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18 pages, 5419 KiB  
Article
Molecular Surveillance and Whole Genomic Characterization of Bovine Rotavirus A G6P[1] Reveals Interspecies Reassortment with Human and Feline Strains in China
by Ahmed H. Ghonaim, Mingkai Lei, Yang Zeng, Qian Xu, Bo Hong, Dongfan Li, Zhengxin Yang, Jiaru Zhou, Changcheng Liu, Qigai He, Yufei Zhang and Wentao Li
Vet. Sci. 2025, 12(8), 742; https://doi.org/10.3390/vetsci12080742 (registering DOI) - 7 Aug 2025
Abstract
Group A rotavirus (RVA) is a leading causative agent of diarrhea in both young animals and humans. In China, multiple genotypes are commonly found within the bovine population. In this study, we investigated 1917 fecal samples from calves with diarrhea between 2022 and [...] Read more.
Group A rotavirus (RVA) is a leading causative agent of diarrhea in both young animals and humans. In China, multiple genotypes are commonly found within the bovine population. In this study, we investigated 1917 fecal samples from calves with diarrhea between 2022 and 2025, with 695 testing positive for RVA, yielding an overall detection rate of 36.25%. The highest positivity rate was observed in Hohhot (38.98%), and annual detection rates ranged from 26.75% in 2022 to 42.22% in 2025. A bovine rotavirus (BRV) strain, designated 0205HG, was successfully isolated from a fecal sample of a newborn calf. Its presence was confirmed through cytopathic effects (CPEs), the indirect immunofluorescence assay (IFA), electron microscopy (EM), and high-throughput sequencing. Genomic characterization identified the strain as having the G6-P[1]-I2-R2-C2-M2-A3-N2-T6-E2-H3 genotype constellation. The structural proteins VP2 and VP7, along with nonstructural genes NSP1–NSP4, shared high sequence identity with Chinese bovine strains, whereas VP1, VP4, and NSP5 clustered more closely with human rotaviruses, and VP3 was related to feline strains. These findings highlight the genetic diversity and interspecies reassortment of BRVs in China, underlining the importance of continued surveillance and evolutionary analysis. Full article
(This article belongs to the Special Issue Viral Infections in Wild and Domestic Animals)
14 pages, 3230 KiB  
Article
CFAP300 Loss-of-Function Mutations with Primary Ciliary Dyskinesia: Evidence from Ex Vivo and ALI Cultures
by Anna G. Demchenko, Tatiana A. Kyian, Elena I. Kondratyeva, Elizaveta E. Bragina, Oksana P. Ryzhkova, Roman V. Veiko, Aleksandra G. Nazarova, Vyacheslav B. Chernykh, Svetlana A. Smirnikhina and Sergey I. Kutsev
Int. J. Mol. Sci. 2025, 26(15), 7655; https://doi.org/10.3390/ijms26157655 (registering DOI) - 7 Aug 2025
Abstract
Primary ciliary dyskinesia (PCD) is a genetically heterogeneous disorder characterized by impaired mucociliary clearance due to defects in motile cilia. This study investigates the impact of loss-of-function mutations in the CFAP300 gene on the ciliary structure and function in three PCD patients. Using [...] Read more.
Primary ciliary dyskinesia (PCD) is a genetically heterogeneous disorder characterized by impaired mucociliary clearance due to defects in motile cilia. This study investigates the impact of loss-of-function mutations in the CFAP300 gene on the ciliary structure and function in three PCD patients. Using a multimodal approach, we integrated molecular genetic testing, transmission electron microscopy, the high-speed video microscopy assay and immunofluorescence staining to analyze ciliary motility and protein expression in both ex vivo and in vitro-obtained ciliary cells. Our results revealed that the pathogenic variant c.198_200delinsCC (p.Phe67ProfsTer10) in CFAP300 led to the absence of the functional CFAP300 protein, the complete loss of outer and inner dynein arms and immotile cilia. Air–liquid interface (ALI)-cultured cells from patients exhibited no ciliary beating, contrasting with healthy controls. Immunostaining confirmed the absence of CFAP300 in patient-derived cilia, underscoring its critical role in dynein arm assembly. These findings highlight the diagnostic utility of ALI cultures combined with functional and protein analyses for PCD, offering a clinically actionable framework that can be readily incorporated into standard diagnostic workflows. Full article
(This article belongs to the Special Issue Molecular and Cellular Therapeutics for Respiratory Diseases)
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19 pages, 544 KiB  
Review
Epidemiology, Clinical Data, and Management of Aseptic Abscess Syndrome: Review of Published Cases Outside France
by Gerasimos Eleftheriotis, Michaela Fragonikolaki, Chrysi Karelaki, Ergina Syrigou, Spyridon Georgiadis, Kyriaki Georgiadi and Elias Skopelitis
Epidemiologia 2025, 6(3), 44; https://doi.org/10.3390/epidemiologia6030044 - 7 Aug 2025
Abstract
Aseptic abscess syndrome is a clinical entity that is being increasingly documented. Unfortunately, apart from the French registry, there are no other studies presenting collective data. In this review, we sought to analyze clinical and laboratory data from case reports published from the [...] Read more.
Aseptic abscess syndrome is a clinical entity that is being increasingly documented. Unfortunately, apart from the French registry, there are no other studies presenting collective data. In this review, we sought to analyze clinical and laboratory data from case reports published from the rest of the world. A total of 107 articles were found through our literature search in PubMed, Scopus, and Google, which contained 108 patients who met our eligibility criteria, including pediatric cases. The mean age at diagnosis was 39.1 years, and 54.6% of the patients were female. Cases were found affecting almost every organ, but the most common abscess locations were the spleen (51.9%), liver (35.2%), and lung (23.1%); 34.3% of the patients had multiorgan disease at diagnosis. An inflammatory syndrome was evident, with fever (79.6%), pain (66.7%), median white blood cell count of 16,200/μL, median C-reactive protein level of 15.5 mg/dL, and mean erythrocyte sedimentation rate of 79 mm/h. In total, 88.9% had an associated disease, with the most frequent being neutrophilic dermatosis (43.5%) and inflammatory bowel disease (31.5%); associated disease was inactive during abscess diagnosis in approximately one-quarter of patients. Moreover, 93.5% received corticosteroids with or without other agents, while 21.3% underwent excision surgery, which led to relapse if immunosuppressants were not concomitantly administered. No deaths were reported due to the syndrome, but 42.4% of cases that provided relevant data relapsed despite the relatively short follow-up period (median 1 year), either in the same or different organs. Combined immunomodulatory treatment, based on subgroup analysis, appeared protective against relapse in females and patients with splenic abscess or C-reactive protein >12 mg/dL (odds ratio 0.16 [95% CI 0.04–0.59]/p = 0.004, 0.09 [95% CI 0.01–0.62]/p = 0.008 and 0.23 [95% CI 0.06–0.92]/p = 0.03, respectively). Infection should always be the working diagnosis in patients with abscesses. However, if the infectious workup is negative, antimicrobials have failed, and no sepsis is present, then aseptic abscess syndrome should be considered; response to high-dose corticosteroids is a therapeutic criterion in almost all cases. Full article
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9 pages, 680 KiB  
Case Report
Borderline Oxacillin-Resistant Staphylococcus aureus (BORSA) Bacteremia—Case Report
by Beverly Buffart, Philippe Clevenbergh, Alina Stiuliuc, Ioannis Raftakis, Mony Hing, Véronique Yvette Miendje Deyi, Olivier Denis, Delphine Martiny and Nicolas Yin
Antibiotics 2025, 14(8), 809; https://doi.org/10.3390/antibiotics14080809 - 7 Aug 2025
Abstract
Introduction: Borderline oxacillin-resistant Staphylococcus aureus (BORSA) represents a rare and poorly characterized phenotype of S. aureus. Its detection remains challenging, even in modern clinical laboratories. Moreover, there is no consensus on the optimal therapeutic approach, and treatment strategies remain controversial. In [...] Read more.
Introduction: Borderline oxacillin-resistant Staphylococcus aureus (BORSA) represents a rare and poorly characterized phenotype of S. aureus. Its detection remains challenging, even in modern clinical laboratories. Moreover, there is no consensus on the optimal therapeutic approach, and treatment strategies remain controversial. In this report, we present a rare case of BORSA bacteremia and discuss potential approaches to improve its detection and management. Case presentation: A 39-year-old woman with systemic lupus erythematosus was admitted for a suspected exacerbation, complicated by multiple serositis and nephritis. She was on chronic treatment with methylprednisolone and hydroxychloroquine. On admission, she was afebrile. Laboratory investigations revealed elevated C-reactive protein and increased D-dimer levels. Later, she developed a septic peripheral venous thrombophlebitis, and treatment was adjusted to amoxicillin–clavulanate. Blood cultures grew S. aureus, prompting a switch to intravenous oxacillin based on a negative penicillin-binding protein 2a test. A discrepancy in the antimicrobial susceptibility test was observed, with cefoxitin showing susceptibility and oxacillin resistance. Further characterizations were carried out, confirming a BORSA infection. Treatment was switched to linezolid and ciprofloxacin with good recovery. Conclusions: This case highlights the complexity of managing a patient with an uncommon and poorly documented infection. The lack of data on BORSA infections and the difficulties in detecting and treating them led to a prolonged delay in the appropriate management of this patient. Full article
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21 pages, 2994 KiB  
Article
A Multi-Omics Integration Framework with Automated Machine Learning Identifies Peripheral Immune-Coagulation Biomarkers for Schizophrenia Risk Stratification
by Feitong Hong, Qiuming Chen, Xinwei Luo, Sijia Xie, Yijie Wei, Xiaolong Li, Kexin Li, Benjamin Lebeau, Crystal Ling, Fuying Dao, Hao Lin, Lixia Tang, Mi Yang and Hao Lv
Int. J. Mol. Sci. 2025, 26(15), 7640; https://doi.org/10.3390/ijms26157640 - 7 Aug 2025
Abstract
Schizophrenia (SCZ) is a complex psychiatric disorder with heterogeneous molecular underpinnings that remain poorly resolved by conventional single-omics approaches, limiting biomarker discovery and mechanistic insights. To address this gap, we applied an artificial intelligence (AI)-driven multi-omics framework to an open access dataset comprising [...] Read more.
Schizophrenia (SCZ) is a complex psychiatric disorder with heterogeneous molecular underpinnings that remain poorly resolved by conventional single-omics approaches, limiting biomarker discovery and mechanistic insights. To address this gap, we applied an artificial intelligence (AI)-driven multi-omics framework to an open access dataset comprising plasma proteomics, post-translational modifications (PTMs), and metabolomics to systematically dissect SCZ pathophysiology. In a cohort of 104 individuals, comparative analysis of 17 machine learning models revealed that multi-omics integration significantly enhanced classification performance, reaching a maximum AUC of 0.9727 (95% CI: 0.8889–1.000) using LightGBMXT, compared to 0.9636 (95% CI: 0.8636–1.0000) with CNNBiLSTM for proteomics alone. Interpretable feature prioritization identified carbamylation at immunoglobulin-constant region sites IGKC_K20 and IGHG1_K8, alongside oxidation of coagulation factor F10 at residue M8, as key discriminative molecular events. Functional analyses identified significantly enriched pathways including complement activation, platelet signaling, and gut microbiota-associated metabolism. Protein interaction networks further implicated coagulation factors F2, F10, and PLG, as well as complement regulators CFI and C9, as central molecular hubs. The clustering of these molecules highlights a potential axis linking immune activation, blood coagulation, and tissue homeostasis, biological domains increasingly recognized in psychiatric disorders. These results implicate immune–thrombotic dysregulation as a critical component of SCZ pathology, with PTMs of immune proteins serving as quantifiable disease indicators. Our work delineates a robust computational strategy for multi-omics integration into psychiatric research, offering biomarker candidates that warrant further validation for diagnostic and therapeutic applications. Full article
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14 pages, 2857 KiB  
Article
Identification of the MADS-Box Gene Family and Development of Simple Sequence Repeat Markers in Chimonanthus praecox
by Huafeng Wu, Bin Liu, Yinzhu Cao, Guanpeng Ma, Xiaowen Zheng, Ximeng Yang, Qianli Dai, Hengxing Zhu, Haoxiang Zhu, Xingrong Song and Shunzhao Sui
Plants 2025, 14(15), 2450; https://doi.org/10.3390/plants14152450 - 7 Aug 2025
Abstract
Chimonanthus praecox, a traditional ornamental plant in China, is admired for its ability to bloom during the cold winter season and is recognized as an outstanding woody cut flower. MADS-box genes encode transcription factors essential for plant growth and development, with key [...] Read more.
Chimonanthus praecox, a traditional ornamental plant in China, is admired for its ability to bloom during the cold winter season and is recognized as an outstanding woody cut flower. MADS-box genes encode transcription factors essential for plant growth and development, with key functions in regulating flowering time and the formation of floral organs. In this study, 74 MADS-box genes (CpMADS1–CpMADS74) were identified and mapped across 11 chromosomes, with chromosome 1 harboring the highest number (13 genes) and chromosome 3 the fewest (3 genes). Physicochemical property analysis revealed that all CpMADS proteins are hydrophilic and predominantly nuclear-localized. Phylogenetic analysis classified these genes into Type I and Type II subfamilies, highlighting a clear divergence in domain structure. Eighty simple sequence repeat (SSR) loci were detected, with dinucleotide repeats being the most abundant, and the majority located in Type II MADS genes. From 23 C. praecox samples, 10 polymorphic SSR markers were successfully developed and PCR-validated, enabling a cluster analysis that grouped these cultivars into three distinct clusters. This study offers significant insights into the regulation of flowering, floral organ development, genetic linkage map construction, and the application of marker-assisted selection in C. praecox. Full article
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18 pages, 2972 KiB  
Article
Flavonoids from Cercidiphyllum japonicum Exhibit Bioactive Potential Against Skin Aging and Inflammation in Human Dermal Fibroblasts
by Minseo Kang, Sanghyun Lee, Dae Sik Jang, Sullim Lee and Daeyoung Kim
Curr. Issues Mol. Biol. 2025, 47(8), 631; https://doi.org/10.3390/cimb47080631 - 7 Aug 2025
Abstract
With increasing interest in natural therapeutic strategies for skin aging, plant-derived compounds have gained attention for their potential to protect against oxidative stress and inflammation. In this study, we investigated the anti-aging and anti-inflammatory effects of flavonoids isolated from Cercidiphyllum japonicum using a [...] Read more.
With increasing interest in natural therapeutic strategies for skin aging, plant-derived compounds have gained attention for their potential to protect against oxidative stress and inflammation. In this study, we investigated the anti-aging and anti-inflammatory effects of flavonoids isolated from Cercidiphyllum japonicum using a tumor necrosis factor-alpha (TNF-α)-stimulated normal human dermal fibroblast (NHDF) model. The aerial parts of C. japonicum were extracted and analyzed by high-performance liquid chromatography (HPLC), leading to the identification of four major compounds: maltol, chlorogenic acid, ellagic acid, and quercitrin. Each compound was evaluated for its antioxidant and anti-aging activities in TNF-α-stimulated NHDFs. Among them, ellagic acid exhibited the most potent biological activity and was selected for further mechanistic analysis. Ellagic acid significantly suppressed intracellular reactive oxygen species (ROS) generation and matrix metalloproteinase-1 (MMP-1) secretion (both p < 0.001), while markedly increasing type I procollagen production (p < 0.01). Mechanistic studies demonstrated that ellagic acid inhibited TNF-α-induced phosphorylation of mitogen-activated protein kinases (MAPKs), downregulated cyclooxygenase-2 (COX-2), and upregulated heme oxygenase-1 (HO-1), a key antioxidant enzyme. Additionally, ellagic acid attenuated the mRNA expression of inflammatory cytokines, including interleukin-6 (IL-6) and interleukin-8 (IL-8), indicating its broad modulatory effects on oxidative and inflammatory pathways. Collectively, these findings suggest that ellagic acid is a promising plant-derived bioactive compound with strong antioxidant and anti-inflammatory properties, offering potential as a therapeutic agent for the prevention and treatment of skin aging. Full article
(This article belongs to the Section Bioorganic Chemistry and Medicinal Chemistry)
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13 pages, 1472 KiB  
Article
Effect of Hydrothermal Pretreatment Time on Biochemical Recovery and Hydrogen Production from Lignocellulosic Feedstocks
by Amer Rouabhia, Carlos José Álvarez-Gallego and Luis Alberto Fernández-Güelfo
Appl. Sci. 2025, 15(15), 8736; https://doi.org/10.3390/app15158736 - 7 Aug 2025
Abstract
This study examines the impact of hydrothermal pretreatment operation time (10, 20, and 30 min) on the following four lignocellulosic feedstocks with different lignin content: sugar beet pulp (SBP), brewers spent grain (BSG), orange peel (OP), and rice husk (RH). The objective of [...] Read more.
This study examines the impact of hydrothermal pretreatment operation time (10, 20, and 30 min) on the following four lignocellulosic feedstocks with different lignin content: sugar beet pulp (SBP), brewers spent grain (BSG), orange peel (OP), and rice husk (RH). The objective of pretreatment is twofold, as follows: (1) to enhance the organic matter solubilization and the release of value-added bioproducts, such as total reducing sugars (TRS), total proteins (PR), and volatile fatty acids (VFAs); and (2) to improve VFA and hydrogen production during a subsequent stage of acidogenic anaerobic digestion (Dark Fermentation, DF). In this context, OP reported the highest overall yields across all pretreatment durations. Specifically, at 30 min, it achieved a maximum solubilization of 57.3 gO2/L in terms of soluble chemical oxygen demand (sCOD), 19.1 gTRS/L and 20.6 gPR/L. Regarding VFA and hydrogen production via dark fermentation, the best results were obtained with SBP pretreated for 20 and 30 min, yielding 15.1 g H-Ac/L and 97.5 mL H2 (n.c.)/g (d.m.), respectively. BSG displayed an intermediate performance, whereas RH consistently showed the lowest yields across all evaluated parameters, primarily due to its high lignin content. These findings highlight the pivotal role of pretreatment duration in the valorization of lignocellulosic biomasses, primarily aimed at the recovery of high-value-added biochemicals and biofuels, such as hydrogen, thereby supporting the development of integrated biorefinery systems. Full article
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20 pages, 5618 KiB  
Article
Age-Related Mitochondrial Alterations Contribute to Myocardial Responses During Sepsis
by Jiayue Du, Qing Yu, Olufisayo E. Anjorin and Meijing Wang
Cells 2025, 14(15), 1221; https://doi.org/10.3390/cells14151221 - 7 Aug 2025
Abstract
Sepsis-induced myocardial injury is age-related and leads to increased mortality. Considering the importance of mitochondrial dysfunction in cardiac impairment, we aimed to investigate whether aging exacerbates the cardiac mitochondrial metabolic response to inflammation, thus leading to increased cardiac dysfunction in the elderly. Cecal [...] Read more.
Sepsis-induced myocardial injury is age-related and leads to increased mortality. Considering the importance of mitochondrial dysfunction in cardiac impairment, we aimed to investigate whether aging exacerbates the cardiac mitochondrial metabolic response to inflammation, thus leading to increased cardiac dysfunction in the elderly. Cecal ligation and puncture (CLP) was conducted in young adult (12–18 weeks) and aged (19–21 months) male C57BL/6 mice. Cardiac function was detected 20 h post-CLP. Additionally, cardiomyocytes isolated from young adult and aged male mice were used for assessments of mitochondrial respiratory function +/– TNFα or LPS. Protein levels of oxidative phosphorylation (OXPHOS), NADPH oxidase (NOX)2, NOX4, phosphor-STAT3 and STAT3 were determined in mouse hearts 24 h post-CLP and in cardiomyocytes following inflammatory stimuli. CLP significantly reduced cardiac contractility in both young and aged mice, with a higher incidence and greater severity of cardiac functional depression in the older group. Mitochondrial respiratory capacity was decreased in cardiomyocytes derived from aged mice, with increased susceptible to inflammatory toxic effects compared to those from young adult mice. The age-dependent changes were observed in myocardial OXPHOS complexes and NOX4. Importantly, CLP led to a significant increase in OXPHOS protein levels in the hearts of older mice, suggesting a possible compensatory response to decreased mitochondrial metabolic function and a greater potential for reactive oxygen species (ROS) generation. Our findings highlight that the response of aging-impaired mitochondria to inflammation may underlie the worsened cardiac functional depression in the aged group during sepsis. Full article
(This article belongs to the Section Cellular Aging)
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14 pages, 632 KiB  
Article
Protein Polarimetry, Perfected: Specific Rotation Measurement for the Refracto-Polarimetric Detection of Cryptic Protein Denaturation
by Lisa Riedlsperger, Heinz Anderle, Andreas Schwaighofer and Martin Lemmerer
Biophysica 2025, 5(3), 34; https://doi.org/10.3390/biophysica5030034 - 7 Aug 2025
Abstract
Protein polarimetry has been evaluated as a simple and straightforward technique to detect the cryptic denaturation of exemplary proteins. The general rules of rotation vs. amino acid and structural composition and the respective knowledge gaps were reviewed, and the specific rotation of cystine [...] Read more.
Protein polarimetry has been evaluated as a simple and straightforward technique to detect the cryptic denaturation of exemplary proteins. The general rules of rotation vs. amino acid and structural composition and the respective knowledge gaps were reviewed, and the specific rotation of cystine was determined in 4 M NaCl solution as [α]D20 = –302.5°. The specific rotations at 589 nm and 436 nm and the ratio were measured for several model proteins, some purified plasma-derived proteins and for three monoclonal antibodies. The immunoglobulin G concentrates all showed a narrow ratio range likely characteristic for this protein class. Heat denaturation experiments were conducted at temperatures between 50 and 85 °C both for short-time (10 min) and for prolonged periods of heat exposure (up to 210 min). Denaturation by heat resulted not only in the known levorotatory shift, but also in a shift in the specific rotation ratio. The stabilizing effect of fatty acids in bovine serum could be demonstrated by this parameter. Polarimetry thus appears to be a particularly sensitive and simple method for the characterization of the identity and the thermal stability of proteins and should therefore be added again as a complimentary method to the toolbox of protein chemistry. Full article
(This article belongs to the Special Issue Investigations into Protein Structure)
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20 pages, 4401 KiB  
Article
Effect of Slightly Acidic Electrolyzed Water Combined with Nano-Bubble Sterilization on Quality of Larimichthys crocea During Refrigerated Storage
by Jiehui Zhong, Hongjin Deng, Na Lin, Mengyao Zheng, Junjie Wu, Quanyou Guo and Saikun Pan
Foods 2025, 14(15), 2754; https://doi.org/10.3390/foods14152754 - 7 Aug 2025
Abstract
The large yellow croaker (Larimichthys crocea) is susceptible to microbial contamination during storage due to its high protein and moisture contents. This study was designed to find a new way to reduce bacteria in large yellow croakers by combining slightly acidic [...] Read more.
The large yellow croaker (Larimichthys crocea) is susceptible to microbial contamination during storage due to its high protein and moisture contents. This study was designed to find a new way to reduce bacteria in large yellow croakers by combining slightly acidic electrolyzed water (SAEW) with nano-bubble (NB) technology. Exploring the effects of available chlorine concentration (ACC), processing time, and water temperature on the bacteria reduction effect of the SAEW-NB treatment for large yellow croakers. Also, the effects of the SAEW-NB combined treatment on sensory evaluation, total viable counts (TVCs), total volatile basic nitrogen (TVB-N), texture, taste profile, and volatile flavor compounds of large yellow croakers were analyzed during the storage period at 4 °C. The results show that the SAEW-NB treatment achieved significantly enhanced microbial reduction compared to individual treatments. Under the conditions of a 4 °C water temperature, 40 mg/L ACC, and 15 min treatment, the SAEW-NB treatment inhibited the increases in physical and chemical indexes such as TVC and TVB-N, maintained the fish texture, and delayed the production of off-flavor volatiles such as aldehydes, alcohols, esters, and ketones, compared with the control group (CG) during storage at 4 °C. In conclusion, the SAEW-NB treatment could better retard fish spoilage, extending the shelf life by approximately 2 days. It might be a promising new industrial approach for large yellow croakers’ storage. Full article
(This article belongs to the Special Issue Innovative Muscle Foods Preservation and Packaging Technologies)
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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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18 pages, 1256 KiB  
Article
Longitudinal Assessment of Body Composition and Inflammatory Status in Rheumatoid Arthritis During TNF Inhibitor Treatment: A Pilot Study
by Natalia Mena-Vázquez, Aimara García-Studer, Fernando Ortiz-Márquez, Sara Manrique-Arija, Arkaitz Mucientes, Jose Manuel Lisbona-Montañez, Paula Borregón-Garrido, Patricia Ruiz-Limón, Rocío Redondo-Rodriguez, Laura Cano-García and Antonio Fernández-Nebro
Int. J. Mol. Sci. 2025, 26(15), 7635; https://doi.org/10.3390/ijms26157635 - 7 Aug 2025
Abstract
Rheumatoid arthritis (RA) is a chronic inflammatory disease frequently associated with alterations in body composition, including reduced lean mass and increased fat mass. These alterations are thought to be driven by persistent systemic inflammation, which may be influenced by inflammatory activity and by [...] Read more.
Rheumatoid arthritis (RA) is a chronic inflammatory disease frequently associated with alterations in body composition, including reduced lean mass and increased fat mass. These alterations are thought to be driven by persistent systemic inflammation, which may be influenced by inflammatory activity and by therapeutic interventions. Objectives: This pilot study aimed to provide preliminary data on changes in body composition and inflammatory activity in biologic-naive patients with active RA during the initial 6 months of TNF inhibitor treatment, and to compare baseline body composition with healthy controls. We conducted a single-center, observational, 24-week pilot study of 70 biologic-naive RA patients with moderate-to-severe disease activity and 70 matched healthy controls. Lean mass, fat mass, and lean mass index (LMI) were measured using dual-energy X-ray absorptiometry at baseline for both groups, and after 6 months only in the RA group. Clinical, laboratory, adipokines, and cytokine parameters were also recorded. At baseline, RA patients had lower lean mass and LMI than controls. Over 6 months, RA patients showed significant clinical and laboratory improvement, with a corresponding increase in lean mass and LMI. No statistically significant change was observed in fat mass. The increase in lean mass was paralleled by a reduction in inflammatory markers. The LMI was inversely associated with female sex (β = −0.562) and C-reactive protein (β = −0.432) and directly associated with body mass index (β = 0.570). Similar associations were observed for total lean mass and change in lean mass, as well as for DAS28 (β = −0.333). This pilot study provides preliminary evidence that TNF inhibitor therapy may be associated with increased lean mass and decreased inflammation in RA patients. Owing to the absence of a comparator RA group not receiving TNF inhibitors, these findings should be interpreted as hypothesis-generating. Full article
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20 pages, 23943 KiB  
Article
A Novel Cysteine Protease from Phytolacca americana Cleaves Pokeweed Antiviral Protein Generating Bioactive Fragments
by Annabelle Audet, Jennifer A. Chivers and Katalin A. Hudak
Plants 2025, 14(15), 2441; https://doi.org/10.3390/plants14152441 - 7 Aug 2025
Abstract
The apoplast is often the first point of contact between plant cells and invading pathogens, serving as an important site for defense signaling. Pokeweed antiviral protein (PAP), a ribosome-inactivating protein from Phytolacca americana (pokeweed), is localized to the apoplast and is hypothesized to [...] Read more.
The apoplast is often the first point of contact between plant cells and invading pathogens, serving as an important site for defense signaling. Pokeweed antiviral protein (PAP), a ribosome-inactivating protein from Phytolacca americana (pokeweed), is localized to the apoplast and is hypothesized to accompany a pathogen to the cytosol, where it would inactivate host ribosomes to prevent pathogen spread. However, it is not known whether PAP interacts with other proteins in the apoplast. In this study, we identified Phytolacca americana cysteine protease 1 (PaCP1), an extracellular cysteine protease, as a novel PAP interactor. Sequence and structural analyses classified PaCP1 as a member of the C1A subfamily of papain-like cysteine proteases. Immunoprecipitation, mass spectrometry, and yeast two-hybrid analysis showed that PAP specifically binds the mature, active form of PaCP1. Curiously, PaCP1 cleaves PAP at its N- and C-termini, generating peptides that enhance MAPK phosphorylation in pokeweed leaves, indicating their potential role in stress signaling. PaCP1 processing of PAP to generate bioactive peptides diversifies the function of a ribosome-inactivating protein beyond its canonical inhibition of translation. Our findings present a novel extracellular role for PAP and advance our understanding of how protein interactions in the apoplast contribute to plant immune responses. Full article
(This article belongs to the Section Plant Molecular Biology)
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14 pages, 1372 KiB  
Article
Risk Factors of Histopathological Crescent Formation in Pediatric IgA Vasculitis Nephritis
by Yanyan Jin, Yi Xie, Qian Lin, Yu Zhu, Limin Huang, Yang He and Haidong Fu
Medicina 2025, 61(8), 1421; https://doi.org/10.3390/medicina61081421 - 6 Aug 2025
Abstract
Background and Objectives: This study aimed to explore the risk factors of histopathological crescent formation in pediatric IgA vasculitis nephritis (IgAVN). Materials and Methods: Enrolled patients with biopsy-proven IgAVN from Zhejiang University’s hospital were split into two groups: 377 with no [...] Read more.
Background and Objectives: This study aimed to explore the risk factors of histopathological crescent formation in pediatric IgA vasculitis nephritis (IgAVN). Materials and Methods: Enrolled patients with biopsy-proven IgAVN from Zhejiang University’s hospital were split into two groups: 377 with no crescents on histopathology (Group 1) and 364 with crescentic nephritis (Group 2). Collected data included clinical features, lab indicators, histopathological grading, and factors causing glomerular sclerosis. Logistic regression was used to assess factors affecting crescent formation in IgAVN. Double-immunofluorescence assay was used to detect TGF-β1, MCP-1, α-SMA, Collagen I, and FN1 in kidney biopsy specimens. The relationship between kidney fibrosis factors and histopathological grade were analyzed using Chi-square and Pearson tests. Results: A total of 741 patients with IgAVN were included in the study. Univariate logistic regression identified potential factors related to crescent formation, including age, gender, clinical classification, hematuria grade, 24 h urine protein level, peripheral white blood cells (WBCs), serum albumin, Cystatin-C, APTT, and PT. Multivariate analysis revealed statistical significance for age, 24 h urine protein, and WBCs across pathological grades (p < 0.05). Mantel–Haenszel Chi-square tests indicated a linear relationship between IgAVN pathological grade and α-SMA, TGF-β1, MCP-1, and FN1. Pearson correlation analysis confirmed a positive correlation between pathological grade and these markers. Conclusions: Age, 24 h urinary protein, and blood WBCs are identified as risk factors for histopathological crescent formation in children with IgAVN. Additionally, a higher pathological grade is associated with more pronounced fibrosis indicators. Full article
(This article belongs to the Section Pediatrics)
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