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14 pages, 2625 KB  
Article
Traditional Korean Doenjang Restores Splenic and NK Cell Function in Cyclophosphamide-Induced Immunosuppressed Rats
by Hak Yong Lee, Young Mi Park, Dong Yeop Shin, Hai Min Hwang, Sung Hak Chun, Sang Jin Lim, Hee-Jong Yang, Gwang Su Ha, Myeong Seon Ryu, Ji Won Seo, Do-Youn Jeong, Jun Sang Bae and Jae Gon Kim
Int. J. Mol. Sci. 2026, 27(5), 2492; https://doi.org/10.3390/ijms27052492 - 8 Mar 2026
Viewed by 366
Abstract
Fermented soybean-based foods contain diverse bioactive compounds with recognized health benefits. Among them, doenjang is widely consumed in East Asia and has been associated with protective effects against several disorders, including immunosuppression. This study evaluated the immunoenhancing effects of doenjang sourced from four [...] Read more.
Fermented soybean-based foods contain diverse bioactive compounds with recognized health benefits. Among them, doenjang is widely consumed in East Asia and has been associated with protective effects against several disorders, including immunosuppression. This study evaluated the immunoenhancing effects of doenjang sourced from four regions of Korea in cyclophosphamide (CP)-induced immunosuppressed rats. Four-week doenjang administration restored spleen weight and improved hematological parameters, including white blood cell, lymphocyte, neutrophil, and monocyte counts. Additionally, doenjang intake enhanced immune function, as evidenced by increased splenic natural killer cell activity, increased splenocyte proliferation under lipopolysaccharide- and concanavalin A-stimulated conditions, and higher levels of interleukin (IL)-2, IL-12, interferon-γ, and immunoglobulin G. Furthermore, the suppressed phosphorylation of mitogen-activated protein kinases/nuclear factor kappa B signaling was recovered, accompanied by improved splenic structure. Collectively, our findings demonstrate that the regional varieties of doenjang effectively mitigate CP-induced immune dysfunction, indicating their potential as functional dietary interventions. Full article
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17 pages, 893 KB  
Article
Effects of Nitrogen Reduction Under Limited Water Micro-Sprinkler Irrigation on Yield, Nitrogen Absorption and Utilization, and Nitrogen Apparent Balance of Winter Wheat
by Mingda Yang, Jiaju Dong, Suyu Zhang, Yahui Cheng, Shuai Li, Shenjiao Yang, Yumei Wang, Jinping Chen and Shoutian Ma
Agronomy 2026, 16(4), 486; https://doi.org/10.3390/agronomy16040486 - 21 Feb 2026
Viewed by 295
Abstract
Reconciling high crop productivity with reduced resource inputs is a primary challenge for sustainable agriculture in water-scarce regions. This study evaluated the feasibility of reducing nitrogen (N) fertilizer application for winter wheat under limited micro-sprinkler irrigation in the Huang-Huai-Hai Plain, China. A field [...] Read more.
Reconciling high crop productivity with reduced resource inputs is a primary challenge for sustainable agriculture in water-scarce regions. This study evaluated the feasibility of reducing nitrogen (N) fertilizer application for winter wheat under limited micro-sprinkler irrigation in the Huang-Huai-Hai Plain, China. A field experiment compared five treatments: a non-fertilized and non-irrigated control (CK), conventional flood irrigation with standard N (FI), and limited micro-sprinkler irrigation (80 mm) with standard N (MI), a 20% N reduction (MI1), and a 40% N reduction (MI2). We analyzed grain yield, water and N use efficiency (WUE and NUE) and the apparent soil N balance. WUE in this study was expressed as grain yield per seasonal evapotranspiration (ET), and NUE was evaluated using agronomic indices. The results showed that the MI1 treatment maintained a high grain yield that was not significantly different from the high-input FI and MI treatments. This high yield was sustained by a compensatory mechanism involving enhanced post-anthesis N assimilation and increased extraction of deep soil water, which offset the reduced inputs. Consequently, MI1 significantly improved WUE, irrigation water use efficiency (IWUE), and NUE, while reducing the apparent soil N surplus by 74.5% compared to FI. In contrast, the greater N reduction (MI2) led to a significant yield penalty. In conclusion, a moderate (20%) reduction in N top-dressing under limited micro-sprinkler irrigation presents a viable strategy to maintain high wheat yield, simultaneously enhance resource-use efficiency, and markedly reduce environmental N losses. Full article
(This article belongs to the Special Issue Crop Management in Water-Limited Cropping Systems)
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20 pages, 11715 KB  
Article
Hypercapnia as a Double-Edged Modulator of Innate Immunity and Alveolar Epithelial Repair: A PRISMA-ScR Scoping Review
by Elber Osorio-Rodríguez, José Correa-Guerrero, Dairo Rodelo-Barrios, María Bonilla-Llanos, Carlos Rebolledo-Maldonado, Jhonny Patiño-Patiño, Jesús Viera-Torres, Mariana Arias-Gómez, María Gracia-Ordoñez, Diego González-Betancur, Yassid Nuñez-Beyeh, Gustavo Solano-Sopó and Carmelo Dueñas-Castell
Int. J. Mol. Sci. 2025, 26(19), 9622; https://doi.org/10.3390/ijms26199622 - 2 Oct 2025
Cited by 2 | Viewed by 1469
Abstract
Lung-protective ventilation and other experimental conditions raise arterial carbon dioxide tension (PaCO2) and alter pH. Short-term benefits are reported in non-infectious settings, whereas infection and/or prolonged exposure are typically harmful. This scoping review systematically maps immune-mediated effects of hypercapnia on innate [...] Read more.
Lung-protective ventilation and other experimental conditions raise arterial carbon dioxide tension (PaCO2) and alter pH. Short-term benefits are reported in non-infectious settings, whereas infection and/or prolonged exposure are typically harmful. This scoping review systematically maps immune-mediated effects of hypercapnia on innate immunity and alveolar epithelial repair. Scoping review per Levac et al. and PRISMA Extension for Scoping Reviews (Open Science Framework protocol: 10.17605/OSF.IO/WV85T; post hoc). We searched original preclinical studies (in vivo/in vitro) in PubMed, Web of Science, ScienceDirect, Cochrane Reviews, and SciELO (2008–2023). PaCO2 (mmHg) was prioritized; %Fraction of inspired Carbon Dioxide (%FiCO2) was recorded when PaCO2 was unavailable; pH was classified as buffered/unbuffered. Data were organized by context, PaCO2, and exposure duration; synthesis used heat maps (0–120 h) and a narrative description for >120 h. Mechanistic axes extracted the following: NF-κB (canonical/non-canonical), Bcl-2/Bcl-xL–Beclin-1/autophagy, AMPK/PKA/CaMKKβ/ERK1/2 and ENaC/Na,K-ATPase trafficking, Wnt/β-catenin in AT2 cells, and miR-183/IDH2/ATP. Thirty-five studies met the inclusion criteria. In non-infectious models, a “protective window” emerged, with moderate PaCO2 and brief exposure (65–95 mmHg; ≤4–6 h), featuring NF-κB attenuation and preserved epithelial ion transport. In infectious models and/or with prolonged exposure or higher PaCO2, harmful signals predominated: reduced phagocytosis/autophagy (Bcl-2/Bcl-xL–Beclin-1 axis), AMPK/PKA/ERK1/2-mediated internalization of ENaC/Na,K-ATPase, depressed β-catenin signaling in AT2 cells, impaired alveolar fluid clearance, and increased bacterial burden. Chronic exposures (>120 h) reinforced injury. Hypercapnia is a context-, dose-, time-, and pH-dependent double-edged modulator. The safe window is narrow; standardized, parallel reporting of PaCO2 and pH—with explicit comparisons of buffered vs. unbuffered hypercapnia—is essential to guide clinical translation. Full article
(This article belongs to the Special Issue Cellular and Molecular Mechanisms of Acute Lung Injury)
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14 pages, 2786 KB  
Article
Immunomodulatory Effects of Traditional Korean Gochujang in Rats Immunosuppressed with Cyclophosphamide
by Hak Yong Lee, Young Mi Park, Dong Yeop Shin, Hai Min Hwang, Sung Hak Chun, Sang Jin Lim, Hee-Jong Yang, Gwang Su Ha, Myeong Seon Ryu, Ji-Won Seo, Do-Youn Jeong, Jun Sang Bae and Jae Gon Kim
Int. J. Mol. Sci. 2025, 26(17), 8325; https://doi.org/10.3390/ijms26178325 - 27 Aug 2025
Cited by 1 | Viewed by 1310
Abstract
Fermented foods are consumed in several cultures worldwide and their health benefits are being increasingly reported. Fermented soybean products in Asia include soybean paste (doenjang), fermented soybeans (cheonggukjang), red pepper paste (gochujang, GCJ), and natto. These fermented [...] Read more.
Fermented foods are consumed in several cultures worldwide and their health benefits are being increasingly reported. Fermented soybean products in Asia include soybean paste (doenjang), fermented soybeans (cheonggukjang), red pepper paste (gochujang, GCJ), and natto. These fermented foods are reportedly associated with health benefits, including the alleviation of colitis and improvement of immune function. In this study, we investigated the immune-enhancing effects of GCJs produced in four different regions of Korea (including a commercial brand) in cyclophosphamide-treated immunosuppressed rats. The GCJs-treated group showed prevention of weight loss, increased levels of butyric acid in the cecum, and increased weight of lymphoid organs such as the thymus and spleen. Whole blood and serum analysis revealed increased numbers of white blood cells, including granulocytes and lymphocytes, pro-inflammatory cytokines (IL-2, IL-12, IFN-γ, and TNF-α), and elevated immunoglobulin G levels. Additionally, splenocyte proliferation, splenic natural killer cell activity, and immune-related signal pathways (MAPK and NF-κB) were increased. Histological analysis revealed improved tissue structure in the GCJs group. In conclusion, these findings show that GCJs enhance immune function by promoting the growth of immune organs, increasing cytokine production, and activating immune-related signaling pathways. These results suggested the potential of traditional Korean GCJs as a dietary intervention to improve immune health. Full article
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24 pages, 3424 KB  
Article
Oxidative Stress, Energy Metabolism Disorder, Mitochondrial Damage, and miR-144 Participated in Molecular Mechanisms of 4-Octylphenol-Caused Cardiac Autophagic Damage in Common Carps (Cyprinus carpio L.)
by Minna Qiu, Chunyu Jiang, Jiatian Liang, Qin Zhou, Yuhao Liu, Zhiyu Hao, Yuhang Liu, Xiumei Liu, Xiaohua Teng, Wei Sun and You Tang
Metabolites 2025, 15(6), 391; https://doi.org/10.3390/metabo15060391 - 11 Jun 2025
Cited by 6 | Viewed by 1522
Abstract
Background/Objectives: In 4-octylphenol (4-OP), a toxic environmental pollutant with endocrine disruptive effect, the use of 4-OP causes pollution in the freshwater environment and poses risks to aquatic organisms. Common carps (Cyprinus carpio L.) live in freshwater and are experimental animals for [...] Read more.
Background/Objectives: In 4-octylphenol (4-OP), a toxic environmental pollutant with endocrine disruptive effect, the use of 4-OP causes pollution in the freshwater environment and poses risks to aquatic organisms. Common carps (Cyprinus carpio L.) live in freshwater and are experimental animals for studying the toxic effects of environmental pollutants on fish. Its heart is susceptible to toxicants. However, whether 4-OP has a toxic effect on common carp heart remains unknown. Methods: Here, we conducted a common carp 4-OP exposure experiment (carp treated with 17 μg/L 4-OP for 45 days), aiming to investigate whether 4-OP has a toxic effect on common carp hearts. We observed the microstructure and ultrastructure of carp heart and detected autophagy genes, mitochondrial fission genes, mitochondrial fusion genes, glycolytic enzymes, AMPK, ATPase, and oxidative stress factors, to investigate the molecular mechanism of 4-OP induced damage in common carp hearts. Results: Our results showed that 4-OP exposure caused mitochondrial damage, autophagy, and damage in common carp hearts. 4-OP exposure increased the levels of miR-144, and eight autophagy factors (Beclin1, RB1CC1, ULK1, LC3-I, LC3-II, ATG5, ATG12, and ATG13), and decreased the levels of four autophagy factors (PI3K, AKT, mTOR, and SQSTM1). Furthermore, 4-OP exposure induced the imbalance between mitochondrial fission and fusion and mitochondrial dynamics imbalance, as demonstrated by the increase in three mitochondrial fission factors (Mff, Drp1, and Fis1) and the decrease in three mitochondrial fusion factors (Mfn1, Mfn2, and Opa1). Moreover, excess 4-OP treatment caused energy metabolism disorder, as demonstrated by the reduction in four ATPase (Na+K+-ATPase, Ca2+Mg2+-ATPase, Ca2+-ATPase, and Mg2+-ATPase), elevation in four glycolysis genes (HK1, HK2, LDHA, and PGK1), reduction in glycolysis gen (PGAM2), and the elevation in energy-sensing AMPK. Finally, 4-OP treatment induced the imbalance between antioxidant and oxidant and oxidative stress, as demonstrated by the increase in oxidant H2O2, and the decreases in five antioxidant factors (CAT, SOD, T-AOC, Nrf2, and HO-1). Conclusions: miR-144 mediated autophagy by targeting PI3K, mTOR, and SQSTM1, and the miR-144/PI3K-AKT-mTOR/ULK1 pathway was involved in 4-OP-induced autophagy. Mff-Drp1 axis took part in 4-OP-caused mitochondrial dynamics imbalance, and mitochondrial dynamics imbalance mediated autophagy via Mfn2-SQSTM1, Mfn2/Beclin1, and Mff-LC3-II axes. Energy metabolism disorder mediated mitochondrial dynamics imbalance through the AMPK-Mff-Drp1 pathway. Oxidative stress mediated energy metabolism disorder via the H2O2-AMPK axis. Taken together, oxidative stress triggered energy metabolism disorder, induced mitochondrial dynamics imbalance, and caused autophagy via the H2O2-AMPK-Mff-LC3-II pathway. Our study provided references for the toxic effects of endocrine disruptor on common carp hearts, and provided a basis for assessing environmental pollutant-induced damage in common carp heart. We only studied the toxic effects of 4-OP on common carp, and the toxic effects of 4-OP on other fish species need to be further studied. Full article
(This article belongs to the Section Cell Metabolism)
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33 pages, 1407 KB  
Article
Detection and In Vivo Validation of Dichorhavirus e-Probes in Meta-Transcriptomic Data via Microbe Finder (MiFi®) Discovers a Novel Host and a Possible New Strain of Orchid Fleck Virus
by Avijit Roy, Jonathan Shao, Andres S. Espindola, Daniel Ramos Lopez, Gabriel Otero-Colina, Yazmín Rivera, Vessela A. Mavrodieva, Mark K. Nakhla, William L. Schneider and Kitty Cardwell
Viruses 2025, 17(3), 441; https://doi.org/10.3390/v17030441 - 19 Mar 2025
Cited by 3 | Viewed by 1380
Abstract
Dichorhavirus is a recently accepted plant virus genus within the family Rhabdoviridae. Species assigned to the genus consist of bi-segmented, negative sense, single-stranded RNA viruses and are transmitted by Brevipalpus spp. Currently, there are five recognized species and two unclassified members in [...] Read more.
Dichorhavirus is a recently accepted plant virus genus within the family Rhabdoviridae. Species assigned to the genus consist of bi-segmented, negative sense, single-stranded RNA viruses and are transmitted by Brevipalpus spp. Currently, there are five recognized species and two unclassified members in the genus Dichorhavirus. Four out of seven-orchid fleck virus (OFV), citrus leprosis virus N, citrus chlorotic spot virus, and citrus bright spot virus-can infect citrus and produce leprosis disease-like symptoms. The E-probe Diagnostic for Nucleic Acid Analysis (EDNA) was developed to reduce computational effort and then integrated within Microbe-Finder (MiFi®) online platform to design and evaluate e-probes in raw High Throughput Sequencing (HTS) data. During this study, Dichorhavirus genomes were downloaded from public databases and e-probes were designed using the MiProbe incorporated into the MiFi® platform. Three different sizes of e-probes, 40, 60, and 80 nucleotides, were developed and selected based on whole genome comparisons with near-neighbor genomes. For curation, each e-probe was searched in the NCBI nucleotide sequence database using BLASTn. All the e-probes that had hits with non-target species with ≥90% identities were removed. The sensitivity and specificity of Dichorhavirus genus, species, strain, and variant-specific e-probes were validated in vivo using HTS meta-transcriptomic libraries generated from Dichorhavirus-suspected citrus, orchid, and ornamentals. Through downstream analysis of HTS data, EDNA not only detected the known hosts of OFV but also discovered an unknown host leopard plant (Farfugium japonicum), and the possible existence of a new ornamental strain of OFV in nature. Full article
(This article belongs to the Special Issue The World of Rhabdoviruses)
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22 pages, 1361 KB  
Review
The Health Benefits and Functional Properties of Gochujang: A Comprehensive Review of Fermentation and Bioactive Compounds
by Young Kyoung Park, Jinwon Kim, Myeong Seon Ryu, Hee-Jong Yang, Do-Youn Jeong and Dong-Hwa Shin
Fermentation 2025, 11(2), 67; https://doi.org/10.3390/fermentation11020067 - 1 Feb 2025
Cited by 3 | Viewed by 10564
Abstract
Gochujang, a traditional Korean fermented red pepper paste, is celebrated for its unique spicy and fermented flavor. This natural, whole food offers several health benefits due to the bioactive compounds formed during fermentation and its diverse ingredients. These bioactive compounds have been shown [...] Read more.
Gochujang, a traditional Korean fermented red pepper paste, is celebrated for its unique spicy and fermented flavor. This natural, whole food offers several health benefits due to the bioactive compounds formed during fermentation and its diverse ingredients. These bioactive compounds have been shown to have anti-cancer properties and anti-inflammatory effects by reducing inflammatory cytokines and suppressing pathways associated with diseases such as colitis and hepatitis. Gochujang has also been shown to help prevent obesity by promoting weight loss, inhibiting fat accumulation, and improving lipid profiles. It has also been shown to aid in the prevention of diabetes by suppressing hepatic glucose production and improving insulin sensitivity. The influence of gochujang on the gut microbiota is remarkable, with the ability to increase beneficial bacteria, improve microbial balance, and alleviate metabolic disorders. The primary agents responsible for these effects are capsaicin, fermentation by-products, and other bioactive compounds. The fermentation process, driven by microorganisms, enhances the nutritional and functional properties of gochujang, strengthening its health-promoting potential. This paper provides a comprehensive review of gochujang’s historical background, production methods, the role of microorganisms in fermentation, and its functional properties, emphasizing its value as a functional food for overall health improvement. Full article
(This article belongs to the Special Issue Fermentation: 10th Anniversary)
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19 pages, 11771 KB  
Article
In Silico Study of the Potential Inhibitory Effects on Escherichia coli DNA Gyrase of Some Hypothetical Fluoroquinolone–Tetracycline Hybrids
by Ioana-Andreea Lungu, Octavia-Laura Oancea and Aura Rusu
Pharmaceuticals 2024, 17(11), 1540; https://doi.org/10.3390/ph17111540 - 16 Nov 2024
Viewed by 2326
Abstract
Background/Objectives: Despite the discovery of antibiotics, bacterial infections persist globally, exacerbated by rising antimicrobial resistance that results in millions of cases, increased healthcare costs, and more extended hospital stays. The urgent need for new antibacterial drugs continues as resistance evolves. Fluoroquinolones and tetracyclines [...] Read more.
Background/Objectives: Despite the discovery of antibiotics, bacterial infections persist globally, exacerbated by rising antimicrobial resistance that results in millions of cases, increased healthcare costs, and more extended hospital stays. The urgent need for new antibacterial drugs continues as resistance evolves. Fluoroquinolones and tetracyclines are versatile antibiotics that are effective against various bacterial infections. A hybrid antibiotic combines two or more molecules to enhance antimicrobial effectiveness and combat resistance better than monotherapy. Fluoroquinolones are ideal candidates for hybridization due to their potent bactericidal effects, ease of synthesis, and ability to form combinations with other molecules. Methods: This study explored the mechanisms of action for 40 hypothetical fluoroquinolone–tetracycline hybrids, all of which could be obtained using a simple, eco-friendly synthesis method. Their interaction with Escherichia coli DNA Gyrase and similarity to albicidin were evaluated using the FORECASTER platform. Results: Hybrids such as Do-Ba, Mi-Fi, and Te-Ba closely resembled albicidin in physicochemical properties and FITTED Scores, while Te-De surpassed it with a better score. Similar to fluoroquinolones, these hybrids likely inhibit DNA synthesis by binding to enzyme–DNA complexes. Conclusions: These hybrids could offer broad-spectrum activity and help mitigate bacterial resistance, though further in vitro and in vivo studies are needed to validate their potential. Full article
(This article belongs to the Special Issue Development of Antibacterial Drugs to Combat Drug-Resistant Bacteria)
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13 pages, 2119 KB  
Article
Isolation of Bacillus altitudinis 5-DSW with Protease Activity from Deep-Sea Mineral Water and Preparation of Functional Active Peptide Fractions from Chia Seeds
by Hao Jin, Eun-Gyo Lee, Faiza Khalid, Seung-Wha Jo and Sang-Ho Baik
Microorganisms 2024, 12(10), 2048; https://doi.org/10.3390/microorganisms12102048 - 10 Oct 2024
Cited by 2 | Viewed by 2406
Abstract
In this study, we successfully isolated Bacillus strains with high protease activity from deep-sea mineral water in Korea and used them to obtain functional peptide fractions from chia seeds. The obtained Bacillus strains showed a high similarity of 99% with B. altitude with [...] Read more.
In this study, we successfully isolated Bacillus strains with high protease activity from deep-sea mineral water in Korea and used them to obtain functional peptide fractions from chia seeds. The obtained Bacillus strains showed a high similarity of 99% with B. altitude with a long rod type (named B. altitudinis 5-DSW) and high protease activity at 40 °C, and 70% of the activity remained even at 70 °C. The defatted chia seed protein (15–50 kDa) was treated with crude protease from B. altitudinis 5-DSW and digested into small peptides below 20 kDa. The obtained chia seed peptides showed 3 times and 1.5 times higher antioxidant activity in DPPH and ABT radical scavenging assays, respectively. Moreover, chia seed peptides showed enhanced AChE inhibitory activity with an IC50 value of 14.48 ± 0.88 μg/mL and BChE inhibition activity with an IC50 value of 10.90 ± 0.80 μg/mL. Our results indicate that the newly isolated B. altitudinis 5-DSW and chia seed protein hydrolysates have potential applications in biotechnology and functional food development, enhancing the nutritional quality and value-added utilization of chia byproducts. Full article
(This article belongs to the Special Issue Beneficial Microbes: Food, Mood and Beyond, 2nd Edition)
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25 pages, 25566 KB  
Article
Comparative Study of sEMG Feature Evaluation Methods Based on the Hand Gesture Classification Performance
by Hiba Hellara, Rim Barioul, Salwa Sahnoun, Ahmed Fakhfakh and Olfa Kanoun
Sensors 2024, 24(11), 3638; https://doi.org/10.3390/s24113638 - 4 Jun 2024
Cited by 18 | Viewed by 4772
Abstract
Effective feature extraction and selection are crucial for the accurate classification and prediction of hand gestures based on electromyographic signals. In this paper, we systematically compare six filter and wrapper feature evaluation methods and investigate their respective impacts on the accuracy of gesture [...] Read more.
Effective feature extraction and selection are crucial for the accurate classification and prediction of hand gestures based on electromyographic signals. In this paper, we systematically compare six filter and wrapper feature evaluation methods and investigate their respective impacts on the accuracy of gesture recognition. The investigation is based on several benchmark datasets and one real hand gesture dataset, including 15 hand force exercises collected from 14 healthy subjects using eight commercial sEMG sensors. A total of 37 time- and frequency-domain features were extracted from each sEMG channel. The benchmark dataset revealed that the minimum Redundancy Maximum Relevance (mRMR) feature evaluation method had the poorest performance, resulting in a decrease in classification accuracy. However, the RFE method demonstrated the potential to enhance classification accuracy across most of the datasets. It selected a feature subset comprising 65 features, which led to an accuracy of 97.14%. The Mutual Information (MI) method selected 200 features to reach an accuracy of 97.38%. The Feature Importance (FI) method reached a higher accuracy of 97.62% but selected 140 features. Further investigations have shown that selecting 65 and 75 features with the RFE methods led to an identical accuracy of 97.14%. A thorough examination of the selected features revealed the potential for three additional features from three specific sensors to enhance the classification accuracy to 97.38%. These results highlight the significance of employing an appropriate feature selection method to significantly reduce the number of necessary features while maintaining classification accuracy. They also underscore the necessity for further analysis and refinement to achieve optimal solutions. Full article
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16 pages, 2866 KB  
Article
Doenjang Ameliorates Diet-Induced Hyperlipidemia and Hepatic Oxidative Damage by Improving Lipid Metabolism, Oxidative Stress, and Inflammation in ICR Mice
by Olivet Chiamaka Edward, Do-Youn Jeong, Hee-Jong Yang, Anna Han and Youn-Soo Cha
Foods 2024, 13(10), 1471; https://doi.org/10.3390/foods13101471 - 10 May 2024
Cited by 12 | Viewed by 2995
Abstract
Hyperlipidemia, characterized by elevated cholesterol, lipids, and triglycerides in the bloodstream, is linked to hepatic oxidative damage. Doenjang, a traditional Korean condiment made from fermented soybeans, is known for its health benefits, yet its anti-hyperlipidemic effects remain understudied. Our study aimed to [...] Read more.
Hyperlipidemia, characterized by elevated cholesterol, lipids, and triglycerides in the bloodstream, is linked to hepatic oxidative damage. Doenjang, a traditional Korean condiment made from fermented soybeans, is known for its health benefits, yet its anti-hyperlipidemic effects remain understudied. Our study aimed to assess the hypolipidemic and hepatic protective effects of Doenjang on male ICR mice fed a high-fat cholesterol diet for 8 weeks. Mice were divided into three groups: the normal diet (ND), the high-fat cholesterol diet (HD), and the Doenjang-supplemented HD diet (DS) group. Doenjang supplementation significantly regulated total cholesterol, triglycerides, LDL cholesterol, and HDL cholesterol levels compared to the HD group. It also downregulated lipogenic genes, including PPARγ, FAS, and ACC, and positively influenced the cholesterol metabolism-related genes HMGCR and LXR. Moreover, Doenjang intake increased serum glutathione levels, activated oxidative stress defense genes (NRF2, SOD, GPx1, and CAT), positively modulated inflammation genes (NF-kB and IL6) in hepatic tissue, and reduced malondialdehyde levels. Our findings highlight the effectiveness of traditional Doenjang in preventing diet-induced hyperlipidemia and protecting against hepatic oxidative damage. Full article
(This article belongs to the Special Issue The Functional Foods: New Trends and Perspectives)
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27 pages, 6460 KB  
Article
Extracellular Vesicles Isolated from Equine Adipose-Derived Stromal Stem Cells (ASCs) Mitigate Tunicamycin-Induced ER Stress in Equine Corneal Stromal Stem Cells (CSSCs)
by Justyna M. Meissner, Aleksandra Chmielińska, Ron Ofri, Anna Cisło-Sankowska and Krzysztof Marycz
Curr. Issues Mol. Biol. 2024, 46(4), 3251-3277; https://doi.org/10.3390/cimb46040204 - 9 Apr 2024
Cited by 4 | Viewed by 2888
Abstract
Corneal ulcers, characterized by severe inflammation of the cornea, can lead to serious, debilitating complications and may be vision-threatening for horses. In this study, we aimed to investigate the role of endoplasmic reticulum (ER) stress in corneal stem progenitor cell (CSSC) dysfunction and [...] Read more.
Corneal ulcers, characterized by severe inflammation of the cornea, can lead to serious, debilitating complications and may be vision-threatening for horses. In this study, we aimed to investigate the role of endoplasmic reticulum (ER) stress in corneal stem progenitor cell (CSSC) dysfunction and explore the potential of equine adipose-derived stromal stem cell (ASC)-derived extracellular vesicles (EVs) to improve corneal wound healing. We showed that CSSCs expressed high levels of CD44, CD45, and CD90 surface markers, indicating their stemness. Supplementation of the ER-stress-inducer tunicamycin to CSSCs resulted in reduced proliferative and migratory potential, accumulation of endoplasmic reticulum (ER)-stressed cells in the G0/G1 phase of the cell cycle, increased expression of proinflammatory genes, induced oxidative stress and sustained ER stress, and unfolded protein response (UPR). Importantly, treatment with EVs increased the proliferative activity and number of cells in the G2/Mitosis phase, enhanced migratory ability, suppressed the overexpression of proinflammatory cytokines, and upregulated the anti-inflammatory miRNA-146a-5p, compared to control and/or ER-stressed cells. Additionally, EVs lowered the expression of ER-stress master regulators and effectors (PERK, IRE1, ATF6, and XBP1), increased the number of mitochondria, and reduced the expression of Fis-1 and Parkin, thereby promoting metabolic homeostasis and protecting against apoptosis in equine CSSCs. Our findings demonstrate that MSCs-derived EVs represent an innovative and promising therapeutic strategy for the transfer of bioactive mediators which regulate various cellular and molecular signaling pathways. Full article
(This article belongs to the Special Issue Molecular Research in Stem Cells)
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18 pages, 3280 KB  
Article
Leucine Supplementation Prevents the Development of Skeletal Muscle Dysfunction in a Rat Model of HFpEF
by Paula Ketilly Nascimento Alves, Antje Schauer, Antje Augstein, Maria-Elisa Prieto Jarabo, Anita Männel, Peggy Barthel, Beatrice Vahle, Anselmo S. Moriscot, Axel Linke and Volker Adams
Cells 2024, 13(6), 502; https://doi.org/10.3390/cells13060502 - 13 Mar 2024
Cited by 6 | Viewed by 3840
Abstract
Heart failure with preserved ejection fraction (HFpEF) is associated with exercise intolerance due to alterations in the skeletal muscle (SKM). Leucine supplementation is known to alter the anabolic/catabolic balance and to improve mitochondrial function. Thus, we investigated the effect of leucine supplementation in [...] Read more.
Heart failure with preserved ejection fraction (HFpEF) is associated with exercise intolerance due to alterations in the skeletal muscle (SKM). Leucine supplementation is known to alter the anabolic/catabolic balance and to improve mitochondrial function. Thus, we investigated the effect of leucine supplementation in both a primary and a secondary prevention approach on SKM function and factors modulating muscle function in an established HFpEF rat model. Female ZSF1 obese rats were randomized to an untreated, a primary prevention, and a secondary prevention group. For primary prevention, leucine supplementation was started before the onset of HFpEF (8 weeks of age) and for secondary prevention, leucine supplementation was started after the onset of HFpEF (20 weeks of age). SKM function was assessed at an age of 32 weeks, and SKM tissue was collected for the assessment of mitochondrial function and histological and molecular analyses. Leucine supplementation prevented the development of SKM dysfunction whereas it could not reverse it. In the primary prevention group, mitochondrial function improved and higher expressions of mitofilin, Mfn-2, Fis1, and miCK were evident in SKM. The expression of UCP3 was reduced whereas the mitochondrial content and markers for catabolism (MuRF1, MAFBx), muscle cross-sectional area, and SKM mass did not change. Our data show that leucine supplementation prevented the development of skeletal muscle dysfunction in a rat model of HFpEF, which may be mediated by improving mitochondrial function through modulating energy transfer. Full article
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19 pages, 1639 KB  
Article
Direct Comparative Analysis of a Pharmacogenomics Panel with PacBio Hifi® Long-Read and Illumina Short-Read Sequencing
by David Barthélémy, Elodie Belmonte, Laurie Di Pilla, Claire Bardel, Eve Duport, Veronique Gautier and Léa Payen
J. Pers. Med. 2023, 13(12), 1655; https://doi.org/10.3390/jpm13121655 - 27 Nov 2023
Cited by 10 | Viewed by 3988 | Correction
Abstract
Background: Pharmacogenetics (PGx) aims to determine genetic signatures that can be used in clinical settings to individualize treatment for each patient, including anti-cancer drugs, anti-psychotics, and painkillers. Taken together, a better understanding of the impacts of genetic variants on the corresponding protein function [...] Read more.
Background: Pharmacogenetics (PGx) aims to determine genetic signatures that can be used in clinical settings to individualize treatment for each patient, including anti-cancer drugs, anti-psychotics, and painkillers. Taken together, a better understanding of the impacts of genetic variants on the corresponding protein function or expression permits the prediction of the pharmacological response: responders, non-responders, and those with adverse drug reactions (ADRs). Objective: This work provides a comparison between innovative long-read sequencing (LRS) and short-read sequencing (SRS) techniques. Methods and Materials: The gene panel captured using PacBio HiFi® sequencing was tested on thirteen clinical samples on GENTYANE’s platform. SRS, using a comprehensive pharmacogenetics panel, was performed in routine settings at the Civil Hospitals of Lyon. We focused on complex regions analysis, including copy number variations (CNVs), structural variants, repeated regions, and phasing-haplotyping for three key pharmacogenes: CYP2D6, UGT1A1, and NAT2. Results: Variants and the corresponding expected star (*) alleles were reported. Although only 38.4% concordance was found for haplotype determination and 61.5% for diplotype, this did not affect the metabolism scoring. A better accuracy of LRS was obtained for the detection of the CYP2D6*5 haplotype in the presence of the duplicated wild-type CYP2D6*2 form. A total concordance was performed for UGT1A1 TA repeat detection. Direct phasing using the LRS approach allowed us to correct certain NAT2 profiles. Conclusions: Combining an optimized variant-calling pipeline and with direct phasing analysis, LRS is a robust technique for PGx analysis that can minimize the risk of mis-haplotyping. Full article
(This article belongs to the Section Pharmacogenetics)
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20 pages, 5473 KB  
Review
Medication-Related Osteonecrosis of the Jaw: A Systematic Review and a Bioinformatic Analysis
by Galina Laputková, Ivan Talian and Vladimíra Schwartzová
Int. J. Mol. Sci. 2023, 24(23), 16745; https://doi.org/10.3390/ijms242316745 - 25 Nov 2023
Cited by 14 | Viewed by 4151
Abstract
The objective was to evaluate the current evidence regarding the etiology of medication-related osteonecrosis of the jaw (MRONJ). This study systematically reviewed the literature by searching PubMed, Web of Science, and ProQuest databases for genes, proteins, and microRNAs associated with MRONJ from the [...] Read more.
The objective was to evaluate the current evidence regarding the etiology of medication-related osteonecrosis of the jaw (MRONJ). This study systematically reviewed the literature by searching PubMed, Web of Science, and ProQuest databases for genes, proteins, and microRNAs associated with MRONJ from the earliest records through April 2023. Conference abstracts, letters, review articles, non-human studies, and non-English publications were excluded. Twelve studies meeting the inclusion criteria involving exposure of human oral mucosa, blood, serum, saliva, or adjacent bone or periodontium to anti-resorptive or anti-angiogenic agents were analyzed. The Cochrane Collaboration risk assessment tool was used to assess the quality of the studies. A total of 824 differentially expressed genes/proteins (DEGs) and 22 microRNAs were extracted for further bioinformatic analysis using Cytoscape, STRING, BiNGO, cytoHubba, MCODE, and ReactomeFI software packages and web-based platforms: DIANA mirPath, OmicsNet, and miRNet tools. The analysis yielded an interactome consisting of 17 hub genes and hsa-mir-16-1, hsa-mir-21, hsa-mir-23a, hsa-mir-145, hsa-mir-186, hsa-mir-221, and hsa-mir-424. A dominance of cytokine pathways was observed in both the cluster of hub DEGs and the interactome of hub genes with dysregulated miRNAs. In conclusion, a panel of genes, miRNAs, and related pathways were found, which is a step toward understanding the complexity of the disease. Full article
(This article belongs to the Special Issue Omics Sciences for Salivary Diagnostics)
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