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BMC Veterinary Research Jun 2024This study aims to describe a rare case of primary ureteral hemangiosarcoma, in which surgical intervention preserved the kidney and ureter after tumor removal.
BACKGROUND
This study aims to describe a rare case of primary ureteral hemangiosarcoma, in which surgical intervention preserved the kidney and ureter after tumor removal.
CASE PRESENTATION
A 13-year-old, neutered male dog, weighing 14 kg, mixed-breed, presented with apathy, anorexia, acute-onset vomiting, and abdominal discomfort during the physical examination. Ultrasonography and pyelography revealed a right-sided dilation of the renal pelvis and ureter due to complete obstruction in the middle third of the ureter. A mass obstructing the lumen of the right ureter was completely resected, and ureteral suturing was performed, preserving the integrity of the involved structures. Histopathology confirmed primary ureteral hemangiosarcoma. Due to the local and non-invasive nature of the mass, chemotherapy was not initiated. The patient's survival was approximately two years, and normal renal function was preserved throughout this period.
CONCLUSIONS
Considering this type of tumor in the differential diagnosis of upper urinary tract obstructive disorders. Furthermore, the preservation of the ureter and kidney is a suitable therapeutic option after surgical resection of non-invasive tumors.
Topics: Animals; Male; Dogs; Hemangiosarcoma; Dog Diseases; Ureteral Neoplasms; Paraplegia; Ureteral Obstruction
PubMed: 38909227
DOI: 10.1186/s12917-024-04114-8 -
Iranian Journal of Kidney Diseases May 2024Shenqi pill (SQP) can be used to treat various kidney related diseases, but its exact mechanism of action remains unclear. We intended to analyze the role and mechanism...
INTRODUCTION
Shenqi pill (SQP) can be used to treat various kidney related diseases, but its exact mechanism of action remains unclear. We intended to analyze the role and mechanism of SQP on renal interstitial fibrosis (RIF).
METHODS
After performing unilateral ureteral obstruction (UUO) surgery following the Institutional Animal Care and Use Committee guidelines, all rats were assigned into the sham group, UUO group, UUO + SQP 1.5 g/kg, UUO + SQP 3 g/kg, and UUO + SQP 6 g/kg groups. After treatment with SQP for 4 weeks, the appearance of kidney, serum creatinine (SCr), and blood urea nitrogen (BUN) levels were monitored in each group. The pathological injury, extracellular matrix (ECM), and Notch1 pathway-related protein levels were measured using H&E staining, Masson staining, immunohistochemistry, and Western blot, respectively.
RESULTS
SQP could obviously ameliorate the appearance of the kidney as well as the levels of SCr and BUN in UUO rats (SCr: 67.6 ± 4.64 μM, 59.66 ± 4.96 μM, 48.76 ± 4.44 μM, 40.43 ± 3.02 μM for UUO, low, medium, and high SQP treatment groups; BUN: 9.09 ± 0.97 mM, 7.72 ± 0.61 mM, 5.42 ± 0.42 mM, 4.24 ± 0.34 mM for UUO, low, medium, and high SQP treatment groups; P < .05). SQP also effectively mitigated renal tissue injury in UUO rats (P < .05). Moreover, we uncovered that SQP significantly inhibited Collagen I, α-SMA, Collagen IV, TGF-B1, Notch1, and Jag1 protein expressions in UUO rats kidney (P < .05).
CONCLUSION
Our data elucidated that SQP can alleviate RIF, and the mechanism may be related to the Notch1/Jag1 pathway. DOI: 10.52547/ijkd.7703.
Topics: Animals; Drugs, Chinese Herbal; Fibrosis; Male; Receptor, Notch1; Kidney; Ureteral Obstruction; Rats; Rats, Sprague-Dawley; Signal Transduction; Jagged-1 Protein; Blood Urea Nitrogen; Disease Models, Animal; Kidney Diseases; Creatinine; Transforming Growth Factor beta1; Actins
PubMed: 38904340
DOI: 10.52547/b56av842 -
BioRxiv : the Preprint Server For... Apr 2024The cannabinoid CB2 receptor (CB2R) is a potential therapeutic target for distinct forms of tissue injury and inflammatory diseases. To thoroughly investigate the role...
The cannabinoid CB2 receptor (CB2R) is a potential therapeutic target for distinct forms of tissue injury and inflammatory diseases. To thoroughly investigate the role of CB2R in pathophysiological conditions and for target validation , optimal pharmacological tool compounds are essential. Despite the sizable progress in the generation of potent and selective CB2R ligands, pharmacokinetic parameters are often neglected for studies. Here, we report the generation and characterization of a tetra-substituted pyrazole CB2R full agonist named RNB-61 with high potency ( 0.13-1.81 nM, depending on species) and a peripherally restricted action due to P-glycoprotein mediated efflux from the brain. H and C labelled RNB-61 showed apparent values < 4 nM towards human CB2R in both cell and tissue experiments. The >6000-fold selectivity over CB1 receptors and negligible off-targets , combined with high oral bioavailability and suitable systemic pharmacokinetic (PK) properties, prompted the assessment of RNB-61 in a mouse ischemia-reperfusion model of acute kidney injury (AKI) and in a rat model of chronic kidney injury/inflammation and fibrosis (CKI) induced by unilateral ureteral obstruction. RNB-61 exerted dose-dependent nephroprotective and/or antifibrotic effects in the AKI/CKI models. Thus, RNB-61 is an optimal CB2R tool compound for preclinical studies with superior biophysical and PK properties over generally used CB2R ligands.
PubMed: 38903103
DOI: 10.1101/2024.04.26.591311 -
Frontiers in Endocrinology 2024The global prevalence of cardiovascular diseases (CVD) continues to rise steadily, making it a leading cause of mortality worldwide. Atherosclerosis (AS) serves as a... (Review)
Review
The global prevalence of cardiovascular diseases (CVD) continues to rise steadily, making it a leading cause of mortality worldwide. Atherosclerosis (AS) serves as a primary driver of these conditions, commencing silently at an early age and culminating in adverse cardiovascular events that severely impact patients' quality of life or lead to fatality. Dyslipidemia, particularly elevated levels of low-density lipoprotein cholesterol (LDL-C), plays a pivotal role in AS pathogenesis as an independent risk factor. Research indicates that abnormal LDL-C accumulation within arterial walls acts as a crucial trigger for atherosclerotic plaque formation. As the disease progresses, plaque accumulation may rupture or dislodge, resulting in thrombus formation and complete blood supply obstruction, ultimately causing myocardial infarction, cerebral infarction, and other common adverse cardiovascular events. Despite adequate pharmacologic therapy targeting LDL-C reduction, patients with cardiometabolic abnormalities remain at high risk for disease recurrence, highlighting the importance of addressing lipid risk factors beyond LDL-C. Recent attention has focused on the causal relationship between triglycerides, triglyceride-rich lipoproteins (TRLs), and their remnants in AS risk. Genetic, epidemiologic, and clinical studies suggest a causal relationship between TRLs and their remnants and the increased risk of AS, and this dyslipidemia may be an independent risk factor for adverse cardiovascular events. Particularly in patients with obesity, metabolic syndrome, diabetes, and chronic kidney disease, disordered TRLs and its remnants levels significantly increase the risk of atherosclerosis and cardiovascular disease development. Accumulation of over-synthesized TRLs in plasma, impaired function of enzymes involved in TRLs lipolysis, and impaired hepatic clearance of cholesterol-rich TRLs remnants can lead to arterial deposition of TRLs and its remnants, promoting foam cell formation and arterial wall inflammation. Therefore, understanding the pathogenesis of TRLs-induced AS and targeting it therapeutically could slow or impede AS progression, thereby reducing cardiovascular disease morbidity and mortality, particularly coronary atherosclerotic heart disease.
Topics: Humans; Cardiovascular Diseases; Lipoproteins; Triglycerides; Atherosclerosis; Animals; Dyslipidemias; Risk Factors
PubMed: 38883601
DOI: 10.3389/fendo.2024.1409653 -
Animal Models and Experimental Medicine Jun 2024Apoptosis signal-regulating kinase 1 (ASK1) is a MAP3K kinase in the MAPK signaling pathway activated by stressors and triggers downstream biological effects such as...
BACKGROUND
Apoptosis signal-regulating kinase 1 (ASK1) is a MAP3K kinase in the MAPK signaling pathway activated by stressors and triggers downstream biological effects such as inflammation and apoptosis; therefore, inhibition of ASK1 kinase activity can protect cells from pathological injury. In this study, we designed and synthesized a novel selective ASK1 inhibitor, CS17919, and investigated its pharmacological effects in various animal models of metabolic injury.
METHODS
First, we validated the ability of CS17919 to inhibit ASK1 in vitro and then tested the safety profile of CS17919 in cell lines compared with Selonsertib (GS-4997), a phase III ASK1 inhibitor. We then conducted pharmacokinetic (PK) studies in mice. Finally, we tested the in vivo efficacy of CS17919 in murine models of chronic kidney disease (CKD) and non-alcoholic steatohepatitis (NASH).
RESULTS
Compared to GS-4997, CS17919 demonstrated comparable inhibition of ASK1 in vitro, exhibited lower toxicity, and provided greater protection in palmitic acid-treated LO2 cells. CS17919 also showed pronounced pharmacokinetic properties such as a high plasma concentration. In the unilateral ureteral obstruction model (UUO), CS17919 and GS-4997 preserved kidney function and showed a non-significant tendency to alleviate kidney fibrosis. In the diabetic kidney disease (DKD) model, CS17919 significantly improved serum creatinine and glomerular sclerosis. In the NASH model, the combination of CS17919 and a THRβ agonist (CS27109) was found to significantly improve liver inflammation and substantially reduced liver fibrosis.
CONCLUSIONS
CS17919 showed cell protective, anti-inflammatory, and antifibrotic effects in vitro and in vivo, suggesting its therapeutic potential for metabolic-related kidney and liver diseases.
PubMed: 38873818
DOI: 10.1002/ame2.12437 -
PloS One 2024Renal fibrosis is the most common pathway in progressive kidney diseases. The unilateral ureteral obstruction (UUO) model is used to induce progressive renal fibrosis....
Renal fibrosis is the most common pathway in progressive kidney diseases. The unilateral ureteral obstruction (UUO) model is used to induce progressive renal fibrosis. We evaluated the effects of irisin on renal interstitial fibrosis in UUO mice. The GSE121190, GSE36496, GSE42303, and GSE96101 datasets were downloaded from the Gene Expression Omnibus (GEO) database. In total, 656 differentially expressed genes (DEGs) were identified in normal and UUO mouse renal samples. Periostin and matrix metalloproteinase-2 (MMP-2) were selected to evaluate the effect of irisin on renal fibrosis in UUO mice. In UUO mice, irisin ameliorated renal function, decreased the expression of periostin and MMP-2, and attenuated epithelial-mesenchymal transition and extracellular matrix deposition in renal tissues. In HK-2 cells, irisin treatment markedly attenuated TGF-β1-induced expression of periostin and MMP-2. Irisin treatment also inhibited TGF-β1-induced epithelial-mesenchymal transition, extracellular matrix formation, and inflammatory responses. These protective effects of irisin were abolished by the overexpression of periostin and MMP-2. In summary, irisin treatment can improve UUO-induced renal interstitial fibrosis through the TGF-β1/periostin/MMP-2 signaling pathway, suggesting that irisin may be used for the treatment of renal interstitial fibrosis.
Topics: Animals; Ureteral Obstruction; Fibrosis; Fibronectins; Mice; Matrix Metalloproteinase 2; Signal Transduction; Transforming Growth Factor beta1; Cell Adhesion Molecules; Epithelial-Mesenchymal Transition; Male; Humans; Kidney Diseases; Kidney; Mice, Inbred C57BL; Cell Line; Disease Models, Animal; Periostin
PubMed: 38870184
DOI: 10.1371/journal.pone.0299389 -
American Journal of Physiology.... Jun 2024Biliary atresia (BA) is the leading indication for pediatric liver transplantation. Rhesus rotavirus (RRV) induced murine BA develops an obstructive cholangiopathy that...
Biliary atresia (BA) is the leading indication for pediatric liver transplantation. Rhesus rotavirus (RRV) induced murine BA develops an obstructive cholangiopathy that mirrors the human disease. We have previously demonstrated the "SRL" motif on RRV's VP4 protein binds to heat shock cognate 70 protein (Hsc70) facilitating entry into cholangiocytes. In this study, we analyzed how binding to Hsc70 affects viral endocytosis, intracellular trafficking, and uniquely activates the signaling pathway that induces murine BA. Inhibition of clathrin- and dynamin-mediated endocytosis in cholangiocytes following infection demonstrated blocking dynamin decreased the infectivity of RRV whereas clathrin inhibition had no effect. Blocking early endosome trafficking resulted in decreased viral titers of RRV while late endosome inhibition had no effect. Following infection, TLR3 expression and p-NF-κB levels increased in cholangiocytes, leading to increased release of CXCL9 and CXCL10. Infected mice knocked out for TLR3 had decreased levels of CXCL9 and CXCL10, resulting in reduced NK cell numbers. Human BA patients experienced an increase in CXCL10 levels, suggesting this as a possible pathway leading to biliary obstruction. Viruses that utilize Hsc70 for cell entry exploit a clathrin-independent pathway and traffic to the early recycling endosome uniquely activating NF-κB through TLR3, leading to the release of CXCL9 and CXCL10, and inducing NK cell recruitment. These results define how the "SRL" peptide found on RRV's VP4 protein modulates viral trafficking, inducing the host response leading to bile duct obstruction.
PubMed: 38860860
DOI: 10.1152/ajpgi.00308.2023 -
World Journal of Critical Care Medicine Jun 2024Discerning the etiology of acute kidney injury (AKI) in cirrhotic patients remains a formidable challenge due to diverse and overlapping causes. The conventional... (Review)
Review
Discerning the etiology of acute kidney injury (AKI) in cirrhotic patients remains a formidable challenge due to diverse and overlapping causes. The conventional approach of empiric albumin administration for suspected volume depletion may inadvertently lead to fluid overload. In the recent past, point-of-care ultrasonography (POCUS) has emerged as a valuable adjunct to clinical assessment, offering advantages in terms of diagnostic accuracy, rapidity, cost-effectiveness, and patient satisfaction. This review provides insights into the strategic use of POCUS in evaluating cirrhotic patients with AKI. The review distinguishes basic and advanced POCUS, emphasizing a 5-point basic POCUS protocol for efficient assessment. This protocol includes evaluations of the kidneys and urinary bladder for obstructive nephropathy, lung ultrasound for detecting extravascular lung water, inferior vena cava (IVC) ultrasound for estimating right atrial pressure, internal jugular vein ultrasound as an alternative to IVC assessment, and focused cardiac ultrasound for assessing left ventricular (LV) systolic function and identifying potential causes of a plethoric IVC. Advanced POCUS delves into additional Doppler parameters, including stroke volume and cardiac output, LV filling pressures and venous congestion assessment to diagnose or prevent iatrogenic fluid overload. POCUS, when employed judiciously, enhances the diagnostic precision in evaluating AKI in cirrhotic patients, guiding appropriate therapeutic interventions, and minimizing the risk of fluid-related complications.
PubMed: 38855271
DOI: 10.5492/wjccm.v13.i2.93812 -
Cell Death & Disease Jun 2024The triggering receptor expressed on myeloid cells 2 (TREM2) is an immune receptor that affects cellular phenotypes by modulating phagocytosis and metabolism, promoting...
The triggering receptor expressed on myeloid cells 2 (TREM2) is an immune receptor that affects cellular phenotypes by modulating phagocytosis and metabolism, promoting cell survival, and counteracting inflammation. Its role in renal injury, in particular, unilateral ureteral obstruction (UUO) or ischemia-reperfusion injury (IRI)-induced renal injury remains unclear. In our study, WT and Trem2 mice were employed to evaluate the role of TREM2 in renal macrophage infiltration and tissue injury after UUO. Bone marrow-derived macrophages (BMDM) from both mouse genotypes were cultured and polarized for in vitro experiments. Next, the effects of TREM2 on renal injury and macrophage polarization in IRI mice were also explored. We found that TREM2 expression was upregulated in the obstructed kidneys. TREM2 deficiency exacerbated renal inflammation and fibrosis 3 and 7 days after UUO, in association with reduced macrophage infiltration. Trem2 BMDM exhibited increased apoptosis and poorer survival compared with WT BMDM. Meanwhile, TREM2 deficiency augmented M1 and M2 polarization after UUO. Consistent with the in vivo observations, TREM2 deficiency led to increased polarization of BMDM towards the M1 proinflammatory phenotype. Mechanistically, TREM2 deficiency promoted M1 and M2 polarization via the JAK-STAT pathway in the presence of TGF-β1, thereby affecting cell survival by regulating mTOR signaling. Furthermore, cyclocreatine supplementation alleviated cell death caused by TREM2 deficiency. Additionally, we found that TREM2 deficiency promoted renal injury, fibrosis, and macrophage polarization in IRI mice. The current data suggest that TREM2 deficiency aggravates renal injury by promoting macrophage apoptosis and polarization via the JAK-STAT pathway. These findings have implications for the role of TREM2 in the regulation of renal injury that justify further evaluation.
Topics: Animals; Apoptosis; Macrophages; Receptors, Immunologic; Membrane Glycoproteins; Mice; Signal Transduction; STAT Transcription Factors; Mice, Inbred C57BL; Janus Kinases; Kidney; Mice, Knockout; Male; Fibrosis; Reperfusion Injury; Ureteral Obstruction; Cell Polarity; TOR Serine-Threonine Kinases; Acute Kidney Injury
PubMed: 38849370
DOI: 10.1038/s41419-024-06756-w -
Southern African Journal of Infectious... 2024HIV patients frequently develop acute kidney injury (AKI) because of sepsis and diarrhoeal disease. Here, we report a case of an HIV-positive man with partially treated...
UNLABELLED
HIV patients frequently develop acute kidney injury (AKI) because of sepsis and diarrhoeal disease. Here, we report a case of an HIV-positive man with partially treated sinonasal plasmablastic lymphoma (PBL) and unexplained AKI. A kidney biopsy revealed two pathological processes.
CONTRIBUTION
While urinary tract obstruction is the most common mechanism by which PBL causes AKI, maintaining a high level of suspicion for multiple pathological processes in cases involving light chain producing PBL.
PubMed: 38841341
DOI: 10.4102/sajid.v39i1.637