Current Therapeutic Research-clinical and Experimental最新文献

{"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}

{"title":"Comparison of Bioavailability of Nitrates and Nitrites in 3 Species of Amaranthus: A Randomized, Double-Blind, Placebo-Controlled, 4-Way Crossover Study in Healthy Subjects Under Fasting Conditions","authors":"Deepa Suhag ,&nbsp;Aparna Nilesh Kodre","doi":"10.1016/j.curtheres.2025.100789","DOIUrl":"10.1016/j.curtheres.2025.100789","url":null,"abstract":"<div><h3>Background</h3><div><em>Amaranthus</em> is a significant source of dietary nitrates, which have been known to improve aerobic capacity and exercise performance in physically active individuals. There is a significant data gap on nonpartitive pharmacokinetics and bioequivalence studies of nitrate and nitrite from 3 species of Amaranth (<em>A. hybridus, A. hypochondriacus</em>, and <em>A. tricolor</em>).</div></div><div><h3>Objective</h3><div>This study aimed to assess the bioavailability of nitrates and nitrites from 3 <em>Amaranthus</em> species in a randomized, placebo-controlled design, thereby filling this gap.</div></div><div><h3>Methods</h3><div>A double-blinded, 4-way crossover study was conducted in 16 healthy participants. Each participant enrolled in the study received a single dose of 2000 mg of <em>Amaranthus</em> extract or a placebo. The plasma and saliva samples were collected at specific intervals over 24 hours. Nitrate and nitrite concentrations were analyzed using a validated LCMS/MS method.</div></div><div><h3>Results</h3><div>After the administration of amaranth extracts, both plasma and saliva samples were observed significantly higher levels of nitrate and nitrite compared with the placebo group. Pharmacokinetic variables (C_max, AUC_0-t24, and AUC0-∞) found a similar pattern for nitrite and nitrate in the 3 amaranth products but were significantly different from placebo (<em>P</em> &lt; 0.05), in both plasma and saliva samples. Bioequivalence analysis confirmed significant bioequivalence among the 3 amaranth extracts for nitrite and nitrate.</div></div><div><h3>Conclusions</h3><div>This study concludes that the 3 species of <em>Amaranthus</em>—<em>A. hybridus, A. hypochondriacus</em>, and <em>A. tricolor</em> are bioequivalent in terms of plasma and saliva nitrate and nitrite levels from a single dose of 2000 mg amaranth extract and have higher bioavailability than placebo. These findings report that <em>Amaranthus</em> extracts could potentially act as a daily diet supplement for improving the cardiovascular and neurogenerative health of the body, particularly aging people.</div></div>","PeriodicalId":10920,"journal":{"name":"Current Therapeutic Research-clinical and Experimental","volume":"103 ","pages":"Article 100789"},"PeriodicalIF":1.6,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144241092","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":"Innovative Solutions for Multidrug-Resistant Organisms’ Infections in Intensive Care Unit: A Joint Efficacy Evaluation of Multidisciplinary Team and SHEL (Software, Hardware, Environment, Liveware) Model","authors":"Xiaoyan Kang MD ,&nbsp;Ping Zhang DNP ,&nbsp;Qing Xu MD ,&nbsp;Zhengqun Feng MD ,&nbsp;Bei Yin MD","doi":"10.1016/j.curtheres.2024.100766","DOIUrl":"10.1016/j.curtheres.2024.100766","url":null,"abstract":"<div><h3>Background</h3><div>The escalating threat of multidrug-resistant organisms (MDROs) in intensive care unit (ICU) demands innovative management strategies to curb the rising infection rates and associated clinical challenges.</div></div><div><h3>Objective</h3><div>To assess the effectiveness of integrating the multidisciplinary team (MDT) approach with the SHEL (Software, Hardware, Environment, Liveware) model in reducing MDRO infections within ICU settings.</div></div><div><h3>Methods</h3><div>From January 2021 to April 2024, a prospective, randomized controlled study was conducted in the ICU of Nantong Fourth People's Hospital, enrolling 411 patients with MDRO infections. These patients were randomly assigned into 3 groups: the MDT group, the SHEL model group, and a combined group. The intervention lasted for 4 weeks, during which the effects on the MDRO detection rate, infection rate, health care staff's infection control execution scores, and the rationality of antibiotic use were assessed, aiming to determine the efficacy of each approach in managing MDROs in the ICU setting.</div></div><div><h3>Results</h3><div>The overall infection rate of MDROs in the ICU of our hospital from 2021 to 2024 was 60.18%, with sputum infection sources accounting for 68.37% of the total sources, making it the primary source of infection. The detection rate of MDROs in the combined group was significantly higher than that in the MDT and the SHEL groups, with the SHEL group having a higher detection rate than the MDT group (<em>P</em> &lt; 0.05). The infection rate of MDROs in the combined group was significantly lower than that in both the MDT and the SHEL groups, with the SHEL group having a lower detection rate than the MDT group (<em>P</em> &lt; 0.05). The implementation scores of the combination group in standard prevention, hand hygiene, antibiotic management, and isolation measures were significantly higher than those of the MDT and SHEL groups, with the SHEL group scoring higher than the MDT group (<em>P</em> &lt; 0.05). The rational use of antibiotics in the combined group was also higher than in both the MDT and the SHEL groups, with the SHEL group having a higher level than the MDT group (<em>P</em> &lt; 0.05).</div></div><div><h3>Conclusions</h3><div>The integrated MDT and SHEL model significantly reduced MDRO infections in ICU, improved health care workers' infection prevention and nursing quality, and promoted the appropriate use of antibiotics, advocating for its clinical application.</div></div>","PeriodicalId":10920,"journal":{"name":"Current Therapeutic Research-clinical and Experimental","volume":"102 ","pages":"Article 100766"},"PeriodicalIF":1.6,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11731589/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143001756","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":"Oral Cyclosporine Treatment for Four Pediatric Patients With Toxic Epidermal Necrolysis That Showed No Response to High-dose Corticosteroids in Combination With Intravenous Immunoglobulin: A Case Series","authors":"Peijing Li MD ,&nbsp;Qin Yao MD ,&nbsp;Yuanyuan Wang MD ,&nbsp;Xipeng Xu MD","doi":"10.1016/j.curtheres.2024.100767","DOIUrl":"10.1016/j.curtheres.2024.100767","url":null,"abstract":"<div><h3>Background</h3><div>Immunosuppressive agents like cyclosporine have proven effective in some pediatric cases, although there are limited case reports considering potential risks such as secondary infections.</div></div><div><h3>Objective</h3><div>This study investigated the safety and efficacy of Cyclosporine A in children who did not respond to high-dose corticosteroids combined with intravenous immunoglobulin (IVIG).</div></div><div><h3>Methods</h3><div>We reported four pediatric patients diagnosed with toxic epidermal necrolysis (TEN) received treatment at our institution. All patients were previously healthy children with a median age of 7 years, comprising three boys and one girl (<span><span>Table 1</span></span>). Epidermal exfoliation and vesicular lesions ranged from 32.5% to 54.5% of the body surface area (BSA). Despite the administration of treatment comprising high-dose corticosteroids and intravenous immunoglobulin (IVIG), new cutaneous herpes continually emerged. This prompted a transition to cyclosporine treatment (3–5 mg/kg/d) administered in 1–2 oral doses.</div></div><div><h3>Results</h3><div>Lesions stopped progressing, and bullous lesions started epithelialization after 13–27 days of hospitalization. Cases 1 and 2 faced secondary bacterial and fungal infections, respectively, and their temperatures stabilized after administration of antibiotics. Cases 3 and 4 experienced fever again when the dosage of corticosteroids was tapered off, with no discernible evidence of infection. The patients’ temperatures normalized upon the continuation of cyclosporine therapy. Among the patients, three presented asymptomatic elevated serum amylase, one of which met the diagnostic criteria for acute pancreatitis. Two children showed mildly raised aminotransferases, with one experiencing mild coronary artery dilation, two contracted onychomadesis, and three developed corneal ulceration/keratitis and atretoblepharia, which eventually resolved after vigorous ophthalmologic treatment. None of the children had any permanent sequelae after being discharged from the hospital for six months.</div></div><div><h3>Conclusions</h3><div>Cyclosporine A is generally safe and effective for children who fail to respond to high-dose corticosteroids in combination with IVIG.</div></div>","PeriodicalId":10920,"journal":{"name":"Current Therapeutic Research-clinical and Experimental","volume":"102 ","pages":"Article 100767"},"PeriodicalIF":1.6,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11733270/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143001800","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":"Nano-Amounts of Glucagon Premixed With Fast-Acting Insulin Lispro: Effect on Insulin Absorption in Pigs","authors":"Ilze Dirnena-Fusini PhD ,&nbsp;Misbah Riaz MSc ,&nbsp;Sverre Christian Christiansen MD, PhD ,&nbsp;Sven Magnus Carlsen MD, PhD","doi":"10.1016/j.curtheres.2025.100803","DOIUrl":"10.1016/j.curtheres.2025.100803","url":null,"abstract":"<div><h3>Background</h3><div>Glucagon leads to substantial but short-lived subcutaneous vasodilation. Using micro-amounts of glucagon at the insulin injection site increases insulin absorption.</div></div><div><h3>Objective</h3><div>We hypothesized that a premixed solution of insulin and nanogram doses of glucagon would improve the pharmacokinetic and pharmacodynamic properties of subcutaneously injected insulin.</div></div><div><h3>Methods</h3><div>In this series of proof-of-concept experiments, 17 anesthetized pigs were included. Nine pigs were included in the control groups; they received a subcutaneous injection of 10 U of insulin lispro (Lyumjev^Ⓡ or Humalog^Ⓡ). Eight pigs were included in the glucagon groups; they received 10 U of a premixed insulin (Lyumjev^Ⓡ or Humalog^Ⓡ)/glucagon solution (5 ng glucagon/unit of insulin). Arterial blood was frequently sampled for 210 minutes to assess insulin and glucose concentrations. The impact on glucose metabolism was evaluated through euglycemic clamp investigation.</div></div><div><h3>Results</h3><div>When premixed insulin Lyumjev^Ⓡ/glucagon was injected, insulin T_max decreased from 33 to 20 minutes (SE = 6.6, <em>P</em> = 0.08), and C_max was 2-fold higher than that in the control group (100 mU/L vs 46 mU/L, SE = 4.8, <em>P</em> = 0.007). When premixed insulin Humalog^Ⓡ/glucagon was injected, T_max and C_max did not change significantly (<em>P</em> = 0.53 and <em>P</em> = 0.83, respectively). Insulin AUC for the first 15 minutes increased two-fold when insulin Lyumjev^Ⓡ/glucagon was injected (946 mU×min/L vs 337 mU×min/L, SE = 196, <em>P</em> = 0.02). A similar trend was observed when Humalog^Ⓡ/glucagon was injected (306 mU×min/L vs 65 mU×min/L, SE = 125), although this difference did not reach statistical significance (<em>P</em> = 0.102) compared with the control groups.</div></div><div><h3>Conclusions</h3><div>This series of proof-of-concept experiments in anesthetized pigs indicate that premixing nanogram doses of glucagon in fast-acting insulin lispro formulations may speed up the absorption of subcutaneously injected insulin.</div></div>","PeriodicalId":10920,"journal":{"name":"Current Therapeutic Research-clinical and Experimental","volume":"103 ","pages":"Article 100803"},"PeriodicalIF":1.6,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144655433","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":"Reversing Morphine Induced Tolerance: Insights Into Cetirizine and Green Tea Extract Efficacy","authors":"Tahereh Eteraf-Oskouei Phd ,&nbsp;Adel Mahmoudi Gharehbaba Phd ,&nbsp;Solmaz Asnaashari Phd ,&nbsp;Zahra Fazli Phd ,&nbsp;Bohloul Habibi Asl Phd","doi":"10.1016/j.curtheres.2025.100783","DOIUrl":"10.1016/j.curtheres.2025.100783","url":null,"abstract":"<div><h3>Background</h3><div>The treatment of chronic pain presents a considerable difficulty, particularly due to opioid dependence, which is marked by tolerance and withdrawal symptoms. Opioids primarily target mu (μ) opioid receptors, providing pain relief while also leading to various side effects. This research aimed to examine the effectiveness of cetirizine and green tea hydroalcoholic extract (EXT) in altering morphine tolerance and improving analgesic effects.</div></div><div><h3>Methods</h3><div>Adult male mice were divided into nine groups. In order to investigate the analgesic tolerance, animals received morphine on 14 consecutive days. Cetirizine (5, 10, 20 mg/kg, i.p.) and EXT (50, 100, 200 mg/kg, i.p.) were given before a test dose of morphine (9 mg/kg, i.p.). The analgesic effects were evaluated by the hot plate test.</div></div><div><h3>Results</h3><div>Cetirizine with doses of 5, 10, 20 mg/kg, and 10 mg/kg showed a significant effect in reducing morphine tolerance 30 min (<em>P</em> &lt; 0.0001) and 45 to 60 min (<em>P</em> &lt; 0.0001) after test dose of morphine (9 mg/kg, i.p.) respectively. While the injection of different doses of the extract did not show any effect on tolerance to morphine. In the combined injection of these two drugs, there was no reduction in tolerance to morphine.</div></div><div><h3>Conclusions</h3><div>Cetirizine but not EXT reversed morphine tolerance. Furthermore, the co-administration of cetirizine and EXT did not yield any significant benefits compared to the individual treatments.</div></div>","PeriodicalId":10920,"journal":{"name":"Current Therapeutic Research-clinical and Experimental","volume":"102 ","pages":"Article 100783"},"PeriodicalIF":1.6,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143768752","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":"Unlocking the Value of Neuropsychological Assessments in Rehabilitation: Perspectives from Persons with Dementia and Their Caregivers","authors":"Takako Yoshimura ,&nbsp;Aiko Osawa ,&nbsp;Shiinchiro Maeshima ,&nbsp;Iikue Ueda ,&nbsp;Koki Kawamura ,&nbsp;Masaki Kamiya ,&nbsp;Naoki Itoh ,&nbsp;Hidenori Arai","doi":"10.1016/j.curtheres.2025.100781","DOIUrl":"10.1016/j.curtheres.2025.100781","url":null,"abstract":"<div><h3>Purpose</h3><div>Various neuropsychological or cognitive assessments are often conducted before rehabilitation to ascertain patients’ function, disability, and environment. However, adequate assessments are not conducted for persons with dementia under the assumption that assessments would burden them. Therefore, this study investigated the perceptions of persons with dementia and their family caregivers regarding cognitive function assessments during hospital rehabilitation and reconsidered the significance of such assessments according to the opinions of those involved.</div></div><div><h3>Methods</h3><div>This cross-sectional observational study was conducted over a 3-month period at a hospital-based rehabilitation center. We administered a semi-structured questionnaire to 31 older persons with dementia (13 men and 18 women; mean age [± SD]: 77 [± 5.7] (range: 66–87 years); mean years of education [± SD]: 12 [± 2.3]; (range: 9–16 years); Alzheimer's disease: 15; mild cognitive impairment (MCI): 15; corticobasal degeneration: 1) and 49 family caregiver dyads (24 men and 25 women, mean age [± SD]: 67 [± 11] years; age range: 46–90 years). The data were interpreted by employing descriptive statistics, and the χ², Fisher's exact, and Kruskal–Wallis tests.</div></div><div><h3>Findings</h3><div>Both groups acknowledged the value of neuropsychological assessments, with 94% (95% CI 84.9–100%) of persons with MCI/dementia and 83% (95% CI 73.3–94.0%) of their family caregivers linking them directly to enhanced treatment and care quality. Their positive attitudes were significantly associated with the belief that such evaluations are integral for personalizing and optimizing rehabilitation strategies.</div></div><div><h3>Implications</h3><div>Most individuals with MCI/dementia and their caregivers value detailed neuropsychological assessments for understanding rehabilitation needs, highlighting the importance of integrating comprehensive evaluations into dementia care. However, the single-center nature of our study limits generalizability. Future research with diverse participants is needed to develop scalable, inclusive rehabilitation strategies.</div></div>","PeriodicalId":10920,"journal":{"name":"Current Therapeutic Research-clinical and Experimental","volume":"102 ","pages":"Article 100781"},"PeriodicalIF":1.6,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143684680","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":"Unleashing the Potential of Givinostat: A Novel Therapy for Duchenne Muscular Dystrophy","authors":"Ahmad Furqan Anjum MBBS, BSc ,&nbsp;Muhammad Burhan Anjum MBBS ,&nbsp;Raza ur Rehman MBBS, Bsc","doi":"10.1016/j.curtheres.2025.100787","DOIUrl":"10.1016/j.curtheres.2025.100787","url":null,"abstract":"<div><h3>Purpose</h3><div>Duchenne muscular dystrophy (DMD) is a progressive neuromuscular disorder with limited treatment options beyond corticosteroids, which have significant adverse effects. Givinostat, a histone deacetylase inhibitor, has recently emerged as a promising disease-modifying therapy. This commentary examines the therapeutic potential of givinostat, its mechanism of action, and the clinical evidence supporting its role in DMD treatment.</div></div><div><h3>Methods</h3><div>A review of the EPIDYS Phase 3 trial and supporting clinical studies was conducted. The study included boys aged 6 to 17 years with genetically confirmed DMD, assessing givinostat's efficacy and safety over 18 months. Key endpoints included the North Star Ambulatory Assessment (NSAA), MRI-based muscle preservation, and adverse event (AE) profiles.</div></div><div><h3>Findings</h3><div>Givinostat-treated patients demonstrated a 1.9-point higher NSAA score compared to placebo (<em>P</em> = 0.03), with significant reductions in muscle fat infiltration (40% lower than placebo; <em>P</em> &lt; 0.05). Functional tests showed trends toward improved stair-climbing ability, though not statistically significant. AEs included thrombocytopenia (20%) and hypertriglyceridemia (10%), necessitating monitoring but remaining manageable.</div></div><div><h3>Implications</h3><div>Givinostat represents a paradigm shift in DMD management, offering benefits beyond corticosteroids by reducing fibrosis and promoting muscle regeneration. While its long-term safety and cost-effectiveness require further evaluation, its combination potential with gene therapies highlights its importance in future DMD treatment strategies. Ongoing studies aim to refine its role in broader neuromuscular disorders.</div></div>","PeriodicalId":10920,"journal":{"name":"Current Therapeutic Research-clinical and Experimental","volume":"102 ","pages":"Article 100787"},"PeriodicalIF":1.6,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143865164","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":"Investigating the Effect of Reducing the Signs and Symptoms of Lid Wiper Epitheliopathy in Patients With Dry Eye Disease With Perfluorohexyloctane","authors":"Chris Lievens OD, MS, PhD, FNAP, FAAO ,&nbsp;Andrew D. Pucker OD, PhD, FAAO ,&nbsp;Quentin Franklin BS ,&nbsp;Stephen M. Montaquila OD, FAAO ,&nbsp;Brad Giedd OD, MS, FAAO ,&nbsp;Gina Wesley OD, MS, FAAO ,&nbsp;Morgan Bromley PhD ,&nbsp;Zackarias Coker MS ,&nbsp;John Meyers MS ,&nbsp;Marta Vianya-Estopa PhD","doi":"10.1016/j.curtheres.2025.100786","DOIUrl":"10.1016/j.curtheres.2025.100786","url":null,"abstract":"<div><h3>Background</h3><div>Perfluorohexyloctane (PFHO) acts to prevent the evaporation of the tear film. It has the potential to limit friction related issues between the eye lid margin and the ocular surface. Prior to the present work, this had not yet been evaluated.</div></div><div><h3>Objective</h3><div>To examine the potential of using perfluorohexyloctane for reducing the signs and symptoms of lid wiper epitheliopathy (LWE).</div></div><div><h3>Methods</h3><div>Data were collected at 4 visits spanning 2 months. Patients who had symptomatic dry eye and a LWE score of ≥1.0 on the Korb LWE scale were recruited. Participants were randomized to PFHO 4 times a day or no treatment. Lid wiper epitheliopathy was graded at each visit with the Korb and photographic LWE (PLWE) scales. Symptoms were assessed using the Standard Patient Evaluation of Eye Dryness questionnaire and visual analog scales (0–100).</div></div><div><h3>Results</h3><div>A total of 52 participants were enrolled (mean ± SD age, 49.7 ± 15.7 years; 79% female). Right eyes in the treatment group were significantly more likely to show an improvement of ≥0.5-units in PLWE scores at 2 months than the no treatment group (<em>P</em> = 0.04), but no left eye differences were noted. Korb and PLWE scores were significantly better in the treatment group compared with the no treatment group starting at 2 weeks and remained so for the duration of the study (all <em>P</em> &lt; 0.001). Standard Patient Evaluation of Eye Dryness scores and dry eye symptoms were significantly better in the treatment than in the no treatment group at the 2-month visit (all <em>P</em> ≤ 0.01).</div></div><div><h3>Conclusions</h3><div>Perfluorohexyloctane significantly reduced LWE and improved dry eye symptoms compared with no treatment, suggesting that PFHO may enhance ocular lubrication and reduce friction-related damage. Masked, randomized, trials are still needed to compare PFHO to other treatments in participants with LWE to support generalizability of results. ClinicalTrials.gov study NCT06671041.</div></div>","PeriodicalId":10920,"journal":{"name":"Current Therapeutic Research-clinical and Experimental","volume":"102 ","pages":"Article 100786"},"PeriodicalIF":1.6,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143816505","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":"Impact of Dipeptidyl Peptidase-4 Inhibitors on Aminotransferases Levels in Patients with Type 2 Diabetes Mellitus With Nonalcoholic Fatty Liver Disease: A Meta-Analysis of Randomized Controlled Trial","authors":"Gang Ma MD ,&nbsp;Song Zhang MD ,&nbsp;Baozhong Yu MD","doi":"10.1016/j.curtheres.2024.100768","DOIUrl":"10.1016/j.curtheres.2024.100768","url":null,"abstract":"<div><h3>Background</h3><div>Type 2 diabetes mellitus (T2DM) and nonalcoholic fatty liver disease (NAFLD) are highly prevalent diseases that constitute enormous public health problems. The efficacy of dipeptidyl peptidase-4 (DPP-4) inhibitors in blood glucose control in T2DM patients with NAFLD has been established, but little is known about its effect on liver enzyme levels.</div></div><div><h3>Objective</h3><div>This meta-analysis aimed to evaluate the influences of DPP-4 inhibitors on alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in patients with T2DM and NAFLD.</div></div><div><h3>Methods</h3><div>To identify the relevant studies, we searched PubMed, Embase, the Cochrane Library, Wanfang Data, and China National Knowledge Infrastructure. Means differences in liver enzymes and metabolic outcomes were meta-analyzed using a random-effects model, with subgroup analyses by gender, age, area, follow-up duration, and type of DPP-4 inhibitor. Quality assessment of the included studies was conducted using the revised Cochrane risk of bias tool.</div></div><div><h3>Results</h3><div>A total of 1323 patients from 16 studies were included in this meta-analysis. The results of analysis of DPP-4 inhibitors showed that the mean difference was –6.19 (95% confidence interval [CI]: –9.45 to –2.92) for ALT and –5.17 (95% CI: –8.10 to –2.23) for AST; this effect was statistically significant from the placebo group which indicates the beneficial effect on liver enzymes. Subgroup analysis revealed that while there were no significant gender differences in enzyme reductions, individuals over 55 years old experienced more pronounced decreases in ALT. Notably, Asian studies showed significant reductions in liver enzymes, contrasting with the minor variations observed in Euramerican regions, and the effectiveness of DPP-4 inhibitors was particularly pronounced during shorter follow-up periods, with effects diminishing over time. Regarding secondary outcomes, there was a notable improvement in gamma-glutamyl transpeptidase, with a mean reduction, and in HbA1c levels, indicating improved glycemic control. Homeostatic model assessment for insulin resistance levels also improved, reflecting better insulin sensitivity. Additionally, adverse event analysis confirmed that DPP-4 inhibitors were well-tolerated with a favorable safety profile.</div></div><div><h3>Conclusions</h3><div>DPP-4 inhibitors appear to enhance glycemic control and improve liver enzyme levels, suggesting a potentially effective therapeutic approach for managing T2DM/NAFLD and highlighting their broader metabolic benefits.</div></div>","PeriodicalId":10920,"journal":{"name":"Current Therapeutic Research-clinical and Experimental","volume":"102 ","pages":"Article 100768"},"PeriodicalIF":1.6,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11741081/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143001750","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}