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International Journal of Molecular... Jun 2024Arrhythmogenic cardiomyopathy (ACM) is a rare genetic cardiac disease characterized by the progressive substitution of myocardium with fibro-fatty tissue. Clinically,... (Review)
Review
Arrhythmogenic cardiomyopathy (ACM) is a rare genetic cardiac disease characterized by the progressive substitution of myocardium with fibro-fatty tissue. Clinically, ACM shows wide variability among patients; symptoms can include syncope and ventricular tachycardia but also sudden death, with the latter often being its sole manifestation. Approximately half of ACM patients have been found with variations in one or more genes encoding cardiac intercalated discs proteins; the most involved genes are plakophilin 2 (), desmoglein 2 (), and desmoplakin (). Cardiac intercalated discs provide mechanical and electro-metabolic coupling among cardiomyocytes. Mechanical communication is guaranteed by the interaction of proteins of desmosomes and adheren junctions in the so-called , whereas electro-metabolic coupling between adjacent cardiac cells depends on gap junctions. Although ACM has been first described almost thirty years ago, the pathogenic mechanism(s) leading to its development are still only partially known. Several studies with different animal models point to the involvement of the Wnt/β-catenin signaling in combination with the Hippo pathway. Here, we present an overview about the existing murine models of ACM harboring variants in intercalated disc components with a particular focus on the underlying pathogenic mechanisms. Prospectively, mechanistic insights into the disease pathogenesis will lead to the development of effective targeted therapies for ACM.
Topics: Animals; Humans; Disease Models, Animal; Arrhythmogenic Right Ventricular Dysplasia; Plakophilins; Desmoplakins; Wnt Signaling Pathway; Desmoglein 2; Desmosomes; Mice
PubMed: 38892395
DOI: 10.3390/ijms25116208 -
International Journal of Molecular... May 2024Trained immunity is a concept in immunology in which innate immune cells, such as monocytes and macrophages, exhibit enhanced responsiveness and memory-like... (Review)
Review
Trained immunity is a concept in immunology in which innate immune cells, such as monocytes and macrophages, exhibit enhanced responsiveness and memory-like characteristics following initial contact with a pathogenic stimulus that may promote a more effective immune defense following subsequent contact with the same pathogen. , a bacterium that colonizes the stomach lining, is etiologically associated with various gastrointestinal diseases, including gastritis, peptic ulcer, gastric adenocarcinoma, MALT lymphoma, and extra gastric disorders. It has been demonstrated that repeated exposure to can induce trained immunity in the innate immune cells of the gastric mucosa, which become more responsive and better able to respond to subsequent infections. However, interactions between and trained immunity are intricate and produce both beneficial and detrimental effects. infection is characterized histologically as the presence of both an acute and chronic inflammatory response called acute-on-chronic inflammation, or gastritis. The clinical outcomes of ongoing inflammation include intestinal metaplasia, gastric atrophy, and dysplasia. These same mechanisms may also reduce immunotolerance and trigger autoimmune pathologies in the host. This review focuses on the relationship between trained immunity and and underscores the dynamic interplay between the immune system and the pathogen in the context of gastric colonization and inflammation.
Topics: Humans; Helicobacter Infections; Helicobacter pylori; Immunity, Innate; Immune Tolerance; Animals; Gastric Mucosa; Gastritis; Immunologic Memory; Trained Immunity
PubMed: 38892046
DOI: 10.3390/ijms25115856 -
International Journal of Molecular... May 2024Intermediate filaments are one of three polymeric structures that form the cytoskeleton of epithelial cells. In the epithelium, these filaments are made up of a variety... (Review)
Review
Intermediate filaments are one of three polymeric structures that form the cytoskeleton of epithelial cells. In the epithelium, these filaments are made up of a variety of keratin proteins. Intermediate filaments complete a wide range of functions in keratinocytes, including maintaining cell structure, cell growth, cell proliferation, cell migration, and more. Given that these functions are intimately associated with the carcinogenic process, and that hyperkeratinization is a quintessential feature of oral leukoplakias, the utility of keratins in oral leukoplakia is yet to be fully explored. This scoping review aims to outline the current knowledge founded on original studies on human tissues regarding the expression and utility of keratins as diagnostic, prognostic, and predictive biomarkers in oral leukoplakias. After using a search strategy developed for several scientific databases, namely, PubMed, Scopus, Web of Science, and OVID, 42 papers met the inclusion and exclusion criteria. One more article was added when it was identified through manually searching the list of references. The included papers were published between 1989 and 2024. Keratins 1-20 were investigated in the 43 included studies, and their expression was assessed in oral leukoplakia and dysplasia cases. Only five studies investigated the prognostic role of keratins in relation to malignant transformation. No studies evaluated keratins as a diagnostic adjunct or predictive tool. Evidence supports the idea that dysplasia disrupts the terminal differentiation pathway of primary keratins. Gain of keratin 17 expression and loss of keratin 13 were significantly observed in differentiated epithelial dysplasia. Also, the keratin 19 extension into suprabasal cells has been associated with the evolving features of dysplasia. The loss of keratin1/keratin 10 has been significantly associated with high-grade dysplasia. The prognostic value of cytokeratins has shown conflicting results, and further studies are required to ascertain their role in predicting the malignant transformation of oral leukoplakia.
Topics: Humans; Leukoplakia, Oral; Keratins; Prognosis; Biomarkers, Tumor
PubMed: 38891785
DOI: 10.3390/ijms25115597 -
Virology Journal Jun 2024The persistent infection of high-risk Human papillomavirus(HPV) is considered the main cause of cervical intraepithelial neoplasia and cervical cancer. But various...
BACKGROUND
The persistent infection of high-risk Human papillomavirus(HPV) is considered the main cause of cervical intraepithelial neoplasia and cervical cancer. But various cervical lesions caused by HPV infection can be properly prevented by timely vaccination. However, the distribution of HPV genotypes varies geographically.
METHODS
Retrospective analysis of high-risk HPV prevalence of 16,150 women from 2020 to 2022 in xianning of China. HPV genotyping was performed using a PCR-RDB Kit that can detect 18 high-risk HPV genotypes recommended by China's National Medical Products Administration. The prevalence of 18 high-risk HPV genotypes and their relationship with cervical lesions as well as vaccine efficacy were analyzed.
RESULTS
A total of 2431 women were confirmed to have different types of high-risk HPV infections. The overall positive rate reached 15.05%(2431/16,150). The most prevalent high-risk HPV genotypes were HPV52, 16, 58, 53, and 51. The prevalence of high-risk HPV reached peak at age ≤ 20(20.95%) and age ≥ 61(20.56%). The most prevalent high-risk HPV genotypes were HPV16, 58, 18, 33 and 52 in cervical cancer cases, HPV16, 52, 58, 33 and 18 in CIN2/3 cases, and HPV52, 58, 16, 53 and 18 in CIN1 cases, respectively.
CONCLUSION
HPV16, 58 and 18 are the most dangerous and carcinogenic genotypes in xianning, China. Conducting epidemiological investigations on high-risk HPV has significant clinical value in guiding HPV vaccination work.
Topics: Humans; Female; China; Papillomavirus Infections; Genotype; Prevalence; Adult; Middle Aged; Young Adult; Retrospective Studies; Papillomaviridae; Uterine Cervical Neoplasms; Adolescent; Aged; Uterine Cervical Dysplasia; Papillomavirus Vaccines; Human Papillomavirus Viruses
PubMed: 38890675
DOI: 10.1186/s12985-024-02413-y -
Nature Communications Jun 2024Traumatic brain injury (TBI) can result in long-lasting changes in hippocampal function. The changes induced by TBI on the hippocampus contribute to cognitive deficits....
Traumatic brain injury (TBI) can result in long-lasting changes in hippocampal function. The changes induced by TBI on the hippocampus contribute to cognitive deficits. The adult hippocampus harbors neural stem cells (NSCs) that generate neurons (neurogenesis), and astrocytes (astrogliogenesis). While deregulation of hippocampal NSCs and neurogenesis have been observed after TBI, it is not known how TBI may affect hippocampal astrogliogenesis. Using a controlled cortical impact model of TBI in male mice, single cell RNA sequencing and spatial transcriptomics, we assessed how TBI affected hippocampal NSCs and the neuronal and astroglial lineages derived from them. We observe an increase in NSC-derived neuronal cells and a concomitant decrease in NSC-derived astrocytic cells, together with changes in gene expression and cell dysplasia within the dentate gyrus. Here, we show that TBI modifies NSC fate to promote neurogenesis at the cost of astrogliogenesis and identify specific cell populations as possible targets to counteract TBI-induced cellular changes in the adult hippocampus.
Topics: Animals; Male; Brain Injuries, Traumatic; Neurogenesis; Hippocampus; Astrocytes; Mice; Neural Stem Cells; Neurons; Mice, Inbred C57BL; Dentate Gyrus; Disease Models, Animal; Cell Differentiation; Transcriptome
PubMed: 38890340
DOI: 10.1038/s41467-024-49299-6 -
ERJ Open Research May 2024Worldwide, 1-2% of children are born premature and at risk for developing bronchopulmonary dysplasia (BPD). Preterm-born adults are at risk for early cardiovascular...
BACKGROUND
Worldwide, 1-2% of children are born premature and at risk for developing bronchopulmonary dysplasia (BPD). Preterm-born adults are at risk for early cardiovascular disease. The role of BPD is unclear. This study aims to examine cardiorespiratory function during submaximal exercise in young adult survivors of extreme prematurity, with or without BPD.
METHODS
40 preterm-born young adults, 20 with BPD (median gestational age 27 weeks, interquartile range (IQR) 26-28 weeks) and 20 without BPD (median gestational age 28 weeks, IQR 27-29 weeks) were prospectively compared to age-matched at term-born adults (median gestational age 39 weeks, IQR 38-40 weeks). Participants underwent exercise testing and cardiovascular magnetic resonance with submaximal exercise.
RESULTS
Resting heart rate in BPD subjects was higher than in at term-born subjects (69±10 mL 61±7 mL, p=0.01). Peak oxygen uptake during maximal cardiopulmonary exercise testing was decreased in BPD subjects (91±18% 106±17% of predicted, p=0.01). In BPD subjects, cardiac stroke volume change with exercise was impaired compared to at term-born subjects (11±13% 25±10%; p<0.001). With exercise, left ventricular end-diastolic volume decreased more in preterm-born subjects with without BPD (-10±8% -3±8%; p=0.01) and compared to at term-born subjects (0±5%; p<0.001). Exploratory data analysis revealed that exercise stroke volume and end-diastolic volume change were inversely correlated with oxygen dependency in those born prematurely.
CONCLUSIONS
In preterm-born young adults, particularly those with BPD, resting cardiac function, exercise performance and cardiac response to exercise is impaired compared to controls. Exercise cardiovascular magnetic resonance may reveal an important predisposition for heart disease later in life.
PubMed: 38887679
DOI: 10.1183/23120541.00501-2023 -
Frontiers in Cardiovascular Medicine 2024Spontaneous coronary artery dissection (SCAD), an uncommon cause of acute coronary syndrome, continues to be a poorly understood disease predominantly affecting females.... (Review)
Review
Spontaneous coronary artery dissection (SCAD), an uncommon cause of acute coronary syndrome, continues to be a poorly understood disease predominantly affecting females. It is characterized by an abrupt separation in the coronary arterial wall due to intramural bleeding. Fibromuscular dysplasia (FMD) is a non-atherosclerotic arteriopathy manifesting in medium and small-sized arteries. It is a concomitant disease found among SCAD patients. In some studies, FMD prevalence in SCAD patients ranges between 25%-86%, which can be explained through varying screening techniques or modalities. The potential association has been elucidated in some studies; notably, not only has a genetic link been recently delineated between SCAD and FMD, but there is data to suggest that FMD not only can predispose to SCAD but can also be a potential predictor of its recurrence. However, a clear-cut correlation between the two has still not been established due to conflicting reports in the literature. To further dive into its pathology, it is crucial to highlight the importance of systematic screening in SCAD in order to identify associated risk factors and to be used as a method of FMD detection in such patients. Together, the two pathologies pose unique challenges in understanding its pathophysiology, diagnosis and management, as there is no clear evidence of a definitive treatment plan for patients with SCAD and FMD. A potentially beneficial modality of management is physical exercise, which is currently understudied in the long-term approach to treatment for patients with concomitant SCAD and FMD. Limited research in this field brings disadvantages to the understanding of the association between these two diseases, in order to give rise to better management recommendations. This mini-review aims to highlight the recent developments in the association between SCAD and FMD, its potential genetic association and some insights in screening, diagnosis, and management.
PubMed: 38883987
DOI: 10.3389/fcvm.2024.1409278 -
Clinical Case Reports Jun 2024We report a patient with nonimmune fetal hydrops and multiple pathologic fractures. RNA analysis revealed a novel variant. This report is the first to elucidate...
We report a patient with nonimmune fetal hydrops and multiple pathologic fractures. RNA analysis revealed a novel variant. This report is the first to elucidate PIEZO1's role as a critical regulator of bone mass and strength.
PubMed: 38883227
DOI: 10.1002/ccr3.9082 -
Cureus May 2024Spondyloenchondrodysplasia with immune dysregulation (SPENCDI) is a rare autosomal recessive genetic disorder caused by a homozygous mutation of the ACP5 gene....
Spondyloenchondrodysplasia with immune dysregulation (SPENCDI) is a rare autosomal recessive genetic disorder caused by a homozygous mutation of the ACP5 gene. Spondyloenchondrodysplasia is a type of immune-osseous dysplasia manifesting with skeletal dysplasia, immunologic dysfunction, and neurological manifestations. We report the case of a six-year-old boy with SPENCDI who presented with post-viral illness Coombs-positive hemolytic anemia, thrombocytopenia, and fever, based on which he was diagnosed with Evans syndrome. He was previously diagnosed with spastic diplegia, short stature, and celiac disease. The diagnosis was confirmed with genetic testing which displayed a homozygous frameshift mutation of the ACP5 gene c.549del p.(Gln184Serfs*28). This case report discusses the clinical presentation of SPENCDI and highlights the importance of considering this rare genetic disorder in patients presenting with short stature, immunologic dysregulation, and neurological involvement.
PubMed: 38883133
DOI: 10.7759/cureus.60314 -
Cureus May 2024Septo-optic dysplasia (SOD) is a rare congenital disorder characterized by optic nerve hypoplasia, brain midline structure anomalies, and hypothalamic-pituitary axis...
Septo-optic dysplasia (SOD) is a rare congenital disorder characterized by optic nerve hypoplasia, brain midline structure anomalies, and hypothalamic-pituitary axis hypoplasia. This case report aims to highlight the association between SOD and neurodevelopmental disorders, focusing on attention-deficit/hyperactivity disorder (ADHD) in addition to the well-established link with autism spectrum disorder (ASD). A six-year-old male diagnosed with SOD presented with behavioral concerns, including attention and impulse control issues. A comprehensive psychological evaluation confirmed the diagnosis of ADHD and ruled out ASD. Ophthalmological assessments were integral to understanding the patient's condition. This case underscores the importance of recognizing neurodevelopmental disorders in individuals with SOD, with a particular focus on the less common association with ADHD. The co-occurrence of these conditions underscores the complexity of neurodevelopmental disorders and the need for comprehensive evaluation and management. Collaboration between ophthalmologists and mental health specialists is crucial for addressing the diverse needs of these patients. Early identification and intervention for ADHD are essential for optimal developmental outcomes. This case underscores the necessity for further research to elucidate the relationship between SOD and ADHD, emphasizing the importance of holistic patient care and interdisciplinary collaboration in managing individuals with SOD spectrum conditions.
PubMed: 38883061
DOI: 10.7759/cureus.60441