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Translational Research : the Journal of... Apr 2021An increasing body of evidence shows a role for macrophages and monocytes (as their precursors) in hypertension, but with conflicting results with regard to whether they... (Meta-Analysis)
Meta-Analysis
An increasing body of evidence shows a role for macrophages and monocytes (as their precursors) in hypertension, but with conflicting results with regard to whether they are protective or harmful. Therefore, we systematically reviewed the effect of macrophage interventions on blood pressure in animal models, to explore which factors determine the blood pressure increasing vs. decreasing effect. A search in PubMED and EMBASE yielded 9620 records, 26 of which were included. Eighteen studies (involving 22 different experiments (k = 22)) performed macrophage depletion, whereas 12 studies specifically deleted certain macrophage proteins. The blood pressure effects of macrophage depletion were highly various and directed toward both directions, as expected, which could not be reduced to differences in animal species or methods of hypertension induction. Prespecified subgroup analysis did reveal a potential role for the route in which the macrophage-depleting agent is being administrated (intraperitoneal vs intravenous subgroup difference of P = 0.07 (k = 22), or P < 0.001 in studies achieving considerable (ie, >50%) depletion (k = 18)). Along with findings from specific macrophage protein deletion studies-showing that deletion of one single macrophage protein (like TonEBP, endothelin-B, EP, NOX-2 and the angiotensin II type 1 receptor) can alter blood pressure responses to hypertensive stimuli-the indication that each route has its specific depletion pattern regarding targeted tissues and macrophage phenotypes suggests a determinative role for these features. These hypothesis-generating results encourage more detailed depletion characterization of each technique by direct experimental comparisons, providing a chance to obtain more knowledge on which macrophages are beneficial versus detrimental in hypertension development.
Topics: Animals; Blood Pressure; Humans; Hypertension; Macrophages; Risk Factors
PubMed: 33166696
DOI: 10.1016/j.trsl.2020.11.002 -
International Journal of Molecular... Mar 2023Although diagnosis and treatment of vestibular schwannomas (VSs) improved in recent years, no factors have yet been identified as being capable of predicting tumor...
Although diagnosis and treatment of vestibular schwannomas (VSs) improved in recent years, no factors have yet been identified as being capable of predicting tumor growth. Molecular rearrangements occur in neoplasms before any macroscopic morphological changes become visible, and the former are the underlying cause of disease behavior. Tumor microenvironment (TME) encompasses cellular and non-cellular elements interacting together, resulting in a complex and dynamic key of tumorigenesis, drug response, and treatment outcome. The aim of this systematic, narrative review was to assess the level of knowledge on TME implicated in the biology, behavior, and prognosis of sporadic VSs. A search (updated to November 2022) was run in Scopus, PubMed, and Web of Science electronic databases according to the PRISMA guidelines, retrieving 624 titles. After full-text evaluation and application of inclusion/exclusion criteria, 37 articles were included. VS microenvironment is determined by the interplay of a dynamic ecosystem of stromal and immune cells which produce and remodel extracellular matrix, vascular networks, and promote tumor growth. However, evidence is still conflicting. Further studies will enhance our understanding of VS biology by investigating TME-related biomarkers able to predict tumor growth and recognize immunological and molecular factors that could be potential therapeutic targets for medical treatment.
Topics: Humans; Ecosystem; Neuroma, Acoustic; Treatment Outcome; Tumor Burden; Tumor Microenvironment
PubMed: 37047498
DOI: 10.3390/ijms24076522 -
Pharmaceuticals (Basel, Switzerland) Feb 2024(1) Background: We aimed to estimate the pooled effectiveness and safety of vaccination in follicular lymphoma (FL) and discuss implications for immunotherapy... (Review)
Review
(1) Background: We aimed to estimate the pooled effectiveness and safety of vaccination in follicular lymphoma (FL) and discuss implications for immunotherapy development. (2) Methods: We included randomized trials (RCTs) of therapeutic vaccines in patients with FL. Progression-free survival (PFS) was the primary outcome. We searched databases (PubMed, Embase, Scopus, Web of Science Core, medRxiv) and registries (PROSPERO, CENTRAL, ClinicalTrials.gov, EuCTR, WHO ICTRP) and conducted online, citation, and manual searches. We assessed risks of bias across outcomes using RoB 2.0 and across studies using ROB-ME and a contour-enhanced funnel plot. (3) Results: Three RCTs were included (813 patients, both previously treated and untreated). Patients with a complete or partial response after chemotherapy were randomized to either a patient-specific recombinant idiotype keyhole limpet hemocyanin (Id-KLH) vaccine plus granulocyte-macrophage colony-stimulating factor (GM-CSF) or placebo immunotherapy (KLH + GM-CSF). Meta-analyses showed that PFS was worse with the vaccine, but not significantly: hazard ratio, 1.09 (95% CI 0.91-1.30). The GRADE certainty of evidence was moderate. Adverse event data were mixed. (4) Conclusions: We are moderately certain that Id-KLH results in little to no difference in PFS in FL. (5) Funding: Russian Science Foundation grant #22-25-00516. (6) Registration: PROSPERO CRD42023457528.
PubMed: 38543058
DOI: 10.3390/ph17030272 -
Medicine Mar 2024Endometriosis (EMT) a common gynecological condition in women, an inflammatory disease characterized by the presence of endometrial tissue on organs and tissues in the...
BACKGROUND
Endometriosis (EMT) a common gynecological condition in women, an inflammatory disease characterized by the presence of endometrial tissue on organs and tissues in the pelvis, and is mainly associated with chronic pelvic pain and infertility. As the etiology has not been fully elucidated, current treatment is limited to surgery, hormones and painkillers, with more side effects and difficulty in achieving long-term relief. Oxidative stress manifests itself as an overproduction of reactive oxygen species, which has an integral impact in the pathology of female reproductive disorders. In this review, we evaluate the mechanisms of iron overload-induced oxidative stress and ferroptosis in EMT and their pathophysiological implications.
METHODS
Because the etiology has not been fully elucidated, current treatments are limited to surgery, hormones, and painkillers, which have many side effects and are difficult to achieve long-term relief.
RESULTS
We interpreted that antioxidants as well as ferroptosis inducers show promising results in the treatment of EMT, but their application in this population needs to be further investigated.
CONCLUSION
In combination with the interpretation of previous studies, it was shown that iron overload is present in the peritoneal fluid, endometriotic lesions, peritoneum and macrophages in the abdominal cavity. However, the programmed cellular ferroptosis associated with iron overload is resisted by endometriotic foci, which is critical to the pathophysiology of EMT with local iron overload and inflammation.
Topics: Female; Humans; Endometriosis; Ferroptosis; Oxidative Stress; Iron Overload; Hormones
PubMed: 38489713
DOI: 10.1097/MD.0000000000037421 -
Frontiers in Cellular Neuroscience 2022To compare the safety and effectiveness of transplanted cells from different sources for spinal cord injury (SCI).
OBJECTIVE
To compare the safety and effectiveness of transplanted cells from different sources for spinal cord injury (SCI).
DESIGN
A systematic review and Bayesian network meta-analysis.
DATA SOURCES
Medline, Embase, and the Cochrane Central Register of Controlled Trials.
STUDY SELECTION
We included randomized controlled trials, case-control studies, and case series related to cell transplantation for SCI patients, that included at least 1 of the following outcome measures: American Spinal Cord Injury Association (ASIA) Impairment Scale (AIS grade), ASIA motor score, ASIA sensory score, the Functional Independence Measure score (FIM), International Association of Neurorestoratology Spinal Cord Injury Functional Rating Scale (IANR-SCIFRS), or adverse events. Follow-up data were analyzed at 6 and 12 months.
RESULTS
Forty-four eligible trials, involving 1,266 patients, investigated 6 treatments: olfactory ensheathing cells (OECs), neural stem cells/ neural progenitor cells (NSCs), mesenchymal stem cells (MSCs), Schwann cells, macrophages, and combinations of cells (MSCs plus Schwann cells). Macrophages improved the AIS grade at 12 months (mean 0.42, 95% credible interval: 0-0.91, low certainty) and FIM score at 12 months (42.83, 36.33-49.18, very low certainty). MSCs improved the AIS grade at 6 months (0.42, 0.15-0.73, moderate certainty), the motor score at 6 months (4.43, 0.91-7.78, moderate certainty), light touch at 6 (10.01, 5.81-13.88, moderate certainty) and 12 months (11.48, 6.31-16.64, moderate certainty), pinprick score at 6 (14.54, 9.76-19.46, moderate certainty) and 12 months (12.48, 7.09-18.12, moderate certainty), and the IANR-SCIFRS at 6 (3.96, 0.62-6.97, moderate certainty) and 12 months (5.54, 2.45-8.42, moderate certainty). OECs improved the FIM score at 6 months (9.35, 1.71-17.00, moderate certainty). No intervention improved the motor score significantly at 12 months. The certainty of other interventions was low or very low. Overall, the number of adverse events associated with transplanted cells was low.
CONCLUSIONS
Patients with SCI who receive transplantation of macrophages, MSCs, NSCs, or OECs may have improved disease prognosis. MSCs are the primary recommendations. Further exploration of the mechanism of cell transplantation in the treatment of SCI, transplantation time window, transplantation methods, and monitoring of the number of transplanted cells and cell survival is needed.
SYSTEMATIC REVIEW REGISTRATION
https://www.crd.york.ac.uk/PROSPERO/#recordDetails, identifier: CRD 42021282043.
PubMed: 35444516
DOI: 10.3389/fncel.2022.860131 -
Frontiers in Cardiovascular Medicine 2021The purpose of this study was to determine the prevalence of healed plaque and its characteristics under optical coherence tomography (OCT) through a formal systematic...
Prevalence of Healed Plaque and Factors Influencing Its Characteristics Under Optical Coherence Tomography in Patients With Coronary Artery Disease: A Systematic Review, Meta-Analysis, and Meta-Regression.
The purpose of this study was to determine the prevalence of healed plaque and its characteristics under optical coherence tomography (OCT) through a formal systematic review, meta-analysis, and meta-regression. Thirteen studies were selected from MEDLINE, EMBASE, Cochrane, and online databases. The overall incidence of healed plaques was 40% (95% CI: 39-42), with 37% (95% CI: 35-39) in patients with acute coronary syndrome (ACS) and with 46% (95% CI: 43-49) in patients with stable angina pectoris (SAP). The incidence of healed plaque among culprit plaques (48%, 95% CI: 46-50) was nearly two times higher than that among non-culprit plaques (24%, 95% CI: 21-27). The incidence of thin cap fibroatheroma (TCFA), plaque rupture, microvessel, macrophage accumulation, and calcification was significantly higher in the healed plaque group. Meta-regression revealed an association between smoking ( = 0.033) and healed plaque rupture. Gender ( = 0.047) was independently associated with macrophage accumulation, and mean low-density lipoprotein cholesterol (LDL-C) was independently associated with microvessel. In summary, with a total incidence of 40%, the incidence of healed plaques under OCT was higher in SAP than in ACS, and higher in culprit plaques than in non-culprit plaques. Higher incidence of TCFA, plaque rupture, microvessel, macrophage accumulation, and calcification was found in the healed-plaque group. Smoking, gender, and mean LDL-C level were associated with healed-plaque characteristics.
PubMed: 34881310
DOI: 10.3389/fcvm.2021.761208 -
Bioengineering (Basel, Switzerland) Jan 2023Bone healing is a multifarious process involving mesenchymal stem cells, osteoprogenitor cells, macrophages, osteoblasts and -clasts, and chondrocytes to restore the... (Review)
Review
Bone healing is a multifarious process involving mesenchymal stem cells, osteoprogenitor cells, macrophages, osteoblasts and -clasts, and chondrocytes to restore the osseous tissue. Particularly in long bones including the tibia, clavicle, humerus and femur, this process fails in 2-10% of all fractures, with devastating effects for the patient and the healthcare system. Underlying reasons for this failure are manifold, from lack of biomechanical stability to impaired biological host conditions and wound-immanent intricacies. In this review, we describe the cellular components involved in impaired bone healing and how they interfere with the delicately orchestrated processes of bone repair and formation. We subsequently outline and weigh the risk factors for the development of non-unions that have been established in the literature. Therapeutic prospects are illustrated and put into clinical perspective, before the applicability of biomarkers is finally discussed.
PubMed: 36671657
DOI: 10.3390/bioengineering10010085 -
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 -
Journal of Neuroinflammation May 2023Increasing pre-clinical evidence suggests that aerobic exercise positively modulates neuroimmune responses following traumatic nerve injury. However, meta-analyses on... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Increasing pre-clinical evidence suggests that aerobic exercise positively modulates neuroimmune responses following traumatic nerve injury. However, meta-analyses on neuroimmune outcomes are currently still lacking. This study aimed to synthesize the pre-clinical literature on the effects of aerobic exercise on neuroimmune responses following peripheral nerve injury.
METHODS
MEDLINE (via Pubmed), EMBASE and Web of Science were searched. Controlled experimental studies on the effect of aerobic exercise on neuroimmune responses in animals with a traumatically induced peripheral neuropathy were considered. Study selection, risk of bias assessment and data extraction were performed independently by two reviewers. Results were analyzed using random effects models and reported as standardized mean differences. Outcome measures were reported per anatomical location and per class of neuro-immune substance.
RESULTS
The literature search resulted in 14,590 records. Forty studies were included, reporting 139 comparisons of neuroimmune responses at various anatomical locations. All studies had an unclear risk of bias. Compared to non-exercised animals, meta-analyses showed the following main differences in exercised animals: (1) in the affected nerve, tumor necrosis factor-α (TNF-α) levels were lower (p = 0.003), while insulin-like growth factor-1 (IGF-1) (p < 0.001) and Growth Associated Protein 43 (GAP43) (p = 0.01) levels were higher; (2) At the dorsal root ganglia, brain-derived neurotrophic factor (BDNF)/BDNF mRNA levels (p = 0.004) and nerve growth factor (NGF)/NGF mRNA (p < 0.05) levels were lower; (3) in the spinal cord, BDNF levels (p = 0.006) were lower; at the dorsal horn, microglia (p < 0.001) and astrocyte (p = 0.005) marker levels were lower; at the ventral horn, astrocyte marker levels (p < 0.001) were higher, and several outcomes related to synaptic stripping were favorably altered; (4) brainstem 5-HT2A receptor levels were higher (p = 0.001); (5) in muscles, BDNF levels (p < 0.001) were higher and TNF-α levels lower (p < 0.05); (6) no significant differences were found for systemic neuroimmune responses in blood or serum.
CONCLUSION
This review revealed widespread positive modulatory effects of aerobic exercise on neuroimmune responses following traumatic peripheral nerve injury. These changes are in line with a beneficial influence on pro-inflammatory processes and increased anti-inflammatory responses. Given the small sample sizes and the unclear risk of bias of the studies, results should be interpreted with caution.
Topics: Animals; Brain-Derived Neurotrophic Factor; Nerve Growth Factor; Tumor Necrosis Factor-alpha; Peripheral Nerve Injuries; Spinal Cord Dorsal Horn; Exercise; RNA, Messenger
PubMed: 37138291
DOI: 10.1186/s12974-023-02777-y -
Translational Stroke Research Dec 2021Although several studies have suggested that anti-inflammatory strategies reduce secondary infarct growth in animal stroke models, clinical studies have not yet... (Meta-Analysis)
Meta-Analysis
Although several studies have suggested that anti-inflammatory strategies reduce secondary infarct growth in animal stroke models, clinical studies have not yet demonstrated a clear benefit of immune modulation in patients. Potential reasons include systematic differences of post-ischemic neuroinflammation between humans and rodents. We here performed a systematic review and meta-analysis to summarize and compare the spatial and temporal distribution of immune cell infiltration in human and rodent stroke. Data on spatiotemporal distribution of immune cells (T cells, macrophages, and neutrophils) and infarct volume were extracted. Data from all rodent studies were pooled by means of a random-effect meta-analysis. Overall, 20 human and 188 rodent stroke studies were included in our analyses. In both patients and rodents, the infiltration of macrophages and neutrophils preceded the lymphocytic influx. Macrophages and neutrophils were the predominant immune cells within 72 h after infarction. Although highly heterogeneously across studies, the temporal profile of the poststroke immune response was comparable between patients and rodents. In rodent stroke, the extent of the immune cell infiltration depended on the duration and location of vessel occlusion and on the species. The density of infiltrating immune cells correlated with the infarct volume. In summary, we provide the first systematic analysis and comparison of human and rodent post-ischemic neuroinflammation. Our data suggest that the inflammatory response in rodent stroke models is comparable to that in patients with stroke. However, the overall heterogeneity of the post-ischemic immune response might contribute to the translational failure in stroke research.
Topics: Animals; Brain; Brain Ischemia; Disease Models, Animal; Humans; Ischemic Stroke; Mice; Mice, Inbred C57BL; Rats; Stroke
PubMed: 33496918
DOI: 10.1007/s12975-021-00887-4