Discovery medicine最新文献

{"title":"TWEAK Knockdown Alleviates Post-Cardiac Arrest Brain Injury via the p38 MAPK/NF-κB Pathway.","authors":"Haifang Zhang,&nbsp;Ran Wang","doi":"10.24976/Discov.Med.202335177.51","DOIUrl":"https://doi.org/10.24976/Discov.Med.202335177.51","url":null,"abstract":"<p><strong>Background: </strong>Cardiac arrest (CA) and subsequent cardiopulmonary resuscitation (CPR) can cause brain injury, which is one of the factors affecting the recovery of brain function in CA patients. There is increasing evidence that tumor necrosis factor-like weak apoptosis-inducing factor (TWEAK) is associated with the brain injury diseases. This study was aimed to investigate the modulation mechanism of TWEAK involved in brain injury after cardiac arrest/subsequent cardiopulmonary resuscitation (CA/CPR).</p><p><strong>Materials and methods: </strong>For <i>in vivo</i> experiments, healthy male Sprague-Dawley (SD) rats were applied to establish CA/CPR model, and oxygen-glucose deprivation/reoxygenation (OGD/R)-stimulated neurons model was established <i>in vitro</i>. TWEAK short hairpin RNAs (shRNAs) were injected into the lateral ventricle of CA/CPR rats or transfected into OGD/R cell culture to analyze the consequent alteration in neurological scores, behavioral tests, cell proliferation, cell apoptosis, and neuroinflammation through immunofluorescence staining, terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL) staining and enzyme linked immunosorbent assay (ELISA).</p><p><strong>Results: </strong>There were high expressions of TWEAK and fibroblast growth factor-inducible 14 (Fn14) in the cerebral cortex of CA/CPR rats and OGD/R-stimulated neuronal cells. TWEAK knockdown attenuated cell apoptosis, inflammation and showed better behavioral tests in CA/CPR rats. Furthermore, TWEAK shRNAs obviously facilitated cell proliferation, suppressed apoptosis and inflammation after OGD/R injury. Western blotting results stated that TWEAK silencing promoted phosphorylated p38 (p-p38) and phosphorylated p65 (p-p65) expressions.</p><p><strong>Conclusions: </strong>TWEAK might be involved in the pathogenesis of CA/CPR through inhibiting p38 MAPK/NF-κB pathway.</p>","PeriodicalId":11379,"journal":{"name":"Discovery medicine","volume":null,"pages":null},"PeriodicalIF":1.4,"publicationDate":"2023-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10493987","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exploring Influenza A Virus-Induced Lung Injury and Immune Response Based on Humanized Lung-on-Chip.","authors":"Shaoyan Gu,&nbsp;Pan Pan,&nbsp;Jiang Wang,&nbsp;Yinghan Shi,&nbsp;Feng Shi,&nbsp;Yuhan Zhang,&nbsp;Wei Guan,&nbsp;Yan Cao,&nbsp;Haimao Qin,&nbsp;Qingzhong Wang,&nbsp;Lixin Xie","doi":"10.24976/Discov.Med.202335177.55","DOIUrl":"10.24976/Discov.Med.202335177.55","url":null,"abstract":"<p><strong>Background: </strong>Influenza is an important respiratory tract pathogen that causes substantial seasonal and pandemic morbidity and mortality. The aim of this study was to systematically analyze the transcriptome characteristics of peripheral blood mononuclear cells (PBMCs) after influenza A virus infection by constructing a human lung microarray model composed of PBMCs to simulate the influenza A virus infection process.</p><p><strong>Methods: </strong>A human lung microarray model was constructed using alveolar epithelial cells, vascular endothelial cells, alveolar macrophages and PBMCs, for simulation of the process of influenza A virus infection. The transcriptome characteristics of PBMCs after influenza A virus infection were analyzed by a single-cell RNA sequencing system.</p><p><strong>Results: </strong>The study could realistically mimic the structure and physiological functions of the alveoli <i>in vitro</i> using immunofluorescence staining and expression of the specific marker. After the influenza A virus infected the upper lung chip channels, the epithelial cells underwent a high inflammatory response and spread to endothelial cells. Under experimental conditions, the Influenza A virus infection did not compromise the integrity of epithelial cells, but caused damage to endothelial cells and barrier dysfunction. Single-cell RNA sequencing of PBMCs showed that B and cluster of differentiation 4 (CD4) T cells played important immunomodulatory roles in response to influenza A virus infection, including significantly activating type I interferon signaling pathway, regulating cytokine and chemokine signaling pathway. Especially genes involved in cellular communication were significantly highly expressed post-infection.</p><p><strong>Conclusions: </strong>All these results suggested that the interactions among immune cells played a crucial role in endothelial cell injury and immune cell recruitment after influenza virus infection. This lung-on-chip infection model combined with single-cell RNA sequencing provided a unique platform that can closely investigate the lung immune response to influenza A virus infection and new therapeutic strategies for influenza.</p>","PeriodicalId":11379,"journal":{"name":"Discovery medicine","volume":null,"pages":null},"PeriodicalIF":1.4,"publicationDate":"2023-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10195769","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Role of ON and OFF Visual Pathways in Rod- and Cone-Driven Flicker Responses.","authors":"Fei Liao,&nbsp;Haitao Liu,&nbsp;Alejandro Gallego-Ortega,&nbsp;Francisco Germain,&nbsp;Pedro de la Villa","doi":"10.24976/Discov.Med.202335177.56","DOIUrl":"https://doi.org/10.24976/Discov.Med.202335177.56","url":null,"abstract":"<p><strong>Purpose: </strong>To evaluate the effects of various retinal neurotransmitters on temporal resolution, particularly, on the Critical Flicker Fusion Frequency (CFF), which has been previously applied in ophthalmic pathophysiologic research.</p><p><strong>Methods: </strong>A binocular physiologic electroretinogram was performed on adult mice. Animals in the control group were injected in the right eye with 1 μL of phosphate-buffered saline (PBS). Animals in the experimental group were injected in the left eye with 1 μL of PBS and in the right eye with 1 μL of PBS to which different molecules were added: 2-amino-4-phosphonobutyric acid (APB), Glutamate, γ-aminobutyric acid (GABA), 6,7-dinitroquinoxaline-2,3-dione (DNQX), Bicuculline, Glycine, and 4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid (HEPES). Initially, rod response was recorded and later the cone response.</p><p><strong>Results: </strong>APB suppressed the rod-driven, but not the cone-driven flicker response. The other agents severely affected the lower flickering frequency response amplitude, in particular, at 3 Hz. The threshold of CFF was lowered from 50 Hz to 40 Hz after applying APB, Glycine, and HEPES. GABA remarkably enhanced rod-driven and cone-driven flicker response at 3 Hz, whereas Glutamate and GABA/Glutamate only did in rod-driven flicker response.</p><p><strong>Conclusions: </strong>Both ON and OFF visual pathways were implied in cone-driven response, but only the ON visual pathway appears to play a relevant role in rod-driven flicker response. Flicker response seems to be enhanced by horizontal cells both in rod-driven and cone-driven response. In addition, due to the greater sensitivity of the flicker at low frequencies, it is suggested that pathophysiological studies should be carried out at said frequencies.</p>","PeriodicalId":11379,"journal":{"name":"Discovery medicine","volume":null,"pages":null},"PeriodicalIF":1.4,"publicationDate":"2023-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10195771","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Significance of Serum IgG4/IgG and IgG4/IgG1 Ratio in the Diagnosis Value of IgG4-Related Diseases.","authors":"Wei Wang,&nbsp;Yuanyuan Li,&nbsp;He Feng","doi":"10.24976/Discov.Med.202335177.48","DOIUrl":"https://doi.org/10.24976/Discov.Med.202335177.48","url":null,"abstract":"<p><strong>Objective: </strong>Elevated serum immunoglobulin G4 (IgG4) is one of the important features of patients with IgG4-related diseases (IgG4-RD). But diagnosing these diseases using IgG4 alone is tricky because the tests can sometimes give inaccurate results. Our research is focused on studying the ratio of IgG4 to two other substances, immunoglobulin G (IgG) and immunoglobulin G1 (IgG1), in the blood. We hope this approach will lead to more accurate diagnoses of IgG4-RD.</p><p><strong>Methods: </strong>We conducted a study on 68 patients diagnosed with IgG4-related diseases (IgG4-RD) and 160 individuals suffering from other autoimmune diseases (AID) at our hospital between June 2018 and June 2022. Eighty healthy people who underwent physical examination in our hospital at the same time were randomly selected as controls, and medical records were collected for all subjects. The serum IgG and IgG subclasses were detected, and the IgG4/IgG and IgG4/IgG1 ratios were calculated.</p><p><strong>Results: </strong>We found that patients with IgG4-RD have significantly higher average levels of serum IgG4 and more elevated IgG4/IgG and IgG4/IgG1 ratios compared to individuals with other AID patients and those in good health (<i>p</i> < 0.001). The receiver operating characteristic (ROC) curve analysis showed that the diagnostic effectiveness area under the curve (AUC) of the serum IgG4/IgG ratio for IgG4-RD was 0.906 (95% confidence interval [CI], 0.865-0.947) and 0.921 (95% CI, 0.876-0.965) when comparing with other AID patients and healthy individuals, respectively. The optimal cut-off value for the IgG4/IgG ratio was 0.147 (with 72.1% sensitivity and 94.4% specificity) compared with AID patients and 0.129 (with 77.9% sensitivity and 96.2% specificity) compared with healthy individuals. Similarly, the AUC of the serum IgG4/IgG1 ratio for diagnosing IgG4-RD was 0.919 (95% CI, 0.882-0.956) and 0.916 (95% CI, 0.870-0.962) when compared with patients with other AID and healthy individuals, respectively. When we divided our study participants into a high IgG4/IgG ratio group (>0.129) and a normal IgG4/IgG ratio group (≤0.129) using a cut-off point of 0.129, we found through logistic regression analysis that those with a high IgG4/IgG ratio were more likely to be associated with IgG4-RD (odds ratio [OR], 31.25; 95% CI, 15.31-63.79; <i>p</i> < 0.001). Likewise, a high IgG4/IgG1 ratio was also significantly linked to an increased risk of IgG4-RD (OR, 36.39; 95% CI, 17.57-75.38; <i>p</i> < 0.001).</p><p><strong>Conclusions: </strong>The serum's IgG4/IgG and IgG4/IgG1 ratios are independently linked to IgG4-RD and are valuable in its diagnosis.</p>","PeriodicalId":11379,"journal":{"name":"Discovery medicine","volume":null,"pages":null},"PeriodicalIF":1.4,"publicationDate":"2023-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10493983","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Development and Comparative Analysis of an Early Prediction Model for Acute Kidney Injury within 72-Hours Post-ICU Admission Using Evidence from the MIMIC-III Database.","authors":"Yan Luo,&nbsp;Wenling Ye,&nbsp;Yawei Sun,&nbsp;Heling Bao,&nbsp;Hui Liu","doi":"10.24976/Discov.Med.202335177.61","DOIUrl":"https://doi.org/10.24976/Discov.Med.202335177.61","url":null,"abstract":"<p><strong>Background: </strong>Prompt recognition of patients predisposed to acute kidney injury (AKI) within 72 hours of intensive care unit (ICU) admission holds significant clinical importance as it can considerably lower mortality rates. However, existing AKI prediction models often require complex data collection yet yield only moderate performance. This study aims to develop a straightforward and efficient AKI prediction model, providing ICU physicians with a powerful tool to expedite the detection of AKI patients.</p><p><strong>Methods: </strong>This study proposed a novel generative adversarial imputation networks-least absolute shrinkage and selection operator-extreme gradient boosting (Gain-Lasso-XGBoost) framework and developed an AKI prediction model on the basis of the medical information mart for intensive care (MIMIC-III) database. All the steps, including data preprocessing, feature selection, development, and optimization of prediction models, are organically integrated into the framework which has strong scalability. To compare the performance of our model with current models, we conducted a systematic review to collect all studies on the basis of the MIMIC-III database with similar objectives.</p><p><strong>Results: </strong>From 15 demographic and clinical variables, 8 features and 5 features were identified as the optimal group of features and processed into the model development. The model optimization further improved the performance of our proposed framework, and the area under curve (AUC) results with 8 and 5 feature vectors achieved 0.849 and 0.830, respectively. Compared with other studies, our method extracted only 8 or 5 feature vectors and obtained superior performance, with an average AUC 1.9% higher than the state-of-the-art approaches in the same type.</p><p><strong>Conclusions: </strong>Our study suggested that the onset of AKI be effectively and quickly predicted using simplified features, and not just for more specific patient groups. It may help clinicians accurately identify patients at risk of AKI after ICU admission and provide timely monitoring and treatment.</p>","PeriodicalId":11379,"journal":{"name":"Discovery medicine","volume":null,"pages":null},"PeriodicalIF":1.4,"publicationDate":"2023-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10140772","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Potential Role of TRPM8 in Cold-Induced Hypertension and Its Clinical Implications.","authors":"Undurti Narasimha Das","doi":"10.24976/Discov.Med.202335177.46","DOIUrl":"https://doi.org/10.24976/Discov.Med.202335177.46","url":null,"abstract":"<p><p>Seasonal variation in blood pressure that is higher in winter and lower in summer has been attributed to several factors that include changes in the activity of autonomic nervous system, vasopressin and expression of endothelial nitric oxide synthase (eNOS). Transient receptor potential melastatin 8 (TRPM8), a non-selective Ca²⁺-permeable cationic channel, serves as a molecular transducer to sense cold by the somatosensory system. TRPM8 is sensitive to protein kinase C (PKC) and phosphatidyl inositol-4,5-biphosphate [PI(4,5)P₂] suggesting that TRPM8 is stimulated by phospholipase C (PLC)-coupled receptors. Activated PLC inhibits TRPM8 by reducing cellular PI(4,5)P₂ levels and by activating PKC via diacyl glycerol. Bradykinin and prostaglandin E2 (PGE2), which are pro-inflammatory molecules, reduce the responses to cold, suggesting that phospholipase A2 (PLA2), which releases polyunsaturated fatty acids (PUFAs), the precursors of various eicosanoids, from the cell membrane lipid pool can modulate the function of TRPM8. TRPM8 functions as a nociceptor and modulates immune response. These and other studies indicate that cold-induced activation of transient receptor potential melastatin 8 (TRPM8) plays a role in the pathobiology of hypertension, preeclampsia and in the regulation of inflammation and immunity.</p>","PeriodicalId":11379,"journal":{"name":"Discovery medicine","volume":null,"pages":null},"PeriodicalIF":1.4,"publicationDate":"2023-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10493984","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Animal Feasibility Study of a Novel Spinal Cord Stimulation Multicolumn Lead (Heron Lead).","authors":"Patrick Mertens,&nbsp;Maria Celeste Cantone,&nbsp;Alessandro Antonini,&nbsp;Sandro Ferrari,&nbsp;Valentina Ferpozzi,&nbsp;Alaa Abd-Elsayed","doi":"10.24976/Discov.Med.202335177.62","DOIUrl":"https://doi.org/10.24976/Discov.Med.202335177.62","url":null,"abstract":"<p><strong>Background: </strong>Currently available spinal cord stimulation paddle leads require a laminectomy, limiting the types of clinicians who can implant and increasing the risk of complications. Recently, WISE S.r.l. designed a prototype multicolumn lead named the Heron® lead that can be implanted percutaneously. The purpose of the study was to examine the efficiency of placing a paddle lead percutaneously.</p><p><strong>Methods: </strong>Ten sheep were assigned to either the Heron lead group (n = 7) or the control group (n = 3). The sheep were observed for 13 weeks after implantation. Neurological and clinical examinations were conducted prior to surgery and then during the follow-up period. The implantation sites were evaluated through macroscopic observations during the article explantation and the lead migration was evaluated by comparing the article positioning at the surgery, four weeks after the surgery and at the explantation day through fluoroscope images. A qualitative comparison was made between the results collected with the test article and the control article.</p><p><strong>Results: </strong>Observations at the surgical sites indicate that test animals appeared to have less swelling around the surgical wound than control ones in the first 14 days, but no impact on wound healing was noticed. Additionally, no clear difference was observed in pain scores between the two groups, with observations tending to show that the maximum pain was occurring later in the test group with respect to the control group. General clinical observations showed no major difference between the two groups, and determined clinical abnormalities were not directly related to the procedure. Lastly, neurological deficits frequency decreased from the first to last animal operated, regardless of their test or control status.</p><p><strong>Conclusions: </strong>Our study concluded that the Heron lead is safe to implant, with a safety profile similar to the control article. Additionally, we conclude that the Heron lead is effective in reducing lead migration events.</p>","PeriodicalId":11379,"journal":{"name":"Discovery medicine","volume":null,"pages":null},"PeriodicalIF":1.4,"publicationDate":"2023-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10140774","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"FMO1 Promotes Nonalcoholic Fatty Liver Disease Progression by Regulating PPARα Activation and Inducing Ferroptosis.","authors":"Lin Zou,&nbsp;Qin Shi,&nbsp;Yingxuan Li,&nbsp;Zhen Yuan,&nbsp;Li Peng,&nbsp;Jiancan Lu,&nbsp;Hongling Zhu,&nbsp;Junhua Ma","doi":"10.24976/Discov.Med.202335177.60","DOIUrl":"https://doi.org/10.24976/Discov.Med.202335177.60","url":null,"abstract":"<p><strong>Background: </strong>The function of flavin containing dimethylaniline monooxygenase 1 (FMO1), which is known to play a part in lipid metabolism, remains unclear in the development of nonalcoholic fatty liver disease (NAFLD). This research has the objective of examining the contributions of FMO1 in the progression of NAFLD and the associated mechanisms, particularly the peroxisome proliferator activated receptor alpha (PPARα) and ferroptosis pathways.</p><p><strong>Methods: </strong>An <i>in vitro</i> NAFLD model was established by treating L02 cells with free fatty acids (FFAs). The FMO1 and ferroptosis levels were examined in the cellular NAFLD model. <i>FMO1</i> was knocked down using short-interfering RNA transfection. The effects of <i>FMO1</i> knockdown on lipid accumulation, PPARα expression, and ferroptosis were examined in the cellular NAFLD model. Additionally, the effects of <i>FMO1</i> and/or <i>PPARα</i> overexpression on lipid metabolism and ferroptosis were analyzed. Furthermore, L02 cells were pre-treated with GW7647 (PPARα agonist) or RSL3 (ferroptosis activator) and stimulated with FFAs.</p><p><strong>Results: </strong>The levels of FMO1 and ferroptosis were upregulated in the <i>in vitro</i> NAFLD model. <i>FMO1</i> knockdown suppressed the FFA-induced accumulation of lipids in hepatocytes, downregulation of PPARα expression, and upregulation of ferroptosis. In contrast, <i>FMO1</i> overexpression dysregulated lipid metabolism and downregulated PPARα levels. Meanwhile, <i>PPARα</i> overexpression mitigated the <i>FMO1</i> overexpression-induced upregulation of ferroptosis and lipid accumulation. Treatment with RSL3 suppressed the effects of <i>PPARα</i> overexpression on lipid accumulation and FMO1 expression.</p><p><strong>Conclusions: </strong>FMO1 upregulates ferroptosis by suppressing PPARα in NAFLD, which leads to the dysregulation of lipid metabolism.</p>","PeriodicalId":11379,"journal":{"name":"Discovery medicine","volume":null,"pages":null},"PeriodicalIF":1.4,"publicationDate":"2023-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10195772","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mice, Rats and Guinea Pigs Exhibit Significant Variations in the Plasma, Urine and Tissue Levels of Taurine, Betaine, Sarcosine and Other Osmolyte-Active Amino Acids.","authors":"Lenka Tomasova,&nbsp;Klaudia Maksymiuk,&nbsp;Dawid Chabowski,&nbsp;Emilia Samborowska,&nbsp;Marcin Ufnal","doi":"10.24976/Discov.Med.202335177.50","DOIUrl":"https://doi.org/10.24976/Discov.Med.202335177.50","url":null,"abstract":"<p><strong>Background: </strong>Osmolytes are naturally occurring compounds that protect cells from osmotic stress in high-osmolarity tissues, such as the kidney medulla. Some amino acids, including taurine, betaine, glycine, alanine, and sarcosine, are known to act as osmolytes. This study aimed to establish the levels of these amino acids in body fluids and tissues of laboratory animals used as models for human diseases in biomedical research.</p><p><strong>Methods: </strong>Liquid chromatography coupled with mass spectrometry was used to quantify taurine, glycine, betaine, alanine, beta-alanine, and sarcosine in plasma, urine, and tissues of adult, male mice, rats and guinea pigs.</p><p><strong>Results: </strong>Among the species analyzed, taurine was found to have the highest tissue concentrations across all compounds, with the heart containing the greatest amount. In guinea pigs, betaine levels were higher in the renal medulla than in the renal cortex (<i>p</i> < 0.01), while in rats and mice, there were no significant differences in betaine levels between the kidney cortex and medulla. The urine of guinea pigs had lower levels of sarcosine compared to rats (<i>p</i> < 0.001), while the plasma (<i>p</i> < 0.05; > 0.05), heart (<i>p</i> < 0.05; < 0.05), lungs (<i>p</i> < 0.01; < 0.01), liver (<i>p</i> < 0.001; < 0.05), and kidneys (<i>p</i> < 0.01; < 0.01) of rats exhibited notably higher concentrations of sarcosine compared to both mice and guinea pigs, respectively.</p><p><strong>Conclusions: </strong>There are pronounced differences in the concentrations of taurine, betaine, and other amino acids across the investigated species. It is important to acknowledge these differences when selecting animal models for preclinical studies and to account for variations in amino acid concentrations when selecting amino acids doses for interventional studies.</p>","PeriodicalId":11379,"journal":{"name":"Discovery medicine","volume":null,"pages":null},"PeriodicalIF":1.4,"publicationDate":"2023-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10493986","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Inflammatory Mediators and GBM Malignancy: Current Scenario and Future Prospective.","authors":"Ilya Ulasov,&nbsp;Vaishali Singh,&nbsp;Anastasia Laevskaya,&nbsp;Peter Timashev,&nbsp;Rajesh Kumar Kharwar","doi":"10.24976/Discov.Med.202335177.47","DOIUrl":"https://doi.org/10.24976/Discov.Med.202335177.47","url":null,"abstract":"<p><p>Glioblastoma multiforme is one of the most widespread and dangerous forms of brain tumor with high inflammation. The tumor microenvironment comprises diverse tumor cells, different types of immune cells, and the extracellular matrix. Inflammatory mediators like chemokines, cytokines, and growth factors possibly serve as a capable therapeutic target to quash their tumor-promoting properties in glioblastoma multiforme (GBM). Cytokines are a heterogeneous group of soluble functional proteins which are also associated with the induction and progression of tumors. These are supposed to have both pro-inflammatory (such as tumor necrosis factor-α (TNF-α), interleukin-17A (IL-17A), interferon-γ (IFN-γ), IL-4, IL-2, IL-6, IL-12, IL-13) and anti-inflammatory (such as transforming growth factor-β (TGF-β), IL-10, and granulocyte-macrophage colony-stimulating factor (GM-CSF)) actions and are the crucial communications channels in the tumor microenvironment. In the present minireview we discuss the tumor microenvironment and inflammatory mediators and focus on the involvement of cytokines in establishing communication with the tumor microenvironment. The presented data highlight the possible roles of cytokines in communication between glioblastoma cells and tumor microenvironment. Cytokines formed by immune cells protect the host organs while cytokines secreted by tumor cells are used for their advantage. Though the clinical trials with a number of immunotherapeutic agents are going on around the globe, there is still a requirement for thorough investigation of the regulatory mechanism managing GBM growth, recurrence, and tumor response to the therapy.</p>","PeriodicalId":11379,"journal":{"name":"Discovery medicine","volume":null,"pages":null},"PeriodicalIF":1.4,"publicationDate":"2023-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10493985","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}