Raza Ur Rehman MBBS, Ahmad Furqan Anjum MBBS, Rida Fatima MBBS
{"title":"Tarlatamab and the Future of Immunotherapy: A New Approach to Small Cell Lung Cancer","authors":"Raza Ur Rehman MBBS, Ahmad Furqan Anjum MBBS, Rida Fatima MBBS","doi":"10.1016/j.curtheres.2024.100773","DOIUrl":"10.1016/j.curtheres.2024.100773","url":null,"abstract":"","PeriodicalId":10920,"journal":{"name":"Current Therapeutic Research-clinical and Experimental","volume":"102 ","pages":"Article 100773"},"PeriodicalIF":1.6,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11772990/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143058343","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":"Ethnomedicine Knowledge Among Iranian Patients With Gastrointestinal And Liver Disorders: A Cross-Sectional Study","authors":"Fatemeh Sadat Hasheminasab MD,Ph.D , Yasaman Zamanian MD , Saiedeh Haji-Maghsoudi Ph.D , Alireza Bakhshipour MD , Maryam Azimi MD,Ph.D","doi":"10.1016/j.curtheres.2024.100774","DOIUrl":"10.1016/j.curtheres.2024.100774","url":null,"abstract":"<div><h3>Introduction</h3><div>The role of complementary and alternative medicine (CAM) in healthcare is substantial and frequently overlooked, with widespread use in both developed and developing countries. This study aimed to explore the ethnomedicinal knowledge including prevalence, socio-demographic, and health related characteristics related to gastroenterology and hepatology disorders in Kerman province.</div></div><div><h3>Materials and methods</h3><div>This study included 400 eligible patients attending gastroenterology and hepatology outpatient clinic. Data collection was conducted using various assessment tools, that is, a self-administered demographic and ethnomedicine questionnaire, and quality of life questionnaire.</div></div><div><h3>Results</h3><div>The findings of the present study revealed that 40.3% of the patients surveyed commonly used CAM. Among the participants, 63.4% did not alter their medication intake while using CAM, and 85.7% were satisfied with its effectiveness. The majority of consumers relied on friends and family, making up 41.6% of the sources of information on CAM, with only 14.9% disclosing their CAM usage to physicians. Furthermore, CAM users have a significantly higher level of education, with the physical functioning being a key aspect of QOL.</div></div><div><h3>Conclusion</h3><div>Although the results of this study may not be broadly generalizable, specific points in the findings are still significant. The utilization of CAM treating for gastrointestinal and liver issues is becoming more prevalent among patients in the area. It is essential to educate patients about the real effects of CAM in disease prevention and treatment, particularly considering patient concerns about side effects, and untrustworthy information sources.</div></div>","PeriodicalId":10920,"journal":{"name":"Current Therapeutic Research-clinical and Experimental","volume":"102 ","pages":"Article 100774"},"PeriodicalIF":1.6,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143142208","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":"Efficacy of Cevimeline on Xerostomia in Sjögren's Syndrome Patients: A Systematic Review and Meta-Analysis of Randomized Clinical Trials","authors":"Mehdi Karimi MD , Fatemeh Ahmadi Hajikolaei MD , Fahime Hoseinpour MD , Seyed-Ali Hashemi MD , Anita Fatehi MD , Seyed-Abbas Pakmehr MD , Niloofar Deravi MD , Mahdyieh Naziri MSc , Mohaddeseh Belbasi MD , Sahar Khoshravesh MD , Seyed Hossein Vaezzadeh MD","doi":"10.1016/j.curtheres.2024.100770","DOIUrl":"10.1016/j.curtheres.2024.100770","url":null,"abstract":"<div><h3>Background</h3><div>Xerostomia, or dry mouth, is a common and debilitating symptom in patients with Sjögren's syndrome, affecting their quality of life. Although Cevimeline, a muscarinic agonist, has been investigated as a potential treatment, its efficacy and optimal dosage remain uncertain. This study aims to assess the effectiveness of Cevimeline in relieving xerostomia in patients with Sjögren's syndrome by a meta-analysis of randomized clinical trials (RCT).</div></div><div><h3>Method</h3><div>A comprehensive search was conducted across PubMed, Scopus, Cochrane, and Web of Science databases, utilizing Medical Subject Headings terms and keywords related to “cevimeline,” “xerostomia,” and “Sjögren's syndrome” from inception until January 3, 2024. Studies were selected based on predefined inclusion criteria, focusing on clinical trials involving human subjects treated with cevimeline for xerostomia in Sjögren's syndrome. Data extraction was performed systematically, and statistical analysis was conducted using STATA software.</div></div><div><h3>Result</h3><div>This meta-analysis included three RCTs with a total of 302 patients with Sjögren's syndrome (Cevimeline = 187; Placebo = 115). The analysis demonstrated that Cevimeline significantly reduces xerostomia (regarded as salivary flow, mouth dryness) in patients with Sjögren's syndrome with a pooled odds ratio –5.79 (95% CI [–10.55, –1.03]; <em>I</em><strong><sup>2</sup></strong> = 39.6%).</div></div><div><h3>Conclusions</h3><div>In summary, cevimeline significantly increases salivary flow secretion rates in patients with Sjögren's syndrome. With a favorable safety profile at recommended dosages, cevimeline represents a viable therapeutic option for managing xerostomia, particularly in patients with mild to moderate salivary gland destruction.</div></div>","PeriodicalId":10920,"journal":{"name":"Current Therapeutic Research-clinical and Experimental","volume":"102 ","pages":"Article 100770"},"PeriodicalIF":1.6,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11764655/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143045872","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":"Exploring the Use of Mobile Health Applications in Palestinian Community Pharmacy Practice","authors":"Ahmed Nouri PharmD, MSc","doi":"10.1016/j.curtheres.2025.100782","DOIUrl":"10.1016/j.curtheres.2025.100782","url":null,"abstract":"<div><h3>Background</h3><div>Mobile health applications have become essential tools in modern healthcare, enabling professionals to access real-time drug information, clinical guidelines, and patient management resources. While globally embraced, the adoption of these apps in resource-limited settings like Palestine remains under-researched, particularly among community pharmacists, who are pivotal to the healthcare system.</div></div><div><h3>Aims</h3><div>This study explores the perceptions, awareness, and challenges faced by Palestinian community pharmacists regarding mobile health applications. It aims to assess the feasibility of integrating these tools into their practice to improve pharmaceutical care and patient outcomes.</div></div><div><h3>Methods</h3><div>A cross-sectional online survey was conducted in 2023 among community pharmacists in Palestine. A self-administered electronic questionnaire was distributed via social media, targeting registered pharmacists. Data were collected using a structured, validated questionnaire addressing demographics, app usage patterns, perceived benefits, and barriers. Descriptive and inferential analyses were performed using SPSS® software, with P-values ≤0.05 considered statistically significant.</div></div><div><h3>Results</h3><div>The study included 400 community pharmacists, predominantly female (65.8%). Pharmacists frequently used information resources for verifying drug interactions (89%) and dosages (98%), citing quick access to reliable information as a major advantage. Barriers included time constraints (92.3%) and concerns about patient trust (77.8%). No significant associations were found between demographics (e.g., gender, years of experience) and perceptions of app usefulness or trust. A strong positive correlation (<em>P</em> < 0.001) was observed between community pharmacists’ support for mobile health applications and their perception of the applications’ reliability. This indicates that pharmacists who perceive mobile apps as reliable are more likely to support their use in practice.</div></div><div><h3>Conclusion</h3><div>Limited app use among Palestinian community pharmacists impacts medication safety, patient trust, and care quality. Adopting mobile tools can improve efficiency, reduce errors, and align pharmacy practice with modern standards, highlighting the need for future research.</div></div>","PeriodicalId":10920,"journal":{"name":"Current Therapeutic Research-clinical and Experimental","volume":"102 ","pages":"Article 100782"},"PeriodicalIF":1.6,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143684679","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":"Effect of Hematopoietic Stem Cell Transplantation Regimen on Tacrolimus Pharmacokinetics","authors":"Haruno Oku BS , Saki Yoshida BS , Takumi Hotta BS , Hirohito Muroi BS , Keizo Fukushima PhD , Kei Irie PhD , Tatsuya Hirano BS , Yoshimitsu Shimomura MD , Takayuki Ishikawa MD, PhD , Hiroaki Ikesue PhD , Nobuyuki Muroi PhD , Tohru Hashida PhD , Nobuyuki Sugioka PhD","doi":"10.1016/j.curtheres.2024.100775","DOIUrl":"10.1016/j.curtheres.2024.100775","url":null,"abstract":"<div><h3>Objectives</h3><div>Treatment with tacrolimus requires strict control of the whole-blood concentration in patients undergoing allogeneic hematopoietic stem cell transplantation (HSCT). In patients undergoing cord blood transplantation (CBT), there is a negative correlation between volume of distribution of tacrolimus and hemoglobin levels, which reflect the red blood cell (RBC) count. In this study, we evaluated the influence of the conditioning regimen (myeloablative and reduced-intensity conditioning) or donor source (cord blood, bone marrow, and peripheral blood stem cells) on the pharmacokinetics of tacrolimus in patients undergoing HSCT, including those undergoing CBT. We also examined applicability of dosing strategy of tacrolimus considering the RBC count.</div></div><div><h3>Methods</h3><div>We retrospectively analyzed clinical data—including whole-blood tacrolimus concentrations—from patients with HSCT. The observation period spanned from first continuous intravenous infusions until switch to oral medication, transfer to another hospital, relapse, or death. Population pharmacokinetic analysis was performed on whole-blood tacrolimus concentrations obtained from therapeutic drug monitoring during the observation period. Patient characteristics and laboratory data were evaluated as covariates.</div></div><div><h3>Results</h3><div>We enrolled 91 patients undergoing HSCT (CBT: <em>n</em> = 56; bone marrow transplantation: <em>n</em> = 22; and peripheral blood stem cell transplantation: <em>n</em> = 13); 58 and 33 patients received myeloablative conditioning and reduced-intensity conditioning, respectively. Whole-blood tacrolimus concentrations were accurately captured (<em>n</em> = 1,658 measurements) using a one-compartment and additive error model. The conditioning regimen and donor source did not have an impact on the pharmacokinetics of tacrolimus. Therefore, these factors were not considered when forming the dosing strategy. Nevertheless, a negative correlation between volume of distribution and hemoglobin level was confirmed, indicating that monitoring the RBC count is useful in assessing the dosing strategy.</div></div><div><h3>Conclusions</h3><div>A tacrolimus dosing strategy that considers the variability in hemoglobin levels applies to all patients undergoing HSCT.</div></div>","PeriodicalId":10920,"journal":{"name":"Current Therapeutic Research-clinical and Experimental","volume":"102 ","pages":"Article 100775"},"PeriodicalIF":1.6,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11788801/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143122229","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 Effect of Stem Cell Secretome on the Improvement of Diabetic Wound Recovery: A Systematic Review and Meta-Analysis of In Vivo Studies","authors":"Cecep Suhandi MSc , Gofarana Wilar PhD , Khaled M. Elamin PhD , Audry Rahma Dewayani BSc , Salsabil Ghaliya BSc , Astriani Abdullah BSc , Nasrul Wathoni PhD","doi":"10.1016/j.curtheres.2025.100778","DOIUrl":"10.1016/j.curtheres.2025.100778","url":null,"abstract":"<div><h3>Background</h3><div>Diabetic wounds, characterized by their chronic nature, represent a critical challenge for patients with diabetes, often leading to amputation and mortality. Although stem cells show great promise, their use is limited by challenges related to stability and tumorigenicity. The secretome of stem cells, comprising molecules released by these cells, offers a potential alternative to the challenges associated with stem cell therapy and provides a promising solution for diabetic wound healing.</div></div><div><h3>Objective</h3><div>We conducted a systematic review and meta-analysis of relevant preclinical studies to evaluate the effectiveness of stem cell secretomes in treating diabetic wounds.</div></div><div><h3>Methods</h3><div>The protocol registration for this systematic review and meta-analysis was recorded in the PROSPERO database (CRD42023473726). Databases were searched from their inception until November 20, 2023. The quality assessment of the included studies was performed utilizing the CAMARADES 10-item Quality Checklist. Statistical analyses were conducted using a random-effects model to calculate standardized mean differences (SMD) and 95% confidence intervals (CI), with heterogeneity assessed via the <em>I²</em> statistic. The primary outcome evaluated was the wound closure rate, while secondary outcomes included parameters such as the number of fibroblasts, neutrophils, and macrophages.</div></div><div><h3>Results</h3><div>Twenty studies were included, comprising 382 animal subjects, and five of which were eligible for quantitative evaluation in a meta-analysis. The stem cell secretome significantly improved the wound closure rate (SMD = 9.63; 95% CI = 2.01 −17.25; <em>P</em> = 0.01, I<sup>2</sup> = 76%) and reduced the number of neutrophils (SMD = −8.47; 95% CI = −13.05 to −3.90; <em>P</em> = 0.0003) and macrophages (SMD = −5.32; 95% CI = −9.09 to −1.55; <em>P</em> = 0.006).</div></div><div><h3>Conclusion</h3><div>This review suggests that stem cell secretomes have potential as a novel therapeutic strategy for diabetic wound healing, enhancing wound closure rates and reducing inflammation. These findings support the use of stem cell secretomes as a safer and more stable alternative to direct stem cell therapy, but further clinical studies are needed to confirm these results in human patients.</div></div>","PeriodicalId":10920,"journal":{"name":"Current Therapeutic Research-clinical and Experimental","volume":"102 ","pages":"Article 100778"},"PeriodicalIF":1.6,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143526717","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}
Peter Kunc MD, PhD , Jaroslav Fabry MD, PhD , Michaela Matiscakova MD , Katarina Istvankova DVM , Zuzana Diamant MD, PhD , Juraj Majtan PhD, DSc , Milos Jesenak MD, PhD
{"title":"Effect of a Pleuran-Based Supplement on Salivary IgA Secretion in Children With Recurrent Respiratory Infections","authors":"Peter Kunc MD, PhD , Jaroslav Fabry MD, PhD , Michaela Matiscakova MD , Katarina Istvankova DVM , Zuzana Diamant MD, PhD , Juraj Majtan PhD, DSc , Milos Jesenak MD, PhD","doi":"10.1016/j.curtheres.2025.100780","DOIUrl":"10.1016/j.curtheres.2025.100780","url":null,"abstract":"<div><h3>Background</h3><div>ß-glucans isolated from natural sources have demonstrated pluripotent immunomodulatory potential, making them a promising supportive treatment for the management of recurrent respiratory infections (RRIs) in children. This study aimed to evaluate the effects of a pleuran-based supplement (ß-glucan isolated from <em>Pleurotus ostreatus</em> in combination with vitamin D and zinc) on mucosal immunity –through modulating salivary secretory immunoglobulin A (sIgA) levels –in children with RRIs.</div></div><div><h3>Methods</h3><div>This monocentric, prospective, open-label pilot study investigated the effect of an orally administered pleuran/vitamin D/zinc supplement (1–2 chewable tablets daily depending on body weight) on the dynamics of sIgA secretion measured in saliva samples collected at three timepoints: at baseline and after 4–6 and 8–10 days.</div></div><div><h3>Results</h3><div>This study included 49 children aged 6-11 years (mean age: 8.2 ± 1.6 years) with a history of one or more of the following conditions in the inclusion criteria: RRIs, allergy, and asthma. After 8–10 days with daily administration of the chewable pleuran/vitamin D/zinc supplement, children exhibited a statistically significant increase in salivary sIgA concentrations compared with baseline (227 ± 211 µg/mL; <em>P</em> = 0.045). No adverse events were observed during the course of the study in relation to the administration of pleuran-based supplement.</div></div><div><h3>Conclusions</h3><div>We demonstrated the beneficial effects of the short-term administration of a pleuran-based chewable supplement on mucosal immunity through increasing salivatory sIgA levels. This study confirms the favourable safety profile of this pleuran/vitamin D/zinc combination, which could be beneficial for children with acute or recurrent respiratory infections, including children with allergies and/or asthma. Moreover, the significant increases in salivary sIgA concentrations that were observed after a few days of supplementation support the use of pleuran in not only the prevention but also the treatment of acute respiratory infections.</div></div>","PeriodicalId":10920,"journal":{"name":"Current Therapeutic Research-clinical and Experimental","volume":"102 ","pages":"Article 100780"},"PeriodicalIF":1.6,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143576715","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}
Zi-Hao Duan MS , Chun-Yuan He MS , Jie Chen BS , Jun-Jie Jiang BS , Zhi-Xiang Zhu PhD , Jing Li MS , Fa-Cai Wang MD
{"title":"A Clinical Nomogram for Predicting Substandard Serum Valproic Acid Concentrations in Chinese Patients With Epilepsy","authors":"Zi-Hao Duan MS , Chun-Yuan He MS , Jie Chen BS , Jun-Jie Jiang BS , Zhi-Xiang Zhu PhD , Jing Li MS , Fa-Cai Wang MD","doi":"10.1016/j.curtheres.2024.100771","DOIUrl":"10.1016/j.curtheres.2024.100771","url":null,"abstract":"<div><h3>Background</h3><div>It is well-known that substandard serum valproic acid (VPA) concentrations may lead to treatment failure of epilepsy. However, there is still a lack of a quick method to predict whether a patient's serum VPA concentration will reach the standard.</div></div><div><h3>Objective</h3><div>The aims of this study were to investigate the factors leading to substandard serum VPA concentrations in Chinese patients with epilepsy and develop a related nomogram for risk prediction.</div></div><div><h3>Methods</h3><div>From January 2019 to March 2022, a total of 1143 serum VPA concentrations were collected from 630 hospitalized Chinese patients with epilepsy who were monitored by the Department of Pharmacy of Lu'an People's Hospital, and complete clinical data were collected from the corresponding patients for retrospective analysis. All monitored serum VPA concentrations were further divided into a training cohort and a validation cohort. For the training cohort, serum VPA concentrations below 50 µg/mL and between 50 and 100 µg/mL were classified into the subtherapeutic group and therapeutic group, respectively. The variables were selected from the clinical data, and differences between the variables of the subtherapeutic and therapeutic groups were analyzed. The influencing factors leading to substandard serum VPA concentrations were screened via logistic regression analysis, and the screened influencing factors were used to establish the nomogram prediction model.</div></div><div><h3>Results</h3><div>Multivariate logistic regression analysis revealed that the daily dose per unit of body weight (mg/kg/d), route of administration, presence of hepatic lesions, hypoalbuminemia, and combination with carbapenems or barbiturates were independent factors influencing the occurrence of substandard serum VPA concentrations. On the basis of the results of the multivariate logistic regression analysis, a nomogram risk prediction model for substandard serum VPA concentration was established. The values of the C-index and internal verification results indicated that the nomogram model had good accuracy and discrimination. The decision curve revealed that the nomogram that predicted the risk of substandard serum VPA concentration had a greater net benefit value (ranging from 12% to 94%), indicating that the model had a wide prediction interval.</div></div><div><h3>Conclusions</h3><div>Our study established a nomogram risk prediction model for substandard serum VPA concentrations in Chinese patients with epilepsy, which can help doctors or patients control the serum VPA concentration within the target concentration range as soon as possible.</div></div>","PeriodicalId":10920,"journal":{"name":"Current Therapeutic Research-clinical and Experimental","volume":"102 ","pages":"Article 100771"},"PeriodicalIF":1.6,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11783061/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143078876","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}
María José Torres PhD , Juan Carlos Ríos PhD , Alexandra Valle MSc , Sebastián Indo PhD , Kevin Brockway GV MSc , Fernanda López-Moncada PhD , Mario Faúndez PhD , Enrique A. Castellón PhD , Héctor R. Contreras PhD
{"title":"Alpha-Lipoic Acid-Mediated Inhibition of LTB4 Synthesis Suppresses Epithelial-Mesenchymal Transition, Modulating Functional and Tumorigenic Capacities in Non-Small Cell Lung Cancer A549 Cells","authors":"María José Torres PhD , Juan Carlos Ríos PhD , Alexandra Valle MSc , Sebastián Indo PhD , Kevin Brockway GV MSc , Fernanda López-Moncada PhD , Mario Faúndez PhD , Enrique A. Castellón PhD , Héctor R. Contreras PhD","doi":"10.1016/j.curtheres.2024.100765","DOIUrl":"10.1016/j.curtheres.2024.100765","url":null,"abstract":"<div><h3>Background</h3><div>Leukotriene B<sub>4</sub> (LTB<sub>4</sub>) plays a crucial role in carcinogenesis by inducing epithelial-mesenchymal transition (EMT), a process associated with tumor progression. The synthesis of LTB<sub>4</sub> is mediated by leukotriene A<sub>4</sub> hydrolase (LTA<sub>4</sub>H), and it binds to the receptors BLT<sub>1</sub> and BLT<sub>2</sub>. Dysregulation in LTB<sub>4</sub> production is linked to the development of various pathologies. Therefore, the identification or design of inhibitors of LTB<sub>4</sub> synthesis or receptor antagonists represents an ongoing challenge. In this context, our laboratory previously demonstrated that alpha-lipoic acid (ALA) inhibits LTA<sub>4</sub>H. The objective of this study was to evaluate the effect of ALA on the expression of canonical EMT markers and the functional and tumorigenic capacities induced by LTB<sub>4</sub> in A549 cells.</div></div><div><h3>Methods</h3><div>The expression of cPLA<sub>2</sub>, 5LOX, FLAP, LTA<sub>4</sub>H, BLT1, and LTB<sub>4</sub> production in human adenocarcinomic alveolar basal epithelial A549 cells was assessed using Western blot, RT-qPCR, and ELISA, respectively. Subsequently, the expression of canonical EMT markers was evaluated by Western blot. Functional assays were performed to assess cell viability, proliferation, invasion, migration, and clonogenicity using MTT, Western blot, Transwell assays, and colony formation assays, respectively. Results were expressed as median with interquartile range (n≥3) and analyzed using the Kruskal-Wallis or Tukey multiple comparisons tests.</div></div><div><h3>Results</h3><div>A549 cells express key proteins involved in LTB<sub>4</sub> synthesis and receptor binding, including LTA<sub>4</sub>H and BLT<sub>1</sub>, and ALA inhibits the production of LTB<sub>4</sub>. Additionally, LTA<sub>4</sub>H and BLT1 were detected in lung adenocarcinoma tissue samples. LTB<sub>4</sub> was found to induce EMT, whereas ALA treatment enhanced the expression of epithelial markers and reduced the expression of mesenchymal markers. Furthermore, ALA treatment resulted in a decrease in LTB<sub>4</sub> levels and attenuated the functional and tumorigenic capacities of A549 cells, including their viability, migration, invasion, and clonogenic potential.</div></div><div><h3>Conclusions</h3><div>These findings suggest that ALA may offer therapeutic potential in the context of lung cancer, as it could be integrated into conventional pharmacological therapies to enhance treatment efficacy and mitigate the adverse effects associated with chemotherapy. Further studies are warranted to confirm the clinical applicability of ALA as an adjunctive treatment in lung cancer.</div></div>","PeriodicalId":10920,"journal":{"name":"Current Therapeutic Research-clinical and Experimental","volume":"102 ","pages":"Article 100765"},"PeriodicalIF":1.6,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11731977/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143001711","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 Effect of Anthocyanin Supplementation on Pro-Inflammatory Biomarkers in Patients With Metabolic Disorders: A Grade-Assessed Systematic Review and Meta-Analysis","authors":"Fatemeh Babaee Kiadehi MSc , Pegah Samani MSc , Sanaz Barazandeh MSc , Pedram Pam MSc , Ali Hajipour MSc , Narges Goli MSc , Ali Asadi PhD","doi":"10.1016/j.curtheres.2024.100772","DOIUrl":"10.1016/j.curtheres.2024.100772","url":null,"abstract":"<div><h3>Introduction and Aim</h3><div>Patients with metabolic disorders benefit from using anthocyanins. Nevertheless, the findings drawn from extant trials remain contentious. Thus, this meta-analysis evaluated anthocyanin's effect on inflammatory biomarkers in patients with metabolic disorders.</div></div><div><h3>Materials and Methods</h3><div>We comprehensively searched electronic databases, including PubMed, Scopus, Web of Science, and CENTRAL, from their inception to June 14, 2024.</div></div><div><h3>Findings</h3><div>A total of 11 randomized controlled clinical trials with 14 arms were analyzed. There was no significant effect of anthocyanin supplementation on interleukin (IL)-1β levels (standardized mean difference [SMD] = –0.01, 95% CI: –0.33, 0.31; <em>P</em> = 0.941, <em>I</em><sup>2</sup> = 62.4%, <em>P</em> = 0.031), tumor necrosis factor-α (TNF-α) (SMD = –0.49, 95% CI: –1.07, 0.09; <em>P</em> = 0.098, <em>I</em><sup>2</sup> = 94.0%, <em>P</em> < 0.001) and IL-6 (SMD = –0.69, 95% CI: –1.45, 0.06; <em>P</em> = 0.073, <em>I</em><sup>2</sup> = 95.2%, <em>P</em> < 0.001), respectively. A significant between-study heterogeneity was identified, which was reduced when subgrouping by sample size, dosage, and study population. However, subgroup analysis showed that it might decrease TNF-α and IL-6 in patients with hypertension, and if the intervention lasted less than 12 weeks.</div></div><div><h3>Conclusions</h3><div>There was no significant impact of anthocyanin supplementation on IL-1β, TNF-α, and IL-6; however, it should be noted that the intervention has a decreasing impact on individuals with hypertension. Our observed effect sizes on IL-1β, TNF-α, and IL-6 are not clinically important.</div></div>","PeriodicalId":10920,"journal":{"name":"Current Therapeutic Research-clinical and Experimental","volume":"102 ","pages":"Article 100772"},"PeriodicalIF":1.6,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143402896","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}