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20 pages, 4430 KB  
Article
The N-Terminal Extension of the Mycobacterium avium Rel Protein Is a Dual Regulator of the Bifunctional Enzyme and Represents a Novel Target
by Tuck Choy Fong, Priya Ragunathan, Reema Alag, Carlos Silvester, Svarika Sonthalia, Vikneswaran Mathiyazakan, Vandana Grover and Gerhard Grüber
Antibiotics 2025, 14(10), 964; https://doi.org/10.3390/antibiotics14100964 - 25 Sep 2025
Abstract
Background: Mycobacterium avium (Mav) is a leading cause of pulmonary disease among non-tuberculous mycobacteria (NTMs) due to its extensive antibiotic resistance profile. The essential Rel protein is a bifunctional enzyme, which is sensitive to environmental stress and regulates cellular guanosine-3′,5′-bispyrophosphate [...] Read more.
Background: Mycobacterium avium (Mav) is a leading cause of pulmonary disease among non-tuberculous mycobacteria (NTMs) due to its extensive antibiotic resistance profile. The essential Rel protein is a bifunctional enzyme, which is sensitive to environmental stress and regulates cellular guanosine-3′,5′-bispyrophosphate ((p)ppGpp). Increased levels of the alarmone thereby initiate a survival response, contributing to bacterial persistence and virulence. Objectives: MavRel harbors an unusual extension at the N-terminal domain (NTD), which we aim to characterize its possible regulatory role in maintaining (p)ppGpp homeostasis. We also studied whether the TGS domain retains its regulation capacity in MavRel and the binding propensity of the ACT domain to valine. Methods: Molecular dissection of MavRel was performed to generate a series of truncates to quantify the synthetase and hydrolase activities. Binding experiments with tRNA and valine were carried out via tryptophan quenching assay and NMR, respectively. Results: Bi-catalytic regulation of MavRel was found to be predominantly governed by the residues 37–50 at the NTD extension in its free state. The TGS domain was shown to harbor the capacity to bind with deacylated tRNA and represses synthetase activity to a lower degree compared to the NTD extension. We also characterized the dimeric Mav ACT-domain and the interacting residues contributing to its affinity with valine to function as a nutrient sensor. Conclusions: The mapping of the unique NTD regulatory element of MavRel reveals its functional relevance to coordinate the catalytic states of synthetase and hydrolase, hence underscores the prospect to drive inhibitor development targeting this novel site against Mav infections. Full article
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20 pages, 1150 KB  
Review
Uraemic Cardiomyopathy: A Nephrology-Centric Review of Pathophysiology, Clinical Features, and Emerging Management Strategies
by Mahmoud Elshehawy, Alaa Amr Abdelgawad, Elamin Mohammed, Mirza Yasar Baig, Hana Morrissey and Patrick Anthony Ball
J. CardioRenal Med. 2025, 1(1), 2; https://doi.org/10.3390/jcrm1010002 - 25 Sep 2025
Abstract
Background: Uraemic cardiomyopathy (UCM), the cardiac manifestation of chronic kidney disease, represents a significant clinical challenge that is often underdiagnosed despite being one of the strongest predictors of mortality in the chronic kidney disease (CKD) population. It develops through pathophysiological mechanisms unique to [...] Read more.
Background: Uraemic cardiomyopathy (UCM), the cardiac manifestation of chronic kidney disease, represents a significant clinical challenge that is often underdiagnosed despite being one of the strongest predictors of mortality in the chronic kidney disease (CKD) population. It develops through pathophysiological mechanisms unique to the uraemic state—left ventricular hypertrophy, myocardial fibrosis, and diastolic dysfunction—that often progress silently, sometimes even without traditional cardiovascular risk factors. Purpose: This review synthesises nephrology-centric mechanisms with clinical phenotypes and contemporary imaging (including CMR T1/T2 mapping and ECV), and proposes a CKD-stage–tailored diagnostic–therapeutic framework. It offers a distinct perspective by integrating the complex pathophysiology of UCM with practical diagnostic approaches and evolving management strategies, differentiating it from prior cardiology-focused overviews. Methods: A comprehensive literature search was conducted across Ovid MEDLINE, Embase, PubMed, Google Scholar, BMJ Best Practice, and UpToDate for studies published up to March 2025. Key findings were extracted from the final evidence set and manually verified for relevance. This review introduces a patho-mechanical cascade model of uraemic cardiomyopathy, integrating toxin-driven, metabolic, and haemodynamic axes. Nephrology-led screening protocols are proposed, leveraging proteomics and strain echo, and advocate mineralocorticoid receptor antagonists with sodium–glucose co-transporter-2 (SGLT2) inhibitor initiation at CKD Stage 3a. Cardiorenal clinics are essential for improved outcomes. Key Insights: UCM develops from a multifactorial process. This involves neurohormonal activation, oxidative stress, chronic inflammation, and exposure to toxins such as indoxyl sulfate and p-cresyl sulfate, arising from uraemia. Diagnosis is challenging, masked by overlapping features of fluid overload and anaemia. SGLT2 inhibitors, non-steroidal mineralocorticoid antagonists, and renin–angiotensin–aldosterone system modulation offer promising interventions. The effect of the dialysis modality, its timing, and renal transplantation on cardiac remodelling also emerging from recent studies. Conclusions: UCM sits at the intersection of two failing organ systems. Managing it effectively requires a paradigm shift to incorporate pharmacological and early diagnostic interventions and the integration of cardiology and nephrology care, and the timely implementation of interventions. Full article
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18 pages, 8498 KB  
Article
Plasma Metabolomic Profiling Reveals Systemic Alterations in a Mouse Model of Type 2 Diabetes
by Masuma Akter Brishti, Fregi Vazhappully Francis and M. Dennis Leo
Metabolites 2025, 15(9), 564; https://doi.org/10.3390/metabo15090564 - 22 Aug 2025
Viewed by 638
Abstract
Background: Type 2 diabetes (T2D), the most common form of diabetes, is associated with a significantly elevated risk of cardiovascular and cerebrovascular complications. However, circulating metabolic signatures that reliably predict the transition to insulin resistance, and are potentially linked to increased vascular risk, [...] Read more.
Background: Type 2 diabetes (T2D), the most common form of diabetes, is associated with a significantly elevated risk of cardiovascular and cerebrovascular complications. However, circulating metabolic signatures that reliably predict the transition to insulin resistance, and are potentially linked to increased vascular risk, remain incompletely characterized. Rodent models, particularly those induced by a high-fat diet (HFD) combined with low-dose streptozotocin (STZ), are widely used to study the progression of T2D. However, the systemic metabolic shifts associated with this model, especially at the plasma level, are poorly defined. Methods: In this study, we performed untargeted liquid chromatography–mass spectrometry (LC-MS)-based metabolomic profiling on plasma samples from control, HFD-only (obese, insulin-sensitive), and HFD + STZ (obese, insulin-resistant) C57BL/6 mice. Results: In the HFD + STZ cohort, plasma profiles showed a global shift toward lipid classes; depletion of aromatic and branched-chain amino acids (BCAAs); accumulation of phenylalanine-derived co-metabolites, consistent with gut–liver axis dysregulation; elevations in glucose, fructose-6-phosphate, and nucleoside catabolites, indicating impaired glucose handling and heightened nucleotide turnover; increased free fatty acids, reflecting membrane remodeling and lipotoxic stress; and higher cAMP, thyroxine, hydrocortisone, and uric acid, consistent with endocrine and redox imbalance. By contrast, HFD-only mice exhibited elevations in aromatic amino acids and BCAAs relative to controls, a pattern compatible with early obesity-associated adaptation while insulin signaling remained partially preserved. KEGG analysis revealed disturbances in carbohydrate metabolism, amino acid degradation, nucleotide turnover, and hormone-related pathways, and HMDB mapping linked these changes to T2D, obesity, heart failure, and renal dysfunction. Conclusion: Collectively, these findings delineate insulin resistance-specific plasma signatures of metabolic inflexibility and inflammatory stress in the HFD + STZ model, distinguishing it from HFD alone and supporting its utility for mechanistic studies and biomarker discovery. Importantly, this plasma metabolomics study shows that insulin-sensitive and insulin-resistant states exhibit distinct variation in circulating metabolites and cardiovascular risk factors, underscoring the translational value of plasma profiling. Full article
(This article belongs to the Topic Animal Models of Human Disease 3.0)
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15 pages, 1684 KB  
Article
Dysfunctional Electron Transport Chain Assembly in COXPD8
by Gisela Beutner, Heidie L. Huyck, Gail Deutsch, Gloria S. Pryhuber and George A. Porter Jr.
J. Cardiovasc. Dev. Dis. 2025, 12(8), 318; https://doi.org/10.3390/jcdd12080318 - 20 Aug 2025
Viewed by 487
Abstract
Combined oxidative phosphorylation deficiency type 8 (COXPD8) is an autosomal recessive mitochondrial disorder caused by a mutation of the nuclear encoded mitochondrial alanyl-tRNA synthetase gene (AARS2). Clinical manifestations of COXPD8 include lethal infantile hypertrophic cardiomyopathy, pulmonary hypoplasia, generalized muscle weakness, and neurological involvement. [...] Read more.
Combined oxidative phosphorylation deficiency type 8 (COXPD8) is an autosomal recessive mitochondrial disorder caused by a mutation of the nuclear encoded mitochondrial alanyl-tRNA synthetase gene (AARS2). Clinical manifestations of COXPD8 include lethal infantile hypertrophic cardiomyopathy, pulmonary hypoplasia, generalized muscle weakness, and neurological involvement. We report a patient with COXPD8 caused by two mutations in the AARS2 gene. The c.1738 C>G mutation has not been previously reported, while the c.2872 C>T mutation has been associated with pulmonary hypoplasia and hypertrophic cardiomyopathy. Cardiac tissue, obtained through the LungMAP program, showed that, compared to other patients of similar ages, these two mutations affect not only the assembly of functional monomeric complexes (Cx) I and IV of the electron transport chain (ETC) but also limit the formation of respiratory supercomplexes. This patient had altered expression of some ETC proteins but normal expression of several enzymes of the tricarboxylic acid cycle. We also show that one of the control/comparison patients had an undiagnosed ETC Cx IV deficiency. In conclusion, our data demonstrate that the two mutations of the AARS2 gene are associated with failed assembly of Cx I and Cx IV and reduced formation of respiratory supercomplexes of the ETC, likely leading to acute bioenergetic stress. Full article
(This article belongs to the Section Cardiac Development and Regeneration)
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12 pages, 556 KB  
Article
Characterization of the Left Ventricular Myocardium in Systemic Sclerosis
by Briella K. Egberts, Rajiv Ananthakrishna, Ranjit Shah, Antony Chun Fai So, Jennifer Walker, Sivabaskari Pasupathy, Susanna Proudman and Joseph B. Selvanayagam
J. Clin. Med. 2025, 14(16), 5627; https://doi.org/10.3390/jcm14165627 - 8 Aug 2025
Viewed by 439
Abstract
Background/Objectives: Cardiac involvement in systemic sclerosis (SSc) ranges from subclinical to severe. While pulmonary artery hypertension (PAH) is well-documented, the mechanism of left ventricular (LV) ischemia remains unclear. Oxygen-sensitive cardiovascular magnetic resonance (OS-CMR) imaging offers a novel approach to assessing myocardial oxygenation and [...] Read more.
Background/Objectives: Cardiac involvement in systemic sclerosis (SSc) ranges from subclinical to severe. While pulmonary artery hypertension (PAH) is well-documented, the mechanism of left ventricular (LV) ischemia remains unclear. Oxygen-sensitive cardiovascular magnetic resonance (OS-CMR) imaging offers a novel approach to assessing myocardial oxygenation and ischemia. This study evaluated the changes in myocardial deoxygenation in response to stress using LV OS-CMR in SSc patients without known cardiac disease. Methods: We prospectively recruited SSc patients without prior cardiac disease or risk factors, and age- and sex-matched healthy volunteers (HVs). All participants underwent transthoracic echocardiography (TTE) and 3T CMR, including native T1 mapping, rest/stress OS-CMR, stress perfusion, and late gadolinium enhancement (LGE). The primary outcome was a change in the LV OS-CMR signal intensity (SI) after adenosine stress. Results: Thirty-three participants (23 SSc, 10 HV) were enrolled. SSc patients had significantly lower global LV OS-CMR SI compared to HV (13.4 ± 6.5 vs. 19.5 ± 3.6, p = 0.011). OS-CMR SI change ≤ 10% was observed in at least one segment in 20 (87%) SSc patients and globally in 12 (52%). LGE was present in 5 (22%) patients, and 18 (78%) had ≥1 abnormal T1 mapping segment. LV global longitudinal strain (GLS) was reduced in SSc patients compared to the HVs (−19.04 ± 3.86 vs. −21.92 ± 3.72, p = 0.045). All HVs had normal CMR and TTE findings. Conclusions: SSc patients without known cardiovascular disease or PAH demonstrated subclinical LV ischemia with an impaired myocardial oxygenation response to stress. They further demonstrated LV myocardial deformation abnormalities and LV diffuse fibrosis when compared to an age-matched control group. Our findings support the presence of early coronary microvascular dysfunction and LV myocardial fibrosis in this population, which may explain the adverse cardiovascular risk seen in this population, independent of the presence of PAH. Full article
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17 pages, 4471 KB  
Technical Note
Agronomic Information Extraction from UAV-Based Thermal Photogrammetry Using MATLAB
by Francesco Paciolla, Giovanni Popeo, Alessia Farella and Simone Pascuzzi
Remote Sens. 2025, 17(15), 2746; https://doi.org/10.3390/rs17152746 - 7 Aug 2025
Viewed by 799
Abstract
Thermal cameras are becoming popular in several applications of precision agriculture, including crop and soil monitoring, for efficient irrigation scheduling, crop maturity, and yield mapping. Nowadays, these sensors can be integrated as payloads on unmanned aerial vehicles, providing high spatial and temporal resolution, [...] Read more.
Thermal cameras are becoming popular in several applications of precision agriculture, including crop and soil monitoring, for efficient irrigation scheduling, crop maturity, and yield mapping. Nowadays, these sensors can be integrated as payloads on unmanned aerial vehicles, providing high spatial and temporal resolution, to deeply understand the variability of crop and soil conditions. However, few commercial software programs, such as PIX4D Mapper, can process thermal images, and their functionalities are very limited. This paper reports on the implementation of a custom MATLAB® R2024a script to extract agronomic information from thermal orthomosaics obtained from images acquired by the DJI Mavic 3T drone. This approach enables us to evaluate the temperature at each point of an orthomosaic, create regions of interest, calculate basic statistics of spatial temperature distribution, and compute the Crop Water Stress Index. In the authors’ opinion, the reported approach can be easily replicated and can serve as a valuable tool for scientists who work with thermal images in the agricultural sector. Full article
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16 pages, 1308 KB  
Review
Multimodality Imaging in Aldosterone-Induced Cardiomyopathy: Early Detection and Prognostic Implications
by Francesca Zoccatelli, Gabriele Costa, Matteo Merlo, Francesca Pizzolo, Simonetta Friso and Luigi Marzano
Diagnostics 2025, 15(15), 1896; https://doi.org/10.3390/diagnostics15151896 - 29 Jul 2025
Cited by 1 | Viewed by 735
Abstract
Primary aldosteronism (PA), the most common cause of secondary hypertension, is increasingly recognized as an independent driver of adverse cardiac remodeling, mediated through mechanisms beyond elevated blood pressure alone. Chronic aldosterone excess leads to myocardial fibrosis, left ventricular hypertrophy, and diastolic dysfunction via [...] Read more.
Primary aldosteronism (PA), the most common cause of secondary hypertension, is increasingly recognized as an independent driver of adverse cardiac remodeling, mediated through mechanisms beyond elevated blood pressure alone. Chronic aldosterone excess leads to myocardial fibrosis, left ventricular hypertrophy, and diastolic dysfunction via mineralocorticoid receptor activation, oxidative stress, inflammation, and extracellular matrix dysregulation. These changes culminate in a distinct cardiomyopathy phenotype, often underrecognized in early stages. Multimodality cardiac imaging, led primarily by conventional and speckle-tracking echocardiography, and complemented by exploratory cardiac magnetic resonance (CMR) techniques such as T1 mapping and late gadolinium enhancement, enables non-invasive assessment of structural, functional, and tissue-level changes in aldosterone-mediated myocardial damage. While numerous studies have established the diagnostic and prognostic relevance of imaging in PA, several gaps remain. Specifically, the relative sensitivity of different modalities in detecting subclinical myocardial changes, the long-term prognostic significance of imaging biomarkers, and the differential impact of adrenalectomy versus medical therapy on cardiac reverse remodeling require further clarification. Moreover, the lack of standardized imaging-based criteria for defining and monitoring PA-related cardiomyopathy hinders widespread clinical implementation. This narrative review aims to synthesize current knowledge on the pathophysiological mechanisms of aldosterone-induced cardiac remodeling, delineate the strengths and limitations of existing imaging modalities, and critically evaluate the comparative effects of surgical and pharmacologic interventions. Emphasis is placed on early detection strategies, identification of imaging biomarkers with prognostic utility, and integration of multimodal imaging into clinical decision-making pathways. By outlining current evidence and highlighting key unmet needs, this review provides a framework for future research aimed at advancing personalized care and improving cardiovascular outcomes in patients with PA. Full article
(This article belongs to the Section Pathology and Molecular Diagnostics)
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16 pages, 4352 KB  
Article
Multi-Time Point Transcriptome Analysis and Functional Validation Revealed Bol4CL41 Negatively Regulates Black Rot Resistance in Cabbage
by Hongxue Ma, Siping Deng, Congcong Kong, Yulun Zhang, Tong Zhao, Jialei Ji, Yong Wang, Yangyong Zhang, Mu Zhuang, Limei Yang, Marina Lebedeva, Vasiliy Taranov, Anna M. Artemyeva, Zhiyuan Fang, Jingquan Yu, Zhangjian Hu and Honghao Lv
Int. J. Mol. Sci. 2025, 26(13), 6179; https://doi.org/10.3390/ijms26136179 - 26 Jun 2025
Viewed by 447
Abstract
4-coumarate-CoA ligase (4CL) plays a crucial role in the phenylpropanoid metabolic pathway and is a key enzyme involved in plant growth and stress responses. Black rot, caused by Xanthomonas campestris pv. campestris (Xcc) is a major bacterial disease affecting the production [...] Read more.
4-coumarate-CoA ligase (4CL) plays a crucial role in the phenylpropanoid metabolic pathway and is a key enzyme involved in plant growth and stress responses. Black rot, caused by Xanthomonas campestris pv. campestris (Xcc) is a major bacterial disease affecting the production of global cruciferous crop-like cabbage (Brassica oleracea var. capitata). However, the role of 4CL genes in cabbage resistance to black rot remains unclear. In this study, transcriptome sequencing was conducted using resistant cabbage MY and susceptible cabbage LY at 0, 6, 24, and 48 h post-inoculation. KEGG analysis identified the enrichment of the phenylpropanoid biosynthesis pathway, and significant expression changes of 4CL genes were determined through the expression heat map. Further genome-wide analysis revealed 43 Bol4CL gene family members on the cabbage genome distributed across nine chromosomes. Gene structure and protein motif analysis revealed similarities in motifs within the same evolutionary branch, but variations in gene structure. A combination of Bol4CL gene expression profiles and differentially expressed genes (DEGs) from the transcriptome identified Bol4CL41 as a key gene for further study. Inoculation of overexpressed Bol4CL41 T2 generation stably expressed cabbage seedlings demonstrated significantly larger lesion areas compared to wild type cabbage, indicating that Bol4CL41 negatively regulates resistance to black rot in cabbage. The analysis of multi-time point transcriptomes in cabbage and the functional study of the Bol4CL gene family enhance our understanding of the mechanisms underlying plant disease resistance. This provides compelling evidence and experimental support for elucidating the mechanisms of black rot resistance in cabbage. Full article
(This article belongs to the Special Issue New Insights into Plant Pathology and Abiotic Stress)
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19 pages, 4349 KB  
Article
The Spatial and Temporal Heterogeneity of Ecosystem Service Trade-Offs and Synergies, and Their Implications for Spatial Planning and Management: A Case Study of the Tarim River Basin
by Zhigang Li, Yanyan Shen, Wenhui Fu, Yanbing Qi and Xin Wei
Forests 2025, 16(6), 1024; https://doi.org/10.3390/f16061024 - 19 Jun 2025
Cited by 1 | Viewed by 554
Abstract
Arid regions face multiple challenges such as population expansion, water scarcity, land degradation, and biodiversity reduction. Understanding temporal and spatial patterns of ecosystem service trade-offs and synergies is critical for sustainable development and effective ecosystem service management in arid regions under environmental stress. [...] Read more.
Arid regions face multiple challenges such as population expansion, water scarcity, land degradation, and biodiversity reduction. Understanding temporal and spatial patterns of ecosystem service trade-offs and synergies is critical for sustainable development and effective ecosystem service management in arid regions under environmental stress. Taking the Tarim River Basin in China as an example, five ecosystem services (carbon sequestration, water yield, sediment delivery ratio, habitat quality, and food production) were studied at different scales in 1990, 2000, 2010, and 2020 in the inland arid region. Spearman correlation, geographical weighted regression, and self-organizing mapping were used to analyze the ecosystem service trade-offs and synergies. The results showed that the ecosystem services in the basin increased gradually; in particular, the water yield increased from 15.38 × 109 m3 to 29.8 × 10 m3, and the food production increased from 11.03 × 106 t to 29.26 × 106 t. There was a significant positive correlation between carbon sequestration, water yield, and habitat quality, but a negative correlation between sediment delivery ratio and food production. The spatial distribution of trade-offs and synergies of ecosystem services varies in different years and on different scales. The area change in ecosystem service bundles at the pixel scale is relatively small, while the area change at the sub-basin scale is relatively large. This paper provides policy suggestions for the ecological management and sustainable development of the Tarim River Basin through the analysis of ecosystem service trade-offs and synergies. Full article
(This article belongs to the Section Forest Ecology and Management)
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28 pages, 1776 KB  
Review
Nutrition and Diet Patterns as Key Modulators of Metabolic Reprogramming in Melanoma Immunotherapy
by Katerina Grafanaki, Alexandros Maniatis, Alexandra Anastogianni, Angelina Bania, Efstathia Pasmatzi and Constantinos Stathopoulos
J. Clin. Med. 2025, 14(12), 4193; https://doi.org/10.3390/jcm14124193 - 12 Jun 2025
Viewed by 5403
Abstract
Background: Melanoma, one of the most aggressive forms of skin cancer, has seen significant therapeutic advances with immune checkpoint inhibitors (ICIs). However, many patients fail to respond or develop resistance, creating the need for adjunct strategies. Objective: The objective of this [...] Read more.
Background: Melanoma, one of the most aggressive forms of skin cancer, has seen significant therapeutic advances with immune checkpoint inhibitors (ICIs). However, many patients fail to respond or develop resistance, creating the need for adjunct strategies. Objective: The objective of this study is to critically evaluate how specific dietary patterns and nutrient-derived metabolites modulate melanoma metabolism and immunotherapy outcomes, emphasizing translational implications. Methods: We performed an integrative review of preclinical and clinical studies investigating dietary interventions in melanoma models and ICI-treated patients. Mechanistic insights were extracted from studies on nutrient transport, immunometabolism, and microbiome–immune interactions, including data from ongoing nutritional clinical trials. Results: Diets rich in fermentable fibers, plant polyphenols, and unsaturated lipids, such as Mediterranean and ketogenic diets, seem to contribute to the reprogramming of tumor metabolism and enhance CD8+ T-cell activity. Fasting-mimicking and methionine-restricted diets modulate T-cell fitness and tumor vulnerability via nutrient stress sensors (e.g., UPR, mTOR). High fiber intake correlates with favorable gut microbiota and improved ICI efficacy, while excess protein, methionine, or refined carbohydrates impair immune surveillance via lactate accumulation and immunosuppressive myeloid recruitment. Several dietary molecules act as network-level modulators of host and microbial proteins, with parallels to known drug scaffolds. Conclusions: Integrating dietary interventions into melanoma immunotherapy can significantly influence metabolic reprogramming by targeting metabolic vulnerabilities and reshaping the tumor–immune–microbiome axis. When combined with AI-driven nutrient–protein interaction mapping, this approach offers a precision nutrition paradigm that supports both physicians and patients, emerging as a novel layer to enhance and consolidate existing therapeutic strategies. Full article
(This article belongs to the Section Clinical Nutrition & Dietetics)
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21 pages, 14030 KB  
Article
Impact of Type 1 Diabetes on Testicular Microtubule Dynamics, Sperm Physiology, and Male Reproductive Health in Rat
by Alessandra Biasi, Maria Rosaria Ambruosi, Maria Zelinda Romano, Serena Boccella, Sara Falvo, Francesca Guida, Francesco Aniello, Sabatino Maione, Massimo Venditti and Sergio Minucci
Int. J. Mol. Sci. 2025, 26(10), 4579; https://doi.org/10.3390/ijms26104579 - 10 May 2025
Cited by 2 | Viewed by 1075
Abstract
Type 1 diabetes (T1D) is a chronic metabolic disease defined by sustained hyperglycemia, leading to oxidative stress (OS) and systemic complications, including male subfertility. This study investigates the potential impact of T1D-induced OS on microtubule (MTs) dynamics and microtubule-associated proteins (MAPs) in the [...] Read more.
Type 1 diabetes (T1D) is a chronic metabolic disease defined by sustained hyperglycemia, leading to oxidative stress (OS) and systemic complications, including male subfertility. This study investigates the potential impact of T1D-induced OS on microtubule (MTs) dynamics and microtubule-associated proteins (MAPs) in the testis and spermatozoa (SPZ). Using a streptozotocin-induced T1D rat model, we examined the expression and localization of key MAPs, including Microtubule Affinity-Regulating Kinase 4 (MARK4), Microtubule-Associated Protein 1A (MAP1A), Dynein Light Chain LC8-Type 1 (DYNLL1), Prolyl Endopeptidase (PREP), and Radial Spoke Head 6 Homolog A (RSPH6A), alongside sperm functional parameters. Our findings showed that T1D significantly impaired the expression and distribution of these proteins, which may affect MTs organization and be associated with cytoskeletal disorganization, and impaired germ cell differentiation. Moreover, T1D rats exhibited reduced sperm count, viability, and motility, accompanied by increased DNA fragmentation and chromatin defects. Elevated levels of 4-hydroxy-2-nonenal (4-HNE), a marker of OS, were detected in SPZ, particularly in the acrosome and flagellum, correlating with mitochondrial dysfunction and ATP depletion. Additionally, decreased intracellular Ca2+ levels, downregulation of Cation Channel of Sperm (CATSPER) and Voltage-Dependent Anion Channel 3 (VDAC3), and altered tubulin acetylation, possibly due to imbalanced Alpha-Tubulin N-Acetyltransferase 1 (ATAT1) and Histone Deacetylase 6 (HDAC6) expression, were also associated with impaired sperm motility. The combined data suggest that T1D-induced OS is linked to disrupted MTs dynamics, which may contribute to testicular dysfunction and reduced sperm quality, potentially affecting male fertility. A better understanding of these associations may support the development of therapeutic strategies to mitigate the reproductive consequences of T1D and improve male fertility outcomes. Full article
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18 pages, 4617 KB  
Article
Hydroxy-Selenomethionine Supplementation During Gestation and Lactation Improve Reproduction of Sows by Enhancing the Antioxidant Capacity and Immunity Under Heat Stress Conditions
by Juan Wang, Hua Sun, Zhe Peng, Shao-Qing Wang, Yi-Qin Yan, Wei-Cai Luo, Ren-Gui Yang, Wei-Cheng Bei, Lv-Hui Sun and Jia-Cheng Yang
Antioxidants 2025, 14(5), 525; https://doi.org/10.3390/antiox14050525 - 27 Apr 2025
Viewed by 905
Abstract
The objective of this study was to determine whether hydroxy-selenomethionine (OH-SeMet) exerts better protective effects on sows against heat stress than sodium selenite (SeNa) or seleno-yeast (SeY). A total of 60 sows (Landrace × Yorkshire) were randomly allocated into the three groups and [...] Read more.
The objective of this study was to determine whether hydroxy-selenomethionine (OH-SeMet) exerts better protective effects on sows against heat stress than sodium selenite (SeNa) or seleno-yeast (SeY). A total of 60 sows (Landrace × Yorkshire) were randomly allocated into the three groups and fed a base diet supplemented with SeNa, SeY, or OH-SeMet at 0.3 mg Se/kg under a heat stress condition for a reproductive cycle. Compared to SeNa or SeY, OH-SeMet could more effectively sustain offspring growth performance, as evidenced by an increased number of live-born piglets, higher litter weight at day 21, and greater litter body weight gain from days 1 to 21. OH-SeMet was more effective in supporting endogenous redox systems, as shown by enhanced levels of TXNRD and GSH and reduced levels of GSSG in the serum of sows, improved T-AOC, TXNRD, and GSH alongside decreased MDA and GSSG in the serum of piglets, and heightened T-AOC in the jejunum of piglets. Furthermore, among the two tested organic Se sources, OH-SeMet was more effective than SeY in regulating immune responses compared to SeNa. OH-SeMet reduced inflammation-related markers CRP, HP, MAP, LPS, IL-1β, IL-6, and TNF-α, some or all of which were reduced in the serum of sows and their offspring. In addition, OH-SeMet also showed reduced glucose, TG, and NEFA levels, along with elevated insulin levels in the serum of sows. Correspondingly, among the two organic forms of Se, particularly those sows fed OH-SeMet showed better gut protection for the sows’ offspring, as indicated by a reduced crypt depth and increased villus height/crypt depth ratio in the duodenum, jejunum, and ileum than those fed SeNa. Specifically, compared to SeNa or SeY, OH-SeMet upregulated the expression of selenoproteins (GPX6, TXNRD3, GPX4, and SELENON), the tight junction protein (ZO-1), and host defense peptide gene (pBD1, pBD2, pBD3, NPG3, NPG4), along with downregulating levels of inflammation factor (IL-1β, IL-6 and TNF-α) and pro-apoptotic factor (P53) in the jejunum of piglets. Taken together, OH-SeMet more effectively mitigated the adverse effects induced by heat stress in sows and their offspring. Full article
(This article belongs to the Special Issue Redox Homeostasis in Poultry/Animal Production)
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15 pages, 1072 KB  
Review
The Potential Role of GLP1-RAs Against Anticancer-Drug Cardiotoxicity: A Scoping Review
by Filippo Biondi and Rosalinda Madonna
J. Clin. Med. 2025, 14(8), 2705; https://doi.org/10.3390/jcm14082705 - 15 Apr 2025
Cited by 3 | Viewed by 2142
Abstract
Background: GLP1 receptor agonists (GLP1-RAs) have become a central component in the treatment of type 2 diabetes mellitus (T2DM) and are gaining prominence in the cardiovascular field. Semaglutide and other GLP1-RA molecules possess cardioprotective properties. Cardiotoxicity, a term used to refer to cardiovascular [...] Read more.
Background: GLP1 receptor agonists (GLP1-RAs) have become a central component in the treatment of type 2 diabetes mellitus (T2DM) and are gaining prominence in the cardiovascular field. Semaglutide and other GLP1-RA molecules possess cardioprotective properties. Cardiotoxicity, a term used to refer to cardiovascular disease caused by anticancer treatment, is a collection of common and severe conditions. Its pharmacological prevention or mitigation is a clinical unmet need as options are few and limited to some specific clinical settings. GLP1-RAs have a promising pharmacological profile given their activity on a number of pathophysiological targets and signaling pathways including oxidative stress, autophagy, and STAT3 activation. Interestingly, abnormalities in some of the GLP-1-modulated pathways have been linked to cardiotoxicity. This scoping review aims to map the extent and assess the main characteristics of research on the role of GLP1-RAs in the prevention and/or mitigation of anticancer-related cardiotoxicity. Methods: The selection process led to the inclusion of thirteen studies chosen from reports retrieved through the search string: (“semaglutide” OR “exenatide” OR “liraglutide” OR “dulaglutide” OR “tirzepatide” OR “GLP1 receptor agonist” OR “GLP1RA” OR “GLP1-RA” OR “GLP1” OR “Glucagon-like Peptide-1 Agonists”) AND (“cardioncology” OR “cardiotoxicity” OR “chemotherapy” OR “anti-cancer treatment” OR “anti-cancer therapy”). The study complied with the PRISMA guidelines on scoping reviews. Results: Two studies were clinical and conducted on registries, eight used animal models, two were conducted on cell cultures, and one was conducted on both animal models and cell cultures. Evidence in favor of cardioprotection and a number of putative mechanisms emerged. Conclusions: Evidence on GLP1-RAs’ effect on cardiotoxicity is limited in both quantity and quality and suffers from poor study standardization. However, most included studies documented a rigorously defined cardioprotective effect and demonstrated changes in several pathophysiologically relevant targets and pathways, including NF-κB, IL-6, reactive oxygen species, and caspase-3. Further clinical studies are warranted. Full article
(This article belongs to the Section Cardiovascular Medicine)
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23 pages, 4985 KB  
Article
Genome-Wide Dissection of Novel QTLs and Genes Associated with Weed Competitiveness in Early-Backcross Selective Introgression-Breeding Populations of Rice (Oryza sativa L.)
by Kim Diane Nocito, Varunseelan Murugaiyan, Jauhar Ali, Ambika Pandey, Carlos Casal, Erik Jon De Asis and Niña Gracel Dimaano
Biology 2025, 14(4), 413; https://doi.org/10.3390/biology14040413 - 13 Apr 2025
Viewed by 1897
Abstract
The direct-seeded rice (DSR) system is poised to become the dominant rice cultivation method due to its advantages, including reduced water usage, less labor requirements, decreased greenhouse gas emissions, and improved adaptation to climate change. However, weeds, particularly jungle rice (Echinochloa colona [...] Read more.
The direct-seeded rice (DSR) system is poised to become the dominant rice cultivation method due to its advantages, including reduced water usage, less labor requirements, decreased greenhouse gas emissions, and improved adaptation to climate change. However, weeds, particularly jungle rice (Echinochloa colona), significantly hinder DSR and cause substantial yield losses. This study aimed to develop rice cultivars competitive against jungle rice through selective breeding, focusing on early seed germination (ESG) and seedling vigor (ESV). We utilized 181 early-backcross selective introgression breeding lines (EB-SILs) developed using Green Super Rice (GSR) technology by backcrossing Weed Tolerant Rice1 (WTR1) with three donor parents, Haoannong, Cheng Hui 448, and Y134. Using the tunable genotyping-by-sequencing (tGBS®, Data2Bio Technologies, Ames, IA, USA) method, we identified 3971 common single nucleotide polymorphisms (SNPs) that facilitated the mapping of 19 novel quantitative trait loci (QTLs) associated with weed competitiveness—eight linked to ESG traits and eleven to ESV traits. Notably, all QTLs were novel except qRPH1, linked to relative plant height at 14 and 21 days after sowing. Key QTLs were located on chromosomes 2, 3, 5, 6, 8, 9, 10, and 12. Candidate genes identified within these QTLs are implicated in the plant’s response to various abiotic and biotic stresses. Our findings enhance the understanding of the genetic basis for ESG and ESV traits critical for weed competitiveness, supporting marker-assisted and genomic selection approaches for breeding improved rice varieties. Furthermore, this research lays the groundwork for employing gene expression, cloning, and CRISPR editing strategies to combat jungle rice, with potential applications for other weed species and contributing to effective integrated weed management in the DSR system. Full article
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16 pages, 2378 KB  
Communication
In Silico Targeting and Immunological Profiling of PpiA in Mycobacterium tuberculosis: A Computational Approach
by Mohammad J. Nasiri, Lily Rogowski and Vishwanath Venketaraman
Pathogens 2025, 14(4), 370; https://doi.org/10.3390/pathogens14040370 - 9 Apr 2025
Viewed by 972
Abstract
Tuberculosis (TB) remains a leading cause of mortality, with drug resistance highlighting the need for new vaccine targets. Peptidyl-prolyl isomerase A (PpiA), a conserved Mycobacterium tuberculosis (Mtb) protein, plays a role in bacterial stress adaptation and immune evasion, making it a potential target [...] Read more.
Tuberculosis (TB) remains a leading cause of mortality, with drug resistance highlighting the need for new vaccine targets. Peptidyl-prolyl isomerase A (PpiA), a conserved Mycobacterium tuberculosis (Mtb) protein, plays a role in bacterial stress adaptation and immune evasion, making it a potential target for immunotherapy. This study uses computational methods to assess PpiA’s antigenicity, structural integrity, and immunogenic potential. The PpiA sequence was retrieved from NCBI and analyzed for antigenicity and allergenicity using VaxiJen, AllerTOP, and AllergenFP. Physicochemical properties were evaluated using ProtParam, and structural models were generated through PSIPRED and SWISS-MODEL. Structural validation was performed with MolProbity, QMEANDisCo, and ProSA-Web. B-cell epitopes were predicted using BepiPred 2.0 and IEDB, while T-cell epitopes were mapped via IEDB’s MHC-I and MHC-II tools. Epitope conservation across Mtb strains was confirmed using ConSurf. Results indicate PpiA is highly antigenic, non-allergenic, and stable, with several immunogenic epitopes identified for both B- and T-cells. This study supports PpiA as a promising immunogenic target for TB vaccine development. Full article
(This article belongs to the Special Issue Computational Approaches in Mechanisms of Pathogenesis)
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