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22 pages, 9750 KiB  
Article
SIK2 Drives Pulmonary Fibrosis by Enhancing Fibroblast Glycolysis and Activation
by Jianhan He, Ruihan Dong, Huihui Yue, Fengqin Zhang, Xinran Dou, Xuan Li, Hui Li and Huilan Zhang
Biomedicines 2025, 13(8), 1919; https://doi.org/10.3390/biomedicines13081919 - 6 Aug 2025
Abstract
Background: Pulmonary fibrosis (PF), the end-stage manifestation of interstitial lung disease, is defined by excessive extracellular matrix deposition and alveolar destruction. Activated fibroblasts, the primary matrix producers, rely heavily on dysregulated glucose metabolism for their activation. While Salt Inducible Kinase 2 (SIK2) regulates [...] Read more.
Background: Pulmonary fibrosis (PF), the end-stage manifestation of interstitial lung disease, is defined by excessive extracellular matrix deposition and alveolar destruction. Activated fibroblasts, the primary matrix producers, rely heavily on dysregulated glucose metabolism for their activation. While Salt Inducible Kinase 2 (SIK2) regulates glycolytic pathways in oncogenesis, its specific contributions to fibroblast activation and therapeutic potential in PF pathogenesis remain undefined. This study elucidates the functional role of SIK2 in PF and assesses its viability as a therapeutic target. Methods: SIK2 expression/localization in fibrosis was assessed by Western blot and immunofluorescence. Fibroblast-specific Sik2 KO mice evaluated effects on bleomycin-induced fibrosis. SIK2’s role in fibroblast activation and glucose metabolism impact (enzyme expression, metabolism assays, metabolites) were tested. SIK2 inhibitors were screened and evaluated therapeutically in fibrosis models. Results: It demonstrated significant SIK2 upregulation, specifically within activated fibroblasts of fibrotic lungs from both PF patients and murine models. Functional assays demonstrated that SIK2 is crucial for fibroblast activation, proliferation, and migration. Mechanistically, SIK2 enhances fibroblast glucose metabolism by increasing the expression of glycolysis-related enzymes. Additionally, this study demonstrated that the SIK2 inhibitor YKL06-061 effectively inhibited PF in both bleomycin and FITC-induced PF mouse models with the preliminary safety profile. Furthermore, we identified a novel therapeutic application for the clinically approved drug fostamatinib, demonstrating it inhibits fibroblast activation via SIK2 targeting and alleviates PF in mice. Conclusions: Our findings highlight SIK2 as a promising therapeutic target and provide compelling preclinical evidence for two distinct anti-fibrotic strategies with significant potential for future PF treatment. Full article
(This article belongs to the Special Issue New Insights in Respiratory Diseases)
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25 pages, 1504 KiB  
Article
Systemic Sclerosis with Interstitial Lung Disease: Identification of Novel Immunogenetic Markers and Ethnic Specificity in Kazakh Patients
by Lina Zaripova, Abay Baigenzhin, Zhanar Zarkumova, Zhanna Zhabakova, Alyona Boltanova, Maxim Solomadin and Alexey Pak
Epidemiologia 2025, 6(3), 41; https://doi.org/10.3390/epidemiologia6030041 - 6 Aug 2025
Abstract
Systemic sclerosis (SSc) is an autoimmune connective tissue disorder characterized by vascular abnormalities, immune dysfunction, and progressive fibrosis. One of the most common manifestations of SSc is interstitial lung disease (ILD), known by a progressive course leading to significant morbidity and mortality. Aim: [...] Read more.
Systemic sclerosis (SSc) is an autoimmune connective tissue disorder characterized by vascular abnormalities, immune dysfunction, and progressive fibrosis. One of the most common manifestations of SSc is interstitial lung disease (ILD), known by a progressive course leading to significant morbidity and mortality. Aim: to investigate autoantibodies, cytokines, and genetic markers in SSc-ILD through a systematic review and analysis of a Kazakh cohort of SSc-ILD patients. Methods: A PubMed search over the past 10 years was performed with “SSc-ILD”, “autoantibodies”, “cytokines”, and “genes”. Thirty patients with SSc were assessed for lung involvement, EScSG score, and modified Rodnan skin score. IL-6 was measured by ELISA, antinuclear factor on HEp-2 cells by indirect immunofluorescence, and specific autoantibodies by immunoblotting. Genetic analysis was performed using a 120-gene AmpliSeq panel on the Ion Proton platform. Results: The literature review identified 361 articles, 26 addressed autoantibodies, 20 genetic variants, and 12 cytokine profiles. Elevated levels of IL-6, TGF-β, IL-33, and TNF-α were linked to SSc. Based on the results of the systemic review, we created a preliminary immunogenic panel for SSc-ILD with following analysis in Kazakh patients with SSc (n = 30). Fourteen of them (46.7%) demonstrated signs of ILD and/or lung hypertension, with frequent detection of antibodies such as Scl-70, U1-snRNP, SS-A, and genetic variants in SAMD9L, REL, IRAK1, LY96, IL6R, ITGA2B, AIRE, TREX1, and CD40 genes. Conclusions: Current research confirmed the presence of the broad range of autoantibodies and variations in IRAK1, TNFAIP3, SAMD9L, REL, IRAK1, LY96, IL6R, ITGA2B, AIRE, TREX1, CD40 genes in of Kazakhstani cohort of SSc-ILD patients. Full article
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21 pages, 1058 KiB  
Review
The Role of Vitamin K Deficiency in Chronic Kidney Disease—A Scoping Review
by Valdemar Tybjerg Wegge, Mette Kjær Torbensen, Allan Linneberg and Julie Aaberg Lauridsen
Nutrients 2025, 17(15), 2559; https://doi.org/10.3390/nu17152559 - 5 Aug 2025
Abstract
Background/objectives: Chronic kidney disease (CKD) affects up to 15% of the global population and is driven by vascular and interstitial damage, and is most prevalent in persons with hypertension and diabetes. Vitamin K, a necessary cofactor for activation of vitamin K-dependent proteins [...] Read more.
Background/objectives: Chronic kidney disease (CKD) affects up to 15% of the global population and is driven by vascular and interstitial damage, and is most prevalent in persons with hypertension and diabetes. Vitamin K, a necessary cofactor for activation of vitamin K-dependent proteins may modulate these processes. It is well established that vitamin K deficiency is associated with CKD, but the therapeutic effects of supplementation on kidney function are still uncertain. We aimed to review the current evidence on the effect of vitamin K deficiency and supplementation on any marker of renal function and kidney disease, across general adult populations and CKD patient populations. Methods: A search was conducted in PubMed, targeting terms related to vitamin K status and CKD. Studies were included if they reported data on vitamin K status or supplementation in relation to kidney function outcomes. Results: A total of 16 studies were included. Nine interventional studies were included and confirmed that vitamin K supplementation improves biomarkers of vitamin K status but showed no consistent beneficial effects on renal function. Seven observational studies across populations found significant associations between vitamin K status and decline in kidney function; however, associations were often attenuated after adjustments. Conclusions: No clear effect of supplementation was observed on the reported kidney markers in patient populations. A clear association between low vitamin K status and impaired kidney function was confirmed. Studying heterogeneity makes the comparability and generalizability of the results difficult. Our review highlights the need for more cohort studies and clinical trials in general or patient populations. Full article
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20 pages, 6034 KiB  
Article
Pexidartinib and Nintedanib Combination Therapy Targets Macrophage Polarization to Reverse Pulmonary Fibrosis: A Preclinical Study
by Ji-Hee Kim, Jae-Kyung Nam, Min-Sik Park, Seungyoul Seo, Hyung Chul Ryu, Hae-June Lee, Jeeyong Lee and Yoon-Jin Lee
Int. J. Mol. Sci. 2025, 26(15), 7570; https://doi.org/10.3390/ijms26157570 - 5 Aug 2025
Abstract
Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive interstitial lung disease with limited therapeutic options and increasing global incidence, with a median survival of only 2–5 years. The clinical utility of macrophage polarization to regulate the progression of pulmonary fibrosis remains understudied. This [...] Read more.
Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive interstitial lung disease with limited therapeutic options and increasing global incidence, with a median survival of only 2–5 years. The clinical utility of macrophage polarization to regulate the progression of pulmonary fibrosis remains understudied. This study determined the efficacy of nintedanib and pexidartinib (PLX3397) combination therapy for treating IPF. Combination treatment effectively inhibited the progression of radiation-induced pulmonary fibrosis (RIPF) and prolonged survival in bleomycin-treated mice. Micro-CT analysis revealed a significant tissue repair efficacy. The therapy significantly normalized the abnormal vascular structure observed during RIPF and bleomycin-induced pulmonary fibrosis progression and was accompanied by a decrease in the M2 population. Polarized M1 macrophages enhanced normalized tube formation of irradiated endothelial cells (ECs) in vitro; M2 macrophages increased adhesion in irradiated ECs and abnormal tube formation. Single-cell RNA sequencing data from patients with IPF further supports colony stimulating factor (CSF) 1 upregulation in macrophages and downregulation of capillary EC markers. This study highlights a promising combination strategy to overcome the therapeutic limitations of monotherapy with nintedanib for the treatment of IPF. Full article
(This article belongs to the Section Molecular Pharmacology)
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15 pages, 258 KiB  
Article
The Pulmonary Manifestation of Mastocytosis: Experiences of the National Reference Centre of Excellence
by Marlena Sztormowska, Aleksandra Górska, Maciej Piskunowicz, Lucyna Górska, Wojciech Nazar, Marta Chełmińska, Krzysztof Kuziemski, Ewa Jassem and Marek Niedoszytko
J. Clin. Med. 2025, 14(15), 5455; https://doi.org/10.3390/jcm14155455 - 3 Aug 2025
Viewed by 157
Abstract
Background: Patients with mastocytosis may present with exacerbated respiratory symptoms and lung diseases resulting from mast cell mediator release. However, their prevalence and severity level remain under debate. The study aims to analyze the prevalence of respiratory symptoms and the usefulness of lung [...] Read more.
Background: Patients with mastocytosis may present with exacerbated respiratory symptoms and lung diseases resulting from mast cell mediator release. However, their prevalence and severity level remain under debate. The study aims to analyze the prevalence of respiratory symptoms and the usefulness of lung function tests like spirometry, diffusing capacity of the lung for carbon monoxide (DLCO), and high-resolution computed tomography (HRCT) of the chest in mastocytosis patients presenting with dyspnea, cough, and exercise intolerance. Methods: We included 104 patients with mastocytosis and 71 healthy controls. Data collection encompassed patient interview, clinical examination, spirometry, DLCO, and chest HRCT. Diagnosis of mastocytosis included bone marrow biopsies and serum tryptase measurements. Results: Compared to controls, patients with mastocytosis exhibited significantly lower values in FEV1/VC ratio, absolute DLCO/VA, predicted DLCO/VA, absolute DLCOcSB, and predicted DLCOcSB (p < 0.001). Commonly reported respiratory symptoms included dyspnea (36.5%), chest tightness (22.1%), and wheezing (9.6%). Airway obstruction was identified in 7.7% of patients; however, it appeared to be independent of the mastocytosis subtype. A decreased DLCO/VA ratio was observed in 4.8% of patients, but HRCT did not reveal any evidence of underlying lung disease. Conclusions: Mastocytosis appears to be a risk factor for the occurrence and exacerbation of respiratory symptoms. However, airway obstruction and impairment of the alveolar–capillary membrane seem to occur independently of the clinical subtype of mastocytosis. Additionally, the causal relationship between pulmonary involvement, mast cell infiltration of the alveolar–capillary membrane, and the systemic circulation of mast cell mediators remains unclear and requires further research. Full article
(This article belongs to the Section Respiratory Medicine)
13 pages, 441 KiB  
Article
Pulmonary Involvement in Patients with Positive Myositis Antibodies in Rheumatology: A Retrospective Monocentric Analysis
by Falk Schumacher, Malte Kanbach, Maximilian Zimmermann, Daniel Majorski, Wigbert Schulze, Maximilian Wollsching-Strobel, Doreen Kroppen, Sarah Bettina Stanzel, Wolfram Windisch, Johannes Strunk and Melanie Berger
J. Clin. Med. 2025, 14(15), 5443; https://doi.org/10.3390/jcm14155443 - 1 Aug 2025
Viewed by 280
Abstract
Background: Pulmonary involvement is the most common prognosis-related organ involvement in idiopathic inflammatory myopathy (IIM). Owing to the large number of antibodies, the evidence for lung involvement and rare antibodies is limited. In everyday clinical practice, the interpretation of positive myositis antibodies represents [...] Read more.
Background: Pulmonary involvement is the most common prognosis-related organ involvement in idiopathic inflammatory myopathy (IIM). Owing to the large number of antibodies, the evidence for lung involvement and rare antibodies is limited. In everyday clinical practice, the interpretation of positive myositis antibodies represents a challenge. Methods: This study is a retrospective monocentric analysis. The data collection regarding positive myositis antibodies and possible pulmonary involvement was carried out from July 2019 to May 2022. Data analysis revealed positive results for one of the following antibodies: EJ, PL7, OJ, PL12, Mi-2α, TIF1γ, MDA5, SAE, NXP2, SRP, Ku, PM-Scl100 and PM-Scl75. In our analysis, patients with IIM, patients with inflammatory rheumatic disease other than IIM and patients without inflammatory rheumatic disease are described. The results of high-resolution computed tomography (HRCT), pulmonary function tests, echocardiographic examinations and their associated clinical findings are examined. Results: In the entire cohort, 209 patients with positive myositis antibodies were detected. In total, 22 (10.5%) patients had interstitial lung disease (ILD) patterns on HRCT. In the subgroup of patients with IIM, a significantly higher proportion of patients with lung involvement (n = 13, 35.1%) was found than in the group with other inflammatory rheumatic diseases (IRDs) (n = 6, 6.7%) or in the group without IRDs (n = 3, 3.7%). When the antibody groups were considered, the PL12-positive patients had the largest proportion of ILD (42%), followed by the MDA5-positive patients (40%). Conclusions: In patients with IIM, myositis antibodies are highly relevant for assessing the risk of lung involvement. In groups with other IRD or without IRD, antibody detection does not represent this high relevance for lung involvement. A differentiated assessment of the various MSAs or MAAs detected, as well as clinical parameters, allows for further important risk assessment for prognosis-relevant lung involvement. Full article
(This article belongs to the Section Immunology)
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24 pages, 936 KiB  
Article
Anti-Ku Antibodies: Clinical Associations, Organ Damage, and Prognostic Implications in Connective Tissue Diseases
by Céline La, Julie Smet, Carole Nagant and Muhammad Soyfoo
Int. J. Mol. Sci. 2025, 26(15), 7433; https://doi.org/10.3390/ijms26157433 - 1 Aug 2025
Viewed by 170
Abstract
Anti-Ku antibodies are rare autoantibodies associated with connective tissue diseases (CTDs), but their clinical significance remains poorly understood due to limited studies. Semi-quantitative immunodot assays yield positive, negative, or borderline results, with the clinical relevance of borderline findings remaining unclear. The purpose of [...] Read more.
Anti-Ku antibodies are rare autoantibodies associated with connective tissue diseases (CTDs), but their clinical significance remains poorly understood due to limited studies. Semi-quantitative immunodot assays yield positive, negative, or borderline results, with the clinical relevance of borderline findings remaining unclear. The purpose of this study is to characterize the clinical spectrum of anti-Ku-positive patients and evaluate the clinical significance of anti-Ku-borderline results in CTD management. A retrospective cohort study was conducted at Hôpital Erasme, including all patients with anti-Ku-positive or borderline results, over a 10-year period. Clinical and biological data were collected from medical records and analyzed for disease associations, organ involvement, and outcomes. Among 47 anti-Ku-positive patients, systemic lupus erythematosus (SLE) and Sjögren’s syndrome (SS) were the most common diagnoses. Interstitial lung disease (ILD) occurred in 23.4% and renal involvement in 12.8% of patients. Cytopenia was significantly associated with glomerulonephritis. Organ damage, particularly pulmonary and renal involvement, correlated with increased mortality. In the borderline group (n = 33), SLE and SS remained the predominant diagnoses. During follow-up, three patients died (all with isolated ILD without associated CTD), one required chronic dialysis, and one underwent lung transplantation. ILD was present in 7/22 (31.8%) borderline patients, and renal involvement in 7/32 (21.9%). This study demonstrates significant associations between anti-Ku antibodies and organ damage, with increased mortality risk. The high prevalence of pulmonary and renal involvement in anti-Ku-borderline patients suggests that these results carry substantial clinical significance and should prompt comprehensive CTD evaluation. These findings support treating borderline anti-Ku results with the same clinical vigilance as positive results, given their similar association with severe organ involvement and adverse outcomes. Full article
(This article belongs to the Section Molecular Immunology)
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11 pages, 245 KiB  
Review
The Impact of Insulin Resistance on Lung Volume Through Right Ventricular Dysfunction in Diabetic Patients—Literature Review
by Daniel Radu, Oana-Andreea Parlițeanu, Andra-Elena Nica, Cristiana Voineag, Octavian-Sabin Alexe, Alexandra Maria Cristea, Livia Georgescu, Roxana Maria Nemeș, Andreea Taisia Tiron and Alexandra Floriana Nemeș
J. Pers. Med. 2025, 15(8), 336; https://doi.org/10.3390/jpm15080336 - 1 Aug 2025
Viewed by 228
Abstract
Insulin resistance (IR), a core component in the development of type 2 diabetes mellitus (T2DM), is increasingly recognized for its role in cardiovascular and pulmonary complications. This review explores the relationship between IR, right ventricular dysfunction (RVD), and decreased lung volume in patients [...] Read more.
Insulin resistance (IR), a core component in the development of type 2 diabetes mellitus (T2DM), is increasingly recognized for its role in cardiovascular and pulmonary complications. This review explores the relationship between IR, right ventricular dysfunction (RVD), and decreased lung volume in patients with T2DM. Emerging evidence suggests that IR contributes to early structural and functional alterations in the right ventricle, independent of overt cardiovascular disease. The mechanisms involved include oxidative stress, inflammation, dyslipidemia, and obesity—factors commonly found in metabolic syndrome and T2DM. These pathophysiological changes compromise right ventricular contractility, leading to reduced pulmonary perfusion and respiratory capacity. RVD has been associated with chronic lung disease, pulmonary hypertension, and obstructive sleep apnea, all of which are prevalent in the diabetic population. As RVD progresses, it can result in impaired gas exchange, interstitial pulmonary edema, and exercise intolerance—highlighting the importance of early recognition and management. Therapeutic strategies should aim to improve insulin sensitivity and cardiac function through lifestyle interventions, pharmacological agents such as SGLT2 inhibitors and GLP-1/GIP analogs, and routine cardiac monitoring. These approaches may help slow the progression of RVD and its respiratory consequences. Considering the global burden of diabetes and obesity, and the growing incidence of related complications, further research is warranted to clarify the mechanisms linking IR, RVD, and respiratory dysfunction. Understanding this triad will be crucial for developing targeted interventions that improve outcomes and quality of life in affected patients. Full article
(This article belongs to the Section Mechanisms of Diseases)
9 pages, 6176 KiB  
Case Report
Concurrent Leydig and Sertoli Cell Tumors Associated with Testicular Mycosis in a Dog: A Case Report and Literature Review
by Mirosław Kuberka, Przemysław Prządka and Stanisław Dzimira
Pathogens 2025, 14(8), 752; https://doi.org/10.3390/pathogens14080752 - 31 Jul 2025
Viewed by 194
Abstract
Mycosis is caused by, among other factors, filamentous fungi, ubiquitous molds belonging to Aspergillus spp. which are often opportunistic pathogens. Over 100 species of Aspergillus have been described. The most common species responsible for diseases in humans and animals are Aspergillus fumigatus and [...] Read more.
Mycosis is caused by, among other factors, filamentous fungi, ubiquitous molds belonging to Aspergillus spp. which are often opportunistic pathogens. Over 100 species of Aspergillus have been described. The most common species responsible for diseases in humans and animals are Aspergillus fumigatus and Aspergillus niger, with Aspergillus flavus and Aspergillus clavatus being somewhat rarer. Aspergillus causes a range of diseases, from localized colonization and hypersensitivity reactions, through chronic necrotizing infections, to rapidly progressing angioinvasion and dissemination, leading to death. Testicular mycosis is extremely rarely described in both humans and animals. No studies in the literature report a simultaneous occurrence of testicular tumors and fungal infection of the organ, so the aim of this paper was to describe, for the first time, a case of two independent testicular tumors coexisting with testicular mycosis. A histopathological examination was performed on the left testicle of a male dog, specifically a mixed-breed dog resembling a husky weighing 22 kg and with an age of 8 years. Bilateral orchidectomy was performed for medical reasons due to the altered outline of the left testicle, leading to scrotal deformation. The dog did not show any clinical signs of illness, and the testicles were not painful. The right testicle, according to the operating veterinarian, showed no macroscopic changes, so histopathological verification was not performed. Microscopic imaging of the changes clearly indicated the coexistence of a tumor process involving Leydig cells (Leydigoma, interstitial cell tumor, ICT), Sertoli cells (Sertolioma), and fungal infection of the testis. The case suggests the possibility of the coexistence of tumor processes, which may have impaired local immune response of the tissue, with an infectious, in this case fungal, inflammatory process. Based on the literature, this paper is the first report on the occurrence of two independent histotype testicular tumors and their associated mycosis. Full article
(This article belongs to the Special Issue Rare Fungal Infection Studies)
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13 pages, 5919 KiB  
Brief Report
Co-Occurrence of Anti-Synthetase Syndrome and Sjögren Disease: A Case-Based Review
by Andrea Pilato, Giorgio D’Avanzo, Francesca Di Nunzio, Annalisa Marino, Alessia Gallo, Irene Genovali, Letizia Pia Di Corcia, Chiara Taffon, Giuseppe Perrone, Vasiliki Liakouli, Luca Navarini, Roberto Giacomelli, Onorina Berardicurti and Raffaele Antonelli Incalzi
J. Clin. Med. 2025, 14(15), 5395; https://doi.org/10.3390/jcm14155395 - 31 Jul 2025
Viewed by 224
Abstract
Background: Anti-synthetase Syndrome (ASyS) is an idiopathic inflammatory myopathy characterized by muscle weakness and inflammatory infiltrates in muscles. Sjogren’s disease (SD) is an autoimmune condition primarily affecting exocrine glands. Both these conditions may present lung involvement. We describe a female patient with [...] Read more.
Background: Anti-synthetase Syndrome (ASyS) is an idiopathic inflammatory myopathy characterized by muscle weakness and inflammatory infiltrates in muscles. Sjogren’s disease (SD) is an autoimmune condition primarily affecting exocrine glands. Both these conditions may present lung involvement. We describe a female patient with anti-synthetase/SD overlap syndrome and review the literature to identify published cases describing this overlap, aiming to better define its clinical, radiological, and serological features. Methods: The case description was based on a retrospective collection of clinical, laboratory, and imaging data related to the patient’s diagnostic process and clinical course. Data were anonymized and handled in accordance with the competent territorial Ethics Committee. A literature review was performed using the MEDLINE and Scopus databases by combining the keywords “Anti-Synthetase syndrome”, “Sjögren disease”, “Sjögren syndrome”, “Myositis”, and “Interstitial lung disease” (ILD). Published cases were selected if they met the 2016 EULAR/ACR criteria for SD and at least one of the currently proposed classification criteria for ASyS. Results: The described case concerns a 68-year-old woman with rapidly progressive ILD. The diagnosis of anti-synthetase/SD overlap syndrome was based on clinical, serological (anti-Ro52 and anti-PL7 antibodies), histological, and radiological findings. Despite immunosuppressive and antifibrotic treatment, the clinical course worsened, leading to a poor outcome. In addition, six relevant cases were identified in the literature. Clinical presentations, autoantibody profiles, radiological findings, and outcomes were highly heterogeneous. Among the reported cases, no standardized treatment protocols were adopted, reflecting the lack of consensus in managing this rare condition. Conclusions: In anti-synthetase/SD overlap syndrome, ILD may follow a rapidly progressive course. Early recognition can be challenging, especially in the absence of muscular involvement. This case-based review highlights the need for more standardized approaches to the diagnosis and management of this rare and complex overlap syndrome. Full article
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22 pages, 1916 KiB  
Article
Freeze-Dried Probiotic Fermented Camel Milk Enriched with Ajwa Date Pulp: Evaluation of Functional Properties, Probiotic Viability, and In Vitro Antidiabetic and Anticancer Activities
by Sally S. Sakr and Hassan Barakat
Foods 2025, 14(15), 2698; https://doi.org/10.3390/foods14152698 - 31 Jul 2025
Viewed by 338
Abstract
Noncommunicable diseases (NCDs) like diabetes and cancer drive demand for therapeutic functional foods. This study developed freeze-dried fermented camel milk (FCM) with Ajwa date pulp (ADP), evaluating its physical and functional properties, probiotic survival, and potential benefits for diabetes and cancer. To achieve [...] Read more.
Noncommunicable diseases (NCDs) like diabetes and cancer drive demand for therapeutic functional foods. This study developed freeze-dried fermented camel milk (FCM) with Ajwa date pulp (ADP), evaluating its physical and functional properties, probiotic survival, and potential benefits for diabetes and cancer. To achieve this target, six FCM formulations were prepared using ABT-5 starter culture (containing Lactobacillus acidophilus, Bifidobacterium bifidum, and Streptococcus thermophilus) with or without Lacticaseibacillus rhamnosus B-1937 and ADP (12% or 15%). The samples were freeze-dried, and their functional properties, such as water activity, dispersibility, water absorption capacity, water absorption index, water solubility index, insolubility index, and sedimentation, were assessed. Reconstitution properties such as density, flowability, air content, porosity, loose bulk density, packed bulk density, particle density, carrier index, Hausner ratio, porosity, and density were examined. In addition, color and probiotic survivability under simulated gastrointestinal conditions were analyzed. Also, antidiabetic potential was assessed via α-amylase and α-glucosidase inhibition assays, while cytotoxicity was evaluated using the MTT assay on Caco-2 cells. The results show that ADP supplementation significantly improved dispersibility (up to 72.73% in FCM15D+L). These improvements are attributed to changes in particle size distribution and increased carbohydrate and mineral content, which facilitate powder rehydration and reduce clumping. All FCM variants demonstrated low water activity (0.196–0.226), indicating good potential for shelf stability. The reconstitution properties revealed that FCM powders with ADP had higher bulk and packed densities but lower particle density and porosity than controls. Including ADP reduced interstitial air and increased occluded air within the powders, which may minimize oxidation risks and improve packaging efficiency. ADP incorporation resulted in a significant decrease in lightness (L*) and increases in redness (a*) and yellowness (b*), with greater pigment and phenolic content at higher ADP levels. These changes reflect the natural colorants and browning reactions associated with ADP, leading to a more intense and visually distinct product. Probiotic survivability was higher in ADP-fortified samples, with L. acidophilus and B. bifidum showing resilience in intestinal conditions. The FCM15D+L formulation exhibited potent antidiabetic effects, with IC50 values of 111.43 μg mL−1 for α-amylase and 77.21 μg mL−1 for α-glucosidase activities, though lower than control FCM (8.37 and 10.74 μg mL−1, respectively). Cytotoxicity against Caco-2 cells was most potent in non-ADP samples (IC50: 82.22 μg mL−1 for FCM), suggesting ADP and L. rhamnosus may reduce antiproliferative effects due to proteolytic activity. In conclusion, the study demonstrates that ADP-enriched FCM is a promising functional food with enhanced probiotic viability, antidiabetic potential, and desirable physical properties. This work highlights the potential of camel milk and date synergies in combating some NCDs in vitro, suggesting potential for functional food application. Full article
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11 pages, 284 KiB  
Article
A Pragmatic Tele-Nursing Program Improves Satisfaction of Patients with Pulmonary Fibrosis and Their Caregivers—A Pilot Study
by Mireia Baiges, David Iglesias, Sara Persentili, Marta Jiménez, Pilar Ortega and Jaume Bordas-Martinez
Medicina 2025, 61(8), 1385; https://doi.org/10.3390/medicina61081385 - 30 Jul 2025
Viewed by 330
Abstract
Background and Objectives: Specialized nurses play an essential role in managing pulmonary fibrosis. While tele-nursing has the potential to optimize disease management, current evidence regarding its impact remains limited. This study aimed to evaluate a tele-nursing intervention that provided unscheduled access to [...] Read more.
Background and Objectives: Specialized nurses play an essential role in managing pulmonary fibrosis. While tele-nursing has the potential to optimize disease management, current evidence regarding its impact remains limited. This study aimed to evaluate a tele-nursing intervention that provided unscheduled access to a specialized nurse via phone or email for both patients and caregivers. Materials and Methods: This was a prospective, single-center, open-label, and pre–post pilot study. Participants and their caregivers were provided with direct access to a specialized nurse, by phone and email, for unscheduled consultations. Patient-reported experience measures (PREMs) and patient-reported outcome measures (PROMs) were collected at baseline and after three months of tele-nursing access. PREMs were assessed using a 10-point Likert scale questionnaire, and PROMs were evaluated using the King’s Brief Interstitial Lung Disease (K-BILD) and the Living with Pulmonary Fibrosis (L-PF) questionnaires. Results: A total of 47 patients with pulmonary fibrosis receiving antifibrotic drugs were enrolled. At three months, 44 patients and 34 caregivers completed the questionnaires. Four patients did not complete the study due to death, lung transplantation, or transition to end-of-life care. No significant changes were observed in PROMs. However, PREMs showed significant improvements, with most scores exceeding 9/10. Patient satisfaction increased by 28% (p < 0.001), and caregiver satisfaction by 30% (p < 0.001). Caregivers of patients who did not complete the study also reported high satisfaction, comparable to that of other caregivers. Conclusions: A pragmatic and affordable tele-nursing program, based on direct phone and email consultations, may enhance patient and caregiver satisfaction in the management of pulmonary fibrosis. Full article
(This article belongs to the Special Issue Advances in Interstitial Lung Diseases: From Diagnosis to Treatment)
14 pages, 1906 KiB  
Article
Integrating CT-Based Lung Fibrosis and MRI-Derived Right Ventricular Function for the Detection of Pulmonary Hypertension in Interstitial Lung Disease
by Kenichi Ito, Shingo Kato, Naofumi Yasuda, Shungo Sawamura, Kazuki Fukui, Tae Iwasawa, Takashi Ogura and Daisuke Utsunomiya
J. Clin. Med. 2025, 14(15), 5329; https://doi.org/10.3390/jcm14155329 - 28 Jul 2025
Viewed by 388
Abstract
Background/Objectives: Interstitial lung disease (ILD) is frequently complicated by pulmonary hypertension (PH), which is associated with reduced exercise capacity and poor prognosis. Early and accurate non-invasive detection of PH remains a clinical challenge. This study evaluated whether combining quantitative CT analysis of [...] Read more.
Background/Objectives: Interstitial lung disease (ILD) is frequently complicated by pulmonary hypertension (PH), which is associated with reduced exercise capacity and poor prognosis. Early and accurate non-invasive detection of PH remains a clinical challenge. This study evaluated whether combining quantitative CT analysis of lung fibrosis with cardiac MRI-derived measures of right ventricular (RV) function improves the diagnostic accuracy of PH in patients with ILD. Methods: We retrospectively analyzed 72 ILD patients who underwent chest CT, cardiac MRI, and right heart catheterization (RHC). Lung fibrosis was quantified using a Gaussian Histogram Normalized Correlation (GHNC) software that computed the proportions of diseased lung, ground-glass opacity (GGO), honeycombing, reticulation, consolidation, and emphysema. MRI was used to assess RV end-systolic volume (RVESV), ejection fraction, and RV longitudinal strain. PH was defined as a mean pulmonary arterial pressure (mPAP) ≥ 20 mmHg and pulmonary vascular resistance ≥ 3 Wood units on RHC. Results: Compared to patients without PH, those with PH (n = 21) showed significantly reduced RV strain (−13.4 ± 5.1% vs. −16.4 ± 5.2%, p = 0.026) and elevated RVESV (74.2 ± 18.3 mL vs. 59.5 ± 14.2 mL, p = 0.003). CT-derived indices also differed significantly: diseased lung area (56.4 ± 17.2% vs. 38.4 ± 12.5%, p < 0.001), GGO (11.8 ± 3.6% vs. 8.65 ± 4.3%, p = 0.005), and honeycombing (17.7 ± 4.9% vs. 12.8 ± 6.4%, p = 0.0027) were all more prominent in the PH group. In receiver operating characteristic curve analysis, diseased lung area demonstrated an area under the curve of 0.778 for detecting PH. This increased to 0.847 with the addition of RVESV, and further to 0.854 when RV strain was included. Combined models showed significant improvement in risk reclassification: net reclassification improvement was 0.700 (p = 0.002) with RVESV and 0.684 (p = 0.004) with RV strain; corresponding IDI values were 0.0887 (p = 0.03) and 0.1222 (p = 0.01), respectively. Conclusions: Combining CT-based fibrosis quantification with cardiac MRI-derived RV functional assessment enhances the non-invasive diagnosis of PH in ILD patients. This integrated imaging approach significantly improves diagnostic precision and may facilitate earlier, more targeted interventions in the management of ILD-associated PH. Full article
(This article belongs to the Section Nuclear Medicine & Radiology)
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13 pages, 1542 KiB  
Case Report
Reclassification of Seronegative Rheumatoid Arthritis as Anti-PL-12 Antisynthetase Syndrome with Interstitial Lung Disease and Joint Involvement–Case Report
by Diana Elena Cosău, Alexandru Dan Costache, Irina Iuliana Costache Enache, Ionela Lăcrămioara Șerban, Luiza Andreea Petrariu, Cristina Pomîrleanu, Mara Russu, Vladia Lăpuște and Codrina Ancuța
Reports 2025, 8(3), 123; https://doi.org/10.3390/reports8030123 - 26 Jul 2025
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Abstract
Background and Clinical Significance: Antisynthetase syndrome (ASyS) is a rare autoimmune entity defined by the presence of anti-aminoacyl-t ribonucleic acid (RNA) synthetase autoantibodies and classically associated with a triad of interstitial lung disease (ILD), inflammatory myopathy, and arthritis. Additional clinical features may include [...] Read more.
Background and Clinical Significance: Antisynthetase syndrome (ASyS) is a rare autoimmune entity defined by the presence of anti-aminoacyl-t ribonucleic acid (RNA) synthetase autoantibodies and classically associated with a triad of interstitial lung disease (ILD), inflammatory myopathy, and arthritis. Additional clinical features may include Raynaud’s phenomenon and “mechanic’s hands”. Among antisynthetase antibodies, anti-PL-12 is notably associated with predominant or isolated ILD and may occur in the absence of clinically evident myositis, thereby complicating timely diagnosis. Case Presentation: We are presenting a 45-year-old non-smoking female patient with a prior diagnosis of seronegative rheumatoid arthritis (RA) who developed progressive dyspnea, dry cough, and sicca symptoms. High-resolution computed tomography revealed a nonspecific interstitial pneumonia (NSIP) pattern. Despite normal creatine kinase and lactate dehydrogenase levels, serological work-up revealed positive anti-PL-12 and anti-Ro52 antibodies, supporting a diagnosis of antisynthetase syndrome without myositis, fulfilling the diagnostic criteria for ASyS per Connors and Solomon. Treatment with corticosteroids and cyclophosphamide induced clinical and functional respiratory improvement, while azathioprine was initiated for maintenance. Conclusions: This case underscores the clinical heterogeneity of antisynthetase syndrome and highlights the diagnostic challenge posed by anti-PL-12–associated ILD in the absence of myositis. Importantly, it demonstrates that in patients with pre-existing rheumatologic diagnoses, the emergence of atypical pulmonary manifestations warrants repeat serologic evaluation to assess ASyS and other autoimmune conditions. Early diagnosis and immunosuppressive treatment are essential to optimize outcomes. Full article
(This article belongs to the Section Critical Care/Emergency Medicine/Pulmonary)
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10 pages, 351 KiB  
Article
Role of Antipseudomonal Antibiotics in Older Patients with Aspiration Pneumonia: A Nationwide Database Study in Japan
by Ryohei Kudoh, Daisuke Yoneoka, Akihiko Hagiwara, Hisayuki Shuto, Shota Omori, Kiyohide Fushimi and Kosaku Komiya
Antibiotics 2025, 14(8), 743; https://doi.org/10.3390/antibiotics14080743 - 24 Jul 2025
Viewed by 298
Abstract
Background: Aspiration pneumonia is increasingly recognized as a fatal pulmonary disease among older people. Although antipseudomonal antibiotics are commonly used in clinical practice, their efficacy in this population remains uncertain. Methods: Nationwide data collected from patients aged ≥65 years who were [...] Read more.
Background: Aspiration pneumonia is increasingly recognized as a fatal pulmonary disease among older people. Although antipseudomonal antibiotics are commonly used in clinical practice, their efficacy in this population remains uncertain. Methods: Nationwide data collected from patients aged ≥65 years who were hospitalized due to aspiration pneumonia from January 2018 to December 2018 were analyzed. The in-hospital mortality between patients who received antipseudomonal antibiotics within 3 days of hospital admission and those who did not were compared. A logistic regression analysis was performed to assess the effect of antipseudomonal antibiotics on in-hospital mortality after adjusting for potential prognostic confounders. Results: This study included 46,980 patients, and 13,340 (28.4%) patients received antipseudomonal antibiotics. In total, 7011 (14.9%) patients died during hospitalization. Advanced age, male sex, a lower body mass index, decreased Barthel Index, impaired consciousness, interstitial pneumonia, malignancy, renal failure, and use of immunosuppressive agents were significantly associated with increased in-hospital mortality. After adjusting for the confounders, the use of antipseudomonal antibiotics was found to be associated with an elevated in-hospital mortality (odds ratio: 1.33; 95% confidence interval: 1.26–1.41; p < 0.001). Conclusions: In this nationwide data analysis of older patients with aspiration pneumonia, early antipseudomonal antibiotic administration did not improve prognosis. Therefore, the routine use of antipseudomonal antibiotics should be avoided in older patients with aspiration pneumonia. Full article
(This article belongs to the Special Issue Antibiotic Therapy in Respiratory Tract Infections (RTIs))
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