Current Therapeutic Research-clinical and Experimental最新文献

{"title":"Assessing the Impact of Frailty Interventions on Older Patients With Frailty","authors":"Miaoyu Zhang,&nbsp;Lingling Zhong","doi":"10.1016/j.curtheres.2024.100769","DOIUrl":"10.1016/j.curtheres.2024.100769","url":null,"abstract":"<div><h3>Background</h3><div>As the global population ages, frailty-marked by diminished physiological reserves and increased vulnerability, poses significant health risks such as falls, hospitalization, and mortality. Exercise therapy, enhancing muscle strength and balance, has shown promise in mitigating frailty's effects, while nursing interventions ensure tailored, comprehensive care. However, the combined impact of these interventions remains underexplored. This study investigates the clinical effectiveness of integrating active exercise with nursing interventions to manage frailty in elderly patients, aiming to improve their physical function and quality of life.</div></div><div><h3>Methods</h3><div>This retrospective study analyzed 100 elderly patients (≥80 years) admitted to our hospital with mild to moderate frailty. Participants were randomly assigned to either a control group (n = 50), receiving a standard exercise program, or an experimental group (n = 50), receiving the same program with personalized interventions under nursing assistance. Assessments were conducted at baseline and at 1, 3, 6, and 12 months. Outcome measures included assessing functional mobility, physical dependence in activities of daily living (ADLs), balance, muscle strength, degree of frailty and patient satisfaction with the nursing care.</div></div><div><h3>Results</h3><div>There were no significant differences in the baseline characteristics between the two groups (<em>P</em> ˃ 0.05). However, both groups exhibited significant improvements from baseline in functional mobility (<em>P</em> &lt; 0.001), physical dependence in ADLs (<em>P</em> &lt; 0.001), balance (<em>P</em> &lt; 0.001), muscle strength (<em>P</em> &lt; 0.001), and degree of frailty (<em>P</em> &lt; 0.001). Importantly, from 3 months onward, the experimental group showed significantly greater improvements in all these parameters compared to the control group (<em>P</em> &lt; 0.001 for each measure). Additionally, patient satisfaction was higher in the experimental group, with a satisfaction rate of 94.0% compared to 72.0% in the control group (<em>P</em> = 0.013).</div></div><div><h3>Conclusions</h3><div>This study demonstrates that combining active exercise with nursing interventions significantly improves physical performance, independence, balance, muscle strength, and reduces frailty in elderly patients. Furthermore, the high levels of patient satisfaction underscore the effectiveness and favorable reception of this intervention. These findings suggest that the implemented interventions can be a valuable approach in improving the overall health and well-being of elderly patients with frailty.</div></div>","PeriodicalId":10920,"journal":{"name":"Current Therapeutic Research-clinical and Experimental","volume":"102 ","pages":"Article 100769"},"PeriodicalIF":1.6,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144068429","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","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 ,&nbsp;Saki Yoshida BS ,&nbsp;Takumi Hotta BS ,&nbsp;Hirohito Muroi BS ,&nbsp;Keizo Fukushima PhD ,&nbsp;Kei Irie PhD ,&nbsp;Tatsuya Hirano BS ,&nbsp;Yoshimitsu Shimomura MD ,&nbsp;Takayuki Ishikawa MD, PhD ,&nbsp;Hiroaki Ikesue PhD ,&nbsp;Nobuyuki Muroi PhD ,&nbsp;Tohru Hashida PhD ,&nbsp;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":"Randomized, Double-Blind, Crossover Study Comparing the Bioavailability of 4 Ashwagandha (Withania somnifera (L.) Dunal) Extracts in Healthy Adults Under Fasting Condition","authors":"Priyank Rathi MD ,&nbsp;Se-Kwon Kim PhD","doi":"10.1016/j.curtheres.2025.100805","DOIUrl":"10.1016/j.curtheres.2025.100805","url":null,"abstract":"<div><h3>Background</h3><div><em>Withania somnifera</em> (L.) Dunal, commonly known as ashwagandha, is a well-known plant in ayurvedic medicine, widely valued for its therapeutic potential. Although numerous clinical studies have explored its diverse health benefits, limited data are available on the pharmacokinetic (PK) properties and comparative bioavailability of its key bioactive constituents in humans.</div></div><div><h3>Objective</h3><div>This study aimed to evaluate and compare the oral bioavailability of 4 commercially standardized ashwagandha extracts under fasting conditions in healthy adults.</div></div><div><h3>Methods</h3><div>This randomized, double-blind, 4-treatment, 4-period, 4-sequence, single dose, 4-way crossover study was conducted in 16 healthy human volunteers. Participants received a single oral dose of 1 of 4 ashwagandha extracts, with varying compositions of 35% (<em>Withania somnifera</em> [WS]-35) or 10% (WS-10) withanolide glycosides, or 5% (WS-5) or 2.5% (WS-2.5) withanolides, each standardized to deliver 185 mg of total withanolides. Seventeen blood samples were collected over a 24-hour period after dose administration. Plasma concentrations of withanolide A, withanoside IV, withaferin A, and total withanolides were quantified, and PK parameters were calculated.</div></div><div><h3>Results</h3><div><em>Withania somnifera</em>-35 had significantly superior bioavailability compared with the other extracts. The AUC_0–t for total withanolides per gram of WS-35 was 118.28, 226.11, and 267.83 times better than WS-10, WS-5, and WS-2.5 respectively. <em>Withania somnifera</em>-35 exhibited a significantly higher C_max, longer half-life, extended mean residence time, and lower systemic clearance, attributable to its higher withanolide glycoside content.</div></div><div><h3>Conclusions</h3><div>These findings emphasize the critical role of withanolide glycosides in determining the PK performance of ashwagandha supplements. The enhanced bioavailability of WS-35 supports its preferential use in therapeutic applications and provides a strong rationale for further investigation into dose-response relationships and the long-term efficacy of standardized, high-bioavailability formulations. Clinical Trial Registry of India identifier: CTRI/2020/10/028397.</div></div>","PeriodicalId":10920,"journal":{"name":"Current Therapeutic Research-clinical and Experimental","volume":"103 ","pages":"Article 100805"},"PeriodicalIF":1.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144738188","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effect of a Pleuran-Based Supplement on Salivary IgA Secretion in Children With Recurrent Respiratory Infections","authors":"Peter Kunc MD, PhD ,&nbsp;Jaroslav Fabry MD, PhD ,&nbsp;Michaela Matiscakova MD ,&nbsp;Katarina Istvankova DVM ,&nbsp;Zuzana Diamant MD, PhD ,&nbsp;Juraj Majtan PhD, DSc ,&nbsp;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}

{"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 ,&nbsp;Gofarana Wilar PhD ,&nbsp;Khaled M. Elamin PhD ,&nbsp;Audry Rahma Dewayani BSc ,&nbsp;Salsabil Ghaliya BSc ,&nbsp;Astriani Abdullah BSc ,&nbsp;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, I² = 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}

{"title":"The Effect of Berberis (Vulgaris and Integerrima) on Cardiovascular Risk Factors in Patients With Type 2 Diabetes Mellitus: A Systematic Review, Meta-Analysis, and GRADE Assessment","authors":"Vali Musazadeh ,&nbsp;Niloofar Hamidi ,&nbsp;Morvarid Noormohammadi ,&nbsp;Farzad Shidfar","doi":"10.1016/j.curtheres.2025.100788","DOIUrl":"10.1016/j.curtheres.2025.100788","url":null,"abstract":"<div><h3>Introduction and Aim</h3><div>Type 2 diabetes mellitus (T2DM) raises cardiovascular disease risk, but evidence on Berberis's impact is limited and inconsistent. This systematic review and meta-analysis aimed to assess effect of Berberis supplement on cardiovascular risk factors in patients with T2DM.</div></div><div><h3>Materials and Methods</h3><div>We extensively searched Embase, Web of Science, Scopus, PubMed, and the Cochrane Library for randomized controlled trials (RCTs) up to October 25, 2024. This study primarily assesses Berberis's impact on improving glycemic indices, with secondary measures including obesity, blood pressure and lipid profile parameters.</div></div><div><h3>Findings</h3><div>After reviewing 784 articles, we included data from eight RCTs involving 451 participants with T2DM. The results of meta-analysis indicated that Berberis administration significantly reduced weight (WMD: -2.25; 95% CI: -3.11 to -1.39), body mass index (BMI, WMD: -0.57; 95% CI: -0.98 to -0.17), TG (WMD: -19.32; 95% CI: -30.95 to -1.69), TC (WMD: -28.57; 95% CI: -30.22 to -21.51), LDL-C (WMD: -17.47; 95% CI: -24.18 to -10.75), FBS (WMD: -14.54; 95% CI: -23.83, -5.25), HbA1c (WMD: -0.65; 95% CI: -1.30, -0.00), HOMA-IR (WMD: -1.82; 95% CI: -3.60, -0.05), and insulin (WMD: -4.40; 95% CI: -7.15, -1.65). However, no statistically significant effect on blood pressure and HDL-C level was observed with Berberis intervention.</div></div><div><h3>Conclusion</h3><div>This meta-analysis hints at Berberis's potential benefits for T2DM. However, more extensive trials are needed to confirm its advantages definitively.</div></div>","PeriodicalId":10920,"journal":{"name":"Current Therapeutic Research-clinical and Experimental","volume":"102 ","pages":"Article 100788"},"PeriodicalIF":1.6,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144134708","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Clinical Nomogram for Predicting Substandard Serum Valproic Acid Concentrations in Chinese Patients With Epilepsy","authors":"Zi-Hao Duan MS ,&nbsp;Chun-Yuan He MS ,&nbsp;Jie Chen BS ,&nbsp;Jun-Jie Jiang BS ,&nbsp;Zhi-Xiang Zhu PhD ,&nbsp;Jing Li MS ,&nbsp;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}

{"title":"Safety and Efficacy of a Mesenchymal Stem Cell Secretome Therapy (KPI-012) for Persistent Corneal Epithelial Defects: A Phase 1b Trial","authors":"Valeria Sánchez Huerta MD ,&nbsp;Hugo Quiroz-Mercado MD ,&nbsp;Enrique O. Graue-Hernández MD, MSc ,&nbsp;Alejandro Navas MD, MSc ,&nbsp;Spencer Alford PhD ,&nbsp;Darius Kharabi JD, MBA ,&nbsp;Stephen Pflugfelder MD","doi":"10.1016/j.curtheres.2025.100799","DOIUrl":"10.1016/j.curtheres.2025.100799","url":null,"abstract":"<div><h3>Background</h3><div>Persistent corneal epithelial defect (PCED) is a condition often refractory to conventional treatments. KPI-012 is a topical mesenchymal stem cell secretome therapy under investigation for PCED management.</div></div><div><h3>Objective</h3><div>To assess the safety, tolerability, and corneal wound healing efficacy of KPI-012 in a phase 1b, proof-of-concept, open-label, single-arm clinical trial.</div></div><div><h3>Methods</h3><div>The safety profile and tolerability of topical self-administered KPI-012 therapy (twice daily, 1-week duration) were first evaluated in an initial safety cohort of participants with pre-existing permanent vision loss and no active corneal disease (n = 3). The safety profile and efficacy of KPI-012 were then assessed in participants with PCED of several etiologies (n = 9), who self-administered KPI-012 twice daily for up to 4 weeks with one participant self-administering for 8 weeks (efficacy cohort).</div></div><div><h3>Results</h3><div>KPI-012 was well tolerated in both the safety profile and efficacy cohorts. In the efficacy cohort (n = 9), 6 of 8 participants (75%) demonstrated complete healing of the lesion during the treatment period, with 4 of 8 (50%) achieving complete healing within 1 week of commencing KPI-012 therapy (a nontreatment-related adverse event meant 1 participant was withdrawn by the investigator). KPI-012 was well tolerated, with only 1 participant experiencing treatment-related adverse events. In patients who reported PCED-related ocular pain at baseline (n = 7), pain levels decreased in all participants after 1 week, and after 3 weeks, no participant reported ocular pain.</div></div><div><h3>Conclusions</h3><div>The results from this small phase 1b open-label trial suggest that in participants with PCED of multiple etiologic origin, twice daily KPI-012 therapy exhibits a favorable safety profile-efficacy profile and may promote rapid wound healing. The small sample size limits the generalizability of the findings, and thus a later-phase clinical investigation with a larger sample size is warranted to establish the statistically driven therapeutic effect.</div></div>","PeriodicalId":10920,"journal":{"name":"Current Therapeutic Research-clinical and Experimental","volume":"103 ","pages":"Article 100799"},"PeriodicalIF":1.6,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144241091","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Effects of Cocoons of Larinus Hedenborgi (Coleoptera: Curculionidae) Extracts on Inflammation and Clinical Outcomes in Patients With Coronavirus Disease 2019: A Double-Blinded Randomized Controlled Clinical Trial","authors":"Mahdi Keshani ,&nbsp;Sayid Mahdi Mirghazanfari ,&nbsp;Naseh Pahlavani ,&nbsp;Faezeh Baniyaghoobi ,&nbsp;Vahid Hadi ,&nbsp;Mohammad Bagherniya ,&nbsp;Zahra Heidari ,&nbsp;Amirhossein Sahebkar ,&nbsp;Mohsen Mohajeri ,&nbsp;Saeid Hadi","doi":"10.1016/j.curtheres.2025.100811","DOIUrl":"10.1016/j.curtheres.2025.100811","url":null,"abstract":"<div><h3>Background</h3><div>Severe acute respiratory syndrome coronavirus 2, the causative agent of coronavirus disease 2019 (COVID-19), is an inflammatory disease that manifests with symptoms including dry cough, fever, myalgia, and even pneumonia. Despite antiviral treatments, no definitive therapy has been proven effective. <em>Trehala manna</em> (TM), the edible cocoon of <em>Larinus hedenborgi</em> (Coleoptera: Curculionidae) weevil, as a natural product, is traditionally used to alleviate respiratory symptoms because of its antibacterial, anti-inflammatory, and antifungal properties.</div></div><div><h3>Objective</h3><div>The current study aimed to determine the effects of TM add-on treatment on inflammatory biomarkers and some clinical outcomes in patients with COVID-19.</div></div><div><h3>Methods</h3><div>The present study was a randomized controlled trial conducted on 60 patients who were randomly allocated to TM (5 g, twice a day) or a placebo for 1 week. The main outcomes of the current study include C-reactive protein (CRP) level, erythrocyte sedimentation rate (ESR), blood urea nitrogen level, creatinine level, fasting blood sugar level, systolic blood pressure, and visual analog scale (VAS) score for cough, which were evaluated at both the beginning and end of the study.</div></div><div><h3>Results</h3><div>Our finding revealed that CRP level, ESR, blood urea nitrogen level, creatinine level, fasting blood sugar level, systolic blood pressure, and VAS score for cough were significantly reduced in the TM group after intervention (<em>P</em> &lt; 0.05), and CRP level, ESR, VAS score for cough, and fever were significantly reduced in the TM group compared with the control after 7 days (<em>P</em> &lt; 0.05).</div></div><div><h3>Conclusions</h3><div><em>Trehala mann</em> is a natural remedy with potential as an adjunctive therapy for reducing inflammatory biomarkers and improving certain clinical symptoms in patients with COVID-19. No adverse effects were observed during the trial. Iranian Registry of Clinical Trials identifier: IRCT20211029052904N1.</div></div>","PeriodicalId":10920,"journal":{"name":"Current Therapeutic Research-clinical and Experimental","volume":"103 ","pages":"Article 100811"},"PeriodicalIF":1.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145010609","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"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 ,&nbsp;Juan Carlos Ríos PhD ,&nbsp;Alexandra Valle MSc ,&nbsp;Sebastián Indo PhD ,&nbsp;Kevin Brockway GV MSc ,&nbsp;Fernanda López-Moncada PhD ,&nbsp;Mario Faúndez PhD ,&nbsp;Enrique A. Castellón PhD ,&nbsp;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 B₄ (LTB₄) plays a crucial role in carcinogenesis by inducing epithelial-mesenchymal transition (EMT), a process associated with tumor progression. The synthesis of LTB₄ is mediated by leukotriene A₄ hydrolase (LTA₄H), and it binds to the receptors BLT₁ and BLT₂. Dysregulation in LTB₄ production is linked to the development of various pathologies. Therefore, the identification or design of inhibitors of LTB₄ synthesis or receptor antagonists represents an ongoing challenge. In this context, our laboratory previously demonstrated that alpha-lipoic acid (ALA) inhibits LTA₄H. 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 LTB₄ in A549 cells.</div></div><div><h3>Methods</h3><div>The expression of cPLA₂, 5LOX, FLAP, LTA₄H, BLT1, and LTB₄ 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 LTB₄ synthesis and receptor binding, including LTA₄H and BLT₁, and ALA inhibits the production of LTB₄. Additionally, LTA₄H and BLT1 were detected in lung adenocarcinoma tissue samples. LTB₄ 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 LTB₄ 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}