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Keywords = S100B and LDH

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20 pages, 5964 KB  
Article
Synthesis and Characterization of Bioactive Coatings with Bone Regeneration Potential and Anti-Resorptive Effect
by Maxim V. Maximov, Lea Sleiman, Oana Cristina Maximov, Roxana Doina Trușcă, Ludmila Motelica, Angela Spoială, Denisa Ficai, Anton Ficai and Sorina Dinescu
Coatings 2025, 15(10), 1120; https://doi.org/10.3390/coatings15101120 - 26 Sep 2025
Viewed by 375
Abstract
Bioactive coatings are of great interest for orthopedic applications, as they combine mechanical stability with biological functionality. In this study, stainless steel discs were coated with 45S5 bioactive glass doped with 1.0 wt% samarium by spin coating, followed by surface functionalization with benfotiamine [...] Read more.
Bioactive coatings are of great interest for orthopedic applications, as they combine mechanical stability with biological functionality. In this study, stainless steel discs were coated with 45S5 bioactive glass doped with 1.0 wt% samarium by spin coating, followed by surface functionalization with benfotiamine through spraying. This strategy integrates three components: a metallic substrate as a stable and inexpensive support, a bioactive glass layer with well-known osteogenic potential, and a superficial organic layer of benfotiamine, a lipid-soluble analog of vitamin B1 with higher bioavailability. Samarium doping was selected based on previously reported antimicrobial potential against clinically relevant staphylococci, while the rationale for benfotiamine functionalization derives from literature describing vitamin B1 derivatives with anti-resorptive and osteogenic activity. The coatings were characterized by scanning electron microscopy (SEM) and Fourier-transform infrared (FTIR) microscopy. Bioactivity was assessed by immersion in simulated body fluid (SBF), where phosphate bands indicated the formation of calcium phosphate phases (CaPs). Wettability tests showed a reduced contact angle after benfotiamine functionalization. Cytocompatibility was evaluated by LDH and MTT assays with MC3T3-E1 cells, suggesting overall biocompatibility and enhanced cell viability after 7 days for the benfotiamine-functionalized coatings. The present findings support a simple and cost-effective route to multifunctional coatings with potential relevance for future orthopedic applications. Full article
(This article belongs to the Special Issue Films and Coatings with Biomedical Applications)
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16 pages, 2460 KB  
Article
First Look at Chemopreventive Properties of Chlorella pyrenoidosa Water Extract in Human Endometrial Adenocarcinoma Cells—Preliminary In Vitro Study
by Weronika Rzeska, Michał Chojnacki, Aneta Adamiak-Godlewska, Andrzej Semczuk and Marta Kinga Lemieszek
Int. J. Mol. Sci. 2025, 26(18), 9142; https://doi.org/10.3390/ijms26189142 - 19 Sep 2025
Viewed by 478
Abstract
Chlorella species are classified as functional food, with great anticancer effects. Despite the huge popularity of Chlorella-based products, there is a lack of evidence showing their usefulness in the prevention and treatment of endometrial cancer. The study presented here aimed to enrich knowledge [...] Read more.
Chlorella species are classified as functional food, with great anticancer effects. Despite the huge popularity of Chlorella-based products, there is a lack of evidence showing their usefulness in the prevention and treatment of endometrial cancer. The study presented here aimed to enrich knowledge resources in this area. The chemopreventive effect of water extracts of Chlorella pyrenoidosa was investigated in human endometrial adenocarcinoma HEC-1-B, KLE and EDC cells using MTT, BrdU, LDH, Wound assays, Cell Death Detection ELISA and nuclear double staining. C. pyrenoidosa extract inhibited the metabolic activity, DNA synthesis and migratory capacity of endometrial cancer cells. Moreover, the extract eliminated cancer cells, causing damage to their cell membranes and inducing apoptosis. The cells most resistant to chlorella extract were EDC cells (low grade), while the best response to the treatment was noted in KLE cells (high grade). The performed study revealed the chemopreventive properties of C. pyrenoidosa extract based on inhibition of endometrial cancer cell viability, proliferation and migratory capacity, as well as induction of cytotoxicity and apoptosis. Collected data suggested enhancement of extract chemopreventive properties with increasing advancement and malignancy of cancer cells. Obtained results encourage future clinical research and detailed chemical evaluation to specify the extract’s phytochemical composition. Full article
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15 pages, 3006 KB  
Article
Metabolic Regulation of Influenza Vaccine Responses in Racially Diverse Hispanics
by Daniela Frasca, Maria Romero and Suresh Pallikkuth
Vaccines 2025, 13(9), 938; https://doi.org/10.3390/vaccines13090938 - 2 Sep 2025
Viewed by 673
Abstract
Background: Racial and ethnic differences in vaccine responses, particularly within Hispanic populations, remain underexplored. Disparities in immune function may be influenced by metabolic and inflammatory mechanisms. Methods: The current study investigated humoral immune responses to influenza vaccination in a diverse cohort of Hispanic [...] Read more.
Background: Racial and ethnic differences in vaccine responses, particularly within Hispanic populations, remain underexplored. Disparities in immune function may be influenced by metabolic and inflammatory mechanisms. Methods: The current study investigated humoral immune responses to influenza vaccination in a diverse cohort of Hispanic individuals from South Florida, encompassing both White and Black Hispanics. Antibody responses were assessed post-vaccination, and B cell phenotypes were analyzed to evaluate inflammatory and metabolic characteristics. In vitro experiments were conducted to determine whether blocking metabolic pathways could alter the inflammatory phenotype of B cells. Data were analyzed using an unpaired Student’s t-test (two-tailed), and correlation analysis was conducted with Pearson correlation. Results: Our findings indicated that Black Hispanic individuals exhibited significantly reduced antibody responses compared to White Hispanics (p < 0.01) following influenza vaccination. This diminished humoral response correlated with inversely with serum LDH (r = −0.58; p = 0.0005) and other intrinsic inflammatory phenotypes in blood-derived B cells and was supported by changes in metabolic activity. In vitro blockade of metabolic pathways effectively reduced the inflammatory phenotype of B cells from Black Hispanic individuals, suggesting a mechanistic link between metabolic dysfunction and impaired vaccine-induced immunity. Conclusion: This study is the first to reveal racial disparities in influenza vaccine responses within a Hispanic population, highlighting reduced antibody production in Black Hispanics. These findings suggest that metabolically driven B cell inflammation may play a critical role and point to potential therapeutic strategies to address disparities in vaccine-induced immunity. Full article
(This article belongs to the Special Issue Influenza Vaccines and Influenza Vaccination in Europe)
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23 pages, 11376 KB  
Article
Hyssopus cuspidatus Boriss Volatile Extract (SXC): A Dual-Action Antioxidant and Antifungal Agent Targeting Candida albicans Pathogenicity and Vulvovaginal Candidiasis via Host Oxidative Stress Modulation and Fungal Metabolic Reprogramming
by Yun-Dan Guo, Ming-Xuan Zhang, Quan-Yong Yu, Lu-Lu Wang, Yan-Xing Han, Tian-Le Gao, Yuan Lin, Cai Tie and Jian-Dong Jiang
Antioxidants 2025, 14(9), 1046; https://doi.org/10.3390/antiox14091046 - 25 Aug 2025
Cited by 1 | Viewed by 772
Abstract
Background and purpose: Vulvovaginal candidiasis (VVC), caused by Candida albicans (C. albicans), is exacerbated by oxidative stress and uncontrolled inflammation. Pathogens like C. albicans generate reactive oxygen species (ROS) to enhance virulence, while host immune responses further amplify oxidative damage. This [...] Read more.
Background and purpose: Vulvovaginal candidiasis (VVC), caused by Candida albicans (C. albicans), is exacerbated by oxidative stress and uncontrolled inflammation. Pathogens like C. albicans generate reactive oxygen species (ROS) to enhance virulence, while host immune responses further amplify oxidative damage. This study investigates the antioxidant and antifungal properties of Hyssopus cuspidatus Boriss volatile extract (SXC), a traditional Uyghur medicinal herb, against fluconazole-resistant VVC. We hypothesize that SXC’s bioactive volatiles counteract pathogen-induced oxidative stress while inhibiting fungal growth and inflammation. Methods: GC-MS identified SXC’s major bioactive components, while broth microdilution assays determined minimum inhibitory concentrations (MICs) against bacterial/fungal pathogens, and synergistic interactions with amphotericin B (AmB) or fluconazole (FLC) were assessed via time–kill kinetics. Anti-biofilm activity was quantified using crystal violet/XTT assays, and in vitro studies evaluated SXC’s effects on C. albicans-induced cytotoxicity (LDH release in A431 cells) and inflammatory responses (cytokine production in LPS-stimulated RAW264.7 macrophages). A murine VVC model, employing estrogen-mediated pathogenesis and intravaginal C. albicans challenge, confirmed SXC’s in vivo effects. Immune modulation was assessed using ELISA and RT-qPCR targeting inflammatory and antioxidative stress mediators, while UPLC-MS was employed to profile metabolic perturbations in C. albicans. Results: Gas chromatography-mass spectrometry identified 10 key volatile components contributing to SXC’s activity. SXC exhibited broad-spectrum antimicrobial activity with MIC values ranging from 0.125–16 μL/mL against bacterial and fungal pathogens, including fluconazole-resistant Candida strains. Time–kill assays revealed that combinations of AmB-SXC and FLC-SXC achieved sustained synergistic bactericidal activity across all tested strains. Mechanistic studies revealed SXC’s dual antifungal actions: inhibition of C. albicans hyphal development and biofilm formation through downregulation of the Ras1-cAMP-Efg1 signaling pathway, and attenuation of riboflavin-mediated energy metabolism crucial for fungal proliferation. In the VVC model, SXC reduced vaginal fungal burden, alleviated clinical symptoms, and preserved vaginal epithelial integrity. Mechanistically, SXC modulated host immune responses by suppressing oxidative stress and pyroptosis through TLR4/NF-κB/NLRP3 pathway inhibition, evidenced by reduced caspase-1 activation and decreased pro-inflammatory cytokines (IL-1β, IL-6, TNF-α). Conclusions: SXC shows promise as a broad-spectrum natural antimicrobial against fungal pathogens. It inhibited C. albicans hyphal growth, adhesion, biofilm formation, and invasion in vitro, while reducing oxidative and preserving vaginal mucosal integrity in vivo. By disrupting fungal metabolic pathways and modulating host immune responses, SXC offers a novel approach to treating recurrent, drug-resistant VVC. Full article
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9 pages, 629 KB  
Communication
Circulating Calprotectin Distinguishes Metastatic Melanoma and Predicts Liver Metastasis
by István Szász, Viktória Koroknai, Tünde Várvölgyi, Gabriella Emri, Imre Lőrinc Szabó and Margit Balázs
Int. J. Mol. Sci. 2025, 26(16), 8028; https://doi.org/10.3390/ijms26168028 - 20 Aug 2025
Viewed by 573
Abstract
Calprotectin, a heterodimer of the S100A8 and S100A9 proteins, has been implicated in cancer-related inflammation and metastasis. Its role in melanoma progression, particularly in organ-specific metastasis, remains underexplored. In this retrospective study, plasma calprotectin levels were measured in 201 individuals, including healthy controls [...] Read more.
Calprotectin, a heterodimer of the S100A8 and S100A9 proteins, has been implicated in cancer-related inflammation and metastasis. Its role in melanoma progression, particularly in organ-specific metastasis, remains underexplored. In this retrospective study, plasma calprotectin levels were measured in 201 individuals, including healthy controls (n = 22), melanoma patients without evidence of metastasis (n = 71), and patients with metastatic melanoma (n = 108). Calprotectin concentrations were determined using the ELISA assay. Receiver operating characteristic (ROC) curve analyses were used to evaluate its diagnostic value, both alone and in combination with established biomarkers S100B and LDH. Plasma calprotectin levels were significantly elevated in patients with metastatic melanoma compared to non-metastatic patients (p < 0.001). Calprotectin showed moderate diagnostic value (AUC = 0.672), which improved to 0.755 when combined with S100B and LDH. Organ-specific analysis revealed that patients with liver metastases exhibited the highest calprotectin concentrations, with good discriminatory power (AUC = 0.710). No significant association was found between calprotectin levels and the type of metastasis identified (lymphatic vs. hematogenous). Logistic regression analysis showed that calprotectin levels above 2728 ng/mL were associated with a 7.4-fold increased risk of liver metastasis. Calprotectin is a promising blood-based biomarker that may enhance the detection of metastatic melanoma, particularly in cases with liver involvement. These findings suggest that calprotectin could be integrated into multivariable prediction models to improve risk stratification in clinical practice. Full article
(This article belongs to the Special Issue Melanoma: Molecular Mechanism and Therapy, 2nd Edition)
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22 pages, 1654 KB  
Article
Astaxanthin Attenuates Chlorpyrifos-Induced Pulmonary Cytotoxicity by Modulating Mitochondrial Redox and Inflammatory Pathways
by Mediha Demet Okudan Altındaş and Adem Güner
Curr. Issues Mol. Biol. 2025, 47(8), 663; https://doi.org/10.3390/cimb47080663 - 17 Aug 2025
Viewed by 785
Abstract
Chlorpyrifos (CPF), an organophosphate pesticide, is known to induce pulmonary toxicity through oxidative stress, mitochondrial dysfunction, and inflammation. Astaxanthin (ASX), a xanthophyll carotenoid derived primarily from marine microalgae (Haematococcus pluvialis), possesses strong antioxidant properties and has demonstrated cellular protective effects in numerous oxidative [...] Read more.
Chlorpyrifos (CPF), an organophosphate pesticide, is known to induce pulmonary toxicity through oxidative stress, mitochondrial dysfunction, and inflammation. Astaxanthin (ASX), a xanthophyll carotenoid derived primarily from marine microalgae (Haematococcus pluvialis), possesses strong antioxidant properties and has demonstrated cellular protective effects in numerous oxidative stress studies. However, its efficacy against CPF-induced lung cell damage remains uncharacterized. This study revealed the protective role of ASX, as a pretreatment and co-treatment, against CPF-induced cytotoxicity in human A549 lung adenocarcinoma cells by assessing cell viability, intracellular reactive oxygen species (IROS), total oxidative status (TOS), total antioxidant capacity (TAC), mitochondrial membrane potential (MMP), intracellular calcium ions (Ca2+), lactate dehydrogenase (LDH) release, malondialdehyde (MDA) levels, glutathione peroxidase (GPx) activity, superoxide dismutase (SOD) activity, DNA fragmentation, and apoptosis/inflammation-associated gene expression. CPF treatment significantly decreased cell viability and TAC, while elevating IROS, TOS, MMP, intracellular Ca2+, and LDH release. CPF also increased MDA levels and suppressed GPx and SOD activities. DNA fragmentation and quantitative polymerase chain reaction (qPCR) analysis revealed upregulation of pro-apoptotic and inflammatory markers such as BCL2-associated X protein (BAX), caspase-3 (CASP3), tumor protein p53 (TP53), tumor necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1β), nuclear factor kappa B (NFκB), and voltage-dependent anion-selective channel protein 1 (VDAC1) and suppression of anti-apoptotic B-cell lymphoma 2 (BCL2) and antioxidant defense genes nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1). ASX treatment, particularly when administered as a pretreatment, significantly reversed CPF-induced oxidative and inflammatory responses by restoring SOD, GPx, and TAC levels, reducing IROS, TOS, MDA, and LDH release, and downregulating apoptotic and inflammatory gene expressions. ASX pretreatment notably decreased MMP and intracellular Ca2+ levels, indicating protection against mitochondrial dysfunction and calcium dysregulation. ASX upregulated Nrf2 and HO-1 expression and restored the BCL2/BAX balance, suggesting inhibition of mitochondrial-mediated apoptosis. Additionally, ASX significantly attenuated CPF-induced anti-angiogenic effects in the in ovo Hen’s Egg Test Chorioallantoic Membrane (HET-CAM) assay. These findings demonstrate, for the first time, that ASX exerts a broad spectrum of protective effects against CPF-induced cytotoxicity in lung cells, mainly through the stabilization of mitochondrial redox status and modulation of apoptosis- and inflammation-related gene pathways, highlighting ASX as a promising candidate for further therapeutic development. Furthermore, the pronounced efficacy observed in the pretreatment regimen suggests that ASX can be evaluated as a potential nutritional preventive strategy in high-risk populations with occupational or environmental CPF exposure. Full article
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13 pages, 686 KB  
Article
Predictive Power of Baseline [18F]FDG PET/CT for Adverse Events in DLBCL Patients Undergoing CAR-T Cell Therapy
by Helena A. Peters, Emil Novruzov, Ben-Niklas Bärmann, Daniel Weiss, Matthias Boschheidgen, Vivien Lorena Ivan, Nora Liebers, Johannes Fischer, Eduards Mamlins, Aleksandar Radujkovic, Guido Kobbe, Julian Kirchner, Peter Minko, Kathrin Nachtkamp, Paul Jäger, Christina Antke, Frederik L. Giesel, Sascha Dietrich, Gerald Antoch and Kai Jannusch
Diagnostics 2025, 15(16), 2025; https://doi.org/10.3390/diagnostics15162025 - 13 Aug 2025
Viewed by 622
Abstract
Objectives: Evaluation of the predictive potential of pre-CAR-T [18F]FDG PET/CT in Diffuse Large B-Cell Lymphoma (DLBCL) patients concerning Cytokine Release Syndrome (CRS) and Immune Effector Cell-associated Neurotoxicity Syndrome (ICANS). Methods: Eighteen DLBCL patients (mean age: 60 ± 12 years) [...] Read more.
Objectives: Evaluation of the predictive potential of pre-CAR-T [18F]FDG PET/CT in Diffuse Large B-Cell Lymphoma (DLBCL) patients concerning Cytokine Release Syndrome (CRS) and Immune Effector Cell-associated Neurotoxicity Syndrome (ICANS). Methods: Eighteen DLBCL patients (mean age: 60 ± 12 years) who underwent pre-therapeutic [18F]FDG-PET/CT and CAR-T cell therapy were retrospectively included. Median follow-up time was ten months (IQR6-16) after CAR-T cell infusion. Age, sex, serum lactate dehydrogenase (LDH), interleukin-6 (IL-6), C-reactive protein (CRP), and modified Endothelial Activation and Stress Index (mEASIX) were obtained. Potential occurrence of CRS/ICANS and the SUVmax were evaluated. Pearson and Spearman correlations, group comparisons (Mann–Whitney U-test) and the odds ratio (OR) were calculated. P values below 0.05 were defined as statistically significant and 95%-confidence intervals (CI) were calculated. Results: Pre-therapeutic SUVmax correlated positively with LDH (r = 0.5; p = 0.02), with the grade of CRS (r = 0.5; p = 0.03) and with the grade of ICANS (r = 0.6; p = 0.01). Appearance of ICANS was significantly correlated with pre-therapeutic SUVmax (p = 0.03; U = 7.0; Z = −2.2). Using ROC analysis and Youden’s index, an SUVmax threshold of 17 (AUC: 0.865; p < 0.01) was defined. Patients exceeding a pre-therapeutic SUVmax of 17 had a significantly higher risk of CRS grade > 1 (OR = 22; CI 2, 314; p = 0.03) and ICANS grade > 1 (OR = 18; CI 1, 271; p = 0.04). Conclusions: Pre-therapeutic SUVmax may be a useful marker for identifying DLBCL patients at risk for CRS and ICANS. Full article
(This article belongs to the Special Issue PET/CT Imaging in Oncology: Clinical Advances and Perspectives)
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25 pages, 10636 KB  
Article
Qifu Decoction Alleviates Lipopolysaccharide-Induced Myocardial Dysfunction by Inhibiting TLR4/NF-κB/NLRP3 Inflammatory Pathway and Activating PPARα/CPT Pathway
by Lingxin Zhuo, Mingxuan Ma, Jiayi Zhang, Jiayu Zhou, Yuqi Zheng, Aiyin Liang, Qingqing Sun, Jia Liu and Wenting Liao
Pharmaceuticals 2025, 18(8), 1109; https://doi.org/10.3390/ph18081109 - 25 Jul 2025
Viewed by 963
Abstract
Background/Objectives: Sepsis-induced cardiomyopathy (SIC) is a serious clinical disorder with a high death rate. Qifu decoction (QFD) is a renowned traditional Chinese medicine with documented pharmacological actions, such as anti-inflammatory, anti-oxidant and anti-apoptosis activities, and it has good therapeutic effects on cardiovascular [...] Read more.
Background/Objectives: Sepsis-induced cardiomyopathy (SIC) is a serious clinical disorder with a high death rate. Qifu decoction (QFD) is a renowned traditional Chinese medicine with documented pharmacological actions, such as anti-inflammatory, anti-oxidant and anti-apoptosis activities, and it has good therapeutic effects on cardiovascular diseases. This study aimed to reveal the cardioprotective effects and underlying mechanisms of QFD against SIC. Methods: Electrocardiography, histopathological examination, and biochemical indicator determination were carried out to investigate the cardioprotective effects of QFD in the treatment of LPS-induced SIC mice. Metabolomics and network pharmacology strategies were employed to preliminarily analyze and predict the mechanisms of QFD against SIC. Molecular docking and Western blot were further applied to validate the core targets and potential pathways for the treatment of SIC in in vitro and in vivo models. Results: It was found that QFD considerably enhanced cardiac function; attenuated myocardial injury; and reduced the serum levels of LDH, CK-MB, IL-1β, and TNF-α by 28.7%, 32.3%, 38.6%, and 36.7%, respectively. Metabolomic analysis showed that QFD could regulate seven metabolic pathways, namely, glutathione metabolism; alanine, aspartate, and glutamate metabolism; arachidonic acid metabolism; glycerophospholipid metabolism; purine metabolism; sphingolipid metabolism; and fatty acid metabolism. Network pharmacology suggested that the anti-SIC effect of QFD may be mediated through the TNF, toll-like receptor, NOD-like receptor, NF-κB, and PPAR signaling pathways. Additionally, 26 core targets were obtained. Molecular docking revealed that active ingredients such as formononetin, kaempferol, quercetin, and (R)-norcoclaurine in QFD had a high affinity for binding to PPARα and TLR4. Further Western blot validation indicated that QFD could regulate the protein levels of NLRP3, TLR4, NF-κB, IL-6, TNF-α, COX2, sPLA2, PPARα, CPT1B, and CPT2. Conclusions: This study demonstrates that QFD can alleviate SIC by suppressing the TLR4/NF-κB/NLRP3 inflammatory pathway and modulating impaired FAO through the activation of the PPARα/CPT pathway, highlighting QFD as a promising candidate drug for SIC treatment. Full article
(This article belongs to the Section Natural Products)
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21 pages, 869 KB  
Article
Variation in Immune and Inflammatory Blood Markers in Advanced Melanoma Patients Treated with PD-1 Inhibitors: A Preliminary Exploratory Study
by Lucica Madalina Bolovan, Marieta Elena Panait, Antonela Busca, Adina Elena Stanciu, Daniela Chiriac, Corina Elena Mihalcea, Camelia Mia Hotnog, Mihai Teodor Georgescu, Silviu Cristian Voinea, Virgiliu Mihail Prunoiu, Lorelei Irina Brasoveanu and Laurentia Nicoleta Gales
Biomedicines 2025, 13(6), 1378; https://doi.org/10.3390/biomedicines13061378 - 4 Jun 2025
Cited by 1 | Viewed by 985
Abstract
Background: Immune checkpoint inhibitors (ICIs) used for the treatment of advanced melanoma have yielded significant results, with long-term responses and improved survival rates, but not for all treated patients. Therefore, predictive biomarkers of response to ICI therapy have been intensively explored. Our study [...] Read more.
Background: Immune checkpoint inhibitors (ICIs) used for the treatment of advanced melanoma have yielded significant results, with long-term responses and improved survival rates, but not for all treated patients. Therefore, predictive biomarkers of response to ICI therapy have been intensively explored. Our study aimed to evaluate the dynamics of peripheral blood lymphocyte variation and their correlation with a set of related inflammatory factors in Nivolumab-treated advanced melanoma patients. Methods: The immunophenotypic assessment of peripheral blood immune cell subpopulations (CD3+, CD4+, and CD8+ T cells; CD19+ B cells; CD16+CD56+ NK cells; and CD4+/CD8+ ratio) was performed by the flow cytometry technique, concomitantly with a complete blood count; levels of S100, IL-6, and TNF-α proteins were quantified in serum by immunoassays, and lactate dehydrogenase (LDH) by a chemiluminescence assay. Results: Approximately 85% and 79% of patients recorded a trend of increasing levels of CD8+ lymphocytes and NK cells, respectively, during therapy. The percentage of NK cells negatively correlated with CD3+, CD4+, and CD19+ cells; the last three cell populations also established negative correlations with the inflammatory neutrophile/lymphocyte ratio (NLR). Furthermore, CD19+ cells were negatively correlated with the systemic inflammatory response index (SIRI) and systemic immune-inflammation index (SII). The evaluation of progression biomarkers showed that LDH levels directly correlated with IL-6 and S100 proteins, but no correlation was found with TNFα; IL-6 levels negatively correlated with percentages of CD3+, CD4+, and CD8+ lymphocytes. Conclusions: Variation in lymphocyte subpopulations during immunotherapy of advanced melanoma patients, associated with other cellular and/or molecular inflammatory markers, might provide insights about immune system response, but additional prospective studies are needed. Full article
(This article belongs to the Special Issue Molecular Research and New Therapy in Melanoma)
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14 pages, 1040 KB  
Article
Unveiling the Effects of Two Polycyclic Aromatic Hydrocarbons and Two Temperatures on the Trout RTL-W1 Cell Line Expression of Detoxification-Related Target Genes
by Margarida Vilaça, Telma Esteves, Rosária Seabra, Eduardo Rocha and Célia Lopes
J. Xenobiot. 2025, 15(3), 84; https://doi.org/10.3390/jox15030084 - 1 Jun 2025
Cited by 1 | Viewed by 1136
Abstract
Polycyclic aromatic hydrocarbons (PAHs), prevalent aquatic contaminants, arise from burning fossil fuels, a major source of greenhouse gases driving global warming. PAHs and warmer temperatures individually exert diverse negative effects on aquatic organisms. However, the effects of PAH exposure and/or rising temperature remain [...] Read more.
Polycyclic aromatic hydrocarbons (PAHs), prevalent aquatic contaminants, arise from burning fossil fuels, a major source of greenhouse gases driving global warming. PAHs and warmer temperatures individually exert diverse negative effects on aquatic organisms. However, the effects of PAH exposure and/or rising temperature remain largely unknown. Liver in vitro models, like the rainbow trout (Oncorhynchus mykiss) RTL-W1 liver cell line, have been employed to unravel PAH-exposure effects, primarily on cell viability and enzymatic activity. Here, monolayer-cultured (2D) RTL-W1 cells were used to assess the co-exposure effects of temperature (18 and 21 °C) and two PAHs, benzo[a]pyrene (B[a]P) and benzo[k]fluoranthene (B[k]F), at 10 and 100 nM. After a 72 h exposure, the cell density and viability were evaluated using the trypan blue and LDH assays. The mRNA levels of the detoxification-associated genes aryl hydrocarbon receptor (AhR), cytochrome P450 (CYP)1A, CYP3A27, glutathione S-transferase omega 1 (GSTO1), uridine diphosphate–glucuronosyltransferase (UGT), catalase (CAT), and multidrug resistance-associated protein 2 (MRP2) were measured by RT-qPCR. Temperature influenced cell viability and LDH leakage. Both PAHs reduced the cell density and upregulated the mRNA levels of AhR, CYP1A, CYP3A27, and UGT, while GSTO1 and MRP2 were only augmented after the higher B[k]F concentration. Temperature influenced CAT and UGT expression. There was no interaction between temperature and the PAHs. Overall, the results show that B[k]F has more effects on detoxification targets than B[a]P, whereas a temperature increase mildly affects gene expression. The RTL-W1 in 2D seems useful for unravelling not only the liver effects of PAH but also the impact of temperature stress. Full article
(This article belongs to the Section Ecotoxicology)
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19 pages, 6271 KB  
Article
Acclimation Time Enhances Adaptation of Heterotrophic Nitrifying-Aerobic Denitrifying Microflora to Linear Anionic Surfactant Stress
by Huihui Han, Peizhen Chen, Wenjie Zhao, Shaopeng Li and Keyu Zhang
Microorganisms 2025, 13(5), 1031; https://doi.org/10.3390/microorganisms13051031 - 29 Apr 2025
Cited by 1 | Viewed by 623
Abstract
Linear anionic surfactants (LAS) pose significant stress to microbial denitrification in wastewater treatment. This study investigated the performance and adaptation mechanisms of heterotrophic nitrification-aerobic denitrification (HN-AD) microbial consortia under LAS exposure after short-term (SCM, 2 months) and long-term (LCM, 6 months) acclimation. Results [...] Read more.
Linear anionic surfactants (LAS) pose significant stress to microbial denitrification in wastewater treatment. This study investigated the performance and adaptation mechanisms of heterotrophic nitrification-aerobic denitrification (HN-AD) microbial consortia under LAS exposure after short-term (SCM, 2 months) and long-term (LCM, 6 months) acclimation. Results showed a dose-dependent inhibition of total nitrogen (TN) removal, with LCM achieving 97.40% TN removal under 300 mg/L LAS, which was 16.89% higher than SCM. Biochemical assays indicated that LCM exhibited lower reactive oxygen species (ROS) levels, a higher ATP content, and reduced LDH release, suggesting enhanced oxidative stress resistance and membrane stability. EPS secretion also increased in LCM, contributing to environmental tolerance. Metagenomic analysis revealed that long-term acclimation enriched key genera including Pseudomonas, Aeromonas, and Stutzerimonas, which maintained higher expression of denitrification (e.g., nosZ, nirS) and ammonium assimilation genes (glnA, gltB). Although high LAS concentrations reduced overall community diversity and led to convergence between SCM and LCM structures, LCM retained greater functional capacity and stress resistance. These findings underscore the importance of acclimation in sustaining denitrification performance under surfactant pressure and offer valuable insights for engineering robust microbial consortia in complex wastewater environments. Full article
(This article belongs to the Section Microbiomes)
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18 pages, 7539 KB  
Article
Identification of a Novel Antagonist of BRS-3 from Natural Products and Its Protective Effects Against H2O2-Induced Cardiomyocyte Injury
by Jihong Lu, Lehao Wu, Jianzheng Zhu, Han Zhou, Mingzhu Fang, Hongshuo Liang, Miao Guo, Mo Chen, Yuhang Zhu, Jixia Wang, Hua Xiao and Yan Zhang
Int. J. Mol. Sci. 2025, 26(6), 2745; https://doi.org/10.3390/ijms26062745 - 18 Mar 2025
Cited by 2 | Viewed by 877
Abstract
The identification of exogenous ligands from natural products is an alternative strategy to explore the unrevealed physiological functions of orphan G-protein-coupled receptors (GPCRs). In this study, we have successfully identified and pharmacologically characterized licoisoflavone A (LIA) as a novel selective antagonist of BRS-3, [...] Read more.
The identification of exogenous ligands from natural products is an alternative strategy to explore the unrevealed physiological functions of orphan G-protein-coupled receptors (GPCRs). In this study, we have successfully identified and pharmacologically characterized licoisoflavone A (LIA) as a novel selective antagonist of BRS-3, an orphan GPCR. Functional studies showed that pretreatment with LIA ameliorated hydrogen peroxide (H2O2)-induced cardiomyocyte injury. Furthermore, LIA pretreatment significantly restored the activities of malondialdehyde (MDA), superoxide dismutase (SOD), and catalase (CAT), as well as lactate dehydrogenase (LDH) levels, in H9c2 cells following H2O2 exposure. The protective effect of LIA was also evident in primary cardiomyocytes from rats and mice against H2O2-induced cell injury but was absent in primary cardiomyocytes derived from bombesin receptor subtype-3 knockout (Brs3−/y) mice, strongly confirming the mechanism of LIA’s action through BRS-3 antagonism. Proteomics studies further revealed that LIA exerted its protective effects via activating the integrin/ILK/AKT and ERK/MAPK signaling pathways. Complementary findings from Bantag-1, a well-recognized antagonist of BRS-3, in human embryonic kidney 293 mBRS-3 (HEK293-mBRS-3) stable cells and B16 cell lines, which demonstrated resistance to H2O2-induced damage, further supported the pivotal role of BRS-3 in oxidative stress-induced cell injury. Our study contributes to expanding our understanding of the potential pharmacological functions of BRS-3, unveiling previously unknown pharmacological functionality of this orphan receptor. Full article
(This article belongs to the Special Issue Natural Products in Drug Discovery and Development)
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12 pages, 6351 KB  
Article
MoS2/MgAl-LDH Composites for the Photodegradation of Rhodamine B Dye
by Jingjing Dai, Guofei Li, Yuanyuan Wang, Cancan Zhang, Hui Nan and Guijun Yang
Inorganics 2025, 13(3), 88; https://doi.org/10.3390/inorganics13030088 - 17 Mar 2025
Viewed by 927
Abstract
During the process of producing potassium fertilizer from salt lake resources, a large amount of waste liquid brine, rich in raw materials such as magnesium chloride, is generated. In this work, a MoS2/MgAl-LDH composite material was constructed using the secondary hydrothermal [...] Read more.
During the process of producing potassium fertilizer from salt lake resources, a large amount of waste liquid brine, rich in raw materials such as magnesium chloride, is generated. In this work, a MoS2/MgAl-LDH composite material was constructed using the secondary hydrothermal technique. Characterizations including X-ray diffractometer (XRD), scanning electron microscopy (SEM), and X-ray photoelectron spectroscopy (XPS) confirmed the distribution of MoS2 nanosheets on the surface of MgAl-LDH. Under full-spectrum irradiation, the degradation efficiency of Rhodamine B reached 85.5%, which was 69.2% higher than that of MgAl-LDH alone. The results from the electrochemical, UV-Vis, and XPS-VB tests indicate that the internal electric field accelerated the separation and transportation of charge carriers between MoS2 and MgAl-LDH. These findings demonstrate the great potential of MoS2/MgAl-LDH as a photocatalyst in the degradation of organic dyes, which will aid in the green recycling utilization of magnesium resources from salt lake by-products. Full article
(This article belongs to the Special Issue Photoelectric Research in Advanced Energy Materials)
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18 pages, 1622 KB  
Review
What We Know and Do Not Yet Know About the Canine Model of Lymphoma in Human Medicine—The Current State of Knowledge
by Daria Będkowska, Sara Al-Ameri, Agnieszka Wieczorek, Joanna Bubak and Marta Miszczak
Cancers 2025, 17(4), 596; https://doi.org/10.3390/cancers17040596 - 10 Feb 2025
Cited by 2 | Viewed by 3916 | Correction
Abstract
This review comprehensively compares lymphoma in humans and dogs, highlighting the canine model’s utility in translational research. Canine lymphoma (cL), predominantly diffuse large B-cell lymphoma (DLBCL), mirrors human non-Hodgkin’s lymphoma (NHL) in its clinical presentation, including lymphadenopathy, systemic symptoms (e.g., fever, weight loss), [...] Read more.
This review comprehensively compares lymphoma in humans and dogs, highlighting the canine model’s utility in translational research. Canine lymphoma (cL), predominantly diffuse large B-cell lymphoma (DLBCL), mirrors human non-Hodgkin’s lymphoma (NHL) in its clinical presentation, including lymphadenopathy, systemic symptoms (e.g., fever, weight loss), and hematological abnormalities. Morphologically, cL and NHL share similarities in DLBCL subtypes (centroblastic, immunoblastic, anaplastic), although some variations exist, such as the presence of macronuclear medium-sized cells in canine polymorphonuclear centroblastic lymphoma, not observed in humans. Canine and human lymphomas share molecular mechanisms, including the activation of key pathways like NF-κB and mTOR, and genetic and epigenetic alterations. The tumor microenvironment influences tumor growth and immune evasion in both species. Both species exhibit similar responses to chemotherapy, primarily CHOP-based protocols, although canine lymphoma often progresses more rapidly, offering advantages for shorter clinical trials. Molecular targeted therapy is emerging as a promising treatment, with human therapies like rituximab and chimeric antigen receptor T-cell therapy showing efficacy, and canine treatments still developing. Epidemiological data reveal overlapping risk factors, including exposure to environmental carcinogens (e.g., household chemicals, pollution) and the potential influence of sex hormones, although the role of sex hormones requires further investigation in canines. While staging systems differ slightly (Lugano modification of Ann Arbor for humans, WHO system for dogs), both consider disease extent and systemic involvement. Prognostic factors, such as lactate dehydrogenase (LDH) levels, are relevant in human NHL but have not shown consistent utility in cL. This study concludes that the spontaneous development of cL in immunocompetent dogs, coupled with its clinical, histological, and therapeutic similarities to human NHL, makes the canine model invaluable for preclinical research, accelerating the development of novel diagnostic tools and therapies for both human and canine lymphoma. The shared environmental risk factors and shorter disease progression in dogs further enhance the translational potential of this model, promoting a One Health approach to cancer research. Full article
(This article belongs to the Section Clinical Research of Cancer)
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21 pages, 17150 KB  
Article
Spray-Induced Gene Silencing (SIGS): Nanocarrier-Mediated dsRNA Delivery Improves RNAi Efficiency in the Management of Lettuce Gray Mold Caused by Botrytis cinerea
by Maria Spada, Claudio Pugliesi, Marco Fambrini, Diego Palpacelli, Andrea Caneo and Susanna Pecchia
Agronomy 2025, 15(1), 194; https://doi.org/10.3390/agronomy15010194 - 15 Jan 2025
Cited by 4 | Viewed by 3590
Abstract
The plant pathogenic fungus Botrytis cinerea causes significant losses in agricultural production and it is rather difficult to control due to its broad host range and environmental persistence. The management of gray mold disease is still mainly based on the use of chemicals, [...] Read more.
The plant pathogenic fungus Botrytis cinerea causes significant losses in agricultural production and it is rather difficult to control due to its broad host range and environmental persistence. The management of gray mold disease is still mainly based on the use of chemicals, which could have harmful effects not only due to impacts on the environment and human health, but also because they favor the development of fungicide-resistant strains. In this scenario, the strategy of RNA interference (RNAi) is being widely considered, and Spray-Induced Gene Silencing (SIGS) is gaining interest as a versatile, sustainable, effective, and environmentally friendly alternative to the use of chemicals in the protection of crops. The SIGS approach was evaluated to control B. cinerea infection on lettuce plants. In vitro-synthesized dsRNA molecules (BcBmp1-, BcBmp3-, and BcPls1-dsRNAs) were used naked, or complexed to small layered double hydroxide (sLDH) clay nanosheets. Therefore, treatments were applied by pressure spraying whole lettuce plants lately inoculated with B. cinerea. All sprayed dsRNAs proved effective in reducing disease symptoms with a notable reduction compared to controls. The effectiveness of SIGS in reducing disease caused by B. cinerea was high overall and increased significantly with the use of sLDH clay nanosheets. The sLDH clay nanosheet–dsRNA complexes showed better plant protection over time compared to the use of naked dsRNA and this was particularly evident at 27 days post-inoculation. RNAi-based biocontrol could be an excellent alternative to chemical fungicides, and several RNAi-based products are expected to be approved soon, although they will face several challenges before reaching the market. Full article
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