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Frontiers in Immunology 2022Rheumatoid arthritis (RA), which affects nearly 1% of the world's population, is a debilitating autoimmune disease. Bone erosion caused by periarticular osteopenia and...
INTRODUCTION
Rheumatoid arthritis (RA), which affects nearly 1% of the world's population, is a debilitating autoimmune disease. Bone erosion caused by periarticular osteopenia and synovial pannus formation is the most destructive pathological changes of RA, also leads to joint deformity and loss of function,and ultimately affects the quality of life of patients. Osteoclasts (OCs) are the only known bone resorption cells and their abnormal differentiation and production play an important role in the occurrence and development of RA bone destruction; this remains the main culprit behind RA.
METHOD
Based on the latest published literature and research progress at home and abroad, this paper reviews the abnormal regulation mechanism of OC generation and differentiation in RA and the possible targeted therapy.
RESULT
OC-mediated bone destruction is achieved through the regulation of a variety of cytokines and cell-to-cell interactions, including gene transcription, epigenetics and environmental factors. At present, most methods for the treatment of RA are based on the regulation of inflammation, the inhibition of bone injury and joint deformities remains unexplored.
DISCUSSION
This article will review the mechanism of abnormal differentiation of OC in RA, and summarise the current treatment oftargeting cytokines in the process of OC generation and differentiation to reduce bone destruction in patients with RA, which isexpected to become a valuable treatment choice to inhibit bone destruction in RA.
Topics: Humans; Osteoclasts; Quality of Life; Cell Differentiation; Arthritis, Rheumatoid; Cytokines
PubMed: 36466887
DOI: 10.3389/fimmu.2022.1034050 -
Advances in Therapy Jul 2023Randomized controlled trials (RCTs) of biologics in patients with severe, uncontrolled asthma have shown differential results by baseline blood eosinophil count (BEC).... (Review)
Review
INTRODUCTION
Randomized controlled trials (RCTs) of biologics in patients with severe, uncontrolled asthma have shown differential results by baseline blood eosinophil count (BEC). In the absence of head-to-head trials, we describe the effects of biologics on annualized asthma exacerbation rate (AAER) by baseline BEC in placebo-controlled RCTs. Exacerbations associated with hospitalization or an emergency room visit, pre-bronchodilator forced expiratory volume in 1 s, Asthma Control Questionnaire score, and Asthma Quality of Life Questionnaire score were also summarized.
METHODS
MEDLINE (via PubMed) was searched for RCTs of biologics in patients with severe, uncontrolled asthma and with AAER reduction as a primary or secondary endpoint. AAER ratios and change from baseline in other outcomes versus placebo were compared across baseline BEC subgroups. Analysis was limited to US Food and Drug Administration-approved biologics.
RESULTS
In patients with baseline BEC ≥ 300 cells/μL, AAER reduction was demonstrated with all biologics, and other outcomes were generally improved. In patients with BEC 0 to < 300 cells/μL, consistent AAER reduction was demonstrated only with tezepelumab; improvements in other outcomes were inconsistent across biologics. In patients with BEC 150 to < 300 cells/μL, consistent AAER reduction was demonstrated with tezepelumab and dupilumab (300 mg dose only), and in those with BEC 0 to < 150 cells/μL, AAER reduction was demonstrated only with tezepelumab.
CONCLUSION
The efficacy of all biologics in reducing AAER in patients with severe asthma increases with higher baseline BEC, with varying profiles across individual biologics likely due to differing mechanisms of action.
Topics: Humans; Eosinophils; Anti-Asthmatic Agents; Biological Products; Asthma; Leukocyte Count; Eosinophilia; Double-Blind Method
PubMed: 37233876
DOI: 10.1007/s12325-023-02514-0 -
The Cochrane Database of Systematic... Feb 2016Malignant neoplasms of the lymphoid or myeloid cell lines including lymphoma, leukaemia and myeloma are referred to as haematological malignancies. Complementary and... (Review)
Review
BACKGROUND
Malignant neoplasms of the lymphoid or myeloid cell lines including lymphoma, leukaemia and myeloma are referred to as haematological malignancies. Complementary and alternative treatment options such as meditation practice or yoga are becoming popular by treating all aspects of the disease including physical and psychological symptoms. However, there is still unclear evidence about meditation's effectiveness, and how its practice affects the lives of haematologically-diseased patients.
OBJECTIVES
This review aims to assess the benefits and harms of meditation practice as an additional treatment to standard care for adults with haematological malignancies.
SEARCH METHODS
We searched the Cochrane Central Register of Controlled Trials (CENTRAL, Issue 8, 2015), MEDLINE (1950 to August 2015), databases of ongoing trials, the metaRegister of Controlled Trials (mRCT) (http://www.controlled-trials.com/mrct/), conference proceedings of annual meetings of: the American Society of Hematology; American Society of Clinical Oncology; European Hematology Association; European Congress for Integrative Medicine; and Global Advances in Health and Medicine (2010 to 2015).
SELECTION CRITERIA
We included randomised controlled trials (RCTs) using meditation practice for adult patients with haematological malignancies.
DATA COLLECTION AND ANALYSIS
Two review authors independently extracted data from eligible studies and assessed the risk of bias according to predefined criteria. We evaluated quality of life and depression. The other outcomes of overall survival, anxiety, fatigue, quality of sleep and adverse events could not be evaluated, because they were not assessed in the included trial.
MAIN RESULTS
We included only one small trial published as an abstract article. The included study investigated the effects of meditation practice on patients newly hospitalised with acute leukaemia. Ninety-one participants enrolled in the study, but only 42 participants remained in the trial throughout the six-month follow-up period and were eligible for analysis. There was no information provided about the average age and sex of the study population. We found a high risk for attrition bias and unclear risk for reporting bias, performance and detection bias because of missing data due to abstract publication only, thus we judged the overall risk of bias as high. According to the GRADE criteria, we judged the overall quality of the body of evidence for all predefined outcomes as 'very low', due to the extent of missing data on the study population, and the small sample size.As the abstract publication did not provide numbers and results except P values, we are not able to give more details.Meditation practice might be beneficial for the quality of life of haematologically-diseased patients, with higher scores for participants in the mediation arms compared to the participants in the usual care control group (low quality of evidence). Levels of depression decreased for those practising meditation in both the spiritually-framed meditation group and the secularly-focused meditation group in comparison to the usual care control group, whose levels of depression remained constant (low quality of evidence). The influence of meditation practice on overall survival, fatigue, anxiety, quality of sleep and adverse events remained unclear, as these outcomes were not evaluated in the included trial.
AUTHORS' CONCLUSIONS
To estimate the effects of meditation practice for patients suffering from haematological malignancies, more high quality randomised controlled trials are needed. At present there is not enough information available on the effects of meditation in haematologically-diseased patients to draw any conclusion.
Topics: Acute Disease; Adult; Depression; Hematologic Neoplasms; Humans; Leukemia; Meditation; Randomized Controlled Trials as Topic
PubMed: 26840029
DOI: 10.1002/14651858.CD011157.pub2 -
BMC Infectious Diseases Nov 2023The neutrophil to lymphocyte ratio (NLR), an inflammatory biomarker, measures innate-adaptive immune system balance. In this systematic review and meta-analysis, we aim... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
The neutrophil to lymphocyte ratio (NLR), an inflammatory biomarker, measures innate-adaptive immune system balance. In this systematic review and meta-analysis, we aim to analyze the current literature to evaluate the diagnostic role of NLR in neonatal sepsis.
METHODS
PubMed, Web of Science, and Scopus were used to conduct a systematic search for relevant publications published before May 14, 2022.
RESULTS
Thirty studies, including 2328 neonates with sepsis and 1800 neonates in the control group, were included in our meta-analysis. The results indicated that NLR is higher in neonates with sepsis compared to healthy controls (SMD = 1.81, 95% CI = 1.14-2.48, P-value < 0.001) in either prospective (SMD = 2.38, 95% CI = 1.40-3.35, P-value < 0.001) or retrospective studies (SMD = 0.87, 95% CI = 0.63-1.12, P-value < 0.001) with a pooled sensitivity of 79% (95% CI = 62-90%), and a pooled specificity of 91% (95% CI = 73-97%). Also, we found that NLR is higher in neonates with sepsis compared to those who were suspected of sepsis but eventually had negative blood cultures (SMD =1.99, 95% CI = 0.76-3.22, P-value = 0.002) with a pooled sensitivity of 0.79% (95% CI = 0.69-0.86%), and a pooled specificity of 73% (95% CI = 54-85%). In addition, neonates with sepsis had elevated levels of NLR compared to other ICU admitted neonates (SMD = 0.73, 95% CI = 0.63-0.84, P < 0.001). The pooled sensitivity was 0.65 (95% CI, 0.55-0.80), and the pooled specificity was 0.80 (95% CI, 0.68-0.88).
CONCLUSION
Our findings support NLR as a promising biomarker that can be readily integrated into clinical settings to aid in diagnosing neonatal sepsis. As evidenced by our results, restoring balance to the innate and adaptive immune system may serve as attractive therapeutic targets. Theoretically, a reduction in NLR values could be used to measure therapeutic efficacy, reflecting the restoration of balance within these systems.
Topics: Infant, Newborn; Humans; Neutrophils; Neonatal Sepsis; Retrospective Studies; Prospective Studies; Lymphocytes; Biomarkers; Sepsis
PubMed: 38012554
DOI: 10.1186/s12879-023-08800-0 -
Frontiers in Immunology 2023Over 1.1 billion people smoke worldwide. The alkaloid nicotine is a prominent and addictive component of tobacco. In addition to tumors and cardiovascular disorders,...
BACKGROUND
Over 1.1 billion people smoke worldwide. The alkaloid nicotine is a prominent and addictive component of tobacco. In addition to tumors and cardiovascular disorders, tobacco consumption is associated with a variety of chronic-inflammatory diseases. Although neutrophilic granulocytes (neutrophils) play a role in the pathogenesis of many of these diseases, the impact of nicotine on neutrophils has not been systematically reviewed so far.
OBJECTIVES
The aim of this systematic review was to evaluate the direct influence of nicotine on human neutrophil functions, specifically on cell death/damage, apoptosis, chemotaxis, general motility, adhesion molecule expression, eicosanoid synthesis, cytokine/chemokine expression, formation of neutrophil extracellular traps (NETs), phagocytosis, generation of reactive oxygen species (ROS), net antimicrobial activity, and enzyme release.
MATERIAL AND METHODS
This review was conducted according to the PRISMA guidelines. A literature search was performed in the databases NCBI Pubmed and Web of Science™ in February 2023. Inclusion criteria comprised English written research articles, showing studies on the direct impact of nicotine on specified human neutrophil functions.
RESULTS
Of the 532 originally identified articles, data from 34 articles were finally compiled after several evaluation steps. The considered studies highly varied in methodological aspects. While at high concentrations (>3 mmol/l) nicotine started to be cytotoxic to neutrophils, concentrations typically achieved in blood of smokers (in the nmol/l range) applied for long exposure times (24-72h) supported the survival of neutrophils. Smoking-relevant nicotine concentrations also increased the chemotaxis of neutrophils towards several chemoattractants, elevated their production of elastase, lipocalin-2, CXCL8, leukotriene B4 and prostaglandin E2, and reduced their integrin expression. Moreover, while nicotine impaired the neutrophil phagocytotic and anti-microbial activity, a range of studies demonstrated increased NET formation. However, conflicting effects were found on ROS generation, selectin expression and release of β-glucuronidase and myeloperoxidase.
CONCLUSION
Nicotine seems to support the presence in the tissue and the inflammatory and selected tissue-damaging activity of neutrophils and reduces their antimicrobial functions, suggesting a direct contribution of nicotine to the pathogenesis of chronic-inflammatory diseases via influencing the neutrophil biology.
Topics: Humans; Extracellular Traps; Neutrophils; Nicotine; Reactive Oxygen Species; Granulocytes
PubMed: 38077313
DOI: 10.3389/fimmu.2023.1281685 -
Therapeutic Advances in Gastroenterology 2023Long-term management of inflammatory bowel diseases (IBD) is challenging and the identification of reliable predictors for treatment outcomes is an unmet need.... (Review)
Review
BACKGROUND
Long-term management of inflammatory bowel diseases (IBD) is challenging and the identification of reliable predictors for treatment outcomes is an unmet need. Neutrophil-related biomarkers have been mainly studied in the feces, but blood analyses have inherent advantages.
OBJECTIVE
To review the recent learnings on the ability of blood-based neutrophil-expressed biomarkers to predict treatment outcomes in IBD.
DESIGN
Systematic scoping review.
DATA SOURCES AND METHODS
We performed a literature search in Pubmed, EMBASE, SCOPUS, Web of Science, ScienceDirect, and Cochrane Central Register of Controlled Trials from inception until May 2022 according to Preferred Reporting Items for Systematic reviews and Meta-Analyses guidelines. All human studies associating blood-based neutrophil-related compounds with the prediction of disease progression, complication onset, or treatment outcomes were included.
RESULTS
From 1032 retrieved entries, 34 studies were selected, 32 published in 2013 or later. In all, 17 biomarkers from granules, cytoplasm, plasmatic membrane, and plasma were explored. In total, 1850 Crohn's disease (CD) and 1122 ulcerative colitis non-duplicated patients were included. The most mentioned biomarkers were nCD64, serum calprotectin (SC), oncostatin M (OSM), neutrophil elastase-generated calprotectin fragment (CPa9-HNE), and triggering receptor expressed on myeloid cells 1 (TREM1). Six biomarkers showed promising results: OSM, SC, eNAMPT, nCD64, TREM1, and CPa9-HNE. Variable positive signals were found for human neutrophil peptide 1-3, LL-37, S100A12, and neutrophil gelatinase-associated lipocalin. No predictive ability was found for the remaining markers. Sharing a neutrophil compartment did not indicate similar behavior.
CONCLUSION
Advances in the last decade began to unveil the untapped potential of the readily accessible blood neutrophil-expressed biomarkers, especially nCD64, TREM1, and CPa9-HNE. Current evidence suggests that future research should focus on well-defined subpopulations instead of a one-size-fits-all biomarker.
REGISTRATION
https://osf.io/kes9a.
PubMed: 36923488
DOI: 10.1177/17562848231155987 -
Occupational and Environmental Medicine Sep 2020Recent evidence has accumulated that the immune system is intimately intertwined with cancer development. Two key characteristics of carcinogens in which the immune... (Review)
Review
OBJECTIVE
Recent evidence has accumulated that the immune system is intimately intertwined with cancer development. Two key characteristics of carcinogens in which the immune system plays a central role are chronic inflammation and immunosuppression. In this systematic review, we investigated the association of chronic inflammatory and immunosuppressive outcomes with benzene, a widely used industrial chemical. Benzene has been confirmed to cause acute myeloid leukaemia and suspected to cause non-Hodgkin lymphoma, two cancers of the blood-forming system that affect immune cells.
METHODS
We systematically searched PubMed and Embase for all relevant studies using a combination of Medical Subject Headings (MeSH) and selected key words. The detailed review protocol, including search strategy, was registered with PROSPERO, the international prospective register of systematic reviews (#CRD42019138611).
RESULTS
Based on all human studies selected in the final review, we report new evidence of a benzene-induced immunosuppressive effect on the immune system and activation of the immune system to cause inflammation. In particular, benzene significantly lowers the number of white blood cells, particularly lymphocytes such as CD4 T-cells, B-cells and natural killer cells, and increases proinflammatory biomarkers at low levels of exposure.
CONCLUSION
To the best of our knowledge, this is the first comprehensive review of benzene's immunotoxicity in humans. Based on results obtained from this review, we propose two potential immunotoxic mechanisms of how benzene induces leukaemia/lymphoma: (1) cancer invasion caused by proinflammatory cytokine production, and (2) cancer promotion via impaired immunosurveillance. Further studies will be required to confirm the connection between benzene exposure and its effects on the immune system.
PubMed: 32938756
DOI: 10.1136/oemed-2020-106517 -
Frontiers in Immunology 2021The presence of anti-desmocollin (Dsc) antibodies is rarely described in autoimmune blistering diseases patients. Moreover, several clinical phenotypes of pemphigus may...
The presence of anti-desmocollin (Dsc) antibodies is rarely described in autoimmune blistering diseases patients. Moreover, several clinical phenotypes of pemphigus may be associated with these antibodies. In this review we analyze clinicopathological, immunologic and outcome features of anti-Dsc autoimmune blistering diseases patients, to improve their diagnosis and management. We conducted a systematic search of PubMed and Embase (1990-present) for studies reporting cases of autoimmune blistering diseases with anti-Dsc antibodies. We classified the selected patients as patients with exclusively anti-Dsc autoantibodies, and patients with anti-Dsc and other autoantibodies. Of 93 cases with anti-Dsc autoantibodies included, 38 (41%) had exclusively these antibodies. Only 18% of patients presented with the typical clinicopathological phenotype of pemphigus vulgaris or pemphigus foliaceous. Mucosal involvement was seen in approximately half of the patients. Up to 18% of cases were associated with neoplasms. Acantholysis was described in 54% of cases with histopathological information. Treatments and outcomes vary in the different clinical phenotypes. The presence of anti-Dsc antibodies must be suspected mainly in those patients with either atypical pemphigus, in special with clinical pustules, or in cases showing intraepithelial or dermal neutrophilic/eosinophilic infiltrate on histological examination and dual pattern by direct immunofluorescence examination.
Topics: Acantholysis; Animals; Autoantibodies; Autoimmunity; Desmocollins; Desmogleins; Eosinophils; Humans; Neutrophils; Pemphigus; Phenotype; Skin
PubMed: 34567003
DOI: 10.3389/fimmu.2021.740820 -
Journal of Immunology Research 2023Spontaneous preterm birth is one of the most common pregnancy complications in obstetric clinical practice, and its etiology is complex. The problems of low survival and... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Spontaneous preterm birth is one of the most common pregnancy complications in obstetric clinical practice, and its etiology is complex. The problems of low survival and high morbidity rates of premature infants need to be solved urgently. The platelet-to-lymphocyte ratio (PLR) and lymphocyte-to-monocyte ratio (LMR) are two novel biomarkers of inflammation, and several studies have linked PLR and LMR to spontaneous preterm birth. These systematic review and meta-analysis are aimed at analyzing the relationship between PLR and LMR in patients with spontaneous preterm birth to provide new ideas for the early prevention and treatment of spontaneous preterm births.
METHODS
Cochrane Library, EMBASE, PubMed, and China National Knowledge Infrastructure databases were inspected to gather PLR and LMR in patients with spontaneous preterm birth, all from the database to February 2022. Interstudy heterogeneity was evaluated using Cochran's test and statistic. Differences in PLR and LMR between patients with spontaneous preterm birth and full-term controls were evaluated by computing standardized mean differences and 95% confidence intervals. Publication bias and sensitivity analyses were also performed.
RESULTS
Nine studies were included in the meta-analysis based on the inclusion and exclusion criteria. The meta-analysis showed that serum PLR values were remarkably larger for patients with spontaneous preterm birth than for full-term controls (SMD = 0.49, 95% CI: 0.13 to 0.84, = 0.007), whereas the difference between serum LMR in patients with spontaneous preterm birth and full-term controls was not statistically significant (SMD: 0.35, 95% CI: -0.18, 0.88, = 0.199). The results of Begg's and Egger's tests revealed that the publication bias of the meta-analysis was not significant. The outcomes of the sensitivity analysis showed that the individual studies did not influence the meta-analysis results.
CONCLUSIONS
Current evidence shows that PLR is strongly associated with spontaneous preterm birth, whereas LMR is not. PLR has a certain clinical value in diagnosing and treating spontaneous preterm births, and our research will provide strong theoretical support for clinical work. In the future, it will be necessary to further explore the reasons for the increased PLR in the serum of patients with spontaneous preterm birth and other mechanisms inducing spontaneous preterm birth.
Topics: Infant, Newborn; Pregnancy; Female; Humans; Monocytes; Premature Birth; Lymphocytes; Blood Platelets; Biomarkers
PubMed: 36814523
DOI: 10.1155/2023/6841344 -
Canadian Journal of Gastroenterology &... 2022Nonalcoholic steatohepatitis (NASH) and liver fibrosis are the most common complications of nonalcoholic fatty liver disease (NAFLD). In this systematic review and... (Meta-Analysis)
Meta-Analysis Review
INTRODUCTION
Nonalcoholic steatohepatitis (NASH) and liver fibrosis are the most common complications of nonalcoholic fatty liver disease (NAFLD). In this systematic review and meta-analysis, we aim to analyze the current literature to evaluate the association of neutrophil to lymphocyte ratio (NLR) with NASH and fibrosis in patients with NAFLD.
METHODS
PubMed, Web of Science, and Scopus were used to conduct a systematic search for relevant publications published before May 24, 2022. The Newcastle-Ottawa scale was used for quality assessment.
RESULTS
Thirteen studies were included in our study. The pooled results showed that NAFLD patients with significant NASH had elevated levels of NLR compared to those with nonsignificant or without NASH (SMD = 0.97, 95% CI = 0.59-1.39, < 0.001). The pooled sensitivity and specificity of NLR were 78.16% (95% CI = 73.70%-82.04%), and 76.93% (95% CI = 70.22%-82.50%), respectively. In addition, NAFLD patients with significant liver fibrosis had elevated levels of NLR compared to those with nonsignificant or without fibrosis (SMD = 1.59, 95% CI = 0.76-2.43, < 0.001). The pooled sensitivity and specificity of NLR were 82.62% (95% CI = 70.235%-90.55%) and 81.22% (95% CI = 75.62%-85.78%), respectively.
CONCLUSION
Our findings support NLR to be a promising biomarker that can be readily integrated into clinical settings to aid in the prediction and prevention of NASH and fibrosis among patients with NAFLD.
Topics: Humans; Prognosis; Non-alcoholic Fatty Liver Disease; Neutrophils; Liver Cirrhosis; Lymphocytes
PubMed: 37601979
DOI: 10.1155/2022/1554079