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Scientific Reports Mar 2024Radiation-induced cystitis is an inflammatory condition affecting the urinary bladder, which can develop as a side effect of abdominopelvic radiotherapy, specifically...
Radiation-induced cystitis is an inflammatory condition affecting the urinary bladder, which can develop as a side effect of abdominopelvic radiotherapy, specifically external-beam radiation therapy or myeloablative radiotherapy. A possible involvement of mast cells in the pathophysiology of radiation-induced cystitis has been indicated in cases of external-beam radiation therapy; however, there is no evidence that these findings apply to the myeloablative aetiology. As such, this study investigated potential changes to urinary bladder mast cell prevalence when exposed to myeloablative radiation. Lethally irradiated C57BL/6J mice that received donor rescue bone marrow cells exhibited an increased mast cell frequency amongst host leukocytes 1 week following irradiation. By 4 weeks, no significant difference in either frequency or cell density was observed. However mast cell diameter was smaller, and a significant increase in mast cell number in the adventitia was observed. This study highlights that mast cells constitute a significant portion of the remaining host leukocyte population following radiation exposure, with changes to mast cell distribution and decreased cell diameter four weeks following radiation-induced injury.
Topics: Mice; Animals; Urinary Bladder; Mast Cells; Mice, Inbred C57BL; Cystitis; Pelvis
PubMed: 38485999
DOI: 10.1038/s41598-024-56655-5 -
Journal of Neurosurgery. Case Lessons Mar 2024The authors report the case of a patient with occipital headache whose imaging studies revealed no abnormalities but who died 1 day later due to vertebral artery (VA)...
BACKGROUND
The authors report the case of a patient with occipital headache whose imaging studies revealed no abnormalities but who died 1 day later due to vertebral artery (VA) aneurysm rupture.
OBSERVATIONS
A male in his 40s with no relevant medical history had been taking over-the-counter medication for headache several times a month. One day before he visited our neurosurgery department, he experienced occipital headache, took the usual medicine, and applied a warm compress. Brain magnetic resonance imaging (MRI) and magnetic resonance angiography (MRA) studies returned no abnormal findings, and he went home. On the following day, his wife found his lifeless body in rigor mortis and requested a medicolegal autopsy. Preautopsy brain computed tomography showed diffuse subarachnoid hemorrhage (SAH). Histopathologically, there was no obvious VA dissection. The vascular wall at the rupture site lacked internal elastic lamina and media, it was covered only with thin fibrous connective tissue, and the adventitia was expanded. The cause of death was determined to be SAH due to rupture of a VA blister aneurysm.
LESSONS
In our patient, brain MRI and MRA studies returned no abnormal findings. However, he died suddenly the next day. Autopsy identified SAH due to rupture of a blister-like VA aneurysm without dissection.
PubMed: 38467045
DOI: 10.3171/CASE23723 -
BMC Urology Mar 2024Mast cells have been implicated in the pathology of various urinary bladder disorders. However, the distribution of mast cells throughout urinary bladder tissue remains...
BACKGROUND
Mast cells have been implicated in the pathology of various urinary bladder disorders. However, the distribution of mast cells throughout urinary bladder tissue remains uncertain despite mast cell prevalence being relatively well-defined. Using a mouse tissue model, this study aims to characterise the prevalence and distribution of mast cells throughout the urinary bladder.
METHODS
Bladder tissues were collected from six C57BL/6J female mice. Mast cell prevalence was quantified by flow cytometry, based on the expression of the following characteristic markers: CD45, CD117 and FcɛRIα. The toluidine blue stain assessed mast cell distribution, size, and proximity to vasculature. A repeated measures one-way ANOVA was used to evaluate the density of mast cells between the discrete layers of the urinary bladder, and an ordinary one-way ANOVA was used to assess potential differences between mast cell size across the urinary bladder wall.
RESULTS
It was determined that mast cells compose less than 4% of all live leukocytes in the urinary bladder. They were also found to be more prominent in the lamina propria and detrusor muscle layers, compared to the urothelium and adventitia. In addition, 20.89% of mast cells were located near vasculature, which may be an important factor in consideration of their function and potential to contribute to various bladder pathologies, such as cystitis or overactive bladder.
CONCLUSION
These findings provide a baseline understanding of mast cell prevalence and distribution throughout the urinary bladder.
Topics: Female; Mice; Animals; Mice, Inbred C57BL; Urinary Bladder; Mast Cells; Prevalence; Pelvis; Disease Models, Animal
PubMed: 38443866
DOI: 10.1186/s12894-024-01435-6 -
Integrative Medicine (Encinitas, Calif.) Jan 2024We report on 6 patients in our care who were harboring atherosclerotic plaque in the carotid arteries. This condition poses a risk of acute ischemic stroke and indicates...
We report on 6 patients in our care who were harboring atherosclerotic plaque in the carotid arteries. This condition poses a risk of acute ischemic stroke and indicates potential atherosclerosis elsewhere in the vascular system. The plaque was revealed by routine ultrasound measurement of carotid intima-medial thickness (CIMT) defined as the distance between the lumen-intima interface and the media-adventitia interface. Recent improvements in image resolution and edge detection algorithms have resulted in improved reliability and clinical usefulness of the technology. The patients were enrolled in a systems-based functional medicine program of cardiology prevention to address root causes. The program provided personalized interventions that included drug therapy, dietary supplements, and lifestyle modification. The 6 patients followed the integrative regimen, which successfully managed existing cardiovascular symptoms and risk factors while keeping various biomarkers under control. However, they continued to exhibit carotid plaque with no improvement. A novel dietary supplement that targets endothelial glycocalyx regeneration was added to the personalized intervention programs. The supplement contains a proprietary extract of rhamnan sulfate from the green seaweed The 6 participants consumed the supplement daily, and their plaque burden was measured after 6 months using the same CIMT technology. In every case, the total plaque burden was reduced, with an average reduction in the 6 patients of 5.55 mm, which is statistically significant. Significant reductions in maximum carotid plaque thickness were also observed at the end of the 6 months. The study suggests that rhamnan sulfate from may provide a safe and effective intervention for reducing atherosclerotic plaque, and should be evaluated as an adjunct therapy for prevention and treatment of cardiovascular disease.
PubMed: 38404609
DOI: No ID Found -
Journal of Clinical Medicine Feb 2024We have previously reported that endothelial-to-mesenchymal transition (EndMT) is an active process in patients with idiopathic pulmonary fibrosis (IPF) contributing to...
TGF-β1, pSmad-2/3, Smad-7, and β-Catenin Are Augmented in the Pulmonary Arteries from Patients with Idiopathic Pulmonary Fibrosis (IPF): Role in Driving Endothelial-to-Mesenchymal Transition (EndMT).
We have previously reported that endothelial-to-mesenchymal transition (EndMT) is an active process in patients with idiopathic pulmonary fibrosis (IPF) contributing to arterial remodelling. Here, we aim to quantify drivers of EndMT in IPF patients compared to normal controls (NCs). Lung resections from thirteen IPF patients and eleven NCs were immunohistochemically stained for EndMT drivers, including TGF-β1, pSmad-2/3, Smad-7, and β-catenin. Intima, media, and adventitia were analysed for expression of each EndMT driver in pulmonary arteries. Computer- and microscope-assisted Image ProPlus7.0 image analysis software was used for quantifications. Significant TGF-β1, pSmad-2/3, Smad-7, and β-catenin expression was apparent across all arterial sizes in IPF ( < 0.05). Intimal TGF-β1, pSmad-2/3, Smad-7, and β-catenin were augmented in the arterial range of 100-1000 μm ( < 0.001) compared to NC. Intimal TGF-β1 and β-catenin percentage expression showed a strong correlation with the percentage expression of intimal vimentin (r' = 0.54, = 0.05 and r' = 0.61, = 0.02, respectively) and intimal N-cadherin (r' = 0.62, = 0.03 and r' = 0.70, = 0.001, respectively). Intimal TGF-β1 and β-catenin expression were significantly correlated with increased intimal thickness as well (r' = 0.52, = 0.04; r' = 0.052, = 0.04, respectively). Moreover, intimal TGF-β1 expression was also significantly associated with increased intimal elastin deposition (r' = 0.79, = 0.002). Furthermore, total TGF-β1 expression significantly impacted the percentage of DLCO (r' = -0.61, = 0.03). This is the first study to illustrate the involvement of active TGF-β/Smad-2/3-dependent and β-catenin-dependent Wnt signalling pathways in driving EndMT and resultant pulmonary arterial remodelling in patients with IPF. EndMT is a potential therapeutic target for vascular remodelling and fibrosis in general in patients with IPF.
PubMed: 38398472
DOI: 10.3390/jcm13041160 -
Arteriosclerosis, Thrombosis, and... Mar 2024The metabolic alterations occurring within the arterial architecture during atherosclerosis development remain poorly understood, let alone those particular to each... (Observational Study)
Observational Study
BACKGROUND
The metabolic alterations occurring within the arterial architecture during atherosclerosis development remain poorly understood, let alone those particular to each arterial tunica. We aimed first to identify, in a spatially resolved manner, the specific metabolic changes in plaque, media, adventitia, and cardiac tissue between control and atherosclerotic murine aortas. Second, we assessed their translatability to human tissue and plasma for cardiovascular risk estimation.
METHODS
In this observational study, mass spectrometry imaging (MSI) was applied to identify region-specific metabolic differences between atherosclerotic (n=11) and control (n=11) aortas from low-density lipoprotein receptor-deficient mice, via histology-guided virtual microdissection. Early and advanced plaques were compared within the same atherosclerotic animals. Progression metabolites were further analyzed by MSI in 9 human atherosclerotic carotids and by targeted mass spectrometry in human plasma from subjects with elective coronary artery bypass grafting (cardiovascular risk group, n=27) and a control group (n=27).
RESULTS
MSI identified 362 local metabolic alterations in atherosclerotic mice (log2 fold-change ≥1.5; ≤0.05). The lipid composition of cardiac tissue is altered during atherosclerosis development and presents a generalized accumulation of glycerophospholipids, except for lysolipids. Lysolipids (among other glycerophospholipids) were found at elevated levels in all 3 arterial layers of atherosclerotic aortas. LPC(18:0) (lysophosphatidylcholine; =0.024) and LPA(18:1) (lysophosphatidic acid; =0.025) were found to be significantly elevated in advanced plaques as compared with mouse-matched early plaques. Higher levels of both lipid species were also observed in fibrosis-rich areas of advanced- versus early-stage human samples. They were found to be significantly reduced in human plasma from subjects with elective coronary artery bypass grafting (<0.001 and =0.031, respectively), with LPC(18:0) showing significant association with cardiovascular risk (odds ratio, 0.479 [95% CI, 0.225-0.883]; =0.032) and diagnostic potential (area under the curve, 0.778 [95% CI, 0.638-0.917]).
CONCLUSIONS
An altered phospholipid metabolism occurs in atherosclerosis, affecting both the aorta and the adjacent heart tissue. Plaque-progression lipids LPC(18:0) and LPA(18:1), as identified by MSI on tissue, reflect cardiovascular risk in human plasma.
Topics: Humans; Animals; Mice; Plaque, Atherosclerotic; Cardiovascular Diseases; Risk Factors; Atherosclerosis; Aorta; Aortic Diseases; Glycerophospholipids; Heart Disease Risk Factors
PubMed: 38299357
DOI: 10.1161/ATVBAHA.123.320278 -
Journal of Clinical Medicine Jan 2024The abdominal aortic aneurysm (AAA) is defined as an increase in aortic diameter by more than 50% and is associated with a high risk of rupture and mortality without...
BACKGROUND
The abdominal aortic aneurysm (AAA) is defined as an increase in aortic diameter by more than 50% and is associated with a high risk of rupture and mortality without treatment. The aim of this study is to analyze the role of aortic adventitial collagen photocrosslinking by UV-A irradiation on the biomechanical profile of the aortic wall.
METHODS
This experimental study is structured in two parts: the first part includes in vitro uniaxial biomechanical evaluation of porcine adventitial tissue subjected to either short-term elastolysis or long-term collagenolysis in an attempt to duplicate two extreme situations as putative stages of aneurysmal degeneration. In the second part, we included biaxial biomechanical evaluation of in vitro human abdominal aortic adventitia and human AAA adventitia specimens. Biomechanical profiles were examined for porcine and human aortic tissue before and after irradiation with UV-A light (365 nm wavelength).
RESULTS
On the porcine aortic sample, the enhancing effect of irradiation was evident both on the tissue subjected to elastolysis, which had a high collagen-to-elastin ratio, and on the tissue subjected to prolonged collagenolysis despite being considerably depleted in collagen. Further, the effect of irradiation was conclusively demonstrated in the human adventitia samples, where significant post-irradiation increases in Cauchy stress (longitudinal axis: = 0.001, circumferential axis: = 0.004) and Young's modulus (longitudinal axis: = 0.03, circumferential axis: = 0.004) were recorded. Moreover, we have a stronger increase in the strengthening of the AAA adventitia samples following the exposure to UV-A irradiation ( = 0.007) and a statistically significant but not very important increase ( = 0.021) regarding the stiffness in the circumferential axis.
CONCLUSIONS
The favorable effect of UV irradiation on the strength and stiffness of degraded aortic adventitia in experimental situations mimicking early and later stages of aneurysmal degeneration is essential for the development and potential success of procedures to prevent aneurysmal ruptures. The experiments on human normal and aneurysmal adventitial tissue confirmed the validity and potential success of a procedure based on exposure to UV-A radiation.
PubMed: 38276139
DOI: 10.3390/jcm13020633 -
Journal of Gastrointestinal Oncology Dec 2023Lymph node metastasis is the main type of metastasis in esophageal squamous cell carcinoma (ESCC), especially when the primary tumor invasion depth reaches above the...
BACKGROUND
Lymph node metastasis is the main type of metastasis in esophageal squamous cell carcinoma (ESCC), especially when the primary tumor invasion depth reaches above the adventitia layer (T3 stage), the incidence of lymph node metastasis increases sharply. Abnormal expression of long non-coding RNAs (lncRNAs) has been confirmed in ESCC, but there are still many unknown connections between lncRNAs and lymph node metastasis.
METHODS
We used transcriptome sequencing (RNA-seq) to analyze 10 pairs of ESCC tissues with primary tumor stage T3 and their paired normal epithelium. Quantitative real-time polymerase chain reaction (qRT-PCR) was used to further verify the sequencing results, and survival curve analysis, logistic regression analysis, and receiver operating characteristic (ROC) curve analysis were used to investigate its clinical application value. We investigated the growth and metastasis effects of lncRNA GAS6-AS1 on ESCC cell lines TE-1 and KYSE410 in vitro and in vivo. Other functional experiments included cell apoptosis and cell cycle experiments.
RESULTS
Based on our RNA-seq data, lncRNA GAS6-AS1 is highly expressed in ESCC tissues, especially in cancer tissues with lymph node metastasis. The qRT-PCR experiment analysis showed that high expression of GAS6-AS1 was related to poor tumor differentiation and tumor stage. Logistic regression analysis showed that it was an independent risk factor for lymph node metastasis, and ROC analysis validated that it could predict lymph node metastasis. Further survival analysis suggested that high expression of GAS6-AS1 was associated with patients' poor prognosis. In vitro experiments, knocking down GAS6-AS1 inhibited the growth and metastasis of ESCC cells and inhibited tumor growth in vivo. In addition, knocking down GAS6-AS1 can inhibit cell cycle and promote cell apoptosis.
CONCLUSIONS
Our results revealed that lncRNA GAS6-AS1 obtained from RNA-seq can be used as an independent risk factor for ESCC lymph node metastasis and an effective biomarker to predict, and that it was related to the growth and metastasis of ESCC. It may represent a new biomarker to aid in the assessment of the lymph node metastasis of ESCC.
PubMed: 38196547
DOI: 10.21037/jgo-23-798 -
JCI Insight Jan 2024Abdominal aortic aneurysm (AAA) is a chronic inflammatory disease characterized by the expansion of the aortic wall. One of the most significant features is the...
Abdominal aortic aneurysm (AAA) is a chronic inflammatory disease characterized by the expansion of the aortic wall. One of the most significant features is the infiltration of macrophages in the adventitia, which drives vasculature remodeling. The role of macrophage-derived interferon regulatory factor 5 (IRF5) in macrophage infiltration and AAA formation remains unknown. RNA sequencing of AAA adventitia identified Irf5 as the top significantly increased transcription factor that is predominantly expressed in macrophages. Global and myeloid cell-specific deficiency of Irf5 reduced AAA progression, with a marked reduction in macrophage infiltration. Further cellular investigations indicated that IRF5 promotes macrophage migration by direct regulation of downstream phosphoinositide 3-kinase γ (PI3Kγ, Pik3cg). Pik3cg ablation hindered AAA progression, and myeloid cell-specific salvage of Pik3cg restored AAA progression and macrophage infiltration derived from Irf5 deficiency. Finally, we found that IRF5 and PI3Kγ expression in the adventitia is significantly increased in patients with AAA. These findings reveal that the IRF5-dependent regulation of PI3Kγ is essential for AAA formation.
Topics: Humans; Adventitia; Phosphatidylinositol 3-Kinases; Aortic Aneurysm, Abdominal; Macrophages; Interferon Regulatory Factors
PubMed: 38175709
DOI: 10.1172/jci.insight.171488