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10 pages, 649 KiB  
Opinion
The Role of Vericiguat in Early Phases of Anterior Myocardial Infarction: A Potential Game-Changer?
by Federico Cacciapuoti, Ciro Mauro, Valentina Capone, Salvatore Chianese, Luca Gaetano Tarquinio, Rossella Gottilla, Fabio Marsico, Salvatore Crispo and Fulvio Cacciapuoti
Medicina 2024, 60(10), 1595; https://doi.org/10.3390/medicina60101595 (registering DOI) - 28 Sep 2024
Abstract
Anterior myocardial infarction is a critical condition with significant implications for cardiac function and patient prognosis. Despite advancements in reperfusion therapies, optimizing recovery during the early phases of myocardial infarction remains challenging. Anterior myocardial infarction can lead to substantial long-term effects on a [...] Read more.
Anterior myocardial infarction is a critical condition with significant implications for cardiac function and patient prognosis. Despite advancements in reperfusion therapies, optimizing recovery during the early phases of myocardial infarction remains challenging. Anterior myocardial infarction can lead to substantial long-term effects on a patient’s health due to extensive damage to the heart muscle, particularly the left ventricle, impacting both quality of life and overall prognosis. Vericiguat, a soluble guanylate cyclase stimulator, has shown promise in heart failure, but its role in early anterior myocardial infarction has not yet been fully explored. By enhancing soluble guanylate cyclase activity, vericiguat may increase cyclic guanosine monophosphate production, leading to vasodilation, inhibition of platelet aggregation, and potential cardioprotective effects. Currently, treatment options for anterior myocardial infarction primarily focus on reperfusion strategies and managing complications. However, there is a critical need for adjunctive therapies that specifically target the pathophysiological changes occurring in the early phases of myocardial infarction. Vericiguat’s mechanism of action offers a novel approach to improving vascular function and myocardial health, potentially contributing to innovative treatment strategies that could transform the care and prognosis of patients with anterior myocardial infarction. Full article
(This article belongs to the Section Cardiology)
22 pages, 1928 KiB  
Review
Revolutionizing CAR T-Cell Therapies: Innovations in Genetic Engineering and Manufacturing to Enhance Efficacy and Accessibility
by Lorenzo Giorgioni, Alessandra Ambrosone, Maria Francesca Cometa, Anna Laura Salvati, Robert Nisticò and Armando Magrelli
Int. J. Mol. Sci. 2024, 25(19), 10365; https://doi.org/10.3390/ijms251910365 - 26 Sep 2024
Viewed by 563
Abstract
Chimeric antigen receptor (CAR) T-cell therapy has achieved notable success in treating hematological cancers but faces significant challenges in solid-tumor treatment and overall efficacy. Key limitations include T-cell exhaustion, tumor relapse, immunosuppressive tumor microenvironments (TME), immunogenicity, and antigen heterogeneity. To address these issues, [...] Read more.
Chimeric antigen receptor (CAR) T-cell therapy has achieved notable success in treating hematological cancers but faces significant challenges in solid-tumor treatment and overall efficacy. Key limitations include T-cell exhaustion, tumor relapse, immunosuppressive tumor microenvironments (TME), immunogenicity, and antigen heterogeneity. To address these issues, various genetic engineering strategies have been proposed. Approaches such as overexpression of transcription factors or metabolic armoring and dynamic CAR regulation are being explored to improve CAR T-cell function and safety. Other efforts to improve CAR T-cell efficacy in solid tumors include targeting novel antigens or developing alternative strategies to address antigen diversity. Despite the promising preclinical results of these solutions, challenges remain in translating CAR T-cell therapies to the clinic to enable economically viable access to these transformative medicines. The efficiency and scalability of autologous CAR T-cell therapy production are hindered by traditional, manual processes which are costly, time-consuming, and prone to variability and contamination. These high-cost, time-intensive processes have complex quality-control requirements. Recent advancements suggest that smaller, decentralized solutions such as microbioreactors and automated point-of-care systems could improve production efficiency, reduce costs, and shorten manufacturing timelines, especially when coupled with innovative manufacturing methods such as transposons and lipid nanoparticles. Future advancements may include harmonized consumables and AI-enabled technologies, which promise to streamline manufacturing, reduce costs, and enhance production quality. Full article
(This article belongs to the Special Issue State-of-the-Art Cancer Immunotherapies—2nd Edition)
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19 pages, 5444 KiB  
Article
Metabolomic Profiling Reveals That Exercise Lowers Biomarkers of Cardiac Dysfunction in Rats with Type 2 Diabetes
by Tutu Wang, Miaomiao Ning, Yurou Mo, Xinyu Tian, Yu Fu, Ismail Laher and Shunchang Li
Antioxidants 2024, 13(10), 1167; https://doi.org/10.3390/antiox13101167 - 26 Sep 2024
Viewed by 432
Abstract
The increasing prevalence of type 2 diabetes mellitus (T2DM) leads to significant global health challenges, including cardiac structural and functional deficits, which in severe cases can progress to heart failure that can further strain healthcare resources. Aerobic exercise can ameliorate cardiac dysfunction in [...] Read more.
The increasing prevalence of type 2 diabetes mellitus (T2DM) leads to significant global health challenges, including cardiac structural and functional deficits, which in severe cases can progress to heart failure that can further strain healthcare resources. Aerobic exercise can ameliorate cardiac dysfunction in individuals with diabetes, although a comprehensive understanding of its underlying mechanisms remains elusive. This study utilizes untargeted metabolomics to reveal aerobic-exercise-activated metabolic biomarkers in the cardiac tissues of Sprague Dawley rats with T2DM. Metabolomics analysis revealed that diabetes altered 1029 myocardial metabolites, while aerobic exercise reversed 208 of these metabolites, of which 112 were upregulated and 96 downregulated. Pathway topology analysis suggested that these metabolites predominantly contributed to purine metabolism and arginine biosynthesis. Furthermore, receiver operating characteristic curve analysis identified 10 potential biomarkers, including xanthine, hypoxanthine, inosine, dGMP, l-glutamic acid, l-arginine, l-tryptophan, (R)-3-hydroxybutyric acid, riboflavin, and glucolepidiin. Finally, data from Pearson correlation analysis indicated that some metabolic biomarkers strongly correlated with cardiac function. Our data suggest that certain metabolic biomarkers play an important role in ameliorating diabetes-related cardiac dysfunction by aerobic exercise. Full article
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22 pages, 919 KiB  
Review
Signaling Paradigms of H2S-Induced Vasodilation: A Comprehensive Review
by Constantin Munteanu, Cristina Popescu, Andreea-Iulia Vlădulescu-Trandafir and Gelu Onose
Antioxidants 2024, 13(10), 1158; https://doi.org/10.3390/antiox13101158 - 25 Sep 2024
Viewed by 393
Abstract
Hydrogen sulfide (H2S), a gas traditionally considered toxic, is now recognized as a vital endogenous signaling molecule with a complex physiology. This comprehensive study encompasses a systematic literature review that explores the intricate mechanisms underlying H2S-induced vasodilation. The vasodilatory [...] Read more.
Hydrogen sulfide (H2S), a gas traditionally considered toxic, is now recognized as a vital endogenous signaling molecule with a complex physiology. This comprehensive study encompasses a systematic literature review that explores the intricate mechanisms underlying H2S-induced vasodilation. The vasodilatory effects of H2S are primarily mediated by activating ATP-sensitive potassium (K_ATP) channels, leading to membrane hyperpolarization and subsequent relaxation of vascular smooth muscle cells (VSMCs). Additionally, H2S inhibits L-type calcium channels, reducing calcium influx and diminishing VSMC contraction. Beyond ion channel modulation, H2S profoundly impacts cyclic nucleotide signaling pathways. It stimulates soluble guanylyl cyclase (sGC), increasing the production of cyclic guanosine monophosphate (cGMP). Elevated cGMP levels activate protein kinase G (PKG), which phosphorylates downstream targets like vasodilator-stimulated phosphoprotein (VASP) and promotes smooth muscle relaxation. The synergy between H2S and nitric oxide (NO) signaling further amplifies vasodilation. H2S enhances NO bioavailability by inhibiting its degradation and stimulating endothelial nitric oxide synthase (eNOS) activity, increasing cGMP levels and potent vasodilatory responses. Protein sulfhydration, a post-translational modification, plays a crucial role in cell signaling. H2S S-sulfurates oxidized cysteine residues, while polysulfides (H2Sn) are responsible for S-sulfurating reduced cysteine residues. Sulfhydration of key proteins like K_ATP channels and sGC enhances their activity, contributing to the overall vasodilatory effect. Furthermore, H2S interaction with endothelium-derived hyperpolarizing factor (EDHF) pathways adds another layer to its vasodilatory mechanism. By enhancing EDHF activity, H2S facilitates the hyperpolarization and relaxation of VSMCs through gap junctions between endothelial cells and VSMCs. Recent findings suggest that H2S can also modulate transient receptor potential (TRP) channels, particularly TRPV4 channels, in endothelial cells. Activating these channels by H2S promotes calcium entry, stimulating the production of vasodilatory agents like NO and prostacyclin, thereby regulating vascular tone. The comprehensive understanding of H2S-induced vasodilation mechanisms highlights its therapeutic potential. The multifaceted approach of H2S in modulating vascular tone presents a promising strategy for developing novel treatments for hypertension, ischemic conditions, and other vascular disorders. The interaction of H2S with ion channels, cyclic nucleotide signaling, NO pathways, ROS (Reactive Oxygen Species) scavenging, protein sulfhydration, and EDHF underscores its complexity and therapeutic relevance. In conclusion, the intricate signaling paradigms of H2S-induced vasodilation offer valuable insights into its physiological role and therapeutic potential, promising innovative approaches for managing various vascular diseases through the modulation of vascular tone. Full article
(This article belongs to the Special Issue Hydrogen Sulfide Signaling in Biological Systems)
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19 pages, 11922 KiB  
Article
The Potential Related Genes and Mechanisms Involved in Improving the Treadmill Exercise Ability of APP/PS1 Mice
by Zhe Zhao, Xingqing Wu, Weijia Wu, Yingzhe Tang, Xiangyuan Meng, Mei Peng, Changfa Tang, Lan Zheng and Wenfeng Liu
Int. J. Mol. Sci. 2024, 25(19), 10244; https://doi.org/10.3390/ijms251910244 - 24 Sep 2024
Viewed by 216
Abstract
Alzheimer’s disease (AD) causes a decline in skeletal muscle function, which can further exacerbate the cognitive dysfunction of patients with AD. It has been widely established that exercise improves AD brain pathology, but the role of skeletal muscle in AD is still poorly [...] Read more.
Alzheimer’s disease (AD) causes a decline in skeletal muscle function, which can further exacerbate the cognitive dysfunction of patients with AD. It has been widely established that exercise improves AD brain pathology, but the role of skeletal muscle in AD is still poorly understood. In this study, we investigated the effects of treadmill exercise on the exercise ability of APP/PS1 transgenic AD mice and explored potential gene expression changes in their skeletal muscle. The APP/PS1 mice were subjected to a treadmill exercise for 12 weeks, followed by the Morris water maze and the open field test. After behavioral experiments, the changes in morphology, area, collagen fiber deposition, and ultrastructure of the skeletal muscle were determined; the balance of skeletal muscle protein synthesis and decomposition was analyzed; and changes in gene expression were investigated using RNA-Seq. We found that this exercise strategy can promote the learning and memory abilities of AD mice, reduce their anxiety-like behavior, improve their exercise ability, alleviate skeletal muscle atrophy, and optimize the microstructure. It can also enhance skeletal muscle protein synthesis and decomposition and improve several signaling pathways, such as the JAK–STAT, Wnt, and NOD-like receptors while decreasing calcium, cAMP, cGMP–PKG, and other signaling pathways. Six KEGG enrichment signaling pathways were downregulated and five signaling pathways were upregulated in the AD mice compared with wild-type mice, and these pathways were precisely reversed after the treadmill exercise. The expression of transcription factors such as Fosb and Egr1 in the skeletal muscle of AD mice decreased, followed by a decrease in the regulated target genes Socs1, Srrm4, and Il1b, a trend that was reversed following the exercise intervention. After exercise, AD mice exhibited a similar gene expression to that of wild-type mice, indicating enhanced exercise ability. The potential regulatory pathways and related genes identified in this study provide valuable insights for the clinical management and treatment of AD. Full article
(This article belongs to the Special Issue Exercise and Health: Cellular and Molecular Perspectives)
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21 pages, 3622 KiB  
Article
Multidrug-Resistant Proteus mirabilis and Other Gram-Negative Species Isolated from Native Egyptian Chicken Carcasses
by Bassant Ashraf El-Saeed, Hend Ali Elshebrawy, Amira Ibrahim Zakaria, Adel Abdelkhalek, Kálmán Imre, Adriana Morar, Viorel Herman and Khalid Ibrahim Sallam
Trop. Med. Infect. Dis. 2024, 9(9), 217; https://doi.org/10.3390/tropicalmed9090217 - 18 Sep 2024
Viewed by 522
Abstract
Poultry carcasses may be reservoirs for the zoonotic transmission of antimicrobial-resistant bacteria to humans and pose a major public health hazard. During the isolation of Salmonella from poultry and other foods, many of the presumptive typical Salmonella colonies on xylose lysine deoxycholate (XLD) [...] Read more.
Poultry carcasses may be reservoirs for the zoonotic transmission of antimicrobial-resistant bacteria to humans and pose a major public health hazard. During the isolation of Salmonella from poultry and other foods, many of the presumptive typical Salmonella colonies on xylose lysine deoxycholate (XLD) agar were found to lack the invA gene, which is the specific target gene for Salmonella spp. Therefore, the current study aimed to estimate the prevalence and antimicrobial resistance profiles of extensively drug-resistant invA-negative non-Salmonella isolates recovered from native Egyptian chicken carcasses as presumptive Salmonella colonies on XLD agar. The non-Salmonella isolates were detected in 84% (126/150) of the examined native Egyptian chicken carcasses and classified into five genera, with prevalence rates of 64% (96/150), 14% (21/150), 6.7% (10/150), 3.3% (5/150), and 1.3% (2/150) for Proteus, Citrobacter, Shigella, Pseudomonas, and Edwardsiella, respectively. One hundred and ninety-five invA-negative, non-verified presumptive Salmonella isolates were recovered and classified at the species level into Proteus mirabilis (132/195; 67.7%), Proteus vulgaris (11/195; 5.6%), Citrobacter freundii (26/195; 13.3%), Shigella flexneri (8/195; 4.1%), Shigella sonnei (6/195; 3.1%), Shigella dysenteriae (3/195; 1.5%), Pseudomonas fluorescens (6/195; 3.1%), and Edwardsiella tarda (3/195; 1.5%). All (195/195; 100%) of these isolates showed resistance against cefaclor and fosfomycin. Additionally, these isolates showed high resistance rates of 98%, 92.8%, 89.7%, 89.2%, 89.2%, 86.7%, 80%, 78.5%, 74.4%, and 73.9% against cephalothin, azithromycin, vancomycin, nalidixic acid, tetracycline, sulfamethoxazole/trimethoprim, cefepime, gentamicin, cefotaxime, and ciprofloxacin, respectively. Interestingly, all (195/195; 100%) of the identified isolates were resistant to at least five antibiotics and exhibited an average MAR (multiple antibiotic resistance) index of 0.783. Furthermore, 73.9% of the examined isolates were classified as extensively drug-resistant, with an MAR index equal to 0.830. The high prevalence of extensively drug-resistant foodborne Proteus, Citrobacter, Shigella, Pseudomonas, and Edwardsiella isolated from native chicken carcasses poses a great hazard to public health and necessitates more monitoring and concern about the overuse and misuse of antibiotics in humans and animals. This study also recommends the strict implementation of GHP (good hygienic practices) and GMP (good manufacturing practices) in the chicken meat supply chain to protect consumer health. Full article
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20 pages, 9173 KiB  
Article
Immune, Oxidative, and Morphological Changes in the Livers of Tibetan Sheep after Feeding Resveratrol and β-Hydroxy-β-methyl Butyric Acid: A Transcriptome–Metabolome Integrative Analysis
by Xuan Chen, Fengshuo Zhang, Sayed Haidar Abbas Raza, Zhenling Wu, Quyangangmao Su, Qiurong Ji, Tingli He, Kaina Zhu, Yu Zhang, Shengzhen Hou and Linsheng Gui
Int. J. Mol. Sci. 2024, 25(18), 9865; https://doi.org/10.3390/ijms25189865 - 12 Sep 2024
Viewed by 298
Abstract
This study investigated the effects of dietary resveratrol (RES) and β-Hydroxy-β-methyl butyric acid (HMB) on immune, oxidative, and morphological changes in the livers of Tibetan sheep using transcriptomics and metabolomics. One hundred and twenty male Tibetan lambs of a similar initial weight (15.5 [...] Read more.
This study investigated the effects of dietary resveratrol (RES) and β-Hydroxy-β-methyl butyric acid (HMB) on immune, oxidative, and morphological changes in the livers of Tibetan sheep using transcriptomics and metabolomics. One hundred and twenty male Tibetan lambs of a similar initial weight (15.5 ± 0.14 kg) were randomly divided into four groups with thirty lambs per treatment: (1) H group (basal diet without RES or HMB); (2) H-RES group (1.5 g/day of RES); (3) H-HMB group (1250 mg/day of HMB); (4) H-RES-HMB group (1.5 g/day of RES and 1250 mg/day of HMB). The experiment was conducted for 100 days, including a pre-test period of 10 days and a formal period of 90 days. The results showed significantly increased concentrations of glutathione peroxidase, superoxide dismutase, and IgM in the H-RES-HMB group (p < 0.05), while the malondialdehyde levels were significantly decreased (p < 0.05). The glycolytic indices including creatinine kinase (CK), malate dehydrogenase (MDH), and succinate dehydrogenase (SDH) were significantly increased in the H-RES-HMB group compared with the others (p < 0.05). A histological analysis showed that the hepatic plate tissue in the H-RES-HMB group appeared normal with multiple cells. The transcriptomic analysis showed that the expression of genes associated with the calcium signaling pathway (MYLK2, CYSLTR2, ADCY1, HRH1, ATP2B2, NOS2, HRC, ITPR1, and CAMK2B) and the NF-κB signaling pathway (BCL2 and CARD14) in the H-RES-HMB group were upregulated. The key differential metabolites (d-pyroglutamic acid, DL-serine, DL-threonine, fumarate, and glyceric acid) were enriched in the pathways associated with D-amino acid metabolism, the citrate cycle (TCA cycle), and carbon metabolism. The combined transcriptomic and non-targeted metabolomic analyses showed the co-enrichment of differential genes (NOS2 and GLUD1) and metabolites (fumarate) in arginine biosynthesis-regulated glycolytic activity, whereas the differential genes (ME1, SCD5, FABP2, RXRG, and CPT1B) and metabolites (Leukotriene b4) co-enriched in the PPAR signaling pathway affected the immune response by regulating the PI3K/AKT and cGMP/PKG signaling. In conclusion, the dietary RES and HMB affected the hepatic antioxidant capacity, immune response, and glycolytic activity through modulating the transcriptome (BCL2, CAMK2B, ITPR1, and IL1R1) and metabolome (DL-serine, DL-threonine, fumaric acid, and glycolic acid). Full article
(This article belongs to the Section Molecular Immunology)
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26 pages, 14555 KiB  
Article
The Effect of Chronic Treatment with the Inhibitor of Phosphodiesterase 5 (PDE5), Sildenafil, in Combination with L-DOPA on Asymmetric Behavior and Monoamine Catabolism in the Striatum and Substantia Nigra of Unilaterally 6-OHDA-Lesioned Rats
by Elżbieta Lorenc-Koci, Kinga Kamińska, Tomasz Lenda and Jolanta Konieczny
Molecules 2024, 29(18), 4318; https://doi.org/10.3390/molecules29184318 - 11 Sep 2024
Viewed by 530
Abstract
The use of phosphodiesterase inhibitors in the treatment of Parkinson’s disease is currently widely discussed. The study aimed to investigate the impact of acute and chronic treatment with the phosphodiesterase 5 inhibitor, sildenafil, at low and moderate doses of 2 mg/kg and 6 [...] Read more.
The use of phosphodiesterase inhibitors in the treatment of Parkinson’s disease is currently widely discussed. The study aimed to investigate the impact of acute and chronic treatment with the phosphodiesterase 5 inhibitor, sildenafil, at low and moderate doses of 2 mg/kg and 6 mg/kg, and L-DOPA (12.5 mg/kg), alone or in combination, on asymmetric behavior and dopamine (DA) and serotonin metabolism in the striatum and substantia nigra of unilaterally 6-OHDA-lesioned rats. Acute administration of sildenafil at both tested doses jointly with L-DOPA significantly increased the number of contralateral rotations during a 2 h measurement compared to L-DOPA alone. The effect of a lower dose of sildenafil combined with L-DOPA was much greater in the second hour of measurement. However, the acute combined administration of a higher dose of sildenafil with L-DOPA resulted in an immediate and much stronger increase in the number of contralateral rotations compared to L-DOPA alone, already visible in the first hour of measurement. Interestingly, the chronic combined administration of 2 mg/kg of sildenafil and L-DOPA significantly reduced the number of contralateral rotations, especially during the first hour of measurement, compared to the long-term treatment with L-DOPA alone. Such an effect was not observed after the long-term combined treatment of a higher dose of sildenafil and L-DOPA compared to L-DOPA alone. The concentration of DA in the ipsilateral striatum and substantia nigra after the last combined chronic dose of sildenafil (2 or 6 mg/kg) and L-DOPA (12.5 mg/kg) was significantly higher than after L-DOPA alone. In spite of much stronger increases in the DA concentration in the ipsilateral striatum and substantia nigra, the number of contralateral rotations was reduced in the group of rats treated with the combination of 2 mg/kg sildenafil and L-DOPA compared to the group receiving L-DOPA alone. Moreover, the combined treatment with a low dose of sildenafil and L-DOPA had an opposite effect on DA catabolism, as assessed by DOPAC/DA and HVA/DA indexes, and these indexes were reduced in the ipsilateral striatum but increased in the contralateral striatum and substantia nigra compared to the treatment with L-DOPA alone. The results of the present study show that the addition of a low dose of a PDE5 inhibitor to the standard L-DOPA therapy differently modulates rotational behavior, the tissue DA concentration and its catabolism in the striatum and substantia nigra. Full article
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24 pages, 2183 KiB  
Review
A Comprehensive Review on Studying and Developing Guidelines to Standardize the Inspection of Properties and Production Methods for Mycelium-Bound Composites in Bio-Based Building Material Applications
by Worawoot Aiduang, Praween Jinanukul, Wandee Thamjaree, Tanongkiat Kiatsiriroat, Tanut Waroonkun and Saisamorn Lumyong
Biomimetics 2024, 9(9), 549; https://doi.org/10.3390/biomimetics9090549 - 11 Sep 2024
Viewed by 685
Abstract
Mycelium-bound composites (MBCs) represent a promising advancement in bio-based building materials, offering sustainable alternatives for engineering and construction applications. This review provides a comprehensive overview of the current research landscape, production methodologies, and standardization ideas related to MBCs. A basic search on Scopus [...] Read more.
Mycelium-bound composites (MBCs) represent a promising advancement in bio-based building materials, offering sustainable alternatives for engineering and construction applications. This review provides a comprehensive overview of the current research landscape, production methodologies, and standardization ideas related to MBCs. A basic search on Scopus revealed over 250 publications on MBCs between 2020 and 2024, with more than 30% focusing on engineering and materials science. Key studies have investigated the physical and mechanical properties of MBCs, optimizing parameters such as substrate type, fungal species, incubation time, and post-processing to enhance material performance. Standardizing the inspection of MBC properties is crucial for ensuring quality and reliability. Various testing standards, including those from the American Society for Testing and Materials (ASTM), the International Organization for Standardization (ISO), the Japanese Industrial Standard (JIS), European Standards (EN), Deutsches Institut für Normung (DIN), and the Thai Industrial Standards Institute (TIS), are utilized to evaluate density, water absorption, compression strength, tensile strength, insulation, and other critical properties. This review highlights the distinction between lab-scale and apply-scale testing methodologies, emphasizing the need for comprehensive evaluation protocols. Additionally, the production process of MBCs involves critical steps like substrate preparation, fungal species selection, and mycelium growth, necessitating the implementation of good manufacturing practices (GMPs) to ensure consistency and quality. The internal and external structures of MBCs significantly influence their performance, necessitating standardized inspection methods using advanced techniques such as scanning electron microscopy (SEM), X-ray computed tomography (CT) scanning, and surface profilometry. By establishing robust inspection protocols and production standards, the industry can enhance the reliability and adoption of MBCs, contributing to innovations in materials science and promoting environmental sustainability. This review underscores the importance of interdisciplinary collaboration, advanced characterization tools, and regulatory frameworks to address challenges and advance the field of MBCs. Full article
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17 pages, 3258 KiB  
Article
BpfD Is a c-di-GMP Effector Protein Playing a Key Role for Pellicle Biosynthesis in Shewanella oneidensis
by Jean-Pierre Poli, Anne Boyeldieu, Alexandre Lutz, Amélie Vigneron-Bouquet, Amine Ali Chaouche, Marie-Thérèse Giudici-Orticoni, Michel Fons and Cécile Jourlin-Castelli
Int. J. Mol. Sci. 2024, 25(17), 9697; https://doi.org/10.3390/ijms25179697 - 7 Sep 2024
Viewed by 419
Abstract
The aquatic γ-proteobacterium Shewanella oneidensis is able to form two types of biofilms: a floating biofilm at the air–liquid interface (pellicle) and a solid surface-associated biofilm (SSA-biofilm). S. oneidensis possesses the Bpf system, which is orthologous to the Lap system first described in [...] Read more.
The aquatic γ-proteobacterium Shewanella oneidensis is able to form two types of biofilms: a floating biofilm at the air–liquid interface (pellicle) and a solid surface-associated biofilm (SSA-biofilm). S. oneidensis possesses the Bpf system, which is orthologous to the Lap system first described in Pseudomonas fluorescens. In the Lap systems, the retention of a large adhesin (LapA) at the cell surface is controlled by LapD, a c-di-GMP effector protein, and LapG, a periplasmic protease targeting LapA. Here, we showed that the Bpf system is mandatory for pellicle biogenesis, but not for SSA-biofilm formation, indicating that the role of Bpf is somewhat different from that of Lap. The BpfD protein was then proved to bind c-di-GMP via its degenerated EAL domain, thus acting as a c-di-GMP effector protein like its counterpart LapD. In accordance with its key role in pellicle formation, BpfD was found to interact with two diguanylate cyclases, PdgA and PdgB, previously identified as involved in pellicle formation. Finally, BpfD was shown to interact with CheY3, the response regulator controlling both chemotaxis and biofilm formation. Altogether, these results indicate that biofilm formation in S. oneidensis is under the control of a large c-di-GMP network. Full article
(This article belongs to the Special Issue Mechanisms in Biofilm Formation, Tolerance and Control: 2nd Edition)
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21 pages, 5041 KiB  
Article
Prevention of Transition from Acute Kidney Injury to Chronic Kidney Disease Using Clinical-Grade Perinatal Stem Cells in Non-Clinical Study
by Agne Gryguc, Justinas Maciulaitis, Lukas Mickevicius, Arvydas Laurinavicius, Neringa Sutkeviciene, Ramune Grigaleviciute, Vilma Zigmantaite, Romaldas Maciulaitis and Inga Arune Bumblyte
Int. J. Mol. Sci. 2024, 25(17), 9647; https://doi.org/10.3390/ijms25179647 - 6 Sep 2024
Viewed by 666
Abstract
Acute kidney injury (AKI) is widely recognized as a precursor to the onset or rapid progression of chronic kidney disease (CKD). However, there is currently no effective treatment available for AKI, underscoring the urgent need for the development of new strategies to improve [...] Read more.
Acute kidney injury (AKI) is widely recognized as a precursor to the onset or rapid progression of chronic kidney disease (CKD). However, there is currently no effective treatment available for AKI, underscoring the urgent need for the development of new strategies to improve kidney function. Human placental mesenchymal stromal cells (hpMSCs) were isolated from donor placentas, cultured, and characterized with regard to yield, viability, flow cytometry, and potency. To mimic AKI and its progression to CKD in a rat model, a dedicated sensitive non-clinical bilateral kidney ischemia-reperfusion injury (IRI) model was utilized. The experimental group received 3 × 105 hpMSCs into each kidney, while the control group received IRI and saline and the untreated group received IRI only. Urine, serum, and kidney tissue samples were collected over a period of 28 days. The hpMSCs exhibited consistent yields, viability, and expression of mesenchymal lineage markers, and were also shown to suppress T cell proliferation in a dose-dependent manner. To ensure optimal donor selection, manufacturing optimization, and rigorous quality control, the rigorous Good Manufacturing Practice (GMP) conditions were utilized. The results indicated that hpMSCs increased rat survival rates and improved kidney function by decreasing serum creatinine, urea, potassium, and fractionated potassium levels. Furthermore, the study demonstrated that hpMSCs can prevent the initial stages of kidney structural fibrosis and improve kidney function in the early stages by mitigating late interstitial fibrosis and tubular atrophy. Additionally, a robust manufacturing process with consistent technical parameters was established. Full article
(This article belongs to the Special Issue Mesenchymal Stem Cells in Health and Disease 3.0)
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12 pages, 2186 KiB  
Article
Antihypertensive Effects of Lindera erythrocarpa Makino via NO/cGMP Pathway and Ca2+ and K+ Channels
by Sujin Shin, Junkyu Park, Ho-Young Choi, Youngmin Bu and Kyungjin Lee
Nutrients 2024, 16(17), 3003; https://doi.org/10.3390/nu16173003 - 5 Sep 2024
Viewed by 681
Abstract
Studies have demonstrated the therapeutic effects of Lindera plants. This study was undertaken to reveal the antihypertensive properties of Lindera erythrocarpa leaf ethanolic extract (LEL). Aorta segments of Sprague–Dawley rats were used to study the vasodilatory effect of LEL, and the mechanisms involved [...] Read more.
Studies have demonstrated the therapeutic effects of Lindera plants. This study was undertaken to reveal the antihypertensive properties of Lindera erythrocarpa leaf ethanolic extract (LEL). Aorta segments of Sprague–Dawley rats were used to study the vasodilatory effect of LEL, and the mechanisms involved were evaluated by treating specific inhibitors or activators that affect the contractility of blood vessels. Our results revealed that LEL promotes a vasorelaxant effect through the nitric oxide/cyclic guanosine 3′,5′-monophosphate pathway, blocking the Ca2+ channels, opening the K+ channels, and inhibiting the vasoconstrictive action of angiotensin II. In addition, the effects of LEL on blood pressure were investigated in spontaneously hypertensive rats by the tail-cuff method. LEL (300 or 1000 mg/kg) was orally administered to the rats, and 1000 mg/kg of LEL significantly lowered the blood pressure. Systolic blood pressure decreased by −20.06 ± 4.87%, and diastolic blood pressure also lowered by −30.58 ± 5.92% at 4 h in the 1000 mg/kg LEL group. Overall, our results suggest that LEL may be useful to treat hypertensive diseases, considering its vasorelaxing and hypotensive effects. Full article
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14 pages, 2945 KiB  
Article
Low-Cost CO2 NDIR Sensors: Performance Evaluation and Calibration Using Machine Learning Techniques
by Ravish Dubey, Arina Telles, James Nikkel, Chang Cao, Jonathan Gewirtzman, Peter A. Raymond and Xuhui Lee
Sensors 2024, 24(17), 5675; https://doi.org/10.3390/s24175675 - 31 Aug 2024
Viewed by 622
Abstract
The study comprehensively evaluates low-cost CO2 sensors from different price tiers, assessing their performance against a reference-grade instrument and exploring the possibility of calibration using different machine learning techniques. Three sensors (Sunrise AB by Senseair, K30 CO2 by Senseair, and GMP [...] Read more.
The study comprehensively evaluates low-cost CO2 sensors from different price tiers, assessing their performance against a reference-grade instrument and exploring the possibility of calibration using different machine learning techniques. Three sensors (Sunrise AB by Senseair, K30 CO2 by Senseair, and GMP 343 by Vaisala) were tested alongside a reference instrument (Los Gatos precision greenhouse gas analyzer). The results revealed differences in sensor performance, with the higher cost Vaisala sensors exhibiting superior accuracy. Despite its lower price, the Sunrise sensors still demonstrated reasonable accuracy. Meanwhile, the K30 sensor measurements displayed higher variability and noise. Machine learning models, including linear regression, gradient boosting regression, and random forest regression, were employed for sensor calibration. In general, linear regression models performed best for extrapolating data, whereas decision tree-based models were generally more useful in handling non-linear datasets. Notably, a stack ensemble model combining these techniques outperformed the individual models and significantly improved sensor accuracy by approximately 65%. Overall, this study contributes to filling the gap in intercomparing CO2 sensors across different price categories and underscores the potential of machine learning for enhancing sensor accuracy, particularly in low-cost sensor applications. Full article
(This article belongs to the Section Environmental Sensing)
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15 pages, 4088 KiB  
Article
[68Ga]Ga-FAP-2286—Synthesis, Quality Control and Comparison with [18F]FDG PET/CT in a Patient with Suspected Cholangiocellular Carcinoma
by Anton Amadeus Hörmann, Gregor Schweighofer-Zwink, Gundula Rendl, Kristina Türk, Samuel Nadeje, Kristina Haas, Theresa Jung, Ursula Huber-Schönauer, Lukas Hehenwarter, Mohsen Beheshti and Christian Pirich
Pharmaceuticals 2024, 17(9), 1141; https://doi.org/10.3390/ph17091141 - 29 Aug 2024
Viewed by 484
Abstract
[68Ga]Ga-FAP-2286 is a new peptide-based radiopharmaceutical for positron-emission tomography (PET) that targets fibroblast activation protein (FAP). This article describes in detail the automated synthesis of [68Ga]Ga-FAP-2286 using a commercially available synthesis tool that includes quality control for routine clinical [...] Read more.
[68Ga]Ga-FAP-2286 is a new peptide-based radiopharmaceutical for positron-emission tomography (PET) that targets fibroblast activation protein (FAP). This article describes in detail the automated synthesis of [68Ga]Ga-FAP-2286 using a commercially available synthesis tool that includes quality control for routine clinical applications. The synthesis was performed using a Scintomics GRP-3V module and a GMP grade 68Ge/68Ga generator. A minor alteration for transferring the eluate to the module was established, eliminating the need for new method programming. Five batches of [68Ga]Ga-FAP-2286 were tested to validate the synthesis. A stability analysis was conducted up to 3 h after production to determine the shelf-life of the finished product. The automated synthesis on the Scintomics GRP-3V synthesis module was found to be compliant with all quality control requirements. The shelf-life of the product was set to 2 h post-production based on the stability study. A patient suffering from cholangiocellular carcinoma that could not be clearly detected by conventional imaging, including a [18F]FDG-PET/CT, highlights the potential use of [68Ga]Ga-FAP-PET/CT. Full article
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18 pages, 6984 KiB  
Article
Exploring the Molecular Mechanism of Skeletal Muscle Development in Ningxiang Pig by Weighted Gene Co-Expression Network Analysis
by Zonggang Yu, Nini Ai, Xueli Xu, Peiwen Zhang, Zhao Jin, Xintong Li and Haiming Ma
Int. J. Mol. Sci. 2024, 25(16), 9089; https://doi.org/10.3390/ijms25169089 - 22 Aug 2024
Viewed by 446
Abstract
With the continuous improvement in living standards, people’s demand for high-quality meat is increasing. Ningxiang pig has delicious meat of high nutritional value, and is loved by consumers. However, its slow growth and low meat yield seriously restrict its efficient utilization. Gene expression [...] Read more.
With the continuous improvement in living standards, people’s demand for high-quality meat is increasing. Ningxiang pig has delicious meat of high nutritional value, and is loved by consumers. However, its slow growth and low meat yield seriously restrict its efficient utilization. Gene expression is the internal driving force of life activities, so in order to fundamentally improve its growth rate, it is key to explore the molecular mechanism of skeletal muscle development in Ningxiang pigs. In this paper, Ningxiang boars were selected in four growth stages (30 days: weaning period, 90 days: nursing period, 150 days: early fattening period, and 210 days: late fattening period), and the longissimus dorsi (LD) muscle was taken from three boars in each stage. The fatty acid content, amino acid content, muscle fiber diameter density and type of LD were detected by gas chromatography, acidolysis, hematoxylin eosin (HE) staining and immunofluorescence (IF) staining. After transcription sequencing, weighted gene co-expression network analysis (WGCNA) combined with the phenotype of the LD was used to explore the key genes and signaling pathways affecting muscle development. The results showed that 10 modules were identified by WGCNA, including 5 modules related to muscle development stage, module characteristics of muscle fiber density, 5 modules characteristic of muscle fiber diameter, and a module characteristic of palmitoleic acid (C16:1) and linoleic acid (C18:2n6C). Gene ontology (GO) enrichment analysis found that 52 transcripts relating to muscle development were enriched in these modules, including 44 known genes and 8 novel genes. The Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis showed that these genes were enriched in the auxin, estrogen and cyclic guanosine monophosphate-protein kinase G (cGMP-PKG) pathways. Twelve of these genes were transcription factors, there were interactions among 20 genes, and the interactions among 11 proteins in human, pig and mouse were stable. To sum up, through the integrated analysis of phenotype and transcriptome, this paper analyzed the key genes and possible regulatory networks of skeletal muscle development in Ningxiang pigs at various stages, to provide a reference for the in-depth study of skeletal muscle development. Full article
(This article belongs to the Section Molecular Biology)
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