International Journal of Immunopathology and Pharmacology最新文献

{"title":"CXC ligand 13 orchestrates an immunoactive microenvironment and enhances immunotherapy response in head and neck squamous cell carcinoma.","authors":"Xiaohu Lin, Xiaomei Zhao, Yiming Chen, Rong Yang, Zhenlin Dai, Wei Li, Chengzhong Lin, Wei Cao","doi":"10.1177/03946320241227312","DOIUrl":"10.1177/03946320241227312","url":null,"abstract":"<p><p><i>Objectives</i>: This study aims to systematically explore the role of chemokine CXC ligand 13 (CXCL13) in head and neck squamous cell carcinoma (HNSCC). <i>Methods</i>: The Genotype-Tissue Expression (GTEx) and The Cancer Genome Atlas (TCGA) databases provided the RNA-seq data for cancer and normal tissues, respectively. Gene set enrichment analysis was applied to search the cancer hallmarks associated with CXCL13 expression. TIMER2.0 was the main platform used to investigate the immune cell infiltration related to CXCL13. Immunohistochemistry was applied to explore the relationship between CXCL13 and patients' prognosis and the relationship between CXCL13 and tertiary lymphoid structures (TLSs). <i>Results</i>: The expression of CXCL13 was upregulated in most tumors, including HNSCC. The higher expression of CXCL13 was closely related to the positive prognosis of HNSCC. CXCL13 was mainly expressed in B cells and CD8 + T cells, revealing the relationship between its expression and immune activation in the tumor microenvironment. Furthermore, immunohistochemistry and multiple fluorescence staining analysis of HNSCC samples showed a powerful correlation between CXCL13 expression, TLSs formation, and positive prognosis. Finally, CXCL13 significantly increased the response to cancer immunotherapy. <i>Conclusions</i>: CXCL13 may function as a potential biomarker for predicting prognosis and immunotherapy response and associate with TLSs in HNSCC.</p>","PeriodicalId":48647,"journal":{"name":"International Journal of Immunopathology and Pharmacology","volume":null,"pages":null},"PeriodicalIF":3.5,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10807398/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139522193","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The use of inhibition assay in Api g 7 suspected allergy in a female patient with anaphylaxis: A case report.","authors":"Natalia Ukleja-Sokołowska, Kinga Lis, Małgorzata Graczyk, Marcelina Bartuzi, Zbigniew Bartuzi","doi":"10.1177/03946320231223004","DOIUrl":"10.1177/03946320231223004","url":null,"abstract":"<p><p>The symptoms of celery allergy are mainly presented as oral allergy symptom, but there are several case reports of patients who experienced anaphylaxis. Defensin (Api g 7), as a novel allergen in celery root, was described in 2022 r. The female patient had a history of several episodes of dyspnea and cough, associated with ingestion of spice mixes containing dried celery. Up to the point of hospitalization, there were no objective tests, either sIgE or skin prick tests, that would confirm celery sensitization. During hospitalization, patient had a positive double-blind placebo-controlled food challenge with cooked celery. The patient was sensitized to mugwort defensin Art v 1. An inhibition assay with celery allergen extract was performed to prove cross-sensitization between Art v 1 and celery allergen responsible for symptoms in the patient. In conclusion, Api g 7 is an important celery allergen that can be responsible for severe reactions. Its cross-reactivity with Art v 1 is characteristic. Negative diagnostic tests with celery do not exclude Api g 7 sensitization.</p>","PeriodicalId":48647,"journal":{"name":"International Journal of Immunopathology and Pharmacology","volume":null,"pages":null},"PeriodicalIF":3.5,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10788074/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139467151","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Icariin protects testicular damage in streptozotocin-induced diabetic rats through regulation of glycolysis pathway.","authors":"Fang Liu, Biyun Liao, Yan-Lan Ling, Xian-Zong Meng, Jun-Li Wang, Lin-Lin Hu, Xiao-Qiong Luo, Feng-Lian Yang","doi":"10.1177/03946320241279525","DOIUrl":"10.1177/03946320241279525","url":null,"abstract":"<p><strong>Objective: </strong>This study aims to investigate potential beneficial actions of icariin (ICA) on testicular spermatogenic function in male rats with streptozotocin (STZ)-induced diabetes and to explore the underlying mechanisms. <b>Background:</b> ICA was found to reduce blood glucose, regulate the endocrine function of the reproductive system, and improve testicular spermatogenic function.</p><p><strong>Methods: </strong>Adult rats were intraperitoneally injected with STZ (65 mg/kg) to induce type 1 diabetes mellitus (T1DM). Diabetic rats were randomly classified intoT1DM (<i>n</i> = 6) and T1DM + ICA (<i>n</i> = 6) groups. Rats without STZ and ICA treatment were assigned as control group (<i>n</i> = 6). The morphology of testicular tissues was examined by histological staining. The mRNA and protein expression levels were determined by quantitative real-time PCR, Western blot and immunostaining, respectively.</p><p><strong>Results: </strong>Rats from T1DM group showed a reduction in epididymis and testis weight, and a decrease in sperm count when compared to control group (<i>p</i> < 0.01), which was attenuated by ICA treatment (<i>p</i> < 0.05) Diabetic rats from T1DM group also exhibited reduced diameter and area of seminiferous tubules, along with decreased spermatogonia and primary spermatocytes number when compared to control group (<i>p</i> < 0.01), which was partially reversed by ICA treatment (<i>p</i> < 0.05) Rats from T1DM group exhibited down-regulation of PCNA mRNA and protein in the testis when compared to control group (<i>p</i> < 0.01); while ICA treatment up-regulated PCNA expression in the testis of diabetic rats compared to T1DM group (<i>p</i> < 0.05). Rats from T1DM group showed up-regulation of Bax and capase-3 and down-regulation of Bcl-2, PKM2, HK2 and lactate dehydrogenase A in the testes when compared to control group (<i>p</i> < 0.05), which was reversed by ICA treatment (<i>p</i> < 0.05).</p><p><strong>Conclusion: </strong>These findings suggest that ICA may exert its protective effects on testicular damage in diabetic rats through modulation of glycolysis pathway and suppression of apoptosis.</p>","PeriodicalId":48647,"journal":{"name":"International Journal of Immunopathology and Pharmacology","volume":null,"pages":null},"PeriodicalIF":3.5,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11344256/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142047350","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Resection of extensive segments of inferior vena cava without reconstruction in the treatment of renal carcinoma with inferior vena cava tumor thrombus: A case report.","authors":"Kun Shang, Changjiu Li, Jun Chen, Ning Li, Huadong He","doi":"10.1177/03946320241272549","DOIUrl":"10.1177/03946320241272549","url":null,"abstract":"<p><p>We present a 55-year-old male patient with right renal carcinoma with long inferior vena cava (IVC) tumor thrombus who underwent robot-assisted laparoscopic radical nephrectomy with extensive IVC resection and left renal vein ligation. The patient had a history of hematuria only prior to admission. Our case involved resection of the entire abdominal segment of the IVC and left renal vein without reconstruction. Unfortunately, the patient passed away over a year after the surgery due to brain metastasis.</p>","PeriodicalId":48647,"journal":{"name":"International Journal of Immunopathology and Pharmacology","volume":null,"pages":null},"PeriodicalIF":3.5,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11301719/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141894667","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Revealing the potential of solute carrier family 31 (copper transporters), member 1: Insights into its role in bladder cancer progression and therapeutic implications.","authors":"Yun-Zhi Lin, Wei-Hui Liu, Yu-Peng Wu, Hai Cai, Qing-Shui Zheng, Yong Wei, Ning Xu, Xue-Yi Xue","doi":"10.1177/03946320241240706","DOIUrl":"10.1177/03946320241240706","url":null,"abstract":"<p><p><b>Introduction:</b> Bladder cancer represents a significant public health concern with diverse genetic alterations influencing disease onset, progression, and therapy response. In this study, we explore the multifaceted role of Solute Carrier Family 31 Member 1 (SLC31A1) in bladder cancer, a pivotal gene involved in copper homeostasis. <b>Methods:</b> Our research involved analyzing the SLC31A1 gene expression via RT-qPCR, promoter methylation via targeted bisulfite sequencing, and mutational status via Next Generation Sequencing (NGS) using the clinical samples sourced by the local bladder cancer patients. Later on, The Cancer Genome Atlas (TCGA) datasets were utilized for validation purposes. Moreover, prognostic significance, gene enrichment terms, and therapeutic drugs of SLC31A1 were also explored using KM Plotter, DAVID, and DrugBank databases. <b>Results:</b> We observed that SLC31A1 was significantly up-regulated at both the mRNA and protein levels in bladder cancer tissue samples, suggesting its potential involvement in bladder cancer development and progression. Furthermore, our investigation into the methylation status revealed that SLC31A1 was significantly hypomethylated in bladder cancer tissues, which may contribute to its overexpression. The ROC analysis of the SLC31A1 gene indicated promising diagnostic potential, emphasizing its relevance in distinguishing bladder cancer patients from normal individuals. However, it is crucial to consider other factors such as cancer stage, metastasis, and recurrence for a more accurate evaluation in the clinical context. Interestingly, mutational analysis of SLC31A1 demonstrated only benign mutations, indicating their unknown role in the SLC31A1 disruption. In addition to its diagnostic value, high SLC31A1 expression was associated with poorer overall survival (OS) in bladder cancer patients, shedding light on its prognostic relevance. Gene enrichment analysis indicated that SLC31A1 could influence metabolic and copper-related processes, further underscoring its role in bladder cancer. Lastly, we explored the DrugBank database to identify potential therapeutic agents capable of reducing SLC31A1 expression. Our findings unveiled six important drugs with the potential to target SLC31A1 as a treatment strategy. <b>Conclusion:</b> Our comprehensive investigation highlights SLC31A1 as a promising biomarker for bladder cancer development, progression, and therapy.</p>","PeriodicalId":48647,"journal":{"name":"International Journal of Immunopathology and Pharmacology","volume":null,"pages":null},"PeriodicalIF":3.5,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11080779/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140855592","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Gemcitabine and synthesized silver nanoparticles impact on chemically induced hepatocellular carcinoma in male rats.","authors":"Mohamed R Mohamed, Soheir A Osman, Asmaa A Hassan, Amany I Raafat, Mahmoud M Refaat, Shadia A Fathy","doi":"10.1177/03946320241263352","DOIUrl":"10.1177/03946320241263352","url":null,"abstract":"<p><p><b>Objective:</b> Gemcitabine (GEM) is a deoxycytidine analog chemotherapeutic drug widely used to treat many cancers. Silver nanoparticles (AgNPs) are important nanomaterials used to treat many diseases. Using gamma radiation in nanoparticle preparation is a new eco-friendly method. This study aims to evaluate the efficiency of co-treating gemcitabine and silver nanoparticles in treating hepatocellular carcinoma. <b>Method:</b> The AgNPs were characterized using UV-visible spectroscopy, XRD, TEM, and EDX. The MTT cytotoxicity in vitro assay of gemcitabine, doxorubicin, and cyclophosphamide was assessed against Wi38 normal fibroblast and HepG2 HCC cell lines. After HCC development, rats received (10 µg/g b.wt.) of AgNPs three times a week for 4 weeks and/or GEM (5 mg/kg b.wt.) twice weekly for 4 weeks. Liver function enzymes were investigated. Cytochrome P450 and miR-21 genes were studied. Apoptosis was determined by using flow cytometry, and apoptotic modifications in signaling pathways were evaluated via Bcl-2, Bax, Caspase-9, and SMAD-4. <b>Results:</b> The co-treatment of GEM and AgNPs increased apoptosis by upregulating Bax and caspase 9 while diminishing Bcl2 and SMAD4. It also improved cytochrome P450 m-RNA relative expression. The results also proved the cooperation between GEM and AgNPs in deactivating miR21. The impact of AgNPs as an adjuvant treatment with GEM was recognized. <b>Conclusions:</b> The study showed that co-treating AgNPs and GEM can improve the efficiency of GEM alone in treating HCC. This is achieved by enhancing intrinsic and extrinsic apoptotic pathways while diminishing some drawbacks of using GEM alone.</p>","PeriodicalId":48647,"journal":{"name":"International Journal of Immunopathology and Pharmacology","volume":null,"pages":null},"PeriodicalIF":3.5,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11271163/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141753062","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Flavone attenuates nicotine-induced lung injury in rats exposed to gamma radiation via modulating PI3K/Nrf2 and FoxO1/NLRP3 inflammasome.","authors":"Nora A Elsayed, Mohammed A Marzouk, Fatma Sm Moawed, Esraa Sa Ahmed, Omayma Ar Abo-Zaid","doi":"10.1177/03946320241272642","DOIUrl":"10.1177/03946320241272642","url":null,"abstract":"<p><p>Prolonged exposure to different occupational or environmental toxicants triggered oxidative stress and inflammatory reactions mediated lung damage. This study was designed to explore the influence and protective impact of flavone on lung injury in rats intoxicated with nicotine (NIC) and exposed to radiation (IR). Forty rats were divided into four groups; group I control, group II flavone; rats were administered with flavone (25 mg/kg/day), group III NIC + IR; rats were injected intraperitoneally with NIC (1 mg/kg/day) and exposed to γ-IR (3.5 Gy once/week for 2 weeks) while group IV NIC + IR + flavone; rats were injected with NIC, exposed to IR and administered with flavone. Redox status parameters and histopathological changes in lung tissue were evaluated. Nuclear factor-kappa B (NF-κB), forkhead box O-class1 (FoxO1) and nucleotide-binding domain- (NOD-) like receptor pyrin domain-containing-3 (NLRP3) gene expression were measured in lung tissues. Moreover, nuclear factor (erythroid-derived 2)-like 2 (Nrf2) and phosphatidylinositol three kinase (PI3K) were measured using ELISA kits. Our data demonstrates, for the first time, that flavone protects the lung from NIC/IR-associated cytotoxicity, by attenuating the disrupted redox status and aggravating the antioxidant defence mechanism via activation of the PI3K/Nrf2. Moreover, flavone alleviates pulmonary inflammation by inhibiting the inflammatory signaling pathway FOXO1/NF-κB/NLRP3- Inflammasome. Collectively, the obtained results exhibited a notable efficiency of flavone in alleviating lung injury induced by NIC and IR via modulating PI3K/Nrf2 and FoxO1/NLRP3 Inflammasome.</p>","PeriodicalId":48647,"journal":{"name":"International Journal of Immunopathology and Pharmacology","volume":null,"pages":null},"PeriodicalIF":3.5,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11298058/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141890630","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Immunomodulatory effects of the induced pluripotent stem cells through expressing IGF-related factors and IL-10 in vitro.","authors":"Paria Bayati, Marjan Taherian, Nazanin Mojtabavi","doi":"10.1177/03946320241276899","DOIUrl":"10.1177/03946320241276899","url":null,"abstract":"<p><strong>Background: </strong>Induced Pluripotent Stem Cells (IPSCs) represent an innovative strategy for addressing challenging diseases, including various rheumatologic conditions. Aside from their regenerative capacities, some studies have shown the potential of these cells in the modulation of inflammatory responses. The underlying mechanisms by which they exert their effects have yet to be fully comprehended. Therefore, we aimed to explore the gene expression linked to the IGF pathway as well as IL-10 and TGF-β, which are known to exert immunomodulatory effects.</p><p><strong>Methods: </strong>A C57/Bl6 pregnant mouse was used for obtaining mouse embryonic fibroblasts (MEFs), then the IPSCs were induced using lentiviral vectors expressing the pluripotency genes (OCT4, SOX2, KLF1, and c-MYC). Cells were cultured for 72 h in DMEM high glucose plus leukemia inhibitory factor; Evaluating the gene expression was conducted using specific primers for Igf1, Igf2, Igfbp3, Igfbp4, Irs1, Il-10, and Tgf-β genes, as well as SYBR green qPCR master mix. The data were analyzed using the 2^-ΔΔCT method and were compared by employing the <i>t</i> test; the results were plotted using GraphPad PRISM software. MEFs were utilized as controls.</p><p><strong>Results: </strong>Gene expression analyses revealed that Igf-1, Igf-bp3, Igf-bp4, and Il-10 were significantly overexpressed (<i>p</i> ≤ .01), while Igf-2 and Tgf-b genes were significantly downregulated in the lysates from IPSCs in comparison with the control MEFs. The Irs1 gene expression was not altered significantly.</p><p><strong>Conclusion: </strong>IPSCs are potentially capable of modulating inflammatory responses through the expression of various anti-inflammatory mediators from the IGF signaling, as well as IL-10. This discovery uncovers a previously unknown dimension of IPSCs' therapeutic effects, potentially leading to more advanced in vivo research and subsequent clinical trials.</p>","PeriodicalId":48647,"journal":{"name":"International Journal of Immunopathology and Pharmacology","volume":null,"pages":null},"PeriodicalIF":3.5,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11337182/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142005586","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mapping the psoriasis research landscape: A comprehensive bibliometric analysis from 2012-2023.","authors":"Sneha Garg, Muskan Chawla, Muskan Dixit, Arushal Sharma, Manjinder Singh, Varinder Singh, Sheikh F Ahmad, Sabry M Attia","doi":"10.1177/03946320241290341","DOIUrl":"10.1177/03946320241290341","url":null,"abstract":"<p><p>An extensive investigation explores the complex terrain of psoriasis, a persistent inflammatory dermatological disorder that impacts between 1% and 3% of the worldwide populace. Acknowledging the intricate interplay between environmental, genetic, and immunological influences on the etiology of psoriasis, the study utilizes sophisticated bibliometric techniques to investigate patterns, gaps in knowledge, and emergent trends within the field. The study utilizes advanced bibliometric techniques to analyze patterns, gaps in knowledge, and emerging trends in the field while acknowledging the intricate interplay between environmental, genetic, and immune-related influences on the etiology of psoriasis. An examination of 18,765 documents from December 2012 to December 2023 was conducted using machine learning techniques and the Scopus database. The explanation for conducting analysis is rooted in its capacity to provide significant perspectives on the dynamic progression of psoriasis research. The study facilitates the identification of significant subject areas, exposes patterns in publication trends, emphasizes influential authors and journals, and outlines the worldwide contributions to the field. The study demonstrates a steady and progressive increase in publications, with significant contributions from the Journal of the American Academy of Dermatology, the British Journal of Dermatology, and the Journal of the European Academy of Dermatology and Venereology. Prominent scholars in research output, such as the United States, China, and Germany, as well as authors including Feldman, Wu, Griffiths, Puig, and Reich K., are identified. Biochemistry, genetics, and molecular biology come to the forefront as esteemed fields that make substantial contributions to the study of psoriasis alongside medicine. This research highlights the interdisciplinary aspects of psoriasis by uncovering knowledge hubs and international collaborations between authors and organizations. The findings highlight the global reach of research on psoriasis and the importance of international cooperation.</p>","PeriodicalId":48647,"journal":{"name":"International Journal of Immunopathology and Pharmacology","volume":null,"pages":null},"PeriodicalIF":3.5,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11492216/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142407064","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A gradient model of renal ischemia reperfusion injury to investigate renal interstitial fibrosis.","authors":"Fan Yang, Baoping Zhu, Elyce Ozols, Haitao Bai, Mengjie Jiang, Frank Y Ma, David J Nikolic-Paterson, Xiaoyun Jiang","doi":"10.1177/03946320241288426","DOIUrl":"10.1177/03946320241288426","url":null,"abstract":"<p><p><b>Background:</b> The progression from acute kidney injury to chronic kidney disease poses a significant health challenge. Nonetheless, a constraint in existing animal models of renal ischemia/reperfusion (I/R) injury is the necessity for a severe injury, almost reaching a life-threatening level, to trigger the subsequent onset of renal fibrosis. Hence, we explored an adapted gradient approach to induce I/R injury, aiming to promote the progression of renal fibrosis while preserving the overall normal functioning of the kidney. <b>Methods:</b> In each group, 6-8 male C57BL/6 mice were used for model construction, with all undergoing sodium pentobarbital anesthesia and left kidney removal. Subsequently, a silk thread was passed beneath the lower renal branch, elevating the right kidney under a 20-g weight's tension via a pulley system for durations of 30, 40, or 60 min. Afterwards, we lowered the kidney, sutured the wound, and administered intraperitoneal saline. Mice in different groups were euthanized following reperfusion for 1, 3, 7, or 28 days. <b>Results:</b> We observed a complete cessation of blood flow in the lower pole, while an incomplete cessation in the upper pole in the elevated kidney. Significant renal impairment was evident on day 1 with a 60min ischemic period (187.0 ± 65.3 vs 17.9 ± 4.8 μmol/L serum creatinine in normal; <i>p</i> < .001), but not with 30 or 40min. On day 1, tubular necrosis and hyaline cast formation was evident in both lower and upper poles. On day 3, renal function returned to normal and remained normal through day 28. Histologic damage resolved in the upper pole over days 3 to 7, resulting in normal histology on day 28. By contrast, there was sustained tubular damage tubular in the lower pole on days 3 and 7, which failed to resolve and led to significant renal fibrosis by day 28. <b>Conclusion:</b> We created a model demonstrating clinically \"silent\" renal fibrosis.</p>","PeriodicalId":48647,"journal":{"name":"International Journal of Immunopathology and Pharmacology","volume":null,"pages":null},"PeriodicalIF":3.5,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11526246/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142373287","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}