International Journal of Molecular Sciences

27 pages, 534 KiB

Open AccessReview

Comorbid Pathologies and Their Impact on Dementia with Lewy Bodies—Current View

by Kurt A. Jellinger

Int. J. Mol. Sci. 2025, 26(16), 7674; https://doi.org/10.3390/ijms26167674 (registering DOI) - 8 Aug 2025

Dementia with Lewy bodies (DLB), the second common primary degenerative neurocognitive disorder after Alzheimer disease (AD), frequently presents concurrent co-pathologies that impact clinical presentation and progression. Neuropathological studies have demonstrated a high prevalence of coexistent AD-related neuropathological changes (ADNC), TAR DNA-binding protein 43 [...] Read more.

Dementia with Lewy bodies (DLB), the second common primary degenerative neurocognitive disorder after Alzheimer disease (AD), frequently presents concurrent co-pathologies that impact clinical presentation and progression. Neuropathological studies have demonstrated a high prevalence of coexistent AD-related neuropathological changes (ADNC), TAR DNA-binding protein 43 (TDP-43) proteinopathies, and cardiac and aging-related disorders, while frontotemporal lobar degeneration (FTLD) and tau-related syndromes play a minor role as DLB-related co-pathologies. Cerebrovascular lesions, including cerebral amyloid angiopathy, are the most prevalent non-neurodegenerative co-pathologies. Cardiovascular disorders, hypertension, and hyperlipidemia are also frequent comorbidities. Due to their high prevalence and clinical impact on DLB patients, clinical trials should account for these and other co-pathologies in their design and selection. Evaluation of these co-pathologies using and interpreting biomarkers may allow greater clinical diagnostic accuracy and the opportunity to better predict clinical progression. Therefore, there is an increasing need for biomarkers in dementia research. This review discusses the kind and frequency of the different co-pathologies in DLB and their clinical impact. It evaluates the possible value of disease-specific biomarkers and how they are helpful in the assessment and prevention of DLB and its co-pathologies. Full article

(This article belongs to the Special Issue Recent Advances in Dementia with Lewy Bodies and Alzheimer’s Disease)

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22 pages, 3909 KiB

Open AccessArticle

The Sweet Side of IVF: Biological Role and Diagnostic Potential of Galectin-9 in Female Infertility

by Beata Polgar, Matyas Meggyes, Krisztina Godony, Akos Varnagy, Kalman Kovacs, Peter Mauchart, Peter Matrai, Krisztina Kovacs, David Semjen, Tamas Tornoczki and Laszlo Szereday

Int. J. Mol. Sci. 2025, 26(16), 7672; https://doi.org/10.3390/ijms26167672 (registering DOI) - 8 Aug 2025

Abstract

Infertility rates are indeed increasing globally, which emphasizes a pressing need to identify novel biomarkers exhibiting superior potential for laboratory diagnosis and personalized clinical management. This study aimed to explore the biological role of Galectin-9 (Gal-9) in female fertility and evaluate its diagnostic [...] Read more.

Infertility rates are indeed increasing globally, which emphasizes a pressing need to identify novel biomarkers exhibiting superior potential for laboratory diagnosis and personalized clinical management. This study aimed to explore the biological role of Galectin-9 (Gal-9) in female fertility and evaluate its diagnostic potential in the In Vitro Fertilization (IVF) program. A prospective cohort study was performed on 83 follicular fluids (FF) and 19 serum-FF pairs from IVF patients, 16 serum samples from fertile women, and 12 tissue sections. Gal-9 expression was characterized by immunostaining and ELISA. The ROC analysis was employed to evaluate the overall diagnostic performance. Cell-specific ovarian Gal-9 expression and significant differences in soluble Gal-9 levels were identified in the serum and FF of fertile and infertile women. Elevated intrafollicular Gal-9 levels were linked to poor ovarian reserve, served as a predictive marker for ovarian hyperstimulation, and marked unfavorable IVF outcomes. Follicular Gal-9 levels positively correlated with peak estradiol and total daily FSH dosage. ROC analysis revealed an excellent diagnostic value of Gal-9 for predicting fertilization success and a moderate ability to predict IVF outcomes. Our findings suggest a potential role for Gal-9 in oogenesis and its promise as a diagnostic marker for predicting fertilization success in IVF. However, further studies are needed to confirm its clinical utility in assisted reproduction. Full article

(This article belongs to the Special Issue Exploring Molecular Mechanism in Infertility)

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23 pages, 5953 KiB

Open AccessArticle

Computational Profiling of Monoterpenoid Phytochemicals: Insights for Medicinal Chemistry and Drug Design Strategies

by André Nogueira Cardeal dos Santos, Paulo Elesson Guimarães de Oliveira, José Ednésio da Cruz Freire, Sara Araújo dos Santos, José Eduardo Ribeiro Honório Júnior, Claudia Roberta de Andrade, Bruno Lopes de Sousa, Wildson Max Barbosa da Silva, Ariclécio Cunha de Oliveira, Vânia Marilande Ceccatto, José Henrique Leal Cardoso, Adélia Justina Aguiar Aquino and Andrelina Noronha Coelho de Sousa

Int. J. Mol. Sci. 2025, 26(16), 7671; https://doi.org/10.3390/ijms26167671 (registering DOI) - 8 Aug 2025

Abstract

Monoterpenoids are a structurally diverse class of natural products with a long-standing history of therapeutic use. Despite their promising bioactivities, their clinical development has been limited by dose-dependent toxicities, poor pharmacokinetics, and suboptimal drug-like properties. In this work, a comprehensive in silico pipeline [...] Read more.

Monoterpenoids are a structurally diverse class of natural products with a long-standing history of therapeutic use. Despite their promising bioactivities, their clinical development has been limited by dose-dependent toxicities, poor pharmacokinetics, and suboptimal drug-like properties. In this work, a comprehensive in silico pipeline was employed to evaluate 1175 monoterpenoid compounds retrieved from ChEBI, aiming to identify structurally diverse candidates that possess favorable drug-like characteristics. A total of 54 molecular parameters were calculated using thirteen computational tools, covering physicochemical parameters, ADMET profiles, and toxicological risk assessments. Stepwise filtering was employed to retain only compounds meeting stringent thresholds across multiple domains, followed by chemoinformatic analysis. Structure–activity relationship mapping and target prediction were subsequently conducted to explore mechanistic plausibility. This workflow led to the identification of seven top-performing monoterpenoids that exhibited ideal physicochemical profiles, high gastrointestinal absorption, low predicted toxicity, and full compliance with medicinal chemistry rules. Notably, target prediction revealed a convergence on GPCRs, enzymatic and nuclear receptors, highlighting potential anti-inflammatory and neuromodulatory effects. The identification of conserved pharmacophores across selected scaffolds further reinforces their translational potential. Our results highlight the value of multi-parameter computational triage in natural product drug discovery and reveal a subset of overlooked monoterpenoids with promising preclinical applications. Full article

(This article belongs to the Special Issue Recent Research on Biomimetic Chromatography, QSAR and Chemoinformatics in Molecular Modeling and Drug Design)

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22 pages, 1229 KiB

Open AccessArticle

Circulating FGF-21 as a Disease-Modifying Factor Associated with Distinct Symptoms and Cognitive Profiles in Myalgic Encephalomyelitis and Fibromyalgia

by Ghazaleh Azimi, Wesam Elremaly, Mohamed Elbakry, Anita Franco, Christian Godbout and Alain Moreau

Int. J. Mol. Sci. 2025, 26(16), 7670; https://doi.org/10.3390/ijms26167670 (registering DOI) - 8 Aug 2025

Abstract

Myalgic encephalomyelitis (ME) and fibromyalgia (FM) are overlapping syndromes characterized by persistent fatigue, cognitive difficulties, and post-exertional malaise (PEM), yet they lack objective biomarkers for diagnosis and treatment. Fibroblast growth factor 21 (FGF-21), a stress-responsive metabolic hormone, may offer a promising avenue to [...] Read more.

Myalgic encephalomyelitis (ME) and fibromyalgia (FM) are overlapping syndromes characterized by persistent fatigue, cognitive difficulties, and post-exertional malaise (PEM), yet they lack objective biomarkers for diagnosis and treatment. Fibroblast growth factor 21 (FGF-21), a stress-responsive metabolic hormone, may offer a promising avenue to distinguish subtypes within these patient populations. In this cross-sectional study, plasma FGF-21 levels were measured in 250 patients (FM = 47; ME = 99; ME + FM = 104) and 54 healthy controls. Participants were categorized based on FGF-21 levels into three groups: low (0–50 pg/mL), normal (51–200 pg/mL), and high (>200 pg/mL). Symptoms burden and cognitive function were assessed using validated questionnaires (SF-36, MFI-20, DSQ, DPEMQ) and the BrainCheck platform. A standardized mechanical provocation maneuver was used to induce PEM. Results showed that elevated FGF-21 levels were frequently observed in ME and ME + FM but varied widely across all groups. Stratification by circulating FGF-21 levels, rather than diagnosis alone, revealed distinct symptom and cognitive profiles. Low FGF-21 levels were linked to worsened PEM perception in FM, increased PEM severity and immune/autonomic symptoms in ME, and poorer mental health in ME + FM. Conversely, high FGF-21 levels correlated with better cognition in ME but greater fatigue in ME + FM. These findings suggest that FGF-21 may serve as a valuable biomarker for identifying clinically meaningful subtypes within ME and FM, supporting the development of personalized treatments. Furthermore, discrepancies between DSQ and DPEMQ highlight the need for objective PEM assessment tools. Overall, FGF-21 shows potential as a biomarker to guide precision medicine in these complex conditions. Full article

(This article belongs to the Special Issue Molecular Pathologies and Treatment for Myalgic Encephalomyelitis/Chronic Fatigue Syndrome)

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24 pages, 11368 KiB

Open AccessArticle

Co-Supplementation of Policosanol and Banaba Leaf Extract Exhibited a Cooperative Effect Against Hyperglycemia and Dyslipidemia in Zebrafish: Highlighting Vital Organ Protection Against High-Cholesterol and High-Galactose Diet

by Kyung-Hyun Cho, Sang Hyuk Lee, Yunki Lee, Ashutosh Bahuguna, Ji-Eun Kim and Cheolmin Jeon

Int. J. Mol. Sci. 2025, 26(16), 7669; https://doi.org/10.3390/ijms26167669 (registering DOI) - 8 Aug 2025

Abstract

The efficacy of Lagerstroemia speciosa (banaba) leaf extract (BLE), policosanol (POL), and their combination (BLE+POL) was evaluated in zebrafish (Danio rerio) against high cholesterol (HC)- and galactose (HG)-induced metabolic stress and organ toxicity. After 12 weeks of dietary intervention, BLE+POL significantly [...] Read more.

The efficacy of Lagerstroemia speciosa (banaba) leaf extract (BLE), policosanol (POL), and their combination (BLE+POL) was evaluated in zebrafish (Danio rerio) against high cholesterol (HC)- and galactose (HG)-induced metabolic stress and organ toxicity. After 12 weeks of dietary intervention, BLE+POL significantly reduced HC+HG-augmented weight gain and improved hepatic and nephromegaly. Compared with BLE or POL alone, the combined intake of BLE+POL more effectively alleviated dyslipidemia and blood glucose levels. Likewise, BLE+POL effectively reduced blood malondialdehyde (MDA), aspartate aminotransferase (AST), and alanine aminotransferase (ALT) levels and boosted plasma sulfhydryl content, ferric ion reduction ability (FRA), and paraoxonase (PON) activity. Histological outcomes suggest that BLE+POL has higher efficacy than either BLE or POL in mitigating HC+HG-induced fatty liver changes, hepatic inflammation, kidney senescence, and reactive oxygen species (ROS) production. Consistently, BLE+POL augmented the spermatozoa counts in the testes, enhanced mature vitellogenic oocytes in ovaries, and protected them from the HC+HG-induced oxidative stress. Compared with either BLE or POL, a combined intake of BLE+POL displayed a superior effect in inhibiting the apoptosis and accumulation of lipid peroxidation species 4-hyrdoxynonenal (4-HNE) in the brain. A combined intake of BLE+POL exhibited a pronounced impact than the BLE and POL alone and can be utilized as an effective formulation to counteract the HC+HG-induced events. Full article

(This article belongs to the Special Issue Molecules and Mechanisms of Oxidative Stress Relevant in the Pathophysiology of Diseases)

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19 pages, 751 KiB

Open AccessReview

Cardio-Pulmonary Features of Long COVID: From Molecular and Histopathological Characteristics to Clinical Implications

by Giovanni Cimmino, Saverio D’Elia, Mariarosaria Morello, Gisella Titolo, Ettore Luisi, Achille Solimene, Chiara Serpico, Stefano Conte, Francesco Natale, Francesco S. Loffredo, Andrea Bianco and Paolo Golino

Int. J. Mol. Sci. 2025, 26(16), 7668; https://doi.org/10.3390/ijms26167668 (registering DOI) - 8 Aug 2025

Abstract

Long COVID is a persistent post-viral syndrome with the significant involvement of both the cardiovascular and pulmonary systems, often extending well beyond the acute phase of SARS-CoV-2 infection. Emerging evidence has highlighted a spectrum of chronic alterations, including endothelial dysfunction, microvascular inflammation, perivascular [...] Read more.

Long COVID is a persistent post-viral syndrome with the significant involvement of both the cardiovascular and pulmonary systems, often extending well beyond the acute phase of SARS-CoV-2 infection. Emerging evidence has highlighted a spectrum of chronic alterations, including endothelial dysfunction, microvascular inflammation, perivascular fibrosis, and in some cases, the persistence of viral components in the cardiac and pulmonary tissues. At the molecular level, a sustained inflammatory milieu—characterized by elevated pro-inflammatory cytokines such as interleukin 6 (IL-6)—and chronic platelet hyperreactivity contribute to a prothrombotic state. These mechanisms are implicated in microvascular damage, cardiac strain, and impaired gas exchange, correlating with clinical manifestations such as fatigue, dyspnea, chest discomfort, and reduced exercise capacity. In certain patients, especially those who were not hospitalized during the acute phase, cardiac MRI and myocardial biopsy may reveal signs of myocardial inflammation and autonomic dysregulation. These often subclinical cardiovascular alterations underscore the need for improved diagnostic strategies, integrating molecular and histopathological markers during post-COVID evaluations. Recognizing persistent inflammatory and thrombotic activity may inform risk stratification and individualized therapeutic approaches. The interdependence between pulmonary fibrosis and cardiac dysfunction highlights the importance of multidisciplinary care. In this context, molecular and tissue-based diagnostics play a pivotal role in elucidating the long-term cardio-pulmonary sequelae of long COVID and guiding targeted interventions. Early identification and structured follow-up are essential to mitigate the burden of chronic complications in affected individuals. Full article

(This article belongs to the Special Issue Cardiovascular Diseases: Histopathological and Molecular Diagnostics)

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26 pages, 1870 KiB

Open AccessReview

Biomarkers in Localized Prostate Cancer: From Diagnosis to Treatment

by Marta Lopez-Valcarcel, Fernando Lopez-Campos, Juan Zafra-Martín, Irene Cienfuegos Belmonte, José Daniel Subiela, María Ruiz-Vico, Sandra Fernandez Alonso, Jose Angel Garcia Cuesta and Felipe Couñago

Int. J. Mol. Sci. 2025, 26(16), 7667; https://doi.org/10.3390/ijms26167667 (registering DOI) - 8 Aug 2025

Abstract

Prostate-specific antigen (PSA) has been the primary biomarker used for the detection and monitoring of prostate cancer for decades. However, its limited specificity and prognostic accuracy have led to the development of novel molecular and imaging biomarkers aimed at improving the clinical characterization [...] Read more.

Prostate-specific antigen (PSA) has been the primary biomarker used for the detection and monitoring of prostate cancer for decades. However, its limited specificity and prognostic accuracy have led to the development of novel molecular and imaging biomarkers aimed at improving the clinical characterization of localized disease. This review critically examines recent advances in urinary biomarkers (e.g., PCA3, SelectMDx), tissue-based genomic assays (Oncotype DX Prostate, Prolaris, Decipher), and imaging techniques such as multiparametric magnetic resonance imaging (mpMRI) and prostate-specific membrane antigen positron emission tomography (PET-PSMA). We evaluate their diagnostic performance, prognostic value, and clinical utility in risk stratification and individualized treatment decision-making. Methodological and clinical barriers to their routine implementation are also discussed. Current evidence supports the multidisciplinary integration of these biomarkers to overcome the limitations of PSA, improve biopsy decision-making, better distinguish indolent from aggressive tumors, and optimize therapeutic strategies. Finally, future research directions aimed at validating and incorporating emerging biomarkers into clinical practice are outlined, with the goal of improving outcomes in patients with localized prostate cancer. Full article

(This article belongs to the Special Issue Advancing Precision Medicine in Urological Cancers: Integrating Multi-Omics and Optimizing Therapeutic Approaches)

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16 pages, 1049 KiB

Open AccessArticle

Cobalt Ion Removal by Activated Carbon and Biochar Derived from Sargassum sp.

by Julie Mallouhi, Emőke Sikora, Kitti Gráczer, Olivér Bánhidi, Sarra Gaspard, Marckens Francoeur, Yeray Alvarez-Galvan, Francesca Goudou, Béla Viskolcz, Emma Szőri-Dorogházi and Béla Fiser

Int. J. Mol. Sci. 2025, 26(16), 7666; https://doi.org/10.3390/ijms26167666 (registering DOI) - 8 Aug 2025

Abstract

Activated carbon (AC) and biochar (BC) are porous substances derived from any carbonous material known to be highly effective adsorbents, making them valuable for removing pollutants like heavy metals. This study evaluated and compared the potential of AC and BC produced from Sargassum [...] Read more.

Activated carbon (AC) and biochar (BC) are porous substances derived from any carbonous material known to be highly effective adsorbents, making them valuable for removing pollutants like heavy metals. This study evaluated and compared the potential of AC and BC produced from Sargassum sp. by chemical activation and pyrolysis process for heavy metal removal, specifically Co²⁺ ions, to commercial AC (COMAC). Various techniques were employed to characterize these samples including FTIR, zeta potential, and surface area. Additionally, considering parameters such as pH, initial solution concentration, and the effect of AC/BC dose were investigated. The adsorption isotherm was also assessed. The results showed that a strong dependence of the adsorption capacity on pH was observed with optimal performance at ~6.8. Additionally, the optimal initial solution concentration was determined to be ~2 mmol/L. According to the Langmuir isotherm model, AC derived-Sargassum sp. exhibited maximum uptakes of 468.97 mg/g, higher than COMAC and BC. The experiment at different adsorbent dosages revealed that AC from Sargassum sp. outperformed other samples, with adsorption capacity observed at 94.94% as the dosage increased. Full article

(This article belongs to the Section Physical Chemistry and Chemical Physics)

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19 pages, 1152 KiB

Open AccessArticle

Phenanthrene Monomers and Dimers from Juncus tenuis with Antiproliferative Activity and Synergistic Effect with Doxorubicin Against Human Colon Cancer Cell Lines

by Anita Barta, Annamária Kincses, Dragica Purger, Gabriella Spengler, Judit Hohmann and Andrea Vasas

Int. J. Mol. Sci. 2025, 26(16), 7665; https://doi.org/10.3390/ijms26167665 (registering DOI) - 8 Aug 2025

Abstract

Continuing our search for bioactive compounds in species from the Juncaceae family, we investigated Juncus tenuis. The structures of five previously undescribed phenanthrenes—tenuins A–E (1–5)—and 14 known phenanthrenes (6–19), along with other components, were [...] Read more.

Continuing our search for bioactive compounds in species from the Juncaceae family, we investigated Juncus tenuis. The structures of five previously undescribed phenanthrenes—tenuins A–E (1–5)—and 14 known phenanthrenes (6–19), along with other components, were isolated and characterized using nuclear magnetic resonance and high-resolution mass spectrometry measurements. The antiproliferative activity of all of the isolated phenanthrenes was evaluated against the human colorectal adenocarcinoma cell lines COLO 205 (doxorubicin-sensitive) and COLO 320 (doxorubicin-resistant), as well as a non-tumorigenic human fibroblast cell line (CCD-19Lu), using the MTT viability assay. Diphenanthrenes 4, 5, and 19 showed the most potent antiproliferative effects, with IC₅₀ values ranging from 7.60 to 17.32 μM; however, these compounds lacked selectivity toward cancer cells. To explore potential chemosensitizing properties, the synergistic effects of the phenanthrenes with the anticancer drug doxorubicin were also examined in the COLO 320 cells. Notably, compound 2 exhibited very strong synergism (CI = 0.021), indicating a highly potent interaction. These findings highlight J. tenuis as a valuable source of phenanthrenes and demonstrate the synergistic anticancer potential of natural phenanthrenes with doxorubicin, offering promising prospects for overcoming multidrug resistance in colorectal cancer therapy. Full article

(This article belongs to the Special Issue Plant-Derived Bioactive Compounds for Pharmacological Applications)

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22 pages, 11543 KiB

Open AccessArticle

Molecular Mechanisms of Phytochemicals from Chaga Mushroom (Inonotus obliquus) Against Colorectal Cancer: Insights from Network Pharmacology, Molecular Docking, and Bioinformatics

by Yingzi Wu, Jiayin Liu, Jinhai Luo and Baojun Xu

Int. J. Mol. Sci. 2025, 26(16), 7664; https://doi.org/10.3390/ijms26167664 (registering DOI) - 8 Aug 2025

Abstract

This study aimed to explore the molecular mechanisms of phytochemicals from Chaga mushroom (Inonotus obliquus) against colorectal cancer (CRC) using a combination of network pharmacology, molecular docking, and bioinformatics. Active components and targets of Chaga mushroom and CRC were collected from [...] Read more.

This study aimed to explore the molecular mechanisms of phytochemicals from Chaga mushroom (Inonotus obliquus) against colorectal cancer (CRC) using a combination of network pharmacology, molecular docking, and bioinformatics. Active components and targets of Chaga mushroom and CRC were collected from databases. A drug-compound-target-disease network was constructed, and protein–protein interaction (PPI) analysis was performed to identify core targets. KEGG and GO enrichment analyses were conducted to elucidate the involved pathways. Molecular docking estimated the binding affinities of key compounds to their targets, and bioinformatics analysis assessed differential gene expression and immune infiltration. The study identified 26 bioactive compounds and 244 potential targets. Core targets included AKT1, IFNG, and MMP9. Molecular docking showed strong binding affinities, and bioinformatics analysis revealed significant differential expression and immune infiltration patterns. These findings suggest that Chaga mushroom phytochemicals may exert anticancer effects through multiple pathways, highlighting their potential as novel CRC treatments. This study provides a comprehensive understanding of the molecular mechanisms underlying the anticancer effects of Chaga mushroom phytochemicals on CRC. Future research should focus on experimental validation and further exploration of their therapeutic potential. Full article

(This article belongs to the Special Issue Artificial Intelligence and Computer-Aided Design: Molecular Simulation Technology in Exploring Bioactive Compounds for Health Promotion)

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18 pages, 1504 KiB

Open AccessArticle

Angiotensin-Converting Enzyme Inhibition and/or Angiotensin Receptor Blockade Modulate Cytokine Profiles and Improve Clinical Outcomes in Experimental COVID-19 Infection

by Yasmin da Silva-Santos, Roberta Liberato Pagni, Thais Helena Martins Gamon, Marcela Santiago Pacheco de Azevedo, Maria Laura Goussain Darido, Danielle Bruna Leal de Oliveira, Edson Luiz Durigon, Maria Cecília Rui Luvizotto, Hans Christian Ackerman, Claudio Romero Farias Marinho, Leonardo José de Moura Carvalho and Sabrina Epiphanio

Int. J. Mol. Sci. 2025, 26(16), 7663; https://doi.org/10.3390/ijms26167663 (registering DOI) - 8 Aug 2025

Abstract

The regulation of angiotensin-converting enzyme 2 (ACE2) expression by medications such as ACE inhibitors (ACEis) and angiotensin receptor blockers (ARBs) has raised critical questions regarding their potential benefits and risks during COVID-19. ACE2, a regulator of blood pressure through the renin–angiotensin system (RAS), [...] Read more.

The regulation of angiotensin-converting enzyme 2 (ACE2) expression by medications such as ACE inhibitors (ACEis) and angiotensin receptor blockers (ARBs) has raised critical questions regarding their potential benefits and risks during COVID-19. ACE2, a regulator of blood pressure through the renin–angiotensin system (RAS), is the primary receptor for SARS-CoV-2. ACEis and ARBs can modulate ACE2 expression, potentially exacerbating viral load. However, the risks of higher viral load could be mitigated by favorable anti-inflammatory responses associated with ACEi and ARB use, highlighting the complexity of their impact on viral replication and disease outcomes. This study investigates the effects of sustained Losartan monotherapy (ARB) and combination Losartan + Lisinopril (ARB + ACEi) on viral replication, inflammation, lung function, and clinical measures of disease severity in a murine model of severe COVID-19 involving humanized ACE2 transgenic mice infected with SARS-CoV-2 Wuhan strain. Both ARB and ARB + ACEi treatments led to increased ACE2 expression in the lungs and higher viral load post-infection. Despite this, the ARB + ACEi combination improved clinical scores, reduced weight loss and inflammatory cytokine levels, and preserved lung function, though it did not improve survival. Overall, the results of these controlled experiments provide insight into the complex dynamics of ACEi and ARB use in COVID-19; while these drugs induce expression of the ACE2 receptor and increase viral load, they provide compensatory modulation of the inflammatory response that appears to diminish severity of the infection. Full article

(This article belongs to the Special Issue Renin-Angiotensin System in Health and Diseases)

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11 pages, 537 KiB

Open AccessArticle

Cross-Sectional Study of Serum Galectin-3 Levels in Patients with Type 2 Diabetes and Colorectal Polyps

by Monika Storman, Adam Przybyłkowski and Leszek Czupryniak

Int. J. Mol. Sci. 2025, 26(16), 7662; https://doi.org/10.3390/ijms26167662 (registering DOI) - 8 Aug 2025

Abstract

Galectin-3 (Gal-3) secreted by activated macrophages is involved in inflammation, fibrosis, and tumorigenesis. It is considered a potential biomarker and therapeutic target. This study assessed the association between serum Gal-3, type 2 diabetes (T2D), and colorectal polyps (CRPs). In this cross-sectional study, 80 [...] Read more.

Galectin-3 (Gal-3) secreted by activated macrophages is involved in inflammation, fibrosis, and tumorigenesis. It is considered a potential biomarker and therapeutic target. This study assessed the association between serum Gal-3, type 2 diabetes (T2D), and colorectal polyps (CRPs). In this cross-sectional study, 80 non-cancer patients undergoing colonoscopy were divided into four subgroups based on T2D and CRP status. Serum Gal-3 and metabolic parameters were measured. All patients’ mean serum Gal-3 level was 13.63 ng/mL. Gal-3 levels were significantly higher in T2D+ than in the T2D− group (14.93 ng/mL, p = 0.02). Gal-3 concentration correlated significantly with age (rho = 0.281; p = 0.012), gender (rho = 0.220; p = 0.049), serum peptide C levels (rho = 0.957; p = 0.006), and serum IGF-1 levels (rho = −0.417; p < 0.001) in all patients, and for patients T2D-, it also correlated significantly with fasting plasma glucose levels (rho = −0.406; p = 0.009). A logistic regression analysis of the risk of polyps was conducted (CRP+ vs. CRP−) considering factors such as gender, age, body weight, waist circumference, T2D, HOMA-IR, insulin, API, IGF-1, total cholesterol, and Gal-3. Gal-3 serum was shown to be a strong independent predictor of CRPs regardless of the presence of T2D+ (p = 0.031). Gal-3 may correlate with the development of CRPs and might be a candidate biomarker of CRPs/cancer development. Full article

(This article belongs to the Section Molecular Endocrinology and Metabolism)

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27 pages, 11354 KiB

Open AccessArticle

Tetraarsenic Hexoxide Enhanced the Anticancer Effects of Artemisia annua L. Polyphenols by Inducing Autophagic Cell Death and Apoptosis in Oxalplatin-Resistant HCT116 Colorectal Cancer Cells

by Eun Joo Jung, Hye Jung Kim, Sung Chul Shin, Gon Sup Kim, Jin-Myung Jung, Soon Chan Hong, Choong Won Kim and Won Sup Lee

Int. J. Mol. Sci. 2025, 26(16), 7661; https://doi.org/10.3390/ijms26167661 (registering DOI) - 8 Aug 2025

Abstract

It was reported that polyphenols extracted from Korean Artemisia annua L. (pKAL) have higher anticancer effects in oxaliplatin-resistant (OxPt-R) HCT116 cells than in HCT116 cells. In this study, it was tested whether and how As₄O₆ enhances anticancer effects of pKAL [...] Read more.

It was reported that polyphenols extracted from Korean Artemisia annua L. (pKAL) have higher anticancer effects in oxaliplatin-resistant (OxPt-R) HCT116 cells than in HCT116 cells. In this study, it was tested whether and how As₄O₆ enhances anticancer effects of pKAL in HCT116 and HCT116-OxPt-R colorectal cancer cells. The CCK-8 assay, phase-contrast microscopy, and colony formation assay revealed that As₄O₆ enhanced anticancer effects of pKAL, with induction of nuclear deformity and intracytoplasmic vesicle formation in both cells. Western blot analysis revealed that co-treatment with As₄O₆ and pKAL significantly decreased the expression of NF-kB, EGFR, cyclin D1, CD44, and β-catenin, and upregulated the expression of p62 and LC3B in both cells. It also induced the activation of caspase-8 and γ-H2AX and the cleavage of β-catenin, PARP1, lamin A/C, and p62. These phenomena were inhibited by wortmannin, and further suppressed by co-treatment of wortmannin with an ROS inhibitor, N-acetyl cysteine. This study suggests that As₄O₆ enhanced the anticancer effects of pKAL by inducing autophagic cell death accompanied by apoptosis in both parental HCT116 and HCT116-OxPt-R cells. It also suggests that ROS generation and the downregulation of AKT, NF-κB p65, cyclin D1, EGFR, and β-catenin may play an important role in the As₄O₆-enhanced anticancer effect of pKAL. Full article

(This article belongs to the Special Issue Enhanced Anticancer Properties of Natural Products)

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Int. J. Mol. Sci., Volume 26, Issue 16 (August-2 2025) – 13 articles

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