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19 pages, 787 KiB  
Review
Comparison of Polynucleotide and Polydeoxyribonucleotide in Dermatology: Molecular Mechanisms and Clinical Perspectives
by Sung Tae Kim
Pharmaceutics 2025, 17(8), 1024; https://doi.org/10.3390/pharmaceutics17081024 (registering DOI) - 7 Aug 2025
Abstract
Polynucleotide (PN) and polydeoxyribonucleotide (PDRN) are DNA-derived biopolymers increasingly recognized for their potential in dermatology. Despite their structural similarities, PN and PDRN exhibit distinct functions due to differences in polymer length and molecular weight. PN, composed of longer DNA fragments, plays a key [...] Read more.
Polynucleotide (PN) and polydeoxyribonucleotide (PDRN) are DNA-derived biopolymers increasingly recognized for their potential in dermatology. Despite their structural similarities, PN and PDRN exhibit distinct functions due to differences in polymer length and molecular weight. PN, composed of longer DNA fragments, plays a key role in extracellular matrix remodeling. Conversely, PDRN, composed of relatively shorter oligonucleotide sequences than those of PN, enhances skin condition through adenosine receptor activations and supports nucleotide synthesis via both the salvage and de novo pathways. This review provides a critical comparison of the molecular characteristics and functions of PN and PDRN with particular emphasis on their dermatological applications. By delineating their respective roles in esthetic and regenerative medicine, we aim to highlight recent advances that may guide the development of optimized treatment strategies and foster evidence-based clinical practice. Full article
(This article belongs to the Collection Advanced Pharmaceutical Science and Technology in Korea)
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25 pages, 1677 KiB  
Review
Sustainable, Targeted, and Cost-Effective Laccase-Based Bioremediation Technologies for Antibiotic Residues in the Ecosystem: A Comprehensive Review
by Rinat Ezra, Gulamnabi Vanti and Segula Masaphy
Biomolecules 2025, 15(8), 1138; https://doi.org/10.3390/biom15081138 (registering DOI) - 7 Aug 2025
Abstract
Widespread antibiotic residues are accumulating in the environment, potentially causing adverse effects for humans, animals, and the ecosystem, including an increase in antibiotic-resistant bacteria, resulting in worldwide concern. There are various commonly used physical, chemical, and biological treatments for the degradation of antibiotics. [...] Read more.
Widespread antibiotic residues are accumulating in the environment, potentially causing adverse effects for humans, animals, and the ecosystem, including an increase in antibiotic-resistant bacteria, resulting in worldwide concern. There are various commonly used physical, chemical, and biological treatments for the degradation of antibiotics. However, the elimination of toxic end products generated by physicochemical methods and the need for industrial applications pose significant challenges. Hence, environmentally sustainable, green, and readily available approaches for the transformation and degradation of these antibiotic compounds are being sought. Herein, we review the impact of sustainable fungal laccase-based bioremediation strategies. Fungal laccase enzyme is considered one of the most active enzymes for biotransformation and biodegradation of antibiotic residue in vitro. For industrial applications, the low laccase yields in natural and genetically modified hosts may constitute a bottleneck. Methods to screen for high-laccase-producing sources, optimizing cultivation conditions, and identifying key genes and metabolites involved in extracellular laccase activity are reviewed. These include advanced transcriptomics, proteomics, and metagenomics technologies, as well as diverse laccase-immobilization technologies with different inert carrier/support materials improving enzyme performance whilst shifting from experimental assays to in situ monitoring of residual toxicity. Still, more basic and applied research on laccase-mediated bioremediation of pharmaceuticals, especially antibiotics that are recalcitrant and prevalent, is needed. Full article
(This article belongs to the Special Issue Recent Advances in Laccases and Laccase-Based Bioproducts)
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21 pages, 1727 KiB  
Review
Immune Evasion in Head and Neck Squamous Cell Carcinoma: Roles of Cancer-Associated Fibroblasts, Immune Checkpoints, and TP53 Mutations in the Tumor Microenvironment
by Chung-Che Tsai, Yi-Chiung Hsu, Tin-Yi Chu, Po-Chih Hsu and Chan-Yen Kuo
Cancers 2025, 17(15), 2590; https://doi.org/10.3390/cancers17152590 (registering DOI) - 7 Aug 2025
Abstract
Head and neck squamous cell carcinoma (HNSCC) is a highly aggressive malignancy characterized by complex interactions within the tumor microenvironment (TME) that facilitate immune evasion and tumor progression. The TME consists of diverse cellular components, including cancer-associated fibroblasts, immune and endothelial cells, and [...] Read more.
Head and neck squamous cell carcinoma (HNSCC) is a highly aggressive malignancy characterized by complex interactions within the tumor microenvironment (TME) that facilitate immune evasion and tumor progression. The TME consists of diverse cellular components, including cancer-associated fibroblasts, immune and endothelial cells, and extracellular matrix elements, that collectively modulate tumor growth, metastasis, and resistance to therapy. Immune evasion in HNSCC is orchestrated through multiple mechanisms, including the suppression of cytotoxic T lymphocytes, recruitment of immunosuppressive cells, such as regulatory T and myeloid-derived suppressor cells, and upregulation of immune checkpoint molecules (e.g., PD-1/PD-L1 and CTLA-4). Natural killer (NK) cells, which play a crucial role in anti-tumor immunity, are often dysfunctional within the HNSCC TME due to inhibitory signaling and metabolic constraints. Additionally, endothelial cells contribute to tumor angiogenesis and immune suppression, further exacerbating disease progression. Recent advancements in immunotherapy, particularly immune checkpoint inhibitors and NK cell-based strategies, have shown promise in restoring anti-tumor immunity. Moreover, TP53 mutations, frequently observed in HNSCC, influence tumor behavior and therapeutic responses, highlighting the need for personalized treatment approaches. This review provides a comprehensive analysis of the molecular and cellular mechanisms governing immune evasion in HNSCC with a focus on novel therapeutic strategies aimed at improving patient outcomes. Full article
(This article belongs to the Special Issue Oral Cancer: Prevention and Early Detection (2nd Edition))
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11 pages, 365 KiB  
Review
Precision Oncology in Hodgkin’s Lymphoma: Immunotherapy and Emerging Therapeutic Frontiers
by Adit Singhal, David Mueller, Benjamin Ascherman, Pratik Shah, Wint Yan Aung, Edward Zhou and Maria J. Nieto
Lymphatics 2025, 3(3), 24; https://doi.org/10.3390/lymphatics3030024 (registering DOI) - 6 Aug 2025
Abstract
Hodgkin’s Lymphoma (HL) affects approximately 8500 individuals annually in the United States. The 5-year relative survival rate has improved to 88.5%, driven by transformative advances in immunotherapy and precision oncology. The integration of Brentuximab vedotin (BV) and immune checkpoint inhibitors (ICIs) has redefined [...] Read more.
Hodgkin’s Lymphoma (HL) affects approximately 8500 individuals annually in the United States. The 5-year relative survival rate has improved to 88.5%, driven by transformative advances in immunotherapy and precision oncology. The integration of Brentuximab vedotin (BV) and immune checkpoint inhibitors (ICIs) has redefined treatment paradigms. The phase III SWOG S1826 trial established nivolumab plus doxorubicin, vinblastine, and dacarbazine (N + AVD) as an emerging new standard for advanced-stage HL, achieving a 2-year progression-free survival (PFS) of 92% compared to 83% for BV plus AVD (HR 0.48, 95% CI: 0.33–0.70), with superior safety, particularly in patients over 60. In relapsed/refractory HL, pembrolizumab outperforms BV, with a median PFS of 13.2 versus 8.3 months (HR 0.65, 95% CI: 0.48–0.88), as demonstrated in the KEYNOTE-204 trial. Emerging strategies, including novel ICI combinations, minimal residual disease (MRD) monitoring via circulating tumor DNA (ctDNA), and artificial intelligence (AI)-driven diagnostics, promise to further personalize therapy. This review synthesizes HL’s epidemiology, pathogenesis, diagnostic innovations, and therapeutic advances, highlighting the role of precision medicine in addressing unmet needs and disparities in HL care. Full article
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34 pages, 1221 KiB  
Review
Unmasking Pediatric Asthma: Epigenetic Fingerprints and Markers of Respiratory Infections
by Alessandra Pandolfo, Rosalia Paola Gagliardo, Valentina Lazzara, Andrea Perri, Velia Malizia, Giuliana Ferrante, Amelia Licari, Stefania La Grutta and Giusy Daniela Albano
Int. J. Mol. Sci. 2025, 26(15), 7629; https://doi.org/10.3390/ijms26157629 - 6 Aug 2025
Abstract
Pediatric asthma is a multifactorial and heterogeneous disease determined by the dynamic interplay of genetic susceptibility, environmental exposures, and immune dysregulation. Recent advances have highlighted the pivotal role of epigenetic mechanisms, in particular, DNA methylation, histone modifications, and non-coding RNAs, in the regulation [...] Read more.
Pediatric asthma is a multifactorial and heterogeneous disease determined by the dynamic interplay of genetic susceptibility, environmental exposures, and immune dysregulation. Recent advances have highlighted the pivotal role of epigenetic mechanisms, in particular, DNA methylation, histone modifications, and non-coding RNAs, in the regulation of inflammatory pathways contributing to asthma phenotypes and endotypes. This review examines the role of respiratory viruses such as respiratory syncytial virus (RSV), rhinovirus (RV), and other bacterial and fungal infections that are mediators of infection-induced epithelial inflammation that drive epithelial homeostatic imbalance and induce persistent epigenetic alterations. These alterations lead to immune dysregulation, remodeling of the airways, and resistance to corticosteroids. A focused analysis of T2-high and T2-low asthma endotypes highlights unique epigenetic landscapes directing cytokines and cellular recruitment and thereby supports phenotype-specific aspects of disease pathogenesis. Additionally, this review also considers the role of miRNAs in the control of post-transcriptional networks that are pivotal in asthma exacerbation and the severity of the disease. We discuss novel and emerging epigenetic therapies, such as DNA methyltransferase inhibitors, histone deacetylase inhibitors, miRNA-based treatments, and immunomodulatory probiotics, that are in preclinical or early clinical development and may support precision medicine in asthma. Collectively, the current findings highlight the translational relevance of including pathogen-related biomarkers and epigenomic data for stratifying pediatric asthma patients and for the personalization of therapeutic regimens. Epigenetic dysregulation has emerged as a novel and potentially transformative approach for mitigating chronic inflammation and long-term morbidity in children with asthma. Full article
(This article belongs to the Special Issue Molecular Research in Airway Diseases)
28 pages, 845 KiB  
Review
Circulating Tumor DNA in Prostate Cancer: A Dual Perspective on Early Detection and Advanced Disease Management
by Stepan A. Kopytov, Guzel R. Sagitova, Dmitry Y. Guschin, Vera S. Egorova, Andrei V. Zvyagin and Alexey S. Rzhevskiy
Cancers 2025, 17(15), 2589; https://doi.org/10.3390/cancers17152589 - 6 Aug 2025
Abstract
Prostate cancer (PC) remains a leading cause of malignancy in men worldwide, with current diagnostic methods such as prostate-specific antigen (PSA) testing and tissue biopsies facing limitations in specificity, invasiveness, and ability to capture tumor heterogeneity. Liquid biopsy, especially analysis of circulating tumor [...] Read more.
Prostate cancer (PC) remains a leading cause of malignancy in men worldwide, with current diagnostic methods such as prostate-specific antigen (PSA) testing and tissue biopsies facing limitations in specificity, invasiveness, and ability to capture tumor heterogeneity. Liquid biopsy, especially analysis of circulating tumor DNA (ctDNA), has emerged as a transformative tool for non-invasive detection, real-time monitoring, and treatment selection for PC. This review examines the role of ctDNA in both localized and metastatic PCs, focusing on its utility in early detection, risk stratification, therapy selection, and post-treatment monitoring. In localized PC, ctDNA-based biomarkers, including ctDNA fraction, methylation patterns, fragmentation profiles, and mutations, demonstrate promise in improving diagnostic accuracy and predicting disease recurrence. For metastatic PC, ctDNA analysis provides insights into tumor burden, genomic alterations, and resistance mechanisms, enabling immediate assessment of treatment response and guiding therapeutic decisions. Despite challenges such as the low ctDNA abundance in early-stage disease and the need for standardized protocols, advances in sequencing technologies and multimodal approaches enhance the clinical applicability of ctDNA. Integrating ctDNA with imaging and traditional biomarkers offers a pathway to precision oncology, ultimately improving outcomes. This review underscores the potential of ctDNA to redefine PC management while addressing current limitations and future directions for research and clinical implementation. Full article
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45 pages, 4319 KiB  
Review
Advancements in Radiomics-Based AI for Pancreatic Ductal Adenocarcinoma
by Georgios Lekkas, Eleni Vrochidou and George A. Papakostas
Bioengineering 2025, 12(8), 849; https://doi.org/10.3390/bioengineering12080849 (registering DOI) - 6 Aug 2025
Abstract
The advancement of artificial intelligence (AI), deep learning, and radiomics has introduced novel methodologies for the detection, classification, prognosis, and treatment evaluation of pancreatic ductal adenocarcinoma (PDAC). As the integration of AI into medical imaging continues to evolve, its potential to enhance early [...] Read more.
The advancement of artificial intelligence (AI), deep learning, and radiomics has introduced novel methodologies for the detection, classification, prognosis, and treatment evaluation of pancreatic ductal adenocarcinoma (PDAC). As the integration of AI into medical imaging continues to evolve, its potential to enhance early detection, refine diagnostic precision, and optimize treatment strategies becomes increasingly evident. However, despite significant progress, various challenges remain, particularly in terms of clinical applicability, generalizability, interpretability, and integration into routine practice. Understanding the current state of research is crucial for identifying gaps in the literature and exploring opportunities for future advancements. This literature review aims to provide a comprehensive overview of the existing studies on AI applications in PDAC, with a focus on disease detection, classification, survival prediction, treatment response assessment, and radiogenomics. By analyzing the methodologies, findings, and limitations of these studies, we aim to highlight the strengths of AI-driven approaches while addressing critical gaps that hinder their clinical translation. Furthermore, this review aims to discuss future directions in the field, emphasizing the need for multi-institutional collaborations, explainable AI models, and the integration of multi-modal data to advance the role of AI in personalized medicine for PDAC. Full article
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20 pages, 2614 KiB  
Article
Porphyrin-Modified Polyethersulfone Ultrafiltration Membranes for Enhanced Bacterial Inactivation and Filtration Performance
by Funeka Matebese, Nonkululeko Malomane, Meladi L. Motloutsi, Richard M. Moutloali and Muthumuni Managa
Membranes 2025, 15(8), 239; https://doi.org/10.3390/membranes15080239 - 6 Aug 2025
Abstract
Municipal wastewaters pose a severe risk to the environment and human health when discharged untreated. This is due to their high content of pathogens, such as viruses and bacteria, which can cause diseases like cholera. Herein, the research and development of porphyrin-modified polyethersulfone [...] Read more.
Municipal wastewaters pose a severe risk to the environment and human health when discharged untreated. This is due to their high content of pathogens, such as viruses and bacteria, which can cause diseases like cholera. Herein, the research and development of porphyrin-modified polyethersulfone (PES) ultrafiltration (UF) membranes was conducted to improve bacterial inactivation in complex municipal wastewater and enhance the fouling resistance and filtration performance. The synthesis and fabrication of porphyrin nanofillers and the resultant membrane characteristics were studied. The incorporation of porphyrin-based nanofillers improved the membrane’s hydrophilicity, morphology, and flux (247 Lm−2 h−1), with the membrane contact angle (CA) decreasing from 90° to ranging between 58° and 50°. The membrane performance was monitored for its flux, antifouling properties, reusability potential, municipal wastewater, and humic acid. The modified membranes demonstrated an effective application in wastewater treatment, achieving notable antibacterial activity, particularly under light exposure. The In-BP@SW/PES membrane demonstrated effective antimicrobial photodynamic effects against both Gram-positive S. aureus and Gram-negative E. coli. It achieved at least a 3-log reduction in bacterial viability, meeting Food and Drug Administration (FDA) standards for efficient antimicrobial materials. Among the variants tested, membranes modified with In-PB@SW nanofillers exhibited superior antifouling properties with flux recovery ratios (FRRs) of 78.9% for the humic acid (HA) solution and 85% for the municipal wastewater (MWW), suggesting a strong potential for long-term filtration use. These results highlight the promise of porphyrin-functionalized membranes as multifunctional tools in advanced water treatment technologies. Full article
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19 pages, 1226 KiB  
Article
Improving Endodontic Radiograph Interpretation with TV-CLAHE for Enhanced Root Canal Detection
by Barbara Obuchowicz, Joanna Zarzecka, Michał Strzelecki, Marzena Jakubowska, Rafał Obuchowicz, Adam Piórkowski, Elżbieta Zarzecka-Francica and Julia Lasek
J. Clin. Med. 2025, 14(15), 5554; https://doi.org/10.3390/jcm14155554 - 6 Aug 2025
Abstract
Objective: The accurate visualization of root canal systems on periapical radiographs is critical for successful endodontic treatment. This study aimed to evaluate and compare the effectiveness of several image enhancement algorithms—including a novel Total Variation–Contrast-Limited Adaptive Histogram Equalization (TV-CLAHE) technique—in improving the detectability [...] Read more.
Objective: The accurate visualization of root canal systems on periapical radiographs is critical for successful endodontic treatment. This study aimed to evaluate and compare the effectiveness of several image enhancement algorithms—including a novel Total Variation–Contrast-Limited Adaptive Histogram Equalization (TV-CLAHE) technique—in improving the detectability of root canal configurations in mandibular incisors, using cone-beam computed tomography (CBCT) as the gold standard. A null hypothesis was tested, assuming that enhancement methods would not significantly improve root canal detection compared to original radiographs. Method: A retrospective analysis was conducted on 60 periapical radiographs of mandibular incisors, resulting in 420 images after applying seven enhancement techniques: Histogram Equalization (HE), Contrast-Limited Adaptive Histogram Equalization (CLAHE), CLAHE optimized with Pelican Optimization Algorithm (CLAHE-POA), Global CLAHE (G-CLAHE), k-Caputo Fractional Differential Operator (KCFDO), and the proposed TV-CLAHE. Four experienced observers (two radiologists and two dentists) independently assessed root canal visibility. Subjective evaluation was performed using an own scale inspired by a 5-point Likert scale, and the detection accuracy was compared to the CBCT findings. Quantitative metrics including Peak Signal-to-Noise Ratio (PSNR), Signal-to-Noise Ratio (SNR), image entropy, and Structural Similarity Index Measure (SSIM) were calculated to objectively assess image quality. Results: Root canal detection accuracy improved across all enhancement methods, with the proposed TV-CLAHE algorithm achieving the highest performance (93–98% accuracy), closely approaching CBCT-level visualization. G-CLAHE also showed substantial improvement (up to 92%). Statistical analysis confirmed significant inter-method differences (p < 0.001). TV-CLAHE outperformed all other techniques in subjective quality ratings and yielded superior SNR and entropy values. Conclusions: Advanced image enhancement methods, particularly TV-CLAHE, significantly improve root canal visibility in 2D radiographs and offer a practical, low-cost alternative to CBCT in routine dental diagnostics. These findings support the integration of optimized contrast enhancement techniques into endodontic imaging workflows to reduce the risk of missed canals and improve treatment outcomes. Full article
(This article belongs to the Section Dentistry, Oral Surgery and Oral Medicine)
23 pages, 3580 KiB  
Review
Computational Chemistry Insights into Pollutant Behavior During Coal Gangue Utilization
by Xinyue Wang, Xuan Niu, Xinge Zhang, Xuelu Ma and Kai Zhang
Sustainability 2025, 17(15), 7135; https://doi.org/10.3390/su17157135 - 6 Aug 2025
Abstract
Coal serves as the primary energy source for China, with production anticipated to reach 4.76 billion tons in 2024. However, the mining process generates a significant amount of gangue, with approximately 800 million tons produced in 2023 alone. Currently, China faces substantial gangue [...] Read more.
Coal serves as the primary energy source for China, with production anticipated to reach 4.76 billion tons in 2024. However, the mining process generates a significant amount of gangue, with approximately 800 million tons produced in 2023 alone. Currently, China faces substantial gangue stockpiles, characterized by a low comprehensive utilization rate that fails to meet the country’s ecological and environmental protection requirements. The environmental challenges posed by the treatment and disposal of gangue are becoming increasingly severe. This review employs bibliometric analysis and theoretical perspectives to examine the latest advancements in gangue utilization, specifically focusing on the application of computational chemistry to elucidate the structural features and interaction mechanisms of coal gangue, and to collate how these insights have been leveraged in the literature to inform its potential utilization routes. The aim is to promote the effective resource utilization of this material, and key topics discussed include evaluating the risks of spontaneous combustion associated with gangue, understanding the mechanisms governing heavy metal migration, and modifying coal byproducts to enhance both economic viability and environmental sustainability. The case studies presented in this article offer valuable insights into the gangue conversion process, contributing to the development of more efficient and eco-friendly methods. By proposing a theoretical framework, this review will support ongoing initiatives aimed at the sustainable management and utilization of coal gangue, emphasizing the critical need for continued research and development in this vital area. This review uniquely combines bibliometric analysis with computational chemistry to identify new trends and gaps in coal waste utilization, providing a roadmap for future research. Full article
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17 pages, 2609 KiB  
Article
Residual Tumor Resection After Anti-PD-1 Therapy: A Promising Treatment Strategy for Overcoming Immune Evasive Phenotype Induced by Anti-PD-1 Therapy in Gastric Cancer
by Hajime Matsuida, Kosaku Mimura, Shotaro Nakajima, Katsuharu Saito, Sohei Hayashishita, Chiaki Takiguchi, Azuma Nirei, Tomohiro Kikuchi, Hiroyuki Hanayama, Hirokazu Okayama, Motonobu Saito, Tomoyuki Momma, Zenichiro Saze and Koji Kono
Cells 2025, 14(15), 1212; https://doi.org/10.3390/cells14151212 - 6 Aug 2025
Abstract
Background: Anti-programmed death 1 receptor (PD-1) therapy is a promising treatment strategy for patients with unresectable advanced or recurrent gastric/gastroesophageal junction (G/GEJ) cancer. However, its response rate and survival benefits are still limited; an immunological analysis of the residual tumor after anti-PD-1 therapy [...] Read more.
Background: Anti-programmed death 1 receptor (PD-1) therapy is a promising treatment strategy for patients with unresectable advanced or recurrent gastric/gastroesophageal junction (G/GEJ) cancer. However, its response rate and survival benefits are still limited; an immunological analysis of the residual tumor after anti-PD-1 therapy would be important. Methods: We evaluated the clinical efficacy of tumor resection (TR) after chemotherapy or anti-PD-1 therapy in patients with unresectable advanced or recurrent G/GEJ cancer and analyzed the immune status of tumor microenvironment (TME) by immunohistochemistry using their surgically resected specimens. Results: Patients treated with TR after anti-PD-1 therapy had significantly longer survival compared to those treated with chemotherapy and anti-PD-1 therapy alone. Expression of human leukocyte antigen (HLA) class I and major histocompatibility complex (MHC) class II on tumor cells was markedly downregulated after anti-PD-1 therapy compared to chemotherapy. Furthermore, the downregulation of HLA class I may be associated with the activation of transforming growth factor-β signaling pathway in the TME. Conclusions: Immune escape from cytotoxic T lymphocytes may be induced in the TME in patients with unresectable advanced or recurrent G/GEJ cancer after anti-PD-1 therapy due to the downregulation of HLA class I and MHC class II expression on tumor cells. TR may be a promising treatment strategy for these patients when TR is feasible after anti-PD-1 therapy. Full article
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19 pages, 1548 KiB  
Article
Phytochemical Analysis, Antioxidant Activity, and Anticancer Potential of Afzelia quanzensis Welw—Bark Extract: A Traditional Remedy Utilized by Indigenous Communities in KwaZulu-Natal and Eastern Cape Provinces of South Africa
by Siphamandla Qhubekani Njabuliso Lamula, Thando Bhanisa, Martha Wium, Juliano Domiraci Paccez, Luiz Fernando Zerbini and Lisa V. Buwa-Komoreng
Int. J. Mol. Sci. 2025, 26(15), 7623; https://doi.org/10.3390/ijms26157623 - 6 Aug 2025
Abstract
Despite the significant advancements in treatment and prevention, the fight against cancer is ongoing worldwide. This study evaluated the pharmacological properties and anticancer activity of Afzelia quanzensis bark, traditionally used by the indigenous communities of KwaZulu Natal and Eastern Cape Provinces of South [...] Read more.
Despite the significant advancements in treatment and prevention, the fight against cancer is ongoing worldwide. This study evaluated the pharmacological properties and anticancer activity of Afzelia quanzensis bark, traditionally used by the indigenous communities of KwaZulu Natal and Eastern Cape Provinces of South Africa to treat cancer and related illnesses. Phytochemical screening, high-performance liquid chromatography–diode array detection (HPLC-DAD), and Fourier-transform infrared spectroscopy (FTIR) analyses were carried out using established protocols. The antioxidant activity was assessed via the 2,2-diphenyl-1-picrylhydrazyl (DPPH) scavenging capacity and nitric oxide radicals. The anticancer activity was evaluated using the MTT assay (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide). Phytochemical analysis revealed the presence of saponins, flavonoids, terpenoids, alkaloids, steroids, cardiac glycosides, and phlobatannins. The HPLC-DAD analysis detected seven distinctive peaks in the aqueous extract and three distinctive peaks in the methanolic extract. The FTIR spectra of the aqueous extract displayed characteristic peaks corresponding to O-H, C=O, C=C, and =C–H functional groups. Among the tested extracts, the methanol extract exhibited the strongest antioxidant activity, followed by the ethanolic extract, in both DPPH and nitric oxide. The methanol extract showed a higher cell proliferation inhibition against the DU-145 cancer cell line with the percentage of inhibition of 37.8%, followed by the aqueous extract with 36.3%. In contrast, limited activity was observed against PC-3, SK-UT-1, and AGS cell lines. The results demonstrated notable dose-dependent antioxidant and antiproliferative activities supporting the ethnomedicinal use of Afzelia quanzensis bark in cancer management. These findings warrant further investigation into its bioactive constituents and mechanisms of action. Full article
(This article belongs to the Section Bioactives and Nutraceuticals)
41 pages, 865 KiB  
Review
Navigating the Landscape of Liquid Biopsy in Colorectal Cancer: Current Insights and Future Directions
by Pina Ziranu, Andrea Pretta, Giorgio Saba, Dario Spanu, Clelia Donisi, Paolo Albino Ferrari, Flaviana Cau, Alessandra Pia D’Agata, Monica Piras, Stefano Mariani, Marco Puzzoni, Valeria Pusceddu, Ferdinando Coghe, Gavino Faa and Mario Scartozzi
Int. J. Mol. Sci. 2025, 26(15), 7619; https://doi.org/10.3390/ijms26157619 - 6 Aug 2025
Abstract
Liquid biopsy has emerged as a valuable tool for the detection and monitoring of colorectal cancer (CRC), providing minimally invasive insights into tumor biology through circulating biomarkers such as circulating tumor DNA (ctDNA), circulating tumor cells (CTCs), microRNAs (miRNAs), long non-coding RNAs (lncRNAs), [...] Read more.
Liquid biopsy has emerged as a valuable tool for the detection and monitoring of colorectal cancer (CRC), providing minimally invasive insights into tumor biology through circulating biomarkers such as circulating tumor DNA (ctDNA), circulating tumor cells (CTCs), microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs). Additional biomarkers, including tumor-educated platelets (TEPs) and exosomal RNAs, offer further potential for early detection and prognostic role, although ongoing clinical validation is still needed. This review summarizes the current evidence on the diagnostic, prognostic, and predictive capabilities of liquid biopsy in both metastatic and non-metastatic CRC. In the non-metastatic setting, liquid biopsy is gaining traction in early detection through screening and in identifying minimal residual disease (MRD), potentially guiding adjuvant treatment and reducing overtreatment. In contrast, liquid biopsy is more established in metastatic CRC for monitoring treatment responses, clonal evolution, and mechanisms of resistance. The integration of ctDNA-guided treatment algorithms into clinical practice could optimize therapeutic strategies and minimize unnecessary interventions. Despite promising advances, challenges remain in assay standardization, early-stage sensitivity, and the integration of multi-omic data for comprehensive tumor profiling. Future efforts should focus on enhancing the sensitivity of liquid biopsy platforms, validating emerging biomarkers, and expanding multi-omic approaches to support more targeted and personalized treatment strategies across CRC stages. Full article
(This article belongs to the Special Issue Cancer Biology and Epigenetic Modifications)
47 pages, 7003 KiB  
Review
Phthalocyanines Conjugated with Small Biologically Active Compounds for the Advanced Photodynamic Therapy: A Review
by Kyrylo Chornovolenko and Tomasz Koczorowski
Molecules 2025, 30(15), 3297; https://doi.org/10.3390/molecules30153297 - 6 Aug 2025
Abstract
Phthalocyanines (Pcs) are well-established photosensitizers in photodynamic therapy, valued for their strong light absorption, high singlet oxygen generation, and photostability. Recent advances have focused on covalently conjugating Pcs, particularly zinc phthalocyanines (ZnPcs), with a wide range of small bioactive molecules to improve selectivity, [...] Read more.
Phthalocyanines (Pcs) are well-established photosensitizers in photodynamic therapy, valued for their strong light absorption, high singlet oxygen generation, and photostability. Recent advances have focused on covalently conjugating Pcs, particularly zinc phthalocyanines (ZnPcs), with a wide range of small bioactive molecules to improve selectivity, efficacy, and multifunctionality. These conjugates combine light-activated reactive oxygen species (ROS) production with targeted delivery and controlled release, offering enhanced treatment precision and reduced off-target toxicity. Chemotherapeutic agent conjugates, including those with erlotinib, doxorubicin, tamoxifen, and camptothecin, demonstrate receptor-mediated uptake, pH-responsive release, and synergistic anticancer effects, even overcoming multidrug resistance. Beyond oncology, ZnPc conjugates with antibiotics, anti-inflammatory drugs, antiparasitics, and antidepressants extend photodynamic therapy’s scope to antimicrobial and site-specific therapies. Targeting moieties such as folic acid, biotin, arginylglycylaspartic acid (RGD) and epidermal growth factor (EGF) peptides, carbohydrates, and amino acids have been employed to exploit overexpressed receptors in tumors, enhancing cellular uptake and tumor accumulation. Fluorescent dye and porphyrinoid conjugates further enrich these systems by enabling imaging-guided therapy, efficient energy transfer, and dual-mode activation through pH or enzyme-sensitive linkers. Despite these promising strategies, key challenges remain, including aggregation-induced quenching, poor aqueous solubility, synthetic complexity, and interference with ROS generation. In this review, the examples of Pc-based conjugates were described with particular interest on the synthetic procedures and optical properties of targeted compounds. Full article
(This article belongs to the Section Organic Chemistry)
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14 pages, 340 KiB  
Article
FLOT Versus CROSS—What Is the Optimal Therapeutic Approach for Locally Advanced Adenocarcinoma of the Esophagus and the Esophagogastric Junction?
by Martin Leu, Hannes Mahler, Johanna Reinecke, Ute Margarethe König, Leif Hendrik Dröge, Manuel Guhlich, Benjamin Steuber, Marian Grade, Michael Ghadimi, Volker Ellenrieder, Stefan Rieken and Alexander Otto König
Cancers 2025, 17(15), 2587; https://doi.org/10.3390/cancers17152587 - 6 Aug 2025
Abstract
Background/Objectives: Neoadjuvant radiochemotherapy and perioperative chemotherapy are both well-established treatment strategies for locally advanced adenocarcinoma of the esophagus (EAC) and the esophagogastric junction (AEGJ). However, recent knowledge controversially discusses whether neoadjuvant radiotherapy or perioperative chemotherapy represents superior therapeutic options to prolong survival or [...] Read more.
Background/Objectives: Neoadjuvant radiochemotherapy and perioperative chemotherapy are both well-established treatment strategies for locally advanced adenocarcinoma of the esophagus (EAC) and the esophagogastric junction (AEGJ). However, recent knowledge controversially discusses whether neoadjuvant radiotherapy or perioperative chemotherapy represents superior therapeutic options to prolong survival or cause less toxicity. Methods: We retrospectively analyzed 76 patients with locally advanced EAC or AEGJ treated at our tertiary cancer center between January 2015 and March 2023. Patients received either perioperative FLOT chemotherapy (n = 36) or neoadjuvant radiochemotherapy following the CROSS protocol (n = 40), followed by surgical resection and standardized follow-up. We compared survival outcomes, toxicity profiles, treatment compliance, and surgical results between the two groups. Results: There were no statistically significant differences between FLOT and CROSS treatments in five-year loco-regional controls (LRC: 61.5% vs. 68.6%; p = 0.81), progression-free survival (PFS: 33.9% vs. 42.8%; p = 0.82), overall survival (OS: 60.2% vs. 63.4%; p = 0.91), or distant controls (DC: 42.1% vs. 56.5%; p = 0.39). High-grade hematologic toxicities did not significantly differ between groups (p > 0.05). Treatment compliance was lower in the FLOT group, with 50% (18/36) not completing all the planned chemotherapy cycles, compared to 17.5% (7/40) in the CROSS group. All the patients in the CROSS group received the full radiotherapy dose. Surgical outcomes and post-surgical tumor status were comparable between the groups. Conclusions: Although perioperative chemotherapy with FLOT has recently become a standard of care for locally advanced EAC and AEGJ, neoadjuvant radiochemotherapy per the CROSS protocol remains a well-tolerated alternative. In appropriately selected patients, both approaches yield comparable oncological outcomes. Full article
(This article belongs to the Special Issue Current Treatments of Esophageal and Esophagogastric Junction Cancers)
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