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Dual Inhibition of HIF-1α and HIF-2α as a Promising Treatment for VHL-Associated Hemangioblastomas: A Pilot Study Using Patient-Derived Primary Cell Cultures
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The Effect of Fungal Nutraceutical Supplementation on Postoperative Complications, Inflammatory Factors and Fecal Microbiota in Patients Undergoing Colorectal Cancer Surgery with Curative Intent
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Evaluation of the Effects of the Quaternary Ammonium Silane K21 on Zebrafish Viability, Toxicity, Growth, and Development
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Integrative Approaches in the Management of Hypertrophic Cardiomyopathy: A Comprehensive Review of Current Therapeutic Modalities
Journal Description
Biomedicines
Biomedicines
is an international, peer-reviewed, open access journal on biomedicines published monthly online by MDPI.
- Open Access— free for readers, with article processing charges (APC) paid by authors or their institutions.
- High Visibility: indexed within Scopus, SCIE (Web of Science), PubMed, PMC, CAPlus / SciFinder, and other databases.
- Journal Rank: JCR - Q1 (Pharmacology and Pharmacy) / CiteScore - Q1 (Medicine (miscellaneous))
- Rapid Publication: manuscripts are peer-reviewed and a first decision is provided to authors approximately 17 days after submission; acceptance to publication is undertaken in 2.9 days (median values for papers published in this journal in the first half of 2025).
- Recognition of Reviewers: reviewers who provide timely, thorough peer-review reports receive vouchers entitling them to a discount on the APC of their next publication in any MDPI journal, in appreciation of the work done.
- Companion journals for Biomedicines include: IJTM, BioMed, Anesthesia Research and Emergency Care and Medicine.
Impact Factor:
3.9 (2024);
5-Year Impact Factor:
4.2 (2024)
Latest Articles
Metabolic Dysfunction-Associated Steatotic Liver Disease as a Risk Factor for Chronic Kidney Disease: A Narrative Review
Biomedicines 2025, 13(9), 2162; https://doi.org/10.3390/biomedicines13092162 - 4 Sep 2025
Abstract
Metabolic dysfunction-associated steatotic liver disease (MASLD)—previously known as non-alcoholic fatty liver disease (NAFLD)—is currently the most common chronic liver disease globally. Observational studies have reported that MASLD is independently associated with extrahepatic disorders, such as chronic kidney disease (CKD). Severe forms of MASLD
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Metabolic dysfunction-associated steatotic liver disease (MASLD)—previously known as non-alcoholic fatty liver disease (NAFLD)—is currently the most common chronic liver disease globally. Observational studies have reported that MASLD is independently associated with extrahepatic disorders, such as chronic kidney disease (CKD). Severe forms of MASLD (i.e., steatohepatitis and liver fibrosis) are even more strongly associated with the risk of incident kidney dysfunction. Hypothetically, MASLD could directly promote CKD through liver-derived endocrine and metabolic mediators, hemodynamic alterations, immune-mediated mechanisms, and oxidative or cellular stress. However, proving that MASLD directly causes CKD is difficult due to the multiple shared cardiometabolic and systemic risk factors, such as obesity, hypertension, and type 2 diabetes mellitus, which serve as confounding variables. Moreover, studies on the association between MASLD and CKD have differed in their designs, sampling methods, disease definitions, and inclusion criteria, precluding more robust evidence supporting a causal relationship. Furthermore, few studies have explored specific issues, such as the new nomenclature for steatotic liver disease, the relationship between these diseases in pediatric populations, the impact of MASLD plus alcohol intake (MetALD) on CKD, and therapeutic options targeting MASLD and CKD simultaneously. Answers to these issues are essential, as the appropriate management of patients with MASLD may prevent or ameliorate kidney dysfunction. The aims of the present study are to describe shared risk factors between MASLD and CKD, the possible direct pathogenic effect of MASLD on kidney structure and function, and gaps in the current literature, to indicate future research directions.
Full article
(This article belongs to the Special Issue Advances in Hepatology)
Open AccessArticle
Distinct Markers of Discordant Treatment Response to Lifestyle Intervention in MASLD, Independent of Weight Loss
by
Ling Luo, Congxiang Shao, Zhi Dong, Shuyu Zhuo, Shiting Feng, Wei Wang, Junzhao Ye and Bihui Zhong
Biomedicines 2025, 13(9), 2161; https://doi.org/10.3390/biomedicines13092161 - 4 Sep 2025
Abstract
Background/Objectives: Weight loss is the primary therapy for metabolic dysfunction-associated steatotic liver disease (MASLD). However, the proportion and factors influencing therapeutic changes in the liver condition contrary to weight loss remain unclear. Methods: This observational cohort study spanned between January 2015 and
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Background/Objectives: Weight loss is the primary therapy for metabolic dysfunction-associated steatotic liver disease (MASLD). However, the proportion and factors influencing therapeutic changes in the liver condition contrary to weight loss remain unclear. Methods: This observational cohort study spanned between January 2015 and January 2024, with a 48-week lifestyle modification until January 2025. The liver fat content (LFC) determined using MRI-PDFF and liver stiffness measurement (LSM) via 2D-SWE were assessed at baseline and 48 weeks. The weight loss target (WLT) was determined as a reduction of ≥3% in body weight for lean/normal-weight patients and ≥5% for patients who were overweight/obese. Results: Overall, 397 patients with MASLD (30.5% achieving WLT) were included. For participants with WLT, 24.8% presented MRI-PDFF non-response, which was associated with moderate–vigorous physical activity (MVPA) ≥ 150 min/week, indicating a lower likelihood of non-response. Alanine aminotransferase (ALT) non-response occurred in 29.6% of patients and was linked to changes in LFC (ΔLFC, calculated as the baseline minus week 48). LSM non-response was observed in 48.2%, with high free fatty acid (FFA) levels identified as a risk factor. Among individuals without WLT, 29.0% demonstrated an MRI-PDFF response that correlated with greater reductions in low-density lipoprotein cholesterol; 39.4% exhibited an ALT response, which was associated with more significant reductions in LFC. The LSM response was 37.8%, also correlating with a reduction in LFC. Conclusions: Our results identified that MVPA, baseline steatosis degree, FFA, and their responses served as significant markers for treatment response contrary to weight loss in MASLD.
Full article
(This article belongs to the Section Endocrinology and Metabolism Research)
Open AccessReview
STING-Activating Nanoparticles Combined with PD-1/PD-L1 Blockade: A Synergistic Approach in Cancer Immunotherapy
by
Dorota Bartusik-Aebisher, Kacper Rogóż and David Aebisher
Biomedicines 2025, 13(9), 2160; https://doi.org/10.3390/biomedicines13092160 - 4 Sep 2025
Abstract
Objectives: Immunotherapy combining agonists of the cyclic GMP-AMP synthase–stimulator of interferon genes (cGAS-STING) pathway with PD-1/PD-L1 blockade shows promising preclinical results, although in clinical practice, it faces pharmacokinetic barriers, systemic toxicity, and an immunosuppressive tumor microenvironment (TME). Recent advances in and expansion of
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Objectives: Immunotherapy combining agonists of the cyclic GMP-AMP synthase–stimulator of interferon genes (cGAS-STING) pathway with PD-1/PD-L1 blockade shows promising preclinical results, although in clinical practice, it faces pharmacokinetic barriers, systemic toxicity, and an immunosuppressive tumor microenvironment (TME). Recent advances in and expansion of the cGAS-STING pathway as a therapeutic target have further highlighted its central role in innate and adaptive immune activation. The aim of this paper is to review combination strategies of STING and PD-1/PD-L1 checkpoint blockade therapies, triple-therapy strategies using a third component such as chemotherapy, radiotherapy, photodynamic therapy (PDT), and others, and the use of nanoparticles as carriers for these drugs. Methods: Reports in the literature on the mechanisms of STING + PD-1/PD-L1 synergy, as well as with the use of a third component and delivery systems, were analyzed. Current challenges and limitations, as well as prospects for the development of these therapies, are noted. Results: Activation of the cGAS-STING synergizes with blocking the PD-1/PD-L1 axis. The addition of a third component further enhances the anti-tumor effect through a stronger induction of immunogenic cell death (ICD), increased production of interferons and pro-inflammatory cytokines, repolarization of macrophages, and enhanced infiltration of T lymphocytes. Conclusions: Therapy with STING agonists and PD-1/PD-L1 checkpoint inhibitors, supported by nanotechnology vehicles and using a third therapeutic component, overcomes key pharmacological and immunological limitations. This multimodal immunotherapeutic strategy holds high translational promise, offering more effective and safer solutions in cancer immunotherapy.
Full article
(This article belongs to the Special Issue Advances Research on Nanomedicine)
Open AccessArticle
Long-Term Osteoporosis Risk in Colorectal Cancer Survivors: A Nationwide Longitudinal Cohort with up to 16 Years of Follow-Up
by
Ho Suk Kang, Joo-Hee Kim, Eun Soo Kim, Dae Myoung Yoo, Kyeong Min Han, Nan Young Kim, Hyo Geun Choi, Ha Young Park and Mi Jung Kwon
Biomedicines 2025, 13(9), 2159; https://doi.org/10.3390/biomedicines13092159 - 4 Sep 2025
Abstract
Background/Objectives: Colorectal cancer (CRC) survivors may face long-term health consequences, yet the relationship between CRC and osteoporosis remains underexplored, particularly in Asia. We conducted a nationwide, retrospective longitudinal cohort study with matched controls using the Korean National Health Insurance Service–National Sample Cohort (2005–2019)
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Background/Objectives: Colorectal cancer (CRC) survivors may face long-term health consequences, yet the relationship between CRC and osteoporosis remains underexplored, particularly in Asia. We conducted a nationwide, retrospective longitudinal cohort study with matched controls using the Korean National Health Insurance Service–National Sample Cohort (2005–2019) to assess whether CRC increases osteoporosis risk or not. Methods: We identified 8733 CRC patients and 34,932 matched controls (1:4 ratio) based on age, sex, income, residence, and index date, excluding individuals with pre-existing osteoporosis. Osteoporosis was defined via ICD-10 codes (M80–M82) plus confirmatory bone imaging claims. Propensity score overlap weighting was applied, and adjusted hazard ratios (HRs) with 95% confidence intervals (CIs) were calculated using Cox proportional hazards models, with subgroup analyses based on demographic and clinical factors. Results: With up to 16 years of follow-up, osteoporosis incidence rates were 13.80 and 14.30 per 1000 person-years in CRC and control groups, respectively. Adjusted Cox models revealed no significant association between CRC and osteoporosis (HR = 0.95; 95% CI = 0.87–1.04). Subgroup analysis showed a slightly lower risk among CRC survivors aged ≥65 years (adjusted HR = 0.84; 95% CI = 0.75–0.95), though no associations were observed by sex, income, region, or comorbidities. Conclusions: These findings suggest CRC may not be an independent risk factor for osteoporosis in the Korean population. The unexpected age-specific variation warrants cautious interpretation, possibly reflecting competing mortality risks or detection biases.
Full article
(This article belongs to the Section Molecular and Translational Medicine)
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Open AccessReview
Nucleic Acid Diversity in cGAS-STING Pathway Activation and Immune Dysregulation
by
Jingwei Guo, Mingjun Lu, Chenyang Wang, Dongchang Wang and Teng Ma
Biomedicines 2025, 13(9), 2158; https://doi.org/10.3390/biomedicines13092158 - 4 Sep 2025
Abstract
The cGAS-STING pathway initiates the core cascade of innate immune defense by recognizing pathogen-associated and self-derived abnormal nucleic acids, and key molecules (such as cGAS, STING, downstream IFN-β, IL-6, etc.) may serve as biomarkers in various diseases. The diverse mechanisms by which distinct
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The cGAS-STING pathway initiates the core cascade of innate immune defense by recognizing pathogen-associated and self-derived abnormal nucleic acids, and key molecules (such as cGAS, STING, downstream IFN-β, IL-6, etc.) may serve as biomarkers in various diseases. The diverse mechanisms by which distinct nucleic acids activate this pathway provide novel insights for therapeutic strategies targeting infectious diseases, cancer, and autoimmune disorders. To prevent aberrant cGAS-STING pathway activation, cells employ multiple regulatory mechanisms, including restricting self-DNA recognition and terminating downstream signaling. Strategies to mitigate pathological activation involve reducing nucleic acid accumulation through nuclease degradation (e.g., of mitochondrial DNA or neutrophil extracellular traps, NETs) or directly inhibiting cGAS or STING. This review elucidates the molecular mechanism of nucleic acid-mediated regulation of cGAS-STING and its role in disease regulation.
Full article
(This article belongs to the Topic Biomarkers of Disease: Discovery and Clinical Applications)
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Open AccessReview
The Use of Rituximab in Glomerulonephritis: What Is the Evidence?
by
Wenjuan Zhu, Haiyan He and Pearl Pai
Biomedicines 2025, 13(9), 2157; https://doi.org/10.3390/biomedicines13092157 - 4 Sep 2025
Abstract
Rituximab has been increasingly used as a choice of treatment in various forms of glomerulonephritis. Recent evidence and the KDIGO guideline establish Rituximab as the first-line treatment for Primary Membranous Nephropathy and ANCA-associated vasculitis. It is also recommended in cases of steroid-dependent or
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Rituximab has been increasingly used as a choice of treatment in various forms of glomerulonephritis. Recent evidence and the KDIGO guideline establish Rituximab as the first-line treatment for Primary Membranous Nephropathy and ANCA-associated vasculitis. It is also recommended in cases of steroid-dependent or frequently relapsing Minimal Change Disease and Focal Segmental Glomerulosclerosis, as well as in refractory Lupus Nephritis. In this review, we set out to analyze the evidence behind its use and some of its shortfalls, including gaps in understanding the dosing and redosing schedule, as well as long-term safety, which advocate for further research. Finally, we also provide some practical tips on patient use.
Full article
(This article belongs to the Special Issue Immunosuppressive Treatment in Glomerular Diseases)
Open AccessSystematic Review
Topical Zinc Oxide Nanoparticle Formulations for Acne Vulgaris: A Systematic Review of Pre-Clinical and Early-Phase Clinical Evidence
by
Daniela Crainic, Roxana Popescu, Cristina-Daliborca Vlad, Daniela-Vasilica Serban, Daniel Popa, Cristina Annemari Popa and Ana-Olivia Toma
Biomedicines 2025, 13(9), 2156; https://doi.org/10.3390/biomedicines13092156 - 4 Sep 2025
Abstract
Background and objectives: Antibiotic resistance in Cutibacterium acnes is undermining topical macrolides and clindamycin, prompting renewed interest in zinc oxide nanoparticles (ZnO-NPs) as non-antibiotic alternatives. We aimed to (i) determine the antimicrobial and anti-inflammatory performance of topical ZnO-NP formulations across in vitro, animal
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Background and objectives: Antibiotic resistance in Cutibacterium acnes is undermining topical macrolides and clindamycin, prompting renewed interest in zinc oxide nanoparticles (ZnO-NPs) as non-antibiotic alternatives. We aimed to (i) determine the antimicrobial and anti-inflammatory performance of topical ZnO-NP formulations across in vitro, animal and early human models; (ii) identify physicochemical parameters that modulate potency and tolerance; and (iii) delineate translational gaps and priority design elements for randomised trials. Methods: We systematically searched PubMed, Scopus and Web of Science until 1 June 2025 for in vitro, animal and human studies that evaluated ≤100 nm ZnO-NPs applied topically to C. acnes cultures, extracting data on bacterial load, lesion counts, biophysical skin parameters and acute toxicity. Eight eligible investigations (five in vitro, two animal, one exploratory human) analysed particles 20–50 nm in diameter carrying mildly anionic zeta potentials. Results: Hyaluronic acid-coated ZnO-NPs achieved a sixteen-fold higher selective kill ratio over Staphylococcus epidermidis at 32 µg mL1, while centrifugally spun polyvinyl alcohol dressings reduced C. acnes burden by 3.1 log10 on porcine skin within 24 h, and plant-derived nanogels generated inhibition zones that were 11% wider than benzoyl-peroxide’s 5%. In human subjects, twice-daily 0.5% hyaluronic–ZnO nanogel cut inflammatory-lesion counts by 58% at week four and lowered transepidermal water loss without erythema. Preclinical safety was reassuring, zero mortality among animals at 100 µg mL1 and no irritation among patients, although high-dose sunscreen-grade ZnO (20 nm) delayed rat wound closure by 38%, highlighting dose-dependent differences. Conclusions: Collectively, the evidence indicates that nanoscale reformulation markedly augments zinc’s antibacterial and anti-inflammatory performance while maintaining favourable acute tolerance, supporting progression to rigorously designed, adequately powered randomised trials that will benchmark ZnO-NPs against benzoyl peroxide and retinoids, optimise dosing for efficacy versus phototoxicity, and establish long-term dermatological safety.
Full article
(This article belongs to the Section Nanomedicine and Nanobiology)
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Open AccessArticle
Association of Heart Rate Variability and Acceleration Plethysmography with Systemic Comorbidity Burden in Patients with Glaucoma
by
Yuto Yoshida, Hinako Takei, Misaki Ukisu, Keigo Takagi and Masaki Tanito
Biomedicines 2025, 13(9), 2155; https://doi.org/10.3390/biomedicines13092155 - 4 Sep 2025
Abstract
Background: Autonomic nervous system (ANS) and vascular factors are associated with glaucoma. However, the association between systemic comorbidity burden and ANS and hemodynamic function in patients with glaucoma remains unclear. This study aimed to examine the association between heart rate variability (HRV)
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Background: Autonomic nervous system (ANS) and vascular factors are associated with glaucoma. However, the association between systemic comorbidity burden and ANS and hemodynamic function in patients with glaucoma remains unclear. This study aimed to examine the association between heart rate variability (HRV) and acceleration plethysmography (APG) parameters and the age-adjusted Charlson Comorbidity Index (ACCI) in patients with glaucoma. Methods: A total of 260 subjects (260 eyes), including 186 with primary open-angle glaucoma (PG) and 74 with exfoliation glaucoma (EG), were enrolled at Shimane University Hospital from June 2023 to July 2024. HRV and APG were assessed using a sphygmograph (TAS9 Pulse Analyzer Plus View). HRV parameters included time-domain measures (SDNN, RMSSD, CVRR) and frequency-domain measures (TP, VLF, LF, HF, LF/HF). APG parameters included the a, b, c, d, and e components of the accelerated pulse wave, and the following vascular types: Type A, Type B, and Type C. The association between ACCI and HRV and APG parameters was evaluated using Spearman’s rank correlation and multivariate regression adjusted for sex, body mass index, pulse rate, systolic and diastolic blood pressure, intraocular pressure, medication score, mean deviation, and glaucoma type. Results: By univariate analysis, against ACCI, significant inverse correlations were observed for several parameters: LnLF (R = −0.17, p = 0.0062); LnLF/LnHF (R = −0.24, p = 0.00012); b peak (R = −0.14, p = 0.031); d peak (R = −0.17, p = 0.0072); and e peak (R = −0.15, p = 0.015). Regarding HRV parameters, multivariate linear regression models showed that ACCI was significantly positively associated with RMSSD (coefficient: 2.861; 95% CI: 0.447 to 5.274) and significantly negatively associated with the frequency-domain parameters LnLF (coefficient: −0.127; 95% CI: −0.245 to −0.009) and LnLF/LnHF (coefficient: −0.038; 95% CI: −0.062 to −0.014). In APG parameters, the c peak was significant associated with ACCI (coefficient: −12.6; 95% CI: −22.5 to −2.69). ACCI was significantly associated with Type B (coefficient: 0.305; 95% CI: 0.057 to 0.552). Conclusions: Greater systemic comorbidity burden may be related to impaired ANS regulation and increased vascular stiffness in glaucoma patients.
Full article
(This article belongs to the Special Issue Glaucoma: New Diagnostic and Therapeutic Approaches, 3rd Edition)
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Open AccessCommunication
A Biological-Driven Approach to Explore Dose-Escalated Ultra-Hypofractionation in Breast Cancer Radiotherapy
by
Marco Calvaruso, Denis Panizza, Riccardo Ray Colciago, Valeria Faccenda, Gaia Pucci, Elena De Ponti, Giusi Irma Forte, Giorgio Russo, Luigi Minafra and Stefano Arcangeli
Biomedicines 2025, 13(9), 2154; https://doi.org/10.3390/biomedicines13092154 - 4 Sep 2025
Abstract
To explore a more personalized approach to radiation therapy for adjuvant whole-breast irradiation in triple-negative breast cancer (TNBC), we analyzed the cell lines BT549 and MDA-MB-231 as in vitro models for radiobiological characterization. The local disease-free survival (LSR) values were determined for both
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To explore a more personalized approach to radiation therapy for adjuvant whole-breast irradiation in triple-negative breast cancer (TNBC), we analyzed the cell lines BT549 and MDA-MB-231 as in vitro models for radiobiological characterization. The local disease-free survival (LSR) values were determined for both cell lines’ median, maximum, and minimum α and β parameters to achieve an LSR probability of close to 100% in a five-fraction schedule. Based on these findings, fifteen treatment plans were created for BC to simulate the proposed dose schedule. For the MDA-MB-231 cell line, the α/β ratios were 3.79 Gy (minimum), 15 Gy (maximum), and 7 Gy (median). For the BT-549 cell line, the α/β ratios were 5.95 Gy (minimum), 22.93 Gy (maximum), and 16.51 Gy (median). To achieve an LSR probability of close to 100%, the required doses per fraction were 5.2 Gy, 5.3 Gy, and 7.3 Gy for MDA-MB-231 and 8 Gy, 9.1 Gy, and 9.9 Gy for BT-549. We selected the highest dose per fraction, 9.9 Gy × 5, to simulate the worst-case scenario. To achieve 100% cell death effectiveness in TNBC, it is likely that higher radiation doses are required—doses that are not feasible within the setting of adjuvant whole-breast irradiation. Our model, which relies on the intrinsic biological features of the tumor, paves the way to reach more tailored RT plans and to improve the classic LQ model.
Full article
(This article belongs to the Special Issue Latest Advancements in Radiotherapy)
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Open AccessCommunication
Tissue-Cultured Chondrocytes Survive After Irradiation in 1300 Gy Dose
by
Denis Baranovskii, Anna Smirnova, Anna Yakimova, Anastas Kisel, Sergey Koryakin, Dmitrii Atiakshin, Michael Ignatyuk, Mikhail Potievskiy, Vyacheslav Saburov, Sergey Budnik, Yana Sulina, Vasiliy N. Stepanenko, Roman Churyukin, Bagavdin Akhmedov, Peter Shegay, Andrey D. Kaprin and Ilya Klabukov
Biomedicines 2025, 13(9), 2153; https://doi.org/10.3390/biomedicines13092153 - 4 Sep 2025
Abstract
Background/Objectives: Radiobiology has shown heterogeneity in the sensitivity of cells to ionizing radiation, depending on a variety of conditions. The presence of an extracellular matrix (ECM) appears to confer a radioprotective effect on cells and can influence the cellular microenvironment by modulating
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Background/Objectives: Radiobiology has shown heterogeneity in the sensitivity of cells to ionizing radiation, depending on a variety of conditions. The presence of an extracellular matrix (ECM) appears to confer a radioprotective effect on cells and can influence the cellular microenvironment by modulating the availability of oxygen and nutrients, which can affect cellular metabolism and stress responses. A three-dimensional cell culture allows the synergistic effect on cell survival to be obtained based not only on the radioprotective properties of the extracellular matrix but also on the stress-resistant endogenous properties of the cell culture. The aim of this study was to investigate the survival of chondrocytes in a 3D cell culture during high-dose ionizing irradiation. Methods: The properties of nasal chondrocytes were evaluated using a pellet culture model in which the cells were surrounded by a de novo synthesized extracellular matrix. Tissue cultures were exposed by gamma radiation at doses of 10, 100, and 1300 Gy. Cell viability was assessed after 2 days of irradiation by live/dead staining using confocal scanning laser microscopy. Results: Tissue-cultured chondrocytes survive after gamma-irradiation of low (10 Gy), medium (100 Gy), and high (1300 Gy) dosages; however, after irradiation of 1300 Gy, the percentage of surviving cells was lower. The average percentages of viable cells were evaluated as 82%, 79%, and 63% in low-, medium-, and high-dose groups, respectively. Conclusions: Under determined conditions, human cells are able to survive at doses of ionizing radiation that are significantly higher than the current limits.
Full article
(This article belongs to the Special Issue Latest Advancements in Radiotherapy)
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Open AccessArticle
Estrogen-like Activity of Scrophularia buergeriana Root Extracts in MCF-7 Cells
by
Hye-Yeong Song, Jinsu Choi, Eunwoo Jeong, Harang Park, Juyeong Moon, Min-ah Kim, Javokhir Rustamov, Hwan-Soo Yoo and Tack-Joong Kim
Biomedicines 2025, 13(9), 2151; https://doi.org/10.3390/biomedicines13092151 - 4 Sep 2025
Abstract
Background/Objectives: Estrogen deficiency-related menopause is associated with various physical and psychological symptoms. Although hormone replacement therapy (HRT) effectively alleviates these symptoms, its long-term use is associated with several side effects such as an increased risk of breast cancer and cardiovascular disease. Consequently,
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Background/Objectives: Estrogen deficiency-related menopause is associated with various physical and psychological symptoms. Although hormone replacement therapy (HRT) effectively alleviates these symptoms, its long-term use is associated with several side effects such as an increased risk of breast cancer and cardiovascular disease. Consequently, there is a growing interest in some plant-derived phytoestrogens that are considered safer alternatives to estrogen. Recent studies on Scrophularia buergeriana confirmed their anti-inflammatory and antioxidant properties; however, their effects on menopausal health remain unclear. Therefore, the aim of this study was to investigate the estrogen-like effects of S. buergeriana root (SB-R) extract, a potential phytoestrogen. Methods: Briefly, the MCF-7 cell line, a widely used in vitro model for assessing estrogen-like activity, was treated with SB-R extract and 17β-estradiol (E2; positive control) in the presence or absence of ICI 182,780 (Fulvestrant), an estrogen receptor antagonist. An E-screen assay and flow cytometry were performed to assess the effects of the treatments on cell proliferation and the cell cycle, respectively. Additionally, Western blotting and immunofluorescence assays were performed to elucidate the potential mechanisms underlying the estrogen-like effects of SB-R. Result: Treatment with SB-R extract promoted MCF-7 cell proliferation in a manner similar to E2. However, ICI 182,780 co-treatment inhibited the SB-R extract-induced increase in MCF-7 cell proliferation. Additionally, SB-R extract promoted cell cycle progression by increasing the proportion of cells in the S and G2/M phases. Moreover, Western blotting and immunofluorescence assays showed that SB-R extract increased the expression of estrogen receptor alpha (ERα). Furthermore, SB-R treatment activated downstream signaling pathways by enhancing AKT and ERK phosphorylation and upregulated the expression of cell cycle regulators, including cyclin D1, cyclin dependent kinase 4 (CDK4), cyclin E1, and cyclin dependent kinase 2 (CDK2). Conclusions: SB-R exhibits estrogen-like activity by activating ERα-mediated AKT and ERK pathways and thereby increasing the expression of proteins involved in cell cycle regulation. This makes it a promising phytoestrogen candidate and a safer alternative to conventional hormonal therapy for alleviating menopausal symptoms.
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(This article belongs to the Section Cell Biology and Pathology)
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Open AccessArticle
Antimicrobial Activity of Natural Extracts Against Catheter-Colonizing Methicillin-Resistant Staphylococcus aureus Clinical Isolates
by
José Avendaño-Ortiz, Alba Tribaldo, Luna Ballestero, Luis Antonio Gómez, Ignacio Gracia, Juan Francisco Rodríguez, Natalia Bejarano Ramírez, Raquel Bodoque-Villar, María Ángeles Vaz-Salgado, Rosa del Campo and Francisco Javier Redondo-Calvo
Biomedicines 2025, 13(9), 2150; https://doi.org/10.3390/biomedicines13092150 - 4 Sep 2025
Abstract
Background: Intravascular catheters (ICs) are critical medical devices but require frequent replacement due to the risk of bacterial colonization, which can lead to bloodstream infections. This process causes patient discomfort and incurs significant health and economic costs. Aim: To evaluate the inhibitory activity
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Background: Intravascular catheters (ICs) are critical medical devices but require frequent replacement due to the risk of bacterial colonization, which can lead to bloodstream infections. This process causes patient discomfort and incurs significant health and economic costs. Aim: To evaluate the inhibitory activity of natural extracts as potential IC coatings to prevent colonization by methicillin-resistant Staphylococcus aureus (MRSA). Methods: Thirty-six clinical MRSA isolates, obtained from ICs using the Maki technique, were tested. Three natural extracts were evaluated: garlic extract enriched in thiosulfinates (allicin: 7 mg/g), grape extract enriched in proanthocyanidins (92% proanthocyanidins), and propolis extract. Chlorhexidine gluconate (CHG) served as the bactericidal control. The minimum inhibitory concentration (MIC) was determined using the broth microdilution technique with optical density measurements and resazurin-based viability confirmation. The minimum bactericidal concentration (MBC) was assessed from viable cells in wells exceeding the MIC. Results: All tested extracts exhibited bacteriostatic activity against MRSA isolates. The grape extract demonstrated the lowest MIC90 (3.125 mg/mL), followed by propolis extract (MIC90 = 12.5 mg/mL) and garlic extract (MIC90 = 50 mg/mL). Only the propolis extract showed bactericidal activity (MBC = 25 mg/mL). While CHG outperformed the natural extracts, their activity against MRSA suggests potential clinical utility. Conclusion: The natural extracts studied display promising bacteriostatic activity against MRSA isolates from ICs, with propolis extract additionally showing bactericidal effects. Although less potent than CHG, these extracts offer a potential alternative for combating multidrug-resistant pathogens in clinical settings, warranting further investigation for use as IC coatings.
Full article
(This article belongs to the Special Issue Drug-Resistant Bacterial Infections and Alternative Therapies—2nd Edition)
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Open AccessArticle
Placental Morphology and Metabolomic Profile in Uncomplicated Metabolically Healthy Obese Pregnancy
by
Ousseynou Sarr, Akasham Rajagopaul, Shuang Zhao, Xiaohang Wang, David Grynspan, Genevieve Eastabrook, Liang Li, Timothy R. H. Regnault and Barbra de Vrijer
Biomedicines 2025, 13(9), 2149; https://doi.org/10.3390/biomedicines13092149 - 3 Sep 2025
Abstract
Background/Objectives: Metabolically healthy obesity (MHO) and metabolically unhealthy obesity (MUO) in pregnancy represent two distinct cardiometabolic populations, each potentially necessitating alternative clinical management. However, the understanding of the unique physiological effects of uncomplicated MHO on fetoplacental growth and metabolism remains limited. This study
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Background/Objectives: Metabolically healthy obesity (MHO) and metabolically unhealthy obesity (MUO) in pregnancy represent two distinct cardiometabolic populations, each potentially necessitating alternative clinical management. However, the understanding of the unique physiological effects of uncomplicated MHO on fetoplacental growth and metabolism remains limited. This study aimed to identify changes in placental morphology and metabolites associated with maternal obesity, independent of pregnancy-related cardiometabolic complications. Methods: Placentae from women with a prepregnancy body mass index (BMI) < 25 kg/m2 (control; n = 15) and women with MHO (prepregnancy BMI > 30 kg/m2 with no cardiometabolic diseases; n = 15) were analyzed for indices of placental growth and untargeted metabolomics. Complementary assessments were conducted on proinflammatory genes as well as antioxidant defence system genes, proteins, and enzymes, along with lipid peroxidation markers. Results: A clear placentomegaly without histopathological changes was observed in uncomplicated MHO pregnancies. The metabolite 3-aminoisobutanoic acid emerged as the top-ranked feature distinguishing MHO from control placentae, and cysteine, methionine, and vitamin B6 metabolism pathways were among the most distinct changes identified. Conclusions: These findings illustrate an altered placental morphology and metabolomic profile specific to uncomplicated MHO, offering new insights into how obesity, without cardiometabolic complications, may influence fetoplacental growth and metabolism. They may also represent a crucial first step towards marker identification for MHO pregnancies and underscore the importance of alternative care pathways when obesity is present but metabolic comorbidities are absent.
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(This article belongs to the Section Endocrinology and Metabolism Research)
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Open AccessArticle
Characterization of the Anticholinesterase and Antioxidant Properties of Phytochemicals from Moringa oleifera as a Potential Treatment for Alzheimer’s Disease
by
Adel M. Aljadaan, Ayman M. AlSaadi, Ibrahim A. Shaikh, Alison Whitby, Arundhati Ray, Dong-Hyun Kim and Wayne G. Carter
Biomedicines 2025, 13(9), 2148; https://doi.org/10.3390/biomedicines13092148 - 3 Sep 2025
Abstract
Background/Objectives: Alzheimer’s disease (AD) is the most prevalent form of dementia and is characterized by a decline in cognition that may be due, in part, to deficient cholinergic signalling. Cholinesterase inhibitors (ChEIs) are the first-line pharmacotherapies for treating the diminished cholinergic function in
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Background/Objectives: Alzheimer’s disease (AD) is the most prevalent form of dementia and is characterized by a decline in cognition that may be due, in part, to deficient cholinergic signalling. Cholinesterase inhibitors (ChEIs) are the first-line pharmacotherapies for treating the diminished cholinergic function in AD patients. Plant phytochemicals may provide useful ChEIs and mitigate other elements of AD pathology, including oxidative stress. Methods: Herein, the phytochemicals present in Moringa oleifera aqueous and methanolic extracts were identified by LC-MS/MS and the potential of several phytochemicals (4-O-caffeoylquinic acid (4-CQA), quercetin 3-β-D-glucoside (Q3-β-D), chlorogenic acid (CGA), and rutin) to act as ChEIs and antioxidants was assessed. Results: The phytochemicals inhibited human acetylcholinesterase (AChE) in the following order of potency: 4-CQA > Q3-β-D > CGA > rutin; for AChE from Electrophorus electricus, the order of potency was Q3-β-D > 4-CQA > CGA > rutin. For human butyrylcholinesterase (hBuChE), the order of potency was rutin > 4-CQA > Q3-β-D > CGA and for equine serum BuChE, it was 4-CQA > Q3-β-D > rutin > CGA. Molecular docking validated the binding of the phytochemicals to cholinesterases, with binding affinities comparable to or higher than those of ChEI drugs. All the phytochemicals displayed potent radical-scavenging and antioxidant activities across six assays. 4-CQA was the most effective antioxidant in three of the assays. Conclusions: M. oleifera contains phytochemicals with weak ChEI activity and potent antioxidant capacity, with potential use as nutraceuticals to treat the cholinergic signalling deficit and oxidative stress that typifies AD pathology.
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(This article belongs to the Section Drug Discovery, Development and Delivery)
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Open AccessArticle
Urodynamic Predictive Factors for Successful Treatment Outcomes Following Intravesical Botulinum Toxin a Injection in Patients with Detrusor Overactivity
by
Yu Khun Lee and Hann-Chorng Kuo
Biomedicines 2025, 13(9), 2147; https://doi.org/10.3390/biomedicines13092147 - 3 Sep 2025
Abstract
Purpose: This study aimed to identify the predictive factors for successful or failed treatment outcomes following intravesical injection of botulinum toxin A (BoNT-A) through an analysis of baseline video urodynamic characteristics and parameters. Methods: This study retrospectively analyzed the therapeutic outcomes
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Purpose: This study aimed to identify the predictive factors for successful or failed treatment outcomes following intravesical injection of botulinum toxin A (BoNT-A) through an analysis of baseline video urodynamic characteristics and parameters. Methods: This study retrospectively analyzed the therapeutic outcomes of intravesical BoNT-A injection in patients who had an overactive bladder (OAB), who were diagnosed with detrusor overactivity (DO), and who had been refractory to OAB medications or intolerant of the adverse events associated with them. Treatment outcomes were classified as successful, improved, or failed according to the patients’ subjective report of improvement in OAB symptoms at three months post-injection. The patients were split into male and female cohorts and neurogenic or non-neurogenic DO for data analysis. The video urodynamic study characteristics and parameters were compared across the successful, improved, and failed subgroups. Results: This study included 571 patients who received intravesical BoNT-A injections for treating their OAB and urodynamic DO, of which 272 were men and 299 were women. The treatment outcome of BoNT-A injection was successful in 55.7%, improved in 27.8%, and failed in 16.5% of the patients. Patients with urodynamic detrusor underactivity (DU) and neurogenic DO due to diseases of the central nervous system did not usually achieve a successful outcome. The following factors predicted successful treatment outcomes following BoNT-A injection: lower baseline detrusor pressure, higher maximum flow rate (Qmax), larger voided volume, and smaller post-void residual (PVR) in men; larger voided volume and smaller PVR in women. Conclusions: The therapeutic success of intravesical BoNT-A injection for treating refractory OAB can be predicted by lower Pdet, higher Qmax, larger voided volume, and smaller PVR in men and by higher Qmax and smaller PVR in women. Patients with neurogenic DO and DU usually have unsuccessful treatment outcomes.
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(This article belongs to the Topic Clinical, Translational, and Basic Research and Novel Therapy on Functional Bladder Diseases and Lower Urinary Tract Dysfunctions)
Open AccessArticle
Fulminant Myocarditis with VA-ECMO Support: Clinical Characteristics and Prognosis in a Cohort from a Tertiary Transplant Center
by
Borja Guerrero Cervera, Raquel López-Vilella, Ricardo Gimeno Costa, Francisca Pérez Esteban, Manuel Pérez Guillén, Isabel Madrid, Víctor Donoso Trenado, Julia Martínez-Solé, Álvaro Castellanos, Luis Martínez Dolz, Juan Martínez León, Salvador Torregrosa and Luis Almenar-Bonet
Biomedicines 2025, 13(9), 2146; https://doi.org/10.3390/biomedicines13092146 - 3 Sep 2025
Abstract
Background/Objectives: Fulminant myocarditis (FM) is an uncommon but potentially reversible form of myocardial inflammation that can rapidly progress to cardiogenic shock (CS). In patients who are refractory to conventional treatment, venoarterial extracorporeal membrane oxygenation (VA-ECMO) represents an effective life support strategy. However, the
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Background/Objectives: Fulminant myocarditis (FM) is an uncommon but potentially reversible form of myocardial inflammation that can rapidly progress to cardiogenic shock (CS). In patients who are refractory to conventional treatment, venoarterial extracorporeal membrane oxygenation (VA-ECMO) represents an effective life support strategy. However, the factors that determine functional recovery remain uncertain. The primary objective of this study was to characterize patients who recover ventricular function. Secondary objectives included analyzing VA-ECMO-related complications and overall patient survival. Methods: This was a retrospective, single-center, observational study including all consecutive patients diagnosed with FM between 2008 and 2025 who were supported with VA-ECMO (n = 22). Clinical, biochemical, echocardiographic, and imaging variables were collected. Patients were classified based on their outcomes as either recovery or death/transplantation. Differential factors potentially affecting myocardial recovery, survival, and complications were analyzed. Results: The mean age was 49.7 ± 11 years, with 36% being male. Severe cardiogenic shock was the most common initial presentation (86%), and the average time from symptom onset to hospital admission was 5.7 days. Regarding mechanical support, the non-recovery group required longer ECMO support (328 ± 225 h vs. 188 ± 103 h; p = 0.03). The presence of fibrosis on cardiac magnetic resonance imaging (MRI) was associated with a lower probability of recovery (100% vs. 44.4%; p = 0.03). Renal failure and vascular complications were more frequent in the non-recovery group, with a significantly higher rate of surgical reintervention (50% vs. 10%; p = 0.04). Echocardiography performed before discharge (recovery group) vs. before death/transplant (non-recovery group) showed significant differences in left ventricular ejection fraction (51.1% vs. 29.5%; p = 0.04), along with better levels of creatinine, N-terminal pro-B-type natriuretic peptide (NT-proBNP), leukocytes, and C-reactive protein (CRP) in the recovery group. In-hospital survival for the entire cohort was 63.6%, significantly higher in the recovery group (100% vs. 33.3%; p < 0.01). One-year survival was 59%, which was also greater among those who recovered (90% vs. 33.3%; p = 0.02). Conclusions: FM is associated with an acceptable in-hospital survival rate. The presence of myocardial fibrosis on MRI and longer ECMO support duration were observed to be associated with a lower likelihood of cardiac recovery. Patients who recovered showed better ventricular function at discharge, as well as reduced systemic inflammation and renal dysfunction. These findings highlight the importance of early identification of predictors of myocardial recovery to optimize management and therapeutic decision making in this high-risk population.
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(This article belongs to the Special Issue The Treatment of Cardiovascular Diseases in the Critically Ill)
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Combined Serum IL-6 and CYFRA 21-1 as Potential Biomarkers for Radon-Associated Lung Cancer Risk: A Pilot Study
by
Narongchai Autsavapromporn, Aphidet Duangya, Pitchayaponne Klunklin, Imjai Chitapanarux, Chutima Kranrod, Churdsak Jaikang, Tawachai Monum and Shinji Tokonami
Biomedicines 2025, 13(9), 2145; https://doi.org/10.3390/biomedicines13092145 - 3 Sep 2025
Abstract
Background: Radon, a naturally occurring radioactive gas, is increasingly recognized as a major risk factor for lung cancer (LC), especially among non-smokers. The objective of this study was to identify serum biomarkers for the early detection of LC in individuals at high
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Background: Radon, a naturally occurring radioactive gas, is increasingly recognized as a major risk factor for lung cancer (LC), especially among non-smokers. The objective of this study was to identify serum biomarkers for the early detection of LC in individuals at high risk due to prolonged residential radon exposure in Chiang Mai, Thailand, and to assess whether the use of single or combined biomarkers improves the sensitivity and specificity of detection. Methods: A total of 15 LC patients and 30 healthy controls (HC) were enrolled. The HC group was further stratified into two subgroups: low radon (LR, n = 15) and high radon (HR, n = 15) exposure. All participants were non-smokers or former smokers. Serum levels of cytokeratin 19 fragment (CYFRA 21-1), carcinoembryonic antigen (CEA), interleukin-6 (IL-6), interleukin-8 (IL-8), transforming growth factor-alpha (TGF-alpha), and indoleamine 2,3-dioxygenase-1 (IDO-1) were measured using the Milliplex® Kit on a Luminex® Multiplexing Instrument (MAGPIX® System). Results: Serum CEA, IL-6 and IL-8 levels were significantly higher in LC patients compared to the HC group (p < 0.05). Among analyzed biomarkers, only IL-8 was significantly elevated in LC patients compared to the HR group (p = 0.04). Notably, CYFRA 21-1 was the only biomarker that significantly differed between LR and HR groups (p = 0.004). The diagnostic potential of these biomarkers was evaluated using receiver operating characteristic (ROC) analysis. Individually, IL-6 showed the highest discriminative ability for differentiating LC patients from both HC and HR groups, with high specificity but moderate sensitivity. Combining IL-6 and IL-8 improved specificity and increased the area under the ROC curve (AUC), though it did not enhance sensitivity for distinguishing LC from HC. For distinguishing LC from HR individuals, IL-6 and CYFRA 21-1 exhibited strong diagnostic performance. Their combination significantly improved diagnostic accuracy, yielding the highest AUC, sensitivity, and specificity. In contrast, CEA, IL-8, TGF-alpha, and IDO-1 demonstrated limited diagnostic utility. Conclusions: Based on the available literature, this is the first study to evaluate the combined use of IL-6 and CYFRA 21-1 as potential biomarkers for LC screening in individuals with high residential radon exposure. Our findings highlight their utility, particularly in combination, for improving diagnostic accuracy in this high-risk population.
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(This article belongs to the Special Issue Thoracic Malignancies: From Pathophysiology to Novel Therapeutic Approaches)
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A Prospective Observational Study of a 2-Week Integrative Inpatient Therapy on Patients with Fibromyalgia Syndrome
by
Sandra Utz, Christine Uecker, Stefanie Kropač and Jost Langhorst
Biomedicines 2025, 13(9), 2144; https://doi.org/10.3390/biomedicines13092144 - 2 Sep 2025
Abstract
Background: The fibromyalgia syndrome (FMS) is classified as a functional somatic syndrome and is characterized primarily by chronic pain in multiple body regions and physical and/or mental fatigue. The German S3-guideline recommends a multimodal therapy for severe forms. Since research on non-pharmacologic
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Background: The fibromyalgia syndrome (FMS) is classified as a functional somatic syndrome and is characterized primarily by chronic pain in multiple body regions and physical and/or mental fatigue. The German S3-guideline recommends a multimodal therapy for severe forms. Since research on non-pharmacologic complementary, naturopathic, and integrative therapy approaches shows positive and promising effects, integrative methods are firmly anchored in the S3 guideline. Objective/Methods: Aim of the present study was to investigate whether a multimodal integrative treatment program can be effective in reducing the primary symptoms of FMS (pain and fatigue) and improving psychological aspects such as quality of life (QoL), anxiety, depression, and perceived stress. Another aim of the study is to explore whether potential effects appear only in the short term (immediately after discharge) or persist long term (six months after discharge). The treatment concept is based on mind–body medicine and elements of classical European naturopathy (including fasting interventions) and focusses on stress reduction and lifestyle modification. Results: Of N = 134 originally included longstanding fibromyalgia patients (mean time since diagnosis 9.2 ± 8.5 years), 101 data sets could be analyzed. Results show a significant improvement in both short-term and long-term pain and fatigue intensity (about 12% improvement). Long-term reductions in pain intensity appear to be supported by medical fasting interventions. Regarding psychological aspects and quality of life, there are long-lasting reductions regarding anxiety, depression, perceived stress, and helplessness and a long-lasting increase in self-efficacy, quality of life and current working ability. Conclusions: The two-weeks inpatient stay therefore leads to significant improvements in all mentioned aspects. Therefore, the concept may be a promising component for integration into medical guidelines and thus in the care of FMS patients. Future research including randomized controlled trials is necessary to further evaluate the program.
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(This article belongs to the Special Issue Advanced Research on Fibromyalgia (3rd Edition))
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Diagnostic Use of Selected Metalloproteinases in Endometrioid Ovarian Cancer
by
Ewa Gacuta, Aleksandra Kicman, Paweł Ławicki, Michał Ławicki, Monika Kulesza, Paweł Malinowski, Marcin Chlabicz, Monika Zajkowska and Sławomir Ławicki
Biomedicines 2025, 13(9), 2143; https://doi.org/10.3390/biomedicines13092143 - 2 Sep 2025
Abstract
Background/Objectives: Endometrioid ovarian cancer (EnOC) is a late-diagnosed gynecological cancer with limited diagnostic methods that, when detected at an early stage, has a good prognosis. This study is the first to evaluate the plasma concentrations and diagnostic utility of selected metalloproteinases as new
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Background/Objectives: Endometrioid ovarian cancer (EnOC) is a late-diagnosed gynecological cancer with limited diagnostic methods that, when detected at an early stage, has a good prognosis. This study is the first to evaluate the plasma concentrations and diagnostic utility of selected metalloproteinases as new biomarkers for EnOC. Methods: The study group consisted of 50 newly diagnosed, untreated patients with EnOC; the control group consisted of 25 patients with endometrial cysts, 25 patients with serous cysts, and 50 healthy women. Selected matrilysins and stromelysins were determined by means of immunoenzymatic assay (ELISA) and routine markers (CA125 and HE4) using the chemiluminescence (CMIA) method. Results: Higher levels of MMP-7, MMP-10, MMP-11, and MMP-26 were found in patients with EnOC when compared to healthy women. Concentrations of MMP-7, MMP-10, and MMP-11 were higher in women with EnOC when compared to benign lesions (BL). The highest SE (98.55%), NPV (95.41%), ACC (57.58%), and AUC (0.9658) values were obtained for MMP-7. High values of diagnostic parameters were also obtained for MMP-11 and MMP-26. Conclusions: These results suggest the usefulness of MMP-7, MMP-26, and MMP-11 in the diagnosis of EnOC as new biomarkers in this pilot study.
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(This article belongs to the Special Issue New Advances in Ovarian Cancer)
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Open AccessArticle
Prognostic Impact of KRAS and SMARCA4 Mutations and Co-Mutations on Survival in Non-Small Cell Lung Cancer: Insights from the AACR GENIE BPC Dataset
by
Peter Manolakos, Yu-Bo Wang, Janice Withycombe, Luigi Boccuto and Diana Ivankovic
Biomedicines 2025, 13(9), 2142; https://doi.org/10.3390/biomedicines13092142 - 2 Sep 2025
Abstract
Background/Objectives: KRAS mutations are among the most prevalent oncogenic drivers in non-small cell lung cancer (NSCLC), with their impact on survival influenced by co-mutations. SMARCA4 mutations are increasingly associated with poor prognosis and can be classified as class 1 or class 2
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Background/Objectives: KRAS mutations are among the most prevalent oncogenic drivers in non-small cell lung cancer (NSCLC), with their impact on survival influenced by co-mutations. SMARCA4 mutations are increasingly associated with poor prognosis and can be classified as class 1 or class 2 mutations. This study evaluates the prognostic implications of KRAS and SMARCA4 mutations, including their co-mutations and their impact on NSCLC patients by utilizing real-world evidence. Methods: A retrospective analysis was conducted using the AACR GENIE Biopharma Collaborative (BPC) NSCLC 2.0 dataset. NSCLC patients with KRAS mutations, SMARCA4 mutations, or KRAS/SMARCA4 co-mutations were identified. Survival outcomes were assessed using univariate and multivariate Cox proportional hazards models, incorporating key clinical variables such as sex, race, smoking history, and stage. Results: Among 659 NSCLC patients with KRAS or SMARCA4 mutations analyzed, KRAS mutations were the most prevalent (79%, n = 518). SMARCA4 mutations were identified in 14% of cases (n = 95) across two classes. Six percent (n = 41) with class 1 mutations and 8% (n = 54) with class 2. Neither SMARCA4 class was associated with worse survival outcomes compared to KRAS-mutated patients (p = 0.438 & 0.720). Patients harboring KRAS/SMARCA4 class 1 co-mutations (3%, n = 18) had significantly worse overall survival compared to those with KRAS mutations alone (hazard ratio [HR] = 3.23, p < 0.001). In contrast, KRAS/SMARCA4 class 2 co-mutations (4%, n = 28) did not significantly impact survival compared to KRAS-mutated patients (HR = 1.34, p = 0.205). Conclusions: KRAS/SMARCA4 class 1 co-mutations are associated with significantly worse overall survival compared to KRAS-mutated NSCLC patients. Our multivariate analysis demonstrates the critical need to incorporate routine next-generation sequencing (NGS) testing in managing NSCLC patients at the time of metastatic diagnosis, with particular emphasis on identifying SMARCA4 mutation class as a potential prognostic biomarker in those with KRAS co-mutations.
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(This article belongs to the Section Molecular Genetics and Genetic Diseases)
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