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Search Results (2,683)

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Keywords = therapeutic outcome evaluation

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16 pages, 655 KiB  
Review
Seeing Opportunity in Virtual Reality: A Rapid Review of the Use of VR as a Tool in Vision Care
by Kiana Masoudi, Madeline Wong, Danielle Tchao, Ani Orchanian-Cheff, Michael Reber and Lora Appel
Technologies 2025, 13(8), 342; https://doi.org/10.3390/technologies13080342 - 6 Aug 2025
Abstract
(1) Virtual reality (VR) technologies have shown significant potential for diagnosing and treating vision-related impairments. This rapid review evaluates and characterizes the existing literature on VR technologies for diagnosing and treating vision-based diseases. (2) Methods: A systematic search was conducted across Ovid MEDLINE, [...] Read more.
(1) Virtual reality (VR) technologies have shown significant potential for diagnosing and treating vision-related impairments. This rapid review evaluates and characterizes the existing literature on VR technologies for diagnosing and treating vision-based diseases. (2) Methods: A systematic search was conducted across Ovid MEDLINE, Ovid Embase, the Cochrane Database of Systematic Reviews (Ovid), and the Cochrane Central Register of Controlled Trials (Ovid). Abstracts were screened using Rayyan QCRI, followed by full-text screening and data extraction. Eligible studies were published in peer-reviewed journals, written in English, focused on human participants, used immersive and portable VR devices as the primary intervention, and reported on the clinical effectiveness of VR for therapeutic, diagnostic, or screening purposes for vision or auditory–visual impairments. Various study characteristics, including design and participant details, were extracted, and the MMAT assessment tool was used to evaluate study quality. (3) Results: Seventy-six studies met the inclusion criteria. Among these, sixty-four (84.2%) were non-randomized studies exploring VR’s effectiveness, while twenty-two (15.8%) were randomized-controlled trials. Of the included studies, 38.2% focused on diagnosing, 21.0% on screening, and 38.2% on treating vision impairments. Glaucoma and amblyopia were the most commonly studied visual impairments. (4) Conclusions: The use of standalone, remotely controlled VR headsets for screening and diagnosing visual diseases represents a promising advancement in ophthalmology. With ongoing technological developments, VR has the potential to revolutionize eye care by improving accessibility, efficiency, and personalization. Continued research and innovation in VR applications for vision care are expected to further enhance patient outcomes. Full article
(This article belongs to the Section Assistive Technologies)
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12 pages, 441 KiB  
Article
Cytokine Regulation and Oxidative Stress in Helicobacter Pylori-Associated Gastric Adenocarcinoma at Different Stages: Insights from a Cross-Sectional Study
by Olga Smirnova, Aleksander Sinyakov and Eduard Kasparov
Int. J. Mol. Sci. 2025, 26(15), 7609; https://doi.org/10.3390/ijms26157609 - 6 Aug 2025
Abstract
Gastric adenocarcinoma is a malignant tumor that develops from the glandular cells of the inner wall of the stomach. The prevalence of this type of disease varies from 90 to 95% of all types of gastric cancer. The aim of our study was [...] Read more.
Gastric adenocarcinoma is a malignant tumor that develops from the glandular cells of the inner wall of the stomach. The prevalence of this type of disease varies from 90 to 95% of all types of gastric cancer. The aim of our study was to investigate the differences in the content of cytokines and oxidative stress markers in patients with gastric adenocarcinoma associated with H. pylori infection depending on the stage. The study included 281 patients with gastric cancer. At stage I of the disease—75 people, stage II—70 people, stage III—69 people, and stage IV of the disease—67 people. The levels of TNF-α, IL-2, IL-8, IFNγ, TNF-β, IL-17A, IL-6, IL-10, and IL-4 in the blood serum of patients and healthy individuals were determined by enzyme immunoassay and plasma oxidative stress scores (MDA, SOD, CAT, GST, GPO, CP). The present study revealed that H. pylori-infected gastric adenocarcinoma at different stages is associated with different plasma levels of cytokines, lipid peroxidation products, and antioxidant defense factors. Further studies are needed to evaluate the effectiveness of therapeutic strategies combining cytokine regulation and oxidative stress to improve clinical outcomes in gastric cancer. Full article
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12 pages, 1850 KiB  
Article
Pancreatic Cancer with Liver Oligometastases—Different Patterns of Disease Progression May Suggest Benefits of Surgical Resection
by Nedaa Mahamid, Arielle Jacover, Angam Zabeda, Tamar Beller, Havi Murad, Yoav Elizur, Ron Pery, Rony Eshkenazy, Talia Golan, Ido Nachmany and Niv Pencovich
J. Clin. Med. 2025, 14(15), 5538; https://doi.org/10.3390/jcm14155538 - 6 Aug 2025
Abstract
Background: Pancreatic adenocarcinoma (PDAC) with liver oligometastases (LOM) presents a therapeutic challenge, with optimal management strategies remaining uncertain. This study evaluates the long-term outcomes, patterns of disease progression, and potential factors influencing prognosis in this patient subset. Methods: Patients diagnosed with PDAC and [...] Read more.
Background: Pancreatic adenocarcinoma (PDAC) with liver oligometastases (LOM) presents a therapeutic challenge, with optimal management strategies remaining uncertain. This study evaluates the long-term outcomes, patterns of disease progression, and potential factors influencing prognosis in this patient subset. Methods: Patients diagnosed with PDAC and LOM were retrospectively analyzed. Disease progression patterns, causes of death, and predictors of long-term outcomes were assessed. Results: Among 1442 patients diagnosed with metastatic PDAC between November 2009 and July 2024, 129 (9%) presented with LOM, defined as ≤3 liver lesions each measuring <2 cm. Patients with LOM had significantly improved overall survival (OS) compared to those with high-burden disease (p = 0.026). The cause of death (local regional disease vs. systemic disease) could be determined in 74 patients (57%), among whom age at diagnosis, history of smoking, and white blood cell (WBC) count differed significantly between groups. However, no significant difference in OS was observed between the two groups (p = 0.64). Sixteen patients (22%) died from local complications of the primary tumor, including 6 patients (7%) who showed no evidence of new or progressive metastases. In competing risk and multivariable analysis, a history of smoking remained the only factor significantly associated with death due to local complications. Conclusions: Approximately one in five patients with PDAC-LOM died from local tumor-related complications—some without metastatic progression—highlighting a potential role for surgical intervention. Further multicenter studies are warranted to refine diagnostic criteria and better identify patients who may benefit from surgery. Full article
(This article belongs to the Section General Surgery)
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13 pages, 1625 KiB  
Article
Difficulties of Eating and Masticating Solid Food in Children with Spinal Muscular Atrophy—Preliminary Study
by Ewa Winnicka, Adrianna Łabuz, Zbigniew Kułaga, Tomasz Grochowski and Piotr Socha
Nutrients 2025, 17(15), 2561; https://doi.org/10.3390/nu17152561 - 6 Aug 2025
Abstract
Background: Spinal muscular atrophy (SMA) is a neuromuscular disorder that frequently affects bulbar function, including feeding and swallowing. Although disease-modifying therapies have improved motor outcomes, little is known about the persistence of oromotor difficulties, particularly with regard to solid food intake. Objective: [...] Read more.
Background: Spinal muscular atrophy (SMA) is a neuromuscular disorder that frequently affects bulbar function, including feeding and swallowing. Although disease-modifying therapies have improved motor outcomes, little is known about the persistence of oromotor difficulties, particularly with regard to solid food intake. Objective: This study aimed to evaluate mastication and swallowing performance in children with SMA undergoing treatment, and to investigate the association between tongue strength and feeding efficiency. Methods: Twenty-two children with SMA types 1–3 were assessed using the Test of Masticating and Swallowing Solids in Children (TOMASS-C) and the Iowa Oral Performance Instrument (IOPI). Key TOMASS-C outcomes included the number of bites, chewing cycles, swallows, and total eating time. Tongue strength was measured in kilopascals. Results: Most participants showed deviations from age-specific normative values in at least one TOMASS-C parameter. Tongue strength was significantly lower than reference values in 86% of participants and correlated negatively with all TOMASS-C outcomes (p < 0.001). Children with weaker tongue pressure required more swallows, more chewing cycles, and longer eating times. Conclusions: Despite pharmacological treatment, children with SMA experience persistent difficulties in eating solid foods. Tongue strength may serve as a non-invasive biomarker for bulbar dysfunction and support dietary decision-making and therapeutic planning. Full article
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19 pages, 332 KiB  
Review
Redefining Treatment Paradigms in Thyroid Eye Disease: Current and Future Therapeutic Strategies
by Nicolò Ciarmatori, Flavia Quaranta Leoni and Francesco M. Quaranta Leoni
J. Clin. Med. 2025, 14(15), 5528; https://doi.org/10.3390/jcm14155528 - 6 Aug 2025
Abstract
Background: Thyroid eye disease (TED) is a rare autoimmune orbital disorder predominantly associated with Graves’ disease. It is characterized by orbital inflammation, tissue remodeling, and potential visual morbidity. Conventional therapies, particularly systemic glucocorticoids, offer only partial symptomatic relief, failing to reverse chronic structural [...] Read more.
Background: Thyroid eye disease (TED) is a rare autoimmune orbital disorder predominantly associated with Graves’ disease. It is characterized by orbital inflammation, tissue remodeling, and potential visual morbidity. Conventional therapies, particularly systemic glucocorticoids, offer only partial symptomatic relief, failing to reverse chronic structural changes such as proptosis and diplopia, and are associated with substantial adverse effects. This review aims to synthesize recent developments in understandings of TED pathogenesis and to critically evaluate emerging therapeutic strategies. Methods: A systematic literature review was conducted using MEDLINE, Embase, and international clinical trial registries focusing on pivotal clinical trials and investigational therapies targeting core molecular pathways involved in TED. Results: Current evidence suggests that TED pathogenesis is primarily driven by the autoimmune activation of orbital fibroblasts (OFs) through thyrotropin receptor (TSH-R) and insulin-like growth factor-1 receptor (IGF-1R) signaling. Teprotumumab, a monoclonal IGF-1R inhibitor and the first therapy approved by the U.S. Food and Drug Administration for TED, has demonstrated substantial clinical benefit, including improvements in proptosis, diplopia, and quality of life. However, concerns remain regarding relapse rates and treatment-associated adverse events, particularly hearing impairment. Investigational therapies, including next-generation IGF-1R inhibitors, small-molecule antagonists, TSH-R inhibitors, neonatal Fc receptor (FcRn) blockers, cytokine-targeting agents, and gene-based interventions, are under development. These novel approaches aim to address both inflammatory and fibrotic components of TED. Conclusions: Teprotumumab has changed TED management but sustained control and toxicity reduction remain challenges. Future therapies should focus on targeted, mechanism-based, personalized approaches to improve long-term outcomes and patient quality of life. Full article
(This article belongs to the Section Ophthalmology)
13 pages, 873 KiB  
Article
Impact of Endoscopic Band Ligation on Gastric Complications Associated with Portal Hypertension
by Maria Luisa Gambardella, Giulia Fabiano, Rocco Spagnuolo, Rosanna De Marco, Ileana Luppino, Giusi Franco, Francesco Rettura, Mario Verta, Francesco Luzza and Ludovico Abenavoli
Gastroenterol. Insights 2025, 16(3), 28; https://doi.org/10.3390/gastroent16030028 - 6 Aug 2025
Abstract
Background/Objectives: Clinically significant portal hypertension (CSPH) in cirrhotic patients impacts mortality rates and quality of life. CSPH increases the risk of systemic decompensation and could predispose to the deterioration of portal hypertension (PH)–gastric complications, such as portal hypertensive gastropathy (PHG) and portal hypertensive [...] Read more.
Background/Objectives: Clinically significant portal hypertension (CSPH) in cirrhotic patients impacts mortality rates and quality of life. CSPH increases the risk of systemic decompensation and could predispose to the deterioration of portal hypertension (PH)–gastric complications, such as portal hypertensive gastropathy (PHG) and portal hypertensive polyps (PHPs). In the management of CSPH with high-risk varices, endoscopic band ligation (EBL) is effective in preventing variceal bleeding. However, this procedure has several drawbacks, ranging from its inability to treat PH to the potential development of significant PH–gastric complications. The aim of our study is to evaluate endoscopic changes in PHG, PHPs, and gastric varices before and after the obliteration of esophageal varices, highlighting the potential risks of EBL. Methods: We retrospectively evaluated forty-four patients who underwent EBL for esophageal varices in emergency and elective settings, according to Baveno VII guidelines. We assessed the presence and severity of PHG, the status of gastric varices, and the number of PHPs before and after the eradication of esophageal varices. We used Fisher’s exact test and t-tests to compare the endoscopic and clinical-laboratory data statistically. A p-value < 0.05 was considered statistically significant. Results: This study found that after the eradication of varices, there was a significant worsening of PHG in 28 patients (63%) compared to before the procedure (p < 0.05). The condition remained stable in 14 patients (31%). However, it is worth noting that 90% of the patients exhibited severe PHG at baseline. Additionally, the absence of ascites and the non-administration of beta blockers at baseline were independent risk factors for worsening PHG (p < 0.05). Along with the deterioration of PHG, three patients (7%) developed gastric varices, all classified as type 1 gastroesophageal varices, and in two patients (4.5%), PHPs were formed. In particular, out of these two cases, the number of PHPs increased from one to two compared to the baseline. Conclusions: Our study underscores the association of EBL with a general worsening of PH–gastric complications and the protective effect of beta blockers in this context. Despite these promising results, future studies are needed to assess whether the worsening of PH–gastric complications is sustained over time and whether it is associated with a deterioration in clinical outcomes in patients with cirrhosis. Such evidence could help guide a more informed therapeutic decision between EBL and beta blockers. Full article
(This article belongs to the Special Issue Advances in the Management of Gastrointestinal and Liver Diseases)
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20 pages, 1677 KiB  
Review
Applications of Nanoparticles in the Diagnosis and Treatment of Ovarian Cancer
by Ahmed El-Mallul, Ryszard Tomasiuk, Tadeusz Pieńkowski, Małgorzata Kowalska, Dilawar Hasan, Marcin Kostrzewa, Dominik Czerwonka, Aleksandra Sado, Wiktoria Rogowska, Igor Z. Zubrzycki and Magdalena Wiacek
Nanomaterials 2025, 15(15), 1200; https://doi.org/10.3390/nano15151200 - 6 Aug 2025
Abstract
Nanotechnology offers innovative methodologies for enhancing the diagnosis and treatment of ovarian cancer by utilizing specialized nanoparticles. The utilization of nanoparticles offers distinct advantages, specifically that these entities enhance the bioavailability of therapeutic agents and facilitate the targeted delivery of pharmacological agents to [...] Read more.
Nanotechnology offers innovative methodologies for enhancing the diagnosis and treatment of ovarian cancer by utilizing specialized nanoparticles. The utilization of nanoparticles offers distinct advantages, specifically that these entities enhance the bioavailability of therapeutic agents and facilitate the targeted delivery of pharmacological agents to neoplastic cells. A diverse array of nanoparticles, including but not limited to liposomes, dendrimers, and gold nanoparticles, function as proficient carriers for drug delivery. Nevertheless, notwithstanding the auspicious potential of these applications, challenges pertaining to toxicity, biocompatibility, and the necessity for comprehensive clinical evaluations pose considerable barriers to the widespread implementation of these technologies. The incorporation of nanotechnology into clinical practice holds the promise of significantly transforming the management of ovarian cancer, offering novel diagnostic tools and therapeutic strategies that enhance patient outcomes and prognoses. In summary, the deployment of nanotechnology in the context of ovarian cancer epitomizes a revolutionary paradigm in medical science, amalgamating sophisticated materials and methodologies to enhance both diagnostic and therapeutic outcomes. Continued research and development endeavors are essential to fully realize the extensive potential of these innovative solutions and address the existing challenges associated with their application in clinical settings. Full article
(This article belongs to the Section Biology and Medicines)
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18 pages, 978 KiB  
Review
NUDT15 Pharmacogenetics in Acute Lymphoblastic Leukemia: Synthesizing Progress for Personalized Thiopurine Therapy
by Isfahan Shah Lubis, Kusnandar Anggadiredja, Aluicia Anita Artarini, Nur Melani Sari, Nur Suryawan and Zulfan Zazuli
Med. Sci. 2025, 13(3), 112; https://doi.org/10.3390/medsci13030112 - 5 Aug 2025
Abstract
The management of acute lymphoblastic leukemia (ALL), the most common pediatric malignancy, critically relies on thiopurine therapy, such as 6-mercaptopurine (6-MP), during the maintenance phase. However, significant inter-individual response variety and high risk of myelosuppression often disrupt therapy efficacy. Pharmacogenetics offer crucial strategies [...] Read more.
The management of acute lymphoblastic leukemia (ALL), the most common pediatric malignancy, critically relies on thiopurine therapy, such as 6-mercaptopurine (6-MP), during the maintenance phase. However, significant inter-individual response variety and high risk of myelosuppression often disrupt therapy efficacy. Pharmacogenetics offer crucial strategies to personalized therapy. While thiopurine methyltransferase (TPMT) was initially the primary focus, the discovery of nudix hydrolase 15 (NUDT15) appears as a more comprehensive determinant of thiopurine intolerance. This review aims to consolidate and critically evaluate the advancement achieved in unraveling the biological mechanism and clinical significance of NUDT15 pharmacogenetics in thiopurine therapy. Foundational studies showed the vital role of NUDT15 in the detoxification of active thiopurines, with common genetic variants (for instance, p. Arg139Cys) significantly disrupting its activity, leading to the accumulation of toxic metabolites. Observational studies consistently associated NUDT15 variants with severe myelosuppression, notably in Asian populations. Recent randomized controlled trials (RCTs) confirmed that NUDT15 genotype-guided dosing effectively reduces thiopurine-induced toxicity without interfering with the therapeutic outcome. Despite these advancements, challenges remain present, including the incomplete characterization of rare variants, limited data in the diverse Asian populations, and the need for standardized integration with metabolite monitoring. In conclusion, NUDT15 pharmacogenetics is essential for improving patient safety and thiopurine dosage optimization in the treatment of ALL. For thiopurine tailored medicine to be widely and fairly implemented, future research should focus on increasing genetic data across different populations, improving the dose adjustment algorithm, and harmonizing therapeutic guidelines. Full article
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16 pages, 1701 KiB  
Article
Aromatase Inhibitor-Induced Carpal Tunnel Syndrome Immunohistochemical Analysis and Clinical Evaluation: An Observational, Cross-Sectional, Case–Control Study
by Iakov Molayem, Lucian Lior Marcovici, Roberto Gradini, Massimiliano Mancini, Silvia Taccogna and Alessia Pagnotta
J. Clin. Med. 2025, 14(15), 5513; https://doi.org/10.3390/jcm14155513 - 5 Aug 2025
Abstract
Background/Objectives: Breast cancer was the leading cause of malignant tumors among women in 2022. About two-thirds of breast cancer cases are hormone-receptor-positive. In these patients, aromatase inhibitors are a mainstay of treatment, but associated musculoskeletal symptoms can negatively affect patient compliance. Aromatase-inhibitor-induced [...] Read more.
Background/Objectives: Breast cancer was the leading cause of malignant tumors among women in 2022. About two-thirds of breast cancer cases are hormone-receptor-positive. In these patients, aromatase inhibitors are a mainstay of treatment, but associated musculoskeletal symptoms can negatively affect patient compliance. Aromatase-inhibitor-induced carpal tunnel syndrome represents one of the main causes of aromatase inhibitor discontinuation, with a non-compliance rate of up to 67%, potentially leading to increased cancer mortality. This study investigates estrogen receptor expression in aromatase-inhibitor-induced carpal tunnel syndrome tissues, in order to better define its etiopathogenesis and derive preventive or therapeutic measures that can improve aromatase inhibitor patient compliance. To our knowledge, there is no study on this subject in the literature. Methods: Between 2023 and 2024, we recruited 14 patients at the Jewish Hospital of Rome, including seven patients with aromatase-inhibitor-induced carpal tunnel syndrome (study group) and seven with postmenopausal idiopathic carpal tunnel syndrome (control group). Each patient was evaluated based on a clinical visit, a questionnaire, instrumental exams, and serum hormone dosages and were treated with open carpal tunnel release surgery, during which transverse carpal ligament and flexor tenosynovium samples were collected. For immunohistochemical experiments, sections were treated with anti-estrogen receptor α and anti-estrogen receptor β antibodies. Results: The immunohistochemical features in the study and control groups were similar, demonstrating that tissues affected by aromatase-inhibitor-induced carpal tunnel syndrome are targets of direct estrogen action and that estrogen deprivation is correlated with disease etiogenesis. Surgery was effective in patient treatment. Conclusions: Aromatase-inhibitor-induced carpal tunnel syndrome represents a newly defined form of the disease. This syndrome represents one of the main causes of aromatase inhibitor discontinuation, due to its negative impact on the patient’s quality of life. The identification by clinicians of aromatase inhibitor use as a possible risk factor for carpal tunnel syndrome development is of essential importance, as early diagnosis and prompt management can improve patient compliance and overall breast cancer treatment outcomes. Full article
(This article belongs to the Section General Surgery)
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30 pages, 3316 KiB  
Systematic Review
Preclinical Evidence of Curcuma longa Linn. as a Functional Food in the Management of Metabolic Syndrome: A Systematic Review and Meta-Analysis of Rodent Studies
by Samuel Abiodun Kehinde, Zahid Naeem Qaisrani, Rinrada Pattanayaiying, Wai Phyo Lin, Bo Bo Lay, Khin Yadanar Phyo, Myat Mon San, Nurulhusna Awaeloh, Sasithon Aunsorn, Ran Kitkangplu and Sasitorn Chusri
Biomedicines 2025, 13(8), 1911; https://doi.org/10.3390/biomedicines13081911 - 5 Aug 2025
Abstract
Background/Objectives: Metabolic syndrome (MetS) is a multifactorial condition characterized by abdominal obesity, dyslipidemia, insulin resistance, hypertension, and chronic inflammation. As its global prevalence rises, there is increasing interest in natural, multi-targeted approaches to manage MetS. Curcuma longa Linn. (turmeric), especially its active [...] Read more.
Background/Objectives: Metabolic syndrome (MetS) is a multifactorial condition characterized by abdominal obesity, dyslipidemia, insulin resistance, hypertension, and chronic inflammation. As its global prevalence rises, there is increasing interest in natural, multi-targeted approaches to manage MetS. Curcuma longa Linn. (turmeric), especially its active compound curcumin, has shown therapeutic promise in preclinical studies. This systematic review and meta-analysis evaluated the effects of Curcuma longa and its derivatives on MetS-related outcomes in rodent models. Methods: A comprehensive search was conducted across six databases (PubMed, Scopus, AMED, LILACS, MDPI, and Google Scholar), yielding 47 eligible in vivo studies. Data were extracted on key metabolic, inflammatory, and oxidative stress markers and analyzed using random-effects models. Results were presented as mean differences (MD) with 95% confidence intervals (CI). Results: Meta-analysis showed that curcumin significantly reduced body weight (rats: MD = −42.10; mice: MD = −2.91), blood glucose (rats: MD = −55.59; mice: MD = −28.69), triglycerides (rats: MD = −70.17; mice: MD = −24.57), total cholesterol (rats: MD = −35.77; mice: MD = −52.61), and LDL cholesterol (rats: MD = −69.34; mice: MD = −42.93). HDL cholesterol increased significantly in rats but not in mice. Inflammatory cytokines were markedly reduced, while oxidative stress improved via decreased malondialdehyde (MDA) and elevated superoxide dismutase (SOD) and catalase (CAT) levels. Heterogeneity was moderate to high, primarily due to variations in curcumin dosage (ranging from 10 to 500 mg/kg) and treatment duration (2 to 16 weeks) across studies. Conclusions: This preclinical evidence supports Curcuma longa as a promising functional food component for preventing and managing MetS. Its multi-faceted effects warrant further clinical studies to validate its translational potential. Full article
(This article belongs to the Special Issue The Role of Cytokines in Health and Disease: 3rd Edition)
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22 pages, 2630 KiB  
Review
Transfection Technologies for Next-Generation Therapies
by Dinesh Simkhada, Su Hui Catherine Teo, Nandu Deorkar and Mohan C. Vemuri
J. Clin. Med. 2025, 14(15), 5515; https://doi.org/10.3390/jcm14155515 - 5 Aug 2025
Abstract
Background: Transfection is vital for gene therapy, mRNA treatments, CAR-T cell therapy, and regenerative medicine. While viral vectors are effective, non-viral systems like lipid nanoparticles (LNPs) offer safer, more flexible alternatives. This work explores emerging non-viral transfection technologies to improve delivery efficiency [...] Read more.
Background: Transfection is vital for gene therapy, mRNA treatments, CAR-T cell therapy, and regenerative medicine. While viral vectors are effective, non-viral systems like lipid nanoparticles (LNPs) offer safer, more flexible alternatives. This work explores emerging non-viral transfection technologies to improve delivery efficiency and therapeutic outcomes. Methods: This review synthesizes the current literature and recent advancements in non-viral transfection technologies. It focuses on the mechanisms, advantages, and limitations of various delivery systems, including lipid nanoparticles, biodegradable polymers, electroporation, peptide-based carriers, and microfluidic platforms. Comparative analysis was conducted to evaluate their performance in terms of transfection efficiency, cellular uptake, biocompatibility, and potential for clinical translation. Several academic search engines and online resources were utilized for data collection, including Science Direct, PubMed, Google Scholar Scopus, the National Cancer Institute’s online portal, and other reputable online databases. Results: Non-viral systems demonstrated superior performance in delivering mRNA, siRNA, and antisense oligonucleotides, particularly in clinical applications. Biodegradable polymers and peptide-based systems showed promise in enhancing biocompatibility and targeted delivery. Electroporation and microfluidic systems offered precise control over transfection parameters, improving reproducibility and scalability. Collectively, these innovations address key challenges in gene delivery, such as stability, immune response, and cell-type specificity. Conclusions: The continuous evolution of transfection technologies is pivotal for advancing gene and cell-based therapies. Non-viral delivery systems, particularly LNPs and emerging platforms like microfluidics and biodegradable polymers, offer safer and more adaptable alternatives to viral vectors. These innovations are critical for optimizing therapeutic efficacy and enabling personalized medicine, immunotherapy, and regenerative treatments. Future research should focus on integrating these technologies to develop next-generation transfection platforms with enhanced precision and clinical applicability. Full article
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19 pages, 286 KiB  
Review
Does the Anatomical Type of the Plantaris Tendon Influence the Management of Midportion Achilles Tendinopathy?
by Łukasz Olewnik, Ingrid C. Landfald, Bartosz Gonera, Łukasz Gołek, Aleksandra Szabert-Kajkowska, Andrzej Borowski, Marek Drobniewski, Teresa Vázquez and Kacper Ruzik
J. Clin. Med. 2025, 14(15), 5478; https://doi.org/10.3390/jcm14155478 - 4 Aug 2025
Abstract
Background: Midportion Achilles tendinopathy (Mid-AT) is a complex condition that may be exacerbated by anatomical variations of the plantaris tendon. Recent anatomical studies, particularly the classification proposed by Olewnik et al., have enhanced the understanding of plantaris–Achilles interactions and their clinical implications. Objective: [...] Read more.
Background: Midportion Achilles tendinopathy (Mid-AT) is a complex condition that may be exacerbated by anatomical variations of the plantaris tendon. Recent anatomical studies, particularly the classification proposed by Olewnik et al., have enhanced the understanding of plantaris–Achilles interactions and their clinical implications. Objective: This review aims to assess the anatomical types of the plantaris tendon, their imaging correlates, and the impact of the Olewnik classification on diagnosis, treatment planning, and surgical outcomes in patients with Mid-AT. Methods: We present an evidence-based analysis of the six anatomical types of the plantaris tendon and their relevance to Achilles tendinopathy, with emphasis on MRI and ultrasound (USG) evaluation. A diagnostic and therapeutic algorithm is proposed, and clinical outcomes of both conservative and operative management are compared across tendon types. Results: Types I and V were most strongly associated with symptomatic conflict and showed the highest benefit from surgical resection. Endoscopic approaches were effective in Types II and III, while Type IV typically responded to conservative treatment. Type VI, often misdiagnosed as tarsal tunnel syndrome, required combined neurolysis. The classification significantly improves surgical decision-making, reduces overtreatment, and enhances diagnostic precision. Conclusions: The Olewnik classification provides a reproducible, clinically relevant framework for individualized management of Mid-AT. Its integration into imaging protocols and treatment algorithms may improve therapeutic outcomes and guide future research in orthopaedic tendon pathology. Full article
(This article belongs to the Section Orthopedics)
17 pages, 1812 KiB  
Article
Systemic Metabolic Alterations Induced by Etodolac in Healthy Individuals
by Rajaa Sebaa, Reem H. AlMalki, Hatouf Sukkarieh, Lina A. Dahabiyeh, Maha Al Mogren, Tawfiq Arafat, Ahmed H. Mujamammi, Essa M. Sabi and Anas M. Abdel Rahman
Pharmaceuticals 2025, 18(8), 1155; https://doi.org/10.3390/ph18081155 - 4 Aug 2025
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Abstract
Background/Objective: Pharmacological interventions often exert systemic effects beyond their primary targets, underscoring the need for a comprehensive evaluation of their metabolic impact. Etodolac is a nonsteroidal anti-inflammatory drug (NSAID) that alleviates pain, fever, and inflammation by inhibiting cyclooxygenase-2 (COX-2), thereby reducing prostaglandin synthesis. [...] Read more.
Background/Objective: Pharmacological interventions often exert systemic effects beyond their primary targets, underscoring the need for a comprehensive evaluation of their metabolic impact. Etodolac is a nonsteroidal anti-inflammatory drug (NSAID) that alleviates pain, fever, and inflammation by inhibiting cyclooxygenase-2 (COX-2), thereby reducing prostaglandin synthesis. While its pharmacological effects are well known, the broader metabolic impact and potential mechanisms underlying improved clinical outcomes remain underexplored. Untargeted metabolomics, which profiles the metabolome without prior selection, is an emerging tool in clinical pharmacology for elucidating drug-induced metabolic changes. In this study, untargeted metabolomics was applied to investigate metabolic changes following a single oral dose of etodolac in healthy male volunteers. By analyzing serial blood samples over time, we identified endogenous metabolites whose concentrations were positively or inversely associated with the drug’s plasma levels. This approach provides a window into both therapeutic pathways and potential off-target effects, offering a promising strategy for early-stage drug evaluation and multi-target discovery using minimal human exposure. Methods: Thirty healthy participants received a 400 mg dose of Etodolac. Plasma samples were collected at five time points: pre-dose, before Cmax, at Cmax, after Cmax, and 36 h post-dose (n = 150). Samples underwent LC/MS-based untargeted metabolomics profiling and pharmacokinetic analysis. A total of 997 metabolites were significantly dysregulated between the pre-dose and Cmax time points, with 875 upregulated and 122 downregulated. Among these, 80 human endogenous metabolites were identified as being influenced by Etodolac. Results: A total of 17 metabolites exhibited time-dependent changes closely aligned with Etodolac’s pharmacokinetic profile, while 27 displayed inverse trends. Conclusions: Etodolac influences various metabolic pathways, including arachidonic acid metabolism, sphingolipid metabolism, and the biosynthesis of unsaturated fatty acids. These selective metabolic alterations complement its COX-2 inhibition and may contribute to its anti-inflammatory effects. This study provides new insights into Etodolac’s metabolic impact under healthy conditions and may inform future therapeutic strategies targeting inflammation. Full article
(This article belongs to the Special Issue Advances in Drug Analysis and Drug Development, 2nd Edition)
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16 pages, 1690 KiB  
Article
Effect of Photobiomodulation on Post-Endodontic Pain Following Single-Visit Treatment: A Randomized Double-Blind Clinical Trial
by Glaucia Gonçales Abud Machado, Giovanna Fontgalland Ferreira, Erika da Silva Mello, Ellen Sayuri Ando-Suguimoto, Vinicius Leão Roncolato, Marcia Regina Cabral Oliveira, Janainy Altrão Tognini, Adriana Fernandes Paisano, Cleber Pinto Camacho, Sandra Kalil Bussadori, Lara Jansiski Motta, Cinthya Cosme Gutierrez Duran, Raquel Agnelli Mesquita-Ferrari, Kristianne Porta Santos Fernandes and Anna Carolina Ratto Tempestini Horliana
J. Pers. Med. 2025, 15(8), 347; https://doi.org/10.3390/jpm15080347 - 2 Aug 2025
Viewed by 145
Abstract
The evidence for photobiomodulation in reducing postoperative pain after endodontic instrumentation is classified as low or very low certainty, indicating a need for further research. Longitudinal pain assessments over 24 h are crucial, and studies should explore these pain periods. Background/Objectives: This [...] Read more.
The evidence for photobiomodulation in reducing postoperative pain after endodontic instrumentation is classified as low or very low certainty, indicating a need for further research. Longitudinal pain assessments over 24 h are crucial, and studies should explore these pain periods. Background/Objectives: This double-blind, randomized controlled clinical trial evaluated the effect of PBM on pain following single-visit endodontic treatment of maxillary molars at 4, 8, 12, and 24 h. Primary outcomes included pain at 24 h; secondary outcomes included pain at 4, 8, and 12 h, pain during palpation/percussion, OHIP-14 analysis, and frequencies of pain. Methods: Approved by the Research Ethics Committee (5.598.290) and registered in Clinical Trials (NCT06253767), the study recruited adults (21–70 years) requiring endodontic treatment in maxillary molars. Fifty-eight molars were randomly assigned to two groups: the PBM Group (n = 29), receiving conventional endodontic treatment with PBM (100 mW, 333 mW/cm2, 9 J distributed at 3 points near root apices), and the control group (n = 29), receiving conventional treatment with PBM simulation. Pain was assessed using the Visual Analog Scale. Results: Statistical analyses used chi-square and Mann–Whitney tests, with explained variance (η2). Ten participants were excluded, leaving 48 patients for analysis. No significant differences were observed in postoperative pain at 24, 4, 8, or 12 h, or in palpation/percussion or OHIP-14 scores. Pain frequencies ranged from 12.5% to 25%. Conclusions: PBM does not influence post-treatment pain in maxillary molars under these conditions. These results emphasize the importance of relying on well-designed clinical trials to guide treatment decisions, and future research should focus on personalized dosimetry adapted to the anatomical characteristics of the treated dental region to enhance the accuracy and efficacy of therapeutic protocols. Full article
(This article belongs to the Special Issue Towards Precision Anesthesia and Pain Management)
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Article
Exploring the Implementation of Gamification as a Treatment Modality for Adults with Depression in Malaysia
by Muhammad Akmal bin Zakaria, Koh Ong Hui, Hema Subramaniam, Maziah Binti Mat Rosly, Jesjeet Singh Gill, Lim Yee En, Yong Zhi Sheng, Julian Wong Joon Ip, Hemavathi Shanmugam, Chow Soon Ken and Benedict Francis
Medicina 2025, 61(8), 1404; https://doi.org/10.3390/medicina61081404 - 1 Aug 2025
Viewed by 162
Abstract
Background and Objectives: Depression is a leading cause of disability globally, with treatment challenges including limited access, stigma, and poor adherence. Gamification, which applies game elements such as points, levels, and storytelling into non-game contexts, offers a promising strategy to enhance engagement [...] Read more.
Background and Objectives: Depression is a leading cause of disability globally, with treatment challenges including limited access, stigma, and poor adherence. Gamification, which applies game elements such as points, levels, and storytelling into non-game contexts, offers a promising strategy to enhance engagement and augment traditional treatments. Our research is the first study designed to explore the implementation of gamification within the Malaysian context. The objective was to explore the feasibility of implementation of gamification as an adjunctive treatment for adults with depression. Materials and Methods: Focus group discussions were held with five mental health professionals and ten patients diagnosed with moderate depression. The qualitative component assessed perceptions of gamified interventions, while quantitative measures evaluated participants’ depressive and anxiety symptomatology. Results: Three key themes were identified: (1) understanding of gamification as a treatment option, (2) factors influencing its acceptance, and (3) characteristics of a practical and feasible intervention. Clinicians saw potential in gamification to boost motivation, support psychoeducation, and encourage self-paced learning, but they expressed concerns about possible addiction, stigma, and the complexity of gameplay for some patients. Patients spoke of gaming as a source of comfort, escapism, and social connection. Acceptance was shaped by engaging storylines, intuitive design, balanced difficulty, therapist guidance, and clear safety measures. Both groups agreed that gamification should be used in conjunction with standard treatments, be culturally sensitive, and be presented as a meaningful therapeutic approach rather than merely as entertainment. Conclusions: Gamification emerges as an acceptable and feasible supplementary approach for managing depression in Malaysia. Its success depends on culturally sensitive design, robust clinical oversight, and seamless integration with existing care pathways. Future studies should investigate long-term outcomes and establish guidelines for the safe and effective implementation of this approach. We recommend targeted investment into culturally adapted gamified tools, including training, policy development, and collaboration with key stakeholders to realistically implement gamification as a mental health intervention in Malaysia. Full article
(This article belongs to the Section Psychiatry)
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