Biomedicines最新文献

{"title":"Regulation of Stemness by NR1D2 in Colorectal Cancer.","authors":"Sandra Alonso-García, Paula Sánchez-Uceta, Sara Moreno-SanJuan, Jorge Casado, Jose D Puentes-Pardo, Huda Khaldy, David Lopez-Pérez, María Sol Zurita-Saavedra, Cristina González-Puga, Angel Carazo, Josefa León","doi":"10.3390/biomedicines13061500","DOIUrl":"10.3390/biomedicines13061500","url":null,"abstract":"<p><p><b>Background</b>: Nuclear Receptor Subfamily 1 Group D Member 2 (NR1D2), a transcription factor that regulates the circadian clock, has been described as an oncogene in colorectal cancer (CRC). In several types of cancer, NR1D2 regulates cancer progression and relapse through cancer stem cells (CSCs), although this aspect has not been studied in CRC. On the other hand, p53 is a tumour suppressor gene that appears mutated in approximately a 50% CRCs. Interestingly, p53 is considered to be a crucial nexus between circadian clock deregulation and cancer. In addition, p53 regulates CSC phenotypes. <b>Methods</b>: We developed an in vitro model in which NR1D2 was silenced in three isogenic cell lines with different p53 status. In addition, we analysed the expression of NR1D2 in a cohort of patients and determined its relationship with the characteristics of patients and tumours. <b>Results</b>: In the in vitro model, NRID2 silencing reduces cell growth and decreases stemness, although only in cells harbouring a wild type p53. In contrast, in cells lacking a functional p53 or harbouring a mutated one, NR1D2 knockout increases cell growth and stemness. In patients, NR1D2 expression correlates with poorly differentiated tumours and high expression of CSCs markers, although only in tumours with a wild type p53, corroborating the results obtained in the in vitro model. <b>Conclusions</b>: Although more research is needed to analyse the mechanism by which NR1D2 regulates stemness in a p53-dependent manner, our results highlight the possibility of using NR1D2 antagonists for treating this type of patient and to develop personalised medicine.</p>","PeriodicalId":8937,"journal":{"name":"Biomedicines","volume":"13 6","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12191377/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144494297","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Neutrophil-Lymphocyte Ratio in Fibromyalgia and Axial Spondyloarthritis: A Potential Biomarker for Diagnosis and Disease Activity.","authors":"Miriam Almirall, Esther Espartal, Xabier Michelena, Carlos Suso-Ribera, Mayte Serrat, Sara Marsal, Alba Erra","doi":"10.3390/biomedicines13061497","DOIUrl":"10.3390/biomedicines13061497","url":null,"abstract":"<p><p><b>Objective</b>: The Neutrophil-Lymphocyte Ratio (NLR) has been proposed as an inflammatory biomarker in several diseases, including Fibromyalgia, with controversial results. The objectives of this study were to: (1) compare NLR values among participants with Fibromyalgia, Axial Spondyloarthritis, and healthy controls; (2) assess the relationship between NLR and disease activity; and (3) establish diagnostic and activity cut-off values. <b>Methods</b>: A total of 112 age and gender-matched participants were included in each group. NLR values were compared between groups, correlations with disease activity were analyzed, and cut-off values were calculated using Receiver Operating Characteristic (ROC) curves. <b>Results</b>: The NLR was significantly higher in Fibromyalgia patients compared with healthy controls (1.8 ± 0.5 vs. 1.4 ± 0.2; <i>p</i> < 0.001) and in Axial Spondyloarthritis patients compared with both Fibromyalgia patients (2.1 ± 0.3 vs. 1.8 ± 0.5; <i>p</i> < 0.001) and healthy controls (2.1 ± 0.3 vs. 1.4 ± 0.2; <i>p</i> < 0.001). Within disease groups, the NLR was also significantly higher in patients with severe Fibromyalgia (FIQ ≥ 59) compared with non-severe cases (1.9 ± 0.5 vs. 1.7 ± 0.4; <i>p</i> = 0.008) and in patients with high/very high Axial Spondyloarthritis activity compared with those with low/inactive disease (2.3 ± 0.3 vs. 1.9 ± 0.2; <i>p</i> < 0.001). ROC analysis identified the NLR cut-off values of 1.54 for Fibromyalgia diagnosis, 1.64 for severe disease, 1.61 for Axial Spondyloarthritis diagnosis and 1.95 for high/very high disease activity. <b>Conclusions</b>: The NLR may serve as a cost-effective, rapid, and accessible biomarker for establishing diagnosis and disease activity in Axial Spondyloarthritis and, to a lesser extent, in Fibromyalgia. Further research is needed to validate these findings and explore NLR's role alongside other inflammatory markers.</p>","PeriodicalId":8937,"journal":{"name":"Biomedicines","volume":"13 6","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12191192/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144494232","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Enteroviral Transverse Myelitis Presenting as Acute Ataxia in Children: A Case Series.","authors":"Luka Švitek, Dominik Ljubas, Nina Krajcar, Maja Vrdoljak Pažur, Ana Tripalo Batoš, Irena Tabain, Srđan Roglić, Lorna Stemberger Marić","doi":"10.3390/biomedicines13061492","DOIUrl":"10.3390/biomedicines13061492","url":null,"abstract":"<p><p><b>Background</b>: Enteroviruses, members of the <i>Picornaviridae</i> family, typically cause asymptomatic or mild infections. However, they can also result in central nervous system (CNS) involvement, with transverse myelitis (TM) occurring only on rare occasions. TM is a syndrome characterized by acute or subacute spinal cord dysfunction, leading to neurological deficits below the level of the lesion. <b>Case report</b>: We report a case series of eight pediatric patients admitted over a three-month period, June to August 2024. All patients presented with ataxia and/or other neurological symptoms, alongside abnormal cerebrospinal fluid (CSF) findings. Although ataxia is commonly associated with cerebellitis, magnetic resonance imaging (MRI) in this cohort revealed findings consistent with TM. Notably, all patients demonstrated similar MRI abnormalities. The onset of symptoms occurred over a short time during an enterovirus epidemic. Enteroviral RNA was detected, or the virus was isolated in seven patients, while one patient had a close epidemiological link to the virus. All patients achieved full recovery following immunomodulatory therapy. <b>Conclusions</b>: This case series underscores that ataxia may be an atypical symptom associated with TM. Furthermore, there was a notable distinction between the clinical presentation and neuroradiological findings. Immunomodulatory therapy with immunoglobulins and corticosteroids has been shown to be effective and safe, supporting the hypothesis of an immune-mediated pathogenesis in these patients.</p>","PeriodicalId":8937,"journal":{"name":"Biomedicines","volume":"13 6","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12190920/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144494174","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Multi-Metal Exposure Profiling in ALS Patients in South Korea via Hair Analysis: A Cross-Sectional Study.","authors":"Jae-Kook Yoo, Soon-Hee Kwon, Sul-Hee Yoon, Jeong-Eun Lee, Jong-Un Chun, Je-Hyuk Chung, Sang-Yoon Lee, Jeong-Hwan Lee, Yu-Ra Chae","doi":"10.3390/biomedicines13061496","DOIUrl":"10.3390/biomedicines13061496","url":null,"abstract":"<p><strong>Objectives: </strong>Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease with an unclear etiology. This study aimed to assess chronic heavy metal exposure in ALS patients in South Korea by comparing hair concentrations of common (Hg, Pb, Cd) and rare (U, Th, Pt) metals with healthy controls.</p><p><strong>Methods: </strong>Hair samples were collected from 66 ALS patients and 70 healthy individuals at Rodem Hospital between 2022 and 2025. Metal concentrations were measured using inductively coupled plasma mass spectrometry (ICP-MS) following standardized washing and digestion protocols.</p><p><strong>Results: </strong>ALS patients showed significantly higher levels of Hg, Pb, Cd, Al, As, and U than controls (<i>p</i> < 0.05). Notably, 40% of ALS patients had Hg levels exceeding 50% of the reference upper limit, compared to only 10% of controls. Elevated levels of uranium and other rare metals were also observed in specific ALS cases.</p><p><strong>Conclusions: </strong>These findings suggest a possible association between heavy metal exposure and ALS in South Korea. Hair analysis may serve as a useful tool for identifying environmental factors contributing to ALS pathogenesis.</p>","PeriodicalId":8937,"journal":{"name":"Biomedicines","volume":"13 6","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12190663/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144494227","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Optimization, Characterization and Pharmacological Validation of the Endotoxin-Induced Acute Pneumonitis Mouse Model.","authors":"Emese Ritter, Kitti Hohl, László Kereskai, Ágnes Kemény, Dóra Hargitai, Veronika Szombati, Anikó Perkecz, Eszter Pakai, Andras Garami, Ákos Zsembery, Zsuzsanna Helyes, Kata Csekő","doi":"10.3390/biomedicines13061498","DOIUrl":"10.3390/biomedicines13061498","url":null,"abstract":"<p><p><b>Background/Objectives</b>: In preclinical research of airway inflammation, the endotoxin (lipopolysaccharide: LPS)-induced acute interstitial pneumonitis is the most commonly used mechanism model. However, studies apply different LPS serotypes, doses, administration routes, and reference compounds, making result interpretation challenging and drawing conclusions difficult. Therefore, here we aimed to optimize, characterize, and validate this model with dexamethasone in mice. <b>Methods</b>: Pneumonitis was induced by intratracheal LPS (0.25, 1, 2.5, 5 mg/kg; <i>E. coli</i> O111:B4) in C57BL/6J and NMRI mice; controls received phosphate-buffered saline (PBS). Dexamethasone (5 mg/kg i.p.) was used as a positive control. Respiratory functions were measured by restrained plethysmography 24 h after induction, and core body temperature was monitored. Lungs were excised and weighed, and then myeloperoxidase (MPO) activity and histopathological analysis were performed to assess pulmonary inflammation. <b>Results</b>: LPS-induced significant body weight loss, perivascular pulmonary edema, MPO activity increase, neutrophil infiltration, and respiratory function impairment in a dose-independent manner. However, LPS-induced hypothermia dynamics and duration were dose-dependent. The inhibitory effects of the reference compound dexamethasone were only detectable in the case of the 0.25 mg/kg LPS dose on most inflammatory parameters. These results did not differ substantially between C57BL/6J and NMRI mouse strains. <b>Conclusions</b>: Very low doses of LPS induce characteristic functional and morphological inflammatory alterations in the lung, which do not worsen in response to even 20 times higher doses. Since the effect of pharmacological interventions is likely to be detectable in the case of the 0.25 mg/kg LPS dose, we suggest this protocol for testing novel anti-inflammatory agents.</p>","PeriodicalId":8937,"journal":{"name":"Biomedicines","volume":"13 6","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12191197/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144494257","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Serum NT-ProBNP/Chloride Ratio Predicts Adverse Cardiovascular Outcomes in Patients with Acute Heart Failure.","authors":"Victor José Leal-Alcántara, Eder González-Macedo, Ana Cristina Maldonado-May, Alberto Santiago-Hernández, Eder Jonathan Amaro-Palomo, Sarai Hernandez-Pastrana, Anna Elisa Adib-Gracia, Rodrigo Gopar-Nieto, Daniel Sierra-Lara Martínez, José Luis Briseño-De la Cruz, Héctor González-Pacheco, Alexandra Arias-Mendoza, Diego Araiza-Garaygordobil","doi":"10.3390/biomedicines13061493","DOIUrl":"10.3390/biomedicines13061493","url":null,"abstract":"<p><p><b>Background:</b> Heart failure (HF) is a public health issue. It represents the second most common cause of hospitalization and the leading cause in individuals over 60 years old. Tools that predict adverse outcomes in patients with HF are needed. <b>Objective</b>: This study analyzed the prognostic role of the serum NT-proBNP/chloride ratio as a predictor of major cardiovascular events in patients with acute decompensated HF. <b>Methods</b>: Patients with a confirmed diagnosis of acute decompensated heart failure were retrospectively enrolled in the study; admission NT-proBNP/chloride ratio was used to stratify patients above or below the median (>/<83). The primary composite endpoint consisted of cardiovascular mortality, decompensated HF readmission, and unplanned emergency department visits. <b>Results:</b> A total of 197 individuals were included, of whom 100 (50.7%) were classified above and 97 (49.2%) below the median. Patients showing a high ratio had a lower LVEF (31 vs. 39%), a higher proportion of previous MI (30 vs. 15%), a lower diastolic blood pressure (73 vs. 80 mmHg), and higher BUN (38 vs. 23 mg/dL) and creatinine (1.6 vs. 1.1 mg/dL). After a follow-up period of 92 ± 3 days, 46 patients (23%) presented the primary endpoint; those with a high NT-proBNP/chloride ratio showed an increased risk (HR 3.18, 95% CI 1.55-6.52, <i>p</i> = 0.0015) of the primary endpoint. After multivariate analysis, only serum NT-proBNP/chloride ratio (<i>p</i> = 0.02) and diastolic pressure (0.037) remained significant. The area under the ROC curve for the NT-proBNP/chloride ratio for predicting the primary composite endpoint was significantly superior when compared with AUC for NT-proBNP or chloride alone. <b>Conclusions</b>: The serum NT-proBNP/chloride ratio is a novel, easy to use predictor of short- and medium-term cardiovascular events in patients with acute decompensated HF.</p>","PeriodicalId":8937,"journal":{"name":"Biomedicines","volume":"13 6","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12190525/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144494307","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hashimoto's Thyroiditis and Female Fertility: Endocrine, Immune, and Microbiota Perspectives in Assisted Reproduction-A Narrative Review.","authors":"Emilia Cristina Popa, Laura Maghiar, Teodor Andrei Maghiar, Ilarie Brihan, Laura Monica Georgescu, Bianca Anamaria Toderaș, Liliana Sachelarie, Anca Huniadi","doi":"10.3390/biomedicines13061495","DOIUrl":"10.3390/biomedicines13061495","url":null,"abstract":"<p><p>Hashimoto's thyroiditis is the most prevalent autoimmune thyroid disorder, and it disproportionately affects women of reproductive age. Its impact on fertility and assisted reproductive technologies [ART] has become an area of growing clinical interest. Thyroid autoimmunity can influence female reproductive health through multiple interconnected mechanisms, including subtle thyroid hormone imbalances, reduced ovarian reserve, altered endometrial receptivity, and dysregulated immune responses. Subclinical hypothyroidism and the presence of anti-thyroid antibodies have been linked to increased miscarriage risk and reduced success rates in ART, particularly in intracytoplasmic sperm injection (ICSI) cycles. Although levothyroxine supplementation is widely used, its benefits in euthyroid women remain uncertain. Recent studies suggest that gut microbiota may modulate immune function and affect fertility outcomes among women with autoimmune thyroid conditions. This narrative review synthesizes findings from a broad literature base of over 40 peer-reviewed publications published between 2010 and 2025, with 30 of the most relevant and methodologically robust studies selected for detailed analysis. The review integrates clinical, endocrine, immunological, and microbiome-related perspectives. The evidence supports the need for personalized fertility management in women with Hashimoto's thyroiditis and highlights directions for future research into immune and microbiota-targeted therapies.</p>","PeriodicalId":8937,"journal":{"name":"Biomedicines","volume":"13 6","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12190467/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144494195","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Role of Extracellular Vesicles in Chronic Post-Embolic Pulmonary Hypertension: Data from an Experimental Animal Model and Patients.","authors":"Elva Mendoza-Zambrano, Verónica Sánchez-López, Belén Gómez-Rodríguez, Inés García-Lunar, Daniel Pereda-Arnau, Luis Jara-Palomares, Teresa Elías-Hernández, Ana García-Álvarez, Remedios Otero-Candelera","doi":"10.3390/biomedicines13061499","DOIUrl":"10.3390/biomedicines13061499","url":null,"abstract":"<p><p><b>Background</b>: The pathogenesis of chronic thromboembolic pulmonary hypertension (CTEPH) involves a multifaceted interplay of factors, including incomplete thrombus resolution, endothelial dysfunction, and vascular remodeling. Recent studies have highlighted the role of extracellular vesicles (EVs) in vascular diseases, suggesting their potential involvement in CTEPH progression. This study aims to investigate the role of EVs from various cellular sources in the development of CTEPH. <b>Methods</b>: An experimental study was conducted using 11 male three-month-old Large-White pigs. The EVs of endothelial origin (EEVs; CD146+), leukocyte-derived EVs (LEVs; CD45+, CD44+), and consistent with mesenchymal-origin EVs (CD90+, CD105+) were quantified. Measurements were taken at baseline, after the first embolization, and prior to each subsequent weekly embolization. Embolizations were repeated until chronic pulmonary hypertension (PH) was generated. Based on these findings, a clinical case-control study was performed involving nine patients previously diagnosed with CTEPH and 18 patients with pulmonary embolism who did not develop CTEPH after two years of follow-up. <b>Results</b>: The experimental study, consistent with the mesenchymal-origin EVs, exhibited a progressive decrease below baseline levels; LEVs decreased after PH was established, while EEVs remained elevated throughout the study. Subsequently, in the clinical case-control study, CD45+ LEVs emerged as a significant association of CTEPH, with an odds ratio (OR) of 21.25 (95% CI: 1.91-236.00; <i>p</i> = 0.013). <b>Conclusions</b>: Inflammation involving LEVs and EEVs plays a crucial role in sustaining the vascular alterations leading to pulmonary vasculature remodeling in CTEPH.</p>","PeriodicalId":8937,"journal":{"name":"Biomedicines","volume":"13 6","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12191311/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144494303","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sinusoidal Extremely Low-Frequency Electromagnetic Stimulation (ELF-EMS) Promotes Angiogenesis In Vitro.","authors":"Lena Perez Font, Amanda Moya-Gomez, Hannelore Kemps, Ivo Lambrichts, Jean-Michel Rigo, Bert Brône, Annelies Bronckaers","doi":"10.3390/biomedicines13061490","DOIUrl":"10.3390/biomedicines13061490","url":null,"abstract":"<p><p><b>Background/Objectives</b>: Angiogenesis is the multistep process of the formation of new blood vessels. It is beneficial in scenarios that require tissue repair and regeneration, such as wound healing, bone fracture repair, and recovery from ischemic injuries like stroke, where new blood vessel formation restores oxygen and nutrient supply to damaged areas. Extremely low-frequency electromagnetic stimulation (ELF-EMS), which involves electromagnetic fields in the frequency range of 0-300 Hz, have been shown to reduce ischemic stroke volume by improving cerebral blood flow and recovery effects that are dependent on eNOS. Based on previous results, we herein explore the effects of ELF-EMS treatment (13.5 mT/10 and 60 Hz) on the activation of angiogenic processes in vitro in homeostatic conditions. <b>Methods</b>: Using human microvascular endothelial cells (HMEC-1), we studied cell proliferation, migration, and tube formation in vitro, as well as nitric oxide production and the effect of calcium and nitric oxide (NO) on these processes. Moreover, blood vessel formation was studied using a chicken chorioallantoic membrane (CAM) assay. <b>Results</b>: Our results showed that ELF-EMS increases proliferation, tube formation, and both the migration and transmigration of these cells, the latter of which was mediated via NO. In turn, calcium inhibition decreased ELF-EMF-induced NO production. Furthermore, ELF-EMS significantly increased blood vessel formation in the CAM assay. <b>Conclusions</b>: Our results indicated that ELF-EMS exposure (13.5 mT/10 and 60 Hz) significantly induces angiogenesis in vitro and in ovo, underscoring its potential application in the treatment of conditions characterized by insufficient blood supply.</p>","PeriodicalId":8937,"journal":{"name":"Biomedicines","volume":"13 6","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12190604/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144494310","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Targeting Biomarkers of Proliferation and Inflammation (Ki67, p53, and COX-2) in Actinic Keratoses with Photodynamic Therapy.","authors":"Justyna Ceryn, Aleksandra Lesiak, Magdalena Ciążyńska, Dorota Sobolewska-Sztychny, Marcin Noweta, Olga Stasikowska-Kanicka, Karol Ciążyński, Iris Zalaudek, Joanna Narbutt","doi":"10.3390/biomedicines13061487","DOIUrl":"10.3390/biomedicines13061487","url":null,"abstract":"<p><p><b>Background</b>: Actinic keratoses (AKs) are common pre-neoplastic lesions that may progress to cutaneous squamous cell carcinoma (cSCC). Photodynamic therapy (PDT) is an effective field-directed treatment for AK, but its impact on key biomarkers remains unclear. This study evaluates the clinical, dermatoscopic, and immunohistochemical effects of PDT on AK, with a focus on proliferation (Ki67, p53) and inflammation (COX-2) markers, to assess its efficacy in delaying carcinogenesis. <b>Methods</b>: In our prospective one-center study, we enrolled 31 patients with AK, with no history of previous AK treatment. They underwent three PDT sessions at four-week intervals, with follow-up eight weeks after the final session. Clinical, dermatoscopic, and immunohistochemical analyses of Ki67, p53, and COX-2 expression were performed before and after treatment. <b>Results</b>: Clinically, 54.8% of patients achieved complete lesion clearance, with no residual severe AK lesions. Ki67 and p53 immunoexpression significantly decreased post-PDT (<i>p</i> < 0.05), confirming its antiproliferative effect. COX-2 expression also declined significantly (<i>p</i> < 0.05), supporting PDT's anti-inflammatory role. However, COX-2 remained stable or increased in 35.48% of cases, possibly due to inflammation-induced regeneration. There is a positive correlation between the reduction in Ki67, p53, and COX-2 immunoexpression and the decrease in AK severity (both according to Olsen grade and dermatoscopic grade). <b>Conclusions</b>: PDT effectively reduces AK severity, proliferation, and inflammation markers, potentially delaying carcinogenesis. However, residual biomarker expression suggests that additional treatment sessions or combination therapies may be necessary for complete lesion clearance. Further studies are required to optimize PDT protocols.</p>","PeriodicalId":8937,"journal":{"name":"Biomedicines","volume":"13 6","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12190994/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144494325","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}