In vivoPub Date : 2025-05-01DOI: 10.21873/invivo.13929
Maria Breun, Tim Schulz, Camelia M Monoranu, Ralf-Ingo Ernestus, Cordula Matthies, Mario Löhr, Lan Kluwe
{"title":"Pathogenic Variants and Allele Loss of the NF2 and LZTR1 Gene in Sporadic Vestibular Schwannoma.","authors":"Maria Breun, Tim Schulz, Camelia M Monoranu, Ralf-Ingo Ernestus, Cordula Matthies, Mario Löhr, Lan Kluwe","doi":"10.21873/invivo.13929","DOIUrl":"https://doi.org/10.21873/invivo.13929","url":null,"abstract":"<p><strong>Background/aim: </strong>Pathogenic variants and allele-loss of the <i>NF2</i> gene with Merlin loss as consequence is the driving genetic event for vestibular schwannoma development. Our knowledge about the pathogenic <i>NF2</i> variants in sporadic vestibular schwannoma is insufficient. Therefore, we analyzed a cohort of sporadic vestibular schwannomas by panel-sequencing.</p><p><strong>Patients and methods: </strong>Forty-one sporadic vestibular schwannomas from 26 male and 15 female patients were included. DNA from tumor tissues was sequenced with a custom panel for the <i>NF2</i> and <i>LZTR1</i> genes. Allele-loss of the <i>NF2</i> locus was also examined using multiplex-ligation-dependent probe-amplification. These genetic data were correlated with clinical parameters including hearing, tumor extension and growth.</p><p><strong>Results: </strong>Among the 41 tumor samples, 34 had one pathogenic variant or an allele-loss of <i>NF2</i> gene and one tumor showed a pathogenic variant in the <i>LZTR1</i> gene. Allele frequencies of the total of 46 pathogenic variants varied from 0.05 to 0.82, and none of these variants was found in blood. For 6 tumors, no pathogenic variants were found while 4 of them had allele-loss of the <i>NF2</i> gene. When the tumors were divided into 3 groups according to the counts of inactivating events (pathogenic variants and allele loss), the clinical parameters including hearing, tumor structure in MRI, tumor growth, tumor size and postoperative facial function did not differ significantly.</p><p><strong>Conclusion: </strong>There was no correlation between phenotype and genetic alterations of the <i>NF2 or LZTR1</i> gene in sporadic schwannomas. Genetic inactivating events are the precondition for the development of vestibular schwannomas but do not influence their growth and other features.</p>","PeriodicalId":13364,"journal":{"name":"In vivo","volume":"39 3","pages":"1251-1261"},"PeriodicalIF":1.8,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12042009/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144018392","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
In vivoPub Date : 2025-05-01DOI: 10.21873/invivo.13942
Ning Xu, Gongwu Yuan, Wenbo Zeng, Ximing Liu, M A Wan, Suyang Xu, Yikang Bi, Hai Hu, Yafeng Xu, Shenghui Lan
{"title":"Gefitinib Facilitates Bone Fracture Healing <i>via</i> Inhibition of the EGFR Pathway and Counteracting SOX9-driven Bone Metabolic Reprogramming.","authors":"Ning Xu, Gongwu Yuan, Wenbo Zeng, Ximing Liu, M A Wan, Suyang Xu, Yikang Bi, Hai Hu, Yafeng Xu, Shenghui Lan","doi":"10.21873/invivo.13942","DOIUrl":"https://doi.org/10.21873/invivo.13942","url":null,"abstract":"<p><strong>Background/aim: </strong>To investigate the role of epidermal growth factor receptor (EGFR) inhibition in enhancing bone fracture healing by modulating box transcription factor 9 (SOX9) and bone metabolism.</p><p><strong>Materials and methods: </strong>A rat femoral fracture model was used. Techniques included histological analysis, X-ray scoring, micro-computed tomography, immunohistochemistry, and biomechanical testing. Serum markers were analyzed with enzyme-linked immunosorbent assay, while quantitative real-time polymerase chain reaction and western blotting assessed molecular pathways. Metabolic changes were measured using a Seahorse analyzer. An EGFR inhibitor, gefitinib, was used to examine its impact on periosteal stem cell differentiation and metabolism.</p><p><strong>Results: </strong>EGFR inhibition improved bone callus formation and quality, increased cartilage callus, and upregulated bone formation markers. Gefitinib enhanced oxidative phosphorylation and fatty acid oxidation, counteracting negative effects from lipid-reduced serum on osteoblastic differentiation of periosteal stem cell. SOX9 overexpression reduced the benefits of EGFR inhibition.</p><p><strong>Conclusion: </strong>Gefitinib enhances bone fracture healing by modulating lipid metabolism through SOX9, suggesting its potential as a therapeutic agent for improving fracture outcomes.</p>","PeriodicalId":13364,"journal":{"name":"In vivo","volume":"39 3","pages":"1394-1413"},"PeriodicalIF":1.8,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12042003/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143999857","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
In vivoPub Date : 2025-05-01DOI: 10.21873/invivo.13972
Bogdan Mihai Tarcau, Andra Negru, Alexandra Manuela Buzle, Timea Claudia Ghitea, Eleonora Marian
{"title":"Impact of Genetic Mutations in Hyperhomocysteinemia and Metabolic Syndrome on Physiological Parameters and Quality of Life in Healthy Individuals.","authors":"Bogdan Mihai Tarcau, Andra Negru, Alexandra Manuela Buzle, Timea Claudia Ghitea, Eleonora Marian","doi":"10.21873/invivo.13972","DOIUrl":"https://doi.org/10.21873/invivo.13972","url":null,"abstract":"<p><strong>Background/aim: </strong>Hyperhomocysteinemia (HH) is a metabolic condition linked to cardiovascular and cognitive health risks. This study investigated the prevalence of HH and cardiovascular metabolic syndrome (MS) among patients with symptoms such as fatigue, joint pain, muscle weakness, vertigo, paresthesia, and aphthous stomatitis. The objective was to explore the associations between HH, MS, and quality of life, emphasizing the role of personalized dietary interventions.</p><p><strong>Patients and methods: </strong>A prospective study was conducted between 2019 and 2023, including 86 patients aged 18 years or older who underwent nutrigenetic testing and provided anthropometric data. Participants were divided into three groups: those with HH (45.3%), those without HH or MS (31.4%), and those with MS but without HH (23.3%). Nutrigenetic analyses assessed genetic predispositions related to nutrient metabolism.</p><p><strong>Results: </strong>Patients with HH exhibited reduced quality of life, with lower Short Form-12 Health Survey (SF-12) scores compared to other groups. Sex-specific nutrient needs and age-related changes in dietary requirements were identified. Metabolic conditions, including obesity, hypertension, and hypercholesterolemia, inversely impacted nutrient utilization. Physical activity positively correlated with higher demands for folic acid, vitamin B12, zinc, and magnesium.</p><p><strong>Conclusion: </strong>Nutritional interventions targeting these needs effectively improved metabolic health and alleviated symptoms. HH significantly impacts quality of life and metabolic health. Personalized dietary and lifestyle modifications tailored to genetic predispositions, sex, and age are critical for mitigating cardiometabolic risks. These findings lay the groundwork for targeted interventions aimed at improving health outcomes in individuals with HH and MS.</p>","PeriodicalId":13364,"journal":{"name":"In vivo","volume":"39 3","pages":"1703-1718"},"PeriodicalIF":1.8,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12041972/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143999858","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
In vivoPub Date : 2025-05-01DOI: 10.21873/invivo.13962
Basem H Elesawy, Ahmad El Askary, Osama M Mehanna, Elsayed A Elmorsy, Mohamed M Khalifa, Sanaa E Ali, Amal Abd El Hafez
{"title":"High Serum Levels of Irisin, Visfatin and Adiponectin as Potential Independent Risk Factors for Diabetic Nephropathy Progression in Patients With Type 2 Diabetes Mellitus.","authors":"Basem H Elesawy, Ahmad El Askary, Osama M Mehanna, Elsayed A Elmorsy, Mohamed M Khalifa, Sanaa E Ali, Amal Abd El Hafez","doi":"10.21873/invivo.13962","DOIUrl":"https://doi.org/10.21873/invivo.13962","url":null,"abstract":"<p><strong>Background/aim: </strong>Diabetic nephropathy (DN) is a common devastating complication in type 2 diabetes mellitus (T2DM). In order to investigate novel DN biomarkers, we evaluated serum levels of irisin, adiponectin, visfatin and interleukin 4 (IL-4) in patients with T2DM with normo-, micro- and macro-albuminuria and compared their means with non-diabetic controls.</p><p><strong>Patients and methods: </strong>Clinical data and routine laboratory parameters of metabolic and renal function status were determined in blood and urine samples obtained from 169 participants, divided into four groups according to the presence of diabetes and albuminuria using appropriate biochemical assays/calculations. Serum levels of irisin, adiponectin, visfatin and interleukin 4 (IL4) were assessed using enzyme-linked immunosorbent assay. Means of all tested parameters and biomarkers were compared using appropriate statistical methods. Logistic regression was used to determine albuminuria risk factors in T2DM as an indicator for DN.</p><p><strong>Results: </strong>All tested parameters differed significantly among T2DM groups and controls (<i>p</i><0.001). Irisin, adiponectin, visfatin and IL4 significantly increased in T2DM patients with significant increasing albuminuria. Along with hemoglobin A1C, irisin was the most highly significant risk factor for development and progression of albuminuria (p<0.001). Adiponectin was also a significant independent risk factor (<i>p</i>=0.009), whilst visfatin and IL4 conferred no significant risk.</p><p><strong>Conclusion: </strong>High irisin levels in normo-albuminuric patients indicates their potential to develop DN even prior to detectable albuminuria. Both irisin and adiponectin may be considered as potential biomarkers indicating risk for DN progression in T2DM that might be therapeutically targeted.</p>","PeriodicalId":13364,"journal":{"name":"In vivo","volume":"39 3","pages":"1615-1624"},"PeriodicalIF":1.8,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12041983/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143963247","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
In vivoPub Date : 2025-05-01DOI: 10.21873/invivo.13944
Deniz Sunnetci-Akkoyunlu, Cansu Ugurtas, Nurhan Kulcu-Sarikaya, Tolgahan Ozer, Naci Cine, Seda Eren-Keskin, Aylin Kanli, Hakan Savli
{"title":"Identification of Common miRNAs Differentially Expressed in Periodontitis and Pancreatic Cancer.","authors":"Deniz Sunnetci-Akkoyunlu, Cansu Ugurtas, Nurhan Kulcu-Sarikaya, Tolgahan Ozer, Naci Cine, Seda Eren-Keskin, Aylin Kanli, Hakan Savli","doi":"10.21873/invivo.13944","DOIUrl":"https://doi.org/10.21873/invivo.13944","url":null,"abstract":"<p><strong>Background/aim: </strong>Periodontitis is a prevalent multifactorial, oral infectious disease and is considered a high-risk factor for pancreatic cancer. Nevertheless, there is limited understanding of the underlying epigenetic mechanisms governing this relationship. The aim of this study was to identify dysregulated miRNAs associated with periodontitis and pancreatic cancer, along with their related genes, signaling pathways, and compounds.</p><p><strong>Materials and methods: </strong>miRNA expression datasets for tissues affected by periodontitis and pancreatic cancer were obtained from the Gene Expression Omnibus database. miRNAs differentially expressed relative to normal tissues were detected, and those common to both datasets were determined. Further bioinformatics approaches were used to explore the association of common differentially expressed miRNAs with periodontitis and pancreatic cancer.</p><p><strong>Results: </strong>Twenty shared, differentially expressed miRNAs were identified; 14 exhibited similar expression patterns in both diseases. Among these common differentially expressed miRNAs, 10 were found to be overexpressed. hsa-miR-155, hsa-miR-186, hsa-miR-765, hsa-miR-211 and hsa-miR-375 were the top miRNA nodes in the gene network, with hsa-mir-155 being the sole miRNA node in the transcription factor network. Top candidate miRNA-dysregulated genes included superoxide dismutase 2 (SOD2), nuclear FMR1 interacting protein 2 (NUFIP2), SFT2 domain-containing 2 (SFT2D2), thioredoxin-interacting protein (TXNIP), and cyclin D1 (CCND1), while top dysregulated transcription factors were Argonaute RISC catalytic component 2 (AGO2), AKT serine/threonine kinase 1 (AKT1), BCL6 transcription repressor (BCL6), breakpoint cluster region (BCR), and BRCA1 DNA repair associated (BRCA1). Relevant compounds for targeting these emerged, including 5-fluorouracil, gemcitabine, doxorubicin, ascorbate, diethylstilbestrol, and temozolomide.</p><p><strong>Conclusion: </strong>Our study suggests candidate molecular mechanisms linking periodontitis to pancreatic cancer, highlighting potential compounds that may target both diseases. These findings provide a foundation for guiding future fundamental and clinical research.</p>","PeriodicalId":13364,"journal":{"name":"In vivo","volume":"39 3","pages":"1422-1439"},"PeriodicalIF":1.8,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12042002/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143962684","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
In vivoPub Date : 2025-05-01DOI: 10.21873/invivo.13975
Akira Mima, Takahiro Nakamoto, Takamasa Matsuki, Suguru Kido, Yuta Saito, Takaaki Morikawa, Keishi Matsumoto, Hidemasa Gotoda, Shinji Lee
{"title":"IgA Nephropathy Associated With Infliximab Treatment in Patients With Crohn's Disease: Study of IgA1 and IgA2 Expression in Glomeruli.","authors":"Akira Mima, Takahiro Nakamoto, Takamasa Matsuki, Suguru Kido, Yuta Saito, Takaaki Morikawa, Keishi Matsumoto, Hidemasa Gotoda, Shinji Lee","doi":"10.21873/invivo.13975","DOIUrl":"https://doi.org/10.21873/invivo.13975","url":null,"abstract":"<p><strong>Background/aim: </strong>It is well known that infliximab is an anti-tumor necrosis factor chimeric factor that is effective in treating inflammatory bowel diseases, such as Crohn's disease. Recently, there have been reports of new onset or flare-ups of immunoglobulin A (IgA) nephropathy during infliximab therapy for Crohn's disease. Inflammatory bowel disease-associated IgA nephropathy has been associated with IgA2; However, its activation by infliximab is still unknown.</p><p><strong>Case report: </strong>We report our experience with two patients who experienced acute exacerbations of pre-existing abnormal urinalysis and renal dysfunction 1-18 years following infliximab treatment for Crohn's disease. Renal biopsies at the time of renal disease flare-up revealed IgA nephropathy in one patient and mesangial proliferative nephropathy in the other. Immunostaining results showed no clear predominance of intraglomerular expression of IgA2, and the patient diagnosed with IgA nephropathy entered remission with high dose methylprednisolone pulse therapy and oral corticosteroids, without the need for tonsillectomy. In contrast, the patient with mesangial proliferative nephritis had many devastated glomeruli, thus corticosteroids were not administrated, and the patient was followed up.</p><p><strong>Conclusion: </strong>The clinical course of our patients, along with similar cases reported in the literature, indicates that infliximab therapy for Crohn's disease is linked to a relatively high risk of new-onset IgA nephropathy or disease relapse. This report is notable because it is the first to compare the expression of IgA1 and IgA2 in glomeruli in nephritis associated with infliximab therapy.</p>","PeriodicalId":13364,"journal":{"name":"In vivo","volume":"39 3","pages":"1731-1738"},"PeriodicalIF":1.8,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12041970/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144011106","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
In vivoPub Date : 2025-05-01DOI: 10.21873/invivo.13927
Jessica Gutiérrez-Nájera, Víctor Manuel Mendoza-Núñez
{"title":"Effect of Probiotic Supplementation on Body Fat, Skeletal Muscle Mass, and Body Mass Index in Individuals ≥45 Years Old: A Systematic Review.","authors":"Jessica Gutiérrez-Nájera, Víctor Manuel Mendoza-Núñez","doi":"10.21873/invivo.13927","DOIUrl":"https://doi.org/10.21873/invivo.13927","url":null,"abstract":"<p><strong>Background/aim: </strong>Probiotics are living microorganisms that confer health benefits when administered in adequate amounts. Several studies have shown the positive effects on body fat, muscle mass, and body mass index (BMI) in young adults and athletes; however, the results in adults aged ≥45 years are not conclusive.</p><p><strong>Materials and methods: </strong>A systematic review was conducted in accordance with the PRISMA guidelines, analyzing studies up to December 10, 2024, from nine databases (PubMed, Scopus, Web of Science, LILACS, SciELO, Springer, Redalyc, Cochrane Library and TESIUNAM). Mean differences (MD) were estimated using RevMan V 5.4.1. software.</p><p><strong>Results: </strong>Six hundred and sixty-six studies were identified, of which 15 met the eligibility criteria. A statistically significant decrease in fat mass (%) was found in two studies and in fat mass (kg) in another two studies. Likewise, one study reported a statistically significant increase in skeletal muscle mass.</p><p><strong>Conclusion: </strong>Probiotic supplementation may have a beneficial effect on reducing body fat mass and increasing or preventing skeletal muscle mass loss in adults ≥45 years old; however, further clinical trials are needed to determine the optimal types, doses, and duration of probiotic treatment for best results.</p>","PeriodicalId":13364,"journal":{"name":"In vivo","volume":"39 3","pages":"1220-1236"},"PeriodicalIF":1.8,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12041995/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144012733","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Expression of Galectin 3 and Activating Transcription Factor 3 in Nigral Dopaminergic Neurons of 6-Hydroxydopamine Induced Parkinsonian Rat Model.","authors":"Eun-Jin Lee, Yoon-Jung Choy, Ran-Sook Woo, Tai-Kyoung Baik, Hong-Il Yoo, Dae-Yong Song","doi":"10.21873/invivo.13938","DOIUrl":"https://doi.org/10.21873/invivo.13938","url":null,"abstract":"<p><strong>Background/aim: </strong>Parkinson's disease (PD) is an age-related neurodegenerative disease marked by the relatively progressive dopaminergic neuronal loss in the substantia nigra (SN). Retrograde degeneration of the nigrostriatal dopaminergic neurons by 6-hydroxydopamine (6-OHDA) has been widely used as a PD animal model, while endogenous 6-OHDA promotes the progression of PD pathology. Galectin 3 (Gal3) and activating transcription factor 3 (ATF3) have been implicated in neurodegenerative processes. The aim of this study was to investigate the expression pattern and roles of Gal3 and ATF3 in a Parkinson's disease animal model induced by 6-OHDA.</p><p><strong>Materials and methods: </strong>We investigated temporal and spatial profiles of Gal3 expression in 6-OHDA rat model of PD. Lesions were induced by unilateral stereotactic injections of 6-OHDA into the striatum. Three days prior to 6-OHDA lesion, Fluorogold (FG) was injected at the same coordinates as the subsequent 6-OHDA injection. 6-OHDA induced retrograde degeneration of tyrosine hydroxylase immunopositive and FG immunopositive neurons within SN in a time-dependent manner.</p><p><strong>Results: </strong>Activating transcription factor 3 (ATF3) expression was also upregulated in the SN, in a pattern similar to that of Gal3 immunoreactivity. Finally, we confirmed through triple immunofluorescence staining that ATF3 and Gal3 were colocalized in the dopaminergic neurons labeled with FG. These neurons were damaged by 6-OHDA.</p><p><strong>Conclusion: </strong>Gal3 may play a key role in the signaling pathway of dopaminergic neuronal cell death induced by 6-OHDA. This is the first <i>in vivo</i> demonstration that Gal3 is expressed in dopaminergic neurons injured by 6-OHDA.</p>","PeriodicalId":13364,"journal":{"name":"In vivo","volume":"39 3","pages":"1341-1354"},"PeriodicalIF":1.8,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12041963/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143963457","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Methotrexate Enhances Atherosclerosis Progression <i>via</i> Impairment of Folate Pathway in a Microminipig Model.","authors":"Yuko Onishi, Naoki Miura, Akihide Tanimoto, Hiroaki Kawaguchi","doi":"10.21873/invivo.13930","DOIUrl":"https://doi.org/10.21873/invivo.13930","url":null,"abstract":"<p><strong>Background/aim: </strong>As the pathophysiology of Microminipigs (μMPs) is similar to that of human, μMPs are useful in atherosclerosis research. To clarify the effect of methotrexate (MTX) on atherosclerosis, we investigated the pathology of MTX-induced atherosclerosis lesion exacerbation in μMPs fed a high-fat and high-cholesterol diet (HFHCD).</p><p><strong>Materials and methods: </strong>The μMPs were divided into four groups: HFHCD, HFHCD+MTX, HFHCD+MTX+leucovorin (LV), and HFHCD+MTX+folic acid (FA), and fed for two weeks. Laboratory tests including blood lipid, FA, and homocysteine (Hcy) levels, and pathological evaluation of the atherosclerosis lesion area and thickness were performed. Hepatic and jejunal gene expressions related to lipid and folate metabolism pathways including 5-methyltetrahydrofolate-homocysteine methyltransferase (MTR) were monitored using RT-PCR.</p><p><strong>Results: </strong>The HFHCD+MTX group showed increased blood Hcy (<i>p</i><0.01) and decreased FA levels (<i>p</i><0.05) in accordance with increased hepatic MTR mRNA expression (<i>p</i><0.1) and exacerbation of atherosclerosis (<i>p</i>=0.051 for lesion area and <i>p</i>=0.045 for lesion thickness) compared to the HFHCD group. Administration of LV or FA attenuated the MTX-induced increase in the Hcy level (<i>p</i><0.01), atherosclerosis lesion thickness (<i>p</i><0.1), and MTR mRNA expression (<i>p</i><0.1 in HFHCD+MTX <i>vs.</i> HFHCD+MTX+LV groups).</p><p><strong>Conclusion: </strong>MTX exacerbated HFHCD-induced atherosclerosis mediated through reduced blood FA and the subsequent increase of Hcy in μMPs, indicating that the μMP model may advance cardio-oncology research by providing useful experimental approaches. As MTX is administered for rheumatoid arthritis and malignant tumors in humans, atherosclerosis exacerbation should be acknowledged as a possible adverse effect of MTX treatment.</p>","PeriodicalId":13364,"journal":{"name":"In vivo","volume":"39 3","pages":"1262-1274"},"PeriodicalIF":1.8,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12041998/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143998475","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Endotoxin Activity Assay as a Novel Predictor of Disease Progression in Patients With Mild Cholangitis.","authors":"Koichi Mori, Kentaro Miyake, Ryusei Matsuyama, Koki Goto, Sayaka Arisaka, Yusuke Suwa, Toshiaki Kadokura, Yuki Homma, Itaru Endo","doi":"10.21873/invivo.13970","DOIUrl":"10.21873/invivo.13970","url":null,"abstract":"<p><strong>Background/aim: </strong>Acute cholangitis is a critical biliary infection that can swiftly evolve into sepsis and organ failure. Certain patients with mild acute cholangitis might advance to a more severe status. Identifying predictive factors for such exacerbation is of paramount importance. This study aimed to investigate whether the endotoxin activity assay (EAA) could serve as a predictive biomarker for the progression of mild acute cholangitis.</p><p><strong>Patients and methods: </strong>We conducted a retrospective observational study at Yokohama City University Hospital, enrolling 200 patients hospitalized with acute cholangitis between May 2011 and June 2015. Patients with initially mild acute cholangitis were stratified into two groups based on their severity on Day 1: the stable group (remaining mild) and the exacerbation group (progressing to moderate/severe cholangitis). Clinical parameters were analyzed to assess risk factors for exacerbation.</p><p><strong>Results: </strong>Among 74 patients with mild acute cholangitis at admission, 33 (44.6%) progressed to moderate/severe cholangitis within 24 h. Multivariate logistic regression analysis identified chemotherapy within 28 days [odds ratio (OR)=3.440, 95% confidence interval (CI)=1.170-10.100, <i>p</i>=0.025], serum albumin levels (OR=0.303, 95%CI=0.094-0.975, <i>p</i>=0.045), and EAA ≥0.4 (OR=3.880, 95%CI=1.210-12.500, <i>p</i>=0.023) as independent predictors of disease exacerbation. A predictive equation was developed using the logistic regression model: log (P/1-P)=3.285-1.265×Alb (mg/dl) + 1.291 × (Chemotherapy within 28 days) +1.343 × (EAA ≥0.4) (P: the probability of exacerbation).</p><p><strong>Conclusion: </strong>EAA was identified as the most significant factor for exacerbating mild acute cholangitis. The combination of EAA, albumin levels, and a history of chemotherapy within the past 28 days suggests the potential to predict the progression of mild acute cholangitis to a more severe form.</p>","PeriodicalId":13364,"journal":{"name":"In vivo","volume":"39 3","pages":"1685-1693"},"PeriodicalIF":1.8,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12041978/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144062348","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}