The 2023 MDPI Annual Report has
been released!
 
32 pages, 1578 KiB  
Review
Anticancer Mechanism of Astragalus Polysaccharide and Its Application in Cancer Immunotherapy
by Ziqing He, Xiyu Liu, Simin Qin, Qun Yang, Jintong Na, Zhigang Xue and Liping Zhong
Pharmaceuticals 2024, 17(5), 636; https://doi.org/10.3390/ph17050636 (registering DOI) - 15 May 2024
Abstract
Astragalus polysaccharide (APS) derived from A. membranaceus plays a crucial role in traditional Chinese medicine. These polysaccharides have shown antitumor effects and are considered safe. Thus, they have become increasingly important in cancer immunotherapy. APS can limit the spread of cancer by influencing [...] Read more.
Astragalus polysaccharide (APS) derived from A. membranaceus plays a crucial role in traditional Chinese medicine. These polysaccharides have shown antitumor effects and are considered safe. Thus, they have become increasingly important in cancer immunotherapy. APS can limit the spread of cancer by influencing immune cells, promoting cell death, triggering cancer cell autophagy, and impacting the tumor microenvironment. When used in combination with other therapies, APS can enhance treatment outcomes and reduce toxicity and side effects. APS combined with immune checkpoint inhibitors, relay cellular immunotherapy, and cancer vaccines have broadened the application of cancer immunotherapy and enhanced treatment effectiveness. By summarizing the research on APS in cancer immunotherapy over the past two decades, this review elaborates on the anticancer mechanism of APS and its use in cancer immunotherapy and clinical trials. Considering the multiple roles of APS, this review emphasizes the importance of using APS as an adjunct to cancer immunotherapy and compares other polysaccharides with APS. This discussion provides insights into the specific mechanism of action of APS, reveals the molecular targets of APS for developing effective clinical strategies, and highlights the wide application of APS in clinical cancer therapy in the future. Full article
(This article belongs to the Section Biopharmaceuticals)
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19 pages, 3516 KiB  
Article
Dysregulation of lncRNA MALAT1 Contributes to Lung Cancer in African Americans by Modulating the Tumor Immune Microenvironment
by Jin Li, Pushpa Dhilipkannah, Van K. Holden, Ashutosh Sachdeva, Nevins W. Todd and Feng Jiang
Cancers 2024, 16(10), 1876; https://doi.org/10.3390/cancers16101876 (registering DOI) - 15 May 2024
Abstract
African American (AA) populations present with notably higher incidence and mortality rates from lung cancer in comparison to other racial groups. Here, we elucidated the contribution of long non-coding RNAs (lncRNAs) in the racial disparities and their potential clinical applications in both diagnosis [...] Read more.
African American (AA) populations present with notably higher incidence and mortality rates from lung cancer in comparison to other racial groups. Here, we elucidated the contribution of long non-coding RNAs (lncRNAs) in the racial disparities and their potential clinical applications in both diagnosis and therapeutic strategies. AA patients had elevated plasma levels of MALAT1 and PVT1 compared with cancer-free smokers. Incorporating these lncRNAs as plasma biomarkers, along with smoking history, achieved 81% accuracy in diagnosis of lung cancer in AA patients. We observed a rise in MALAT1 expression, correlating with increased levels of monocyte chemoattractant protein-1 (MCP-1) and CD68, CD163, CD206, indicative of tumor-associated macrophages in lung tumors of AA patients. Forced MALAT1 expression led to enhanced growth and invasiveness of lung cancer cells, both in vitro and in vivo, accompanied by elevated levels of MCP-1, CD68, CD163, CD206, and KI67. Mechanistically, MALAT1 acted as a competing endogenous RNA to directly interact with miR-206, subsequently affecting MCP-1 expression and macrophage activity, and enhanced the tumorigenesis. Targeting MALAT1 significantly reduced tumor sizes in animal models. Therefore, dysregulated MALAT1 contributes to lung cancer disparities in AAs by modulating the tumor immune microenvironment through its interaction with miR-206, thereby presenting novel diagnostic and therapeutic targets. Full article
(This article belongs to the Section Tumor Microenvironment)
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21 pages, 3478 KiB  
Review
Life Cycle Assessment of Pervious Pavements: Integrative Review and Novel Ideas of Analysis
by Igor Catão Martins Vaz, Lucas Niehuns Antunes, Enedir Ghisi and Liseane Padilha Thives
Water 2024, 16(10), 1403; https://doi.org/10.3390/w16101403 (registering DOI) - 15 May 2024
Abstract
Life Cycle Assessment (LCA) and Life Cycle Cost Assessment (LCCA) are essential tools for environmental and economic assessment and decision-making in an evolving world with continuous climate change. In the same conditions, one of the most used and assessed solutions for facing climate [...] Read more.
Life Cycle Assessment (LCA) and Life Cycle Cost Assessment (LCCA) are essential tools for environmental and economic assessment and decision-making in an evolving world with continuous climate change. In the same conditions, one of the most used and assessed solutions for facing climate change is using pervious pavements, with many papers proving its benefits. However, the literature has shown a need for more research on the LCA methodological aspects in the context of new green infrastructure. This research aims to review pervious pavements, LCA and LCCA combined, while discussing possible differences in boundaries, functional units, and other parameters. Thus, a string search was performed, leading to 89 documents. The main results indicate LCA is usually scope-bounded in the field of pervious pavements, with different benefits and characteristics, such as traffic impact, urban heat island effects, and carbonation. As for LCCA, private and public cost differentiation provide a scope definition and monetisation difficulties. In conclusion, both tools offer promising applications in pervious pavements. As a significant deliverable and recommendation of this paper, both LCA and LCCA theoretical frameworks were provided based on the benefits and specific characteristics included in the literature. These frameworks introduce novel ideas and perspectives, inviting further exploration and discussion. Full article
(This article belongs to the Section Urban Water Management)
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11 pages, 1044 KiB  
Case Report
Testing for Level–Degree Interaction Effects in Two-Factor Fixed-Effects ANOVA When the Levels of Only One Factor Are Ordered
by J. C. W. Rayner and G. C. Livingston, Jr.
Stats 2024, 7(2), 481-491; https://doi.org/10.3390/stats7020029 (registering DOI) - 15 May 2024
Abstract
In testing for main effects, the use of orthogonal contrasts for balanced designs with the factor levels not ordered is well known. Here, we consider two-factor fixed-effects ANOVA with the levels of one factor ordered and one not ordered. The objective is to [...] Read more.
In testing for main effects, the use of orthogonal contrasts for balanced designs with the factor levels not ordered is well known. Here, we consider two-factor fixed-effects ANOVA with the levels of one factor ordered and one not ordered. The objective is to extend the idea of decomposing the main effect to decomposing the interaction. This is achieved by defining level–degree coefficients and testing if they are zero using permutation testing. These tests give clear insights into what may be causing a significant interaction, even for the unbalanced model. Full article
(This article belongs to the Section Statistical Methods)
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8 pages, 1956 KiB  
Communication
Anticancer Effects of the Novel Pyrazolyl-Urea GeGe-3
by Ashleigh Williams, Emma Cooper, Bethany Clark, Laura Perry, Marco Ponassi, Erika Iervasi, Chiara Brullo, Alexander Greenhough and Michael Ladomery
Int. J. Mol. Sci. 2024, 25(10), 5380; https://doi.org/10.3390/ijms25105380 (registering DOI) - 15 May 2024
Abstract
In a screen of over 200 novel pyrazole compounds, ethyl 1-(2-hydroxypentyl)-5-(3-(3-(trifluoromethyl) phenyl)ureido)-1H-pyrazole-4-carboxylate (named GeGe-3) has emerged as a potential anticancer compound. GeGe-3 displays potent anti-angiogenic properties through the presumptive targeting of the protein kinase DMPK1 and the Ca2+-binding protein [...] Read more.
In a screen of over 200 novel pyrazole compounds, ethyl 1-(2-hydroxypentyl)-5-(3-(3-(trifluoromethyl) phenyl)ureido)-1H-pyrazole-4-carboxylate (named GeGe-3) has emerged as a potential anticancer compound. GeGe-3 displays potent anti-angiogenic properties through the presumptive targeting of the protein kinase DMPK1 and the Ca2+-binding protein calreticulin. We further explored the anticancer potential of GeGe-3 on a range of established cancer cell lines, including PC3 (prostate adenocarcinoma), SKMEL-28 (cutaneous melanoma), SKOV-3 (ovarian adenocarcinoma), Hep-G2 (hepatocellular carcinoma), MDA-MB231, SKBR3, MCF7 (breast adenocarcinoma), A549 (lung carcinoma), and HeLa (cervix epithelioid carcinoma). At concentrations in the range of 10 μM, GeGe-3 significantly restricted cell proliferation and metabolism. GeGe-3 also reduced PC3 cell migration in a standard wound closure and trans-well assay. Together, these results confirm the anticancer potential of GeGe-3 and underline the need for more detailed pre-clinical investigations into its molecular targets and mechanisms of action. Full article
(This article belongs to the Special Issue Synthesis and Biological Evaluation of Pyrazole Derivatives)
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14 pages, 3603 KiB  
Article
Xyloglucan–Cellulose Nanocrystals Mixtures: A Case Study of Nanocolloidal Hydrogels and Levers for Tuning Functional Properties
by Géraldine Rangel, Céline Moreau, Ana Villares, Christophe Chassenieux and Bernard Cathala
Gels 2024, 10(5), 334; https://doi.org/10.3390/gels10050334 (registering DOI) - 15 May 2024
Abstract
The development of fully biobased hydrogels obtained by simple routes and in the absence of toxic or environmentally harmful reagents is a major challenge in meeting new societal demands. In this work, we discuss the development of hydrogels made from cellulose nanocrystals (CNCs) [...] Read more.
The development of fully biobased hydrogels obtained by simple routes and in the absence of toxic or environmentally harmful reagents is a major challenge in meeting new societal demands. In this work, we discuss the development of hydrogels made from cellulose nanocrystals (CNCs) and xyloglucan (XG), two non-toxic, renewable, and biobased components. We present three strategies to fine-tune the functional properties. The first one consists in varying the XG/CNC ratio that leads to the modulation of the mechanical properties of hydrogels as well as a better comprehension of the gel mechanism formation. The second relies on tuning the XG chains’ interaction by enzymatic modification to achieve thermoresponsive systems. Finally, the third one is based on the increase in the hydrogel solid content by osmotic concentration. The high-solid-content gels were found to have very high mechanical properties and self-healing properties that can be used for molding materials. Overall, these approaches are a case study of potential modifications and properties offered by biobased nanocolloidal hydrogels. Full article
(This article belongs to the Special Issue Cellulose-Based Gels: Synthesis, Properties, and Applications)
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14 pages, 983 KiB  
Review
Polymerase I as a Target for Treating Neurodegenerative Disorders
by Mark S. LeDoux
Biomedicines 2024, 12(5), 1092; https://doi.org/10.3390/biomedicines12051092 (registering DOI) - 15 May 2024
Abstract
Polymerase I (Pol I) is at the epicenter of ribosomal RNA (rRNA) synthesis. Pol I is a target for the treatment of cancer. Given the many cellular commonalities between cancer and neurodegeneration (i.e., different faces of the same coin), it seems rational to [...] Read more.
Polymerase I (Pol I) is at the epicenter of ribosomal RNA (rRNA) synthesis. Pol I is a target for the treatment of cancer. Given the many cellular commonalities between cancer and neurodegeneration (i.e., different faces of the same coin), it seems rational to consider targeting Pol I or, more generally, rRNA synthesis for the treatment of disorders associated with the death of terminally differentiated neurons. Principally, ribosomes synthesize proteins, and, accordingly, Pol I can be considered the starting point for protein synthesis. Given that cellular accumulation of abnormal proteins such as α-synuclein and tau is an essential feature of neurodegenerative disorders such as Parkinson disease and fronto-temporal dementia, reduction of protein production is now considered a viable target for treatment of these and closely related neurodegenerative disorders. Abnormalities in polymerase I activity and rRNA production may also be associated with nuclear and nucleolar stress, DNA damage, and childhood-onset neuronal death, as is the case for the UBTF E210K neuroregression syndrome. Moreover, restraining the activity of Pol I may be a viable strategy to slow aging. Before starting down the road of Pol I inhibition for treating non-cancerous disorders of the nervous system, many questions must be answered. First, how much Pol I inhibition can neurons tolerate, and for how long? Should inhibition of Pol I be continuous or pulsed? Will cells compensate for Pol I inhibition by upregulating the number of active rDNAs? At present, we have no effective and safe disease modulatory treatments for Alzheimer disease, α-synucleinopathies, or tauopathies, and novel therapeutic targets and approaches must be explored. Full article
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14 pages, 2830 KiB  
Article
Radiogenomics Map-Based Molecular and Imaging Phenotypical Characterization in Localised Prostate Cancer Using Pre-Biopsy Biparametric MR Imaging
by Chidozie N. Ogbonnaya, Basim S. O. Alsaedi, Abeer J. Alhussaini, Robert Hislop, Norman Pratt, J. Douglas Steele, Neil Kernohan and Ghulam Nabi
Int. J. Mol. Sci. 2024, 25(10), 5379; https://doi.org/10.3390/ijms25105379 (registering DOI) - 15 May 2024
Abstract
To create a radiogenomics map and evaluate the correlation between molecular and imaging phenotypes in localized prostate cancer (PCa), using radical prostatectomy histopathology as a reference standard. Radiomic features were extracted from T2-weighted (T2WI) and Apparent Diffusion Coefficient (ADC) images of clinically localized [...] Read more.
To create a radiogenomics map and evaluate the correlation between molecular and imaging phenotypes in localized prostate cancer (PCa), using radical prostatectomy histopathology as a reference standard. Radiomic features were extracted from T2-weighted (T2WI) and Apparent Diffusion Coefficient (ADC) images of clinically localized PCa patients (n = 15) across different Gleason score-based risk categories. DNA extraction was performed on formalin-fixed, paraffin-embedded (FFPE) samples. Gene expression analysis of androgen receptor expression, apoptosis, and hypoxia was conducted using the Chromosome Analysis Suite (ChAS) application and OSCHIP files. The relationship between gene expression alterations and textural features was assessed using Pearson’s correlation analysis. Receiver operating characteristic (ROC) analysis was utilized to evaluate the predictive accuracy of the model. A significant correlation was observed between radiomic texture features and copy number variation (CNV) of genes associated with apoptosis, hypoxia, and androgen receptor (p-value ≤ 0.05). The identified radiomic features, including Sum Entropy ADC, Inverse Difference ADC, Sum Variance T2WI, Entropy T2WI, Difference Variance T2WI, and Angular Secondary Moment T2WI, exhibited potential for predicting cancer grade and biological processes such as apoptosis and hypoxia. Incorporating radiomics and genomics into a prediction model significantly improved the prediction of prostate cancer grade (clinically significant prostate cancer), yielding an AUC of 0.95. Radiomic texture features significantly correlate with genotypes for apoptosis, hypoxia, and androgen receptor expression in localised prostate cancer. Integration of these into the prediction model improved prediction accuracy of clinically significant prostate cancer. Full article
(This article belongs to the Special Issue Male Genitourinary Tumors: Molecular and Cellular Mechanism)
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14 pages, 896 KiB  
Review
Chemokines as Prognostic Factor in Colorectal Cancer Patients: A Systematic Review and Meta-Analysis
by Johanna Fellhofer-Hofer, Clemens Franz, Johannes A. Vey, Christoph Kahlert, Eva Kalkum, Arianeb Mehrabi, Niels Halama, Pascal Probst and Fee Klupp
Int. J. Mol. Sci. 2024, 25(10), 5374; https://doi.org/10.3390/ijms25105374 (registering DOI) - 15 May 2024
Abstract
Chemokines orchestrate many aspects of tumorigenic processes such as angiogenesis, apoptosis and metastatic spread, and related receptors are expressed on tumor cells as well as on inflammatory cells (e.g., tumor-infiltrating T cells, TILs) in the tumor microenvironment. Expressional changes of chemokines and their [...] Read more.
Chemokines orchestrate many aspects of tumorigenic processes such as angiogenesis, apoptosis and metastatic spread, and related receptors are expressed on tumor cells as well as on inflammatory cells (e.g., tumor-infiltrating T cells, TILs) in the tumor microenvironment. Expressional changes of chemokines and their receptors in solid cancers are common and well known, especially in affecting colorectal cancer patient outcomes. Therefore, the aim of this current systematic review and meta-analysis was to classify chemokines as a prognostic biomarker in colorectal cancer patients. A systematic literature search was conducted in PubMed, CENTRAL and Web of Science. Information on the chemokine expression of 25 chemokines in colorectal cancer tissue and survival data of the patients were investigated. The hazard ratio of overall survival and disease-free survival with chemokine expression was examined. The risk of bias was analyzed using Quality in Prognosis Studies. Random effects meta-analysis was performed to determine the impact on overall respectively disease survival. For this purpose, the pooled hazard ratios (HR) and their 95% confidence intervals (CI) were used for calculation. Twenty-five chemokines were included, and the search revealed 5556 publications. A total of thirty-one publications were included in this systematic review and meta-analysis. Overexpression of chemokine receptor CXCR4 was associated with both a significantly reduced overall survival (HR = 2.70, 95%-CI: 1.57 to 4.66, p = 0.0003) as well as disease-free survival (HR = 2.68, 95%-CI: 1.41 to 5.08, p = 0.0026). All other chemokines showed either heterogeneous results or few studies were available. The overall risk of bias for CXCR4 was rated low. At the current level of evidence, this study demonstrates that CXCR4 overexpression in patients with colorectal cancer is associated with a significantly diminished overall as well as disease-free survival. Summed up, this systematic review and meta-analysis reveals CXCR4 as a promising prognostic biomarker. Nevertheless, more evidence is needed to evaluate CXCR4 and its antagonists serving as new therapeutic targets. Full article
(This article belongs to the Special Issue Recent Insights into Colorectal Cancer Treatment)
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14 pages, 1733 KiB  
Review
Cannabinoid and Orexigenic Systems Interplay as a New Focus of Research in Alzheimer’s Disease
by Joan Biel Rebassa, Toni Capó, Jaume Lillo, Iu Raïch, Irene Reyes-Resina and Gemma Navarro
Int. J. Mol. Sci. 2024, 25(10), 5378; https://doi.org/10.3390/ijms25105378 (registering DOI) - 15 May 2024
Abstract
Alzheimer’s disease (AD) remains a significant health challenge, with an increasing prevalence globally. Recent research has aimed to deepen the understanding of the disease pathophysiology and to find potential therapeutic interventions. In this regard, G protein-coupled receptors (GPCRs) have emerged as novel potential [...] Read more.
Alzheimer’s disease (AD) remains a significant health challenge, with an increasing prevalence globally. Recent research has aimed to deepen the understanding of the disease pathophysiology and to find potential therapeutic interventions. In this regard, G protein-coupled receptors (GPCRs) have emerged as novel potential therapeutic targets to palliate the progression of neurodegenerative diseases such as AD. Orexin and cannabinoid receptors are GPCRs capable of forming heteromeric complexes with a relevant role in the development of this disease. On the one hand, the hyperactivation of the orexins system has been associated with sleep–wake cycle disruption and Aβ peptide accumulation. On the other hand, cannabinoid receptor overexpression takes place in a neuroinflammatory environment, favoring neuroprotective effects. Considering the high number of interactions between cannabinoid and orexin systems that have been described, regulation of this interplay emerges as a new focus of research. In fact, in microglial primary cultures of APPSw/Ind mice model of AD there is an important increase in CB2R–OX1R complex expression, while OX1R antagonism potentiates the neuroprotective effects of CB2R. Specifically, pretreatment with the OX1R antagonist has been shown to strongly potentiate CB2R signaling in the cAMP pathway. Furthermore, the blockade of OX1R can also abolish the detrimental effects of OX1R overactivation in AD. In this sense, CB2R–OX1R becomes a new potential therapeutic target to combat AD. Full article
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11 pages, 1216 KiB  
Article
Colonization by Extended-Spectrum β-Lactamase-Producing Enterobacterales and Bacteremia in Hematopoietic Stem Cell Transplant Recipients
by Luiza Arcas Gonçalves, Beatriz Barbosa Anjos, Bruno Melo Tavares, Ana Paula Marchi, Marina Farrel Côrtes, Hermes Ryoiti Higashino, Bruna del Guerra de Carvalho Moraes, José Victor Bortolotto Bampi, Liliane Dantas Pinheiro, Fernanda de Souza Spadao, Vanderson Rocha, Thais Guimarães and Silvia Figueiredo Costa
Antibiotics 2024, 13(5), 448; https://doi.org/10.3390/antibiotics13050448 (registering DOI) - 15 May 2024
Abstract
Background: Assessing the risk of multidrug-resistant colonization and infections is pivotal for optimizing empirical therapy in hematopoietic stem cell transplants (HSCTs). Limited data exist on extended-spectrum β-lactamase-producing Enterobacterales (ESBL-E) colonization in this population. This study aimed to assess whether ESBL-E colonization constitutes a [...] Read more.
Background: Assessing the risk of multidrug-resistant colonization and infections is pivotal for optimizing empirical therapy in hematopoietic stem cell transplants (HSCTs). Limited data exist on extended-spectrum β-lactamase-producing Enterobacterales (ESBL-E) colonization in this population. This study aimed to assess whether ESBL-E colonization constitutes a risk factor for ESBL-E bloodstream infection (BSI) and to evaluate ESBL-E colonization in HSCT recipients. Methods: A retrospective analysis of ESBL-E colonization and BSI in HSCT patients was conducted from August 2019 to June 2022. Weekly swabs were collected and cultured on chromogenic selective media, with PCR identifying the β-lactamase genes. Pulsed-field gel electrophoresis (PFGE) and whole-genome sequencing (WGS) assessed the colonizing strains’ similarities. Results: Of 222 evaluated HSCT patients, 59.45% were colonized by ESBL-E, with 48.4% at admission. The predominant β-lactamase genes were blaTEM (52%) and blaSHV (20%). PFGE analysis did not reveal predominant clusters in 26 E. coli and 15 K. pneumoniae strains. WGS identified ST16 and ST11 as the predominant sequence types among K. pneumoniae. Thirty-three patients developed thirty-five Enterobacterales-BSIs, with nine being third-generation cephalosporin-resistant. No association was found between ESBL-E colonization and ESBL-BSI (p = 0.087). Conclusions: Although the patients presented a high colonization rate of ESBL-E upon admission, no association between colonization and infection were found. Thus, it seems that ESBL screening is not a useful strategy to assess risk factors and guide therapy for ESBL-BSI in HSCT-patients. Full article
(This article belongs to the Special Issue Colonization and Infection of Multi-Drug Resistant Organisms)
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16 pages, 8394 KiB  
Article
Design of a Low-Cost Open-Top Chamber Facility for the Investigation of the Effects of Elevated Carbon Dioxide Levels on Plant Growth
by Nicola Novello, Mani Naiker, Haydee Laza, Kerry B. Walsh and Sabine Tausz-Posch
Hardware 2024, 2(2), 138-153; https://doi.org/10.3390/hardware2020007 (registering DOI) - 15 May 2024
Abstract
Open-top chambers (OTCs) consist of semi-open enclosures used to investigate the impact of elevated carbon dioxide [CO2] on crops and larger plant communities. OTCs have lower operational costs than alternatives such as controlled environment cabinets and Free Air Carbon Dioxide Enrichment [...] Read more.
Open-top chambers (OTCs) consist of semi-open enclosures used to investigate the impact of elevated carbon dioxide [CO2] on crops and larger plant communities. OTCs have lower operational costs than alternatives such as controlled environment cabinets and Free Air Carbon Dioxide Enrichment (FACE). A low-cost design is presented for an OTC with a surface area of 1.2 m2 and a target elevated CO2 concentration [CO2] of 650 µmol mol−1 adequate for trials involving cereals or grain legumes. The elevated CO2 chambers maintained an average concentration ± standard deviation of 652 ± 37 µmol mol−1 despite wind and air turbulences, in comparison to 407 ± 10 µmol mol−1 for non-enriched chambers. Relative to ambient (non-chamber) conditions, plants in the chambers were exposed to slightly warmer conditions (2.3 °C in daylight hours; 0.6 °C during night environment). The materials’ cost for constructing the chambers was USD 560 per chamber, while the CO2 control system for four chambers dedicated to CO2-enriched conditions cost USD 5388. To maintain the concentration of 650 µmol mol−1 during daylight hours, each chamber consumed 1.38 L min−1 of CO2. This means that a size G CO2 cylinder was consumed in 8–9 days in the operation of two chambers (at USD 40). Full article
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30 pages, 8533 KiB  
Article
Evaluating the Role of Neddylation Modifications in Kidney Renal Clear Cell Carcinoma: An Integrated Approach Using Bioinformatics, MLN4924 Dosing Experiments, and RNA Sequencing
by Dequan Liu, Guangzhen Wu, Shijin Wang, Xu Zheng and Xiangyu Che
Pharmaceuticals 2024, 17(5), 635; https://doi.org/10.3390/ph17050635 (registering DOI) - 15 May 2024
Abstract
Background: Neddylation, a post-translational modification process, plays a crucial role in various human neoplasms. However, its connection with kidney renal clear cell carcinoma (KIRC) remains under-researched. Methods: We validated the Gene Set Cancer Analysis Lite (GSCALite) platform against The Cancer Genome Atlas (TCGA) [...] Read more.
Background: Neddylation, a post-translational modification process, plays a crucial role in various human neoplasms. However, its connection with kidney renal clear cell carcinoma (KIRC) remains under-researched. Methods: We validated the Gene Set Cancer Analysis Lite (GSCALite) platform against The Cancer Genome Atlas (TCGA) database, analyzing 33 cancer types and their link with 17 neddylation-related genes. This included examining copy number variations (CNVs), single nucleotide variations (SNVs), mRNA expression, cellular pathway involvement, and methylation. Using Gene Set Variation Analysis (GSVA), we categorized these genes into three clusters and examined their impact on KIRC patient prognosis, drug responses, immune infiltration, and oncogenic pathways. Afterward, our objective is to identify genes that exhibit overexpression in KIRC and are associated with an adverse prognosis. After pinpointing the specific target gene, we used the specific inhibitor MLN4924 to inhibit the neddylation pathway to conduct RNA sequencing and related in vitro experiments to verify and study the specificity and potential mechanisms related to the target. This approach is geared towards enhancing our understanding of the prognostic importance of neddylation modification in KIRC. Results: We identified significant CNV, SNV, and methylation events in neddylation-related genes across various cancers, with notably higher expression levels observed in KIRC. Cluster analysis revealed a potential trade-off in the interactions among neddylation-related genes, where both high and low levels of gene expression are linked to adverse prognoses. This association is particularly pronounced concerning lymph node involvement, T stage classification, and Fustat score. Simultaneously, our research discovered that PSMB10 exhibits overexpression in KIRC when compared to normal tissues, negatively impacting patient prognosis. Through RNA sequencing and in vitro assays, we confirmed that the inhibition of neddylation modification could play a role in the regulation of various signaling pathways, thereby influencing the prognosis of KIRC. Moreover, our results underscore PSMB10 as a viable target for therapeutic intervention in KIRC, opening up novel pathways for the development of targeted treatment strategies. Conclusion: This study underscores the regulatory function and potential mechanism of neddylation modification on the phenotype of KIRC, identifying PSMB10 as a key regulatory target with a significant role in influencing the prognosis of KIRC. Full article
(This article belongs to the Special Issue Adjuvant Therapies for Cancer Treatment)
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24 pages, 981 KiB  
Review
Gut–Brain Axis: Focus on Sex Differences in Neuroinflammation
by Mario Caldarelli, Pierluigi Rio, Andrea Marrone, Francesca Ocarino, Monica Chiantore, Marcello Candelli, Antonio Gasbarrini, Giovanni Gambassi and Rossella Cianci
Int. J. Mol. Sci. 2024, 25(10), 5377; https://doi.org/10.3390/ijms25105377 (registering DOI) - 15 May 2024
Abstract
In recent years, there has been a growing interest in the concept of the “gut–brain axis”. In addition to well-studied diseases associated with an imbalance in gut microbiota, such as cancer, chronic inflammation, and cardiovascular diseases, research is now exploring the potential role [...] Read more.
In recent years, there has been a growing interest in the concept of the “gut–brain axis”. In addition to well-studied diseases associated with an imbalance in gut microbiota, such as cancer, chronic inflammation, and cardiovascular diseases, research is now exploring the potential role of gut microbial dysbiosis in the onset and development of brain-related diseases. When the function of the intestinal barrier is altered by dysbiosis, the aberrant immune system response interacts with the nervous system, leading to a state of “neuroinflammation”. The gut microbiota–brain axis is mediated by inflammatory and immunological mechanisms, neurotransmitters, and neuroendocrine pathways. This narrative review aims to illustrate the molecular basis of neuroinflammation and elaborate on the concept of the gut–brain axis by virtue of analyzing the various metabolites produced by the gut microbiome and how they might impact the nervous system. Additionally, the current review will highlight how sex influences these molecular mechanisms. In fact, sex hormones impact the brain–gut microbiota axis at different levels, such as the central nervous system, the enteric nervous one, and enteroendocrine cells. A deeper understanding of the gut–brain axis in human health and disease is crucial to guide diagnoses, treatments, and preventive interventions. Full article
(This article belongs to the Section Molecular Pathology, Diagnostics, and Therapeutics)
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14 pages, 2651 KiB  
Article
Towards Sustainable Viscose-to-Viscose Production: Strategies for Recycling of Viscose Fibres
by Diana Carolina Reyes Forsberg, Jenny Bengtsson, Nadine Hollinger and Tahani Kaldéus
Sustainability 2024, 16(10), 4127; https://doi.org/10.3390/su16104127 (registering DOI) - 15 May 2024
Abstract
The potential for using discarded viscose textiles to produce high-quality viscose fibres is limited by the low molecular weight of the cellulose and its continued reduction in the recycling process. Herein, we present a straightforward approach of reprocessing discarded viscose textiles while achieving [...] Read more.
The potential for using discarded viscose textiles to produce high-quality viscose fibres is limited by the low molecular weight of the cellulose and its continued reduction in the recycling process. Herein, we present a straightforward approach of reprocessing discarded viscose textiles while achieving high-quality recycled viscose fibres. Discarded viscose textile was defibrated and centrifuged, and the resulting fibres were reprocessed under industrially relevant conditions. The produced viscose dope was fluid and resulted in viscose fibres with properties comparable to fibres made from commercial wood cellulose pulp (titer ~2 dtex; dry elongation ~16%, dry tenacity ~15 cN/tex). To explore the potential for a more environmentally friendly production process, the steeping step was performed twice (double-steeping), thereby producing a more homogeneous viscose dope. Through double-steeping, the consumption of carbon disulfide (CS2) could be reduced by 30.5%. The double-steeping method shows to be a suitable approach to reprocess discarded viscose textiles while reducing the environmental impact of the viscose process associated with the use of CS2. Our work demonstrates that discarded viscose textile has the potential to be part of a circular textile value chain. Full article
(This article belongs to the Topic Advances in Sustainable Materials and Products)
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16 pages, 269 KiB  
Article
Selecting and Tailoring Implementation Strategies to Improve Human Papillomavirus Vaccine Uptake in Zambia: A Nominal Group Technique Approach
by Mwansa Ketty Lubeya, Mulindi Mwanahamuntu, Carla J. Chibwesha, Moses Mukosha and Mary Kawonga
Vaccines 2024, 12(5), 542; https://doi.org/10.3390/vaccines12050542 (registering DOI) - 15 May 2024
Abstract
The human papillomavirus (HPV) vaccine is effective in cervical cancer prevention. However, many barriers to uptake exist and strategies to overcome them are needed. Therefore, this study aimed to select and tailor implementation strategies to barriers identified by multiple stakeholders in Zambia. The [...] Read more.
The human papillomavirus (HPV) vaccine is effective in cervical cancer prevention. However, many barriers to uptake exist and strategies to overcome them are needed. Therefore, this study aimed to select and tailor implementation strategies to barriers identified by multiple stakeholders in Zambia. The study was conducted in Lusaka district between January and February 2023. Participants were purposively sampled from three stakeholder groups namely, adolescent girls, parents, and teachers and healthcare workers. With each of the stakeholders’ groups (10–13 participants per group), we used the nominal group technique to gain consensus to tailor feasible and acceptable implementation strategies for mitigating the identified contextual barriers. The identified barriers included low levels of knowledge and awareness about the HPV vaccine, being out of school, poor community sensitisation, lack of parental consent to vaccinate daughters, and myths and misinformation about the HPV vaccine. The lack of knowledge and awareness of the HPV vaccine was a common barrier across the three groups. Tailored strategies included conducting educational meetings and consensus-building meetings, using mass media, changing service sites, re-examining implementation, and involving patients/consumers and their relatives. Our study contributes to the available evidence on the process of selecting and tailoring implementation strategies to overcome contextual barriers. Policymakers should consider these tailored strategies to mitigate barriers and improve HPV vaccine uptake. Full article
(This article belongs to the Special Issue Vaccine Strategies for HPV-Related Cancers)
26 pages, 3495 KiB  
Review
Critical View on the Qualification of Electronic Tongues Regarding Their Performance in the Development of Peroral Drug Formulations with Bitter Ingredients
by Denise Steiner, Alexander Meyer, Laura Isabell Immohr and Miriam Pein-Hackelbusch
Pharmaceutics 2024, 16(5), 658; https://doi.org/10.3390/pharmaceutics16050658 (registering DOI) - 15 May 2024
Abstract
In this review, we aim to highlight the advantages, challenges, and limitations of electronic tongues (e-tongues) in pharmaceutical drug development. The authors, therefore, critically evaluated the performance of e-tongues regarding their qualification to assess peroral formulations containing bitter active pharmaceutical ingredients. A literature [...] Read more.
In this review, we aim to highlight the advantages, challenges, and limitations of electronic tongues (e-tongues) in pharmaceutical drug development. The authors, therefore, critically evaluated the performance of e-tongues regarding their qualification to assess peroral formulations containing bitter active pharmaceutical ingredients. A literature search using the keywords ‘electronic’, ‘tongue’, ‘bitter’, and ‘drug’ in a Web of Science search was therefore initially conducted. Reviewing the publications of the past decade, and further literature where necessary, allowed the authors to discuss whether and how e-tongues perform as expected and whether they have the potential to become a standard tool in drug development. Specifically highlighted are the expectations an e-tongue should meet. Further, a brief insight into the technologies of the utilized e-tongues is given. Reliable protocols were found that enable (i) the qualified performance of e-tongue instruments from an analytical perspective, (ii) proper taste-masking assessments, and (iii) under certain circumstances, the evaluation of bitterness. Full article
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14 pages, 5847 KiB  
Article
Estetrol Inhibits Endometriosis Development in an In Vivo Murine Model
by Ana Sofia Zabala, Rocío Ayelem Conforti, María Belén Delsouc, Verónica Filippa, Maria Magdalena Montt-Guevara, Andrea Giannini, Tommaso Simoncini, Sandra Silvina Vallcaneras and Marilina Casais
Biomolecules 2024, 14(5), 580; https://doi.org/10.3390/biom14050580 (registering DOI) - 15 May 2024
Abstract
Endometriosis is characterized by the growth of endometrial-like tissue outside the uterus, and it is associated with alterations in the expression of hormone receptors and inflammation. Estetrol (E4) is a weak estrogen that recently has been approved for contraception. We evaluated [...] Read more.
Endometriosis is characterized by the growth of endometrial-like tissue outside the uterus, and it is associated with alterations in the expression of hormone receptors and inflammation. Estetrol (E4) is a weak estrogen that recently has been approved for contraception. We evaluated the effect of E4 on the growth of endometriotic-like lesions and the expression of TNF-α, estrogen receptors (ERs), and progesterone receptors (PRs) in an in vivo murine model. Endometriosis was induced surgically in female C57BL/6 mice. E4 was delivered via Alzet pump (3 mg/kg/day) from the 15th postoperative day for 4 weeks. E4 significantly reduced the volume (p < 0.001) and weight (p < 0.05) of ectopic lesions. Histologically, E4 did not affect cell proliferation (PCNA immunohistochemistry) but it did increase cell apoptosis (TUNEL assay) (p < 0.05). Furthermore, it modulated oxidative stress (SOD, CAT, and GPX activity, p < 0.05) and increased lipid peroxidation (TBARS/MDA, p < 0.01). Molecular analysis showed mRNA (RT-qPCR) and protein (ELISA) expression of TNF-α decreased (p < 0.05) and mRNA expression of Esr2 reduced (p < 0.05), in contrast with the increased expression of Esr1 (p < 0.01) and Pgr (p < 0.05). The present study demonstrates for the first time that E4 limited the development and progression of endometriosis in vivo. Full article
(This article belongs to the Special Issue Cellular and Molecular Mechanisms of Endometriosis)
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29 pages, 1051 KiB  
Review
Navigating the Cyber Threat Landscape: An In-Depth Analysis of Attack Detection within IoT Ecosystems
by Samar AboulEla, Nourhan Ibrahim, Sarama Shehmir, Aman Yadav and Rasha Kashef
AI 2024, 5(2), 704-732; https://doi.org/10.3390/ai5020037 (registering DOI) - 15 May 2024
Abstract
The Internet of Things (IoT) is seeing significant growth, as the quantity of interconnected devices in communication networks is on the rise. The increased connectivity of devices has heightened their susceptibility to hackers, underscoring the need to safeguard IoT devices. This research investigates [...] Read more.
The Internet of Things (IoT) is seeing significant growth, as the quantity of interconnected devices in communication networks is on the rise. The increased connectivity of devices has heightened their susceptibility to hackers, underscoring the need to safeguard IoT devices. This research investigates cybersecurity in the context of the Internet of Medical Things (IoMT), which encompasses the cybersecurity mechanisms used for various healthcare devices connected to the system. This study seeks to provide a concise overview of several artificial intelligence (AI)-based methodologies and techniques, as well as examining the associated solution approaches used in cybersecurity for healthcare systems. The analyzed methodologies are further categorized into four groups: machine learning (ML) techniques, deep learning (DL) techniques, a combination of ML and DL techniques, Transformer-based techniques, and other state-of-the-art techniques, including graph-based methods and blockchain methods. In addition, this article presents a detailed description of the benchmark datasets that are recommended for use in intrusion detection systems (IDS) for both IoT and IoMT networks. Moreover, a detailed description of the primary evaluation metrics used in the analysis of the discussed models is provided. Ultimately, this study thoroughly examines and analyzes the features and practicality of several cybersecurity models, while also emphasizing recent research directions. Full article
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15 pages, 7284 KiB  
Article
The [18F]F-FDG PET/CT Radiomics Classifier of Histologic Subtypes and Anatomical Disease Origins across Various Malignancies: A Proof-of-Principle Study
by Ricarda Hinzpeter, Seyed Ali Mirshahvalad, Vanessa Murad, Lisa Avery, Roshini Kulanthaivelu, Andres Kohan, Claudia Ortega, Elena Elimova, Jonathan Yeung, Andrew Hope, Ur Metser and Patrick Veit-Haibach
Cancers 2024, 16(10), 1873; https://doi.org/10.3390/cancers16101873 (registering DOI) - 15 May 2024
Abstract
We aimed to investigate whether [18F]F-FDG-PET/CT-derived radiomics can classify histologic subtypes and determine the anatomical origin of various malignancies. In this IRB-approved retrospective study, 391 patients (age = 66.7 ± 11.2) with pulmonary (n = 142), gastroesophageal (n = 128) and [...] Read more.
We aimed to investigate whether [18F]F-FDG-PET/CT-derived radiomics can classify histologic subtypes and determine the anatomical origin of various malignancies. In this IRB-approved retrospective study, 391 patients (age = 66.7 ± 11.2) with pulmonary (n = 142), gastroesophageal (n = 128) and head and neck (n = 121) malignancies were included. Image segmentation and feature extraction were performed semi-automatically. Two models (all possible subset regression [APS] and recursive partitioning) were employed to predict histology (squamous cell carcinoma [SCC; n = 219] vs. adenocarcinoma [AC; n = 172]), the anatomical origin, and histology plus anatomical origin. The recursive partitioning algorithm outperformed APS to determine histology (sensitivity 0.90 vs. 0.73; specificity 0.77 vs. 0.65). The recursive partitioning algorithm also revealed good predictive ability regarding anatomical origin. Particularly, pulmonary malignancies were identified with high accuracy (sensitivity 0.93; specificity 0.98). Finally, a model for the synchronous prediction of histology and anatomical disease origin resulted in high accuracy in determining gastroesophageal AC (sensitivity 0.88; specificity 0.92), pulmonary AC (sensitivity 0.89; specificity 0.88) and head and neck SCC (sensitivity 0.91; specificity 0.92). Adding PET-features was associated with marginal incremental value for both the prediction of histology and origin in the APS model. Overall, our study demonstrated a good predictive ability to determine patients’ histology and anatomical origin using [18F]F-FDG-PET/CT-derived radiomics features, mainly from CT. Full article
(This article belongs to the Section Cancer Pathophysiology)
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20 pages, 2795 KiB  
Review
Transforming the Management of Articular Fractures in the Foot: A Critical Examination of Current Methods and Future Directions: A Review
by Robert Daniel Dobrotă, Adrian Gheorghe Barbilian, Corina Sporea and Dumitru Ferechide
J. Pers. Med. 2024, 14(5), 525; https://doi.org/10.3390/jpm14050525 (registering DOI) - 15 May 2024
Abstract
This study provides a comprehensive examination of the current methodologies and potential strategies for the treatment of articular fractures of the foot. In the field of orthopedic healthcare, these fractures present a significant challenge due to their complex nature and the fact that [...] Read more.
This study provides a comprehensive examination of the current methodologies and potential strategies for the treatment of articular fractures of the foot. In the field of orthopedic healthcare, these fractures present a significant challenge due to their complex nature and the fact that they affect the routines of patients. The motivation behind this study is based on two main concepts. The first one is represented by the use of emerging medical technologies and personalized medicine to bring a significant transformation in the management of foot fractures and give a better quality of treatment that is accepted by the patient. However, because there are inequities in the availability of the necessary medical care and equipment, as well as uneven incorporation in clinical settings, new technologies cannot be used to treat these types of fractures. Regarding the second concept behind this study, it is indicated that although current treatment methods are essential, they have a number of shortcomings when it comes to properly addressing these types of injuries. An approach is needed that takes into account the biomechanical points of view and the particularities of each patient. This approach could be applied in all hospital settings. Through this study, we want to highlight the progress made in recent years in surgical techniques such as 3D printing, minimally invasive surgery (MIS), and biological products. However, in the application of this new discovery, new obstacles have been discovered that prevent the efficient treatment of these types of injuries. This study examines the effectiveness and limitations of current treatments, as well as how differences in healthcare, such as available equipment, training of medical staff, and technological advances, affect patient outcomes in everyday life. This research wishes to emphasize that continuous innovation, interdisciplinary collaboration, and the use of an optimal approach that is appropriate for each patient, are essential. This study aims to provide new insights and useful recommendations for future research and clinical practice. The main role of this research is to improve the quality of life of patients and increase the standards of care in this complex field, which is in permanent evolution. Full article
(This article belongs to the Section Methodology, Drug and Device Discovery)
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17 pages, 2092 KiB  
Review
HPV and RNA Binding Proteins: What We Know and What Remains to Be Discovered
by Sheila V. Graham
Viruses 2024, 16(5), 783; https://doi.org/10.3390/v16050783 (registering DOI) - 15 May 2024
Abstract
Papillomavirus gene regulation is largely post-transcriptional due to overlapping open reading frames and the use of alternative polyadenylation and alternative splicing to produce the full suite of viral mRNAs. These processes are controlled by a wide range of cellular RNA binding proteins (RPBs), [...] Read more.
Papillomavirus gene regulation is largely post-transcriptional due to overlapping open reading frames and the use of alternative polyadenylation and alternative splicing to produce the full suite of viral mRNAs. These processes are controlled by a wide range of cellular RNA binding proteins (RPBs), including constitutive splicing factors and cleavage and polyadenylation machinery, but also factors that regulate these processes, for example, SR and hnRNP proteins. Like cellular RNAs, papillomavirus RNAs have been shown to bind many such proteins. The life cycle of papillomaviruses is intimately linked to differentiation of the epithelial tissues the virus infects. For example, viral late mRNAs and proteins are expressed only in the most differentiated epithelial layers to avoid recognition by the host immune response. Papillomavirus genome replication is linked to the DNA damage response and viral chromatin conformation, processes which also link to RNA processing. Challenges with respect to elucidating how RBPs regulate the viral life cycle include consideration of the orchestrated spatial aspect of viral gene expression in an infected epithelium and the epigenetic nature of the viral episomal genome. This review discusses RBPs that control viral gene expression, and how the connectivity of various nuclear processes might contribute to viral mRNA production. Full article
(This article belongs to the Special Issue Regulation of the Virus Lifecycle by Cellular RNA-Binding Proteins)
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17 pages, 3158 KiB  
Article
Identification and Evaluation of Celery Germplasm Resources for Salt Tolerance
by Limei Wu, Jiageng Du, Yidan Zhang, Yuqin Xue, Chengyao Jiang, Wei Lu, Yangxia Zheng, Chengbo Zhou, Aisheng Xiong and Mengyao Li
Agronomy 2024, 14(5), 1048; https://doi.org/10.3390/agronomy14051048 (registering DOI) - 15 May 2024
Abstract
This study evaluated the salt tolerance in 40 celery germplasm resources to clarify the different salt tolerances of celery germplasm. A gradient treatment with different concentrations of NaCl solutions (100, 200, and 300 mmol·L−1) was used to simulate salt stress. After [...] Read more.
This study evaluated the salt tolerance in 40 celery germplasm resources to clarify the different salt tolerances of celery germplasm. A gradient treatment with different concentrations of NaCl solutions (100, 200, and 300 mmol·L−1) was used to simulate salt stress. After 15 days of salt treatment, 14 indicators related to plant growth, physiology, and biochemistry were determined. The results showed that different celery varieties responded differently to salt stress. Notably, there were significant variations in below-ground dry weight, root–crown ratio, antioxidant enzyme activity, and soluble protein content among the accessions under salt stress. Principal component analysis was used to identify important indices for evaluating salt tolerance, including plant height, spread, content of soluble protein, and so on. A comprehensive evaluation was conducted utilizing the salt damage index, principal component analysis, affiliation function analysis, and cluster analysis. The 40 celery germplasms were classified into five highly salt-tolerant, seven salt-tolerant, fifteen moderately salt-tolerant, nine salt-sensitive, and four highly salt-sensitive germplasms. SHHXQ, MXKQ, XBQC, XQ, and TGCXBQ were highly salt-tolerant germplasms, and BFMSGQ, HNXQ, ZQ, and MGXQW were highly salt-sensitive germplasms. The results of this study provide a reference for the variety of celery cultivation in saline areas and lay a foundation for the selection and breeding of salt-tolerant varieties of celery. Full article
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