Pathophysiology : the official journal of the International Society for Pathophysiology最新文献

{"title":"Reduced Shear Stress and Longer Blood Flow Time Occur in Both Severe Focal and Mild Diffuse LAD Lesions: Angiograms Alone Don't Always Reveal Their True Impact on Blood Flow.","authors":"Gianluca Rigatelli, Marco Zuin, Niva Mileva, Dobrin Vassilev, Giuseppe Marchese, Ervis Hiso, Andrea Bertolini, Claudio Bilato","doi":"10.3390/pathophysiology32020028","DOIUrl":"10.3390/pathophysiology32020028","url":null,"abstract":"<p><p><b>Background/Objectives:</b> The similarities and differences from a rheological perspective between significant short focal and mild long coronary lesions warrant investigation to elucidate wall shear stress (WSS) angiographic discrepancies. <b>Methods</b>: Patients who underwent coronary computed tomography angiography (CCTA) between 1 January 2023 and 1 September 2024 were selected for computational fluid dynamics (CFD) analysis. The selection criteria included either a focal (≤20 mm) hemodynamically significant stenosis, defined as ≥75% lumen narrowing, or a long (30-40 mm) non-hemodynamically significant lesion showing ≤50% stenosis of the left anterior descending (LAD) artery. Patient-specific models were reconstructed from ECG-gated CCTA images. Wall shear stress (WSS, measured in Pascals) and residence time (RT) were evaluated for each patient. <b>Results</b>: The LAD arteries of 30 patients (mean age 54 years, 63.3% men) were evaluated: 16 with focal, hemodynamically significant coronary stenosis, while 14 with diffuse, long, non-hemodynamically significant coronary lesions. Both groups exhibited a lower mean WSS compared to the non-stenosed segment, with no significant difference in mean WSS between the two groups (<i>p</i> = 0.84). Conversely, both groups demonstrated a higher mean residence time (RT) compared to the non-stenosed segments (0.2 ± 0.06 vs. 0.60 ± 0.03, <i>p</i> < 0.001 and 0.2 ± 0.006 vs. 0.59 ± 0.02, <i>p</i> < 0.001, respectively), and no significant difference in mean RT (<i>p</i> = 0.82). <b>Conclusions</b>: Long, angiographically mild coronary stenoses show similar WSS and RT characteristics compared to short hemodynamically significant coronary stenosis.</p>","PeriodicalId":520741,"journal":{"name":"Pathophysiology : the official journal of the International Society for Pathophysiology","volume":"32 2","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12196448/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144487756","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Slow Hydrogen Sulfide Donor GYY-4137 Partially Improves Vascular Function in Spontaneously Hypertensive Rats Fed a High-Fat Diet.","authors":"Basak G Aydemir, Andrea Berenyiova, Martina Cebova, John D Henderson, Andrej Barta, Sona Cacanyiova","doi":"10.3390/pathophysiology32020027","DOIUrl":"10.3390/pathophysiology32020027","url":null,"abstract":"<p><strong>Background/objectives: </strong>Metabolic syndrome is one of the leading causes of mortality worldwide, with high-fat diet (HFD) intake being a significant driving force. Despite long-term research, new interventions are still being sought to improve cardiovascular disorders associated with metabolic syndrome.</p><p><strong>Methods: </strong>To explore the therapeutic potential of a slow-releasing H₂S donor, we evaluated the effects of 3 weeks of treatment with GYY-4137 on systolic blood pressure (sBP), cardiac parameters, adiposity, selected plasma markers, and the vascular function of the thoracic aortas (TAs) and mesenteric arteries (MAs) isolated from male spontaneously hypertensive rats (SHRs) fed an HFD for 8 weeks.</p><p><strong>Results: </strong>HFD administration induced cardiac remodeling, increased adiposity, and decreased adrenergic contractility in both TAs and MAs. Moreover, although high-fat intake improved TAs relaxation, it decreased aortic protein expression of endothelial NO synthase and the involvement of NO in vasoactive responses of both TAs and MAs. In addition, protein expression of inducible NOS and tumor necrosis factor alpha (TNFα) in aortas was increased, as were plasma levels of chemerin, which has been proposed as a possible link among metabolic and vascular disorders and inflammation. Treatment with GYY-4137 reduced sBP, improved relaxation of the MAs, partially restored the contractility of the TAs, generally restored NO signaling, and decreased the protein expression of the inducible NOS and TNFα, as well as plasma chemerin levels.</p><p><strong>Conclusions: </strong>A slow H₂S-releasing donor could partially ameliorate the metabolic changes induced by increased fat intake during essential hypertension and trigger beneficial vasoactive effects associated with the NO signaling restoration and suppression of inflammation.</p>","PeriodicalId":520741,"journal":{"name":"Pathophysiology : the official journal of the International Society for Pathophysiology","volume":"32 2","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12196443/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144487751","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Linking Lipid Metabolism and Immune Function: New Insights into Chronic Respiratory Diseases.","authors":"Stanislav Kotlyarov","doi":"10.3390/pathophysiology32020026","DOIUrl":"10.3390/pathophysiology32020026","url":null,"abstract":"<p><p>Lipids play important roles in maintaining pulmonary structure, performing physiological functions and controlling the immune status of the lung. There is increasing evidence that lipid metabolism and immune activity are closely linked and that dysfunction in lipid metabolism contributes to the development and progression of chronic respiratory diseases such as COPD and asthma. These diseases are characterized by metabolic and immune dysregulation, with lipid mediators playing a key role in both the development and resolution of inflammation. In this regard, lipid metabolic pathways are attracting increasing attention as promising targets for biomarker detection and therapeutic intervention.</p>","PeriodicalId":520741,"journal":{"name":"Pathophysiology : the official journal of the International Society for Pathophysiology","volume":"32 2","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12195652/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144487755","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Rare Case of Paired Congenital Cervical Aneurysms in a Communicating Vein: Clinical and Imaging Findings in a Pediatric Patient.","authors":"Grigol Keshelava, Zurab Robakidze, Igor Mikadze","doi":"10.3390/pathophysiology32020025","DOIUrl":"10.3390/pathophysiology32020025","url":null,"abstract":"<p><p>A four-year-old female patient was admitted for evaluation after a mass on the right side of her neck was noticed during straining (Valsalva maneuver). The family first observed the mass when the patient was one year old, and noted that it gradually increased in size over time. A family history assessment revealed no known genetic disorders. The patient underwent neck ultrasonography and computed tomography angiography (CTA), which revealed two aneurysms in a right-sided communicating vein. One aneurysm was located above the jugular notch, and the other was located in the retro-parotid region. The presence of two venous aneurysms in a right-sided communicating vein-one above the jugular notch and the other in the retro-parotid region-suggests a rare and apparently benign congenital anomaly. The progressive enlargement of these malformations warrants close monitoring and surgical intervention, and long-term follow-up may be necessary to prevent complications such as thrombosis, rupture, or compression of adjacent structures.</p>","PeriodicalId":520741,"journal":{"name":"Pathophysiology : the official journal of the International Society for Pathophysiology","volume":"32 2","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12196471/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144487750","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Histochemical Assessment of Reticulin-Collagen Patterns in the Mid-Secretory Endometrium Predicts Recurrent Pregnancy Loss.","authors":"Nazerke Oshakhtiyeva, Dmitriy Klyuyev, Zhanna Amirbekova, Rinat Gatin, Anar Turmukhambetova, Kamilya Makhambetova, Irina Kadyrova, Yevgeniy Kamyshanskiy","doi":"10.3390/pathophysiology32020024","DOIUrl":"10.3390/pathophysiology32020024","url":null,"abstract":"<p><strong>Background/objectives: </strong>Normal remodeling of the extracellular matrix of the endometrium is a necessary condition for the implantation of a blastocyst. We evaluated whether the use of histochemical reticulin-collagen staining can improve the assessment of the extracellular matrix of the mid-secretory endometrium in recrudescent clinical/biochemical pregnancy losses in comparison with ultrasound and routine histological examination.</p><p><strong>Methods: </strong>We compared the histochemical pattern of reticulin-collagen endometrial biopsy (21st day of the cycle) with ultrasonography and standard histological examination of the endometrium in the following groups: (1) fertile women with gravidity ≥ 2, (gravidity = parity) and (2) women with two or more clinical/biochemical pregnancy losses.</p><p><strong>Results: </strong>A normal pattern (NP) with ordered reticulin fibers forming cellular structures was determined in 92% of biopsies with physiological reproductive status and 44% of biopsies with recrudescent reproductive failure (<i>p</i> < 0.05), despite the fact that there were no differences in ultrasonography and standard histological examination between the groups (<i>p</i> > 0.05). A histochemical pattern of insufficient secretory endometrial transformation with abnormal noodle-like pattern (aNP) collagen fibers was more common in recrudescent reproductive failure (56%) than in women with physiological reproductive status (8%) (<i>p</i> < 0.001), despite the fact that insufficient secretory endometrial transformation with an abnormal noodle-like pattern with collagenization (aNPC) was detected only in recrudescent reproductive failure, and it was not detected in women with physiological reproductive status (<i>p</i> < 0.00001).</p><p><strong>Conclusions: </strong>We determined the histochemical pattern of the extracellular matrix of the endometrium in terms of the type of reticulin-collagen, associated in our study with recrudescent clinical/biochemical pregnancy loss, with improved predictability compared to ultrasonography and standard histological examination. We propose to use the method of histochemical evaluation of the reticulin-collagen pattern in order to stratify groups of women of fertile age at risk of reproductive failure.</p>","PeriodicalId":520741,"journal":{"name":"Pathophysiology : the official journal of the International Society for Pathophysiology","volume":"32 2","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12196194/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144487754","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Elevated Zinc and Potassium Levels in Renal Calculi Indicate Distinct Pathophysiological Mechanisms in Urolithiasis.","authors":"Maciej Jaromin, Marcin Cichocki, Tomasz Konecki, Piotr Kutwin, Waldemar Maniukiewicz, Piotr Wysocki, Magdalena Gajek, Małgorzata Iwona Szynkowska-Jóźwik, Dariusz Moczulski","doi":"10.3390/pathophysiology32020023","DOIUrl":"10.3390/pathophysiology32020023","url":null,"abstract":"<p><strong>Background/objectives: </strong>Urolithiasis is a common disease in Western societies, affecting approximately 10% of the population, and more often men than women. The formation of renal calculi is a complex process, including various compounds and proteins. The aim of this study is to compare differences between the trace element concentrations in male and female renal calculi as well as differences between the trace element concentrations in different stone types.</p><p><strong>Material and methods: </strong>Renal calculi specimens were obtained during elective nephrolithotripsy procedures. Crystallography of renal calculi was performed using X-ray diffraction; an elemental analysis was performed using Inductively Coupled Plasma-Optical Emission Spectrometry. Statistical analysis was performed to assess the differences in the metal element concentration between men and women. The second part of the analysis measured the differences in the metal element concentration between stones containing calcium phosphate (CaP) and pure calcium oxalate (CaOx) stones.</p><p><strong>Results: </strong>The renal calculi (<i>n</i> = 20) obtained from the male patients had a lower potassium concentration than the calculi (<i>n</i> = 24) from the female patients: 393.4 vs. 792.3 mg/kg, <i>p</i> = 0.007. A comparison of the CaP calculi and CaOx calculi showed a higher zinc concentration (<i>p</i> < 0.001) and potassium concentration (<i>p</i> < 0.001) in the stones containing calcium phosphate.</p><p><strong>Conclusions: </strong>The renal calculi from females had a significantly higher potassium content than those from males. This difference was not correlated with hyperkalemia or the blood potassium levels, suggesting a sex-dependent role of uromodulin in stone formation. The stones containing calcium phosphate exhibited higher zinc and potassium concentrations compared to the pure calcium oxalate stones. The increased presence of zinc and potassium in urine may accelerate the formation of calcium phosphate calculi.</p>","PeriodicalId":520741,"journal":{"name":"Pathophysiology : the official journal of the International Society for Pathophysiology","volume":"32 2","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12196489/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144487752","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Fibrillary Glomerulonephritis Diagnosis Is Enhanced by DNAJB9: Three Cases with Different Clinical, Anatomopathologic Features and Outcomes.","authors":"José C De La Flor, Marco Dominguez Davalos, Tania Linares Grávalos, Marina Alonso-Riaño, Francisco Díaz, Celia Rodríguez Tudero, Rocío Zamora González-Mariño, Michael Cieza Terrones, Jesús Hernández Vaquero","doi":"10.3390/pathophysiology32020022","DOIUrl":"10.3390/pathophysiology32020022","url":null,"abstract":"<p><p><b>Background:</b> Fibrillary glomerulonephritis (FGN) is a rare and poorly understood kidney disease characterized by the deposition of non-amyloid fibrils in the glomeruli. Its clinical heterogeneity and high rate of progression to end-stage renal disease (ESRD) pose significant diagnostic and therapeutic challenges. This case series aims to enhance awareness of FGN and emphasizes the need for further research to improve patient outcomes. <b>Case Reports:</b> We reviewed the clinical, histopathological, and therapeutic data of three patients with FGN diagnosed by kidney biopsy. The cases included variations in clinical presentation from nephrotic syndrome to rapidly progressive glomerulonephritis (RPGN). Diagnostic methods incorporated light microscopy, immunofluorescence, and electron microscopy, with the integration of DnaJ homolog subfamily B member 9 (DNAJB9) staining for confirmation. Patient 1 showed a more favorable response to rituximab, achieving complete remission (CR) at 6 months and maintaining CR after 3 years. Patient 2 showed only partial remission after 2 years following treatment with rituximab. Patient 3 presented with RPGN and rapidly progressed to ESRD despite aggressive immunosuppressive therapy. <b>Discussion:</b> DNAJB9 has emerged as both a specific and sensitive biomarker in patients with FGN and has facilitated accurate differentiation from other glomerulopathies. This series underscores the variability in clinical outcomes and responses to therapy as well as the importance of early and accurate diagnosis. <b>Conclusions</b>: FGN remains a diagnostic and therapeutic challenge due to its rarity and heterogeneity. Advances in biomarkers like DNAJB9 have improved diagnostic accuracy, distinguishing FGN from similar conditions such as immunotactoid glomerulopathy. Further research into pathophysiological mechanisms and targeted therapies is essential to optimize management and outcomes for affected patients.</p>","PeriodicalId":520741,"journal":{"name":"Pathophysiology : the official journal of the International Society for Pathophysiology","volume":"32 2","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-05-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12195910/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144487753","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Vitamin D Serum Levels and the Development of Intensive Care Unit-Acquired Weakness: Insights from a COVID-19 Intensive Care Cohort.","authors":"Jelena Gulišija, Vesna Čapkun, Stefan Golic, Sanda Stojanović Stipić","doi":"10.3390/pathophysiology32020021","DOIUrl":"10.3390/pathophysiology32020021","url":null,"abstract":"<p><p><b>Background/Objectives</b>: The pathogenesis of intensive care unit-acquired weakness (ICU-AW) is multi-factorial, with some of the main risk factors being sepsis, multiorgan failure, and the inflammatory response related to critical illness. Vitamin D is crucial for muscle function, the immune response, and inflammation, and has been identified as a predictor of negative outcomes in intensive care unit (ICU) patients with COVID-19. The objective of this preliminary study was to examine the relationship between vitamin D serum levels and the incidence of ICU-AW in a cohort from the University Hospital of Split. <b>Methods</b>: A prospective observational cohort study was conducted in the University Hospital of Split in ICU from December 2021 to March 2022. The inclusion criteria were as follows: patients over 18 years old who had a confirmed severe acute respiratory coronavirus disease 2 (SARS-CoV-2) infection, patients who were mechanically ventilated for more than 48 h, and patients who were weaned from a ventilator over at least 24 h. The exclusion criteria were a history of neurological or musculoskeletal disorders and a pre-existing poor functional status. Vitamin D was detected in the first routine blood sample. <b>Results</b>: A total of 77 patients were observed, with 36 patients who were successfully weaned from a ventilator over at least 24 h and 1 patient who could not be examined because of impaired consciousness (this patient was excluded from further analysis), and thus a total of 35 patients were analyzed. Of these 35 patients, 12 (34%) developed ICU-AW. The median vitamin D serum level in the ICU-AW group was 17 (7.5-73.3), while that in the non-ICU-AW group was 25.2 (12.3-121). The difference in vitamin D serum levels between the groups was not significantly different from zero (<i>p</i> = 0.567). All patients, except for one, were vitamin D insufficient. <b>Conclusions</b>: Vitamin D serum levels in the ICU-AW group were not statistically different from the non-ICU-AW group, possibly due to the small sample size. Given the known roles of vitamin D in muscle function, immune modulation, and inflammation, a potential etiopathogenetic role in ICU-AW cannot be excluded without additional studies. Therefore, further studies with larger sample sizes than ours are necessary to determine whether vitamin D deficiency contributes to the development of ICU-AW and whether supplementation could have preventive or therapeutic value.</p>","PeriodicalId":520741,"journal":{"name":"Pathophysiology : the official journal of the International Society for Pathophysiology","volume":"32 2","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12101332/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144130040","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Resting State of Dementia of the Alzheimer's Type and Healthy Older Adults Using fNIRS.","authors":"In-Sop Kim, Jaejin Hwang, Chorong Oh, Richard J Morris","doi":"10.3390/pathophysiology32020020","DOIUrl":"10.3390/pathophysiology32020020","url":null,"abstract":"<p><strong>Background/objectives: </strong>This study explores variations in brain activity between individuals with dementia of the Alzheimer's type (DAT) and healthy older adults during a resting state using functional near-infrared spectroscopy (fNIRS).</p><p><strong>Methods: </strong>FNIRS measured brain activity in ten AD patients and six healthy individuals. A device with 16 channels was placed on each participant's forehead to measure oxygenation levels while they kept their eyes closed. The data were analyzed using a support vector machine (SVM) model.</p><p><strong>Results: </strong>The results indicated differences in oxygenated hemoglobin (HbO) levels between the two groups. Specifically, HbO levels were generally higher in the dementia group in the left hemisphere, with a sharp increase after 26 s. Conversely, HbO levels were consistently lower in the right hemisphere of the dementia group. The SVM analysis demonstrated high accuracy in differentiating between the AD and healthy groups based on HbO levels.</p><p><strong>Conclusions: </strong>The study indicates that differences in brain activity during resting state can potentially distinguish people with DAT from healthy individuals. We found relatively reduced hemoglobin activity in the prefrontal areas of those with DAT. Furthermore, the concentration changes in the HbO in the left lateral prefrontal and right medial brain regions emerged as the most informative in distinguishing individuals with DAT from healthy individuals. The results of the current study show that this method could improve current DAT diagnostic practices due to its efficiency.</p>","PeriodicalId":520741,"journal":{"name":"Pathophysiology : the official journal of the International Society for Pathophysiology","volume":"32 2","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12101204/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144130069","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Therapeutic Efficacy of Mesenchymal Stem Cells in Modulating Oxidative Stress in Puromycin-Induced Nephropathy.","authors":"Yusuke Iizuka, Masanori Sasaki, Kojiro Terada, Takuro Sakai, Yoshinobu Nagaoka, Shinobu Fukumura, Jeffery D Kocsis, Takeshi Tsugawa, Osamu Honmou","doi":"10.3390/pathophysiology32020019","DOIUrl":"10.3390/pathophysiology32020019","url":null,"abstract":"<p><p><b><i>Background:</i></b> Podocytes are essential for kidney function, and their dysfunction can result in nephrotic syndrome, such as minimal change disease (MCD). Oxidative stress contributes to podocyte damage. We investigated the therapeutic potential of intravenously infused mesenchymal stem cells (MSCs) in a puromycin aminonucleoside (PAN)-induced rodent MCD model, focusing on oxidative stress modulation. <b><i>Methods:</i></b> Sprague-Dawley rats were divided into three groups: intact, PAN-Vehicle, and PAN-MSC. MCD was induced through subcutaneous PAN injection. MSCs were infused intravenously in the PAN-MSC group on day 7. Urinary albumin, serum albumin, and creatinine levels were assessed. Histological analysis of the renal cortex was performed. Podocyte protein (NPHS1, NPHS2, and PODXL) and antioxidant enzyme (SOD1, SOD2, and GPX1) levels were measured using quantitative real-time reverse-transcription PCR (qRT-PCR). <b><i>Results:</i></b> MSC infusion significantly reduced proteinuria and restored podocyte structure in the PAN-MSC group. Electron microscopy revealed that infused MSCs could inhibit the fusion of the foot process induced by PAN injection. qRT-PCR showed that intravenous infusion of MSCs rescued the inhibition of GPX1 expression. GFP-labeled MSCs accumulated at the podocyte injury sites. <b><i>Conclusion:</i></b> Systemic MSC infusion mitigates PAN-induced MCD by reducing proteinuria, preserving podocyte structure, and modulating oxidative stress via the GPX1 pathway, offering a potential therapeutic approach for nephrotic syndrome.</p>","PeriodicalId":520741,"journal":{"name":"Pathophysiology : the official journal of the International Society for Pathophysiology","volume":"32 2","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12101160/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144130070","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}