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Frontiers in Molecular Biosciences 2023Systemic sclerosis (SSc) is a chronic autoimmune disease, marked by an unpredictable course, high morbidity, and increased mortality risk that occurs especially in the... (Review)
Review
Systemic sclerosis (SSc) is a chronic autoimmune disease, marked by an unpredictable course, high morbidity, and increased mortality risk that occurs especially in the diffuse and rapidly progressive forms of the disease, characterized by fibrosis of the skin and internal organs and endothelial dysfunction. Recent studies suggest that the identification of altered metabolic pathways may play a key role in understanding the pathophysiology of the disease. Therefore, metabolomics might be pivotal in a better understanding of these pathogenic mechanisms. Through a systematic review of the literature following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Guidelines (PRISMA), searches were done in the PubMed, EMBASE, Web of Science, and Scopus databases from 2000 to September 2022. Three researchers independently reviewed the literature and extracted the data based on predefined inclusion and exclusion criteria. Of the screened studies, 26 fulfilled the inclusion criteria. A total of 151 metabolites were differentially distributed between SSc patients and healthy controls (HC). The main deregulated metabolites were those derived from amino acids, specifically homocysteine (Hcy), proline, alpha-N-phenylacetyl-L-glutamine, glutamine, asymmetric dimethylarginine (ADMA), citrulline and ornithine, kynurenine (Kyn), and tryptophan (Trp), as well as acylcarnitines associated with long-chain fatty acids and tricarboxylic acids such as citrate and succinate. Additionally, differences in metabolic profiling between SSc subtypes were identified. The diffuse cutaneous systemic sclerosis (dcSSc) subtype showed upregulated amino acid-related pathways involved in fibrosis, endothelial dysfunction, and gut dysbiosis. Lastly, potential biomarkers were evaluated for the diagnosis of SSc, the identification of the dcSSc subtype, pulmonary arterial hypertension, and interstitial lung disease. These potential biomarkers are within amino acids, nucleotides, carboxylic acids, and carbohydrate metabolism. The altered metabolite mechanisms identified in this study mostly point to perturbations in amino acid-related pathways, fatty acid beta-oxidation, and in the tricarboxylic acid cycle, possibly associated with inflammation, vascular damage, fibrosis, and gut dysbiosis. Further studies in targeted metabolomics are required to evaluate potential biomarkers for diagnosis, prognosis, and treatment response.
PubMed: 37614441
DOI: 10.3389/fmolb.2023.1215039 -
The Journal of Hospital Infection Sep 2023This systematic review and network meta-analysis (NMA) comprehensively compared the effectiveness of different mouth rinses in reducing the viral load/infectivity of... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
This systematic review and network meta-analysis (NMA) comprehensively compared the effectiveness of different mouth rinses in reducing the viral load/infectivity of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) (Part I), alleviating clinical symptoms or severity of disease (Part II), and decreasing the incidence of SARS-CoV-2 infection (Part III).
METHODS
Randomized controlled trials (RCTs) and non-randomized controlled trials (NRCTs) with restrictions were searched up to 3 March 2023. Twenty-three studies (22 RCTs and one NRCT) met the inclusion criteria for this systematic review.
RESULTS
Five RCTs (454 patients and nine interventions) in Part I were eligible for NMA. The NMA results showed that, in comparison with no rinse, sodium chloride (NaCl) was the most effective mouth rinse for reducing the viral load, followed by povidone-iodine (PVP-I), ß-cyclodextrin + citrox (CDCM), hydrogen peroxide (HP), chlorhexidine gluconate (CHX), cetylpyridinium chloride (CPC), placebo and hypochlorous acid (HClO). However, these results were not significant. Based on surface under the cumulative ranking curve scores, PVP-I was likely to be the most efficacious mouth rinse for reducing SARS-CoV-2 viral load, followed by CDCM, HP, NaCl, CHX, CPC, placebo, no rinse and HClO.
CONCLUSION
Due to heterogeneity of the primary studies, the effectiveness of different mouth rinses to reduce viral infectivity, improve clinical symptoms or prevent SARS-CoV-2 infection remains inconclusive.
Topics: Humans; COVID-19; Mouthwashes; Povidone-Iodine; SARS-CoV-2; Sodium Chloride; Network Meta-Analysis; Hydrogen Peroxide; Mouth
PubMed: 37419189
DOI: 10.1016/j.jhin.2023.06.022 -
Antioxidants (Basel, Switzerland) Oct 2023Nitric oxide (NO) has been implicated in the pathology of malaria. This systematic review and meta-analysis describe the association between NO levels and malaria.... (Review)
Review
Nitric oxide (NO) has been implicated in the pathology of malaria. This systematic review and meta-analysis describe the association between NO levels and malaria. Embase, Ovid, PubMed, Scopus, and Google Scholar were searched to identify studies evaluating NO levels in malaria patients and uninfected controls. Meta-regression and subgroup analyses were conducted to discern differences in NO levels between the groups. Of the 4517 records identified, 21 studies were included in the systematic review and meta-analysis. The findings illustrated significant disparities in NO levels based on geographic location and study time frames. Despite the fluctuations, such as higher NO levels in adults compared to children, no significant differences in mean NO levels between patients and uninfected controls ( = 0.25, Hedge's g: 0.35, 95% confidence interval (CI): -0.25-0.96, : 97.39%) or between severe and non-severe malaria cases ( = 0.09, Hedge's g: 0.71, 95% CI: -0.11-1.54, : 96.07%) were detected. The systematic review and meta-analysis highlighted inconsistencies in NO levels in malaria patients. Given the high heterogeneity of the results, further studies using standardized metrics for NO measurements and focusing on biochemical pathways dictating NO responses in malaria are imperative to understand the association between NO and malaria.
PubMed: 37891947
DOI: 10.3390/antiox12101868 -
European Respiratory Review : An... Jan 2024Molecular pathways found to be important in pulmonary fibrosis are also involved in cancer pathogenesis, suggesting common pathways in the development of pulmonary... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Molecular pathways found to be important in pulmonary fibrosis are also involved in cancer pathogenesis, suggesting common pathways in the development of pulmonary fibrosis and lung cancer.
RESEARCH QUESTION
Is pulmonary fibrosis from exposure to occupational carcinogens an independent risk factor for lung cancer?
STUDY DESIGN AND METHODS
A comprehensive search of PubMed, Embase, Web of Science and Cochrane databases with over 100 search terms regarding occupational hazards causing pulmonary fibrosis was conducted. After screening and extraction, quality of evidence and eligibility criteria for meta-analysis were assessed. Meta-analysis was performed using a random-effects model.
RESULTS
52 studies were identified for systematic review. Meta-analysis of subgroups identified silicosis as a risk factor for lung cancer when investigating odds ratios for silicosis in autopsy studies (OR 1.47, 95% CI 1.13-1.90) and for lung cancer mortality in patients with silicosis (OR 3.21, 95% CI 2.67-3.87). Only considering studies with an adjustment for smoking as a confounder identified a significant increase in lung cancer risk (OR 1.58, 95% CI 1.34-1.87). However, due to a lack of studies including cumulative exposure, no adjustments could be included. In a qualitative review, no definitive conclusion could be reached for asbestosis and silicosis as independent risk factors for lung cancer, partly because the studies did not take cumulative exposure into account.
INTERPRETATION
This systematic review confirms the current knowledge regarding asbestosis and silicosis, indicating a higher risk of lung cancer in exposed individuals compared to exposed workers without fibrosis. These individuals should be monitored for lung cancer, especially when asbestosis or silicosis is present.
Topics: Humans; Silicon Dioxide; Lung Neoplasms; Pulmonary Fibrosis; Asbestosis; Silicosis; Occupational Exposure
PubMed: 38355151
DOI: 10.1183/16000617.0224-2023 -
Antioxidants (Basel, Switzerland) Aug 2023Alterations in the circulating concentrations of uric acid and its degradation product, allantoin, might account for the systemic pro-oxidant state and the increased... (Review)
Review
Alterations in the circulating concentrations of uric acid and its degradation product, allantoin, might account for the systemic pro-oxidant state and the increased cardiovascular risk in rheumatoid arthritis (RA). We sought to address this issue by conducting a systematic review and meta-analysis of the association between the plasma/serum concentrations of uric acid and allantoin and RA. We searched PubMed, Scopus, and Web of Science from inception to 20 June 2023 for studies comparing plasma/serum concentrations of uric acid and allantoin between RA patients and healthy controls. We assessed the risk of bias with the JBI Critical Appraisal Checklist for analytical studies and the certainty of evidence with the Grades of Recommendation, Assessment, Development and Evaluation (GRADE) Working Group system. In the 19 studies selected for analysis, there were non-significant differences in uric acid concentrations between RA patients and controls (standard mean difference, SMD = 0.11, 95% CI -0.07 to 0.30, = 0.22; I = 87.9%, < 0.001; low certainty of evidence). By contrast, the concentrations of allantoin were significantly higher in RA patients (SMD = 1.10, 95% CI 0.66 to 1.55, < 0.001; I = 55.6%, = 0.08; extremely low certainty of evidence). In meta-regression, a significant association was observed between the SMD of uric acid concentrations and body mass index, a risk factor for atherosclerosis and cardiovascular disease (t = 3.35, = 0.007). Our study has shown a significant increase in the concentrations of the oxidative stress biomarker allantoin in patients with RA. Further research is warranted to investigate the interplay between uric acid, allantoin, redox balance, and cardiovascular disease in this group. (PROSPERO registration number: CRD42023441127).
PubMed: 37627564
DOI: 10.3390/antiox12081569 -
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 -
International Journal of Molecular... Dec 2023Mitochondria are key cellular organelles whose main function is maintaining cell bioenergetics by producing ATP through oxidative phosphorylation. However, mitochondria... (Review)
Review
Mitochondria are key cellular organelles whose main function is maintaining cell bioenergetics by producing ATP through oxidative phosphorylation. However, mitochondria are involved in a much higher number of cellular processes. Mitochondria are the home of key metabolic pathways like the tricarboxylic acid cycle and β-oxidation of fatty acids, as well as biosynthetic pathways of key products like nucleotides and amino acids, the control of the redox balance of the cell and detoxifying the cell from HS and NH. This plethora of critical functions within the cell is the reason mitochondrial function is involved in several complex disorders (apart from pure mitochondrial disorders), among them inflammatory bowel diseases (IBD). IBD are a group of chronic, inflammatory disorders of the gut, mainly composed of ulcerative colitis and Crohn's disease. In this review, we present the current knowledge regarding the impact of mitochondrial dysfunction in the context of IBD. The role of mitochondria in both intestinal mucosa and immune cell populations are discussed, as well as the role of mitochondrial function in mechanisms like mucosal repair, the microbiota- and brain-gut axes and the development of colitis-associated colorectal cancer.
Topics: Humans; Inflammatory Bowel Diseases; Colitis, Ulcerative; Crohn Disease; Intestinal Mucosa; Mitochondria
PubMed: 38069446
DOI: 10.3390/ijms242317124 -
Journal of Ginseng Research Sep 2023Ginsenosides are bioactive components of Panax ginseng with many functions such as anti-aging, anti-oxidation, anti-inflammatory, anti-fatigue, and anti-tumor.... (Review)
Review
Ginsenosides are bioactive components of Panax ginseng with many functions such as anti-aging, anti-oxidation, anti-inflammatory, anti-fatigue, and anti-tumor. Ginsenosides are categorized into dammarane, oleanene, and ocotillol type tricyclic triterpenoids based on the aglycon structure. Based on the sugar moiety linked to C-3, C-20, and C-6, C-20, dammarane type was divided into protopanaxadiol (PPD) and protopanaxatriol (PPT). The effects of ginsenosides on skin disorders are noteworthy. They play anti-aging roles by enhancing immune function, resisting melanin formation, inhibiting oxidation, and elevating the concentration of collagen and hyaluronic acid. Thus, ginsenosides have previously been widely used to resist skin diseases and aging. This review details the role of ginsenosides in the anti-skin aging process from mechanisms and experimental research.
PubMed: 37720567
DOI: 10.1016/j.jgr.2023.04.005 -
Brain Sciences Nov 2023Emerging evidence highlights moderate hypoxia as a candidate treatment for brain disorders. This systematic review examines findings and the methodological quality of... (Review)
Review
Emerging evidence highlights moderate hypoxia as a candidate treatment for brain disorders. This systematic review examines findings and the methodological quality of studies investigating hypoxia (10-16% O) for ≥14 days in humans, as well as the neurobiological mechanisms triggered by hypoxia in animals, and suggests optimal treatment protocols to guide future studies. We followed the preferred reporting items for systematic reviews and meta-analysis (PRISMA) 2020. Searches were performed on PubMed/MEDLINE, PsycInfo, EMBASE, and the Cochrane Library, in May-September 2023. Two authors independently reviewed the human studies with the following tools: (1) revised Cochrane collaboration's risk of bias for randomized trials 2.0; (2) the risk of bias in nonrandomized studies of interventions. We identified 58 eligible studies (k = 8 human studies with N = 274 individuals; k = 48 animal studies) reporting the effects of hypoxia on cognition, motor function, neuroimaging, neuronal/synaptic morphology, inflammation, oxidative stress, erythropoietin, neurotrophins, and Alzheimer's disease markers. A total of 75% of human studies indicated cognitive and/or neurological benefits, although all studies were evaluated ashigh risk of bias due to a lack of randomization and assessor blinding. Low-dose intermittent or continuous hypoxia repeated for 30-240 min sessions, preferably in combination with motor-cognitive training, produced beneficial effects, and high-dose hypoxia with longer (≥6 h) durations and chronic exposure produced more adverse effects. Larger and methodologically stronger translational studies are warranted.
PubMed: 38137096
DOI: 10.3390/brainsci13121648 -
Annals of Medicine Dec 2023Trimethylamine N-oxide (TMAO) derived from gut microbiota causes kidney-heart damage in chronic kidney disease (CKD) patients. However, it is controversial whether CKD... (Meta-Analysis)
Meta-Analysis
Gut microbiota-derived trimethylamine N-oxide is associated with the risk of all-cause and cardiovascular mortality in patients with chronic kidney disease: a systematic review and dose-response meta-analysis.
BACKGROUND
Trimethylamine N-oxide (TMAO) derived from gut microbiota causes kidney-heart damage in chronic kidney disease (CKD) patients. However, it is controversial whether CKD patients with higher TMAO are associated with a higher risk of death. We aimed to assess the correlation between circulating TMAO concentration and the risk of all-cause and cardiovascular death in CKD patients of different dialysis statuses and different races by dose-response analyses, and the underlying mechanisms were also explored by analyzing the correlations of TMAO with glomerular filtration rate (GFR) and inflammation.
METHOD
PubMed, Web of Science, and EMBASE were systematically searched up to 1 July 2022. A total of 21 studies involving 15,637 individuals were included. Stata 15.0 was used to perform the meta-analyses and dose-response analyses with extracted data. Subgroup analyses were conducted to recognize possible sources of heterogeneity.
RESULTS
The risk of all-cause mortality was increased in non-dialysis CKD patients (RR = 1.26, 95%CI = 1.03-1.54, = 0.028) and non-black dialysis patients (RR = 1.62, 95%CI = 1.19-2.22, = 0.002) with the highest circulating TMAO concentration, and the association was confirmed to be linear. In addition, an increased risk of cardiovascular mortality was also found in non-black dialysis patients with the highest circulating TMAO concentration (RR = 1.72, 95%CI = 1.19-2.47, = 0.004), likewise, a linear association was identified. However, for dialysis patients including blacks with high TMAO concentrations, there was no significant increase in either all-cause mortality (RR = 0.98, 95%CI = 0.94-1.03, = 0.542) or cardiovascular mortality (RR = 0.87, 95% CI = 0.65-1.17, = 0.362). Meanwhile, we verified strong correlations between TMAO and both GFR (= -0.49; 95% CI= -0.75, -0.24; < 0.001) and inflammatory markers ( = 0.43; 95% CI= 0.03, 0.84; = 0.036) in non-dialysis patients.
CONCLUSIONS
Increased circulating TMAO concentrations increase the risk of all-cause mortality in non-dialysis and non-black dialysis CKD patients. Moreover, elevated TMAO levels raise the cardiovascular mortality risk in non-black dialysis patients.Key messagesNon-dialysis and non-black dialysis CKD patients with higher circulating TMAO concentrations are associated with an increased risk of all-cause mortality.Non-black dialysis patients with higher concentrations of TMAO are associated with an increased risk of cardiovascular mortality.Circulating TMAO concentrations have a strong negative correlation with GFR and a positive correlation with inflammation biomarkers in non-dialysis CKD patients.
Topics: Humans; Cardiovascular Diseases; Gastrointestinal Microbiome; Inflammation; Renal Insufficiency, Chronic
PubMed: 37246850
DOI: 10.1080/07853890.2023.2215542