Translation: The University of Toledo Journal of Medical Sciences最新文献

{"title":"Shared and unique transcriptional changes in the orbitofrontal cortex in psychiatric disorders and suicide","authors":"S. O’Donovan, Suleiman Ali, William Deng, Gurnoor Patti, Joshua Wang, M. Eladawi, Ali Imami","doi":"10.46570/utjms.vol11-2023-822","DOIUrl":"https://doi.org/10.46570/utjms.vol11-2023-822","url":null,"abstract":"Psychiatric disorders like major depressive disorder (MDD), schizophrenia (SCZ), and bipolar disorder (BPD), represent a significant global public health concern. Sex differences in the prevalence and presentation of psychiatric disorders, and the association of a psychiatric diagnosis with increased risk of suicide, are well-established. However, the neurobiology underlying these features of disease are not well understood. Dysfunction of the orbitofrontal cortex (OFC), a brain region responsible for decision-making and sensory processing, has been implicated in psychiatric disorders but remains understudied compared to other frontocortical brain regions. \u0000 In this study we investigated sexual dimorphism in psychiatric illnesses and suicide by analyzing publicly available OFC transcriptional profiles (RNAseq data obtained from the Stanley Neuropathology Consortium) from individuals with SCZ, BPD, MDD, and non-psychiatric controls (n=15/group).   \u0000Gene set enrichment analysis (GSEA) revealed significant differences in immune-related processes in male and female comparisons and in psychiatric disorders relative to controls. Analysis of top differentially expressed genes found changes in P2RY12 in males and females who died by suicide. Additionally, downregulation of protein folding processes was observed in female suicide subjects, suggesting an association between dysregulated protein metabolism and suicide. Our results further our understanding of the shared and unique molecular pathways underlying psychiatric disorders and suicide. \u0000 ","PeriodicalId":220681,"journal":{"name":"Translation: The University of Toledo Journal of Medical Sciences","volume":"230 9","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-01-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140489891","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Probiotic Protects Kidneys Exposed to Microcystin-LR","authors":"Yolanda Hu, Irene Sun, Eric Tang, William G. Ryan, Upasana Shrestha, Jyotshana Gautam, Apurva Lad, Jason F. Huntley, Steven Haller, David Kennedy","doi":"10.46570/utjms.vol12-2024-823","DOIUrl":"https://doi.org/10.46570/utjms.vol12-2024-823","url":null,"abstract":"Cyanobacterial Harmful Algal Blooms (CyanoHABs) occur when colonies of photosynthetic bacteria called cyanobacteria grow out of control, usually in warm, nutrient-rich, slow-moving waters. They are becoming increasingly prevalent around the world and release harmful toxins called cyanotoxins into bodies of water, which negatively affect human and ecological health. One such cyanotoxin is microcystin, with microcystin-leucine arginine (MC-LR) being the most widespread. Exposure to MC-LR inhibits serine and threonine protein phosphatase 1 and 2A in humans, causing a myriad of health problems. Fortunately, certain naturally occurring bacteria may be able to degrade MC-LR and reverse its effects. Mice were separated into five experimental groups based on three types of pre-treatments (control drinking water/vehicle, probiotic-supplemented drinking water, and heat-inactivated probiotic-supplemented drinking water) as well as two types of exposures (microcystin-LR and water/vehicle). RNA was extracted from kidneys for sequencing because MC-LR exacerbates kidney disease. Gene expression data were analyzed with 3 Pod Reports, an R package that produces a three-part report consisting of Gene Set Enrichment Analysis (GSEA), EnrichR, and integrative LINCS (iLINCS). MC-LR exposure was associated with upregulated cellular respiration and metabolism pathways and downregulated transcription pathways. Probiotic pre-treatment combined with MC-LR exposure was associated with upregulated lipoprotein particle pathways and downregulated respiration and ribosome pathways. Overall, the probiotic mixture corrected the transcriptional profile resulting from MC-LR exposure. Future high yield pathways that could be targeted for therapeutic benefit include VEGFR inhibitors and increased expression of renal kidney indicator genes such as EGFR.","PeriodicalId":220681,"journal":{"name":"Translation: The University of Toledo Journal of Medical Sciences","volume":"75 4","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-01-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140486272","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"An Unusual Presentation of Granulomatosis with Polyangiitis (GPA): Case Report","authors":"Sabrina Khuder, Caleb Gerber, Samantha Davis, Nathan Gilbert, Rawish Fatima, Nezam Altorok","doi":"10.46570/utjms.vol11-2023-935","DOIUrl":"https://doi.org/10.46570/utjms.vol11-2023-935","url":null,"abstract":"","PeriodicalId":220681,"journal":{"name":"Translation: The University of Toledo Journal of Medical Sciences","volume":"224 16","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138996921","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Effect Of SGLT-2 Inhibitors On Improving Non-Alcoholic Fatty Liver Disease: A Systematic Review and Meta-analysis.","authors":"W. Sayeh, Sudheer M. Dhoop, S. Chinnam, Rayna Patel, Azizullah Beran, Megan Karrick, A. Renno, Ali Nawras","doi":"10.46570/utjms.vol11-2023-933","DOIUrl":"https://doi.org/10.46570/utjms.vol11-2023-933","url":null,"abstract":"Discussion: Our meta-analysis demonstrated that the use of SGLT-2 inhibitors can be beneficial in patients with NAFLD in terms of lowering the level of liver enzymes (ALT and AST) and lowering the fibrosis index score (FIB-4).","PeriodicalId":220681,"journal":{"name":"Translation: The University of Toledo Journal of Medical Sciences","volume":"42 3","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138997808","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"GSK3beta: a key regulator of glomerular podocyte injury in diabetic kidney disease","authors":"Mengxuan Chen, Y. Ge, Lance Dworkin, R. Gong","doi":"10.46570/utjms.vol11-2023-840","DOIUrl":"https://doi.org/10.46570/utjms.vol11-2023-840","url":null,"abstract":"Background: Emerging evidence suggests that glycogen synthase kinase (GSK3β), a critical transducer downstream of the insulin signaling pathway, acts as a convergent point for myriad pathways implicated in kidney injury, repair, and regeneration (1-3). However, its role in the pathogenesis of diabetic kidney disease remains highly controversial and was examined here (4, 5). Methods: Mouse podocytes were cultured under non-permissive conditions and exposed to a diabetic milieu containing high ambient glucose and insulin in the presence of proinflammatory stimulation. Cells were additionally subjected to GSK3β silencing, ectopic expression of a constitutively active GSK3β mutant (S9A), or treatment with tideglusib, a highly-selective small molecule inhibitor of GSK3β. Podocyte injury was assessed and signaling pathways examined. Results: Upon diabetic insult, podocytes demonstrated prominent signs of cytopathic changes, marked by loss of homeostatic marker proteins like synaptopodin, increased oxidative stress and apoptosis, and stress-induced premature senescence, as evidenced by increased staining for the acidic senescence-associated-β-galactosidase activity, amplified formation of γH2AX foci, and elevated expression of mediators of senescence signaling,","PeriodicalId":220681,"journal":{"name":"Translation: The University of Toledo Journal of Medical Sciences","volume":"3 4","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138997839","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hyperinsulinemic milieu elicits glomerular podocyte impairment and dysfunction via inducing GSK3beta hyperactivity","authors":"Mengxuan Chen, Y. Ge, Lance Dworkin, R. Gong","doi":"10.46570/utjms.vol11-2023-841","DOIUrl":"https://doi.org/10.46570/utjms.vol11-2023-841","url":null,"abstract":"Background: Epidemiological evidence suggests that hyperinsulinemia or insulin resistance is a significant risk factor for the development of diabetic complications such as DKD. However, whether hyperinsulinemia per se plays a causative role in the development of diabetic kidney injury is unknown and was explored here. \u0000Methods: Pre-diabetic db/db mice were examined for serum insulin levels, urinary albumin to creatinine ratios and renal histology. Conditionally immortalized mouse podocytes were cultured under non-permissive conditions and exposed to high ambient insulin conditions, following GSK3beta silencing, ectopic expression of a constitutively active GSK3beta mutant (S9A), or treatment with a small molecule GSK3beta inhibitor tideglusib. Podocyte injury was assessed and signaling pathways examined.  \u0000Results: In pre-diabetic db/db mice, hyperinsulinemia was evident and associated with microalbuminuria and early signs of podocyte impairment, including diminished expression of homeostatic marker proteins like synaptopodin, as compared with db/m littermates. In vitro, prolonged exposure of differentiated podocytes to high ambient insulin induced podocytopathic changes, including cellular hypertrophy, loss of synaptopodin, and disruption of actin cytoskeleton integrity. This was associated with a desensitized insulin signaling and diminished inhibitory phosphorylation of GSK3beta, denoting GSK3beta hyperactivity. In pre-diabetic db/db mice, GSK3beta hyperactivity was confirmed in glomerular podocytes, correlating with the level of hyperinsulinemia or microalbuminuria. In cultured podocytes, ectopic expression of S9A caused podocyte hypertrophy and podocytopathic changes, reminiscent of the harmful effect of the hyperinsulinemic milieu. Conversely, GSK3beta knockdown mitigates podocyte injury elicited by hyperinsulinemic milieu. This protective effect was mimicked by the small molecule inhibitor tideglusib. \u0000Conclusions: GSK3beta hyperactivity is required and sufficient for Hyperinsulinemic milieu-elicited glomerular podocyte impairment and dysfunction.        ","PeriodicalId":220681,"journal":{"name":"Translation: The University of Toledo Journal of Medical Sciences","volume":"82 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138998663","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Acute exacerbation of bronchiectasis secondary to Achromobacter xylosoxidans in a patient with Mycobacterium-Avium Intracellulare infection","authors":"Kashvi Patel, Sree Jambunathan, Faraz Badar, Muzdah Anwar, Zaid Zakaria, Amna Al-Tkrit, Fadi Safi","doi":"10.46570/utjms.vol11-2023-871","DOIUrl":"https://doi.org/10.46570/utjms.vol11-2023-871","url":null,"abstract":"copious amounts of mucopurulent secretions. Respiratory culture was negative for acid fast bacilli and fungal smear but positive for Achromobacter xylosoxidans.. Sensitivity testing showed resistance to multiple antibiotics including cephalosporins, penicillin, fluroquinolones, aztreonam","PeriodicalId":220681,"journal":{"name":"Translation: The University of Toledo Journal of Medical Sciences","volume":"29 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138998732","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Late angina due to anomalous Right Coronary Artery","authors":"Nahush Bansal, Catalin Dragomirescu, Mona Mahmoud","doi":"10.46570/utjms.vol11-2023-884","DOIUrl":"https://doi.org/10.46570/utjms.vol11-2023-884","url":null,"abstract":"","PeriodicalId":220681,"journal":{"name":"Translation: The University of Toledo Journal of Medical Sciences","volume":"10 2","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139000837","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"PAVER: Pathway Analysis Visualization with Embedding Representations","authors":"William G. Ryan, Ali S. Imami, Hunter Eby, Robert Mccullumsmith, Rammohan Shukla","doi":"10.46570/utjms.vol11-2023-906","DOIUrl":"https://doi.org/10.46570/utjms.vol11-2023-906","url":null,"abstract":"Interpreting pathway analysis often poses a significant challenge due to the extensive lists of gene ontology (GO) terms that require meticulous manual curation to identify underlying themes. We developed PAVER, a novel R software package, to address this issue by automating theme generation and clustering of GO terms. By utilizing embedding representations and advanced machine learning techniques, PAVER discerns patterns within the GO terms, creating an intuitive visual landscape of clusters for ease of functional interpretation. This method significantly minimizes the time and effort traditionally required for manual curation. We applied PAVER to a previously published dataset, where it demonstrated robustness by generating themes that closely mirrored those produced by manual curation. With PAVER, we present a powerful tool that not only enhances the efficiency of pathway analysis but also broadens its accessibility across various fields, including disease pathway modeling, drug target identification, and comparative genomics. Our work with PAVER marks a significant step towards simplifying the pathway analysis interpretation process in bioinformatics research.","PeriodicalId":220681,"journal":{"name":"Translation: The University of Toledo Journal of Medical Sciences","volume":"39 8","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138995694","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Epigenetic Repression of eNOS in Scleroderma (SSc) Microvascular Endothelial Cells (MVECs) is Related to the Downregulation of MicroRNA-152 by Enhanced DNA Methyltransferase 1 (Dnmt1) Expression.","authors":"Yongqing Wang, B. Kahaleh","doi":"10.46570/utjms.vol11-2023-905","DOIUrl":"https://doi.org/10.46570/utjms.vol11-2023-905","url":null,"abstract":"Objectives: Alteration in Scleroderma (SSc)-microvascular endothelial cells (MVEC) is related to epigenetic influences on gene expression level. Nitric oxide synthase gene (NOS3) repression is a prime example of epigenetic alteration of SSc-MVEC phenotype. The underlying mechanism of epigenetic imprinting in SSc-MVEC remains unknown. MicroRNAs (miRNAs), which are noncoding RNAs that regulate gene expression, are involved in diverse biological functions, including epigenetics regulation. It has been reported that downregulation of microRNA-152 induces aberrant DNA methylation by targeting the maintenance methyl transferase Dnmt1. In this study, we investigated miRNA-152 expression levels in SSc-MVEC and whether it is involved in the regulation of epigenetic imprinting in SSc. Methods: MVEC cells were isolated from skin biopsies of SSc patients and matched control subjects. The NOS3, Dnmt1, and miR-152 expression levels in normal and SSc-MVEC were checked by real-time PCR. The epigenetic regulation of NOS3 was examined by the addition of DNA methyltransferase and histone deacetylase inhibitors to MVEC cultures and by analysis of CpG site methylation in the NOS3 promotor","PeriodicalId":220681,"journal":{"name":"Translation: The University of Toledo Journal of Medical Sciences","volume":"43 35","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138995854","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}