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18 pages, 1188 KiB  
Review
Functional and Neuroplastic Effects of Cross-Education in Anterior Cruciate Ligament Rehabilitation: A Scoping Review with Bibliometric Analysis
by Jorge M. Vélez-Gutiérrez, Andrés Rojas-Jaramillo, Juan D. Ascuntar-Viteri, Juan D. Quintero, Francisco García-Muro San José, Bruno Bazuelo-Ruiz, Roberto Cannataro and Diego A. Bonilla
Appl. Sci. 2025, 15(15), 8641; https://doi.org/10.3390/app15158641 (registering DOI) - 4 Aug 2025
Abstract
Anterior cruciate ligament reconstruction (ACLR) results in prolonged muscle weakness, impaired neuromuscular control, and delayed return to sport. Cross-education (CE), unilateral training of the uninjured limb, has been proposed as an adjunct therapy to promote bilateral adaptations. This scoping review evaluated the functional [...] Read more.
Anterior cruciate ligament reconstruction (ACLR) results in prolonged muscle weakness, impaired neuromuscular control, and delayed return to sport. Cross-education (CE), unilateral training of the uninjured limb, has been proposed as an adjunct therapy to promote bilateral adaptations. This scoping review evaluated the functional and neuroplastic effects of CE rehabilitation post-ACLR. Following PRISMA-ScR and JBI guidelines, PubMed, Scopus, Web of Science, and PEDro were searched up to February 2025. A bibliometric analysis was also conducted to report keyword co-occurrence and identify trends in this line of research. Of 333 screened references, 14 studies (price index: 43% and low-to-moderate risk of bias) involving 721 participants (aged 17–45 years) met inclusion criteria. CE protocols (6–12 weeks; 2–5 sessions/week) incorporating isometric, concentric, and eccentric exercises demonstrated strength gains (10–31%) and strength preservation, alongside improved limb symmetry (5–14%) and dynamic balance (7–18%). There is growing interest in neuroplasticity and corticospinal excitability, although neuroplastic changes were assessed heterogeneously across studies. Findings support CE as a feasible and low-cost strategy to complement early-stage ACLR rehabilitation, especially when direct loading of the affected limb is limited. Standardized protocols for clinical intervention and neurophysiological assessment are needed. Full article
(This article belongs to the Special Issue Novel Approaches of Physical Therapy-Based Rehabilitation)
20 pages, 4055 KiB  
Article
Biphasic Salt Effects on Lycium ruthenicum Germination and Growth Linked to Carbon Fixation and Photosynthesis Gene Expression
by Xinmeng Qiao, Ruyuan Wang, Lanying Liu, Boya Cui, Xinrui Zhao, Min Yin, Pirui Li, Xu Feng and Yu Shan
Int. J. Mol. Sci. 2025, 26(15), 7537; https://doi.org/10.3390/ijms26157537 (registering DOI) - 4 Aug 2025
Abstract
Since the onset of industrialization, the safety of arable land has become a pressing global concern, with soil salinization emerging as a critical threat to agricultural productivity and food security. To address this challenge, the cultivation of economically valuable salt-tolerant plants has been [...] Read more.
Since the onset of industrialization, the safety of arable land has become a pressing global concern, with soil salinization emerging as a critical threat to agricultural productivity and food security. To address this challenge, the cultivation of economically valuable salt-tolerant plants has been proposed as a viable strategy. In the study, we investigated the physiological and molecular responses of Lycium ruthenicum Murr. to varying NaCl concentrations. Results revealed a concentration-dependent dual effect: low NaCl levels significantly promoted seed germination, while high concentrations exerted strong inhibitory effects. To elucidate the mechanisms underlying these divergent responses, a combined analysis of metabolomics and transcriptomics was applied to identify key metabolic pathways and genes. Notably, salt stress enhanced photosynthetic efficiency through coordinated modulation of ribulose 5-phosphate and erythrose-4-phosphate levels, coupled with the upregulation of critical genes encoding RPIA (Ribose 5-phosphate isomerase A) and RuBisCO (Ribulose-1,5-bisphosphate carboxylase/oxygenase). Under low salt stress, L. ruthenicum maintained intact cellular membrane structures and minimized oxidative damage, thereby supporting germination and early growth. In contrast, high salinity severely disrupted PS I (Photosynthesis system I) functionality, blocking energy flow into this pathway while simultaneously inducing membrane lipid peroxidation and triggering pronounced cellular degradation. This ultimately suppressed seed germination rates and impaired root elongation. These findings suggested a mechanistic framework for understanding L. ruthenicum adaptation under salt stress and pointed out a new way for breeding salt-tolerant crops and understanding the mechanism. Full article
(This article belongs to the Section Molecular Biology)
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16 pages, 1287 KiB  
Review
Oxidative Stress in the Regulation of Autosis-Related Proteins
by María Guerra-Andrés, Inés Martínez-Rojo, Alejandra Piedra-Macías, Elena Lavado-Fernández, Marina García-Macia and Álvaro F. Fernández
Antioxidants 2025, 14(8), 958; https://doi.org/10.3390/antiox14080958 (registering DOI) - 4 Aug 2025
Abstract
Physiological levels of reactive oxygen species (ROS) play a crucial role as intracellular signaling molecules, helping to maintain cellular homeostasis. However, when ROS accumulate excessively, they become toxic to cells, leading to damage to lipids, proteins, and DNA. This oxidative stress can impair [...] Read more.
Physiological levels of reactive oxygen species (ROS) play a crucial role as intracellular signaling molecules, helping to maintain cellular homeostasis. However, when ROS accumulate excessively, they become toxic to cells, leading to damage to lipids, proteins, and DNA. This oxidative stress can impair cellular function and lead to various forms of cell death, including apoptosis, necroptosis, ferroptosis, pyroptosis, paraptosis, parthanatos, and oxeiptosis. Despite their significance, the role of ROS in autosis (an autophagy-dependent form of cell death) remains largely unexplored. In this review, we gather current knowledge on autotic cell death and summarize how oxidative stress influences the activity of Beclin-1 and the Na+,K+-ATPase pump, both of which are critical effectors of this pathway. Finally, we discuss the theoretical potential for ROS to modulate this type of cell death, proposing a possible dual role for these species in autosis regulation through effectors such as HIF-1α, TFEB, or the FOXO family, and highlighting the need to experimentally address cellular redox status when working on autotic cell death. Full article
(This article belongs to the Special Issue Crosstalk between Autophagy and Oxidative Stress)
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41 pages, 703 KiB  
Review
Resveratrol as a Novel Therapeutic Approach for Diabetic Retinopathy: Molecular Mechanisms, Clinical Potential, and Future Challenges
by Snježana Kaštelan, Suzana Konjevoda, Ana Sarić, Iris Urlić, Ivana Lovrić, Samir Čanović, Tomislav Matejić and Ana Šešelja Perišin
Molecules 2025, 30(15), 3262; https://doi.org/10.3390/molecules30153262 - 4 Aug 2025
Abstract
Diabetic retinopathy (DR) is a progressive, multifactorial complication of diabetes and one of the major global causes of visual impairment. Its pathogenesis involves chronic hyperglycaemia-induced oxidative stress, inflammation, mitochondrial dysfunction, neurodegeneration, and pathological angiogenesis, as well as emerging systemic contributors such as gut [...] Read more.
Diabetic retinopathy (DR) is a progressive, multifactorial complication of diabetes and one of the major global causes of visual impairment. Its pathogenesis involves chronic hyperglycaemia-induced oxidative stress, inflammation, mitochondrial dysfunction, neurodegeneration, and pathological angiogenesis, as well as emerging systemic contributors such as gut microbiota dysregulation. While current treatments, including anti-vascular endothelial growth factor (anti-VEGF) agents, corticosteroids, and laser photocoagulation, have shown clinical efficacy, they are largely limited to advanced stages of DR, require repeated invasive procedures, and do not adequately address early neurovascular and metabolic abnormalities. Resveratrol (RSV), a naturally occurring polyphenol, has emerged as a promising candidate due to its potent antioxidant, anti-inflammatory, neuroprotective, and anti-angiogenic properties. This review provides a comprehensive analysis of the molecular mechanisms by which RSV exerts protective effects in DR, including modulation of oxidative stress pathways, suppression of inflammatory cytokines, enhancement of mitochondrial function, promotion of autophagy, and inhibition of pathological neovascularisation. Despite its promising pharmacological profile, the clinical application of RSV is limited by poor aqueous solubility, rapid systemic metabolism, and low ocular bioavailability. Various routes of administration, including intravitreal injection, topical instillation, and oral and sublingual delivery, have been investigated to enhance its therapeutic potential. Recent advances in drug delivery systems, including nanoformulations, liposomal carriers, and sustained-release intravitreal implants, offer potential strategies to address these challenges. This review also explores RSV’s role in combination therapies, its potential as a disease-modifying agent in early-stage DR, and the relevance of personalised medicine approaches guided by metabolic and genetic factors. Overall, the review highlights the therapeutic potential and the key translational challenges in positioning RSV as a multi-targeted treatment strategy for DR. Full article
14 pages, 654 KiB  
Article
Impact of Poor Sleep Quality on Task Switching and Reconfiguration Process Among University Students
by Shaoyang Ma, Yue Sun, Yunxin Jia, Jinfu Shi and Yekun Sun
Behav. Sci. 2025, 15(8), 1054; https://doi.org/10.3390/bs15081054 - 4 Aug 2025
Abstract
Task switching is an important cognitive function required for daily life, and task reconfiguration is one of the main explanations for the origins of switching costs. Studies have demonstrated that sleep significantly affects task switching abilities. However, there remains insufficient evidence on how [...] Read more.
Task switching is an important cognitive function required for daily life, and task reconfiguration is one of the main explanations for the origins of switching costs. Studies have demonstrated that sleep significantly affects task switching abilities. However, there remains insufficient evidence on how poor sleep quality impacts task switching abilities among university students. A total of 85 university students were included in this study and classified into a poor sleep quality group (PSQ group, n = 47) and normal control group (NC group, n = 38) based on their Pittsburgh Sleep Quality Index scores. A task-cueing paradigm with different cue-to-target intervals (CTIs) was used to evaluate the participants’ task switching abilities and explore the process of task reconfiguration. An ANCOVA and subsequent simple effect analysis showed that the RT switching costs of the NC group decreased significantly as the CTI increased. However, there was no significant decrease in the PSQ group. Additionally, a significant difference was observed between different CTI conditions in repeat trials for the PSQ group, while no significant difference was observed for the NC group. The results showed that students with poor sleep quality exhibited slower task reconfiguration processes compared to the normal controls. Additionally, their capacity to resist interference and maintain task rules was found to be impaired. Full article
(This article belongs to the Special Issue Sleep Disorders: New Developments)
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23 pages, 5387 KiB  
Article
Tabernanthalog, a Non-Hallucinogenic Psychedelic, Alleviates Cancer-Induced Cognitive Deficits via Serotonergic Pathways
by Masahide Arinaga, Jun Yamada, Shoichiro Maeda, Ayumi Okamura, Yuto Oshima, Liye Zhang, Yiying Han, Kyoko M. Iinuma and Shozo Jinno
Int. J. Mol. Sci. 2025, 26(15), 7519; https://doi.org/10.3390/ijms26157519 (registering DOI) - 4 Aug 2025
Abstract
Cancer-related cognitive impairment (CRCI)—encompassing anxiety, depression, and memory deficits—significantly diminishes the quality of life in patients with cancer, yet remains underrecognized in clinical practice. In this study, we investigated the therapeutic potential of tabernanthalog (TBG), a non-hallucinogenic analog of psychedelic compounds, as a [...] Read more.
Cancer-related cognitive impairment (CRCI)—encompassing anxiety, depression, and memory deficits—significantly diminishes the quality of life in patients with cancer, yet remains underrecognized in clinical practice. In this study, we investigated the therapeutic potential of tabernanthalog (TBG), a non-hallucinogenic analog of psychedelic compounds, as a novel intervention for CRCI using a Lewis lung carcinoma (3LL) mouse model. Behavioral assessments revealed heightened anxiety-like behavior and memory impairment following 3LL cell transplantation. Biochemical analysis revealed reduced tryptophan levels in both blood and hippocampal tissue, accompanied by the downregulation of serotonergic receptor genes and upregulation of pro-inflammatory cytokine genes in the hippocampus of tumor-bearing mice. Additionally, microglial density and morphological activation were markedly elevated. TBG treatment reversed these behavioral deficits, improving both anxiety-related behavior and memory performance. These effects were associated with the normalization of microglial density and morphology, as well as the restoration of serotonergic receptor and cytokine gene expression. In vitro, TBG partially suppressed neuroinflammatory gene expression in BV-2 microglial cells exposed to conditioned medium from 3LL cells. Collectively, these findings suggest that TBG alleviates CRCI-like symptoms by modulating neuroinflammation and microglial activation. This study highlights TBG as a promising therapeutic candidate for improving cognitive and emotional functioning in patients with cancer. Full article
(This article belongs to the Special Issue Physiological Functions and Pathological Effects of Microglia)
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14 pages, 276 KiB  
Article
Inclusion of Hydrolyzed Feather Meal in Diets for Giant River Prawn (Macrobrachium rosenbergii) During the Nursery Phase: Effects on Growth, Digestive Enzymes, and Antioxidant Status
by Eduardo Luis Cupertino Ballester, Angela Trocino, Cecília de Souza Valente, Marlise Mauerwerk, Milena Cia Retcheski, Luisa Helena Cazarolli, Caio Henrique do Nascimento Ferreira and Francesco Bordignon
Appl. Sci. 2025, 15(15), 8627; https://doi.org/10.3390/app15158627 (registering DOI) - 4 Aug 2025
Abstract
We evaluated the inclusion of hydrolyzed feather meal (HFM) as a partial replacement for fishmeal in diets for Macrobrachium rosenbergii post-larvae (PL) over a 32-day nursery feeding trial. Five experimental diets with increasing HFM levels (control, 1.5%, 3.0%, 4.5%, and 6.0%) were tested. [...] Read more.
We evaluated the inclusion of hydrolyzed feather meal (HFM) as a partial replacement for fishmeal in diets for Macrobrachium rosenbergii post-larvae (PL) over a 32-day nursery feeding trial. Five experimental diets with increasing HFM levels (control, 1.5%, 3.0%, 4.5%, and 6.0%) were tested. Survival rates ranged from 73.3 ± 5.44% to 83.3 ± 3.84% without significant differences among groups. Dietary HFM inclusion levels above 3.0% significantly improved prawn performance, including final weight (up to 2.18-fold higher than control), length (1.13-fold), antenna length (1.18-fold), biomass gain (2.14-fold), and feed conversion ratio (1.59-fold lower). Prawn-fed diets at 6.0% HFM showed the highest performance among all experimental groups. No significant effects were observed on antioxidant biomarkers or digestive enzymes in prawns hepatopancreas, which suggests no imbalance in the antioxidant system or impairment of digestive function. Likewise, carcass proximate composition remained stable across experimental groups. These findings suggest that HFM at 3.0–6.0% dietary inclusion levels is a potential alternative to fishmeal in nursery-phase diets for M. rosernbergii PL, promoting prawn growth and welfare and maintaining health and carcass quality. Notably, to the best of our knowledge, this is the first study demonstrating the potential effective use of HFM in feeding the nursery phase of M. rosernbergii. Full article
(This article belongs to the Section Agricultural Science and Technology)
15 pages, 553 KiB  
Systematic Review
The Potential of Virtual Reality-Based Multisensory Interventions in Enhancing Cognitive Function in Mild Cognitive Impairment: A Systematic Review
by Maryam Mehrinejad Khotbehsara, Jeffrey Soar, Sachithra Lokuge, Elham Mehrinejad Khotbehsara and Wing Keung Ip
J. Clin. Med. 2025, 14(15), 5475; https://doi.org/10.3390/jcm14155475 (registering DOI) - 4 Aug 2025
Abstract
Background: This systematic review investigates the role of virtual reality (VR)-based multisensory cognitive training in cognitive function, executive function and wayfinding ability among people diagnosed with mild cognitive impairment (MCI) and Alzheimer’s disease (AD). Methods: The review was carried out using PRISMA guidelines. [...] Read more.
Background: This systematic review investigates the role of virtual reality (VR)-based multisensory cognitive training in cognitive function, executive function and wayfinding ability among people diagnosed with mild cognitive impairment (MCI) and Alzheimer’s disease (AD). Methods: The review was carried out using PRISMA guidelines. PubMed, Scopus, Embase, and Google Scholar were searched up from inception to February 2025 using terms related to MCI, AD, VR, and cognitive functions. Studies were included if they involved participants with MCI or early AD, used VR-based training, collected baseline data, and reported cognitive outcomes. Results: Nine studies with MCI were included, but no eligible studies focused on AD. Seven out of nine eligible studies in MCI reported significant improvements in global cognitive function (MoCA, CERAD-K, MMSE). Some studies showed improvements in executive function (EXIT-25, TMT-A/B, and SCWT), while others found no significant differences. One study reported improved depression/mental status (GDS, MOSES, QoL-AD). Just one study reported improvement in functional ability (IADL). One study reported enhanced cognition and reduced discomfort (SSQ). VR programs were generally well-tolerated, with no significant adverse events reported. Conclusions: VR shows promise for improving cognitive function in MCI. VR also showed potential benefits in executive function and psychological outcomes like depression and quality of life, though consistency varied. Full article
(This article belongs to the Section Clinical Neurology)
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15 pages, 642 KiB  
Article
Evaluation of the Profile of Selected Bioactive Compounds and the Potential of Barley Wort Enriched with Malted and Unmalted Hemp Seeds for Brewing Applications
by Marek Zdaniewicz, Robert Duliński, Jana Lakatošová, Janusz Gołaszewski and Krystyna Żuk-Gołaszewska
Molecules 2025, 30(15), 3261; https://doi.org/10.3390/molecules30153261 - 4 Aug 2025
Abstract
The incorporation of Cannabis sativa L. seeds into barley wort was investigated to enhance the functional profile of beer. Hemp seeds (cv. Henola) were malted via controlled steeping, germination, and kilning, then added to barley malt at 10% and 30% (w/ [...] Read more.
The incorporation of Cannabis sativa L. seeds into barley wort was investigated to enhance the functional profile of beer. Hemp seeds (cv. Henola) were malted via controlled steeping, germination, and kilning, then added to barley malt at 10% and 30% (w/w) in both malted and unmalted forms. Standard congress mashing produced worts whose physicochemical parameters (pH, extract, colour, turbidity, filtration and saccharification times) were assessed, alongside profiles of fermentable sugars, polyphenols, B-group vitamins, and cannabinoids. Addition of hemp seeds reduced extract yield without impairing saccharification or filtration and slightly elevated mash pH and turbidity. Maltose and glucose levels declined significantly at higher hemp dosages, whereas sucrose remained stable. Wort enriched with 30% unmalted seeds exhibited the highest levels of trans-ferulic (20.61 µg/g), gallic (5.66 µg/g), trans-p-coumaric (3.68 µg/g), quercetin (6.07 µg/g), and trans-cinnamic (4.07 µg/g) acids. Malted hemp addition enhanced thiamine (up to 0.302 mg/mL) and riboflavin (up to 178.8 µg/mL) concentrations. Cannabinoids (THCA-A, THCV, CBDV, CBG, CBN) were successfully extracted at µg/mL levels, with the total cannabinoid content peaking at 14.59 µg/mL in the 30% malted treatment. These findings demonstrate that hemp seeds, particularly in malted form, can enrich barley wort with bioactive polyphenols, vitamins, and non-psychoactive cannabinoids under standard mashing conditions, without compromising key brewing performance metrics. Further work on fermentation, sensory evaluation, stability, and bioavailability is warranted to realise hemp-enriched functional beers. Full article
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27 pages, 3015 KiB  
Article
Preparation of Auricularia auricula-Derived Immune Modulators and Alleviation of Cyclophosphamide-Induced Immune Suppression and Intestinal Microbiota Dysbiosis in Mice
by Ming Zhao, Huiyan Huang, Bowen Li, Yu Pan, Chuankai Wang, Wanjia Du, Wenliang Wang, Yansheng Wang, Xue Mao and Xianghui Kong
Life 2025, 15(8), 1236; https://doi.org/10.3390/life15081236 - 4 Aug 2025
Abstract
With the acceleration of the pace of life, increased stress levels, and changes in lifestyle factors such as diet and exercise, the incidence of diseases such as cancer and immunodeficiency has been on the rise, which is closely associated with the impaired antioxidant [...] Read more.
With the acceleration of the pace of life, increased stress levels, and changes in lifestyle factors such as diet and exercise, the incidence of diseases such as cancer and immunodeficiency has been on the rise, which is closely associated with the impaired antioxidant capacity of the body. Polypeptides and polysaccharides derived from edible fungi demonstrate significant strong antioxidant activity and immunomodulatory effects. Auricularia auricula, the second most cultivated mushroom in China, is not only nutritionally rich but also offers considerable health benefits. In particular, its polysaccharides have been widely recognized for their immunomodulatory activities, while its abundant protein content holds great promise as a raw material for developing immunomodulatory peptides. To meet the demand for high-value utilization of Auricularia auricula resources, this study developed a key technology for the stepwise extraction of polypeptides (AAPP1) and polysaccharides (AAPS3) using a composite enzymatic hydrolysis process. Their antioxidant and immunomodulatory effects were assessed using cyclophosphamide (CTX)-induced immune-suppressed mice. The results showed that both AAPP1 and AAPS3 significantly reversed CTX-induced decreases in thymus and spleen indices (p < 0.05); upregulated serum levels of cytokines (e.g., IL-4, TNF-α) and immunoglobulins (e.g., IgA, IgG); enhanced the activities of hepatic antioxidant enzymes SOD and CAT (p < 0.05); and reduced the content of MDA, a marker of oxidative damage. Intestinal microbiota analysis revealed that these compounds restored CTX-induced reductions in microbial α-diversity, increased the abundance of beneficial bacteria (Paramuribaculum, Prevotella; p < 0.05), decreased the proportion of pro-inflammatory Duncaniella, and reshaped the balance of the Bacteroidota/Firmicutes phyla. This study represents the first instance of synergistic extraction of polypeptides and polysaccharides from Auricularia auricula using a single process. It demonstrates their immune-enhancing effects through multiple mechanisms, including “antioxidation-immune organ repair-intestinal microbiota regulation.” The findings offer a theoretical and technical foundation for the deep processing of Auricularia auricula and the development of functional foods. Full article
(This article belongs to the Special Issue Research Progress of Cultivation of Edible Fungi: 2nd Edition)
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17 pages, 972 KiB  
Article
SARS-CoV-2 Main Protease Dysregulates Hepatic Insulin Signaling and Glucose Uptake: Implications for Post-COVID-19 Diabetogenesis
by Praise Tatenda Nhau, Mlindeli Gamede, Andile Khathi and Ntethelelo Sibiya
Pathophysiology 2025, 32(3), 39; https://doi.org/10.3390/pathophysiology32030039 (registering DOI) - 4 Aug 2025
Abstract
Background: There is growing evidence suggesting that SARS-CoV-2 may contribute to metabolic dysfunction. SARS-CoV-2 infection is associated with systemic inflammation, oxidative stress, and metabolic dysregulation, all of which may impair liver function and promote glucose intolerance. This study investigated the role of SARS-CoV-2, [...] Read more.
Background: There is growing evidence suggesting that SARS-CoV-2 may contribute to metabolic dysfunction. SARS-CoV-2 infection is associated with systemic inflammation, oxidative stress, and metabolic dysregulation, all of which may impair liver function and promote glucose intolerance. This study investigated the role of SARS-CoV-2, specifically its Main Protease (Mpro), in accelerating insulin resistance and metabolic dysfunction in HepG2 cells in vitro. Methods: HepG2 cells were treated with varying concentrations of Mpro (2.5, 5, 10, 20, 40, 80, and 160 nmol/mL) for 24 h to assess cytotoxicity and glucose uptake. Based on initial findings, subsequent assays focused on higher concentrations (40, 80, and 160 nmol/mL). The effects of Mpro on cell viability, protein kinase B (AKT) expression, matrix metallopeptidase-1 (MMP1), dipeptidyl peptidase 4 (DPP4), interleukin-6 (IL-6) expression, and lipid peroxidation were investigated. Results: Our findings reveal that the SARS-CoV-2 Mpro treatment led to a concentration-dependent reduction in glucose uptake in HepG2 cells. Additionally, the Mpro treatment was associated with reduced insulin-stimulated AKT activation, particularly at higher concentrations. Inflammatory markers such as IL-6 were elevated in the extracellular medium, while DPP4 expression was decreased. However, extracellular soluble DPP4 (sDPP4) levels did not show a significant change. Despite these changes, cell viability remained relatively unaffected, suggesting that the HepG2 cells were able to maintain overall metabolic functions under Mpro exposure. Conclusions: This study demonstrated the concentration-dependent impairment of hepatic glucose metabolism, insulin signaling, and inflammatory pathways in HepG2 cells acutely exposed to the SARS-CoV-2 Mpro. These findings warrant further investigation to explore the long-term metabolic effects of SARS-CoV-2 and its proteases in the liver and to develop potential therapeutic approaches for post-viral metabolic complications. Full article
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20 pages, 2361 KiB  
Article
Abelmoschus esculentus Ameliorates Cognitive Impairment in Hyperlipidemic ApoE−/− Mice via Modulation of Oxidative Stress and Neuronal Differentiation
by Chiung-Huei Peng, Hsin-Wen Liang, Chau-Jong Wang, Chien-Ning Huang and Huei-Jane Lee
Antioxidants 2025, 14(8), 955; https://doi.org/10.3390/antiox14080955 (registering DOI) - 4 Aug 2025
Abstract
Cardiovascular disease (CVD) and dementia may share common pathogenic factors such as atherosclerosis and hyperlipoproteinemia. Dyslipidemia-induced oxidative stress contributes to dementia comorbidity in CVD. Abelmoschus esculentus (AE, okra) potentiates in alleviating hyperlipidemia and diabetes-related cognitive impairment. This study evaluated the effects of AE [...] Read more.
Cardiovascular disease (CVD) and dementia may share common pathogenic factors such as atherosclerosis and hyperlipoproteinemia. Dyslipidemia-induced oxidative stress contributes to dementia comorbidity in CVD. Abelmoschus esculentus (AE, okra) potentiates in alleviating hyperlipidemia and diabetes-related cognitive impairment. This study evaluated the effects of AE in hyperlipidemic ApoE−/− mice treated with streptozotocin (50 mg/kg) and fed a high-fat diet (17% lard oil, 1.2% cholesterol). AE fractions F1 or F2 (0.65 mg/kg) were administered for 8 weeks. AE significantly reduced serum LDL-C, HDL-C, triglycerides, and glucose, improved cognitive and memory function, and protected hippocampal neurons. AE also lowered oxidative stress markers (8-hydroxy-2′-deoxyguanosine, 8-OHdG) and modulated neuronal nuclei (NeuN) and doublecortin (DCX) expression. In vitro, AE promoted neurite outgrowth and neuronal differentiation in retinoic acid (RA)-differentiated human SH-SY5Y cells under metabolic stress (glucose and palmitate), alongside the upregulation of heme oxygenase-1 (HO-1), Nuclear factor-erythroid 2-related factor 2 (Nrf2), and brain-derived neurotrophic factor (BDNF). These findings suggest AE may counter cognitive decline via oxidative stress regulation and the enhancement of neuronal differentiation. Full article
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14 pages, 1588 KiB  
Case Report
Fatal Cytokine Collision: HLH–AIHA in Advanced AIDS—Case Report and Literature Review
by Xiaoyi Zhang, Maria Felix Torres Nolasco, Wing Fai Li, Toru Yoshino and Manasa Anipindi
Reports 2025, 8(3), 137; https://doi.org/10.3390/reports8030137 - 4 Aug 2025
Abstract
Background and Clinical Significance: Hemophagocytic lymphohistiocytosis (HLH) and autoimmune hemolytic anemia (AIHA) are both life-threatening hematologic syndromes that rarely present together outside of malignancy. Advanced acquired immunodeficiency syndrome (AIDS) creates a milieu of profound immune dysregulation and hyperinflammation, predisposing patients to atypical [...] Read more.
Background and Clinical Significance: Hemophagocytic lymphohistiocytosis (HLH) and autoimmune hemolytic anemia (AIHA) are both life-threatening hematologic syndromes that rarely present together outside of malignancy. Advanced acquired immunodeficiency syndrome (AIDS) creates a milieu of profound immune dysregulation and hyperinflammation, predisposing patients to atypical overlaps of these disorders. Case Presentation: A 30-year-old woman with poorly controlled AIDS presented with three weeks of jaundice, fever, and fatigue. Initial labs revealed pancytopenia, hyperbilirubinemia, and elevated ferritin level. Direct anti-globulin testing confirmed warm AIHA (IgG+/C3d+) with transient cold agglutinins. Despite intravenous immunoglobulin (IVIG), rituximab, and transfusions, she developed hepatosplenomegaly, extreme hyperferritinemia, and sIL-2R > 10,000 pg/mL, meeting HLH-2004 criteria. Bone marrow biopsy excluded malignancy; further work-up revealed Epstein–Barr virus (EBV) viremia and cytomegalovirus (CMV) reactivation. Dexamethasone plus reduced-dose etoposide transiently reduced soluble interleukin-2 receptor (sIL-2R) but precipitated profound pancytopenia, Acute respiratory distress syndrome (ARDS) from CMV/parainfluenza pneumonia, bilateral deep vein thrombosis (DVT), and an ST-elevation myocardial infarction (STEMI). She ultimately died of hemorrhagic shock after anticoagulation despite maximal supportive measures. Conclusions: This case underscores the diagnostic challenges of HLH-AIHA overlap in AIDS, where cytopenias and hyperferritinemia mask the underlying cytokine storm. Pathogenesis likely involved IL-6/IFN-γ overproduction, impaired cytotoxic T-cell function, and molecular mimicry. While etoposide remains a cornerstone of HLH therapy, its myelotoxicity proved catastrophic in this immunocompromised host, highlighting the urgent need for cytokine-targeted agents to mitigate treatment-related mortality. Full article
(This article belongs to the Section Allergy/Immunology)
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24 pages, 2171 KiB  
Review
Induction of Autophagy as a Therapeutic Breakthrough for NAFLD: Current Evidence and Perspectives
by Yanke Liu, Mingkang Zhang and Yazhi Wang
Biology 2025, 14(8), 989; https://doi.org/10.3390/biology14080989 (registering DOI) - 4 Aug 2025
Abstract
Nonalcoholic fatty liver disease (NAFLD) is a clinicopathological syndrome characterised by hepatic steatosis in the absence of significant alcohol consumption or other specific causes of liver injury. It has become one of the leading causes of liver dysfunction worldwide. However, the precise pathophysiological [...] Read more.
Nonalcoholic fatty liver disease (NAFLD) is a clinicopathological syndrome characterised by hepatic steatosis in the absence of significant alcohol consumption or other specific causes of liver injury. It has become one of the leading causes of liver dysfunction worldwide. However, the precise pathophysiological mechanisms underlying NAFLD remain unclear, and effective therapeutic strategies are still under investigation. Autophagy, a vital intracellular process in eukaryotic cells, enables the degradation and recycling of cytoplasmic components through a membrane trafficking pathway. Recent studies have demonstrated a strong association between impaired or deficient autophagy and the development and progression of NAFLD. Restoring autophagic function may represent a key approach to mitigating hepatocellular injury. Nevertheless, due to the complexity of autophagy regulation and its context-dependent effects on cellular function, therapeutic strategies targeting autophagy in NAFLD remain limited. This review aims to summarise the relationship between autophagy and NAFLD, focusing on autophagy as a central mechanism. We discuss the latest research advances regarding interventions such as diet and exercise, pharmacological therapies (including modern pharmacological therapy and plant-derived compounds), and other approaches (such as hormones, nanoparticles, gut microbiota, and vitamins). Furthermore, we briefly highlight potential autophagy-related molecular targets that may offer novel therapeutic insights for NAFLD management. Full article
(This article belongs to the Section Medical Biology)
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17 pages, 2487 KiB  
Article
Personalized Language Training and Bi-Hemispheric tDCS Improve Language Connectivity in Chronic Aphasia: A fMRI Case Study
by Sandra Carvalho, Augusto J. Mendes, José Miguel Soares, Adriana Sampaio and Jorge Leite
J. Pers. Med. 2025, 15(8), 352; https://doi.org/10.3390/jpm15080352 (registering DOI) - 3 Aug 2025
Abstract
Background: Transcranial direct current stimulation (tDCS) has emerged as a promising neuromodulatory tool for language rehabilitation in chronic aphasia. However, the effects of bi-hemispheric, multisite stimulation remain largely unexplored, especially in people with chronic and treatment-resistant language impairments. The goal of this [...] Read more.
Background: Transcranial direct current stimulation (tDCS) has emerged as a promising neuromodulatory tool for language rehabilitation in chronic aphasia. However, the effects of bi-hemispheric, multisite stimulation remain largely unexplored, especially in people with chronic and treatment-resistant language impairments. The goal of this study is to look at the effects on behavior and brain activity of an individualized language training program that combines bi-hemispheric multisite anodal tDCS with personalized language training for Albert, a patient with long-standing, treatment-resistant non-fluent aphasia. Methods: Albert, a right-handed retired physician, had transcortical motor aphasia (TCMA) subsequent to a left-hemispheric ischemic stroke occurring more than six years before the operation. Even after years of traditional treatment, his expressive and receptive language deficits remained severe and persistent despite multiple rounds of traditional therapy. He had 15 sessions of bi-hemispheric multisite anodal tDCS aimed at bilateral dorsal language streams, administered simultaneously with language training customized to address his particular phonological and syntactic deficiencies. Psycholinguistic evaluations were performed at baseline, immediately following the intervention, and at 1, 2, 3, and 6 months post-intervention. Resting-state fMRI was conducted at baseline and following the intervention to evaluate alterations in functional connectivity (FC). Results: We noted statistically significant enhancements in auditory sentence comprehension and oral reading, particularly at the 1- and 3-month follow-ups. Neuroimaging showed decreased functional connectivity (FC) in the left inferior frontal and precentral regions (dorsal stream) and in maladaptive right superior temporal regions, alongside increased FC in left superior temporal areas (ventral stream). This pattern suggests that language networks may be reorganizing in a more efficient way. There was no significant improvement in phonological processing, which may indicate reduced connectivity in the left inferior frontal areas. Conclusions: This case underscores the potential of combining individualized, network-targeted language training with bi-hemispheric multisite tDCS to enhance recovery in chronic, treatment-resistant aphasia. The convergence of behavioral gains and neuroplasticity highlights the importance of precision neuromodulation approaches. However, findings are preliminary and warrant further validation through controlled studies to establish broader efficacy and sustainability of outcomes. Full article
(This article belongs to the Special Issue Personalized Medicine in Neuroscience: Molecular to Systems Approach)
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