Pharmacological Reports最新文献

{"title":"Niraparib induces hyperglycemia in ovarian cancer patients: a preliminary pilot study.","authors":"Konrad Lewandowski, Joanna Stanisławiak-Rudowicz, Edyta Szałek, Anna Wolc, Agnieszka Karbownik","doi":"10.1007/s43440-025-00811-9","DOIUrl":"10.1007/s43440-025-00811-9","url":null,"abstract":"","PeriodicalId":19947,"journal":{"name":"Pharmacological Reports","volume":" ","pages":"597-606"},"PeriodicalIF":3.8,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12975802/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145715443","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dysregulation of store-operated calcium entry in fibroblast lines from adult and juvenile-onset Huntington's disease patients.","authors":"Samuel Oluwafemi Egbuwalo, Ewelina Latoszek, Hana Hansíková, Jiří Klempíř, Alžbeta Mühlbäck, Georg Bernhard Landwehrmeyer, Jacek Kuźnicki, Magdalena Czeredys","doi":"10.1007/s43440-025-00820-8","DOIUrl":"10.1007/s43440-025-00820-8","url":null,"abstract":"<p><strong>Background: </strong>The pathology of Huntington's disease (HD) is marked by the aggregation of mutant huntingtin protein (mHTT), which results from expanded polyglutamine (polyQ) residues encoded by CAG repeats in the HTT gene. These repeats are differentially elongated in adult- and juvenile-onset HD. In striatal neurons, the mHTT disrupts cellular mechanisms such as store-operated calcium entry (SOCE), a process in which endoplasmic reticulum Ca²⁺ depletion triggers extracellular Ca²⁺ influx; however, this process can also be affected in peripheral cells. The aim of this study was to evaluate SOCE in fibroblasts derived from both HD onset patients and age-related controls.</p><p><strong>Methods: </strong>We conducted SOCE analysis in dermal fibroblasts from 12 HD patients (including adult- and juvenile-onset subtypes) and age-related healthy controls using Fura-2 AM ratiometric imaging paired with EGTA-based extracellular calcium chelation protocols. To evaluate SOCE response, we administered two SOC channel inhibitors, 6-bromo-N-(2-phenylethyl)-2,3,4,9-tetrahydro-1 H-carbazol-1-amine hydrochloride (C₂₀H₂₂BrClN₂) and EVP4593, in premanifest HD fibroblasts.</p><p><strong>Results: </strong>In healthy human fibroblast lines, a decline in SOCE was observed between juvenile and adult individuals. In fibroblast lines from adult-onset HD patients (premanifest, early manifest, and manifest stages), we observed increased SOC channel activity. Conversely, juvenile-onset HD fibroblast lines exhibited reduced SOC channel activity compared to controls. Notably, SOCE dysregulation was independent of CAG repeat length in HD lines. Both SOC channel inhibitors attenuated SOCE in adult-onset HD lines.</p><p><strong>Conclusion: </strong>The mHTT upregulates SOCE in adult-onset HD fibroblasts and downregulates it in juvenile-onset HD fibroblast lines; however, SOCE levels do not correlate with the length of CAG repeats encoding mHTT. Despite opposing trends compared to age-related controls, similar levels of SOCE in both HD-onset fibroblasts were detected. Both C₂₀H₂₂BrClN₂ and EVP4593 show potential for stabilizing SOCE in adult-onset HD. These findings suggest that dysregulated SOCE could be investigated as a peripheral target for studying pathological processes potentially associated with Huntington's disease.</p>","PeriodicalId":19947,"journal":{"name":"Pharmacological Reports","volume":" ","pages":"568-581"},"PeriodicalIF":3.8,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12975840/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146011614","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The HPA axis and kynurenine pathway: exploring the role of stress and neuroinflammation in treatment-resistant depression.","authors":"Madhura M Bose, Anusha Govindula, Madhavan Nampoothiri, Devinder Arora, Jayesh Mudgal","doi":"10.1007/s43440-025-00806-6","DOIUrl":"10.1007/s43440-025-00806-6","url":null,"abstract":"<p><p>Treatment-resistant depression (TRD) continues to pose a major challenge in clinical practice, as a large proportion of patients fail to achieve remission despite multiple antidepressant drugs. Growing evidence indicates that dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis, together with epigenetic alterations, neuroinflammation, and kynurenine pathway metabolism, plays a central role in the pathophysiology of TRD. Particularly, prolonged stress-induced glucocorticoid receptor (GR) resistance, persistent hypercortisolaemia, and elevated pro-inflammatory cytokines contribute to neurotoxicity, hippocampal atrophy, and impaired neuroplasticity, aggravating depressive symptoms and reducing treatment response. Additionally, dysregulated tryptophan metabolism and the shift towards neurotoxic kynurenine metabolites further impair neuronal function and resulting in TRD. This review integrates recent findings on the complex interplay between HPA axis dysfunction, neuroimmune responses, and metabolic disturbances in TRD while highlighting novel therapeutic avenues such as ketamine, GR modulators, and anti-inflammatory agents. Further, disruption in the blood-brain barrier as one of the mechanisms of TRD was also reviewed. A deeper understanding of these mechanisms will enable the development of personalized treatment strategies to enhance clinical outcomes for TRD patients.</p>","PeriodicalId":19947,"journal":{"name":"Pharmacological Reports","volume":" ","pages":"374-390"},"PeriodicalIF":3.8,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12975799/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145550027","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exploring the anti-inflammatory activity of sulforaphane metabolites.","authors":"Barbara Pagliarani, Letizia Pruccoli, Chiara Chemello, Morena Zusso, José Cláudio Fonseca Moreira, Andrea Tarozzi, Henrique Mautone Gomes","doi":"10.1007/s43440-026-00823-z","DOIUrl":"10.1007/s43440-026-00823-z","url":null,"abstract":"","PeriodicalId":19947,"journal":{"name":"Pharmacological Reports","volume":" ","pages":"615-624"},"PeriodicalIF":3.8,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146029743","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Docosahexaenoic acid modulates myo-inositol and myo-inositol biosynthetic genes expression: implications for bipolar disorder.","authors":"Marlene Murray, Haley Kang, Taejun Ok, Kimberly Park, Joanne Jee Yeon Lee, Bomi Kim, Hyukje Sung, Talisa Tait, Daniel Colon Hidalgo, Yudy Guzman","doi":"10.1007/s43440-025-00815-5","DOIUrl":"10.1007/s43440-025-00815-5","url":null,"abstract":"","PeriodicalId":19947,"journal":{"name":"Pharmacological Reports","volume":" ","pages":"607-614"},"PeriodicalIF":3.8,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145900921","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effects of psilocybin and chronic mild stress on microglial activation in rat spinal cord: an ex vivo analysis.","authors":"Piotr Olejnik, Katarzyna Kamińska, Krystyna Gołembiowska, Kaja Kasarełło","doi":"10.1007/s43440-026-00824-y","DOIUrl":"10.1007/s43440-026-00824-y","url":null,"abstract":"","PeriodicalId":19947,"journal":{"name":"Pharmacological Reports","volume":" ","pages":"423-430"},"PeriodicalIF":3.8,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146011629","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Metformin in skin diseases: the role of gut microbiota and immune response.","authors":"Aneta Kiecka, Barbara Macura, Marian Szczepanik","doi":"10.1007/s43440-026-00825-x","DOIUrl":"10.1007/s43440-026-00825-x","url":null,"abstract":"","PeriodicalId":19947,"journal":{"name":"Pharmacological Reports","volume":" ","pages":"391-404"},"PeriodicalIF":3.8,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146030045","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Sigma₁ receptor antagonist CM304 potentiates the antinociceptive effects of the cannabinoid receptor agonist delta⁹-tetrahydrocannabinol in rats and mice.","authors":"Elmira Zolali, Mallory Burns, Sebastiano Intagliata, Avi Patel, Nicholas P Ho, Luis F Restrepo, Lea R Gamez-Jimenez, Manuel A Alvarez, Lisa L Wilson, Stephen J Cutler, Lance R McMahon, Takato Hiranita, Samuel Obeng, Christopher R McCurdy","doi":"10.1007/s43440-026-00834-w","DOIUrl":"10.1007/s43440-026-00834-w","url":null,"abstract":"","PeriodicalId":19947,"journal":{"name":"Pharmacological Reports","volume":" ","pages":"431-445"},"PeriodicalIF":3.8,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146143190","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Differential effects of isopropyl alcohol on glucose-induced insulin secretion in INS-1 and MIN6 cells.","authors":"Valérie Pawlowski, Valérie Plaisance, Mathilde Lucas, Emerson Giovanelli, Chloé Derasse, Alexandre Barras, Amar Abderrahmani","doi":"10.1007/s43440-026-00828-8","DOIUrl":"10.1007/s43440-026-00828-8","url":null,"abstract":"","PeriodicalId":19947,"journal":{"name":"Pharmacological Reports","volume":" ","pages":"535-545"},"PeriodicalIF":3.8,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146011572","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Targeting mitochondrial deubiquitinase USP30 to induce mitophagy in heteroplasmic mitochondrial diseases.","authors":"Brígida R Pinho, Vasco Martins, Anitta R Chacko, Célia Nogueira, Michael R Duchen, Jorge M A Oliveira","doi":"10.1007/s43440-026-00829-7","DOIUrl":"10.1007/s43440-026-00829-7","url":null,"abstract":"","PeriodicalId":19947,"journal":{"name":"Pharmacological Reports","volume":" ","pages":"519-534"},"PeriodicalIF":3.8,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12975861/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146053405","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}