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18 pages, 5256 KiB  
Article
Impact of Alginate Oligosaccharides on Ovarian Performance and the Gut Microbial Community in Mice with D-Galactose-Induced Premature Ovarian Insufficiency
by Yan Zhang, Hongda Pan, Dao Xiang, Hexuan Qu and Shuang Liang
Antioxidants 2025, 14(8), 962; https://doi.org/10.3390/antiox14080962 (registering DOI) - 5 Aug 2025
Abstract
Premature ovarian insufficiency (POI) is an important factor in female infertility and is often associated with oxidative stress. Alginate oligosaccharides (AOSs), derived from the degradation of alginate, have been demonstrated to have protective effects against various oxidative stress-related diseases. However, the impact of [...] Read more.
Premature ovarian insufficiency (POI) is an important factor in female infertility and is often associated with oxidative stress. Alginate oligosaccharides (AOSs), derived from the degradation of alginate, have been demonstrated to have protective effects against various oxidative stress-related diseases. However, the impact of AOSs on POI has not been previously explored. The current study explored the effects of AOSs on ovarian dysfunction in a mouse model of POI induced by D-galactose (D-gal). Female C57BL/6 mice were randomly divided into five groups: the control (CON), POI model (D-gal), and low-, medium-, and high-dose AOS groups (AOS-L, 100 mg/kg/day; AOS-M, 150 mg/kg/day; AOS-H, 200 mg/kg/day). For 42 consecutive days, mice in the D-gal, AOS-L, AOS-M, and AOS-H groups received daily intraperitoneal injections of D-gal (200 mg/kg/day), whereas those in the CON group received equivalent volumes of sterile saline. Following D-gal injection, AOSs were administered via gavage at the specified doses; mice in the CON and D-gal groups received sterile saline instead. AOS treatment markedly improved estrous cycle irregularities, normalized serum hormone levels, reduced granulosa cell apoptosis, and increased follicle counts in POI mice. Moreover, AOSs significantly reduced ovarian oxidative stress and senescence in POI mice, as indicated by lower levels of malondialdehyde (MDA), higher activities of catalase (CAT) and superoxide dismutase (SOD), and decreased protein expression of 4-hydroxynonenal (4-HNE), nitrotyrosine (NTY), 8-hydroxydeoxyguanosine (8-OHdG), and p16 in ovarian tissue. Analysis of the gut microbiota through 16S rRNA gene sequencing and short-chain fatty acid (SCFA) analysis revealed significant differences in gut microbiota composition and SCFA levels (acetic acid and total SCFAs) between control and D-gal-induced POI mice. These differences were largely alleviated by AOS treatment. AOSs changed the gut microbiota by increasing the abundance of Ligilactobacillus and decreasing the abundance of Clostridiales, Clostridiaceae, Marinifilaceae, and Clostridium_T. Additionally, AOSs mitigated the decline in acetic acid and total SCFA levels observed in POI mice. Notably, the total SCFA level was significantly correlated with the abundance of Ligilactobacillus, Marinifilaceae, and Clostridium_T. In conclusion, AOS intervention effectively mitigates ovarian oxidative stress, restores gut microbiota homeostasis, and regulates the microbiota–SCFA axis, collectively improving D-gal-induced POI. Therefore, AOSs represent a promising therapeutic strategy for POI management. Full article
(This article belongs to the Section Health Outcomes of Antioxidants and Oxidative Stress)
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18 pages, 2357 KiB  
Article
Nitrogen Fertilizer Reduction in Rice–Eel Co-Culture System Improves the Soil Microbial Diversity and Its Functional Stability
by Mengqian Ma, Weiguang Lv, Yu Huang, Juanqin Zhang, Shuangxi Li, Naling Bai, Haiyun Zhang, Xianpu Zhu, Chenglong Xu and Hanlin Zhang
Plants 2025, 14(15), 2425; https://doi.org/10.3390/plants14152425 - 5 Aug 2025
Abstract
The ecological rice–eel co-culture system is not only beneficial for enhancing productivity and sustainability in agriculture but also plays a crucial role in promoting environmental health. In the present study, based on the long-term positioning trial of the rice–eel co-culture system that began [...] Read more.
The ecological rice–eel co-culture system is not only beneficial for enhancing productivity and sustainability in agriculture but also plays a crucial role in promoting environmental health. In the present study, based on the long-term positioning trial of the rice–eel co-culture system that began in 2016 and was sampled in 2023, the effects of reduced nitrogen fertilizer application on soil physico-chemical properties and the bacterial community were investigated. Treatments included a conventional regular fertilization treatment (RT), rice–eel co-culture system regular fertilization (IT), and nitrogen-reduction 10%, 30%, and 50% fertilization treatments (IT90, IT70, and IT50). Our research demonstrated the following: (1) Compared to RT, IT significantly increased soil water-stable macroaggregates (R0.25), mean weight diameter (MWD), geometric mean diameter (GMD), and available phosphorus content, with the increases of 15.66%, 25.49%, 36.00%, and 18.42%, respectively. Among the nitrogen-reduction fertilization treatments, IT90 showed the most significant effect. Compared to IT, IT90 significantly increased R0.25, MWD, GMD, and available nitrogen content, with increases of 4.4%, 7.81%, 8.82%, and 28.89%, respectively. (2) Compared to RT, at the phylum level, the diversity of Chloroflexi was significantly increased under IT and IT50, and the diversity of Gemmatimonadota was significantly increased under IT90, IT70, and IT50. The diversity of Acidobacteriota was significantly higher in IT90 and IT70 compared to IT. It was shown that the rice–eel co-culture system and nitrogen fertilizer reduction could effectively improve the degradation capacity of organic matter and promote soil nitrogen cycling. In addition, redundancy analysis (RDA) identified total phosphorus, total nitrogen, and available nitrogen (p = 0.007) as the three most important environmental factors driving changes in the bacterial community. (3) The functional prediction analysis of soil microbiota showed that, compared to RT, the diversity of pathways related to biosynthesis (carbohydrate biosynthesis and cell structure biosynthesis) and metabolism (L-glutamate and L-glutamine biosynthesis) was significantly higher under IT70, IT90, IT, and IT50 (in descending order). However, the diversity of pathways associated with degradation/utilization/assimilation (secondary metabolite degradation and amine and polyamine degradation) was significantly lower under all the rice–eel co-culture treatments. In conclusion, the rice–eel co-culture system improved soil physicochemical properties and the soil microbial environment compared with conventional planting, and the best soil improvement was achieved with 10% less N fertilizer application. Full article
(This article belongs to the Special Issue Chemical Properties of Soils and its Impact on Plant Growth)
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28 pages, 2414 KiB  
Review
Breaking Down Osteoarthritis: Exploring Inflammatory and Mechanical Signaling Pathways
by Wafa Ali Batarfi, Mohd Heikal Mohd Yunus, Adila A. Hamid, Manira Maarof and Rizal Abdul Rani
Life 2025, 15(8), 1238; https://doi.org/10.3390/life15081238 - 4 Aug 2025
Abstract
Osteoarthritis (OA) is a chronic progressive joint disease characterized by cartilage degradation, subchondral bone remodeling, and synovial inflammation. This complex disorder arises from the interplay between mechanical stress and inflammatory processes, which is mediated by interconnected molecular signaling pathways. This review explores the [...] Read more.
Osteoarthritis (OA) is a chronic progressive joint disease characterized by cartilage degradation, subchondral bone remodeling, and synovial inflammation. This complex disorder arises from the interplay between mechanical stress and inflammatory processes, which is mediated by interconnected molecular signaling pathways. This review explores the dual roles of inflammatory and mechanical signaling in OA pathogenesis, focusing on crucial pathways such as NF-kB, JAK/STAT, and MAPK in inflammation, as well as Wnt/β-catenin, Integrin-FAK, and Hippo-YAP/TAZ in mechanotransduction. The interplay between these pathways highlights a vicious cycle wherein mechanical stress exacerbates inflammation, and inflammation weakens cartilage, increasing its vulnerability to mechanical damage. Additionally, we discuss emerging therapeutic strategies targeting these pathways, including inhibitors of cartilage-degrading enzymes, anti-inflammatory biologics, cell-based regenerative approaches, and non-pharmacological mechanical interventions. By dissecting the molecular mechanisms underlying OA, this review aims to provide insights into novel interventions that address both inflammatory and mechanical components of the disease, paving the way for precision medicine in OA management. Full article
(This article belongs to the Special Issue Current Views on Knee Osteoarthritis: 3rd Edition)
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15 pages, 1054 KiB  
Review
Assessing the Possibility to Enhance the Stability of Hybrid Perovskite Solar Cells: A Brief Review
by Alexander Axelevitch and David Lugassy
Solar 2025, 5(3), 37; https://doi.org/10.3390/solar5030037 - 4 Aug 2025
Abstract
Solar cells based on the hybrid perovskite absorbers had shown very high growth of their conversion efficiency almost reaching to the Shockley–Queisser limit during last decade. However, low stability prevents to widely use them in industry and in everyday life. Possible reasons and [...] Read more.
Solar cells based on the hybrid perovskite absorbers had shown very high growth of their conversion efficiency almost reaching to the Shockley–Queisser limit during last decade. However, low stability prevents to widely use them in industry and in everyday life. Possible reasons and pathways to remedy of instability and degradation of the perovskite solar cells are considered in this review. Specific attention was paid to the thermodynamical analysis of the hybrid perovskite absorber. Full article
(This article belongs to the Special Issue Developments in Perovskite Solar Cells)
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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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25 pages, 13557 KiB  
Article
Mechanical Properties and Energy Absorption Characteristics of a Combined Gradient BCC Lattice Structure: A Numerical Study
by Xiangheng Zhao, Xiaoqiang Wang and Yunmiao Shang
Materials 2025, 18(15), 3652; https://doi.org/10.3390/ma18153652 - 4 Aug 2025
Abstract
As a new functional graded lattice structure construction strategy, the relative density gradient strategy has a promising future due to its ease of realization in various lattice structures. This paper proposes a BCC lattice structure combining two different lattice single cells. Based on [...] Read more.
As a new functional graded lattice structure construction strategy, the relative density gradient strategy has a promising future due to its ease of realization in various lattice structures. This paper proposes a BCC lattice structure combining two different lattice single cells. Based on this, the single cells of different structures are assigned different relative density gradients, resulting in 18 combined gradient lattice structures. Based on proving the experimental feasibility of numerical simulation, the mechanical properties and energy absorption characteristics of the combined gradient lattice structure are investigated by numerical simulation. When applied to composite lattice structures, the proposed wave-like gradient design significantly improves mechanical properties. Among the various gradient strategies examined, several have achieved mechanical performance close to that of uniform lattice structures. To some extent, this approach mitigates the common drawback of gradient lattice structures—where the relative density of the weakest layer is consistently lower than the interlayer relative density of uniform lattice structures—resulting in varying degrees of mechanical performance degradation compared to their uniform counterparts. The proposed linearly enhanced gradient strategy (Strategy-LE) possesses higher SEA and CLE values when the lattice structure is subjected to compressive loading, with an improvement of 6.36% in SEA and 61.6% in CLE over the uniform structure. Through the relative density gradient design, the adaptability of the BCC lattice structure in actual complex application scenarios is greatly enhanced, and the energy-absorbing properties of the lattice structure are greatly improved. Full article
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21 pages, 3334 KiB  
Article
Protective Efficacy of Lactobacillus plantarum Postbiotic beLP-K in a Dexamethasone-Induced Sarcopenia Model
by Juyeong Moon, Jin-Ho Lee, Eunwoo Jeong, Harang Park, Hye-Yeong Song, Jinsu Choi, Min-ah Kim, Kwon-Il Han, Doyong Kim, Han Sung Kim and Tack-Joong Kim
Int. J. Mol. Sci. 2025, 26(15), 7504; https://doi.org/10.3390/ijms26157504 (registering DOI) - 3 Aug 2025
Viewed by 54
Abstract
Sarcopenia is characterized by a reduction in muscle function and skeletal muscle mass relative to that of healthy individuals. In older adults and those who are less resistant to sarcopenia, glucocorticoid secretion or accumulation during treatment exacerbates muscle protein degradation, potentially causing sarcopenia. [...] Read more.
Sarcopenia is characterized by a reduction in muscle function and skeletal muscle mass relative to that of healthy individuals. In older adults and those who are less resistant to sarcopenia, glucocorticoid secretion or accumulation during treatment exacerbates muscle protein degradation, potentially causing sarcopenia. This study assessed the preventive effects and mechanisms of heat-killed Lactobacillus plantarum postbiotic beLP-K (beLP-K) against dexamethasone (DEX)-induced sarcopenia in C2C12 myotubes and Sprague-Dawley rats. The administration of beLP-K did not induce cytotoxicity and mitigated cell damage caused by DEX. Furthermore, beLP-K significantly reduced the expression of forkhead box O3 α (FoxO3α), muscle atrophy f-box (MAFbx)/atrogin-1, and muscle RING-finger protein-1 (MuRF1), which are associated with muscle protein degradation. DEX induced weight loss in rats; however, in the beLP-K group, weight gain was observed. Micro-computed tomography analysis revealed that beLP-K increased muscle mass, correlating with weight and grip strength. beLP-K alleviated the DEX-induced reduction in grip strength and increased the mass of hind leg muscles. The correlation between beLP-K administration and increased muscle mass was associated with decreased expression levels of muscle degradation-related proteins such as MAFbx/atrogin-1 and MuRF1. Therefore, beLP-K may serve as a treatment for sarcopenia or as functional food material. Full article
(This article belongs to the Section Molecular Biology)
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26 pages, 2221 KiB  
Article
Effects of ε-Poly-L-Lysine/Chitosan Composite Coating on the Storage Quality, Reactive Oxygen Species Metabolism, and Membrane Lipid Metabolism of Tremella fuciformis
by Junzheng Sun, Yingying Wei, Longxiang Li, Mengjie Yang, Yusha Liu, Qiting Li, Shaoxiong Zhou, Chunmei Lai, Junchen Chen and Pufu Lai
Int. J. Mol. Sci. 2025, 26(15), 7497; https://doi.org/10.3390/ijms26157497 (registering DOI) - 3 Aug 2025
Viewed by 53
Abstract
This study aimed to investigate the efficacy of a composite coating composed of 150 mg/L ε-Poly-L-lysine (ε-PL) and 5 g/L chitosan (CTS) in extending the shelf life and maintaining the postharvest quality of fresh Tremella fuciformis. Freshly harvested T. fuciformis were treated [...] Read more.
This study aimed to investigate the efficacy of a composite coating composed of 150 mg/L ε-Poly-L-lysine (ε-PL) and 5 g/L chitosan (CTS) in extending the shelf life and maintaining the postharvest quality of fresh Tremella fuciformis. Freshly harvested T. fuciformis were treated by surface spraying, with distilled water serving as the control. The effects of the coating on storage quality, physicochemical properties, reactive oxygen species (ROS) metabolism, and membrane lipid metabolism were evaluated during storage at (25 ± 1) °C. The results showed that the ε-PL/CTS composite coating significantly retarded quality deterioration, as evidenced by reduced weight loss, maintained whiteness and color, and higher retention of soluble sugars, soluble solids, and soluble proteins. The coating also effectively limited water migration and loss. Mechanistically, the coated T. fuciformis exhibited enhanced antioxidant capacity, characterized by increased superoxide anion (O2) resistance capacity, higher activities of antioxidant enzymes (SOD, CAT, APX), and elevated levels of non-enzymatic antioxidants (AsA, GSH). This led to a significant reduction in malondialdehyde (MDA) accumulation, alongside improved DPPH radical scavenging activity and reducing power. Furthermore, the ε-PL/CTS coating preserved cell membrane integrity by inhibiting the activities of lipid-degrading enzymes (lipase, LOX, PLD), maintaining higher levels of key phospholipids (phosphatidylinositol and phosphatidylcholine), delaying phosphatidic acid accumulation, and consequently reducing cell membrane permeability. In conclusion, the ε-PL/CTS composite coating effectively extends the shelf life and maintains the quality of postharvest T. fuciformis by modulating ROS metabolism and preserving membrane lipid homeostasis. This study provides a theoretical basis and a practical approach for the quality control of fresh T. fuciformis. Full article
(This article belongs to the Section Biochemistry)
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16 pages, 5537 KiB  
Article
Different Light Wavelengths Differentially Influence the Progression of the Hypersensitive Response Induced by Pathogen Infection in Tobacco
by Bao Quoc Tran, Anh Trung Nguyen and Sunyo Jung
Antioxidants 2025, 14(8), 954; https://doi.org/10.3390/antiox14080954 (registering DOI) - 3 Aug 2025
Viewed by 45
Abstract
Using light-emitting diodes (LEDs), we examined how different light wavelengths influence the hypersensitive response (HR) in tobacco plants infected with Pseudomonas syringae pv. tomato (Pst). Pst-infiltrated plants exhibited greater resistance to Pst infection under green and blue light compared to white and red [...] Read more.
Using light-emitting diodes (LEDs), we examined how different light wavelengths influence the hypersensitive response (HR) in tobacco plants infected with Pseudomonas syringae pv. tomato (Pst). Pst-infiltrated plants exhibited greater resistance to Pst infection under green and blue light compared to white and red light, as indicated by reduced HR-associated programmed cell death, lower H2O2 production, and up to 64% reduction in membrane damage. During the late stage of HR, catalase and ascorbate peroxidase activities peaked under green and blue LEDs, with 5- and 10-fold increases, respectively, while superoxide dismutase activity was higher under white and red LEDs. Defense-related genes CHS1, PALa, PR1, and PR2 were more strongly induced by white and red light. The plants treated with green or blue LEDs during Pst infection prompted faster degradation of phototoxic Mg-porphyrins and exhibited smaller declines in Fv/Fm, electron transport rate, chlorophyll content, and LHCB expression compared to those treated with white or red LEDs. By contrast, the induction of the chlorophyll catabolic gene SGR was 54% and 77% lower in green and blue LEDs, respectively, compared to white LEDs. This study demonstrates that light quality differentially affects Pst-mediated HR, with green and blue light more effectively suppressing HR progression, mainly by reducing oxidative stress through enhanced antioxidative capacity and mitigation of photosynthetic impairments. Full article
(This article belongs to the Special Issue Oxidative Stress and Antioxidant Defense in Crop Plants, 2nd Edition)
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23 pages, 6148 KiB  
Article
A Naturally Occurring Urinary Collagen Type I Alpha 1-Derived Peptide Inhibits Collagen Type I-Induced Endothelial Cell Migration at Physiological Concentrations
by Hanne Devos, Ioanna K. Mina, Foteini Paradeisi, Manousos Makridakis, Aggeliki Tserga, Marika Mokou, Jerome Zoidakis, Harald Mischak, Antonia Vlahou, Agnieszka Latosinska and Maria G. Roubelakis
Int. J. Mol. Sci. 2025, 26(15), 7480; https://doi.org/10.3390/ijms26157480 (registering DOI) - 2 Aug 2025
Viewed by 114
Abstract
Collagen type I (COL(I)) is a key component of the extracellular matrix (ECM) and is involved in cell signaling and migration through cell receptors. Collagen degradation produces bioactive peptides (matrikines), which influence cellular processes. In this study, we investigated the biological effects of [...] Read more.
Collagen type I (COL(I)) is a key component of the extracellular matrix (ECM) and is involved in cell signaling and migration through cell receptors. Collagen degradation produces bioactive peptides (matrikines), which influence cellular processes. In this study, we investigated the biological effects of nine most abundant, naturally occurring urinary COL(I)-derived peptides on human endothelial cells at physiological concentrations, using cell migration assays, mass spectrometry-based proteomics, flow cytometry, and AlphaFold 3. While none of the peptides significantly altered endothelial migration by themselves at physiological concentrations, full-length COL(I) increased cell migration, which was inhibited by Peptide 1 (229NGDDGEAGKPGRPGERGPpGp249). This peptide uniquely contains the DGEA and GRPGER motifs, interacting with integrin α2β1. Flow cytometry confirmed the presence of integrin α2β1 on human endothelial cells, and AlphaFold 3 modeling predicted an interaction between Peptide 1 and integrin α2. Mass spectrometry-based proteomics investigating signaling pathways revealed that COL(I) triggered phosphorylation events linked to integrin α2β1 activation and cell migration, which were absent in COL(I) plus peptide 1-treated cells. These findings identify Peptide 1 as a biologically active COL(I)-derived peptide at a physiological concentration capable of modulating collagen-induced cell migration, and provide a foundation for further investigation into its mechanisms of action and role in urine excretion. Full article
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18 pages, 1390 KiB  
Review
Fantastic Ferulic Acid Esterases and Their Functions
by Savvina Leontakianakou, Patrick Adlercreutz and Eva Nordberg Karlsson
Int. J. Mol. Sci. 2025, 26(15), 7474; https://doi.org/10.3390/ijms26157474 - 2 Aug 2025
Viewed by 205
Abstract
Ferulic acid (FA) is one of the most abundant hydroxycinnamic acids found in plant cell walls. Its dehydrodimers play an important role in maintaining the structural rigidity of the plant cell wall. Ferulic acid esterases (FAEs) act as debranching enzymes, cleaving the ester [...] Read more.
Ferulic acid (FA) is one of the most abundant hydroxycinnamic acids found in plant cell walls. Its dehydrodimers play an important role in maintaining the structural rigidity of the plant cell wall. Ferulic acid esterases (FAEs) act as debranching enzymes, cleaving the ester bond between FA and the substituted carbohydrate moieties in FA-containing polysaccharides in the plant cell wall. This enzymatic reaction facilitates the degradation of lignocellulosic materials and is crucial for the efficient utilization of biomass resources. This review focuses on the occurrence of ferulic acid in nature and its different forms and outlines the various classification systems of FAEs, their substrate specificity, and the synergistic interactions of these enzymes with other CAZymes. Additionally, it highlights the various methods that have been developed for detecting hydroxycinnamic acids and estimating the enzyme activity, as well as the versatile applications of ferulic acid. Full article
(This article belongs to the Special Issue The Characterization and Application of Enzymes in Bioprocesses)
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22 pages, 513 KiB  
Review
Unraveling NETs in Sepsis: From Cellular Mechanisms to Clinical Relevance
by Giulia Pignataro, Stefania Gemma, Martina Petrucci, Fabiana Barone, Andrea Piccioni, Francesco Franceschi and Marcello Candelli
Int. J. Mol. Sci. 2025, 26(15), 7464; https://doi.org/10.3390/ijms26157464 - 1 Aug 2025
Viewed by 126
Abstract
Sepsis is a clinical syndrome characterized by a dysregulated host response to infection, frequently resulting in septic shock and multi-organ failure. Emerging evidence highlights the critical role of neutrophil extracellular traps (NETs) in the pathophysiology of sepsis. NETs are extracellular structures composed of [...] Read more.
Sepsis is a clinical syndrome characterized by a dysregulated host response to infection, frequently resulting in septic shock and multi-organ failure. Emerging evidence highlights the critical role of neutrophil extracellular traps (NETs) in the pathophysiology of sepsis. NETs are extracellular structures composed of chromatin DNA, histones, and granular proteins released by neutrophils through a specialized form of cell death known as NETosis. While NETs contribute to the containment of pathogens, their excessive or dysregulated production in sepsis is associated with endothelial damage, immunothrombosis, and organ dysfunction. Several NET-associated biomarkers have been identified, including circulating cell-free DNA (cfDNA), histones, MPO-DNA complexes, and neutrophil elastase–DNA complexes, which correlate with the disease severity and prognosis. Therapeutic strategies targeting NETs are currently under investigation. Inhibition of NET formation using PAD4 inhibitors or ROS scavengers has shown protective effects in preclinical models. Conversely, DNase I therapy facilitates the degradation of extracellular DNA, reducing the NET-related cytotoxicity and thrombotic potential. Additionally, heparin and its derivatives have demonstrated the ability to neutralize NET-associated histones and mitigate coagulopathy. Novel approaches include targeting upstream signaling pathways, such as TLR9 and IL-8/CXCR2, offering further therapeutic promise. Full article
(This article belongs to the Collection Advances in Cell and Molecular Biology)
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26 pages, 956 KiB  
Review
Natural Flavonoids for the Prevention of Sarcopenia: Therapeutic Potential and Mechanisms
by Ye Eun Yoon, Seong Hun Ju, Yebean Kim and Sung-Joon Lee
Int. J. Mol. Sci. 2025, 26(15), 7458; https://doi.org/10.3390/ijms26157458 - 1 Aug 2025
Viewed by 124
Abstract
Sarcopenia, characterized by progressive skeletal muscle loss and functional decline, represents a major public heath challenge in aging populations. Despite increasing awareness, current management strategies—primarily resistance exercise and nutritional support—remain limited by accessibility, adherence, and inconsistent outcomes. This underscores the urgent need for [...] Read more.
Sarcopenia, characterized by progressive skeletal muscle loss and functional decline, represents a major public heath challenge in aging populations. Despite increasing awareness, current management strategies—primarily resistance exercise and nutritional support—remain limited by accessibility, adherence, and inconsistent outcomes. This underscores the urgent need for novel, effective, and scalable therapeutics. Flavonoids, a diverse class of plant-derived polyphenolic compounds, have attracted attention for their muti-targeted biological activities, including anti-inflammatory, antioxidant, metabolic, and myogenic effects. This review aims to evaluate the anti-sarcopenic potential of selected flavonoids—quercetin, rutin, kaempferol glycosides, baicalin, genkwanin, isoschaftoside, naringin, eriocitrin, and puerarin—based on recent preclinical findings and mechanistic insights. These compounds modulate key pathways involved in muscle homeostasis, such as NF-κB and Nrf2 signaling, AMPK and PI3K/Akt activation, mitochondrial biogenesis, proteosomal degradation, and satellite cell function. Importantly, since muscle wasting also features prominently in cancer cachexia—a distinct but overlapping syndrome—understanding flavonoid action may offer broader therapeutic relevance. By targeting shared molecular axes, flavonoids may provide a promising, biologically grounded approach to mitigating sarcopenia and the related muscle-wasting conditions. Further translational studies and clinical trials are warranted to assess their efficacy and safety in human populations. Full article
(This article belongs to the Special Issue Role of Natural Products in Human Health and Disease)
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18 pages, 2892 KiB  
Review
Roles of Type 10 17β-Hydroxysteroid Dehydrogenase in Health and Disease
by Xue-Ying He, Janusz Frackowiak and Song-Yu Yang
J. Pers. Med. 2025, 15(8), 346; https://doi.org/10.3390/jpm15080346 - 1 Aug 2025
Viewed by 143
Abstract
Type 10 17β-hydroxysteroid dehydrogenase (17β-HSD10) is the HSD17B10 gene product. It plays an appreciable part in the carcinogenesis and pathogenesis of neurodegeneration, such as Alzheimer’s disease and infantile neurodegeneration. This mitochondrial, homo-tetrameric protein is a central hub in various metabolic pathways, e.g., branched-chain [...] Read more.
Type 10 17β-hydroxysteroid dehydrogenase (17β-HSD10) is the HSD17B10 gene product. It plays an appreciable part in the carcinogenesis and pathogenesis of neurodegeneration, such as Alzheimer’s disease and infantile neurodegeneration. This mitochondrial, homo-tetrameric protein is a central hub in various metabolic pathways, e.g., branched-chain amino acid degradation and neurosteroid metabolism. It can bind to other proteins carrying out diverse physiological functions, e.g., tRNA maturation. It has also previously been proposed to be an Aβ-binding alcohol dehydrogenase (ABAD) or endoplasmic reticulum-associated Aβ-binding protein (ERAB), although those reports are controversial due to data analyses. For example, the reported km value of some substrate of ABAD/ERAB was five times higher than its natural solubility in the assay employed to measure km. Regarding any reported “one-site competitive inhibition” of ABAD/ERAB by Aβ, the ki value estimations were likely impacted by non-physiological concentrations of 2-octanol at high concentrations of vehicle DMSO and, therefore, are likely artefactual. Certain data associated with ABAD/ERAB were found not reproducible, and multiple experimental approaches were undertaken under non-physiological conditions. In contrast, 17β-HSD10 studies prompted a conclusion that Aβ inhibited 17β-HSD10 activity, thus harming brain cells, replacing a prior supposition that “ABAD” mediates Aβ neurotoxicity. Furthermore, it is critical to find answers to the question as to why elevated levels of 17β-HSD10, in addition to Aβ and phosphorylated Tau, are present in the brains of AD patients and mouse AD models. Addressing this question will likely prompt better approaches to develop treatments for Alzheimer’s disease. Full article
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14 pages, 879 KiB  
Article
Axially Disubstituted Silicon(IV) Phthalocyanine as a Potent Sensitizer for Antimicrobial and Anticancer Photo and Sonodynamic Therapy
by Marcin Wysocki, Daniel Ziental, Zekeriya Biyiklioglu, Malgorzata Jozkowiak, Jolanta Dlugaszewska, Hanna Piotrowska-Kempisty, Emre Güzel and Lukasz Sobotta
Int. J. Mol. Sci. 2025, 26(15), 7447; https://doi.org/10.3390/ijms26157447 - 1 Aug 2025
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Abstract
The unique properties of phthalocyanines (Pcs), such as strong absorption, high photostability, effective singlet oxygen generation, low toxicity and biocompatibility, versatile chemical modifications, broad spectrum of antimicrobial activity, and synergistic effects with other treatment modalities, make them a preferred superior sensitizer in the [...] Read more.
The unique properties of phthalocyanines (Pcs), such as strong absorption, high photostability, effective singlet oxygen generation, low toxicity and biocompatibility, versatile chemical modifications, broad spectrum of antimicrobial activity, and synergistic effects with other treatment modalities, make them a preferred superior sensitizer in the field of antimicrobial photodynamic therapy. The photodynamic and sonodynamic activity of 3-(3-(diethylamino)phenoxy)propanoxy substituted silicon(IV) Pc were evaluated against bacteria and cancer cells. Stability and singlet oxygen generation upon light irradiation and ultrasound (1 MHz, 3 W) were assessed with 1,3-diphenylisobenzofuran. The phthalocyanine revealed high photostability in DMF and DMSO, although the singlet oxygen yields under light irradiation were low. On the other hand, the phthalocyanine revealed excellent sonostability and caused a high rate of DPBF degradation upon excitation by ultrasounds at 1 MHz. The silicon phthalocyanine presented significant bacterial reduction growth, up to 5 log against MRSA and S. epidermidis upon light excitation, whereas the sonodynamic effect was negligible. The phthalocyanine revealed high activity in both photodynamic and sonodynamic manner toward hypopharyngeal tumor (FaDu, 95% and 42% reduction, respectively) and squamous cell carcinoma (SCC-25, 96% and 62% reduction, respectively). The sensitizer showed ca. 30% aldehyde dehydrogenase inhibition in various concentrations and up to 85% platelet-activating factor acetylhydrolase for 0.25 μM, while protease-activated protein C was stimulated up to 66% for 0.75 μM. Full article
(This article belongs to the Section Bioactives and Nutraceuticals)
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