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The Brazilian Journal of Infectious... 2017The current increment of invasive fungal infections and the availability of new broad-spectrum antifungal agents has increased the use of these agents by non-expert... (Review)
Review
The current increment of invasive fungal infections and the availability of new broad-spectrum antifungal agents has increased the use of these agents by non-expert practitioners, without an impact on mortality. To improve efficacy while minimizing prescription errors and to reduce the high monetary cost to the health systems, the principles of pharmacokinetics (PK) and pharmacodynamics (PD) are necessary. A systematic review of the PD of antifungals agents was performed aiming at the practicing physician without expertise in this field. The initial section of this review focuses on the general concepts of antimicrobial PD. In vitro studies, fungal susceptibility and antifungal serum concentrations are related with different doses and dosing schedules, determining the PD indices and the magnitude required to obtain a specific outcome. Herein the PD of the most used antifungal drug classes in Latin America (polyenes, azoles, and echinocandins) is discussed.
Topics: Antifungal Agents; Area Under Curve; Aspergillosis; Azoles; Candidiasis; Dose-Response Relationship, Drug; Echinocandins; Humans; Latin America; Microbial Sensitivity Tests; Polyenes; Triazoles
PubMed: 27821250
DOI: 10.1016/j.bjid.2016.09.009 -
Autoimmunity Reviews Sep 2023Psoriatic arthritis (PsA) is an inflammatory complex condition. Posttranslational modifications influence almost all aspects of normal cell biology and pathogenesis. The... (Review)
Review
BACKGROUND AND AIMS
Psoriatic arthritis (PsA) is an inflammatory complex condition. Posttranslational modifications influence almost all aspects of normal cell biology and pathogenesis. The aim of this systematic review was to collect all published evidence regarding posttranslational modifications in PsA, and the main outcome was to evaluate an association between disease outcomes and specific posttranslational modifications in PsA.
METHODS
A systematic electronic search was performed in Medline, PubMed, Cochrane, Virtual Health Library, and Embase databases. A total of 587 articles were identified; 59 were evaluated after removing duplicates and scanning, of which 47 were included. A descriptive analysis was conducted, with results grouped according to the type of posttranslational modification evaluated. The protocol was registered at the PROSPERO database.
RESULTS
Seven posttranslational modifications were identified: citrullination, carbamylation, phosphorylation, glycosylation, acetylation, methylation, and oxidative stress. Anti-citrullinated peptide and anti-carbamylated protein have been evaluated in rheumatoid arthritis. There is now information suggesting that these antibodies may be helpful in improving the diagnosis of PsA and that they may demonstrate a correlation with worse disease progression (erosions, polyarticular involvement, and poor treatment response). Glycosylation was associated with increased inflammation and phosphorylation products related to the expression of SIRT2 and pSTAT3 or the presence of Th17 and cytokine interleukin-22, suggesting a possible therapeutic target.
CONCLUSIONS
Posttranslational modifications often play a key role in modulating protein function in PsA and correlate with disease outcomes. Citrullination, carbamylation, phosphorylation, glycosylation, acetylation, methylation, and oxidative stress were identified as associated with diagnosis and prognosis.
Topics: Humans; Arthritis, Psoriatic; Protein Processing, Post-Translational; Citrullination; Glycosylation; Arthritis, Rheumatoid
PubMed: 37487969
DOI: 10.1016/j.autrev.2023.103393 -
The Journal of Headache and Pain Dec 2017Calcitonin gene-related peptide (CGRP) is widely distributed in nociceptive pathways in human peripheral and central nervous system and its receptors are also expressed... (Review)
Review
BACKGROUND
Calcitonin gene-related peptide (CGRP) is widely distributed in nociceptive pathways in human peripheral and central nervous system and its receptors are also expressed in pain pathways. CGRP is involved in migraine pathophysiology but its role in non-headache pain has not been clarified.
METHODS
We performed a systematic literature search on PubMed, Embase and ClinicalTrials.gov for articles on CGRP and non-headache pain covering human studies including experimental studies and randomized clinical trials.
RESULTS
The literature search identified 375 citations of which 50 contained relevant original data. An association between measured CGRP levels and somatic, visceral, neuropathic and inflammatory pain was found. In 13 out of 20 studies in somatic pain conditions, CGRP levels had a positive correlation with pain. Increased CGRP levels were reported in plasma, synovial and cerebrospinal fluid in subjects with musculoskeletal pain. A randomized clinical trial on monoclonal antibody, which selectively binds to and inhibits the activity of CGRP (galcanezumab) in patients with osteoarthritis knee pain, failed to demonstrate improvement of pain compared with placebo. No studies to date have investigated the efficacy of monoclonal antibodies against CGRP receptor in non-headache pain conditions.
CONCLUSION
The present review revealed the association between measured CGRP levels and somatic, visceral, neuropathic and inflammatory pain. These data suggest that CGRP may act as a neuromodulator in non-headache pain conditions. However, more studies are needed to fully understand the role of CGRP in nociceptive processing and therapy of chronic pain.
Topics: Calcitonin Gene-Related Peptide; Humans; Pain
PubMed: 28303458
DOI: 10.1186/s10194-017-0741-2 -
Inflammation Research : Official... Nov 2022Gasdermin D (GSDMD) is a cytoplasmic protein that is encoded by the gasdermin family GSDMD gene and is the ultimate executor of pyroptosis. Pyroptosis is a mode of lysis... (Review)
Review
PURPOSE
Gasdermin D (GSDMD) is a cytoplasmic protein that is encoded by the gasdermin family GSDMD gene and is the ultimate executor of pyroptosis. Pyroptosis is a mode of lysis and inflammation that regulates cell death, ultimately leading to cell swelling and rupture. In sepsis, a dysregulated host response to infection frequently results in hyperinflammatory responses and immunosuppression, eventually leading to multiple organ dysfunction. Pyroptosis regulates innate immune defenses and plays an important role in the process of inflammatory cell death, and the absence of any link in the entire pathway from GSDMD to pyroptosis causes bacterial clearance to be hampered. Under normal conditions, the process of pyroptosis occurs much faster than apoptosis, and the threat to the body is also much greater.
MATERIALS AND METHODS
We conducted a systematic review of relevant reviews and experimental articles using the keywords sepsis, Gasdermin D, and Pyroptosis in the PubMed, Scopus, Google Scholar, and Web of Science databases.
CONCLUSION
Combined with the pathogenesis of sepsis, it is not difficult to find that pyroptosis plays a key role in bacterial inflammation and sepsis. Therefore, GSDMD inhibitors may be used as targeted drugs to treat sepsis by reducing the occurrence of pyroptosis. This review mainly discusses the key role of GSDMD in sepsis.
Topics: Humans; Phosphate-Binding Proteins; Intracellular Signaling Peptides and Proteins; Pyroptosis; Sepsis
PubMed: 35969260
DOI: 10.1007/s00011-022-01624-9 -
Medical Oncology (Northwood, London,... Aug 2016C-Jun activation domain-binding protein-1 (Jab1) not only is full but also a subunit (CSN5) of the constitutive photomorphogenesis 9 signalosome (CSN), which is an... (Review)
Review
C-Jun activation domain-binding protein-1 (Jab1) not only is full but also a subunit (CSN5) of the constitutive photomorphogenesis 9 signalosome (CSN), which is an evolutionarily conserved and multifunctional protein that involves in controlling cellular proliferation and apoptosis, affecting a series of pathways, as well as regulating genomic instability and DNA damage and repair. The CSN is a highly conservative protein from yeast to human and interacts with the cullin-RING family of ubiquitin ligases so that it could be execute a process of removing NEDD8, a ubiquitin-like polypeptide (deneddylase activity). The role of Jab1/CSN5's multi-function has been proved as being oncogenic in nature, what is more, Jab1/CSN5 has been confirmed by much evidence that it participates in the carcinogenesis progression and is tightly associated with poor prognosis. However, the biologic implication of Jab1/CSN5 activity during the cancer's development is unclear. We performed a systematic literature review and assessment from PubMed and Medline databases in this article. Jab1/CSN5 is participate in a lot of biologic responses, including cell proliferation, apoptosis, cell cycle regulation, DNA metabolism, invasion, DNA damage and repair, and recurrence. It also promotes cell transformation and tumorigenesis. In this review, we mainly expound the progress in the function and research advances of Jab1/CSN5 and in untangling the Jab1/CSN5 signaling pathway. Based on these bases, its potential as a therapeutic target for cancer can play a greater role in future cancer treatment.
Topics: Animals; COP9 Signalosome Complex; Carcinogenesis; Humans; Intracellular Signaling Peptides and Proteins; Neoplasms; Peptide Hydrolases; Signal Transduction
PubMed: 27412572
DOI: 10.1007/s12032-016-0805-1 -
International Journal of Molecular... May 2023Biomarker development, improvement, and clinical implementation in the context of kidney disease have been a central focus of biomedical research for decades. To this... (Review)
Review
Biomarker development, improvement, and clinical implementation in the context of kidney disease have been a central focus of biomedical research for decades. To this point, only serum creatinine and urinary albumin excretion are well-accepted biomarkers in kidney disease. With their known blind spot in the early stages of kidney impairment and their diagnostic limitations, there is a need for better and more specific biomarkers. With the rise in large-scale analyses of the thousands of peptides in serum or urine samples using mass spectrometry techniques, hopes for biomarker development are high. Advances in proteomic research have led to the discovery of an increasing amount of potential proteomic biomarkers and the identification of candidate biomarkers for clinical implementation in the context of kidney disease management. In this review that strictly follows the PRISMA guidelines, we focus on urinary peptide and especially peptidomic biomarkers emerging from recent research and underline the role of those with the highest potential for clinical implementation. The Web of Science database (all databases) was searched on 17 October 2022, using the search terms "marker *" OR biomarker * AND "renal disease" OR "kidney disease" AND "proteome *" OR "peptid *" AND "urin *". English, full-text, original articles on humans published within the last 5 years were included, which had been cited at least five times per year. Studies based on animal models, renal transplant studies, metabolite studies, studies on miRNA, and studies on exosomal vesicles were excluded, focusing on urinary peptide biomarkers. The described search led to the identification of 3668 articles and the application of inclusion and exclusion criteria, as well as abstract and consecutive full-text analyses of three independent authors to reach a final number of 62 studies for this manuscript. The 62 manuscripts encompassed eight established single peptide biomarkers and several proteomic classifiers, including CKD273 and IgAN237. This review provides a summary of the recent evidence on single peptide urinary biomarkers in CKD, while emphasizing the increasing role of proteomic biomarker research with new research on established and new proteomic biomarkers. Lessons learned from the last 5 years in this review might encourage future studies, hopefully resulting in the routine clinical applicability of new biomarkers.
Topics: Humans; Proteomics; Renal Insufficiency, Chronic; Kidney; Peptides; Biomarkers
PubMed: 37298105
DOI: 10.3390/ijms24119156 -
Scientific Reports Dec 2016We aimed to comprehensively compare two compartmented oral proteomes, the salivary and the dental pellicle proteome. Systematic review and datamining was used to obtain... (Review)
Review
We aimed to comprehensively compare two compartmented oral proteomes, the salivary and the dental pellicle proteome. Systematic review and datamining was used to obtain the physico-chemical, structural, functional and interactional properties of 1,515 salivary and 60 identified pellicle proteins. Salivary and pellicle proteins did not differ significantly in their aliphatic index, hydrophaty, instability index, or isoelectric point. Pellicle proteins were significantly more charged at low and high pH and were significantly smaller (10-20 kDa) than salivary proteins. Protein structure and solvent accessible molecular surface did not differ significantly. Proteins of the pellicle were more phosphorylated and glycosylated than salivary proteins. Ion binding and enzymatic activities also differed significantly. Protein-protein-ligand interaction networks relied on few key proteins. The identified differences between salivary and pellicle proteins could guide proteome compartmentalization and result in specialized functionality. Key proteins could be potential targets for diagnostic or therapeutic application.
Topics: Animals; Data Mining; Dental Enamel Proteins; Dental Pellicle; Humans; Proteome; Salivary Proteins and Peptides
PubMed: 27966577
DOI: 10.1038/srep38882 -
Headache May 2023To systemically review preclinical studies investigating the implication of prolactin signaling in headache and migraine pathophysiology. (Review)
Review
OBJECTIVE
To systemically review preclinical studies investigating the implication of prolactin signaling in headache and migraine pathophysiology.
BACKGROUND
The features of migraine attacks, including characteristics, duration, frequency, and prevalence, are sex-dependent with variability across a lifetime, indicating the involvement of the hypothalamus-pituitary-gonadal axis. Prolactin is a key regulator of this axis, and a new line of evidence implicates prolactin signaling in sex-related differences in pain perception.
METHODS
In this systematic review, we searched PubMed and EMBASE for the terms prolactin, hyperprolactinemia, macroprolactinemia, hypoprolactinemia, migraine, headache, head pain, and trigeminal pain pathway to find preclinical studies investigating prolactin signaling in headache and migraine. Two reviewers independently screened 841 articles for population, intervention, comparison, outcome, and study design. Studies were restricted to the English language and were excluded if they had a nonexperimental methodology.
RESULTS
Of a total of 15 preclinical articles selected, 11 were both ex vivo and in vivo, 3 were ex vivo, and 1 was an in vivo study. The main findings were that prolactin receptors are distributed in the trigeminal pain pathway, and prolactin induced migraine-like behavior in rodents. Moreover, prolactin signaling has a crucial role in calcitonin gene-related peptide (CGRP) release, a key molecule in migraine pathogenesis, and prolactin gene deletion attenuated CGRP-induced migraine-like behavior.
CONCLUSION
Preclinical data indicate a key role of prolactin and its receptors in mechanisms causing migraine. Further randomized and placebo-controlled clinical studies targeting prolactin signaling are needed to further clarify the influences of prolactin in migraine-attack initiation.
Topics: Humans; Calcitonin Gene-Related Peptide; Headache; Migraine Disorders; Pain; Prolactin; Animals; Mice; Rats
PubMed: 36752584
DOI: 10.1111/head.14412 -
Obesity Reviews : An Official Journal... Jun 2023The present study aimed to investigate the evidence on the effects of different long-term training interventions (aerobic [AeT], resistance [RT], and combined [COMB])... (Meta-Analysis)
Meta-Analysis Review
Long-term effects of different exercise training modes on cytokines and adipokines in individuals with overweight/obesity and cardiometabolic diseases: A systematic review, meta-analysis, and meta-regression of randomized controlled trials.
The present study aimed to investigate the evidence on the effects of different long-term training interventions (aerobic [AeT], resistance [RT], and combined [COMB]) and spontaneous physical activity (PA) in modifying cytokines and adipokines in individuals with overweight or obesity with or without cardiometabolic diseases while considering potential confounders. Although exercise interventions have become a potentially effective tool for preventing and treating metabolic diseases, the evidence provided by previous systematic reviews is inconclusive since several potential confounders have yet to be addressed. Therefore, we conducted a systematic literature search in Medline, Cochrane, and Embase databases from January 2000 to July 2022 and performed a meta-analysis. Inclusion criteria retrieved 106 full texts comprising 8,642 individuals with a range BMI of 25.1-43.8 kg m . We found that independently of the training mode, exercise had a beneficial effect on diminishing Adiponectin, C-reactive protein (CRP), IL-6, IL-18, IL-20, Leptin, sICAM, and TNF-α levels circulating levels. Furthermore, by subsequent analysis, we detected differential effects of AeT, RT, and COMB, with sex, age, body composition, and trial length acting as moderators. The comparison of training modes revealed a difference favoring COMB over AeT for regulating the increase in CRP with no differences in the remaining biomarkers. Meta-regression analysis revealed an effect of change in maximal oxygen uptake (VO ) on CRP, IL-6, and TNF-α, while IL-10 was influenced by the change in body fat. The results suggest that all interventions, except PA, are effective in lessening this population's inflammatory status, provided that exercise results in an increase of VO .
Topics: Humans; Overweight; Cytokines; Adipokines; Interleukin-6; Tumor Necrosis Factor-alpha; Randomized Controlled Trials as Topic; Obesity; Exercise; Cardiovascular Diseases
PubMed: 37040899
DOI: 10.1111/obr.13564 -
Metabolism: Clinical and Experimental Jul 2016Adiponectin (APN) is an adipokine with insulin-sensitizing, anti-inflammatory, and vasculoprotective properties. Hypoadiponectinemia has been linked with disease states,... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Adiponectin (APN) is an adipokine with insulin-sensitizing, anti-inflammatory, and vasculoprotective properties. Hypoadiponectinemia has been linked with disease states, such as obesity, type 2 diabetes, and cardiovascular disease. Carotid intima-media thickness (cIMT) is a strong and independent predictor of both coronary and cerebrovascular events, and has been used as a surrogate marker of subclinical atherosclerosis. The aim of this report is to systematically review the evidence on the relationship between APN and cIMT in a wide range of individuals.
MATERIALS AND METHODS
Medline, Embase, Biosis, Scopus, Web of Science, and Pubmed were searched for published studies and conference abstracts. The "sign test" and "vote count" methods were used to estimate the direction and significance of the relationship between APN and cIMT. The quality of the eligible studies was evaluated using an adapted version of the New Castle Ottawa quality assessment scale.
RESULTS
Fifty-five articles fulfilled the inclusion criteria, comprised of only cross-sectional studies, including healthy subjects, general population, and individuals with metabolic, inflammatory, or other chronic diseases. Most associations between APN and cIMT followed a negative direction in the healthier and general populations, and also in cohorts with metabolic disorders and other chronic diseases, but not in those with inflammatory diseases (sign test). These associations were generally found to be weak or non-significant among all cohort groups studied (vote count).
CONCLUSION
Our results are suggestive but not conclusive for an inverse association between APN levels and cIMT in diseased and non-diseased populations.
Topics: Adiponectin; Carotid Intima-Media Thickness; Humans; Metabolic Diseases; Risk Factors
PubMed: 27282868
DOI: 10.1016/j.metabol.2016.03.008