International Journal of Molecular Sciences

14 pages, 2885 KiB

Open AccessArticle

Photodegradation of a Broad-Spectrum Antibiotic Azithromycin Using H₂O₂ under Ultraviolet Irradiation

by Nasser Ibrahim Zouli

Int. J. Mol. Sci. 2024, 25(12), 6702; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms25126702 (registering DOI) - 18 Jun 2024

Abstract

The photodegradation of azithromycin present was carried out in water using H₂O₂ under UV irradiation. The reaction variables considered in this study were the amount of H₂O₂ solution and the initial concentration of azithromycin to evaluate the [...] Read more.

The photodegradation of azithromycin present was carried out in water using H₂O₂ under UV irradiation. The reaction variables considered in this study were the amount of H₂O₂ solution and the initial concentration of azithromycin to evaluate the performance of the photodegradation process. The azithromycin degradation was not observed in the dark during stirring for 20 min. The study showed an efficient photodegradation of azithromycin using H₂O₂ as an oxidant in the presence of UV irradiation. The azithromycin degradation was altered significantly by the pH of the irradiated solution. The degradation was low at an acidic pH and showed an increasing trend as the pH changed to basic. The azithromycin degradation increased with a higher amount (higher concentration) of H₂O₂. The degradation of azithromycin decreased with a higher concentration of azithromycin in the reacting solution. The highest degradation of AZT was achieved in 1 h using a 1.0 ppm AZT solution containing 3 mL of H₂O₂. The experimental data obtained were well-fitted to zero-order reaction kinetics. The results of this study were found quite excellent. They showed 100% degradation in 1 h when compared with those reported in the literature, both with photocatalysis using nanomaterials and photolysis using light irradiation and/or H₂O₂. The UV/H₂O₂ system was found to be quite efficient for the photodegradation of azithromycin, and this system can be applied to degrade other organic pollutants present in industrial wastewater. Full article

(This article belongs to the Special Issue Recent Advances in Photolysis and Photodegradation)

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26 pages, 1365 KiB

Open AccessReview

Tailored Viral-Like Particles as Drivers of Medical Breakthroughs

by Rafael Travassos, Sofia A. Martins, Ana Fernandes, João D. G. Correia and Rita Melo

Int. J. Mol. Sci. 2024, 25(12), 6699; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms25126699 (registering DOI) - 18 Jun 2024

Abstract

Despite the recognized potential of nanoparticles, only a few formulations have progressed to clinical trials, and an even smaller number have been approved by the regulatory authorities and marketed. Virus-like particles (VLPs) have emerged as promising alternatives to conventional nanoparticles due to their [...] Read more.

Despite the recognized potential of nanoparticles, only a few formulations have progressed to clinical trials, and an even smaller number have been approved by the regulatory authorities and marketed. Virus-like particles (VLPs) have emerged as promising alternatives to conventional nanoparticles due to their safety, biocompatibility, immunogenicity, structural stability, scalability, and versatility. Furthermore, VLPs can be surface-functionalized with small molecules to improve circulation half-life and target specificity. Through the functionalization and coating of VLPs, it is possible to optimize the response properties to a given stimulus, such as heat, pH, an alternating magnetic field, or even enzymes. Surface functionalization can also modulate other properties, such as biocompatibility, stability, and specificity, deeming VLPs as potential vaccine candidates or delivery systems. This review aims to address the different types of surface functionalization of VLPs, highlighting the more recent cutting-edge technologies that have been explored for the design of tailored VLPs, their importance, and their consequent applicability in the medical field. Full article

(This article belongs to the Section Materials Science)

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46 pages, 8885 KiB

Open AccessArticle

A Practical Guide to All-Atom and Coarse-Grained Molecular Dynamics Simulations Using Amber and Gromacs: A Case Study of Disulfide-Bond Impact on the Intrinsically Disordered Amyloid Beta

by Pamela Smardz, Midhun Mohan Anila, Paweł Rogowski, Mai Suan Li, Bartosz Różycki and Pawel Krupa

Int. J. Mol. Sci. 2024, 25(12), 6698; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms25126698 (registering DOI) - 18 Jun 2024

Abstract

Intrinsically disordered proteins (IDPs) pose challenges to conventional experimental techniques due to their large-scale conformational fluctuations and transient structural elements. This work presents computational methods for studying IDPs at various resolutions using the Amber and Gromacs packages with both all-atom (Amber ff19SB with [...] Read more.

Intrinsically disordered proteins (IDPs) pose challenges to conventional experimental techniques due to their large-scale conformational fluctuations and transient structural elements. This work presents computational methods for studying IDPs at various resolutions using the Amber and Gromacs packages with both all-atom (Amber ff19SB with the OPC water model) and coarse-grained (Martini 3 and SIRAH) approaches. The effectiveness of these methodologies is demonstrated by examining the monomeric form of amyloid-β (Aβ42), an IDP, with and without disulfide bonds at different resolutions. Our results clearly show that the addition of a disulfide bond decreases the β-content of Aβ42; however, it increases the tendency of the monomeric Aβ42 to form fibril-like conformations, explaining the various aggregation rates observed in experiments. Moreover, analysis of the monomeric Aβ42 compactness, secondary structure content, and comparison between calculated and experimental chemical shifts demonstrates that all three methods provide a reasonable choice to study IDPs; however, coarse-grained approaches may lack some atomistic details, such as secondary structure recognition, due to the simplifications used. In general, this study not only explains the role of disulfide bonds in Aβ42 but also provides a step-by-step protocol for setting up, conducting, and analyzing molecular dynamics (MD) simulations, which is adaptable for studying other biomacromolecules, including folded and disordered proteins and peptides. Full article

(This article belongs to the Special Issue Molecular Simulation and Modeling)

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28 pages, 10222 KiB

Open AccessArticle

Integrated Analysis of Microbiome and Metabolome Reveals Disease-Specific Profiles in Inflammatory Bowel Diseases and Intestinal Behçet’s Disease

by Yehyun Park, Jae Bum Ahn, Da Hye Kim, I Seul Park, Mijeong Son, Ji Hyung Kim, Hyun Woo Ma, Seung Won Kim and Jae Hee Cheon

Int. J. Mol. Sci. 2024, 25(12), 6697; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms25126697 (registering DOI) - 18 Jun 2024

Abstract

The gut microbial and metabolic characteristics of intestinal Behçet’s disease (BD), a condition sharing many clinical similarities with ulcerative colitis (UC) and Crohn’s disease (CD), are largely unexplored. This study investigated the gut microbial and metabolic characteristics of intestinal BD as well as [...] Read more.

The gut microbial and metabolic characteristics of intestinal Behçet’s disease (BD), a condition sharing many clinical similarities with ulcerative colitis (UC) and Crohn’s disease (CD), are largely unexplored. This study investigated the gut microbial and metabolic characteristics of intestinal BD as well as potential biomarkers, comparing them with those in UC, CD, and healthy controls. Colon tissue and stool samples from 100 patients (35 UC, 30 CD, and 35 intestinal BD) and 41 healthy volunteers were analyzed using 16S ribosomal RNA sequencing to assess microbial diversity, taxonomic composition, and functional profiling. Plasma metabolomic analyses were performed using gas chromatography and ultra-performance liquid chromatography-mass spectrometry. Results indicated reduced microbial diversity in CD but not in intestinal BD, with intestinal BD showing fewer changes compared to controls yet distinct taxonomic features from UC, CD, and controls. Common alterations across all diseases included a reduction in beneficial bacteria producing short-chain fatty acids. Intestinal BD-specific changes featured a decreased abundance of Bacteroides fragilis. Metabolomic profiles in intestinal BD were similar to those in CD but distinct from those in UC, displaying significant changes in energy metabolism and genetic information processing. This integrative analysis revealed both shared and unique profiles in intestinal BD compared with UC, CD, and controls, advancing our understanding of the distinctive features of these diseases. Full article

(This article belongs to the Special Issue Gastrointestinal Diseases: Molecular Mechanism, Diagnostics, and Novel Therapeutic Approaches)

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17 pages, 2497 KiB

Open AccessArticle

Microcystis viridis NIES-102 Cyanobacteria Lectin (MVL) Interacts with SARS-CoV-2 Spike Protein Receptor Binding Domains (RBDs) via Protein–Protein Interaction

by Zhengguang Wang, Zhihan Yang, Mami Shishido, Khadija Daoudi, Masafumi Hidaka, Hiroaki Tateno, Eugene Futai and Tomohisa Ogawa

Int. J. Mol. Sci. 2024, 25(12), 6696; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms25126696 (registering DOI) - 18 Jun 2024

Abstract

The emergence of coronavirus disease 2019 (COVID-19) posed a major challenge to healthcare systems worldwide, especially as mutations in the culprit Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) complicated the development of vaccines and antiviral drugs. Therefore, the search for natural products with [...] Read more.

The emergence of coronavirus disease 2019 (COVID-19) posed a major challenge to healthcare systems worldwide, especially as mutations in the culprit Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) complicated the development of vaccines and antiviral drugs. Therefore, the search for natural products with broad anti-SARS-CoV-2 capabilities is an important option for the prevention and treatment of similar infectious diseases. Lectins, which are widely recognized as antiviral agents, could contribute to the development of anti-SARS-CoV-2 drugs. This study evaluated the binding affinity of six lectins (including the cyanobacterial lectin from Microcystis viridis NIES-102 (MVL), and Jacalin, a lectin from the breadfruit, Artocarpus altilis) to the receptor binding domain (RBD) of the spike protein on the original (wild) SARS-CoV-2 and three of its mutants: Alpha, Delta, and Omicron. MVL and Jacalin showed distinct binding affinity to the RBDs of the four SARS-CoV-2 strains. The remaining four lectins (DB1, ConA, PHA-M and CSL3) showed no such binding affinity. Although the glycan specificities of MVL and Jacalin were different, they showed the same affinity for the spike protein RBDs of the four SARS-CoV-2 strains, in the order of effectiveness Alpha > Delta > original > Omicron. The verification of glycan-specific inhibition revealed that both lectins bind to RBDs by glycan-specific recognition, but, in addition, MVL binds to RBDs through protein–protein interactions. Full article

(This article belongs to the Special Issue Antiviral Activity of Lectins)

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16 pages, 5044 KiB

Open AccessArticle

Gut Microbiota Alleviates Intestinal Injury Induced by Extended Exposure to Light via Inhibiting the Activation of NLRP3 Inflammasome in Broiler Chickens

by Dandan Ma, Minhong Zhang and Jinghai Feng

Int. J. Mol. Sci. 2024, 25(12), 6695; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms25126695 (registering DOI) - 18 Jun 2024

Abstract

Light pollution is a potential risk for intestinal health in humans and animals. The gut microbiota is associated with the development of intestinal inflammation induced by extended exposure to light, but the underlying mechanism is not yet clear. The results of this study [...] Read more.

Light pollution is a potential risk for intestinal health in humans and animals. The gut microbiota is associated with the development of intestinal inflammation induced by extended exposure to light, but the underlying mechanism is not yet clear. The results of this study showed that extended exposure to light (18L:6D) damaged intestinal morphology, downregulated the expression of tight junction proteins, and upregulated the expression of the NLRP3 inflammasome and the concentration of pro-inflammatory cytokines. In addition, extended exposure to light significantly decreased the abundance of Lactobacillus, Butyricicoccus, and Sellimonas and increased the abundance of Bifidobacterium, unclassified Oscillospirales, Family_XIII_UCG-001, norank_f__norank_o__Clostridia_vadinBB60_group, and Defluviitaleaceae_UCG-01. Spearman correlation analysis indicated that gut microbiota dysbiosis positively correlated with the activation of the NLRP3 inflammasome. The above results indicated that extended exposure to light induced intestinal injury by NLRP3 inflammasome activation and gut microbiota dysbiosis. Antibiotic depletion intestinal microbiota treatment and cecal microbiota transplantation (CMT) from the 12L:12D group to 18L:6D group indicated that the gut microbiota alleviated intestinal inflammatory injury induced by extended exposure to light via inhibiting the activation of the NLRP3 inflammasome. In conclusion, our findings indicated that the gut microbiota can alleviate intestinal inflammation induced by extended exposure to light via inhibiting the activation of the NLRP3 inflammasome. Full article

(This article belongs to the Special Issue Gut Microbiota in Gastroenterology and Hepatology 2.0)

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16 pages, 4884 KiB

Open AccessArticle

Cinnamic Acid, Perillic Acid, and Tryptophan Metabolites Differentially Regulate Ion Transport and Serotonin Metabolism and Signaling in the Mouse Ileum In Vitro

by Lili Jiang, Youling Hao, Qianjun Li and Zhaolai Dai

Int. J. Mol. Sci. 2024, 25(12), 6694; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms25126694 (registering DOI) - 18 Jun 2024

Abstract

Phytochemicals and tryptophan (Trp) metabolites have been found to modulate gut function and health. However, whether these metabolites modulate gut ion transport and serotonin (5-HT) metabolism and signaling requires further investigation. The aim of this study was to investigate the effects of selected [...] Read more.

Phytochemicals and tryptophan (Trp) metabolites have been found to modulate gut function and health. However, whether these metabolites modulate gut ion transport and serotonin (5-HT) metabolism and signaling requires further investigation. The aim of this study was to investigate the effects of selected phytochemicals and Trp metabolites on the ion transport and 5-HT metabolism and signaling in the ileum of mice in vitro using the Ussing chamber technique. During the in vitro incubation, vanillylmandelic acid (VMA) reduced (p < 0.05) the short-circuit current, and 100 μM chlorogenic acid (CGA) (p = 0.12) and perillic acid (PA) (p = 0.14) had a tendency to reduce the short-circuit current of the ileum. Compared with the control, PA and N-acetylserotonin treatment upregulated the expression of tryptophan hydroxylase 1 (Tph1), while 100 μM cinnamic acid, indolelactic acid (ILA), and 10 μM CGA or indoleacetaldehyde (IAld) treatments downregulated (p < 0.05) the mRNA levels of Tph1. In addition, 10 μM IAld or 100 μM ILA upregulated (p < 0.05) the expression of monoamine oxidase A (Maoa). However, 10 μM CGA or 100 μM PA downregulated (p < 0.05) Maoa expression. All selected phytochemicals and Trp metabolites upregulated (p < 0.05) the expression of Htr4 and Htr7 compared to that of the control group. VMA and CGA reduced (p < 0.05) the ratios of Htr1a/Htr7 and Htr4/Htr7. These findings may help to elucidate the effects of phytochemicals and Trp metabolites on the regulation of gut ion transport and 5-HT signaling-related gut homeostasis in health and disease. Full article

(This article belongs to the Special Issue Ion Movements and Membrane Proteins)

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16 pages, 2826 KiB

Open AccessArticle

Generation of Myeloid-Derived Suppressor Cells Mediated by MicroRNA-125a-5p in Melanoma

by Samantha Lasser, Feyza Gul Ozbay Kurt, Lennart Fritz, Nina Gutzeit, Carolina De La Torre, Peter Altevogt, Jochen Utikal and Viktor Umansky

Int. J. Mol. Sci. 2024, 25(12), 6693; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms25126693 (registering DOI) - 18 Jun 2024

Abstract

The ability of tumor-derived extracellular vesicles (EVs) to modulate the function of myeloid cells is widely recognized. Hence, a comprehensive understanding of the distinct components associated with EVs and the signals that they deliver to myeloid cells could provide potential approaches to impede [...] Read more.

The ability of tumor-derived extracellular vesicles (EVs) to modulate the function of myeloid cells is widely recognized. Hence, a comprehensive understanding of the distinct components associated with EVs and the signals that they deliver to myeloid cells could provide potential approaches to impede the immunosuppression by myeloid-derived suppressor cells (MDSCs). We investigated melanoma EV-associated microRNAs (miRs) using the RET transgenic melanoma mouse model and simulated their transfer to normal myeloid cells by transfecting immature mouse myeloid cells and human monocytes. We observed elevated levels of miR-125a-5p, -125b-5p, and let-7e-5p in mouse melanoma-infiltrating MDSCs. In addition, miR-125a-5p levels in the tumor microenvironment correlated with mouse melanoma progression. The delivery of miR-125a-5p, alone or in combination with let-7e-5p and miR-99b-5p from the same genomic cluster, to normal myeloid cells resulted in their conversion to MDSC-like cells. Our findings indicate that miR-125a-5p could modulate myeloid cell activation in the melanoma microenvironment via a NF-κB-dependent mechanism. Full article

(This article belongs to the Special Issue Role of Extracellular Vesicles in Immunology)

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19 pages, 329 KiB

Open AccessReview

Ocular Changes in Cystic Fibrosis: A Review

by Slawomir Liberski, Filippo Confalonieri, Szczepan Cofta, Goran Petrovski and Jarosław Kocięcki

Int. J. Mol. Sci. 2024, 25(12), 6692; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms25126692 (registering DOI) - 18 Jun 2024

Abstract

Cystic fibrosis (CF), also known as mucoviscidosis, is the most common autosomal recessive genetic disease in the Caucasian population, with an estimated frequency of 1:2000–3000 live births. CF results from the mutation of the cystic fibrosis transmembrane conductance regulator (CFTR) gene localized in [...] Read more.

Cystic fibrosis (CF), also known as mucoviscidosis, is the most common autosomal recessive genetic disease in the Caucasian population, with an estimated frequency of 1:2000–3000 live births. CF results from the mutation of the cystic fibrosis transmembrane conductance regulator (CFTR) gene localized in the long arm of chromosome 7. The product of CFTR gene expression is CFTR protein, an adenosine triphosphate (ATP)-binding cassette (ABC) transporter that regulates the transport of chloride ions (Cl⁻) across the apical cell membrane. Primary manifestations of CF include chronic lung and pancreas function impairment secondary to the production of thick, sticky mucus resulting from dehydrated secretions. It is well known that CF can cause both anterior and posterior ocular abnormalities. Conjunctival and corneal xerosis and dry eye disease symptoms are the most characteristic manifestations in the anterior segment. In contrast, the most typical anatomical and functional changes relating to the posterior segment of the eye include defects in the retinal nerve fiber layer (RNFL), vascular abnormalities, and visual disturbances, such as reduced contrast sensitivity and abnormal dark adaptation. However, the complete background of ophthalmic manifestations in the course of CF has yet to be discovered. This review summarizes the current knowledge regarding ocular changes in cystic fibrosis. Full article

(This article belongs to the Section Molecular Pathology, Diagnostics, and Therapeutics)

12 pages, 2539 KiB

Open AccessArticle

Talaroacids A–D and Talaromarane A, Diterpenoids with Anti-Inflammatory Activities from Mangrove Endophytic Fungus Talaromyces sp. JNQQJ-4

by Guisheng Wang, Jianying Wu, Zhaokun Li, Tao Chen, Yufeng Liu, Bo Wang, Yan Chen and Zhigang She

Int. J. Mol. Sci. 2024, 25(12), 6691; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms25126691 (registering DOI) - 18 Jun 2024

Abstract

Five new diterpenes including four diterpenes with 1,2,3,4,4a,5,6,8a-octalin skeleton talaroacids A–D (1–4) and an isopimarane diterpenoid talaromarane A (5) were isolated from the mangrove endophytic fungus Talaromyces sp. JNQQJ-4. Their structures and absolute configurations were determined by [...] Read more.

Five new diterpenes including four diterpenes with 1,2,3,4,4a,5,6,8a-octalin skeleton talaroacids A–D (1–4) and an isopimarane diterpenoid talaromarane A (5) were isolated from the mangrove endophytic fungus Talaromyces sp. JNQQJ-4. Their structures and absolute configurations were determined by analysis of high-resolution electrospray ionization mass spectroscopy (HRESIMS), 1D/2D Nuclear Magnetic Resonance (NMR) spectra, single-crystal X-ray diffraction, quantum chemical calculation, and electronic circular dichroism (ECD). Talaromarane A (5) contains a rare 2-oxabicyclo [3.2.1] octan moiety in isopimarane diterpenoids. In bioassays, compounds 1, 2, 4, and 5 displayed significant anti-inflammatory activities with the IC₅₀ value from 4.59 to 21.60 μM. Full article

(This article belongs to the Special Issue Nutrients and Active Substances in Natural Products)

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21 pages, 6616 KiB

Open AccessArticle

PCAS: An Integrated Tool for Multi-Dimensional Cancer Research Utilizing Clinical Proteomic Tumor Analysis Consortium Data

by Jin Wang, Xiangrong Song, Meidan Wei, Lexin Qin, Qingyun Zhu, Shujie Wang, Tingting Liang, Wentao Hu, Xinyu Zhu and Jianxiang Li

Int. J. Mol. Sci. 2024, 25(12), 6690; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms25126690 (registering DOI) - 18 Jun 2024

Abstract

Proteomics offers a robust method for quantifying proteins and elucidating their roles in cellular functions, surpassing the insights provided by transcriptomics. The Clinical Proteomic Tumor Analysis Consortium database, enriched with comprehensive cancer proteomics data including phosphorylation and ubiquitination profiles, alongside transcriptomics data from [...] Read more.

Proteomics offers a robust method for quantifying proteins and elucidating their roles in cellular functions, surpassing the insights provided by transcriptomics. The Clinical Proteomic Tumor Analysis Consortium database, enriched with comprehensive cancer proteomics data including phosphorylation and ubiquitination profiles, alongside transcriptomics data from the Genomic Data Commons, allow for integrative molecular studies of cancer. The ProteoCancer Analysis Suite (PCAS), our newly developed R package and Shinyapp, leverages these resources to facilitate in-depth analyses of proteomics, phosphoproteomics, and transcriptomics, enhancing our understanding of the tumor microenvironment through features like immune infiltration and drug sensitivity analysis. This tool aids in identifying critical signaling pathways and therapeutic targets, particularly through its detailed phosphoproteomic analysis. To demonstrate the functionality of the PCAS, we conducted an analysis of GAPDH across multiple cancer types, revealing a significant upregulation of protein levels, which is consistent with its important biological and clinical significance in tumors, as indicated in our prior research. Further experiments were used to validate the findings performed using the tool. In conclusion, the PCAS is a powerful and valuable tool for conducting comprehensive proteomic analyses, significantly enhancing our ability to uncover oncogenic mechanisms and identify potential therapeutic targets in cancer research. Full article

(This article belongs to the Section Biochemistry)

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16 pages, 8280 KiB

Open AccessArticle

Genetic Diversity and Population Structure of Rhodeus uyekii in the Republic of Korea Revealed by Microsatellite Markers from Whole Genome Assembly

by Kang-Rae Kim, So Young Park, Ju Hui Jeong, Yujin Hwang, Heesoo Kim, Mu-Sung Sung and Jeong-Nam Yu

Int. J. Mol. Sci. 2024, 25(12), 6689; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms25126689 (registering DOI) - 18 Jun 2024

Abstract

This study is the first report to characterize the Rhodus uyekii genome and study the development of microsatellite markers and their markers applied to the genetic structure of the wild population. Genome assembly was based on PacBio HiFi and Illumina HiSeq paired-end sequencing, [...] Read more.

This study is the first report to characterize the Rhodus uyekii genome and study the development of microsatellite markers and their markers applied to the genetic structure of the wild population. Genome assembly was based on PacBio HiFi and Illumina HiSeq paired-end sequencing, resulting in a draft genome assembly of R. uyekii. The draft genome was assembled into 2652 contigs. The integrity assessment of the assemblies indicates that the quality of the draft assemblies is high, with 3259 complete BUSCOs (97.2%) in the database of Verbrata. A total of 31,166 predicted protein-coding genes were annotated in the protein database. The phylogenetic tree showed that R. uyekii is a close but distinct relative of Onychostoma macrolepis. Among the 10 fish genomes, there were significant gene family expansions (8–2387) and contractions (16–2886). The average number of alleles amplified by the 21 polymorphic markers ranged from 6 to 23, and the average PIC value was 0.753, which will be useful for evolutionary and genetic analysis. Using population genetic analysis, we analyzed genetic diversity and the genetic structures of 120 individuals from 6 populations. The average number of alleles per population ranged from 7.6 to 9.9, observed heterozygosity ranged from 0.496 to 0.642, and expected heterozygosity ranged from 0.587 to 0.783. Discriminant analysis of principal components According to the analysis method, the population was divided into three populations (BS vs. DC vs. GG, GC, MS, DC). In conclusion, our study provides a useful resource for comparative genomics, phylogeny, and future population studies of R. uyekii. Full article

(This article belongs to the Special Issue Next-Generation Sequencing and Whole-Genome Sequencing in Molecular Research)

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16 pages, 2784 KiB

Open AccessArticle

Biodegradation of Photocatalytic Degradation Products of Sulfonamides: Kinetics and Identification of Intermediates

by Daria Madej-Knysak, Ewa Adamek and Wojciech Baran

Int. J. Mol. Sci. 2024, 25(12), 6688; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms25126688 (registering DOI) - 18 Jun 2024

Abstract

Sulfonamides can be effectively removed from wastewater through a photocatalytic process. However, the mineralization achieved by this method is a long-term and expensive process. The effect of shortening the photocatalytic process is the partial degradation and formation of intermediates. The purpose of this [...] Read more.

Sulfonamides can be effectively removed from wastewater through a photocatalytic process. However, the mineralization achieved by this method is a long-term and expensive process. The effect of shortening the photocatalytic process is the partial degradation and formation of intermediates. The purpose of this study was to evaluate the sensitivity and transformation of photocatalytic reaction intermediates in aerobic biological processes. Sulfadiazine and sulfamethoxazole solutions were used in the study, which were irradiated in the presence of a TiO₂-P25 catalyst. The resulting solutions were then aerated after the addition of river water or activated sludge suspension from a commercial wastewater treatment plant. The reaction kinetics were determined and fifteen products of photocatalytic degradation of sulfonamides were identified. Most of these products were further transformed in the presence of activated sludge suspension or in water taken from the river. They may have been decomposed into other organic and inorganic compounds. The formation of biologically inactive acyl derivatives was observed in the biological process. However, compounds that are more toxic to aquatic organisms than the initial drugs can also be formed. After 28 days, the sulfamethoxazole concentration in the presence of activated sludge was reduced by 66 ± 7%. Sulfadiazine was practically non-biodegradable under the conditions used. The presented results confirm the advisability of using photocatalysis as a process preceding biodegradation. Full article

(This article belongs to the Special Issue Biodegradation of Pollutants in the Environment: Omics Approaches 3.0)

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11 pages, 2363 KiB

Open AccessArticle

Impact of Inflammatory Markers and Senescence-Associated Secretory Phenotype in the Gingival Crevicular Fluid on the Outcomes of Periodontal Regeneration

by Giacomo Baima, Federica Romano, Francesco Franco, Ilaria Roato, Federico Mussano, Giovanni Nicolao Berta and Mario Aimetti

Int. J. Mol. Sci. 2024, 25(12), 6687; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms25126687 (registering DOI) - 18 Jun 2024

Abstract

The aim of this study was to test the molecular expression profile (senescence-associated secretory phenotype; SASP) in gingival crevicular fluid (GCF) prior to surgery in relation to the distribution of clinical success of periodontal regeneration. Forty consecutive patients presenting sites with residual probing [...] Read more.

The aim of this study was to test the molecular expression profile (senescence-associated secretory phenotype; SASP) in gingival crevicular fluid (GCF) prior to surgery in relation to the distribution of clinical success of periodontal regeneration. Forty consecutive patients presenting sites with residual probing pocket depth (PPD) ≥ 6 mm and intrabony defects ≥ 3 mm were treated through a minimally invasive surgical technique. Pre-operatively, GCF was sampled for inflammatory biomarker analysis related to SASP [interleukin (IL)-1β, IL-6, and IL-12; matrix-metalloproteinases (MMP)-8 and -9]. Better or worse responders were classified depending on the achievement of a composite outcome measure at 1-year [COM; PPD ≤ 4 mm and clinical attachment gain (CAL) gain ≥ 3 mm]. Correlation analyses and logistic regression models were performed. Periodontal regeneration led to significant improvements in mean clinical and radiographic parameters. Teeth achieving COM presented significantly lower amounts of SASP factors compared with non-successful teeth. Higher CAL gain, PPD reduction, and radiographic bone fill were negatively correlated with IL-1β and MMP-8 and -9 (p < 0.001), while IL-12 showed a direct relationship with CAL gain (p = 0.005) and PPD reduction (p = 0.038). Sites expressing higher SASP expression in the GCF before periodontal regeneration achieved worse clinical and radiographic outcomes. Full article

(This article belongs to the Special Issue New Advances in Stem Cells in Human Health and Diseases)

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36 pages, 7923 KiB

Open AccessArticle

The Ethyl Acetate Extract of Phyllanthus emblica L. Alleviates Diabetic Nephropathy in a Murine Model of Diabetes

by Cheng-Hsiu Lin and Chun-Ching Shih

Int. J. Mol. Sci. 2024, 25(12), 6686; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms25126686 (registering DOI) - 18 Jun 2024

Abstract

Oil-Gan is the fruit of the genus Phyllanthus emblica L. The fruits have excellent effects on health care and development values. There are many methods for the management of diabetic nephropathy (DN). However, there is a lack of effective drugs for treating DN [...] Read more.

Oil-Gan is the fruit of the genus Phyllanthus emblica L. The fruits have excellent effects on health care and development values. There are many methods for the management of diabetic nephropathy (DN). However, there is a lack of effective drugs for treating DN throughout the disease course. The primary aim of this study was to examine the protective effects (including analyses of urine and blood, and inflammatory cytokine levels) and mechanisms of the ethyl acetate extract of P. emblica (EPE) on db/db mice, an animal model of diabetic nephropathy; the secondary aim was to examine the expression levels of p- protein kinase Cα (PKCα)/t-PKCα in the kidney and its downregulation of vascular endothelial growth factor (VEGF) and fibrosis gene transforming growth factor-β1 (TGF-β1) by Western blot analyses. Eight db/m mice were used as the control group. Forty db/db mice were randomly divided into five groups. Treatments included a vehicle, EPE1, EPE2, EPE3 (at doses of 100, 200, or 400 mg/kg EPE), or the comparative drug aminoguanidine for 8 weeks. After 8 weeks of treatment, the administration of EPE to db/db mice effectively controlled hyperglycemia and hyperinsulinemia by markedly lowering blood glucose, insulin, and glycosylated HbA1c levels. The administration of EPE to db/db mice decreased the levels of BUN and creatinine both in blood and urine and reduced urinary albumin excretion and the albumin creatine ratio (UACR) in urine. Moreover, EPE treatment decreased the blood levels of inflammatory cytokines, including kidney injury molecule-1 (KIM-1), C-reactive protein (CRP), and NLR family pyrin domain containing 3 (NLRP3). Our findings showed that EPE not only had antihyperglycemic effects but also improved renal function in db/db mice. A histological examination of the kidney by immunohistochemistry indicated that EPE can improve kidney function by ameliorating glomerular morphological damage following glomerular injury; alleviating proteinuria by upregulating the expression of nephrin, a biomarker of early glomerular damage; and inhibiting glomerular expansion and tubular fibrosis. Moreover, the administration of EPE to db/db mice increased the expression levels of p- PKCα/t-PKCα but decreased the expression levels of VEGF and renal fibrosis biomarkers (TGF-β1, collagen IV, p-Smad2, p-Smad3, and Smad4), as shown by Western blot analyses. These results implied that EPE as a supplement has a protective effect against renal dysfunction through the amelioration of insulin resistance as well as the suppression of nephritis and fibrosis in a DN model. Full article

(This article belongs to the Special Issue New Insights in Natural Bioactive Compounds 3.0)

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17 pages, 1063 KiB

Open AccessReview

MiRNAs and Microbiota in Non-Small Cell Lung Cancer (NSCLC): Implications in Pathogenesis and Potential Role in Predicting Response to ICI Treatment

by Francesco Nucera, Paolo Ruggeri, Calogera Claudia Spagnolo, Mariacarmela Santarpia, Antonio Ieni, Francesco Monaco, Giovanni Tuccari, Giovanni Pioggia and Sebastiano Gangemi

Int. J. Mol. Sci. 2024, 25(12), 6685; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms25126685 (registering DOI) - 18 Jun 2024

Abstract

Lung cancer (LC) is one of the most prevalent cancers in both men and women and today is still characterized by high mortality and lethality. Several biomarkers have been identified for evaluating the prognosis of non-small cell lung cancer (NSCLC) patients and selecting [...] Read more.

Lung cancer (LC) is one of the most prevalent cancers in both men and women and today is still characterized by high mortality and lethality. Several biomarkers have been identified for evaluating the prognosis of non-small cell lung cancer (NSCLC) patients and selecting the most effective therapeutic strategy for these patients. The introduction of innovative targeted therapies and immunotherapy with immune checkpoint inhibitors (ICIs) for the treatment of NSCLC both in advanced stages and, more recently, also in early stages, has revolutionized and significantly improved the therapeutic scenario for these patients. Promising evidence has also been shown by analyzing both micro-RNAs (miRNAs) and the lung/gut microbiota. MiRNAs belong to the large family of non-coding RNAs and play a role in the modulation of several key mechanisms in cells such as proliferation, differentiation, inflammation, and apoptosis. On the other hand, the microbiota (a group of several microorganisms found in human orgasms such as the gut and lungs and mainly composed by bacteria) plays a key role in the modulation of inflammation and, in particular, in the immune response. Some data have shown that the microbiota and the related microbiome can modulate miRNAs expression and vice versa by regulating several intracellular signaling pathways that are known to play a role in the pathogenesis of lung cancer. This evidence suggests that this axis is key to predicting the prognosis and effectiveness of ICIs in NSCLC treatment and could represent a new target in the treatment of NSCLC. In this review, we highlight the most recent evidence and data regarding the role of both miRNAs and the lung/gut microbiome in the prediction of prognosis and response to ICI treatment, focusing on the link between miRNAs and the microbiome. A new potential interaction based on the underlying modulated intracellular signaling pathways is also shown. Full article

(This article belongs to the Section Molecular Pathology, Diagnostics, and Therapeutics)

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21 pages, 755 KiB

Open AccessReview

Antimicrobial Peptides (AMPs) and the Microbiome in Preterm Infants: Consequences and Opportunities for Future Therapeutics

by Janina Marissen, Lilith Reichert, Christoph Härtel, Mats Ingmar Fortmann, Kirstin Faust, Delfina Msanga, Jürgen Harder, Michael Zemlin, Mercedes Gomez de Agüero, Katja Masjosthusmann and Alexander Humberg

Int. J. Mol. Sci. 2024, 25(12), 6684; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms25126684 (registering DOI) - 18 Jun 2024

Abstract

Antimicrobial peptides (AMPs) are crucial components of the innate immune system in various organisms, including humans. Beyond their direct antimicrobial effects, AMPs play essential roles in various physiological processes. They induce angiogenesis, promote wound healing, modulate immune responses, and serve as chemoattractants for [...] Read more.

Antimicrobial peptides (AMPs) are crucial components of the innate immune system in various organisms, including humans. Beyond their direct antimicrobial effects, AMPs play essential roles in various physiological processes. They induce angiogenesis, promote wound healing, modulate immune responses, and serve as chemoattractants for immune cells. AMPs regulate the microbiome and combat microbial infections on the skin, lungs, and gastrointestinal tract. Produced in response to microbial signals, AMPs help maintain a balanced microbial community and provide a first line of defense against infection. In preterm infants, alterations in microbiome composition have been linked to various health outcomes, including sepsis, necrotizing enterocolitis, atopic dermatitis, and respiratory infections. Dysbiosis, or an imbalance in the microbiome, can alter AMP profiles and potentially lead to inflammation-mediated diseases such as chronic lung disease and obesity. In the following review, we summarize what is known about the vital role of AMPs as multifunctional peptides in protecting newborn infants against infections and modulating the microbiome and immune response. Understanding their roles in preterm infants and high-risk populations offers the potential for innovative approaches to disease prevention and treatment. Full article

(This article belongs to the Special Issue Neonatal Immunology)

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27 pages, 1871 KiB

Open AccessReview

Engineered Antibodies to Improve Efficacy against Neurodegenerative Disorders

by Sarfaraz K. Niazi, Zamara Mariam and Matthias Magoola

Int. J. Mol. Sci. 2024, 25(12), 6683; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms25126683 (registering DOI) - 18 Jun 2024

Abstract

Antibodies that can selectively remove rogue proteins in the brain are an obvious choice to treat neurodegenerative disorders (NDs), but after decades of efforts, only two antibodies to treat Alzheimer’s disease are approved, dozens are in the testing phase, and one was withdrawn, [...] Read more.

Antibodies that can selectively remove rogue proteins in the brain are an obvious choice to treat neurodegenerative disorders (NDs), but after decades of efforts, only two antibodies to treat Alzheimer’s disease are approved, dozens are in the testing phase, and one was withdrawn, and the other halted, likely due to efficacy issues. However, these outcomes should have been evident since these antibodies cannot enter the brain sufficiently due to the blood–brain barrier (BBB) protectant. However, all products can be rejuvenated by binding them with transferrin, preferably as smaller fragments. This model can be tested quickly and at a low cost and should be applied to bapineuzumab, solanezumab, crenezumab, gantenerumab, aducanumab, lecanemab, donanemab, cinpanemab, and gantenerumab, and their fragments. This paper demonstrates that conjugating with transferrin does not alter the binding to brain proteins such as amyloid-β (Aβ) and α-synuclein. We also present a selection of conjugate designs that will allow cleavage upon entering the brain to prevent their exocytosis while keeping the fragments connected to enable optimal binding to proteins. The identified products can be readily tested and returned to patients with the lowest regulatory cost and delays. These engineered antibodies can be manufactured by recombinant engineering, preferably by mRNA technology, as a more affordable solution to meet the dire need to treat neurodegenerative disorders effectively. Full article

(This article belongs to the Special Issue Recent Advances in Autoimmune and Inflammatory Disorders)

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33 pages, 11998 KiB

Open AccessReview

Effects of Cannabinoids on Intestinal Motility, Barrier Permeability, and Therapeutic Potential in Gastrointestinal Diseases

by Kijan Crowley, Łukasz Kiraga, Edyta Miszczuk, Sergiusz Skiba, Joanna Banach, Urszula Latek, Marta Mendel and Magdalena Chłopecka

Int. J. Mol. Sci. 2024, 25(12), 6682; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms25126682 (registering DOI) - 18 Jun 2024

Abstract

Cannabinoids and their receptors play a significant role in the regulation of gastrointestinal (GIT) peristalsis and intestinal barrier permeability. This review critically evaluates current knowledge about the mechanisms of action and biological effects of endocannabinoids and phytocannabinoids on GIT functions and the potential [...] Read more.

Cannabinoids and their receptors play a significant role in the regulation of gastrointestinal (GIT) peristalsis and intestinal barrier permeability. This review critically evaluates current knowledge about the mechanisms of action and biological effects of endocannabinoids and phytocannabinoids on GIT functions and the potential therapeutic applications of these compounds. The results of ex vivo and in vivo preclinical data indicate that cannabinoids can both inhibit and stimulate gut peristalsis, depending on various factors. Endocannabinoids affect peristalsis in a cannabinoid (CB) receptor-specific manner; however, there is also an important interaction between them and the transient receptor potential cation channel subfamily V member 1 (TRPV1) system. Phytocannabinoids such as Δ9-tetrahydrocannabinol (THC) and cannabidiol (CBD) impact gut motility mainly through the CB1 receptor. They were also found to improve intestinal barrier integrity, mainly through CB1 receptor stimulation but also via protein kinase A (PKA), mitogen-associated protein kinase (MAPK), and adenylyl cyclase signaling pathways, as well as by influencing the expression of tight junction (TJ) proteins. The anti-inflammatory effects of cannabinoids in GIT disorders are postulated to occur by the lowering of inflammatory factors such as myeloperoxidase (MPO) activity and regulation of cytokine levels. In conclusion, there is a prospect of utilizing cannabinoids as components of therapy for GIT disorders. Full article

(This article belongs to the Special Issue Natural-Derived Bioactive Compounds in Disease Treatment)

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20 pages, 2397 KiB

Open AccessReview

Adipocyte Mitochondria: Deciphering Energetic Functions across Fat Depots in Obesity and Type 2 Diabetes

by Snehasis Das, Alpana Mukhuty, Gregory P. Mullen and Michael C. Rudolph

Int. J. Mol. Sci. 2024, 25(12), 6681; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms25126681 (registering DOI) - 18 Jun 2024

Abstract

Adipose tissue, a central player in energy balance, exhibits significant metabolic flexibility that is often compromised in obesity and type 2 diabetes (T2D). Mitochondrial dysfunction within adipocytes leads to inefficient lipid handling and increased oxidative stress, which together promote systemic metabolic disruptions central [...] Read more.

Adipose tissue, a central player in energy balance, exhibits significant metabolic flexibility that is often compromised in obesity and type 2 diabetes (T2D). Mitochondrial dysfunction within adipocytes leads to inefficient lipid handling and increased oxidative stress, which together promote systemic metabolic disruptions central to obesity and its complications. This review explores the pivotal role that mitochondria play in altering the metabolic functions of the primary adipocyte types, white, brown, and beige, within the context of obesity and T2D. Specifically, in white adipocytes, these dysfunctions contribute to impaired lipid processing and an increased burden of oxidative stress, worsening metabolic disturbances. Conversely, compromised mitochondrial function undermines their thermogenic capabilities, reducing the capacity for optimal energy expenditure in brown adipocytes. Beige adipocytes uniquely combine the functional properties of white and brown adipocytes, maintaining morphological similarities to white adipocytes while possessing the capability to transform into mitochondria-rich, energy-burning cells under appropriate stimuli. Each type of adipocyte displays unique metabolic characteristics, governed by the mitochondrial dynamics specific to each cell type. These distinct mitochondrial metabolic phenotypes are regulated by specialized networks comprising transcription factors, co-activators, and enzymes, which together ensure the precise control of cellular energy processes. Strong evidence has shown impaired adipocyte mitochondrial metabolism and faulty upstream regulators in a causal relationship with obesity-induced T2D. Targeted interventions aimed at improving mitochondrial function in adipocytes offer a promising therapeutic avenue for enhancing systemic macronutrient oxidation, thereby potentially mitigating obesity. Advances in understanding mitochondrial function within adipocytes underscore a pivotal shift in approach to combating obesity and associated comorbidities. Reigniting the burning of calories in adipose tissues, and other important metabolic organs such as the muscle and liver, is crucial given the extensive role of adipose tissue in energy storage and release. Full article

(This article belongs to the Special Issue Molecular Research in Obesity and Obesity Related Disorders: 2nd Edition)

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31 pages, 15716 KiB

Open AccessArticle

Effect of Short-Term Restraint Stress on the Hypothalamic Transcriptome Profiles of Rats with Inherited Stress-Induced Arterial Hypertension (ISIAH) and Normotensive Wistar Albino Glaxo (WAG) Rats

by Dmitry Yu. Oshchepkov, Yulia V. Makovka, Larisa A. Fedoseeva, Alisa A. Seryapina, Arcady L. Markel and Olga E. Redina

Int. J. Mol. Sci. 2024, 25(12), 6680; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms25126680 (registering DOI) - 18 Jun 2024

Abstract

Emotional stress is one of the health risk factors in the modern human lifestyle. Stress exposure can provoke the manifestation of various pathological conditions, one of which is a sharp increase in the blood pressure level. In the present study, we analyzed changes [...] Read more.

Emotional stress is one of the health risk factors in the modern human lifestyle. Stress exposure can provoke the manifestation of various pathological conditions, one of which is a sharp increase in the blood pressure level. In the present study, we analyzed changes in the transcriptome profiles of the hypothalamus of hypertensive ISIAH and normotensive WAG rats exposed to a single short-term restraint stress (the rat was placed in a tight wire-mesh cage for 2 h). This type of stress can be considered emotional stress. The functional annotation of differentially expressed genes allowed us to identify the most significantly altered biological processes in the hypothalamus of hypertensive and normotensive rats. The study made it possible to identify a group of genes that describe a general response to stress, independent of the rat genotype, as well as a hypothalamic response to stress specific to each strain. The alternatively changing expression of the Npas4 (neuronal PAS domain protein 4) gene, which is downregulated in the hypothalamus of the control WAG rats and induced in the hypothalamus of hypertensive ISIAH rats, is suggested to be the key event for understanding inter-strain differences in the hypothalamic response to stress. The stress-dependent ISIAH strain-specific induction of Fos and Jun gene transcription may play a crucial role in neuronal activation in this rat strain. The data obtained can be potentially useful in the selection of molecular targets for the development of pharmacological approaches to the correction of stress-induced pathologies related to neuronal excitability, taking into account the hypertensive status of the patients. Full article

(This article belongs to the Special Issue Developmental Biology: Computational and Experimental Approaches)

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16 pages, 3996 KiB

Open AccessArticle

Adult Inception of Ketogenic Diet Therapy Increases Sleep during the Dark Cycle in C57BL/6J Wild Type and Fragile X Mice

by Pamela R. Westmark, Timothy J. Swietlik, Ethan Runde, Brian Corsiga, Rachel Nissan, Brynne Boeck, Ricky Granger, Erica Jennings, Maya Nebbia, Andrew Thauwald, Greg Lyon, Rama K. Maganti and Cara J. Westmark

Int. J. Mol. Sci. 2024, 25(12), 6679; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms25126679 (registering DOI) - 18 Jun 2024

Abstract

Sleep problems are a significant phenotype in children with fragile X syndrome. Our prior work assessed sleep–wake cycles in Fmr1^KO male mice and wild type (WT) littermate controls in response to ketogenic diet therapy where mice were treated from weaning (postnatal day [...] Read more.

Sleep problems are a significant phenotype in children with fragile X syndrome. Our prior work assessed sleep–wake cycles in Fmr1^KO male mice and wild type (WT) littermate controls in response to ketogenic diet therapy where mice were treated from weaning (postnatal day 18) through study completion (5–6 months of age). A potentially confounding issue with commencing treatment during an active period of growth is the significant reduction in weight gain in response to the ketogenic diet. The aim here was to employ sleep electroencephalography (EEG) to assess sleep–wake cycles in mice in response to the Fmr1 genotype and a ketogenic diet, with treatment starting at postnatal day 95. EEG results were compared with prior sleep outcomes to determine if the later intervention was efficacious, as well as with published rest-activity patterns to determine if actigraphy is a viable surrogate for sleep EEG. The data replicated findings that Fmr1^KO mice exhibit sleep–wake patterns similar to wild type littermates during the dark cycle when maintained on a control purified-ingredient diet but revealed a genotype-specific difference during hours 4–6 of the light cycle of the increased wake (decreased sleep and NREM) state in Fmr1^KO mice. Treatment with a high-fat, low-carbohydrate ketogenic diet increased the percentage of NREM sleep in both wild type and Fmr1^KO mice during the dark cycle. Differences in sleep microstructure (length of wake bouts) supported the altered sleep states in response to ketogenic diet. Commencing ketogenic diet treatment in adulthood resulted in a 15% (WT) and 8.6% (Fmr1^KO) decrease in body weight after 28 days of treatment, but not the severe reduction in body weight associated with starting treatment at weaning. We conclude that the lack of evidence for improved sleep during the light cycle (mouse sleep time) in Fmr1^KO mice in response to ketogenic diet therapy in two studies suggests that ketogenic diet may not be beneficial in treating sleep problems associated with fragile X and that actigraphy is not a reliable surrogate for sleep EEG in mice. Full article

(This article belongs to the Special Issue From Molecular Mechanism to Therapy in Autism Spectrum Disorder 2.0)

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15 pages, 1093 KiB

Open AccessReview

From Gut Microbiota to Brain Waves: The Potential of the Microbiome and EEG as Biomarkers for Cognitive Impairment

by Mahathi Krothapalli, Lauren Buddendorff, Hariom Yadav, Nathan D. Schilaty and Shalini Jain

Int. J. Mol. Sci. 2024, 25(12), 6678; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms25126678 (registering DOI) - 18 Jun 2024

Abstract

Alzheimer’s disease (AD) is a prevalent neurodegenerative disorder and a leading cause of dementia. Aging is a significant risk factor for AD, emphasizing the importance of early detection since symptoms cannot be reversed once the advanced stage is reached. Currently, there is no [...] Read more.

Alzheimer’s disease (AD) is a prevalent neurodegenerative disorder and a leading cause of dementia. Aging is a significant risk factor for AD, emphasizing the importance of early detection since symptoms cannot be reversed once the advanced stage is reached. Currently, there is no established method for early AD diagnosis. However, emerging evidence suggests that the microbiome has an impact on cognitive function. The gut microbiome and the brain communicate bidirectionally through the gut–brain axis, with systemic inflammation identified as a key connection that may contribute to AD. Gut dysbiosis is more prevalent in individuals with AD compared to their cognitively healthy counterparts, leading to increased gut permeability and subsequent systemic inflammation, potentially causing neuroinflammation. Detecting brain activity traditionally involves invasive and expensive methods, but electroencephalography (EEG) poses as a non-invasive alternative. EEG measures brain activity and multiple studies indicate distinct patterns in individuals with AD. Furthermore, EEG patterns in individuals with mild cognitive impairment differ from those in the advanced stage of AD, suggesting its potential as a method for early indication of AD. This review aims to consolidate existing knowledge on the microbiome and EEG as potential biomarkers for early-stage AD, highlighting the current state of research and suggesting avenues for further investigation. Full article

(This article belongs to the Special Issue The Microbiota-Gut-Brain Axis in Relation to Non-communicable Diseases)

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14 pages, 3931 KiB

Open AccessArticle

Sustainable Synthesis of the Active Pharmaceutical Ingredient Atenolol in Deep Eutectic Solvents

by Debora Procopio, Carlo Siciliano, Assunta Perri, Gabriela Guillena, Diego J. Ramón and Maria Luisa Di Gioia

Int. J. Mol. Sci. 2024, 25(12), 6677; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms25126677 (registering DOI) - 18 Jun 2024

Abstract

Atenolol, one of the top five best-selling drugs in the world today used to treat angina and hypertension, and to reduce the risk of death after a heart attack, faces challenges in current synthetic methods to address inefficiencies and environmental concerns. The traditional [...] Read more.

Atenolol, one of the top five best-selling drugs in the world today used to treat angina and hypertension, and to reduce the risk of death after a heart attack, faces challenges in current synthetic methods to address inefficiencies and environmental concerns. The traditional synthesis of this drug involves a process that generates a large amount of waste and other by-products that need disposal. This study presents a one-pot DES-based sustainable protocol for synthesizing atenolol. The use of the DES allowed the entire process to be conducted with no need for additional bases or catalysts, in short reaction times, under mild conditions, and avoiding chromatographic purification. The overall yield of atenolol was 95%. The scalability of the process to gram-scale production was successfully demonstrated, emphasizing its potential in industrial applications. Finally, the ‘greenness’ evaluation, performed using the First Pass CHEM21 Metrics Toolkit, highlighted the superiority in terms of the atom economy, the reaction mass efficiency, and the overall process mass intensity of the DES-based synthesis compared with the already existing methods. Full article

(This article belongs to the Special Issue Recent Advances in Medicinal Chemistry: Green Synthesis of Bioactive Molecules)

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8 pages, 844 KiB

Open AccessCommunication

Analysis of CYP1B1 Polymorphisms in Lung Cancer Patients Using Novel, Quick and Easy Methods Based on CAPS and ACRS-PCR Techniques

by Adam Dąbrowski, Maciej Nowicki, Aleksandra Budzyńska, Jakub Suchodolski, Rafał Ogórek, Mariusz Chabowski and Katarzyna Przywara

Int. J. Mol. Sci. 2024, 25(12), 6676; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms25126676 (registering DOI) - 18 Jun 2024

Abstract

Within the sequence of the CYP1B1 gene, more than 50 polymorphisms, resulting from single-nucleotide polymorphisms (SNPs), have been described. Some of them play an important role as specific genetic markers in the process of carcinogenesis and for therapeutic purposes. In this publication, we [...] Read more.

Within the sequence of the CYP1B1 gene, more than 50 polymorphisms, resulting from single-nucleotide polymorphisms (SNPs), have been described. Some of them play an important role as specific genetic markers in the process of carcinogenesis and for therapeutic purposes. In this publication, we present methods we have developed that enable the specific and unambiguous identification of four polymorphisms that result in amino acid changes: c. 142C > G, c. 355G > T, c. 1294C > G, and c. 1358A > G. Our studies are based on cleaved amplified polymorphic sequences (CAPSs) and artificially created restriction site (ACRS) PCR techniques; therefore, they require only basic laboratory equipment and low financial outlays. Utilizing the described methods allows for the reduction of research time and cost, and the minimization of errors. Their effectiveness and efficiency depend on the careful design of appropriate primers and the precise selection of suitable restriction enzymes. As a result, further confirmation by sequencing is not necessary. Using the developed method, we examined 63 patients diagnosed with lung cancer and observed a 1.5 to 2.1 times higher frequency of the analyzed single-nucleotide polymorphisms compared to the frequency in the European population. Full article

(This article belongs to the Special Issue Lung Cancers: An Update on Molecular Diagnostics and Therapy)

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13 pages, 6940 KiB

Open AccessArticle

Graphene Far-Infrared Irradiation Can Effectively Relieve the Blood Pressure Level of Rat Untr-HT in Primary Hypertension

by Guanjie Lu, Haotong Guo, Yi Zhang, Meng Zhang, Tao Zhang, Ge Hu and Qian Zhang

Int. J. Mol. Sci. 2024, 25(12), 6675; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms25126675 (registering DOI) - 18 Jun 2024

Abstract

Graphene, when electrified, generates far-infrared radiation within the wavelength range of 4 μm to 14 μm. This range closely aligns with the far-infrared band (3 μm to 15 μm), which produces unique physiological effects. Contraction and relaxation of vascular smooth muscle play a [...] Read more.

Graphene, when electrified, generates far-infrared radiation within the wavelength range of 4 μm to 14 μm. This range closely aligns with the far-infrared band (3 μm to 15 μm), which produces unique physiological effects. Contraction and relaxation of vascular smooth muscle play a significant role in primary hypertension, involving the nitric oxide-soluble guanylate cyclase–cyclic guanosine monophosphate pathway and the renin–angiotensin–aldosterone system. This study utilized spontaneously hypertensive rats (SHRs) as an untr-HT to investigate the impact of far-infrared radiation at specific wavelengths generated by electrified graphene on vascular smooth muscle and blood pressure. After 7 weeks, the blood pressure of the untr-HT group rats decreased significantly with a notable reduction in the number of vascular wall cells and the thickness of the vascular wall, as well as a decreased ratio of vessel wall thickness to lumen diameter. Additionally, blood flow perfusion significantly increased, and the expression of F-actin in vascular smooth muscle myosin decreased significantly. Serum levels of angiotensin II (Ang-II) and endothelin 1 (ET-1) were significantly reduced, while nitric oxide synthase (eNOS) expression increased significantly. At the protein level, eNOS expression decreased significantly, while α-SMA expression increased significantly in aortic tissue. At the gene level, expressions of eNOS and α-SMA in aortic tissue significantly increased. Furthermore, the content of nitric oxide (NO) in the SHR’s aortic tissue increased significantly. These findings confirm that graphene far-infrared radiation enhances microcirculation, regulates cytokines affecting vascular smooth muscle contraction, and modifies vascular morphology and smooth muscle phenotype, offering relief for primary hypertension. Full article

(This article belongs to the Special Issue Advancements in Biocompatible Materials for Dental Applications)

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12 pages, 2062 KiB

Open AccessArticle

Exploring Novel Biomarkers for an Acute Coronary Syndrome Diagnosis Utilizing Plasma Metabolomics

by Masayuki Shibata, Masahiro Sugimoto, Norikazu Watanabe and Atsuo Namiki

Int. J. Mol. Sci. 2024, 25(12), 6674; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms25126674 - 18 Jun 2024

Abstract

Acute coronary syndrome (ACS) is a life-threatening condition that requires a prompt diagnosis and therapeutic intervention. Although serum troponin I and creatinine kinase-MB (CK-MB) are established biomarkers for ACS, reaching diagnostic values for ACS may take several hours. In this study, we attempted [...] Read more.

Acute coronary syndrome (ACS) is a life-threatening condition that requires a prompt diagnosis and therapeutic intervention. Although serum troponin I and creatinine kinase-MB (CK-MB) are established biomarkers for ACS, reaching diagnostic values for ACS may take several hours. In this study, we attempted to explore novel biomarkers for ACS with higher sensitivity than that of troponin I and CK-MB. The metabolomic profiles of 18 patients with ACS upon hospital arrival and those of the age-matched control (HC) group of 24 healthy volunteers were analyzed using liquid chromatography time-of-flight mass spectrometry. Volcano plots showed 24 metabolites whose concentrations differed significantly between the ACS and HC groups. Using these data, we developed a multiple logistic regression model for the ACS diagnosis, in which lysine, isocitrate, and tryptophan were selected as minimum-independent metabolites. The area under the receiver operating characteristic curve value for discriminating ACS from HC was 1.00 (95% confidence interval [CI]: 1.00–1.00). In contrast, those for troponin I and CK-MB were 0.917 (95% confidence interval [CI]: 0.812–1.00) and 0.988 (95% CI: 0.966–1.00), respectively. This study showed the potential for combining three plasma metabolites to discriminate ACS from HC with a higher sensitivity than troponin I and CK-MB. Full article

(This article belongs to the Special Issue Molecular Biomarkers in Cardiovascular Disease)

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11 pages, 571 KiB

Open AccessReview

P2X7 Variants in Pathophysiology

by Anna Pegoraro, Marianna Grignolo, Luigia Ruo, Ludovica Ricci and Elena Adinolfi

Int. J. Mol. Sci. 2024, 25(12), 6673; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms25126673 - 18 Jun 2024

Abstract

P2X7 receptor activation by extracellular adenosine triphosphate (eATP) modulates different intracellular pathways, including pro-inflammatory and tumor-promoting cascades. ATP is released by cells and necrotic tissues during stressful conditions and accumulates mainly in the inflammatory and tumoral microenvironments. As a consequence, both the P2X7 [...] Read more.

P2X7 receptor activation by extracellular adenosine triphosphate (eATP) modulates different intracellular pathways, including pro-inflammatory and tumor-promoting cascades. ATP is released by cells and necrotic tissues during stressful conditions and accumulates mainly in the inflammatory and tumoral microenvironments. As a consequence, both the P2X7 blockade and agonism have been proposed as therapeutic strategies in phlogosis and cancer. Nevertheless, most studies have been carried out on the WT fully functional receptor variant. In recent years, the discovery of P2X7 variants derived by alternative splicing mechanisms or single-nucleotide substitutions gave rise to the investigation of these new P2X7 variants’ roles in different processes and diseases. Here, we provide an overview of the literature covering the function of human P2X7 splice variants and polymorphisms in diverse pathophysiological contexts, paying particular attention to their role in oncological and neuroinflammatory conditions. Full article

(This article belongs to the Section Biochemistry)

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15 pages, 6592 KiB

Open AccessArticle

The Stylo Cysteine-Rich Peptide SgSnakin1 Is Involved in Aluminum Tolerance through Enhancing Reactive Oxygen Species Scavenging

by Xueqiong Guo, Shengnan Zhu, Yingbin Xue, Yan Lin, Jingying Mao, Shuyue Li, Cuiyue Liang, Xing Lu and Jiang Tian

Int. J. Mol. Sci. 2024, 25(12), 6672; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms25126672 - 18 Jun 2024

Abstract

Stylo (Stylosanthes spp.) is an important pasture legume with strong aluminum (Al) resistance. However, the molecular mechanisms underlying its Al tolerance remain fragmentary. Due to the incomplete genome sequence information of stylo, we first conducted full-length transcriptome sequencing for stylo root tips [...] Read more.

Stylo (Stylosanthes spp.) is an important pasture legume with strong aluminum (Al) resistance. However, the molecular mechanisms underlying its Al tolerance remain fragmentary. Due to the incomplete genome sequence information of stylo, we first conducted full-length transcriptome sequencing for stylo root tips treated with and without Al and identified three Snakin/GASA genes, namely, SgSnakin1, SgSnakin2, and SgSnakin3. Through quantitative RT-PCR, we found that only SgSnakin1 was significantly upregulated by Al treatments in stylo root tips. Histochemical localization assays further verified the Al-enhanced expression of SgSnakin1 in stylo root tips. Subcellular localization in both tobacco and onion epidermis cells showed that SgSnakin1 localized to the cell wall. Overexpression of SgSnakin1 conferred Al tolerance in transgenic Arabidopsis, as reflected by higher relative root growth and cell vitality, as well as lower Al concentration in the roots of transgenic plants. Additionally, overexpression of SgSnakin1 increased the activities of SOD and POD and decreased the levels of O₂^·− and H₂O₂ in transgenic Arabidopsis in response to Al stress. These findings indicate that SgSnakin1 may function in Al resistance by enhancing the scavenging of reactive oxygen species through the regulation of antioxidant enzyme activities. Full article

(This article belongs to the Special Issue Plant Responses to Heavy Metals: From Deficiency to Excess)

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21 pages, 9151 KiB

Open AccessArticle

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://0-doi-org.brum.beds.ac.uk/10.3390/ijms25126671 - 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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Int. J. Mol. Sci., Volume 25, Issue 12 (June-2 2024) – 414 articles

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