-
American Journal of Physiology. Heart... Nov 2022We have shown that excessive endothelial cell stretch causes release of growth arrest-specific 6 (GAS6), which activates the tyrosine kinase receptor Axl on monocytes...
We have shown that excessive endothelial cell stretch causes release of growth arrest-specific 6 (GAS6), which activates the tyrosine kinase receptor Axl on monocytes and promotes immune activation and inflammation. We hypothesized that GAS6/Axl blockade would reduce renal and vascular inflammation and lessen renal dysfunction in the setting of chronic aortic remodeling. We characterized a model of aortic remodeling in mice following a 2-wk infusion of angiotensin II (ANG II). These mice had chronically increased pulse wave velocity, and their aortas demonstrated increased mural collagen. Mechanical testing revealed a marked loss of Windkessel function that persisted for 6 mo following ANG II infusion. Renal function studies showed a reduced ability to excrete a volume load, a progressive increase in albuminuria, and tubular damage as estimated by periodic acid Schiff staining. Treatment with the Axl inhibitor R428 beginning 2 mo after ANG II infusion had a minimal effect on aortic remodeling 2 mo later but reduced the infiltration of T cells, γ/δ T cells, and macrophages into the aorta and kidney and improved renal excretory capacity, reduced albuminuria, and reduced evidence of renal tubular damage. In humans, circulating Axl/Siglec6 dendritic cells and phospho-Axl cells correlated with pulse wave velocity and aortic compliance measured by transesophageal echo, confirming chronic activation of the GAS6/Axl pathway. We conclude that brief episodes of hypertension induce chronic aortic remodeling, which is associated with persistent low-grade inflammation of the aorta and kidneys and evidence of renal dysfunction. These events are mediated at least in part by GAS6/Axl signaling and are improved with Axl blockade. In this study, a brief, 2-wk period of hypertension in mice led to progressive aortic remodeling, an increase in pulse wave velocity, and evidence of renal injury, dysfunction, and albuminuria. This end-organ damage was associated with persistent renal and aortic infiltration of CD8 and γ/δ T cells. We show that this inflammatory response is likely due to GAS6/Axl signaling and can be ameliorated by blocking this pathway. We propose that the altered microvascular mechanical forces caused by increased pulse wave velocity enhance GAS6 release from the endothelium, which in turn activates Axl on myeloid cells, promoting the end-organ damage associated with aortic stiffening.
Topics: Animals; Humans; Mice; Albuminuria; Angiotensin II; Aorta; Collagen; Hypertension; Inflammation; Intercellular Signaling Peptides and Proteins; Kidney Diseases; Periodic Acid; Proto-Oncogene Proteins; Pulse Wave Analysis; Receptor Protein-Tyrosine Kinases; Axl Receptor Tyrosine Kinase
PubMed: 36083796
DOI: 10.1152/ajpheart.00253.2022 -
Cureus Oct 2021Certain contemporary histology stains and methods are not the same as those used in the past. This progression has delved into the requirement for more precise, less... (Review)
Review
Certain contemporary histology stains and methods are not the same as those used in the past. This progression has delved into the requirement for more precise, less complex, and efficient staining procedures. The objective of this study is to assess historical and contemporary stains and procedures, as well as the challenges surrounding their improvement. Carmine, hematoxylin, silver nitrate, Giemsa, trichome stain, Gram stain, and mauveine were among the first histological stains discovered in nature. Aside from their utility in the study of tissues at the time, they also laid the groundwork for the development of commercial dyes that are still in use today. Hematoxylin and eosin, Ziehl-Nielsen (ZN) stain, periodic acid-Schiff stain, and Grocott-Gomori methenamine silver stain are some of the most recently developed histological stains. The future of histological stains and processes appears to be influenced by technological advancements and the demand for cost-effective diagnostic approaches in the healthcare system. Thus, currently used histological stains appear to be economical, quick, and reliable tools for interpreting, archiving, and delivering essential diagnoses that could not be achieved by any other means.
PubMed: 34754648
DOI: 10.7759/cureus.18486 -
Medicine and Pharmacy Reports Aug 2021Whipple's disease (WD) is a rare chronic systemic disease caused by the Gram-positive bacillus Tropheryma whipplei. Despite over 100 years of observation and study...
BACKGROUND
Whipple's disease (WD) is a rare chronic systemic disease caused by the Gram-positive bacillus Tropheryma whipplei. Despite over 100 years of observation and study history of this disease, it still remains a difficult diagnostic and therapeutic challenge.
CLINICAL CASE PRESENTATION
Authors report the case of a 38-year-old man with long-time PPIs treatment because of GERD and no other clinical and paraclinical symptoms. Endoscopic slightly enlarged villi, accumulation of whitish matter at the tip of the villi of distal duodenal mucosa and periodic acid-Schiff staining positive inclusions in the stromal tissue may be typical signs of Whipple's disease. In discussion the possible explication of this case are presented.
CONCLUSIONS
It is still a challenge to diagnose Whipple's disease. Histological findings may confirm the diagnosis in patients with a combination of typical clinical manifestations, but histological signs alone are not pathognomic, and are not enough for a definitive diagnosis.
PubMed: 34527918
DOI: 10.15386/mpr-2237 -
Journal of Veterinary Internal Medicine Sep 2020A 7-year-old castrated male French Bulldog was examined for chronic large intestinal enteropathy. A colonic mass and thickened rectal mucosa were identified, and...
A 7-year-old castrated male French Bulldog was examined for chronic large intestinal enteropathy. A colonic mass and thickened rectal mucosa were identified, and histopathologic examination of endoscopic biopsy specimens disclosed eosinophilic proctitis with large (5-20 μm), irregularly shaped, pauciseptate hyphae that were Gomori methenamine silver and periodic acid-Schiff positive. Amplification and sequencing of ribosomal DNA extracted from paraffin-embedded tissues yielded a sequence with 97% identity to GenBank sequences for Basidiobolus ranarum. After itraconazole, terbinafine, and prednisone administration, clinical signs resolved rapidly, and sonographic lesions were largely absent after 6 weeks. Treatment was discontinued by the owner 15 weeks after diagnosis. Three weeks later, the dog collapsed acutely and was euthanized. Necropsy identified metastatic islet cell carcinoma and grossly unremarkable colorectal tissues. However, histopathology of the rectum disclosed multifocal submucosal granulomas with intralesional hyphae morphologically similar to those previously observed. This report is the first to describe medical treatment of gastrointestinal basidiobolomycosis in a dog.
Topics: Animals; Colorectal Neoplasms; Dog Diseases; Dogs; Entomophthorales; Male; Zygomycosis
PubMed: 32681715
DOI: 10.1111/jvim.15859 -
Iranian Journal of Pathology 2023Mucormycosis (also called black fungus) is an opportunistic serious fungal infection caused by mucormycetes. It can occur in diabetes mellitus patients and other...
BACKGROUND & OBJECTIVE
Mucormycosis (also called black fungus) is an opportunistic serious fungal infection caused by mucormycetes. It can occur in diabetes mellitus patients and other immunosuppressive conditions with recent predisposing factors such as maxillofacial surgery and corticosteroid usage.
METHODS
In this study, 14 patients were referred to the otorhinolaryngology or ophthalmology ward of Shafa Hospital (Kerman, Iran) with primary symptoms of nasal fullness and facial nerve dysfunction; they were admitted to the hospital to rule out the fungal infection. An endoscopic biopsy was taken from facial sinuses or orbit, and a microscopic evaluation was performed using hematoxylin and eosin (H&E) and periodic acid-Schiff (PAS) staining methods to rule out mucormycosis.
RESULTS
In the histopathological examination, broad-based nonseptate branching fungal hyphae were found in nasal sinuses through the endoscopic biopsy. Most of the patients had diabetes mellitus with a primary symptom of facial nerve palsy; also, most of them received corticosteroids (intravenous [IV] or intramuscular [IM] injection). All patients have recently been infected with COVID-19 (less than 1 month ago).
CONCLUSION
COVID-19 infection might be a predisposing factor for many opportunistic infections, such as fungal elements); thus, the physician should be aware of the dosage and duration of corticosteroid therapy to prevent the development of these infections.
PubMed: 37600568
DOI: 10.30699/IJP.2023.545953.2845 -
World Journal of Stem Cells Oct 2021End-stage liver disease is a global health complication with high prevalence and limited treatment options. Cell-based therapies using mesenchymal stem cells (MSCs)...
BACKGROUND
End-stage liver disease is a global health complication with high prevalence and limited treatment options. Cell-based therapies using mesenchymal stem cells (MSCs) emerged as an alternative approach to support hepatic regeneration. preconditioning strategies have been employed to strengthen the regenerative and differentiation potential of MSCs towards hepatic lineage. Chemical compounds of the triterpene class; glycyrrhizic acid (GA) and 18β-glycyrrhetinic acid (GT) possess diverse therapeutic properties including hepato-protection and anti-fibrosis characteristics. They are capable of modulating several signaling pathways that are crucial in hepatic regeneration. Preconditioning with hepato-protective triterpenes may stimulate MSC fate transition towards hepatocytes.
AIM
To explore the effect of GA and GT on hepatic differentiation of human umbilical cord-MSCs (hUC-MSCs).
METHODS
hUC-MSCs were isolated and characterized phenotypically by flow cytometry and immunocytochemistry for the expression of MSC-associated surface molecules. Isolated cells were treated with GA, GT, and their combination for 24 h and then analyzed at three time points; day 7, 14, and 21. qRT-PCR was performed for the expression of hepatic genes. Expression of hepatic proteins was analyzed by immunocytochemistry at day 21. Periodic acid Schiff staining was performed to determine the functional ability of treated cells.
RESULTS
The fusiform-shaped morphology of MSCs in the treatment groups in comparison with the untreated control, eventually progressed towards the polygonal morphology of hepatocytes with the passage of time. The temporal transcriptional profile of preconditioned MSCs displayed significant expression of hepatic genes with increasing time of differentiation. Preconditioned cells showed positive expression of hepatocyte-specific proteins. The results were further corroborated by positive periodic acid Schiff staining, indicating the presence of glycogen in their cytoplasm. Moreover, bi-nucleated cells, which is the typical feature of hepatocytes, were also seen in the preconditioned cells.
CONCLUSION
Preconditioning with glycyrrhizic acid, 18β-glycyrrhetinic acid and their combination, successfully differentiates hUC-MSCs into hepatic-like cells. These MSCs may serve as a better therapeutic option for degenerative liver diseases in future.
PubMed: 34786159
DOI: 10.4252/wjsc.v13.i10.1580 -
Respiratory Medicine Case Reports 2022Pulmonary alveolar proteinosis (PAP) is a rare pulmonary syndrome that is characterized by the accumulation of excess surfactant in the alveolar space, leading to...
Pulmonary alveolar proteinosis (PAP) is a rare pulmonary syndrome that is characterized by the accumulation of excess surfactant in the alveolar space, leading to impaired gas exchange. Sirolimus-induced PAP is an extremely rare entity that has only been described in the literature in a small number of case reports. We present a case of a 39-year-old female with acute lymphocytic leukemia who underwent stem cell transplant, complicated by graft-versus-host-disease (GVHD) involving the skin for which she was treated with steroids, photopheresis, sirolimus, and ruxolitinib. She was admitted to the intensive care unit (ICU) for acute on chronic hypoxic respiratory failure requiring intermittent mechanical ventilation. Computed tomography (CT) of the chest showed thickened inter- and intralobular septa with ground glass opacities and consolidation with a limited geographic pattern. Bronchoalveolar lavage fluid was stained with Periodic acid-Schiff (PAS), which was positive for extracellular proteinaceous material. Autoimmune studies including antibody levels for primary autoimmune pulmonary alveolar proteinosis (PAP) were negative. The patient was diagnosed with sirolimus-induced secondary PAP, and sirolimus was discontinued. A year later, she no longer required supplemental oxygen, and repeat CT imaging showed only faint residual disease. This is the only documented case of sirolimus-induced PAP in a stem cell transplant recipient and the first case reported in which the patient developed severe hypoxic respiratory failure requiring mechanical ventilation. In the right clinical context, PAP can be diagnosed with characteristic high resolution computed tomography (HRCT) findings, serum GM-CSF antibody levels, and bronchoscopy with bronchoalveolar lavage.
PubMed: 34976718
DOI: 10.1016/j.rmcr.2021.101566 -
Journal of Oral Biology and... 2021Hyalinization is a process of conversion of stromal connective tissue into a homogeneous, acellular translucent material. Nevertheless, hyalinization could provide... (Review)
Review
BACKGROUND
Hyalinization is a process of conversion of stromal connective tissue into a homogeneous, acellular translucent material. Nevertheless, hyalinization could provide insights into the biologic behaviour and prognosis of pathological lesions. Few studies with limited sample size have intended to assess the correlation of hyalinization and biologic behaviour in oral lesions.
AIM
The current review aims to comprehensively appraise the mechanism of hyalinization in pathological oral hyalinizing lesions (OHL) and its clinical implications with emphasis on differential stains employed.
METHODS
An electronic search was performed in the PubMed database (from year 2000-2020) using the keywords "special stains in oral hyalinizing lesions", "significance of hyalinization in oral lesions" and "hyalinization and biologic behaviour". Original research articles analyzing the effect of hyalinization on biologic characteristics of the lesion were evaluated in this review. Narrative review articles that provided insights into the mechanism of hyalinization and maturity of collagen fibers were also considered for analysis.
CONCLUSION
The presence of hyalinization does seem to have a significant effect on the biologic behaviour of pathological lesions. There is substantial scope to further investigate the process of hyalinization on larger samples and its correlation with the aggressive behaviour of OHLs. Special stains and advanced investigations such as immunohistochemistry for stromal markers would define the nature of hyalinized material and validate the correlation.
CLINICAL SIGNIFICANCE
The prediction of the biologic behaviour of a lesion established through assessment of hyalinization would prevent unwanted over or under treatment leading to a better prognosis.
PubMed: 34094841
DOI: 10.1016/j.jobcr.2021.05.002 -
Heliyon Nov 2023Cisplatin is a chemotherapeutant widely used in treating solid tumors, with the common side effect of acute kidney injury (AKI). Developing effective useful agent for...
Cisplatin is a chemotherapeutant widely used in treating solid tumors, with the common side effect of acute kidney injury (AKI). Developing effective useful agent for preventing or treating cisplatin-induced AKI is of great importance. In this study, we investigate the protective effect of vaccarin, a chemical entity of flavonoid glycoside, against cisplatin-induced AKI. Cisplatin-treated C57BL/6J mice and human kidney-2 (HK-2) cells were used as the model of cisplatin-induced AKI. The levels of blood urea nitrogen (BUN) and creatine (Cr) levels and periodic acid-Schiff staining (PAS) scores decreased when vaccarin was administrated. Vaccarin had no impact on renal platinum accumulation, which was detected by the ICP-MS 6 h after cisplatin injection. Moreover, vaccarin can significantly alleviate the product of reactive oxygen species and the expression of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase 4 (NOX4) in cisplatin-induced AKI, both and . In addition, vaccarin decreased the receptor-interacting protein kinase 1 (RIPK1) related programmed necrosis (necroptosis), cell apoptosis (shown by the protein levels of cleaved-caspase3 and flow cytometry) and inflammation (shown by the decreased levels of NLRP3, p-P65 and the mRNA of several inflammatory factors). NOX4 inhibitor GLX351322 (GLX) and NOX4 kowndown by siRNA have equivalent protective effect of vaccarin . When vaccarin was administered together with GLX or NOX4 siRNA, this protective effect of vaccarin did not further increase, as indicating by the index of oxidative stress, cell viability, necroptosis and apoptosis. In conclusion, vaccarin can alleviate cisplatin-induced AKI via inhibiting NOX4.
PubMed: 38027630
DOI: 10.1016/j.heliyon.2023.e21231 -
Cureus Jan 2024Whipple's disease (WD) is a chronic multisystemic infection caused by . It is a rare condition with a wide spectrum of clinical presentations, necessitating a high...
Whipple's disease (WD) is a chronic multisystemic infection caused by . It is a rare condition with a wide spectrum of clinical presentations, necessitating a high clinical suspicion to arrive at the diagnosis. We present the case of a 65-year-old woman who experienced chronic, intermittent, and migratory polyarthralgia, weight loss, anorexia, and pyrosis. She was admitted due to bilateral deep vein thrombosis (DVT). She exhibited lymphadenopathy without hepatosplenomegaly, and lymph node biopsy revealed reactive lymphadenitis with intrahistiocytic bacilli that reacted positively to periodic acid-Schiff staining. This led to the suspicion of WD, which was subsequently confirmed through small bowel biopsies. She initiated treatment with ceftriaxone and experienced rapid clinical improvement. WD poses a diagnostic challenge. The signs and symptoms are often nonspecific and can result in misdiagnosis as a rheumatic or neoplastic disease. The presentation with DVT, while unusual, has been reported as a manifestation of WD.
PubMed: 38344639
DOI: 10.7759/cureus.51991