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International Reviews of Immunology 2016Human aging is a complex process with pivotal changes in gene expression of biological pathways. Immune system dysfunction has been recognized as one of the most... (Review)
Review
Human aging is a complex process with pivotal changes in gene expression of biological pathways. Immune system dysfunction has been recognized as one of the most important abnormalities induced by senescent names immunosenescence. Emerging evidences suggest miR role in immunosenescence. We aimed to systemically review all relevant reports to clearly state miR effects on immunosenescence process. Sensitive electronic searches carried out. Quality assessment has been performed. Since majority of the included studies were laboratory works, and therefore heterogen, we discussed miR effects on immunological aging process nonstatically. Forty-six articles were found in the initial search. After exclusion of 34 articles, 12 studies enrolled to the final stage. We found that miRs have crucial roles in exact function of immune system. MiRs are involved in the regulation of the aging process in the immune system components and target certain genes, promoting or inhibiting immune system reaction to invasion. Also, miRs control life span of the immune system members by regulation of the genes involved in the apoptosis. Interestingly, we found that immunosenescence is controllable by proper manipulation of the various miRs expression. DNA methylation and histone acetylation have been discovered as novel strategies, altering NF-κB binding ability to the miR promoter sites. Effect of miRs on impairment of immune system function due to the aging is emerging. Although it has been accepted that miRs have determinant roles in the regulation of the immunosenescence; however, most of the reports are concluded from animal/laboratory works, suggesting the necessity of more investigations in human.
Topics: Animals; Apoptosis; B-Lymphocytes; Cell Differentiation; Cytokines; Gene Expression Regulation; Humans; Immune System; Immunosenescence; Lipopolysaccharides; Mice; MicroRNAs; NF-kappa B; Neutrophils; T-Lymphocytes
PubMed: 26327579
DOI: 10.3109/08830185.2015.1077828 -
Asia-Pacific Journal of Clinical... Mar 2016Endocrine therapy is an established and effective treatment strategy for hormone receptor positive metastatic breast cancer. The clinical utility of endocrine therapy is... (Review)
Review
Endocrine therapy is an established and effective treatment strategy for hormone receptor positive metastatic breast cancer. The clinical utility of endocrine therapy is lost over time due to evolving changes in tumor biology and the development of endocrine resistance. Many agents targeting the intracellular signaling pathways associated with endocrine resistance are in development. Encouraging early results have been seen for agents which directly target the estrogen receptor (ER), inhibitors of co-signaling pathways, inhibitors of ER chaperones, ER antagonists able to inhibit mutated or otherwise activated ERs, and modulators of histone acetylation restoring synthesis of ER signaling components. Following our systematic review of treatments with established benefits in this supplement, we review some of the more promising new strategies for overcoming endocrine resistance, looking at the impact on disease control and quality of life for women with hormone receptor positive, HER2 negative breast cancer. We also examine the biomarkers that may guide selection of the best therapy for the individual.
Topics: Breast Neoplasms; Clinical Trials as Topic; Combined Modality Therapy; Female; Humans; Meta-Analysis as Topic; Molecular Targeted Therapy; Neoplasm Proteins; Prognosis; Receptor, ErbB-2; Receptors, Estrogen; Receptors, Progesterone; Signal Transduction
PubMed: 27001209
DOI: 10.1111/ajco.12492 -
Journal of Chromatography. B,... Jul 2017Aloe arborescens Miller (Family Asphodelaceae) is a member of genus Aloe, which is used in traditional medicine to cure various diseases. The extracts of the plant have... (Review)
Review
Aloe arborescens Miller (Family Asphodelaceae) is a member of genus Aloe, which is used in traditional medicine to cure various diseases. The extracts of the plant have been reported to possess anticancer, immunomodulator, antidiabetic, anti-inflammatory and antioxidant activities. The phytochemical investigations have revealed diverse chemical constituents, including phenolics [anthraquinones, anthrones, pyrones, chromones and coumarins], polysaccharides [arborans [(1-4) linked glucomannans, polysaccharide (A, B and C): (A: a linear (1-6)-O-α-glucan, B: a branching (1-2)-O-l-arabinose with (1-2)-O-d-galactose linkages and C: (1-4)-O-β-mannan with 18% acetyl group)]], glycoproteins and carboxypeptidase enzyme. There are many reports, describing the different methodologies developed to perform chemical analysis as well as, separation, detection and identification of these constituents. Different chromatographic techniques were applied such as gas chromatography (GC), high-performance liquid chromatography (HPLC), liquid chromatography-electrospray ionization coupled with mass spectroscopy (LC-ESI/MS/MS) and gel filtration chromatography. Also the isolated compounds were identified based on the spectroscopic analysis; ultraviolet-visible spectroscopy (UV-vis), infra-red spectroscopy (IR), mass spectroscopy (MS) and nuclear-magnetic resonance (NMR). This study aims to pinpoint the active components besides finding out new structural leads for future drugs. Therefore, the review is targeted to provide evidence reported in the relevant literature on qualitative and quantitative research to assist scientists in isolation and characterization of bioactive compounds in A. arborescens.
Topics: Aloe; Chromatography, Gas; Chromatography, High Pressure Liquid; Glycoproteins; Phenols; Plant Extracts; Spectrometry, Mass, Electrospray Ionization; Tandem Mass Spectrometry
PubMed: 28535423
DOI: 10.1016/j.jchromb.2017.04.044 -
Endocrine, Metabolic & Immune Disorders... 2021Immune dysregulation, neuronal inflammation, and oligodendrocyte degradation are key causes for autoimmune disorders like multiple sclerosis (MS) and various other...
Dysregulation of SIRT-1 Signaling in Multiple Sclerosis and Neuroimmune Disorders: A Systematic Review of SIRTUIN Activators as Potential Immunomodulators and their Influences on other Dysfunctions.
Immune dysregulation, neuronal inflammation, and oligodendrocyte degradation are key causes for autoimmune disorders like multiple sclerosis (MS) and various other immune dysregulated neurodegenerative complications responsible for CNS-mediated immune responses. Sirtuin (SIRT-1) is a nicotinamide adenosine dinucleotide (NAD)-dependent transcriptional protein that deacetylases and removes acetyl groups from its transcription factors like P53, FOXO, NF-Κb, PGC-1α. SIRT-1 mediates a wide range of physiological functions, including gene transcription, metabolism, neuronal apoptosis, and glucose production. SIRT-1 dysregulation targets transcription factors, and other molecular alterations such as gene expression modification influence neuronal plasticity, inhibit Th17 cells, and interleukin-1β can aggravate brain diseases. Preclinical and clinical findings show that the upregulation of SIRT-1 reduces autoimmunity, neurodegeneration, and neuroexcitation. Even though drugs are being developed for symptomatic therapies in clinical trials, there are particular pharmacological implications for improving post-operative conditions in neurodegenerative patients where intensive care is required. Understanding the SIRT-1 signaling and identifying immune-mediated neuron deterioration can detect major therapeutic interventions that could prevent neuro complications. Thus, in the current review, we have addressed the manifestations of disease by the downregulation of SIRT-1 that could potentially cause MS and other neurodegenerative disorders and provided data on existing available and effective drug therapies and disease management strategies.
Topics: Animals; Humans; Immunologic Factors; Multiple Sclerosis; Neurodegenerative Diseases; Neuroimmunomodulation; Signal Transduction; Sirtuin 1
PubMed: 33687904
DOI: 10.2174/1871530321666210309112234 -
Academic Radiology Oct 2021There is compelling evidence that neurochemical changes measured by proton magnetic resonance spectroscopy (H-MRS) occur at different phases of Alzheimer's disease (AD).... (Review)
Review
BACKGROUND
There is compelling evidence that neurochemical changes measured by proton magnetic resonance spectroscopy (H-MRS) occur at different phases of Alzheimer's disease (AD). However, the extent to which these neurochemical changes are associated with validated AD biomarkers and/or apolipoprotein (APOE) ε4 is yet to be established.
OBJECTIVE
This systematic review analyzed the available evidence on (1) neurochemical changes; and (2) the relations between brain metabolite and validated cerebrospinal fluid biomarkers, and/or APOE in AD.
METHODS
PubMed, Cochrane, Scopus, and gray literature were systematically screened for studies deemed fit for the purpose of the current systematic review.
RESULTS
Twenty four articles met the inclusion criteria. Decreased levels of N-acetyl aspartate (NAA), NAA/(creatine) Cr, and NAA/(myo-inositol) ml, and increased ml, ml/Cr, Cho (choline)/Cr, and ml/NAA were found in the posterior cingulate cortex/precuneus. Increased ml is associated with increased tau levels, reduced NAA/Cr is associated with increased tau. ml/Cr is negatively correlated with Aβ42, and ml/Cr is positively correlated with t-tau. NAA and glutathione levels are reduced in APOE ε4 carriers. APOE ε4 exerts no modulatory effect on NAA/Cr. There is interaction between APOE ε4, Aβ42, and ml/Cr.
CONCLUSION
NAA, ml, NAA/Cr, NAA/ml and ml/Cr may be potentially useful biomarkers that may highlight functional changes in the clinical stages of AD. The combinations of ml and tau, NAA/Cr and Aβ42, and NAA/Cr and tau may support the diagnostic process of differentiating MCI/AD from healthy individuals. Large, longitudinal studies are required to clarify the effect of APOE ε4 on brain metabolites.
Topics: Alzheimer Disease; Amyloid beta-Peptides; Apolipoproteins; Brain; Humans; Proton Magnetic Resonance Spectroscopy
PubMed: 32651050
DOI: 10.1016/j.acra.2020.06.006 -
Anti-cancer Agents in Medicinal... 2018This systematic review aims to elucidate the role of melatonin (N-acetyl-5-metoxy-tryptamine) (MLT) in the prevention and treatment of cancer. MLT is a pineal gland...
This systematic review aims to elucidate the role of melatonin (N-acetyl-5-metoxy-tryptamine) (MLT) in the prevention and treatment of cancer. MLT is a pineal gland secretory product, an evolutionarily highly conserved molecule; it is also an antioxidant and an impressive protector of mitochondrial bioenergetic activity. MLT is characterized by an ample range of activities, modulating the physiology and molecular biology of the cell. Its physiological functions relate principally to the interaction of G Protein-Coupled MT1 and MT2 trans-membrane receptors (GPCRs), a family of guanidine triphosphate binding proteins. MLT has been demonstrated to suppress the growth of various tumours both, in vivo and in vitro. In this review, we analyze in depth, the antioxidant activity of melatonin, aiming to illustrate the cancer treatment potential of the molecule, by limiting or reversing the changes occurring during cancer development and growth.
Topics: Animals; Antineoplastic Agents; Antioxidants; Humans; Melatonin; Neoplasms; Oxidative Stress; Receptors, Melatonin
PubMed: 29173185
DOI: 10.2174/1871520617666171121120223 -
Critical Care (London, England) Feb 2019With the development of new techniques to easily obtain lower respiratory tract specimens, bronchoalveolar lavage fluid and other lung fluids are gaining importance in... (Meta-Analysis)
Meta-Analysis
BACKGROUND
With the development of new techniques to easily obtain lower respiratory tract specimens, bronchoalveolar lavage fluid and other lung fluids are gaining importance in pulmonary disease diagnosis. We aimed to review and summarize lung fluid biomarkers associated with acute respiratory distress syndrome diagnosis and mortality.
METHODS
After searching PubMed, Embase, Web of Science, and the Cochrane Library for articles published prior to January 11, 2018, we performed a meta-analysis on biomarkers for acute respiratory distress syndrome diagnosis in at-risk patients and those related to disease mortality. From the included studies, we then extracted the mean and standard deviation of the biomarker concentrations measured in the lung fluid, acute respiratory distress syndrome etiologies, sample size, demographic variables, diagnostic criteria, mortality, and protocol for obtaining the lung fluid. The effect size was measured by the ratio of means, which was then synthesized by the inverse-variance method using its natural logarithm form and transformed to obtain a pooled ratio and 95% confidence interval.
RESULTS
In total, 1156 articles were identified, and 49 studies were included. Increases in total phospholipases A2 activity, total protein, albumin, plasminogen activator inhibitor-1, soluble receptor for advanced glycation end products, and platelet activating factor-acetyl choline were most strongly associated with acute respiratory distress syndrome diagnosis. As for biomarkers associated with acute respiratory distress syndrome mortality, interleukin-1β, interleukin-6, interleukin-8, Kerbs von Lungren-6, and plasminogen activator inhibitor-1 were significantly increased in the lung fluid of patients who died. Decreased levels of Club cell protein and matrix metalloproteinases-9 were associated with increased odds for acute respiratory distress syndrome diagnosis, whereas decreased levels of Club cell protein and interleukin-2 were associated with increased odds for acute respiratory distress syndrome mortality.
CONCLUSIONS
This meta-analysis provides a ranking system for lung fluid biomarkers, according to their association with diagnosis or mortality of acute respiratory distress syndrome. The performance of biomarkers among studies shown in this article may help to improve acute respiratory distress syndrome diagnosis and outcome prediction.
Topics: Antigens, Human Platelet; Biomarkers; Bronchoalveolar Lavage Fluid; Hepatocyte Growth Factor; Humans; Interleukin-8; Lung; Plasminogen Activator Inhibitor 1; Platelet Activating Factor; Receptor for Advanced Glycation End Products; Respiratory Distress Syndrome
PubMed: 30755248
DOI: 10.1186/s13054-019-2336-6 -
Nutrition and Cancer Oct 2017Much of the recent research in neoplasia has been focusing on the epigenetics of cancer cells, particularly as regards the search for potential molecular biomarkers that... (Review)
Review
Much of the recent research in neoplasia has been focusing on the epigenetics of cancer cells, particularly as regards the search for potential molecular biomarkers that could be used for early diagnosis, effective treatment, and prognosis of several types of cancer. Carcinogenesis often starts with mutations in oncogenes and tumor suppressor genes, and it leads to anomalies in cellular processes as vital as cell cycle regulation and apoptosis. Because malignant changes arise as a result of genetic as well as epigenetic mechanisms, one possible means of intervention involves reprogramming gene expression, so as to-at least in part-revert the molecular alterations. DNA methylation and demethylation, acetylation and deacetylation of histones, and microRNAs are a few examples of the epigenetic mechanisms responsible for tumor development and progression. Many biologically active compounds present in food-including sulforaphane, curcumin, and epigallocatechin-have been found to modulate those processes. We here systematically review information on the effects of such bioactive dietary compounds on human breast cancer cell lines, and explore the mechanisms underlying those effects with a view to their potential therapeutic application.
Topics: Antineoplastic Agents, Phytogenic; Apoptosis; Breast Neoplasms; Catechin; Cell Cycle; Cell Line, Tumor; Curcumin; Epigenesis, Genetic; Female; Humans; Isothiocyanates; Sulfoxides; Telomerase
PubMed: 28872903
DOI: 10.1080/01635581.2017.1359322 -
Actas Urologicas Espanolas Oct 2016Clinical practice guidelines recommend measuring serum testosterone (ST) during androgenic suppression (AS) to assess its efficacy and define castration resistance (CR).... (Review)
Review
INTRODUCTION
Clinical practice guidelines recommend measuring serum testosterone (ST) during androgenic suppression (AS) to assess its efficacy and define castration resistance (CR). The objectives of this systematic review were to assess the level of scientific evidence that justify checking ST levels during AS, when to perform it and for what purpose.
MATERIAL AND METHODS
We performed a search in PubMed with the following mesh terms: androgen suppression, testosterone, and prostate cancer. The search was narrowed to original articles published in English.
RESULTS
We found 8 publications that analysed the clinical impact of ST concentrations during AS. In all of the series, ST was measured using chemiluminescent assays. However, only indirect methods based on liquid or gas chromatography for its extraction and subsequent quantification using mass spectrometry are recommended, especially for measuring low levels. The endpoints were specific survival and CR-free survival. Six studies were retrospective. The series were not uniform in terms of clinical stage, types of AS and ST assessment methods. In general, low ST levels (<20ng/dL or <32ng/dL) were related to longer CR-free survival. The measurements were performed every 3 or 6 months. Four studies confirmed the beneficial effect of adding bicalutamide when detecting microelevations above 50ng/dL.
CONCLUSIONS
The level of scientific evidence justifying the measurement of ST during AS is low, and the methods employed for quantifying ST levels are inadequate. However, we consider it useful to check ST levels during AS, and there appears to be an association between low ST levels and better disease outcomes. In the event of microelevations above 50ng/dL, we recommend the administration of bicalutamide.
Topics: Androgen Antagonists; Anilides; Antineoplastic Agents, Hormonal; Flutamide; Gonadotropin-Releasing Hormone; Humans; Male; Nitriles; Oligopeptides; Orchiectomy; Prostatic Neoplasms; Testosterone; Tosyl Compounds
PubMed: 26899928
DOI: 10.1016/j.acuro.2016.01.006 -
Sports Medicine (Auckland, N.Z.) Jun 2022The 5' adenosine monophosphate (AMP)-activated protein kinase (AMPK) is a cellular energy sensor that is activated by increases in the cellular AMP/adenosine... (Meta-Analysis)
Meta-Analysis
BACKGROUND
The 5' adenosine monophosphate (AMP)-activated protein kinase (AMPK) is a cellular energy sensor that is activated by increases in the cellular AMP/adenosine diphosphate:adenosine triphosphate (ADP:ATP) ratios and plays a key role in metabolic adaptations to endurance training. The degree of AMPK activation during exercise can be influenced by many factors that impact on cellular energetics, including exercise intensity, exercise duration, muscle glycogen, fitness level, and nutrient availability. However, the relative importance of these factors for inducing AMPK activation remains unclear, and robust relationships between exercise-related variables and indices of AMPK activation have not been established.
OBJECTIVES
The purpose of this analysis was to (1) investigate correlations between factors influencing AMPK activation and the magnitude of change in AMPK activity during cycling exercise, (2) investigate correlations between commonly reported measures of AMPK activation (AMPK-α2 activity, phosphorylated (p)-AMPK, and p-acetyl coenzyme A carboxylase (p-ACC), and (3) formulate linear regression models to determine the most important factors for AMPK activation during exercise.
METHODS
Data were pooled from 89 studies, including 982 participants (93.8% male, maximal oxygen consumption [[Formula: see text]] 51.9 ± 7.8 mL kg min). Pearson's correlation analysis was performed to determine relationships between effect sizes for each of the primary outcome markers (AMPK-α2 activity, p-AMPK, p-ACC) and factors purported to influence AMPK signaling (muscle glycogen, carbohydrate ingestion, exercise duration and intensity, fitness level, and muscle metabolites). General linear mixed-effect models were used to examine which factors influenced AMPK activation.
RESULTS
Significant correlations (r = 0.19-0.55, p < .05) with AMPK activity were found between end-exercise muscle glycogen, exercise intensity, and muscle metabolites phosphocreatine, creatine, and free ADP. All markers of AMPK activation were significantly correlated, with the strongest relationship between AMPK-α2 activity and p-AMPK (r = 0.56, p < 0.001). The most important predictors of AMPK activation were the muscle metabolites and exercise intensity.
CONCLUSION
Muscle glycogen, fitness level, exercise intensity, and exercise duration each influence AMPK activity during exercise when all other factors are held constant. However, disrupting cellular energy charge is the most influential factor for AMPK activation during endurance exercise.
Topics: AMP-Activated Protein Kinases; Acetyl-CoA Carboxylase; Adenosine Diphosphate; Adenosine Monophosphate; Female; Glycogen; Humans; Male; Muscle, Skeletal
PubMed: 34878641
DOI: 10.1007/s40279-021-01610-x