Diseases (Basel, Switzerland)最新文献

{"title":"Elucidating the Role of the T Cell Receptor Repertoire in Myelodysplastic Neoplasms and Acute Myeloid Leukemia.","authors":"Georgios Petros Barakos, Vasileios Georgoulis, Epameinondas Koumpis, Eleftheria Hatzimichael","doi":"10.3390/diseases13010019","DOIUrl":"10.3390/diseases13010019","url":null,"abstract":"<p><p>T cells, as integral components of the adaptive immune system, recognize diverse antigens through unique T cell receptors (TCRs). To achieve this, during T cell maturation, the thymus generates a wide repertoire of TCRs. This is essential for understanding cancer evolution, progression, and the efficacy of immunotherapies. Myelodysplastic neoplasms (MDS) and acute myeloid leukemia (AML) are hematological neoplasms that are characterized by immune evasion mechanisms, with immunotherapy giving only modest results thus far. Our review of TCR repertoire dynamics in these diseases reveals distinct patterns: MDS patients show increased TCR clonality with disease progression, while AML exhibits varied TCR signatures depending on disease stage and treatment response. Understanding these patterns has important clinical implications, as TCR repertoire metrics may serve as potential biomarkers for disease progression and treatment response, particularly in the context of immunotherapy and stem cell transplantation. These insights could guide patient stratification and treatment selection, ultimately improving therapeutic outcomes in MDS and AML.</p>","PeriodicalId":72832,"journal":{"name":"Diseases (Basel, Switzerland)","volume":"13 1","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11765071/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143034923","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}

{"title":"The Relationship Between Cervicovaginal Infection, Human Papillomavirus Infection and Cervical Intraepithelial Neoplasia in Romanian Women.","authors":"Anca Daniela Brăila, Cristian-Viorel Poalelungi, Cristina-Crenguţa Albu, Constantin Marian Damian, Laurențiu Mihai Dȋră, Andreea-Mariana Bănățeanu, Claudia Florina Bogdan-Andreescu","doi":"10.3390/diseases13010018","DOIUrl":"10.3390/diseases13010018","url":null,"abstract":"<p><p>Cervical intraepithelial neoplasia (CIN) is a premalignant cervical condition closely linked to persistent high-risk HPV infection, a major risk factor for cervical cancer. This study aims to investigate the relationship between cervicovaginal infections, HPV infection, and CIN development in 94 Romanian women with cervical lesions. Comprehensive assessments included HPV genotyping, cytology, colposcopy, and histopathology. In 53.20% of cases, vaginal infections were identified, with <i>Candida albicans</i> most frequently associated with HPV. Histopathology revealed 48.94% low-grade CIN, 42.55% high-grade CIN, and 8.51% invasive carcinoma. There was a strong correlation between high-risk HPV types (especially HPV 16 and 18), colposcopic findings, histopathology, and age. This study emphasizes the mutual effect of cervicovaginal infections and HPV infection in increasing the risk of developing CIN and cervical cancer among Romanian women. Persistent infection with high-risk HPV types, particularly HPV 16 and 18, has been confirmed as a primary driver of CIN and cervical cancer progression.</p>","PeriodicalId":72832,"journal":{"name":"Diseases (Basel, Switzerland)","volume":"13 1","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11764336/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143034793","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}

{"title":"Targeting Soluble Amyloid Oligomers in Alzheimer's Disease: A Hypothetical Model Study Comparing Intrathecal Pseudodelivery of mAbs Against Intravenous Administration.","authors":"Manuel Menendez-Gonzalez","doi":"10.3390/diseases13010017","DOIUrl":"10.3390/diseases13010017","url":null,"abstract":"<p><strong>Background/objective: </strong>Neurotoxic soluble amyloid-β (Aβ) oligomers are key drivers of Alzheimer's pathology, with evidence suggesting that early targeting of these soluble forms may slow disease progression. Traditional intravenous (IV) monoclonal antibodies (mAbs) face challenges, including limited brain penetration and risks such as amyloid-related imaging abnormalities (ARIA). This hypothetical study aimed to model amyloid dynamics in early-to-moderate Alzheimer's disease (AD) and compare the efficacy of IV mAn with intrathecal pseudodelivery, a novel method that confines mAbs in a subcutaneous reservoir for selective amyloid clearance in cerebrospinal fluid (CSF) without systemic exposure.</p><p><strong>Methods: </strong>A mathematical framework was employed to simulate Aβ dynamics in patients with early-to-moderate AD. Two therapeutic approaches were compared: IV mAb and intrathecal pseudodelivery of mAb. The model incorporated amyloid kinetics, mAb affinity, protofibril size, and therapy-induced clearance rates to evaluate the impact of both methods on amyloid reduction, PET negativity timelines, and the risk of ARIA.</p><p><strong>Results: </strong>Intrathecal pseudodelivery significantly accelerated Aβ clearance compared to IV administration, achieving amyloid PET scan negativity by month 132, as opposed to month 150 with IV mAb. This method demonstrated no ARIA risk and reduced amyloid reaccumulation. By targeting soluble Aβ species more effectively, intrathecal pseudodelivery emerged as a safer and more efficient strategy for early AD intervention.</p><p><strong>Conclusions: </strong>Intrathecal pseudodelivery offers a promising alternative to IV mAbs, overcoming challenges associated with blood-brain barrier penetration and systemic side effects. Further research should focus on optimizing this approach and exploring combination therapies to enhance clinical outcomes in AD.</p>","PeriodicalId":72832,"journal":{"name":"Diseases (Basel, Switzerland)","volume":"13 1","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11764272/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143034784","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}

{"title":"The Development and Initial Validation of the REST Questionnaire: A Multidimensional Tool for Assessing Fatigue in Individuals with and Without a History of Cancer.","authors":"Giuseppe Di Lorenzo, Carlo Buonerba, Raffaele Baio, Eleonora Monteleone, Francesco Passaro, Antonio Tufano, Vittorino Montanaro, Vittorio Riccio, Ilaria Gallo, Francesca Cappuccio, Federica Fortino, Anna Buonocore, Federica Monaco, Antonio Verde, Anna Rita Amato, Oriana Strianese, Ferdinando Costabile, Luca Scafuri","doi":"10.3390/diseases13010015","DOIUrl":"10.3390/diseases13010015","url":null,"abstract":"<p><strong>Background: </strong>Fatigue is a prevalent and complex condition with significant impacts on well-being. Existing fatigue assessments often lack comprehensiveness or practicality for general population studies.</p><p><strong>Methods: </strong>This study validated the REST Questionnaire, a novel fatigue assessment tool, in a sample of 268 adults. Psychometric properties, including internal consistency and construct validity, were evaluated. REST scores were correlated with WHO-5 well-being, BMI, self-rated health, and chronic conditions. Exploratory factor analysis identified underlying dimensions of fatigue.</p><p><strong>Results: </strong>The REST Questionnaire demonstrated excellent internal consistency (Cronbach's alpha = 0.918) and construct validity. Higher fatigue scores were associated with lower well-being, female gender, and the presence of certain chronic conditions (cancer, kidney stones, gastric ulcers). Two distinct fatigue dimensions, \"physical fatigue and functional impacts\" and \"emotional and social consequences\", were identified.</p><p><strong>Conclusions: </strong>The REST Questionnaire is a reliable and valid tool for assessing fatigue in the general population. Its multidimensional framework and sensitivity to comorbidities offer valuable insights for research and public health applications, with the potential to inform targeted interventions aimed at improving well-being.</p>","PeriodicalId":72832,"journal":{"name":"Diseases (Basel, Switzerland)","volume":"13 1","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11764002/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143034789","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}

{"title":"Impact of Preoperative and Intraoperative Factors on Postoperative Outcomes in Patients with Colorectal Cancer: A 10-Year Retrospective Study.","authors":"Lucian Flavius Herlo, Ioana Golu, Alexandra Herlo, Claudia Raluca Balasa Virzob, Ionescu Alin, Stela Iurciuc, Ionut Eduard Iordache, Luana Alexandrescu, Doina Ecaterina Tofolean, Raluca Dumache","doi":"10.3390/diseases13010016","DOIUrl":"10.3390/diseases13010016","url":null,"abstract":"<p><strong>Background and objectives: </strong>Colorectal cancer is a major contributor to global cancer morbidity and mortality. Surgical resection remains the cornerstone of treatment, but postoperative complications can significantly affect patient outcomes. Identifying factors that influence postoperative morbidity and mortality is crucial for optimizing patient care. This study aims to evaluate the impact of preoperative, intraoperative, and postoperative factors on surgical outcomes in patients with colorectal cancer.</p><p><strong>Methods: </strong>A retrospective cohort study was conducted on 688 patients who underwent colorectal cancer surgery within a 10-year period. Data collected included demographic information, comorbidities, laboratory values, surgical details, and postoperative outcomes. Statistical analyses were performed using chi-square tests for categorical variables and t-tests for continuous variables. Multivariate logistic regression was used to identify independent predictors of postoperative complications and mortality.</p><p><strong>Results: </strong>Postoperative complications occurred in 28.5% of patients, and the 30-day mortality rate was 5.2%. Preoperative factors such as elevated C-reactive protein (CRP) levels (<i>p</i> < 0.001), low albumin levels (<i>p</i> = 0.003), a high American Society of Anesthesiologists (ASA) score (<i>p</i> < 0.001), and presence of comorbidities like diabetes and hypertension (<i>p</i> = 0.005) were significantly associated with increased postoperative complications. Intraoperative factors such as blood loss greater than 500 mL (<i>p</i> < 0.001) and longer operative time (<i>p</i> = 0.021) were also significant predictors of adverse outcomes. Multivariate analysis identified elevated CRP (OR 2.1, 95% CI 1.5-2.9), low albumin (OR 1.8, 95% CI 1.3-2.5), and blood loss > 500 mL (OR 2.4, 95% CI 1.7-3.4) as independent predictors of postoperative complications.</p><p><strong>Conclusions: </strong>Preoperative inflammatory markers, nutritional status, ASA score, comorbidities, and intraoperative factors like blood loss significantly influence postoperative outcomes in colorectal cancer surgery. Recognizing these risk factors allows for better preoperative optimization and surgical planning, potentially reducing postoperative morbidity and mortality.</p>","PeriodicalId":72832,"journal":{"name":"Diseases (Basel, Switzerland)","volume":"13 1","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11765074/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143034926","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}

{"title":"Yaws in Africa: Past, Present and Future.","authors":"Ezekiel K Vicar, Shirley V Simpson, Gloria I Mensah, Kennedy K Addo, Eric S Donkor","doi":"10.3390/diseases13010014","DOIUrl":"10.3390/diseases13010014","url":null,"abstract":"<p><p><b>Background:</b> Yaws is an infectious, neglected tropical disease that affects the skin of many children and adolescents who live in poor, rural, low-income communities in humid, tropical areas of Africa, Southeast Asia, and the Pacific Islands. Yaws is currently endemic in at least 15 countries, but adequate surveillance data are lacking. In line with the WHO's effort to improve early detection, diagnosis, and proper management leading to the eventual eradication of yaws, this article reviews the existing literature on yaws in Africa to highlight the epidemiological pattern, genetic variability, diagnosis modalities, treatment, and control strategies, the challenges and prospects for yaws eradication. <b>Methods</b>: We searched PubMed and Scopus databases to identify published data in line with the review objectives. <b>Results:</b> One hundred and eighty-eight peer-reviewed articles were identified by PubMed and Scopus, out of which thirty were eligible. The studies covered 11 African countries, with the reported prevalence ranging from 0.50% to 43.0%. <b>Conclusions</b>: There is a great prospect for eradication if countries capitalize on the availability of simple, inexpensive, and well-tolerated oral treatment that has proven effective, validated point-of-care diagnostic tests and new molecular tests. Countries should embark on integrated disease control efforts to increase sustainability and improve the quality of life for people living with this NTD in poor communities.</p>","PeriodicalId":72832,"journal":{"name":"Diseases (Basel, Switzerland)","volume":"13 1","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-01-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11764072/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143034756","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}

{"title":"A Scoping Review of Eosinophilic Pneumonia and Antidepressants: An Association Not to Be Overlooked.","authors":"Jaron Steiner, Leonie Steuernagel, Fotios Drakopanagiotakis, Konstantinos Bonelis, Paschalis Steiropoulos","doi":"10.3390/diseases13010013","DOIUrl":"10.3390/diseases13010013","url":null,"abstract":"<p><p><i>Background</i>: Eosinophilic pneumonias denote a rare condition, wherein infiltrating eosinophilic granulocytes accumulate within the lung parenchyma. Although eosinophilic pneumonias may be idiopathic, they are also associated with secondary causes. More than 110 medications have been linked to eosinophilic pneumonia, including several antidepressants. This review presents an analysis of case reports of eosinophilic pneumonia correlated to antidepressants. <i>Objectives</i>: The objectives of this study are to provide a contemporary overview of the literature delineating eosinophilic pneumonia as a potential sequela of antidepressant medication treatment, and to discuss possible pathogenetic mechanisms linking antidepressants to eosinophilic pneumonia. <i>Methods and Data Selection</i>: A literature search was performed in PubMed and Scopus databases from 1963 to October 2024. The search strategy used the terms \"eosinophilic pneumonia AND antidepressants\". Sources included in this review were screened for relevance, focusing on references discussing eosinophilic pneumonia associated with any class of antidepressants. Case reports meeting the diagnostic criteria for acute eosinophilic pneumonia (AEP) or chronic eosinophilic pneumonia (CEP) were included in the review. Clinical, epidemiological, laboratory, radiology and bronchoscopy data, implicated antidepressant and dosage, and therapeutic interventions were reported. <i>Results</i>: This study found that various types of antidepressants are associated with AEP and CEP. The clinical presentation ranges from mild symptoms to respiratory failure and intubation. Outcomes were favorable in most cases, with complete remission achieved after discontinuation of the causative drug and, in severe cases, a short course of corticosteroids. <i>Conclusions</i>: Although a rare cause, antidepressants may lead to eosinophilic pneumonia, and should be considered in the differential diagnosis of unexplained pulmonary infiltrates. Clinical suspicion must be aroused, as early recognition would prevent unnecessary work-up and navigation of the diagnosis.</p>","PeriodicalId":72832,"journal":{"name":"Diseases (Basel, Switzerland)","volume":"13 1","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11764640/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143034920","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}

{"title":"Prevalence of Vitamin K2 Deficiency and Its Association with Coronary Artery Disease: A Case-Control Study.","authors":"Sameh A Ahmed, Abdulaziz A Yar, Anas M Ghaith, Rayan N Alahmadi, Faisal A Almaleki, Hassan S Alahmadi, Waleed H Almaramhy, Ahmed M Alsaedi, Man K Alraddadi, Hussein M Ismail","doi":"10.3390/diseases13010012","DOIUrl":"10.3390/diseases13010012","url":null,"abstract":"<p><strong>Background/objectives: </strong>Vitamin K2 analogs are associated with decreased vascular calcification, which may provide protective benefits for individuals with coronary artery disease (CAD) by stimulating anti-calcific proteins like matrix Gla protein and adjusting innate immune responses. This study addresses a significant gap in understanding the association between serum levels of vitamin K2 analogs in different CAD types and examines their correlations with clinical risk parameters in CAD patients.</p><p><strong>Methods: </strong>This case-control study enrolled CAD patients and healthy controls to assess and compare serum concentrations of two vitamin K2 analogs including menaquinone-4 (MK-4) and menaquinone-7 (MK-7) via ultra-performance liquid chromatography with tandem mass spectrometry (UPLC-MS/MS). CAD risk factors were evaluated and related to serum levels of vitamin K2 analogs. The CAD group was further subdivided into stable angina, STEMI, NSTEMI, and unstable angina groups to investigate potential differences in vitamin K2 analog levels.</p><p><strong>Results: </strong>Patients experiencing acute coronary syndrome exhibited notably reduced serum levels of MK-4 and MK-7 (1.61 ± 0.66, and 1.64 ± 0.59 ng/mL, respectively) in comparison to the control group (2.29 ± 0.54, and 2.16 ± 0.46 ng/mL, respectively), with MK-4 and MK-7 displaying stronger associations with CAD risk indicators. Notable variations in vitamin K2 analog levels were found between CAD patients and control groups (<i>p</i> < 0.001). Unstable angina patients showed the lowest serum levels of MK-4 and MK-7.</p><p><strong>Conclusions: </strong>The present study demonstrated a higher prevalence rate of vitamin K2 deficiency among patients with CAD. The most pronounced decrease in MK-4 and MK-7 was observed in unstable angina patients. Moreover, these outcomes indicate the imperative requirement for an integrative approach that incorporates metabolic, lipid, and vitamin K2-related pathways in the risk stratification and management of CAD.</p>","PeriodicalId":72832,"journal":{"name":"Diseases (Basel, Switzerland)","volume":"13 1","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-01-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11764201/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143034283","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}

{"title":"A Survey of the Knowledge, Attitudes and Practices of a Sample of Albanian Medical Students in Relation to Occupational Exposure to Biological Agents.","authors":"Lorenzo Ippoliti, Luca Coppeta, Ersilia Buonomo, Giuseppina Somma, Giuseppe Bizzarro, Cristiana Ferrari, Andrea Mazza, Agostino Paolino, Claudia Salvi, Vittorio Caputi, Antonio Pietroiusti, Andrea Magrini","doi":"10.3390/diseases13010011","DOIUrl":"10.3390/diseases13010011","url":null,"abstract":"<p><p>(1) Background: Exposure to blood carries the risk of transmission of many infectious diseases. Healthcare workers (HCWs), including hospital-based medical students, face high and often under-reported rates of exposure to needlestick and sharps injuries. Previous studies have shown that students' knowledge of infection control varies, highlighting the importance of pre-placement training. This study aims to assess knowledge, attitudes and practices regarding these risks in a population of medical students from Albania. (2) Methods: A validated questionnaire was administered to 134 medical students in an Italian hospital in May 2023. It assessed HBV vaccination status, adherence to infection control practices, knowledge of pathogen transmission, exposure incidents and attitudes towards infected patients. Three additional questions addressed air-borne transmission of tuberculosis and vaccination recommendations for healthcare workers. (3) Results: Most students (64%) reported being aware of occupational exposure risks. While 93% and 87%, respectively, recognised HIV and HBV as blood-borne pathogens, fewer recognised Treponema pallidum (44%). Awareness of post-exposure prophylaxis for HIV was high (85%), but although 75% reported having received training, only 45% felt it was adequate. Statistical analysis revealed an association between knowledge of infection control, awareness of pathogen transmission and understanding of the importance of vaccination. (4) Conclusions: Our study highlights gaps in medical students' knowledge of occupational infections and highlights the need for improved pre-clerkship education. Improved education could reduce anxiety, ethical issues and misconceptions and promote safer healthcare practices.</p>","PeriodicalId":72832,"journal":{"name":"Diseases (Basel, Switzerland)","volume":"13 1","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11764395/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143034921","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}

{"title":"Valproic Acid Enhances Venetoclax Efficacy in Targeting Acute Myeloid Leukemia.","authors":"Renshi Kawakatsu, Kenjiro Tadagaki, Kenta Yamasaki, Yasumichi Kuwahara, Tatsushi Yoshida","doi":"10.3390/diseases13010010","DOIUrl":"10.3390/diseases13010010","url":null,"abstract":"<p><strong>Background: </strong>Acute myeloid leukemia (AML) is a common and aggressive form of leukemia, yet current treatment strategies remain insufficient. Venetoclax, a BH3-mimetic approved for AML treatment, induces Bcl-2-dependent apoptosis, though its therapeutic efficacy is still limited. Therefore, new strategies to enhance the effect of venetoclax are highly sought. Valproic acid (VPA), commonly used for epilepsy, has also been studied for potential applications in AML treatment.</p><p><strong>Methods: </strong>AML cells were treated with venetoclax, with or without VPA. Cell viability was assessed using the trypan blue dye exclusion assay, while cell cycle progression was analyzed by flow cytometry. The expression of pro-apoptotic proteins Bax and Bak was measured by RT-qPCR.</p><p><strong>Results: </strong>Venetoclax and VPA individually had only mild effects on AML cell proliferation. However, their combination significantly inhibited cell growth and triggered pronounced cell death. This combination also led to the cleavage of poly (ADP-ribose) polymerase (PARP), a substrate of caspases, indicating activation of apoptosis. VPA treatment upregulated the expression of Bax and Bak, further supporting apoptosis induction. The cell death induced by the venetoclax-VPA combination was predominantly apoptotic, as confirmed by the near-complete blockade of cell death by a pan-caspase inhibitor.</p><p><strong>Conclusions: </strong>Our study demonstrates that VPA enhances venetoclax-induced apoptosis in AML cell lines, providing a novel role for VPA and suggesting a promising combinatory strategy for AML treatment. These findings offer valuable insights into potential clinical applications of venetoclax and VPA in AML management.</p>","PeriodicalId":72832,"journal":{"name":"Diseases (Basel, Switzerland)","volume":"13 1","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11764158/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143034797","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}