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PloS One 2021Drug research with animal models is expensive, time-consuming and translation to clinical trials is often poor, resulting in a desire to replace, reduce, and refine the...
Drug research with animal models is expensive, time-consuming and translation to clinical trials is often poor, resulting in a desire to replace, reduce, and refine the use of animal models. One approach to replace and reduce the use of animal models is to use in vitro cell-culture models. To study bone physiology, bone diseases and drugs, many studies have been published using osteoblast-osteoclast co-cultures. The use of osteoblast-osteoclast co-cultures is usually not clearly mentioned in the title and abstract, making it difficult to identify these studies without a systematic search and thorough review. As a result, researchers are all developing their own methods, leading to conceptually similar studies with many methodological differences and, as a consequence, incomparable results. The aim of this study was to systematically review existing osteoblast-osteoclast co-culture studies published up to 6 January 2020, and to give an overview of their methods, predetermined outcome measures (formation and resorption, and ALP and TRAP quantification as surrogate markers for formation and resorption, respectively), and other useful parameters for analysis. Information regarding these outcome measures was extracted and collected in a database, and each study was further evaluated on whether both the osteoblasts and osteoclasts were analyzed using relevant outcome measures. From these studies, additional details on methods, cells and culture conditions were extracted into a second database to allow searching on more characteristics. The two databases presented in this publication provide an unprecedented amount of information on cells, culture conditions and analytical techniques for using and studying osteoblast-osteoclast co-cultures. They allow researchers to identify publications relevant to their specific needs and allow easy validation and comparison with existing literature. Finally, we provide the information and tools necessary for others to use, manipulate and expand the databases for their needs.
Topics: Animals; Bone Resorption; Cell Differentiation; Coculture Techniques; Databases, Factual; Drug Discovery; Humans; Models, Animal; Osteoblasts; Osteoclasts; RANK Ligand
PubMed: 34735456
DOI: 10.1371/journal.pone.0257724 -
European Archives of... Jan 2022Many studies have investigated the prognostic value of tumor-infiltrating lymphocytes (TILs) and tumor-infiltrating macrophages (TIMs) in patients with nasopharyngeal... (Meta-Analysis)
Meta-Analysis Review
PURPOSE
Many studies have investigated the prognostic value of tumor-infiltrating lymphocytes (TILs) and tumor-infiltrating macrophages (TIMs) in patients with nasopharyngeal carcinoma (NPC), but the results remain controversial. Here, we performed a meta-analysis to evaluate the prognostic significance of TILs/TIMs in patients with NPC METHODS: The study was registered with PROSPERO (CRD42021234078). PubMed, Embase, and Web of Science databases were searched up to Dec 30, 2020. We reviewed studies that evaluated the relationship between TILs/TIMs and overall survival (OS), disease-free survival (DFS), or progression-free survival (PFS) in NPC. For TILs, CD3, CD4, CD8, and FOXP3 were searched as T-cell markers, CD19 and CD20 as B-cell markers, and CD56 as a natural killer cell marker. For TIMs, CD68 and CD163 were searched as total and M2 macrophage markers, respectively.
RESULTS
In total, 19 studies with 3708 NPC were included in this meta-analysis. We found that high total numbers of TILs were significantly associated with favorable OS [hazard ratio (HR) 0.46, 95% confidence interval (CI) 0.38-0.57 and PFS (HR 0.48, 95% CI 0.38-0.62)]. In contrast, tumor infiltration by CD3+ T cells (HR 0.55, 95% CI 0.39-0.76), CD4+ T cells (HR 0.40, 95% CI 0.18-0.85), and CD8+ T cells (HR 0.56, 95% CI 0.34-0.93) correlated positively with OS. No significant relationship was found between survival and tumor infiltration by FOXP3+ T cells, CD68+ macrophages, or CD163+ macrophages.
CONCLUSION
Our findings revealed that tumor infiltration by CD3+ , CD4+ , and CD8+ T cells could be prognostic biomarkers in NPC.
Topics: Humans; Lymphocytes, Tumor-Infiltrating; Macrophages; Nasopharyngeal Carcinoma; Nasopharyngeal Neoplasms; Prognosis
PubMed: 34027599
DOI: 10.1007/s00405-021-06879-2 -
Clinical Oral Investigations Apr 2021This integrative review aimed to report the toxic effect of submicron and nano-scale commercially pure titanium (cp Ti) debris on cells of peri-implant tissues. (Review)
Review
OBJECTIVE
This integrative review aimed to report the toxic effect of submicron and nano-scale commercially pure titanium (cp Ti) debris on cells of peri-implant tissues.
MATERIALS AND METHODS
A systematic search was carried out on the PubMed electronic platform using the following key terms: Ti "OR" titanium "AND" dental implants "AND" nanoparticles "OR" nano-scale debris "OR" nanometric debris "AND" osteoblasts "OR "cytotoxicity" OR "macrophage" OR "mutagenic" OR "peri-implantitis". The inclusion criteria involved articles published in the English language, until December 26, 2020, reporting the effect of nano-scale titanium particles as released from dental implants on the toxicity and damage of osteoblasts.
RESULTS
Of 258 articles identified, 14 articles were selected for this integrative review. Submicron and nano-scale cp Ti particles altered the behavior of cells in culture medium. An inflammatory response was triggered by macrophages, fibroblasts, osteoblasts, mesenchymal cells, and odontoblasts as indicated by the detection of several inflammatory mediators such as IL-6, IL-1β, TNF-α, and PGE2. The formation of a bioactive complex composed of calcium and phosphorus on titanium nanoparticles allowed their binding to proteins leading to the cell internalization phenomenon. The nanoparticles induced mutagenic and carcinogenic effects into the cells.
CONCLUSIONS
The cytotoxic effect of debris released from dental implants depends on the size, concentration, and chemical composition of the particles. A high concentration of particles on nanometric scale intensifies the inflammatory responses with mutagenic potential of the surrounding cells.
CLINICAL RELEVANCE
Titanium ions and debris have been detected in peri-implant tissues with different size, concentration, and forms. The presence of metallic debris at peri-implant tissues also stimulates the migration of immune cells and inflammatory reactions. Cp Ti and TiO micro- and nano-scale particles can reach the bloodstream, accumulating in lungs, liver, spleen, and bone marrow.
Topics: Dental Implants; Humans; Macrophages; Osteoblasts; Peri-Implantitis; Titanium
PubMed: 33616805
DOI: 10.1007/s00784-021-03785-z -
International Journal of Molecular... Aug 2022Sepsis is a critical condition characterized by increased levels of pro-inflammatory cytokines and proliferating cells such as neutrophils and macrophages in response to... (Review)
Review
Sepsis is a critical condition characterized by increased levels of pro-inflammatory cytokines and proliferating cells such as neutrophils and macrophages in response to microbial pathogens. Such processes lead to an abnormal inflammatory response and multi-organ failure. MicroRNAs (miRNA) are single-stranded non-coding RNAs with the function of gene regulation. This means that miRNAs are involved in multiple intracellular pathways and thus contribute to or inhibit inflammation. As a result, their variable expression in different tissues and organs may play a key role in regulating the pathophysiological events of sepsis. Thanks to this property, miRNAs may serve as potential diagnostic and prognostic biomarkers in such life-threatening events. In this narrative review, we collect the results of recent studies on the expression of miRNAs in heart, blood, lung, liver, brain, and kidney during sepsis and the molecular processes in which they are involved. In reviewing the literature, we find at least 122 miRNAs and signaling pathways involved in sepsis-related organ dysfunction. This may help clinicians to detect, prevent, and treat sepsis-related organ failures early, although further studies are needed to deepen the knowledge of their potential contribution.
Topics: Gene Expression Regulation; Humans; Macrophages; MicroRNAs; Multiple Organ Failure; Sepsis
PubMed: 36012630
DOI: 10.3390/ijms23169354 -
Diagnostics (Basel, Switzerland) Sep 2021Coronavirus disease 2019 (COVID-19) can potentially affect all organs owing to the ubiquitous diffusion of the angiotensin-converting enzyme II (ACE2) receptor-binding... (Review)
Review
Coronavirus disease 2019 (COVID-19) can potentially affect all organs owing to the ubiquitous diffusion of the angiotensin-converting enzyme II (ACE2) receptor-binding protein. Indeed, the SARS-CoV-2 virus is capable of causing heart disease. This systematic review can offer a new perspective on the potential consequences of COVID-19 through an analysis of the current literature on cardiac involvement. This systematic review, conducted from March 2020 to July 2021, searched the current literature for postmortem findings in patients who were positive for SARS-CoV-2 by combining and meshing the terms "COVID-19", "postmortem", "autopsy", and "heart" in titles, abstracts, and keywords. The PubMed database was searched following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Sixteen papers met the inclusion criteria (case reports and series, original research, only English-written). A total of 209 patients were found (mean age (interquartile range (IQR)), 60.17 years (IQR, 54.75-70.75 years); 122 men (58.37%, ratio of men to women of 1:0.7%)). Each patient tested positive for SARS-CoV-2. Death was mainly the result of respiratory failure. The second most common cause of death was acute heart failure. Few patients specifically died of myocarditis. Variables such as pathological findings, immunohistochemical data, and previous clinical assessments were analyzed. Main cardiac pathological findings were cardiac dilatation, necrosis, lymphocytic infiltration of the myocardium, and small coronary vessel microthrombosis. Immunohistochemical analyses revealed an inflammatory state dominated by the constant presence of CD3+ and CD8+ cytotoxic lymphocytes and CD68+ macrophages. COVID-19 leads to a systemic inflammatory response and a constant prothrombotic state. The results of our systematic review suggest that SARS-CoV-2 was able to cause irreversible changes in several organs, including the heart; this is reflected by the increased cardiac risk in patients who survive COVID-19. Postmortem analysis (including autopsy, histologic, and immunohistochemical examination) is an indispensable tool to better understand pathological changes caused by emerging diseases such as COVID-19. Our results may provide more information on the involvement of the heart in COVID-19 patients.
PubMed: 34573988
DOI: 10.3390/diagnostics11091647 -
Scientific Reports Jul 2022Interleukin 10 (IL-10) is associated with the progression of leishmaniasis because it inhibits the leishmanicidal action of macrophages and the production of mediators... (Meta-Analysis)
Meta-Analysis
Interleukin 10 (IL-10) is associated with the progression of leishmaniasis because it inhibits the leishmanicidal action of macrophages and the production of mediators such as IFN-γ and nitric oxide. Studies have shown that specific polymorphisms are associated with the regulatory role of IL-10 and the development of more relevant clinical forms of leishamaniasis. We performed a systematic review and meta-analysis to determine whether single nucleotide polymorphisms (SNPs) of IL-10 influence the progression of leishmaniasis. The selected articles were read in full and only those consistent with the eligibility criteria were included in our study. Seven studies were eligible according to the inclusion criteria and were included in the present systematic review, but only five were subjected to statistical analysis. The pooled odds ratios showed no significant association between the rs1800871 SNP and the progression of leishmaniasis in all genotype models, including the dominant, recessive, homozygote, heterozygote, and allelic models. Regarding the association between rs1800896 SNP and the progression of leishmaniasis, the pooled odds ratios showed no association under all genotype models. Hence, IL-10 SNPs did not show significant association and were not considered a risk factor for the progression of leishmaniasis.
Topics: Alleles; Genetic Predisposition to Disease; Humans; Interleukin-10; Leishmaniasis; Polymorphism, Single Nucleotide
PubMed: 35778471
DOI: 10.1038/s41598-022-15377-2 -
Seminars in Nuclear Medicine Nov 2023Computed tomography angiography (CTA), magnetic resonance angiography (MRA) and F-FDG-PET have proven clinical value when evaluating patients with carotid... (Review)
Review
Computed tomography angiography (CTA), magnetic resonance angiography (MRA) and F-FDG-PET have proven clinical value when evaluating patients with carotid atherosclerosis. In this systematic review, we will focus on the role of novel molecular imaging tracers in that assessment and their potential strengths to stratify stroke risk. We systematically searched PubMed, Embase, the Web of Science Core Collection, and Cochrane Library for articles reporting on molecular imaging to noninvasively detect or characterize inflammation in carotid atherosclerosis. As our focus was on nonclassical novel targets, we omitted reports solely on F-FDG and F-NaF. We summarized and mapped the selected studies to provide an overview of the current clinical development in molecular imaging in relation to risk factors, imaging and histological findings, diagnostic and prognostic performance. We identified 20 articles in which the utilized tracers to visualize carotid wall inflammation were somatostatin subtype-2- (SST2-) (n = 5), CXC-motif chemokine receptor 4- (CXCR4-) (n = 3), translocator protein- (TSPO-) (n = 2) and aVβ3 integrin-ligands (n = 2) and choline-tracers (n = 2). Tracer uptake correlated with traditional cardiovascular risk factors, that is, age, gender, diabetes, hypercholesterolemia, and hypertension as well as prior cardiovascular disease. We identified discrepancies between tracer uptake and grade of stenosis, plaque calcification, and F-FDG uptake, suggesting the importance of alternative characterization of atherosclerosis beyond classical neuroimaging features. Immunohistochemical analysis linked tracer uptake to markers of macrophage infiltration and neovascularization. Symptomatic carotid arteries showed higher uptake compared to asymptomatic (including contralateral, nonculprit) arteries. Some studies demonstrated a potential role of these novel molecular imaging as a specific intermediary (bio)marker for outcome. Several novel tracers show promise for identification of high-risk plaque inflammation. Based on the current evidence we cautiously propose the SST2-ligands and the choline radiotracers as viable candidates for larger prospective longitudinal outcome studies to evaluate their predictive use in clinical practice.
PubMed: 37996309
DOI: 10.1053/j.semnuclmed.2023.10.004 -
Fundamental & Clinical Pharmacology Apr 2023Macrophage M2 (MP2)-based cell therapy is a novel medicinal treatment for animals with Experimental Autoimmune Encephalomyelitis (EAE) as an experimental model of... (Meta-Analysis)
Meta-Analysis Review
Cell therapy procedure using anti-inflammatory macrophage M2 can potentially reduce Clinical Score in animals with Experimental Autoimmune Encephalomyelitis: A preclinical systematic review and meta-analysis study.
Macrophage M2 (MP2)-based cell therapy is a novel medicinal treatment for animals with Experimental Autoimmune Encephalomyelitis (EAE) as an experimental model of multiple sclerosis (MS). This systematic review and meta-analysis study was designed to assess the overall therapeutic effects of MP2 cell therapy on Clinical Score and motor impairment in EAE-induced animals. All experiments on MP2 cell therapy in animals with EAE were gathered (by October 2, 2022) from English (PubMed, Scopus, WoS, Science Direct, and ISC) and Persian (MagIran and SID) databases. The searching strategy was designed using "Experimental Autoimmune Encephalomyelitis," "Multiple Sclerosis," and "Macrophage M2" keywords. Following primary and secondary screenings, eligible papers were selected based on the PRISMA 2020 guideline, and the study quality was assessed using the Animal Research: Reporting of In Vivo Experiments (ARRIVE) checklist. The difference in means of Clinical Score (score 0-5) as the effect size (ES) was analyzed based on the random effect model (CMA software, v.2). Subgrouping (EAE phases of Onset, Peak, and Recovery) was applied, and I index was used to assess the heterogeneity index. Publication bias and sensitivity indices were also evaluated. P < 0.05 was considered significant, and the confidence interval (CI) was determined 95%. Among 22 gathered papers, medium to high quality studies were selected for meta-analysis. Difference in means, P value, and I for Onset, Peak, and Recovery phases were 0.082 (CI95%: -0.323-0.159, P value: 0.504, I : 67.961%), -0.606 (CI95%: -1.518 to -0.305, P value: 0.192, I : 96.070%), and -1.103 (CI95%: -1.390 to -0.816, P value: 0.000, I : 30.880%), respectively and Overall Effect was found -0.509 (CI95%: -0.689 to -0.328, P value < 0.001). Also, P value (two-tailed) indices for publication bias were 0.366 and 0.583 for Egger's regression intercept and Begg rank correlation, respectively. The P value for sensitivity was detected 0.003. Cell therapy procedure using MP2 can potentially alleviate the Clinical Scores Index and correct the motor defects in Recovery phase of EAE animals. In healthy mice, the brain and myelin surrounding neurons are in a healthy and physiological state (1). To evaluate MS in humans, it is necessary to model this type of disease in animals using EAE procedure through subcutaneous injection of CFA, MOG , MT, and Pert. Thus, inflammation and autoimmunity occur, which finally lead to myelin destruction and motor symptoms (2). By aspiration of progenitor cells available in bone marrow, the MP2 can be isolated and cultured. By activation of these types of cells, a rich collection of MP2 can be prepared for the cell-therapy process (3). After injection through the tail vein or intra-peritoneal procedure, these cells can be located in CNS through crossing from the BBB. They begin their anti-inflammatory activities and help repair the damaged myelin (4). Eventually, the clinical symptoms can be modified considerably, and the animal motor function improves (5). CFA, complete Freund's adjuvant; MOG , myelin oligodendrocyte glycoprotein; MT, Mycobacterium tuberculosis; Pert, pertussis; EAE, Experimental Autoimmune Encephalomyelitis; BM, bone marrow; MP2, macrophage M2; and BBB, blood brain barrier.
Topics: Humans; Mice; Animals; Encephalomyelitis, Autoimmune, Experimental; Multiple Sclerosis; Myelin-Oligodendrocyte Glycoprotein; Anti-Inflammatory Agents; Macrophages; Mice, Inbred C57BL; Peptide Fragments
PubMed: 36300567
DOI: 10.1111/fcp.12844 -
OTO Open 2023Lipid-laden macrophage index (LLMI) has been proposed as a marker for aspiration on bronchoalveolar lavage. It has also been studied as a marker for gastroesophageal... (Review)
Review
OBJECTIVE
Lipid-laden macrophage index (LLMI) has been proposed as a marker for aspiration on bronchoalveolar lavage. It has also been studied as a marker for gastroesophageal reflux and other pulmonary diseases. This review aims to determine the clinical correlation between LLMI and pediatric aspiration.
DATA SOURCES
PubMed (MeSH search), Scopus, and Cochrane Central Register of Controlled Trials (CENTRAL) portals through December 17th, 2020.
REVIEW METHODS
Preferred Reporting Items for Systematic Review and Meta-Analysis criteria were followed, and a quality assessment of included studies was performed using the Methodological Index for Non-Randomized Studies. Search criteria included all occurrences in the title or abstract of the terms "pulmonary aspiration" and "alveolar macrophages."
RESULTS
Five studies describing 720 patients met inclusion, 3 retrospective case-control studies, and 2 prospective observational studies. Four studies suggested a link between elevated LLMI and aspiration, and 1 found no association. Control groups varied and included healthy nonaspirators to nonaspirators with other pulmonary diseases. Diagnosis of aspiration was not standardized across the studies. Three papers proposed cutoff values for LLMI, all different.
CONCLUSION
The existing literature indicates that LLMI is not a sensitive or specific marker for aspiration. Further study is needed to define the utility of LLMI in pediatric aspiration.
PubMed: 36998564
DOI: 10.1002/oto2.33 -
Journal of Leukocyte Biology Mar 2023Despite effective antiretroviral therapies, chronic inflammation and spontaneous viral "blips" occur in HIV-infected patients. Given the roles for monocytes/macrophages...
Despite effective antiretroviral therapies, chronic inflammation and spontaneous viral "blips" occur in HIV-infected patients. Given the roles for monocytes/macrophages in HIV pathogenesis and extracellular vesicles in intercellular communication, we performed this systematic review to delineate the triad of HIV, monocytes/macrophages, and extracellular vesicles in the modulation of immune activation and HIV activities. We searched PubMed, Web of Science, and EBSCO databases for published articles, up to 18 August 2022, relevant to this triad. The search identified 11,836 publications, and 36 studies were deemed eligible and included in this systematic review. Data were extracted for the characteristics of HIV, monocytes/macrophages, and extracellular vesicles used for experiments and the immunologic and virologic outcomes in extracellular vesicle recipient cells. Evidence for the effects on outcomes was synthesized by stratifying the characteristics by outcomes. In this triad, monocytes/macrophages were potential producers and recipients of extracellular vesicles, whose cargo repertoires and functionalities were regulated by HIV infection and cellular stimulation. Extracellular vesicles derived from HIV-infected monocytes/macrophages or the biofluid of HIV-infected patients enhanced innate immune activation and HIV dissemination, cellular entry, replication, and latency reactivation in bystander or infected target cells. These extracellular vesicles could be synthesized in the presence of antiretroviral agents and elicit pathogenic effects in a wide range of nontarget cells. At least eight functional types of extracellular vesicles could be classified based on the diverse extracellular vesicle effects, which were linked to specific virus- and/or host-derived cargos. Thus, the monocyte/macrophage-centered multidirectional crosstalk through extracellular vesicles may help sustain persistent immune activation and residual viral activities during suppressed HIV infection.
Topics: Humans; HIV Infections; Monocytes; Macrophages; Inflammation; Extracellular Vesicles
PubMed: 36802000
DOI: 10.1093/jleuko/qiac021