-
Pathogens (Basel, Switzerland) Jun 2024Cystic echinococcosis (CE) cysts may persist for decades because of immune modulation mechanisms. Here, we characterize the cysts and the blood immune responses in...
BACKGROUND
Cystic echinococcosis (CE) cysts may persist for decades because of immune modulation mechanisms. Here, we characterize the cysts and the blood immune responses in patients with CE.
METHODS
We enrolled 61 patients with CE and 19 control subjects. We received tissue samples from seven patients with CE and a control subject requiring liver cystectomy. The immunohistochemistry evaluation of the immune cell subtypes and cytokines in the pericysts and surrounding liver and the antigen B (AgB)-specific response analysis of whole blood were performed.
RESULTS
In CE, the pericyst and the surrounding liver parenchyma showed aggregates of CD3 T lymphocytes, mainly CD4. B lymphocyte aggregates were present in the liver tissue. Monocytes/granulocytes were rarely observed. Th2 cytokine expression was scarce, whereas IFN-γ expression was present in the CE tissues. The control subject did not show an inflammatory infiltrate. The IL-4-specific response to AgB was increased in the patients with CE compared to the control, and this result was confirmed in a larger cohort ( = 0.003), whereas the IFN-γ-response was similar between the two groups ( = 0.5570).
CONCLUSION
In patients with CE, CD4 lymphocytes infiltrate the pericyst and the surrounding liver tissue with a low IL-4/IL-13 expression level and a moderate IFN-γ expression level; moreover, an IL-4 parasite-specific response is detected in the periphery. These results support adventitia involvement in CE immunopathogenesis.
PubMed: 38921775
DOI: 10.3390/pathogens13060477 -
BioRxiv : the Preprint Server For... Jun 2024Cardiac fibrosis is defined by the excessive accumulation of extracellular matrix (ECM) material resulting in cardiac tissue scarring and dysfunction. While it is...
Cardiac fibrosis is defined by the excessive accumulation of extracellular matrix (ECM) material resulting in cardiac tissue scarring and dysfunction. While it is commonly accepted that myofibroblasts are the major contributors to ECM deposition in cardiac fibrosis, their origin remains debated. By combining lineage tracing and RNA sequencing, our group made the paradigm-shifting discovery that a subpopulation of resident vascular stem cells residing within the aortic, carotid artery, and femoral aartery adventitia (termed AdvSca1-SM cells) originate from mature vascular smooth muscle cells (SMCs) through an reprogramming process. SMC-to-AdvSca1-SM reprogramming and AdvSca1-SM cell maintenance is dependent on induction and activity of the transcription factor, KLF4. However, the molecular mechanism whereby KLF4 regulates AdvSca1-SM phenotype remains unclear. In the current study, leveraging a highly specific AdvSca1-SM cell reporter system, single-cell RNA-sequencing (scRNA-seq), and spatial transcriptomic approaches, we demonstrate the profibrotic differentiation trajectory of coronary artery-associated AdvSca1-SM cells in the setting of Angiotensin II (AngII)-induced cardiac fibrosis. Differentiation was characterized by loss of stemness-related genes, including , but gain of expression of a profibrotic phenotype. Importantly, these changes were recapitulated in human cardiac hypertrophic tissue, supporting the translational significance of profibrotic transition of AdvSca1-SM-like cells in human cardiomyopathy. Surprisingly and paradoxically, AdvSca1-SM-specific genetic knockout of prior to AngII treatment protected against cardiac inflammation and fibrosis, indicating that is essential for the profibrotic response of AdvSca1-SM cells. Overall, our data reveal the contribution of AdvSca1-SM cells to myofibroblasts in the setting of AngII-induced cardiac fibrosis. KLF4 not only maintains the stemness of AdvSca1-SM cells, but also orchestrates their response to profibrotic stimuli, and may serve as a therapeutic target in cardiac fibrosis.
PubMed: 38895472
DOI: 10.1101/2024.06.04.597485 -
Cells May 2024Fibroblasts, among the most prevalent and widely distributed cell types in the human body, play a crucial role in defining tissue structure. They do this by depositing... (Review)
Review
Fibroblasts, among the most prevalent and widely distributed cell types in the human body, play a crucial role in defining tissue structure. They do this by depositing and remodeling extracellular matrixes and organizing functional tissue networks, which are essential for tissue homeostasis and various human diseases. Pulmonary hypertension (PH) is a devastating syndrome with high mortality, characterized by remodeling of the pulmonary vasculature and significant cellular and structural changes within the intima, media, and adventitia layers. Most research on PH has focused on alterations in the intima (endothelial cells) and media (smooth muscle cells). However, research over the past decade has provided strong evidence of the critical role played by pulmonary artery adventitial fibroblasts in PH. These fibroblasts exhibit the earliest, most dramatic, and most sustained proliferative, apoptosis-resistant, and inflammatory responses to vascular stress. This review examines the aberrant phenotypes of PH fibroblasts and their role in the pathogenesis of PH, discusses potential molecular signaling pathways underlying these activated phenotypes, and highlights areas of research that merit further study to identify promising targets for the prevention and treatment of PH.
Topics: Humans; Hypertension, Pulmonary; Fibroblasts; Animals; Signal Transduction; Pulmonary Artery
PubMed: 38891046
DOI: 10.3390/cells13110914 -
Surgical Case Reports Jun 2024The most common curative treatment for gastrointestinal stromal tumors (GISTs) is local excision. For rectal GISTs, however, local excision is difficult because of the...
BACKGROUND
The most common curative treatment for gastrointestinal stromal tumors (GISTs) is local excision. For rectal GISTs, however, local excision is difficult because of the anatomical features of the rectum. The optimal surgical approach is still under debate, and less invasive methods are desired. We herein report a case of transvaginal resection of a rectal GIST in a young woman.
CASE PRESENTATION
A 21-year-old woman was diagnosed with a resectable GIST in the anterior rectal wall and underwent transvaginal tumor resection. The posterior vaginal wall was incised, revealing the tumor fully covered by the rectal mucosa. The rectal adventitia and muscular layer were incised, and the tumor was resected en bloc without rupture. The postoperative course was favorable, and the patient was discharged on postoperative day 12. No findings consistent with recurrence were present 6 months postoperatively.
CONCLUSION
Transvaginal tumor resection is a treatment option as a minimally invasive procedure for GISTs in the anterior rectal wall in female patients.
PubMed: 38886293
DOI: 10.1186/s40792-024-01949-z -
Journal of the Korean Society of... May 2024Primary malignant fibrous histiocytoma (MFH) is a malignant tumor of mesenchymal origin that rarely occurs in the urinary tract, particularly in the urinary bladder....
Primary malignant fibrous histiocytoma (MFH) is a malignant tumor of mesenchymal origin that rarely occurs in the urinary tract, particularly in the urinary bladder. Unlike urothelial carcinoma, which accounts for most bladder cancers, it occurs in the submucosal portion of the bladder wall and consists of the lamina propria, muscularis propria, and adventitia. It is presumed to originate from poorly differentiated pluripotent mesenchymal cells in which fibroblasts and histiocytes are partially differentiated. Radiologically, it is known as the "non-papillary tumor" and is commonly diagnosed as a large mass without necrosis, which shows invasion beyond the muscularis propia. Although the prognosis of this rare malignancy depends on pathological parameters, it generally has a poor prognosis with high local tumor recurrence. Here, we present a case of primary MFH in the urinary bladder with clinical symptoms of lower abdominal pain without gross hematuria that recurred rapidly and showed an aggressive disease course.
PubMed: 38873381
DOI: 10.3348/jksr.2023.0083 -
Journal of the Korean Society of... May 2024A pulmonary artery periadventitial hematoma is a rare complication of a Stanford type A intramural hematoma. As the proximal ascending aorta and pulmonary artery share a...
A pulmonary artery periadventitial hematoma is a rare complication of a Stanford type A intramural hematoma. As the proximal ascending aorta and pulmonary artery share a common adventitial layer, extravasated blood from the intramural hematoma in the ascending thoracic aorta may extend to beneath the adventitia of the pulmonary artery. The authors describe a case involving a 66-year-old male with acute chest pain who presented with a pulmonary artery periadventitial hematoma associated with a Stanford type A intramural hematoma.
PubMed: 38873368
DOI: 10.3348/jksr.2023.0087 -
International Journal of Legal Medicine Jun 2024The authors present the case of a 58-year-old man found hanging from a radiator by his shoelaces. The time of death was approximately 6 h before the body was...
The authors present the case of a 58-year-old man found hanging from a radiator by his shoelaces. The time of death was approximately 6 h before the body was discovered. An autopsy was performed approximately 24 h after the body was found, which revealed hemorrhages in the thoracic aorta at the junctions of the posterior intercostal arteries. Before autopsy, a routine whole-body CT scan was performed. Histologic examination of the aorta and the posterior intercostal arteries revealed a fresh hemorrhage into the tunica adventitia of the aorta. To our knowledge, there is no case description of such findings in hanged persons in the literature. Conclusion: Hemorrhages into the tunica adventitia of the junction of the posterior costal arteries may occur in association with suicidal hanging. The significance of these hemorrhages as a sign of vitality may be debated.
PubMed: 38861166
DOI: 10.1007/s00414-024-03261-9 -
Aging Cell Jun 2024Aortic stiffening is an inevitable manifestation of chronological aging, yet the mechano-molecular programs that orchestrate region- and layer-specific adaptations along...
Aortic stiffening is an inevitable manifestation of chronological aging, yet the mechano-molecular programs that orchestrate region- and layer-specific adaptations along the length and through the wall of the aorta are incompletely defined. Here, we show that the decline in passive cyclic distensibility is more pronounced in the ascending thoracic aorta (ATA) compared to distal segments of the aorta and that collagen content increases in both the medial and adventitial compartments of the ATA during aging. The single-cell RNA sequencing of aged ATA tissues reveals altered cellular senescence, remodeling, and inflammatory responses accompanied by enrichment of T-lymphocytes and rarefaction of vascular smooth muscle cells, compared to young samples. T lymphocyte clusters accumulate in the adventitia, while the activation of mechanosensitive Piezo-1 enhances vasoconstriction and contributes to the overall functional decline of ATA tissues. These results portray the immuno-mechanical aging of the ATA as a process that culminates in a stiffer conduit permissive to the accrual of multi-gerogenic signals priming to disease development.
PubMed: 38825882
DOI: 10.1111/acel.14197 -
Arteriosclerosis, Thrombosis, and... Jul 2024Pericoronary epicardial adipose tissue (EAT) is a unique visceral fat depot that surrounds the adventitia of the coronary arteries without any anatomic barrier. Clinical... (Comparative Study)
Comparative Study
BACKGROUND
Pericoronary epicardial adipose tissue (EAT) is a unique visceral fat depot that surrounds the adventitia of the coronary arteries without any anatomic barrier. Clinical studies have demonstrated the association between EAT volume and increased risks for coronary artery disease (CAD). However, the cellular and molecular mechanisms underlying the association remain elusive.
METHODS
We performed single-nucleus RNA sequencing on pericoronary EAT samples collected from 3 groups of subjects: patients undergoing coronary bypass surgery for severe CAD (n=8), patients with CAD with concomitant type 2 diabetes (n=8), and patients with valvular diseases but without concomitant CAD and type 2 diabetes as the control group (n=8). Comparative analyses were performed among groups, including cellular compositional analysis, cell type-resolved transcriptomic changes, gene coexpression network analysis, and intercellular communication analysis. Immunofluorescence staining was performed to confirm the presence of CAD-associated subclusters.
RESULTS
Unsupervised clustering of 73 386 nuclei identified 15 clusters, encompassing all known cell types in the adipose tissue. Distinct subpopulations were identified within primary cell types, including adipocytes, adipose stem and progenitor cells, and macrophages. macrophages and adipocytes were significantly expanded in CAD. In comparison to normal controls, both disease groups exhibited dysregulated pathways and altered secretome in the primary cell types. Nevertheless, minimal differences were noted between the disease groups in terms of cellular composition and transcriptome. In addition, our data highlight a potential interplay between dysregulated circadian clock and altered physiological functions in adipocytes of pericoronary EAT. ANXA1 (annexin A1) and SEMA3B (semaphorin 3B) were identified as important adipokines potentially involved in functional changes of pericoronary EAT and CAD pathogenesis.
CONCLUSIONS
We built a complete single-nucleus transcriptomic atlas of human pericoronary EAT in normal and diseased conditions of CAD. Our study lays the foundation for developing novel therapeutic strategies for treating CAD by targeting and modifying pericoronary EAT functions.
Topics: Humans; Pericardium; Transcriptome; Female; Male; Middle Aged; Coronary Artery Disease; Aged; Adipose Tissue; Diabetes Mellitus, Type 2; Adipocytes; Heart Valve Diseases; Gene Expression Profiling; Case-Control Studies; Coronary Artery Bypass; Single-Cell Analysis; Macrophages; Gene Regulatory Networks; Epicardial Adipose Tissue
PubMed: 38813696
DOI: 10.1161/ATVBAHA.124.320923 -
Polymers May 2024This study used the roto-evaporation technique to engineer a 6 mm three-layer polyurethane vascular graft (TVG) that mimics the architecture of human coronary artery...
This study used the roto-evaporation technique to engineer a 6 mm three-layer polyurethane vascular graft (TVG) that mimics the architecture of human coronary artery native vessels. Two segmented polyurethanes were synthesized using lysine (SPUUK) and ascorbic acid (SPUAA), and the resulting materials were used to create the intima and adventitia layers, respectively. In contrast, the media layer of the TVG was composed of a commercially available polyurethane, Pearlbond 703 EXP. For comparison purposes, single-layer vascular grafts (SVGs) from individual polyurethanes and a polyurethane blend (MVG) were made and tested similarly and evaluated according to the ISO 7198 standard. The TVG exhibited the highest circumferential tensile strength and longitudinal forces compared to single-layer vascular grafts of lower thicknesses made from the same polyurethanes. The TVG also showed higher suture and burst strength values than native vessels. The TVG withstood up to 2087 ± 139 mmHg and exhibited a compliance of 0.15 ± 0.1%/100 mmHg, while SPUUK SVGs showed a compliance of 5.21 ± 1.29%/100 mmHg, akin to coronary arteries but superior to the saphenous vein. An indirect cytocompatibility test using the MDA-MB-231 cell line showed 90 to 100% viability for all polyurethanes, surpassing the minimum 70% threshold needed for biomaterials deemed cytocompatibility. Despite the non-cytotoxic nature of the polyurethane extracts when grown directly on the surface, they displayed poor fibroblast adhesion, except for SPUUK. All vascular grafts showed hemolysis values under the permissible limit of 5% and longer coagulation times.
PubMed: 38794507
DOI: 10.3390/polym16101314