Pathophysiology最新文献

Factor V Leiden (R506Q), Prothrombin G20210A, and MTHFR C677T Variants and Thrombophilia in Qatar Biobank Participants: A Case Control Study. 卡塔尔生物库参与者的因子 V Leiden (R506Q)、凝血酶原 G20210A 和 MTHFR C677T 变异与血栓性疾病：病例对照研究。

IF 2.7

Pathophysiology Pub Date : 2024-10-21 DOI: 10.3390/pathophysiology31040044

Sapha Shibeeb, Nada Al-Rayashi, Nehal Shams, Tameem Hadvan, Ejaife O Agbani, Atiyeh M Abdallah

{"title":"Factor V Leiden (R506Q), Prothrombin G20210A, and MTHFR C677T Variants and Thrombophilia in Qatar Biobank Participants: A Case Control Study.","authors":"Sapha Shibeeb, Nada Al-Rayashi, Nehal Shams, Tameem Hadvan, Ejaife O Agbani, Atiyeh M Abdallah","doi":"10.3390/pathophysiology31040044","DOIUrl":"https://doi.org/10.3390/pathophysiology31040044","url":null,"abstract":"Background: Thrombophilia, a predisposition to develop blood clots, is very common and can have serious sequelae. Aim: This study aimed to determine the prevalence of three thrombophilia-related genetic variants-factor V Leiden (FVL), prothrombin (F2) G20210A, and MTHFR C677T-in the Qatari population and their associations with self-reported thrombosis. Methods: We analysed samples from 408 Qatari participants [304 controls and 104 with self-reported thrombosis (deep vein thrombosis, pulmonary embolus, or ischaemic stroke)] from the Qatar Biobank. FVL (rs6025), F2 (rs1799963), and MTHFR (rs1801133) variants were genotyped using TaqMan assays. Results: Participants with self-reported thrombosis were older and more likely to be female. FVL A allele carriage (GA + AA vs. GG) was significantly higher in thrombosis cases (OR 3.6, p = 0.0002). In addition, individuals carrying FVL AA and GA genotypes had a lower mean platelet volume on average than those with the GG genotype (p = 0.03). MTHFR C677T did not show a similar association, and the F2 G20210A variant was too rare for analysis. Conclusions: There were significant differences in FVL A allele carriage between individuals with a history of thrombosis and the control group. Future research should explore the complex interplay between genetics and environment in thrombosis risk within this population.","PeriodicalId":19852,"journal":{"name":"Pathophysiology","volume":null,"pages":null},"PeriodicalIF":2.7,"publicationDate":"2024-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11503440/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142505534","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Flavonoid-Mediated Suppression of Tumor Angiogenesis: Roles of Ang-Tie/PI3K/AKT. 类黄酮介导的肿瘤血管生成抑制：Ang-Tie/PI3K/AKT的作用

IF 2.7

Pathophysiology Pub Date : 2024-10-12 DOI: 10.3390/pathophysiology31040043

Shallu Saini, Hardeep Singh Tuli, Reena V Saini, Adesh K Saini, Katrin Sak, Damandeep Kaur, Moyad Shahwan, Ritu Chauhan, Abhishek Chauhan

{"title":"Flavonoid-Mediated Suppression of Tumor Angiogenesis: Roles of Ang-Tie/PI3K/AKT.","authors":"Shallu Saini, Hardeep Singh Tuli, Reena V Saini, Adesh K Saini, Katrin Sak, Damandeep Kaur, Moyad Shahwan, Ritu Chauhan, Abhishek Chauhan","doi":"10.3390/pathophysiology31040043","DOIUrl":"https://doi.org/10.3390/pathophysiology31040043","url":null,"abstract":"Angiogenesis is a process involved in the formation of new blood capillaries from pre-existing ones. It is regulated by several anti-angiogenic molecules involved in tumor growth and metastasis. The endothelial angiopoietin Ang-Tie/PI3K/AKT growth receptor pathway is necessary for healthy vascular development. The activation of AKT is controlled by a multistep process involving phosphoinositide 3-kinase (PI3K). This article aims to provide an overview of the role and mechanism of the Ang-Tie/PI3K/AKT signaling pathways and the potential of flavonoids as anti-angiogenic drugs. Flavonoids have shown great potential in preventing angiogenesis by targeting signaling pathways and exhibit additional anti-cancer properties. Research studies have revealed that the currently available anti-angiogenic drugs do not meet the safety and efficacy standards for treating tumor growth. Phytocompounds have long been a valuable resource for the development of novel therapeutic drugs. This article explores recent findings explaining the role and mechanism of the Ang-Tie/PI3K/AKT signaling pathways, as well as the interaction of flavonoids with angiogenic signaling pathways as a novel therapeutic approach. Several investigations have shown that synergistic studies of natural phytocompounds have great potential to target these pathways to inhibit tumor growth. Therefore, flavonoid-based medications may offer a more effective synergistic strategy to treat cancer.","PeriodicalId":19852,"journal":{"name":"Pathophysiology","volume":null,"pages":null},"PeriodicalIF":2.7,"publicationDate":"2024-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11503374/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142505535","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Pathophysiology and Prevention of Manual-Ventilation-Induced Lung Injury (MVILI). 手动通气诱发肺损伤 (MVILI) 的病理生理学与预防。

IF 2.7

Pathophysiology Pub Date : 2024-10-12 DOI: 10.3390/pathophysiology31040042

Luke A White, Steven A Conrad, Jonathan Steven Alexander

{"title":"Pathophysiology and Prevention of Manual-Ventilation-Induced Lung Injury (MVILI).","authors":"Luke A White, Steven A Conrad, Jonathan Steven Alexander","doi":"10.3390/pathophysiology31040042","DOIUrl":"https://doi.org/10.3390/pathophysiology31040042","url":null,"abstract":"Manual ventilation, most commonly with a bag-valve mask, is a form of short-term ventilation used during resuscitative efforts in emergent and out-of-hospital scenarios. However, compared to mechanical ventilation, manual ventilation is an operator-dependent skill that is less well controlled and is highly subject to providing inappropriate ventilation to the patient. This article first reviews recent manual ventilation guidelines set forth by the American Heart Association and European Resuscitation Council for providing appropriate manual ventilation parameters (e.g., tidal volume and respiratory rate) in different patient populations in the setting of cardiopulmonary resuscitation. There is then a brief review of clinical and manikin-based studies that demonstrate healthcare providers routinely hyperventilate patients during manual ventilation, particularly in emergent scenarios. A discussion of the possible mechanisms of injury that can occur during inappropriate manual hyperventilation follows, including adverse hemodynamic alterations and lung injury such as acute barotrauma, gastric regurgitation and aspiration, and the possibility of a subacute, inflammatory-driven lung injury. Together, these injurious processes are described as manual-ventilation-induced lung injury (MVILI). This review concludes with a discussion that highlights recent progress in techniques and technologies for minimizing manual hyperventilation and MVILI, with a particular emphasis on tidal-volume feedback devices.","PeriodicalId":19852,"journal":{"name":"Pathophysiology","volume":null,"pages":null},"PeriodicalIF":2.7,"publicationDate":"2024-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11503381/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142505537","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Multiple Benefits of Empagliflozin in PCOS: Evidence from a Preclinical Rat Model. Empagliflozin 对多囊卵巢综合征的多重益处：来自临床前大鼠模型的证据

IF 2.7

Pathophysiology Pub Date : 2024-10-09 DOI: 10.3390/pathophysiology31040041

Dejana Rakic, Vladimir Jakovljevic, Vladimir Zivkovic, Jovana Jakovljevic Uzelac, Nikola Jovic, Maja Muric, Bozidar Pindovic, Aleksandra Dimitrijevic, Petar Arsenijevic, Jovan Rakic, Slobodanka Mitrovic, Tatjana Vulovic, Jovana Joksimovic Jovic

{"title":"Multiple Benefits of Empagliflozin in PCOS: Evidence from a Preclinical Rat Model.","authors":"Dejana Rakic, Vladimir Jakovljevic, Vladimir Zivkovic, Jovana Jakovljevic Uzelac, Nikola Jovic, Maja Muric, Bozidar Pindovic, Aleksandra Dimitrijevic, Petar Arsenijevic, Jovan Rakic, Slobodanka Mitrovic, Tatjana Vulovic, Jovana Joksimovic Jovic","doi":"10.3390/pathophysiology31040041","DOIUrl":"https://doi.org/10.3390/pathophysiology31040041","url":null,"abstract":"Polycystic ovary syndrome (PCOS) is the most common complex endocrinological condition of women that is associated with infertility and metabolic disorders during the reproductive period. Recently, a great deal of research has focused on the etiopathogenesis of this disorder and the modulation of therapeutic approaches. There are still many controversies in the choice of therapy, and metformin is one of the most commonly used agents in the treatment of PCOS. Considering the link between metabolic disorders and PCOS, glycemic status is crucial in these patients, and sodium-glucose cotransporter type 2 inhibitors (SGLT2is) represent a potentially promising new therapeutic approach. These drugs have been shown to improve glucose metabolism, reduce adipose tissue, decrease oxidative stress, and protect the cardiovascular system. These data prompted us to investigate the effects of empagliflozin (EMPA) in a PCOS rat model and compare them with the effects of metformin. We confirmed that EMPA positively affects somatometric parameters, glucose and lipid metabolism, and the levels of sex hormones, as well as reduces oxidative stress and improves ovarian function and morphology. Administration of EMPA at doses of 5 mg/kg, 15 mg/kg, and 45 mg/kg during a 4-week treatment period improved, as induced by estradiol valerate and a high-fat diet, the metabolic and reproductive statuses in a PCOS rat model. The best effects, which were comparable to the effects of metformin, were achieved in groups receiving the middle and highest applied doses of EMPA. These results may prompt further clinical research on the use of EMPA in patients with PCOS.","PeriodicalId":19852,"journal":{"name":"Pathophysiology","volume":null,"pages":null},"PeriodicalIF":2.7,"publicationDate":"2024-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11503319/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142505536","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Pathways to Alzheimer's Disease: The Intersecting Roles of Clusterin and Apolipoprotein E in Amyloid-β Regulation and Neuronal Health. 通往阿尔茨海默病的道路：群集素和载脂蛋白 E 在淀粉样蛋白-β调节和神经元健康中的交叉作用。

IF 2.7

Pathophysiology Pub Date : 2024-10-02 DOI: 10.3390/pathophysiology31040040

Alexandru Laslo, Laura Laslo, Eliza-Mihaela Arbănași, Alexandru-Andrei Ujlaki-Nagi, Laura Chinezu, Adrian Dumitru Ivănescu, Emil-Marian Arbănași, Roxana Octavia Cărare, Bogdan Andrei Cordoș, Ioana Adriana Popa, Klara Brînzaniuc

{"title":"Pathways to Alzheimer's Disease: The Intersecting Roles of Clusterin and Apolipoprotein E in Amyloid-β Regulation and Neuronal Health.","authors":"Alexandru Laslo, Laura Laslo, Eliza-Mihaela Arbănași, Alexandru-Andrei Ujlaki-Nagi, Laura Chinezu, Adrian Dumitru Ivănescu, Emil-Marian Arbănași, Roxana Octavia Cărare, Bogdan Andrei Cordoș, Ioana Adriana Popa, Klara Brînzaniuc","doi":"10.3390/pathophysiology31040040","DOIUrl":"https://doi.org/10.3390/pathophysiology31040040","url":null,"abstract":"One of the hallmarks of Alzheimer's disease (AD) is the deposition of amyloid-β (Aβ) within the extracellular spaces of the brain as plaques and along the blood vessels in the brain, a condition also known as cerebral amyloid angiopathy (CAA). Clusterin (CLU), or apolipoprotein J (APOJ), is a multifunctional glycoprotein that has a role in many physiological and neurological conditions, including AD. The apolipoprotein E (APOE) is a significant genetic factor in AD, and while the primary physiological role of APOE in the brain and peripheral tissues is to regulate lipid transport, it also participates in various other biological processes, having three basic human forms: APOE2, APOE3, and APOE4. Notably, the APOE4 allele substantially increases the risk of developing late-onset AD. The main purpose of this review is to examine the roles of CLU and APOE in AD pathogenesis in order to acquire a better understanding of AD pathogenesis from which to develop targeted therapeutic approaches.","PeriodicalId":19852,"journal":{"name":"Pathophysiology","volume":null,"pages":null},"PeriodicalIF":2.7,"publicationDate":"2024-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11503414/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142505538","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Early Radiation-Induced Changes in Lung Tissue and Intercellular Junctions: Implications for Tissue Repair and Fibrosis. 辐射诱发的肺组织和细胞间连接的早期变化：对组织修复和纤维化的影响

IF 2.7

Pathophysiology Pub Date : 2024-09-24 DOI: 10.3390/pathophysiology31040039

Ekaterina S Karetnikova, Alexandra A Livanova, Arina A Fedorova, Alexander G Markov

{"title":"Early Radiation-Induced Changes in Lung Tissue and Intercellular Junctions: Implications for Tissue Repair and Fibrosis.","authors":"Ekaterina S Karetnikova, Alexandra A Livanova, Arina A Fedorova, Alexander G Markov","doi":"10.3390/pathophysiology31040039","DOIUrl":"https://doi.org/10.3390/pathophysiology31040039","url":null,"abstract":"Early changes in lung tissue following ionizing radiation (IR) initiate processes that may lead to either regeneration or fibrosis. Intercellular junction proteins play a crucial role in the organization and function of epithelial tissues, both under normal conditions and after injuries. Alterations in the expression and localization of these proteins can influence the fate of epithelial cells. This study aims to investigate the effects of IR on lung tissue structure, as well as on the levels and distribution of intercellular junction proteins. Wistar rats were subjected to total X-ray irradiation at doses of 2 and 10 Gy. Lung tissue samples were collected for Western blot and histological analysis 72 h post-IR. IR at doses of 2 and 10 Gy led to structural changes in lung tissue and elevated levels of E-cadherin. The 10 Gy IR resulted in increased claudin-4 and occludin in lung parenchyma, decreased claudin-8 and claudin-12 in bronchial epithelium and endothelium, and suppression of apoptosis. Data evaluation indicated that alterations in the protein composition of intercellular junctions are essential processes in lung tissue at early stages after IR, and at least some of these alterations are associated with adaptation.","PeriodicalId":19852,"journal":{"name":"Pathophysiology","volume":null,"pages":null},"PeriodicalIF":2.7,"publicationDate":"2024-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11503413/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142505533","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

ITIH4 in Rheumatoid Arthritis Pathogenesis: Network Pharmacology and Molecular Docking Analysis Identify CXCR4 as a Potential Receptor. 类风湿性关节炎发病机制中的 ITIH4：网络药理学和分子对接分析确定 CXCR4 为潜在受体。

IF 2.7

Pathophysiology Pub Date : 2024-09-20 DOI: 10.3390/pathophysiology31030038

Lovely Joshi, Debolina Chakraborty, Vijay Kumar, Sagarika Biswas

{"title":"ITIH4 in Rheumatoid Arthritis Pathogenesis: Network Pharmacology and Molecular Docking Analysis Identify CXCR4 as a Potential Receptor.","authors":"Lovely Joshi, Debolina Chakraborty, Vijay Kumar, Sagarika Biswas","doi":"10.3390/pathophysiology31030038","DOIUrl":"10.3390/pathophysiology31030038","url":null,"abstract":"Elevated levels of Inter-alpha-trypsin-inhibitor heavy chain 4 (ITIH4) have grabbed attention in rheumatoid arthritis (RA) pathogenesis, though its precise mechanisms remain unexplored. To elucidate these mechanisms, a comprehensive strategy employing network pharmacology and molecular docking was utilized. RA targets were sourced from the DisGeNET Database while interacting targets of ITIH4 were retrieved from the STRING and Literature databases. Venny 2.1 was used to identify overlapping genes, followed by Gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) through Cytoscape 3.10.2 software, and molecular docking was performed in the ClusPro server. The study identified 18 interacting proteins of ITIH4 associated with RA, demonstrating their major involvement in the chemokine signaling pathway by enrichment analysis. Molecular docking of ITIH4 with the 18 proteins revealed that C-X-C chemokine-receptor type 4 (CXCR4), a major protein associated with chemokine signaling, has the highest binding affinity with ITIH4 with energy -1705.7 kcal/mol forming 3 Hydrogen bonds in the active site pocket of ITIH4 with His441, Arg288, Asp443 amino acids. The effect of ITIH4 on CXCR4 was analyzed via knockdown studies in rheumatoid arthritis fibroblast-like synoviocytes (RA-FLS), demonstrating the significant downregulation of CXCR4 protein expression validated by Western blot in RA-FLS. In conclusion, it was speculated that CXCR4 might serve as a potential receptor for ITIH4 to activate the chemokine signaling, exacerbating RA pathogenesis.","PeriodicalId":19852,"journal":{"name":"Pathophysiology","volume":null,"pages":null},"PeriodicalIF":2.7,"publicationDate":"2024-09-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11417925/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142292985","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Pregnancy-Associated Plasma Protein-A and Free β-Human Chorionic Gonadotrophin in Relation with Oxidative Stress in Obese Pregnant Women: A Clinical Cross-Sectional Study. 妊娠相关血浆蛋白-A 和游离β-人绒毛膜促性腺激素与肥胖孕妇氧化应激的关系：一项临床横断面研究。

IF 2.7

Pathophysiology Pub Date : 2024-09-19 DOI: 10.3390/pathophysiology31030037

Vanja Dimitrov, Maria Mikerova, Vladimir Reshetnikov, Victor Mikhailovsky, Sasa Raicevic, Sergey Bolevich, Vladimir Jakovljevic, Tamara Nikolic Turnic

{"title":"Pregnancy-Associated Plasma Protein-A and Free β-Human Chorionic Gonadotrophin in Relation with Oxidative Stress in Obese Pregnant Women: A Clinical Cross-Sectional Study.","authors":"Vanja Dimitrov, Maria Mikerova, Vladimir Reshetnikov, Victor Mikhailovsky, Sasa Raicevic, Sergey Bolevich, Vladimir Jakovljevic, Tamara Nikolic Turnic","doi":"10.3390/pathophysiology31030037","DOIUrl":"10.3390/pathophysiology31030037","url":null,"abstract":"Background: The pathophysiological mechanism underlying pregnancy complications is not entirely known. Although it is currently impossible to predict the occurrence of redox imbalance, it is possible to identify women with a high or medium risk of developing this disease prior to a negative outcome by non-invasive diagnostic methods. The Aim: This study aimed to examine the possible role of the parameter of oxidative stress (OS) measured in early pregnancy in the screening/treatment of obesity and its complications during pregnancy. Methods: This research was designed as a prospective observational cross-sectional clinical study which included 40 non-obese and 31 obese pregnant women between 11 and 13 g.w. who were managed in the Department of Obstetrics, University Clinical Center Kragujevac in Serbia. We collected anthropometric and clinical indicators, maternal and pregnancy factors, and measured prooxidative parameters from blood samples. Results: We observed significantly increased levels of the superoxide anion radical, hydrogen peroxide and the index of lipid peroxidation in the Obese group in comparison with the Non-Obese group and significantly decreased bioavailability of nitrites in the Obese group in comparison with the Non-Obese group. Conclusions: The determination of systemic parameters of OS in early pregnancy could be a good methodological approach in the screening/treatment of obesity during pregnancy and this approach should be followed for the screening of endothelial dysfunction in pregnancy which needs further monitoring and/or treatment.","PeriodicalId":19852,"journal":{"name":"Pathophysiology","volume":null,"pages":null},"PeriodicalIF":2.7,"publicationDate":"2024-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11417915/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142292988","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Impaired Peripheral Vascular Function Following Ischemic Stroke in Mice: Potential Insights into Blood Pressure Variations in the Post-Stroke Patient. 小鼠缺血性卒中后外周血管功能受损：卒中后患者血压变化的潜在启示。

IF 2.7

Pathophysiology Pub Date : 2024-09-05 DOI: 10.3390/pathophysiology31030036

Gokhan Yilmaz, Jonathan Steven Alexander

{"title":"Impaired Peripheral Vascular Function Following Ischemic Stroke in Mice: Potential Insights into Blood Pressure Variations in the Post-Stroke Patient.","authors":"Gokhan Yilmaz, Jonathan Steven Alexander","doi":"10.3390/pathophysiology31030036","DOIUrl":"10.3390/pathophysiology31030036","url":null,"abstract":"High systolic blood pressure and increased blood pressure variability after the onset of ischemic stroke are associated with poor clinical outcomes. One of the key determinants of blood pressure is arteriolar size, determined by vascular smooth muscle tone and vasodilatory and vasoconstrictor substances that are released by the endothelium. The aim of this study is to outline alterations in vasomotor function in isolated peripheral arteries following ischemic stroke. The reactivity of thoracic aortic segments from male C57BL/6 mice to dilators and constrictors was quantified using wire myography. Acetylcholine-induced endothelium-dependent vasodilation was impaired after ischemic stroke (LogIC50 Sham = -7.499, LogIC50 Stroke = -7.350, p = 0.0132, n = 19, 31 respectively). The vasodilatory responses to SNP were identical in the isolated aortas in the sham and stroke groups. Phenylephrine-induced vasoconstriction was impaired in the aortas isolated from the stroke animals in comparison to their sham treatment counterparts (Sham LogEC50= -6.652 vs. Stroke LogEC50 = -6.475, p < 0.001). Our study demonstrates that 24 h post-ischemic stroke, peripheral vascular responses are impaired in remote arteries. The aortas from the stroke animals exhibited reduced vasoconstrictor and endothelium-dependent vasodilator responses, while the endothelium-independent vasodilatory responses were preserved. Since both the vasodilatory and vasoconstrictor responses of peripheral arteries are impaired following ischemic stroke, our findings might explain increased blood pressure variability following ischemic stroke.","PeriodicalId":19852,"journal":{"name":"Pathophysiology","volume":null,"pages":null},"PeriodicalIF":2.7,"publicationDate":"2024-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11417821/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142292984","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Advances in Cathepsin S Inhibition: Challenges and Breakthroughs in Drug Development. 抑制胰蛋白酶 S 的进展：药物开发的挑战与突破。

IF 2.7

Pathophysiology Pub Date : 2024-09-03 DOI: 10.3390/pathophysiology31030035

Temitope A Ajani, Zandisiwe E Magwebu, Chesa G Chauke, Kenechukwu Obikeze

{"title":"Advances in Cathepsin S Inhibition: Challenges and Breakthroughs in Drug Development.","authors":"Temitope A Ajani, Zandisiwe E Magwebu, Chesa G Chauke, Kenechukwu Obikeze","doi":"10.3390/pathophysiology31030035","DOIUrl":"10.3390/pathophysiology31030035","url":null,"abstract":"Cathepsin S (CatS) is a proteolytic enzyme and a member of the cysteine protease family of proteolytic enzymes. Cathepsins S, K, and L are particularly similar in terms of their amino acid sequences and interactions with substrates, and this has made it difficult to develop inhibitors with specificity for either CatS, CatK, or CatL. The involvement of CatS in various disease pathophysiologies (autoimmune disorders, cardiovascular diseases, cancer, etc.) has made it a very important target in drug development. Efforts have been made since the early 1990s to develop a specific CatS inhibitor without any major success. Following many failed efforts to develop an inhibitor for CatS, it was discovered that interactions with the amino acid residues at the S2 and S3 pockets of CatS are critical for the identification of CatS-specific inhibitors. Amino acid residues at these pockets have been the target of recent research focused on developing a non-covalent, reversible, and specific CatS inhibitor. Methods applied in the identification of CatS inhibitors include molecular modeling, in-vitro screening, and in-vivo studies. The molecular modeling process has proven to be very successful in the identification of CatS-specific inhibitors, with R05459072 (Hoffmann-La Roche) and LY3000328 (Eli Lilly Company) which has completed phase 1 clinical trials. CatS inhibitors identified from 2011 to 2023 with promising prospects are discussed in this article.","PeriodicalId":19852,"journal":{"name":"Pathophysiology","volume":null,"pages":null},"PeriodicalIF":2.7,"publicationDate":"2024-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11417842/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142292982","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0