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Circulation Research Mar 2024The cardiovascular system provides blood supply throughout the body and as such is perpetually applying mechanical forces to cells and tissues. Thus, this system is... (Review)
Review
The cardiovascular system provides blood supply throughout the body and as such is perpetually applying mechanical forces to cells and tissues. Thus, this system is primed with mechanosensory structures that respond and adapt to changes in mechanical stimuli. Since their discovery in 2010, PIEZO ion channels have dominated the field of mechanobiology. These have been proposed as the long-sought-after mechanosensitive excitatory channels involved in touch and proprioception in mammals. However, more and more pieces of evidence point to the importance of PIEZO channels in cardiovascular activities and disease development. PIEZO channel-related cardiac functions include transducing hemodynamic forces in endothelial and vascular cells, red blood cell homeostasis, platelet aggregation, and arterial blood pressure regulation, among others. PIEZO channels contribute to pathological conditions including cardiac hypertrophy and pulmonary hypertension and congenital syndromes such as generalized lymphatic dysplasia and xerocytosis. In this review, we highlight recent advances in understanding the role of PIEZO channels in cardiovascular functions and diseases. Achievements in this quickly expanding field should open a new road for efficient control of PIEZO-related diseases in cardiovascular functions.
Topics: Animals; Female; Humans; Blood Pressure; Anemia, Hemolytic, Congenital; Biophysics; Hydrops Fetalis; Hypertension, Pulmonary; Mammals
PubMed: 38422173
DOI: 10.1161/CIRCRESAHA.123.322798 -
Nigerian Journal of Clinical Practice Feb 2024Congenital diseases are still an important medical, social, and economic problem all over the world. In North Cyprus, in addition to other reasons, early prenatal...
BACKGROUND
Congenital diseases are still an important medical, social, and economic problem all over the world. In North Cyprus, in addition to other reasons, early prenatal diagnostic measures are undertaken to prevent births with thalassemia major, a locally widespread genetic disease.
AIM
This study aims to evaluate the results of prenatal invasive diagnostic tests performed in a private obstetrics clinic in Northern Cyprus and show the diagnosis process of thalassemia and chromosomal anomalies.
MATERIALS AND METHODS
This study is a retrospective, descriptive study. Chorionic villus sampling (CVS) results and the amniocentesis tests performed between 1990 and 2022 are evaluated. Thalassemia and chromosome analysis of samples obtained by CVS and amniocentesis tests were performed. To diagnose alpha or beta thalassemia and sickle cell, 239 CVS was performed. And to diagnose chromosomal anomalies, 396 CVS and amniocentesis were performed.
RESULTS
The mean age of the 480 pregnant women included in the study was 31.12 years (18-46) and 30% of them were older than 34 years. The most common indications for invasive prenatal diagnostic test (IPDT) were; mother/father thalassemia minor/major, advanced maternal age, high risk of ultrasonography erase findings, and the noninvasive screening test. The result of IPDT detected 7.3% chromosomal anomaly and 69.5% thalassemia and sickle cell anemia. Of the 239 CVS performed to diagnose alpha or beta thalasemia and sickle cell, 23.4% beta major, 42.3% beta minor, and 2.1% alpha minor were diagnosed. Of the 396 CVS and amniocentesis performed to diagnose chromosomal anormalies; 2.8% of Down syndrome and 4.54% of other chromosomal anomalies were diagnosed.
CONCLUSION
IPDT is important in correctly diagnosing fetal anomalies at the prenatal stage to help families decide at the right time.
Topics: Pregnancy; Female; Humans; Adolescent; Young Adult; Adult; Middle Aged; Retrospective Studies; Cyprus; Prenatal Diagnosis; Chorionic Villi Sampling; Chromosome Aberrations; Chromosome Disorders; Thalassemia; Anemia, Sickle Cell; Diagnostic Tests, Routine
PubMed: 38409146
DOI: 10.4103/njcp.njcp_540_23 -
Biomedicines Jan 2024The +33 C>G variant [NM_000518.5(HBB):c.-18C>G] in the 5' untranslated region (UTR) of the β-globin gene is described in the literature as both mild and silent, while...
The +33 C>G variant [NM_000518.5(HBB):c.-18C>G] in the 5' untranslated region (UTR) of the β-globin gene is described in the literature as both mild and silent, while it causes a phenotype of thalassemia intermedia in the presence of a severe β-thalassemia allele. Despite its potential clinical significance, the determination of its pathogenicity according to established standards requires a greater number of published cases and co-segregation evidence than what is currently available. The present study provides an extensive phenotypic characterization of +33 C>G using 26 heterozygous and 11 compound heterozygous novel cases detected in Cyprus and employs computational predictors (CADD, RegulomeDB) to better understand its impact on clinical severity. Genotype identification of globin gene variants, including α- and δ-thalassemia determinants, and rs7482144 (XmnI) was carried out using Sanger sequencing, gap-PCR, and restriction enzyme digestion methods. The heterozygous state of +33 C>G had a silent phenotype without apparent microcytosis or hypochromia, while compound heterozygosity with a β+ or β0 allele had a spectrum of clinical phenotypes. Awareness of the +33 C>G is required across Mediterranean populations where β-thalassemia is frequent, particularly in Cyprus, with significant relevance in population screening and fetal diagnostic applications.
PubMed: 38397898
DOI: 10.3390/biomedicines12020296 -
International Journal of Molecular... Feb 2024Rosavin, a phenylpropanoid in 's rhizome, and an adaptogen, is known for enhancing the body's response to environmental stress. It significantly affects cellular... (Review)
Review
Rosavin, a phenylpropanoid in 's rhizome, and an adaptogen, is known for enhancing the body's response to environmental stress. It significantly affects cellular metabolism in health and many diseases, particularly influencing bone tissue metabolism. In vitro, rosavin inhibits osteoclastogenesis, disrupts F-actin ring formation, and reduces the expression of osteoclastogenesis-related genes such as cathepsin K, calcitonin receptor (CTR), tumor necrosis factor receptor-associated factor 6 (TRAF6), tartrate-resistant acid phosphatase (TRAP), and matrix metallopeptidase 9 (MMP-9). It also impedes the nuclear factor of activated T-cell cytoplasmic 1 (NFATc1), c-Fos, the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), and mitogen-activated protein kinase (MAPK) signaling pathways and blocks phosphorylation processes crucial for bone resorption. Moreover, rosavin promotes osteogenesis and osteoblast differentiation and increases mouse runt-related transcription factor 2 (Runx2) and osteocalcin (OCN) expression. In vivo studies show its effectiveness in enhancing bone mineral density (BMD) in postmenopausal osteoporosis (PMOP) mice, restraining osteoclast maturation, and increasing the active osteoblast percentage in bone tissue. It modulates mRNA expressions by increasing eukaryotic translation elongation factor 2 (EEF2) and decreasing histone deacetylase 1 (HDAC1), thereby activating osteoprotective epigenetic mechanisms, and alters many serum markers, including decreasing cross-linked C-telopeptide of type I collagen (CTX-1), tartrate-resistant acid phosphatase 5b (TRACP5b), receptor activator for nuclear factor κ B ligand (RANKL), macrophage-colony-stimulating factor (M-CSF), and TRAP, while increasing alkaline phosphatase (ALP) and OCN. Additionally, when combined with zinc and probiotics, it reduces pro-osteoporotic matrix metallopeptidase 3 (MMP-3), interleukin 6 (IL-6), and tumor necrosis factor α (TNF-α), and enhances anti-osteoporotic interleukin 10 (IL-10) and tissue inhibitor of metalloproteinase 3 (TIMP3) expressions. This paper aims to systematically review rosavin's impact on bone tissue metabolism, exploring its potential in osteoporosis prevention and treatment, and suggesting future research directions.
Topics: Animals; Mice; Osteoclasts; Tartrate-Resistant Acid Phosphatase; Osteogenesis; Bone Resorption; Cell Differentiation; NF-kappa B; Metalloproteases; RANK Ligand; NFATC Transcription Factors; Disaccharides
PubMed: 38396794
DOI: 10.3390/ijms25042117 -
BMC Pregnancy and Childbirth Feb 2024Whether or not the effects of anemia in the early phase, while the fetuses attempts to increase cardiac output to meet oxygen requirement in peripheral organs, is...
OBJECTIVE
Whether or not the effects of anemia in the early phase, while the fetuses attempts to increase cardiac output to meet oxygen requirement in peripheral organs, is detrimental to the fetal developing vital organs is little-known. The objective of this is to compare prenatal cardiovascular changes and post-abortal cellular damages in the myocardium as a pumping organ and the brain as a perfused organ between anemic fetuses (using fetal Hb Bart's disease as a study model) in pre-hydropic phase and non-anemic fetuses.
METHODS
Fetuses affected by Hb Bart's disease and non-anemic fetuses at 16-22 weeks were recruited to undergo comprehensive fetal echocardiography. Cord blood analysis was used to confirm the definite diagnosis of fetal Hb Bart's disease and normal fetuses. Fetal cardiac and brain tissues were collected shortly after pregnancy termination for the determination of oxidative stress and mitochondrial function, including mitochondrial ROS production and mitochondrial membrane changes.
RESULTS
A total of 18 fetuses affected by Hb Bart's disease and 13 non-anemic fetuses were recruited. The clinical characteristics of both groups were comparable. The affected fetuses showed a significant increase in cardiac dimensions, cardiac function, cardiac output and brain circulation without deteriorating cardiac contractility and preload. However, in the affected fetuses, mitochondrial dysfunction was clearly demonstrated in brain tissues and in the myocardium, as indicated by a significant increase in the membrane potential change (p-value < 0.001), and a significant increase in ROS production in brain tissues, with a trend to increase in myocardium. The findings indicated cellular damage in spite of good clinical compensation.
CONCLUSION
The new insight is that, in response to fetal anemia, fetal heart increases in size (dilatation) and function to increase cardiac output and blood flow velocity to provide adequate tissue perfusion, especially brain circulation. However, the myocardium and brain showed a significant increase in mitochondrial dysfunction, suggesting cellular damage secondary to anemic hypoxia. The compensatory increase in circulation could not completely prevent subtle brain and heart damage.
Topics: Female; Pregnancy; Humans; Pregnancy Trimester, Second; Reactive Oxygen Species; Hemoglobins, Abnormal; alpha-Thalassemia; Fetal Diseases; Anemia; Fetal Heart; Myocardium; Edema; Cardiac Output; Mitochondrial Diseases
PubMed: 38365664
DOI: 10.1186/s12884-023-06232-x -
Cureus Jan 2024Thalassemia is a hereditary autosomal recessive disorder that is distinguished by a diminished rate of hemoglobin (Hb) synthesis arising from an anomaly in the synthesis...
Thalassemia is a hereditary autosomal recessive disorder that is distinguished by a diminished rate of hemoglobin (Hb) synthesis arising from an anomaly in the synthesis of α or β globin chains. Classical symptoms of β-thalassemia are frequently observed in patients who present late for blood transfusion (BT), which is typical among South Asian countries in light of their limited resources. This case report is an uncommon instance of a typical occurrence that has been infrequently reported in the South Asian region. The reporting of this case will assist healthcare workers in managing cases appropriately. We present a 12-year-old female child diagnosed with β-thalassemia major with a late presentation than usual accompanied by an unusual finding of left hemiparesis at a young age of five years. The patient had been lost to follow-up, presented with easy fatiguability, poor weight gain, and growth restriction, all of which are classic symptoms of β-thalassemia. The patient was treated with a BT and continued to be monitored for transfusion and iron overload management.
PubMed: 38357056
DOI: 10.7759/cureus.52280 -
American Journal of Translational... 2024To understand the genotype and distribution of thalassemia in northern Guangxi.
OBJECTIVE
To understand the genotype and distribution of thalassemia in northern Guangxi.
METHODS
The study subjects were 55,281 individuals who came to the Affiliated Hospital of Guilin Medical University for genetic diagnosis of thalassemia from January 2012 to August 2023. All of their household registration was in the precincts of Guibei District and its affiliated counties. Red blood cell parameters and hemoglobin analysis were used for thalassemia screening. Gap-PCR, PCR-reverse dot blot hybridization (PCR-RDB), and multicolor melting curve analysis (MMCA) were used to identify common thalassemia genes. Multiplex ligation-dependent probe amplification (MLPA), Sanger sequencing, and third-generation single-molecule real-time (SMRT) sequencing were employed to identify rare thalassemia genes.
RESULTS
Among the 55,281 samples, 16,442 (29.74%) were diagnosed with thalassemia. The detection rates of α, β, and α combined β-thalassemia were 18.57%, 9.99% and 1.18%, respectively. Among ethnical groups, allele mutation frequency of thalassemia was the highest in Zhuang (44.97%), followed by Yao (40.11%), Dong (31.33%), Han (29.85%), Miao (24.31%), and Hui (20.6%). A total of 11,659 alleles (21.09%) of 8 types of α-thalassemia were identified in 55,281 samples, primarily -- (53.9%), followed by -α (21.3%), including rare alleles: -- (0.45%) and HKαα (0.38%). A total of 6367 (11.52%) and 14 types of β-thalassemia alleles were identified, mainly CD41-42 (50.12%), followed by CD17 (22.22%), including rare alleles: β (0.16%) and Gγ (Aγδβ)/β (0.05%). A total of 31 genotypes were detected in 10,264 cases of α-thalassemia, and the main types were --/αα (53.23%), -α/αα (19.15%), and -α/αα (7.21%). A total of 34 genotypes were detected in 5525 cases of β-thalassemia, and the main types were β/β (50.53%), β/β (21.77%), and β/β (12.16%). A total of 78 gene types were detected in 653 cases of α- and β-thalassemia, and the main types were --/αα, β/β (18.68%) and -α/αα, β/β (13.02%). There were 580 cases (5.65%) of HbH disease (α/α), and 4 cases of Hemoglobin Bart's Hydrops Foetus syndrome (--/--). In addition, there were 92 cases (1.67%) of intermedia or severe types of β-thalassemia (β/β, β/β, β/β), including 23 cases of combined α-thalassemia. Among the samples screened negative for thalassemia, 3.7% of them were found to carry thalassemia genes, and 91.35% of the genotypes were αα/αα, -α/αα, and -α/αα. In addition, 40.26% of αα/αα, 22.89% of -α/αα, and 18.51% of -α/αα had no hematological phenotype.
CONCLUSION
The population in northern Guangxi exhibited rich ethnic diversity, with high allelic carrying rates among the Zhuang, Yao and Dong ethnic groups. Thalassemia gene mutations are diverse, encompassing a variety of gene types, with α thalassemia predominating, notably the --/αα gene type. The prevalence of intermedia or severe types of thalassemia is not low, but there are still some carriers of thalassemia in people who are initially tested negative.
PubMed: 38322564
DOI: 10.62347/CQDH5278 -
International Journal of Clinical and... 2024Diffuse glioma constitutes 28% of primary brain tumors. Until recently morphologic appearance was the only criterion for classifying these tumors. However, WHO 2016...
INTRODUCTION
Diffuse glioma constitutes 28% of primary brain tumors. Until recently morphologic appearance was the only criterion for classifying these tumors. However, WHO 2016 incorporates molecular information in the primary diagnosis of gliomas such as Isocitrate dehydrogenase 1 (IDH1), Alpha thalassemia/mental retardation syndrome X inked (ATRX) as well as 1p/19q codeletion on FISH. In a resource-limited setup where FISH is not available, Alpha internexin (INA) has been suggested as a surrogate IHC marker.
MATERIAL AND METHODS
Cross-sectional study conducted in the Department of Pathology for two years. Tissue blocks and clinical as well as radiological details were obtained from departmental archives. After assessing the morphologic details, routine IHC markers such as GFAP, Ki67 and P53 along with molecular markers like IDH-1, ATRX, and lNA were applied.
RESULTS
Out of 55 cases of diffuse glioma, 23 cases of astrocytoma and 32 cases of oligodendroglioma with an overall mean age of presentation of 41.49 ± 12.47 years. IDH-1 expression among diffuse glioma was 89.1% in our study. Alteration in the ATRX gene expression was observed in 95.7% of astrocytomas. 75% of oligodendrogliomas expressed INA with no significant difference in expression between the two grades. Based on the algorithmic approach using molecular surrogate markers, diffuse gliomas were categorized into six distinct groups. IDH-mutant, ATRX loss of expression astrocytoma and IDH-mutant, INA positive oligodendroglioma are two categories that do not require further molecular testing. This comprises 72.7% of the cases and these do not warrant further workup.
CONCLUSION
Implementation of combined phenotypic-genotypic diagnosis with the use of histomorphology and immunohistochemical surrogates for molecular genetic alterations will yield more homogeneous and narrowly defined diagnostic entities which will provide better prognostication and definitive treatment. It also is cost-effective in a resource-limited setup.
PubMed: 38322173
DOI: 10.62347/AJCP7971