1,553 results
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2. Ciprofloxacin-, Cefazolin-, and Methicilin-Soaked Graphene Paper as an Antibacterial Medium Suppressing Cell Growth
- Author
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Barbara Nasiłowska, Aneta Bombalska, Marta Kutwin, Agata Lange, Sławomir Jaworski, Kamila Narojczyk, Klaudia Olkowicz, and Zdzisław Bogdanowicz
- Subjects
graphene oxide ,graphene paper ,ciprofloxacin ,cefazolin ,Staphylococcus aureus ,Pseudomonas aeruginosa ,Biology (General) ,QH301-705.5 ,Chemistry ,QD1-999 - Abstract
This paper presents the results of research on the impact of graphene paper on selected bacterial strains. Graphene oxide, from which graphene paper is made, has mainly bacteriostatic properties. Therefore, the main goal of this research was to determine the possibility of using graphene paper as a carrier of a medicinal substance. Studies of the degree of bacterial inhibition were performed on Staphylococcus aureus and Pseudomonas aeruginosa strains. Graphene paper was analyzed not only in the state of delivery but also after the incorporation of the antibiotics ciprofloxacin, cefazolin, and methicillin into its structures. In addition, Fourier-Transform Infrared Spectroscopy, contact angle, and microscopic analysis of bacteria on the surface of the examined graphene paper samples were also performed. Studies have shown that graphene paper with built-in ciprofloxacin had a bactericidal effect on the strains of Staphylococcus aureus and Pseudomonas aeruginosa. In contrast, methicillin, as well as cefazolin, deposited on graphene paper acted mainly locally. Studies have shown that graphene paper can be used as a carrier of selected medicinal substances.
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- 2024
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3. Ciprofloxacin-, Cefazolin-, and Methicilin-Soaked Graphene Paper as an Antibacterial Medium Suppressing Cell Growth.
- Author
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Nasiłowska B, Bombalska A, Kutwin M, Lange A, Jaworski S, Narojczyk K, Olkowicz K, and Bogdanowicz Z
- Subjects
- Humans, Cefazolin pharmacology, Ciprofloxacin pharmacology, Methicillin pharmacology, Anti-Bacterial Agents pharmacology, Staphylococcus aureus, Bacteria, Microbial Sensitivity Tests, Pseudomonas aeruginosa, Graphite pharmacology, Staphylococcal Infections, Pseudomonas Infections
- Abstract
This paper presents the results of research on the impact of graphene paper on selected bacterial strains. Graphene oxide, from which graphene paper is made, has mainly bacteriostatic properties. Therefore, the main goal of this research was to determine the possibility of using graphene paper as a carrier of a medicinal substance. Studies of the degree of bacterial inhibition were performed on Staphylococcus aureus and Pseudomonas aeruginosa strains. Graphene paper was analyzed not only in the state of delivery but also after the incorporation of the antibiotics ciprofloxacin, cefazolin, and methicillin into its structures. In addition, Fourier-Transform Infrared Spectroscopy, contact angle, and microscopic analysis of bacteria on the surface of the examined graphene paper samples were also performed. Studies have shown that graphene paper with built-in ciprofloxacin had a bactericidal effect on the strains of Staphylococcus aureus and Pseudomonas aeruginosa . In contrast, methicillin, as well as cefazolin, deposited on graphene paper acted mainly locally. Studies have shown that graphene paper can be used as a carrier of selected medicinal substances.
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- 2024
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4. Editorial for the Special Issue 'Latest Review Papers in Molecular Oncology 2023'
- Author
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Carmine Stolfi
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n/a ,Biology (General) ,QH301-705.5 ,Chemistry ,QD1-999 - Abstract
Human cancers are products of multistep processes resulting in abnormal cell growth and differentiation, along with a loss of apoptotic function, leading to the uncontrolled expansion of neoplastic cells and their spread to surrounding tissues and, ultimately, distant parts of the body [...]
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- 2024
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5. Special Issue "The Molecular and Cellular Pathophysiologic Mechanisms Underlying Ocular Diseases and Emerging Therapies".
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Kaštelan, Snježana
- Subjects
VISION disorders ,GENE expression ,ANDROGEN receptors ,EYE diseases ,THERAPEUTICS - Abstract
This document is a summary of a special issue of the International Journal of Molecular Sciences titled "The Molecular and Cellular Pathophysiologic Mechanisms Underlying Ocular Diseases and Emerging Therapies." The special issue focuses on the prevalence and rising global public health concerns of visual impairment and ophthalmic diseases. It aims to enhance researchers' and eyecare professionals' understanding of the risk factors, biomarkers, and cellular and molecular mechanisms underlying various eye diseases. The special issue includes eight papers, including original research papers, reviews, and a case report, covering topics such as diabetic retinopathy, retinal diseases, tear biomarkers, and uveal melanoma. The papers provide new advancements in the molecular and cellular pathogenesis of eye diseases and the development of preventive measures and emerging therapies. The document concludes by expressing hope that the special issue will inspire further research and understanding of eye diseases. [Extracted from the article]
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- 2024
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6. Circulating microRNAs in Cancer: A 5-Year Update with a Focus on Breast and Lung Cancers.
- Author
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Siniscalco, Dario, Galderisi, Umberto, Peluso, Gianfranco, and Finicelli, Mauro
- Subjects
LUNG cancer ,BREAST cancer ,MICRORNA ,CANCER research ,NON-coding RNA ,CIRCULAR RNA - Abstract
Circulating microRNAs (c-miRNAs) are non-coding RNAs found in different bodily fluids and are highly investigated for their prognostic potential and biological role in cancer. In this narrative review, we provide an update of the last five years' published papers (2018–2023) on PubMed about c-miRNAs in cancer research. We aim to capture the latest research interests in terms of the highly studied cancers and the insights about c-miRNAs. Our analysis revealed that more than 150 papers focusing on c-miRNAs and cancer were published in the last five years. Among these, there was a high prevalence of papers on breast cancer (BC) and lung cancer (LC), which are estimated to be the most diagnosed cancers globally. Thus, we focus on the main evidence and research trends about c-miRNAs in BC and LC. We report evidence of the effectiveness of c-miRNAs in hot topics of cancer research, such as, early detection, therapeutic resistance, recurrence risk and novel detection platform approaches. Moreover, we look at the deregulated c-miRNAs shared among BC and LC papers, focusing on miR-21 and miR-145. Overall, these data clearly indicate that the role of c-miRNAs in cancer is still a hot topic for oncologic research and that blood is the most investigated matrix. [ABSTRACT FROM AUTHOR]
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- 2024
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7. Special Issue "Neurogenetics in Neurology".
- Author
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Orlacchio, Antonio
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NEUROGENETICS ,NEUROLOGICAL disorders ,NEUROLOGY ,MOLECULAR genetics ,ANIMAL cognition ,ALZHEIMER'S disease ,FRAGILE X syndrome - Abstract
This document is a summary of a special issue titled "Neurogenetics in Neurology" from the International Journal of Molecular Sciences. The issue includes six papers that highlight advancements in molecular genetics and genomics and their impact on human health. The papers cover various topics, such as the molecular mechanisms underlying genetics-based diseases affecting the nervous system, brain calcification as a symptom of systemic and genetic conditions, glioblastoma multiforme metabolism, the role of the survival motor neuron protein in spinal muscular atrophy, the involvement of microRNA-30c in neurological disorders, and the use of long-range interaction maps to identify candidate genes for neurodevelopmental disorders. Overall, the papers contribute to our understanding of molecular genetics and genomics and provide opportunities for further research in the field. [Extracted from the article]
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- 2024
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8. Functional Genomics for Plant Breeding 3.0.
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Maghuly, Fatemeh and Cruz-Rubio, José Manuel
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FUNCTIONAL genomics ,PLANT breeding ,PHYSIOLOGY ,SUSTAINABLE agriculture ,SINGLE nucleotide polymorphisms - Abstract
The article discusses the impact of functional genomics on plant breeding. Functional genomics, with its advancements in genomics and omics technologies, has provided a deeper understanding of the molecular mechanisms governing plant traits and their responses to environmental conditions. This integration has allowed breeders to make informed decisions and develop improved crop varieties with enhanced characteristics. The intersection of functional genomics and plant breeding has also contributed to increased crop yields, sustainability, and resilience in the face of climate change. The article highlights several research papers that explore the intricacies of functional genomics and its relevance to enhancing plant breeding programs. These papers provide valuable insights into various aspects of plant growth, development, photosynthesis, genetic variations, and gene families, ultimately contributing to global food security and sustainability. [Extracted from the article]
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- 2024
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9. Targeting Group 3 Medulloblastoma by the Anti-PRUNE-1 and Anti-LSD1/KDM1A Epigenetic Molecules.
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Bibbò, Francesca, Asadzadeh, Fatemeh, Boccia, Angelo, Sorice, Carmen, Bianco, Orazio, Saccà, Carmen Daniela, Majello, Barbara, Donofrio, Vittoria, Bifano, Delfina, De Martino, Lucia, Quaglietta, Lucia, Cristofano, Adriana, Covelli, Eugenio Maria, Cinalli, Giuseppe, Ferrucci, Veronica, De Antonellis, Pasqualino, and Zollo, Massimo
- Subjects
GLIAL fibrillary acidic protein ,CADHERINS ,MEDULLOBLASTOMA ,SMALL molecules ,EPIGENETICS ,MOLECULES - Abstract
Medulloblastoma (MB) is a highly malignant childhood brain tumor. Group 3 MB (Gr3 MB) is considered to have the most metastatic potential, and tailored therapies for Gr3 MB are currently lacking. Gr3 MB is driven by PRUNE-1 amplification or overexpression. In this paper, we found that PRUNE-1 was transcriptionally regulated by lysine demethylase LSD1/KDM1A. This study aimed to investigate the therapeutic potential of inhibiting both PRUNE-1 and LSD1/KDM1A with the selective inhibitors AA7.1 and SP-2577, respectively. We found that the pharmacological inhibition had a substantial efficacy on targeting the metastatic axis driven by PRUNE-1 (PRUNE-1-OTX2-TGFβ-PTEN) in Gr3 MB. Using RNA seq transcriptomic feature data in Gr3 MB primary cells, we provide evidence that the combination of AA7.1 and SP-2577 positively affects neuronal commitment, confirmed by glial fibrillary acidic protein (GFAP)-positive differentiation and the inhibition of the cytotoxic components of the tumor microenvironment and the epithelial–mesenchymal transition (EMT) by the down-regulation of N-Cadherin protein expression. We also identified an impairing action on the mitochondrial metabolism and, consequently, oxidative phosphorylation, thus depriving tumors cells of an important source of energy. Furthermore, by overlapping the genomic mutational signatures through WES sequence analyses with RNA seq transcriptomic feature data, we propose in this paper that the combination of these two small molecules can be used in a second-line treatment in advanced therapeutics against Gr3 MB. Our study demonstrates that the usage of PRUNE-1 and LSD1/KDM1A inhibitors in combination represents a novel therapeutic approach for these highly aggressive metastatic MB tumors. [ABSTRACT FROM AUTHOR]
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- 2024
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10. Special Issue "Dietary Bioactive Components in Inflammatory Bowel Disease".
- Author
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Gasparrini, Massimiliano and Mazzoni, Luca
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INFLAMMATORY bowel diseases ,BIOACTIVE compounds ,MICROBIAL metabolites ,OATS ,BETA-glucans ,BODY composition ,CROHN'S disease ,DEVELOPING countries - Abstract
This document is a summary of a special issue in the International Journal of Molecular Sciences titled "Dietary Bioactive Components in Inflammatory Bowel Disease." The special issue explores the potential of dietary bioactive compounds, particularly those found in fruits and vegetables, for the prevention and management of inflammatory bowel diseases (IBD). The issue includes seven papers, consisting of five research articles and two reviews, which investigate the effects of various dietary components on IBD, including Crohn's disease, ulcerative colitis, and colorectal cancer. The studies highlight the complex interactions between dietary bioactive compounds, gut microbiota, and immune responses in the context of IBD, and suggest that these compounds may have therapeutic potential in managing the disease. [Extracted from the article]
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- 2024
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11. Corneal Epithelial Changes in Diabetic Patients: A Review.
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Ladea, Lidia, Zemba, Mihail, Calancea, Maria Ioana, Călțaru, Mihai Valeriu, Dragosloveanu, Christiana Diana Maria, Coroleucă, Ruxandra, Catrina, Eduard Lucian, Brezean, Iulian, and Dinu, Valentin
- Subjects
CORNEA ,PEOPLE with diabetes ,DRY eye syndromes ,PROTEOLYTIC enzymes ,HYPERGLYCEMIA ,WOUND healing - Abstract
The relationship between diabetes mellitus and ocular complications has been extensively studied by many authors. Diabetic keratopathy has already been well characterized and defined as a clinical entity. This review focuses on exploring corneal epithelial changes in diabetic patients, aiming to provide a pragmatic overview of the existing knowledge on this topic. The paper systematically examines alterations in corneal epithelial structure and their impact on diabetic patients. Advanced imaging techniques are also discussed for their role in precise characterization and improved diagnostics. Additionally, the paper explores the mechanisms behind corneal epithelial changes in diabetes, looking at factors such as hyperglycemia, oxidative stress, and Advanced Glycation End-Products. The impact of altered corneal epithelial integrity on barrier function and susceptibility to external issues is considered, addressing potential links to heightened proteolytic enzyme activities and delayed wound healing observed in diabetic individuals. The review also covers the practical implications of corneal epithelial changes, including the association with corneal erosions, persistent epithelial defects, and an increased risk of dry eye syndrome in diabetic patients. [ABSTRACT FROM AUTHOR]
- Published
- 2024
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12. An Insight into Fluorinated Imines and Hydrazones as Antibacterial Agents.
- Author
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Sztanke, Małgorzata, Wilk, Agata, and Sztanke, Krzysztof
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ANTIBACTERIAL agents ,IMINES ,SMALL molecules ,TECHNICAL reports ,PHARMACEUTICAL chemistry ,HYDRAZONES - Abstract
Fluorinated imines (Schiff bases) and fluorinated hydrazones are of particular interest in medicinal chemistry due to their potential usefulness in treating opportunistic strains of bacteria that are resistant to commonly used antibacterial agents. The present review paper is focused on these fluorinated molecules revealing strong, moderate or weak in vitro antibacterial activities, which have been reported in the scientific papers during the last fifteen years. Fluorinated building blocks and reaction conditions used for the synthesis of imines and hydrazones are mentioned. The structural modifications, which have an influence on the antibacterial activity in all the reported classes of fluorinated small molecules, are highlighted, focusing mainly on the importance of specific substitutions. Advanced research techniques and innovations for the synthesis, design and development of fluorinated imines and hydrazones are also summarized. [ABSTRACT FROM AUTHOR]
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- 2024
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13. Unseen Weapons: Bacterial Extracellular Vesicles and the Spread of Antibiotic Resistance in Aquatic Environments.
- Author
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Barathan, Muttiah, Ng, Sook-Luan, Lokanathan, Yogeswaran, Ng, Min Hwei, and Law, Jia Xian
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EXTRACELLULAR vesicles ,DRUG resistance in bacteria ,SUSTAINABILITY ,HORIZONTAL gene transfer ,SUSTAINABLE aquaculture ,BIOFILMS ,ECOSYSTEMS - Abstract
This paper sheds light on the alarming issue of antibiotic resistance (ABR) in aquatic environments, exploring its detrimental effects on ecosystems and public health. It examines the multifaceted role of antibiotic use in aquaculture, agricultural runoff, and industrial waste in fostering the development and dissemination of resistant bacteria. The intricate interplay between various environmental factors, horizontal gene transfer, and bacterial extracellular vesicles (BEVs) in accelerating the spread of ABR is comprehensively discussed. Various BEVs carrying resistance genes like blaCTX-M, tetA, floR, and sul/I, as well as their contribution to the dominance of multidrug-resistant bacteria, are highlighted. The potential of BEVs as both a threat and a tool in combating ABR is explored, with promising strategies like targeted antimicrobial delivery systems and probiotic-derived EVs holding significant promise. This paper underscores the urgency of understanding the intricate interplay between BEVs and ABR in aquatic environments. By unraveling these unseen weapons, we pave the way for developing effective strategies to mitigate the spread of ABR, advocating for a multidisciplinary approach that includes stringent regulations, enhanced wastewater treatment, and the adoption of sustainable practices in aquaculture. [ABSTRACT FROM AUTHOR]
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- 2024
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14. Gene Expression Studies in Down Syndrome: What Do They Tell Us about Disease Phenotypes?
- Author
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Chapman, Laura R., Ramnarine, Isabela V. P., Zemke, Dan, Majid, Arshad, and Bell, Simon M.
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GENE expression ,DOWN syndrome ,PHENOTYPES ,AMNIOTIC liquid ,MYELOPROLIFERATIVE neoplasms ,FETAL development - Abstract
Down syndrome is a well-studied aneuploidy condition in humans, which is associated with various disease phenotypes including cardiovascular, neurological, haematological and immunological disease processes. This review paper aims to discuss the research conducted on gene expression studies during fetal development. A descriptive review was conducted, encompassing all papers published on the PubMed database between September 1960 and September 2022. We found that in amniotic fluid, certain genes such as COL6A1 and DSCR1 were found to be affected, resulting in phenotypical craniofacial changes. Additionally, other genes such as GSTT1, CLIC6, ITGB2, C21orf67, C21orf86 and RUNX1 were also identified to be affected in the amniotic fluid. In the placenta, dysregulation of genes like MEST, SNF1LK and LOX was observed, which in turn affected nervous system development. In the brain, dysregulation of genes DYRK1A, DNMT3L, DNMT3B, TBX1, olig2 and AQP4 has been shown to contribute to intellectual disability. In the cardiac tissues, dysregulated expression of genes GART, ETS2 and ERG was found to cause abnormalities. Furthermore, dysregulation of XIST, RUNX1, SON, ERG and STAT1 was observed, contributing to myeloproliferative disorders. Understanding the differential expression of genes provides insights into the genetic consequences of DS. A better understanding of these processes could potentially pave the way for the development of genetic and pharmacological therapies. [ABSTRACT FROM AUTHOR]
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- 2024
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15. Curcumin in Cancer and Inflammation: An In-Depth Exploration of Molecular Interactions, Therapeutic Potentials, and the Role in Disease Management.
- Author
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Moon, Dong-Oh
- Subjects
CURCUMIN ,MOLECULAR interactions ,DISEASE management ,CANCER cell proliferation ,TURMERIC ,MOLECULAR structure - Abstract
This paper delves into the diverse and significant roles of curcumin, a polyphenolic compound from the Curcuma longa plant, in the context of cancer and inflammatory diseases. Distinguished by its unique molecular structure, curcumin exhibits potent biological activities including anti-inflammatory, antioxidant, and potential anticancer effects. The research comprehensively investigates curcumin's molecular interactions with key proteins involved in cancer progression and the inflammatory response, primarily through molecular docking studies. In cancer, curcumin's effectiveness is determined by examining its interaction with pivotal proteins like CDK2, CK2α, GSK3β, DYRK2, and EGFR, among others. These interactions suggest curcumin's potential role in impeding cancer cell proliferation and survival. Additionally, the paper highlights curcumin's impact on inflammation by examining its influence on proteins such as COX-2, CRP, PDE4, and MD-2, which are central to the inflammatory pathway. In vitro and clinical studies are extensively reviewed, shedding light on curcumin's binding mechanisms, pharmacological impacts, and therapeutic application in various cancers and inflammatory conditions. These studies are pivotal in understanding curcumin's functionality and its potential as a therapeutic agent. Conclusively, this review emphasizes the therapeutic promise of curcumin in treating a wide range of health issues, attributed to its complex chemistry and broad pharmacological properties. The research points towards curcumin's growing importance as a multi-faceted natural compound in the medical and scientific community. [ABSTRACT FROM AUTHOR]
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- 2024
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16. Metabolic Signatures: Pioneering the Frontier of Rectal Cancer Diagnosis and Response to Neoadjuvant Treatment with Biomarkers—A Systematic Review.
- Author
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Ciocan, Răzvan Alexandru, Ciocan, Andra, Mihăileanu, Florin Vasile, Ursu, Cristina-Paula, Ursu, Ștefan, Bodea, Cătălin, Cordoș, Ariana-Anamaria, Chiș, Bogdan Augustin, Al Hajjar, Nadim, Dîrzu, Noemi, and Dîrzu, Dan-Sebastian
- Subjects
RECTAL cancer ,NEOADJUVANT chemotherapy ,CANCER diagnosis ,BIOMARKERS ,COLORECTAL cancer ,SURVIVAL analysis (Biometry) ,INSTRUMENTAL variables (Statistics) - Abstract
Colorectal cancer (CRC) is one of the most aggressive, heterogenous, and fatal types of human cancer for which screening, and more effective therapeutic drugs are urgently needed. Early-stage detection and treatment greatly improve the 5-year survival rate. In the era of targeted therapies for all types of cancer, a complete metabolomic profile is mandatory before neoadjuvant therapy to assign the correct drugs and check the response to the treatment given. The aim of this study is to discover specific metabolic biomarkers or a sequence of metabolomic indicators that possess precise diagnostic capabilities in predicting the efficacy of neoadjuvant therapy. After searching the keywords, a total of 108 articles were identified during a timeframe of 10 years (2013–2023). Within this set, one article was excluded due to the use of non-English language. Six scientific papers were qualified for this investigation after eliminating all duplicates, publications not referring to the subject matter, open access restriction papers, and those not applicable to humans. Biomolecular analysis found a correlation between metabolomic analysis of colorectal cancer samples and poor progression-free survival rates. Biomarkers are instrumental in predicting a patient's response to specific treatments, guiding the selection of targeted therapies, and indicating resistance to certain drugs. [ABSTRACT FROM AUTHOR]
- Published
- 2024
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17. Gene Expression-Based Cancer Classification for Handling the Class Imbalance Problem and Curse of Dimensionality.
- Author
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Al-Azani, Sadam, Alkhnbashi, Omer S., Ramadan, Emad, and Alfarraj, Motaz
- Subjects
TUMOR classification ,CANCER genes ,MICROARRAY technology ,GENE expression ,RANDOM forest algorithms ,FEATURE selection ,CAUSE of death statistics - Abstract
Cancer is a leading cause of death globally. The majority of cancer cases are only diagnosed in the late stages of cancer due to the use of conventional methods. This reduces the chance of survival for cancer patients. Therefore, early detection consequently followed by early diagnoses are important tasks in cancer research. Gene expression microarray technology has been applied to detect and diagnose most types of cancers in their early stages and has gained encouraging results. In this paper, we address the problem of classifying cancer based on gene expression for handling the class imbalance problem and the curse of dimensionality. The oversampling technique is utilized to overcome this problem by adding synthetic samples. Another common issue related to the gene expression dataset addressed in this paper is the curse of dimensionality. This problem is addressed by applying chi-square and information gain feature selection techniques. After applying these techniques individually, we proposed a method to select the most significant genes by combining those two techniques (CHiS and IG). We investigated the effect of these techniques individually and in combination. Four benchmarking biomedical datasets (Leukemia-subtypes, Leukemia-ALLAML, Colon, and CuMiDa) were used. The experimental results reveal that the oversampling techniques improve the results in most cases. Additionally, the performance of the proposed feature selection technique outperforms individual techniques in nearly all cases. In addition, this study provides an empirical study for evaluating several oversampling techniques along with ensemble-based learning. The experimental results also reveal that SVM-SMOTE, along with the random forests classifier, achieved the highest results, with a reporting accuracy of 100%. The obtained results surpass the findings in the existing literature as well. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
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18. Elevated Arterial Blood Pressure as a Delayed Complication Following COVID-19—A Narrative Review.
- Author
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Bielecka, Emilia, Sielatycki, Piotr, Pietraszko, Paulina, Zapora-Kurel, Agnieszka, and Zbroch, Edyta
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BLOOD pressure ,COVID-19 ,POST-acute COVID-19 syndrome ,CARDIOVASCULAR diseases risk factors ,ENDOTHELIUM diseases ,RENIN-angiotensin system ,ENDOTHELIUM - Abstract
Arterial hypertension is one of the most common and significant cardiovascular risk factors. There are many well-known and identified risk factors for its development. In recent times, there has been growing concern about the potential impact of COVID-19 on the cardiovascular system and its relation to arterial hypertension. Various theories have been developed that suggest a connection between COVID-19 and elevated blood pressure. However, the precise link between SARS-CoV-2 infection and the long-term risk of developing hypertension remains insufficiently explored. Therefore, the primary objective of our study was to investigate the influence of COVID-19 infection on blood pressure elevation and the subsequent risk of developing arterial hypertension over an extended period. To accomplish this, we conducted a thorough search review of relevant papers in the PubMed and SCOPUS databases up to 3 September 2023. Our analysis encompassed a total of 30 eligible articles. Out of the 30 papers we reviewed, 19 of them provided substantial evidence showing a heightened risk of developing arterial hypertension following COVID-19 infection. Eight of the studies showed that blood pressure values increased after the infection, while three of the qualified studies did not report any notable impact of COVID-19 on blood pressure levels. The precise mechanism behind the development of hypertension after COVID-19 remains unclear, but it is suggested that endothelial injury and dysfunction of the renin–angiotensin–aldosterone system may be contributory. Additionally, changes in blood pressure following COVID-19 infection could be linked to lifestyle alterations that often occur alongside the illness. Our findings emphasize the pressing requirement for thorough research into the relationship between COVID-19 and hypertension. These insights are essential for the development of effective prevention and management approaches for individuals who have experienced COVID-19 infection. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
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19. Molecular Research on Heart Protection.
- Author
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Abdelwahid, Eltyeb and de Carvalho, Katherine Athayde Teixeira
- Subjects
CARDIAC research ,CYTOLOGY ,ARRHYTHMIA ,CELLULAR aging - Abstract
This document is an editorial from the International Journal of Molecular Sciences titled "Molecular Research on Heart Protection." It discusses recent advancements in molecular research on heart protection and their potential impact on diagnosing and treating heart injuries and disorders. The editorial presents original research papers and reviews that explore molecular mechanisms and therapeutic opportunities for heart protection. The studies mentioned in the editorial include investigations on chronic anthracycline-induced cardiomyopathy, genetically modified mesenchymal stem cells for cardiac tissue restoration, the effects of sEVs on cell proliferation and angiogenesis, the role of Nr1d1 in cellular senescence and cardiac aging, the effects of MSC injection on post-infarction arrhythmia, the association between obesity, exercise, and cardiovascular problems, modRNA-based therapy for myocardial infarction, and the protective effect of young blood on mammalian organs. The editorial concludes by emphasizing the importance of integrating emerging molecular events with known networks to improve cardiac function and advance diagnostic and treatment strategies. [Extracted from the article]
- Published
- 2024
- Full Text
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20. Special Issue: "Inflammatory Signaling Pathways Involved in Gastrointestinal Diseases".
- Author
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Lauricella, Marianna and Di Liberto, Diana
- Subjects
GASTROINTESTINAL diseases ,CELLULAR signal transduction ,INFLAMMATORY bowel diseases ,CROHN'S disease ,THERAPEUTICS ,HISTAMINE receptors - Abstract
This document is a special issue of the International Journal of Molecular Sciences titled "Inflammatory Signaling Pathways Involved in Gastrointestinal Diseases." It contains six papers, including two research articles and four reviews, that explore the role of inflammation in gastrointestinal diseases and potential therapeutic strategies. The papers discuss topics such as chronic inflammation in Inflammatory Bowel Disease (IBD), the role of heat shock proteins and histamine in IBD, the use of polyphenols as anti-inflammatory agents, the potential of miR-369-3p as a therapeutic approach for IBD, the relationship between gut disorders and immune system deregulation, and the pathogenesis of Barrett's esophagus. The authors express gratitude to the contributors and declare no conflicts of interest. [Extracted from the article]
- Published
- 2024
- Full Text
- View/download PDF
21. Abscisic Acid Affects Phenolic Acid Content to Increase Tolerance to UV-B Stress in Rhododendron chrysanthum Pall.
- Author
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Zhou, Xiangru, Gong, Fushuai, Dong, Jiawei, Lin, Xiaoru, Cao, Kun, Xu, Hongwei, and Zhou, Xiaofu
- Subjects
ABSCISIC acid ,RADIATION tolerance ,PHENOLIC acids ,OZONE layer depletion ,HYDROXYCINNAMIC acids ,RHODODENDRONS ,ULTRAVIOLET radiation ,ALPINE regions - Abstract
The presence of the ozone hole increases the amount of UV radiation reaching a plant's surface, and UV-B radiation is an abiotic stress capable of affecting plant growth. Rhododendron chrysanthum Pall. (R. chrysanthum) grows in alpine regions, where strong UV-B radiation is present, and has been able to adapt to strong UV-B radiation over a long period of evolution. We investigated the response of R. chrysanthum leaves to UV-B radiation using widely targeted metabolomics and transcriptomics. Although phytohormones have been studied for many years in plant growth and development and adaptation to environmental stresses, this paper is innovative in terms of the species studied and the methods used. Using unique species and the latest research methods, this paper was able to add information to this topic for the species R. chrysanthum. We treated R. chrysanthum grown in a simulated alpine environment, with group M receiving no UV-B radiation and groups N and Q (externally applied abscisic acid treatment) receiving UV-B radiation for 2 days (8 h per day). The results of the MN group showed significant changes in phenolic acid accumulation and differential expression of genes related to phenolic acid synthesis in leaves of R. chrysanthum after UV-B radiation. We combined transcriptomics and metabolomics data to map the metabolic regulatory network of phenolic acids under UV-B stress in order to investigate the response of such secondary metabolites to stress. L-phenylalanine, L-tyrosine and phenylpyruvic acid contents in R. chrysanthum were significantly increased after UV-B radiation. Simultaneously, the levels of 3-hydroxyphenylacetic acid, 2-phenylethanol, anthranilate, 2-hydroxycinnamic acid, 3-hydroxycinnamic acid, α-hydroxycinnamic acid and 2-hydroxy-3-phenylpropanoic acid in this pathway were elevated in response to UV-B stress. In contrast, the study in the NQ group found that externally applied abscisic acid (ABA) in R. chrysanthum had greater tolerance to UV-B radiation, and phenolic acid accumulation under the influence of ABA also showed greater differences. The contents of 2-phenylethanol, 1-o-p-coumaroyl-β-d-glucose, 2-hydroxy-3-phenylpropanoic acid, 3-(4-hydroxyphenyl)-propionic acid and 3-o-feruloylquinic ac-id-o-glucoside were significantly elevated in R. chrysanthum after external application of ABA to protect against UV-B stress. Taken together, these studies of the three groups indicated that ABA can influence phenolic acid production to promote the response of R. chrysanthum to UV-B stress, which provided a theoretical reference for the study of its complex molecular regulatory mechanism. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
22. Effect of THz Waves of Different Orientations on K + Permeation Efficiency in the KcsA Channel.
- Author
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Wang, Yize, Wang, Hongguang, Ding, Wen, Zhao, Xiaofei, Li, Yongdong, and Liu, Chunliang
- Subjects
POTASSIUM channels ,ION channels ,DIHEDRAL angles ,CHANNEL flow ,FREQUENCY stability ,ELECTRIC fields - Abstract
Potassium (K) channels show the highest variability and most frequent alterations in expression in many tumor types, and modulation of K
+ channels may represent a new window for cancer therapy. In previous work, we found that a terahertz (THz) field incident along the z-axis with a frequency of 51.87 THz increased the ion flux through K+ channels. In practice, it is difficult to ensure that the incident electromagnetic (EM) wave is strictly parallel to the direction of channel ion flow. In this paper, we found by changing the direction of the applied electric field that the EM wave of a specific frequency has the largest ion flux when the incident direction is along the ion flow, and the smallest ion flux when the incident direction is perpendicular to the ion flow, and that overall the EM wave of this frequency enhances the ion flow of the K+ channel. Changes in the direction of the applied field at a specific frequency affect the stability of the φ dihedral angle of the GLY77 residue and alter the ion permeation mechanism in the selectivity filter (SF) region, thus affecting the ion flux. Therefore, this frequency can be used to modulate K+ fluxes by THz waves to cause rapid apoptosis in potassium-overloaded tumor cells. This approach consequently represents an important tool for the treatment of cancer and is expected to be applied in practical therapy. [ABSTRACT FROM AUTHOR]- Published
- 2024
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23. Kaempferol as an Alternative Cryosupplement for Bovine Spermatozoa: Cytoprotective and Membrane-Stabilizing Effects.
- Author
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Baňas, Štefan, Tvrdá, Eva, Benko, Filip, Ďuračka, Michal, Čmiková, Natália, Lukáč, Norbert, and Kačániová, Miroslava
- Subjects
FROZEN semen ,PROTEIN kinase C ,SPERMATOZOA ,WESTERN immunoblotting ,FREEZE-thaw cycles ,REACTIVE oxygen species ,FLAVONOIDS ,CYTOCHROME c - Abstract
Kaempferol (KAE) is a natural flavonoid with powerful reactive oxygen species (ROS) scavenging properties and beneficial effects on ex vivo sperm functionality. In this paper, we studied the ability of KAE to prevent or ameliorate structural, functional or oxidative damage to frozen–thawed bovine spermatozoa. The analysis focused on conventional sperm quality characteristics prior to or following thermoresistance tests, namely the oxidative profile of semen alongside sperm capacitation patterns, and the levels of key proteins involved in capacitation signaling. Semen samples obtained from 30 stud bulls were frozen in the presence of 12.5, 25 or 50 μM KAE and compared to native ejaculates (negative control—Ctrl
N ) as well as semen samples cryopreserved in the absence of KAE (positive control—CtrlC ). A significant post-thermoresistance test maintenance of the sperm motility (p < 0.001), membrane (p < 0.001) and acrosome integrity (p < 0.001), mitochondrial activity (p < 0.001) and DNA integrity (p < 0.001) was observed following supplementation with all KAE doses in comparison to CtrlC . Experimental groups supplemented with all KAE doses presented a significantly lower proportion of prematurely capacitated spermatozoa (p < 0.001) when compared with CtrlC . A significant decrease in the levels of the superoxide radical was recorded following administration of 12.5 (p < 0.05) and 25 μM KAE (p < 0.01). At the same time, supplementation with 25 μM KAE in the cryopreservation medium led to a significant stabilization of the activity of Mg2+ -ATPase (p < 0.05) and Na+ /K+ -ATPase (p < 0.0001) in comparison to CtrlC . Western blot analysis revealed that supplementation with 25 μM KAE in the cryopreservation medium prevented the loss of the protein kinase A (PKA) and protein kinase C (PKC), which are intricately involved in the process of sperm activation. In conclusion, we may speculate that KAE is particularly efficient in the protection of sperm metabolism during the cryopreservation process through its ability to promote energy synthesis while quenching excessive ROS and to protect enzymes involved in the process of sperm capacitation and hyperactivation. These properties may provide supplementary protection to spermatozoa undergoing the freeze–thaw process. [ABSTRACT FROM AUTHOR]- Published
- 2024
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24. Roles of Integrin in Cardiovascular Diseases: From Basic Research to Clinical Implications.
- Author
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Zhang, Shuo, Zhang, Qingfang, Lu, Yutong, Chen, Jianrui, Liu, Jinkai, Li, Zhuohan, and Xie, Zhenzhen
- Subjects
CARDIOVASCULAR diseases ,ARRHYTHMIA ,MEDICAL research ,VASCULAR smooth muscle ,INTEGRINS ,MUSCLE cells ,BLOOD platelet aggregation ,HEART fibrosis - Abstract
Cardiovascular diseases (CVDs) pose a significant global health threat due to their complex pathogenesis and high incidence, imposing a substantial burden on global healthcare systems. Integrins, a group of heterodimers consisting of α and β subunits that are located on the cell membrane, have emerged as key players in mediating the occurrence and progression of CVDs by regulating the physiological activities of endothelial cells, vascular smooth muscle cells, platelets, fibroblasts, cardiomyocytes, and various immune cells. The crucial role of integrins in the progression of CVDs has valuable implications for targeted therapies. In this context, the development and application of various integrin antibodies and antagonists have been explored for antiplatelet therapy and anti-inflammatory-mediated tissue damage. Additionally, the rise of nanomedicine has enhanced the specificity and bioavailability of precision therapy targeting integrins. Nevertheless, the complexity of the pathogenesis of CVDs presents tremendous challenges for monoclonal targeted treatment. This paper reviews the mechanisms of integrins in the development of atherosclerosis, cardiac fibrosis, hypertension, and arrhythmias, which may pave the way for future innovations in the diagnosis and treatment of CVDs. [ABSTRACT FROM AUTHOR]
- Published
- 2024
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25. Human Vault RNAs: Exploring Their Potential Role in Cellular Metabolism.
- Author
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Taube, Magdalena, Lisiak, Natalia, Totoń, Ewa, and Rubiś, Błażej
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RNA metabolism ,NON-coding RNA ,AUTOPHAGY ,RNA ,GENE expression ,CELL metabolism ,REGULATOR genes ,METABOLISM - Abstract
Non-coding RNAs have been described as crucial regulators of gene expression and guards of cellular homeostasis. Some recent papers focused on vault RNAs, one of the classes of non-coding RNA, and their role in cell proliferation, tumorigenesis, apoptosis, cancer response to therapy, and autophagy, which makes them potential therapy targets in oncology. In the human genome, four vault RNA paralogues can be distinguished. They are associated with vault complexes, considered the largest ribonucleoprotein complexes. The protein part of these complexes consists of a major vault protein (MVP) and two minor vault proteins (vPARP and TEP1). The name of the complex, as well as vault RNA, comes from the hollow barrel-shaped structure that resembles a vault. Their sequence and structure are highly evolutionarily conserved and show many similarities in comparison with different species, but vault RNAs have various roles. Vaults were discovered in 1986, and their functions remained unclear for many years. Although not much is known about their contribution to cell metabolism, it has become clear that vault RNAs are involved in various processes and pathways associated with cancer progression and modulating cell functioning in normal and pathological stages. In this review, we discuss known functions of human vault RNAs in the context of cellular metabolism, emphasizing processes related to cancer and cancer therapy efficacy. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
26. Optimizing Neural Networks for Chemical Reaction Prediction: Insights from Methylene Blue Reduction Reactions.
- Author
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Malashin, Ivan, Tynchenko, Vadim, Gantimurov, Andrei, Nelyub, Vladimir, and Borodulin, Aleksei
- Subjects
METHYLENE blue ,CHEMICAL reactions ,MACHINE learning ,DRUG design ,VITAMIN C ,FORECASTING - Abstract
This paper offers a thorough investigation of hyperparameter tuning for neural network architectures using datasets encompassing various combinations of Methylene Blue (MB) Reduction by Ascorbic Acid (AA) reactions with different solvents and concentrations. The aim is to predict coefficients of decay plots for MB absorbance, shedding light on the complex dynamics of chemical reactions. Our findings reveal that the optimal model, determined through our investigation, consists of five hidden layers, each with sixteen neurons and employing the Swish activation function. This model yields an NMSE of 0.05, 0.03, and 0.04 for predicting the coefficients A, B, and C, respectively, in the exponential decay equation A + B · e
−x/C . These findings contribute to the realm of drug design based on machine learning, providing valuable insights into optimizing chemical reaction predictions. [ABSTRACT FROM AUTHOR]- Published
- 2024
- Full Text
- View/download PDF
27. Advancements in Regenerative Hydrogels in Skin Wound Treatment: A Comprehensive Review.
- Author
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Olteanu, Gabriel, Neacșu, Sorinel Marius, Joița, Florin Alexandru, Musuc, Adina Magdalena, Lupu, Elena Carmen, Ioniță-Mîndrican, Corina-Bianca, Lupuliasa, Dumitru, and Mititelu, Magdalena
- Subjects
SKIN regeneration ,HYDROGELS ,REGENERATION (Biology) ,WOUND healing ,CONTROLLED release drugs ,SKIN injuries - Abstract
This state-of-the-art review explores the emerging field of regenerative hydrogels and their profound impact on the treatment of skin wounds. Regenerative hydrogels, composed mainly of water-absorbing polymers, have garnered attention in wound healing, particularly for skin wounds. Their unique properties make them well suited for tissue regeneration. Notable benefits include excellent water retention, creating a crucially moist wound environment for optimal healing, and facilitating cell migration, and proliferation. Biocompatibility is a key feature, minimizing adverse reactions and promoting the natural healing process. Acting as a supportive scaffold for cell growth, hydrogels mimic the extracellular matrix, aiding the attachment and proliferation of cells like fibroblasts and keratinocytes. Engineered for controlled drug release, hydrogels enhance wound healing by promoting angiogenesis, reducing inflammation, and preventing infection. The demonstrated acceleration of the wound healing process, particularly beneficial for chronic or impaired healing wounds, adds to their appeal. Easy application and conformity to various wound shapes make hydrogels practical, including in irregular or challenging areas. Scar minimization through tissue regeneration is crucial, especially in cosmetic and functional regions. Hydrogels contribute to pain management by creating a protective barrier, reducing friction, and fostering a soothing environment. Some hydrogels, with inherent antimicrobial properties, aid in infection prevention, which is a crucial aspect of successful wound healing. Their flexibility and ability to conform to wound contours ensure optimal tissue contact, enhancing overall treatment effectiveness. In summary, regenerative hydrogels present a promising approach for improving skin wound healing outcomes across diverse clinical scenarios. This review provides a comprehensive analysis of the benefits, mechanisms, and challenges associated with the use of regenerative hydrogels in the treatment of skin wounds. In this review, the authors likely delve into the application of rational design principles to enhance the efficacy and performance of hydrogels in promoting wound healing. Through an exploration of various methodologies and approaches, this paper is poised to highlight how these principles have been instrumental in refining the design of hydrogels, potentially revolutionizing their therapeutic potential in addressing skin wounds. By synthesizing current knowledge and highlighting potential avenues for future research, this review aims to contribute to the advancement of regenerative medicine and ultimately improve clinical outcomes for patients with skin wounds. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
28. What Is the "Hydrogen Bond"? A QFT-QED Perspective.
- Author
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Renati, Paolo and Madl, Pierre
- Subjects
HYDROGEN bonding ,QUANTUM field theory ,CONDENSED matter ,ELECTROMAGNETIC fields ,SYMMETRY breaking ,GEOMETRIC quantization ,SEMICLASSICAL limits - Abstract
In this paper we would like to highlight the problems of conceiving the "Hydrogen Bond" (HB) as a real short-range, directional, electrostatic, attractive interaction and to reframe its nature through the non-approximated view of condensed matter offered by a Quantum Electro-Dynamic (QED) perspective. We focus our attention on water, as the paramount case to show the effectiveness of this 40-year-old theoretical background, which represents water as a two-fluid system (where one of the two phases is coherent). The HB turns out to be the result of the electromagnetic field gradient in the coherent phase of water, whose vacuum level is lower than in the non-coherent (gas-like) fraction. In this way, the HB can be properly considered, i.e., no longer as a "dipolar force" between molecules, but as the phenomenological effect of their collective thermodynamic tendency to occupy a lower ground state, compatible with temperature and pressure. This perspective allows to explain many "anomalous" behaviours of water and to understand why the calculated energy associated with the HB should change when considering two molecules (water-dimer), or the liquid state, or the different types of ice. The appearance of a condensed, liquid, phase at room temperature is indeed the consequence of the boson condensation as described in the context of spontaneous symmetry breaking (SSB). For a more realistic and authentic description of water, condensed matter and living systems, the transition from a still semi-classical Quantum Mechanical (QM) view in the first quantization to a Quantum Field Theory (QFT) view embedded in the second quantization is advocated. [ABSTRACT FROM AUTHOR]
- Published
- 2024
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29. Assessing Animal Models to Study Impaired and Chronic Wounds.
- Author
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Saeed, Shayan and Martins-Green, Manuela
- Subjects
WOUND healing ,CHRONIC wounds & injuries ,ANIMAL models in research ,MICE ,OXIDATIVE stress ,HEALING ,DRUG approval - Abstract
Impaired healing wounds do not proceed through the normal healing processes in a timely and orderly manner, and while they do eventually heal, their healing is not optimal. Chronic wounds, on the other hand, remain unhealed for weeks or months. In the US alone, chronic wounds impact ~8.5 million people and cost ~USD 28–90 billion per year, not accounting for the psychological and physical pain and emotional suffering that patients endure. These numbers are only expected to rise in the future as the elderly populations and the incidence of comorbidities such as diabetes, hypertension, and obesity increase. Over the last few decades, scientists have used a variety of approaches to treat chronic wounds, but unfortunately, to date, there is no effective treatment. Indeed, while there are thousands of drugs to combat cancer, there is only one single drug approved for the treatment of chronic wounds. This is in part because wound healing is a very complex process involving many phases that must occur sequentially and in a timely manner. Furthermore, models that fully mimic human chronic wounds have not been developed. In this review, we assess various models currently being used to study the biology of impaired healing and chronic non-healing wounds. Among them, this paper also highlights one model which shows significant promise; this model uses aged and obese db/db
−/− mice and the chronic wounds that develop show characteristics of human chronic wounds that include increased oxidative stress, chronic inflammation, damaged microvasculature, abnormal collagen matrix deposition, a lack of re-epithelialization, and the spontaneous development of multi-bacterial biofilm. We also discuss how important it is that we continue to develop chronic wound models that more closely mimic those of humans and that can be used to test potential treatments to heal chronic wounds. [ABSTRACT FROM AUTHOR]- Published
- 2024
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- View/download PDF
30. Zinc, Copper, and Iron in Selected Skin Diseases.
- Author
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Podgórska, Aleksandra, Kicman, Aleksandra, Naliwajko, Sylwia, Wacewicz-Muczyńska, Marta, and Niczyporuk, Marek
- Subjects
SKIN diseases ,COPPER ,SEBORRHEIC dermatitis ,TRACE elements ,ACNE ,IRON ,ZINC ,HOMEOSTASIS - Abstract
Trace elements are essential for maintaining the body's homeostasis, and their special role has been demonstrated in skin physiology. Among the most important trace elements are zinc, copper, and iron. A deficiency or excess of trace elements can be associated with an increased risk of skin diseases, so increasing their supplementation or limiting intake can be helpful in dermatological treatment. In addition, determinations of their levels in various types of biological material can be useful as additional tests in dermatological treatment. This paper describes the role of these elements in skin physiology and summarizes data on zinc, copper, and iron in the course of selected, following skin diseases: psoriasis, pemphigus vulgaris, atopic dermatitis, acne vulgaris and seborrheic dermatitis. In addition, this work identifies the potential of trace elements as auxiliary tests in dermatology. According to preliminary studies, abnormal levels of zinc, copper, and iron are observed in many skin diseases and their determinations in serum or hair can be used as auxiliary and prognostic tests in the course of various dermatoses. However, since data for some conditions are conflicting, clearly defining the potential of trace elements as auxiliary tests or elements requiring restriction/supplement requires further research. [ABSTRACT FROM AUTHOR]
- Published
- 2024
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- View/download PDF
31. Studying the Effects and Competitive Mechanisms of YOYO-1 on the Binding Characteristics of DOX and DNA Molecules Based on Surface-Enhanced Raman Spectroscopy and Molecular Docking Techniques.
- Author
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Li, Yanjie, Li, Zhiwei, Yun, Penglun, Sun, Dan, Niu, Yong, Yao, Baoli, and Wang, Kaige
- Subjects
MOLECULAR spectroscopy ,MOLECULAR docking ,MOLECULES ,PHARMACEUTICAL chemistry ,PHYSICAL biochemistry ,SERS spectroscopy - Abstract
Revealing the interaction mechanisms between anticancer drugs and target DNA molecules at the single-molecule level is a hot research topic in the interdisciplinary fields of biophysical chemistry and pharmaceutical engineering. When fluorescence imaging technology is employed to carry out this kind of research, a knotty problem due to fluorescent dye molecules and drug molecules acting on a DNA molecule simultaneously is encountered. In this paper, based on self-made novel solid active substrates NpAA/(ZnO-ZnCl
2 )/AuNPs, we use a surface-enhanced Raman spectroscopy method, inverted fluorescence microscope technology, and a molecular docking method to investigate the action of the fluorescent dye YOYO-1 and the drug DOX on calf thymus DNA (ctDNA) molecules and the influencing effects and competitive relationships of YOYO-1 on the binding properties of the ctDNA-DOX complex. The interaction sites and modes of action between the YOYO-1 and the ctDNA-DOX complex are systematically examined, and the DOX with the ctDNA-YOYO-1 are compared, and the impact of YOYO-1 on the stability of the ctDNA-DOX complex and the competitive mechanism between DOX and YOYO-1 acting with DNA molecules are elucidated. This study has helpful experimental guidance and a theoretical foundation to expound the mechanism of interaction between drugs and biomolecules at the single-molecule level. [ABSTRACT FROM AUTHOR]- Published
- 2024
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32. Triple Generative Self-Supervised Learning Method for Molecular Property Prediction.
- Author
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Xu, Lei, Xia, Leiming, Pan, Shourun, and Li, Zhen
- Subjects
RECURRENT neural networks ,SUPERVISED learning ,DRUG discovery ,FEATURE extraction ,MOLECULAR graphs ,TRANSFORMER models - Abstract
Molecular property prediction is an important task in drug discovery, and with help of self-supervised learning methods, the performance of molecular property prediction could be improved by utilizing large-scale unlabeled dataset. In this paper, we propose a triple generative self-supervised learning method for molecular property prediction, called TGSS. Three encoders including a bi-directional long short-term memory recurrent neural network (BiLSTM), a Transformer, and a graph attention network (GAT) are used in pre-training the model using molecular sequence and graph structure data to extract molecular features. The variational auto encoder (VAE) is used for reconstructing features from the three models. In the downstream task, in order to balance the information between different molecular features, a feature fusion module is added to assign different weights to each feature. In addition, to improve the interpretability of the model, atomic similarity heat maps were introduced to demonstrate the effectiveness and rationality of molecular feature extraction. We demonstrate the accuracy of the proposed method on chemical and biological benchmark datasets by comparative experiments. [ABSTRACT FROM AUTHOR]
- Published
- 2024
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- View/download PDF
33. Regulation Mechanism and Potential Value of Active Substances in Spices in Alcohol–Liver–Intestine Axis Health.
- Author
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Huang, Jianyu, Huang, Tao, and Li, Jinjun
- Subjects
MICROBIAL metabolites ,SPICES ,INTESTINAL diseases ,MICROBIAL cells ,LIPID metabolism ,MICROBIAL communities ,ODORS - Abstract
Excessive alcohol intake will aggravate the health risk between the liver and intestine and affect the multi-directional information exchange of metabolites between host cells and microbial communities. Because of the side effects of clinical drugs, people tend to explore the intervention value of natural drugs on diseases. As a flavor substance, spices have been proven to have medicinal value, but they are still rare in treating hepatointestinal diseases caused by alcohol. This paper summarized the metabolic transformation of alcohol in the liver and intestine and summarized the potential value of various perfume active substances in improving liver and intestine diseases caused by alcohol. It is also found that bioactive substances in spices can exert antioxidant activity in the liver and intestine environment and reduce the oxidative stress caused by diseases. These substances can interfere with fatty acid synthesis, promote sugar and lipid metabolism, and reduce liver injury caused by steatosis. They can effectively regulate the balance of intestinal flora, promote the production of SCFAs, and restore the intestinal microenvironment. [ABSTRACT FROM AUTHOR]
- Published
- 2024
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- View/download PDF
34. Oxidative Stress Markers and Histopathological Changes in Selected Organs of Mice Infected with Murine Norovirus 1 (MNV-1).
- Author
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Janicka, Paulina, Stygar, Dominika, Chełmecka, Elżbieta, Kuropka, Piotr, Miążek, Arkadiusz, Studzińska, Aleksandra, Pogorzelska, Aleksandra, Pala, Katarzyna, and Bażanów, Barbara
- Subjects
OXIDATIVE stress ,NOROVIRUS diseases ,NOROVIRUSES ,GLUTATHIONE reductase ,LUNGS ,HISTOPATHOLOGY - Abstract
This paper describes the effects of murine norovirus (MNV) infection on oxidative stress and histopathological changes in mice. This study uses histopathological assays, enzymatic and non-enzymatic antioxidant markers, and total oxidative status and capacity (TOS, TAC). The results suggest that MNV infection can lead to significant changes with respect to the above-mentioned parameters in various organs. Specifically, reduced superoxide dismutase (SOD), Mn superoxide dismutase (MnSOD), catalase (CAT), and glutathione reductase (GR) activities were observed in liver tissues, while higher MnSOD activity was observed in kidney tissues of MNV-infected mice when compared to the control. GR activity was lower in all tissues of MNV-infected mice tested, with the exception of lung tissue. This study also showed that norovirus infection led to increased TOS levels in the brain and liver and TAC levels in the brain, while TOS levels were significantly reduced in the kidneys. These changes may be due to the production of reactive oxygen species (ROS) caused by the viral infection. ROS can damage cells and contribute to oxidative stress. These studies help us to understand the pathogenesis of MNV infection and its potential effects on oxidative stress and histopathological changes in mice, and pave the way for further studies of the long-term effects of MNV infection. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
35. On the Possible Effect of Phytic Acid (Myo-Inositol Hexaphosphoric Acid, IP6) on Cytochromes P450 and Systems of Xenobiotic Metabolism in Different Hepatic Models.
- Author
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Frybortova, Veronika, Satka, Stefan, Jourova, Lenka, Zapletalova, Iveta, Srejber, Martin, Briolotti, Philippe, Daujat-Chavanieu, Martine, Gerbal-Chaloin, Sabine, Anzenbacher, Pavel, Otyepka, Michal, and Anzenbacherova, Eva
- Subjects
PHYTIC acid ,CYTOCHROMES ,XENOBIOTICS ,CYTOCHROME P-450 ,LIVER microsomes ,CYTOCHROME c ,PREGNANE X receptor - Abstract
As compounds of natural origin enter human body, it is necessary to investigate their possible interactions with the metabolism of drugs and xenobiotics in general, namely with the cytochrome P450 (CYP) system. Phytic acid (myo-inositol hexaphosphoric acid, IP6) is mainly present in plants but is also an endogenous compound present in mammalian cells and tissues. It has been shown to exhibit protective effect in many pathological conditions. For this paper, its interaction with CYPs was studied using human liver microsomes, primary human hepatocytes, the HepG2 cell line, and molecular docking. Docking experiments and absorption spectra demonstrated the weak ability of IP6 to interact in the heme active site of CYP1A. Molecular docking suggested that IP6 preferentially binds to the protein surface, whereas binding to the active site of CYP1A2 was found to be less probable. Subsequently, we investigated the ability of IP6 to modulate the metabolism of xenobiotics for both the mRNA expression and enzymatic activity of CYP1A enzymes. Our findings revealed that IP6 can slightly modulate the mRNA levels and enzyme activity of CYP1A. However, thanks to the relatively weak interactions of IP6 with CYPs, the chances of the mechanisms of clinically important drug–drug interactions involving IP6 are low. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
36. Exploring Cyclodextrin-Based Nanosponges as Drug Delivery Systems: Understanding the Physicochemical Factors Influencing Drug Loading and Release Kinetics.
- Author
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Pyrak, Bartłomiej, Rogacka-Pyrak, Karolina, Gubica, Tomasz, and Szeleszczuk, Łukasz
- Subjects
DRUG delivery systems ,DRUG delivery devices ,CYCLODEXTRINS - Abstract
Cyclodextrin-based nanosponges (CDNSs) are complex macromolecular structures composed of individual cyclodextrins (CDs) and nanochannels created between cross-linked CD units and cross-linkers. Due to their unique structural and physicochemical properties, CDNSs can possess even more beneficial pharmaceutical features than single CDs. In this comprehensive review, various aspects related to CDNSs are summarized. Particular attention was paid to overviewing structural properties, methods of synthesis, and physicochemical analysis of CDNSs using various analytical methods, such as DLS, PXRD, TGA, DSC, FT-IR, NMR, and phase solubility studies. Also, due to the significant role of CDNSs in pharmaceutical research and industry, aspects such as drug loading, drug release studies, and kinetics profile evaluation of drug–CDNS complexes were carefully reviewed. The aim of this paper is to find the relationships between the physicochemical features and to identify crucial characteristics that are influential for using CDNSs as convenient drug delivery systems. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
37. Advances in the Study of Extracellular Vesicles for Bone Regeneration.
- Author
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Jiao, Yao, Liu, Yitong, Du, Juan, Xu, Junji, Luo, Zhenhua, Liu, Yi, and Guo, Lijia
- Subjects
BONE regeneration ,EXTRACELLULAR vesicles ,BONE diseases ,CELLULAR therapy ,IMMUNE response ,REGENERATION (Biology) - Abstract
Promoting the efficiency of bone regeneration in bone loss diseases is a significant clinical challenge. Traditional therapies often fail to achieve better therapeutic outcomes and shorter treatment times. However, in recent years, extracellular vesicles (EVs) have gained significant attention due to their exceptional osteogenic function in bone regeneration and superior therapeutic effects compared to traditional cell therapy. EVs have emerged as a promising therapy for tissue defect regeneration due to their various physiological functions, such as regulating the immune response and promoting tissue repair and regeneration. Moreover, EVs have good biocompatibility, low immunogenicity, and long-term stability, and can be improved through pretreatment and other methods. Studies investigating the mechanisms by which extracellular vesicles promote bone regeneration and applying EVs from different sources using various methods to animal models of bone defects have increased. Therefore, this paper reviews the types of EVs used for bone regeneration, their sources, roles, delivery pathways, scaffold biomaterials, and applications. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
38. Targeting KRAS G12C Mutation in Colorectal Cancer, A Review: New Arrows in the Quiver.
- Author
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Ros, Javier, Vaghi, Caterina, Baraibar, Iosune, Saoudi González, Nadia, Rodríguez-Castells, Marta, García, Ariadna, Alcaraz, Adriana, Salva, Francesc, Tabernero, Josep, and Elez, Elena
- Subjects
RAS oncogenes ,COLORECTAL cancer ,CETUXIMAB ,PROTEIN-tyrosine kinases ,GENE fusion ,CANCER patient care - Abstract
Kirsten rat sarcoma virus oncogene homolog (KRAS) is the most frequently mutated oncogene in human cancer. In colorectal cancer (CRC), KRAS mutations are present in more than 50% of cases, and the KRAS glycine-to-cysteine mutation at codon 12 (KRAS G12C) occurs in up to 4% of patients. This mutation is associated with short responses to standard chemotherapy and worse overall survival compared to non-G12C mutations. In recent years, several KRAS G12C inhibitors have demonstrated clinical activity, although all patients eventually progressed. The identification of negative feedback through the EGFR receptor has led to the development of KRAS inhibitors plus an anti-EGFR combination, thus boosting antitumor activity. Currently, several KRAS G12C inhibitors are under development, and results from phase I and phase II clinical trials are promising. Moreover, the phase III CodeBreaK 300 trial demonstrates the superiority of sotorasib-panitumumab over trifluridine/tipiracil, establishing a new standard of care for patients with colorectal cancer harboring KRAS G12C mutations. Other combinations such as adagrasib-cetuximab, divarasib-cetuximab, or FOLFIRI-panitumumab-sotorasib have also shown a meaningful response rate and are currently under evaluation. Nonetheless, most of these patients will eventually relapse. In this setting, liquid biopsy emerges as a critical tool to characterize the mechanisms of resistance, consisting mainly of acquired genomic alterations in the MAPK and PI3K pathways and tyrosine kinase receptor alterations, but gene fusions, histological changes, or conformational changes in the kinase have also been described. In this paper, we review the development of KRAS G12C inhibitors in colorectal cancer as well as the main mechanisms of resistance. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
39. Overcoming the Low-Stability Bottleneck in the Clinical Translation of Liposomal Pressurized Metered-Dose Inhalers: A Shell Stabilization Strategy Inspired by Biomineralization.
- Author
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Huang, Yeqi, Chang, Ziyao, Gao, Yue, Ren, Chuanyu, Lin, Yuxin, Zhang, Xuejuan, Wu, Chuanbin, Pan, Xin, and Huang, Zhengwei
- Subjects
METERED-dose inhalers ,BIOMINERALIZATION ,FUNCTIONAL groups ,PATIENT compliance ,LIPOSOMES - Abstract
Currently, several types of inhalable liposomes have been developed. Among them, liposomal pressurized metered-dose inhalers (pMDIs) have gained much attention due to their cost-effectiveness, patient compliance, and accurate dosages. However, the clinical application of liposomal pMDIs has been hindered by the low stability, i.e., the tendency of the aggregation of the liposome lipid bilayer in hydrophobic propellant medium and brittleness under high mechanical forces. Biomineralization is an evolutionary mechanism that organisms use to resist harsh external environments in nature, providing mechanical support and protection effects. Inspired by such a concept, this paper proposes a shell stabilization strategy (SSS) to solve the problem of the low stability of liposomal pMDIs. Depending on the shell material used, the SSS can be classified into biomineralization (biomineralized using calcium, silicon, manganese, titanium, gadolinium, etc.) biomineralization-like (composite with protein), and layer-by-layer (LbL) assembly (multiple shells structured with diverse materials). This work evaluated the potential of this strategy by reviewing studies on the formation of shells deposited on liposomes or similar structures. It also covered useful synthesis strategies and active molecules/functional groups for modification. We aimed to put forward new insights to promote the stability of liposomal pMDIs and shed some light on the clinical translation of relevant products. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
40. Molecular Basis for the Involvement of Mammalian Serum Albumin in the AGE/RAGE Axis: A Comprehensive Computational Study.
- Author
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Belinskaia, Daria A., Jenkins, Richard O., and Goncharov, Nikolay V.
- Subjects
RECEPTOR for advanced glycation end products (RAGE) ,SERUM albumin ,ADVANCED glycation end-products ,MOLECULAR structure ,MOLECULAR dynamics ,CELL communication - Abstract
In mammals, glycated serum albumin (gSA) contributes to the pathogenesis of many metabolic diseases by activating the receptors (RAGE) for advanced glycation end products (AGEs). Many aspects of the gSA–RAGE interaction remain unknown. The purpose of the present paper was to study the interaction of glycated human albumin (gHSA) with RAGE using molecular modeling methods. Ten models of gHSA modified with different lysine residues to carboxymethyl-lysines were prepared. Complexes of gHSA–RAGE were obtained by the macromolecular docking method with subsequent molecular dynamics simulation (MD). According to the MD, the RAGE complexes with gHSA glycated at Lys233, Lys64, Lys525, Lys262 and Lys378 are the strongest. Three-dimensional models of the RAGE dimers with gHSA were proposed. Additional computational experiments showed that the binding of fatty acids (FAs) to HSA does not affect the ability of Lys525 (the most reactive lysine) to be glycated. In contrast, modification of Lys525 reduces the affinity of albumin for FA. The interspecies differences in the molecular structure of albumin that may affect the mechanism of the gSA–RAGE interaction were discussed. The obtained results will help us to learn more about the molecular basis for the involvement of serum albumin in the AGE/RAGE axis and improve the methodology for studying cellular signaling pathways involving RAGE. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
41. Studies on the Application of PGM Nanocatalysts from Spent Automotive Converters for Degradation of Ibuprofen in Aqueous Solutions.
- Author
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Wolańczyk, Zuzanna, Stachowicz, Wiktoria, Rzelewska-Piekut, Martyna, Zembrzuska, Joanna, and Regel-Rosocka, Magdalena
- Subjects
PLATINUM group ,NANOPARTICLES ,AQUEOUS solutions ,SEWAGE disposal plants ,IBUPROFEN ,DRINKING water - Abstract
There is an increasing concern about the presence of various types of pharmaceuticals in drinking water, as long-term exposure of people to even low concentrations of drugs can lead to many problems, such as endocrine disorders or drug resistance. As the removal in sewage treatment plants is not effective enough, as indicated, among others, by the EC and OECD reports, it is justified to search for new materials that will allow for an effective and rapid reduction of these pollutants in water. Therefore, in our work, catalytically active nanomaterials containing platinum group metals (PGMs) were synthesized from model and real multicomponent solutions and examined in reactions of organic compounds. The nanoparticles (NPs) were obtained from real solutions from the hydrometallurgical processing of spent automotive converters (SACs), and to the best of our knowledge, the novelty of the proposed paper is the application of solutions from SAC processing as precursors for PGM–NPs. The synthesized PGM–NPs were deposited on a support (TiO
2 ), characterized and, finally, examined as nanocatalysts in a degradation reaction of ibuprofen (IB) from model aqueous solutions. The degree of IB degradation reached more than 90%. The main products of IB degradation were p-isobutylphenol and CO2 . [ABSTRACT FROM AUTHOR]- Published
- 2024
- Full Text
- View/download PDF
42. The First High-Quality Genome Assembly of Freshwater Pearl Mussel Sinohyriopsis cumingii : New Insights into Pearl Biomineralization.
- Author
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Bai, Zhiyi, Lu, Ying, Hu, Honghui, Yuan, Yongbin, Li, Yalin, Liu, Xiaojun, Wang, Guiling, Huang, Dandan, Wang, Zhiyan, Mao, Yingrui, Wang, He, Chen, Liangbiao, and Li, Jiale
- Subjects
BIOMINERALIZATION ,FRESHWATER mussels ,GENOMES ,GENE expression ,GENOMICS ,CALCIUM carbonate - Abstract
China leads the world in freshwater pearl production, an industry in which the triangle sail mussel (Sinohyriopsis cumingii) plays a pivotal role. In this paper, we report a high-quality chromosome-level genome assembly of S. cumingii with a size of 2.90 Gb—the largest yet reported among bivalves—and 89.92% anchorage onto 19 linkage groups. The assembled genome has 37,696 protein-coding genes and 50.86% repeat elements. A comparative genomic analysis revealed expansions of 752 gene families, mostly associated with biomineralization, and 237 genes under strong positive selection. Notably, the fibrillin gene family exhibited gene family expansion and positive selection simultaneously, and it also exhibited multiple high expressions after mantle implantation by transcriptome analysis. Furthermore, RNA silencing and an in vitro calcium carbonate crystallization assay highlighted the pivotal role played by one fibrillin gene in calcium carbonate deposition and aragonite transformation. This study provides a valuable genomic resource and offers new insights into the mechanism of pearl biomineralization. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
43. The Expanding Diversity of Viruses from Extreme Environments.
- Author
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Manuel, Robert D. and Snyder, Jamie C.
- Subjects
EXTREME environments ,VIRUS diversity ,TECHNOLOGICAL innovations - Abstract
Viruses are nonliving biological entities whose host range encompasses all known forms of life. They are deceptively simple in description (a protein shell surrounding genetic material with an occasional lipid envelope) and yet can infect all known forms of life. Recently, due to technological advancements, viruses from more extreme environments can be studied through both culture-dependent and independent means. Viruses with thermophilic, halophilic, psychrophilic, and barophilic properties are highlighted in this paper with an emphasis on the properties that allow them to exist in said environments. Unfortunately, much of this field is extremely novel and thus, not much is yet known about these viruses or the microbes they infect when compared to non-extremophilic host–virus systems. With this review, we hope to shed some light on these relatively new studies and highlight their intrinsic value. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
44. The Importance of Anharmonicity and Solvent Effects on the OH Radical Attack on Nucleobases.
- Author
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Ekstrøm, Anna Thorn, Hansen, Vera Staun, and Sauer, Stephan P. A.
- Subjects
ANHARMONIC motion ,RADICALS (Chemistry) ,BASE pairs ,ADENINE ,GAS phase reactions ,SOLVENTS ,DIHYDROPYRIMIDINE dehydrogenase - Abstract
Previous theoretical investigations of the reactions between an OH radical and a nucleobase have stated the most important pathways to be the C5-C6 addition for pyrimidines and the C8 addition for purines. Furthermore, the abstraction of a methyl hydrogen from thymine has also been proven an important pathway. The conclusions were based solely on gas-phase calculations and harmonic vibrational frequencies. In this paper, we supplement the calculations by applying solvent corrections through the polarizable continuum model (PCM) solvent model and applying anharmonicity in order to determine the importance of anharmonicity and solvent effects. Density functional theory (DFT) at the ω B97-D/6-311++G(2df,2pd) level with the Eckart tunneling correction is used. The total reaction rate constants are found to be 1.48 × 10 − 13 cm
3 molecules−1 s−1 for adenine, 1.02 × 10 − 11 cm3 molecules−1 s−1 for guanine, 5.52 × 10 − 13 cm3 molecules−1 s−1 for thymine, 1.47 × 10 − 13 cm3 molecules−1 s−1 for cytosine and 7.59 × 10 − 14 cm3 molecules−1 s−1 for uracil. These rates are found to be approximately two orders of magnitude larger than experimental values. We find that the tendencies observed for preferred pathways for reactions calculated in a solvent are comparable to the preferred pathways for reactions calculated in gas phase. We conclude that applying a solvent has a larger impact on more parameters compared to the inclusion of anharmonicity. For some reactions the inclusion of anharmonicity has no effect, whereas for others it does impact the energetics. [ABSTRACT FROM AUTHOR]- Published
- 2024
- Full Text
- View/download PDF
45. A Combination of Library Screening and Rational Mutagenesis Expands the Available Color Palette of the Smallest Fluorogen-Activating Protein Tag nanoFAST.
- Author
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Baleeva, Nadezhda S., Bogdanova, Yulia A., Goncharuk, Marina V., Sokolov, Anatolii I., Myasnyanko, Ivan N., Kublitski, Vadim S., Smirnov, Alexander Yu., Gilvanov, Aidar R., Goncharuk, Sergey A., Mineev, Konstantin S., and Baranov, Mikhail S.
- Subjects
MUTAGENESIS ,PROTEINS ,AMINO acids - Abstract
NanoFAST is the smallest fluorogen-activating protein, consisting of only 98 amino acids, used as a genetically encoded fluorescent tag. Previously, only a single fluorogen with an orange color was revealed for this protein. In the present paper, using rational mutagenesis and in vitro screening of fluorogens libraries, we expanded the color palette of this tag. We discovered that E46Q is one of the key substitutions enabling the range of possible fluorogens to be expanded. The introduction of this and several other substitutions has made it possible to use not only orange but also red and green fluorogens with the modified protein. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
46. Extracorporeal Photopheresis in Dermatological Diseases.
- Author
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Terhaar, Hanna, Saleem, Mohammad, and Yusuf, Nabiha
- Subjects
T-cell lymphoma ,MYCOSIS fungoides ,THERAPEUTICS ,ATOPIC dermatitis ,SKIN diseases - Abstract
Extracorporeal photopheresis (ECP) is an apheresis procedure that is conventionally used as a first-line treatment for cutaneous and leukemic subtypes of T-cell lymphoma, such as Sezary's syndrome and mycosis fungoides. Over the past three decades, its immunotherapeutic properties have been tested on a variety of autoimmune conditions, including many dermatologic diseases. There is ample evidence of ECP's ability to modify leukocytes and alter cytokine production for certain dermatologic diseases that have been refractory to first-line treatments, such as atopic dermatitis. However, the evidence on the efficacy of ECP for the treatment of these dermatologic diseases is unclear and/or lacks sufficient evidence. The purpose of this paper is to review the literature on the utilization and clinical efficacy of ECP in the treatment of several [autoimmune] dermatologic diseases and discuss its applications, guidelines, recommendations, and future implementation for dermatologic diseases. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
47. Streptomycetes as Microbial Cell Factories for the Biotechnological Production of Melanin.
- Author
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Kordjazi, Talayeh, Mariniello, Loredana, Giosafatto, Concetta Valeria Lucia, Porta, Raffaele, and Restaino, Odile Francesca
- Subjects
MELANINS ,MICROBIAL cells ,FOOD packaging ,MANUFACTURING processes ,STREPTOMYCES ,METAL ions ,PHOTOVOLTAIC power systems - Abstract
Melanins are complex, polymeric pigments with interesting properties like UV-light absorbance ability, metal ion chelation capacity, antimicrobial action, redox behaviors, and scavenging properties. Based on these characteristics, melanins might be applied in different industrial fields like food packaging, environmental bioremediation, and bioelectronic fields. The actual melanin manufacturing process is not environmentally friendly as it is based on extraction and purification from cuttlefish. Synthetic melanin is available on the market, but it is more expensive than animal-sourced pigment and it requires long chemical procedures. The biotechnological production of microbial melanin, instead, might be a valid alternative. Streptomycetes synthesize melanins as pigments and as extracellular products. In this review, the melanin biotechnological production processes by different Streptomyces strains have been revised according to papers in the literature. The different fermentation strategies to increase melanin production such as the optimization of growth conditions and medium composition or the use of raw sources as growth substrates are here described. Diverse downstream purification processes are also reported as well as all the different analytical methods used to characterize the melanin produced by Streptomyces strains before its application in different fields. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
48. Efficient Estimates of Surface Diffusion Parameters for Spatio-Temporally Resolved Virus Replication Dynamics.
- Author
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Knodel, Markus M., Wittum, Gabriel, and Vollmer, Jürgen
- Subjects
VIRAL replication ,PARTIAL differential equations ,HEPATITIS C virus ,SURFACE diffusion ,VIRUS removal (Water purification) ,DIFFUSION coefficients ,VIRAL nonstructural proteins - Abstract
Advanced methods of treatment are needed to fight the threats of virus-transmitted diseases and pandemics. Often, they are based on an improved biophysical understanding of virus replication strategies and processes in their host cells. For instance, an essential component of the replication of the hepatitis C virus (HCV) proceeds under the influence of nonstructural HCV proteins (NSPs) that are anchored to the endoplasmatic reticulum (ER), such as the NS5A protein. The diffusion of NSPs has been studied by in vitro fluorescence recovery after photobleaching (FRAP) experiments. The diffusive evolution of the concentration field of NSPs on the ER can be described by means of surface partial differential equations (sufPDEs). Previous work estimated the diffusion coefficient of the NS5A protein by minimizing the discrepancy between an extended set of sufPDE simulations and experimental FRAP time-series data. Here, we provide a scaling analysis of the sufPDEs that describe the diffusive evolution of the concentration field of NSPs on the ER. This analysis provides an estimate of the diffusion coefficient that is based only on the ratio of the membrane surface area in the FRAP region to its contour length. The quality of this estimate is explored by a comparison to numerical solutions of the sufPDE for a flat geometry and for ten different 3D embedded 2D ER grids that are derived from fluorescence z-stack data of the ER. Finally, we apply the new data analysis to the experimental FRAP time-series data analyzed in our previous paper, and we discuss the opportunities of the new approach. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
49. Molecular Frontiers in Melanoma: Pathogenesis, Diagnosis, and Therapeutic Advances.
- Author
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Kim, Hyun Jee and Kim, Yeong Ho
- Subjects
MELANOMA ,DIAGNOSIS ,SKIN cancer ,C-kit protein ,INDIVIDUALIZED medicine - Abstract
Melanoma, a highly aggressive skin cancer, is characterized by rapid progression and high mortality. Recent advances in molecular pathogenesis have shed light on genetic and epigenetic changes that drive melanoma development. This review provides an overview of these developments, focusing on molecular mechanisms in melanoma genesis. It highlights how mutations, particularly in the BRAF, NRAS, c-KIT, and GNAQ/GNA11 genes, affect critical signaling pathways. The evolution of diagnostic techniques, such as genomics, transcriptomics, liquid biopsies, and molecular biomarkers for early detection and prognosis, is also discussed. The therapeutic landscape has transformed with targeted therapies and immunotherapies, improving patient outcomes. This paper examines the efficacy, challenges, and prospects of these treatments, including recent clinical trials and emerging strategies. The potential of novel treatment strategies, including neoantigen vaccines, adoptive cell transfer, microbiome interactions, and nanoparticle-based combination therapy, is explored. These advances emphasize the challenges of therapy resistance and the importance of personalized medicine. This review underlines the necessity for evidence-based therapy selection in managing the increasing global incidence of melanoma. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
50. From Case Reports to Molecular Insight: Examining the Outcomes and Underlying Mechanisms of Squamous Cell Carcinoma in Breast Implant Patients—A Systematic Review.
- Author
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Camicia, Alexandra, Foppiani, Jose A., Raska, Otakar, Hernandez Alvarez, Angelica, Lee, Daniela, Taritsa, Iulianna C., Schuster, Kirsten A., Wan, Rou, Neradová, Sylva, Lin, Gavin J., Lee, Theodore C., Molitor, Martin, Zikan, Michal, and Lin, Samuel J.
- Subjects
BREAST implants ,ANAPLASTIC large-cell lymphoma ,SQUAMOUS cell carcinoma ,LITERATURE reviews ,DISEASE progression - Abstract
There is extensive coverage in the existing literature on implant-associated lymphomas like anaplastic large-cell lymphoma, but breast implant-associated squamous cell carcinoma (BIA-SCC) has received limited scholarly attention since its first case in 1992. Thus, this study aims to conduct a qualitative synthesis focused on the underexplored association between breast implants and BIA-SCC. A systematic review was conducted utilizing the PubMed, Web of Science, and Cochrane databases to identify all currently reported cases of BIA-SCC. Additionally, a literature review was performed to identify potential biochemical mechanisms that could lead to BIA-SCC. Studies were vetted for quality using the NIH quality assessment tool. From an initial pool of 246 papers, 11 met the quality criteria for inclusion, examining a total of 14 patients aged between 40 and 81 years. BIA-SCC was found in a diverse range of implants, including those with smooth and textured surfaces, as well as those filled with saline and silicone. The condition notably manifested a proclivity for aggressive clinical progression, as evidenced by a mortality rate approximating 21.4% within a post-diagnostic interval of six months. Our literature review reveals that chronic inflammation, driven by various external factors such as pathogens and implants, can initiate carcinogenesis through epigenetic modifications and immune system alterations. This includes effects from exosomes and macrophage polarization, showcasing potential pathways for the pathogenesis of BIA-SCC. The study highlights the pressing need for further investigation into BIA-SCC, a subject hitherto inadequately addressed in the academic sphere. This necessitates the urgency for early screening and intervention to improve postoperative outcomes. While the review is confined by its reliance on case reports and series, it serves as a valuable reference for future research endeavors. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
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