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31 pages, 3387 KiB  
Review
Glucosinolates in Human Health: Metabolic Pathways, Bioavailability, and Potential in Chronic Disease Prevention
by Sara Baldelli, Mauro Lombardo, Alfonsina D’Amato, Sercan Karav, Gianluca Tripodi and Gilda Aiello
Foods 2025, 14(6), 912; https://doi.org/10.3390/foods14060912 (registering DOI) - 7 Mar 2025
Abstract
Glucosinolates (GSLs) are sulfur-containing compounds predominantly found in cruciferous vegetables such as broccoli, kale, and Brussels sprouts, and are recognized for their health-promoting properties. Upon consumption, GSLs undergo hydrolysis by the enzyme myrosinase, resulting in bioactive compounds like isothiocyanates and specific indole glucosinolate [...] Read more.
Glucosinolates (GSLs) are sulfur-containing compounds predominantly found in cruciferous vegetables such as broccoli, kale, and Brussels sprouts, and are recognized for their health-promoting properties. Upon consumption, GSLs undergo hydrolysis by the enzyme myrosinase, resulting in bioactive compounds like isothiocyanates and specific indole glucosinolate degradation products, such as indole-3-carbinol (I3C) and 3,3′-diindolylmethane (DIM), which contribute to a range of health benefits, including anti-cancer, anti-inflammatory, and cardioprotective effects. This review explores the structure, metabolism, and bioavailability of GSLs. Recent evidence supports the protective role of GSLs in chronic diseases, with mechanisms including the modulation of oxidative stress, inflammation, and detoxification pathways. Furthermore, the innovative strategies to enhance GSL bioactivity, such as biofortification, genetic introgression, and optimized food processing methods, have been examined. These approaches seek to increase GSL content in edible plants, thereby maximizing their health benefits. This comprehensive review provides insights into dietary recommendations, the impact of food preparation, and recent advances in GSL bioavailability enhancement, highlighting the significant potential of these bioactive compounds in promoting human health and preventing chronic diseases. Full article
(This article belongs to the Special Issue Unraveling the Nexus of Food Processing, Digestion, and Health)
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<p>Overview of strategies to increase glucosinolate content in plants, highlighting genetic and molecular approaches (e.g., transporter manipulation, genetic introgression, genome editing) and agronomic and technical approaches (e.g., biofortification, nanofertilizers, elicitation techniques). These strategies aim to improve both the nutritional value and functional properties of Brassica crops.</p>
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17 pages, 2313 KiB  
Article
Prognostic and Therapeutic Implications of Alamandine Receptor MrgD Expression in Clear Cell Renal Cell Carcinoma with Development of Metastatic Disease
by Gorka Larrinaga, Jon Danel Solano-Iturri, Inés Arrieta-Aguirre, Asier Valdivia, David Lecumberri, Ane Miren Iturregui, Charles H. Lawrie, María Armesto, Juan F. Dorado, Caroline E. Nunes-Xavier, Rafael Pulido, José I. López and Javier C. Angulo
Biomolecules 2025, 15(3), 387; https://doi.org/10.3390/biom15030387 (registering DOI) - 7 Mar 2025
Abstract
Despite advances in the management of advanced clear cell renal cell carcinoma (ccRCC), robust biomarkers for prognosis and therapeutic response prediction remain elusive. Dysregulation of the intrarenal renin–angiotensin system (RAS) has been implicated in renal carcinogenesis but little explored, particularly regarding biomarker discovery [...] Read more.
Despite advances in the management of advanced clear cell renal cell carcinoma (ccRCC), robust biomarkers for prognosis and therapeutic response prediction remain elusive. Dysregulation of the intrarenal renin–angiotensin system (RAS) has been implicated in renal carcinogenesis but little explored, particularly regarding biomarker discovery and therapeutic innovation. Consequently, this study investigates the immunohistochemical expression and clinical relevance of the Mas-related G-protein-coupled receptor D (MrgD) in patients with ccRCC who developed metastatic disease (mccRCC). A cohort of 132 patients treated between 2008 and 2018 with nephrectomy and tyrosine kinase inhibitor (TKI)-based sequential therapy was analyzed. Treatment response was assessed using both the MASS and RECIST scoring systems. High MrgD expression in primary tumors was significantly associated with larger size, advanced stage, higher histological grade, and worse overall survival. Among 81 patients with metachronous metastases, high MrgD expression independently predicted shorter disease-free survival. High MrgD staining intensity correlated with poorer TKI responses in first-line therapy but improved outcomes with second-line mTORC1 inhibitors. These findings suggest that MrgD may be a useful biomarker of RAS linked to tumor aggressiveness in ccRCC. MrgD holds potential for identifying high-risk patients and guiding treatment selection in advanced disease. Further research is needed to unlock its clinical potential. Full article
(This article belongs to the Special Issue New Insights into Kidney Disease Development and Therapy Strategies)
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<p><b>MrgD expression in advanced clear cell renal cell carcinoma (mccRCC).</b> (<b>a</b>) Hematoxylin-eosin (H&amp;E) staining of the non-tumor part of the nephrectomized kidney shows proximal convoluted tubules with granular eosinophilic cells (arrows) and glomeruli (asterisks) but also distal nephron tubules (arrowheads). (<b>b</b>) MrgD staining of the non-tumor tissue reveals an intense granular cytoplasmic staining of the proximal tubules (arrows) and weak staining of the distal tubules (arrowheads). Notice that glomeruli can be used as internal negative control (asterisk). (<b>c</b>,<b>d</b>) Low-grade ccRCC shows weak MrgD staining, whereas the high-grade tumor (<b>e</b>,<b>f</b>) shows intense staining. Original magnification ×250.</p>
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<p><b>Immunohistochemical staining of MrgD in mccRCC tumors based on clinical and pathological variables</b> grouped according to histological grade (<b>a</b>), size (<b>b</b>), local invasion (pT) (<b>c</b>), lymph node (N) (<b>d</b>), distant metastasis (M) (<b>e</b>), and NCCN stage at diagnosis (<b>f</b>). IMDC risk criteria (<b>g</b>) and ECOG performance status (<b>h</b>) were evaluated at the time of initiating TKI-therapy. MrgD staining intensity was grouped as negative and positive. The “%” symbol on the Y-axis of the graph represents the percentage of cases that were MrgD positive or negative. The χ<sup>2</sup> test was used for data analysis. N0: No lymph node metastasis; N1: lymph node metastasis; M0: No distant metastasis; M1: synchronous distant metastasis.</p>
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<p><b>Immunohistochemical staining of MrgD in mccRCC tumors according to patients’ response to first- and second-line therapies.</b> MrgD expression was significantly higher in mccRCCs treated with TKIs as first-line therapy with unfavorable responses (MASS) but lower in cases treated with mTORC1 inhibitors as second-line therapy. The “%” symbol on the Y-axis of the graph represents the percentage of cases that were MrgD positive or negative. CR: Complete response; PR: partial response; SD: stable disease. MrgD staining intensity was grouped as negative or positive. The χ<sup>2</sup> test was used for data analysis.</p>
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<p><b>MrgD expression in mccRCC and patients’ survival.</b> Kaplan–Meier curves and log–rank test demonstrated the significant association between MrgD positivity and 10-year overall (<b>a</b>) and disease-free (<b>b</b>) survival. The number of patients at risk is shown at specific time points throughout the follow-up period.</p>
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7 pages, 2689 KiB  
Case Report
Cryptic KMT2A::AFDN Fusion Due to AFDN Insertion into KMT2A in a Patient with Acute Monoblastic Leukemia
by Qing Wei, Gokce A. Toruner, Beenu Thakral, Keyur P. Patel, Naveen Pemmaraju, Sa A. Wang, Rashmi Kanagal-Shamanna, Guilin Tang, Ghayas C. Issa, Sanam Loghavi, L Jeffrey Medeiros and Courtney DiNardo
Genes 2025, 16(3), 317; https://doi.org/10.3390/genes16030317 (registering DOI) - 7 Mar 2025
Abstract
Background: KMT2A rearrangements occur in ~10% of acute myeloid leukemia (AML) cases and are critical for classification, risk stratification, and use of targeted therapy. However, insertions involving the KMT2A gene can evade detection using chromosomal analysis and/or fluorescence in situ hybridization (FISH). Methods: [...] Read more.
Background: KMT2A rearrangements occur in ~10% of acute myeloid leukemia (AML) cases and are critical for classification, risk stratification, and use of targeted therapy. However, insertions involving the KMT2A gene can evade detection using chromosomal analysis and/or fluorescence in situ hybridization (FISH). Methods: We present a case of a 22-year-old woman with acute monoblastic leukemia harboring a cryptic KMT2A::AFDN fusion identified by RNA sequencing. Initial FISH showed a 3′ KMT2A deletion, while conventional karyotyping and the automated bioinformatic pipeline for optical genome mapping (OGM) did not identify the canonical translocation. Results: To resolve these discrepancies, metaphase KMT2A FISH (break-apart fusion probe) was performed to assess whether KMT2A was translocated to another chromosome. However, the results did not support this possibility. As the fusion signal remained on the normal chromosome 11, with the 5′ KMT2A signal localized to the derivative chromosome 11. A subsequent manual review of the OGM data revealed a cryptic ~300 kb insertion of AFDN into the 3′ region of KMT2A, reconciling the discrepancies between chromosomal analysis, FISH, and RNA fusion results. Conclusions: This case highlights the importance of integrating multiple testing modalities with expert review when there is a discrepancy. Our findings emphasize the need for a comprehensive approach to genomic assessment to enhance diagnostic accuracy and guide therapeutic decision-making. Full article
(This article belongs to the Special Issue Clinical Molecular Genetics in Hematologic Diseases)
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<p>Morphologic and immunophenotypic findings in peripheral blood and bone marrow specimens. (<b>A</b>,<b>B</b>): Peripheral blood (<b>A</b>) and bone marrow aspirate (<b>B</b>) smears show large blasts with open chromatin, variably conspicuous nucleoli, round to indented nuclear membranes, and moderate basophilic cytoplasm. No Auer rods were identified (×1000). (<b>C</b>): The bone marrow biopsy specimen shows a hypercellular bone marrow with sheets of large blasts displaying a starry-sky appearance (×400). (<b>D</b>): Immunohistochemical analysis shows that the blasts are positive for lysozyme (×400). (<b>E</b>–<b>I</b>): Flow cytometric immunophenotypic analysis shows that the blasts are positive for CD34, CD117, CD4, CD33, CD38, CD64, CD123, HLA-DR, TdT, and MPO (dim, ~5%).</p>
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<p>Chromosomal analysis, interphase FISH, RNA fusion panel, and metaphase FISH results. (<b>A</b>): Chromosomal analysis reveals a complex karyotype, 47,XX,+8,del(9)(q21q31)[<a href="#B11-genes-16-00317" class="html-bibr">11</a>]/47,idem,inv(11)(q14q23)[<a href="#B8-genes-16-00317" class="html-bibr">8</a>]. (<b>B</b>): Interphase FISH using a <span class="html-italic">KMT2A</span> break-apart probe shows one intact yellow fusion signal and one green signal, indicating a 3′ <span class="html-italic">KMT2A</span> deletion. (<b>C</b>): RNA fusion panel identifies fusion transcripts between exon 8 of <span class="html-italic">KMT2A</span> and exon 2 of <span class="html-italic">AFDN</span>. (<b>D</b>): Metaphase FISH reveals a normal chromosome 11 with a yellow fusion signal (yellow arrow) and a derivative chromosome 11 with only a 5′ <span class="html-italic">KMT2A</span> green signal (green arrow) and loss of 3′ <span class="html-italic">KMT2A</span>.</p>
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<p>OGM results. (<b>A</b>) The OGM circos plot reveals trisomy 8, a deletion on the long arm of chromosome 9, and an interchromosomal translocation between chromosomes 9 and 10. Additionally, within chromosome 11q23, one inversion (marked by a blue dot), one deletion (marked by a red dot), and several intrachromosomal rearrangements are detected. (<b>B</b>) Initial review of OGM near the <span class="html-italic">KMT2A</span> locus highlights a 3′ end deletion of <span class="html-italic">KMT2A</span>, indicated by a thick red arrow and line on the reference chromosome 11, corresponding to the red dot in the circos plot (<b>A</b>). Furthermore, an inversion involving the <span class="html-italic">CBL</span> gene is denoted by a thick blue arrow and line on the reference chromosome 11, corresponding to the blue dot in the circos plot (<b>A</b>). (<b>C</b>) Detailed manual review of the insertion event reveals an insertion encompassing exons 2–11 of the <span class="html-italic">AFDN</span> gene, depicted by yellow bars within the red box on consensus map 2. This pattern of yellow bars matches that observed in (<b>D</b>). (<b>D</b>) Reference map and consensus map of chromosome 4 further illustrate the pattern of the <span class="html-italic">AFDN</span> (exon 2-11)). Throughout these figures, the OGM data are represented with specific visual elements to aid interpretation. The blue lines depict the alignment of the sample’s OGM map data (consensus map) to the reference genome. Within these blue lines, blue bars identify regions of consistent alignment or matched segments, while yellow bars pinpoint regions where structural variations—such as deletions or insertions—have been detected.</p>
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14 pages, 2771 KiB  
Article
Prognostic Significance of DNAJB4 Expression in Gastric Cancer: Correlation with CD31, Caspase-3, and Tumor Progression
by Chiao-Yin Cheng, Yen-Lin Chen, Hua Ho, Chun-Yen Huang, Sheng-En Chu and Yao-Jen Liang
Diagnostics 2025, 15(6), 652; https://doi.org/10.3390/diagnostics15060652 (registering DOI) - 7 Mar 2025
Abstract
Background/Objectives: Gastric cancer is one of the most common and lethal cancers worldwide, with particularly high incidence and mortality rates in East Asia and Europe. DNAJB4 has been shown to have prognostic implications in other cancer types; however, its expression patterns and role [...] Read more.
Background/Objectives: Gastric cancer is one of the most common and lethal cancers worldwide, with particularly high incidence and mortality rates in East Asia and Europe. DNAJB4 has been shown to have prognostic implications in other cancer types; however, its expression patterns and role in gastric cancer have not been extensively studied. This study aimed to analyze DNAJB4 expression in gastric cancer and explore its association with clinical characteristics, molecular markers, and patient outcomes. Methods: We selected suitable tumor samples from 189 gastric cancer patients who had not undergone chemotherapy or radiotherapy, with 188 patients ultimately included in the analysis. Tissue microarray and immunohistochemistry were used to evaluate DNAJB4 expression, and the samples were divided into high- and low-expression groups based on the H-score. Multivariate logistic regression and survival analysis were conducted to identify influencing factors. Results: High DNAJB4 expression was significantly correlated with increased CD31 levels but was inversely associated with advanced cancer stages. Subgroup analysis revealed that in patients with advanced gastric cancer, high DNAJB4 expression was associated with increased caspase-3 levels and with elevated CD31 and decreased E-cadherin levels. Conclusions: High DNAJB4 expression was associated with both angiogenesis and apoptosis, indicating its complex role in gastric cancer progression. Although DNAJB4 promoted angiogenesis by increasing CD31 levels, it may also enhance apoptosis in tumor cells through caspase-3-induced apoptosis. Full article
(This article belongs to the Special Issue Advances in the Diagnosis of Gastrointestinal Diseases—2nd Edition)
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<p>Differential staining intensities of DNAJB4 in tumor paraffin sections under immunohistochemistry (grades 0 to 3).</p>
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<p>Immunohistochemistry of CD31, pERK, pSTAT3, pAXL, EhpA5, and β-catenin in the high and low DNAJB4 expression groups. (<b>A</b>) Low DNAJB4 expression. (<b>B</b>) High DNAJB4 expression. Scale bar, 20 μm for 400× magnification.</p>
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<p>Kaplan–Meier analysis survival curves in the high and low DNAJB4 expression groups. Pink, high DNAJB4 expression group; purple, low DNAJB4 expression group. * <span class="html-italic">p</span> &lt; 0.05.</p>
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19 pages, 3630 KiB  
Article
Bioactive Secondary Metabolites of Two Chinese Edible Boletes, Phlebopus portentosus and Butyriboletus roseoflavus
by Zhixuan Wang, Wei Zhou, Yuhang He, Zeyu Zhao, Yang Cao, Shunzhen Luo, Guangyan Ji, Kaiping Ji, Jing Chen, Jiyang Li and Juan Xiong
Molecules 2025, 30(6), 1197; https://doi.org/10.3390/molecules30061197 (registering DOI) - 7 Mar 2025
Abstract
This study investigated the phytochemical profiles and bioactivities of two edible boletes from Southwestern China, Phlebopus portentosus and Butyriboletus roseoflavus. A total of 33 secondary metabolites, comprising 15 alkaloids, 4 pulvinic acid derivative pigments, and 14 ergosterols, were isolated and identified. To [...] Read more.
This study investigated the phytochemical profiles and bioactivities of two edible boletes from Southwestern China, Phlebopus portentosus and Butyriboletus roseoflavus. A total of 33 secondary metabolites, comprising 15 alkaloids, 4 pulvinic acid derivative pigments, and 14 ergosterols, were isolated and identified. To our best knowledge, boletesine A (1), boletesine B (2), and cis-xerocomic acid (16) were new compounds/were previously undescribed. The new structures were established by extensive spectroscopic methods and chemical calculations. Compound 1 features a hitherto unknown hybrid skeleton formed between a 2-formylpyrrole-alkaloid and a dopacetic acid (DOPAC) via a Michael addition reaction. Bioactivity assays revealed the neuroprotective effects of compounds 18 and 19 against Aβ25–35- or H2O2-induced toxicity. In a cytotoxic assay against a small panel of cancer cell lines, compound 9 exhibited significant activity against HeLa cells (IC50 = 10.76 µM), while 33 demonstrated broad-spectrum cytotoxicity against Hela229, SGC7901, PC-3, and BEL7402 cells (IC50s in the range of 20~30 µM). Of particular note is the anti-influenza virus activities against A/H3N2 and B/Victoria strains of compounds 22 and 26 (EC50 values ranging from 3.6 to 9.6 µM). Along with these, compound 29 showed a moderate antiviral effect against coxsackievirus B3. These findings underscore the therapeutic potential of the two edible boletes in addressing neurodegenerative diseases, cancer, and viral infections, paving the way for their prospective applications in the development of functional foods and pharmaceuticals. Full article
(This article belongs to the Section Natural Products Chemistry)
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<p>Chemical structures of compounds <b>1</b>–<b>33</b>. Compounds <b>8</b>, <b>9</b>, <b>11</b>, <b>16</b>–<b>18</b>, <b>20</b>–<b>29</b>, and <b>33</b> isolated from artificially cultivated <span class="html-italic">P. portentosus</span> and compounds <b>2</b>–<b>6</b> and <b>8</b>–<b>15</b> isolated from wild <span class="html-italic">P. portentosus</span>; compounds <b>1</b>, <b>7</b>, <b>17</b>–<b>19</b>, <b>20</b>, <b>22</b>, <b>25</b>–<b>27</b>, and <b>30</b>–<b>33</b> isolated from wild <span class="html-italic">B. roseoflavus</span>.</p>
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<p>Key HMBC correlations (H → C) of compound <b>1</b>.</p>
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<p>Calculated and experimental ECD curves of <b>1a</b> and <b>1b</b> in MeOH.</p>
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<p>Key HMBC correlations (H → C) of compound <b>16</b>.</p>
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<p>Neuroprotective activity of compounds <b>18</b> (<b>a</b>) and <b>19</b> (<b>b</b>) in SH-SY5Y cells. The cell viability was assessed by measuring the MTT reduction. Epigallocatechin gallate (EGCG) and <span class="html-italic">N</span>-acetylcysteine (NAC) were positive controls. Four independent experiments were carried out in triplicate. The data are expressed as a percentage of control value and are represented by means ± SEM. <sup>###</sup> <span class="html-italic">p</span> &lt; 0.00l vs. control group, *** <span class="html-italic">p</span> &lt; 0.001 vs. Aβ<sub>25–35</sub> group (<b>a</b>) or *** <span class="html-italic">p</span> &lt; 0.001 vs. H<sub>2</sub>O<sub>2</sub> group (<b>b</b>).</p>
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<p>Morphological assessment of compound <b>29</b> against CVB in vitro (magnification: 100×). CVB-infected Vero cells were treated with 100 μg/mL of compound <b>29</b> and ribavirin (positive control). Cell morphology was assessed by microscope. (<b>a</b>) CVB-uninfected Vero cells. (<b>b</b>) CVB-infected Vero cells. (<b>c</b>) CVB-infected Vero cells treated with ribavirin. (<b>d</b>) CVB-infected Vero cells treated with compound <b>29</b>.</p>
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<p>Cytopathic effect (CPE) images of MDCK cells. Ribavirin was used as a positive control. (<b>a</b>) CPE images of compounds <b>22</b> and <b>26</b> against influenza virus A/H3N2 strain. (<b>b</b>) CPE images of compounds <b>22</b> and <b>26</b> against influenza virus B/Victoria strain.</p>
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<p>Proposed biosynthetic pathway of compound <b>1</b>.</p>
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8 pages, 1007 KiB  
Case Report
A Case of a Neuroendocrine Tumor in a Liver Transplant Patient: Diagnostic and Management Difficulties
by Carmen Colaci, Caterina Mercuri, Alessandro Corea, Rocco Spagnuolo and Patrizia Doldo
Life 2025, 15(3), 421; https://doi.org/10.3390/life15030421 (registering DOI) - 7 Mar 2025
Abstract
Neuroendocrine tumors (NETs) of the liver are a rare entity. NETs are often poorly recognized, with diagnostic difficulties and differential challenges between primary tumors of the liver and metastases from other organs, mainly from the gastrointestinal tract. Multidisciplinary and multi-technical diagnosis is mandatory [...] Read more.
Neuroendocrine tumors (NETs) of the liver are a rare entity. NETs are often poorly recognized, with diagnostic difficulties and differential challenges between primary tumors of the liver and metastases from other organs, mainly from the gastrointestinal tract. Multidisciplinary and multi-technical diagnosis is mandatory to properly treat these tumors. This case describes the complex history and the treatment course of a 68-year-old man with a history of NET onset after liver transplantation. Liver transplantation is the treatment of choice for patients with advanced liver disease or acute liver failure, but careful pre- and post-transplant patient monitoring is required. Liver transplant patients receive immunosuppressive therapy, and donor livers should be screened to exclude potential malignancies. This clinical case, in addition to emphasizing the diagnostic and therapeutic difficulty of hepatic NET, underlines the role of post-transplant immunosuppressive therapy and pre-transplant screening, which includes a thorough evaluation of donor and recipient history, physical examination, and laboratory tests. Moreover, post-transplant immunosuppressive therapy is essential to maintain the viability of the transplanted organ, but it is not free from potential risks, including an increased risk of cancer. Therefore, close monitoring of therapy is necessary to optimize long-term results and the patient’s quality of life. Full article
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<p>Ultrasound image of biopsied liver segment VI lesion. The arrow indicates the presence of the VI liver segment.</p>
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<p>F1 esophageal varices in gastroscopy: the <b>left</b> image shows the portion of the middle esophagus; the <b>right</b> image shows the distal esophagus.</p>
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<p>Normal colonoscopy findings: the <b>left</b> image shows the cecum; the <b>right</b> image shows the descending colon.</p>
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16 pages, 2224 KiB  
Review
The Value of Stingless Bee Bioproducts for Human Health and Conservation: A Systematic Review
by Evodia Silva-Rivera, Guillermo Vázquez-Domínguez, Óscar Hipólito Mota-Sánchez, Itzayana Hernández-De la Cruz, Rubí Marisol Franco-José, Noé Velázquez-Rosas and Rodolfo Martínez-Mota
Diversity 2025, 17(3), 191; https://doi.org/10.3390/d17030191 (registering DOI) - 7 Mar 2025
Abstract
In this systematic review, we look to the long-established medical relationship between humans and stingless bees to support the notion that health and conservation research needs to look differently at examples of the relationship between human health and biodiversity. Through the PRISMA statement, [...] Read more.
In this systematic review, we look to the long-established medical relationship between humans and stingless bees to support the notion that health and conservation research needs to look differently at examples of the relationship between human health and biodiversity. Through the PRISMA statement, we synthesized 1128 Web of Science references between 2000 and 2024 regarding the clinical or experimental therapeutic applications of stingless bee bioproducts (honey and propolis) for human health. We aligned this trend with 2023’s leading morbidities in Mexico and people’s perceptions of healing experiences using stingless bee bioproducts. We found that the honey and propolis of 28 stingless bee species can aid in treating 8 out of the 19 most prevalent diseases in Mexico, primarily cancer, type-2 diabetes, obesity, and COVID-19. Although there is limited evidence from studies regarding the therapeutic applications of stingless bee bioproducts in the Americas, people can actively contribute to conservation as stewards of biodiversity by recognizing and appreciating the health benefits these bioproducts offer. We conclude that traditional meliponiculture systems safeguard knowledge that can be used to improve socio-ecosystem health. This is significant for strengthening locally based healthcare systems while fostering collaborative tropical landscape conservation. Full article
(This article belongs to the Section Biodiversity Conservation)
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<p>PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) flow diagram of studies identified in the Web of Science and used in the present study.</p>
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<p>The proportion of selected studies (<b>A</b>) and stingless bee species (<b>B</b>) by country. Country names adhere to ISO standard abbreviations: Argentina = AR, Brazil = BR, India = IN, Indonesia = ID, Malaysia = MY, Philippines = PH, Thailand = TH, Vietnam = VN.</p>
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<p>The proportion of research conducted on propolis (brown) and honey (yellow), along with their correlation to the most reported morbidities in Mexico as of 2023 by the Ministry of Health [<a href="#B33-diversity-17-00191" class="html-bibr">33</a>]. Morbidities follow the same order as that presented in <a href="#app1-diversity-17-00191" class="html-app">Appendix A</a>.</p>
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<p>Types of traditional hives used in Totonac meliponiculture in Papantla, Veracruz, Mexico include clay pots (<b>a</b>), wooden boxes (<b>b</b>), and bamboo stems (<b>c</b>). Photos by Guillermo Vázquez-Domínguez.</p>
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13 pages, 466 KiB  
Review
Hyperglycemia and Lung Cancer—A Possible Relationship
by Spasoje Popevic, Nikola Maric, Branislav Ilic, Slobodan Belic, Ivana Sekulovic Radovanovic, Sanja Dimic-Janjic and Mihailo Stjepanovic
Diagnostics 2025, 15(6), 651; https://doi.org/10.3390/diagnostics15060651 (registering DOI) - 7 Mar 2025
Abstract
Glucose is the main source of energy in human cells. Elevated levels of glucose are one of the most common metabolic disorders, and it has been shown to have a significant, mostly negative, effect on multiple chronic and acute diseases. Lung cancer remains [...] Read more.
Glucose is the main source of energy in human cells. Elevated levels of glucose are one of the most common metabolic disorders, and it has been shown to have a significant, mostly negative, effect on multiple chronic and acute diseases. Lung cancer remains one of the biggest challenges for treatment in modern medicine, with a high prevalence, incidence and mortality. Hyperglycemia is not uncommon in patients with lung cancer; however, it is usually overlooked. Patients with unregulated glycemia and lung cancer have been shown to have worse outcomes, reduced therapeutic effect and more complications during treatment. Studies have identified multiple molecular pathways common in both hyperglycemia and lung cancer; however, no clear correlation has been identified. By understanding these signaling pathways, we can influence the outcome therapeutically and thereby improve the survival of patients with lung cancer. Full article
(This article belongs to the Special Issue Hyperglycemia in Respiratory Diseases—Impact and Challenges)
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<p>Signs and symptoms of hyperglycemia and LC, with overlap.</p>
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21 pages, 1408 KiB  
Review
Current Understanding Regarding the Glioma Microenvironment and Impact of the Immune System
by Enes Demir, Deondra Montgomery, Ammar Saloum, Nasser Yaghi and Michael Karsy
Neuroglia 2025, 6(1), 13; https://doi.org/10.3390/neuroglia6010013 (registering DOI) - 7 Mar 2025
Abstract
High-grade gliomas are aggressive, primary, central nervous system tumors with low survival rates due to recurrence and resistance to current therapy models. Recent studies have highlighted the importance between the interaction of glioma cancer cells and cells of the tumor microenvironment (TME). Cancer [...] Read more.
High-grade gliomas are aggressive, primary, central nervous system tumors with low survival rates due to recurrence and resistance to current therapy models. Recent studies have highlighted the importance between the interaction of glioma cancer cells and cells of the tumor microenvironment (TME). Cancer stem cells and immune cells play a critical role in the TME of gliomas. TMEs in glioma include the perivascular TME, hypoxic TME, and invasive TME, each of which have evolved as our understanding of the involved cellular players has improved. This review discusses the multidimensional aspects of the current targeted therapies and interactions between glioma cells and the TME with specific focus on targeted immunotherapies. Understanding the complexities of the TME and elucidating the various tumor-cell interactions will be critical for facilitating the development of novel precision strategies, ultimately enabling better patient outcomes. Full article
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<p>The TME niches and molecular landscape of HGG (<b>a</b>) Overview of the TME of glioblastomas, with immunological players, and the three main niches showing a certain presence of specific molecular profiles. (<b>b</b>) The <span class="html-italic">vascular niche</span>: This niche is characterized by pronounced angiogenesis with a correspondingly increased VEGF; tumor macrophages accumulate here. Cytokines such as IL-6 and IL-8 are increased. Likewise, PTEN leads to increased matrix cross-linking proteins, resulting in accelerated angiogenesis. (<b>c</b>) The <span class="html-italic">hypoxic niche</span> contributes to glioma growth and resistance. PTEN is increased, and HIF contributes to the upregulation of VEGF and IL-8 and supports stem cell presence indicated via increased CD133. Via tyrosine hydroxylase activity, inflammatory cytokines are reduced. (<b>d</b>) The <span class="html-italic">invasive niche</span>: This niche is marked by a normal vessel distribution and the transition to normal brain tissue. Stem cells are associated with the vessel structure, glioma cells and microglia go along in tumor growth, and glioma stem cells are associated with endothelial cells via CXCL12/CXCR4. The cellular matrix also supports invasive tumor growth. CD133, CD133–prominin 1, PROM1, is a transmembrane protein; CXCL12. C-X-C motif chemokine ligand 12; CXCR4, C-X-C chemokine receptor type 4; EGFR, epidermal growth factor receptor; HIF-1α, hypoxia-inducible factor 1-alpha; HIF-2α, hypoxia-inducible factor 2-alpha; IL-6, interleukin (6); INFy, interferon gamma; MGMT, O6-methylguanine–DNA methyltransferase; PD-L1, programmed death-ligand 1; PTEN, phosphatase and tensin homolog; TNF-α, tumor necrosis factor-alpha; VEGF, vascular endothelial growth factor. Reproduced with permission from Barthel et al. under Creative Commons CC BY License [<a href="#B3-neuroglia-06-00013" class="html-bibr">3</a>].</p>
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<p>Molecular pathways implicated in the various TME of HGG. (<b>a</b>) The integrated hypoxic peri-arteriolar niche is a combined concept from the 5 interplayed niches. (<b>b</b>) Interaction between peri-vascular niche and hypoxia/necrotic niche via VEGF, SDF1α, and CXCR4. (<b>c</b>) ECM niche. (<b>d</b>) interaction between immune niche and hypoxia/necrotic niche via HIF1α, HIF2α, lymphocytes, CD8+ T cells, interferon-γ, CD4+ T cells, pSTAT pathway, CCL2, CFS1, macrophages, Foxp3+ Tregs, Th17 cells, TCR, CD4+ type1 Treg, and CD4+ T helper 17. (<b>e</b>) GSC hypoxia/necrotic niche. (<b>f</b>) Interaction between immune niche and peri-arteriolar niche via CD177, MMP9, OPN, and CD68+ macrophages. Reproduced with permission from Shi et al. under Creative Commons CC BY License [<a href="#B7-neuroglia-06-00013" class="html-bibr">7</a>].</p>
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<p>Interaction between the TME and glioma. The interactions between TME and glioma cells are complex, as the multiple players of widespread origin show. Intracellular factors, pathways, cytokines, genetic alterations, or environmental properties are involved, and the molecular characteristics of glioma cells are dependent on these parameters. Furthermore, the glioma molecular patterns influence the TME composition. 1p19q, combined loss of the short-arm chromosome 1 (i.e., 1p) and the long-arm chromosome 19 (i.e., 19q); ATRX, transcriptional regulator ATRX also known as ATP-dependent helicase ATRX (-mut, mutation); BRAF (human gene that encodes a protein called B-Raf); CCL2, CC-chemokine-ligand-2; CCR2, C–C chemokine receptor type 2; CDK4/6, cyclin-dependent kinase 4 and 6; CD133, CD133–prominin 1, PROM1, is a transmembrane protein; EGFR, epidermal growth factor receptor (vIII, variant III); EVs, extracellular vesicles; IDH1, isocitrate dehydrogenase-(1) (mut, mutation; wt, wild type); IL- family, interleukin family; KIAA1549-BRAAF, KIAA1549 (protein- coding gene); LOX, lysyl oxidase, also known as protein-lysine 6-oxidase; MGMT, O6-methylguanine–DNA methyltransferase; mTOR, mechanistic target of rapamycin; NF1, neurofibromatosis type 1; NF-κB, nuclear factor “kappa-light-chain-enhancer” of activated B-cells; P53, tumor protein P53 or tumor suppressor p53; PD-L1, programmed death-ligand 1; PHD, prolyl hydroxylase domain enzymes; PTEN, phosphatase and tensin homolog; RAS, RAS proteins control signaling pathways that are key regulators of normal cell growth and malignant transformation; RB1, RB transcriptional core- pressor 1; TME, tumor microenvironment; TNF, tumor necrosis fac- tor; WNT, Wnt signaling pathway; antiporter system xc. Reproduced with permission from Barthel et al. under Creative Commons CC BY License [<a href="#B3-neuroglia-06-00013" class="html-bibr">3</a>].</p>
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<p>Various targeted therapies directed at the TME of HGG. The targeting of specific areas of the TME in preclinical and clinical trials is shown. Various areas include the activation of effector cells using dendric cell vaccines or oncolytic viruses, targeting genetic lesions, neoantigens, and tumor-associated antigens, inhibition of secretory factors, inhibition of immunosuppressive cells, and immune checkpoint inhibitors. CAR-T: chimeric antigen receptor T cells; DAMP: damage-associated molecular pattern; EGFR: epidermal growth factor; GM-CSF: granulocyte-macrophage colony-stimulating factor; HSP: heat shock protein; IDH1: isocitrate dehydrogenase 1; PAMP: Pathogen-Associated Molecular Patterns; NK cell: natural killer cell; VEGF: vascular endothelial growth factor.</p>
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16 pages, 3213 KiB  
Article
Epigallocatechin Gallate Promotes Cuproptosis via the MTF1/ATP7B Axis in Hepatocellular Carcinoma
by Yuhan Fu, Lirui Hou, Kai Han, Chong Zhao, Hongbo Hu and Shutao Yin
Cells 2025, 14(6), 391; https://doi.org/10.3390/cells14060391 (registering DOI) - 7 Mar 2025
Abstract
Background: Cuproptosis is a form of copper-dependent non-apoptotic cell death. Cancer cells that prefer to use aerobic glycolysis for energy generation are commonly insensitive to cuproptosis, which hinders its application for cancer treatment. Epigallocatechin gallate (EGCG) possesses diverse pharmacological activities. However, the association [...] Read more.
Background: Cuproptosis is a form of copper-dependent non-apoptotic cell death. Cancer cells that prefer to use aerobic glycolysis for energy generation are commonly insensitive to cuproptosis, which hinders its application for cancer treatment. Epigallocatechin gallate (EGCG) possesses diverse pharmacological activities. However, the association between EGCG and cuproptosis has not been studied. Methods: The cell viability, proliferation, and cuproptosis-related protein levels were detected to investigate whether EGCG enhances the sensitivity of HCC cells to cuproptosis. The intracellular copper level, related copper metabolism proteins, and gene expression were detected to explore the mechanisms. In addition, a nude mouse xenograft model was established to determine the effects of EGCG on cuproptosis in tumor tissues. Results: The combination of EGCG and copper ionophores significantly enhanced the mortality of HCC cells and heightened the sensitivity of HCC cells to cuproptosis. There was a notable reduction in the expression of copper export protein copper-transporting P-type ATPase (ATP7B). EGCG effectively suppressed metal regulatory transcription factor (MTF1) expression and subsequently hindered the transcriptional regulation of ATP7B. EGCG also facilitated the intratumoral accumulation of copper and augmented susceptibility to cuproptosis in vivo. Conclusions: EGCG can increase the sensitivity of hepatocellular carcinoma cells to cuproptosis by promoting intracellular copper accumulation through the MTF1/ATP7B axis. Full article
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<p>ECGG enhanced copper ionophore-mediated hepatocellular carcinoma cell death in vitro. (<b>A</b>,<b>B</b>) Cell viability of HepG2 (<b>A</b>) and SMMC-7721 (<b>B</b>) after gradient concentrations of ES 24 h treatment with DMSO or 100 μM EGCG was measured with crystal violet staining. (<b>C</b>,<b>D</b>) The cell death rate and quantification of 100 μM EGCG combined with 30 nM ES or 3 μM 8-HQ treatment of HepG2 and SMMC-7721 cells for 24 h using flow cytometry. (<b>E</b>,<b>F</b>) Colony formation after treatment with 50 μM EGCG combined with 20 nM ES or 2 μM 8-HQ in HepG2. For (<b>A</b>–<b>F</b>), media were supplemented with 2 μM CuCl<sub>2</sub>. (The data are presented as the mean ± standard deviation. n = 3, *** <span class="html-italic">p</span> &lt; 0.001.).</p>
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<p>EGCG combined with copper ionophores promotes hepatocellular carcinoma cell cuproptosis. (<b>A</b>) Diagram of apoptosis, necroptosis, ferroptosis, and pyroptosis mechanisms. (<b>B</b>) Heatmap of cell viability after 100 μM EGCG combined with 30 nM ES or 3 μM 8-HQ treatment for 24 h with 20 μM Z-Vad-fmk, 20 μM DPQ, 10 μM Ac-FLTD-cmk, 10 μM Nec-1, 10 μM NSA, 10 μM Fer-1, 10 μM DFO, and 10 μM autophagy inhibitor CQ. (<b>C</b>–<b>F</b>) Expression of HSP70 in liver cancer cells treated with 100 μM EGCG combined with 30 nM ES and 3 μM 8-HQ for 24 h. (<b>G</b>) DLAT protein aggregation was analyzed using immunofluorescence (green, DLAT; blue, DAPI). White scale bars on full tiles are 10 μm. (<b>H</b>,<b>I</b>) Western blotting detection of DLAT protein aggregation in liver cancer cells. For (<b>B</b>–<b>I</b>), media were supplemented with 2 μM CuCl<sub>2</sub>. (The data are presented as the mean ± standard deviation. n = 3, ** <span class="html-italic">p</span> &lt; 0.01, and *** <span class="html-italic">p</span> &lt; 0.001.).</p>
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<p>EGCG inhibited ATP7B expression and increased intracellular copper accumulation. (<b>A</b>) Copper levels were assessed via ICP-MS in HepG2 cells treated with 30 nM ES with or without 100 μM EGCG for 18 h (n = 3). (<b>B</b>) Representative images of copper fluorescence in HepG2 cells treated with or without drugs for 18 h (red, copper; blue, DAPI). White scale bars on full tiled images are 100 μm. (<b>C</b>–<b>H</b>) ATP7B and CTR1 protein expression in HepG2 and SMMC-7721 cells treated with or without drugs for 18 h (n= 3). For A-H, media were supplemented with 2 μM CuCl<sub>2</sub>. The data are presented as the mean ± standard deviation. ** <span class="html-italic">p</span> &lt; 0.01, *** <span class="html-italic">p</span> &lt; 0.001, and ns indicates no significant difference.</p>
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<p>EGCG regulates ATP7B transcription through MTF1. (<b>A</b>–<b>C</b>) Cell viability (n = 3) (<b>A</b>), ATP7B expression (<b>B</b>), and quantification (n = 3) (<b>C</b>) after pretreatment with 50 nM BafA1 and 10 μM MG132 for 6 h followed by drug treatment for 18 h. (<b>D</b>) Relative mRNA levels of genes of CTR1 and ATP7B in HepG2 cells after 12 h of drug treatment (n = 3). (<b>E</b>) A correlation analysis was performed to evaluate the association between MTF1 and ATP7B using GEPIA2, (<b>F–I</b>) MTF1 expression levels in HCC cells treated with drugs after 12 h. The concentration of EGCG was 100 μM, ES was 30 nM, and 8-HQ was 3 μM. For (<b>A</b>–<b>I</b>), media were supplemented with 2 μM CuCl<sub>2</sub>. (The data are presented as the mean ± standard deviation. * <span class="html-italic">p</span> &lt; 0.05, *** <span class="html-italic">p</span> &lt; 0.001, and ns indicates no significant difference.).</p>
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<p>ECGG promoted cuproptosis in liver cancer in vivo. (<b>A</b>) Establishment of a xenograft model in nude mice and an experimental schematic diagram (n = 6). (<b>B</b>) Tumor growth curve. (<b>C</b>) Photographs of tumors. (<b>D</b>) Tumor weight. (<b>E</b>) Body weight of mice. (<b>F</b>) Tumor copper levels. (<b>G,H</b>) Protein content of tumor tissues. (The data are expressed as mean ± standard deviation, * <span class="html-italic">p</span> &lt; 0.05, ** <span class="html-italic">p</span> &lt; 0.01, *** <span class="html-italic">p</span> &lt; 0.001 and ns indicates no significant difference.).</p>
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12 pages, 26448 KiB  
Article
Three-Dimensional Bioprinted Autologous Minimally Manipulated Homologous Adipose Tissue for Skin Defects After Wide Excision of Skin Cancer Provides Early Wound Closure and Good Esthetic Patient Satisfaction
by Reina Matsumura, Hajime Matsumura, Yuichiro Kawai, Jeehee Kim, Min-Chae Lee, Yeongseo Yu, Miki Fujii, Kazuki Shimada and Takako Komiya
J. Clin. Med. 2025, 14(6), 1795; https://doi.org/10.3390/jcm14061795 (registering DOI) - 7 Mar 2025
Abstract
Background: An autologous minimally manipulated homologous adipose tissue (AMHAT) fabricated using three-dimensional (3D) bioprinting has shown potential in the treatment of diabetic foot ulcers and other chronic wounds. Methods: This study assessed the efficacy of AMHAT fabricated using 3D bioprinting for treating skin [...] Read more.
Background: An autologous minimally manipulated homologous adipose tissue (AMHAT) fabricated using three-dimensional (3D) bioprinting has shown potential in the treatment of diabetic foot ulcers and other chronic wounds. Methods: This study assessed the efficacy of AMHAT fabricated using 3D bioprinting for treating skin defects after a wide excision of skin cancer lesions where primary closure was not feasible. A total of 10 consecutive patients were included. The wounds were photographed and analyzed using AI, and the fat tissue harvested from the lower abdomen was processed into an AMHAT patch using a 3D bioprinter. The wound area was measured weekly until complete wound closure was achieved. Results: The area of the skin defects ranged from 1.77–6.22 cm2, averaging 2.72 cm2. Complete closure was achieved in 3–5 (average, 4.2) weeks. The residual area decreased from 52% after 1 week to 3% after 4 weeks. The scar appearance was esthetically favorable, with one patient showing mild nostril asymmetry. Furthermore, patient-reported outcome evaluation using the Japanese version of SCAR-Q for postoperative scars showed a very high level of satisfaction. Conclusions: The 3D bioprinted AMHAT accelerates wound healing with minimal scarring, offering an important option for skin defects where esthetics are a priority. Full article
(This article belongs to the Special Issue New Advances in Wound Healing and Skin Wound Treatment)
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<p>This figure shows the process of fabricating the 3D bioprinted AMHAT in case 1. (<b>a</b>) The adipose tissue is minced using scissors. (<b>b</b>) Micronization of the graft using a fat separator (Dr. INVIVO AI Regen KIT, ROKIT HEALTHCARE, Inc.). (<b>c</b>) Skin defects after skin cancer excision are scanned using an automated 3D modeling system (AiD Regen, ROKIT HEALTHCARE Inc.). (<b>d</b>,<b>e</b>) Creation of a scaffold by 3D printing using PCL. (<b>f</b>) Application of the 3D bioprinted AMHAT directly to the wound bed. AMHAT, autologous minimally manipulated homologous adipose tissue; 3D, three-dimensional; PCL, polycaprolactone.</p>
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<p>A Kaplan–Meier plot of wound area reduction.</p>
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18 pages, 4915 KiB  
Article
Novel Molecular Signatures Selectively Predict Clinical Outcomes in Colon Cancer
by Sarrah Lahorewala, Chandramukhi S. Panda, Karina Aguilar, Daley S. Morera, Huabin Zhu, Adriana L. Gramer, Tawhid Bhuiyan, Meera Nair, Amanda Barrett, Roni J. Bollag and Vinata B. Lokeshwar
Cancers 2025, 17(6), 919; https://doi.org/10.3390/cancers17060919 (registering DOI) - 7 Mar 2025
Abstract
Among the 152,810 estimated new cases of adenocarcinoma of the colon (COAD) and the rectum (READ) in 2024, the rates of colorectal cancer (CRC) are increasing in young adults (age < 55 years) [...] Full article
(This article belongs to the Special Issue Colorectal Cancer Awareness Month)
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<p>Differential transcript expression of 15 HA-family and EMT markers in Clinical Cohort-1. Scatter plot for each marker, where each dot represents a single specimen. Line represents the median marker level for each group. <span class="html-italic">p</span>-values were two-tailed and calculated using the Mann–Whitney test. (<b>A</b>–<b>C</b>) Comparison of marker levels between normal (<span class="html-italic">n</span> = 27) and CRC (<span class="html-italic">n</span> = 67) specimens. (<b>D</b>–<b>F</b>) Comparison of marker levels between non-metastatic (<span class="html-italic">n</span> = 43) and metastatic (<span class="html-italic">n</span> = 24) specimens.</p>
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<p>Association of the HA-family/EMT signatures with clinical outcome in cohort-1. (<b>A</b>) Hierarchical clustering of tumor specimens in cohort-1 by marker expression. The expression data of each marker, calculated using the Z-score, were used for generating the heatmap. (<b>B</b>,<b>C</b>) HYAL1 + N-Cadh (CM-2) and HYAL-1 + HAS-2 + N-Cadh + Slug + SNAI1 + MMP-9 (CM-6) signature expression in tumor specimens was stratified by metastasis. The line represents the Mean value of the signature value in each group. <span class="html-italic">p</span>-values were two-tailed and calculated using the Mann–Whitney test. (<b>B</b>) CM-2. (<b>C</b>) CM-6. (<b>D</b>,<b>E</b>) Kaplan–Meier plots for metastasis; risk was stratified by CM-2 (<b>D</b>) and CM-6 (<b>E</b>) signatures. The low and high levels of each signature were stratified by the Youden index, calculated from the ROC curve. <span class="html-italic">p</span>-value Log-Rank test.</p>
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<p>HA and HAase levels and the expression of HA-family/EMT protein markers and the signatures in clinical cohorts 1 and 2. (<b>A</b>,<b>B</b>) HA (<b>A</b>) and HAase (<b>B</b>) levels were measured in normal colon and tumor tissue extracts using HA and HAase tests. The levels were normalized to total protein. Each dot represents HA or HAase levels in a tissue. (<b>C</b>) Immunoblot analysis of normal colon and tumor specimens (<span class="html-italic">n</span> = 2/category) for the indicated proteins; actin: loading control. Tumor specimens were from patients who either developed or did not develop metastasis (Met) during follow-up. The uncropped blots and row data are shown in <a href="#app1-cancers-17-00919" class="html-app">Figure S2</a> (<b>D</b>) Normal colon and tumor specimens from the metastasis and non-metastasis groups were stained via immunohistochemistry for individual markers. Representative images are shown; magnification: 400×. (<b>E</b>) Quantification of the IHC staining scores in clinical cohort-2 for tumor specimens. Tumor specimens were stratified based on the development of metastasis. (<b>F</b>) Signature expression by combining either two (CM-2) or four (CM-4) markers in tumor specimens stratified based on the development of metastasis. Note the markers were combined based on a combination reaching statistical significance.</p>
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<p>Association of HA-family/EMT protein biomarker signatures with clinical outcomes. (<b>A</b>) Hierarchical clustering of tumor specimens in clinical cohort-2 by IHC staining scores for each marker and the indicated CM-2 and CM-4 expression signatures. Expression data of each marker, calculated from the Z-score, were used for generating the heatmap. (<b>B</b>–<b>F</b>) Kaplan–Meier plots of metastasis risk stratified by the indicated HA-family/EMT signatures. The low and high levels of each signature were stratified by the Youden index calculated from the ROC curve. <span class="html-italic">p</span>-value Log-Rank test.</p>
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<p>Differential expression of HA-family, EMT markers, and HA-family/EMT signatures in the TCGA COADREAD dataset. (<b>A</b>) Hierarchical clustering of the specimens in the TCGA COADREAD dataset (n-383) by the expression of the six markers (HYAL-1, HAS-2, N-Cadh, SNAI1, Slug, and MMP-9) expression. Expression data of each marker, calculated from the Z-score, were used for generating the heatmap. (<b>B</b>,<b>C</b>) Kaplan–Meier plots for overall survival (OS); risk stratified by CM-2 (HYAL1 + N-Cadh) (<b>B</b>) and CM-6 (HYAL-1 + HAS-2 + N-Cadh + Slug + SNAI1 + MMP-9 (<b>C</b>) signatures. (<b>D</b>,<b>E</b>) The expression of CM-2 and CM-6 signatures was analyzed in the COAD subset: Colon adenocarcinoma, <span class="html-italic">n</span> = 245; colon mucinous adenocarcinoma, <span class="html-italic">n</span> = 37. Kaplan–Meier plots for overall survival (OS); risk stratified by CM-2 (<b>D</b>) and CM-6 (<b>E</b>) signatures. (<b>F</b>,<b>G</b>) The expression of CM-2 and CM-6 signatures was analyzed in the READ subset: Rectal adenocarcinoma, <span class="html-italic">n</span> = 87; rectal mucinous adenocarcinoma, <span class="html-italic">n</span> = 5. (<b>B</b>–<b>G</b>) The low and high levels of each signature were stratified by the Youden index calculated from the ROC curve. <span class="html-italic">p</span>-value Log-Rank test.</p>
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50 pages, 5064 KiB  
Systematic Review
Design, Algorithms, and Applications of Microstrip Antennas for Image Acquisition: Systematic Review
by Luis Fernando Guerrero-Vásquez, Nathalia Alexandra Chacón-Reino, Byron Steven Sigüenza-Jiménez, Felipe Tomas Zeas-Loja, Jorge Osmani Ordoñez-Ordoñez and Paúl Andrés Chasi-Pesantez
Electronics 2025, 14(6), 1063; https://doi.org/10.3390/electronics14061063 (registering DOI) - 7 Mar 2025
Abstract
This systematic literature review investigates microstrip antenna applications in image acquisition, focusing on their design characteristics, reconstruction algorithms, and application areas. We applied the PRISMA methodology for article selection. From selected studies, classifications were identified based on antenna patch geometry, substrate types, and [...] Read more.
This systematic literature review investigates microstrip antenna applications in image acquisition, focusing on their design characteristics, reconstruction algorithms, and application areas. We applied the PRISMA methodology for article selection. From selected studies, classifications were identified based on antenna patch geometry, substrate types, and image reconstruction algorithms. According to inclusion criteria, a significant increase in publications on this topic has been observed since 2013. Considering this trend, our study focuses on a 10-year publication range, including articles up to 2023. Results indicate that medical applications, particularly breast cancer detection, dominate this field. However, emerging areas are gaining attention, including stroke detection, bone fracture monitoring, security surveillance, avalanche radars, and weather monitoring. Our study highlights the need for more efficient algorithms, system miniaturization, and improved models to achieve precise medical imaging. Visual tools such as heatmaps and box plots are used to provide a deeper analysis, identify knowledge gaps, and offer valuable insights for future research and development in this versatile technology. Full article
(This article belongs to the Section Microwave and Wireless Communications)
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<p>PRISMA method scheme.</p>
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<p>Publication scheme of articles by year.</p>
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<p>Distribution of studies by countries.</p>
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<p>Article classification by geometry design.</p>
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<p>Types of antenna designs, including (<b>a</b>) Slot insertion, (<b>b</b>) Basic geometry, (<b>c</b>) Array antenna, (<b>d</b>) Slit insertion, (<b>e</b>) Vivaldi geometry, (<b>f</b>) Bowtie slot, (<b>g</b>) Fractal slot (<b>h</b>) Fractal array (<b>i</b>) Spiral (<b>j</b>) Bowtie Array. Each design has unique characteristics related to image adquisition applications. These are representative figures of antennas, intended as a visual reference for the design type, but not necessarily functional with the current dimensions.</p>
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<p>Article classification by substrates used in microstrip antennas.</p>
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<p>Article classification by image reconstruction algorithms.</p>
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<p>Article classification by application type.</p>
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<p>Article classification by application type and antenna bandwidth.</p>
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<p>Article classification by application type and antenna operating frequency.</p>
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<p>Article classification by application type and antenna size.</p>
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<p>Article classification by reconstruction algorithms and antenna bandwidth.</p>
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<p>Article classification by reconstruction algorithms and antenna operating frequency.</p>
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<p>Article classification by reconstruction algorithm and antenna area.</p>
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<p>Standard deviation values of different dimensions of our review.</p>
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<p>Article classification by application and image reconstruction algorithm.</p>
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<p>Article classification by applications and frequency bands.</p>
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<p>Article classification by applications and antenna geometry.</p>
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<p>Article classification by application and substrate.</p>
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<p>Classification of frequency bands and image reconstruction algorithms.</p>
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<p>Article classification by antenna geometry and frequency band.</p>
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<p>Article classification by antenna geometry and substrate.</p>
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<p>Article classification by substrate and image reconstruction algorithms.</p>
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<p>Article classification by substrate and frequency band.</p>
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<p>Article classification by antenna geometry and image reconstruction algorithm.</p>
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20 pages, 2200 KiB  
Article
Quality of Single-Cone Obturation Using Different Sizes of Matching Gutta-Percha Points of Two Reciprocating Single-File Systems in Curved and Straight Root Canals
by Shakiba Arvaneh, René Schwesig, Shahpar Haghighat and Christian Ralf Gernhardt
Medicina 2025, 61(3), 465; https://doi.org/10.3390/medicina61030465 (registering DOI) - 7 Mar 2025
Abstract
Background and Objectives: Endodontic success depends on eliminating infection and creating a durable seal to prevent recontamination. The goal of this study was to assess the impact of different ISO sizes on the obturation quality using two reciprocating single-file systems, WaveOne® Gold [...] Read more.
Background and Objectives: Endodontic success depends on eliminating infection and creating a durable seal to prevent recontamination. The goal of this study was to assess the impact of different ISO sizes on the obturation quality using two reciprocating single-file systems, WaveOne® Gold and Procodile®, in two different canal morphologies. Material and Methods: Overall, 140 root canals from human permanent teeth were randomly assigned to 14 groups based on selected ISO sizes and straight and curved canal curvatures, and the two file systems, WaveOne® Gold files in ISO sizes 20, 25, and 45, and Procodile® files in ISO sizes 20, 25, 40, and 45, were employed for canal preparation. These 140 canals were obturated using corresponding gutta-percha points and AH-Plus sealer and the quality of the obturation was assessed after sectioning the roots (apical, middle, coronal third) by evaluating the resulting 420 sections under a digital fluorescence microscope with regard to the proportion of gutta-percha, sealer, and unfilled areas. The results were analyzed using nonparametric tests. Results: For both systems, there was a significant difference in the percentage of gutta-percha-filled areas (PGFA, p < 0.001) and sealer-filled areas (PSFA, p < 0.001 among the different ISO sizes). However, no significant difference was observed in the percentage of unfilled areas (PUA, p = 0.354). ISO 40 demonstrated the best results, with the highest percentage of gutta-percha-filled areas (87%) and the lowest percentages of sealer-filled areas (13%) and voids (0.5%). In contrast, the lowest percentages of gutta-percha filled areas were observed in root canal fillings with ISO 20 (81%) and ISO 25 (81%). Regarding both reciprocating file system sizes, ISO 45 in WaveOne® Gold and ISO 40 in Procodile® demonstrated significantly improved (p < 0.05) filling quality, with PGFA of 85% and 87%, respectively. The differences between both systems were not significant. Conclusions: The results presented suggest that larger sizes provide better filling results, especially in the apical region. These results underline the importance of selecting appropriate preparation sizes adjusted to the initial anatomical specifications to optimize root canal obturation and ensure a high quality and durable seal. Full article
(This article belongs to the Section Dentistry and Oral Health)
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<p>Sample selection and distribution within the different experimental groups.</p>
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<p>Steps in root canal treatment: 1. trepanation; 2. shaping and cleaning; 3. obturation using a single cone Gutta-percha and sealer.</p>
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<p>(<b>a</b>) The root-filled tooth was sectioned at three levels (apical, middle, and coronal). (<b>b</b>) A schematic representation of sections under a microscope (magnification 6×): red—gutta-percha; yellow—sealer; black—voids.</p>
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<p>Percentage of gutta-percha, sealer, and unfilled areas regarding different ISO sizes.</p>
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<p>Percentage of gutta-percha, sealer, and unfilled area per ISO size depending on two systems.</p>
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<p>Percentage of areas filled with gutta-percha, sealer, and unfilled area for ISO size depending on curved and straight canals.</p>
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10 pages, 780 KiB  
Article
Isolated Liver Recurrence After Cytoreduction in High-Grade Serous Ovarian Carcinoma: Experience of a Tertiary Center in Turkey
by Hande Esra Koca Yıldırım, İzzet Özgürlük, Burak Ersak, Dilek Yüksel, Eyüp Gökhan Turmuş, Baran Yeşil, Çiğdem Kılıç, Sevgi Koç, Nurettin Boran, Sadun Sucu and Caner Çakır
J. Clin. Med. 2025, 14(6), 1791; https://doi.org/10.3390/jcm14061791 (registering DOI) - 7 Mar 2025
Abstract
Background: Serous epithelial ovarian cancer is typically diagnosed at an advanced stage and often recurs following treatment. Isolated organ recurrence is rare in this disease, making treatment planning a critical decision. Therefore, we investigated the survival rates of patients who developed isolated liver [...] Read more.
Background: Serous epithelial ovarian cancer is typically diagnosed at an advanced stage and often recurs following treatment. Isolated organ recurrence is rare in this disease, making treatment planning a critical decision. Therefore, we investigated the survival rates of patients who developed isolated liver recurrence. Methods: The entire cohort included patients who underwent cytoreductive surgery between January 1993 and December 2020. We evaluated patients who completed primary chemotherapy after cytoreductive surgery based on their status of isolated liver recurrence. We created two groups: patients with isolated parenchymal recurrence and patients with isolated capsular recurrence. Staging was based on the International Federation of Gynecology and Obstetrics (FIGO) 2014 staging criteria. For patients treated before 2014, cancer staging was adapted to the FIGO 2014 system based on a surgical and pathological assessment. Results: The mean ages of patients with liver capsule and parenchymal recurrence at the time of primary surgery were 47 ± 10.6 and 49 ± 8.9 years, respectively. The median recurrence of patients with capsular recurrence was 13 (2–70) months. In patients with parenchymal recurrence, the duration was 10 months (4–80) and was statistically insignificant. While survival was 41.5 (5–120) months in patients with capsular recurrence, it was 34 (12–120) months in patients with parenchymal recurrence, but there was no statistical difference. Conclusions: In our 27 years’ of experience with EOC management, we have studied patients with isolated liver recurrences. The finding that either capsular or parenchymal liver recurrence has no significant impact on overall survival suggests that both types of recurrence can be managed with similar treatment and follow-up approaches. This observation could simplify patient management and improve outcomes by allowing clinicians to focus on optimal surgical and systemic treatment strategies rather than the anatomic pattern of recurrence. Full article
(This article belongs to the Section Obstetrics & Gynecology)
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<p>DFS: Disease-free survival.</p>
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<p>OS: overall survival.</p>
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