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International Journal of Molecular... Jun 2020Acupuncture is clinically used to treat various diseases and exerts positive local and systemic effects in several nervous system diseases. Advanced molecular and... (Review)
Review
Acupuncture is clinically used to treat various diseases and exerts positive local and systemic effects in several nervous system diseases. Advanced molecular and clinical studies have continually attempted to decipher the mechanisms underlying these effects of acupuncture. While a growing understanding of the pathophysiology underlying several nervous system diseases shows it to be related to inflammation and impair cell regeneration after ischemic events, the relationship between the therapeutic mechanism of acupuncture and the p38 MAPK signal pathway has yet to be elucidated. This review discusses the latest advancements in the identification of the effect of acupuncture on the p38 signaling pathway in several nervous system diseases. We electronically searched databases including PubMed, Embase, and the Cochrane Library from their inception to April 2020, using the following keywords alone or in various combinations: "acupuncture", "p38 MAPK pathway", "signaling", "stress response", "inflammation", "immune", "pain", "analgesic", "cerebral ischemic injury", "epilepsy", "Alzheimer's disease", "Parkinson's disease", "dementia", "degenerative", and "homeostasis". Manual acupuncture and electroacupuncture confer positive therapeutic effects by regulating proinflammatory cytokines, ion channels, scaffold proteins, and transcription factors including TRPV1/4, Na, BDNF, and NADMR1; consequently, p38 regulates various phenomena including cell communication, remodeling, regeneration, and gene expression. In this review article, we found the most common acupoints for the relief of nervous system disorders including GV20, GV14, ST36, ST37, and LI4. Acupuncture exhibits dual regulatory functions of activating or inhibiting different p38 MAPK pathways, contributing to an overall improvement of clinical symptoms and function in several nervous system diseases.
Topics: Acupuncture Therapy; Animals; Brain-Derived Neurotrophic Factor; Humans; MAP Kinase Signaling System; Motion Sickness; Nerve Regeneration; Nervous System Diseases; TRPV Cation Channels; p38 Mitogen-Activated Protein Kinases
PubMed: 32630156
DOI: 10.3390/ijms21134693 -
Pharmacological Research Mar 2022Senescence suppresses tumor growth, while also developing a tumorigenic state in the nearby cells that is mediated by senescence-associated secretory phenotypes (SASPs)....
Senescence suppresses tumor growth, while also developing a tumorigenic state in the nearby cells that is mediated by senescence-associated secretory phenotypes (SASPs). The dual function of cellular senescence stresses the need for identifying multi-targeted agents directed towards the promotion of cell senescence in cancer cells and suppression of the secretion of pro-tumorigenic signaling mediators in neighboring cells. Natural secondary metabolites have shown favorable anticancer responses in recent decades, as some have been found to target the senescence-associated mediators and pathways. Furthermore, phenolic compounds and polyphenols, terpenes and terpenoids, alkaloids, and sulfur-containing compounds have shown to be promising anticancer agents through the regulation of paracrine and autocrine pathways. Plant secondary metabolites are potential regulators of SASPs factors that suppress tumor growth through paracrine mediators, including growth factors, cytokines, extracellular matrix components/enzymes, and proteases. On the other hand, ataxia-telangiectasia mutated, ataxia-telangiectasia and Rad3-related, extracellular signal-regulated kinase/mitogen-activated protein kinase, phosphatidylinositol 3-kinase/Akt/mammalian target of rapamycin, nuclear factor-κB, Janus kinase/signal transducer and activator of transcription, and receptor tyrosine kinase-associated mediators are main targets of candidate phytochemicals in the autocrine senescence pathway. Such a regulatory role of phytochemicals on senescence-associated pathways is associated with cell cycle arrest and the attenuation of apoptotic/inflammatory/oxidative stress pathways. The current systematic review highlights the critical roles of natural secondary metabolites in the attenuation of autocrine and paracrine cellular senescence pathways, while also elucidating the chemopreventive and chemotherapeutic capabilities of these compounds. Additionally, we discuss current challenges, limitations, and future research indications.
Topics: Antineoplastic Agents; Ataxia Telangiectasia; Cellular Senescence; Humans; Neoplasms; Phytochemicals; Signal Transduction
PubMed: 34718135
DOI: 10.1016/j.phrs.2021.105961 -
Journal of Global Oncology Dec 2015We conducted a literature-based meta-analysis of the risk of cardiovascular toxicities associated with MEK inhibitors. (Review)
Review
PURPOSE
We conducted a literature-based meta-analysis of the risk of cardiovascular toxicities associated with MEK inhibitors.
METHODS
Eligible trials included randomized phase II and III trials of patients with cancer who were given a mitogen activated protein (MAP)/extracellular signal-regulated kinase (ERK) kinase (MEK) inhibitor (trametinib, selumetinib, or cobimetinib) and that described events of hypertension and decreased ejection fraction.
RESULTS
Our search strategy yielded 300 potentially relevant citations from PubMed/MEDLINE, Google Scholar, and Cochrane Central Register of Controlled Trials. After ineligible studies were excluded, a total of 10 clinical trials were considered eligible for the meta-analysis. The relative risk for all grades of hypertension was 1.54 (95% CI, 1.02 to 2.32; = .05), 1.85 (95% CI, 1.01 to 3.40; = .05) for high-grade hypertension, and 4.92 (95% CI, 2.93 to 8.25; < .001) for decreased ejection fraction. Subgroup analysis revealed no difference between trametinib and selumetinib for risk of hypertension.
CONCLUSION
Our meta-analysis demonstrated that MEK inhibitor-based treatment is associated with an increased risk of all-grade and high-grade hypertension and asymptomatic decrease in ejection fraction. Clinicians should be aware of this risk and perform regular assessment.
PubMed: 28804776
DOI: 10.1200/JGO.2015.000802 -
JAMA Oncology Mar 2017Multiple effective first-line systemic treatment options are available for patients with advanced BRAF-mutated melanoma. A lack of head-to-head randomized clinical... (Meta-Analysis)
Meta-Analysis Review
IMPORTANCE
Multiple effective first-line systemic treatment options are available for patients with advanced BRAF-mutated melanoma. A lack of head-to-head randomized clinical trials (RCTs) comparing targeted and immunotherapies leaves uncertainty regarding optimal first-line treatment.
OBJECTIVE
To estimate the relative efficacy and safety of systemic therapies for advanced, treatment-naive, BRAF-mutated melanoma.
DATA SOURCES
We searched MEDLINE, Embase, and the Cochrane Central Registry of Controlled Trials for phase 2 or 3 RCTs published up until April 29, 2016.
STUDY SELECTION
We included RCTs in which at least 1 intervention was a targeted (BRAF or MEK) or an immune checkpoint (cytotoxic T-lymphocyte-associated antigen 4 [CTLA-4] or programmed cell death 1 [PD-1]) inhibitor.
DATA EXTRACTION AND SYNTHESIS
Two reviewers performed study selection, data abstraction, and risk of bias assessment. We performed a Bayesian network meta-analysis using a fixed-effect model to combine direct comparisons with indirect evidence. We estimated hazard ratios (HRs) for overall survival (OS) and progression-free survival (PFS), and odds ratios (OR) for objective response rate (ORR) and serious adverse events.
RESULTS
Sixteen eligible articles reporting 15 RCTs involving 6662 patients assigned to 1 of 10 treatment strategies were included. Both BRAF/MEK and PD-1 were associated with improved OS benefit compared with all other treatments except CTLA-4/granulocyte macrophage colony-stimulating factor. There was no significant difference in OS between BRAF/MEK and PD-1 (HR, 1.02; 95% credible interval [CrI], 0.72-1.45). The network meta-analysis showed a significant advantage of BRAF/MEK compared with all other treatment strategies for PFS. BRAF/MEK was associated with higher ORR (OR, 2.00; 95% CrI, 1.64-2.45) compared with BRAF alone, with both being superior in achieving ORR compared with other treatments. Chemotherapy and PD-1 were associated with lowest risk of serious adverse events. There was no significant difference in the risk of serious adverse events between chemotherapy and PD-1 (OR, 1.00; 95% CrI, 0.74-1.34).
CONCLUSIONS AND RELEVANCE
Compared with other treatments, BRAF/MEK and PD-1 inhibition significantly improved OS. The favorable safety profile of PD-1 inhibitors supports using this option as first-line therapy in circumstances where rapid response is not a priority.
Topics: Antineoplastic Combined Chemotherapy Protocols; CTLA-4 Antigen; Disease-Free Survival; Humans; Melanoma; Mitogen-Activated Protein Kinase Kinases; Molecular Targeted Therapy; Mutation; Programmed Cell Death 1 Receptor; Protein Kinase Inhibitors; Proto-Oncogene Proteins B-raf; Randomized Controlled Trials as Topic; Skin Neoplasms; Survival Analysis; Treatment Outcome
PubMed: 27787543
DOI: 10.1001/jamaoncol.2016.4877 -
Venous Blood Derivatives as FBS-Substitutes for Mesenchymal Stem Cells: A Systematic Scoping Review.Brazilian Dental Journal 2017Although the biological properties of mesenchymal stem cells (MSC) are well-characterized in vitro, MSC clinical application is still far away to be achieved, mainly due... (Review)
Review
Although the biological properties of mesenchymal stem cells (MSC) are well-characterized in vitro, MSC clinical application is still far away to be achieved, mainly due to the need of xenogeneic substances for cell expansion, such as fetal bovine serum (FBS). FBS presents risks regarding pathogens transmissions and internalization of animal's proteins, which can unleash antigenic responses in patients after MSC implantation. A wide range of venous blood derivatives (VBD) has been reported as FBS substitutes showing promising results. Thus, the aim of this study was to conduct a systematic scoping review to analyze whether VBD are effective FBS substitutes for MSC ex vivo expansion. The search was performed in SciVerse ScopusTM, PubMed, Web of ScienceTM, BIREME, Cochrane library up to January 2016. The keywords were selected using MeSH and entry terms. Two independent reviewers scrutinized the records obtained considering specific inclusion criteria. The included studies were evaluated in accordance with a modified Arksey and O' Malley's framework. From 184 found studies, 90 were included. Bone marrow mesenchymal stem cells (BMMSC) were presented in most of these studies. Overall, VBD allowed for either, maintenance of MCS's fibroblast-like morphology, high proliferation, high colony-formation ability and maintenance of multipotency. Besides. MSC expanded in VBD supplements presented higher mitogen activity than FBS. VBD seems to be excellent xeno-free serum for ex vivo expansion of mesenchymal stem cells. However, an accentuated heterogeneity was observed between the carried out protocols for VBD isolation did not allowing for direct comparisons between the included studies.
Topics: Animals; Blood Substitutes; Cattle; Culture Media; Humans; Mesenchymal Stem Cells; Veins
PubMed: 29211118
DOI: 10.1590/0103-6440201701646 -
Frontiers in Oncology 2022Chronic diseases including cancer have high case numbers as well as mortality rates. The efficient treatment of chronic diseases is a major ongoing medical challenge...
Chronic diseases including cancer have high case numbers as well as mortality rates. The efficient treatment of chronic diseases is a major ongoing medical challenge worldwide, because of their complexity and many inflammatory pathways such as JNK, p38/MAPK, MEK/ERK, JAK/STAT3, PI3K and NF-κB among others being implicated in their pathogenesis. Together with the versatility of chronic disease classical mono-target therapies are often insufficient. Therefore, the anti-inflammatory as well as anti-cancer capacities of polyphenols are currently investigated to complement and improve the effect of classical anti-inflammatory drugs, chemotherapeutic agents or to overcome drug resistance of cancer cells. Currently, research on Calebin A, a polyphenolic component of turmeric (), is becoming of growing interest with regard to novel treatment strategies and has already been shown health-promoting as well as anti-tumor properties, including anti-oxidative and anti-inflammatory effects, in diverse cancer cells. Within this review, we describe already known anti-inflammatory activities of Calebin A modulation of NF-κB and its associated signaling pathways, linked with TNF-α, TNF-β and COX-2 and further summarize Calebin A's tumor-inhibiting properties that are known up to date such as reduction of cancer cell viability, proliferation as well as metastasis. We also shed light on possible future prospects of Calebin A as an anti-cancer agent.
PubMed: 36185259
DOI: 10.3389/fonc.2022.962066 -
Phytotherapy Research : PTR Oct 2019Traditionally, sesame oil (SO) has been used as a popular food and medicine. The review aims to summarize the antioxidant and antiinflammatory effects of SO and its...
A systematic review on antioxidant and antiinflammatory activity of Sesame (Sesamum indicum L.) oil and further confirmation of antiinflammatory activity by chemical profiling and molecular docking.
Traditionally, sesame oil (SO) has been used as a popular food and medicine. The review aims to summarize the antioxidant and antiinflammatory effects of SO and its identified compounds as well as further fatty acid profiling and molecular docking study to correlate the interaction of its identified constituents with cyclooxygenase-2 (COX-2). For this, a literature study was made using Google Scholar, Pubmed, and SciFinder databases. Literature study demonstrated that SO has potential antioxidant and antiinflammatory effects in various test systems, including humans, animals, and cultured cells through various pathways such as inhibition of COX, nonenzymatic defense mechanism, inhibition of proinflammatory cytokines, NF-kB or mitogen-activated protein kinase signaling, and prostaglandin synthesis pathway. Fatty acid analysis of SO using gas chromatography identified known nine fatty acids. In silico study revealed that sesamin, sesaminol, sesamolin, stigmasterol, Δ5-avenasterol, and Δ7-avenasterol (-9.6 to -10.7 kcal/mol) were the most efficient ligand for interaction and binding with COX-2. The known fatty acid also showed binding efficiency with COX-2 to some extent (-6.0 to -8.4 kcal/mol). In summary, it is evident that SO may be one of promising traditional medicines that we could use in the prevention and management of diseases associated with oxidative stress and inflammation.
Topics: Animals; Anti-Inflammatory Agents; Antioxidants; Humans; Molecular Docking Simulation; Oxidative Stress; Sesame Oil
PubMed: 31373097
DOI: 10.1002/ptr.6428 -
PeerJ 2022Titanium dioxide dental implants have a controversial effect on reactive oxygen species (ROS) production. ROS is necessary for cellular signal transmission and proper... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Titanium dioxide dental implants have a controversial effect on reactive oxygen species (ROS) production. ROS is necessary for cellular signal transmission and proper metabolism, but also has the ability to cause cell death as well as DNA, RNA, and proteins damage by excessive oxidative stress. This study aimed to systematically review the effect of titanium dioxide dental implant-induced oxidative stress and its role on the osteogenesis-angiogenesis coupling in bone remodeling.
METHODS
This systematic review was performed conforming to preferred reporting items for systematic review and meta-analysis (PRISMA) model. Four different databases (PubMed, Science Direct, Scopus and Medline databases) as well as manual searching were adopted. Relevant studies from January 2000 till September 2021 were retrieved. Critical Appraisal Skills Programme (CASP) was used to assess the quality of the selected studies.
RESULTS
Out of 755 articles, only 14 which met the eligibility criteria were included. Six studies found that titanium dioxide nanotube (TNT) reduced oxidative stress and promoted osteoblastic activity through its effect on Wnt, mitogen-activated protein kinase (MAPK) and forkhead box protein O1 (FoxO1) signaling pathways. On the other hand, three studies confirmed that titanium dioxide nanoparticles (TiONPs) induce oxidative stress, reduce ostegenesis and impair antioxidant defense system as a significant negative correlation was found between decreased SIR3 protein level and increased superoxide (O ). Moreover, five studies proved that titanium implant alloy enhances the generation of ROS and induces cytotoxicity of osteoblast cells via its effect on NOX pathway.
CONCLUSION
TiONPs stimulate a wide array of oxidative stress related pathways. Scientific evidence are in favor to support the use of TiO nanotube-coated titanium implants to reduce oxidative stress and promote osteogenesis in bone remodeling. To validate the cellular and molecular cross talk in bone remodeling of the present review, well-controlled clinical trials with a large sample size are required.
Topics: Reactive Oxygen Species; Titanium; Dental Implants; Oxidative Stress; Bone Remodeling
PubMed: 35261818
DOI: 10.7717/peerj.12951 -
Journal of Endodontics Nov 2015Signaling molecules and responding dental pulp stem cells are the 2 main control keys of dentin regeneration/dentinogenesis. The aim of this study was to present a... (Review)
Review
INTRODUCTION
Signaling molecules and responding dental pulp stem cells are the 2 main control keys of dentin regeneration/dentinogenesis. The aim of this study was to present a systematic review investigating the gene expression of various dental pulp cells in response to different variants of tricalcium silicate cements.
METHODS
A systematic search of the literature was performed by 2 independent reviewers followed by article selection and data extraction. Studies analyzing all sorts of dental pulp cells (DPCs) and any variant of tricalcium silicate cement either as the experimental or as the control group were included.
RESULTS
A total of 39 articles were included in the review. Among the included studies, ProRoot MTA (Dentsply, Tulsa Dental, OK) was the most commonly used tricalcium silicate cement variant. The extracellular signal regulated kinase/mitogen-activated protein kinase pathway was the most commonly activated pathway to be identified, and similarly, dentin sialophosphoprotein osteocalcin dentin matrix acidic phosphoprotein 1, alkaline phosphatase, bone sialoprotein, osteopontin, type I collagen, and Runx2 were the most commonly expressed genes in that order of frequency.
CONCLUSIONS
Biodentine (Septodont Ltd, Saint Maur des Faussés, France), Bioaggregate (Innovative Bioceramix, Vancouver, BC, Canada), and mineral trioxide aggregate stimulate the osteogenic/odontogenic capacity of DPCs by proliferation, angiogenesis, and biomineralization through the activation of the extracellular signal regulated kinase ½, nuclear factor E2 related factor 2, p38, c-Jun N-terminal kinase mitogen-activated protein kinase, p42/p44 mitogen-activated protein kinase, nuclear factor kappa B, and fibroblast growth factor receptor pathways. When DPCs are placed into direct contact with tricalcium silicate cements, they show higher levels of gene activation, which in turn could translate into more effective pulpal repair and faster and more predictable formation of reparative dentin.
Topics: Calcium Compounds; Cell Proliferation; Cytokines; Dental Materials; Dental Pulp; Gene Expression Profiling; Humans; Osteogenesis; Silicates
PubMed: 26381895
DOI: 10.1016/j.joen.2015.07.015 -
The International Journal of... Dec 2022Cardiac magnetic resonance (CMR) derived left ventricular global longitudinal strain (LV-GLS) for evaluating dilated cardiomyopathy patients has been addressed in... (Meta-Analysis)
Meta-Analysis
Prognostic value of cardiac magnetic resonance derived global longitudinal strain analysis in patients with ischaemic and non-ischaemic dilated cardiomyopathy: a systematic review and meta-analysis.
Cardiac magnetic resonance (CMR) derived left ventricular global longitudinal strain (LV-GLS) for evaluating dilated cardiomyopathy patients has been addressed in studies with contradictory results. We therefore performed the first systematic review evaluating evidence on the prognostic value of CMR derived LV-GLS for ischaemic (IDCM) and non-ischaemic dilated cardiomyopathy (NDCM) patients. Systematic review (PROSPERO CRD42020171582) identified studies up to January 2021 that measured LV-GLS for predicting major adverse cardiac events among dilated cardiomyopathy patients. Studies were identified from MEDLINE, Embase and PubMed by two independent reviewers. 2099 studies were screened. Three prospective and three retrospective observational studies comprising of 1758 patients (29% IDCM patients; 71% NDCM patients) with a weighted mean follow up of 3 years (SD = 1 year) were identified. All six studies included mortality in the primary composite outcome. LV-GLS was associated with increase primary composite outcome among mild to moderately impaired left ventricular ejection fraction (LVEF) IDCM and NDCM patients (> 30%) in univariable and multivariable analysis. Association was lost among severely impaired LVEF patients (< 30%). From sensitivity analysis, LV-GLS showed significant association with death among NDCM patients (HR 1.27; 95% CI 1.10-1.46; p = 0.001; I = 59%) but insignificant for heart transplant outcome (HR 1.23; 95% CI 0.46-3.33; p = 0.68, I = 44%). LV-GLS threshold for effectively stratifying patients is - 12.5% to - 13.5%. LVEF in IDCM and NDCM became an insignificant prognostic marker in multivariable analysis. CMR LV-GLS shows promise as an independent predictor of mortality in IDCM and NDCM patients. However, in patients with LVEF < 30% LV-GLS may have less prognostic value.Prospero Registration: CRD42020171582.
Topics: Humans; Prognosis; Stroke Volume; Cardiomyopathy, Dilated; Retrospective Studies; Prospective Studies; Ventricular Function, Left; Predictive Value of Tests; Magnetic Resonance Spectroscopy
PubMed: 36445666
DOI: 10.1007/s10554-022-02679-9