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17 pages, 2518 KiB  
Article
Pyramiding Recessive Resistance Genes Enhances Bacterial Leaf Spot Resistance in Peppers by Suppressing in planta Bacterial Growth
by Mousami Poudel, Sophia McDuffee, Gerald V. Minsavage, Samuel F. Hutton, Anuj Sharma and Jeffrey B. Jones
Plants 2025, 14(16), 2559; https://doi.org/10.3390/plants14162559 (registering DOI) - 17 Aug 2025
Abstract
Bacterial spot of the pepper (BSP) and the tomato (BST) caused by multiple Xanthomonas spp. remains a major constraint to production of both crops worldwide. The widespread breakdown of dominant resistance genes, such as Bs2, due to the emergence of virulent races, [...] Read more.
Bacterial spot of the pepper (BSP) and the tomato (BST) caused by multiple Xanthomonas spp. remains a major constraint to production of both crops worldwide. The widespread breakdown of dominant resistance genes, such as Bs2, due to the emergence of virulent races, like Xanthomonas euvesicatoria P6, has underscored the need for more durable, non-race-specific resistance. The recessive genes, bs5; bs6; and bs8, have emerged as promising alternatives, conferring broad-spectrum resistance without triggering a hypersensitive response. In this study, we systematically evaluated the individual and combinatorial effects of these three recessive resistance genes against three Xanthomonas species, X. euvesicatoria (Xe), X. hortorum pv. gardneri (Xhg), and X. perforans (Xp). Using near-isogenic lines (NILs) developed in the susceptible Early Calwonder (ECW) background, we assessed the in planta bacterial population growth and symptom development across a panel of eight genotypes carrying different gene combinations. Our results demonstrate that bs5, particularly when combined with either bs6 or bs8, significantly reduces bacterial growth and disease severity across all three Xanthomonas species. The triple-stacked line (ECW568 (i.e., bs5, bs6, and bs8)) consistently displayed the strongest suppression of pathogen proliferation and symptom development. By contrast, bs6 and bs8, alone or in combination, were largely ineffective. In some cases, combining bs6 with bs8 was less effective than bs8 alone. These findings reinforce the central role of bs5 in conferring quantitative resistance and highlight the additive benefit of pyramiding recessive resistance genes. Furthermore, we have demonstrated that these recessive resistance genes are effective in limiting the ability of the emerging pathogen, X. perforans, to grow in planta, and thus are predicted to offer a high level of resistance in the field. Our work provides key insights for breeding durable, broad-spectrum resistance into commercial pepper cultivars and offers a framework for integrated disease management strategies in the face of rapidly evolving bacterial pathogens Full article
(This article belongs to the Section Plant Protection and Biotic Interactions)
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13 pages, 3136 KiB  
Communication
Transfer of Downy Mildew Resistance Genes from Wild Cucumbers to Beit Alpha Types
by Rivka S. Hammer, Yariv Ben Naim, Arnon Brand and Yigal Cohen
J. Fungi 2025, 11(8), 597; https://doi.org/10.3390/jof11080597 (registering DOI) - 16 Aug 2025
Abstract
Downy mildew, caused by the oomycete Pseudoperonospora cubensis, is the most destructive foliar disease of cucumbers. While partially resistant slicer cultivars (with spined fruits) are commercially available, no resistant Beit Alpha cultivars (characterized by smooth, dark green fruit) have been developed to [...] Read more.
Downy mildew, caused by the oomycete Pseudoperonospora cubensis, is the most destructive foliar disease of cucumbers. While partially resistant slicer cultivars (with spined fruits) are commercially available, no resistant Beit Alpha cultivars (characterized by smooth, dark green fruit) have been developed to date. Here, we report the successful breeding of downy mildew-resistant Beit Alpha cucumber lines. Resistance was transferred from the wild Sikkim cucumber accessions PI 197088 and PI 330628 (characterized by round fruit, with heavily netted brown rind). The resistance and fruit phenotype were restored through backcrosses to elite commercial susceptible cultivars. Due to the recessive nature of the resistance genes and their distribution across multiple chromosomes, the breeding program required multiple backcrosses and stringent selections for both resistance and fruit type. Full article
(This article belongs to the Special Issue Plant Fungal Diseases and Crop Protection, 2nd Edition)
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22 pages, 2051 KiB  
Article
Global Hypomethylation as Minimal Residual Disease (MRD) Biomarker in Esophageal and Esophagogastric Junction Adenocarcinoma
by Elisa Boldrin, Maria Assunta Piano, Alice Volpato, Rita Alfieri, Monica Franco, Tiziana Morbin, Annalisa Masier, Stefano Realdon, Genny Mattara, Giovanna Magni, Antonio Rosato, Pierluigi Pilati, Alberto Fantin and Matteo Curtarello
Cancers 2025, 17(16), 2668; https://doi.org/10.3390/cancers17162668 - 15 Aug 2025
Abstract
Background/Objectives: Esophageal and esophagogastric junction adenocarcinoma (EADC-EGJA), which mainly develops from Barrett’s esophagus (BE), low-grade dysplasia (LGD), and high-grade dysplasia (HGD), has a poor prognosis and several unmet clinical needs, among which is the detection of minimal residual disease (MRD) after endoscopic/surgical [...] Read more.
Background/Objectives: Esophageal and esophagogastric junction adenocarcinoma (EADC-EGJA), which mainly develops from Barrett’s esophagus (BE), low-grade dysplasia (LGD), and high-grade dysplasia (HGD), has a poor prognosis and several unmet clinical needs, among which is the detection of minimal residual disease (MRD) after endoscopic/surgical resection. Long interspersed nuclear element-1 (LINE-1), a surrogate marker of global methylation, is considered an emerging biomarker for MRD monitoring. The aim of this study was to determine, by LINE-1 methylation analysis, at which carcinogenesis step global methylation is affected and whether this biomarker could be followed in longitudinal to monitor the disease behavior post-surgery. Methods: Cell-free DNA of 90 patients with non-dysplastic Barrett’s esophagus (NDBE), HGD/early EADC-EGJA, or locally advanced/advanced EADC-EGJA were analyzed for LINE-1 methylation, by Methylation-Sensitive Restriction Enzyme droplet digital PCR (MSRE-ddPCR). Twenty-six patients were longitudinally studied by repetitive blood sampling. Results: Global hypomethylation increased during carcinogenesis, with significant difference between locally advanced/advanced EADC-EGJA and NDBE patients (p = 0.028). Longitudinal cases confirmed the rareness of hypomethylation in NDBE cases. The majority of HGD/early EADC-EGJA and locally advanced/advanced EADC-EGJA patients showed methylation changes after resection according to clinical status. Conclusions: This study suggests that global hypomethylation occurs just prior to cancer invasiveness and that it is a promising biomarker to monitor MRD. Full article
(This article belongs to the Special Issue Circulating Tumour DNA and Liquid Biopsy in Oncology)
22 pages, 1258 KiB  
Article
Liposomal Formulations for Efficient Delivery of a Novel, Highly Potent Pyrimidine-Based Anticancer Drug
by Sofia Teixeira, Débora Ferreira, Ana Rita O. Rodrigues, Ligia R. Rodrigues, Elisabete M. S. Castanheira and Maria Alice Carvalho
Pharmaceuticals 2025, 18(8), 1210; https://doi.org/10.3390/ph18081210 - 15 Aug 2025
Abstract
Background/Objectives: Cancer is one of the deadliest diseases worldwide. Despite the existing treatments, the adverse side effects and the increasing drug resistance to the current therapies lead to a reduced quality of life for patients and poor prognosis. The pyrimido[5,4-d]pyrimidine compound [...] Read more.
Background/Objectives: Cancer is one of the deadliest diseases worldwide. Despite the existing treatments, the adverse side effects and the increasing drug resistance to the current therapies lead to a reduced quality of life for patients and poor prognosis. The pyrimido[5,4-d]pyrimidine compound (PP) was identified as a promising new anticancer drug due to its potent activity against colorectal and triple-negative breast cancers; however it showed poor aqueous solubility and safety profile. This study aimed the synthesis of compound PP, its encapsulation in liposomal formulations based on phosphatidylcholines (PC), the characterization of liposomal formulations and its biological evaluation. Methods: A new synthesis method for PP was developed. The compound was incorporated into different liposomal formulations. The hydrodynamic size, polydispersity, and zeta potential of loaded and non-loaded formulations were measured by DLS. The cytotoxic effects of compound PP, placebo nanoformulations, and PP-loaded nanoformulations were assessed in colorectal (HCT 116) and triple-negative breast cancer (MDA-MB-231) cell lines, as well as in non-tumor BJ-5ta cells. Results: The PP compound was efficiently synthesized. The PP-loaded liposomal formulations exhibit sizes below 150 nm, low polydispersity, and long-time stability upon storage at 4 °C. The antitumor compound was encapsulated with excellent efficiency, and sustained release profiles were obtained. The PP compound showed high activity against HCT 116 (IC50 = 2.04 ± 0.45 µM) and MDA-MB-231 (IC50 = 5.24 ± 0.24 µM) cell lines. DPPC-containing formulations were effective against cancer cells, but showed toxicity comparable to free PP in BJ-5ta normal cells. Conversely, PP-EggPC-Chol-L formulation displayed strong anticancer activity with residual toxicity to normal cells. Conclusions: The PP-loaded liposomal formulation, composed of 70% PC from egg yolk (EggPC) and 30% cholesterol (Chol), designated as PP-EggPC-Chol-L, was the most promising formulation, showing effective anticancer activity in both cancer cell lines and a significant improvement in the safety profile which is of utmost importance to progress to the next phase of drug development. Full article
(This article belongs to the Special Issue Drug Formulation: Solubilization and Controlled-Release Strategies)
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11 pages, 251 KiB  
Article
Intravenous Liposomal Amphotericin B for Complicated Pediatric Cutaneous Leishmaniasis: A Case Series
by Moshe Shmueli, Siham Elamour, Galina Ling and Shalom Ben-Shimol
Parasitologia 2025, 5(3), 43; https://doi.org/10.3390/parasitologia5030043 - 15 Aug 2025
Viewed by 27
Abstract
Background: First-line treatments for cutaneous leishmaniasis (CL), including topical agents, are often limited in cases of complicated disease involving multiple, facial, or treatment-resistant lesions. Data on intravenous liposomal amphotericin B (L-AmB) are scarce, especially in children. We report our experience using L-AmB to [...] Read more.
Background: First-line treatments for cutaneous leishmaniasis (CL), including topical agents, are often limited in cases of complicated disease involving multiple, facial, or treatment-resistant lesions. Data on intravenous liposomal amphotericin B (L-AmB) are scarce, especially in children. We report our experience using L-AmB to treat pediatric CL, focusing on treatment rationale, safety, and clinical effectiveness. Methods: A retrospective case series. Diagnosis was confirmed by PCR. Data on demographics, clinical presentation, treatment rationale, adverse events, lab findings, and outcomes, during treatment and follow-up, were collected. Results: Twenty-seven children were included, most (96%) with Leishmania major. The mean number of lesions per child was 5.71 ± 6.19. All had facial involvement; 41% nasal and 15% eyelid. Most lesions were ulcerated (78%). Prior treatment failure was common (78%), with the use of topical antimicrobials, liposomal amphotericin gel, and paromomycin-containing ointments (59%, 38%, 19%, respectively). Twenty-four children (89%) completed treatment successfully. Adverse events occurred in 41% of cases but were mostly mild and reversible: flushing, rash, shortness of breath, and vomiting (11%, each). One case of transient renal impairment and one case with neutropenia were recorded. Early improvement was noted by day 10, with 50% (n = 12) of cases exhibiting crust falling/reduced ulceration and a 50% lesion size reduction. By day 30–90, 92% achieved substantial healing without the need for further therapy. Nevertheless, scarring was noted in 79% of cases. Conclusions: L-AmB treatment appears to be safe and effective for pediatric CL, particularly in cases with facial lesions or prior treatment failure. Clinical improvement was notable, although scarring was common. Full article
11 pages, 1246 KiB  
Article
Evaluation of Papaya Plants Tolerant to PRSV Obtained Through Conventional Genetic Improvement
by Luz María Sánchez-Noriega, Manuel R. Kirchmayr, Benjamín Rodríguez-Garay, Diego E. Navarro-López and Antonia Gutiérrez-Mora
Stresses 2025, 5(3), 51; https://doi.org/10.3390/stresses5030051 - 15 Aug 2025
Viewed by 37
Abstract
Papaya cultivation is severely affected by the papaya ring spot virus (PRSV), for which one of the alternatives to counteract its damage is to use genetic sources of species and/or varieties tolerant or resistant to the virus. This study aimed to determine the [...] Read more.
Papaya cultivation is severely affected by the papaya ring spot virus (PRSV), for which one of the alternatives to counteract its damage is to use genetic sources of species and/or varieties tolerant or resistant to the virus. This study aimed to determine the tolerance or resistance of different papaya plant lines obtained through crosses and backcrosses between the Maradol variety and a wild species of Vasconcellea tolerant to PRSV. In this work, an evaluation was conducted on plant lines from a cross between a PRSV-tolerant species (Vasconcellea cauliflora) and the Maradol variety (Carica papaya), both belonging to the Caricaceae family. The study used RT-qPCR to measure the viral load and analyzed disease symptoms at two points (97 and 532 days after planting). Initially, it was observed that all the resulting papaya plants developed symptoms of PSRV; however, as time passed, the results showed that lines resulting from the Criolla, M4, and 54 crosses exhibited moderate tolerance, while papaya lines 89 and 90 proved to have high tolerance. Additionally, it was observed that the M4, 89, and 90 papaya lines exhibited disease recovery, as reflected in a decrease in viral loads and the characteristic symptomatology of the virus. Restoration from a viral infection can be associated with the activation of the plant’s RNA silencing mechanism, which can degrade or prevent the translation of viral RNA in plant cells, thus favoring recovery from the disease. Plants evaluated due to their tolerance and resistance levels could use the mechanisms mentioned above to recover from the damage caused by the PRSV. Full article
(This article belongs to the Collection Feature Papers in Plant and Photoautotrophic Stresses)
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20 pages, 2524 KiB  
Article
Wild Fauna in Oman: Foot-and-Mouth Disease Outbreak in Arabyan Oryx (Oryx leucorix)
by Massimo Giangaspero, Salah Al Mahdhouri, Sultan Al Bulushi and Metaab K. Al-Ghafri
Animals 2025, 15(16), 2389; https://doi.org/10.3390/ani15162389 - 14 Aug 2025
Viewed by 138
Abstract
The Sultanate of Oman boasts remarkable biodiversity, exemplified by such species as the Arabian leopard (Panthera pardus nimr) and the Arabian oryx (Oryx leucoryx), national symbols that highlight the extensive conservation efforts required to protect the country’s natural heritage. [...] Read more.
The Sultanate of Oman boasts remarkable biodiversity, exemplified by such species as the Arabian leopard (Panthera pardus nimr) and the Arabian oryx (Oryx leucoryx), national symbols that highlight the extensive conservation efforts required to protect the country’s natural heritage. During decades, Omani authorities have taken significant measures to safeguard wildlife and preserve the natural environment. A sanctuary dedicated to the reintroduction of the Arabian Oryx, after extinction in nature in 1972, was established in 1980 in the Al Wusta Governorate under the patronage of the Royal Diwan and currently administrated by the recently established Environment Authority. During the almost 40 years since the reintroduction and the creation of the sanctuary, the oryx population has grown slowly but constantly. In 2021, the sanctuary hosted 738 oryx, allowing the start of the reintroduction of the species into the natural environment. Small groups of animals were released into the wild in selected areas. No animal health adverse events were recorded, and mortality was generally due to injuries received as a consequence of fighting, in particular during mating season. Standard veterinary care, including control of internal and external parasites, was regularly provided. In some occasions, immunization against certain diseases, such as clostridial infections, pasteurellosis, or mycoplasmosis, was also applied. In 2023, an FMD outbreak in cattle reported in Dhofar, about 500 km from the Al Wusta sanctuary, motivated specific prophylactic actions to prevent the risk of diffusion to oryx. From December 2023 to January 2024, an immunization program was undertaken using an FMD vaccine against serotypes A, O, and SAT 1, mostly in male oryx, while pregnant oryx were avoided for abortion risk due to handling. The following year, in January 2025, a severe outbreak occurred in oryx herds held in the sanctuary. The rapid onset and the spread of clinical symptoms among animals (100% morbidity in the second day after the first appearance of signs in some individuals) were suggestive of a highly contagious disease. The animals suffered from severe depression and inappetence, rapidly followed by abundant salivation, erosions of the oral mucosa and tongue, and diarrhea, with a short course characterized by prostration and death of the animal in the most severe cases. Therapeutical attempts (administration of antibiotics and rehydration) were mostly ineffective. Laboratory investigations (ELISA and PCR) ruled out contagious bovine pleuropneumonia (CBPP), Johne’s disease and Peste des petits ruminants (PPR). Both serology and antigen detection showed positiveness to foot-and-mouth disease (FMD). Out of a total population of 669 present in the sanctuary at the beginning of the outbreak, 226 (33.78%) oryx died. Despite the vaccinal status, the 38.49% of dead animals resulted being vaccinated against FMD. Taking into account the incalculable value of the species, the outbreak represented a very dangerous event that risked wiping out the decades of conservation efforts. Therefore, all the available means, such as accrued biosecurity and adequate prophylaxis, should be implemented to prevent the recurrence of such health risks. The delicate equilibrium of wild fauna in Oman requires study and support for an effective protection, in line with the national plan “Vision 2040”, targeting the inclusion of the Sultanate within the 20 best virtuous countries for wildlife protection. Full article
(This article belongs to the Special Issue Wildlife Diseases: Pathology and Diagnostic Investigation)
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19 pages, 1906 KiB  
Review
The Duodenum-Centered Neurohormonal Hypothesis of Type 2 Diabetes: A Mechanistic Review and Therapeutic Perspective
by Athena N. Kapralou, Christos Yapijakis and George P. Chrousos
Curr. Issues Mol. Biol. 2025, 47(8), 657; https://doi.org/10.3390/cimb47080657 - 14 Aug 2025
Viewed by 258
Abstract
Type 2 diabetes mellitus (T2DM) is a multifactorial disorder defined by insulin resistance, β-cell dysfunction, and chronic hyperglycemia. Although peripheral mechanisms have been extensively studied, increasing evidence implicates the gastrointestinal tract in disease onset. Insights from bariatric surgery, gut hormone signaling, and incretin-based [...] Read more.
Type 2 diabetes mellitus (T2DM) is a multifactorial disorder defined by insulin resistance, β-cell dysfunction, and chronic hyperglycemia. Although peripheral mechanisms have been extensively studied, increasing evidence implicates the gastrointestinal tract in disease onset. Insights from bariatric surgery, gut hormone signaling, and incretin-based therapies suggest that the gut contributes actively beyond nutrient absorption. Yet, a cohesive framework integrating these observations remains absent, leaving a critical gap in our understanding of T2DM’s upstream pathophysiology. This work builds upon the anti-incretin theory, which posits that nutrient-stimulated neurohormonal signals—termed “anti-incretins”—arise from the proximal intestine to counteract incretin effects and regulate glycemic homeostasis. The excess of anti-incretin signals, perhaps stimulated by macronutrient composition or chemical additives of modern diets, disrupts this balance and may cause insulin resistance and β-cell depletion, leading to T2D. We hypothesize that the neuroendocrine signals produced by cholecystokinin (CCK)-I and secretin-S cells, both located in the proximal intestine, function as endogenous anti-incretins. In this context, we hypothesize a novel model centered on the chronic overstimulation of I and S cells by high-fat, high glycemic index modern diets. This drives what we term “amplified digestion”—a state marked by heightened vagal and hormonal stimulation of biliary and pancreatic secretions, increased enzymatic and bile acid activity, and alterations in bile acid composition. This condition leads to an extended breakdown of carbohydrates, lipids, and proteins into absorbable units, thereby promoting excessive nutrient absorption and ultimately contributing to insulin resistance and progressive β-cell failure. Multiple lines of clinical, surgical, and experimental evidence converge to support our model, rooted in the physiology of digestion and absorption. Western dietary patterns appear to induce an over-digestive adaptation—marked by excessive vagal and hormonal stimulation of biliary and pancreatic secretion—which amplifies digestive signaling. This heightened state correlates with increased nutrient absorption, insulin resistance, and β-cell dysfunction. Interventions that disrupt this maladaptive signaling—such as truncal vagotomy combined with duodenal bypass—may offer novel, physiology-based strategies for T2DM treatment. This hypothesis outlines a potential upstream contributor to insulin resistance and T2DM, grounded in digestive tract-derived neurohormonal dysregulation. This gut-centered model may provide insight into early, potentially reversible stages of the disease and identify a conceptual therapeutic target. Nonetheless, both the hypothesis and the accompanying surgical strategy—truncal vagotomy combined with proximal intestinal bypass—remain highly exploratory and require systematic validation through mechanistic and clinical studies. Further investigation is warranted to clarify the molecular regulation of I and S enteroendocrine cells, including the genetic and epigenetic factors that may drive hypersecretion. While speculative, interventions—surgical or pharmacologic—designed to modulate these digestive signals could represent a future avenue for research into T2DM prevention or remission, pending rigorous evidence. Full article
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16 pages, 251 KiB  
Article
A Short-Term Comparative Evaluation of Multiple Treatment Modalities for Meibomian Gland Dysfunction: A Prospective Clinical Study
by Mübeccel Bulut, Ali Hakim Reyhan and Gökhan Yüzbaşı
Healthcare 2025, 13(16), 1992; https://doi.org/10.3390/healthcare13161992 - 14 Aug 2025
Viewed by 115
Abstract
Purpose: The aim of this study was to evaluate the different approaches used in the treatment of meibomian gland dysfunction (MGD). Materials and Methods: This open-label, single-center, prospective pilot study with a parallel-group design was conducted in February 2025. Ninety-two patients presenting to [...] Read more.
Purpose: The aim of this study was to evaluate the different approaches used in the treatment of meibomian gland dysfunction (MGD). Materials and Methods: This open-label, single-center, prospective pilot study with a parallel-group design was conducted in February 2025. Ninety-two patients presenting to our clinic with symptoms and signs of MGD were enrolled and diagnosed according to Japanese MGD diagnostic criteria. Patients were assigned to five treatment groups: conservative management alone, conservative management plus intense pulsed light (IPL) therapy, conservative management plus oral azithromycin, conservative management plus oral doxycycline, and conservative management plus topical cyclosporine. Conservative management consisted of preservative-free artificial tears containing polyvinyl alcohol and povidone, warm compresses, and eyelid hygiene. Primary outcome measures included ocular surface parameters such as the Ocular Surface Disease Index (OSDI), tear break-up time (TBUT), Standard Patient Evaluation of Eye Dryness (SPEED) scores, and meibomian gland parameters evaluated using a slit-lamp examination. All parameters were assessed at baseline and during follow-up examinations after treatment initiation to observe changes in symptoms and signs. Results: A statistically significant increase was determined in meibum grade plugging (grades 0–3; higher = greater obstruction) and Marx line scores with IPL therapy (p < 0.05). The group receiving doxycycline treatment exhibited a significant improvement in OSDI and SPEED scores, plugging, TBUT, and meibum grades. The group receiving cyclosporine registered a significant improvement in OSDI and SPEED scores, plugging, TBUT, and meibum grades. A statistically significant increase was observed in the conservative treatment group in terms of lid margin irregularity, Marx line score, and OSDI and SPEED scores. In the group receiving azithromycin treatment, plugging, lid margin irregularity, TBUT, and OSDI and SPEED scores increased significantly. Compared with conservative care, the doxycycline group exhibited lengthened TBUT and lowered meibomian gland plugging and symptoms (p < 0.05), and the oral azithromycin group achieved a similar TBUT gain with slightly greater symptom relief. The topical cyclosporine group principally registered improved lid vascularity and meibum quality (p < 0.05), while the IPL group achieved the greatest overall improvements, reducing plugging and Marx line scores and adding ≈3 s to TBUT (p < 0.05 for all endpoints). Doxycycline exhibited notable short-term improvements, with 35.26% meibum grade improvement and a 40.48% foaming response, while IPL therapy demonstrated substantial OSDI improvements at 54.06%, with traditional parameters indicating limited treatment responsiveness. Conclusions: Various methods can be used in the treatment of MGD. All the conservative treatment methods used in this study were successful. Full article
(This article belongs to the Section Health Assessments)
14 pages, 2160 KiB  
Article
Arthrospira Platensis Attenuates Endothelial Inflammation and Monocyte Activation
by Ilaria Leone, Valentino Costabile, Giovanni Smaldone, Monica Franzese, Andrea Soricelli and Anna D’Agostino
Int. J. Mol. Sci. 2025, 26(16), 7844; https://doi.org/10.3390/ijms26167844 - 14 Aug 2025
Viewed by 98
Abstract
Cardiovascular diseases (CVDs) remain the leading cause of morbidity and mortality in industrialized countries. Coronary artery disease (CAD) represents the most prevalent form of cardiovascular disease and remains a leading cause of morbidity, mortality, and long-term disability worldwide. Therefore, the identification of early [...] Read more.
Cardiovascular diseases (CVDs) remain the leading cause of morbidity and mortality in industrialized countries. Coronary artery disease (CAD) represents the most prevalent form of cardiovascular disease and remains a leading cause of morbidity, mortality, and long-term disability worldwide. Therefore, the identification of early biomarkers and clarification of the mechanism of action of pharmacological adjuvants is urgently needed. Nutraceuticals such as Arthrospira platensis (commonly known as spirulina) have emerged as promising modulators for their notable vascular anti-inflammatory properties. In this study, we provide novel evidence of the anti-inflammatory and anti-atherosclerotic potential of Arthrospira platensis toward endothelial cells and immune interactions, combining in vitro assays with bioinformatic profiling. Spirulina treatment significantly attenuated endothelial and angiogenic activation, reducing pro-inflammatory cytokine and VEGFA/VEGFR2 expression. Additionally, it also decreased the activation and adhesion capabilities of THP-1 monocytic cell lines. Through computational analysis of the complex molecular mixture present in Arthrospira platensis, we have identified a subset of compounds exhibiting high structural similarity to CHEMBL3559503, a well-characterized synthetic molecule with dual activity as a TLR9 agonist and anti-angiogenic agent. This represents a novel insight, suggesting that spirulina may serve as a natural source of analogues capable of modulating both immune and angiogenic pathways. These results highlight Arthrospira platensis as a promising candidate nutraceutical for targeting endothelial/immune crosstalk in the context of atherosclerosis prevention, offering both mechanistic insights and translational potential. Full article
(This article belongs to the Special Issue Molecular Pathophysiology and Treatment of Coronary Artery Disease)
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16 pages, 1703 KiB  
Article
Analysis of the Proteome and Biochemistry of Venom from Tityus confluens, a Scorpion That Can Be Involved in Severe Envenomation Cases in Brazil
by Laís Corrêa Lima, Henrique Ranieri Covali-Pontes, Ohanna Gabriely Souza Leite, Renata Trentin Perdomo, Luiz Filipe Ramalho Nunes de Moraes, Ludovico Migliolo, Mauricio Nogueira Moyses, Natália Gabrielly Pereira dos Santos, Daniel Carvalho Pimenta, Mariana Soares Rodrigues, Karen Morais-Zani, Guilherme Rabelo Coelho and Malson Neilson Lucena
Toxins 2025, 17(8), 406; https://doi.org/10.3390/toxins17080406 - 14 Aug 2025
Viewed by 215
Abstract
In Brazil, the annual scorpion sting cases surpass those of other neglected tropical diseases, highlighting a significant public health issue. The severity of scorpion envenomation relates to the venom’s rapid action, complex composition, species identification challenges, and limited antivenom availability. This work aimed [...] Read more.
In Brazil, the annual scorpion sting cases surpass those of other neglected tropical diseases, highlighting a significant public health issue. The severity of scorpion envenomation relates to the venom’s rapid action, complex composition, species identification challenges, and limited antivenom availability. This work aimed to characterize the venom of Tityus confluens through proteomic, enzymatic, and biological analyses while also assessing its reactivity to anti-scorpion antivenom. The electrophoretic analysis revealed seven protein bands, with the most prominent bands at 30, 15, and 10 kDa. The C18-RP-HPLC analysis isolated sixteen primary fractions. The proteomic analysis identified various toxins, including potassium channel toxins, sodium channel toxins, and antimicrobial peptides, as well as other proteins such as hypotensin and metalloproteinases. Antigenic components were identified in the T. confluens venom, which displayed dose-dependent but time-independent amylolytic activity. The ATPase activity significantly increased with 1–10 μg of venom. No cytotoxic effects were observed on carcinoma or non-tumoral cell lines. The T. confluens venom features a complex protein composition rich in toxins that target ion channels and enzymes. It exhibits active enzymatic and antigenic properties, and displays low cytotoxicity. This is the first proteomic research on the composition of T. confluens venom and may provide valuable insights into understanding the clinical manifestations of scorpion stings. Full article
(This article belongs to the Special Issue Transcriptomic and Proteomic Study on Animal Venom: Looking Forward)
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24 pages, 1548 KiB  
Review
Onychomycosis in Diabetics: A Common Infection with Potentially Serious Complications
by Aditya K. Gupta, Amanda Liddy, Lee Magal, Avner Shemer, Elizabeth A. Cooper, Ditte Marie L. Saunte and Tong Wang
Life 2025, 15(8), 1285; https://doi.org/10.3390/life15081285 - 13 Aug 2025
Viewed by 272
Abstract
Onychomycosis is a prevalent and clinically relevant complication among individuals with diabetes. It is associated with an elevated risk of secondary fungal and bacterial infections, foot ulceration, and, in advanced cases, amputation. Factors contributing to the increased prevalence of onychomycosis in this population [...] Read more.
Onychomycosis is a prevalent and clinically relevant complication among individuals with diabetes. It is associated with an elevated risk of secondary fungal and bacterial infections, foot ulceration, and, in advanced cases, amputation. Factors contributing to the increased prevalence of onychomycosis in this population include age, peripheral vascular disease, poor glycemic control, neuropathy, suboptimal foot hygiene, and nail trauma. While dermatophytes are the most common pathogens, diabetic patients are more prone to mixed infections involving Candida species with varying antifungal susceptibility profiles, necessitating accurate identification to guide therapy. Prompt diagnosis and early intervention are important to prevent complications. Systemic antifungals such as terbinafine and itraconazole are considered first-line therapies, particularly for moderate to severe onychomycosis. However, drug interactions, renal, hepatic, and metabolic comorbidities may necessitate individualized treatment plans. For patients with mild to moderate disease, or contraindications to oral therapy, topical agents such as efinaconazole or tavaborole offer viable alternatives. Adjunctive measures, including education on foot hygiene, prompt treatment of tinea pedis, and environmental sanitization, are important in preventing recurrence and reinfection. This review summarizes the epidemiology, diagnosis, and treatment considerations for onychomycosis in diabetic patients, emphasizing the need for individualized care to improve outcomes in this high-risk population. Full article
(This article belongs to the Section Medical Research)
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23 pages, 4597 KiB  
Article
High-Throughput UAV Hyperspectral Remote Sensing Pinpoints Bacterial Leaf Streak Resistance in Wheat
by Alireza Sanaeifar, Ruth Dill-Macky, Rebecca D. Curland, Susan Reynolds, Matthew N. Rouse, Shahryar Kianian and Ce Yang
Remote Sens. 2025, 17(16), 2799; https://doi.org/10.3390/rs17162799 - 13 Aug 2025
Viewed by 298
Abstract
Bacterial leaf streak (BLS), caused by Xanthomonas translucens pv. undulosa, has become an intermittent yet economically significant disease of wheat in the Upper Midwest during the last decade. Because chemical and cultural controls remain ineffective, breeders rely on developing resistant varieties, yet [...] Read more.
Bacterial leaf streak (BLS), caused by Xanthomonas translucens pv. undulosa, has become an intermittent yet economically significant disease of wheat in the Upper Midwest during the last decade. Because chemical and cultural controls remain ineffective, breeders rely on developing resistant varieties, yet visual ratings in inoculated nurseries are labor-intensive, subjective, and time-consuming. To accelerate this process, we combined unmanned-aerial-vehicle hyperspectral imaging (UAV-HSI) with a carefully tuned chemometric workflow that delivers rapid, objective estimates of disease severity. Principal component analysis cleanly separated BLS, leaf rust, and Fusarium head blight, with the first component explaining 97.76% of the spectral variance, demonstrating in-field pathogen discrimination. Pre-processing of the hyperspectral cubes, followed by robust Partial Least Squares (RPLS) regression, improved model reliability by managing outliers and heteroscedastic noise. Four variable-selection strategies—Variable Importance in Projection (VIP), Interval PLS (iPLS), Recursive Weighted PLS (rPLS), and Genetic Algorithm (GA)—were evaluated; rPLS provided the best balance between parsimony and accuracy, trimming the predictor set from 244 to 29 bands. Informative wavelengths clustered in the near-infrared and red-edge regions, which are linked to chlorophyll loss and canopy water stress. The best model, RPLS with optimal preprocessing and variable selection based on the rPLS method, showed high predictive accuracy, achieving a cross-validated R2 of 0.823 and cross-validated RMSE of 7.452, demonstrating its effectiveness for detecting and quantifying BLS. We also explored the spectral overlap with Sentinel-2 bands, showing how UAV-derived maps can nest within satellite mosaics to link plot-level scouting to landscape-scale surveillance. Together, these results lay a practical foundation for breeders to speed the selection of resistant lines and for agronomists to monitor BLS dynamics across multiple spatial scales. Full article
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12 pages, 510 KiB  
Review
Emerging Ornamental Plant Diseases and Their Management Trends in Northern Italy
by Maria Lodovica Gullino, Domenico Bertetti, Massimo Pugliese and Angelo Garibaldi
Horticulturae 2025, 11(8), 955; https://doi.org/10.3390/horticulturae11080955 - 13 Aug 2025
Viewed by 150
Abstract
The ornamental plant sector is characterized by the production of a large variety of genera, species and cultivars that are much more numerous than those of other agricultural production sectors. Many countries throughout the world are involved in an intensive exchange of potted [...] Read more.
The ornamental plant sector is characterized by the production of a large variety of genera, species and cultivars that are much more numerous than those of other agricultural production sectors. Many countries throughout the world are involved in an intensive exchange of potted plants, cut flowers and propagation material. This intense trade exchange favors the introduction of the causal agents of new diseases on farms, in parks, along tree-lined avenues and in city gardens. Global warming can favor plant pathogens that thrive under high temperatures. Moreover, the interaction between the ongoing increase in temperature and in the CO2 concentration has caused a significant increase in the disease severity of many pathosystems. The numerous reports of new plant pathogens on ornamental plants in Italy in recent years fall into this context. In plant pathology research, living labs incorporate the complexities and variability of natural conditions, and they can thus be used to conduct experiments and test hypotheses. A private garden, located in the hamlet of Bariola (Piedmont, Biella province, northern Italy), has become an ideal living lab that is used to monitor the evolution of the phytosanitary situation of ornamental plants. The results obtained in this living lab are reported hereafter. Moreover, new trends in disease prevention and management, such as the adoption of appropriate prevention practices, water and fertilization management and use of environmentally friendly methods to reduce pesticide use as part of an integrated pest management approach, are also examined. Full article
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40 pages, 480 KiB  
Review
The Role of Epigenetic Biomarkers as Diagnostic, Predictive and Prognostic Factors in Colorectal Cancer
by Zuzanna Chilimoniuk, Konrad Gładysz, Natalia Moniczewska, Katarzyna Chawrylak, Zuzanna Pelc and Radosław Mlak
Cancers 2025, 17(16), 2632; https://doi.org/10.3390/cancers17162632 - 12 Aug 2025
Viewed by 374
Abstract
Colorectal cancer (CRC) remains one of the leading causes of cancer-related morbidity and mortality worldwide. Despite significant advances in screening and treatment, the prognosis for advanced-stage disease continues to be poor. One thriving area of research focuses on the use of epigenetic alterations [...] Read more.
Colorectal cancer (CRC) remains one of the leading causes of cancer-related morbidity and mortality worldwide. Despite significant advances in screening and treatment, the prognosis for advanced-stage disease continues to be poor. One thriving area of research focuses on the use of epigenetic alterations for the diagnosis, prediction of treatment response, and prognosis of CRC. In this study, we evaluated original studies and meta-analyses published within the past five years to identify the most clinically relevant epigenetic biomarkers. DNA methylation-based assays, particularly those targeting SDC2 and SEPT9 in stool and plasma, exhibit superior diagnostic accuracy compared to other epigenetic modalities. Circulating microRNAs (miRNAs), including miR-211, miR-197, and miR-21, as well as specific long non-coding RNAs (lncRNAs) such as SNHG14, LINC01485, and ASB16-AS1, also show promising diagnostic potential. Furthermore, panels combining multiple epigenetic markers, especially those incorporating DNA methylation targets, have demonstrated improved sensitivity and specificity for early-stage CRC detection. In the context of therapeutic prediction, microRNAs such as miR-140, miR-21, and miR-4442 have been associated with chemotherapy resistance and recurrence risk. DNA methylation markers like LINE-1, mSEPT9 and ERCC1 have also shown predictive value, while lncRNAs including MALAT1 and GAS6-AS1 remain less validated. Regarding prognosis, miRNAs appear to be the most promising biomarkers, with miR-675-5p and miR-150 being associated with poor survival, while miR-767-5p and miR-215 predict favorable outcomes. Methylation of NKX6.1, IGFBP3, and LMX1A has been identified as an independent negative prognostic factor, while SFRP2 hypermethylation is linked to better prognosis. Selected lncRNAs, including THOR and LINC01094, have also demonstrated significant prognostic value. Despite these advances, challenges persist, including inconsistent reporting, limited external validation, and a lack of replication by independent research groups. Full article
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