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16 pages, 1769 KiB  
Review
SGLT2 Inhibitors and GLP-1 Receptor Agonists in Cardiovascular–Kidney–Metabolic Syndrome
by Aryan Gajjar, Arvind Kumar Raju, Amani Gajjar, Mythili Menon, Syed Asfand Yar Shah, Sourbha Dani and Andrew Weinberg
Biomedicines 2025, 13(8), 1924; https://doi.org/10.3390/biomedicines13081924 - 7 Aug 2025
Abstract
Cardiovascular–Kidney–Metabolic (CKM) syndrome symbolizes a single pathophysiologic entity including obesity, type 2 diabetes, chronic kidney disease, and cardiovascular disease. These conditions altogether accelerate adverse outcomes when they coexist. Recent evidence has shown that the function of glucagon-like peptide-1 receptor agonists (GLP-1RA) and sodium–glucose [...] Read more.
Cardiovascular–Kidney–Metabolic (CKM) syndrome symbolizes a single pathophysiologic entity including obesity, type 2 diabetes, chronic kidney disease, and cardiovascular disease. These conditions altogether accelerate adverse outcomes when they coexist. Recent evidence has shown that the function of glucagon-like peptide-1 receptor agonists (GLP-1RA) and sodium–glucose cotransporter-2 inhibitors (SGLT2i) alleviate stress on multiple organs. SGLT2i has been demonstrated to benefit heart failure, hemodynamic regulation, and renal protection while GLP-1RA on the other hand has been shown to demonstrate a strong impact on glycemic management, weight loss, and atherosclerotic cardiovascular disease. This review will aim to understand and evaluate the mechanistic rationalization, clinical evidence, and the potential therapeutic treatment of SGLT2 inhibitors and GLP-1 receptor agonists to treat individuals who have CKM syndrome. This analysis also assesses whether combination therapy can be a synergistic approach that may benefit patients but is still underutilized because of the lack of clear guidelines, the associated costs, and disparities in accessibility. Therefore, in this review, we will be discussing the combination therapy’s additive and synergistic effects, current recommendations and clinical evidence, and mechanistic insights of these GLT2 inhibitors and GLP-1 receptor agonists in CKM syndrome patients. Overall, early and combination usage of GLP-1RA and SGLT2i may be essential to demonstrating a significant shift in modern cardiometabolic therapy toward patient-centered care. Full article
(This article belongs to the Section Endocrinology and Metabolism Research)
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14 pages, 2320 KiB  
Article
Differentiated Microbial Strategies in Carbon Metabolic Processes Responding to Salt Stress in Cold–Arid Wetlands
by Yongman Wang, Mingqi Wang, Tiezheng Wu, Jialin Zhao, Junyi Li, Hongliang Xie, Lixin Wang and Linhui Wu
Land 2025, 14(8), 1607; https://doi.org/10.3390/land14081607 - 7 Aug 2025
Abstract
With the rising concerns about climate change and continuous increase in the salinity of soil, it is essential to understand the C-cycling functioning of saline soil to better predict the ecological functions and health of soil. Microbes play critical roles in C-cycling. However, [...] Read more.
With the rising concerns about climate change and continuous increase in the salinity of soil, it is essential to understand the C-cycling functioning of saline soil to better predict the ecological functions and health of soil. Microbes play critical roles in C-cycling. However, limited research has been conducted to understand the impact of soil salinity on the microbial functional genes involved in C-cycling. In this study, effects of varying soil salinity levels in wetlands on the C-cycling functions and diversity of soil microbes were investigated by metagenomic sequencing. The results showed a higher relative abundance of genes related to decomposition of easily degradable organic C at low salinity. On the other hand, higher abundance of genes participating in the decomposition of recalcitrant organic C were observed at high salinity. These findings indicate distinct metabolic bias of soil microbes based on the salinity levels. Proteobacteria and Actinobacteria were dominant in soils with low to medium salinity levels, while Bacteroidetes phyla was prominent in highly saline soils. Furthermore, partial least squares path modeling (PLS-PM) identified electrical conductivity, total nitrogen, and total phosphorus as key regulators of C-cycling gene expression. Overall, the present study highlights the intricate connections between salinity, microbial attributes, and carbon metabolism in soil, suggesting that the soil microbes adapt to saline stress through divergent eco-adaptations. The findings of this study highlight the significance of exploring these microbial interactions for effective management and conservation of saline wetlands. Full article
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11 pages, 571 KiB  
Article
Effects of a Positive Psychology Intervention on Mental Health and Well-Being Among Mothers in Riyadh, Saudi Arabia
by Munira Abdullah AlHugail and Deemah Ateeq AlAteeq
Healthcare 2025, 13(15), 1925; https://doi.org/10.3390/healthcare13151925 - 6 Aug 2025
Abstract
Background: Concerns over women’s mental health have intensified globally, especially among mothers managing dual careers and family responsibilities. Positive Psychology Interventions (PPIs), such as gratitude journaling and well-being workshops, have demonstrated promise in enhancing mental health; however, their applicability in Arab contexts remains [...] Read more.
Background: Concerns over women’s mental health have intensified globally, especially among mothers managing dual careers and family responsibilities. Positive Psychology Interventions (PPIs), such as gratitude journaling and well-being workshops, have demonstrated promise in enhancing mental health; however, their applicability in Arab contexts remains underexplored. This study aims to investigate the effectiveness of PPIs on mothers’ well-being, gratitude, depression, anxiety, and stress in Saudi Arabia. Methods: This quasi-experimental, one-group pretest–posttest study assessed the effects of a four-week PPI on 37 Saudi working mothers (aged 21–50 years) employed at a private school in Riyadh. The intervention included guided gratitude journaling thrice weekly and two workshops on positive psychology and gratitude. Pre- and post-intervention assessments used validated Arabic versions of the Depression Anxiety Stress Scale (DASS-21), WHO-5 Well-being Index, and Gratitude Questionnaire (GQ-6). Results: Significant improvements were found post-intervention: depression, anxiety, and stress scores decreased (p < 0.001), while well-being and gratitude increased (p = 0.001). However, participants with lower household income (<50,000 SAR) showed less improvement, indicating a potential moderating effect of socioeconomic status. Conclusions: The intervention demonstrated promising short-term improvements in mental health and well-being among Saudi mothers. The findings underscore the importance of culturally appropriate PPIs and highlight the need for further research using controlled, long-term designs. Limitations include the small, non-random sample, absence of a control group, and restriction to a single geographic region. Full article
(This article belongs to the Topic Global Mental Health Trends)
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17 pages, 962 KiB  
Article
Impact of COVID-19 on Mental Health in Nursing Students and Non-Nursing Students: A Cross-Sectional Study
by Verena Dresen, Liliane Sigmund, Siegmund Staggl, Bernhard Holzner, Gerhard Rumpold, Laura R. Fischer-Jbali, Markus Canazei and Elisabeth Weiss
Nurs. Rep. 2025, 15(8), 286; https://doi.org/10.3390/nursrep15080286 - 6 Aug 2025
Abstract
Background/Objective: Nursing and non-nursing students experience high stress levels, making them susceptible to mental health issues. This study compared stress, anxiety, and depression between these two groups after 2 years of the COVID-19 pandemic. Additionally, it explored the relationship between perceived helplessness, [...] Read more.
Background/Objective: Nursing and non-nursing students experience high stress levels, making them susceptible to mental health issues. This study compared stress, anxiety, and depression between these two groups after 2 years of the COVID-19 pandemic. Additionally, it explored the relationship between perceived helplessness, self-efficacy, and symptoms of mental stress and strain resulting from challenging internship conditions for nursing students. Methods: This cross-sectional study included 154 nursing students (mean age = 22.43 years) and 291 non-nursing students (mean age = 27.7 years). Data were collected using the Depression Anxiety Stress Scales (DASS-21), Perceived Stress Scale-10 (PSS-10), and a questionnaire on mental stress and strain. Results: Nursing students reported significantly higher scores in the DASS-21 subscales depression (ηp2 = 0.016) and anxiety (ηp2 = 0.037), and global stress (PSS-10; ηp2 = 0.029) compared to non-nursing students, but no significant difference on the DASS-21 Stress subscale. The observed group differences in the present study may be partially attributed to group differences in demographic factors. Helplessness correlated strongly with nearly all scales of mental stress and strain during internships (all p’s < 0.001), while self-efficacy showed a strong negative correlation with non-occupational difficulties, health impairment, and emotional problems (all p’s < 0.001). Conclusions: Nursing students experience elevated depression, anxiety, and perceived stress levels compared to non-nursing students. Stronger feelings of helplessness and lower confidence in their ability to overcome challenges were strongly correlated with mental stress and strain during clinical training. Targeted interventions such as cognitive behavioral training and stress management should be integrated into nursing curricula to enhance resilience and coping strategies. Full article
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16 pages, 1185 KiB  
Article
Hematological, Enzymatic, and Endocrine Response to Intense Exercise in Lidia Breed Cattle During the Roping Bull Bullfighting Celebration
by Julio Sedeño, Salvador Ruiz, Germán Martín and Juan Carlos Gardón
Animals 2025, 15(15), 2303; https://doi.org/10.3390/ani15152303 - 6 Aug 2025
Abstract
The Lidia cattle breed is featured in several traditional popular bullfighting festivals throughout Spain, including the “Toro de Cuerda” event, in which the animals are subjected to intense physical exercise. However, the physiological impact and welfare implications of these activities remain poorly characterized. [...] Read more.
The Lidia cattle breed is featured in several traditional popular bullfighting festivals throughout Spain, including the “Toro de Cuerda” event, in which the animals are subjected to intense physical exercise. However, the physiological impact and welfare implications of these activities remain poorly characterized. This study aimed to evaluate the stress response and muscle damage in Lidia breed bulls during roping bull celebrations through comprehensive blood analysis. Blood samples were collected from 53 adult male Lidia bulls before and after a standardized 45 min continuous running exercise during traditional roping bull events in four Spanish autonomous regions. Hematological parameters, muscle enzymes (creatine kinase, lactate dehydrogenase, lactate), and stress hormones (cortisol and ACTH) were analyzed. Significant increases (p < 0.05) were observed in leukocytes, lymphocytes, monocytes, eosinophils, neutrophils, erythrocytes, hematocrit, hemoglobin, and post-exercise platelets. Muscle enzymes showed marked elevations, with creatine kinase increasing up to 10-fold above baseline values. Stress hormones, cortisol and ACTH, also demonstrated significant increases. Despite the magnitude of these changes, all parameters remained within established reference ranges for the bovine species. This study provides the first physiological assessment of Lidia cattle during popular bullfighting celebrations, establishing baseline data for evidence-based welfare evaluation and management protocols. Full article
(This article belongs to the Section Cattle)
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14 pages, 541 KiB  
Review
Foreign Language Syndrome: Neurological and Psychiatric Aspects
by Ansam Eghzawi, Ali Madha and Rany Aburashed
Neurol. Int. 2025, 17(8), 122; https://doi.org/10.3390/neurolint17080122 - 6 Aug 2025
Abstract
Foreign Language Syndrome (FLS) is a rare neuropsychiatric condition characterized by the sudden, involuntary use of a non-native language, with concurrent loss or suppression of the native language. Distinct from Foreign Accent Syndrome (FAS), FLS often arises acutely following anesthesia, brain injury, or [...] Read more.
Foreign Language Syndrome (FLS) is a rare neuropsychiatric condition characterized by the sudden, involuntary use of a non-native language, with concurrent loss or suppression of the native language. Distinct from Foreign Accent Syndrome (FAS), FLS often arises acutely following anesthesia, brain injury, or psychological stress. Although neuroimaging typically reveals no structural pathology, functional disconnection within bilingual language control systems has been hypothesized. Case reports suggest contributions from both neurological disruptions—such as transient cortical dysfunction—and psychiatric mechanisms, including dissociation and conversion phenomena. This review synthesizes the clinical features, diagnostic strategies, neurocognitive models, and psychiatric interpretations of FLS. It emphasizes the importance of multidisciplinary evaluation and treatment and outlines prognosis patterns. The need for longitudinal follow-up, functional imaging studies, and centralized case databases is highlighted to better understand the pathophysiology and clinical management of this enigmatic syndrome. Full article
(This article belongs to the Section Brain Tumor and Brain Injury)
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16 pages, 2440 KiB  
Article
Dog–Stranger Interactions Can Facilitate Canine Incursion into Wilderness: The Role of Food Provisioning and Sociability
by Natalia Rojas-Troncoso, Valeria Gómez-Silva, Annegret Grimm-Seyfarth and Elke Schüttler
Biology 2025, 14(8), 1006; https://doi.org/10.3390/biology14081006 - 6 Aug 2025
Abstract
Most research on domestic dog (Canis familiaris) behavior has focused on pets with restricted movement. However, free-ranging dogs exist in diverse cultural contexts globally, and their interactions with humans are less understood. Tourists can facilitate unrestricted dog movement into wilderness areas, [...] Read more.
Most research on domestic dog (Canis familiaris) behavior has focused on pets with restricted movement. However, free-ranging dogs exist in diverse cultural contexts globally, and their interactions with humans are less understood. Tourists can facilitate unrestricted dog movement into wilderness areas, where they may negatively impact wildlife. This study investigated which stimuli—namely, voice, touch, or food—along with inherent factors (age, sex, sociability) motivate free-ranging dogs to follow a human stranger. We measured the distance (up to 600 m) of 129 free-ranging owned and stray dogs from three villages in southern Chile as they followed an experimenter who presented them one of the above stimuli or none (control). To evaluate the effect of dog sociability (i.e., positive versus stress-related or passive behaviors), we performed a 30 s socialization test (standing near the dog without interacting) before presenting a 10 s stimulus twice. We also tracked whether the dog was in the company of other dogs. Each focus dog was video-recorded and tested up to three times over five days. Generalized linear mixed-effects models revealed that the food stimulus significantly influenced dogs’ motivation to follow a stranger, as well as a high proportion of sociable behaviors directed towards humans and the company of other dogs present during the experiment. Juveniles tended to follow a stranger more than adults or seniors, but no effects were found for the dog’s sex, whether an owner was present, the repetition of trials, the location where the study was performed, or for individuals as a random variable. This research highlights that sociability as an inherent factor shapes dog–stranger interactions in free-ranging dogs when food is given. In the context of wildlife conservation, we recommend that managers promote awareness among local communities and tourists to avoid feeding dogs, especially in the context of outdoor activities close to wilderness. Full article
(This article belongs to the Special Issue Biology, Ecology, Management and Conservation of Canidae)
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23 pages, 2767 KiB  
Article
Sustainable Cotton Production in Sicily: Yield Optimization Through Varietal Selection, Mycorrhizae, and Efficient Water Management
by Giuseppe Salvatore Vitale, Nicolò Iacuzzi, Noemi Tortorici, Giuseppe Indovino, Loris Franco, Carmelo Mosca, Antonio Giovino, Aurelio Scavo, Sara Lombardo, Teresa Tuttolomondo and Paolo Guarnaccia
Agronomy 2025, 15(8), 1892; https://doi.org/10.3390/agronomy15081892 - 6 Aug 2025
Abstract
This study explores the revival of cotton (Gossypium spp. L.) farming in Italy through sustainable practices, addressing economic and water-related challenges by integrating cultivar selection, arbuscular mycorrhizal fungi (AMF) inoculation, and deficit irrigation under organic farming. Field trials evaluated two widely grown [...] Read more.
This study explores the revival of cotton (Gossypium spp. L.) farming in Italy through sustainable practices, addressing economic and water-related challenges by integrating cultivar selection, arbuscular mycorrhizal fungi (AMF) inoculation, and deficit irrigation under organic farming. Field trials evaluated two widely grown Mediterranean cultivars (Armonia and ST-318) under three irrigation levels (I-100: 100% crop water requirement; I-70: 70%; I-30: 30%) across two Sicilian soil types (sandy loam vs. clay-rich). Under I-100, lint yields reached 0.99 t ha−1, while severe deficit (I-30) yielded only 0.40 t ha−1. However, moderate deficit (I-70) maintained 75–79% of full yields, proving a viable strategy. AMF inoculation significantly enhanced plant height (68.52 cm vs. 65.85 cm), boll number (+22.1%), and seed yield (+12.5%) (p < 0.001). Cultivar responses differed: Armonia performed better under water stress, while ST-318 thrived with full irrigation. Site 1, with higher organic matter, required 31–38% less water and achieved superior irrigation water productivity (1.43 kg m−3). Water stress also shortened phenological stages, allowing earlier harvests—important for avoiding autumn rains. These results highlight the potential of combining adaptive irrigation, resilient cultivars, and AMF to restore sustainable cotton production in the Mediterranean, emphasizing the importance of soil-specific management. Full article
(This article belongs to the Section Farming Sustainability)
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13 pages, 2344 KiB  
Article
Study on the Risk of Reservoir Wellbore Collapse Throughout the Full Life Cycle of the Qianmiqiao Bridge Carbonate Rock Gas Storage Reservoir
by Yan Yu, Fuchun Tian, Feixiang Qin, Biao Zhang, Shuzhao Guo, Qingqin Cai, Zhao Chi and Chengyun Ma
Processes 2025, 13(8), 2480; https://doi.org/10.3390/pr13082480 - 6 Aug 2025
Abstract
Underground gas storage (UGS) in heterogeneous carbonate reservoirs is crucial for energy security but frequently faces wellbore instability challenges, which traditional static methods struggle to address due to dynamic full life cycle changes. This study systematically analyzes the dynamic evolution of wellbore stress [...] Read more.
Underground gas storage (UGS) in heterogeneous carbonate reservoirs is crucial for energy security but frequently faces wellbore instability challenges, which traditional static methods struggle to address due to dynamic full life cycle changes. This study systematically analyzes the dynamic evolution of wellbore stress in the Bs8 well (Qianmiqiao carbonate UGS) during drilling, acidizing, and injection-production operations, establishing a quantitative risk assessment model based on the Mohr–Coulomb criterion. Results indicate a significantly higher wellbore instability risk during drilling and initial gas injection stages, primarily manifested as shear failure, with greater severity observed in deeper well sections (e.g., 4277 m) due to higher in situ stresses. During acidizing, while the wellbore acid column pressure can reduce principal stress differences, the process also significantly weakens rock strength (e.g., by approximately 30%), inherently increasing the risk of wellbore instability, though the primary collapse mode remains shallow shear breakout. In the injection-production phase, increasing formation pressure is identified as the dominant factor, shifting the collapse mode from initial shallow shear failure to predominant wide shear collapse, notably at 90°/270° from the maximum horizontal stress direction, thereby significantly expanding the unstable zone. This dynamic assessment method provides crucial theoretical support for full life cycle integrity management and optimizing safe operation strategies for carbonate gas storage wells. Full article
(This article belongs to the Section Energy Systems)
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35 pages, 8516 KiB  
Article
Study on Stress Monitoring and Risk Early Warning of Flexible Mattress Deployment in Deep-Water Sharp Bend Reaches
by Chu Zhang, Ping Li, Zebang Cui, Kai Wu, Tianyu Chen, Zhenjia Tian, Jianxin Hao and Sudong Xu
Water 2025, 17(15), 2333; https://doi.org/10.3390/w17152333 - 6 Aug 2025
Abstract
This study addresses the complex challenges associated with flexible mattress (soft mattress) installation in the sharply curved and deep-water sections of the Yangtze River, particularly in the Yaozui revetment reconstruction project. Under extreme hydrodynamic conditions—water depths exceeding 30 m and velocities over 2.5 [...] Read more.
This study addresses the complex challenges associated with flexible mattress (soft mattress) installation in the sharply curved and deep-water sections of the Yangtze River, particularly in the Yaozui revetment reconstruction project. Under extreme hydrodynamic conditions—water depths exceeding 30 m and velocities over 2.5 m/s—the risk of structural failures such as displacement, flipping, or tearing of the mattress becomes significant. To improve construction safety and stability, the study integrates numerical modeling and on-site strain monitoring to analyze the mechanical response of flexible mattresses during deployment. A three-dimensional finite element model based on the catenary theory was developed to simulate stress distributions under varying flow velocities and angles, revealing stress concentrations at the mattress’s upper edge and reinforcement junctions. Concurrently, a real-time monitoring system using high-precision strain sensors was deployed on critical shipboard components, with collected data analyzed through a remote IoT platform. The results demonstrate strong correlations between mattress strain, flow velocity, and water depth, enabling the identification of high-risk operational thresholds. The proposed monitoring and early-warning framework offers a practical solution for managing construction risks in extreme riverine environments and contributes to the advancement of intelligent construction management for underwater revetment works. Full article
(This article belongs to the Section Oceans and Coastal Zones)
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17 pages, 1396 KiB  
Article
Dose-Dependent Effect of the Polyamine Spermine on Wheat Seed Germination, Mycelium Growth of Fusarium Seed-Borne Pathogens, and In Vivo Fusarium Root and Crown Rot Development
by Tsvetina Nikolova, Dessislava Todorova, Tzenko Vatchev, Zornitsa Stoyanova, Valya Lyubenova, Yordanka Taseva, Ivo Yanashkov and Iskren Sergiev
Agriculture 2025, 15(15), 1695; https://doi.org/10.3390/agriculture15151695 - 6 Aug 2025
Abstract
Wheat (Triticum aestivum L.) is a crucial global food crop. The intensive crop farming, monoculture cultivation, and impact of climate change affect the susceptibility of wheat cultivars to biotic stresses, mainly caused by soil fungal pathogens, especially those belonging to the genus [...] Read more.
Wheat (Triticum aestivum L.) is a crucial global food crop. The intensive crop farming, monoculture cultivation, and impact of climate change affect the susceptibility of wheat cultivars to biotic stresses, mainly caused by soil fungal pathogens, especially those belonging to the genus Fusarium. This situation threatens yield and grain quality through root and crown rot. While conventional chemical fungicides face resistance issues and environmental concerns, biological alternatives like seed priming with natural metabolites are gaining attention. Polyamines, including putrescine, spermidine, and spermine, are attractive priming agents influencing plant development and abiotic stress responses. Spermine in particular shows potential for in vitro antifungal activity against Fusarium. Optimising spermine concentration for seed priming is crucial to maximising protection against Fusarium infection while ensuring robust plant growth. In this research, we explored the potential of the polyamine spermine as a seed treatment to enhance wheat resilience, aiming to identify a sustainable alternative to synthetic fungicides. Our findings revealed that a six-hour seed soak in spermine solutions ranging from 0.5 to 5 mM did not delay germination or seedling growth. In fact, the 5 mM concentration significantly stimulated root weight and length. In complementary in vitro assays, we evaluated the antifungal activity of spermine (0.5–5 mM) against three Fusarium species. The results demonstrated complete inhibition of Fusarium culmorum growth at 5 mM spermine. A less significant effect on Fusarium graminearum and little to no impact on Fusarium oxysporum were found. The performed analysis revealed that the spermine had a fungistatic effect against the pathogen, retarding the mycelium growth of F. culmorum inoculated on the seed surface. A pot experiment with Bulgarian soft wheat cv. Sadovo-1 was carried out to estimate the effect of seed priming with spermine against infection with isolates of pathogenic fungus F. culmorum on plant growth and disease severity. Our results demonstrated that spermine resulted in a reduced distribution of F. culmorum and improved plant performance, as evidenced by the higher fresh weight and height of plants pre-treated with spermine. This research describes the efficacy of spermine seed priming as a novel strategy for managing Fusarium root and crown rot in wheat. Full article
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18 pages, 732 KiB  
Article
L-Arginine Effect as an Additive on Overall Performance, Health Status, and Expression of Stress Molecular Markers in Nile Tilapia (Oreochromis niloticus) Under Chronic Salinity Exposure
by Andrea Itzel Munguía-Casillas, María Teresa Viana, Miroslava Vivanco-Aranda, Luis Eduardo Ruiz-González, Emyr Saul Peña-Marín and Oscar Basilio Del Rio-Zaragoza
Fishes 2025, 10(8), 387; https://doi.org/10.3390/fishes10080387 - 6 Aug 2025
Abstract
Growing freshwater fish in saline environments is being explored as a potential solution to the freshwater shortage. However, growing these organisms in suboptimal salinity conditions leads to chronic stress that can be challenging to manage. To address this goal, it is crucial to [...] Read more.
Growing freshwater fish in saline environments is being explored as a potential solution to the freshwater shortage. However, growing these organisms in suboptimal salinity conditions leads to chronic stress that can be challenging to manage. To address this goal, it is crucial to improve the health of fish through the use of dietary supplements. This study evaluated the effects of varying levels of arginine supplementation on the growth, health status, and expression of stress-related molecular markers in juveniles of Nile tilapia exposed to chronic salinity stress. The tilapia were fed four experimental diets supplemented with 0, 1, 2, and 3% of L-arginine (T0, T1, T2, and T3). After an acclimatization period, the tilapias were exposed to a salinity level of 20‰ for 57 days in a recirculating aquaculture system. Our findings revealed that overall performance parameters were significantly influenced by L-arginine supplementation, except for the condition factor, viscerosomatic index, and hepatosomatic index. Additionally, intermediate levels of L-arginine supplementation positively influenced various blood parameters, including hematological profiles (hemoglobin and leukocytes), blood chemistry (total protein, albumin, globulin, and triglycerides), and the frequency of certain nuclear abnormalities. Furthermore, L-arginine supplementation appeared to regulate the expression of molecular markers related to stress and the immune system. In conclusion, this study indicates that L-arginine supplementation can help alleviate the chronic stress caused by salinity in juvenile Nile tilapia. Full article
(This article belongs to the Special Issue Fish Hematology)
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25 pages, 4393 KiB  
Article
Development and Preclinical Evaluation of Fixed-Dose Capsules Containing Nicergoline, Piracetam, and Hawthorn Extract for Sensorineural Hearing Loss
by Lucia Maria Rus, Andrei Uncu, Sergiu Parii, Alina Uifălean, Simona Codruța Hegheș, Cristina Adela Iuga, Ioan Tomuță, Ecaterina Mazur, Diana Șepeli, Irina Kacso, Fliur Macaev, Vladimir Valica and Livia Uncu
Pharmaceutics 2025, 17(8), 1017; https://doi.org/10.3390/pharmaceutics17081017 - 5 Aug 2025
Abstract
Background: Fixed-dose combinations have advanced in many therapeutic areas, including otorhinolaryngology, where hearing disorders are increasingly prevalent. Objectives: The present study focuses on developing and evaluating a new capsule combining nicergoline (NIC), piracetam (PIR), and hawthorn extract (HE) for the management of sensorineural [...] Read more.
Background: Fixed-dose combinations have advanced in many therapeutic areas, including otorhinolaryngology, where hearing disorders are increasingly prevalent. Objectives: The present study focuses on developing and evaluating a new capsule combining nicergoline (NIC), piracetam (PIR), and hawthorn extract (HE) for the management of sensorineural hearing loss. Methods: The first phase methodology comprised preformulation studies (DSC, FTIR, and PXRD) to assess compatibility among active substances and excipients. Subsequently, four formulations were prepared and tested for flowability, dissolution behavior in acidic and neutral media, and stability under oxidative, thermal, and photolytic stress. Quantification of the active substances and flavonoids was performed using validated spectrophotometric and HPLC-UV methods. Results: Among the tested variants, the F1 formulation (4.5 mg NIC, 200 mg PIR, 50 mg HE, 2.5 mg magnesium stearate, 2.5 mg sodium starch glycolate, and 240.5 mg monohydrate lactose per capsule) displayed optimal technological properties, superior dissolution in acidic media, and was further selected for evaluation. The antioxidant activity of the formulation was confirmed through the 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay, Trolox Equivalent Antioxidant Capacity (TEAC), and iron chelation tests, and was primarily attributed to the flavonoid content of the HE. Acute toxicity tests in mice and rats indicated a high safety margin (LD50 > 2500 mg/kg), while ototoxicity assessments showed no adverse effects on auditory function. Conclusions: The developed formulation displayed good stability, safety, and therapeutic potential, while the applied workflow could represent a model for the development of future fixed-dose combinations. Full article
(This article belongs to the Special Issue Natural Product Pharmaceuticals, 2nd Edition)
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20 pages, 8344 KiB  
Article
Gum Acacia–Dexamethasone Combination Attenuates Sepsis-Induced Acute Kidney Injury in Rats via Targeting SIRT1-HMGB1 Signaling Pathway and Preserving Mitochondrial Integrity
by Fawaz N. Alruwaili, Omnia A. Nour and Tarek M. Ibrahim
Pharmaceuticals 2025, 18(8), 1164; https://doi.org/10.3390/ph18081164 - 5 Aug 2025
Abstract
Background/Objective: Sepsis-associated acute kidney injury (SA-AKI) is a substantial contributor to mortality in critically ill patients. This study aimed to investigate the impact of gum acacia (GA) and dexamethasone (DEX) combination on lipopolysaccharide (LPS)-induced SA-AKI in rats. Methods: Thirty-six male Sprague Dawley [...] Read more.
Background/Objective: Sepsis-associated acute kidney injury (SA-AKI) is a substantial contributor to mortality in critically ill patients. This study aimed to investigate the impact of gum acacia (GA) and dexamethasone (DEX) combination on lipopolysaccharide (LPS)-induced SA-AKI in rats. Methods: Thirty-six male Sprague Dawley rats were separated into six groups, including the control, GA group, LPS-induced AKI group, DEX + LPS group, GA + LPS group, and GA + DEX + LPS group. AKI was induced in rats using LPS (10 mg/kg, i.p.). GA was administered orally (7.5 g/kg) for 14 days before LPS injection, and DEX was injected (1 mg/kg, i.p.) 2 h after LPS injection. Results: LPS injection significantly (p < 0.05, vs. control group) impaired renal function, as evidenced through increased levels of kidney function biomarkers, decreased creatinine clearance, and histopathological alterations in the kidneys. LPS also significantly (p < 0.05, vs. control group) elevated levels of oxidative stress markers, while it reduced levels of antioxidant enzymes. Furthermore, LPS triggered an inflammatory response, manifested by significant (p < 0.05, vs. control group) upregulation of Toll-like receptor 4, myeloid differentiation primary response 88, interleukin-1β, tumor necrosis factor-α, and nuclear factor-κB, along with increased expression of high-mobility group box 1. Administration of GA significantly ameliorated LPS-induced renal impairment by enhancing antioxidant defenses and suppressing inflammatory pathways (p < 0.05, vs. LPS group). Furthermore, GA-DEX-treated rats showed improved kidney function, reduced oxidative stress, and attenuated inflammatory markers (p < 0.05, vs. LPS group). Conclusions: The GA-DEX combination exhibited potent renoprotective effects against LPS-induced SA-AKI, possibly due to their antioxidant and anti-inflammatory properties. These results suggest that the GA-DEX combination could be a promising and effective therapeutic agent for managing SA-AKI. Full article
(This article belongs to the Section Pharmacology)
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30 pages, 3316 KiB  
Systematic Review
Preclinical Evidence of Curcuma longa Linn. as a Functional Food in the Management of Metabolic Syndrome: A Systematic Review and Meta-Analysis of Rodent Studies
by Samuel Abiodun Kehinde, Zahid Naeem Qaisrani, Rinrada Pattanayaiying, Wai Phyo Lin, Bo Bo Lay, Khin Yadanar Phyo, Myat Mon San, Nurulhusna Awaeloh, Sasithon Aunsorn, Ran Kitkangplu and Sasitorn Chusri
Biomedicines 2025, 13(8), 1911; https://doi.org/10.3390/biomedicines13081911 - 5 Aug 2025
Abstract
Background/Objectives: Metabolic syndrome (MetS) is a multifactorial condition characterized by abdominal obesity, dyslipidemia, insulin resistance, hypertension, and chronic inflammation. As its global prevalence rises, there is increasing interest in natural, multi-targeted approaches to manage MetS. Curcuma longa Linn. (turmeric), especially its active [...] Read more.
Background/Objectives: Metabolic syndrome (MetS) is a multifactorial condition characterized by abdominal obesity, dyslipidemia, insulin resistance, hypertension, and chronic inflammation. As its global prevalence rises, there is increasing interest in natural, multi-targeted approaches to manage MetS. Curcuma longa Linn. (turmeric), especially its active compound curcumin, has shown therapeutic promise in preclinical studies. This systematic review and meta-analysis evaluated the effects of Curcuma longa and its derivatives on MetS-related outcomes in rodent models. Methods: A comprehensive search was conducted across six databases (PubMed, Scopus, AMED, LILACS, MDPI, and Google Scholar), yielding 47 eligible in vivo studies. Data were extracted on key metabolic, inflammatory, and oxidative stress markers and analyzed using random-effects models. Results were presented as mean differences (MD) with 95% confidence intervals (CI). Results: Meta-analysis showed that curcumin significantly reduced body weight (rats: MD = −42.10; mice: MD = −2.91), blood glucose (rats: MD = −55.59; mice: MD = −28.69), triglycerides (rats: MD = −70.17; mice: MD = −24.57), total cholesterol (rats: MD = −35.77; mice: MD = −52.61), and LDL cholesterol (rats: MD = −69.34; mice: MD = −42.93). HDL cholesterol increased significantly in rats but not in mice. Inflammatory cytokines were markedly reduced, while oxidative stress improved via decreased malondialdehyde (MDA) and elevated superoxide dismutase (SOD) and catalase (CAT) levels. Heterogeneity was moderate to high, primarily due to variations in curcumin dosage (ranging from 10 to 500 mg/kg) and treatment duration (2 to 16 weeks) across studies. Conclusions: This preclinical evidence supports Curcuma longa as a promising functional food component for preventing and managing MetS. Its multi-faceted effects warrant further clinical studies to validate its translational potential. Full article
(This article belongs to the Special Issue The Role of Cytokines in Health and Disease: 3rd Edition)
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