{"title":"Expression and prognostic value of PIM-1 kinase in gliomas.","authors":"Zelin Li, Hu Wang, Guangxiu Wang, Anling Zhang, Chen Wang, Lidong Mo, Zhifan Jia, Xiaoguang Tong","doi":"10.14670/HH-18-845","DOIUrl":"https://doi.org/10.14670/HH-18-845","url":null,"abstract":"<p><strong>Objective: </strong>This study aimed to explore the correlation of PIM-1 with the clinicopathological features and prognosis of patients.</p><p><strong>Method: </strong>The MTERF3 mRNA and protein expression levels in tissues were detected by western blot and immunohistochemistry. The expression and survival of PIM-1 in patients with glioma were analysed using the Gene Expression Profiling Interactive Analysis database, the Gene Expression Database of Normal and Tumor Tissues 2, and the Chinese Glioma Genome Atlas database. The relationship between PIM-1 expression and immune cells and chemokines was analysed using the Tumor Immune Estimation Resource Version 2.0 tool and the Tumor and Immune System Interactions Database. A Kaplan-Meier plot was used to estimate the correlation between PIM-1 expression and the survival of patients with glioma.</p><p><strong>Results: </strong>The expression of PIM-1 was upregulated in glioma and was positively correlated with tumour grade. The expression of PIM-1 was significantly inhibited on the second day after transfection (<i>p</i><0.05), and the inhibition was most obvious on the sixth day (<i>p</i><0.01). The results of the co-expression pattern of PIM-1 showed that the expression of 5,012 genes was positively correlated with PIM-1, while the expression of 3,651 genes was negatively correlated with PIM-1. Macrophages (<i>p</i><0.001), myeloid dendritic cells (<i>p</i><0.001), NK cells (<i>p</i><0.001), CD4 T cells (<i>p</i><0.001), cancer-associated fibroblasts (<i>p</i><0.001), and neutrophils (<i>p</i><0.001) were positively correlated with the expression of PIM-1 in low-grade glioma.</p><p><strong>Conclusion: </strong>PIM-1 is overexpressed in glioma and is related to the prognosis of glioblastoma multiforme, and PIM-1 may be a prognostic biomarker and therapeutic target for glioma.</p>","PeriodicalId":13164,"journal":{"name":"Histology and histopathology","volume":" ","pages":"18845"},"PeriodicalIF":2.5,"publicationDate":"2024-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142681759","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Paeonol regulates glycolytic metabolism by downregulating BACH1 to ameliorate stemness, angiogenesis, and EMT in SiHa cervical cancer cells.","authors":"Shaoqin Sheng, Jing Xu, Danhong Hu, Weiwei Qian, Xiangqian Xu, Jing He","doi":"10.14670/HH-18-844","DOIUrl":"https://doi.org/10.14670/HH-18-844","url":null,"abstract":"<p><p>As a common reproductive malignancy of the female reproductive system, cervical cancer has increasingly become a public health concern. Paeonol, which is a natural phenolic monomer, has been found to possess substantial anticancer effects in some human cancers. The present study was conceived to explore the role and mechanism of paeonol in cervical cancer. Initially, the cytotoxicity of paeonol on immortalized H8 cervical epithelial cells and the proliferation of SiHa cervical cancer cells with paeonol treatment were detected using the CCK-8 assay. Cell stemness was assessed with the spheroid formation assay while western blot was applied for the measurement of proteins associated with cell stemness. The tube formation assay was used to detect the angiogenesis of human umbilical vein endothelial cells (HUVECs) and western blot was used to estimate the expression of EMT- and angiogenesis-related proteins. The extracellular acidification rate (ECAR) and oxygen consumption rate (OCR) of cells were appraised via a Seahorse XFe24 Flux Analyzer. Lactate production, glucose consumption, and ATP levels were evaluated with corresponding assay kits. Western blot was applied for the evaluation of GLUT1 and HK2. The mRNA and protein expression of BACH1 before and after transfection were detected using RT-qPCR and western blot. The luciferase reporter assay was used to detect the activities of GLUT1 and HK2 promoters. In this study, we found that paeonol inhibited cell proliferation, cell stemness, EMT progress, angiogenesis, and glycolysis in cervical cancer via downregulating BACH1. In summary, paeonol impeded the progression of cervical cancer by regulating glycolytic metabolism through the inhibition of BACH1.</p>","PeriodicalId":13164,"journal":{"name":"Histology and histopathology","volume":" ","pages":"18844"},"PeriodicalIF":2.5,"publicationDate":"2024-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142675689","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"The methyltransferase KIAA1429 potentiates cervical cancer tumorigenesis via modulating LARP1 mRNA m6A modification and stability.","authors":"Xi Feng, Liuping Shu","doi":"10.14670/HH-18-843","DOIUrl":"10.14670/HH-18-843","url":null,"abstract":"<p><p>Cervical cancer (CC) is one of the most common gynecological malignancies in the world and poses a great threat to public health. There is inadequate knowledge of the molecular mechanisms underlying CC. This study aimed to explore the prognostic value of KIAA1429 (VIRMA, vir-Like m6A methyltransferase associated) in patients with CC and analyze its molecular mechanisms. The level of KIAA1429 in tumor specimens was tested using RT-qPCR and western blotting. Cellular biological processes were assessed using CCK-8 and Transwell assays. Xenograft experiments were used to verify the function of KIAA1429 in CC <i>in vivo</i>. The results manifested that KIAA1429 expression was enhanced in CC. Downregulation of KIAA1429 hindered the viability, migration, and invasion of CC cells. Moreover, LARP1 (La-related protein 1) was uncovered to be positively modulated by KIAA1429. Further, the anti-tumor impacts of KIAA1429 depletion on the phenotype of CC cells were counteracted by LARP1 amplification. Additionally, KIAA1429 deficiency suppressed the stability of LARP1 through methylating LARP1. Collectively, KIAA1429 can boost the tumorigenesis of CC via modifying LARP1 through m6A methylation to promote its stability. This work highlights the promoting effects of KIAA1429 on CC development and presents new targets for its treatment.</p>","PeriodicalId":13164,"journal":{"name":"Histology and histopathology","volume":" ","pages":"18843"},"PeriodicalIF":2.5,"publicationDate":"2024-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142667647","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Berberine inhibits the malignant cell phenotype by inactivating PI3K/AKT/mTOR signaling in laryngeal squamous cell carcinoma.","authors":"Ling Lin, Zhen Chen, Ping Huang, Wei Chen, Zhefei Zou, Yexian Zheng, Chang He, Xiang Gu, Dan Yu, Qiong Zhang","doi":"10.14670/HH-18-753","DOIUrl":"10.14670/HH-18-753","url":null,"abstract":"<p><strong>Background: </strong>Berberine is an active compound found in different herbs used in Chinese medicine and is well-known for its potential anticancer properties. The study aimed to figure out the role of berberine in regulating the malignant behavior of laryngeal squamous cell carcinoma (LSCC) cells.</p><p><strong>Methods: </strong>LSCC cell lines (SNU-899 and AMC-HN-8) were treated with different concentrations of berberine (0-200 μM) to determine its cytotoxicity. The migration, invasion, and apoptosis of LSCC cells were measured by wound healing assays, Transwell assays, and flow cytometry. Western blot was performed for the quantification of proteins involved in PI3K/AKT/mTOR signaling.</p><p><strong>Results: </strong>The viability of LSCC cells was dose-dependently reduced by berberine. Berberine dampened LSCC cell migration and invasion while augmenting cell apoptosis, as evidenced by a reduced wound closure rate, a decrease in invaded cell number, and a surge in cell apoptosis in the context of berberine stimulation. Importantly, the effects of berberine on the cancer cell process were enhanced by LY294002 (an inhibitor for PI3K) treatment. Moreover, the protein levels of phosphorylated PI3K, AKT, and mTOR were markedly reduced in response to berberine treatment.</p><p><strong>Conclusion: </strong>Berberine inhibits cell viability, migration, and invasion but augments cell apoptosis by inactivating PI3K/AKT/mTOR signaling in LSCC.</p>","PeriodicalId":13164,"journal":{"name":"Histology and histopathology","volume":" ","pages":"1527-1536"},"PeriodicalIF":2.5,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140854142","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Yuxia Zhao, Lianqun Wang, Rui Dong, Xuejun Cheng, Liqun Jia, Dan Qu, Lin Zhang
{"title":"Expression of CCL2 signaling pathway genes in patients with periodontitis and atherosclerosis.","authors":"Yuxia Zhao, Lianqun Wang, Rui Dong, Xuejun Cheng, Liqun Jia, Dan Qu, Lin Zhang","doi":"10.14670/HH-18-754","DOIUrl":"10.14670/HH-18-754","url":null,"abstract":"<p><strong>Objective: </strong>Periodontitis and atherosclerosis are chronic inflammatory diseases characterized by leukocyte infiltration. We investigated the expression of CCL4, CCR5, c-Jun, c-Fos, NF-κB, and CCL2 as well as the possible mechanism involved in the regulation of CCL2 in human periodontitis tissues and atherosclerotic aorta based on previous research on the CCL4/CCR5/c-Jun and c-Fos/CCL2 pathway leading to CCL2 expression in collagen-induced arthritis (CIA) rat.</p><p><strong>Methods: </strong>Sixty-five volunteers were recruited and the condition of their gingiva and coronary arteries were assessed. The subjects were divided into four groups: healthy control, chronic periodontitis (CP), coronary artery diseases (CAD), and noncoronary artery diseases (non-CAD). Total RNA was isolated from gingiva in periodontitis patients and control populations and from the aorta in patients with and without CAD. PCR was used to examine CCL4, CCR5, c-Jun, c-Fos, NF-κB, and CCL2 levels. The production of CCL2 in the gingiva and aorta was analyzed by immunostaining.</p><p><strong>Results: </strong>PCR revealed that CCL4, CCR5, and CCL2 mRNA levels were increased in CP patients' gingivae and aortas from coronary artery bypass grafting (CABG) patients. Marked c-Jun, c-Fos, and NF-κB gene productions were detected in CP patients' gingivae but did not show statistical differences between the CAD and non-CAD groups. Stronger immunoreactivity against CCL2 was observed in periodontitis gingiva and aorta from CABG patients.</p><p><strong>Conclusions: </strong>Our findings suggest that the CCL4/CCR5/c-Jun and c-Fos/CCL2 pathways may be involved in CCL2 expression in periodontitis. CCL4, CCR5, and CCL2 might act as possible nodes to link the presence of periodontitis and atherosclerosis.</p>","PeriodicalId":13164,"journal":{"name":"Histology and histopathology","volume":" ","pages":"1537-1546"},"PeriodicalIF":2.5,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140898089","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Shreya Das, B Preethi, Sapana Kushwaha, Richa Shrivastava
{"title":"Therapeutic strategies to modulate gut microbial health: Approaches for sarcopenia management.","authors":"Shreya Das, B Preethi, Sapana Kushwaha, Richa Shrivastava","doi":"10.14670/HH-18-730","DOIUrl":"10.14670/HH-18-730","url":null,"abstract":"<p><p>Sarcopenia is a progressive and generalized loss of skeletal muscle and functions associated with ageing with currently no definitive treatment. Alterations in gut microbial composition have emerged as a significant contributor to the pathophysiology of multiple diseases. Recently, its association with muscle health has pointed to its potential role in mediating sarcopenia. The current review focuses on the association of gut microbiota and mediators of muscle health, connecting the dots between the influence of gut microbiota and their metabolites on biomarkers of sarcopenia. It further delineates the mechanism by which the gut microbiota affects muscle health with progressing age, aiding the formulation of a multi-modal treatment plan involving nutritional supplements and pharmacological interventions along with lifestyle changes compiled in the review. Nutritional supplements containing proteins, vitamin D, omega-3 fatty acids, creatine, curcumin, kefir, and ursolic acid positively impact the gut microbiome. Dietary fibres foster a conducive environment for the growth of beneficial microbes such as <i>Bifidobacterium, Faecalibacterium, Ruminococcus, and Lactobacillus</i>. Probiotics and prebiotics act by protecting against reactive oxygen species (ROS) and inflammatory cytokines. They also increase the production of gut microbiota metabolites like short-chain fatty acids (SCFAs), which aid in improving muscle health. Foods rich in polyphenols are anti-inflammatory and have an antioxidant effect, contributing to a healthier gut. Pharmacological interventions like faecal microbiota transplantation (FMT), non-steroidal anti-inflammatory drugs (NSAIDs), ghrelin mimetics, angiotensin-converting enzyme inhibitors (ACEIs), and butyrate precursors lead to the production of anti-inflammatory fatty acids and regulate appetite, gut motility, and microbial impact on gut health. Further research is warranted to deepen our understanding of the interaction between gut microbiota and muscle health for developing therapeutic strategies for ameliorating sarcopenic muscle loss.</p>","PeriodicalId":13164,"journal":{"name":"Histology and histopathology","volume":" ","pages":"1395-1425"},"PeriodicalIF":2.5,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140143327","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Blood-brain barrier disruption following brain injury: Implications for clinical practice.","authors":"Ruojing Bai, Xintong Ge","doi":"10.14670/HH-18-740","DOIUrl":"10.14670/HH-18-740","url":null,"abstract":"<p><p>The blood-brain barrier (BBB) plays a critical role in regulating the exchange of substances between peripheral blood and the central nervous system and in maintaining the stability of the neurovascular unit in neurological diseases. To guide clinical treatment and basic research on BBB protection following brain injury, this manuscript reviews how BBB disruption develops and influences neural recovery after stroke and traumatic brain injury (TBI). By summarizing the pathological mechanisms of BBB damage, we underscore the critical role of promoting BBB repair in managing brain injury. We also emphasize the potential for personalized and precise therapeutic strategies and the need for continued research and innovation. From this, broadening insights into the mechanisms of BBB disruption and repair could pave the way for breakthroughs in the treatment of brain injury-related diseases.</p>","PeriodicalId":13164,"journal":{"name":"Histology and histopathology","volume":" ","pages":"1435-1441"},"PeriodicalIF":2.5,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140868492","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
L Díaz-Flores, R Gutiérrez, M P García-Suárez, M González-Gómez, J L Carrasco, J F Madrid, L Díaz-Flores
{"title":"\"Vascular tuft sign\" in neuroendocrine tumors of the pancreas.","authors":"L Díaz-Flores, R Gutiérrez, M P García-Suárez, M González-Gómez, J L Carrasco, J F Madrid, L Díaz-Flores","doi":"10.14670/HH-18-787","DOIUrl":"10.14670/HH-18-787","url":null,"abstract":"<p><p>The often well-developed microvasculature in pancreatic neuroendocrine tumors (PanNETs) has been studied from different perspectives. However, some detailed structural findings have received less attention. Our objective is to study an overlooked event in PanNETs: \"enclosed vascular tufts\" (EVTs). For this purpose, 39 cases of PanNETs were examined with conventional (including serial sections) and immunochemistry procedures. In typical EVTs, the results show: 1) an insulated terminal vascular area, with a globular (glomeruloid) aspect, formed by a cluster of coiled microvessels, presenting CD31-, CD34-positive endothelial cells, αSMA-positive pericytes, and perivascular CD34-positive stromal cells/telocytes, separated by a pseudoglandular space from the surrounding trabeculae of tumor neuroendocrine cells; and 2) a pedicle joining the insulated terminal vascular area, with connective tissue tracts around the enclosing tumor trabeculae. EVTs predominate in the trabecular and nested gyriform pattern of PanNETs, with tumor trabeculae that follow a ribbon coil (winding ribbon pattern) around small vessels, which acquire a tufted image. In EVTs, secondary modifications may occur (fibrosis, hyalinization, myxoid changes, and calcification), coinciding or not with those of the connective tracts. In conclusion, the typical characteristics of unnoticed EVTs allow them to be considered as a morphological sign of PanNETs (a vascular tuft sign). Further in-depth studies are required, mainly to assess the molecular pathways that participate in vascular tuft formation and its pathophysiological implications.</p>","PeriodicalId":13164,"journal":{"name":"Histology and histopathology","volume":" ","pages":"1457-1472"},"PeriodicalIF":2.5,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141723536","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Allana Maryel Tobita, Anna Paula Weinhardt Baptista Strazzi, Maria Fernanda Cassino Portugal, Nelson Wolosker, Ricardo Aun, Frederico de Lima Jacy Monteiro, Erasmo Simão da Silva, Igor Rafael Sincos
{"title":"Biomechanical and histological analyses of a multilayer stent in a swine model of suprarenal aortic aneurysm.","authors":"Allana Maryel Tobita, Anna Paula Weinhardt Baptista Strazzi, Maria Fernanda Cassino Portugal, Nelson Wolosker, Ricardo Aun, Frederico de Lima Jacy Monteiro, Erasmo Simão da Silva, Igor Rafael Sincos","doi":"10.14670/HH-18-842","DOIUrl":"https://doi.org/10.14670/HH-18-842","url":null,"abstract":"<p><strong>Objectives: </strong>To analyze and compare, in an animal model, the treatment of thoracoabdominal aneurysms with multilayer stents and its hemodynamic effects through the biomechanical and histological analysis of the aortic wall in contact with the stent.</p><p><strong>Methods: </strong>Large White pigs were randomized into two groups: Stent (n=6) and Control (n=5, non-stent). All animals were subjected to the creation of a suprarenal aneurysm with a bovine pericardial patch. In the Stent group, a multilayer stent was implanted immediately after aneurysm formation. After four weeks, all animals were subjected to angiographic assessment and intravascular ultrasound, and the stent was explanted before euthanasia for histological and biomechanical analyses.</p><p><strong>Results: </strong>At histological analysis, the groups did not differ significantly in maximum thickness of the intima (<i>p</i>=0.526), media (<i>p</i>=0.129), or adventitia (<i>p</i>=0.662). Thrombus formation was observed in 100% of the animals on the intima and media layers of the stented aorta vs. none in the Control group (<i>p</i>=0.048). At biomechanical analysis, no statistical differences were observed in aortic wall elasticity (<i>p</i>=0.158), strength (<i>p</i>=0.360), or thickness (<i>p</i>=0.323).</p><p><strong>Conclusion: </strong>We identified thrombosis of the aneurysmal sac through the presence of thrombi on the intima of the aorta in 100% of the animals in the Stent group; as for the biomechanical analysis, this study showed no statistical differences in vessel wall thickness, strength, and elasticity between groups.</p>","PeriodicalId":13164,"journal":{"name":"Histology and histopathology","volume":" ","pages":"18842"},"PeriodicalIF":2.5,"publicationDate":"2024-10-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142647350","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Fortunellin attenuates sepsis-induced acute kidney injury by inhibiting inflammation and ferroptosis via the TLR4/NF-κB pathway.","authors":"Yanmin Zhang, Tianzhi Liu, Zhigang Zuo","doi":"10.14670/HH-18-841","DOIUrl":"10.14670/HH-18-841","url":null,"abstract":"<p><strong>Objective: </strong>To investigate the potential protective effect of fortunellin in sepsis-induced acute kidney injury (AKI) and its underlying mechanisms.</p><p><strong>Methods: </strong>Lipopolysaccharide (LPS)-treated human kidney proximal tubular epithelial (HK-2) cells were used as a cell model and sepsis-induced AKI was induced by cecal ligation and puncture (CLP) surgery in mice. Cell Counting Kit-8 (CCK8) assays and flow cytometry analysis were performed to examine the viability of HK-2 cells. Enzyme-linked immunosorbent assay (ELISA) was performed to investigate the content of tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), and interleukin-1 beta (IL-1β) <i>in vivo</i> and <i>in vitro</i>. The levels of malondialdehyde (MDA), superoxide dismutase (SOD), glutathione (GSH), and free iron (Fe<sup>2+</sup>) were measured as indicators of ferroptosis. The phosphorylation levels of Interleukin-1 Receptor-Associated Kinase 4 (p-IRAK4), p65 (p-65), and inhibitor of kappa B alpha (p-IκBα) were detected by western blot as an indication of nuclear factor kappa-B (NF-κB) pathway activation.</p><p><strong>Results: </strong>Our cell and animal experiments revealed that fortunellin exhibits significant anti-inflammatory and cytoprotective properties. Fortunellin counteracted LPS-induced cellular damage in HK-2 cells, enhancing cell survival and suppressing the secretion of pro-inflammatory cytokines. Additionally, fortunellin demonstrated potent antioxidant effects, reducing MDA and Fe<sup>2+</sup> levels while increasing SOD activity and GSH content. The protective effect of fortunellin was further corroborated in the mouse model of sepsis-induced AKI. Notably, fortunellin suppressed activation of the TLR4/NF-κB pathway in the AKI model, as evidenced by decreased levels of p-p65 and p-IκBα proteins.</p><p><strong>Conclusion: </strong>Fortunellin ameliorates inflammation and oxidative stress in sepsis-induced AKI, possibly through the modulation of the TLR4/NF-κB pathway. These findings suggest fortunellin's potential as a therapeutic agent for sepsis-associated AKI.</p>","PeriodicalId":13164,"journal":{"name":"Histology and histopathology","volume":" ","pages":"18841"},"PeriodicalIF":2.5,"publicationDate":"2024-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142619271","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}