that revealed potential clinical benefits of lidocaine in cancer treatment to explore the probable molecular mechanisms and the appropriate dose.

A mathematical model of metabolic insulin signaling pathways

2002 ◽  
Vol 283 (5) ◽  
pp. E1084-E1101 ◽  
Author(s):  
Ahmad R. Sedaghat ◽  
Arthur Sherman ◽  
Michael J. Quon
Keyword(s):  
Experimental Data ◽  
Mathematical Model ◽  
Insulin Receptor ◽  
Signaling Pathways ◽  
Insulin Signaling ◽  
Molecular Mechanisms ◽  
Glucose Transporter ◽  
Insulin Dose ◽  
Model Parameters ◽  
Insight Into

We develop a mathematical model that explicitly represents many of the known signaling components mediating translocation of the insulin-responsive glucose transporter GLUT4 to gain insight into the complexities of metabolic insulin signaling pathways. A novel mechanistic model of postreceptor events including phosphorylation of insulin receptor substrate-1, activation of phosphatidylinositol 3-kinase, and subsequent activation of downstream kinases Akt and protein kinase C-ζ is coupled with previously validated subsystem models of insulin receptor binding, receptor recycling, and GLUT4 translocation. A system of differential equations is defined by the structure of the model. Rate constants and model parameters are constrained by published experimental data. Model simulations of insulin dose-response experiments agree with published experimental data and also generate expected qualitative behaviors such as sequential signal amplification and increased sensitivity of downstream components. We examined the consequences of incorporating feedback pathways as well as representing pathological conditions, such as increased levels of protein tyrosine phosphatases, to illustrate the utility of our model for exploring molecular mechanisms. We conclude that mathematical modeling of signal transduction pathways is a useful approach for gaining insight into the complexities of metabolic insulin signaling.

scholarly journals Oridonin Promotes Apoptosis and Restrains the Viability and Migration of Bladder Cancer by Impeding TRPM7 Expression via the ERK and AKT Signaling Pathways

2021 ◽  
Vol 2021 ◽  
pp. 1-9
Author(s):  
Xianping Che ◽  
Jiangtao Zhan ◽  
Fan Zhao ◽  
Zunhe Zhong ◽  
Mianchuan Chen ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Signaling Pathways ◽  
Molecular Mechanisms ◽  
Transient Receptor Potential ◽  
Akt Signaling ◽  
Bladder Cancer Cell Line ◽  
Anticancer Efficacy ◽  
T24 Cells

Background. Oridonin is a powerful anticancer compound found in Rabdosia rubescens. However, its potential impact on bladder cancer remains uninvestigated. In this work, we aimed to detect the anticancer effect of oridonin on bladder cancer and explore the molecular mechanisms involved. Methods. The anticancer activity of oridonin was assessed in vitro with a CCK8 assay, an annexin V-FITC apoptosis analysis, and colony formation and Transwell migration assays which were performed with the human bladder cancer cell line T24. Levels of apoptosis-related proteins, melastatin transient receptor potential channel 7 (TRPM7), and signaling molecules were examined in oridonin-treated T24 cells by western blotting or RT-PCR. Oridonin anticancer efficacy was further validated in vivo with a T24 xenograft mouse model. Results. Oridonin repressed the proliferative, colony-forming, and migratory capacities of T24 cells, triggered extensive apoptosis in vitro, and retarded tumor growth in vivo. Moreover, oridonin treatment significantly increased expression levels of p53 and cleaved caspase-3 and reduced expression of TRPM7, p-AKT, and p-ERK. Conclusion. Oridonin exhibited outstanding antiproliferative and antimigratory effects on bladder cancer, and these effects were at least partially associated with targeting of TRPM7 through inactivation of the ERK and AKT signaling pathways. These findings provide insight for the clinical application of oridonin in bladder cancer prevention.

Ras-Related Signaling Pathways in Valve Development: Ebb and Flow

Physiology ◽  
2005 ◽  
Vol 20 (6) ◽  
pp. 390-397 ◽  
Author(s):  
Katherine E. Yutzey ◽  
Melissa Colbert ◽  
Jeffrey Robbins
Keyword(s):  
Signaling Pathways ◽  
Congenital Heart ◽  
Molecular Mechanisms ◽  
Heart Defects ◽  
Neurofibromatosis Type ◽  
Ras Signaling ◽  
Live Births ◽  
Valve Development ◽  
Insight Into

Congenital heart defects affect ~1 in every 100 live births, and deficits in the formation of the mitral, tricuspid, and outflow tract valves account for 20–25% of all cardiac malformations. Mutations in genes that affect Ras signaling have been identified in individuals with congenital valve disease associated with Noonan syndrome and neurofibromatosis type 1. Dissection of Ras-related signaling pathways during valvulogenesis provides seminal insight into cellular and molecular mechanisms that contribute to congenital heart disease.

scholarly journals Methylene Blue Application to Lessen Pain: Its Analgesic Effect and Mechanism

2021 ◽  
Vol 15 ◽  
Author(s):  
Seung Won Lee ◽  
Hee Chul Han
Keyword(s):  
Methylene Blue ◽  
Pain Relief ◽  
Sodium Current ◽  
Public Attention ◽  
Analgesic Effects ◽  
Relieve Pain ◽  
Discogenic Low Back Pain ◽  
Current Reduction ◽  
Insight Into ◽  
Anti Inflammation

Methylene blue (MB) is a cationic thiazine dye, widely used as a biological stain and chemical indicator. Growing evidence have revealed that MB functions to restore abnormal vasodilation and notably it is implicated even in pain relief. Physicians began to inject MB into degenerated disks to relieve pain in patients with chronic discogenic low back pain (CDLBP), and some of them achieved remarkable outcomes. For osteoarthritis and colitis, MB abates inflammation by suppressing nitric oxide production, and ultimately relieves pain. However, despite this clinical efficacy, MB has not attracted much public attention in terms of pain relief. Accordingly, this review focuses on how MB lessens pain, noting three major actions of this dye: anti-inflammation, sodium current reduction, and denervation. Moreover, we showed controversies over the efficacy of MB on CDLBP and raised also toxicity issues to look into the limitation of MB application. This analysis is the first attempt to illustrate its analgesic effects, which may offer a novel insight into MB as a pain-relief dye.

scholarly journals The Ameliorating Effect of Plasma Protein from Tachypleus tridentatus on Cyclophosphamide-Induced Acute Kidney Injury in Mice

Marine Drugs ◽  
2019 ◽  
Vol 17 (4) ◽  
pp. 227 ◽  
Author(s):  
Xinhuang Kang ◽  
Mengyao Jing ◽  
Guoguang Zhang ◽  
Lanzheng He ◽  
Pengzhi Hong ◽  
...  
Keyword(s):  
Acute Kidney Injury ◽  
Signaling Pathways ◽  
P38 Mapk ◽  
Plasma Protein ◽  
Renal Cell ◽  
Molecular Mechanisms ◽  
Kidney Injury ◽  
Akt Signaling ◽  
Growth Effect ◽  
Tachypleus Tridentatus

In the study, the protective effect of plasma protein from Tachypleus tridentatus (PPTT) on acute kidney injury (AKI) and the related molecular mechanisms were first investigated by Western blotting analyses, TdT-mediated dUTP Nick-End Labeling (TUNEL) assay, and immunohistochemistry. It was found that PPTT had an obviously inhibitory effect on Reactive oxygen species (ROS) in cyclophosphamide (CTX)-exposed mice. Furthermore, results demonstrated that the renal cell death mode is due to inducing apoptosis and autophagy inhibited by dose-dependent PPTT in mice treated with CTX by decreasing the protein expression of bax, beclin-1, and LC3 and increasing the expression of bcl-2. Moreover, the p38 MAPK and PI3K/Akt signaling pathways were observed to take part in the PPTT-induced renal cell growth effect by enhancing the upregulation of the expression of Akt and p-Akt as well as the downregulation of the expression of p38 and p-p38, which indicated a PPTT ameliorating effect on AKI CTX-induced in mice through p38 MAPK and PI3K/Akt signaling pathways. Briefly, this article preliminarily studies the mechanism of the PPTT ameliorating effect on AKI CTX-induced in mice, which helps to provide a reference for PPTT clinical application in AKI therapy.

scholarly journals Suppressive Effects of Rosmarinic Acid Rich Fraction from Perilla on Oxidative Stress, Inflammation and Metastasis Ability in A549 Cells Exposed to PM via C-Jun, P-65-Nf-Κb and Akt Signaling Pathways

Biomolecules ◽  
2021 ◽  
Vol 11 (8) ◽  
pp. 1090
Author(s):  
Komsak Pintha ◽  
Wittaya Chaiwangyen ◽  
Supachai Yodkeeree ◽  
Maitree Suttajit ◽  
Payungsak Tantipaiboonwong
Keyword(s):  
Oxidative Stress ◽  
Signaling Pathways ◽  
Rosmarinic Acid ◽  
Molecular Mechanisms ◽  
Cancer Metastasis ◽  
A549 Cells ◽  
Akt Signaling ◽  
Seed Meal ◽  
Ros Production ◽  
Perilla Seed

Particulate matter from forest fires (PMFF) is an environmental pollutant causing oxidative stress, inflammation, and cancer cell metastasis due to the presence of polycyclic aromatic hydrocarbons (PAHs). Perilla seed meal contains high levels of polyphenols, including rosmarinic acid (RA). The aim of this study is to determine the anti-oxidative stress, anti-inflammation, and anti-metastasis actions of rosmarinic acid rich fraction (RA-RF) from perilla seed meal and its underlying molecular mechanisms in A549 cells exposed to PMFF. PMFF samples were collected via the air sampler at the University of Phayao, Thailand, and their PAH content were analyzed using GC-MS. Fifteen PAH compounds were detected in PMFF. The PMFF significantly induced intracellular reactive oxygen species (ROS) production, the mRNA expression of pro-inflammatory cytokines, MMP-9 activity, invasion, migration, the overexpression of c-Jun and p-65-NF-κB, and Akt phosphorylation. Additionally, the RA-RF significantly reduced ROS production, IL-6, IL-8, TNF-α, and COX-2. RA-RF could also suppress MMP-9 activity, migration, invasion, and the phosphorylation activity of c-Jun, p-65-NF-κB, and Akt. Our findings revealed that RA-RF has antioxidant, anti-inflammatory, and anti-metastasis properties via c-Jun, p-65-NF-κB, and Akt signaling pathways. RA-RF may be further developed as an inhalation agent for the prevention of lung inflammation and cancer metastasis induced by PM exposure.

scholarly journals Molecular Mechanisms Underlying Autophagy-Mediated Treatment Resistance in Cancer

Cancers ◽  
2019 ◽  
Vol 11 (11) ◽  
pp. 1775 ◽  
Author(s):  
Cally J. Ho ◽  
Sharon M. Gorski
Keyword(s):  
Tumor Progression ◽  
Signaling Pathways ◽  
Cancer Patients ◽  
Targeted Therapies ◽  
Molecular Mechanisms ◽  
Treatment Resistance ◽  
Akt Signaling ◽  
Diagnostic Tools ◽  
Cancer Types

Despite advances in diagnostic tools and therapeutic options, treatment resistance remains a challenge for many cancer patients. Recent studies have found evidence that autophagy, a cellular pathway that delivers cytoplasmic components to lysosomes for degradation and recycling, contributes to treatment resistance in different cancer types. A role for autophagy in resistance to chemotherapies and targeted therapies has been described based largely on associations with various signaling pathways, including MAPK and PI3K/AKT signaling. However, our current understanding of the molecular mechanisms underlying the role of autophagy in facilitating treatment resistance remains limited. Here we provide a comprehensive summary of the evidence linking autophagy to major signaling pathways in the context of treatment resistance and tumor progression, and then highlight recently emerged molecular mechanisms underlying autophagy and the p62/KEAP1/NRF2 and FOXO3A/PUMA axes in chemoresistance.

scholarly journals Age-related increase in matrix stiffness downregulates α-Klotho in chondrocytes and induces cartilage degeneration

2021 ◽  
Author(s):  
Hirotaka Iijima ◽  
Gabrielle Gilmer ◽  
Kai Wang ◽  
Allison Bean ◽  
Yuchen He ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Cartilage Degeneration ◽  
Akt Signaling ◽  
Cartilage Tissue ◽  
Matrix Stiffness ◽  
Knee Cartilage ◽  
Human Knee ◽  
Age Related ◽  
Insight Into ◽  
Upstream Regulators

ABSTRACTEnhanced mechanistic insight into age-related knee osteoarthritis (KOA) is an essential step to promote successful translation of animal research to bedside interventions. To this end, the goal of these studies was to interrogate molecular mechanisms driving age-related KOA in a mouse model and correspond findings to human knee cartilage. Unbiased mass spectrometry proteomics of cartilage tissue revealed PI3K/Akt signaling was the predominant pathway disrupted over time in male, but not female, mice. This finding was consistent with a significantly accelerated KOA progression in males when compared to female counterparts. In probing for upstream regulators of these age-dependent alterations, we found that α-Klotho, a suppressor of PI3K/Akt signaling and potent longevity protein, significantly decreased with aging in both mouse and human knee cartilage. Upstream of these alterations, we found that age-related increases in matrix stiffness initiated a cascade of altered nuclear morphology and downregulated α-Klotho expression, ultimately impairing chondrocyte health. Conversely, reducing matrix stiffness increased α-Klotho expression in chondrocytes, thus enhancing their chondrogencity and cartilage integrity. Collectively, our findings establish a novel mechanistic link between age-related alterations in ECM biophysical properties and regulation of cartilage health by α-Klotho.

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