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Antioxidants (Basel, Switzerland) Aug 2022Genetic association studies have discovered the intergenic region as a strong susceptibility locus for multiple autoimmune disorders, with the missense mutation... (Review)
Review
Genetic association studies have discovered the intergenic region as a strong susceptibility locus for multiple autoimmune disorders, with the missense mutation rs201802880 as the causal polymorphism. In this work, we aimed to perform a comprehensive meta-analysis of the association of the locus with various autoimmune diseases and to provide a systemic review on potential mechanisms underlying the effect of the causal risk variants. The frequencies of the two most extensively investigated polymorphisms within the locus, rs117026326 and rs201802880, vary remarkably across the world, with the highest frequencies in East Asian populations. Meta-analysis showed that the locus is significantly associated with primary Sjögren's syndrome, systemic lupus erythematosus, systemic sclerosis, and neuromyelitis optica spectrum disorder. The causal rs201802880 polymorphism leads to an amino acid substitution of p.Arg90His in the p47phox subunit of the phagocyte NADPH oxidase. The autoimmune disease risk His90 variant results in a reduced ROS production in phagocytes. Clinical and experimental evidence shows that the hypoactive His90 variant might contribute to the development of autoimmune disorders via multiple mechanisms, including impairing the clearance of apoptotic cells, regulating the mitochondria ROS-associated formation of neutrophil extracellular traps, promoting the activation and differentiation of autoreactive T cells, and enhancing type I IFN responses. In conclusion, the identification of the association of with autoimmune disorders demonstrates that ROS is an essential regulator of immune tolerance and autoimmunity mediated disease manifestations.
PubMed: 36009308
DOI: 10.3390/antiox11081589 -
Obesity Reviews : An Official Journal... Nov 2019Obesity is associated with the production of inflammatory cytokines that are implicated in insulin resistance (IR), and if not addressed, can lead to type 2 diabetes...
Obesity is associated with the production of inflammatory cytokines that are implicated in insulin resistance (IR), and if not addressed, can lead to type 2 diabetes (T2D). The role of the immune system in skeletal muscle (SM) inflammation and insulin sensitivity is not yet well characterized. As SM IR is an important determinant of glycaemia, it is critical that the muscle-immune phenotype is mapped to help design interventions to target T2D. This systematic review synthesized the evidence for SM macrophage content and phenotype in humans and murine models of obesity, and the association of muscle macrophage content and phenotype with IR. Results were synthesized narratively, as we were unable to conduct a meta-analysis. We included 28 studies (n=10 human, n=18 murine), and all studies detected macrophage markers in SM. Macrophage content was positively associated with IR. In humans and mice, there was variability in muscle macrophage content and phenotype in obesity. Overall certainty in the evidence was low due to heterogeneity in detection methods and incompleteness of data reporting. Macrophages are detected in human and murine SM in obesity and a positive association between macrophage content and IR is noted; however, the standardization of markers, detection methods, and reporting of study details is warranted to accurately characterize macrophages and improve the potential for creating specific and targeted immune-based therapies in obesity.
Topics: Animals; Diabetes Mellitus, Type 2; Disease Models, Animal; Glucose Clamp Technique; Humans; Inflammation; Insulin Resistance; Macrophage Activation; Macrophages; Mice; Muscle, Skeletal; Obesity
PubMed: 31410961
DOI: 10.1111/obr.12922 -
Frontiers in Immunology 2023Ageing research is establishing macrophages as key immune system regulators that undergo functional decline. Due to heterogeneity between species and tissue populations,... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
Ageing research is establishing macrophages as key immune system regulators that undergo functional decline. Due to heterogeneity between species and tissue populations, a plethora of data exist and the power of scientific conclusions can vary substantially. This meta-analysis by information content (MAIC) and systematic literature review (SLR) aims to determine overall changes in macrophage gene and protein expression, as well as function, with age.
METHODS
PubMed was utilized to collate peer-reviewed literature relating to macrophage ageing. Primary studies comparing macrophages in at least two age groups were included. Data pertaining to gene or protein expression alongside method used were extracted for MAIC analysis. For SLR analysis, data included all macrophage-specific changes with age, as well as species, ontogeny and age of groups assessed.
RESULTS
A total of 240 studies were included; 122 of which qualified for MAIC. The majority of papers focussed on changes in macrophage count/infiltration as a function of age, followed by gene and protein expression. The MAIC found iNOS and TNF to be the most commonly investigated entities, with 328 genes and 175 proteins showing consistent dysregulation with age across the literature. Overall findings indicate that cytokine secretion and phagocytosis are reduced and reactive oxygen species production is increased in the ageing macrophage.
DISCUSSION
Collectively, our analysis identifies critical regulators in macrophage ageing that are consistently dysregulated, highlighting a plethora of targets for further investigation. Consistent functional changes with age found here can be used to confirm an ageing macrophage phenotype in specific studies and experimental models.
Topics: Macrophages; Phagocytosis
PubMed: 37520567
DOI: 10.3389/fimmu.2023.1222308 -
Clinical and Experimental Dental... Jun 2023Macrophages are among the first cells to interact with the dental implant surface and are critical regulators for controlling the immune response toward biomaterials.... (Review)
Review
A systematic review comparing the macrophage inflammatory response to hydrophobic and hydrophilic sandblasted large grit, acid-etched titanium or titanium-zirconium surfaces during in vitro studies.
OBJECTIVES
Macrophages are among the first cells to interact with the dental implant surface and are critical regulators for controlling the immune response toward biomaterials. Macrophages can polarize between two main phenotypes: proinflammatory M1 macrophages and anti-inflammatory M2 macrophages. This systematic review aims to determine if a differing macrophage inflammatory response exists on hydrophilic sandblasted large grit, acid-etched (SLActive) surfaces compared to sandblasted large grit, acid-etched (SLA) titanium or titanium-zirconium surfaces during in vitro studies. MATERIAL AND METHODS: A systematic search of three electronic databases, Medline, DOSS (Dentistry and Oral Sciences Source), and WoS (Web of Science), was performed. Only in vitro studies were included in this systematic review. The electronic search was supplemented with a search of the references. Genetic expression and production of proinflammatory and anti-inflammatory proteins were assessed. The synthesis of quantitative data was completed by narrative synthesis.
RESULTS
A total of 906 studies were found with the systematic search. Eight studies remained after the application of inclusion and exclusion criteria. Six studies used murine macrophages, while two used human macrophages. Discs were used in six studies, while dental implants were used in the remaining two studies. Genetic expression and cytokine production of proinflammatory cytokines on SLActive surfaces were reduced compared to SLA. Anti-inflammatory genetic expression and cytokine production was increased on SLActive surfaces. The overall quality of the included studies was low to moderate.
CONCLUSIONS
SLActive surfaces modulate macrophages to reduce proinflammatory and increase anti-inflammatory gene expression and cytokine production compared to SLA surfaces. The in vitro nature of the included studies does not replicate the in vivo healing cascade. Further in vivo studies are required to assess the macrophage response toward SLActive implant surfaces compared to SLA surfaces.
Topics: Mice; Humans; Animals; Dental Implants; Titanium; Zirconium; Surface Properties; Macrophages; Cytokines; Anti-Inflammatory Agents
PubMed: 36991526
DOI: 10.1002/cre2.730 -
Cancer Prevention Research... Sep 2017Obesity and its associated metabolic dysregulation are established risk factors for many cancers. However, the biologic mechanisms underlying this relationship remain... (Review)
Review
Obesity and its associated metabolic dysregulation are established risk factors for many cancers. However, the biologic mechanisms underlying this relationship remain incompletely understood. Given the rising rates of both obesity and cancer worldwide, and the challenges for many people to lose excess adipose tissue, a systematic approach to identify potential molecular and metabolic targets is needed to develop effective mechanism-based strategies for the prevention and control of obesity-driven cancer. Epidemiologic, clinical, and preclinical data suggest that within the growth-promoting, proinflammatory microenvironment accompanying obesity, crosstalk between adipose tissue (comprised of adipocytes, macrophages and other cells) and cancer-prone cells may occur via obesity-associated hormones, cytokines, and other mediators that have been linked to increased cancer risk and/or progression. We report here a systematic review on the direct "crosstalk" between adipose tissue and carcinomas in humans. We identified 4,641 articles with = 20 human clinical studies, which are summarized as: (i) breast ( = 7); (ii) colorectal ( = 4); (iii) esophageal ( = 2); (iv) esophageal/colorectal ( = 1); (v) endometrial ( = 1); (vi) prostate ( = 4); and (vii) ear-nose-throat (ENT) cancer ( = 1). Findings from these clinical studies reinforce preclinical data and suggest organ-dependent crosstalk between adipose tissue and carcinomas via VEGF, IL6, TNFα, and other mechanisms. Moreover, visceral white adipose tissue plays a more central role, as it is more bioenergetically active and is associated with a more procancer secretome than subcutaneous adipose tissue. Efforts to eavesdrop and ultimately interfere with this cancer-enhancing crosstalk may lead to new targets and strategies for decreasing the burden of obesity-related cancers. .
Topics: Adipocytes; Adipokines; Adipose Tissue; Carcinoma; Cytokines; Disease Progression; Humans; Inflammation; Macrophages; Obesity; Risk Factors; Signal Transduction; Tumor Microenvironment
PubMed: 28864539
DOI: 10.1158/1940-6207.CAPR-16-0322 -
Journal of Diabetes Research 2023Glycated hemoglobin (HbA1c) is a commonly used clinical marker to monitor the control of type 2 diabetes mellitus patients (T2DM). However, it is unable to identify the... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Glycated hemoglobin (HbA1c) is a commonly used clinical marker to monitor the control of type 2 diabetes mellitus patients (T2DM). However, it is unable to identify the ongoing inflammatory changes in the body. These factors could be easily identified and monitored by the neutrophil-to-lymphocyte ratio (NLR). Therefore, this study is aimed at investigating the relationship between NLR and glycemic control in T2DM.
METHOD
A comprehensive search of eligible studies was performed in various databases published until July 2021. A random effect model was used to estimate the standardized mean difference (SMD). A metaregression, subgroup, and sensitivity analysis were conducted to search for potential sources of heterogeneity.
RESULT
A total of 13 studies were included in this study. Accordingly, the SMD of the NLR values between the poor and good glycemic control groups was 0.79 (95% CI, 0.46-1.12). Our study also showed that high NLR was significantly associated with poor glycemic control in T2DM patients (OR = 1.50, 95% CI: 1.30-1.93).
CONCLUSION
The results of this study suggest an association between high NLR values and an elevated HbA1C in T2DM patients. Therefore, NLR should be considered a marker of glycemic control in addition to HbA1c in T2DM patients.
Topics: Humans; Diabetes Mellitus, Type 2; Glycated Hemoglobin; Glycemic Control; Neutrophils; Lymphocytes
PubMed: 37305430
DOI: 10.1155/2023/3117396 -
Clinical and Experimental Dental... Aug 2022This systematic review aimed to assess in vitro studies that evaluated neutrophil interactions with different roughness levels in titanium and zirconia implant surfaces. (Review)
Review
OBJECTIVES
This systematic review aimed to assess in vitro studies that evaluated neutrophil interactions with different roughness levels in titanium and zirconia implant surfaces.
MATERIAL AND METHODS
An electronic search for literature was conducted on PubMed, Embase, Scopus, and Web of Science and a total of 14 studies were included. Neutrophil responses were assessed based on adhesion, cell number, surface coverage, cell structure, cytokine secretion, reactive oxygen species (ROS) production, neutrophil activation, receptor expression, and neutrophil extracellular traps (NETs) release. The method of assessing the risk of bias was done using the toxicological data reliability assessment tool (TOXRTOOL).
RESULTS
Ten studies have identified a significant increase in neutrophil functions, such as surface coverage, cell adhesion, ROS production, and NETs released when interacting with rough titanium surfaces. Moreover, neutrophil interaction with rough-hydrophilic surfaces seems to produce less proinflammatory cytokines and ROS when compared to naive smooth and rough titanium surfaces. Regarding membrane receptor expression, two studies have reported that the FcγIII receptor (CD16) is responsible for initial neutrophil adhesion to hydrophilic titanium surfaces. Only one study compared neutrophil interaction with titanium alloy and zirconia toughened alumina surfaces and reported no significant differences in neutrophil cell count, activation, receptor expression, and death.
CONCLUSIONS
There are not enough studies to conclude neutrophil interactions with titanium and zirconia surfaces. However, different topographic modifications such as roughness and hydrophilicity might influence neutrophil interactions with titanium implant surfaces.
Topics: Dental Implants; Neutrophils; Reactive Oxygen Species; Reproducibility of Results; Surface Properties; Titanium; Zirconium
PubMed: 35535662
DOI: 10.1002/cre2.582 -
The Journal of Investigative Dermatology Nov 2022Because burn injuries are often followed by a derailed immune response and excessive inflammation, a thorough understanding of the occurring reactions is key to... (Meta-Analysis)
Meta-Analysis
Because burn injuries are often followed by a derailed immune response and excessive inflammation, a thorough understanding of the occurring reactions is key to preventing secondary complications. This systematic review, which includes 247 animal studies, shows the postburn response of 14 different immune cell types involved in immediate and long-term effects in both wound tissue and circulation. Peripheral blood neutrophil and monocyte numbers increased directly after burns, whereas thrombocyte numbers increased near the end of the first week. However, lymphocyte numbers were decreased for at least 2 weeks. In burn wound tissue, neutrophil and macrophage numbers accumulated during the first 3 weeks. Burns also altered cellular functions because we found an increased migratory potential of leukocytes, impaired antibacterial activity of neutrophils, and enhanced inflammatory mediator production by macrophages. Neutrophil surges were positively associated with burn size and were highest in rats. Altogether, this comprehensive overview of the temporal immune cell dynamics shows that unlike normal wound healing, burn injury induces a long-lasting inflammatory response. It provides a fundamental research basis to improve experimental set-ups, burn care, and outcomes.
Topics: Rats; Animals; Burns; Neutrophils; Macrophages; Anti-Bacterial Agents; Inflammation Mediators
PubMed: 35623415
DOI: 10.1016/j.jid.2022.05.004 -
Chest Jul 2023Monocyte distribution width (MDW) is an emerging biomarker for infection. It is available easily and quickly as part of the CBC count, which is performed routinely on... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Monocyte distribution width (MDW) is an emerging biomarker for infection. It is available easily and quickly as part of the CBC count, which is performed routinely on hospital admission. The increasing availability and promising results of MDW as a biomarker in sepsis has prompted an expansion of its use to other infectious diseases.
RESEARCH QUESTION
What is the diagnostic performance of MDW across multiple infectious disease outcomes and care settings?
STUDY DESIGN AND METHODS
A systematic review of the diagnostic performance of MDW across multiple infectious disease outcomes was conducted by searching PubMed, Embase, Scopus, and Web of Science through February 4, 2022. Meta-analysis was performed for outcomes with three or more reports identified (sepsis and COVID-19). Diagnostic performance measures were calculated for individual studies with pooled estimates created by linear mixed-effects models.
RESULTS
We identified 29 studies meeting inclusion criteria. Most examined sepsis (19 studies) and COVID-19 (six studies). Pooled estimates of diagnostic performance for sepsis differed by reference standard (Second vs Third International Consensus Definitions for Sepsis and Septic Shock criteria) and tube anticoagulant used and ranged from an area under the receiver operating characteristic curve (AUC) of 0.74 to 0.94, with mean sensitivity of 0.69 to 0.79 and mean specificity of 0.57 to 0.86. For COVID-19, the pooled AUC of MDW was 0.76, mean sensitivity was 0.79, and mean specificity was 0.59.
INTERPRETATION
MDW exhibited good diagnostic performance for sepsis and COVID-19. Diagnostic thresholds for sepsis should be chosen with consideration of reference standard and tube type used.
TRIAL REGISTRY
Prospero; No.: CRD42020210074; URL: https://www.crd.york.ac.uk/prospero/.
Topics: Humans; Monocytes; COVID-19; Sepsis; Biomarkers; Communicable Diseases; COVID-19 Testing
PubMed: 36681146
DOI: 10.1016/j.chest.2022.12.049 -
Langenbeck's Archives of Surgery Feb 2023Inflammation plays an important role in tumor growth. Novel serum blood biomarkers, including neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR),... (Meta-Analysis)
Meta-Analysis Review
Prognostic role of platelet-to-lymphocyte ratio, neutrophil-to-lymphocyte, and lymphocyte-to-monocyte ratio in operated rectal cancer patients: systematic review and meta-analysis.
BACKGROUND
Inflammation plays an important role in tumor growth. Novel serum blood biomarkers, including neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and lymphocyte-to-monocyte ratio (LMR), have been proposed as useful prognostic indexes in cancer patients. However, their role in rectal cancer is controversial.
METHODS
A comprehensive literature review was conducted including MEDLINE/Pubmed, EMBASE, SCOPUS, and the Cochrane Database of Systematic Reviews through May 2022. The systematic review and meta-analysis were conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. Quality was appraised with the Methodological Index for Non-Randomized Studies (MINORS) tool. Aim of the study was to summarize available literature on PLR, NLR, and LMR in patients with rectal cancer undergoing resection.
RESULTS
Forty-seven observational studies (14,205 patients) were included; there were 42 retrospective and 5 prospective cohort studies with an average MINORS score of 14.6 (range: 12-18). Worse overall survival was associated with high NLR (HR 1.81; 95%CI 1.52-2.15; p < 0.001), high PLR (HR 1.24; 95%CI 1.06-1.46; p = 0.009), and low LMR (HR 0.67; 95%CI 0.49-0.91; p = 0.01). High NLR and low LMR were also associated with disease-free-survival (HR 1.68; 95%CI 1.35-2.08; p < 0.001 and HR 0.71; 95%CI 0.58-0.87; p < 0.001, respectively).
CONCLUSIONS
NLR, PLR, and LMR are independent clinical predictors for overall survival in patients with rectal cancer treated with curative surgery. NLR and LMR are also good predictors for disease free survival. These biomarkers, which are readily available, appear optimal prognostic indexes and may help clinicians predict the prognosis of rectal cancer and develop individualized treatment strategies.
Topics: Humans; Prognosis; Neutrophils; Monocytes; Retrospective Studies; Prospective Studies; Lymphocytes; Biomarkers; Rectal Neoplasms
PubMed: 36781510
DOI: 10.1007/s00423-023-02786-8