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17 pages, 4768 KiB  
Article
New Functional Food for the Treatment of Gastric Ulcer Based on Bioadhesive Microparticles Containing Sage Extract: Anti-Ulcerogenic, Anti-Helicobacter pylori, and H+/K+-ATPase-Inhibiting Activity Enhancement
by Yacine Nait Bachir, Ryma Nait Bachir, Meriem Medjkane, Nouara Boudjema and Roberta Foligni
Foods 2025, 14(15), 2757; https://doi.org/10.3390/foods14152757 (registering DOI) - 7 Aug 2025
Abstract
Salvia officinalis is an aromatic plant of Mediterranean origin traditionally used to treat inflammatory, cardiovascular, endocrine, and digestive diseases. In this work, the ability of the Salvia officinalis extract in the treatment of gastric ulcers was evaluated, and an innovative administration system was [...] Read more.
Salvia officinalis is an aromatic plant of Mediterranean origin traditionally used to treat inflammatory, cardiovascular, endocrine, and digestive diseases. In this work, the ability of the Salvia officinalis extract in the treatment of gastric ulcers was evaluated, and an innovative administration system was proposed to increase the therapeutic effect of this plant. Salvia officinalis ethanolic extract was prepared and analyzed by HPLC/UV-DAD and encapsulated in a matrix based on gelatin and pectin using an emulsion–coacervation process. The prepared microcapsules were analyzed by laser particle size, optical microscopy, in vitro dissolution kinetics, and ex vivo bioadhesion. In order to determine the action mechanism of Salvia officinalis extract, in the treatment of gastric ulcer, the in vivo anti-ulcerogenic activity in rats, using the ulcer model induced by ethanol; the in vivo anti-Helicobacter pylori activity; and in vitro inhibitory activity of H+/K+-ATPase were carried out. These three biological activities were evaluated for ethanolic extract and microcapsules to determine the effect of formulation on biological activities. Ethanolic extract of Salvia officinalis was mainly composed of polyphenols (chlorogenic acid 7.43%, rutin 21.74%, rosmarinic acid 5.88%, and quercitrin 14.39%). Microencapsulation of this extract allowed us to obtain microcapsules of 104.2 ± 7.5 µm in diameter, an encapsulation rate of 96.57 ± 3.05%, and adequate bioadhesion. The kinetics of in vitro dissolution of the extract increase significantly after its microencapsulation. Percentages of ulcer inhibition for 100 mg/kg of extract increase from 71.71 ± 2.43% to 89.67 ± 2.54% after microencapsulation. In vitro H+/K+-ATPase-inhibiting activity resulted in an IC50 of 86.08 ± 8.69 µM/h/mg protein for free extract and 57.43 ± 5.78 µM/h/mg protein for encapsulated extract. Anti-Helicobacter pylori activity showed a similar Minimum Inhibitory Concentration (MIC) of 50 µg/mL for the extract and microcapsules. Salvia officinalis ethanolic extract has a significant efficacy for the treatment of gastric ulcer; its mechanism of action is based on its gastroprotective effect, anti-Helicobacter pylori, and H+/K+-ATPase inhibitor. Moreover, the microencapsulation of this extract increases its gastroprotective and H+/K+-ATPase-inhibiting activities significantly. Full article
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19 pages, 684 KiB  
Article
Does the Timing of Response Impact the Outcome of Relapsed/Refractory Acute Myeloid Leukemia Treated with Venetoclax in Combination with Hypomethylating Agents? A Proof of Concept from a Monocentric Observational Study
by Ermelinda Longo, Fanny Erika Palumbo, Andrea Duminuco, Laura Longo, Daniela Cristina Vitale, Serena Brancati, Cinzia Maugeri, Marina Silvia Parisi, Giuseppe Alberto Palumbo, Giovanni Luca Romano, Filippo Drago, Francesco Di Raimondo, Lucia Gozzo and Calogero Vetro
J. Clin. Med. 2025, 14(15), 5586; https://doi.org/10.3390/jcm14155586 (registering DOI) - 7 Aug 2025
Abstract
Background: Relapsed/refractory acute myeloid leukemia (R/R AML) remains a therapeutic challenge due to disease heterogeneity, resistance mechanisms, and poor tolerability to intensive regimens. Venetoclax (VEN), a BCL-2 inhibitor, has shown promise in combination with hypomethylating agents (HMAs), but data on response timing [...] Read more.
Background: Relapsed/refractory acute myeloid leukemia (R/R AML) remains a therapeutic challenge due to disease heterogeneity, resistance mechanisms, and poor tolerability to intensive regimens. Venetoclax (VEN), a BCL-2 inhibitor, has shown promise in combination with hypomethylating agents (HMAs), but data on response timing in the R/R setting are limited. The aim of this study was to assess the efficacy, safety, and kinetics of response to HMA-VEN therapy in a real-world cohort of R/R AML patients, with particular focus on early versus late responders. Methods: This prospective single-center study included 33 adult patients with R/R AML treated with VEN plus either azacitidine (AZA) or decitabine (DEC) from 2018 to 2021. The primary endpoint was the composite complete remission (cCR) rate and the rate of early and late response, respectively, occurring within two cycles of therapy or later; secondary endpoints included overall survival (OS), relapse-free survival (RFS), time to relapse (TTR), and safety. Results: The cCR was 58%, with complete remission (CR) or CR with incomplete recovery (CRi) achieved in 52% of patients. Median OS was 9 months. No significant differences in OS or TTR were observed between early (≤2 cycles) and late (>2 cycles) responders. Eight responders (42%) underwent allogeneic hematopoietic stem cell transplantation (HSCT), with comparable transplant rates in both groups of responders. Toxicity was manageable. Grade 3–4 neutropenia occurred in all patients, and febrile neutropenia occurred in 44% of patients. An Eastern Cooperative Oncology Group (ECOG) score >2 was associated with inferior response and shorter treatment duration. Conclusions: HMA-VEN therapy is effective and safe in R/R AML, including for patients with delayed responses. The absence of a prognostic disadvantage for late responders supports flexible treatment schedules and suggests that the continuation of therapy may be beneficial even without early blast clearance. Tailored approaches based on performance status and comorbidities are warranted, and future studies should incorporate minimal residual disease (MRD)-based monitoring to refine response assessment. Full article
(This article belongs to the Section Hematology)
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20 pages, 4142 KiB  
Article
Repeated Administration of Guar Gum Hydrogel Containing Sesamol-Loaded Nanocapsules Reduced Skin Inflammation in Mice in an Irritant Contact Dermatitis Model
by Vinicius Costa Prado, Bruna Rafaela Fretag de Carvalho, Kauani Moenke, Amanda Maccangnan Zamberlan, Samuel Felipe Atuati, Ana Clara Perazzio Assis, Evelyne da Silva Brum, Raul Edison Luna Lazo, Andréa Inês Horn Adams, Luana Mota Ferreira, Sara Marchesan Oliveira and Letícia Cruz
Pharmaceutics 2025, 17(8), 1029; https://doi.org/10.3390/pharmaceutics17081029 (registering DOI) - 7 Aug 2025
Abstract
Background/Objectives: Dermatitis is frequently treated with dexamethasone cutaneous application, which causes adverse effects mainly when it is chronically administered. Sesamol is a phytochemical compound known for its anti-inflammatory activity and low toxicity. Therefore, this study reports the optimization of a guar gum [...] Read more.
Background/Objectives: Dermatitis is frequently treated with dexamethasone cutaneous application, which causes adverse effects mainly when it is chronically administered. Sesamol is a phytochemical compound known for its anti-inflammatory activity and low toxicity. Therefore, this study reports the optimization of a guar gum hydrogel with enhanced physicochemical and microbiological stability, providing an effective dosage form for topical application of sesamol nanocapsules to treat irritant contact dermatitis. Methods: Nano-based hydrogel containing 1 mg/g sesamol was prepared by adding the nanocapsule suspension to form a 2.5% (w/v) guar gum dispersion. Dynamic rheological analysis indicates that the formulations exhibit a non-Newtonian flow with pseudoplastic behavior. Hydrogels were evaluated by Fourier-transformed infrared (FTIR) spectroscopy, and, following spectrum acquisition, an unsupervised chemometrics model was developed to identify crucial variables. Additionally, the physicochemical and microbiological stability of the hydrogel was evaluated over a 60-day period. Results: ATR-FTIR spectra of all hydrogels evaluated are very similar after preparation and 60 days of storage. However, it showed a slight increase in average diameter and PDI and decreased pH values after 60 days. Microbiological assessment demonstrated that the hydrogel met the requirements for the microbial count over 60 days. The dermatitis model was induced by repeated applications of croton oil in the right ears of mice. The effectiveness of the hydrogels was evaluated by assessing ear edema and migration of polymorphonuclear cells. The nano-based hydrogel exhibited anti-inflammatory properties similar to those of dexamethasone. Conclusions: Therefore, the nano-based hydrogel containing sesamol exhibits therapeutic potential for treating cutaneous inflammatory diseases. Full article
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13 pages, 1971 KiB  
Article
Clinical Outcomes of Iron Supplement Therapy in Non-Anemic Female CKD Stage 3 Patients with Low Serum Ferritin Level: A Multi-Institutional TriNetX Analysis
by Hsi-Chih Chen, Min-Tser Liao, Joshua Wang, Kuo-Wang Tsai, Chia-Chao Wu and Kuo-Cheng Lu
J. Clin. Med. 2025, 14(15), 5575; https://doi.org/10.3390/jcm14155575 - 7 Aug 2025
Abstract
Background/Objectives: Iron deficiency without anemia (IDWA) is common among female patients with chronic kidney disease (CKD), yet the clinical implications of iron therapy in this population remain uncertain. While iron supplementation is frequently used in anemic CKD patients, evidence regarding its outcomes [...] Read more.
Background/Objectives: Iron deficiency without anemia (IDWA) is common among female patients with chronic kidney disease (CKD), yet the clinical implications of iron therapy in this population remain uncertain. While iron supplementation is frequently used in anemic CKD patients, evidence regarding its outcomes in non-anemic, iron-deficient individuals is limited and conflicting. Methods: This retrospective cohort study utilized the multi-institutional TriNetX database to examine the 5-year outcomes of iron therapy in adult women with stage 3 CKD, normal hemoglobin (≥12 g/dL), normal mean corpuscular volume (MCV), and low serum ferritin (<100 ng/mL). Primary outcomes included all-cause mortality, major adverse cardiovascular events (MACE), acute kidney injury (AKI), pneumonia, progression to advanced CKD (estimated glomerular filtration rate ≤30 mL/min/1.73 m2), and gastrointestinal (GI) bleeding. Results: We identified 53,769 eligible non-anemic patients with stage 3 CKD, low serum ferritin levels, and normal MCV. Propensity score matching (1:1) was conducted on demographic variables to compare iron-treated (n = 6638) and untreated (n = 6638) cohorts. Over the 5-year follow-up, iron therapy in non-anemic females with stage 3 CKD, low ferritin levels, and iron supplementation was significantly associated with increased risks of MACE, AKI, pneumonia, CKD progression, and GI bleeding (log-rank p < 0.0001). No significant difference in all-cause mortality was observed. Data on transferrin saturation and the dosage of iron supplementation were unavailable. Conclusions: In non-anemic women with stage 3 CKD and low ferritin levels, iron supplementation was linked to increased MACE, renal, and pneumonia risks without evident survival benefits. These findings suggest that iron therapy in this group of patients may not confer cardiovascular benefit and may pose risks. Full article
(This article belongs to the Section Nephrology & Urology)
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13 pages, 249 KiB  
Review
A Review of the Current Clinical Aspects of Sjögren’s Disease: Geographical Difference, Classification/Diagnostic Criteria, Recent Advancements in Diagnostic Methods, and Molecular Targeted Therapy
by Yoshiro Horai, Shota Kurushima, Toshimasa Shimizu, Hideki Nakamura and Atsushi Kawakami
J. Clin. Med. 2025, 14(15), 5577; https://doi.org/10.3390/jcm14155577 - 7 Aug 2025
Abstract
Sjögren’s Disease (SjD) is an autoimmune disorder characterized by sicca symptoms arising from impaired salivary and lacrimal gland function and accompanying extraglandular involvement. SjD is recognized as an illness of female dominance for which the 2002 American–European Consensus Group Classification Criteria and the [...] Read more.
Sjögren’s Disease (SjD) is an autoimmune disorder characterized by sicca symptoms arising from impaired salivary and lacrimal gland function and accompanying extraglandular involvement. SjD is recognized as an illness of female dominance for which the 2002 American–European Consensus Group Classification Criteria and the American College of Rheumatology/European Alliance of Associations for Rheumatology 2016 classification criteria are utilized for inclusion in clinical trials, and treatment recommendations from countries belonging to the American College of Rheumatology or the European Alliance of Associations for Rheumatology are globally recognized. It is presumed that there are geographical differences among female sufferers, and unique diagnostic criteria and recommendations are used in clinical practice in Japan. In addition to the items included in the classification criteria, several methods to measure saliva secretion, serum biomarkers, and artificial intelligence tools have recently been reported to be useful for the assessment of SjD. While symptomatic therapies including tear drops, artificial saliva, and muscarinic agonists are still the mainstay for treating SjD, several kinds of molecular targeted drugs, such as biological drugs and Janus kinase inhibitors, that are expected to improve the prognosis of SjD have been tested in recent clinical trials. Full article
(This article belongs to the Special Issue Diagnosis and Treatment of Sjogren’s Syndrome: 2nd Edition)
12 pages, 258 KiB  
Article
Effect of Anti-Diabetic Medication Use on Sepsis Risk in Type 2 Diabetes Mellitus: A Multivariate Analysis
by Battamir Ulambayar, Amr Sayed Ghanem and Attila Csaba Nagy
Geriatrics 2025, 10(4), 108; https://doi.org/10.3390/geriatrics10040108 - 7 Aug 2025
Abstract
Background: Type 2 diabetes mellitus (T2DM) increases sepsis risk due to immune dysfunction and chronic inflammation. Antidiabetic medications, while primarily used for glycemic control, may modulate sepsis susceptibility through immune and inflammatory pathways. This study investigates the association between antidiabetic medication use and [...] Read more.
Background: Type 2 diabetes mellitus (T2DM) increases sepsis risk due to immune dysfunction and chronic inflammation. Antidiabetic medications, while primarily used for glycemic control, may modulate sepsis susceptibility through immune and inflammatory pathways. This study investigates the association between antidiabetic medication use and sepsis risk in T2DM patients. Methods: A longitudinal cohort study was conducted using clinical registry data from 5009 T2DM patients at the University Hospital, Debrecen, Hungary (2016–2020). Sepsis cases were identified via ICD-10 code A41, and antidiabetic medication use was categorized using ATC codes. Baseline comorbidities and laboratory parameters were extracted. Chi-square and Wilcoxon rank–sum tests assessed associations between sepsis and categorical/numerical variables, respectively. Time-adjusted multivariate logistic regression evaluated predictors of sepsis risk, with odds ratios (ORs) and 95% confidence intervals (CIs) reported. Results: Age, hypertension, ischemic heart disease, nephropathy, elevated blood glucose, C-reactive protein, and creatinine also independently increased sepsis risk. Insulin use was associated with a 2.6-fold increased sepsis risk (OR = 2.6, 95% CI: 2.09–3.34, p < 0.001), while SGLT2 inhibitors (OR = 0.56, 95% CI: 0.34–0.91, p = 0.02) and GLP-1 receptor agonists (OR = 0.39, 95% CI: 0.19–0.79, p = 0.009) were protective. Conclusions: Insulin-treated patients may require closer infection monitoring, while SGLT2 inhibitors and GLP-1 RAs could be prioritized in high-risk individuals. These findings highlight the potential to inform risk stratification and guide personalized antidiabetic therapy to reduce sepsis risk in T2DM. Full article
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16 pages, 1769 KiB  
Review
SGLT2 Inhibitors and GLP-1 Receptor Agonists in Cardiovascular–Kidney–Metabolic Syndrome
by Aryan Gajjar, Arvind Kumar Raju, Amani Gajjar, Mythili Menon, Syed Asfand Yar Shah, Sourbha Dani and Andrew Weinberg
Biomedicines 2025, 13(8), 1924; https://doi.org/10.3390/biomedicines13081924 - 7 Aug 2025
Abstract
Cardiovascular–Kidney–Metabolic (CKM) syndrome symbolizes a single pathophysiologic entity including obesity, type 2 diabetes, chronic kidney disease, and cardiovascular disease. These conditions altogether accelerate adverse outcomes when they coexist. Recent evidence has shown that the function of glucagon-like peptide-1 receptor agonists (GLP-1RA) and sodium–glucose [...] Read more.
Cardiovascular–Kidney–Metabolic (CKM) syndrome symbolizes a single pathophysiologic entity including obesity, type 2 diabetes, chronic kidney disease, and cardiovascular disease. These conditions altogether accelerate adverse outcomes when they coexist. Recent evidence has shown that the function of glucagon-like peptide-1 receptor agonists (GLP-1RA) and sodium–glucose cotransporter-2 inhibitors (SGLT2i) alleviate stress on multiple organs. SGLT2i has been demonstrated to benefit heart failure, hemodynamic regulation, and renal protection while GLP-1RA on the other hand has been shown to demonstrate a strong impact on glycemic management, weight loss, and atherosclerotic cardiovascular disease. This review will aim to understand and evaluate the mechanistic rationalization, clinical evidence, and the potential therapeutic treatment of SGLT2 inhibitors and GLP-1 receptor agonists to treat individuals who have CKM syndrome. This analysis also assesses whether combination therapy can be a synergistic approach that may benefit patients but is still underutilized because of the lack of clear guidelines, the associated costs, and disparities in accessibility. Therefore, in this review, we will be discussing the combination therapy’s additive and synergistic effects, current recommendations and clinical evidence, and mechanistic insights of these GLT2 inhibitors and GLP-1 receptor agonists in CKM syndrome patients. Overall, early and combination usage of GLP-1RA and SGLT2i may be essential to demonstrating a significant shift in modern cardiometabolic therapy toward patient-centered care. Full article
(This article belongs to the Section Endocrinology and Metabolism Research)
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18 pages, 435 KiB  
Review
Molecular and Glycosylation Pathways in Osteosarcoma: Tumor Microenvironment and Emerging Strategies Toward Personalized Oncology
by Georgian Longin Iacobescu, Antonio-Daniel Corlatescu, Horia Petre Costin, Razvan Spiridonica, Mihnea-Ioan-Gabriel Popa and Catalin Cirstoiu
Curr. Issues Mol. Biol. 2025, 47(8), 629; https://doi.org/10.3390/cimb47080629 - 7 Aug 2025
Abstract
Osteosarcoma (OS) is the most common primary bone malignancy in children and adolescents, which is also considered an aggressive disease due to its rapid growth rate, ability to metastasize early, and complex and heterogeneous tumor microenvironment (TME). Although we are developing improved surgical [...] Read more.
Osteosarcoma (OS) is the most common primary bone malignancy in children and adolescents, which is also considered an aggressive disease due to its rapid growth rate, ability to metastasize early, and complex and heterogeneous tumor microenvironment (TME). Although we are developing improved surgical and chemotherapeutic approaches, the presence of metastatic or recurrent disease is still detrimental to the patient’s outcome. Major advances in understanding the molecular mechanisms of OS are needed to substantially improve outcomes for patients being treated for OS. This review integrates new data on the molecular biology, pathophysiology, and immune landscape of OS, as well as introducing salient areas of tumorigenesis underpinning these findings, such as chromothripsis; kataegis; cancer stem cell dynamics; and updated genetic, epigenetic, and glycosylation modifiers. In addition, we review promising biomarkers, diagnostic platforms, and treatments, including immunotherapy, targeted small molecule inhibitors, and nanomedicine. Using genomic techniques, we have defined OS for its significant genomic instability due to TP53 and RB1 mutations, chromosomal rearrangements, and aberrant glycosylation. The TME is also characterized as immunosuppressive and populated by tumor-associated macrophages, myeloid-derived suppressor cells, and regulatory T cells, ultimately inhibiting immune checkpoint inhibitors. Emerging fields such as glycomics and epigenetics, as well as stem cell biology, have defined promising biomarkers and targets. Preclinical studies have identified that glycan-directed CAR therapies could be possible, as well as metabolic inhibitors and 3D tumor models, which presented some preclinical success and could allow for tumoral specificity and enhanced efficacy. OS is a biologically and clinically complex disease; however, advances in exploring the molecular and immunologic landscape of OS present new opportunities in biomarkers and the development of new treatment options with adjunctive care. Successful treatments in the future will require personalized, multi-targeted approaches to account for tumor heterogeneity and immune evasion. This will help us turn the corner in providing improved outcomes for patients with this resilient malignancy. Full article
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41 pages, 2949 KiB  
Review
Nanocarriers Containing Curcumin and Derivatives for Arthritis Treatment: Mapping the Evidence in a Scoping Review
by Beatriz Yurie Sugisawa Sato, Susan Iida Chong, Nathalia Marçallo Peixoto Souza, Raul Edison Luna Lazo, Roberto Pontarolo, Fabiane Gomes de Moraes Rego, Luana Mota Ferreira and Marcel Henrique Marcondes Sari
Pharmaceutics 2025, 17(8), 1022; https://doi.org/10.3390/pharmaceutics17081022 - 6 Aug 2025
Abstract
Background/Objectives: Curcumin (CUR) is well known for its therapeutic properties, particularly attributed to its antioxidant and anti-inflammatory effects in managing chronic diseases such as arthritis. While CUR application for biomedical purposes is well known, the phytochemical has several restrictions given its poor water [...] Read more.
Background/Objectives: Curcumin (CUR) is well known for its therapeutic properties, particularly attributed to its antioxidant and anti-inflammatory effects in managing chronic diseases such as arthritis. While CUR application for biomedical purposes is well known, the phytochemical has several restrictions given its poor water solubility, physicochemical instability, and low bioavailability. These limitations have led to innovative formulations, with nanocarriers emerging as a promising alternative. For this reason, this study aimed to address the potential advantages of associating CUR with nanocarrier systems in managing arthritis through a scoping review. Methods: A systematic literature search of preclinical (in vivo) and clinical studies was performed in PubMed, Scopus, and Web of Science (December 2024). General inclusion criteria include using CUR or natural derivatives in nano-based formulations for arthritis treatment. These elements lead to the question: “What is the impact of the association of CUR or derivatives in nanocarriers in treating arthritis?”. Results: From an initial 536 articles, 34 were selected for further analysis (31 preclinical investigations and three randomized clinical trials). Most studies used pure CUR (25/34), associated with organic (30/34) nanocarrier systems. Remarkably, nanoparticles (16/34) and nanoemulsions (5/34) were emphasized. The formulations were primarily presented in liquid form (23/34) and were generally administered to animal models through intra-articular injection (11/31). Complete Freund’s Adjuvant (CFA) was the most frequently utilized among the various models to induce arthritis-like joint damage. The findings indicate that associating CUR or its derivatives with nanocarrier systems enhances its pharmacological efficacy through controlled release and enhanced solubility, bioavailability, and stability. Moreover, the encapsulation of CUR showed better results in most cases than in its free form. Nonetheless, most studies were restricted to the preclinical model, not providing direct evidence in humans. Additionally, inadequate information and clarity presented considerable challenges for preclinical evidence, which was confirmed by SYRCLE’s bias detection tools. Conclusions: Hence, this scoping review highlights the anti-arthritic effects of CUR nanocarriers as a promising alternative for improved treatment. Full article
(This article belongs to the Special Issue Advances in Polymer-Based Devices and Platforms for Pain Management)
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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16 pages, 1169 KiB  
Review
Bispecific Antibodies—A New Hope for Patients with Diffuse Large B-Cell Lymphoma
by Romeo Gabriel Mihaila and Samuel B. Todor
J. Clin. Med. 2025, 14(15), 5534; https://doi.org/10.3390/jcm14155534 - 6 Aug 2025
Abstract
T-cell-engaging antibodies are a promising new type of treatment for patients with refractory or relapsed (R/R) diffuse large B-cell lymphoma, which has changed the prognosis and evolution of these patients in clinical trials. Bispecific antibodies (BsAbs) bind to two different targets (B and [...] Read more.
T-cell-engaging antibodies are a promising new type of treatment for patients with refractory or relapsed (R/R) diffuse large B-cell lymphoma, which has changed the prognosis and evolution of these patients in clinical trials. Bispecific antibodies (BsAbs) bind to two different targets (B and T lymphocytes) at the same time and in this way mimic the action of CAR (chimeric antigen receptor) T-cells. They are the T-cell-engaging antibodies most used in practice and are a solution for patients who do not respond to second- or later-line therapies, including chemoimmunotherapy, followed by salvage chemotherapy and hematopoietic stem cell transplantation. They are a therapeutic option for patients who are ineligible for CAR T-cell therapy and are also active in those with prior exposure to CAR T-cell treatment. A remarkable advantage of BsAbs is their rapid availability, even if the disease progresses rapidly, unlike CAR T-cell treatment, and they avoid the practical and financial challenges raised by autologous CAR T-cell therapies. CAR-T has been proven to have better efficacy compared to BsAbs, but cytokine release syndrome and neurotoxicity have appeared significantly more frequently in patients treated with CAR T-cells. The possibility of combining BsAbs with chemotherapy and their administration for relapses or as a frontline therapy is being studied to increase their efficacy. BsAbs are a life-saving therapy for many patients with diffuse large B-cell malignant non-Hodgkin’s lymphoma (NHL) who have a poor prognosis with classical therapies, but are not without adverse effects and require careful monitoring. Full article
(This article belongs to the Special Issue Immunotherapy of Hematological Malignancies: The State of the Art)
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29 pages, 2060 KiB  
Review
Revitalizing Colchicine: Novel Delivery Platforms and Derivatives to Expand Its Therapeutic Potential
by Natallia V. Dubashynskaya, Anton N. Bokatyi, Mikhail M. Galagudza and Yury A. Skorik
Int. J. Mol. Sci. 2025, 26(15), 7591; https://doi.org/10.3390/ijms26157591 - 6 Aug 2025
Abstract
Colchicine is a potent alkaloid with well-established anti-inflammatory properties. It shows significant promise in treating classic immune-mediated inflammatory diseases, as well as associated cardiovascular diseases, including atherosclerosis. However, its clinical use is limited by a narrow therapeutic window, dose-limiting systemic toxicity, variable bioavailability, [...] Read more.
Colchicine is a potent alkaloid with well-established anti-inflammatory properties. It shows significant promise in treating classic immune-mediated inflammatory diseases, as well as associated cardiovascular diseases, including atherosclerosis. However, its clinical use is limited by a narrow therapeutic window, dose-limiting systemic toxicity, variable bioavailability, and clinically significant drug–drug interactions, partly mediated by modulation of P-glycoprotein and cytochrome P450 3A4 metabolism. This review explores advanced delivery strategies designed to overcome these limitations. We critically evaluate lipid-based systems, such as solid lipid nanoparticles, liposomes, transferosomes, ethosomes, and cubosomes; polymer-based nanoparticles; microneedles; and implants, including drug-eluting stents. These systems ensure targeted delivery, improve pharmacokinetics, and reduce toxicity. Additionally, we discuss chemical derivatization approaches, such as prodrugs, codrugs, and strategic ring modifications (A-, B-, and C-rings), aimed at optimizing both the efficacy and safety profile of colchicine. Combinatorial nanoformulations that enable the co-delivery of colchicine with synergistic agents, such as glucocorticoids and statins, as well as theranostic platforms that integrate therapeutic and diagnostic functions, are also considered. These innovative delivery systems and derivatives have the potential to transform colchicine therapy by broadening its clinical applications while minimizing adverse effects. Future challenges include scalable manufacturing, long-term safety validation, and the translation of research into clinical practice. Full article
(This article belongs to the Section Macromolecules)
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17 pages, 1396 KiB  
Article
Dose-Dependent Effect of the Polyamine Spermine on Wheat Seed Germination, Mycelium Growth of Fusarium Seed-Borne Pathogens, and In Vivo Fusarium Root and Crown Rot Development
by Tsvetina Nikolova, Dessislava Todorova, Tzenko Vatchev, Zornitsa Stoyanova, Valya Lyubenova, Yordanka Taseva, Ivo Yanashkov and Iskren Sergiev
Agriculture 2025, 15(15), 1695; https://doi.org/10.3390/agriculture15151695 - 6 Aug 2025
Abstract
Wheat (Triticum aestivum L.) is a crucial global food crop. The intensive crop farming, monoculture cultivation, and impact of climate change affect the susceptibility of wheat cultivars to biotic stresses, mainly caused by soil fungal pathogens, especially those belonging to the genus [...] Read more.
Wheat (Triticum aestivum L.) is a crucial global food crop. The intensive crop farming, monoculture cultivation, and impact of climate change affect the susceptibility of wheat cultivars to biotic stresses, mainly caused by soil fungal pathogens, especially those belonging to the genus Fusarium. This situation threatens yield and grain quality through root and crown rot. While conventional chemical fungicides face resistance issues and environmental concerns, biological alternatives like seed priming with natural metabolites are gaining attention. Polyamines, including putrescine, spermidine, and spermine, are attractive priming agents influencing plant development and abiotic stress responses. Spermine in particular shows potential for in vitro antifungal activity against Fusarium. Optimising spermine concentration for seed priming is crucial to maximising protection against Fusarium infection while ensuring robust plant growth. In this research, we explored the potential of the polyamine spermine as a seed treatment to enhance wheat resilience, aiming to identify a sustainable alternative to synthetic fungicides. Our findings revealed that a six-hour seed soak in spermine solutions ranging from 0.5 to 5 mM did not delay germination or seedling growth. In fact, the 5 mM concentration significantly stimulated root weight and length. In complementary in vitro assays, we evaluated the antifungal activity of spermine (0.5–5 mM) against three Fusarium species. The results demonstrated complete inhibition of Fusarium culmorum growth at 5 mM spermine. A less significant effect on Fusarium graminearum and little to no impact on Fusarium oxysporum were found. The performed analysis revealed that the spermine had a fungistatic effect against the pathogen, retarding the mycelium growth of F. culmorum inoculated on the seed surface. A pot experiment with Bulgarian soft wheat cv. Sadovo-1 was carried out to estimate the effect of seed priming with spermine against infection with isolates of pathogenic fungus F. culmorum on plant growth and disease severity. Our results demonstrated that spermine resulted in a reduced distribution of F. culmorum and improved plant performance, as evidenced by the higher fresh weight and height of plants pre-treated with spermine. This research describes the efficacy of spermine seed priming as a novel strategy for managing Fusarium root and crown rot in wheat. Full article
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16 pages, 1302 KiB  
Article
Screening of Medicinal Herbs Identifies Cimicifuga foetida and Its Bioactive Component Caffeic Acid as SARS-CoV-2 Entry Inhibitors
by Ching-Hsuan Liu, Yu-Ting Kuo, Chien-Ju Lin, Feng-Lin Yen, Shu-Jing Wu and Liang-Tzung Lin
Viruses 2025, 17(8), 1086; https://doi.org/10.3390/v17081086 - 5 Aug 2025
Abstract
The emergence of SARS-CoV-2 variants highlights the urgent need for novel therapeutic strategies, particularly entry inhibitors that could efficiently prevent viral infection. Medicinal herbs and herbal combination formulas have long been recognized for their effects in treating infectious diseases and their antiviral properties, [...] Read more.
The emergence of SARS-CoV-2 variants highlights the urgent need for novel therapeutic strategies, particularly entry inhibitors that could efficiently prevent viral infection. Medicinal herbs and herbal combination formulas have long been recognized for their effects in treating infectious diseases and their antiviral properties, thus providing abundant resources for the discovery of antiviral candidates. While many candidates have been suggested to have antiviral activity against SARS-CoV-2 infection, few have been validated for their mechanisms, including possible effects on viral entry. This study aimed to identify SARS-CoV-2 entry inhibitors from medicinal herbs and herbal formulas that are known for heat-clearing and detoxifying properties and/or antiviral activities. A SARS-CoV-2 pseudoparticle (SARS-CoV-2pp) system was used to assess mechanism-specific entry inhibition. Our results showed that the methanol extract of Anemarrhena asphodeloides rhizome, as well as the water extracts of Cimicifuga foetida rhizome, Xiao Chai Hu Tang (XCHT), and Sheng Ma Ge Gen Tang (SMGGT), have substantial inhibitory effects on the entry of SARS-CoV-2pps into host cells. Given the observation that Cimicifuga foetida exhibited the most potent inhibition and is a constituent of SMGGT, we further investigated the major compounds of the herb and identified caffeic acid as a bioactive component for blocking SARS-CoV-2pp entry. Entry inhibition of Cimicifuga foetida and caffeic acid was validated on both wild-type and the currently dominant JN.1 strain SARS-CoV-2pp systems. Moreover, caffeic acid was able to both inactivate the pseudoparticles and prevent their entry into pretreated host cells. The results support the traditional use of these herbal medicines and underscore their potential as valuable resources for identifying active compounds and developing therapeutic entry inhibitors for the management of COVID-19. Full article
(This article belongs to the Section Coronaviruses)
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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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