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Frontiers in Immunology 2023Novel biomarkers of inflammation and oxidative stress might enhance the early recognition, management, and clinical outcomes of patients with rheumatic diseases (RDs).... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
Novel biomarkers of inflammation and oxidative stress might enhance the early recognition, management, and clinical outcomes of patients with rheumatic diseases (RDs). We assessed the available evidence regarding the pathophysiological role of neopterin, the oxidation product of 7,8-dihydroneopterin, a pteridine generated in macrophages activated by interferon-γ, by conducting a systematic review and meta-analysis of studies reporting its concentrations in biological fluids in RD patients and healthy controls.
METHODS
We searched electronic databases for relevant articles published between inception and 31 August 2023. The risk of bias and the certainty of evidence were assessed using the Joanna Briggs Institute Critical Appraisal Checklist and the Grades of Recommendation, Assessment, Development and Evaluation Working Group system, respectively.
RESULTS
In 37 studies, when compared to healthy controls, RD patients had significantly higher concentrations of neopterin both in plasma or serum (standard mean difference, SMD=1.31, 95% CI 1.01 to 1.61; p<0.001; moderate certainty of evidence) and in the urine (SMD=1.65, 95% CI 0.86 to 2.43, p<0.001; I = 94.2%, p<0.001; low certainty of evidence). The results were stable in sensitivity analysis. There were non-significant associations in meta-regression and subgroup analysis between the effect size and age, male to female ratio, year of publication, sample size, RD duration, C-reactive protein, erythrocyte sedimentation rate, specific type of RD, presence of connective tissue disease, analytical method used, or biological matrix investigated (plasma . serum). By contrast, the effect size was significantly associated with the geographical area in studies assessing serum or plasma and with the type of RD in studies assessing urine.
DISCUSSION
Pending additional studies that also focus on early forms of disease, our systematic review and meta-analysis supports the proposition that neopterin, a biomarker of inflammation and oxidative stress, can be useful for the identification of RDs. (PROSPERO registration number: CRD42023450209).
SYSTEMATIC REVIEW REGISTRATION
PROSPERO, identifier CRD42023450209.
Topics: Humans; Male; Female; Neopterin; Inflammation; Oxidation-Reduction; Oxidative Stress; Rheumatic Diseases; Biomarkers
PubMed: 37799718
DOI: 10.3389/fimmu.2023.1271383 -
Neurology, Psychiatry, and Brain... Sep 2020To describe the main neurological manifestations related to coronavirus infection in humans. (Review)
Review
OBJECTIVE
To describe the main neurological manifestations related to coronavirus infection in humans.
METHODOLOGY
A systematic review was conducted regarding clinical studies on cases that had neurological manifestations associated with COVID-19 and other coronaviruses. The search was carried out in the electronic databases PubMed, Scopus, Embase, and LILACS with the following keywords: "coronavirus" or "Sars-CoV-2" or "COVID-19" and "neurologic manifestations" or "neurological symptoms" or "meningitis" or "encephalitis" or "encephalopathy," following the Systematic Reviews and Meta-Analyses (PRISMA) guidelines.
RESULTS
Seven studies were included. Neurological alterations after CoV infection may vary from 17.3% to 36.4% and, in the pediatric age range, encephalitis may be as frequent as respiratory disorders, affecting 11 % and 12 % of patients, respectively. The Investigation included 409 patients diagnosed with CoV infection who presented neurological symptoms, with median age range varying from 3 to 62 years. The main neurological alterations were headache (69; 16.8 %), dizziness (57, 13.9 %), altered consciousness (46; 11.2 %), vomiting (26; 6.3 %), epileptic crises (7; 1.7 %), neuralgia (5; 1.2 %), and ataxia (3; 0.7 %). The main presumed diagnoses were acute viral meningitis/encephalitis in 25 (6.1 %) patients, hypoxic encephalopathy in 23 (5.6 %) patients, acute cerebrovascular disease in 6 (1.4 %) patients, 1 (0.2 %) patient with possible acute disseminated encephalomyelitis, 1 (0.2 %) patient with acute necrotizing hemorrhagic encephalopathy, and 2 (1.4 %) patients with CoV related to Guillain-Barré syndrome.
CONCLUSION
Coronaviruses have important neurotropic potential and they cause neurological alterations that range from mild to severe. The main neurological manifestations found were headache, dizziness and altered consciousness.
PubMed: 32834527
DOI: 10.1016/j.npbr.2020.05.008 -
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 -
International Journal of Molecular... Jul 2023Maresins are lipid mediators derived from omega-3 fatty acids with anti-inflammatory and pro-resolving properties, capable of promoting tissue regeneration and... (Review)
Review
Maresins are lipid mediators derived from omega-3 fatty acids with anti-inflammatory and pro-resolving properties, capable of promoting tissue regeneration and potentially serving as a therapeutic agent for chronic inflammatory diseases. The aim of this review was to systematically investigate preclinical and clinical studies on maresin to inform translational research. Two independent reviewers performed comprehensive searches with the term "Maresin (NOT) Review" on PubMed. A total of 137 studies were included and categorized into 11 human organ systems. Data pertinent to clinical translation were specifically extracted, including delivery methods, optimal dose response, and specific functional efficacy. Maresins generally exhibit efficacy in treating inflammatory diseases, attenuating inflammation, protecting organs, and promoting tissue regeneration, mostly in rodent preclinical models. The nervous system has the highest number of original studies ( = 25), followed by the cardiovascular system, digestive system, and respiratory system, each having the second highest number of studies ( = 18) in the field. Most studies considered systemic delivery with an optimal dose response for mouse animal models ranging from 4 to 25 μg/kg or 2 to 200 ng via intraperitoneal or intravenous injection respectively, whereas human in vitro studies ranged between 1 and 10 nM. Although there has been no human interventional clinical trial yet, the levels of MaR1 in human tissue fluid can potentially serve as biomarkers, including salivary samples for predicting the occurrence of cardiovascular diseases and periodontal diseases; plasma and synovial fluid levels of MaR1 can be associated with treatment response and defining pathotypes of rheumatoid arthritis. Maresins exhibit great potency in resolving disease inflammation and bridging tissue regeneration in preclinical models, and future translational development is warranted.
Topics: Animals; Humans; Mice; Anti-Inflammatory Agents; Chronic Disease; Docosahexaenoic Acids; Inflammation; Macrophages
PubMed: 37446190
DOI: 10.3390/ijms241311012 -
Clinical and Experimental Dental... Jun 2023Macrophages are among the first cells to interact with the dental implant surface and are critical regulators for controlling the immune response toward biomaterials.... (Review)
Review
A systematic review comparing the macrophage inflammatory response to hydrophobic and hydrophilic sandblasted large grit, acid-etched titanium or titanium-zirconium surfaces during in vitro studies.
OBJECTIVES
Macrophages are among the first cells to interact with the dental implant surface and are critical regulators for controlling the immune response toward biomaterials. Macrophages can polarize between two main phenotypes: proinflammatory M1 macrophages and anti-inflammatory M2 macrophages. This systematic review aims to determine if a differing macrophage inflammatory response exists on hydrophilic sandblasted large grit, acid-etched (SLActive) surfaces compared to sandblasted large grit, acid-etched (SLA) titanium or titanium-zirconium surfaces during in vitro studies. MATERIAL AND METHODS: A systematic search of three electronic databases, Medline, DOSS (Dentistry and Oral Sciences Source), and WoS (Web of Science), was performed. Only in vitro studies were included in this systematic review. The electronic search was supplemented with a search of the references. Genetic expression and production of proinflammatory and anti-inflammatory proteins were assessed. The synthesis of quantitative data was completed by narrative synthesis.
RESULTS
A total of 906 studies were found with the systematic search. Eight studies remained after the application of inclusion and exclusion criteria. Six studies used murine macrophages, while two used human macrophages. Discs were used in six studies, while dental implants were used in the remaining two studies. Genetic expression and cytokine production of proinflammatory cytokines on SLActive surfaces were reduced compared to SLA. Anti-inflammatory genetic expression and cytokine production was increased on SLActive surfaces. The overall quality of the included studies was low to moderate.
CONCLUSIONS
SLActive surfaces modulate macrophages to reduce proinflammatory and increase anti-inflammatory gene expression and cytokine production compared to SLA surfaces. The in vitro nature of the included studies does not replicate the in vivo healing cascade. Further in vivo studies are required to assess the macrophage response toward SLActive implant surfaces compared to SLA surfaces.
Topics: Mice; Humans; Animals; Dental Implants; Titanium; Zirconium; Surface Properties; Macrophages; Cytokines; Anti-Inflammatory Agents
PubMed: 36991526
DOI: 10.1002/cre2.730 -
Journal of Functional Biomaterials May 2023Exosomes have been proven to play a positive role in tendon and tendon-bone healing. Here, we systematically review the literature to evaluate the efficacy of exosomes... (Review)
Review
Exosomes have been proven to play a positive role in tendon and tendon-bone healing. Here, we systematically review the literature to evaluate the efficacy of exosomes in tendon and tendon-bone healing. Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, a systematic and comprehensive review of the literature was performed on 21 January 2023. The electronic databases searched included Medline (through PubMed), Web of Science, Embase, Scopus, Cochrane Library and Ovid. In the end, a total of 1794 articles were systematically reviewed. Furthermore, a "snowball" search was also carried out. Finally, forty-six studies were included for analysis, with the total sample size being 1481 rats, 416 mice, 330 rabbits, 48 dogs, and 12 sheep. In these studies, exosomes promoted tendon and tendon-bone healing and displayed improved histological, biomechanical and morphological outcomes. Some studies also suggested the mechanism of exosomes in promoting tendon and tendon-bone healing, mainly through the following aspects: (1) suppressing inflammatory response and regulating macrophage polarization; (2) regulating gene expression, reshaping cell microenvironment and reconstructing extracellular matrix; (3) promoting angiogenesis. The risk of bias in the included studies was low on the whole. This systematic review provides evidence of the positive effect of exosomes on tendon and tendon-bone healing in preclinical studies. The unclear-to-low risk of bias highlights the significance of standardization of outcome reporting. It should be noted that the most suitable source, isolation methods, concentration and administration frequency of exosomes are still unknown. Additionally, few studies have used large animals as subjects. Further studies may be required on comparing the safety and efficacy of different treatment parameters in large animal models, which would be conducive to the design of clinical trials.
PubMed: 37367263
DOI: 10.3390/jfb14060299 -
Cytokine Sep 2023Biliary tract cancer (BTC) is a highly malignant tumor that originates from bile duct epithelium and is categorized into intrahepatic cholangiocarcinoma (iCCA),... (Review)
Review
Biliary tract cancer (BTC) is a highly malignant tumor that originates from bile duct epithelium and is categorized into intrahepatic cholangiocarcinoma (iCCA), perihilar cholangiocarcinoma (pCCA), distal cholangiocarcinoma (dCCA) and gallbladder cancer (GBC) according to the anatomic location. Inflammatory cytokines generated by chronic infection led to an inflammatory microenvironment which influences the carcinogenesis of BTC. Interleukin-6 (IL-6), a multifunctional cytokine secreted by kupffer cells, tumor-associated macrophages, cancer-associated fibroblasts (CAFs) and cancer cells, plays a central role in tumorigenesis, angiogenesis, proliferation, and metastasis in BTC. Besides, IL-6 serves as a clinical biomarker for diagnosis, prognosis, and monitoring for BTC. Moreover, preclinical evidence indicates that IL-6 antibodies could sensitize tumor immune checkpoint inhibitors (ICIs) by altering the number of infiltrating immune cells and regulating the expression of immune checkpoints in the tumor microenvironment (TME). Recently, IL-6 has been shown to induce programmed death ligand 1 (PD-L1) expression through the mTOR pathway in iCCA. However, the evidence is insufficient to conclude that IL-6 antibodies could boost the immune responses and potentially overcome the resistance to ICIs for BTC. Here, we systematically review the central role of IL-6 in BTC and summarize the potential mechanisms underlying the improved efficacy of treatments combining IL-6 antibodies with ICIs in tumors. Given this, a future direction is proposed for BTC to increase ICIs sensitivity by blocking IL-6 pathways.
Topics: Humans; Interleukin-6; Biliary Tract Neoplasms; Cholangiocarcinoma; Cytokines; Antibodies; Bile Duct Neoplasms; Bile Ducts, Intrahepatic; Tumor Microenvironment
PubMed: 37331095
DOI: 10.1016/j.cyto.2023.156271 -
The British Journal of Nutrition Mar 2024Phytosterols/phytostanols are bioactive compounds found in vegetable oils, nuts and seeds and added to a range of commercial food products. Consumption of... (Review)
Review
Phytosterols/phytostanols are bioactive compounds found in vegetable oils, nuts and seeds and added to a range of commercial food products. Consumption of phytosterols/phytostanols reduces levels of circulating LDL-cholesterol, a causative biomarker of CVD, and is linked to a reduced risk of some cancers. Individuals who consume phytosterols/phytostanols in their diet may do so for many years as part of a non-pharmacological route to lower cholesterol or as part of a healthy diet. However, the impact of long term or high intakes of dietary phytosterols/phytostanols has not been on whole-body epigenetic changes before. The aim of this systematic review was to identify all publications that have evaluated changes to epigenetic mechanisms (post-translation modification of histones, DNA methylation and miRNA expression) in response to phytosterols/phytostanols. A systematic search was performed that returned 226 records, of which eleven were eligible for full-text analysis. Multiple phytosterols were found to inhibit expression of histone deacetylase (HDAC) enzymes and were also predicted to directly bind and impair HDAC activity. Phytosterols were found to inhibit the expression and activity of DNA methyl transferase enzyme 1 and reverse cancer-associated gene silencing. Finally, phytosterols have been shown to regulate over 200 miRNA, although only five of these were reported in multiple publications. Five tissue types (breast, prostate, macrophage, aortic epithelia and lung) were represented across the studies, and although phytosterols/phytostanols alter the molecular mechanisms of epigenetic inheritance in these mammalian cells, studies exploring meiotic or transgenerational inheritance were not found.
Topics: Male; Animals; Humans; Phytosterols; Noncommunicable Diseases; Cholesterol; Epigenesis, Genetic; Neoplasms; MicroRNAs; Mammals
PubMed: 37955052
DOI: 10.1017/S0007114523002532 -
European Respiratory Review : An... Dec 2023Autoimmune pulmonary alveolar proteinosis (aPAP) results from impaired macrophage-mediated clearance of alveolar surfactant lipoproteins. Whole lung lavage has been the... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Autoimmune pulmonary alveolar proteinosis (aPAP) results from impaired macrophage-mediated clearance of alveolar surfactant lipoproteins. Whole lung lavage has been the first-line treatment but recent reports suggest the efficacy of granulocyte-macrophage colony-stimulating factor (GM-CSF). We aimed to review the efficacy and safety of nebulised GM-CSF in aPAP.
METHODS
We conducted a systematic review and meta-analysis searching Embase, CINAHL, MEDLINE and Cochrane Collaborative databases (1946-1 April 2022). Studies included patients aged >18 years with aPAP receiving nebulised GM-CSF treatment and a comparator cohort. Exclusion criteria included secondary or congenital pulmonary alveolar proteinosis, GM-CSF allergy, active infection or other serious medical conditions. The protocol was prospectively registered with PROSPERO (CRD42021231328). Outcomes assessed were St George's Respiratory Questionnaire (SGRQ), 6-min walk test (6MWT), gas exchange (diffusing capacity of the lung for carbon monoxide ( ) % predicted) and arterial-alveolar oxygen gradient.
RESULTS
Six studies were identified for review and three for meta-analysis, revealing that SGRQ score (mean difference -8.09, 95% CI -11.88- -4.3, p<0.0001), functional capacity (6MWT) (mean difference 21.72 m, 95% CI -2.76-46.19 m, p=0.08), gas diffusion ( % predicted) (mean difference 5.09%, 95% CI 2.05-8.13%, p=0.001) and arterial-alveolar oxygen gradient (mean difference -4.36 mmHg, 95% CI -7.19- -1.52 mmHg, p=0.003) all significantly improved in GM-CSF-treated patients with minor statistical heterogeneity (I=0%). No serious trial-related adverse events were reported.
CONCLUSIONS
Patients with aPAP treated with inhaled GM-CSF demonstrated significant improvements in symptoms, dyspnoea scores, lung function, gas exchange and radiology indices after treatment with nebulised GM-CSF of varying duration. There is an important need to review comparative effectiveness and patient choice in key clinical outcomes between the current standard of care, whole lung lavage, with the noninvasive treatment of nebulised GM-CSF in aPAP.
Topics: Humans; Pulmonary Alveolar Proteinosis; Granulocyte-Macrophage Colony-Stimulating Factor; Administration, Inhalation; Oxygen
PubMed: 37993127
DOI: 10.1183/16000617.0080-2023 -
AIDS Research and Human Retroviruses Sep 2022Cervical cancer is the fourth cancer in incidence and the third in mortality among women worldwide. Women living with HIV have a significantly increased risk of cervical... (Review)
Review
Cervical cancer is the fourth cancer in incidence and the third in mortality among women worldwide. Women living with HIV have a significantly increased risk of cervical cancer. The immune response of the host is crucial to determine the course of the human papillomavirus (HPV) infection and cytokines play an important role modulating viral multiplication and concentrating the immune response in the Th1 or Th2 pattern. The aim of this study is to evaluate the available evidence on the concentration of genital cytokines and their role in HPV infection in HIV-infected women. A systematic search of the literature was performed using MEDLINE by PubMed, Embase, Cochrane, LILACS, Scopus, Science direct, and Web of Science databases on November, 2020, in which the following clusters of terms were applied: HIV infection, HPV infection, and cytokine. Initially, 728 articles were selected, but only 17 were eligible for full-text review, and among them, 9 were included in the qualitative analysis. No restriction was applied in language, publication date, or status. The most studied cytokines in the articles included in this review were interferon (IFN)-γ and interleukin (IL)-10 (six articles), tumor necrosis factor (TNF) and IL-6 (five articles), and macrophage inflammatory protein (four articles). The main findings show that there is a reduction in the number of cells expressing IFN-γ ( = .02) and TNF-α ( = .01), in the cervices of HIV-HPV co-infected women compared with those infected only by HPV. In addition, levels of IL-6 ( = .039) and IL-10 ( = .02) are increased in the cervical secretions of HIV-positive women compared to seronegative patients. Despite these findings, there is a clear need of larger studies to understand the role of these immune factors in HPV-induced cervical neoplasia of women co-infected with HIV.
Topics: Alphapapillomavirus; Cervix Uteri; Coinfection; Cytokines; Female; HIV Infections; Humans; Interleukin-6; Papillomaviridae; Papillomavirus Infections; Tumor Necrosis Factor-alpha; Uterine Cervical Neoplasms
PubMed: 35435746
DOI: 10.1089/AID.2021.0139