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Immunological Medicine May 2024In recent years, rapid advances in research methods have made single cell analysis possible. Systemic sclerosis (SSc), a disease characterized by the triad of immune... (Review)
Review
In recent years, rapid advances in research methods have made single cell analysis possible. Systemic sclerosis (SSc), a disease characterized by the triad of immune abnormalities, fibrosis, and vasculopathy, has also been the subject of various analyses. To summarize the results of single cell analysis in SSc accumulated to date and to deepen our understanding of SSc. Four databases were used to perform a database search on 23rd June 2023. Assessed Grading of Recommendations Assessment, Development and Evaluation certainty of evidence were performed according to PRISMA guidelines. The analysis was completed on July 2023. 17 studies with 358 SSc patients were included. Three studies used PBMCs, six used skin, nine used lung with SSc-interstitial lung diseases (ILDs), and one used lung with SSc-pulmonary arterial hypertension (PAH). The cells studied included immune cells such as T cells, natural killer cells, monocytes, macrophages, and dendritic cells, as well as endothelial cells, fibroblasts, keratinocytes, alveolar type I cells, basal epithelial cells, smooth muscle cells, mesothelial cells, etc. This systematic review revealed the results of single cell analysis, suggesting that PBMCs, skin, SSc-ILD, and SSc-PAH show activation and dysfunction of cells associated with immune-abnormalities, fibrosis, and vasculopathy, respectively.
PubMed: 38818750
DOI: 10.1080/25785826.2024.2360690 -
Arthroscopy : the Journal of... May 2024To assess the current scientific literature on the microbiome's relationship with knee osteoarthritis (OA), with specific focuses on the gut microbiome-joint axis and... (Review)
Review
PURPOSE
To assess the current scientific literature on the microbiome's relationship with knee osteoarthritis (OA), with specific focuses on the gut microbiome-joint axis and joint microbiome-joint axis.
METHODS
A systematic review was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines, searching PubMed, Embase, and Cochrane databases for relevant English-language clinical studies on the gut and/or joint microbiomes' association with knee OA in humans. Bias was evaluated using the methodological index for non-randomized studies score.
RESULTS
Thirty-five thousand bacterial species comprise the gut microbiome; approximately 90% are members of the phyla Bacteroides and Firmicutes. Symbiosis between the gut microbiome and host under normal physiological conditions positively affects host growth, development, immunity, and longevity. Gut microbiome imbalance can negatively influence various physiological processes, including immune response, inflammation, metabolism, and joint health including development of knee OA. In addition, next generation gene sequencing suggests the presence of microorganisms in the synovial fluid of osteoarthritic knees, and distinct microbiome profiles detected are presumed to play a role in the development of OA. With regard to the gut microbiome, consistent alterations in microbial composition between OA patients and controls are noted, in addition to several associations between certain gut bacteria with OA-related knee pain, patient-reported outcome measure performance, imaging findings, and changes in metabolic and inflammatory pathways. Regarding the joint microbiome, studies revealed increased levels of lipopolysaccharide (LPS) and LPS-binding protein in synovial fluid are associated with activated macrophages, and correlated with worsened osteophyte severity, joint space narrowing, and pain scores in knee OA patients. In addition, studies demonstrated various microbial composition differences in OA patients compared to control, with certain joint microbes directly associated with OA pathogenesis, inflammation, and metabolic dysregulation.
CONCLUSIONS
The gut microbiome-joint axis and joint microbiome shows alterations in microbial composition between osteoarthritic patients and controls. These alterations are associated with perturbations of metabolic and inflammatory pathways, imaging findings, osteoarthritis-related pain, and patient reported outcome measure performance.
LEVEL OF EVIDENCE
Systematic Review; Level III.
PubMed: 38797504
DOI: 10.1016/j.arthro.2024.05.010 -
Modern Rheumatology May 2024This systematic review assessed the efficacy and safety of tumor necrosis factor (TNF) inhibitors in patients with systemic juvenile idiopathic arthritis (JIA).
OBJECTIVES
This systematic review assessed the efficacy and safety of tumor necrosis factor (TNF) inhibitors in patients with systemic juvenile idiopathic arthritis (JIA).
METHODS
Studies were searched using PubMed, Embase, Cochrane, Ichushi-Web, and clinical trial registries (from 2000 to 2021). The risk of bias was assessed using the Cochrane Risk of Bias version 2 for randomized controlled trials (RCTs) and the manual for development clinical practice guidelines by Minds, a project promoting evidence-based medicine in Japan, for observational studies.
RESULTS
One RCT and 22 observational studies were included. In the RCT on infliximab, the American College of Rheumatology pediatric (ACR Pedi) 30/50/70 responses at 14 weeks were 63.8%/50.0%/22.4%, with relative risks of 1.30 (95% confidence interval [CI]: 0.94-1.79)/1.48 (95% CI: 0.95-2.29)/1.89 (95% CI: 0.81-4.40), respectively. In the observational studies, ACR Pedi 30/50/70 responses for etanercept at 12 months were 76.7%/64.7%/46.4%, respectively. Infliximab treatment caused anaphylaxis in 17% and an infusion reaction in 23% of patients. The incidence of macrophage activation syndrome, serious infection and malignancy caused by TNF inhibitors was 0%-4%.
CONCLUSIONS
Thus, although TNF inhibitors were relatively safe, they were unlikely to be preferentially administered in patients with systemic JIA because of their inadequate efficacy. Further studies, particularly well-designed RCTs, are necessary to confirm the efficacy and safety of TNF inhibitors for systemic JIA.
PubMed: 38795057
DOI: 10.1093/mr/roae050 -
Biomedicines Apr 2024Achilles tendon (AT) pathologies are common musculoskeletal conditions that can significantly impair function. Despite various traditional treatments, recovery is often... (Review)
Review
Achilles tendon (AT) pathologies are common musculoskeletal conditions that can significantly impair function. Despite various traditional treatments, recovery is often slow and may not restore full functionality. The use of extracellular vesicles (EVs) has emerged as a promising therapeutic option due to their role in cell signaling and tissue regeneration. This systematic review aims to consolidate current in vivo animal study findings on the therapeutic effects of EVs on AT injuries. An extensive literature search was conducted using the PubMed, Scopus, and Embase databases for in vivo animal studies examining the effects of EVs on AT pathologies. The extracted variables included but were not limited to the study design, type of EVs used, administration methods, efficacy of treatment, and proposed therapeutic mechanisms. After screening, 18 studies comprising 800 subjects were included. All but one study reported that EVs augmented wound healing processes in the AT. The most proposed mechanisms through which this occurred were gene regulation of the extracellular matrix (ECM), the enhancement of macrophage polarization, and the delivery of therapeutic microRNAs to the injury site. Further research is warranted to not only explore the therapeutic potential of EVs in the context of AT pathologies, but also to establish protocols for their clinical application.
PubMed: 38790904
DOI: 10.3390/biomedicines12050942 -
Modern Rheumatology May 2024This systematic review assessed the efficacy and safety of abatacept in patients with systemic juvenile idiopathic arthritis (JIA).
OBJECTIVES
This systematic review assessed the efficacy and safety of abatacept in patients with systemic juvenile idiopathic arthritis (JIA).
METHODS
Studies published between 2000 and 2021 were searched using PubMed, Embase, Cochrane, Ichushi-Web and clinical trial registries. The risk of bias was assessed according to the manual for development clinical practice guidelines by Minds, a project to promote evidence-based medicine in Japan.
RESULTS
Seven observational studies were included. American College of Rheumatology pediatric 30/50/70 responses at 3, 6 and 12 months were 64.8%/50.3%/27.9%, 85.7%/71.4%/42.9% and 80.0%/50.0%/40.0%, respectively. Outcomes on systemic symptoms, joint symptoms and activities of daily living were not obtained. No macrophage activation syndrome or infusion reaction occurred. Serious infection occurred in 2.6% of cases.
CONCLUSIONS
Abatacept improved the disease activity index. In addition, abatacept was as safe as interleukin-6 (IL -6) and IL-1 inhibitors. However, both the efficacy and safety data in this systematic review should be reviewed with caution because their quality of evidence is low or very low. Further studies are needed to confirm the efficacy and safety of abatacept for systemic JIA, especially its efficacy on joint symptoms.
PubMed: 38753302
DOI: 10.1093/mr/roae046 -
The Lancet. Gastroenterology &... Jul 2024Microsatellite instability (MSI) status and tumour-infiltrating lymphocytes (TIL) are established prognostic factors in colorectal cancer. Previous studies evaluating... (Meta-Analysis)
Meta-Analysis
Clinical significance of combined tumour-infiltrating lymphocytes and microsatellite instability status in colorectal cancer: a systematic review and network meta-analysis.
BACKGROUND
Microsatellite instability (MSI) status and tumour-infiltrating lymphocytes (TIL) are established prognostic factors in colorectal cancer. Previous studies evaluating the combination of TIL and MSI status identified distinct colorectal cancer subtypes with unique prognostic associations. However, these studies were often limited by sample size, particularly for MSI-high (MSI-H) tumours, and there is no comprehensive summary of the available evidence. We aimed to review the literature to compare the survival outcomes associated with the subtypes derived from the integrated MSI-TIL classification in patients with colorectal cancer.
METHODS
In this systematic review and network meta-analysis, we searched PubMed, Embase, Scopus, and the Cochrane Library without language restrictions, for articles published between Jan 1, 1990, and March 13, 2024. Patient cohorts comparing different combinations of TIL (high or low) and MSI status (MSI or microsatellite stable [MSS]) in patients with surgically resected colorectal cancer were included. Studies were excluded if they focused on neoadjuvant therapy or on other immune markers such as B cells or macrophages. Methodological quality assessment was done with the Newcastle-Ottawa scale; data appraisal and extraction was done independently by two reviewers. Summary estimates were extracted from published reports. The primary outcomes were overall survival, disease-free survival, and cancer-specific survival. A frequentist network meta-analysis was done to compare hazard ratios (HRs) and 95% CI for each outcome. The MSI-TIL subgroups were prognostically ranked based on P-score, bias, magnitude, and precision of associations with each outcome. The protocol is registered with PROSPERO (CRD42023461108).
FINDINGS
Of 302 studies initially identified, 21 studies (comprising 14 028 patients) were included in the systematic review and 19 (13 029 patients) in the meta-analysis. Nine studies were identified with a low risk of bias and the remaining ten had a moderate risk of bias. The MSI-TIL-high (MSI-TIL-H) subtype exhibited longer overall survival (HR 0·45, 95% CI 0·34-0·61; I=77·7%), disease-free survival (0·43, 0·32-0·58; I=61·6%), and cancer-specific survival (0·53, 0·43-0·66; I=0%), followed by the MSS-TIL-H subtype for overall survival (HR 0·53, 0·41-0·69; I=77·7%), disease-free survival (0·52, 0·41-0·64; I=61·6%), and cancer-specific survival (0·55, 0·47-0·64; I=0%) than did patients with MSS-TIL-low tumours (MSS-TIL-L). Patients with the MSI-TIL-L subtype had similar overall survival (0·88, 0·66-1·18; I=77·7%) and disease-free survival (0·93, 0·69-1·26; I=61·6%), but a modestly longer cancer-specific survival (0·72, 0·57-0·90; I=0%) than did the MSS-TIL-L subtype. Results from the direct and indirect evidence were strongly congruous.
INTERPRETATION
The findings from this network meta-analysis suggest that better survival was only observed among patients with TIL-H colorectal cancer, regardless of MSI or MSS status. The integrated MSI-TIL classification should be further explored as a predictive tool for clinical decision-making in early-stage colorectal cancer.
FUNDING
German Research Council (HO 5117/2-2).
Topics: Humans; Microsatellite Instability; Lymphocytes, Tumor-Infiltrating; Colorectal Neoplasms; Prognosis; Network Meta-Analysis; Disease-Free Survival; Clinical Relevance
PubMed: 38734024
DOI: 10.1016/S2468-1253(24)00091-8 -
Iranian Journal of Public Health Jan 2024Cell aging is associated with changes in telomeres due to DNA damage arising from chronic inflammation in obese patients. The aim of the systematic review and... (Review)
Review
BACKGROUND
Cell aging is associated with changes in telomeres due to DNA damage arising from chronic inflammation in obese patients. The aim of the systematic review and meta-analysis was to find the relationship between obesity and aging or senescence.
METHODS
The systematic review was conducted through PRISMA guideline, beginning with literature search within 2012-2022 in several databases (PubMed, EBSCOHost, Science Direct, Scopus, and Cochrane) followed by screening process using predetermined PICO criteria. Original studies on the topic of obesity and senescence (aging), from preclinical studies to clinical research (cohort or cross-sectional studies) that were published within the last ten years. All studies were appraised using SYRCLE risk of bias tool for preclinical studies and Newcastle-Ottawa Scale (NOS) for cross-sectional and cohort studies. The data extraction on the studies' characteristic and outcome on aging or senescence were followed by quantitative analysis using MetaXL process on prevalence ratio and hazard ratio of obesity to comorbidities and mortality.
RESULTS
Fifteen studies were enrolled. Obesity and white adipose tissue cause increased levels of pro-inflammatory and pro-senescence cytokine and macrophage whilst the aging process lowers metabolism with increased insulin resistance and linked to increased risk of obesity. Obesity occurs in 22% (95% CI 18%-26%) of elderly population with higher prevalence rate in the women population. Obesity is associated with significant increased risk of multimorbidity by 56% (OR = 1.58 [95% CI 1.48-1.96]).
CONCLUSION
The obesity and aging or senescence has reciprocal relationship between each other.
PubMed: 38694856
DOI: 10.18502/ijph.v53i1.14679 -
The Journal of Tehran Heart Center Oct 2023Among its functions, brain-derived neurotrophic factor (BDNF) regulates endothelial and macrophage activation, possibly playing a role in atherosclerotic plaque... (Review)
Review
BACKGROUND
Among its functions, brain-derived neurotrophic factor (BDNF) regulates endothelial and macrophage activation, possibly playing a role in atherosclerotic plaque pathophysiology. Given contradicting reports, this study sought to investigate whether blood levels of BDNF differed between patients with coronary heart disease (CHD) and controls.
METHODS
We explored PubMed, Embase, Web of Science, and Cochrane Library for studies comparing BDNF blood levels in patients with CHD and controls. Random-effect meta-analysis was conducted to calculate the standardized mean differences (SMD) and 95% confidence intervals (CI). The Newcastle-Ottawa scale was used to evaluate the quality of included articles, and statistical analyses were conducted using R version 4.0.4.
RESULTS
The final analysis comprised 12 investigations covering 1422 CHD cases and 929 controls with mean ages of 59.66±13.56 and 53.78±13.61 years, respectively. The initial analyses revealed a tendency toward low levels of BDNF in the CHD group compared with the control group (SMD= -0.41; 95% CI, -1.12 to 0.30; P=0.26). After the removal of outliers, the difference achieved statistical difference (SMD= -0.56; 95% CI, -0.93 to -0.19; P<0.01). Subgroup analysis demonstrated no significant difference between serum and plasma BDNF levels (P=0.54); however, subgroup analyses of studies investigating plasma BDNF showed that patients with CHD had significantly lower BDNF levels.
CONCLUSION
Serum and plasma BDNF concentrations were considerably lower in patients with CHD than in healthy controls. Further studies of higher quality are required on the potential role of BDNF as a biomarker of CHD pathophysiology and severity.
PubMed: 38680638
DOI: 10.18502/jthc.v18i4.14823 -
Natural Product Research Apr 2024Inflammation is a complex and necessary mechanism of an organ's response to biological, chemical and/or physical stimuli. In recent years, investigations on natural... (Review)
Review
Inflammation is a complex and necessary mechanism of an organ's response to biological, chemical and/or physical stimuli. In recent years, investigations on natural compounds with therapeutic actions for the treatment of different diseases have increased. Among these compounds, bromelain is highlighted, as a cysteine protease isolated from the (pineapple) stem. This review aimed to evaluate the anti-inflammatory activity of bromelain, as well as its pathways on inflammatory mediators, through a systematic review with studies on different cell lines. The search was performed in PubMed, Science Direct, Scopus, Cochrane Library and Web of Science databases. Bromelain reduced IL-1β, IL-6 and TNF-α secretion when immune cells were already stimulated in an overproduction condition by proinflammatory cytokines, generating a modulation in the inflammatory response through prostaglandins reduction and activation of a cascade reactions that trigger neutrophils and macrophages, in addition to accelerating the healing process.
PubMed: 38676413
DOI: 10.1080/14786419.2024.2342553 -
Cancer Treatment Reviews Jun 2024Gastric cancer (GC), known for its unfavorable prognosis, has been classified in four distinct molecular subtypes. These subtypes not only exhibit differences in their... (Review)
Review
BACKGROUND
Gastric cancer (GC), known for its unfavorable prognosis, has been classified in four distinct molecular subtypes. These subtypes not only exhibit differences in their genome and transcriptome but also in the composition of their tumor immune microenvironment. The microsatellite instable (MSI) and Epstein-Barr virus (EBV) positive GC subtypes show clear clinical benefits from immune checkpoint blockade, likely due to a neoantigen-driven and virus-driven antitumor immune response and high expression of immune checkpoint molecule PD-L1. However, even within these subtypes response to checkpoint inhibition is variable, which is potentially related to heterogeneity in the tumor immune microenvironment (TIME) and expression of co-inhibitory molecules. We conducted a systematic review to outline the current knowledge about the immunological features on the TIME of MSI and EBV + GCs.
METHODS
A systematic search was performed in PubMed, EMBASE and Cochrane Library. All articles from the year 1990 and onwards addressing immune features of gastric adenocarcinoma were reviewed and included based on predefined in- and exclusion criteria.
RESULTS
In total 5962 records were screened, of which 139 were included that reported immunological data on molecular GC subtypes. MSI and EBV + GCs were reported to have a more inflamed TIME compared to non-MSI and EBV- GC subtypes. Compared to microsatellite stable (MSS) tumors, MSI tumors were characterized by higher numbers of CD8 + and FoxP3 + T cells, and tumor infiltrating pro- and anti-inflammatory macrophages. HLA-deficiency was most common in MSI tumors compared to other molecular GC subtypes and associated with lower T and B cell infiltrates compared to HLA-proficient tumors. EBV + was associated with a high number of CD8 + T cells, Tregs, NK cells and macrophages. Expression of PD-L1, CTLA-4, Granzyme A and B, Perforin and interferon-gamma was enriched in EBV + tumors. Overall, MSI tumors harbored a more heterogeneous TIME in terms of immune cell composition and immune checkpoints compared to the EBV + tumors.
DISCUSSION AND CONCLUSION
MSI and EBV + GCs are highly Handbook for Conducting a Literature-Based Health Assessment Using OHAT Approach for Systematic Review and Evidence Integration.; 2019pro-inflammatory immune cell populations. Although studies on the direct comparison of EBV + and MSI tumors are limited, EBV + tumors show less intra-subgroup heterogeneity compared to MSI tumors. More studies are needed to identify how Intra-subgroup heterogeneity impacts response to immunotherapy efficacy.
Topics: Humans; Stomach Neoplasms; Tumor Microenvironment; Epstein-Barr Virus Infections; DNA Mismatch Repair; Herpesvirus 4, Human; Microsatellite Instability
PubMed: 38669788
DOI: 10.1016/j.ctrv.2024.102737