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Cellular Physiology and Biochemistry :... Mar 2023Trazodone is a selective serotonin reuptake inhibitor; however, other mechanisms of the drug's anti-depressive properties have also been postulated. Hence, the aim of...
BACKGROUND/AIMS
Trazodone is a selective serotonin reuptake inhibitor; however, other mechanisms of the drug's anti-depressive properties have also been postulated. Hence, the aim of the study was to perform a systematic review and assess antiglycoxidative properties of trazodone in in vitro models.
METHODS
Trazodone's scavenging and chelating properties were measured with spectrophotometric method. The impact of the drug on carbonyl/oxidative stress was marked in the bovine serum albumin (BSA) model where sugars (glucose, fructose, galactose, ribose) and aldehydes (glyoxal and methylglyoxal) were used as glycation agents. Aminoguanidine and N-acetylcysteine (NAC) were applied as reference glycation/free radical inhibitors. Glycation biomarkers (kynurenine, N-formylkynurenine, dityrosine as well as advanced glycation end products contents) were assessed spectrofluorometrically. Concentrations of oxidation parameters (total thiols (TTs), protein carbonyls (PCs) and also advanced oxidation protein products (AOPPs) levels) were determined spectrophotometrically.
RESULTS
We demonstrated that trazodone poorly scavenged radicals (hydroxyl radical, nitric oxide, hydrogen peroxide and 2,2-diphenyl-1-picrylhydrazyl radical) and showed low ferrous ion chelating, unlike aminoguanidine and NAC. Sugars/aldehydes caused enhancement of glycation parameters, as well as a decrease of TTs and an increase of PCs and AOPPs levels compared to BSA incubated alone. Trazodone did not reduce oxidation parameters to the baseline (BSA) and significantly exacerbated glycation markers in comparison with both BSA and BSA+glycators. The content of glycation products was markedly lower in aminoguanidine and NAC than in trazodone. The molecular docking of trazodone to BSA revealed its very low affinity, which may indicate non-specific binding of trazodone, facilitating the attachment of glycation factors.
CONCLUSION
According to our findings, it may be concluded that trazodone poorly counteracts oxidation and intensifies glycation in vitro. A possible mechanism for antiglycoxidative effect of trazodone in vivo may be the enhancement of the body's adaptive response, as indicated by the results of our systematic review.
Topics: Antioxidants; Trazodone; Glycosylation; Advanced Oxidation Protein Products; Molecular Docking Simulation; Glycation End Products, Advanced; Serum Albumin, Bovine; Glyoxal; Glucose
PubMed: 36988041
DOI: 10.33594/000000617 -
Seminars in Arthritis and Rheumatism Dec 2020The phenomenon of pregnancy-induced remission of rheumatoid arthritis (RA) was first reported by Philip Hench in 1938. Despite extensive efforts, the underlying... (Review)
Review
BACKGROUND
The phenomenon of pregnancy-induced remission of rheumatoid arthritis (RA) was first reported by Philip Hench in 1938. Despite extensive efforts, the underlying scientific basis has remained elusive. A number of different potential mechanisms have been investigated. We have undertaken a systematic review of the available peer-reviewed articles involving pregnant patients with RA in order to establish the depth of current scientific understanding of this important topic.
METHODS
This review was conducted according to guidelines of preferred reporting items for systematic reviews and meta-analyses. Studies were identified by a thorough search of multiple databases including Medline, PubMed and EMBASE. Search terms used were different combinations of the keywords: rheumatoid arthritis, inflammatory arthritis, pregnancy, mechanisms, disease activity, relapse and remission. Non-English language articles and studies that were not directly relevant were excluded. Two independent reviewers (CR and KA) screened the retrieved articles by reading the title and abstract to identify studies that addressed potential mechanisms determining RA activity in pregnancy. Articles were further refined after reading the full text. A data extraction sheet was developed for the purpose of this review and used by the independent reviewers.
RESULTS
After exclusion of irrelevant, duplicate and foreign language articles, a final total of 37 original articles were identified. The largest body of literature concerned glycosylation of immunoglobulins, with 9 published articles. There is evidence of an association between increasing levels of galactosylation of immunoglobulins and reduced RA disease activity in pregnancy. Other identified articles comprised 5 on cytokine changes in pregnancy, 5 on human leucocyte antigen (HLA) incompatibility, 5 on changes in peripheral blood mononuclear cell (PBMC) gene expression; 4 on changes in corticosteroids; 3 on pregnancy associated α2-glycoprotein; 2 on changes in rheumatoid factor (RF)/anti-citrullinated protein antibody (ACPA); and 1 each on microchimerism, gamma delta T cells, regulatory T cells, and mannose-binding lectin. The results of these studies were heterogenous and occasionally conflicting. Selected studies varied greatly in terms of population size, methodology and use of controls and disease activity assessments.
CONCLUSION
This systematic review has found that the cause of the pregnancy-induced amelioration of RA remains to be determined, despite extensive efforts. It is unclear which of the various transitory changes in pregnancy may be responsible for initiating downstream anti-inflammatory immunological mechanisms. We discuss limitations of the current literature and suggest areas for future study.
Topics: Arthritis, Rheumatoid; Cytokines; Female; Humans; Leukocytes, Mononuclear; Pregnancy; Rheumatoid Factor
PubMed: 32224046
DOI: 10.1016/j.semarthrit.2020.03.006 -
European Journal of Clinical... Jul 2023Galectins are β-galactoside-binding proteins. Galectin-4 has shown an effect on cancer progression/metastasis, especially in cancers of the digestive system. This can... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Galectins are β-galactoside-binding proteins. Galectin-4 has shown an effect on cancer progression/metastasis, especially in cancers of the digestive system. This can be attributed to altered glycosylation pattern of cell membrane molecules, which is a characteristic attribute of oncogenesis. The aim of this paper is to systematically review galectin-4 in different cancers and its role in disease progression.
METHODS
The study was designed on the basis of Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) guidelines. PubMed, Scopus, Web of Science, and Science Direct were used to search relevant literature with keywords "galectin-4 AND cancer", "galectin-4", "LGALS4", and "LGALS4 AND cancer". Inclusion criteria for study selection were availability of full-text articles, articles in English language and articles relevant to current topic, that is, galectin-4 and cancer. Exclusion criteria were studies that investigated other disease conditions, interventions unrelated to cancer or galectin-4 and bias outcome.
RESULTS
A total of 73 articles were retrieved after removing duplication from databases, out of which 40 studies were included in the review that followed the inclusion criteria, including low to moderate bias. These included 23 studies in digestive system, 5 in reproductive system, 4 in respiratory system, and 2 in brain and urothelial cancers.
CONCLUSIONS
A differential expression of galectin-4 was observed in different cancer stages/ and types. Furthermore, galectin-4 was found to modulate disease progression. A meta-analysis and comprehensive mechanistic studies, pertaining to different aspects of galectin-4 biology, could give statistically driven correlations, elucidating multifaceted role of galectin-4 in cancer.
Topics: Humans; Galectin 4; Neoplasms; Galectins; Bias; Disease Progression
PubMed: 36932875
DOI: 10.1111/eci.13987 -
Journal of Global Health Nov 2022To reduce mortality associated with hepatitis B virus (HBV) infection, timely detection of cirrhosis and early-stage hepatocellular carcinoma (HCC) is essential. In...
BACKGROUND
To reduce mortality associated with hepatitis B virus (HBV) infection, timely detection of cirrhosis and early-stage hepatocellular carcinoma (HCC) is essential. In low-income countries, however, HBV-infected people have limited access to liver histopathology, a reference test. Recently, Asian studies have suggested the usefulness of an inexpensive serum biomarker called Mac-2 binding protein glycosylation isomer (M2BPGi) in staging liver fibrosis and predicting HCC in HBV-infected patients.
METHODS
We systematically searched PubMed for studies examining the performance of M2BPGi in staging liver fibrosis in HBV-infected people, published up to September 21, 2021, to elucidate the knowledge gap. We then conducted a cross-sectional study of 339 HBV-infected patients in The Gambia (cirrhosis = 65, HCC = 73, non-cirrhosis non-HCC = 201). We evaluated the association of M2BPGi with cirrhosis and HCC by computing odds ratios (ORs) derived from logistic regression. We also assessed the performance of M2BPGi to stage liver fibrosis in 49 patients who underwent liver biopsy (derivation set) and 217 patients with transient elastography (validation set). Using the derivation set we drew the receiver operating characteristics (ROC) curves to identify optimal M2BPGi thresholds to indicate significant fibrosis and cirrhosis using biopsy as a reference. We then applied these cut-offs to the validation set to obtain its sensitivity and specificity for indicating significant fibrosis and cirrhosis using transient elastography as a reference.
RESULTS
The systematic review identified 13 studies, all of which were conducted in East Asia and none in Africa. In The Gambia, positive M2BPGi was significantly associated with both cirrhosis (adjusted OR = 7.8, 95% CI = 3.1-19.7) and HCC (adjusted OR = 10.1, 2.6-40.2). The areas under the ROC curve (AUROC) in the derivation and validation set were 0.62 and 0.78, respectively, to diagnose significant fibrosis, and 0.80 and 0.89, respectively, to diagnose cirrhosis. By applying the optimal cut-offs, the sensitivity and specificity in the validation set were 61.5% and 93.4%, respectively, to diagnose significant fibrosis, and 72.5% and 92.2%, respectively, for cirrhosis.
CONCLUSIONS
To the best of our knowledge, this is the first evaluation of M2BPGi in HBV-infected African population. The findings supported its accuracy in the diagnosis of cirrhosis in HBV-infected patients in West Africa.
Topics: Humans; Hepatitis B virus; Glycosylation; Cross-Sectional Studies; Liver Cirrhosis; Carcinoma, Hepatocellular; Hepatitis B; Liver Neoplasms
PubMed: 36370422
DOI: 10.7189/jogh.12.04076 -
Frontiers in Aging Neuroscience 2022D-ribose is an aldehyde sugar and a necessary component of all living cells. Numerous reports have focused on D-ribose intervention in animal models to assess the...
BACKGROUND
D-ribose is an aldehyde sugar and a necessary component of all living cells. Numerous reports have focused on D-ribose intervention in animal models to assess the negative effects of D-ribose on cognition. However, the results across these studies are inconsistent and the doses and actual effects of D-ribose on cognition remain unclear. This systematic review aimed to evaluate the effect of D-ribose on cognition in rodents.
METHODS
The articles from PubMed, Embase, Sciverse Scopus, Web of Science, the Chinese National Knowledge Infrastructure, SinoMed, Wanfang, and Cqvip databases were screened. The results from the abstract on cognitive-related behavioral tests and biochemical markers from the included articles were extracted and the reporting quality was assessed.
RESULTS
A total of eight trials involving 289 rodents met the eligibility criteria, and both low- and high-dose groups were included. Meta-analyses of these studies showed that D-ribose could cause a significant decrease in the number of platform crossings (standardized mean difference [SMD]: -0.80; 95% CI: -1.14, -0.46; < 0.00001), percentage of distance traversed in the target quadrant (SMD: -1.20; 95% CI: -1.47, -0.92; < 0.00001), percentage of time spent in the target quadrant (SMD: -0.93; 95% CI: -1.18, -0.68; < 0.00001), and prolonged escape latency (SMD: 0.41; 95% CI: 0.16, 0.65; = 0.001) in the Morris water maze test. Moreover, D-ribose intervention increased the levels of advanced glycation end products (AGEs) in the brain (SMD: 0.49; 95% CI: 0.34, 0.63; < 0.00001) and blood (SMD: 0.50; 95% CI: 0.08, 0.92; = 0.02). Subsequently, subgroup analysis for the dose of D-ribose intervention revealed that high doses injured cognitive function more significantly than low D-ribose doses.
CONCLUSION
D-ribose treatment caused cognitive impairment, and cognition deteriorated with increasing dose. Furthermore, the increase in AGEs in the blood and brain confirmed that D-ribose may be involved in cognitive impairment through non-enzymatic glycosylation resulting in the generation of AGEs. These findings provide a new research idea for unveiling basic mechanisms and prospective therapeutic targets for the prevention and treatment of patients with cognitive impairment.
PubMed: 36438006
DOI: 10.3389/fnagi.2022.1036315 -
Journal of Nephrology Mar 2024IgA nephropathy (IgAN) is a common primary glomerular disease. The O-glycosylation status of IgA1 plays a crucial role in disease pathophysiology. The level of... (Review)
Review
BACKGROUND
IgA nephropathy (IgAN) is a common primary glomerular disease. The O-glycosylation status of IgA1 plays a crucial role in disease pathophysiology. The level of poorly-O-galactosylated IgA1, or galactose-deficient IgA1 (Gd-IgA1), has also been identified as a potential biomarker in IgAN. We sought to examine the value of serum Gd-IgA1 as a biomarker in IgAN, by investigating its association with clinical, laboratory, and histopathological features of IgAN.
METHODS
The review followed Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) recommendations and was registered in PROSPERO (CRD42021287423). The literature search was conducted in PubMed, Web of Science, Cochrane, and Scopus, and the selected articles were evaluated for eligibility based on predefined criteria. The methodological quality of the studies was assessed using the Newcastle-Ottawa Scale. Statistical analysis was performed to calculate effect sizes and assess heterogeneity among the studies.
RESULTS
This review analyzed 29 out of 1,986 studies, conducted between 2005 and 2022, with participants from multiple countries. Gd-IgA1 levels were not associated with age and gender, while associations with hypertension, hematuria, and proteinuria were inconsistent. In the meta-analyses, a correlation between serum Gd-IgA1 and estimated glomerular filtration rate was identified, however, the relationships between Gd-IgA1 levels and chronic kidney disease (CKD) stage and progression to kidney failure were inconsistent.
CONCLUSIONS
Serum Gd-IgA1 levels were not associated with validated prognostic risk factors, but were negatively correlated with kidney function. Further research in larger studies using standardized assays are needed to establish the value of Gd-IgA1 as a prognostic risk factor in IgAN.
PubMed: 38427309
DOI: 10.1007/s40620-023-01874-8 -
Viruses Dec 2022The baculovirus expression vector systems (BEVS) have been widely used for the recombinant production of proteins in insect cells and with high insert capacity. However,... (Review)
Review
The baculovirus expression vector systems (BEVS) have been widely used for the recombinant production of proteins in insect cells and with high insert capacity. However, baculovirus does not replicate in mammalian cells; thus, the BacMam system, a heterogenous expression system that can infect certain mammalian cells, was developed. Since then, the BacMam system has enabled transgene expression via mammalian-specific promoters in human cells, and later, the MultiBacMam system enabled multi-protein expression in mammalian cells. In this review, we will cover the continual development of the BEVS in combination with CRPISPR-Cas technologies to drive genome-editing in mammalian cells. Additionally, we highlight the use of CRISPR-Cas in glycoengineering to potentially produce a new class of glycoprotein medicines in insect cells. Moreover, we anticipate CRISPR-Cas9 to play a crucial role in the development of protein expression systems, gene therapy, and advancing genome engineering applications in the future.
Topics: Animals; Humans; Baculoviridae; CRISPR-Cas Systems; Genetic Vectors; Genetic Therapy; Mammals
PubMed: 36680093
DOI: 10.3390/v15010054 -
Annals of Gastroenterology 2022A minimally invasive tool to promptly predict hepatocellular carcinoma (HCC) in chronic hepatitis B (CHB) is currently needed. In this study, we aimed via a...
Baseline serum Mac-2 binding protein glycosylation isomer as a predictor of hepatocellular carcinoma in chronic hepatitis B patients: a systematic review and meta-analysis.
BACKGROUND
A minimally invasive tool to promptly predict hepatocellular carcinoma (HCC) in chronic hepatitis B (CHB) is currently needed. In this study, we aimed via a meta-analysis to identify the serum Mac-2 binding protein glycosylation isomer (M2BPGi) as a novel glycoprotein-based liver fibrosis marker for predicting HCC in CHB patients.
METHODS
We conducted a systematic search on PubMed, Scopus, ProQuest, Wiley Online Library, and CINAHL Plus (via EBSCOhost). The articles were screened based on several eligibility criteria and were further assessed for study qualities using the Newcastle-Ottawa Scale. The outcomes were presented as standard mean difference (SMD), hazard ratio (HR), and predictive accuracy parameters of a baseline cutoff index (COI) for serum M2BPGi.
RESULTS
Fourteen studies involving 5918 CHB patients were included in this systematic review and meta-analysis. Baseline COI serum M2BPGi was significantly higher in CHB patients who developed HCC than in those who did not (SMD 1.32, 95% confidence interval [CI] 0.91-1.72). A significant HCC risk prediction was also observed (multivariate HR 1.18, 95%CI 1.05-1.32). Baseline COI serum M2BPGi could predict HCC with a pooled sensitivity of 74% (95%CI 50-89%), specificity of 80% (95%CI 65-90%), and area under the summary receiver operating characteristic curve of 0.84 (95%CI 0.81-0.87).
CONCLUSION
High baseline COI serum M2BPGi may predict the development of HCC in CHB patients with moderate-to-high accuracy.
PubMed: 36406974
DOI: 10.20524/aog.2022.0751 -
Journal of Inherited Metabolic Disease May 2020Since the first description of galactosemia in 1908 and despite decades of research, the pathophysiology is complex and not yet fully elucidated. Galactosemia is an...
Since the first description of galactosemia in 1908 and despite decades of research, the pathophysiology is complex and not yet fully elucidated. Galactosemia is an inborn error of carbohydrate metabolism caused by deficient activity of any of the galactose metabolising enzymes. The current standard of care, a galactose-restricted diet, fails to prevent long-term complications. Studies in cellular and animal models in the past decades have led to an enormous progress and advancement of knowledge. Summarising current evidence in the pathophysiology underlying hereditary galactosemia may contribute to the identification of treatment targets for alternative therapies that may successfully prevent long-term complications. A systematic review of cellular and animal studies reporting on disease complications (clinical signs and/or biochemical findings) and/or treatment targets in hereditary galactosemia was performed. PubMed/MEDLINE, EMBASE, and Web of Science were searched, 46 original articles were included. Results revealed that Gal-1-P is not the sole pathophysiological agent responsible for the phenotype observed in galactosemia. Other currently described contributing factors include accumulation of galactose metabolites, uridine diphosphate (UDP)-hexose alterations and subsequent impaired glycosylation, endoplasmic reticulum (ER) stress, altered signalling pathways, and oxidative stress. galactokinase (GALK) inhibitors, UDP-glucose pyrophosphorylase (UGP) up-regulation, uridine supplementation, ER stress reducers, antioxidants and pharmacological chaperones have been studied, showing rescue of biochemical and/or clinical symptoms in galactosemia. Promising co-adjuvant therapies include antioxidant therapy and UGP up-regulation. This systematic review provides an overview of the scattered information resulting from animal and cellular studies performed in the past decades, summarising the complex pathophysiological mechanisms underlying hereditary galactosemia and providing insights on potential treatment targets.
Topics: Animals; Disease Models, Animal; Galactokinase; Galactose; Galactosemias; Genotype; Humans; Oxidative Stress; Phenotype; UDPglucose 4-Epimerase; UTP-Hexose-1-Phosphate Uridylyltransferase
PubMed: 31808946
DOI: 10.1002/jimd.12202 -
Nonimmune hydrops fetalis and congenital disorders of glycosylation: A systematic literature review.Journal of Inherited Metabolic Disease Mar 2020Numerous etiologies may lead to nonimmune hydrops fetalis (NIHF) including congenital disorders of glycosylation (CDG). Recognition of CDG in NIHF is challenging. This...
Numerous etiologies may lead to nonimmune hydrops fetalis (NIHF) including congenital disorders of glycosylation (CDG). Recognition of CDG in NIHF is challenging. This study reviews prenatal and neonatal characteristics of CDG presenting with NIHF. A systematic literature search was performed. Thirteen articles met the inclusion criteria. Twenty-one cases with NIHF associated with a CDG were reported. There were 17 live births, three pregnancy terminations, and one fetal demise. Timing of CDG diagnosis was reported mostly postnatally (90%; 10/11). Postnatal genetic testing was reported in 18 patients; three patients were diagnosed by isoelectric focusing of serum transferrin that showed a type 1 pattern. The genes reported for CDG with NIHF for 15 distinct families include: PMM2 in 47% (7/15), ALG9 in 20% (3/15), ALG8 in 13% (2/15), ALG1 in 7% (1/15), MGAT2 in 7% (1/15), and COG6 7% (1/15). In our review, 81% (17/21) reported facial dysmorphism, 52% (11/21) reported CNS abnormalities, most commonly cerebellar atrophy (64%; 7/11), and 38% (8/21) reported cardiovascular abnormalities, most commonly hypertrophic cardiomyopathy (63%; 5/8). Among live births, 71% (12/17) infants died at a median age of 34 days (range 1-185). Thrombocytopenia was reported in 53% (9/17) patients. Of those who survived past the neonatal period, 80% (4/5) had significant reported developmental delays. CDG should be on the differential diagnosis of NIHF in the presence of cerebellar atrophy, hypertrophic cardiomyopathy, or thrombocytopenia. Our review highlights the poor prognosis in infants with NIHF due to CDG and demonstrates the importance of identifying these disorders prenatally to guide providers in their counseling with families regarding pregnancy management. SYNOPSIS: Poor prognosis in fetuses and infants with nonimmune hydrops fetalis due to congenital disorders of glycosylation highlights the importance of prenatal diagnosis of this disorder.
Topics: Congenital Disorders of Glycosylation; Female; Fetal Death; Glycosylation; Humans; Hydrops Fetalis; Infant, Newborn; Phosphotransferases (Phosphomutases); Pregnancy; Prenatal Diagnosis
PubMed: 31420886
DOI: 10.1002/jimd.12162