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Journal of Musculoskeletal & Neuronal... Mar 2021Osteosarcoma (OS) is the most common type of primary malignant bone tumor, The effect of tumor microenvironment components on OS oncogenesis remains unknown. (Meta-Analysis)
Meta-Analysis
OBJECTIVES
Osteosarcoma (OS) is the most common type of primary malignant bone tumor, The effect of tumor microenvironment components on OS oncogenesis remains unknown.
METHODS
To investigate the function of immune cells in osteosarcoma, we provided a text-based GMT (Gene Matrix Transposed) file in which each line defines one of lm22 with their markers. We used STRING to draw DEG's PPI network and selected hub genes and modules. Then, survival analysis was conducted to hub genes. We identified 10,390 common genes, and identified 218 DEGs based on the combined t-value and Z scores.
RESULTS
The KEGG and GSEA enrichment analysis showed that macrophages are significantly activated in osteosarcoma. PPI network analysis revealed that hub gene CD163 molecule. We found that the expression of CD163 was negatively associated with the OS of osteosarcoma patients. These results suggest that macrophages are a risk factor in patients with osteosarcoma.
CONCLUSIONS
This study has systematically validated results of the studies carried out previously and filled up the gap in the field of OS on large-scaled meta-analysis. In addition, for the hub gene (CD163) and the macrophage cell capable of being used as a novel biomarker in promoting early diagnosis and development of therapeutic approaches.
Topics: Antigens, CD; Antigens, Differentiation, Myelomonocytic; Bone Neoplasms; Databases, Genetic; Gene Regulatory Networks; Humans; Immunity, Cellular; Macrophages; Osteosarcoma; Prognosis; Protein Array Analysis; Receptors, Cell Surface; Tumor Microenvironment
PubMed: 33657763
DOI: No ID Found -
European Spine Journal : Official... Jun 2021Macrophages play an important role in mediating damage after Spinal cord injury (SCI) by secreting macrophage migration inhibitory factor (MMIF) as a secondary injury... (Review)
Review
PURPOSE
Macrophages play an important role in mediating damage after Spinal cord injury (SCI) by secreting macrophage migration inhibitory factor (MMIF) as a secondary injury mediator. We aimed to systematically review the role of MMIF as a therapeutic target after traumatic SCI.
METHODS
Our systematic review has been performed according to the PRISMA 2009 Checklist. A systematic search in the scientific databases was carried out for studies published before 20 February 2019 from major databases. Two researchers independently screened titles. The risk of bias of eligible articles was assessed, and data were extracted. Finally, we systematically analyzed and interpreted related data.
RESULTS
785 papers were selected for the title and abstract screening. 12 papers were included for data extraction. Eight animal studies were of high quality and the remaining two were of medium quality. One of the two human studies was of poor quality and the other was of fair quality. MMIF as a pro-inflammatory mediator can cause increased susceptibility to glutamate-related neurotoxicity, increased nitrite production, increased ERK activation, and increased COX2/PGE2 signaling pathway activation and subsequent stimulation of CCL5-related chemotaxis. Two human studies and six animal studies demonstrated that MMIF level increases after SCI. MMIF inhibition might be a potential therapeutic target in SCI by multiple different mechanisms (6/12 studies).
CONCLUSION
Most animal studies demonstrate significant neurologic improvement after administration of MMIF inhibitors, but these inhibitors have not been studied in humans yet. Further clinical trials are need to further understand MMIF inhibitor utility in acute or chronic SCI.
LEVEL OF EVIDENCE I
Diagnostic: individual cross-sectional studies with the consistently applied reference standard and blinding.
Topics: Animals; Cross-Sectional Studies; Humans; Macrophage Migration-Inhibitory Factors; Spinal Cord; Spinal Cord Injuries
PubMed: 33486594
DOI: 10.1007/s00586-021-06718-2 -
SN Comprehensive Clinical Medicine 2021With the increased spread of severe acute respiratory syndrome coronavirus 2 infection, more patients with multisystem inflammatory syndrome in children (MIS-C) are...
UNLABELLED
With the increased spread of severe acute respiratory syndrome coronavirus 2 infection, more patients with multisystem inflammatory syndrome in children (MIS-C) are being reported worldwide. This systematic review with meta-analysis aims to analyse the clinical features, proposed pathogenesis and current treatment options for effective management of children with this novel entity. Electronic databases (Medline, Google Scholar, WHO, CDC, UK National Health Service, LitCovid, and other databases with unpublished pre-prints) were extensively searched, and all articles on MIS-C published from January 1, 2020, to October 10, 2020, were retrieved. English language studies were included. This systematic review analysed 17 studies with 992 MIS-C patients from low-income and middle-income countries (LMICs) and developed countries (France, the UK, Italy, Spain, Chile and the US CDC data). Fever (95%) was the most common clinical manifestation followed by gastrointestinal (78%), cardiovascular (75.5%), and respiratory system (55.3%) involvement. Laboratory or epidemiologic evidence of inflammation and SARS-CoV-2 infection was present. Though the exact pathogenesis remains elusive, virus-induced post-infective immune dysregulation appears to play a predominant role. Features resembling Kawasaki disease, toxic shock syndrome or macrophage activation syndrome were present; 49% had shock; 32% had myocarditis; 18% had coronary vessel abnormalities and 9% had congestive cardiac failure. Sixty-three percent of the patients were admitted in paediatric intensive care unit (PICU); 63% received intravenous immunoglobulin, 58% received corticosteroids and 19% received alternate agents like tocilizumab; there were 22 (2.2%) deaths. Only 9/144 children in LMICs received tocilizumab that was significantly less than children in developed countries ( < 0.0001). This systematic review delineates and summarises recently published data on MIS-C from LMICs and developed countries. Although most needed PICU admission and received treatment with IVIG and steroids, most of the patients survived. Significantly fewer patients in developing countries received tocilizumab therapy than those in developed countries. It is crucial for clinician to recognise MIS-C, to differentiate it from other defined inflammatory conditions and initiate early treatment. Further studies are needed for long-term prognosis, especially relating to cardiac complications of MIS-C.
SUPPLEMENTARY INFORMATION
The online version of this article (10.1007/s42399-020-00690-6) contains supplementary material, which is available to authorized users.
PubMed: 33432304
DOI: 10.1007/s42399-020-00690-6 -
Journal of Autoimmunity Feb 2021The diverse clinical manifestations of COVID-19 is emerging as a hallmark of the Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) infection. While the...
The diverse clinical manifestations of COVID-19 is emerging as a hallmark of the Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) infection. While the initial target of SARS-CoV-2 is the respiratory tract, it is becoming increasingly clear that there is a complex interaction between the virus and the immune system ranging from mild to controlling responses to exuberant and dysfunctional multi-tissue directed autoimmune responses. The immune system plays a dual role in COVID-19, being implicated in both the anti-viral response and in the acute progression of the disease, with a dysregulated response represented by the marked cytokine release syndrome, macrophage activation, and systemic hyperinflammation. It has been speculated that these immunological changes may induce the loss of tolerance and/or trigger chronic inflammation. In particular, molecular mimicry, bystander activation and epitope spreading are well-established proposed mechanisms to explain this correlation with the likely contribution of HLA alleles. We performed a systematic literature review to evaluate the COVID-19-related autoimmune/rheumatic disorders reported between January and September 2020. In particular, we investigated the cases of incident hematological autoimmune manifestations, connective tissue diseases, antiphospholipid syndrome/antibodies, vasculitis, Kawasaki-like syndromes, acute arthritis, autoimmune-like skin lesions, and neurologic autoimmune conditions such as Guillain-Barré syndrome. We screened 6263 articles and report herein the findings of 382 select reports which allow us to conclude that there are 2 faces of the immune response against SARS-CoV-2, that include a benign virus controlling immune response and a many faceted range of dysregulated multi-tissue and organ directed autoimmune responses that provides a major challenge in the management of this viral disease. The number of cases for each disease varied significantly while there were no reported cases of adult onset Still disease, systemic sclerosis, or inflammatory myositis.
Topics: Animals; Autoimmune Diseases; COVID-19; Chronic Disease; Humans; Immunity; Incidence; Inflammation; Janus Kinases; SARS-CoV-2
PubMed: 33401171
DOI: 10.1016/j.jaut.2020.102592 -
Infection, Genetics and Evolution :... Jan 2021Tuberculosis (TB) is one of the deadliest diseases since ancient times and is still a global health problem. So, there is a need to develop new approaches for early... (Comparative Study)
Comparative Study Meta-Analysis
Tuberculosis (TB) is one of the deadliest diseases since ancient times and is still a global health problem. So, there is a need to develop new approaches for early detection of TB and understand the host-pathogen relationship. In the present study, we have analyzed microarray data sets and compared the transcriptome profiling of the healthy individual with latent infection (LTBI) and active TB (TB) patients, and identified the differentially expressed genes (DEGs). Next, we performed the systematic network meta-analysis of the DEGs, which identified the seven most influencing hub genes (IL6, IL1B, TNF, NFKB1, STAT1, JAK2, and MAPK8) as the potential therapeutic target in the tuberculosis disease. These target genes are involved in many biological processes like cell cycle control, apoptosis, complement signalling, enhanced cytokine & chemokine signalling, pro-inflammatory responses, and host immune responses. Additionally, we also identified 22 inferred genes that are mainly engaged in the induction of innate immune response, cellular response to interleukin-6, inflammatory response, apoptotic process, I-kappaB-phosphorylation, JAK-STAT signalling pathway, macrophage activation, cell growth, and cell signalling. The proper attention of these inferred genes may open up a new horizon to understand the defensive mechanisms of TB disease. The transcriptome profiling and network approach can enhance the understanding of the molecular pathogenesis of tuberculosis infection and have implications for the plan and execution of mRNA expression tools to support early diagnostics and treatment of Mycobacterium tuberculosis (M.tb).
Topics: Antitubercular Agents; Biomarkers; Gene Expression Profiling; Genes, Bacterial; Genetic Variation; Healthy Volunteers; Humans; Latent Tuberculosis; Mycobacterium tuberculosis; Network Meta-Analysis; Protein Array Analysis; Transcriptome
PubMed: 33271338
DOI: 10.1016/j.meegid.2020.104649 -
Clinical and Experimental Immunology Feb 2021Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening, hyperinflammatory disorder, characterized by multiorgan failure, fever and cytopenias. The diagnosis of... (Meta-Analysis)
Meta-Analysis
Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening, hyperinflammatory disorder, characterized by multiorgan failure, fever and cytopenias. The diagnosis of HLH and its subtype Macrophage Activation Syndrome (MAS) remains a challenge. Interleukin 18 (IL-18) is emerging as a potential biomarker for HLH/MAS but is currently not a part of diagnostic criteria. This systematic review aimed to assess the potential role of IL-18 in the diagnosis and monitoring of HLH and MAS, and was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. PubMed and Embase were searched on 30 January 2020. Studies included all subtypes of HLH and a range of underlying disorders in both children and adults. A total of 14 studies were included. Generally, serum IL-18 was elevated in both primary and secondary HLH (> 1000 pg/ml) compared with other inflammatory conditions and with healthy individuals; thus, serum IL-18 may be able to discriminate between HLH and other inflammatory conditions. Significantly increased IL-18 (> 10 000 pg/ml) was also consistently described in MAS compared with other subtypes of HLH. The ability of IL-18 to distinguish MAS from systemic juvenile idiopathic arthritis (JIA) is less unambiguous, as IL-18 levels > 100 000 pg/ml were described in sJIA patients both with and without MAS. IL-18 may help to differentiate between HLH subtypes and other inflammatory conditions. As HLH and MAS are rare disorders, only few and relatively small studies exist on the subject. Larger, prospective multi-center studies are called for to assess the diagnostic precision of IL-18 for HLH and MAS.
Topics: Animals; Diagnosis, Differential; Humans; Interleukin-18; Lymphohistiocytosis, Hemophagocytic; Macrophage Activation; Macrophage Activation Syndrome; Macrophages; Monitoring, Immunologic; Phenotype
PubMed: 33128796
DOI: 10.1111/cei.13543 -
Human Reproduction Update Jan 2021Adenomyosis is a benign gynecological disorder associated with subfertility, pelvic pain and abnormal uterine bleeding that have significant consequences for the health...
BACKGROUND
Adenomyosis is a benign gynecological disorder associated with subfertility, pelvic pain and abnormal uterine bleeding that have significant consequences for the health and quality of life of women. Histologically, it is defined as the presence of ectopic endometrial islets within the myometrium. Its pathogenesis has not yet been elucidated and several pieces of the puzzle are still missing. One process involved in the development of adenomyosis is the increased capacity of some endometrial cells to infiltrate the myometrium. Moreover, the local and systemic immune systems are associated with the onset of the disease and with maintaining it. Numerous observations have highlighted the activation of immune cells and the release of immune soluble factors in adenomyosis. The contribution of immunity occurs in conjunction with hormonal aberrations and activation of the epithelial to mesenchymal transition (EMT) pathway, which promotes migration of endometrial cells. Here, we review current knowledge on the immunological changes in adenomyosis, with the aim of further elucidation of the pathogenesis of this disease.
OBJECTIVE AND RATIONALE
The objective was to systematically review the literature regarding the role of the immune system in development of adenomyosis in the inner and the outer myometrium, in humans.
SEARCH METHODS
A systematic review of published human studies was performed in MEDLINE, EMBASE and Cochrane Library databases from 1970 to February 2019 using the combination of Medical Subject Headings (MeSH): Adenomyosis AND ('Immune System' OR 'Gonadal Steroid Hormones'), and free-text terms for the following search terms (and their variants): Adenomyosis AND (immunity OR immune OR macrophage OR 'natural killer cell' OR lymphocyte* OR leucocyte* OR HLA OR inflammation OR 'sex steroid' OR 'epithelial to mesenchymal transition' OR 'EMT'). Studies in which no comparison was made with control patients, without adenomyosis (systemic sample and/or eutopic endometrium), were excluded.
OUTCOMES
A total of 42 articles were included in our systematic review. Changes in innate and adaptive immune cell numbers were described in the eutopic and/or ectopic endometrium of women with adenomyosis compared to disease-free counterparts. They mostly described an increase in lymphocyte and macrophage cell populations in adenomyosis eutopic endometrium compared to controls. These observations underscore the immune contributions to the disease pathogenesis. Thirty-one cytokines and other markers involved in immune pathways were studied in the included articles. Pro-inflammatory cytokines (interleukin (IL) 6, IL1β, interferon (IFN) α, tumor necrosis factor α, IFNγ) as well as anti-inflammatory or regulatory mediators (IL10, transforming growth factor β…) were found to be elevated in the eutopic endometrium and/or in the ectopic endometrium of the myometrium in women with adenomyosis compared to controls. Moreover, in women affected by adenomyosis, immunity was reported to be directly or indirectly linked to sex steroid hormone aberrations (notably changes in progesterone receptor in eutopic and ectopic endometrium) in three studies and to EMT in four studies.
WIDER IMPLICATIONS
The available literature clearly depicts immunological changes that are associated with adenomyosis. Both systemic and local immune changes have been described in women affected by adenomyosis, with the coexistence of changes in inflammatory as well as anti-inflammatory signals. It is likely that these immune changes, through an EMT mechanism, stimulate the migration of endometrial cells into the myometrium that, together with an endocrine imbalance, promote this inflammatory process. In light of the considerable impact of adenomyosis on women's health, a better understanding of the role played by the immune system in adenomyosis is likely to yield new research opportunities to better understand its pathogenesis.
Topics: Adenomyosis; Endometriosis; Endometrium; Epithelial-Mesenchymal Transition; Female; Humans; Myometrium; Quality of Life
PubMed: 33099635
DOI: 10.1093/humupd/dmaa038 -
Advances in Rheumatology (London,... Sep 2020The COVID-19 outbreak caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has become a global major concern. In this review, we addressed a...
The COVID-19 outbreak caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has become a global major concern. In this review, we addressed a theoretical model on immunopathogenesis associated with severe COVID-19, based on the current literature of SARS-CoV-2 and other epidemic pathogenic coronaviruses, such as SARS and MERS. Several studies have suggested that immune dysregulation and hyperinflammatory response induced by SARS-CoV-2 are more involved in disease severity than the virus itself.Immune dysregulation due to COVID-19 is characterized by delayed and impaired interferon response, lymphocyte exhaustion and cytokine storm that ultimately lead to diffuse lung tissue damage and posterior thrombotic phenomena.Considering there is a lack of clinical evidence provided by randomized clinical trials, the knowledge about SARS-CoV-2 disease pathogenesis and immune response is a cornerstone to develop rationale-based clinical therapeutic strategies. In this narrative review, the authors aimed to describe the immunopathogenesis of severe forms of COVID-19.
Topics: Age Factors; Angiotensin-Converting Enzyme 2; Animals; Antibody Formation; Betacoronavirus; Blood Coagulation Disorders; COVID-19; Comorbidity; Coronavirus Infections; Cytokine Release Syndrome; Humans; Immunity, Innate; Inflammation; Lung; Lymphopenia; Mice; Middle East Respiratory Syndrome Coronavirus; Pandemics; Peptidyl-Dipeptidase A; Pneumonia, Viral; Respiratory Distress Syndrome; Risk Factors; SARS-CoV-2; Severe Acute Respiratory Syndrome; Severity of Illness Index; Sex Factors; Virus Internalization
PubMed: 32962761
DOI: 10.1186/s42358-020-00151-7 -
Immunology Letters Jul 2020Notch pathway is highly conserved across species and is involved in the regulation of cell differentiation and activity both in embryonic development and adult life....
BACKGROUND
Notch pathway is highly conserved across species and is involved in the regulation of cell differentiation and activity both in embryonic development and adult life. Notch signaling has an important role in the development of hematopoietic stem cells and their differentiation to committed lineages, as well as in the regulation of several non-hematopoietic cell lines.
OBJECTIVE
As Notch signaling has been implicated in various inflammatory and autoimmune diseases, it is of interest to elucidate what role do Notch receptors and ligands have in inflammatory arthritides.
METHODS
We performed a search on the role of Notch receptors (1-4) and Notch ligands Delta-like (DLL) 1, 3, 4 and Jagged (Jag) 1 and 2 in animal models of inflammatory arthritis and most common types of human inflammatory arthritis (rheumatoid arthritis, psoriatic arthritis or ankylosing spondylitis). The initial search identified 135 unique articles, of which 24 were ultimately deemed relevant and included in this systematic review.
RESULTS
Overall, identified articles describe roles for Notch ligands and receptors in inflammatory arthritis, with Notch activation resulting in enhanced Th1/17 polarization, osteoclast differentiation, macrophage activation and fibroblast-like synoviocyte proliferation. However, the inhibitory role of Notch signaling, especially by Jag1 is also described.
CONCLUSION
There is evidence that Notch pathway activation affects multiple cell lineages present within the arthritic environment, therefore potentially acting as one of the drivers of disease pathogenesis. Since cell lineage-selective transgenic mouse models and specific Notch receptor inhibitors are becoming increasingly available, it can be expected that future research will evaluate whether Notch signaling components initiate crucial pathogenic impulses and, therefore, present viable therapeutic targets in inflammatory arthritis.
Topics: Animals; Arthritis; Cell Differentiation; Disease Models, Animal; Humans; Inflammation; Intracellular Signaling Peptides and Proteins; Membrane Proteins; Osteoclasts; Receptors, Notch; Serrate-Jagged Proteins; Th1 Cells; Th17 Cells
PubMed: 32325090
DOI: 10.1016/j.imlet.2020.04.010 -
Digestive Diseases and Sciences Mar 2021Hemophagocytic lymphohistiocytosis (HLH) is a rare and aggressive syndrome of excessive cytokine requiring prompt recognition and aggressive therapy.
BACKGROUND
Hemophagocytic lymphohistiocytosis (HLH) is a rare and aggressive syndrome of excessive cytokine requiring prompt recognition and aggressive therapy.
AIMS
We aimed to systematically characterize HLH in moderate-to-severe inflammatory bowel disease (IBD).
METHODS
We performed a systematic review of the literature (PubMED; EMBASE) and FDA Adverse Event Reporting System in accordance with the PRISMA statement. Use of biologics was used as a surrogate definition for disease severity (consistent with usual and contemporary clinical management), to enable identification of rare HLH cases with the highest fidelity.
RESULTS
58 cases of HLH occurring in IBD patients are known (mean age: 26.0 years, 70% male, 83% with Crohn's disease, mean disease duration 7.0 years). 34.5% of patients were undergoing induction therapy at HLH diagnosis. All cases occurred on patients exposed to anti-TNF agents, but cases with anti-integrin or anti-IL-12/23 exposure were reported. 2/3 of cases did not report prior AZA/6MP exposure. Underlying opportunistic infection or lymphoma was found in > 80% of cases. Survival was 70% if promptly recognized and treated. Five patients restarted biologics after HLH resolved, and one patient developed recurrent HLH.
CONCLUSIONS
HLH is rare among IBD patients exposed to biologic therapy. Most cases had an identifiable infection or malignancy at the time of diagnosis as well as history of immunomodulator use. Risk factors may include younger age, male gender, presence of Crohn's disease, and induction phase of treatment. Our study is not intended to assess risk of HLH with specific IBD therapies.
Topics: Adult; Biological Products; Crohn Disease; Female; Humans; Immunologic Factors; Inflammatory Bowel Diseases; Lymphohistiocytosis, Hemophagocytic; Male; Tumor Necrosis Factor Inhibitors
PubMed: 32300936
DOI: 10.1007/s10620-020-06252-z