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Search Results (361)

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18 pages, 1744 KB  
Article
Protective Effects of Momordica charantia Fruit Extract on Male Sexual Dysfunction and Testicular Damage in Rats Induced by Chronic Unpredictable Stressors
by Therachon Kamollerd, Suwit Uopasai, Tarinee Sawatpanich, Nongnut Uabundit, Supatcharee Arun, Nareelak Tangsrisakda, Chayakorn Taoto, Chadaporn Chaimontri, Natthapol Lapyuneyong, Wipawee Thukhammee, Sararat Innoi and Sitthichai Iamsaard
Life 2025, 15(10), 1559; https://doi.org/10.3390/life15101559 - 4 Oct 2025
Viewed by 278
Abstract
Chronic stress (CS) is known to induce testicular oxidative stress and apoptosis. Fruit of Momordica charantia (FMC) has antioxidant capacity to protect tissue damage, but its effect on sexual activity and testicular damage caused by CS has never been documented. This study aimed [...] Read more.
Chronic stress (CS) is known to induce testicular oxidative stress and apoptosis. Fruit of Momordica charantia (FMC) has antioxidant capacity to protect tissue damage, but its effect on sexual activity and testicular damage caused by CS has never been documented. This study aimed to investigate the impact of FMC extract against testicular damage and sexual dysfunction in chronic unpredictable stress (CUS) rats. Rats were divided into four groups and pretreated with vehicle or FMC (40 and 80 mg/kg) before CUS induction for 56 days. Sexual behaviors, serum hormones, and sperm quality were analyzed. Testes were collected to determine daily sperm production (DSP), malondialdehyde (MDA) level, and expressions of cleaved apoptotic proteins. Testicular DNA fragmentation, as revealed by TUNEL and morphometric analysis, was observed. FMC improved sexual activity, increased testosterone levels, and sperm count with improvements in DSP, testicular morphometrics, and MDA levels. Moreover, TUNEL-positive cells and expression of caspase 3 in the testis were decreased in FMC rats. FMC has antioxidant potential and could protect against male sexual dysfunction and testicular damage caused by stress-related apoptosis. It is a potential extract to be developed as a supplement in preventing CS-male subfertility. However, future studies about the optimal dose and clinical trials are required. Full article
(This article belongs to the Section Plant Science)
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14 pages, 1570 KB  
Article
Response of Pearl Millet (Pennisetum glaucum [L.] R. Br.) Growth to Post-Emergence Water Stress
by Lazare Vourbouè Bazie, Inoussa Drabo, Koussao Some, Armel Rouamba and Pauline Bationo (Kando)
Agronomy 2025, 15(10), 2321; https://doi.org/10.3390/agronomy15102321 - 30 Sep 2025
Viewed by 221
Abstract
Pearl millet is primarily grown under rainfed conditions in Sub-Saharan Africa. Early droughts are prevalent in the Sahel region, where pearl millet is widely cultivated, and they severely impact pearl millet growth and productivity by affecting plant stand and reducing plant density in [...] Read more.
Pearl millet is primarily grown under rainfed conditions in Sub-Saharan Africa. Early droughts are prevalent in the Sahel region, where pearl millet is widely cultivated, and they severely impact pearl millet growth and productivity by affecting plant stand and reducing plant density in the field. Consequently, genetic improvement for early drought tolerance is a promising strategy to enhance productivity in these regions. This study aims to identify pearl millet lines that are tolerant to water stress at the seedling stage by assessing various water-stress-tolerance traits. Two hundred pearl millet inbred lines were screened for drought tolerance by inducing water stress with polyethylene glycol 6000 (PEG 6000) in the laboratory. The experiment was repeated in the greenhouse using pot screening. The experimental design was an alpha lattice with 10 entries × 20 blocks in two replications. Four treatments (0 g/L, 115 g/L, 235 g/L, 289 g/L) were applied in the laboratory: one control and three concentrations of PEG 6000. Control and stress were applied in the greenhouse. Data were collected on germination rate and growth parameters, including root and seedling length, leaf length and width, and chlorophyll content. Results revealed significant differences among the pearl millet inbred lines under both drought and well-watered conditions. The inbred lines IP-16403 and IP-18062 were the most tolerant in both the greenhouse and laboratory. Water stress significantly reduced plant growth, although an increase in root length was observed in some lines. The number of days to 50% emergence was positively and strongly correlated with survival time (+0.45), while leaf width was negatively correlated with survival time (−0.29) and water stress tolerance (−0.37). The drought-tolerant and drought-susceptible pearl millet inbred lines identified in this study provide valuable genetic resources for enhancing pearl millet productivity in arid and semi-arid environments, especially in the face of unpredictable climate variability. Full article
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25 pages, 2736 KB  
Article
Therapeutic Effects of Intranasal Administration of Mesenchymal Stem Cell-Derived Secretome in Rats Exposed to Chronic Unpredictable Mild Stress
by Alba Ávila, María Eugenia Riveros, Sofía Adasme, Coram Guevara, Rodrigo Del Rio, Fernando C. Ortiz, Nicole Leibold and Fernando Ezquer
Pharmaceutics 2025, 17(9), 1129; https://doi.org/10.3390/pharmaceutics17091129 - 29 Aug 2025
Viewed by 845
Abstract
Background: Major depression is a significant source of suffering and economic loss. Despite efforts to understand this condition and find better treatments, the burden imposed by this disease continues to rise. Most approved pharmacological treatments for depression focus on controlling the availability [...] Read more.
Background: Major depression is a significant source of suffering and economic loss. Despite efforts to understand this condition and find better treatments, the burden imposed by this disease continues to rise. Most approved pharmacological treatments for depression focus on controlling the availability of monoamines in synapses. However, accumulating evidence suggests that neuroinflammation, oxidative stress, and reduced hippocampal neurogenesis play key roles as causal factors in the development of major depression symptoms. Therefore, preclinical testing of pharmacological approaches targeting these factors is essential. Mesenchymal stem cells (MSCs) are known for their potential as powerful antioxidants and anti-inflammatory agents, exerting neuroprotective actions in the brain. They produce various therapeutic molecules in a paracrine manner, collectively known as secretome. Methods: In this work, we evaluated the antidepressant potential of repeated intranasal administration of MSC-derived secretome in an animal model of major depressive disorder induced by chronic mild unpredictable stress. Results: We observed that intranasal administration of MSC-derived secretome reduced the appearance of some of the behavioral parameters commonly associated with major depression, including anhedonic, apathetic, and anxious behaviors, inducing a strong reduction in the overall depression score compared to vehicle-treated animals. At the structural level, secretome administration prevented increased astrocyte density and the atrophy of astrocyte processes observed in vehicle-treated stressed animals. Additionally, secretome administration induced an increase in myelin levels and oligodendroglia in the cortex. Conclusions: Our data suggests that intranasal administration of MSC-derived secretome may represent a potential therapeutic alternative to current treatments for this devastating pathology. Full article
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28 pages, 57007 KB  
Article
Hybrid B5G-DTN Architecture with Federated Learning for Contextual Communication Offloading
by Manuel Jesús-Azabal, Meichun Zheng and Vasco N. G. J. Soares
Future Internet 2025, 17(9), 392; https://doi.org/10.3390/fi17090392 - 29 Aug 2025
Viewed by 676
Abstract
In dense urban environments and large-scale events, Internet infrastructure often becomes overloaded due to high communication demand. Many of these communications are local and short-lived, exchanged between users in close proximity but still relying on global infrastructure, leading to unnecessary network stress. In [...] Read more.
In dense urban environments and large-scale events, Internet infrastructure often becomes overloaded due to high communication demand. Many of these communications are local and short-lived, exchanged between users in close proximity but still relying on global infrastructure, leading to unnecessary network stress. In this context, delay-tolerant networks (DTNs) offer an alternative by enabling device-to-device (D2D) communication without requiring constant connectivity. However, DTNs face significant challenges in routing due to unpredictable node mobility and intermittent contacts, making reliable delivery difficult. Considering these challenges, this paper presents a hybrid Beyond 5G (B5G) DTN architecture to provide private context-aware routing in dense scenarios. In this proposal, dynamic contextual notifications are shared among relevant local nodes, combining federated learning (FL) and edge artificial intelligence (AI) to estimate the optimal relay paths based on variables such as mobility patterns and contact history. To keep the local FL models updated with the evolving context, edge nodes, integrated as part of the B5G architecture, act as coordinating entities for model aggregation and redistribution. The proposed architecture has been implemented and evaluated in simulation testbeds, studying its performance and sensibility to the node density in a realistic scenario. In high-density scenarios, the architecture outperforms state-of-the-art routing schemes, achieving an average delivery probability of 77%, with limited latency and overhead, demonstrating relevant technical viability. Full article
(This article belongs to the Special Issue Distributed Machine Learning and Federated Edge Computing for IoT)
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19 pages, 3100 KB  
Article
Diminished Estrogen Induced Mitochondrial Protection and Immunosuppressive Microenvironment in Gastric Cancer with Depression
by Yixin Liu, Sheng Tian, Yujia Tan, Picheng Yan, Pan Liu, Huiying Zhu, Sachiyo Nomura, Tianhe Huang and Yongchang Wei
Cancers 2025, 17(17), 2789; https://doi.org/10.3390/cancers17172789 - 26 Aug 2025
Viewed by 718
Abstract
Background: It is established that depression significantly contributes to tumor development, yet its molecular link to gastric cancer progression remains unclear. Methods: In this study, we examined depression-related gene expression profiles in relation to clinical prognosis and identified estradiol and the NOTCH3 gene [...] Read more.
Background: It is established that depression significantly contributes to tumor development, yet its molecular link to gastric cancer progression remains unclear. Methods: In this study, we examined depression-related gene expression profiles in relation to clinical prognosis and identified estradiol and the NOTCH3 gene as critical factors involved in gastric cancer progression in the context of depression. Using a chronic unpredictable stress-induced tumor-bearing mouse model, we validated the impact of depression on tumor development. Additionally, the underlying molecular mechanisms were explored through a range of biological techniques, including Western blotting, immunofluorescence, flow cytometry and immunohistochemistry. Results: Depression significantly accelerated gastric cancer growth in our mouse model, characterized by decreased estradiol levels and increased NOTCH3 expression. Importantly, exogenous estradiol supplementation effectively counteracted depression-induced tumor growth. Consistently, in vitro studies showed that estradiol treatment suppressed NOTCH3 expression in HGC-27 and YTN3 cell lines. Furthermore, NOTCH3 was shown to modulate intracellular reactive oxygen species levels by regulating SOD2 activity, thereby influencing cell proliferation. Conclusions: This work identified the estrogen/NOTCH3 signaling as a key link between depression and gastric cancer development, offering promising therapeutic strategies to improve outcomes for patients suffering from psychological disorders. Full article
(This article belongs to the Special Issue Gastrointestinal Malignancy: Epidemiology and Risk Factors)
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27 pages, 11958 KB  
Article
In Silico and In Vivo Studies Reveal the Potential Preventive Impact of Cuminum cyminum and Foeniculum vulgare Essential Oil Nanocapsules Against Depression-like States in Mice Fed a High-Fat Diet and Exposed to Chronic Unpredictable Mild Stress
by Karem Fouda and Rasha S. Mohamed
Sci. Pharm. 2025, 93(3), 37; https://doi.org/10.3390/scipharm93030037 - 14 Aug 2025
Viewed by 909
Abstract
Hyperlipidemia, oxidative stress, and excessive inflammatory cytokine production are risk factors for depression. The potential preventive effects of essential oils (EOs) such as cumin and fennel EOs on depression may stem from their hypolipidemic, antioxidant, and anti-inflammatory activities. This work aimed to investigate [...] Read more.
Hyperlipidemia, oxidative stress, and excessive inflammatory cytokine production are risk factors for depression. The potential preventive effects of essential oils (EOs) such as cumin and fennel EOs on depression may stem from their hypolipidemic, antioxidant, and anti-inflammatory activities. This work aimed to investigate the effects of cumin and fennel EO nanocapsules in a mouse model of depression caused by a high-fat diet (HFD) and chronic mild stress (CMS) using both in silico and in vivo studies. The cumin and fennel EOs were extracted, analyzed by GC-MS, and encapsulated in nano-form using gum Arabic and maltodextrin as wall materials. The freeze-dried nanocapsules were evaluated in HFD/CMS-treated mice. Molecular docking was used to examine the significance of the oils’ compounds in blocking the active sites of hydroxymethylglutaryl-CoA (HMG-CoA) and indoleamine 2,3-dioxygenase (IDO). According to the molecular docking results, the interactions between EO components and HMG-CoA or IDO indicate that these EOs may have hypercholesterolemic and antidepressive effects. Cumin and fennel EO nanocapsules showed hypolipidemic, antioxidant, and anti-inflammatory effects in vivo. This was demonstrated by the down-regulation of oxidants (ROS, MDA, and NO) and inflammatory markers (TLR4, TNF-α, and IL-6) in the brain, changes in lipid profile parameters, and the up-regulation of antioxidant enzymes (SOD, CAT, and GSH). The in silico and in vivo outputs revealed the potential preventive impact of cumin and fennel EO nanocapsules against depression-like states in the mouse model through the prevention of dyslipidemia, neuroxidation, and neuroinflammation. More human studies are needed to fully understand the antidepressive effects of cumin and fennel EO nanocapsules. Full article
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18 pages, 1482 KB  
Article
Optimizing Power Sharing and Demand Reduction in Distributed Energy Resources for Apartments Through Tenant Incentivization
by Janak Nambiar, Samson Yu, Jag Makam and Hieu Trinh
Energies 2025, 18(15), 4073; https://doi.org/10.3390/en18154073 - 31 Jul 2025
Viewed by 421
Abstract
The increasing demand for electricity in multi-tenanted residential areas has placed unforeseen strain on sub-transformers, particularly in dense urban environments. This strain compromises overall grid performance and challenges utilities with shifting and rising peak demand periods. This study presents a novel approach to [...] Read more.
The increasing demand for electricity in multi-tenanted residential areas has placed unforeseen strain on sub-transformers, particularly in dense urban environments. This strain compromises overall grid performance and challenges utilities with shifting and rising peak demand periods. This study presents a novel approach to enhance the operation of a virtual power plant (VPP) comprising a microgrid (MG) integrated with renewable energy sources (RESs) and energy storage systems (ESSs). By employing an advanced monitoring and control system, the proposed topology enables efficient energy management and demand-side control within apartment complexes. The system supports controlled electricity distribution, reducing the likelihood of unpredictable demand spikes and alleviating stress on local infrastructure during peak periods. Additionally, the model capitalizes on the large number of tenancies to distribute electricity effectively, leveraging locally available RESs and ESSs behind the sub-transformer. The proposed research provides a systematic framework for managing electricity demand and optimizing resource utilization, contributing to grid reliability and a transition toward a more sustainable, decentralized energy system. Full article
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31 pages, 6501 KB  
Review
From Hormones to Harvests: A Pathway to Strengthening Plant Resilience for Achieving Sustainable Development Goals
by Dipayan Das, Hamdy Kashtoh, Jibanjyoti Panda, Sarvesh Rustagi, Yugal Kishore Mohanta, Niraj Singh and Kwang-Hyun Baek
Plants 2025, 14(15), 2322; https://doi.org/10.3390/plants14152322 - 27 Jul 2025
Viewed by 2383
Abstract
The worldwide agriculture industry is facing increasing problems due to rapid population increase and increasingly unfavorable weather patterns. In order to reach the projected food production targets, which are essential for guaranteeing global food security, innovative and sustainable agricultural methods must be adopted. [...] Read more.
The worldwide agriculture industry is facing increasing problems due to rapid population increase and increasingly unfavorable weather patterns. In order to reach the projected food production targets, which are essential for guaranteeing global food security, innovative and sustainable agricultural methods must be adopted. Conventional approaches, including traditional breeding procedures, often cannot handle the complex and simultaneous effects of biotic pressures such as pest infestations, disease attacks, and nutritional imbalances, as well as abiotic stresses including heat, salt, drought, and heavy metal toxicity. Applying phytohormonal approaches, particularly those involving hormonal crosstalk, presents a viable way to increase crop resilience in this context. Abscisic acid (ABA), gibberellins (GAs), auxin, cytokinins, salicylic acid (SA), jasmonic acid (JA), ethylene, and GA are among the plant hormones that control plant stress responses. In order to precisely respond to a range of environmental stimuli, these hormones allow plants to control gene expression, signal transduction, and physiological adaptation through intricate networks of antagonistic and constructive interactions. This review focuses on how the principal hormonal signaling pathways (in particular, ABA-ET, ABA-JA, JA-SA, and ABA-auxin) intricately interact and how they affect the plant stress response. For example, ABA-driven drought tolerance controls immunological responses and stomatal behavior through antagonistic interactions with ET and SA, while using SnRK2 kinases to activate genes that react to stress. Similarly, the transcription factor MYC2 is an essential node in ABA–JA crosstalk and mediates the integration of defense and drought signals. Plants’ complex hormonal crosstalk networks are an example of a precisely calibrated regulatory system that strikes a balance between growth and abiotic stress adaptation. ABA, JA, SA, ethylene, auxin, cytokinin, GA, and BR are examples of central nodes that interact dynamically and context-specifically to modify signal transduction, rewire gene expression, and change physiological outcomes. To engineer stress-resilient crops in the face of shifting environmental challenges, a systems-level view of these pathways is provided by a combination of enrichment analyses and STRING-based interaction mapping. These hormonal interactions are directly related to the United Nations Sustainable Development Goals (SDGs), particularly SDGs 2 (Zero Hunger), 12 (Responsible Consumption and Production), and 13 (Climate Action). This review emphasizes the potential of biotechnologies to use hormone signaling to improve agricultural performance and sustainability by uncovering the molecular foundations of hormonal crosstalk. Increasing our understanding of these pathways presents a strategic opportunity to increase crop resilience, reduce environmental degradation, and secure food systems in the face of increasing climate unpredictability. Full article
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55 pages, 4973 KB  
Review
Zebrafish as a Model Organism for Post-Traumatic Stress Disorder: Insights into Stress Mechanisms and Behavioral Assays
by Alexey Sarapultsev, Maria Komelkova, Oleg Lookin, Sergey Khatsko, Alexander Zhdanov, Stanislav Fedorov, Evgenii Gusev, Alexander Trofimov, Tursonjan Tokay and Desheng Hu
Biology 2025, 14(8), 939; https://doi.org/10.3390/biology14080939 - 25 Jul 2025
Viewed by 1463
Abstract
The zebrafish (Danio rerio) has emerged as a powerful model organism for investigating the mechanisms of post-traumatic stress disorder (PTSD), offering unique advantages in translational relevance, genetic trackability, and cost-effectiveness. As a logical continuation of our recent systematic review, this manuscript [...] Read more.
The zebrafish (Danio rerio) has emerged as a powerful model organism for investigating the mechanisms of post-traumatic stress disorder (PTSD), offering unique advantages in translational relevance, genetic trackability, and cost-effectiveness. As a logical continuation of our recent systematic review, this manuscript critically examines the spectrum of experimental strategies used to model PTSD in zebrafish, with a focus on the comparative efficacy and validity of acute, chronic, and complex stress paradigms. Among these, 14–15-day chronic unpredictable stress (CUS/UCS) protocols are identified as the gold standard, reliably inducing core PTSD-like phenotypes—such as anxiety-like behavior, cortisol dysregulation, and neuroinflammatory gene activation. We discuss the influence of environmental, developmental, and genetic factors on stress responses, and highlight the importance of standardized behavioral and molecular endpoints for model validation. While alternative paradigms—including acute, social, pharmacological, and predator-based models—offer mechanistic insights, their translational relevance remains limited without further refinement. We conclude by outlining future directions for zebrafish-based PTSD research, emphasizing the need for protocol harmonization, integration of multi-modal readouts, and exploration of individual variability to enhance the translational value of this model system. Full article
(This article belongs to the Special Issue Social Behavior in Zebrafish)
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35 pages, 1752 KB  
Review
Recent Advances in Biodegradable Magnesium Alloys for Medical Implants: Evolution, Innovations, and Clinical Translation
by Mykyta Aikin, Vadim Shalomeev, Volodymyr Kukhar, Andrii Kostryzhev, Ihor Kuziev, Viktoriia Kulynych, Oleksandr Dykha, Volodymyr Dytyniuk, Oleksandr Shapoval, Alvydas Zagorskis, Vadym Burko, Olha Khliestova, Viacheslav Titov and Oleksandr Hrushko
Crystals 2025, 15(8), 671; https://doi.org/10.3390/cryst15080671 - 23 Jul 2025
Cited by 3 | Viewed by 3335
Abstract
Biodegradable magnesium alloys have emerged as promising alternatives to permanent metallic implants due to their unique combination of mechanical compatibility with bone and complete resorption, addressing the persistent issues of stress shielding and secondary removal surgeries. This review critically examines the historical development [...] Read more.
Biodegradable magnesium alloys have emerged as promising alternatives to permanent metallic implants due to their unique combination of mechanical compatibility with bone and complete resorption, addressing the persistent issues of stress shielding and secondary removal surgeries. This review critically examines the historical development of magnesium-based biomaterials, highlighting advances in alloy design, manufacturing processes, and surface engineering that now enable tailored degradation and improved clinical performance. Drawing on recent clinical and preclinical studies, we summarize improvements in corrosion resistance, mechanical properties, and biocompatibility that have supported the clinical translation of magnesium alloys across a variety of orthopedic and emerging medical applications. However, challenges remain, including unpredictable in vivo degradation kinetics, limited long-term safety data, lack of standardized testing protocols, and ongoing regulatory uncertainties. We conclude that while magnesium-based biomaterials have advanced from experimental concepts to clinically validated solutions, further progress in personalized degradation control, real-time monitoring, and harmonized regulatory frameworks is needed to fully realize their transformative clinical potential. Full article
(This article belongs to the Special Issue Development of Light Alloys and Their Applications)
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21 pages, 13574 KB  
Article
Effect of Processing-Induced Oxides on the Fatigue Life Variability of 6082 Al-Mg-Si Alloy Extruded Components
by Viththagan Vivekanandam, Shubham Sanjay Joshi, Jaime Lazaro-Nebreda and Zhongyun Fan
J. Manuf. Mater. Process. 2025, 9(7), 247; https://doi.org/10.3390/jmmp9070247 - 21 Jul 2025
Viewed by 903
Abstract
Aluminium alloy 6082 is widely used in the automotive and aerospace industries due to its high strength-to-weight ratio. However, its structural integrity can sometimes be affected by an early fatigue failure. This study investigates the fatigue performance of extruded 6082-T6 samples through a [...] Read more.
Aluminium alloy 6082 is widely used in the automotive and aerospace industries due to its high strength-to-weight ratio. However, its structural integrity can sometimes be affected by an early fatigue failure. This study investigates the fatigue performance of extruded 6082-T6 samples through a series of fatigue tests conducted at varying stress levels. The material showed significant variability under identical fatigue conditions, suggesting the presence of microstructural defects. Scanning electron microscopy with energy-dispersive spectroscopy (SEM/EDS) and scanning transmission electron microscopy (S/TEM) were used to identify the nature and location of the defects and evaluate the underlying mechanisms influencing the fatigue performance. Computer tomography (CT) also confirmed the presence of oxide inclusions on the fracture surface and near the edges of the samples. These oxide inclusions are distributed throughout the material heterogeneously and in the form of broken oxide films, suggesting that they might have originated during the material’s early processing stages. These oxides acted as stress concentrators, initiating microcracks that led to catastrophic and unpredictable early failure, ultimately reducing the fatigue life of micro-oxide-containing samples. These results highlight the need for better casting control and improved post-processing techniques to minimise the effect of oxide presence in the final components, thus enhancing their fatigue life. Full article
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17 pages, 5091 KB  
Article
Immunomodulatory Effects of Cucurbita pepo L. Extract in Chronic Stress-Induced Dysregulation of Lymphoid Organs in Rats
by Safa H. Qahl, Hailah M. Almohaimeed, Sami A. Algaidi, Ashwaq H. Batawi, Zuhair M. Mohammedsaleh, Tarek Hamdy Abd-Elhamid, Nawal H. Almohammadi, Nasra N. Ayuob and Amany Refaat Mahmoud
Pharmaceuticals 2025, 18(7), 1046; https://doi.org/10.3390/ph18071046 - 17 Jul 2025
Cited by 1 | Viewed by 870
Abstract
Objectives: Recently, increased attention has been given to pumpkin due to its proved nutritional components, which include antioxidant, antifatigue, and anti-inflammatory effects. The aim of the present work was to assess the impact of Cucurbita pepo L. (CP) on chronic [...] Read more.
Objectives: Recently, increased attention has been given to pumpkin due to its proved nutritional components, which include antioxidant, antifatigue, and anti-inflammatory effects. The aim of the present work was to assess the impact of Cucurbita pepo L. (CP) on chronic unpredictable mild stress (CUMS)-induced changes in lymphoid organs through evaluating its effect on the histological structure of spleen, thymus gland, and lymph nodes compared to the antidepressant fluoxetine (FLU). Materials and Methods: Fifty male albino rats equally distributed into five groups that included control, control + CP, CUMS-exposed, FLU-treated, and CP-treated groups were used in this study. Rats were exposed to CUMS for 4 weeks, and treatment (either with FLU or CP) was started after 14 days of exposure. Behavior of the rats, serum corticosterone, oxidants/antioxidants profile, proinflammatory cytokines, and gene expression of glucocorticoid receptor (GR) and β-adrenergic receptor (β2-AR) were assessed after 28 days. Spleen, thymus gland, and lymph nodes were histopathologically assessed. Results: CP administration significantly reduced the CUMS-induced behavioural changes evident by the significant reduction in immobility time (p = 0.02) and corticosterone level (p < 0.001). Biochemically, CP reduced TNF-α and IL-6 (p < 0.001) and markedly alleviated the changes in oxidants/antioxidants in the serum and lymphoid organs compared to fluoxetine. CP significantly (p < 0.001) reduced CUMS-induced changes in GR and (β2-AR). Histopathologically, CP alleviated changes observed in the spleen, lymph nodes, and thymus gland. It significantly reduced the number of CD4, CD8, CD68, CD20, and caspase-3 immunopositive cells in the studied organs. Conclusions: This study proved the potential efficacy of CP in alleviating depression-associated immunodysregulation either alone or in combination with antidepressant therapy. Full article
(This article belongs to the Section Pharmacology)
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15 pages, 463 KB  
Article
Impaired Quality of Life in Croatian IBD Patients in the Era of Advanced Treatment Options
by Alen Bišćanin, Leon Palac, Zdravko Dorosulić, Dominik Kralj, Petra Ćaćić, Filip Babić, Doris Ogresta, Davor Hrabar and Vedran Tomašić
Healthcare 2025, 13(14), 1681; https://doi.org/10.3390/healthcare13141681 - 12 Jul 2025
Viewed by 474
Abstract
Background/Objectives: Inflammatory bowel disease (IBD) is a chronic gastrointestinal disorder marked by relapsing episodes of gastrointestinal inflammation, potentially causing severe symptoms. These unpredictable acute episodes, paired with chronic disabilities, such as fatigue and malabsorption, and extensive pharmacological and surgical treatments, can severely impact [...] Read more.
Background/Objectives: Inflammatory bowel disease (IBD) is a chronic gastrointestinal disorder marked by relapsing episodes of gastrointestinal inflammation, potentially causing severe symptoms. These unpredictable acute episodes, paired with chronic disabilities, such as fatigue and malabsorption, and extensive pharmacological and surgical treatments, can severely impact patients’ quality of life. This study aimed to assess which aspects of the patients’ lives IBD impacts, and how IBD patients perceive their disease. Methods: All IBD patients who had an appointment in our tertiary centre from 10 October 2022 to 21 February 2023, were invited to complete anonymous questionnaires. The questionnaires used were IBDQ-32, WPAI, and IBD Disk, all designed specifically to assess the IBD patients’ quality of life. Results: The questionnaires were completed by a total of 159 participants, 51% of whom were males, 47.9% who had UC, and 49.4% who had been or were currently treated with biologics. There was no statistically significant difference in the answers from patients with CD compared to UC, as well as those treated with conventional therapies compared to those with advanced options. Most of them considered their health to be good, but only a few (12.8%) claimed, with absolute certainty, that their health was at the level of healthy individuals, and only 13 (8.3%) claimed their health was excellent. A total of 95 (60.1%) participants expressed at least minor limitations when performing strenuous activities, but lighter forms of activities were not affected as much by the disease. A significant portion (48.7%) of the participants believed they were exposed to more stress than others, and their current pharmacological therapy was the cause of fear in 26.5%. A total of 119 (75.3%) participants believed that the disease affected their lives at least mildly during remission. Conclusions: Our study showed that IBD patients have diminished quality of life, not only in the periods of active disease but also during clinical remission. The decline in quality of life was not solely attributed to physical symptoms, as previously thought. Other factors, such as mental health issues, were found to impact quality of life as well. We firmly believe that restoring quality of life should be emphasised in guidelines as one of the most important therapeutic goals. Full article
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27 pages, 15733 KB  
Article
Effects of Lactation Lactoferrin Deficiency on Intestinal Microbiota in Different Mice Models
by Wenli Wang, Qin An, Yunxia Zou, Qingyong Meng and Yali Zhang
Nutrients 2025, 17(13), 2248; https://doi.org/10.3390/nu17132248 - 7 Jul 2025
Viewed by 1085
Abstract
Background/Objectives: The establishment of early gut microbiota is crucial for host health. Lactoferrin (LF), which is present in breast milk, positively impacts gut microbiota composition. However, the effect of lactation LF on the establishment and composition of early gut microbiota in different disease [...] Read more.
Background/Objectives: The establishment of early gut microbiota is crucial for host health. Lactoferrin (LF), which is present in breast milk, positively impacts gut microbiota composition. However, the effect of lactation LF on the establishment and composition of early gut microbiota in different disease models in adulthood remains unclear. Methods: Lactation-LF-deficient mice were established using systemically LF–knocked-out maternal mice. This study assessed the maturity of the gut microbiota in LF feeding-deficient mice in relation to age and changes in the gut microbiota in adult high-fat diet (HFD)-induced obesity, dextran sodium sulfate (DSS)-induced acute colitis, and chronic unpredictable mild stress (CUMS)-induced depression models. Results: Compared to LF intake during lactation, LF deficiency during lactation increased the abundance of potentially pathogenic bacteria in the gut, resulting in abnormal microbial maturation. LF intake during lactation aggravated gut microbiota dysbiosis induced via HFD, DSS, and CUMS in adulthood and may change the function of Enterorhabdus, GCA-900066575, Peptococcus, Tuzzerella, Akkermansia, and Desulfovibrio. Comparing the different models revealed that bacteria that were jointly upregulated via HFD and DSS exhibited increased levels of inflammation and oxidation. LF deficiency during lactation may weaken the association between an HFD and inflammatory bowel disease (IBD). The changing trends in many gut microbes caused by DSS and HFD were opposite to those that changed with age. Conclusions: Lactoferrin deficiency increases the abundance of potential pathogens and disrupts microbial maturation. This lack of LF exacerbates dysbiosis in models of obesity, colitis, and depression. Regulating the gut microbiota according to the rules of microbial succession during the maturation process of gut microbiota may improve gut microbiota dysbiosis in patients with obesity and IBD. Full article
(This article belongs to the Section Pediatric Nutrition)
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38 pages, 4834 KB  
Article
Neuro-Inflammatory and Behavioral Changes Are Selectively Reversed by Sceletium tortuosum (Zembrin®) and Mesembrine in Male Rats Subjected to Unpredictable Chronic Mild Stress
by Johané Gericke, Stephan F. Steyn, Francois P. Viljoen and Brian H. Harvey
Cells 2025, 14(13), 1029; https://doi.org/10.3390/cells14131029 - 4 Jul 2025
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Abstract
Sceletium tortuosum (ST) induces antidepressant and anxiolytic effects, purportedly by monoamine regulation, anti-inflammatory and antioxidant properties, and phosphodiesterase 4 (PDE4) inhibition. These multimodal actions have not been demonstrated in an animal model of major depressive disorder. Wistar rats (both sexes) were subjected to [...] Read more.
Sceletium tortuosum (ST) induces antidepressant and anxiolytic effects, purportedly by monoamine regulation, anti-inflammatory and antioxidant properties, and phosphodiesterase 4 (PDE4) inhibition. These multimodal actions have not been demonstrated in an animal model of major depressive disorder. Wistar rats (both sexes) were subjected to 8-week unpredictable chronic mild stress, subsequently receiving saline, a standardized ST extract, Zembrin® 25 and 12.5 mg/kg (ZEM25 and ZEM12.5), its primary alkaloid mesembrine (MES), or escitalopram (20 mg/kg) for 36 days. Sucrose preference, open field, Barnes maze, and forced swim tests were performed, with cortico-hippocampal monoamines, inflammatory and oxidative stress markers analyzed post-mortem. Male, but not female rats, presented with increased anhedonia and anxiety but not despair. Males presented with increased hippocampal PDE4B expression, increased dopamine metabolites, and decreased cortical serotonin. In males, ZEM12.5 decreased anhedonia- and anxiety-like behavior, decreased cortical and hippocampal PDE4B, and increased plasma interleukin-10. MES induced a transient decrease in anhedonia-like behavior and increased hippocampal serotonergic and cortical dopaminergic activity, whilst decreasing hippocampal PDE4B. ZEM25 increased plasma interleukin-10 but decreased cortical glutathione, indicating paradoxical anti-inflammatory and prooxidant effects. ZEM12.5 and MES more effectively addressed anxious–depressive-like behavior and stress-induced inflammation and monoaminergic alterations, respectively. Multitargeted actions on monoamines, redox-inflammation, and PDE4 may provide ST with antidepressant effects across multiple symptom domains, although mutually synergistic/antagonistic effects of constituent alkaloids should be considered. Full article
(This article belongs to the Special Issue Neuroinflammation in Brain Health and Diseases)
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