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Search Results (291)

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Keywords = factor H-like protein 1

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33 pages, 8117 KiB  
Article
Induced Microglial-like Cells Derived from Familial and Sporadic Alzheimer’s Disease Peripheral Blood Monocytes Show Abnormal Phagocytosis and Inflammatory Response to PSEN1 E280A Cholinergic-like Neurons
by Viviana Soto-Mercado, Miguel Mendivil-Perez, Carlos Velez-Pardo and Marlene Jimenez-Del-Rio
Int. J. Mol. Sci. 2025, 26(15), 7162; https://doi.org/10.3390/ijms26157162 - 24 Jul 2025
Viewed by 373
Abstract
In familial Alzheimer’s disease (FAD), presenilin 1 (PSEN1) E280A cholinergic-like neurons (ChLNs) induce aberrant secretion of extracellular amyloid beta (eAβ). How PSEN1 E280A ChLNs-eAβ affects microglial activity is still unknown. We obtained induced microglia-like cells (iMG) from human peripheral blood cells (hPBCs) in [...] Read more.
In familial Alzheimer’s disease (FAD), presenilin 1 (PSEN1) E280A cholinergic-like neurons (ChLNs) induce aberrant secretion of extracellular amyloid beta (eAβ). How PSEN1 E280A ChLNs-eAβ affects microglial activity is still unknown. We obtained induced microglia-like cells (iMG) from human peripheral blood cells (hPBCs) in a 15-day differentiation process to investigate the effect of bolus addition of Aβ42, PSEN1 E280A cholinergic-like neuron (ChLN)-derived culture supernatants, and PSEN1 E280A ChLNs on wild type (WT) iMG, PSEN1 E280A iMG, and sporadic Alzheimer’s disease (SAD) iMG. We found that WT iMG cells, when challenged with non-cellular (e.g., lipopolysaccharide, LPS) or cellular (e.g., Aβ42, PSEN1 E280A ChLN-derived culture supernatants) microenvironments, closely resemble primary human microglia in terms of morphology (resembling an “amoeboid-like phenotype”), expression of surface markers (Ionized calcium-binding adapter molecule 1, IBA-1; transmembrane protein 119, TMEM119), phagocytic ability (high pHrodo™ Red E. coli BioParticles™ phagocytic activity), immune metabolism (i.e., high generation of reactive oxygen species, ROS), increase in mitochondrial membrane potential (ΔΨm), response to ATP-induced transient intracellular Ca2+ influx, cell polarization (cluster of differentiation 68 (CD68)/CD206 ratio: M1 phenotype), cell migration activity according to the scratch wound assay, and especially in their inflammatory response (secretion of cytokine interleukin-6, IL-6; Tumor necrosis factor alpha, TNF-α). We also found that PSEN1 E280A and SAD iMG are physiologically unresponsive to ATP-induced Ca2+ influx, have reduced phagocytic activity, and diminished expression of Triggering Receptor Expressed on Myeloid Cells 2 (TREM2) protein, but when co-cultured with PSEN1 E280A ChLNs, iMG shows an increase in pro-inflammatory phenotype (M1) and secretes high levels of cytokines IL-6 and TNF-α. As a result, PSEN1 E280A and SAD iMG induce apoptosis in PSEN1 E280A ChLNs as evidenced by abnormal phosphorylation of protein TAU at residue T205 and cleaved caspase 3 (CC3). Taken together, these results suggest that PSEN1 E280A ChLNs initiate a vicious cycle between damaged neurons and M1 phenotype microglia, resulting in excessive ChLN death. Our findings provide a suitable platform for the exploration of novel therapeutic approaches for the fight against FAD. Full article
(This article belongs to the Special Issue Role of Glia in Human Health and Disease)
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14 pages, 1664 KiB  
Article
Depletion of IGFALS Serum Level up to 3 Months After Cardiac Surgery, with Exploration of Potential Relationships to Surrogates of Organ Failures and Clinical Outcomes
by Krzysztof Laudanski, Mohamed A. Mahmoud, Hossam Gad and Daniel A. Diedrich
Curr. Issues Mol. Biol. 2025, 47(8), 581; https://doi.org/10.3390/cimb47080581 - 23 Jul 2025
Viewed by 215
Abstract
The insulin-like growth factor binding protein, acid-labile subunit (IGFALS), plays a crucial role in glucose metabolism and immune regulation, key processes in recovery from surgery. Here, we studied the perioperative serum IGFALS dynamics and explored potential clinical implications. A total of 79 patients [...] Read more.
The insulin-like growth factor binding protein, acid-labile subunit (IGFALS), plays a crucial role in glucose metabolism and immune regulation, key processes in recovery from surgery. Here, we studied the perioperative serum IGFALS dynamics and explored potential clinical implications. A total of 79 patients undergoing elective cardiac surgery with implementation of cardiopulmonary bypass had their serum isolated at baseline, 24 h, seven days, and three months postoperatively to assess serum concentrations of IGFALS and insulin growth factor 1 (IGF-1). Markers of perioperative injury included troponin I (TnI), high-mobility group box 1 (HMGB-1), and heat shock protein 60 (Hsp-60). Inflammatory status was assessed via interleukin-6 (IL-6) and interleukin-8 (IL-8). Additionally, we measured in vitro cytokine production to viral stimulation of whole blood and monocytes. Surrogates of neuronal distress included neurofilament light chain (NF-L), total tau (τ), phosphorylated tau at threonine 181 (τp181), and amyloid β40 and β42. Renal impairment was defined by RIFLE criteria. Cardiac dysfunction was denoted by serum N-terminal pro-brain natriuretic peptide (NT-proBNP) levels. Serum IGFALS levels declined significantly after surgery and remained depressed even at 3 months. Administration of acetaminophen and acetylsalicylic acid differentiated IGFALS levels at the 24 h postoperatively. Serum IGFALS 24 h post-operatively correlated with production of cytokines by leukocytes after in vitro viral stimulation. Serum amyloid-β1-42 was significantly associated with IGFALS at baseline and 24 h post-surgery Patients discharged home had higher IGFALS levels at 28 days and 3 months than those discharged to healthcare facilities or who died. These findings suggest that IGFALS may serve as a prognostic biomarker for recovery trajectory and postoperative outcomes in cardiac surgery patients. Full article
(This article belongs to the Special Issue The Role of Neuroinflammation in Neurodegenerative Diseases)
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20 pages, 1903 KiB  
Article
Study on the Regulatory Effect of Water Extract of Artemisia annua L. on Antioxidant Function of Mutton Sheep via the Keap1/Nrf2 Signaling Pathway
by Gen Gang, Ruiheng Gao, Ruizhen Li, Xiao Jin, Yuanyuan Xing, Sumei Yan, Yuanqing Xu and Binlin Shi
Antioxidants 2025, 14(7), 885; https://doi.org/10.3390/antiox14070885 - 18 Jul 2025
Viewed by 348
Abstract
This study was conducted through in vivo and in vitro experiments and aimed to reveal the regulatory effect of water extract of Artemisia annua L. (WEAA) on the antioxidant function of mutton sheep and the underlying mechanism. In the in vivo experiment, 32 [...] Read more.
This study was conducted through in vivo and in vitro experiments and aimed to reveal the regulatory effect of water extract of Artemisia annua L. (WEAA) on the antioxidant function of mutton sheep and the underlying mechanism. In the in vivo experiment, 32 Dorper × Han female sheep (3 months old; avg. body weight: 24 ± 0.09 kg) were allocated to four groups (eight lambs/group) and fed a diet containing 0, 500, 1000, and 1500 mg/kg WEAA, respectively. In the in vitro experiments, peripheral blood lymphocytes (PBLs) were cultured with different doses of WEAA (0, 25, 50, 100, 200, 400 µg/mL) to determine the optimal concentration, followed by a 2 × 2 factorial experiment with four treatment groups (six replicates per treatment group): the ML385(−)/WEAA(−) group, the ML385(−)/WEAA(+) group, the ML385(+)/WEAA(−) group, and the ML385(+)/WEAA(+) group. The results showed that WEAA supplementation dose-dependently increased serum, liver and spleen tissue total antioxidant capacity, glutathione peroxidase (GSH-Px), and catalase (CAT) activity while reducing malondialdehyde level (p < 0.05). Moreover, WEAA supplementation significantly upregulated the liver and spleen expression of nuclear factor erythroid 2-related factor 2, superoxide dismutase 2, GSH-Px, CAT and NAD(P)H quinone dehydrogenase 1 (p < 0.05) while significantly downregulating the kelch-like ECH associated protein 1 expression in a dose-dependent manner (p < 0.05), thereby activating the Keap1/Nrf2 pathway with the peak effect observed in the 1000 mg/kg WEAA group. Additionally, supplementation with 100 µg/mL of WEAA had significant antioxidation activity in the culture medium of PBLs. Its action mechanism involved the Keap1/Nrf2 pathway; specifically, WEAA exerted its antioxidant effect by upregulating the gene expression related to the Keap1/Nrf2 pathway. In conclusion, WEAA enhances sheep’s antioxidant capacity by up-regulating Keap1/Nrf2 pathway genes and boosting antioxidant enzyme activity. The results provided experimental support for the potential application of WEAA in intensive mutton sheep farming. Full article
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13 pages, 1535 KiB  
Article
L-Lysine from Bacillus subtilis M320 Induces Salicylic-Acid–Dependent Systemic Resistance and Controls Cucumber Powdery Mildew
by Ja-Yoon Kim, Dae-Cheol Choi, Bong-Sik Yun and Hee-Wan Kang
Int. J. Mol. Sci. 2025, 26(14), 6882; https://doi.org/10.3390/ijms26146882 - 17 Jul 2025
Viewed by 325
Abstract
Powdery mildew caused by Sphaerotheca fusca poses a significant threat to cucumber (Cucumis sativus L.) production worldwide, underscoring the need for sustainable disease management strategies. This study investigates the potential of L-lysine, abundantly produced by Bacillus subtilis M 320 (BSM320), to prime [...] Read more.
Powdery mildew caused by Sphaerotheca fusca poses a significant threat to cucumber (Cucumis sativus L.) production worldwide, underscoring the need for sustainable disease management strategies. This study investigates the potential of L-lysine, abundantly produced by Bacillus subtilis M 320 (BSM320), to prime systemic acquired resistance (SAR) pathways in cucumber plants. Liquid chromatography–mass spectrometry analysis identified L-lysine as the primary bioactive metabolite in the BSM320 culture filtrate. Foliar application of purified L-lysine significantly reduced powdery mildew symptoms, lowering disease severity by up to 92% at concentrations ≥ 2500 mg/L. However, in vitro spore germination assays indicated that L-lysine did not exhibit direct antifungal activity, indicating that its protective effect is likely mediated through the activation of plant immune responses. Quantitative reverse transcription PCR revealed marked upregulation of key defense-related genes encoding pathogenesis-related proteins 1 and 3, lipoxygenase 1 and 23, WRKY transcription factor 20, and L-type lectin receptor kinase 6.1 within 24 h of treatment. Concurrently, salicylic acid (SA) levels increased threefold in lysine-treated plants, confirming the induction of an SA-dependent SAR pathway. These findings highlight L-lysine as a sustainable, residue-free priming agent capable of enhancing broad-spectrum plant immunity, offering a promising approach for amino acid-based crop protection. Full article
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16 pages, 361 KiB  
Article
Identifying Cortical Molecular Biomarkers Potentially Associated with Learning in Mice Using Artificial Intelligence
by Xiyao Huang, Carson Gauthier, Derek Berger, Hao Cai and Jacob Levman
Int. J. Mol. Sci. 2025, 26(14), 6878; https://doi.org/10.3390/ijms26146878 - 17 Jul 2025
Viewed by 201
Abstract
In this study, we identify cortical molecular biomarkers potentially associated with learning in mice using artificial intelligence (AI), inclusive of established and novel feature selection combined with supervised learning technologies. We applied multiple machine learning (ML) algorithms, using public domain ML software, to [...] Read more.
In this study, we identify cortical molecular biomarkers potentially associated with learning in mice using artificial intelligence (AI), inclusive of established and novel feature selection combined with supervised learning technologies. We applied multiple machine learning (ML) algorithms, using public domain ML software, to a public domain dataset, in order to support reproducible findings. We developed technologies tasked with predicting whether a given mouse was shocked to learn, based on protein expression levels extracted from their cortices. Results indicate that it is possible to predict whether a mouse has been shocked to learn or not based only on the following cortical molecular biomarkers: brain-derived neurotrophic factor (BDNF), NR2A subunit of N-methyl-D-aspartate receptor, B-cell lymphoma 2 (BCL2), histone H3 acetylation at lysine 18 (H3AcK18), protein kinase R-like endoplasmic reticulum kinase (pERK), and superoxide dismutase 1 (SOD1). These results were obtained with a novel redundancy-aware feature selection method. Five out of six protein expression biomarkers (BDNF, NR2A, H3AcK18, pERK, SOD1) identified have previously been associated with aspects of learning in the literature. Three of the proteins (BDNF, NR2A, and BCL2) have previously been associated with pruning, and one has previously been associated with apoptosis (BCL2), implying a potential connection between learning and both cortical pruning and apoptosis. The results imply that these six protein expression profiles (BDNF, NR2A, BCL2, H3AcK18, pERK, SOD1) are highly predictive of whether or not a mouse has been shocked to learn. Full article
(This article belongs to the Section Molecular Neurobiology)
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30 pages, 3973 KiB  
Review
V-ATPase and Lysosomal Energy Sensing in Periodontitis and Medicine-Related Osteonecrosis of the Jaw
by Xianrui Yang and Lexie Shannon Holliday
Biomolecules 2025, 15(7), 997; https://doi.org/10.3390/biom15070997 - 11 Jul 2025
Viewed by 338
Abstract
Diabetes is a risk factor for periodontitis. Increasing evidence suggests that a central player in this link is the vacuolar H+-ATPase (V-ATPase), which provides a physical and functional core for regulation by the catabolic lysosomal AMP-activated protein kinase complex (L-AMPK) and the anabolic [...] Read more.
Diabetes is a risk factor for periodontitis. Increasing evidence suggests that a central player in this link is the vacuolar H+-ATPase (V-ATPase), which provides a physical and functional core for regulation by the catabolic lysosomal AMP-activated protein kinase complex (L-AMPK) and the anabolic mammalian target of rapamycin complex 1 (mTORC1). These complexes detect levels of various cellular nutrients, including glucose at the lysosome, and promote cellular responses to restore homeostasis. The high-glucose conditions of diabetes foster anabolic mTORC1 signaling that increases inflammation and inflammatory bone resorption in response to periodontal infections. Here, we review the structure and composition of V-ATPase, L-AMPK, mTORC1, and other elements of the energy-sensing platform. Mechanisms by which V-ATPase passes signals to the complexes are examined and recent data are reviewed. Current anti-bone resorptive therapeutics, bisphosphonates and denosumab, enhance the risk of medicine-related osteonecrosis of the jaw (MRONJ) and are not used to treat periodontal bone loss. Accumulating data suggest that it may be possible to target inflammatory bone resorption through agents that stimulate L-AMPK, including metformin and glucagon-like peptide-1 agonists. This approach may reduce inflammatory bone resorption without major effects on overall bone remodeling or increased risk of MRONJ. Full article
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18 pages, 5392 KiB  
Article
Kaempferol Alleviates Carbon Tetrachloride-Induced Liver Fibrosis in Mice by Regulating Intestinal Short-Chain Fatty Acids
by Siqi Zhang, Fei Tang, Zhe Zhou, Linhui Li, Yang Tang, Kaiwen Fu, Yang Tan and Ling Li
Int. J. Mol. Sci. 2025, 26(14), 6666; https://doi.org/10.3390/ijms26146666 - 11 Jul 2025
Viewed by 329
Abstract
Liver fibrosis remains a critical health concern with limited therapeutic options. Kaempferol (Kae) is a natural flavonoid widely present in natural plants, yet its role in modulating gut–liver axis interactions during fibrosis is unexplored. This study investigates the hepatoprotective effects of Kae on [...] Read more.
Liver fibrosis remains a critical health concern with limited therapeutic options. Kaempferol (Kae) is a natural flavonoid widely present in natural plants, yet its role in modulating gut–liver axis interactions during fibrosis is unexplored. This study investigates the hepatoprotective effects of Kae on alleviating carbon tetrachloride (CCl4)-induced liver fibrosis, and its underlying mechanisms, focusing on oxidative stress, gut microbiota, and short-chain fatty acids (SCFAs), are revealed. A mouse model of hepatic fibrosis was built by the subcutaneous injection of CCl4. Meanwhile, Kae was administered by gavage at doses of 25, 50, and 100 mg/kg body weight. Serum biomarkers, liver histopathology, oxidative damage markers, and nuclear factor erythroid 2-related factor 2 (Nrf2)/kelch-like ECH-associated protein 1 (Keap1)/heme oxygenase 1 (HO-1) signaling were analyzed. AML12 hepatocytes were pretreated with Kae or SCFAs (acetate, propionate, butyrate) before H2O2-induced oxidative injury. The changes in gut microbiota and the levels of SCFAs were assessed via 16S rRNA sequencing and GC-MS, respectively. Kae effectively alleviated the destruction of the liver morphology and tissue structure, reduced the infiltration of inflammatory cells, collagen deposition in the liver, and the expression of fibrotic factors, and downregulated the oxidative stress level in the liver of mice with liver fibrosis by activating the Nrf2/Keap1/HO-1 pathway (p < 0.05 or 0.01). In vitro, Kae significantly mitigated H2O2-induced cytotoxicity and oxidative damage (p < 0.05 or 0.01). Furthermore, Kae restored gut microbiota diversity, increased beneficial genera (e.g., Lactobacillus), and elevated both intestinal and hepatic SCFA levels (p < 0.01). The discrepant SCFA pretreatment similarly protected AML12 cells by activating Nrf2 signaling (p < 0.05 or 0.01). Our research suggests that Kae could inhibit CCl4-induced liver fibrosis by restoring the levels of intestinal metabolite SCFAs to reduce oxidative damage. Full article
(This article belongs to the Section Molecular Pharmacology)
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19 pages, 10222 KiB  
Article
Molecular Hydrogen Improves Blueberry Main Fruit Traits via Metabolic Reprogramming
by Longna Li, Jiaxin Gong, Ke Jiang, Liqin Huang, Lijun Gan, Yan Zeng, Xu Cheng, Didier Pathier and Wenbiao Shen
Plants 2025, 14(14), 2137; https://doi.org/10.3390/plants14142137 - 10 Jul 2025
Viewed by 343
Abstract
Fruit yield and quality improvement are challenges for researchers and farmers. This study reveals that the main fruit traits of blueberry (Vaccinium ashei ‘Bluegem’) were significantly improved after hydrogen (H2)-based irrigation, assessed by the increased single fruit weight (14.59 ± [...] Read more.
Fruit yield and quality improvement are challenges for researchers and farmers. This study reveals that the main fruit traits of blueberry (Vaccinium ashei ‘Bluegem’) were significantly improved after hydrogen (H2)-based irrigation, assessed by the increased single fruit weight (14.59 ± 6.66%) and fruit equatorial diameter (4.19 ± 2.39%), decreased titratable acidity, increased solid–acid and sugar–acid ratios. The enhancement of fruit quality was confirmed by the increased total volatiles, vitamin C contents, and antioxidant capacity. Using weighted protein co-expression network analysis (WPCNA), proteomic interrogation revealed that serine carboxypeptidase-like proteins I/II (SCPLI/II), ADP ribosylation factor 1/2 (ARF1/2), and UDP-glucosyltransferase 85A (UGT85A) might be functionally associated with the increased fruit weight and size driven by H2. Reduced organic acid accumulation was caused by the regulation of the specific enzymes involved in sucrose metabolism (e.g., α-amylase, endoglucanase, β-glucosidase, etc.). H2 regulation of fatty acid degradation (e.g., acyl CoA oxidase 1 (ACX1), acetyl CoA acyltransferase 1 (ACAA1), etc.) and phenylpropanoid metabolism were used to explain the improved fruit aroma and anthocyanin accumulation. Meanwhile, the upregulated heat shock protein 20/70 matched with the enhanced antioxidant activity. Together, this study provides a novel approach for yield and quality improvement in horticultural crops. Full article
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21 pages, 5721 KiB  
Article
Macroalgae-Inspired Brominated Chalcones as Cosmetic Ingredients with the Potential to Target Skin Inflammaging
by Ana Jesus, Sara Gimondi, Sónia A. Pinho, Helena Ferreira, Nuno M. Neves, Andreia Palmeira, Emília Sousa, Isabel F. Almeida, Maria T. Cruz and Honorina Cidade
Mar. Drugs 2025, 23(7), 278; https://doi.org/10.3390/md23070278 - 2 Jul 2025
Viewed by 537
Abstract
Skin aging is mainly caused by external factors like sunlight, which triggers oxidative stress and chronic inflammation. Natural halogenated flavonoids have demonstrated anti-inflammatory properties. Inspired by the macroalgae-derived bromophenol BDDE, we investigated the anti-inflammatory potential of structure-related chalcones (17 [...] Read more.
Skin aging is mainly caused by external factors like sunlight, which triggers oxidative stress and chronic inflammation. Natural halogenated flavonoids have demonstrated anti-inflammatory properties. Inspired by the macroalgae-derived bromophenol BDDE, we investigated the anti-inflammatory potential of structure-related chalcones (17). Chalcones 1 and 7 showed the least cytotoxicity in keratinocyte and macrophage cells. Chalcones 1, 2, 4, and 5 exhibited the most significant anti-inflammatory effects in murine macrophages after lipopolysaccharide stimulation, with chalcone 1 having the lowest IC50 value (≈0.58 μM). A SNAP assay confirmed that chalcones do not exert their effects through direct NO scavenging. Symmetrical bromine atoms and 3,4-dimethoxy groups on both aromatic rings improved the anti-inflammatory activity, indicating a relevant structure–activity relationship. Chalcones 1 and 2 were selected for study to clarify their mechanisms of action. At a concentration of 7.5 μM, chalcone 2 demonstrated a rapid and effective inhibitory action on the protein levels of inducible nitric oxide synthase (iNOS), while chalcone 1 exhibited a gradual inhibitory action. Moreover, chalcone 1 effectively activated the nuclear factor erythroid 2-related factor 2 (Nrf2) pathway with around a 3.5-fold increase at the end of 24 h at 7.5 μM, highlighting its potential as a modulator of oxidative stress responses. These findings place chalcone 1 as a promising candidate for skincare products targeting inflammation and skin aging. Full article
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15 pages, 1622 KiB  
Article
Chicken Primordial Germ Cell Surface Marker
by Tamara J. Gough, Terry G. Wise, Matthew P. Bruce, Timothy J. Doran, Daniel S. Layton and Andrew G. D. Bean
Animals 2025, 15(13), 1868; https://doi.org/10.3390/ani15131868 - 24 Jun 2025
Viewed by 412
Abstract
The creation of transgenic chickens holds significant promise for the agricultural and biotechnological sectors, offering potential improvements in disease resistance and production efficiency. The preferred method for generating gene-edited chickens involves the genetic manipulation of primordial germ cells (PGCs), making the identification and [...] Read more.
The creation of transgenic chickens holds significant promise for the agricultural and biotechnological sectors, offering potential improvements in disease resistance and production efficiency. The preferred method for generating gene-edited chickens involves the genetic manipulation of primordial germ cells (PGCs), making the identification and isolation of these cells a growing focus of research. PGCs are the precursors to sperm and oocytes, responsible for transmitting genetic material to the next generation. In humans, PGCs are characterized by their large size, round nuclei, and refractive lipids in the cytoplasm, and can be identified using periodic acid–Schiff (PAS) staining and the surface marker stage-specific embryonic antigen 1 (SSEA1). Similarly, chicken PGCs express SSEA1, but their most specific marker is the chicken vasa homologue (CVH), the avian equivalent of the RNA-binding factor gene vasa. However, SSEA1, along with other known surface markers, does not bind to all PGCs or lacks specificity, while CVH, although highly specific to PGCs, is intracellular and unsuitable for isolating viable cells. This study aims to develop an antibody targeting a PGC surface marker with the same specificity as CVH. Despite the importance of identifying surface markers for PGC characterization, to date, such reagents are limited. To address this, whole chicken PGCs were injected into mice, leading to the generation of a panel of monoclonal antibodies. One antibody was found to bind cultured chicken PGCs and showed reduced expression upon differentiation with retinoic acid, indicating its specificity to PGCs. Immunoprecipitation followed by mass spectrometry identified the antigen as myosin heavy chain-like (MYH9) protein. The antibody, αMYH9, was further characterized and shown to bind circulating PGCs and embryonic gonadal PGCs (Hamburger Hamilton (H-H) stage 30, embryonic day 6.5–7). Whilst our primary aim was to determine the binding to PGCs, further investigation is required to determine potential binding to somatic cells. In conclusion, this study provides the characterization of a surface marker for chicken PGCs, with significant implications for advancements in avian genetic preservation, agriculture, and biotechnology. Full article
(This article belongs to the Special Issue Advances in Genetic Analysis of Important Traits in Poultry)
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26 pages, 1739 KiB  
Review
A Comprehensive Perspective on the Biological Effects of Intermittent Fasting and Periodic Short-Term Fasting: A Promising Strategy for Optimizing Metabolic Health
by Barbara Ciastek, Karolina Kapłon and Przemysław Domaszewski
Nutrients 2025, 17(13), 2061; https://doi.org/10.3390/nu17132061 - 20 Jun 2025
Viewed by 1901
Abstract
It is well established that different fasting strategies offer a range of benefits and may even serve as potential therapeutic approaches for metabolic diseases. The biological effects of intermittent fasting (IF) are multidimensional, involving the induction of metabolic switching from glucose to fatty [...] Read more.
It is well established that different fasting strategies offer a range of benefits and may even serve as potential therapeutic approaches for metabolic diseases. The biological effects of intermittent fasting (IF) are multidimensional, involving the induction of metabolic switching from glucose to fatty acid and ketone utilization, thereby enhancing fat metabolism and improving glucose tolerance and insulin sensitivity. In addition, IF modulates the growth hormone/insulin-like growth factor 1 (GH/IGF-1) axis by lowering IGF-1 levels, a change associated with enhanced cellular protection, reduced tumorigenesis, and delayed aging. Moreover, IF modulates key signaling pathways, including mitogen-activated protein kinases, Notch, and nuclear factor kappa B, which collectively contribute to reduced oxidative stress, attenuated inflammation, and hepatoprotection. Although fasting may present certain challenges, it is essential to be adequately informed about its potential benefits and appropriate preparatory strategies before undertaking various fasting protocols. This review summarizes the current knowledge on various IF protocols and periodic short-term fasting (PSTF) lasting more than 24 h and up to 72 h, highlighting the signaling pathways through which these interventions affect metabolic processes. Additionally, it aims to provide a practical guide for the safe preparation for PSTF lasting more than 24 h and up to 72 h. Full article
(This article belongs to the Special Issue Intermittent Fasting: A Heart-Healthy Dietary Strategy?)
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17 pages, 2175 KiB  
Article
Rutin Attenuates Oxidative Stress Responses and Hepatocyte Metabolomics in β-Hydroxybutyric Acid-Induced Hepatocyte Injury in Calves
by Kun Yang, Haixia Zhao, Min Gao, Honglian Hu and Dabiao Li
Int. J. Mol. Sci. 2025, 26(12), 5878; https://doi.org/10.3390/ijms26125878 - 19 Jun 2025
Viewed by 413
Abstract
: Negative energy balance (NEB) in dairy cows induces excessive lipolysis, leading to elevated levels of β-hydroxybutyric acid (BHBA), which, when accumulated, can cause liver damage. Rutin (RT), a natural flavonoid with antioxidant and anti-inflammatory properties, has demonstrated potential hepatoprotective effects; however, its [...] Read more.
: Negative energy balance (NEB) in dairy cows induces excessive lipolysis, leading to elevated levels of β-hydroxybutyric acid (BHBA), which, when accumulated, can cause liver damage. Rutin (RT), a natural flavonoid with antioxidant and anti-inflammatory properties, has demonstrated potential hepatoprotective effects; however, its ability to mitigate BHBA-induced hepatocellular injury in calves remains unclear. This study first assessed the impact of various BHBA concentrations on oxidative stress in calf hepatocytes, then explored the protective effects and underlying mechanisms of RT, and finally employed untargeted metabolomics to further elucidate RT’s mode of action. The results showed that exposure to 1.2 mM BHBA significantly increased malondialdehyde (MDA), nitric oxide (NO) contents, and reactive oxygen species (ROS) levels, while markedly decreasing glutathione (GSH) content and catalase (CAT) activity compared with the blank control. Notably, pretreatment with 100 μg/mL RT resulted in the greatest increase in GSH contents (180%) compared to BHBA treatment alone, while 150 μg/mL RT led to the most pronounced reduction in MDA contents (220%). Furthermore, BHBA treatment significantly upregulated the expression of Kelch-like ECH-associated protein 1 (Keap1) and downregulated nuclear factor erythroid 2-related factor 2 (Nrf2), NAD(P)H quinone dehydrogenase 1 (NQO1), and heme oxygenase-1 (HO-1) at both the mRNA and protein levels. These alterations were effectively reversed by pretreatment with 100 μg/mL RT. Non-targeted metabolomics identified 1525 metabolites in total. Based on OPLS-DA, metabolites with a variable importance in projection (VIP) > 1 and p < 0.05 were considered significantly altered. Compared with the blank control, BHBA treatment upregulated 47 metabolites—including 8-hydroxy-2′-deoxyguanosine, 3-hydroxyisovaleric acid, and N-palmitoyl-sphingosine—and downregulated 58 metabolites, such as betaine, linolenic acid, and arachidonic acid. In contrast, RT pretreatment upregulated 207 metabolites relative to the BHBA treatment, including linolenic acid, taurocholic acid, and 4-hydroxybenzoic acid, and downregulated 126 metabolites, including 3-hydroxyisovaleric acid, 8-hydroxy-2′-deoxyguanosine, and pyruvaldehyde. Pathway enrichment analysis indicated that RT alleviated BHBA-induced hepatocyte injury primarily by modulating the fatty acid degradation pathway. In summary, RT mitigated BHBA-induced oxidative stress in calf hepatocytes by regulating the Keap1/Nrf2 signaling pathway and further exerted protective effects through metabolic reprogramming. Full article
(This article belongs to the Section Molecular Biology)
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19 pages, 5427 KiB  
Article
Screening and Identification of Drought-Tolerant Genes in Tomato (Solanum lycopersicum L.) Based on RNA-Seq Analysis
by Yue Ma, Yushan Li, Fan Wang, Quan Qing, Chengzhu Deng, Hao Wang and Yu Song
Plants 2025, 14(10), 1471; https://doi.org/10.3390/plants14101471 - 14 May 2025
Viewed by 815
Abstract
Drought is one of the major abiotic stresses that inhibits plant growth and development. Therefore, it is critical to explore drought resistance genes in crops to obtain high-quality breeding materials. In this study, the drought-sensitive tomato line “FQ118” and the resistant line “FQ119” [...] Read more.
Drought is one of the major abiotic stresses that inhibits plant growth and development. Therefore, it is critical to explore drought resistance genes in crops to obtain high-quality breeding materials. In this study, the drought-sensitive tomato line “FQ118” and the resistant line “FQ119” were treated with PEG-6000 and, at 0 h (CK), 6 h, 24 h, 36 h and 48 h, the plants were evaluated for growth and physiological indicators, and leaf tissues were collected for RNA-seq. The growth indicators (growth trend, dry and fresh weights above- and below-ground, etc.) and the antioxidant enzyme system reflect that “FQ119” has stronger drought tolerance. Through RNA-seq analysis, a total of 68,316 transcripts (37,908 genes) were obtained. The largest number of significant differentially expressed genes (DEGs) in the comparison of “FQ118” and “FQ119” was observed at 6 h and 48 h. KEGG analysis demonstrated the significant enrichment of certain pathways associated with drought stress, such as glycerolipid metabolism and galactose metabolism. Co-expression analysis revealed that 7 hub DEGs, including genes encoding a photosystem reaction center subunit protein, chlorophyll a-b binding protein, glyceraldehyde-3-phosphate dehydrogenase A (GAPDH), and others, were coenriched in both comparisons. In addition, three hub genes specific to the comparison during the 6-h processing stage, encoding oxygen-evolving enhancer protein 1, receptor-like serine/threonine-protein kinase and calcium-transporting ATPase, were identified. The above hub genes were related to plant resistance to drought stress, and RT‒qPCR verified that the overall magnitudes of the differences in expression between the two lines gradually increased over time. Virus-induced gene silencing (VIGS) experiments have demonstrated that GAPDH plays a relevant role in the drought resistance pathway. In addition, the differences in expression of 7 DEGs encoding transcription factors, including Dofs, WRKYs, MYBs, and MYCs, also tended to increase with increasing duration of drought treatment, as determined via qPCR. In summary, this study identified several valuable genes related to plant drought resistance by screening genes with differential transcription under drought stress. This in-depth gene mining may provide valuable references and resources for future breeding for drought resistance in tomato. Full article
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15 pages, 3256 KiB  
Article
Effect of Hyaluronan in Collagen Biomaterials on Human Macrophages and Fibroblasts In Vitro
by Nancy Avila-Martinez, Maren Pfirrmann, Madalena L. N. P. Gomes, Roman Krymchenko, Elly M. M. Versteeg, Marcel Vlig, Martijn Verdoes, Toin H. van Kuppevelt, Bouke K. H. L. Boekema and Willeke F. Daamen
J. Funct. Biomater. 2025, 16(5), 167; https://doi.org/10.3390/jfb16050167 - 8 May 2025
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Abstract
In adults, scars are formed after deep skin wound injuries like burns. However, the fetal microenvironment allows for scarless skin regeneration. One component that is abundantly present in the fetal extracellular matrix is hyaluronan (HA). To study whether biomaterials with HA improve wound [...] Read more.
In adults, scars are formed after deep skin wound injuries like burns. However, the fetal microenvironment allows for scarless skin regeneration. One component that is abundantly present in the fetal extracellular matrix is hyaluronan (HA). To study whether biomaterials with HA improve wound healing, type I collagen scaffolds with and without HA were prepared and characterized. Their immune effect was tested using macrophages and their phenotypes were analyzed through cell surface markers and cytokine expression after 48 h. Since fibroblasts are the main cellular component in the dermis, adult, fetal and eschar-derived cells were cultured on scaffolds for 14 days and evaluated using histology, gene and protein expression analyses. Biochemical assays demonstrated that HA was successfully incorporated and evenly distributed throughout the scaffolds. Macrophages (M0) cultured on Col I+HA scaffolds exhibited a profile resembling the M2c-like phenotype (CD206high, CD163high and IL10high). HA did not significantly affect gene expression in adult and fetal fibroblasts, but significantly reduced scarring-related genes, such as transforming growth factor beta 1 (TGFB1) and type X collagen alpha 1 chain (COL10A1), in myofibroblast-like eschar cells. These findings highlight the potential of incorporating HA into collagen-based skin substitutes to improve the wound healing response. Full article
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18 pages, 1223 KiB  
Article
Influence of Traditional Vanilla Curing on Its Physicochemical Properties and Aromatic Profile
by Isabel Janid Perez-Viveros, Sergio Erick García-Barrón, Blanca Elizabeth Hernández-Rodríguez, Ariadna Isabel Barrera-Rodríguez, Claudia Ariadna Acero-Ortega and Anastacio Espejel-García
Foods 2025, 14(9), 1652; https://doi.org/10.3390/foods14091652 - 7 May 2025
Viewed by 692
Abstract
Vanilla is native to Mexico and has social-cultural and economic importance. It is sensory characteristics are developed during the curing process, which is associated with the region where it is carried out since the know-how of each locality is involved. In this sense, [...] Read more.
Vanilla is native to Mexico and has social-cultural and economic importance. It is sensory characteristics are developed during the curing process, which is associated with the region where it is carried out since the know-how of each locality is involved. In this sense, this work aimed to evaluate the influence of the curing process. Four different processes from four regions (SJA, SLP, CQ and EPM) were considered, taking into account two curing conditions. Additionally, sample control was considered. The moisture content, protein, ether extract, ash and pH were analyzed. The aromatic profile was evaluated by the RATA methodology and liking level. Except for ash content, the process influenced the other physicochemical parameters. The moisture contents of SLP and CQ samples from Period 1, as well as SLP samples from Period 2, comply with the current Mexican Standard. SJA vanilla was “slightly” accepted in both periods, surpassing the control sample. In contrast, the CQ sample was the least preferred. Thirty-five aromatic descriptors were generated. At the sensory level, a clear separation of vanillas was observed according to the type of curing. The attributes described included caramel, dry fruit, fruity, honey, maltol, rancid, sweet, tree bark, vanilla and ashes, which boosted the liking level. On the other hand, the descriptors chemical, moisture, dairy, spicy, wood and lipids had a negative effect, proving that these factors can alter the aromatic balance, giving an unpleasant smell and reducing preference. It was confirmed that the curing process influences physicochemical parameters, the aromatic profile and the liking level. However, it would be necessary to consider other variables. Full article
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