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Gynecological Endocrinology : the... Dec 2023Over the last decade, an emerging role of novel cytokines in the pathogenesis of gestational diabetes mellitus (GDM) has been proposed. The present study was... (Meta-Analysis)
Meta-Analysis
Over the last decade, an emerging role of novel cytokines in the pathogenesis of gestational diabetes mellitus (GDM) has been proposed. The present study was implemented to provide a more accurate estimate of the effect size of the association between leptin, tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6) and the risk of GDM. Online databases were looked up to January 2023 using the search string: (leptin OR TNF-α OR IL-6) AND "gestational diabetes." Observational studies investigating the association of selected cytokines and GDM risk were included. Odds ratios and their 95% confidence intervals (CIs) were extracted and random-effects models were used to estimate the pooled effect. Twenty-four studies were included in the meta-analysis. A significant association was found between higher circulating leptin and the risk of GDM and the pooled estimate was 1.16 (95%CI: 1.07, 1.27). Higher circulating levels of IL-6 and TNF-α were associated with increased risk of GDM, and the pooled estimates were 1.35 (95%CI: 1.05, 1.73) and 1.28 (95%CI: 1.01, 1.62), respectively. The studied cytokines could be implicated in the GDM pathogenesis and used as potential biomarkers for assessing the GDM risk. Additional longitudinal studies with large sample sizes are needed for a further evaluation of these findings.
Topics: Pregnancy; Female; Humans; Diabetes, Gestational; Leptin; Tumor Necrosis Factor-alpha; Interleukin-6; Cytokines
PubMed: 36944372
DOI: 10.1080/09513590.2023.2183049 -
The Cochrane Database of Systematic... Jan 2022Interleukin-1 (IL-1) blocking agents have been used for treating severe coronavirus disease 2019 (COVID-19), on the premise that their immunomodulatory effect might be... (Review)
Review
BACKGROUND
Interleukin-1 (IL-1) blocking agents have been used for treating severe coronavirus disease 2019 (COVID-19), on the premise that their immunomodulatory effect might be beneficial in people with COVID-19.
OBJECTIVES
To assess the effects of IL-1 blocking agents compared with standard care alone or with placebo on effectiveness and safety outcomes in people with COVID-19. We will update this assessment regularly.
SEARCH METHODS
We searched the Cochrane COVID-19 Study Register and the COVID-19 L-OVE Platform (search date 5 November 2021). These sources are maintained through regular searches of MEDLINE, Embase, CENTRAL, trial registers and other sources. We also checked the World Health Organization International Clinical Trials Registry Platform, regulatory agency websites, Retraction Watch (search date 3 November 2021).
SELECTION CRITERIA
We included randomised controlled trials (RCTs) evaluating IL-1 blocking agents compared with standard care alone or with placebo for people with COVID-19, regardless of disease severity.
DATA COLLECTION AND ANALYSIS
We followed Cochrane methodology. The protocol was amended to reduce the number of outcomes considered. Two researchers independently screened and extracted data and assessed the risk of bias with the Cochrane Risk of Bias 2 tool. We rated the certainty of evidence using the GRADE approach for the critical outcomes of clinical improvement (Day 28; ≥ D60); WHO Clinical Progression Score of level 7 or above (i.e. the proportion of participants with mechanical ventilation +/- additional organ support OR death) (D28; ≥ D60); all-cause mortality (D28; ≥ D60); incidence of any adverse events; and incidence of serious adverse events.
MAIN RESULTS
We identified four RCTs of anakinra (three published in peer-reviewed journals, one reported as a preprint) and two RCTs of canakinumab (published in peer-reviewed journals). All trials were multicentre (2 to 133 centres). Two trials stopped early (one due to futility and one as the trigger for inferiority was met). The median/mean age range varied from 58 to 68 years; the proportion of men varied from 58% to 77%. All participants were hospitalised; 67% to 100% were on oxygen at baseline but not intubated; between 0% and 33% were intubated at baseline. We identified a further 16 registered trials with no results available, of which 15 assessed anakinra (four completed, four terminated, five ongoing, three not recruiting) and one (completed) trial assessed canakinumab. Effectiveness of anakinra for people with COVID-19 Anakinra probably results in little or no increase in clinical improvement at D28 (risk ratio (RR) 1.08, 95% confidence interval (CI) 0.97 to 1.20; 3 RCTs, 837 participants; absolute effect: 59 more per 1000 (from 22 fewer to 147 more); moderate-certainty evidence. The evidence is uncertain about an effect of anakinra on 1) the proportion of participants with a WHO Clinical Progression Score of level 7 or above at D28 (RR 0.67, 95% CI 0.36 to 1.22; 2 RCTs, 722 participants; absolute effect: 55 fewer per 1000 (from 107 fewer to 37 more); low-certainty evidence) and ≥ D60 (RR 0.54, 95% CI 0.30 to 0.96; 1 RCT, 606 participants; absolute effect: 47 fewer per 1000 (from 72 fewer to 4 fewer) low-certainty evidence); and 2) all-cause mortality at D28 (RR 0.69, 95% CI 0.34 to 1.39; 2 RCTs, 722 participants; absolute effect: 32 fewer per 1000 (from 68 fewer to 40 more); low-certainty evidence). The evidence is very uncertain about an effect of anakinra on 1) the proportion of participants with clinical improvement at ≥ D60 (RR 0.93, 95% CI 0.78 to 1.12; 1 RCT, 115 participants; absolute effect: 59 fewer per 1000 (from 186 fewer to 102 more); very low-certainty evidence); and 2) all-cause mortality at ≥ D60 (RR 1.03, 95% CI 0.68 to 1.56; 4 RCTs, 1633 participants; absolute effect: 8 more per 1000 (from 84 fewer to 147 more); very low-certainty evidence). Safety of anakinra for people with COVID-19 Anakinra probably results in little or no increase in adverse events (RR 1.02, 95% CI 0.94 to 1.11; 2 RCTs, 722 participants; absolute effect: 14 more per 1000 (from 43 fewer to 78 more); moderate-certainty evidence). The evidence is uncertain regarding an effect of anakinra on serious adverse events (RR 0.95, 95% CI 0.58 to 1.56; 2 RCTs, 722 participants; absolute effect: 12 fewer per 1000 (from 104 fewer to 138 more); low-certainty evidence). Effectiveness of canakinumab for people with COVID-19 Canakinumab probably results in little or no increase in clinical improvement at D28 (RR 1.05, 95% CI 0.96 to 1.14; 2 RCTs, 499 participants; absolute effect: 42 more per 1000 (from 33 fewer to 116 more); moderate-certainty evidence). The evidence of an effect of canakinumab is uncertain on 1) the proportion of participants with a WHO Clinical Progression Score of level 7 or above at D28 (RR 0.72, 95% CI 0.44 to 1.20; 2 RCTs, 499 participants; absolute effect: 35 fewer per 1000 (from 69 fewer to 25 more); low-certainty evidence); and 2) all-cause mortality at D28 (RR:0.75; 95% CI 0.39 to 1.42); 2 RCTs, 499 participants; absolute effect: 20 fewer per 1000 (from 48 fewer to 33 more); low-certainty evidence). The evidence is very uncertain about an effect of canakinumab on all-cause mortality at ≥ D60 (RR 0.55, 95% CI 0.16 to 1.91; 1 RCT, 45 participants; absolute effect: 112 fewer per 1000 (from 210 fewer to 227 more); very low-certainty evidence). Safety of canakinumab for people with COVID-19 Canakinumab probably results in little or no increase in adverse events (RR 1.02; 95% CI 0.86 to 1.21; 1 RCT, 454 participants; absolute effect: 11 more per 1000 (from 74 fewer to 111 more); moderate-certainty evidence). The evidence of an effect of canakinumab on serious adverse events is uncertain (RR 0.80, 95% CI 0.57 to 1.13; 2 RCTs, 499 participants; absolute effect: 44 fewer per 1000 (from 94 fewer to 28 more); low-certainty evidence).
AUTHORS' CONCLUSIONS
Overall, we did not find evidence for an important beneficial effect of IL-1 blocking agents. The evidence is uncertain or very uncertain for several outcomes. Sixteen trials of anakinra and canakinumab with no results are currently registered, of which four are completed, and four terminated. The findings of this review are updated on the COVID-NMA platform (covid-nma.com).
Topics: Aged; Female; Humans; Interleukin-1; Male; Middle Aged; Randomized Controlled Trials as Topic; Respiration, Artificial; COVID-19 Drug Treatment
PubMed: 35080773
DOI: 10.1002/14651858.CD015308 -
Nutrients Oct 2022A ketogenic diet characterized by high fat and low carbohydrate can drive the body to produce a large number of ketone bodies, altering human metabolism. Unlike normal... (Meta-Analysis)
Meta-Analysis
A ketogenic diet characterized by high fat and low carbohydrate can drive the body to produce a large number of ketone bodies, altering human metabolism. Unlike normal cells, tumor cells have difficulty in consuming ketone bodies. Therefore, the application of ketogenic diets in cancer therapy is gaining attention. However, the effect of ketogenic diets on body parameters of cancer patients is not well established. This meta-analysis aimed to summarize the effects of ketogenic diets on cancer patients in earlier controlled trials. PubMed, Embase, and Cochrane Library were searched for clinical trials that enrolled cancer patients who received ketogenic diets intervention. Ten controlled trials were included in this meta-analysis. Data were extracted and checked by three authors independently. Pooled effect sizes revealed a significant effect of ketogenic diets on body weight (SMD −1.83, 95% CI −2.30 to −1.35; p < 0.00001) and fat mass (SMD −1.52, 95% CI −1.92 to −1.07; p < 0.00001). No significant effect on blood glucose, insulin, or lipid profile except triglycerides was found in the analysis. It had no effect on liver and kidney function except that GGT were decreased a little. There were no significant changes in IGF-1 and TNF-α related to tumor growth. Mental health improvement of cancer patients was supported by several trials. Taken together, findings in this study confirmed that the ketogenic diet was a safe approach for cancer patients reducing body weight and fat mass. In addition, cancer treatment-related indicators changed insignificantly. Ketogenic diets may be beneficial to the quality of life of cancer patients. However, intervention duration in most studies is shorter than 6 months, and the effect of a long-term ketogenic diet is still required further validation. More trials with a larger sample size are necessary to give a more conclusive result; PROSPERO registration number: CRD42021277559.
Topics: Blood Glucose; Body Composition; Body Weight; Diet, Ketogenic; Humans; Insulin-Like Growth Factor I; Insulins; Ketone Bodies; Neoplasms; Quality of Life; Triglycerides; Tumor Necrosis Factor-alpha
PubMed: 36235844
DOI: 10.3390/nu14194192 -
Experimental Gerontology Jun 2023Ageing is associated with several physiological changes, including changes in the immune system. Age-related changes in the innate and adaptive immune system are thought... (Review)
Review
INTRODUCTION
Ageing is associated with several physiological changes, including changes in the immune system. Age-related changes in the innate and adaptive immune system are thought to contribute to frailty. Understanding the immunological determinants of frailty could help to develop and deliver more effective care to older people. This systematic review aims to study the association between biomarkers of the ageing immune system and frailty.
METHODS
The search strategy was performed in PubMed and Embase, using the keywords "immunosenescence", "inflammation", "inflammaging" and "frailty". We included studies that investigated the association of biomarkers of the ageing immune system and frailty cross-sectionally in older adults, without an active disease that affects immune parameters. Three independent researchers selected the studies and performed data extraction. Study quality was assessed using the Newcastle-Ottawa scale adapted for cross-sectional studies.
RESULTS
A total of 44 studies, with a median number of 184 participants, was included. Study quality was good in 16 (36 %), moderate in 25 (57 %) and poor in 3 (7 %) of studies. The most frequently studied inflammaging biomarkers were IL-6, CRP and TNF-α. Associations with frailty were observed for increased levels of (i) IL-6 in 12 of 24 studies, (ii) CRP in 7 of 19 studies, and (ii) TNF-α in 4 of 13 studies. In none of the other studies were associations observed of frailty with these biomarkers. Different types of T-lymphocyte subpopulations were studied but each subset was studied only once, and the study sample sizes were low.
CONCLUSION
Our review of 44 studies on the relation between immune biomarkers and frailty identified IL-6 and CRP as the biomarkers that were most consistently associated with frailty. T-lymphocyte subpopulations were investigated but too infrequently to draw strong conclusions yet, although initial results are promising. Additional studies are required in order to further validate these immune biomarkers in larger cohorts. Furthermore, prospective studies in more uniform settings and larger cohorts are needed to further investigate the association with immune candidate biomarkers for which potential associations with ageing and frailty were previously observed, before these can be used in clinical practice to help assess frailty and improve the care treatments of older patients.
Topics: Humans; Aged; Prospective Studies; Tumor Necrosis Factor-alpha; Cross-Sectional Studies; Interleukin-6; Aging; Frailty; Biomarkers; Immune System; Frail Elderly
PubMed: 37028607
DOI: 10.1016/j.exger.2023.112163 -
Heart, Lung & Circulation Aug 2023Statins are well-established for their treatment of cardiovascular disease (CVD) due to their cholesterol-lowering effects and potential anti-inflammatory properties.... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Statins are well-established for their treatment of cardiovascular disease (CVD) due to their cholesterol-lowering effects and potential anti-inflammatory properties. Although previous systematic reviews demonstrate that statins reduce inflammatory biomarkers in the secondary prevention of CVD, none examine their effects on cardiac and inflammatory biomarkers in a primary prevention setting.
METHODS
We conducted a systematic review and meta-analysis to examine the effects of statins on cardiovascular and inflammatory biomarkers among individuals without established CVD. The biomarkers included are: cardiac troponin, N-terminal pro B-type natriuretic peptide (NT-proBNP), C-reactive protein (CRP), tumour necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), soluble vascular cell adhesion molecule (sVCAM), soluble intercellular adhesion molecule (sICAM), soluble E-selectin (sE-selectin) and endothelin-1 (ET-1). A literature search was performed through Ovid MEDLINE, Embase and CINAHL Plus for randomised controlled trials (RCTs) published up to June 2021.
RESULTS
Overall, 35 RCTs with 26,521 participants were included in our meta-analysis. Data was pooled using random effects models presented as standardised mean differences (SMD) with 95% confidence intervals (CI). Combining 36 effect sizes from 29 RCTs, statin use resulted in a significant reduction in CRP levels (SMD -0.61; 95% CI -0.91, -0.32; P<0.001). This reduction was observed for both hydrophilic (SMD -0.39; 95% CI -0.62, -0.16; P<0.001) and lipophilic statins (SMD -0.65; 95% CI -1.01, -0.29; P<0.001). There were no significant changes in serum concentrations of cardiac troponin, NT-proBNP, TNF-α, IL-6, sVCAM, sICAM, sE-selectin and ET-1.
CONCLUSION
This meta-analysis demonstrates that statin use reduces serum CRP levels in a primary prevention setting for CVD, with no clear effect on the other eight biomarkers studied.
Topics: Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Interleukin-6; Tumor Necrosis Factor-alpha; Biomarkers; Cardiovascular Diseases; Troponin
PubMed: 37291001
DOI: 10.1016/j.hlc.2023.04.300 -
Medicina (Kaunas, Lithuania) Jul 2022: Sudden Sensorineural Hearing Loss (SSNHL) is a quite common clinical finding in otolaryngology. Most cases are classified as idiopathic and there is a dearth of... (Meta-Analysis)
Meta-Analysis Review
: Sudden Sensorineural Hearing Loss (SSNHL) is a quite common clinical finding in otolaryngology. Most cases are classified as idiopathic and there is a dearth of information on factors able to predict the response to treatment and hearing recovery. The main aim of this systematic review and meta-analysis was to assess and critically discuss the role of circulating inflammatory biomarkers in SSNHL. : A search was conducted of the English literature published between 1 January 2009 and 7 July 2022 on Pubmed, Scopus, Web of Science, ScienceDirect, and Cochrane following PRISMA guidelines. : A total of 256 titles were retrieved from the search. After full-text screening and application of inclusion/exclusion criteria, 13 articles were included. Twelve out of thirteen studies reported significant differences in biomarkers values in SSNHL patients, of which Tumor Necrosis Factor alpha (TNF-α) and C-reactive Protein (CRP) were the most analyzed. Our meta-analysis for CRP's mean values in SSNHL groups vs. controls showed significantly higher CRP levels with a pooled overall difference of 1.07; confidence interval (CI) at 95%: 0.03; 2.11. For TNF-α, discordant results were found: three studies showed significantly higher levels in SSNHL patients vs. controls, whereas other three investigations showed lower levels in the SSNHL groups (overall pooled difference 1.97; 95% CI: -0.90; 4.84). A high between-study heterogeneity was found. : This systematic review pointed out that, although there exists a growing literature in the field of circulatory biomarkers identification in SSNHL, there is a high heterogeneity of results and low quality of evidence. CRP resulted to be higher in SSNHL patients than in controls, while TNF-α showed more heterogeneous behavior. The data reported herein needs to be confirmed in well-designed prospective multicenter randomized studies, with the objective of improving SSNHL treatment and outcome and thereby reducing the social burden of hearing loss.
Topics: Biomarkers; Hearing Loss, Sensorineural; Hearing Loss, Sudden; Humans; Multicenter Studies as Topic; Prognosis; Prospective Studies; Retrospective Studies; Tumor Necrosis Factor-alpha
PubMed: 35888682
DOI: 10.3390/medicina58070963 -
Cytokine Dec 2023Interleukin-36s (IL-36s) are a category of inflammatory cytokines and an increasing number of studies over the past decade have found that different kinds of IL-36s play... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Interleukin-36s (IL-36s) are a category of inflammatory cytokines and an increasing number of studies over the past decade have found that different kinds of IL-36s play different roles in cancers. This systematic review and meta-analysis aimed to evaluate the prognostic value of IL-36s in different cancer types.
METHOD
Two reviewers independently searched in PubMed, Cochrane Library and EMBASE up to December 13, 2022. We extracted the hazard ratio (HR) and the confidence intervals (CIs) of the related prognostic outcomes and analyzed the pooled HR.
RESULTS
We included 12 studies including 1925 patients. In all, six studies including IL-36α, five including IL-36γ and one including IL-36β. A high expression of IL-36α was associated with better overall survival (OS) (HR = 0.48, 95 %CI: 0.37-0.62, P < 0.001) of cancer patients. The expression of IL-36γ was not related with cancers. Further, subgroup analysis showed that the expression of IL-36γ had no correlation with the OS of colorectal cancer (CRC) and non‑small cell lung cancer (NSCLC) patients. Interestingly, a high expression of IL-36γ played contrasting prognostic roles in hepatocellular carcinoma (HCC) (HR = 0.43, 95 %CI: 0.27-0.69, P < 0.001) patients and gastric cancer (GC) (HR = 1.58, 95 %CI: 1.33-1.87, P < 0.001) patients. The only IL-36β related study showed the expression of IL-36β was not correlated with the prognosis of CRC patients (P > 0.05).
CONCLUSION
IL-36α, IL-36β and IL-36γ possibly play different roles in different cancers. High expression of IL-36α may be associated with good prognostic value in cancer patients, especially in CRC patients. The association between cancers prognosis and expression of IL-36β or IL-36γ needs further evaluation. These conclusions need more clinical prognostic data for confirmation.
Topics: Humans; Interleukin-1; Prognosis; Carcinoma, Hepatocellular; Carcinoma, Non-Small-Cell Lung; Liver Neoplasms; Lung Neoplasms; Interleukins
PubMed: 37922622
DOI: 10.1016/j.cyto.2023.156397 -
International Journal of Environmental... Feb 2023Several heterogeneous pathophysiology pathways have been hypothesized for being involved in the onset and course of Post-Traumatic Stress Disorder (PTSD). This... (Review)
Review
Several heterogeneous pathophysiology pathways have been hypothesized for being involved in the onset and course of Post-Traumatic Stress Disorder (PTSD). This systematic review aims to summarize the current evidence on the role of inflammation and immunological dysregulations in PTSD, investigating possible peripheral biomarkers linked to the neuroimmune response to stress. A total of 44 studies on the dysregulated inflammatory and metabolic response in subjects with PTSD with respect to controls were included. Eligibility criteria included full-text publications in the English language, human adult samples, studies involving both subjects with a clinical diagnosis of PTSD and a healthy control group. The research was focused on specific blood neuroimmune biomarkers, namely IL-1β, TNF-α, IL-6 and INF-γ, as well as on the potential harmful role of reduced antioxidant activity (involving catalase, superoxide dismutase and glutathione peroxidase). The possible role of the inflammatory-altered tryptophan metabolism was also explored. The results showed conflicting data on the role of pro-inflammatory cytokines in individuals with PTSD, and a lack of study regarding the other mediators investigated. The present research suggests the need for further studies in human samples to clarify the role of inflammation in the pathogenesis of PTSD, to define potential peripheral biomarkers.
Topics: Adult; Humans; Stress Disorders, Post-Traumatic; Cytokines; Tumor Necrosis Factor-alpha; Inflammation; Biomarkers
PubMed: 36833633
DOI: 10.3390/ijerph20042937 -
European Journal of Medical Research Sep 2022In both the general population and people with multiple sclerosis (PwMS), physical exercise is associated with improved mental well-being. Moreover, there is evidence of... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
In both the general population and people with multiple sclerosis (PwMS), physical exercise is associated with improved mental well-being. Moreover, there is evidence of the possible protection of physical activity against disease progression in multiple sclerosis (MS). However, the question arises if acute or regular exercise has any impact on the immune system in PwMS. To answer this question, we performed a systematic review and meta-analysis on both plasma and serum cytokine levels (IL-6 and TNF-α) before and after acute and regular exercise among PwMS and compared to healthy controls.
METHOD
We performed an online search via PubMed, EMBASE, SCOPUS, Web of Science, and Cochrane Library till September 2021 to identify original studies on IL-6 and TNF-α changes after acute and regular exercise in PwMS and controls. Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA), 11 original studies were included in the meta-analysis. Sensitivity analyses were used to identify the origins of heterogeneity. R 4.0.4 was used to perform the meta-analysis of IL-6 and TNF-α levels before and after acute and regular exercise in PwMS, compared to controls. This study does not qualify for a clinical trial number.
RESULTS
IL-6 levels did neither increase nor decrease after acute and regular exercise in PwMS, and compared to controls (pre- vs. post-intervention: Standardized Mean Difference (SMD) -0.09, 95% CI [-0.29; 0.11], p-value = 0.37, PwMS vs. Control: SMD -0.08, 95% CI [-0.33; 0.16], p-value = 0.47). In PwMS, TNF-α levels decreased after regular exercise and when TNF-α levels of both acute and regular exercise were pooled (pre- vs. post-intervention: SMD -0.51, 95% CI [-0.91; 0.11], p-value = 0.01, PwMS vs. Control: SMD -0.23, 95% CI [-0.66; 0.18], p-value = 0.26). TNF-α levels did neither increase nor decrease after acute and regular exercise in PwMS, when compared to controls.
CONCLUSION
This systematic review and meta-analysis show that exercise does not lead to significant changes in peripheral levels of IL-6 in PwMS in contrast to the observed response in healthy subjects and other medical contexts. However, regular exercise had a specific anti-inflammatory effect on blood TNF-α levels in PwMS. It remains to be investigated why PwMS display this different exercise-induced pattern of cytokines.
Topics: Adult; Anti-Inflammatory Agents; Cytokines; Exercise; Humans; Interleukin-6; Multiple Sclerosis; Tumor Necrosis Factor-alpha
PubMed: 36156182
DOI: 10.1186/s40001-022-00814-9 -
Journal of Nanobiotechnology Oct 2023This systematic review and meta-analysis aimed to evaluate the efficacy of engineered extracellular vesicles (EEVs) in the treatment of ischemic stroke (IS) in... (Meta-Analysis)
Meta-Analysis
BACKGROUND
This systematic review and meta-analysis aimed to evaluate the efficacy of engineered extracellular vesicles (EEVs) in the treatment of ischemic stroke (IS) in preclinical studies and to compare them with natural extracellular vesicles (EVs). The systematic review provides an up-to-date overview of the current state of the literature on the use of EEVs for IS and informs future research in this area.
METHODS
We searched PubMed, EMBASE, Web of Science, Cochrane Library, and Scopus databases for peer-reviewed preclinical studies on the therapeutic effect of EEVs on IS.Databases ranged from the inception to August 1, 2023. The outcome measures included infarct volumes, neurological scores, behavioral scores, apoptosis rates, numbers of neurons, and levels of IL-1β, IL-6, and TNF-α. The CAMARADES checklist was used to assess the quality and bias risks of the studies. All statistical analyses were performed using RevMan 5.4 software.
RESULTS
A total of 28 studies involving 1760 animals met the inclusion criteria. The results of the meta-analysis showed that compared to natural EVs, EEVs reduced infarct volume (percentage: SMD = -2.33, 95% CI: -2.92, -1.73; size: SMD = -2.36, 95% CI: -4.09, -0.63), improved neurological scores (mNSS: SMD = -1.78, 95% CI: -2.39, -1.17; Zea Longa: SMD = -2.75, 95% CI: -3.79, -1.71), promoted behavioral recovery (rotarod test: SMD = 2.50, 95% CI: 1.81, 3.18; grid-walking test: SMD = -3.45, 95% CI: -5.15, -1.75; adhesive removal test: SMD = -2.60, 95% CI: -4.27, -0.93; morris water maze test: SMD = -3.91, 95% CI: -7.03, -0.79), and reduced the release of proinflammatory factors (IL-1β: SMD = -2.02, 95% CI: -2.77, -1.27; IL-6: SMD = -3.01, 95% CI: -4.47, -1.55; TNF-α: SMD = -2.72, 95% CI: -4.30, -1.13), increasing the number of neurons (apoptosis rate: SMD = -2.24, 95% CI: -3.32, -1.16; the number of neurons: SMD = 3.70, 95% CI: 2.44, 4.96). The funnel plots for the two main outcome measures were asymmetric, indicating publication bias. The median score on the CAMARADES checklist was 7 points (IQR: 6-9).
CONCLUSIONS
This meta-analysis shows that EEVs are superior to natural EVs for the treatment of IS. However, research in this field is still at an early stage, and more research is needed to fully understand the potential therapeutic mechanism of EEVs and their potential use in the treatment of IS.
PROSPERO REGISTRATION NUMBER
CRD42022368744.
Topics: Animals; Ischemic Stroke; Interleukin-6; Tumor Necrosis Factor-alpha; Extracellular Vesicles; Infarction
PubMed: 37904204
DOI: 10.1186/s12951-023-02114-8