The 2023 MDPI Annual Report has
been released!
 
22 pages, 3276 KiB  
Review
The Role of Biophysical Factors in Organ Development: Insights from Current Organoid Models
by Yofiel Wyle, Nathan Lu, Jason Hepfer, Rahul Sayal, Taylor Martinez and Aijun Wang
Bioengineering 2024, 11(6), 619; https://doi.org/10.3390/bioengineering11060619 (registering DOI) - 18 Jun 2024
Abstract
Biophysical factors play a fundamental role in human embryonic development. Traditional in vitro models of organogenesis focused on the biochemical environment and did not consider the effects of mechanical forces on developing tissue. While most human tissue has a Young’s modulus in the [...] Read more.
Biophysical factors play a fundamental role in human embryonic development. Traditional in vitro models of organogenesis focused on the biochemical environment and did not consider the effects of mechanical forces on developing tissue. While most human tissue has a Young’s modulus in the low kilopascal range, the standard cell culture substrate, plasma-treated polystyrene, has a Young’s modulus of 3 gigapascals, making it 10,000–100,000 times stiffer than native tissues. Modern in vitro approaches attempt to recapitulate the biophysical niche of native organs and have yielded more clinically relevant models of human tissues. Since Clevers’ conception of intestinal organoids in 2009, the field has expanded rapidly, generating stem-cell derived structures, which are transcriptionally similar to fetal tissues, for nearly every organ system in the human body. For this reason, we conjecture that organoids will make their first clinical impact in fetal regenerative medicine as the structures generated ex vivo will better match native fetal tissues. Moreover, autologously sourced transplanted tissues would be able to grow with the developing embryo in a dynamic, fetal environment. As organoid technologies evolve, the resultant tissues will approach the structure and function of adult human organs and may help bridge the gap between preclinical drug candidates and clinically approved therapeutics. In this review, we discuss roles of tissue stiffness, viscoelasticity, and shear forces in organ formation and disease development, suggesting that these physical parameters should be further integrated into organoid models to improve their physiological relevance and therapeutic applicability. It also points to the mechanotransductive Hippo-YAP/TAZ signaling pathway as a key player in the interplay between extracellular matrix stiffness, cellular mechanics, and biochemical pathways. We conclude by highlighting how frontiers in physics can be applied to biology, for example, how quantum entanglement may be applied to better predict spontaneous DNA mutations. In the future, contemporary physical theories may be leveraged to better understand seemingly stochastic events during organogenesis. Full article
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15 pages, 4776 KiB  
Article
Impacts of Millipedes on Acari and Collembola Communities—A Microcosm Experiment
by Wenjin Chang, Peng Zhang, Jianwei Li, Nonillon M. Aspe, Jiahua Hao, Siyuan Lu, Zhuoma Wan and Donghui Wu
Insects 2024, 15(6), 456; https://doi.org/10.3390/insects15060456 (registering DOI) - 18 Jun 2024
Abstract
Ecosystem engineers influence the structure and function of soil food webs through non-trophic interactions. The activity of large soil animals, such as earthworms, has a significant impact on the soil microarthropod community. However, the influence of millipedes on soil microarthropod communities remains largely [...] Read more.
Ecosystem engineers influence the structure and function of soil food webs through non-trophic interactions. The activity of large soil animals, such as earthworms, has a significant impact on the soil microarthropod community. However, the influence of millipedes on soil microarthropod communities remains largely unknown. In this microcosm experiment, we examined the effects of adding, removing, and restricting millipede activity on Acari and Collembola communities in litter and soil by conducting two destructive sampling sessions on days 10 and 30, respectively. At the time of the first sampling event (10 d), Acari and Collembola abundance was shown to increase and the alpha diversity went higher in the treatments with millipedes. At the time of the second sampling event (30 d), millipedes significantly reduced the Collembola abundance and alpha diversity. The results were even more pronounced as the millipedes moved through the soil, which caused the collembolans to be more inclined to inhabit the litter, which in turn resulted in the increase in the abundance and diversity of Acari in the soil. The rapid growth of Collembola in the absence of millipedes significantly inhibited the abundance of Acari. The presence of millipedes altered the community structure of Acari and Collembola, leading to a stronger correlation between the two communities. Changes in these communities were driven by the dominant taxa of Acari and Collembola. These findings suggest that millipedes, as key ecosystem engineers, have varying impacts on different soil microarthropods. This study enhances our understanding of biological interactions and offers a theoretical foundation for soil biodiversity conservation. Full article
(This article belongs to the Special Issue Diversity and Function of Collembola)
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16 pages, 3195 KiB  
Article
HDetect-VS: Tiny Human Object Enhancement and Detection Based on Visual Saliency for Maritime Search and Rescue
by Zhennan Fei, Yingjiang Xie, Da Deng, Lingshuai Meng, Fu Niu and Jinggong Sun
Appl. Sci. 2024, 14(12), 5260; https://doi.org/10.3390/app14125260 (registering DOI) - 18 Jun 2024
Abstract
Strong sun glint noise is an inevitable obstruction for tiny human object detection in maritime search and rescue (SAR) tasks, which can significantly deteriorate the performance of local contrast method (LCM)-based algorithms and cause high false alarm rates. For SAR tasks in noisy [...] Read more.
Strong sun glint noise is an inevitable obstruction for tiny human object detection in maritime search and rescue (SAR) tasks, which can significantly deteriorate the performance of local contrast method (LCM)-based algorithms and cause high false alarm rates. For SAR tasks in noisy environments, it is more important to find tiny objects than localize them. Hence, considering background clutter and strong glint noise, in this study, a noise suppression methodology for maritime scenarios (HDetect-VS) is established to achieve tiny human object enhancement and detection based on visual saliency. To this end, the pixel intensity value distributions, color characteristics, and spatial distributions are thoroughly analyzed to separate objects from background and glint noise. Using unmanned aerial vehicles (UAVs), visible images with rich details, rather than infrared images, are applied to detect tiny objects in noisy environments. In this study, a grayscale model mapped from the HSV model (HSV-gray) is used to suppress glint noise based on color characteristic analysis, and large-scale Gaussian Convolution is utilized to obtain the pixel intensity surface and suppress background noise based on pixel intensity value distributions. Moreover, based on a thorough analysis of the spatial distribution of objects and noise, two-step clustering is employed to separate objects from noise in a salient point map. Experiments are conducted on the SeaDronesSee dataset; the results illustrate that HDetect-VS has more robust and effective performance in tiny object detection in noisy environments than other pixel-level algorithms. In particular, the performance of existing deep learning-based object detection algorithms can be significantly improved by taking the results of HDetect-VS as input. Full article
(This article belongs to the Special Issue Advanced Image Analysis and Processing Technologies and Applications)
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4 pages, 169 KiB  
Editorial
Introduction to the Special Issue of Genealogy on Surnames
by Richard Coates and Harry Parkin
Genealogy 2024, 8(2), 77; https://doi.org/10.3390/genealogy8020077 (registering DOI) - 18 Jun 2024
Abstract
Giving personal names to individual children is a cultural universal [...] Full article
(This article belongs to the Special Issue Family Names: Origins, History, Anthropology and Sociology)
14 pages, 5016 KiB  
Article
Real-Time Trajectory Smoothing and Obstacle Avoidance: A Method Based on Virtual Force Guidance
by Yongbin Su, Chenying Lin and Tundong Liu
Sensors 2024, 24(12), 3935; https://doi.org/10.3390/s24123935 (registering DOI) - 18 Jun 2024
Abstract
In dynamic environments, real-time trajectory planners are required to generate smooth trajectories. However, trajectory planners based on real-time sampling often produce jerky trajectories that necessitate post-processing steps for smoothing. Existing local smoothing methods may result in trajectories that collide with obstacles due to [...] Read more.
In dynamic environments, real-time trajectory planners are required to generate smooth trajectories. However, trajectory planners based on real-time sampling often produce jerky trajectories that necessitate post-processing steps for smoothing. Existing local smoothing methods may result in trajectories that collide with obstacles due to the lack of a direct connection between the smoothing process and trajectory optimization. To address this limitation, this paper proposes a novel trajectory-smoothing method that considers obstacle constraints in real time. By introducing virtual attractive forces from original trajectory points and virtual repulsive forces from obstacles, the resultant force guides the generation of smooth trajectories. This approach enables parallel execution with the trajectory-planning process and requires low computational overhead. Experimental validation in different scenarios demonstrates that the proposed method not only achieves real-time trajectory smoothing but also effectively avoids obstacles. Full article
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22 pages, 2836 KiB  
Article
Efficacy of Lactococcus lactis subsp. lactis LY-66 and Lactobacillus plantarum PL-02 in Enhancing Explosive Strength and Endurance: A Randomized, Double-Blinded Clinical Trial
by Mon-Chien Lee, Yi-Ju Hsu, Mu-Tsung Chen, Yi-Wei Kuo, Jia-Hung Lin, Yu-Chieh Hsu, Yen-Yu Huang, Ching-Min Li, Shin-Yu Tsai, Ko-Chiang Hsia, Hsieh-Hsun Ho and Chi-Chang Huang
Nutrients 2024, 16(12), 1921; https://doi.org/10.3390/nu16121921 (registering DOI) - 18 Jun 2024
Abstract
Probiotics are posited to enhance exercise performance by influencing muscle protein synthesis, augmenting glycogen storage, and reducing inflammation. This double-blind study randomized 88 participants to receive a six-week intervention with either a placebo, Lactococcus lactis subsp. lactis LY-66, Lactobacillus plantarum PL-02, or a [...] Read more.
Probiotics are posited to enhance exercise performance by influencing muscle protein synthesis, augmenting glycogen storage, and reducing inflammation. This double-blind study randomized 88 participants to receive a six-week intervention with either a placebo, Lactococcus lactis subsp. lactis LY-66, Lactobacillus plantarum PL-02, or a combination of both strains, combined with a structured exercise training program. We assessed changes in maximal oxygen consumption (VO2max), exercise performance, and gut microbiota composition before and after the intervention. Further analyses were conducted to evaluate the impact of probiotics on exercise-induced muscle damage (EIMD), muscle integrity, and inflammatory markers in the blood, 24 and 48 h post-intervention. The results demonstrated that all probiotic groups exhibited significant enhancements in exercise performance and attenuation of muscle strength decline post-exercise exhaustion (p < 0.05). Notably, PL-02 intake significantly increased muscle mass, whereas LY-66 and the combination therapy significantly reduced body fat percentage (p < 0.05). Analysis of intestinal microbiota revealed an increase in beneficial bacteria, especially a significant rise in Akkermansia muciniphila following supplementation with PL-02 and LY-66 (p < 0.05). Overall, the combination of exercise training and supplementation with PL-02, LY-66, and their combination improved muscle strength, explosiveness, and endurance performance, and had beneficial effects on body composition and gastrointestinal health, as evidenced by data obtained from non-athlete participants. Full article
(This article belongs to the Special Issue Nutrition for Muscular Strength, Power and Endurance)
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17 pages, 1200 KiB  
Article
Outcome of an Accelerated Treatment Algorithm for Patients Developing Diarrhea as a Complication of Ipilimumab-Based Cancer Immunotherapy in a Community Practice
by Clarice Ho and Wolfram Samlowski
Curr. Oncol. 2024, 31(6), 3529-3545; https://doi.org/10.3390/curroncol31060260 (registering DOI) - 18 Jun 2024
Abstract
Immune-mediated diarrhea represents a serious complication of checkpoint inhibitor therapy, especially following ipilimumab-based treatment. Efficient diagnosis and control of diarrhea remains an ongoing challenge. We developed an accelerated management paradigm for patients with ipilimumab-induced diarrhea. Patients who developed significant diarrhea (>five loose stools/day) [...] Read more.
Immune-mediated diarrhea represents a serious complication of checkpoint inhibitor therapy, especially following ipilimumab-based treatment. Efficient diagnosis and control of diarrhea remains an ongoing challenge. We developed an accelerated management paradigm for patients with ipilimumab-induced diarrhea. Patients who developed significant diarrhea (>five loose stools/day) were presumed to be developing immune colitis. Therapy was interrupted and patients were treated with a methylprednisolone dose pack. If diarrhea was not completely resolved, high-dose steroids and infliximab were promptly added. Only non-responding patients underwent further evaluation for infection or other causes of diarrhea. A total of 242 patients were treated with ipilimumab-based regimens. Forty-six developed significant diarrhea (19%) and thirty-four (74.4%) had a rapid resolution of diarrhea following glucocorticosteroid and infliximab treatment. The median time to resolution of diarrhea was only 8.5 ± 16.4 days. Accelerated treatment for presumed immune-mediated diarrhea resulted in the rapid control of symptoms in the majority of patients. There were no intestinal complications or deaths. Immunosuppressive therapy for diarrhea did not appear to decrease the remission rate or survival. After the control of diarrhea, most patients were able to continue their planned immunotherapy. Further testing in 11/46 patients with unresponsive diarrhea revealed additional diagnoses, allowing their treatment to be adjusted. Full article
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21 pages, 9151 KiB  
Article
A Color Indicator Based on 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium Bromide (MTT) and a Biodegradable Poly(ester amide) for Detecting Bacterial Contamination
by María José Lovato, María del Carmen De Lama-Odría, Jordi Puiggalí, Luis J. del Valle and Lourdes Franco
Int. J. Mol. Sci. 2024, 25(12), 6671; https://doi.org/10.3390/ijms25126671 (registering DOI) - 18 Jun 2024
Abstract
Bacterial contamination is a hazard in many industries, including food, pharmaceuticals, and healthcare. The availability of a rapid and simple method for detecting this type of contamination in sterile areas enables immediate intervention to avoid or reduce detrimental effects. Among these methods, colorimetric [...] Read more.
Bacterial contamination is a hazard in many industries, including food, pharmaceuticals, and healthcare. The availability of a rapid and simple method for detecting this type of contamination in sterile areas enables immediate intervention to avoid or reduce detrimental effects. Among these methods, colorimetric indicators are becoming increasingly popular due to their affordability, ease of use, and quick visual interpretation of the signal. In this article, a bacterial contamination indicator system was designed by incorporating MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) into an electrospun PADAS matrix, which is a biodegradable poly(ester amide) synthesized from L-alanine, 1,12-dodecanediol, and sebacic acid. Uniaxial stress testing, thermogravimetric analysis and scanning electron microscopy were used to examine the mechanical properties, thermal stability, and morphology of the mats, respectively. The capacity for bacterial detection was not only analyzed with agar and broth assays but also by replicating important environmental conditions. Among the MTT concentrations tested in this study (0.2%, 2%, and 5%), it was found that only with a 2% MTT content the designed system produced a color response visible to the naked eye with optimal intensity, a sensitivity limit of 104 CFU/mL, and 86% cell viability, which showed the great potential for its use to detect bacterial contamination. In summary, by means of the process described in this work, it was possible to obtain a simple, low-cost and fast-response bacterial contamination indicator that can be used in mask filters, air filters, or protective clothing. Full article
(This article belongs to the Special Issue Polymers in Biological Systems)
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16 pages, 2175 KiB  
Article
Role of MalQ Enzyme in a Reconstructed Maltose/Maltodextrin Pathway in Actinoplanes sp. SE50/110
by Camilla März, Sophia Nölting, Lars Wollenschläger, Alfred Pühler and Jörn Kalinowski
Microorganisms 2024, 12(6), 1221; https://doi.org/10.3390/microorganisms12061221 (registering DOI) - 18 Jun 2024
Abstract
The pseudotetrasaccharide acarbose, produced by Actinoplanes sp. SE50/110, is a relevant secondary metabolite used in diabetes type II medication. Although maltose plays a crucial role in acarbose biosynthesis, the understanding of the maltose/maltodextrin metabolism and its involvement in acarbose production is at an [...] Read more.
The pseudotetrasaccharide acarbose, produced by Actinoplanes sp. SE50/110, is a relevant secondary metabolite used in diabetes type II medication. Although maltose plays a crucial role in acarbose biosynthesis, the understanding of the maltose/maltodextrin metabolism and its involvement in acarbose production is at an early stage. Here, we reconstructed the predicted maltose–maltodextrin pathway that involves four enzymes AmlE, MalZ, MalP, and MalQ. An investigation of enzyme activities was conducted through in vitro assays, leading to an expansion of previously postulated substrate spectra. The maltose-induced α-glucosidase AmlE is noteworthy for its high hydrolysis rate of linear α-1,4-glucans, and its capability to hydrolyze various glycosidic bonds. The predicted maltodextrin glucosidase MalZ showed slow hydrolysis activity on linear α-glucans, but it was resistant to acarbose and capable of releasing glucose from acarbose. AmlE compensates for the low activity of MalZ to ensure glucose supply. We determined the enzyme activity of MalP and its dual function as maltodextrin and glycogen phosphorylase. The 4-α-glucanotransferase MalQ plays a central role in the maltose/maltodextrin metabolism, alongside MalP. This study confirmed the simultaneous degradation and synthesis of long-chain α-glucans. The product distribution showed that with an increasing number of glycosidic bonds, less glucose is formed. We found that MalQ, like its sequence homolog AcbQ from the acarbose biosynthetic gene cluster, is involved in the formation of elongated acarviosyl metabolites. However, MalQ does not participate in the elongation of acarbose 7-phosphate, which is likely the more readily available acceptor molecule in vivo. Accordingly, MalQ is not involved in the formation of acarviosyl impurities in Actinoplanes sp. SE50/110. Full article
(This article belongs to the Special Issue Specialized Metabolites from Microorganisms)
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14 pages, 3080 KiB  
Article
Frequency-Dependent Neural Modulation of Dorsal Horn Neurons by Kilohertz Spinal Cord Stimulation in Rats
by Dong Wang, Kwan Yeop Lee, Zachary B. Kagan, Kerry Bradley and Dongchul Lee
Biomedicines 2024, 12(6), 1346; https://doi.org/10.3390/biomedicines12061346 (registering DOI) - 18 Jun 2024
Abstract
Kilohertz high-frequency spinal cord stimulation (kHF-SCS) is a rapidly advancing neuromodulatory technique in the clinical management of chronic pain. However, the precise cellular mechanisms underlying kHF-SCS-induced paresthesia-free pain relief, as well as the neural responses within spinal pain circuits, remain largely unexplored. In [...] Read more.
Kilohertz high-frequency spinal cord stimulation (kHF-SCS) is a rapidly advancing neuromodulatory technique in the clinical management of chronic pain. However, the precise cellular mechanisms underlying kHF-SCS-induced paresthesia-free pain relief, as well as the neural responses within spinal pain circuits, remain largely unexplored. In this study, using a novel preparation, we investigated the impact of varying kilohertz frequency SCS on dorsal horn neuron activation. Employing calcium imaging on isolated spinal cord slices, we found that extracellular electric fields at kilohertz frequencies (1, 3, 5, 8, and 10 kHz) induce distinct patterns of activation in dorsal horn neurons. Notably, as the frequency of extracellular electric fields increased, there was a clear and significant monotonic escalation in neuronal activity. This phenomenon was observed not only in superficial dorsal horn neurons, but also in those located deeper within the dorsal horn. Our study demonstrates the unique patterns of dorsal horn neuron activation in response to varying kilohertz frequencies of extracellular electric fields, and we contribute to a deeper understanding of how kHF-SCS induces paresthesia-free pain relief. Furthermore, our study highlights the potential for kHF-SCS to modulate sensory information processing within spinal pain circuits. These insights pave the way for future research aimed at optimizing kHF-SCS parameters and refining its therapeutic applications in the clinical management of chronic pain. Full article
(This article belongs to the Section Biomedical Engineering and Materials)
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17 pages, 812 KiB  
Review
Hypercalcemia in Cancer: Causes, Effects, and Treatment Strategies
by Patrycja Bartkiewicz, Dominika Kunachowicz, Michał Filipski, Agata Stebel, Julia Ligoda and Nina Rembiałkowska
Cells 2024, 13(12), 1051; https://doi.org/10.3390/cells13121051 (registering DOI) - 18 Jun 2024
Abstract
Calcium plays central roles in numerous biological processes, thereby, its levels in the blood are under strict control to maintain homeostatic balance and enable the proper functioning of living organisms. The regulatory mechanisms ensuring this balance can be affected by pathologies such as [...] Read more.
Calcium plays central roles in numerous biological processes, thereby, its levels in the blood are under strict control to maintain homeostatic balance and enable the proper functioning of living organisms. The regulatory mechanisms ensuring this balance can be affected by pathologies such as cancer, and as a result, hyper- or hypocalcemia can occur. These states, characterized by elevated or decreased calcium blood levels, respectively, have a significant effect on general homeostasis. This article focuses on a particular form of calcium metabolism disorder, which is hypercalcemia in neoplasms. It also constitutes a summary of the current knowledge regarding the diagnosis of hypercalcemia and its management. Hypercalcemia of malignancy is estimated to affect over 40% of cancer patients and can be associated with both solid and blood cancers. Elevated calcium levels can be an indicator of developing cancer. The main mechanism of hypercalcemia development in tumors appears to be excessive production of parathyroid hormone-related peptides. Among the known treatment methods, bisphosphonates, calcitonin, steroids, and denosumab should be mentioned, but ongoing research promotes progress in pharmacotherapy. Given the rising global cancer prevalence, the problem of hypercalcemia is of high importance and requires attention. Full article
(This article belongs to the Section Cellular Pathology)
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16 pages, 4654 KiB  
Systematic Review
Tissue-Mimicking Material Fabrication and Properties for Multiparametric Ultrasound Phantoms: A Systematic Review
by Adel Jawli, Wadhhah Aldehani, Ghulam Nabi and Zhihong Huang
Bioengineering 2024, 11(6), 620; https://doi.org/10.3390/bioengineering11060620 (registering DOI) - 18 Jun 2024
Abstract
Medical imaging has allowed for significant advancements in the field of ultrasound procedures over the years. However, each imaging modality exhibits distinct limitations that differently affect their accuracy. It is imperative to ensure the quality of each modality to identify and eliminate these [...] Read more.
Medical imaging has allowed for significant advancements in the field of ultrasound procedures over the years. However, each imaging modality exhibits distinct limitations that differently affect their accuracy. It is imperative to ensure the quality of each modality to identify and eliminate these limitations. To achieve this, a tissue-mimicking material (TMM) phantom is utilised for validation. This study aims to perform a systematic analysis of tissue-mimicking materials used for creating ultrasound phantoms. We reviewed 234 studies on the use of TMM phantoms in ultrasound that were published from 2013 to 2023 from two research databases. Our focus was on studies that discussed TMMs’ properties and fabrication for ultrasound, elastography, and flow phantoms. The screening process led to the selection of 16 out of 234 studies to include in the analysis. The TMM ultrasound phantoms were categorised into three groups based on the solvent used; each group offers a broad range of physical properties. The water-based material most closely aligns with the properties of ultrasound. This study provides important information about the materials used for ultrasound phantoms. We also compared these materials to real human tissues and found that PVA matches most of the human tissues the best. Full article
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24 pages, 3538 KiB  
Systematic Review
Effects of Cocoa Consumption on Cardiometabolic Risk Markers: Meta-Analysis of Randomized Controlled Trials
by Tainah O. P. Arisi, Diego Silveira da Silva, Elana Stein, Camila Weschenfelder, Patrícia Caetano de Oliveira, Aline Marcadenti, Alexandre Machado Lehnen and Gustavo Waclawovsky
Nutrients 2024, 16(12), 1919; https://doi.org/10.3390/nu16121919 (registering DOI) - 18 Jun 2024
Abstract
Background: We conducted a systematic review and meta-analysis to examine the effect of dietary intake of cocoa on anthropometric measurements, lipid and glycemic profiles, and blood pressure levels in adults, with and without comorbidities. Methods: The databases used were MEDLINE (PubMed), EMBASE, Web [...] Read more.
Background: We conducted a systematic review and meta-analysis to examine the effect of dietary intake of cocoa on anthropometric measurements, lipid and glycemic profiles, and blood pressure levels in adults, with and without comorbidities. Methods: The databases used were MEDLINE (PubMed), EMBASE, Web of Science, Cochrane, LILACS, and SciELO. The eligible studies were randomized clinical trials (RCTs) involving adults undergoing cocoa consumption (cocoa extract or ≥70% cocoa dark chocolate) for ≥4 weeks that evaluated at least one of the following markers: body weight, body mass index (BMI), waist/abdominal circumference, total cholesterol, LDL-c, triglycerides, HDL-c, blood glucose, glycated hemoglobin (HbA1c), and systolic and diastolic blood pressure (SBP/DBP). Results: Thirty-one studies were included, totaling 1986 participants. Cocoa consumption showed no effects on body weight, BMI, waist circumference, triglycerides, HDL-c and HbA1c. Yet, there was a reduction in total cholesterol (−8.35 mg/dL, 95% CI −14.01; −2.69 mg/dL), LDL-c (−9.47 mg/dL, 95% CI −13.75; −5.20 mg/dL), fasting blood glucose (−4.91 mg/dL, 95% CI −8.29; −1.52 mg/dL), SBP (−2.52 mmHg, 95% CI −4.17; −0.88 mmHg), and DBP (−1.58 mmHg, 95% CI −2.54; −0.62 mmHg). Conclusions: The consumption of cocoa showed protective effects on major cardiometabolic risk markers that have a clinical impact in terms of cardiovascular risk reduction. Full article
(This article belongs to the Section Phytochemicals and Human Health)
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5 pages, 181 KiB  
Editorial
Emerging and Endemic Infections in Wildlife: Epidemiology, Ecology and Management in a Changing World
by Andrew W. Byrne and Eric R. Morgan
Pathogens 2024, 13(6), 513; https://doi.org/10.3390/pathogens13060513 (registering DOI) - 18 Jun 2024
Abstract
The importance of gaining a greater understanding of the infectious diseases of wild animal populations and the impact of emerging and re-emerging pathogens has never been more sharply in focus than in the current post-COVID-19 world [...] Full article
21 pages, 6781 KiB  
Review
Synthetic Modifications of Andrographolide Targeting New Potential Anticancer Drug Candidates: A Comprehensive Overview
by Gatien Messire, Patrick Rollin, Isabelle Gillaizeau and Sabine Berteina-Raboin
Molecules 2024, 29(12), 2884; https://doi.org/10.3390/molecules29122884 (registering DOI) - 18 Jun 2024
Abstract
This review collects the synthetic modifications performed on andrographolide, a natural molecule derived from Andrographis paniculata, for oncology applications. Various pharmacomodulations were carried out, and the products were tested on different cancer cell lines. The impact of these modifications was analyzed with [...] Read more.
This review collects the synthetic modifications performed on andrographolide, a natural molecule derived from Andrographis paniculata, for oncology applications. Various pharmacomodulations were carried out, and the products were tested on different cancer cell lines. The impact of these modifications was analyzed with the aim of mapping the positions essential for activity to facilitate future research in this field. However, this study makes it clear that, in addition to structural modifications of the molecule, which can result in varying degrees of effectiveness in targeting interactions, the lipophilic capacity of the structures obtained through hemisynthesis is of significant importance. Full article
(This article belongs to the Special Issue Featured Reviews in Organic Chemistry 2024)
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15 pages, 2141 KiB  
Article
Structural, Biophysical, and Computational Studies of a Murine Light Chain Dimer
by Ricardo H. Arriaza, A. Brenda Kapingidza, Coleman Dolamore, Kriti Khatri, Andrea O’Malley, Jill Glesner, Sabina Wuenschmann, Noah P. Hyduke, William Easley, Charline Chhiv, Anna Pomés and Maksymilian Chruszcz
Molecules 2024, 29(12), 2885; https://doi.org/10.3390/molecules29122885 (registering DOI) - 18 Jun 2024
Abstract
Antibodies are widely used in medicinal and scientific research due to their ability to bind to a specific antigen. Most often, antibodies are composed of heavy and light chain domains. Under physiological conditions, light chains are produced in excess, as compared to the [...] Read more.
Antibodies are widely used in medicinal and scientific research due to their ability to bind to a specific antigen. Most often, antibodies are composed of heavy and light chain domains. Under physiological conditions, light chains are produced in excess, as compared to the heavy chain. It is now known that light chains are not silent partners of the heavy chain and can modulate the immune response independently. In this work, the first crystal structure of a light chain dimer originating from mice is described. It represents the light chain dimer of 6A8, a monoclonal antibody specific to the allergen Der f 1. Building on the unexpected occurrence of this kind of dimer, we have demonstrated that this light chain is stable in solution alone. Moreover, enzyme-linked immunosorbent assays (ELISA) have revealed that, when the light chain is not partnered to its corresponding heavy chain, it interacts non-specifically with a wide range of proteins. Computational studies were used to provide insight on the role of the 6A8 heavy chain domain in the specific binding to Der f 1. Overall, this work demonstrates and supports the ongoing notion that light chains can function by themselves and are not silent partners of heavy chains. Full article
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26 pages, 2421 KiB  
Review
Overcoming Treatment Resistance in Medulloblastoma: Underlying Mechanisms and Potential Strategies
by Hasan Slika, Aanya Shahani, Riddhpreet Wahi, Jackson Miller, Mari Groves and Betty Tyler
Cancers 2024, 16(12), 2249; https://doi.org/10.3390/cancers16122249 (registering DOI) - 18 Jun 2024
Abstract
Medulloblastoma is the most frequently encountered malignant brain tumor in the pediatric population. The standard of care currently consists of surgical resection, craniospinal irradiation, and multi-agent chemotherapy. However, despite this combination of multiple aggressive modalities, recurrence of the disease remains a substantial concern, [...] Read more.
Medulloblastoma is the most frequently encountered malignant brain tumor in the pediatric population. The standard of care currently consists of surgical resection, craniospinal irradiation, and multi-agent chemotherapy. However, despite this combination of multiple aggressive modalities, recurrence of the disease remains a substantial concern, and treatment resistance is a rising issue. The development of this resistance results from the interplay of a myriad of anatomical properties, cellular processes, molecular pathways, and genetic and epigenetic alterations. In fact, several efforts have been directed towards this domain and characterizing the major contributors to this resistance. Herein, this review highlights the different mechanisms that drive relapse and are implicated in the occurrence of treatment resistance and discusses them in the context of the latest molecular-based classification of medulloblastoma. These mechanisms include the impermeability of the blood-brain barrier to drugs, the overactivation of specific molecular pathways, the resistant and multipotent nature of cancer stem cells, intratumoral and intertumoral heterogeneity, and metabolic plasticity. Subsequently, we build on that to explore potential strategies and targeted agents that can abrogate these mechanisms, undermine the development of treatment resistance, and augment medulloblastoma’s response to therapeutic modalities. Full article
(This article belongs to the Special Issue Molecular Insights into Drug Resistance in Cancer)
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15 pages, 1698 KiB  
Article
Flow Properties of Coarse Powders Used in Food Extrusion as a Function of Moisture Content
by Cameron McGuire, Kaliramesh Siliveru, Snehasis Chakraborty, Kingsly Ambrose and Sajid Alavi
Processes 2024, 12(6), 1246; https://doi.org/10.3390/pr12061246 (registering DOI) - 18 Jun 2024
Abstract
The extrusion processing of food powder relies heavily on its moisture content to aid in flow and proper cooking, shaping, and/or puffing. This study focused on the impact of the moisture content on the dynamic flow and shear properties of coarse food powders [...] Read more.
The extrusion processing of food powder relies heavily on its moisture content to aid in flow and proper cooking, shaping, and/or puffing. This study focused on the impact of the moisture content on the dynamic flow and shear properties of coarse food powders (corn meal, wheat farina, and granulated sugar). The dynamic flow properties explored were the specific basic flowability energy (SBFE), specific energy, stability index, and flow rate index. The shear properties were the angle of internal friction, unconfined yield strength, major principal stress, wall friction angle, flow factor (FF), and compressibility. Corn meal exhibited an increase in SBFE as the moisture content increased (6.70 mJ/g at 13.13% to 9.14 mJ/g at 19.61%) but no change in FF (4.94 to 5.11); wheat farina also showed an increase in energy requirement as the moisture increased (5.81 mJ/g at 13.73% to 9.47 mJ/g 19.57%) but a marked decrease in FF ratings (18.47 to 6.1); granulated sugar showed a decrease in energy requirements as the moisture increased (51.73 mJ/g at 0.06% moisture content to 13.58 mJ/g at 0.78% moisture content) and a decrease in FF ratings (8.53 to 3.47). Overall, upon the addition of moisture, corn meal became cohesive yet free-flowing; wheat farina became less compressible and more cohesive; and granulated sugar became more cohesive and compressible and less free-flowing. Full article
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14 pages, 2564 KiB  
Article
CBP/P300 Inhibition Impairs CD4+ T Cell Activation: Implications for Autoimmune Disorders
by Lucas Wilhelmus Picavet, Anoushka A. K. Samat, Jorg Calis, Lotte Nijhuis, Rianne Scholman, Michal Mokry, David F. Tough, Rabinder K. Prinjha, Sebastiaan J. Vastert and Jorg van Loosdregt
Biomedicines 2024, 12(6), 1344; https://doi.org/10.3390/biomedicines12061344 (registering DOI) - 18 Jun 2024
Abstract
T cell activation is critical for an effective immune response against pathogens. However, dysregulation contributes to the pathogenesis of autoimmune diseases, including Juvenile Idiopathic Arthritis (JIA). The molecular mechanisms underlying T cell activation are still incompletely understood. T cell activation promotes the acetylation [...] Read more.
T cell activation is critical for an effective immune response against pathogens. However, dysregulation contributes to the pathogenesis of autoimmune diseases, including Juvenile Idiopathic Arthritis (JIA). The molecular mechanisms underlying T cell activation are still incompletely understood. T cell activation promotes the acetylation of histone 3 at Lysine 27 (H3K27ac) at enhancer and promoter regions of proinflammatory cytokines, thereby increasing the expression of these genes which is essential for T cell function. Co-activators E1A binding protein P300 (P300) and CREB binding protein (CBP), collectively known as P300/CBP, are essential to facilitate H3K27 acetylation. Presently, the role of P300/CBP in human CD4+ T cells activation remains incompletely understood. To assess the function of P300/CBP in T cell activation and autoimmune disease, we utilized iCBP112, a selective inhibitor of P300/CBP, in T cells obtained from healthy controls and JIA patients. Treatment with iCBP112 suppressed T cell activation and cytokine signaling pathways, leading to reduced expression of many proinflammatory cytokines, including IL-2, IFN-γ, IL-4, and IL-17A. Moreover, P300/CBP inhibition in T cells derived from the inflamed synovium of JIA patients resulted in decreased expression of similar pathways and preferentially suppressed the expression of disease-associated genes. This study underscores the regulatory role of P300/CBP in regulating gene expression during T cell activation while offering potential insights into the pathogenesis of autoimmune diseases. Our findings indicate that P300/CBP inhibition could potentially be leveraged for the treatment of autoimmune diseases such as JIA in the future. Full article
(This article belongs to the Special Issue Epigenetic Regulation and Its Impact for Medicine)
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13 pages, 1015 KiB  
Article
Nutritional Behavior of Patients with Bone Diseases: A Cross-Sectional Study from Austria
by Daniel A. Kraus, Amadea Medibach, Martina Behanova, Annemarie Kocijan, Judith Haschka, Jochen Zwerina and Roland Kocijan
Nutrients 2024, 16(12), 1920; https://doi.org/10.3390/nu16121920 (registering DOI) - 18 Jun 2024
Abstract
Background: A balanced diet rich in calcium and protein is recommended for bone-healthy people and osteoporosis patients, but it may also be important for rare bone disease (RBD). Little data is available on RBD and diet. Therefore, the aim of this study was [...] Read more.
Background: A balanced diet rich in calcium and protein is recommended for bone-healthy people and osteoporosis patients, but it may also be important for rare bone disease (RBD). Little data is available on RBD and diet. Therefore, the aim of this study was to evaluate the nutritional behavior of patients with RBD. Methods: This single-center, cross-sectional, questionnaire-based study assessed the nutritional behavior of RBD patients (X-linked hypophosphatemia (XLH), osteogenesis imperfecta (OI), hypophosphatasia (HPP)), osteoporosis (OPO) patients and healthy controls (CTRL). The nutritional questionnaire comprised 25 questions from seven nutritional areas. The associations between socioeconomic factors and BMI were assessed by age-adjusted univariate analysis of covariance (ANCOVA). Results: Fifty patients with RBD (17 OI, 17 HPP, 16 XLH; mean age of 48.8 ± 15.9, 26.0% male, mean BMI 26.2 ± 5.6), 51 with OPO (mean age 66.6 ± 10.0, 9.8% male, mean BMI 24.2 ± 3.9) and 52 CTRL (mean age 50.8 ± 16.3, 26.9% male, mean BMI 26.4 ± 4.7) participated. Twenty-six (52.0%) RBD, 17 (33.4%) OPO and 24 (46.1%) CTRL were overweight or obese according to BMI. Only a minority of RBD, OPO and CTRL had a daily intake of at least three portions of milk or milk products (17.3% RBD, 15.6% OPO, 11.6% CTRL, p = 0.453). In general, similar nutritional behavior was observed between the three subgroups. However, significant differences were found in caffeine consumption (p = 0.016), fruit/vegetable juice consumption (p = 0.034), portions of fish per week (p = 0.044), high-fat meals per week (p = 0.015) and consumption of salty snacks (p = 0.001). Conclusion: Nutritional counseling, controlling BMI and ensuring sufficient calcium and protein intake are crucial in patients with osteoporosis as well as in rare bone diseases. Vitamin D does not appear to be sufficiently supplied by the diet, and therefore supplementation should be considered in patients with bone diseases. Full article
(This article belongs to the Special Issue Vitamin D Deficiency and Supplementation in Human Metabolic Diseases)
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13 pages, 873 KiB  
Article
Hemogram-Derived Inflammatory Markers in Cats with Chronic Kidney Disease
by Martina Krofič Žel, Alenka Nemec Svete, Nataša Tozon and Darja Pavlin
Animals 2024, 14(12), 1813; https://doi.org/10.3390/ani14121813 (registering DOI) - 18 Jun 2024
Abstract
Chronic kidney disease (CKD) is characterized by chronic inflammation, which mediates the progressive replacement of functional nephrons by fibrotic tissue. Hemogram-derived inflammatory markers are known to serve as markers of pathological conditions; however, their diagnostic value in feline CKD is still unknown. The [...] Read more.
Chronic kidney disease (CKD) is characterized by chronic inflammation, which mediates the progressive replacement of functional nephrons by fibrotic tissue. Hemogram-derived inflammatory markers are known to serve as markers of pathological conditions; however, their diagnostic value in feline CKD is still unknown. The aim of this retrospective study was to investigate selected hemogram-derived inflammatory markers (neutrophil-to-lymphocyte ratio (NLR), monocyte-to-lymphocyte ratio (MLR), platelet-to-lymphocyte ratio (PLR) and the systemic immune-inflammatory index (SII)) in cats at different clinical stages of CKD. Eighty-eight client-owned cats with CKD and thirty-two healthy control cats were included. Cats with CKD were divided into two groups: early CKD (IRIS stage 1 and 2; 62 cats) and progressed CKD (IRIS stage 3 and 4; 26 cats). The values of inflammatory markers were compared between the two CKD groups and the control group. All investigated hemogram-derived inflammatory markers were significantly (p < 0.05) greater in cats with advanced CKD than in those in the other two groups. Additionally, we demonstrated a statistically significant weak to moderate correlation between serum urea, creatinine, selected hematologic and urinary parameters, and the investigated inflammatory markers in cats with CKD. Chronic inflammation can be easily and inexpensively assessed with hemogram-derived markers. Full article
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13 pages, 9510 KiB  
Article
Potentials of Polyacrylonitrile Substitution by Lignin for Continuous Manufactured Lignin/Polyacrylonitrile-Blend-Based Carbon Fibers
by Daniel Sebastian Jens Wolz, Robert Seidel-Greiff, Thomas Behnisch, Iris Kruppke, Irina Kuznik, Paul Bertram, Hubert Jäger, Maik Gude and Chokri Cherif
Fibers 2024, 12(6), 50; https://doi.org/10.3390/fib12060050 (registering DOI) - 18 Jun 2024
Abstract
While carbon fibers (CFs) are still the most attractive reinforcement material for lightweight structures, they are mostly manufactured using crude oil-based process chains. To achieve a higher eco-efficiency, the partial substitution of polyacrylonitrile (PAN) by renewable materials, such as lignin, is investigated. So [...] Read more.
While carbon fibers (CFs) are still the most attractive reinforcement material for lightweight structures, they are mostly manufactured using crude oil-based process chains. To achieve a higher eco-efficiency, the partial substitution of polyacrylonitrile (PAN) by renewable materials, such as lignin, is investigated. So far, this investigation has only been carried out for batch manufacturing studies, neglecting the transfer and validation to continuous CF manufacturing. Therefore, this work is the first to investigate the possibility of partial substituting lignin for PAN in a continuous process. Lignin/PAN-blended CFs with up to 15 wt.-% lignin were able to attain mechanical properties comparable to unmodified PAN-based carbon fibers, achieving tensile strengths of up to 2466 MPa and a Young’s Modulus of 200 Pa. In summary, this study provides the basis for continuous Lignin/PAN-blended CF manufacturing. Full article
(This article belongs to the Special Issue Carbon Fibers from Sustainable Precursors II)
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13 pages, 4553 KiB  
Article
A Radiomic Approach for Evaluating Intra-Subgroup Heterogeneity in SHH and Group 4 Pediatric Medulloblastoma: A Preliminary Multi-Institutional Study
by Marwa Ismail, Hyemin Um, Ralph Salloum, Fauzia Hollnagel, Raheel Ahmed, Peter de Blank and Pallavi Tiwari
Cancers 2024, 16(12), 2248; https://doi.org/10.3390/cancers16122248 (registering DOI) - 18 Jun 2024
Abstract
Medulloblastoma (MB) is the most frequent malignant brain tumor in children with extensive heterogeneity that results in varied clinical outcomes. Recently, MB was categorized into four molecular subgroups, WNT, SHH, Group 3, and Group 4. While SHH and Group 4 are known for [...] Read more.
Medulloblastoma (MB) is the most frequent malignant brain tumor in children with extensive heterogeneity that results in varied clinical outcomes. Recently, MB was categorized into four molecular subgroups, WNT, SHH, Group 3, and Group 4. While SHH and Group 4 are known for their intermediate prognosis, studies have reported wide disparities in patient outcomes within these subgroups. This study aims to create a radiomic prognostic signature, medulloblastoma radiomics risk (mRRisk), to identify the risk levels within the SHH and Group 4 subgroups, individually, for reliable risk stratification. Our hypothesis is that this signature can comprehensively capture tumor characteristics that enable the accurate identification of the risk level. In total, 70 MB studies (48 Group 4, and 22 SHH) were retrospectively curated from three institutions. For each subgroup, 232 hand-crafted features that capture the entropy, surface changes, and contour characteristics of the tumor were extracted. Features were concatenated and fed into regression models for risk stratification. Contrasted with Chang stratification that did not yield any significant differences within subgroups, significant differences were observed between two risk groups in Group 4 (p = 0.04, Concordance Index (CI) = 0.82) on the cystic core and non-enhancing tumor, and SHH (p = 0.03, CI = 0.74) on the enhancing tumor. Our results indicate that radiomics may serve as a prognostic tool for refining MB risk stratification, towards improved patient care. Full article
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