Pharmacological Reports最新文献

{"title":"Gastrointestinal adverse events associated with axitinib: pharmacovigilance analysis of the Japanese adverse drug event report database.","authors":"Keiko Hosohata, Riku Nakamoto, Yuko Kanbayashi","doi":"10.1007/s43440-026-00906-x","DOIUrl":"https://doi.org/10.1007/s43440-026-00906-x","url":null,"abstract":"<p><strong>Background: </strong>Axitinib is widely used to treat metastatic renal cell carcinoma; however, the characteristics of its gastrointestinal adverse events (AEs) remain poorly understood. This study evaluated gastrointestinal AEs associated with axitinib using the Japanese Adverse Drug Event Report database.</p><p><strong>Methods: </strong>Reports submitted between April 2004 and December 2024 were analyzed. Gastrointestinal AE reports were extracted, and disproportionality was evaluated by calculating reporting odds ratios (RORs).</p><p><strong>Results: </strong>Among 3,221,393 reports analyzed, 5,609 involved axitinib, including 800 gastrointestinal AEs. Signals were detected for 20 gastrointestinal AEs. Fatal outcomes were reported for four events, with gastrointestinal perforation and intestinal perforation showing the highest proportions of reported fatal outcomes. Median time to onset ranged from 44 to 148 days. Weibull distribution analysis was performed for AEs with sufficient reports. Diarrhoea showed an early failure pattern, whereas nausea exhibited a wear-out failure pattern with an increasing reporting hazard over time. Decreased appetite, gastrointestinal perforation, pneumatosis intestinalis, and rectal haemorrhage demonstrated a random failure pattern, occurring throughout the treatment period.</p><p><strong>Conclusions: </strong>This post-marketing analysis identified gastrointestinal AEs associated with axitinib, including several serious events with fatal outcomes. These AEs may occur both early and later during treatment, underscoring the need for continuous monitoring to facilitate prompt detection and management of severe gastrointestinal complications.</p>","PeriodicalId":19947,"journal":{"name":"Pharmacological Reports","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2026-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149040313","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":"Transcriptional and epigenetic regulation of the cannabinoid receptor type-1 (CB1R) in health and disease: an overview.","authors":"Keyla Tamara Cerdán-Centeno, Julio Morán, Abel Santamaría","doi":"10.1007/s43440-026-00901-2","DOIUrl":"https://doi.org/10.1007/s43440-026-00901-2","url":null,"abstract":"<p><p>The endocannabinoid system (ECS) is a highly plastic signaling network whose components are dynamically regulated in a context-dependent manner. Among its components, the cannabinoid type 1 receptor (CB1R), encoded by the CNR1 gene, is involved in multiple processes, including neuromodulation, neurodevelopment, metabolic regulation, nociception, appetite regulation, redox homeostasis, and inflammatory signaling. Alterations in CB1R expression occur selectively and progressively and have been linked to numerous metabolic disorders, cancer, and neurodegenerative diseases. Recent studies have begun to unveil the transcriptional and epigenetic mechanisms regulating CB1R expression, involving inflammatory transcription factors, nuclear receptors, metabolic regulators, redox-sensitive pathways, hormone-responsive factors, as well as chromatin remodeling marks and promoter methylation. These modulatory programs collectively shape CB1R abundance and availability and may critically influence the efficacy and safety of cannabinoid-based therapies. In this review, we discuss current knowledge of the transcriptional and epigenetic regulation of the CNR1 gene in response to various pathologies and drugs, highlighting context-dependent modulatory mechanisms. Additionally, we performed an in silico analysis to identify potential transcription factor binding sites (TFBS) in the CNR1 promoter and to elucidate candidate regulatory networks underlying its differential expression in health and disease.</p>","PeriodicalId":19947,"journal":{"name":"Pharmacological Reports","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2026-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149025797","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":"Cancer therapy-related cognitive impairment, part 1: an integrative clinical-mechanistic framework from phenotypes to convergent neurobiological pathways.","authors":"Selene Tertemiz, Jan Detka, Kinga Sałat","doi":"10.1007/s43440-026-00902-1","DOIUrl":"https://doi.org/10.1007/s43440-026-00902-1","url":null,"abstract":"<p><p>Cancer therapy-related cognitive impairment (CRCI) is a frequent complication of cancer treatment. It involves multiple biological mechanisms: neuroinflammation, oxidative stress, mitochondrial dysfunction, impaired neurogenesis, and altered brain connectivity. Although these mechanisms have been extensively studied, evidence across cytotoxic chemotherapy, endocrine therapy, and targeted therapies is often presented separately. This review is the first of a two-part series addressing the mechanisms underlying CRCI and current and emerging therapeutic strategies for its prevention and management. It integrates available clinical and mechanistic research results across treatment classes, highlighting shared biological pathways, biomarkers, neuroimaging findings, and objective versus subjective cognitive outcomes to provide a comprehensive overview of CRCI.</p>","PeriodicalId":19947,"journal":{"name":"Pharmacological Reports","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2026-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148991156","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":"Is teriparatide linked to osteosarcoma? A disproportionality analysis of the FAERS database.","authors":"Nunzia Balzano, Raffaella Di Napoli, Ludovica Vittoria Laino, Rosanna Ruggiero, Concetta Rafaniello, Liberata Sportiello, Francesco Rossi, Annamaria Mascolo, Annalisa Capuano","doi":"10.1007/s43440-026-00900-3","DOIUrl":"https://doi.org/10.1007/s43440-026-00900-3","url":null,"abstract":"<p><strong>Background: </strong>Teriparatide is approved for the treatment of osteoporosis and is generally well-tolerated. However, concerns remain about a possible association with osteosarcoma, a rare but aggressive bone malignancy. This pharmacovigilance study aims to evaluate the reporting frequency of osteosarcoma associated with teriparatide in the Food and Drug Administration Adverse Event Reporting System (FAERS).</p><p><strong>Methods: </strong>Individual case safety reports (ICSRs) listing teriparatide as a suspected drug and osteosarcoma as an adverse event were extracted from the FAERS public dashboard up to 20 February 2025. Both descriptive and disproportionality analyses were performed.</p><p><strong>Results: </strong>A total of 112,798 ICSRs involving teriparatide were retrieved, of which 29 were reported. Most cases involved female patients (72.4%) and older patients (48.3%). Almost all reports (96.6%) were classified as serious, with death being the most common outcome (44.8%). Of the reports with information on concomitant medications, 31% included five or more medications, with vitamins being the most common. The disproportionality analysis showed a significantly higher reporting frequency of osteosarcoma with teriparatide compared to all other drugs (reporting odds ratio, ROR: 15.31; 95% CI: 10.53-22.26). This signal remained consistent when the analysis was restricted to reports submitted since 2006 (ROR: 15.88; 95% CI: 10.92-23.09). The information component (IC) analysis confirmed this finding (IC: 3.56; 95% CI: 2.95-4), and similar results were observed for the post-2006 subset (IC: 3.60; 95% CI: 2.99-4.05). However, the analysis compared to another osteoporosis drug (romosozumab) did not confirm any safety signal for teriparatide.</p><p><strong>Conclusions: </strong>This study highlights a disproportionate signal between teriparatide use and osteosarcoma when compared to all other drugs but not compared to romosozumab. Based on this and considering that previous evidence did not support an increased risk, further research is warranted to better understand this association.</p>","PeriodicalId":19947,"journal":{"name":"Pharmacological Reports","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2026-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148991144","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":"Tetrahydrocurcumin suppresses FcεRI- and MRGPRX2-mediated mast cell activation and attenuates peanut-induced anaphylaxis in an in vitro and in vivo study.","authors":"Gyeongseo Suk, Jiyoon Mun, Ji Yeon Park, Minae Park, Ee Taek Hwang, Hae Woong Choi","doi":"10.1007/s43440-026-00899-7","DOIUrl":"https://doi.org/10.1007/s43440-026-00899-7","url":null,"abstract":"<p><strong>Background: </strong>Tetrahydrocurcumin (THC), a major reductive metabolite of curcumin, possesses improved chemical stability and anti-inflammatory properties. However, its direct effects on mast cell-mediated allergic responses remain poorly defined. We investigated whether THC suppresses FcεRI-dependent and selected IgE-independent mast cell activation and protects against peanut-induced anaphylaxis in vivo.</p><p><strong>Methods: </strong>Primary murine bone marrow-derived mast cells and human LAD2 mast cells were stimulated through IgE/FcεRI crosslinking or MRGPRX2-related activation. Mast cell degranulation, cytokine production (CCL2, TNF, IL-6, and IL-13), and cytotoxicity were evaluated. The in vivo efficacy of orally administered THC was assessed in a mouse model of peanut-induced anaphylaxis.</p><p><strong>Results: </strong>THC dose-dependently inhibited IgE/FcεRI-mediated mast cell degranulation and suppressed inflammatory cytokine production without detectable cytotoxicity. Under the tested conditions, THC exhibited greater inhibitory activity than pemirolast potassium. THC also suppressed ionomycin- and MRGPRX2-mediated mast cell activation and remained effective when administered before or at the initiation of activation. In peanut-sensitized mice, repeated oral THC administration significantly reduced anaphylactic hypothermia and intestinal inflammatory responses.</p><p><strong>Conclusion: </strong>THC suppresses FcεRI-dependent and MRGPRX2-dependent pathways and attenuates peanut-induced anaphylactic responses in vivo. These findings support the potential of THC as a mast cell-modulating compound for allergic and anaphylactic disorders.</p>","PeriodicalId":19947,"journal":{"name":"Pharmacological Reports","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2026-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148970698","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":"Cancer therapy-related cognitive impairment, part 2: from bench to bedside-and back: why candidate therapies for cancer therapy-related cognitive impairment fail to translate.","authors":"Selene Tertemiz, Jan Detka, Kinga Sałat","doi":"10.1007/s43440-026-00893-z","DOIUrl":"https://doi.org/10.1007/s43440-026-00893-z","url":null,"abstract":"<p><p>Although numerous pharmacological and nonpharmacological strategies have been proposed for the prevention or treatment of cancer therapy-related cognitive impairment (CRCI), only a few have achieved robust clinical translation. This review, the second part of a two-part series, first critically summarizes current candidate pharmacological and nonpharmacological interventions for CRCI, discussing their biological rationale, mechanisms of action, and the available preclinical and clinical evidence. It then reports why many of these promising approaches fail to translate into effective clinical therapies. We critically analyse the methodological gaps between preclinical models and cancer survivorship, including the use of non-tumour-bearing animals, inadequate modelling of age, sex, and hormonal status, mismatched behavioural and clinical endpoints, poor biomarker alignment, and insufficient assessment of potential interactions between neuroprotective agents and anticancer efficacy. Finally, we propose a translational roadmap for developing mechanism-informed, clinically predictive, and oncologically safe interventions for CRCI and explain why the preclinical efficacy of many candidate therapies has not yet translated into robust clinical benefit.</p>","PeriodicalId":19947,"journal":{"name":"Pharmacological Reports","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2026-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148945159","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":"Drugs associated with retroperitoneal fibrosis: assessment of the 1969-2025 Food and Drug Administration (FDA) pharmacovigilance database.","authors":"Sara Baldini, Nicolo' Schifano, Kiyara Fernando, Matteo Coschignano, Alessio Villano, Ilaria Elena Zais, Gabriele Antonini, Paolo Capogrosso, Federico Deho'","doi":"10.1007/s43440-026-00894-y","DOIUrl":"https://doi.org/10.1007/s43440-026-00894-y","url":null,"abstract":"<p><strong>Background: </strong>Retroperitoneal fibrosis (RPF) is a rare fibroinflammatory disorder characterized by the development of fibrotic tissue around the abdominal aorta, often leading to ureteral entrapment and renal dysfunction. Several pharmacological agents have been implicated as potential triggers. Despite scattered case reports and limited series, comprehensive quantitative assessments of drug-related RPF signals remain scarce. This study aimed to identify and quantify signals of disproportionate reporting of RPF associated with specific medications using data from a large pharmacovigilance database.</p><p><strong>Methods: </strong>The Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS) was queried from 1969 to 2025 to identify RPF-related adverse event reports. Drugs associated with more than twenty RPF reports were included in a disproportionality analysis; this threshold was arbitrarily defined to focus on medications with a relatively higher volume of reports. This selection aimed to ensure adequate statistical power and reduce noise from underreported associations. For each, the Reporting Odds Ratio (ROR), 95% Confidence Intervals (CI), Proportional Reporting Ratio (PRR), chi-square values, and p-values were calculated. A signal was considered statistically significant when PRR > 2, chi-square > 4, and p < 0.05. The total number of reports in the FAERS database was 30,668,520.</p><p><strong>Results: </strong>A total of 1,013 RPF cases were identified. Of these, 392 (38.7%) were linked to eleven drugs, each associated with more than twenty RPF reports. Methysergide showed the strongest association (ROR: 5332.28; 95% CI: 4292.96-6623.21; PRR: 4604.65; chi-square: 429,546.30; p < 0.0001), followed by pergolide (ROR: 923.85; 95% CI: 686.60-1243.09; PRR: 897.76; chi-square: 40,148.64; p < 0.0001) and bromocriptine (ROR: 311.30; 95% CI: 224.78-431.13; PRR: 308.26; chi-square: 11,201.91; p < 0.0001). Several widely used medications such as bisoprolol, atenolol, and metformin also showed significant, though less pronounced, associations (p < 0.0001). The remaining drugs included etanercept, prednisone, rituximab, propranolol, and cyclophosphamide, all of which exhibited significant levels of disproportionate reporting (p < 0.0001).</p><p><strong>Conclusions: </strong>This pharmacovigilance analysis identified multiple medications, spanning different therapeutic classes, that demonstrated a disproportionate association with reports of RPF. Notably, some drugs with well-established safety profiles also emerged as potential signals, warranting increased clinical awareness. While this analysis reveals pharmacovigilance signals suggestive of drug-induced RPF, the observational nature of FAERS data limits causal inference. These findings underscore the need for further clinical research and mechanistic studies to better understand the etiopathogenic role of these agents in RPF development.</p>","PeriodicalId":19947,"journal":{"name":"Pharmacological Reports","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2026-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148945173","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":"Interactions of ACEA and WIN 55,212-2 mesylate with temozolomide and cisplatin in neuroblastoma and glioblastoma cell lines: an isobolographic analysis.","authors":"Katarzyna Załuska-Ogryzek, Paula Wróblewska-Łuczka, Agnieszka Góralczyk, Michał Chojnacki, Jarogniew J Łuszczki","doi":"10.1007/s43440-026-00898-8","DOIUrl":"https://doi.org/10.1007/s43440-026-00898-8","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;Glioblastoma is still the most aggressive primary brain tumor in adults. Recently, several advanced experimental treatment options have been proposed for glioblastoma patients, including the application of cannabinoids as an add-on therapy.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;In the MTT, LDH, and BrdU assays, the anti-proliferative effects of arachidonyl-2'-chloroethylamide (ACEA - a potent selective cannabinoid CB&lt;sub&gt;1&lt;/sub&gt; receptor agonist) and WIN 55,212-2 mesylate (a non-selective cannabinoid CB&lt;sub&gt;1&lt;/sub&gt; and CB&lt;sub&gt;2&lt;/sub&gt; receptor agonist) on neuroblastoma and glioblastoma cell lines (CHP-134, KELLY, U-87MG, T98G, and C6) were determined. The interaction profiles of ACEA and WIN 55,212-2 mesylate in combinations with cisplatin and temozolomide (two chemotherapeutic drugs) in CHP-134, KELLY, U-87MG, T98G, and C6 were assessed isobolographically in the MTT test. Additionally, the impact of ACEA and WIN 55,212-2 mesylate on cannabinoid CB&lt;sub&gt;1&lt;/sub&gt; receptors expressed on all the tested cell lines was examined with the Western blot technique. Pre-incubation with a selective cannabinoid CB&lt;sub&gt;1&lt;/sub&gt; receptor antagonist/invert agonist (AM281) and consecutive exposure of the neuroblastoma CHP-134 and glioblastoma T98G cell lines to ACEA or WIN 55,212-2 mesylate at various treatment times (24, 48, and 72 h) in the MTT assay was studied. Expression of Bax and Bcl-2 proteins in response to ACEA or WIN 55,212-2 mesylate treatment was examined with Western blot.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;ACEA and WIN 55,212-2 mesylate produced anti-proliferative effects on the tested cell lines. The selectivity index for ACEA ranged from 2.61 to 5.95, and that for WIN 55,212-2 mesylate ranged from 4.32 to 12.85. The combinations of ACEA with cisplatin (at the fixed ratio of 1:1) exerted additive interactions in all the tested cell lines. In contrast, WIN 55,212-2 mesylate, when combined with cisplatin, exerted a synergistic interaction in the CHP-134 cell line (p &lt; 0.05) and additive interactions in the remaining (KELLY, U-87MG, T98G, and C6) cell lines in the MTT test. The combinations of ACEA with temozolomide (at the fixed-ratio of 1:1) exerted antagonistic interactions in two (CHP-134 at p &lt; 0.05; and C6 at p &lt; 0.0001) cell lines and additive interactions in three (KELLY, U-87MG, T98G) cell lines in the MTT assay. In contrast, WIN 55,212-2 mesylate, when combined with temozolomide, produced antagonistic interactions in three (KELLY at p &lt; 0.05; T98G at p &lt; 0.01, and C6 at p &lt; 0.01) cell lines and additive interactions in the remaining (CHP-134 and U-87MG) cell lines in the MTT test. Western blot analysis confirmed that all the tested cell lines (CHP-134, KELLY, U-87MG, T98G, and C6) exposed to ACEA or WIN 55,212-2 mesylate changed the expression of cannabinoid CB&lt;sub&gt;1&lt;/sub&gt; receptors. Pre-incubation with AM281 and subsequent exposition of the CHP-134 and T98G cell lines to ACEA or WIN 55,212-2 mesylate revealed that the pr","PeriodicalId":19947,"journal":{"name":"Pharmacological Reports","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2026-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148920059","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":"Unveiling novel transcriptomic prognostic biomarkers for specific breast cancer subtypes and treatment regimens.","authors":"Krittin Pitinanon, Chotiphuk Kusalasaiyanon, Wathunya Hawhan, Yu-Yu Liu, Pasrawin Taechawattananant, Varalee Yodsurang","doi":"10.1007/s43440-026-00895-x","DOIUrl":"https://doi.org/10.1007/s43440-026-00895-x","url":null,"abstract":"<p><strong>Background: </strong>Breast cancer (BRCA) is the most common cancer in women worldwide, yet current gene expression panels offer limited insight into treatment responses across different subtypes and therapies. This study aimed to identify reliable biomarkers for predicting treatment outcomes in specific BRCA subtypes and treatment regimens.</p><p><strong>Methods: </strong>This study analyzed transcriptomic data from The Cancer Genome Atlas to identify differentially expressed genes (DEGs) in patient groups treated with different combinations of hormone therapy (H), chemotherapy (C), radiotherapy (R), and targeted therapy (T). Non-negative matrix factorization clustering was performed to stratify patients into clusters representing different BRCA subtypes. Functional enrichment analysis was performed, and survival assessments were conducted using the METABRIC dataset.</p><p><strong>Results: </strong>A total of 1,148 DEGs were identified across treatment regimens, with 75 common DEGs shared across multiple regimens. Among these, 12 candidate biomarkers were associated with luminal subtypes treated with H, including LRP1B, of which high expression predicted cancer recurrence. In triple-negative breast cancer (TNBC) treated with C, 76 candidate biomarkers were identified, including TTYH1 for recurrence and ANXA8L1 and MPZ for non-recurrence. Functional analyses identified intermediate filament organization and keratinization as pathways associated with specific candidate biomarkers of TNBC following C. Survival analysis using METABRIC strengthened the prognostic ability of LRP1B and TTYH1 to predict worse survival and ANXA8L1 and MPZ to predict prolonged survival, with four additional prognostic biomarkers.</p><p><strong>Conclusion: </strong>This study identified gene expression prognostic biomarkers for luminal and TNBC subtypes, thereby supporting personalized therapies. Further experimental validation is required to confirm these findings for clinical application.</p><p><strong>Clinical trial registry: </strong>No.</p>","PeriodicalId":19947,"journal":{"name":"Pharmacological Reports","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2026-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148920127","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":"Gut microbiota as a modulator of HDAC: insights into Alzheimer's disease treatment.","authors":"Ekta Verma, Shweta Mishra, Hanish Singh Jayasingh Chellammal, Prasanna Shama Khandige, Amin Gasmi","doi":"10.1007/s43440-026-00897-9","DOIUrl":"https://doi.org/10.1007/s43440-026-00897-9","url":null,"abstract":"<p><p>The human gut microbiota (GMB) has a significant impact on physiological function, including gastrointestinal health, immune regulation, and redox homeostasis. It consists of diverse microorganisms that support digestion, nutrient absorption, and intestinal barrier function. Emerging evidence suggests that gut microbiota-derived metabolites may influence the gut-brain axis and regulate epigenetic mechanisms through modulation of histone deacetylases (HDAC). HDAC are key enzymes involved in gene expression, neuronal survival, neuroinflammation, and the pathogenesis of Alzheimer's disease (AD). Gut microbiota-derived metabolites have been reported to modulate HDAC activity and may contribute to neuroprotective and anti-inflammatory effects. Through these mechanisms, the GMB may influence cognitive function and the progression of AD. However, the precise molecular mechanisms involved in these interactions are not yet fully understood and continue to be extensively investigated. Therefore, this review focuses on the correlation between HDAC and the restoration of a healthy GMB as a therapeutic approach for the treatment and prevention of AD. It emphasizes the role of gut-derived metabolites, peptides, and dietary bioactive compounds in regulating HDAC-mediated epigenetic pathways. These interactions may influence gene expression, neurotransmitter biosynthesis, neuroinflammation, and neuroprotective signalling associated with cognitive function. Furthermore, the review delineates the bidirectional interplay among neurotransmitter signalling, GMB composition, and HDAC-mediated epigenetic regulation, along with their potential roles in the pathophysiology of neurodegenerative disorders.</p>","PeriodicalId":19947,"journal":{"name":"Pharmacological Reports","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2026-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148920051","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}