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Current Pain and Headache Reports Apr 2024Fibromyalgia syndrome (FMS) is a disease of unknown pathophysiology, with the diagnosis being based on a set of clinical criteria. Proteomic analysis can provide... (Review)
Review
PURPOSE OF REVIEW
Fibromyalgia syndrome (FMS) is a disease of unknown pathophysiology, with the diagnosis being based on a set of clinical criteria. Proteomic analysis can provide significant biological information for the pathophysiology of the disease but may also reveal biomarkers for diagnosis or therapeutic targets. The present systematic review aims to synthesize the evidence regarding the proteome of adult patients with FMS using data from observational studies.
RECENT FINDINGS
An extensive literature search was conducted in MEDLINE/PubMed, CENTRAL, and clinicaltrials.gov from inception until November 2022. The study protocol was published in OSF. Two independent reviewers evaluated the studies and extracted data. The quality of studies was assessed using the modified Newcastle-Ottawa scale adjusted for proteomic research. Ten studies fulfilled the protocol criteria, identifying 3328 proteins, 145 of which were differentially expressed among patients with FMS against controls. The proteins were identified in plasma, serum, cerebrospinal fluid, and saliva samples. The control groups included healthy individuals and patients with pain (inflammatory and non-inflammatory). The most important proteins identified involved transferrin, α-, β-, and γ-fibrinogen chains, profilin-1, transaldolase, PGAM1, apolipoprotein-C3, complement C4A and C1QC, immunoglobin parts, and acute phase reactants. Weak correlations were observed between proteins and pain sensation, or quality of life scales, apart from the association of transferrin and a2-macroglobulin with moderate-to-severe pain sensation. The quality of included studies was moderate-to-good. FMS appears to be related to protein dysregulation in the complement and coagulation cascades and the metabolism of iron. Several proteins may be dysregulated due to the excessive oxidative stress response.
PubMed: 38652420
DOI: 10.1007/s11916-024-01244-4 -
Diabetes, Obesity & Metabolism Apr 2024To perform a systematic review of studies that sought to identify diagnostic biomarkers for the diagnosis of cardiovascular diseases (CVDs) and diabetes mellitus (DM),... (Review)
Review
AIMS
To perform a systematic review of studies that sought to identify diagnostic biomarkers for the diagnosis of cardiovascular diseases (CVDs) and diabetes mellitus (DM), which could be used in low- and middle-income countries (LMICs) where there is a lack of diagnostic equipment, treatments and training.
MATERIALS AND METHODS
Papers were sourced from six databases: the British Nursing Index, Google Scholar, PubMed, Sage, Science Direct and Scopus. Articles published between January 2002 and January 2023 were systematically reviewed by three reviewers and appropriate search terms and inclusion/exclusion criteria were applied.
RESULTS
A total of 18 studies were yielded, as well as 234 diagnostic biomarkers (74 for CVD and 160 for DM). Primary biomarkers for the diagnosis of CVDs included growth differentiation factor 15 and neurogenic locus notch homologue protein 1 (Notch1). For the diagnosis of DM, alpha-2-macroglobulin, C-peptides, isoleucine, glucose, tyrosine, linoleic acid and valine were frequently reported across the included studies. Advanced analytical techniques, such as liquid chromatography mass spectrometry, enzyme-linked immunosorbent assays and vibrational spectroscopy, were also repeatedly reported in the included studies and were utilized in combination with traditional and alternative matrices such as fingernails, hair and saliva.
CONCLUSIONS
While advanced analytical techniques are expensive, laboratories in LMICs should carry out a cost-benefit analysis of their use. Alternatively, laboratories may want to explore emerging techniques such as infrared, Fourier transform-infrared and near-infrared spectroscopy, which allow sensitive noninvasive analysis.
PubMed: 38637978
DOI: 10.1111/dom.15593 -
Journal of Alzheimer's Disease Reports 2023The relationship between alpha 2-macroglobulin (A2M) gene and Alzheimer's disease (AD) has been widely studied across populations; however, the results are inconsistent.
BACKGROUND
The relationship between alpha 2-macroglobulin (A2M) gene and Alzheimer's disease (AD) has been widely studied across populations; however, the results are inconsistent.
OBJECTIVE
This study aimed to evaluate the association of A2M gene with AD by the application of meta-analysis.
METHODS
Relevant studies were identified by comprehensive searches. The quality of each study was assessed using the Newcastle-Ottawa Scale. Allele and genotype frequencies were extracted from each of the included studies. Odds ratio (OR) with corresponding 95% confidence intervals (CI) was calculated using a random-effects or fixed-effects model. The Cochran Q statistic and I metric was used to evaluate heterogeneity, and Egger's test and Funnel plot were used to assess publication bias.
RESULTS
A total of 62 studies were identified and included in the current meta-analysis. The G allele of rs226380 reduced AD risk (OR: 0.64, 95% CI: 0.47-0.87, pFDR = 0.012), but carrier with the TT genotype was more likely to develop AD in Asian populations (OR: 1.56, 95% CI: 1.12-2.19, pFDR = 0.0135). The V allele of the A2M-I/V (rs669) increased susceptibility to AD in female population (OR, 95% CI: 2.15, 1.38-3.35, pFDR = 0.0024); however, the II genotype could be a protective factor in these populations (OR, 95% CI: 0.43, 0.26-0.73, pFDR = 0.003). Sensitivity analyses confirmed the reliability of the original results.
CONCLUSIONS
Existing evidence indicate that A2M single nucleotide polymorphisms (SNPs) may be associated with AD risk in sub-populations. Future studies with larger sample sizes will be necessary to confirm the results.
PubMed: 38143774
DOI: 10.3233/ADR-230131 -
Sao Paulo Medical Journal = Revista... 2022Chronically elevated alpha-2-macroglobulin (A2MG) in the blood has been correlated with diabetes and the HbA1c profile; however, no systematic review has been conducted... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Chronically elevated alpha-2-macroglobulin (A2MG) in the blood has been correlated with diabetes and the HbA1c profile; however, no systematic review has been conducted to evaluate the association of A2MG salivary levels and glycemia or HbA1c levels in diabetes mellitus type 2 (DM2) patients.
OBJECTIVE
To evaluate whether A2MG salivary levels are related to the glycemia or HbA1c levels in DM2 patients.
DESIGN AND SETTING
Systematic review developed at Universidade Federal de Uberlândia (UFU), Brazil.
METHODS
Eight databases were used as research sources. The eligibility criteria included studies that reported data regarding mean salivary A2MG and the correlation between glycemia and/or HbA1c levels of DM2 subjects (uncontrolled and well-controlled) and non-diabetic subjects. The risk of bias of the studies selected was assessed using the Joanna Briggs Institute (JBI) critical appraisal tools for use in JBI systematic reviews. Pooled correlation coefficients were estimated using the Hunter-Schmidt method. Study estimates were weighted according to their sample size, and heterogeneity was calculated using the chi-square statistic.
RESULTS
Four studies on DM2 patients were included in this systematic review after careful analysis of 1482 studies. Three studies compared A2MG with HbA1c and glycemia. Overall, the correlation between A2MG and HbA1c was strong (r = 0.838). In contrast, the correlation between A2MG and glycemia was low (r = 0.354).
CONCLUSION
The strong association between HbA1C and salivary A2MG suggests that this salivary protein has the potential to be a surrogate for HbA1C, if corroboratory further evidence is obtained through large-scale studies.
Topics: Humans; Blood Glucose; Diabetes Mellitus, Type 2; Glycated Hemoglobin; Pregnancy-Associated alpha 2-Macroglobulins
PubMed: 36102452
DOI: 10.1590/1516-3180.2021.0816.R2.19052022 -
International Journal of Molecular... Sep 2022Biological material is one of the most important aspects that allow for the correct diagnosis of the disease, and tears are an interesting subject of research because of... (Review)
Review
Biological material is one of the most important aspects that allow for the correct diagnosis of the disease, and tears are an interesting subject of research because of the simplicity of collection, as the well as the relation to the components similar to other body fluids. In this review, biomarkers for Alzheimer's disease (AD), Parkinson's disease (PD), and multiple sclerosis (MS) in tears are investigated and analyzed. Records were obtained from the PubMed and Google Scholar databases in a timeline of 2015-2022. The keywords were: tear film/tear biochemistry/tear biomarkers + diseases (AD, PD, or MS). The recent original studies were analyzed, discussed, and biomarkers present in tears that can be used for the diagnosis and management of AD, PD, and MS diseases were shown. α-synTotal and α-synOligo, lactoferrin, norepinephrine, adrenaline, epinephrine, dopamine, α-2-macroglobulin, proteins involved in immune response, lipid metabolism and oxidative stress, apolipoprotein superfamily, and others were shown to be biomarkers in PD. For AD as potential biomarkers, there are: lipocalin-1, lysozyme-C, and lacritin, amyloid proteins, t-Tau, p-Tau; for MS there are: oligoclonal bands, lipids containing choline, free carnitine, acylcarnitines, and some amino acids. Information systematized in this review provides interesting data and new insight to help improve clinical outcomes for patients with neurodegenerative disorders.
Topics: Alzheimer Disease; Biomarkers; Humans; Lacrimal Apparatus Diseases; Multiple Sclerosis; Parkinson Disease; Tears
PubMed: 36077520
DOI: 10.3390/ijms231710123 -
Pain Medicine (Malden, Mass.) Sep 2022Neuropathic pain is a complex condition that can be refractory to conventional management and can cause persistent suffering in patients. Current pharmacologic...
BACKGROUND
Neuropathic pain is a complex condition that can be refractory to conventional management and can cause persistent suffering in patients. Current pharmacologic treatments can provide temporary symptomatic relief; however, the mechanism of these therapies does not address the underlying cause of neuropathic pain. The use of injectable biologics for neuropathic pain has multiple proposed mechanisms for analgesia including attenuation of inflammatory mediated processes, arrest or delay of the degenerative process, inhibition of apoptotic pathways, and augmentation of the survival and recovery of injured and uninjured nerves.
STUDY DESIGN
A systematic review of human studies involving the use of injectable biologics for neuropathic pain.
METHODS
A comprehensive search of several data bases including Ovid MEDLINE ® and Epub Ahead of Print, In Process & Other Non-Indexed Citations and Daily, and Ovid Embase from inception to November 24, 2020.
RESULTS
The initial search yielded 3,450 studies with an additional 6 studies identified through other resources. Twenty-seven studies were included after independent review by two of the investigators. The included studies assessed the efficacy of injectable biologics for the treatment of neuropathic pain defined as pain reduction. Secondary outcome measures included functional improvement as well as safety of the procedures. A qualitative assessment of the literature without meta-analysis was performed due to the heterogeneity of the data.
CONCLUSION
According to the GRADE criteria, there is very low certainty of evidence in support of the efficacy of injectable biologics for treatment of neuropathic pain. Future efforts should focus on creating a standardized methodology and study design with respect to preparation, dosage and route of administration of biologics. This will serve as a catalyst for higher quality randomized trials with generation of more useful data to help drive informed clinical decision making.
Topics: Biological Products; Humans; Neuralgia
PubMed: 35482528
DOI: 10.1093/pm/pnac066 -
Therapeutic Apheresis and Dialysis :... Aug 2022Medium cut-off (MCO) dialyzers were designed to provide better clearance of uremic toxins. We conducted a meta-analysis comparing MCO with high-flux (HF) dialyzers for... (Meta-Analysis)
Meta-Analysis
Medium cut-off (MCO) dialyzers were designed to provide better clearance of uremic toxins. We conducted a meta-analysis comparing MCO with high-flux (HF) dialyzers for the effect on uremic toxins in maintenance hemodialysis (HD) patients. Five databases were systematically searched for relevant studies and nine studies were identified finally. Reduction ratio (RR) of urea, urea, creatinine, β2-macroglobulin (β2-MG), kappa free light chain (κFLC), and lambda FLC (λFLC) levels were not significantly different between MCO and HF dialyzers. But RR of β2-MG, κFLC, and λFLC were greater for MCO than HF dialyzers. MCO dialyzers could better reduce tumor necrosis factor-α (TNF-α) levels. Subgroup analysis stratified by study design indicated that in randomized controlled trial (RCT) studies, albumin levels was lower in MCO than HF dialyzers group, but the two dialyzers treatments were equivalent in non-RCT subgroup. Compared with HF dialyzers, MCO dialyzers provided higher middle-molecules uremic toxins clearance and obviously reduced TNF-α levels.
Topics: Creatinine; Hemodiafiltration; Humans; Immunoglobulin Light Chains; Membranes, Artificial; Renal Dialysis; Tumor Necrosis Factor-alpha; Urea
PubMed: 34773675
DOI: 10.1111/1744-9987.13755 -
The British Journal of Ophthalmology Dec 2022This study aims to assess the contribution of biallelic variants in patients with different forms of glaucoma, especially primary open-angle glaucoma (POAG) and primary...
BACKGROUND/AIMS
This study aims to assess the contribution of biallelic variants in patients with different forms of glaucoma, especially primary open-angle glaucoma (POAG) and primary angle-closure glaucoma (PACG), based on a systematic analysis of exome sequencing (ES).
METHODS
Potentially pathogenic variants were selected from the ES data of 5307 subjects with various eye conditions through multiple bioinformatics analyses. Of the 5307 subjects, 1221 probands had different forms of primary glaucoma. The genotype-phenotype correlation was assessed by a systematic review of biallelic variants that including our data and data from the literature. The expression profile of in human tissues was determined at the mRNA and protein levels.
RESULTS
Biallelic variants, including one frameshift and six missense variants, were exclusively present and significantly enriched in patients with glaucoma (one with juvenile open-angle glaucoma (JOAG), two with POAG and two with PACG) compared with none of the 4086 probands with other eye conditions in this cohort (p=4.1E-07). The effect of variants in these patients is relatively mild compared with that reported in patients with anterior segment dysgenesis or primary congenital glaucoma. mRNA was highly expressed in the optic nerve, ciliary body, retina and iris, whereas the CPAMD8 protein was mainly detected in the nonpigmented epithelium of the iris and ciliary process, determined by immunohistochemistry.
CONCLUSIONS
The data from this study not only provide further evidence to support the association of biallelic variants with JOAG but also suggest that biallelic variants might be associated with POAG and PACG.
Topics: Humans; Glaucoma, Open-Angle; Glaucoma, Angle-Closure; Eye Abnormalities; Glaucoma; RNA, Messenger; alpha-Macroglobulins; Complement C3; Trypsin Inhibitor, Kazal Pancreatic
PubMed: 34154991
DOI: 10.1136/bjophthalmol-2020-318668 -
Angiology Oct 2021This study aimed to determine the efficacy of alprostadil in preventing contrast-induced nephropathy (CIN). Eligible studies were searched using the keywords through the... (Meta-Analysis)
Meta-Analysis
This study aimed to determine the efficacy of alprostadil in preventing contrast-induced nephropathy (CIN). Eligible studies were searched using the keywords through the databases of PubMed, Cochrane, Embase, China Biological Medicine Database, China National Knowledge Infrastructure, and Vanfun. Quality evaluation of the included studies was conducted according to international evidence evaluation and recommended Grades of Recommendations Assessment, Development, and Evaluation standards. We included 29 studies with 5623 patients. Compared with hydration, 10 µg/d alprostadil or 20 µg/d alprostadil plus hydration significantly decreased the incidence of CIN. Compared with hydration, alprostadil plus hydration significantly reduced serum creatinine and blood urea nitrogen at 24, 48, and 72 hours and 7 days after coronary angiography (CAG). Alprostadil (20 µg/d) plus hydration significantly decreased serum cystatin versus hydration at 24, 48, and 72 hours after CAG. Compared with hydration, alprostadil plus hydration significantly increased glomerular filtration rate at 24 and 72 hours after CAG. Alprostadil plus hydration significantly decreased neutrophil gelatinase-associated lipocalin levels compared to hydration at 24, 48, and 72 hours after CAG. Alprostadil plus hydration significantly decreased urine macroglobulin versus hydration at 24 and 48 hours after CAG.
Topics: Acute Kidney Injury; Alprostadil; Combined Modality Therapy; Contrast Media; Coronary Angiography; Female; Fluid Therapy; Humans; Male; Middle Aged; Protective Agents; Protective Factors; Risk Assessment; Risk Factors; Treatment Outcome
PubMed: 33853365
DOI: 10.1177/00033197211004412 -
Ageing Research Reviews Jul 2020In order to gauge the impact of proteomics in discovery of Alzheimer's disease (AD) blood-based biomarkers, this study had systematically reviewed articles published... (Meta-Analysis)
Meta-Analysis
In order to gauge the impact of proteomics in discovery of Alzheimer's disease (AD) blood-based biomarkers, this study had systematically reviewed articles published between 1984-2019. Articles that fulfilled the inclusion criteria were assessed for risk of bias. A meta-analysis was performed for replicable candidate biomarkers (CB). Of the 1651 articles that were identified, 17 case-control and two cohort studies, as well as three combined case-control and longitudinal designs were shortlisted. A total of 207 AD and mild cognitive impairment (MCI) CB were discovered, with 48 reported in >2 studies. This review highlights six CB, namely alpha-2-macroglobulin (α2M), pancreatic polypeptide (PP), apolipoprotein A-1 (ApoA-1), afamin, insulin growth factor binding protein-2 (IGFBP-2) and fibrinogen-γ-chain, all of which exhibited consistent pattern of regulation in >three independent cohorts. They are involved in AD pathogenesis via amyloid-beta (Aβ), neurofibrillary tangles, diabetes and cardiovascular diseases (CVD). Meta-analysis indicated that ApoA-1 was significantly downregulated in AD (SMD = -1.52, 95% CI: -1.89, -1.16, p < 0.00001), with low inter-study heterogeneity (I = 0%, p = 0.59). α2M was significantly upregulated in AD (SMD = 0.83, 95% CI: 0.05, 1.62, p = 0.04), with moderate inter-study heterogeneity (I = 41%, p = 0.19). Both CB are involved in Aβ formation. These findings provide important insights into blood-based AD biomarkers discovery via proteomics.
Topics: Alzheimer Disease; Biomarkers; Cognitive Dysfunction; Cohort Studies; Humans; Proteomics
PubMed: 32294542
DOI: 10.1016/j.arr.2020.101066