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Journal of Cardiovascular Pharmacology May 2024Hydroxychloroquine (HCQ) and chloroquine (CQ) are foundational treatments for several systemic autoimmune rheumatic diseases, including systemic lupus erythematosus...
Hydroxychloroquine and Chloroquine-Induced Cardiac Arrhythmias and Sudden Cardiac Death in Patients with Systemic Autoimmune Rheumatic Diseases: A Systematic Review and Meta-Analysis.
Hydroxychloroquine (HCQ) and chloroquine (CQ) are foundational treatments for several systemic autoimmune rheumatic diseases, including systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA). Concerns regarding the risk of cardiac arrhythmia and death have been raised, yet the burden of HCQ and CQ-related cardiac toxicities remains unclear. A systematic literature search was conducted in the MEDLINE and Embase databases for articles published between the earliest date and April 2023 reporting cardiac conduction abnormalities in patients with systemic autoimmune rheumatic diseases taking HCQ or CQ. Meta-analysis was performed to calculate the difference in mean QTc and odds ratio of prolonged QTc in those taking HCQ or CQ versus not. Of 2673 unique records, 34 met the inclusion criteria, including 70,609 subjects. Thirty-three studies reported outcomes in HCQ and 9 in CQ. Five studies reported outcomes in RA, 11 in SLE, and 18 in populations with mixed rheumatic diseases. Eleven studies reported mean QTc and OR for prolonged QTc for meta-analysis, all reporting outcomes in HCQ. There was a significant increase in mean QTc among HCQ users in patients with RA (10.29 ms, p = 0.458). There was no difference in mean QTc between HCQ and non-HCQ users in other systemic autoimmune rheumatic diseases. When rheumatic diseases were pooled, HCQ users were more likely to have prolonged QTc (odds ratio 1.57, 95%CI: 1.19, 2.08). QTc prolongation was more likely in patients with systemic autoimmune rheumatic diseases. Clinicians should be aware of potential adverse cardiac events of HCQ and consider QTc monitoring.
PubMed: 38922589
DOI: 10.1097/FJC.0000000000001589 -
Journal of Clinical Immunology Jun 2024Moesin (MSN) deficiency is a recently reported combined immunodeficiency, and few cases have been reported to date. We describe a Chinese patient with a novel mutation...
PURPOSE
Moesin (MSN) deficiency is a recently reported combined immunodeficiency, and few cases have been reported to date. We describe a Chinese patient with a novel mutation causing MSN deficiency and a novel phenotype.
METHODS
Clinical and immunological data were collected. Whole-exome sequencing was performed to identify gene mutations. MSN protein expression and T cell proliferation and activation were determined by flow cytometry. Cell migration was confirmed with a Transwell assay. Autoantibody levels were analyzed using antigen microarrays.
RESULTS
The patient was a 10-year-old boy who presented with recurrent fever, oral ulcers and dermatomyositis-like symptoms, such as periorbital edema, facial swelling, elevated creatine kinase levels, and abnormal electromyography and muscle biopsy results. Epstein-Barr virus (EBV) DNA was detected in the serum, cells and tissues of this patient. He further developed nasal-type NK/T-cell lymphoma. A novel hemizygous mutation (c.68 A > G, p.N23S) in the MSN gene was found. The immunological phenotype of this patient included persistent decreases in T and B lymphocyte counts but normal immunoglobulin IgG levels. The patient had attenuated MSN protein expression and impaired T-cell proliferation and migration. The proportions of Tfh cells and CD21 B cells in the patient were higher than those in the controls. Moreover, 82 IgG and 102 IgM autoantibodies were more abundant in the patient than in the healthy controls.
CONCLUSIONS
The novel mutation N23S is pathogenic and leads to a severe clinical phenotype. EBV infection, tumor, and dermatomyositis-like autoimmune symptoms may be associated with MSN deficiency, further expanding the understanding of the disease.
Topics: Humans; Male; Epstein-Barr Virus Infections; Dermatomyositis; Child; Microfilament Proteins; Mutation; Herpesvirus 4, Human; Exome Sequencing; Immunologic Deficiency Syndromes; Autoantibodies; Phenotype; T-Lymphocytes
PubMed: 38922539
DOI: 10.1007/s10875-024-01755-0 -
Molecular Neurobiology Jun 2024Evidence suggests that long non-coding RNAs (lncRNAs) play a significant role in autism. Herein, we explored the functional role and possible molecular mechanisms of...
Evidence suggests that long non-coding RNAs (lncRNAs) play a significant role in autism. Herein, we explored the functional role and possible molecular mechanisms of NEAT1 in valproic acid (VPA)-induced autism spectrum disorder (ASD). A VPA-induced ASD rat model was constructed, and a series of behavioral tests were performed to examine motor coordination and learning-memory abilities. qRT-PCR and western blot assays were used to evaluate target gene expression levels. Loss-and-gain-of-function assays were conducted to explore the functional role of NEAT1 in ASD development. Furthermore, a combination of mechanistic experiments and bioinformatic tools was used to assess the relationship and regulatory role of the NEAT1-YY1-UBE3A axis in ASD cellular processes. Results showed that VPA exposure induced autism-like developmental delays and behavioral abnormalities in the VPA-induced ASD rat model. We found that NEAT1 was elevated in rat hippocampal tissues after VPA exposure. NEAT1 promoted VPA-induced autism-like behaviors and mitigated apoptosis, oxidative stress, and inflammation in VPA-induced ASD rats. Notably, NEAT1 knockdown improved autism-related behaviors and ameliorated hippocampal neuronal damage. Mechanistically, it was observed that NEAT1 recruited the transcription factor YY1 to regulate UBE3A expression. Additionally, in vitro experiments further confirmed that NEAT1 knockdown mitigated hippocampal neuronal damage, oxidative stress, and inflammation through the YY1/UBE3A axis. In conclusion, our study demonstrates that NEAT1 is highly expressed in ASD, and its inhibition prominently suppresses hippocampal neuronal injury and oxidative stress through the YY1/UBE3A axis, thereby alleviating ASD development. This provides a new direction for ASD-targeted therapy.
PubMed: 38922486
DOI: 10.1007/s12035-024-04309-y -
Archives of Gynecology and Obstetrics Jun 2024The aim of this study was to examine whether there is a correlation between different types of ventricular septal defects (VSD) and chromosomal abnormalities in the...
PURPOSE
The aim of this study was to examine whether there is a correlation between different types of ventricular septal defects (VSD) and chromosomal abnormalities in the low-risk setting of non-invasive prenatal testing (NIPT) and to evaluate the prognosis of fetuses with varying types of VSD.
METHODS
Cases of pregnant women who underwent amniocentesis due to fetal VSD were collected by Tianjin Central Hospital of Obstetrics and Gynecology from May 2017 to May 2022. Exclusions were made for those without NIPT, with high-risk NIPT results, genetic disorders, and those lost to follow-up. Data collected included ultrasound classification of VSD, prenatal NIPT results, copy-number variations (CNVs) results, and neonatal outcomes.
RESULTS
The prevalence of pathogenic CNVs was investigated in 74 cases of VSDs. Of these cases, 45 were isolated VSDs (9 muscular and 36 non-muscular) and 29 were non-isolated VSDs (10 with intracardiac and 19 with extra-cardiac structural anomalies). The results revealed that the incidence of pathogenic CNVs was lower in isolated VSDs compared to non-isolated VSDs in a low-risk NIPT condition (χ2 = 9.344, P = 0.002). There was no significant difference in the prevalence of pathogenic CNVs between VSDs with intracardiac and extra-cardiac structural anomalies (P = 0.541). Moreover, VSDs associated with intracardiac structural anomalies had the highest rate of surgical intervention.
CONCLUSION
When NIPT is low-risk and VSD is isolated, the likelihood of fetal chromosomal defects is not increased. However, if there are intra- or extra-cardiac structural abnormalities present alongside VSD, the possibility of pathogenic CNV is considerably greater, necessitating invasive prenatal diagnosis. Isolated muscular VSDs usually do not require surgery, which can be used as a basis for prenatal counseling regarding fetal VSD.
PubMed: 38922412
DOI: 10.1007/s00404-024-07566-3 -
Naunyn-Schmiedeberg's Archives of... Jun 2024Diabetes is one of the most common endocrine metabolic diseases and is associated with the accumulation of beta-amyloid plaques in the brain. Amyloid beta (Aβ) and...
Diabetes is one of the most common endocrine metabolic diseases and is associated with the accumulation of beta-amyloid plaques in the brain. Amyloid beta (Aβ) and abnormal tau proteins are effective in the development of Alzheimer's disease. The aim of this study is to investigate the therapeutic and protective effects of curcumin on beta-amyloid (Aβ) accumulation and tau protein expression levels, as well as biochemical and oxidative changes in streptozotocin-induced diabetes in rats. The study comprised five groups, each consisting of eight rats: control, diabetic, curcumin, curcumin during diabetic induction, and curcumin post-diabetic induction. Groups 2 and 4 were administered a single dose of 45 mg/kg streptozotocin on day 1, while group 5 received it on day 28. Curcumin was orally administered via gavage at a dose of 100 mg/kg/day for 35 days to the third, fourth, and fifth groups. At the end of the trial (day 35), blood sugar levels and insulin resistance were similar between the control and curcumin-treated groups but significantly higher in the diabetic groups (P < 0.05). The protective effect of curcumin is tested during induction and active diabetes. The results indicated that diabetic rats displayed increased levels of Aβ, tau protein, and total oxidant capacity (TOS) compared to the curcumin-treated groups. Additionally, the total antioxidant capacity (TAS) levels were lower in the diabetic rats (P < 0.05). Aβ protein levels are lower in both the serum and brain of rats with active diabetes and treated with curcumin compared to control rats (P > 0.05). In addition, serum TAS levels were higher in rats treated with curcumin following the induction of diabetes than pre-induction of diabetes (P > 0.05). The TOS levels in the serum were higher in the rats treated with curcumin during active diabetes compared to the rats treated prior to the induction of diabetes (P < 0.05). However, no significant difference was observed in the brain. The above results show that curcumin has an effect on reducing oxidative stress caused by diabetes and increasing antioxidant activity.
PubMed: 38922352
DOI: 10.1007/s00210-024-03231-3 -
CoDAS 2024To analyze the influence of ankyloglossia on the prevalence and duration of exclusive breastfeeding of full-term infants up to the sixth month of life.
PURPOSE
To analyze the influence of ankyloglossia on the prevalence and duration of exclusive breastfeeding of full-term infants up to the sixth month of life.
METHODS
Prospective cohort study, carried out with 225 mother-infant dyads who were followed up in the first six months of life in a center specialized in breastfeeding in a tertiary hospital. Full-term infants with asymptomatic ankyloglossia (no need for surgery) were compared with infants without change at monthly follow-up. Ankyloglossia was diagnosed using the Bristol Tongue Assessment Tool, with a positive diagnosis being considered for those with a score less than or equal to 5 considering functional and anatomical aspects. Statistical analyzes were performed using descriptive statistics, logistic regression (weaning determinants), relative risk, and survival curves (to analyze breastfeeding duration between groups with and without ankyloglossia).
RESULTS
Ankyloglossia was associated with weaning (considered even partial) before the sixth month of life. After adjusted analysis, a higher risk of weaning was detected in infants with this alteration, with a risk present from the second month of life. In the survival analysis, the duration of breastfeeding in infants with ankyloglossia was shorter when compared to children without alterations.
CONCLUSION
Compared to infants with normal lingual frenulum, babies with ankyloglossia had shorter exclusive breastfeeding time, but well above the average observed in the general population. The risk of weaning for this group was also higher.
Topics: Humans; Breast Feeding; Ankyloglossia; Prospective Studies; Infant, Newborn; Female; Male; Infant; Time Factors; Cohort Studies; Adult; Lingual Frenum; Weaning; Prevalence; Brazil; Risk Factors
PubMed: 38922259
DOI: 10.1590/2317-1782/20242023108pt -
Brazilian Dental Journal 2024This cross-sectional study aimed to investigate the association between developmental defects of enamel (DDE) and single nucleotide polymorphisms (SNPs) in the genes...
This cross-sectional study aimed to investigate the association between developmental defects of enamel (DDE) and single nucleotide polymorphisms (SNPs) in the genes encoding the vitamin D receptor (VDR) and parathyroid hormone (PTH). Orthodontic patients receiving treatment at a dental school were selected through convenience sampling. Intra-oral photographs were used to assess DDE, which were classified according to the criteria proposed by Ghanim et al. (2015) by a single calibrated examiner (Kappa>0.80). Enamel hypoplasia, molar-incisor hypomineralization (MIH), hypomimineralized second primary molar (HSPM), and non-MIH/HSPM demarcated opacities were considered for the analysis. Genomic DNA was extracted from buccal cells. The SNPs in VDR (rs7975232) and PHT (rs694, rs6256, and rs307247) were genotyped using real-time polymerase chain reactions (PCR). Statistical analyses were performed using the PLINK software (version 1.03, designed by Shaun Purcell, EUA). Chi-square or Fisher's exact tests were performed at a significance level of 5%. Ninety-one (n=91) patients (49 females and 42 males) (mean age of 14.1±5.8 years) were included. The frequency of DDE was 38.5% (35 patients). Genotype distributions were in Hardy-Weinberg equilibrium. No significant statistical association was found between DDE and the SNPs evaluated. A borderline association (p=0.09) was observed between DDE and the CC haplotype for SNP rs7975232 in VDR. In conclusion, the selected SNPs in VDR and PTH genes were not associated with DDE in the studied samples.
Topics: Humans; Receptors, Calcitriol; Polymorphism, Single Nucleotide; Female; Cross-Sectional Studies; Male; Parathyroid Hormone; Dental Enamel Hypoplasia; Child; Adolescent; Dental Enamel; Real-Time Polymerase Chain Reaction; Genotype
PubMed: 38922252
DOI: 10.1590/0103-6440202405900 -
Brazilian Journal of Biology = Revista... 2024Plants that produce allelopathic compounds against weeds have emerged as a potential solution for the development of ecologically correct bioherbicides. Talinum...
Plants that produce allelopathic compounds against weeds have emerged as a potential solution for the development of ecologically correct bioherbicides. Talinum triangulare is noteworthy in this regard, as its phytochemical composition encompasses flavonoids, alkaloids and other metabolites that can be used to develop inhibitory weed growth solutions. Lactuca sativa (lettuce) has been widely applied as a bioindicator species for bioherbicides and several chemicals, animal waste, water and soil quality, and atmospheric contamination, among others. In this context, this study aimed to assess the potential allelopathic effect of aqueous T. triangulare extracts on the development of L. sativa seedlings. A completely randomized design employing a 2x4 factorial scheme (shoot and root extracts) x the concentration of each extract (0, 2.5, 5, 7.5%) was applied, comprising four replications. Lactuca sativa seeds were sown on germitest papers soaked with the extracts in a germination chamber at 20°C. Physiological seed evaluations comprising the germination test, where normal and abnormal seedlings are counted on the seventh day after sowing, first normal seedling counts on the fourth day after sowing, and seedling and root length measurements. At the end of the germination test, L. sativa seedlings were separated for morphoanatomical characterizations and chlorophyll a fluorescence analyses. The T. triangulare extracts significantly influenced L. sativa root growth, with shoot extract exposure leading to more abnormal plants and lower root lengths at increasing concentrations and compared to the root extract. Root extract exposure led to evident cellular changes and lower non-photochemical quenching and unregulated dissipation quantum yields at a 5% exposure dose compared to shoot extract exposure. These findings suggest that both aqueous T. triangulare root and shoot extracts from 5% exposure doses exhibit high potential as bioherbicides, acting directly on plant structure, anatomy, quality, size and physiology.
Topics: Lactuca; Seedlings; Plant Extracts; Germination; Allelopathy
PubMed: 38922190
DOI: 10.1590/1519-6984.279983 -
Revista Paulista de Pediatria : Orgao... 2024To verify the prevalence and perform the clinical characterization of oral clefts in a sample of patients with trisomy of chromosome 18 in Southern Brazil.
OBJECTIVE
To verify the prevalence and perform the clinical characterization of oral clefts in a sample of patients with trisomy of chromosome 18 in Southern Brazil.
METHODS
This was a retrospective cross-sectional study, performed in a reference clinical genetic service in Southern Brazil. The initial sample consisted of 77 patients diagnosed in the neonatal period with trisomy 18 treated at the Clinical Genetics Service of a referral hospital at Federal University of Health Sciences of Porto Alegre (UFCSPA). The patients' diagnosis was confirmed by karyotype and care was provided during their stay in the intensive care unit (ICU) of the hospital that is a reference in Southern Brazil for care for malformed patients. The period covered was from 1975 to 2020.
RESULTS
During the study period, 77 patients diagnosed with trisomy 18 were treated, most of them in the ICU. Of these, 13 individuals were excluded due to incomplete data. The final sample consisted of 64 patients with an average age of 2.4 years of life, ranging from one day to 16 years old, the majority of whom were female. Regarding face dysmorphisms identified in the sample, three (4,68%) patients had cleft lip and two (3,11%) had cleft lip and palate.
CONCLUSIONS
This study contributed to the recognition of the characteristics and prevalence of oral clefts in individuals with trisomy 18 in a sample of patients from Southern Brazil. In addition, we described the clinical alterations found in patients with oral clefts, as well as other associated comorbidities, such as cardiac, neurological and pulmonary comorbidities, as well as cranial and facial dysmorphisms.
Topics: Humans; Cross-Sectional Studies; Female; Retrospective Studies; Male; Trisomy 18 Syndrome; Prevalence; Adolescent; Infant, Newborn; Brazil; Child; Infant; Child, Preschool; Cleft Palate; Cleft Lip
PubMed: 38922187
DOI: 10.1590/1984-0462/2024/42/2023169 -
Toxins May 2024Cardiovascular disease (CVD) frequently occurs in patients with chronic kidney disease (CKD), particularly those undergoing dialysis. The mechanisms behind this may be... (Review)
Review
Cardiovascular disease (CVD) frequently occurs in patients with chronic kidney disease (CKD), particularly those undergoing dialysis. The mechanisms behind this may be related to traditional risk factors and CKD-specific factors that accelerate atherosclerosis and vascular calcification in CKD patients. The accumulation of uremic toxins is a significant factor in CKD-related systemic disorders. Basic research suggests that indoxyl sulfate (IS), a small protein-bound uremic toxin, is associated with macrophage dysfunctions, including increased oxidative stress, exacerbation of chronic inflammation, and abnormalities in lipid metabolism. Strategies to mitigate the toxicity of IS include optimizing gut microbiota, intervening against the abnormality of intracellular signal transduction, and using blood purification therapy with higher efficiency. Further research is needed to examine whether lowering protein-bound uremic toxins through intervention leads to a reduction in CVD in patients with CKD.
Topics: Indican; Humans; Atherosclerosis; Macrophages; Animals; Uremia; Renal Insufficiency, Chronic; Uremic Toxins; Gastrointestinal Microbiome; Oxidative Stress
PubMed: 38922148
DOI: 10.3390/toxins16060254