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International Journal of Molecular... Feb 2024Juvenile Idiopathic Arthritis (JIA) is currently the most common chronic rheumatic disease in children. It is known to have no single identity, but a variety of... (Review)
Review
UNLABELLED
Juvenile Idiopathic Arthritis (JIA) is currently the most common chronic rheumatic disease in children. It is known to have no single identity, but a variety of diagnoses. Under-diagnosis is a barrier to early treatment and reduced complications of the disease. Other immune-mediated diseases may coexist in the same patient, making research in this area relevant. The main objective was to analyse whether links could be established between the molecular basis of JIA and other immune-mediated diseases. Early diagnosis may benefit patients with JIA, which in most cases goes undetected, leading to under-diagnosis, which can have a negative impact on children affected by the disease as they grow up.
METHODS
We performed a PRISMA systematic review focusing on immune molecules present in different autoimmune diseases.
RESULTS
A total of 13 papers from different countries dealing with the molecular basis of JIA and other immune diseases were evaluated and reviewed.
CONCLUSIONS
Most of the autoimmune diseases analysed responded to the same group of drugs. Unfortunately, the reason for the under-diagnosis of these diseases remains unknown, as no evidence has been found to correlate the immunomolecular basis with the under-diagnosis of these immune-mediated diseases. The lack of information in this area means that further research is needed in order to provide a sound basis for preventing the development of immune-mediated diseases, especially in children, and to improve their quality of life through early diagnosis and treatment.
Topics: Child; Humans; Arthritis, Juvenile; Quality of Life; Rheumatic Diseases
PubMed: 38474052
DOI: 10.3390/ijms25052803 -
Genome Research Apr 2024Mitochondrial DNA (mtDNA) variants cause a range of diseases from severe pediatric syndromes to aging-related conditions. The percentage of mtDNA copies carrying a...
Mitochondrial DNA (mtDNA) variants cause a range of diseases from severe pediatric syndromes to aging-related conditions. The percentage of mtDNA copies carrying a pathogenic variant, variant allele frequency (VAF), must reach a threshold before a biochemical defect occurs, termed the biochemical threshold. Whether the often-cited biochemical threshold of >60% VAF is similar across mtDNA variants and cell types is unclear. In our systematic review, we sought to identify the biochemical threshold of mtDNA variants in relation to VAF by human tissue/cell type. We used controlled vocabulary terms to identify articles measuring oxidative phosphorylation (OXPHOS) complex activities in relation to VAF. We identified 76 eligible publications, describing 69, 12, 16, and 49 cases for complexes I, III, IV, and V, respectively. Few studies evaluated OXPHOS activities in diverse tissue types, likely reflective of clinical access. A number of cases with similar VAFs for the same pathogenic variant had varying degrees of residual activity of the affected complex, alluding to the presence of modifying variants. Tissues and cells with VAFs <60% associated with low complex activities were described, suggesting the possibility of a biochemical threshold of <60%. Using Kendall rank correlation tests, the VAF of the m.8993T > G variant correlated with complex V activity in skeletal muscle (τ = -0.58, = 0.01, n = 13); however, no correlation was observed in fibroblasts ( = 0.7, n = 9). Our systematic review highlights the need to investigate the biochemical threshold over a wider range of VAFs in disease-relevant cell types to better define the biochemical threshold for specific mtDNA variants.
Topics: Humans; DNA, Mitochondrial; Gene Frequency; Genetic Variation; Mitochondria; Mitochondrial Diseases; Oxidative Phosphorylation
PubMed: 38627095
DOI: 10.1101/gr.278200.123 -
Orphanet Journal of Rare Diseases Feb 2024Late-onset multiple acyl-CoA dehydrogenase deficiency (MADD) is the most common lipid storage myopathy. There are sex differences in fat metabolism and it is not known... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Late-onset multiple acyl-CoA dehydrogenase deficiency (MADD) is the most common lipid storage myopathy. There are sex differences in fat metabolism and it is not known whether late-onset MADD affects men and women equally.
METHODS
In this systematic review and meta-analysis, the PubMed, Embase, Web of Science, CNKI, CBM, and Wanfang databases were searched until 01/08/2023. Studies reporting sex distribution in patients with late-onset MADD were included. Two authors independently screened studies for eligibility, extracted data, and assessed risk of bias. Pre-specified outcomes of interest were the male-to-female ratio (MFR) of patients with late-onset MADD, the differences of clinical characteristics between the sexes, and factors influencing the MFR.
RESULTS
Of 3379 identified studies, 34 met inclusion criteria, yielding a total of 609 late-onset MADD patients. The overall pooled percentage of males was 58% (95% CI, 54-63%) with low heterogeneity across studies (I = 2.99%; P = 0.42). The mean onset ages, diagnostic delay, serum creatine kinase (CK), and allelic frequencies of 3 hotspot variants in ETFDH gene were similar between male and female patients (P > 0.05). Meta-regressions revealed that ethnic group was associated with the MFR in late-onset MADD, and subgroup meta-analyses demonstrated that East-Asian patients had a higher percentage of male, lower CK, and higher proportion of hotspot variants in ETFDH gene than non-East-Asian patients (P < 0.05).
CONCLUSIONS
Male patients with late-onset MADD were more common than female patients. Ethnicity was proved to be a factor influencing the MFR in late-onset MADD. These findings suggest that male sex may be a risk factor for the disease.
Topics: Humans; Male; Female; Multiple Acyl Coenzyme A Dehydrogenase Deficiency; Mutation; Delayed Diagnosis; Electron-Transferring Flavoproteins; Iron-Sulfur Proteins; Oxidoreductases Acting on CH-NH Group Donors; Acyl-CoA Dehydrogenase
PubMed: 38365830
DOI: 10.1186/s13023-024-03072-6 -
Biomedicine & Pharmacotherapy =... Jul 2024Central nervous system (CNS) disorders exhibit exceedingly intricate pathogenic mechanisms. Pragmatic and effective solutions remain elusive, significantly compromising... (Review)
Review
Central nervous system (CNS) disorders exhibit exceedingly intricate pathogenic mechanisms. Pragmatic and effective solutions remain elusive, significantly compromising human life and health. Activating transcription factor 4 (ATF4) participates in the regulation of multiple pathophysiological processes, including CNS disorders. Considering the widespread involvement of ATF4 in the pathological process of CNS disorders, the targeted regulation of ATF4 by plant-derived bioactive compounds (PDBCs) may become a viable strategy for the treatment of CNS disorders. However, the regulatory relationship between PDBCs and ATF4 remains incompletely understood. Here, we aimed to comprehensively review the studies on PDBCs targeting ATF4 to ameliorate CNS disorders, thereby offering novel directions and insights for the treatment of CNS disorders. A computerized search was conducted on PubMed, Embase, Web of Science, and Google Scholar databases to identify preclinical experiments related to PDBCs targeting ATF4 for the treatment of CNS disorders. The search timeframe was from the inception of the databases to December 2023. Two assessors conducted searches using the keywords "ATF4," "Central Nervous System," "Neurological," "Alzheimer's disease," "Parkinson's Disease," "Stroke," "Spinal Cord Injury," "Glioblastoma," "Traumatic Brain Injury," and "Spinal Cord Injury." Overall, 31 studies were included, encompassing assessments of 27 PDBCs. Combining results from in vivo and in vitro studies, we observed that these PDBCs, via ATF4 modulation, prevent the deposition of amyloid-like fibers such as Aβ, tau, and α-synuclein. They regulate ERS, reduce the release of inflammatory factors, restore mitochondrial membrane integrity to prevent oxidative stress, regulate synaptic plasticity, modulate autophagy, and engage anti-apoptotic mechanisms. Consequently, they exert neuroprotective effects in CNS disorders. Numerous PDBCs targeting ATF4 have shown potential in facilitating the restoration of CNS functionality, thereby presenting expansive prospects for the treatment of such disorders. However, future endeavors necessitate high-quality, large-scale, and comprehensive preclinical and clinical studies to further validate this therapeutic potential.
Topics: Activating Transcription Factor 4; Humans; Central Nervous System Diseases; Animals; Phytochemicals; Neuroprotective Agents
PubMed: 38795641
DOI: 10.1016/j.biopha.2024.116811 -
Chronic Obstructive Pulmonary Diseases... Jan 2024Alpha-1 antitrypsin deficiency (AATD) is an often-overlooked genetic condition that makes individuals susceptible to early onset of chronic obstructive pulmonary disease...
Pulmonary Rehabilitation for Chronic Obstructive Pulmonary Disease Patients with Underlying Alpha-1 Antitrypsin Deficiency: A Systematic Review and Practical Recommendations.
BACKGROUND
Alpha-1 antitrypsin deficiency (AATD) is an often-overlooked genetic condition that makes individuals susceptible to early onset of chronic obstructive pulmonary disease (COPD). The established benefits of exercise-based pulmonary rehabilitation (PR) for usual COPD patients are unclear for those with underlying AATD, especially given potentially differing muscle adaptations to exercise. This review seeks to compare PR outcomes between AATD and usual COPD patients and to consolidate current knowledge on exercise intervention outcomes for the AATD population.
METHODS
A thorough search of 4 databases (Ovid, Medline, CINAHL, CENTRAL) was conducted based on 3 search concepts: (1) alpha-1 antitrypsin deficiency, (2) pulmonary rehabilitation OR exercise, and (3) muscle morphology. A dual review process and quality assessment were independently implemented throughout all stages of the review.
RESULTS
Four studies highlighted modest exercise capacity and quality of life in AATD patients undergoing PR. However, one study reported unique muscle and mitochondrial responses compared to usual COPD patients. Additionally, a moderate exercise session did not alter pro-inflammatory cytokine levels in AATD patients, despite higher levels of tumor necrosis factor-α levels in muscle biopsies compared to usual COPD patients.
CONCLUSIONS
The current literature base insufficiently addresses the efficacy of PR on AATD, with indications that exercise adaptation may deviate from that of usual COPD patients. Further research is needed to optimize PR, particularly in identifying the most suitable exercise intensity, and delivery setting, and addressing specific educational needs for individuals with AATD.
PubMed: 37813825
DOI: 10.15326/jcopdf.2023.0434 -
Arquivos Brasileiros de Cardiologia Apr 2024Obesity is associated with the development of cardiovascular diseases and is a serious public health problem. In animal models, high-fat diet (HFD) feeding impairs...
BACKGROUND
Obesity is associated with the development of cardiovascular diseases and is a serious public health problem. In animal models, high-fat diet (HFD) feeding impairs cardiac structure and function and promotes oxidative stress and apoptosis. Resistance exercise training (RT), however, has been recommended as coadjutant in the treatment of cardiometabolic diseases, including obesity, because it increases energy expenditure and stimulates lipolysis.
OBJECTIVE
In this systematic review, we aimed to assess the benefits of RT on the heart of rats and mice fed HFD.
METHODS
Original studies were identified by searching PubMed, Scopus, and Embase databases from December 2007 to December 2022. This study was conducted in accordance with the criteria established by PRISMA and registered in PROSPERO (CRD42022369217). The risk of bias and methodological quality was evaluated by SYRCLE and CAMARADES, respectively. Eligible studies included original articles published in English that evaluated cardiac outcomes in rodents submitted to over 4 weeks of RT and controlled by a sedentary, HFD-fed control group (n = 5).
RESULTS
The results showed that RT mitigates cardiac oxidative stress, inflammation, and endoplasmic reticulum stress. It also modifies the activity of structural remodeling markers, although it does not alter biometric parameters, histomorphometric parameters, or the contractile function of cardiomyocytes.
CONCLUSION
Our results indicate that RT partially counteracts the HFD-induced adverse cardiac remodeling by increasing the activity of structural remodeling markers; elevating mitochondrial biogenesis; reducing oxidative stress, inflammatory markers, and endoplasmic reticulum stress; and improving hemodynamic, anthropometric, and metabolic parameters.
Topics: Animals; Diet, High-Fat; Resistance Training; Rats; Physical Conditioning, Animal; Mice; Ventricular Remodeling; Oxidative Stress; Obesity; Disease Models, Animal
PubMed: 38695409
DOI: 10.36660/abc.20230490 -
CNS Neuroscience & Therapeutics Mar 2024Mitochondrial complex III (CIII) deficiency is an autosomal recessive disease characterized by symptoms such as ataxia, cognitive dysfunction, and spastic paraplegia....
BACKGROUND
Mitochondrial complex III (CIII) deficiency is an autosomal recessive disease characterized by symptoms such as ataxia, cognitive dysfunction, and spastic paraplegia. Multiple genes are associated with complex III defects. Among them, the mutation of TTC19 is a rare subtype.
METHODS
We screened a Chinese boy with weakness of limbs and his non-consanguineous parents by whole exome sequencing and targeted sequencing.
RESULTS
We report a Chinese boy diagnosed with mitochondrial complex III defect type 2 carrying a homozygous variant (c.719-732del, p.Leu240Serfs*17) of the TTC19 gene. According to the genotype analysis of his family members, this is an autosomal recessive inheritance. We provide his clinical manifestation.
CONCLUSIONS
A new type of TTC19 mutation (c.719-732del, p.Leu240Serfs*17) was found, which enriched the TTC19 gene mutation spectrum and provided new data for elucidating the pathogenesis of CIII-deficient diseases.
Topics: Male; Humans; Electron Transport Complex III; Membrane Proteins; Mutation; Peripheral Nervous System Diseases; Movement Disorders; Pedigree; Mitochondrial Diseases
PubMed: 37927170
DOI: 10.1111/cns.14425 -
Frontiers in Endocrinology 2024Acetaldehyde dehydrogenase 2 (ALDH2) had reported as a prominent role in the development of cardiometabolic diseases among Asians. Our study aims to investigate the... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
Acetaldehyde dehydrogenase 2 (ALDH2) had reported as a prominent role in the development of cardiometabolic diseases among Asians. Our study aims to investigate the relationship between ALDH2 polymorphism and cardiometabolic risk factors in East Asian population.
METHOD
We searched databases of PubMed, Web of Science, and Embase updated to Oct 30, 2023. We extracted data of BMI, Hypertension, SBP, DBP, T2DM, FBG, PPG, HbA1c, TG, TC, LDL-C and HDL-C.
RESULT
In total, 46 studies were finally included in our meta-analysis, containing, 54068 GG and, 36820 GA/AA participants. All outcomes related to blood pressure revealed significant results (hypertension OR=0.83 [0.80, 0.86]; SBP MD=-1.48 [-1.82, -1.14]; DBP MD=-1.09 [-1.58, -0.61]). FBG showed a significant difference (MD=-0.10 [-0.13, -0.07]), and the lipid resulted significantly in some outcomes (TG MD=-0.07 [-0.09, -0.04]; LDL-C MD=-0.04 [-0.05, -0.02]). As for subgroups analysis, we found that in populations without severe cardiac-cerebral vascular diseases (CCVDs), GG demonstrated a significantly higher incidence of T2DM (T2DM OR=0.88 [0.79, 0.97]), while the trend was totally opposite in population with severe CCVDs (T2DM OR=1.29 [1.00, 1.66]) with significant subgroup differences.
CONCLUSION
Our updated meta-analysis demonstrated that ALDH2 rs671 GG populations had significantly higher levels of BMI, blood pressure, FBG, TG, LDL-C and higher risk of hypertension than GA/AA populations. Besides, to the best of our knowledge, we first report GG had a higher risk of T2DM in population without severe CCVDs, and GA/AA had a higher risk of T2DM in population with severe CCVDs. https://www.crd.york.ac.uk/PROSPERO, identifier CRD42023389242.
Topics: Humans; Aldehyde Dehydrogenase, Mitochondrial; Asian People; Cardiometabolic Risk Factors; Cholesterol, LDL; Diabetes Mellitus, Type 2; East Asian People; Hypertension
PubMed: 38567307
DOI: 10.3389/fendo.2024.1333595