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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 -
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 -
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 -
ESMO Open Apr 2021Approved first-line treatments for patients with BRAF V600-mutant advanced melanoma include nivolumab (a programmed cell death protein 1 inhibitor) plus ipilimumab (a...
BACKGROUND
Approved first-line treatments for patients with BRAF V600-mutant advanced melanoma include nivolumab (a programmed cell death protein 1 inhibitor) plus ipilimumab (a cytotoxic T lymphocyte antigen-4 inhibitor; NIVO+IPI) and the BRAF/MEK inhibitors dabrafenib plus trametinib (DAB+TRAM), encorafenib plus binimetinib (ENCO+BINI), and vemurafenib plus cobimetinib (VEM+COBI). Results from prospective randomized clinical trials (RCTs) comparing these treatments have not yet been reported. This analysis evaluated the relative efficacy and safety of NIVO+IPI versus DAB+TRAM, ENCO+BINI, and VEM+COBI in patients with BRAF-mutant advanced melanoma using a matching-adjusted indirect comparison (MAIC).
PATIENTS AND METHODS
A systematic literature review identified RCTs for DAB+TRAM, ENCO+BINI, and VEM+COBI in patients with BRAF-mutant advanced melanoma. Individual patient-level data for NIVO+IPI were derived from the phase III CheckMate 067 trial (BRAF-mutant cohort) and restricted to match the inclusion/exclusion criteria of the comparator trials. Treatment effects for overall survival (OS) and progression-free survival (PFS) were estimated using Cox proportional hazards and time-varying hazard ratio (HR) models. Safety outcomes (grade 3 or 4 treatment-related adverse events) with NIVO+IPI and the comparators were compared.
RESULTS
In the Cox proportional hazards analysis, NIVO+IPI showed improved OS compared with DAB+TRAM (HR = 0.53; 95% confidence interval [CI], 0.39-0.73), ENCO+BINI (HR = 0.60; CI, 0.42-0.85), and VEM+COBI (HR = 0.50; CI, 0.36-0.70) for the overall study period. In the time-varying analysis, NIVO+IPI was associated with significant improvements in OS and PFS compared with the BRAF/MEK inhibitors 12 months after treatment initiation. There were no significant differences between NIVO+IPI and BRAF/MEK inhibitor treatment from 0 to 12 months. Safety outcomes favored DAB+TRAM over NIVO+IPI, whereas NIVO+IPI was comparable to VEM+COBI.
CONCLUSION
Results of this MAIC demonstrated durable OS and PFS benefits for patients with BRAF-mutant advanced melanoma treated with NIVO+IPI compared with BRAF/MEK inhibitors, with the greatest benefits noted after 12 months.
Topics: Antineoplastic Combined Chemotherapy Protocols; Humans; Ipilimumab; Melanoma; Mitogen-Activated Protein Kinase Kinases; Nivolumab; Proto-Oncogene Proteins B-raf
PubMed: 33556898
DOI: 10.1016/j.esmoop.2021.100050 -
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 -
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 -
Medicine Mar 2019The prognostic significance of PBK/TOPK overexpression in solid tumors remains controversial. Therefore, we carried out a meta-analysis to evaluate the impact of... (Meta-Analysis)
Meta-Analysis
BACKGROUND
The prognostic significance of PBK/TOPK overexpression in solid tumors remains controversial. Therefore, we carried out a meta-analysis to evaluate the impact of PBK/TOPK overexpression in solid tumors on patients' overall survival (OS) and disease-free survival (DFS).
METHODS
Relevant articles were identified through searching the PubMed, Embase and Web of Science up to May 2017. The pooled hazard ratio (HR) with 95% confidence interval (CI) was used to estimate the effects.
RESULTS
In this meta-analysis, 12 studies involving 1571 participants were included, PBK/TOPK overexpression was significantly associated with poor OS (pooled HR = 1.91, 95%CI = 1.22-3.00, P = .005) and short DFS (pooled HR = 1.95, 95%CI = 1.46-2.58, P < .001).
CONCLUSIONS
PBK/TOPK overexpression was associated with poor survival in human solid tumors which may be a valuable prognosis biomarker and a potential therapeutic target of solid tumors.
Topics: Biomarkers, Tumor; Gene Expression Regulation, Neoplastic; Humans; Mitogen-Activated Protein Kinase Kinases; Neoplasms; Prognosis
PubMed: 30855480
DOI: 10.1097/MD.0000000000014766 -
Breast Cancer Research : BCR Aug 2015Several studies have suggested that anti-diabetic insulin analogue treatment might increase cancer risk. The aim of this study was to review the postulated association... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
Several studies have suggested that anti-diabetic insulin analogue treatment might increase cancer risk. The aim of this study was to review the postulated association between insulin and insulin analogue treatment and breast cancer development, and plausible mechanisms.
METHOD
A systematic literature search was performed on breast cell-line, animal and human studies using the key words 'insulin analogue' and 'breast neoplasia' in MEDLINE at PubMed, EMBASE, and ISI Web of Science databases. A quantitative and qualitative review was performed on the epidemiological data; due to a limited number of reported estimates, a meta-analysis was performed for glargine only. A comprehensive overview was composed for in vitro and animal studies. Protein and gene expression was analysed for the cell lines most frequently used in the included in vitro studies.
RESULTS
In total 16 in vitro, 5 animal, 2 in vivo human and 29 epidemiological papers were included. Insulin AspB10 showed mitogenic properties in vitro and in animal studies. Glargine was the only clinically available insulin analogue for which an increased proliferative potential was found in breast cancer cell lines. However, the pooled analysis of 13 epidemiological studies did not show evidence for an association between insulin glargine treatment and an increased breast cancer risk (HR 1.04; 95 % CI 0.91-1.17; p=0.49) versus no glargine in patients with diabetes mellitus. It has to be taken into account that the number of animal studies was limited, and epidemiological studies were underpowered and suffered from methodological limitations.
CONCLUSION
There is no compelling evidence that any clinically available insulin analogue (Aspart, Determir, Glargine, Glulisine or Lispro), nor human insulin increases breast cancer risk. Overall, the data suggests that insulin treatment is not involved in breast tumour initiation, but might induce breast tumour progression by up regulating mitogenic signalling pathways.
Topics: Animals; Breast Neoplasms; Cell Line, Tumor; Diabetes Mellitus, Type 2; Female; Humans; Hypoglycemic Agents; Insulin Glargine; MCF-7 Cells; Risk
PubMed: 26242987
DOI: 10.1186/s13058-015-0611-2 -
BioMed Research International 2021Acute respiratory distress syndrome (ARDS) is defined as the acute onset of noncardiogenic edema and subsequent gas-exchange impairment due to a severe inflammatory... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
Acute respiratory distress syndrome (ARDS) is defined as the acute onset of noncardiogenic edema and subsequent gas-exchange impairment due to a severe inflammatory process known as cytokine storm. Xuebijing injection (hereinafter referred to as Xuebijing) is a patent drug that was used to treat ARDS or severe pneumonia (SP) in China. However, its efficacy and mechanism of actions remain unclear. In this study, we used meta-analysis and network pharmacology to assess these traits of Xuebijing.
METHODS
We searched PubMed, Embase, Cochrane Library, China National Knowledge Infrastructure (CNKI), and Wanfang databases for randomized controlled trials (RCTs) that evaluated Xuebijing therapy for ARDS or SP. The outcomes were total mortality, intensive care unit (ICU) stay time, and TNF- and IL-6 levels. We performed a meta-analysis using RevMan 5.3 software. The putative targets, top 10 proteins, and possible pathway of Xuebinjing on ARDS were analyzed by network pharmacology. TNF- and IL-6 were further docked with the six main active components of Xuebinjing using AutoDock 4.2.6 and PyMol 1.5.0.3 software.
RESULTS
Fifteen RCTs involving 2778 patients (13 ARDS and 2 SP) were included. Compared with the control, Xuebijing treatment significantly reduced the mortality rate (risk ratio, 0.64 (95% credible interval (CrI), 0.54-0.77)), reduced the ICU stay time (mean difference (MD), -4.51 (95% CrI, -4.97--4.06)), reduced the TNF- ((MD), -1.23 (95% CrI, -1.38--1.08)) and IL-6 ((MD), -1.15 (95% CrI, -1.52--0.78)) levels. The 56 putative targets, top 10 proteins (MAPK1 (mitogen-activated protein kinase 1), MAPK8 (mitogen-activated protein kinase 8), RELA (transcription factor p65), NFKB1 (nuclear factor NF-kappa-B p105 subunit), JUN (transcription factor AP-1), SRC (proto-oncogene tyrosine-protein kinase), TNF (tumor necrosis factor), HRAS (GTPase HRas), IL6 (interleukin-6), and APP (amyloid-beta A4 protein)), and possible pathways (Ret tyrosine kinase, IL2-mediated signaling events, CD4+/CD8+ T cell-related TCR signaling, p75(NTR)-mediated signaling, CXCR4-mediated signaling events, LPA receptor-mediated events, IL12-mediated signaling events, FAS (CD95) signaling pathway, and immune system) of Xuebinjing's action on ARDS were obtained. The molecular docking results showed that all the six components of Xuebinjing docked with TNF-, and two components docked with IL-6 got the binding energies lower than -5.
CONCLUSION
Our results recommended Xuebijing treatment for patients with ARDS. Xuebijing has therapeutic effects on ARDS patients partly by regulating the immune cell/cytokine pathways and thus inhibiting the cytokine storm. TNF- is the cytokine both directly and indirectly inhibited by Xuebijing, and IL-6 is the cytokine mainly indirectly inhibited by Xuebijing.
Topics: Drugs, Chinese Herbal; Gene Expression Regulation; Humans; Intensive Care Units; Proto-Oncogene Mas; Respiratory Distress Syndrome; Signal Transduction
PubMed: 34124260
DOI: 10.1155/2021/8824059 -
Translational Cancer Research Oct 2020Lung cancer is the leading cause of cancer-related deaths worldwide and the overall survival of patients with non-small cell lung cancer has not been improved. Let-7...
BACKGROUND
Lung cancer is the leading cause of cancer-related deaths worldwide and the overall survival of patients with non-small cell lung cancer has not been improved. Let-7 family has been shown to act as tumor suppressors by inhibiting oncogenes and key regulators of mitogenic pathways, while far fewer clinical studies addressing the association between let-7 expression and the disease prognosis have been published up to date. Therefore, our meta-analysis aims to determine the prognostic significance of let-7 expression in lung cancer patients.
METHODS
PubMed, EMBASE, the Web of Science and China National Knowledge Infrastructure (CNKI) databases were searched for full-text literature citations. We applied the hazard ratio (HR) with 95% confidence interval (CI) as the appropriate summarized statistics. Q-test and I2 statistic were used to estimate the level of heterogeneity. The publication bias was detected by Begg's test and Egger's test.
RESULTS
Seven eligible studies involving 2,262 patients were selected for this meta-analysis. The combined HR for the seven eligible studies was 0.61 (95% CI: 0.53-0.70, P<0.00001) and heterogeneity of overall prognosis was relatively high (I=76.4%, P=0.000). We conducted a further subgroup analysis, including an evaluation of the relationship between let-7 expression, lung cancer pathology, race, and sample size. All the results revealed that a significantly low let-7 expression in patients was an indicator of poor survival. Neither Begg's test nor Egger's test found publication bias in any analysis.
CONCLUSIONS
The present evidence indicates that the low let-7 expression can be considered as a significant predictor of worse prognosis in patients with lung cancer. The findings of our meta-analysis may be further confirmed in the future by the use of more updated review pooling and more relevant investigations.
PubMed: 35117243
DOI: 10.21037/tcr-20-1240