Biomedicines

11 pages, 411 KiB

Open AccessArticle

HD-OCT Angiography and SD-OCT in Patients with Mild or No Clinically Apparent Diabetic Retinopathy

by Maja Vinković, Andrijana Kopić, Tvrtka Benašić, Dubravka Biuk, Ivanka Maduna and Stela Vujosevic

Biomedicines 2025, 13(5), 1251; https://doi.org/10.3390/biomedicines13051251 (registering DOI) - 20 May 2025

Abstract

Purpose: To analyze the retinal and choriocapillaris changes in diabetic patients with no or with early signs of diabetic retinopathy using high-definition (HD) angio optical coherence tomography angiography (OCTA) software and spectral-domain (SD) OCT. Methods: A total of 112 eyes (54 eyes from [...] Read more.

Purpose: To analyze the retinal and choriocapillaris changes in diabetic patients with no or with early signs of diabetic retinopathy using high-definition (HD) angio optical coherence tomography angiography (OCTA) software and spectral-domain (SD) OCT. Methods: A total of 112 eyes (54 eyes from 27 diabetic patients and 58 eyes from 29 control subjects) were included in this retrospective cross-sectional study of healthy and diabetic adults. Retinal microvascular changes were assessed by using HD-OCTA software to calculate vascular density (VD) and foveal avascular zone (FAZ). SD-OCT was used to assess retinal thickness and volume in parafovea as well as ganglion cell complex (GCC) parameters. Results: The VD-whole image was significantly higher in the healthy control group (MW z = 1109.5, p = 0.012; t = 2.611, p = 0.010). Also, VD-parafovea was significantly higher in the healthy subjects (MW z = 1053.5, p = 0.004; t = 3.207, p = 0.002). GCC focal loss volume (FLV) was significantly decreased in diabetic patients (p = 0.051). Non-flow FAZ did not show a statistically significant difference between groups, although the FAZ was larger in the diabetic patients. Conclusions: Diabetic patients with no or early signs of diabetic retinopathy have decreased VD compared to healthy individuals. They also present retinal changes at the GCC that are correlated with initial neurodegeneration. HD-OCTA and SD-OCT can detect vascular changes and structural signs of retinal neurodegeneration before clinically apparent diabetic retinopathy. Potentially, these methods may offer new biomarkers for monitoring disease progression and visual prognosis. Full article

(This article belongs to the Special Issue Emerging Issues in Retinal Degeneration)

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16 pages, 3260 KiB

Open AccessArticle

Effective Management of Chronic Low Back Pain in the Elderly: A One-Year Cohort Study of Oxygen–Ozone Therapy Under CT Guidance Combined with Alpha Lipoic Acid, Palmitoylethanolamide, and Myrrh

by Matteo Bonetti, Michele Frigerio, Gian Maria Ottaviani, Giannantonio Pellicanò, Alessio Zambello, Mario Muto, Francesco Carinci and Federico Maffezzoni

Biomedicines 2025, 13(5), 1250; https://doi.org/10.3390/biomedicines13051250 (registering DOI) - 20 May 2025

Abstract

Background and Objective: This observational study aimed to evaluate the clinical efficacy of combined oxygen–ozone (O₂-O₃) therapy under CT guidance with the oral administration of alpha-lipoic acid (ALA), palmitoylethanolamine (PEA), and myrrh in elderly patients suffering from chronic low [...] Read more.

Background and Objective: This observational study aimed to evaluate the clinical efficacy of combined oxygen–ozone (O₂-O₃) therapy under CT guidance with the oral administration of alpha-lipoic acid (ALA), palmitoylethanolamine (PEA), and myrrh in elderly patients suffering from chronic low back pain (LBP). Given the rising prevalence of degenerative spinal diseases in older adults, this study addresses the need for effective, minimally invasive treatment options. Methods: A total of 276 patients aged 65 to 92 years, with chronic unilateral or bilateral LBP, underwent CT-guided paravertebral infiltrations with an O₂-O₃gas mixture. This treatment was complemented with a 30-day regimen of ALA (800 mg/day), PEA (600 mg/day), and myrrh (200 mg/day). Clinical outcomes were assessed at one month and one year post-treatment using the Visual Analog Scale (VAS) and the modified McNab method. Results: At one month, 32.94% of patients reported an excellent improvement, with the mean VAS score dropping from 8.17 to 2.81. At the one-year follow-up, 68.15% cumulatively experienced positive outcomes, with 17.78% reporting the complete resolution of pain. In this occasion, the mean VAS score was 3.57. Conclusions: The study demonstrates that the combination of oxygen–ozone therapy and oral ALA, PEA, and myrrh is a promising alternative for managing chronic low back pain in the elderly, leading to significant pain reduction and improved quality of life. Findings emphasize the need for further research to validate these results and explore the long-term benefits. Full article

(This article belongs to the Special Issue Mechanisms and Pharmacological Targets for Pain)

17 pages, 6775 KiB

Open AccessArticle

Bioinformatics-Guided Experimental Validation Identifies NQO1 as a Senescence-Ferroptosis Hub in Liver Fibrosis

by Xinying Zhang, Chunmeng Fu, Ziyue Yang, Yue Tan, Huan Li, Xiangqian Zhang, Mengru Chen, Fang Peng and Ning Li

Biomedicines 2025, 13(5), 1249; https://doi.org/10.3390/biomedicines13051249 - 20 May 2025

Abstract

Background: As a pivotal point for the development of liver diseases, liver fibrosis (LF) is closely associated with cellular senescence and ferroptosis. However, there is a lack of effective markers that accurately predict LF status. This study aims to identify key genes involved [...] Read more.

Background: As a pivotal point for the development of liver diseases, liver fibrosis (LF) is closely associated with cellular senescence and ferroptosis. However, there is a lack of effective markers that accurately predict LF status. This study aims to identify key genes involved in LF through bioinformatics analysis and experimental validation. Methods: We used bioinformatics analysis of Gene Expression Omnibus (GEO) data to investigate the gene functions, prognostic value, and immune associations of characteristic genes in LF. Functional enrichment analysis of DEGs was performed using GO and KEGG. Immune cell types and their proportions were estimated with CIBERSORTx. In addition, we analyzed the role of NQO1 in LF using IHC, WB, PCR, and flow cytometry. Results: Bioinformatics analysis identified 10 hub genes, including AR, CDKN1A, GJA1, CTSB, HIF1A, HMGB1, NQO1, PARP1, PTEN, and TXN. Among them, NQO1 was strongly correlated with immune cell activity. Experimental validation confirmed that NQO1 is upregulated and promotes αSMA and COL1A1 expression in hepatic stellate cells (HSCs). Knockdown of NQO1 significantly affected the proliferation of HSCs. Conclusions: NQO1 plays a critical role in HSC senescence and ferroptosis, promoting HSC activation and contributing to LF progression. Our findings suggest that NQO1 may serve as a potential biomarker for LF. Full article

(This article belongs to the Special Issue Liver Disease: Etiology, Pathology, and Treatment)

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17 pages, 4197 KiB

Open AccessArticle

Systemic Ozone Therapy Improves Oral Hard and Soft Tissue Healing in Medication-Related Osteonecrosis of the Jaw (MRONJ): A Study in Senescent Female Rats

by Leonardo Alan Delanora, Tiburtino José de Lima Neto, Tiago Esgalha da Rocha, Glauco Rodrigues Carmo Silveira, Liran Levin, Jamil Awad Shibli, Edilson Ervolino, Carlos Fernando Mourão and Leonardo P. Faverani

Biomedicines 2025, 13(5), 1248; https://doi.org/10.3390/biomedicines13051248 - 20 May 2025

Abstract

Background/Objectives: Medication-related osteonecrosis of the jaw (MRONJ) is a challenging condition often associated with bisphosphonate use, leading to impaired bone healing and difficult clinical management. Given the lack of predictable therapeutic options, this study investigated the effects of systemic ozone therapy on [...] Read more.

Background/Objectives: Medication-related osteonecrosis of the jaw (MRONJ) is a challenging condition often associated with bisphosphonate use, leading to impaired bone healing and difficult clinical management. Given the lack of predictable therapeutic options, this study investigated the effects of systemic ozone therapy on MRONJ healing. This study aimed to analyze the effects of systemic ozone therapy on oral hard and soft tissue healing in senescent rats with medication-related osteonecrosis of the jaw (MRONJ) induced by antiresorptive therapy. Methods: Twenty-eight senescent Wistar rats, aged eighteen months and weighing ~350 g, were used for this study. The animals were divided into four groups. The negative control (SAL) group received saline applications, while the control-treated (SAL+OZ) group received saline applications and ozone therapy (0.7 mg/kg). The MRONJ (ZOL) group received Zoledronate, an intravenous antiresorptive drug (100 μg/kg), and the MRONJ-treated (ZOL+OZ) group received zoledronate application and was treated with systemic ozone therapy (0.7 mg/kg). All rats underwent molar extraction in the third week of the experiment and were euthanized in the seventh week of the experiment. The mandibles were resected, reduced, and prepared for microtomographic analysis, histopathological/histometric analysis, and immunohistochemistry. Results: The ZOL group presented characteristics of vitreous, non-vital, and dense bone, poor vascularization, and high values of inflammation markers compatible with MRONJ. In contrast, the ZOL+OZ group exhibited improvement in alveolar bone and soft tissue healing, a decrease in nonvital bone area, and modulation of local inflammation. Conclusions: It can be concluded that Ozone therapy improved oral hard and soft tissue healing of MRONJ in senescent female rats subjected to antiresorptive drugs and might be considered for future clinical applications. Full article

(This article belongs to the Collection Feature Papers in Biomedical Materials)

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19 pages, 16275 KiB

Open AccessArticle

Targeting the ZMYM2-ANXA9 Axis with FLT3 Inhibitor G749 Overcomes Oxaliplatin Resistance in Colorectal Cancer

by Dezheng Lin, Yucheng Xu, Huanmiao Zhan, Yufan Liang, Riyun Liu, Jun Liu, Dandong Luo, Xiaochuan Chen, Jiawei Cai and Yifeng Zou

Biomedicines 2025, 13(5), 1247; https://doi.org/10.3390/biomedicines13051247 - 20 May 2025

Abstract

Background: Chemoresistance and tumor recurrence remain major obstacles in colorectal cancer (CRC) therapy. Elucidating the molecular mechanisms underlying treatment resistance is critical for improving therapeutic outcomes. Methods: We analyzed transcriptomic profiles from public datasets (TCGA and GSE39582) to identify differentially expressed genes [...] Read more.

Background: Chemoresistance and tumor recurrence remain major obstacles in colorectal cancer (CRC) therapy. Elucidating the molecular mechanisms underlying treatment resistance is critical for improving therapeutic outcomes. Methods: We analyzed transcriptomic profiles from public datasets (TCGA and GSE39582) to identify differentially expressed genes associated with a poor response to neoadjuvant chemotherapy in CRC patients. Among 298 candidate genes, ANXA9 emerged as significantly overexpressed in chemoresistant tumors and associated with a poor prognosis. These findings were further validated in an independent cohort of 146 Stage III CRC patients using immunohistochemistry and survival analysis. The expression of ANXA9 was evaluated in oxaliplatin acquired-resistant CRC cell lines via qPCR and Western blot. Functional studies, including RNA interference, colony formation, apoptosis assays, and drug sensitivity testing, were performed in vitro and in vivo to assess the role of ANXA9. A high-throughput drug screen identified G749, a FLT3 inhibitor, as a potential therapeutic agent. Results: ANXA9 expression was significantly elevated in non-responders to chemotherapy and oxaliplatin-resistant CRC cell lines. The knockdown of ANXA9 reduced proliferation and enhanced oxaliplatin sensitivity. G749 was found to suppress ANXA9 expression in a dose-dependent manner and inhibit CRC cell growth in vitro and in patient-derived organoids. In a CRC xenograft mouse model, G749 reduced the tumor burden without observable toxicity. Mechanistically, we identified ZMYM2 as a transcriptional regulator of ANXA9. ChIP-qPCR confirmed ZMYM2 binding to the ANXA9 promoter, especially in resistant cells. Silencing ZMYM2 suppressed tumor cell growth and restored chemosensitivity. Conclusions: The ZMYM2-ANXA9 signaling axis drives chemoresistance and tumor progression in CRC. FLT3 inhibition by G749 effectively downregulates ANXA9 and sensitizes tumors to chemotherapy, highlighting a novel therapeutic approach for chemoresistant CRC. Full article

(This article belongs to the Special Issue Progress in Immunopharmacy)

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12 pages, 1280 KiB

Open AccessArticle

Structured Early Follow-Up in Head and Neck Squamous Cell Carcinomas: Retrospective Cohort Study

by Philipp Dittmann, Bernhard Lehnert, Friedrich Ihler, Chia-Jung Busch and Markus Blaurock

Biomedicines 2025, 13(5), 1246; https://doi.org/10.3390/biomedicines13051246 - 20 May 2025

Abstract

Background/Objectives: The various head and neck squamous cell carcinoma (HNSCC) subtypes are among the most common cancers globally, with significant recurrence rates within the first two years post-treatment. Despite advancements in treatment, structured early follow-up remains crucial for timely diagnosis and effective salvage [...] Read more.

Background/Objectives: The various head and neck squamous cell carcinoma (HNSCC) subtypes are among the most common cancers globally, with significant recurrence rates within the first two years post-treatment. Despite advancements in treatment, structured early follow-up remains crucial for timely diagnosis and effective salvage treatment. Methods: This retrospective study examines the impact of implementing a structured initial restaging between three and six months after the conclusion of initial treatment. The study population included 532 patients treated with curative intent at the University Medicine of Greifswald, Germany, between 2010 and 2019. Patients were divided into two groups: standard follow-up (SF) and adapted follow-up (AF). The AF group received standardized post-treatment restaging, including imaging and panendoscopy or PET-CT exams. Results: We found a trend towards earlier diagnosis and a reduction in recurrences, although these differences were not statistically significant. Secondary cancers were observed more frequently in the AF group, significantly affecting overall survival. Conclusions: Our cohort supports structured initial cancer follow-up in HNSCC. Although not significant, an initial multimodal exam after treatment was well tolerated and showed a trend toward earlier diagnosis. Full article

(This article belongs to the Special Issue Head and Neck Tumors, 4th Edition)

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13 pages, 4321 KiB

Open AccessArticle

ML210 Antagonizes ABCB1- Not ABCG2-Mediated Multidrug Resistance in Colorectal Cancer

by Yan-Chi Li, Yu-Meng Xiong, Ze-Ping Long, Yi-Ping Huang, Yu-Bin Shu, Ke He, Hong-Yan Sun and Zhi Shi

Biomedicines 2025, 13(5), 1245; https://doi.org/10.3390/biomedicines13051245 - 20 May 2025

Abstract

Objectives: ABCB1-mediated multidrug resistance (MDR) compromises chemotherapy efficacy in colorectal cancer (CRC). Despite decades of research, no selective ABCB1 inhibitor has achieved clinical success. This study investigates ML210 as a novel ABCB1-specific inhibitor to reverse ABCB1-driven MDR. Methods: Cytotoxicity assays (MTT) were performed [...] Read more.

Objectives: ABCB1-mediated multidrug resistance (MDR) compromises chemotherapy efficacy in colorectal cancer (CRC). Despite decades of research, no selective ABCB1 inhibitor has achieved clinical success. This study investigates ML210 as a novel ABCB1-specific inhibitor to reverse ABCB1-driven MDR. Methods: Cytotoxicity assays (MTT) were performed on ABCB1-overexpressing HCT-8/V and ABCG2-overexpressing S1-M1-80 CRC cells. Drug accumulation (doxorubicin/mitoxantrone) was quantified via flow cytometry, and cell cycle effects were analyzed using propidium iodide staining. Molecular docking utilized the ABCB1 crystal structure. Results: ML210 selectively reversed ABCB1-mediated resistance to doxorubicin and vincristine in HCT-8/V cells, enhancing intracellular drug accumulation without affecting ABCG2 activity. It induced cell cycle arrest in ABCB1-overexpressing cells and did not alter ABCB1 protein expression. Molecular docking revealed stable binding of ML210 within the ABCB1 substrate pocket through hydrophobic interactions and hydrogen bonding. Conclusions: ML210 is a selective ABCB1 inhibitor that circumvents MDR via direct transport blockade, offering a targeted strategy against ABCB1-mediated chemoresistance in CRC. Its specificity for ABCB1 over ABCG2 highlights potential clinical advantages. Full article

(This article belongs to the Section Drug Discovery, Development and Delivery)

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15 pages, 618 KiB

Open AccessReview

New Insights into the Diagnosis and Treatment of Hepatocellular Carcinoma

by Chengbo Li, Bingjiu Lu and Baocheng Deng

Biomedicines 2025, 13(5), 1244; https://doi.org/10.3390/biomedicines13051244 - 20 May 2025

Abstract

Hepatocellular carcinoma remains one of the leading contributors to global cancer mortality, frequently stemming from chronic liver conditions, such as viral hepatitis, non-alcoholic fatty liver disease, and alcohol-induced cirrhosis. While antiviral treatments have made significant strides, the rising prevalence of hepatocellular carcinoma linked [...] Read more.

Hepatocellular carcinoma remains one of the leading contributors to global cancer mortality, frequently stemming from chronic liver conditions, such as viral hepatitis, non-alcoholic fatty liver disease, and alcohol-induced cirrhosis. While antiviral treatments have made significant strides, the rising prevalence of hepatocellular carcinoma linked to non-infectious causes underscores the pressing demand for more effective diagnostic tools and therapeutic interventions. Advances in imaging and liquid biopsy technologies have facilitated early detection and diagnosis, and treatment strategies are diversifying to include immune checkpoint inhibitors, tyrosine kinase inhibitors, and interventional therapies. Translational therapies for advanced hepatocellular carcinoma have improved surgical opportunities and patient survival. Artificial intelligence has played a transformative role in the diagnosis and treatment of hepatocellular carcinoma, in terms of image analysis, histopathologic classification, drug development, and targeted therapy. The future of hepatocellular carcinoma treatment lies in precision oncology and the collaboration of multidisciplinary teams, as well as in early detection. The ultimate goal is to keep patients alive longer and reduce the global burden of this complex malignancy. Full article

(This article belongs to the Special Issue New Insights into the Diagnosis and Treatment of Hepatocellular Carcinoma)

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20 pages, 10972 KiB

Open AccessArticle

Renalase Overexpression-Mediated Excessive Metabolism of Peripheral Dopamine, DOPAL Accumulation, and α-Synuclein Aggregation in Baroreflex Afferents Contribute to Neuronal Degeneration and Autonomic Dysfunction

by Xue Xiong, Yin-Zhi Xu, Yan Zhang, Hong-Fei Zhang, Tian-Min Dou, Xing-Yu Li, Zhao-Yuan Xu, Chang-Peng Cui, Xue-Lian Li and Bai-Yan Li

Biomedicines 2025, 13(5), 1243; https://doi.org/10.3390/biomedicines13051243 - 20 May 2025

Abstract

Background/Objectives: Increasing evidence reveals the likely peripheral etiology of Parkinson’s disease; however, the mechanistic insight into α-Synuclein aggregation in the periphery remains unclear. This study aimed to explore the effect of abnormal expression of renalase on dopamine metabolism, toxic DOPAL generation, and [...] Read more.

Background/Objectives: Increasing evidence reveals the likely peripheral etiology of Parkinson’s disease; however, the mechanistic insight into α-Synuclein aggregation in the periphery remains unclear. This study aimed to explore the effect of abnormal expression of renalase on dopamine metabolism, toxic DOPAL generation, and subsequently, α-Synuclein aggregation. Methods: Blood pressure (BP) was monitored while changing the body position of rats; the serum level of renalase was detected by ELISA; the mRNA/protein of renalase and α-Synuclein were determined by qRT-PCR/Western blot; DOPAL was measured using HPLC; renalase distribution was explored by immunostaining; cell viability and ultrastructure were examined by TUNEL and electron microscopy, respectively. Results: The results showed that, in PD model rats, the serum level of renalase was increased time-dependently with up-regulated renalase gene/protein expression in the nodose ganglia, nucleus tractus solitarius, and heart; a reduced dopamine content was also detected by the renalase overexpression in PC12 cells. Strikingly, up-regulated renalase and orthostatic BP changes were observed before the behavior changes in the model rats. Meanwhile, the levels of DOPAL and α-Synuclein were increased time-dependently. Intriguingly, the low molecular weight of α-Synuclein declined coordinately with the increase in the higher molecular weight of α-Synuclein. Clear ultrastructure damages at the cellular level supported the notion of molecular findings. Notably, the α-Synuclein aggregation-induced impairment of the axonal transport function predates neuronal degeneration mediated by renalase overexpression. Conclusions: Our results demonstrate that abnormal peripheral dopamine metabolism mediated by overexpressed renalase promotes the DOPAL-induced α-Synuclein and leads to baroreflex afferent neuronal degeneration and early autonomic failure. Full article

(This article belongs to the Special Issue Challenges in the Diagnosis and Treatment of Parkinson’s Disease)

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10 pages, 1127 KiB

Open AccessBrief Report

Significant Microvascular Abnormalities Present in Autonomic Nervous System Dysfunction: Results of a Cross-Sectional Study

by Sehreen Mumtaz, Karissa Arca, Vikas Majithia, William Cheshire, David Hodge and Florentina Berianu

Biomedicines 2025, 13(5), 1242; https://doi.org/10.3390/biomedicines13051242 - 20 May 2025

Abstract

Purpose: The prevalence and phenotype of capillaroscopic abnormalities in patients with autonomic nervous system dysfunction have not yet been investigated. Multiorgan involvement in dysautonomia entails abnormal vasoreactivity. We aim to correlate the diagnosis of autonomic dysfunction with certain clinical manifestations, which may provide [...] Read more.

Purpose: The prevalence and phenotype of capillaroscopic abnormalities in patients with autonomic nervous system dysfunction have not yet been investigated. Multiorgan involvement in dysautonomia entails abnormal vasoreactivity. We aim to correlate the diagnosis of autonomic dysfunction with certain clinical manifestations, which may provide prognostic or diagnostic information using a noninvasive technique, i.e., nailfold video capillaroscopy (NVC). Methods: Patients with autonomic nervous system dysfunction were recruited from rheumatology and neurology clinics with voluntary NVC procedures from 31 January 2024 to 10 January 2024, and a comparison with normal controls was performed. Additional recorded information include demographics and diagnoses of autonomic dysfunction types by autonomic testing, including, but not limited to, the following: reflex screen, sweat test, Valsalva maneuver, nerve fiber density, electromyography (EMG), serology, and history of autoimmune diseases. NVC was performed on a total of 27 patients. This study was approved by the Mayo Clinic Institutional Review Board. Results: The autonomic dysfunction group consisted of small-fiber neuropathy (37%), orthostatic hypotension (48%), autonomic neuropathy (30%), limited autonomic neuropathy (7%), postural orthostatic tachycardia syndrome (POTS) (7%), and connective tissue disease (7%), among other types. Patients with autonomic dysfunction had statistically significant increases in microhemorrhages, dilated capillaries, and ramifications when compared to controls. Conclusions: Autonomic dysfunction was associated with statistically significant microvascular abnormalities compared to normal controls with a distinct NVC pattern. There was a statistically significant correlation between age and BMI with microvascular abnormalities. Here, we demonstrate the diagnostic potential of NVC in autonomic dysfunction and advocate for further study of capillary structures in autonomic dysfunction. Full article

(This article belongs to the Special Issue Neurovascular Dysfunction: Mechanisms and Therapeutic Strategies)

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11 pages, 1521 KiB

Open AccessCommunication

The Chemokine (C-C Motif) Receptor 1 Antagonist BX471 Improves Fluid Resuscitation in Rat Models of Hemorrhagic Shock

by Elizabeth A. Cook, Ololade Ogunsina, Xianlong Gao and Matthias Majetschak

Biomedicines 2025, 13(5), 1241; https://doi.org/10.3390/biomedicines13051241 - 20 May 2025

Abstract

Background/Objectives: We reported previously that antagonists at chemokine receptors CCR2 and CCR3 have fluid-sparing effects during resuscitation from hemorrhagic shock. Because CCR1 shares several chemokine ligands with CCR2/3, we tested whether the CCR1 antagonist BX471 also reduces fluid requirements to maintain hemodynamics. [...] Read more.

Background/Objectives: We reported previously that antagonists at chemokine receptors CCR2 and CCR3 have fluid-sparing effects during resuscitation from hemorrhagic shock. Because CCR1 shares several chemokine ligands with CCR2/3, we tested whether the CCR1 antagonist BX471 also reduces fluid requirements to maintain hemodynamics. Methods: Sprague Dawley rats were hemorrhaged for 30 min, followed by fluid resuscitation to maintain blood pressure for 60 min (series 1) and 180 min (series 2). Series 1: Animals received vehicle (n = 5), 0.05 μmol/kg (n = 5), or 0.5 μmol/kg (n = 4) BX471 at t = 30 min. Series 2: Animals received vehicle (n = 8) or 0.5 μmol/kg (n = 7) BX471 at t = 30 min. Hemodynamics, fluid requirements, blood gases, and lactate were monitored. Serum concentrations of CCR1 ligands (CCL3/4/5/7) were determined at baseline and at the conclusion of the experiments. Tissue (small/large intestine, lung) wet/dry (W/D) weight ratios, lung myeloperoxidase activity, and a panel of inflammation markers in tissue extracts were measured. Results: All animals could be resuscitated to target blood pressures. Series 1: A total of 0.5 μmol/kg BX471 reduced fluid requirements by more than 60% (p < 0.05 vs. vehicle and 0.05 μmol/kg BX471). Series 2: Systemic CCL3/5/7 levels increased during the experiment (p < 0.05). BX471-treatment reduced fluid requirements by more than 60% (p < 0.05) and prevented increases in CCL3/7. W/D ratios of large intestine and of the sum of all tissues were lower with BX471 treatment (p < 0.05). BX471-treatment reduced TNFα and IL6 concentrations in large intestine extracts (p < 0.05). Conclusions: Our findings suggest CCR1 as a new therapeutic target to reduce fluid requirements during resuscitation from hemorrhagic shock. Full article

(This article belongs to the Section Cell Biology and Pathology)

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18 pages, 2924 KiB

Open AccessArticle

The Potential Role of SP-G and PLUNC in Tumor Pathogenesis and Wound Healing in the Human Larynx

by Aurelius Scheer, Lars Bräuer, Markus Eckstein, Heinrich Iro, Friedrich Paulsen, Fabian Garreis, Martin Schicht and Antoniu-Oreste Gostian

Biomedicines 2025, 13(5), 1240; https://doi.org/10.3390/biomedicines13051240 - 20 May 2025

Abstract

Background: Immunological and rheological properties are important factors of the surfactant protein (SP) family, whose impact on tumorigenesis is not yet known, although some SPs have been identified as tumor marker candidates for various malignancies. This study describes the detection of the two [...] Read more.

Background: Immunological and rheological properties are important factors of the surfactant protein (SP) family, whose impact on tumorigenesis is not yet known, although some SPs have been identified as tumor marker candidates for various malignancies. This study describes the detection of the two surfactant family proteins SP-G and PLUNC in healthy glottis, the presence of SP-G in glottic cancer, and the in vitro tissue regeneration potential of SP-G and PLUNC on epithelial cells. Methods: The expression and distribution of SP-G and PLUNC were investigated immunohistochemically in squamous cell carcinomas of the vocal folds. The expression of both proteins was analyzed by Western blot in micro-dissected healthy vocal fold mucosa from body donors. The hypopharyngeal squamous carcinoma cell line (FaDu) was used as an in vitro model for wound healing experiments with Electric cell–substrate impedance sensing (ECIS). Results: The results show the presence of SP-G and PLUNC in epithelial cells of the healthy vocal folds and the submucosal glands of the vestibular folds. SP-G was detected in squamous cell carcinomas of the vocal folds. SP-G and PLUNC show accelerated wound healing of FaDu cells in vitro. Conclusions: SP-G and PLUNC were first detected in the vocal fold of the human larynx. SP-G shows a distinct presence in glottic carcinoma, whose relevance needs to be determined in future studies. SP-G and PLUNC exhibit a positive influence on the repair mechanisms of epithelial lesions of the glottis. The data presented form the basis for follow-up studies focusing on the impact of SP-G in glottic cancer development and the potentially meaningful clinical effect of SP-G and PLUNC on tissue repair of the human vocal fold. Full article

(This article belongs to the Special Issue Head and Neck Tumors, 4th Edition)

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16 pages, 1321 KiB

Open AccessArticle

In Vitro Evaluation of the PMN Reaction on a Collagen-Based Purified Reconstituted Bilayer Matrix (PRBM) Using the Autologous Blood Concentrate PRF

by Eva Dohle, Hongyu Zuo, Büşra Bayrak, Anja Heselich, Birgit Schäfer, Robert Sader and Shahram Ghanaati

Biomedicines 2025, 13(5), 1239; https://doi.org/10.3390/biomedicines13051239 - 20 May 2025

Abstract

Background/Objectives: The body’s reaction after the implantation of a biomaterial is a non-specific inflammatory response that is mainly initiated via the recruitment of polymorphonuclear cells (PMNs) to the implant site secreting cytokines and growth factors, followed by activation of monocytes/macrophages, finally leading [...] Read more.

Background/Objectives: The body’s reaction after the implantation of a biomaterial is a non-specific inflammatory response that is mainly initiated via the recruitment of polymorphonuclear cells (PMNs) to the implant site secreting cytokines and growth factors, followed by activation of monocytes/macrophages, finally leading to wound healing. The wound healing process is dependent on the priming of the PMNs that can be guided towards an inflammatory or a regenerative phenotype with the associated characteristic PMN cytokine profiles. Since the collagen-based Purified Reconstituted Bilayer Matrix (PRBM) triggers the wound healing process at the implant site in vivo, it is hypothesized that this positive effect might be due to a material-mediated priming of the PMNs towards the regenerative phenotype. With the use of the blood concentrate platelet-rich fibrin (PRF) containing high concentrations of leukocytes, including PMNs, the natural environment of the body after the implantation of a material can be mimicked in vitro. The aim of the present study was to characterize the phenotype of native blood-derived PMNs within PRF in response to the PRBM. Methods: PMNs within PRF gained from different relative centrifugal forces were characterized in a first step before PRF was combined with the PRBM for 4 h. Supernatants were harvested to analyze the phenotype of the PMNs via the evaluation of eight different cytokines using the ELISA. Results: Analysis of the PMN phenotype could assess cytokines commonly associated with neutrophils of the proinflammatory phenotype, such as TNFα, IL15, and IL1, as lower in supernatants when PRF was incubated in the presence of the PRBM and compared to the control PRF. On the other hand, cytokines related to the PMN regenerative phenotype, like TGFβ and IL10, could be detected as higher when PRF was incubated in the presence of the PRBM. Conclusions: This might suggest that PRBM significantly activates and primes neutrophils to the regenerative phenotype, leading to the resolution of inflammation. This might trigger the process of wound healing and tissue regeneration, making the PRBM a beneficial material for therapeutic applications. Full article

(This article belongs to the Section Molecular and Translational Medicine)

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1 pages, 142 KiB

Open AccessCorrection

Correction: Kim et al. Novel Gene Polymorphisms for Stable Warfarin Dose in a Korean Population: Genome-Wide Association Study. Biomedicines 2023, 11, 2308

by Jung Sun Kim, Sak Lee, Jeong Yee, Kyemyung Park, Eun Jeong Jang, Byung Chul Chang and Hye Sun Gwak

Biomedicines 2025, 13(5), 1238; https://doi.org/10.3390/biomedicines13051238 - 20 May 2025

Abstract

There was an error in the original publication [...] Full article

(This article belongs to the Section Molecular Genetics and Genetic Diseases)

18 pages, 4314 KiB

Open AccessArticle

A CECT-Based Radiomics Nomogram Predicts the Overall Survival of Patients with Hepatocellular Carcinoma After Surgical Resection

by Peng Zhang, Yue Shi, Maoting Zhou, Qi Mao, Yunyun Tao, Lin Yang and Xiaoming Zhang

Biomedicines 2025, 13(5), 1237; https://doi.org/10.3390/biomedicines13051237 - 19 May 2025

Abstract

Objective: The primary objective of this study was to develop and validate a predictive nomogram that integrates radiomic features derived from contrast-enhanced computed tomography (CECT) images with clinical variables to predict overall survival (OS) in patients with hepatocellular carcinoma (HCC) after surgical [...] Read more.

Objective: The primary objective of this study was to develop and validate a predictive nomogram that integrates radiomic features derived from contrast-enhanced computed tomography (CECT) images with clinical variables to predict overall survival (OS) in patients with hepatocellular carcinoma (HCC) after surgical resection. Methods: This retrospective study analyzed the preoperative enhanced CT images and clinical data of 202 patients with HCC who underwent surgical resection at the Affiliated Hospital of North Sichuan Medical College (Institution 1) from June 2017 to June 2021 and at Nanchong Central Hospital (Institution 2) from June 2020 to June 2022. Among these patients, 162 patients from Institution 1 were randomly divided into a training cohort (112 patients) and an internal validation cohort (50 patients) at a 7:3 ratio, whereas 40 patients from Institution 2 were assigned as an independent external validation cohort. Univariate and multivariate Cox proportional hazards regression analyses were performed to identify clinical risk factors associated with OS after HCC resection. Using 3D-Slicer software, tumor lesions were manually delineated slice by slice on preoperative non-contrast-enhanced (NCE) CT, arterial phase (AP), and portal venous phase (PVP) images to generate volumetric regions of interest (VOIs). Radiomic features were subsequently extracted from these VOIs. LASSO Cox regression analysis was employed for dimensionality reduction and feature selection, culminating in the construction of a radiomic signature (Radscore). Cox proportional hazards regression models, including a clinical model, a radiomic model, and a radiomic–clinical model, were subsequently developed for OS prediction. The predictive performance of these models was assessed via the concordance index (C-index) and time–ROC curves. The optimal performance model was further visualized as a nomogram, and its predictive accuracy was evaluated via calibration curves and decision curve analysis (DCA). Finally, the risk factors in the optimal performance model were interpreted via Shapley additive explanations (SHAP). Results: Univariate and multivariate Cox regression analyses revealed that BCLC stage, the albumin–bilirubin index (ALBI), and the NLR–PLR score were independent predictors of OS after HCC resection. Among these three models, the radiomic–clinical model exhibited the highest predictive performance, with C-indices of 0.789, 0.726, and 0.764 in the training, internal and external validation cohorts, respectively. Furthermore, the time–ROC curves for the radiomic–clinical model showed 1-year and 3-year AUCs of 0.837 and 0.845 in the training cohort, 0.801 and 0.880 in the internal validation cohort, and 0.773 and 0.840 in the external validation cohort. Calibration curves and DCA demonstrated the model’s excellent calibration and clinical applicability. Conclusions: The nomogram combining CECT radiomic features and clinical variables provides an accurate prediction of OS after HCC resection. This model is beneficial for clinicians in developing individualized treatment strategies for patients with HCC. Full article

(This article belongs to the Special Issue New Insights into the Diagnosis and Treatment of Hepatocellular Carcinoma)

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13 pages, 644 KiB

Open AccessArticle

Prevalence of Viral and Bacterial Co-Infections in SARS-CoV-2-Positive Individuals in Cyprus 2020–2022

by George Krashias, Christina Tryfonos, Stavros Bashiardes, Jan Richter and Christina Christodoulou

Biomedicines 2025, 13(5), 1236; https://doi.org/10.3390/biomedicines13051236 - 19 May 2025

Abstract

The COVID-19 pandemic has had a profound impact on healthcare systems worldwide, with severe consequences on the global economy and society. The clinical presentation of SARS-CoV-2 infection varies widely, ranging from asymptomatic cases to severe disease and death. Coinfection with other respiratory pathogens [...] Read more.

The COVID-19 pandemic has had a profound impact on healthcare systems worldwide, with severe consequences on the global economy and society. The clinical presentation of SARS-CoV-2 infection varies widely, ranging from asymptomatic cases to severe disease and death. Coinfection with other respiratory pathogens in SARS-CoV-2-positive individuals may exacerbate symptom severity and lead to poorer clinical outcomes. Background/Objectives: This study is the first to investigate the prevalence of viral and bacterial co-infections in SARS-CoV-2-positive individuals in Cyprus. Methods: A total of 1111 SARS-CoV-2-positive nasopharyngeal swab samples collected from non-hospitalized patients were analyzed for the presence of 18 viral and 3 bacterial respiratory pathogens. Results: Of these, 51 samples (4.6%) were found to have at least one additional respiratory pathogen. The most frequently detected viruses were rhinovirus/enterovirus (n = 28; 2.5%) and adenovirus (n = 8; 0.7%), while the bacterial pathogens identified were Legionella pneumophila (n = 1; 0.1%) and Bordetella pertussis (n = 1; 0.1%). The highest proportion of co-infections was observed in the youngest age group (<10 years), where 52.9% of co-infections were identified, followed by the 30–39 age group, which accounted for 15.7% of cases. Among single respiratory virus co-infections, rhinovirus/enterovirus (27.5%) and adenovirus (13.7%) were the most frequently detected in the <10 age group, followed by RSV (3.9%), bocavirus, influenza B, HMPV A + B, and coronavirus NL63 (each at 2%). Conclusions: The current study underscores the importance of simultaneous testing for SARS-CoV-2 and other respiratory pathogens, as this may have significant implications for both individual patient care and healthcare services. Full article

(This article belongs to the Special Issue Advanced Biomedical Research on COVID-19 (2nd Edition))

17 pages, 2147 KiB

Open AccessArticle

Predictive Accuracy of a Clinical Model for Carriage of Pathogenic/Likely Pathogenic Variants in Patients with Dementia and a Positive Family History at PUMCH

by Jialu Bao, Yuyue Qiu, Tianyi Wang, Li Shang, Shanshan Chu, Wei Jin, Wenjun Wang, Yuhan Jiang, Bo Li, Yixuan Huang, Bo Hou, Longze Sha, Yunfan You, Yuanheng Li, Meiqi Wu, Yutong Zou, Yifei Wang, Li Huo, Ling Qiu, Qi Xu, Feng Feng, Chenhui Mao, Liling Dong and Jing Gao Show full author list Hide full author list

Biomedicines 2025, 13(5), 1235; https://doi.org/10.3390/biomedicines13051235 - 19 May 2025

Abstract

Background and Objectives: Identifying carriers of Pathogenic/Likely Pathogenic Variants in patients with dementia is crucial for risk stratification, particularly in individuals with a family history. This study developed and validated a clinical prediction model using whole-exome sequencing-confirmed cohorts. Methods: A total of 601 [...] Read more.

Background and Objectives: Identifying carriers of Pathogenic/Likely Pathogenic Variants in patients with dementia is crucial for risk stratification, particularly in individuals with a family history. This study developed and validated a clinical prediction model using whole-exome sequencing-confirmed cohorts. Methods: A total of 601 Chinese patients with dementia and a family history were enrolled at Peking Union Medical College Hospital, with 476 in a retrospective derivation cohort and 125 in a temporal validation cohort. Predictive factors included age at onset, APOE ε4 status, and family history characteristics. Model performance was assessed using discrimination and calibration metrics. Results: In the derivation cohort (median age at onset 66 years), 10.3% carried Pathogenic/Likely Pathogenic Variants. Among patients with dementia, those with age at onset < 55 years (OR 2.56, p = 0.0098), more than two affected relatives (OR 3.32, p = 0.0039), parental disease history (OR 4.72, p = 0.015), and early-onset cases in the family (OR 2.61, p = 0.0096) were positively associated with Pathogenic/Likely Pathogenic Variant carriage, whereas APOE ε4 carriage was inversely associated (OR 0.36, p = 0.0041). The model achieved an area under the curve of 0.776 (95% CI, 0.701–0.853) in the derivation cohort and 0.781 (95% CI, 0.647–0.914) in the validation cohort (median age at onset 58 years), with adequate calibration. Conclusions: This model demonstrated strong predictive performance for Pathogenic/Likely Pathogenic Variant carriage, supporting its clinical utility in guiding genetic testing. Further research is needed to refine the model. Full article

(This article belongs to the Special Issue Neurodegeneration in Cognitive Impairment and Mood Disorders for Experimental, Clinical, and Translational Neuropsychiatry—Second Edition)

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25 pages, 4627 KiB

Open AccessArticle

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

by Ana B. Perona-Moratalla, Blanca Carrión, Karina Villar Gómez de las Heras, Lourdes Arias-Salazar, Blanca Yélamos-Sanz, Tomás Segura and Gemma Serrano-Heras

Biomedicines 2025, 13(5), 1234; https://doi.org/10.3390/biomedicines13051234 - 19 May 2025

Abstract

Background: Von Hippel-Lindau (VHL) disease, a hereditary cancer syndrome, is characterized by mutations in the VHL gene, which result in the stabilization of hypoxia-inducible factors (HIF)-1α and -2α, ultimately leading to the development of highly vascularized tumors, such as hemangioblastomas of the central [...] Read more.

Background: Von Hippel-Lindau (VHL) disease, a hereditary cancer syndrome, is characterized by mutations in the VHL gene, which result in the stabilization of hypoxia-inducible factors (HIF)-1α and -2α, ultimately leading to the development of highly vascularized tumors, such as hemangioblastomas of the central nervous system (CNS-HBs). The standard treatment for these brain tumors is neurosurgical resection. However, multiple surgeries are often necessary due to tumor recurrence, which increases the risk of neurological sequelae. Thus, elucidation of the proliferative behavior of hemangioblastomas (with the aim of identifying biomarkers associated with tumor progression) and the development of pharmacological therapies could reduce the need for repeated surgical interventions and provide alternative treatment options for unresectable CNS-HBs. Belzutifan (Welireg™), a selective HIF-2α inhibitor and the only FDA-approved non-surgical option, has shown limited efficacy in CNS-HBs, highlighting the need for alternative therapeutic strategies. Results: In this study, primary cell cultures were successfully established from CNS-HB tissue samples of VHL patients, achieving a 75% success rate. These cultures were predominantly composed of stromal cells and pericytes. The proliferative patterns of patient-derived HB cell cultures significantly correlated with tumor burden and recurrence in VHL patients. Furthermore, flow cytometry, reverse transcription-PCR, and Western blot analyses revealed marked overexpression of both HIF-1α and HIF-2α isoforms in primary HB cells. In addition, evaluation of the therapeutic potential of acriflavine, a dual HIF-1α/HIF-2α inhibitor, demonstrated reduced HB cells viability, induced G2/M cell cycle arrest, and predominantly triggered necrotic cell death in patient-derived HB cultures. Conclusions: These results suggest that the in vitro proliferative dynamics of HB cell cultures may reflect clinical characteristics associated with CNS-HB progression, potentially serving as indicators to predict tumor development in patients with VHL. Furthermore, our findings support the simultaneous targeting of both HIF-1α and HIF-2α isoforms as a promising non-invasive therapeutic strategy. Full article

(This article belongs to the Special Issue New Insights in Hypoxic Response Modulation)

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31 pages, 1738 KiB

Open AccessArticle

Vitamin D Imbalance and Hydro-Electrolyte Disturbances in Hospitalized Children: A Comparation Between Post-COVID-19 Status and SARS-CoV-2/EBV Coinfection

by Carmen Loredana Petrea (Cliveți), Diana-Andreea Ciortea, Gabriela Gurău, Nicoleta Mădălina Matei, Ciprian Adrian Dinu, Simona-Elena Bergheș (Oprea), Gabriela Isabela Verga (Răuță) and Sorin Ion Berbece

Biomedicines 2025, 13(5), 1233; https://doi.org/10.3390/biomedicines13051233 - 19 May 2025

Abstract

Background/Objectives: SARS-CoV-2 infection has the potential to cause multi-organ involvement and, when associated with Epstein–Barr virus (EBV) coinfection, may worsen the course of disease in pediatric patients by influencing the immune response. Methods: Our retrospective–observational study included 406 hospitalized children with post-COVID-19 status [...] Read more.

Background/Objectives: SARS-CoV-2 infection has the potential to cause multi-organ involvement and, when associated with Epstein–Barr virus (EBV) coinfection, may worsen the course of disease in pediatric patients by influencing the immune response. Methods: Our retrospective–observational study included 406 hospitalized children with post-COVID-19 status or SARS-CoV-2/EBV coinfection. Results: Hypovitaminosis D was more common in the coinfected sublot (59.18%) than in the COVID-19 one (50.74%), with a higher frequency of severe vitamin D deficiency (16.33% vs. 7.35%). Hypovitaminosis D was significantly associated with female sex (p = 0.033) only in the COVID-19 subgroup. Hypervitaminosis D, although rare, was only associated with severe forms of the disease (7.69%). Between clinical severity and vitamin D level, a statistically significant association of moderate intensity was identified only in the COVID-19 subgroup (χ² = 11.708, φ = 0.293, p = 0.020). In the same subgroup, a significant correlation was found between vitamin D levels and serum potassium values (χ² = 10.527, p = 0.032). Moreover, in the COVID-19 subgroup, an association between abnormal sodium levels and increased D-dimer levels was found (χ² = 7.074, p = 0.029). Conclusions: These results underline the importance of monitoring immunologic, vitamin, and electrolyte imbalance in the management of these cases and highlight the need for personalized therapeutic strategies to prevent long-term complications. Full article

(This article belongs to the Section Cell Biology and Pathology)

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25 pages, 2527 KiB

Open AccessReview

Optimizing Biologic Therapy for the Prevention of Post-Operative Recurrence in Crohn’s Disease: Current Evidence and Future Perspectives

by Reem Aljabri, Saqer Al-Saraie and Ahmed Alhouti

Biomedicines 2025, 13(5), 1232; https://doi.org/10.3390/biomedicines13051232 - 19 May 2025

Abstract

Crohn’s disease (CD) imposes a substantial burden on patients due to its chronic, relapsing nature, often necessitating surgical intervention. However, surgery is not curative, and post-operative recurrence (POR) remains a major clinical challenge, with up to 80% of patients developing endoscopic recurrence within [...] Read more.

Crohn’s disease (CD) imposes a substantial burden on patients due to its chronic, relapsing nature, often necessitating surgical intervention. However, surgery is not curative, and post-operative recurrence (POR) remains a major clinical challenge, with up to 80% of patients developing endoscopic recurrence within one year if left untreated. The pathophysiology of POR is multifactorial, involving dysregulated immune responses, gut microbiota alterations, and mucosal healing impairment, highlighting the need for targeted therapeutic strategies. This review aims to explore the current landscape of POR management, focusing on biologic therapies and emerging advanced treatments. Conventional management relies on early prophylactic therapy with anti-TNF agents such as infliximab and adalimumab, which have demonstrated efficacy in reducing endoscopic and clinical recurrence. However, newer biologics, including IL-23 inhibitors (risankizumab) and Janus kinase (JAK) inhibitors (upadacitinib), have shown promise in CD management, though their role in POR remains underexplored. The lack of direct clinical evidence for advanced biologics in POR prevention, combined with inter-individual variability in treatment response, underscores the need for further research. Future directions should focus on optimizing therapeutic strategies through personalized medicine, identifying predictive biomarkers, and conducting robust trials to establish the efficacy of novel agents in POR prevention. A tailored, evidence-driven approach is essential to improving long-term outcomes and minimizing disease recurrence in post-operative CD patients. Full article

(This article belongs to the Special Issue Crohn’s Disease and Ulcerative Colitis: From Pathophysiology to Novel Therapeutic Approaches (3rd Edition))

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19 pages, 2322 KiB

Open AccessArticle

A Cross-Tissue Transcriptome-Wide Association Study Reveals Novel Susceptibility Genes for Diabetic Kidney Disease in the FinnGen Cohort

by Menghan Liu, Zehua Li, Yao Lu, Pingping Sun, Ying Chen and Li Yang

Biomedicines 2025, 13(5), 1231; https://doi.org/10.3390/biomedicines13051231 - 19 May 2025

Abstract

Background/Objectives: Diabetic kidney disease (DKD) is a common diabetic complication, driven by a multifactorial pathogenesis that includes various genetic components. However, the precise causative genes and their underlying biological pathways remain poorly understood. Methods: We performed a cross-tissue transcriptome-wide association study [...] Read more.

Background/Objectives: Diabetic kidney disease (DKD) is a common diabetic complication, driven by a multifactorial pathogenesis that includes various genetic components. However, the precise causative genes and their underlying biological pathways remain poorly understood. Methods: We performed a cross-tissue transcriptome-wide association study (TWAS) of DKD using expression quantitative trait loci (eQTL) data from 49 tissues in the Genotype—Tissue Expression (GTEx) version 8 (v8) resource. Five complementary analytical frameworks—sparse canonical correlation analysis (sCCA), functional summary-based imputation (FUSION), fine-mapping of causal gene sets (FOCUS), summary-data-based Mendelian randomization (SMR), and multi-marker analysis of genomic annotation (MAGMA)—were integrated to nominate candidate genes. Causal inference was refined using Mendelian randomization (MR), and biological significance was evaluated through pathway enrichment, protein interaction networks, and druggability profiling. Results: We identified 23 candidate genes associated with DKD risk, of which 13 were supported by MR analysis. Among these, 10 represent previously unreported susceptibility genes. Notably, four genes—HLA-DRB1, HLA-DRB5, NOTCH4, and CYP21A2—encode potentially druggable proteins, with HLA-DRB5 and CYP21A2 both qualifying as novel susceptibility genes and therapeutic targets. These genes converge on immune modulation, steroid biosynthesis, DNA repair, and transcriptional regulation—processes central to DKD pathogenesis. Conclusions: Our study represents the first systematic cross-tissue TWAS of DKD, revealing a prioritized set of genetically and functionally supported susceptibility genes. The identification of druggable targets among these genes provides critical insight into the mechanistic underpinnings of DKD and highlights their potential for future therapeutic development. These findings enhance our understanding of DKD pathophysiology and offer a foundation for precision medicine strategies in nephrology. Full article

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

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28 pages, 1299 KiB

Open AccessReview

Cardiac Amyloidosis: A Narrative Review of Diagnostic Advances and Emerging Therapies

by Dana Emilia Movila, Alexandru Catalin Motofelea, Dragos Cozma, Oana Albai, Alexandra Christa Sima, Minodora Andor, Tudor Ciocarlie and Simona Ruxanda Dragan

Biomedicines 2025, 13(5), 1230; https://doi.org/10.3390/biomedicines13051230 - 19 May 2025

Abstract

Background/Objectives: Cardiac amyloidosis (CA) is an underdiagnosed and potentially life-threatening infiltrative cardiomyopathy characterized by the extracellular deposition of misfolded amyloid fibrils in cardiac tissue. It is most commonly associated with light-chain (AL) amyloidosis and transthyretin (ATTR) amyloidosis, either hereditary or wild-type. The [...] Read more.

Background/Objectives: Cardiac amyloidosis (CA) is an underdiagnosed and potentially life-threatening infiltrative cardiomyopathy characterized by the extracellular deposition of misfolded amyloid fibrils in cardiac tissue. It is most commonly associated with light-chain (AL) amyloidosis and transthyretin (ATTR) amyloidosis, either hereditary or wild-type. The disease often presents with non-specific symptoms, leading to delayed diagnosis and treatment. This study aims to provide a comprehensive overview of the pathophysiology, diagnostic strategies, and current therapeutic approaches for cardiac amyloidosis, with a focus on improving early detection and clinical outcomes. Methods: A narrative review was conducted using databases such as PubMed and Scopus, covering the period from September 2016 to March 2025. Keywords such as “cardiac amyloidosis”, “cardiac amyloidosis from transthyretin”, “cardiomyopathy”, “transthyretin”, “immunoglobulin light-chain amyloidosis”, and “familial amyloidosis” were used. Relevant clinical trials and guideline-based management recommendations were also included. Results: This review highlights that non-invasive imaging modalities and serum biomarker analyses are key to reducing diagnostic delays. New therapeutic developments, including gene-editing technologies and RNA-based therapies, show promise in early trials. Multidisciplinary management and increased awareness are crucial for timely diagnosis and treatment optimization. Conclusions: The early recognition of cardiac amyloidosis remains a major clinical challenge. Advances in non-invasive diagnostics and emerging disease-modifying therapies are transforming the prognosis of affected patients. Continued research and heightened clinical suspicion are essential to improve outcomes in this complex and heterogeneous disease. Full article

(This article belongs to the Section Molecular and Translational Medicine)

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26 pages, 1402 KiB

Open AccessReview

Exosome Therapy in Stress Urinary Incontinence: A Comprehensive Literature Review

by Manouchehr Nasrollahzadeh Saravi, Mahdi Mohseni, Iman Menbari Oskouie, Jafar Razavi, Ernesto Delgado Cidranes and Masoumeh Majidi Zolbin

Biomedicines 2025, 13(5), 1229; https://doi.org/10.3390/biomedicines13051229 - 19 May 2025

Abstract

Stress urinary incontinence (SUI) is characterized by the involuntary leakage of urine when bladder pressure exceeds urethral closing pressure during routine activities such as physical exertion, coughing, exercise, or sneezing. SUI is the most prevalent form of urinary incontinence, with a reported prevalence [...] Read more.

Stress urinary incontinence (SUI) is characterized by the involuntary leakage of urine when bladder pressure exceeds urethral closing pressure during routine activities such as physical exertion, coughing, exercise, or sneezing. SUI is the most prevalent form of urinary incontinence, with a reported prevalence ranging from 10% to 70%, and its incidence increases with age. As the global population continues to age, the prevalence and clinical significance of SUI are expected to rise accordingly. The pathophysiology of SUI is primarily driven by two mechanisms: urethral hypermobility, resulting from compromised supporting structures, and intrinsic urethral sphincter deficiency, characterized by the deterioration of urethral mucosa and muscle tone. Current treatment options for SUI include conservative management strategies, which heavily rely on patient adherence and are associated with high recurrence rates, and surgical interventions, such as sling procedures, which offer effective solutions but are costly and carry the risk of adverse side effects. These limitations highlight the urgent need for more effective and comprehensive treatment modalities. Exosomes, nano-sized (30–150 nm) extracellular vesicles secreted by nearly all cell types, have emerged as a novel therapeutic option due to their regenerative, anti-fibrotic, pro-angiogenic, anti-apoptotic, anti-inflammatory, and anti-hypoxic properties. These biological functions position exosomes as a promising alternative to conventional therapies for SUI. Exosome therapy has the potential to enhance tissue regeneration, restore urethral function, and repair nerve and muscle damage, thereby reducing symptom burden and improving patients’ quality of life. Additionally, exosome-based treatments could offer a less invasive alternative to surgery, potentially decreasing the need for repeated interventions and minimizing complications associated with current procedures. In this literature review, we critically assess the current state of research on the potential use of exosomes in treating SUI, highlighting their therapeutic mechanisms and potential clinical benefits. Full article

(This article belongs to the Section Molecular and Translational Medicine)

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22 pages, 1695 KiB

Open AccessReview

Pushing the Limits of Interlimb Connectivity: Neuromodulation and Beyond

by Jane A. Porter, Trevor S. Barss, Darren J. Mann, Zahra Karamzadeh, Deborah O. Okusanya, Sisuri G. Hemakumara, E. Paul Zehr, Taryn Klarner and Vivian K. Mushahwar

Biomedicines 2025, 13(5), 1228; https://doi.org/10.3390/biomedicines13051228 - 19 May 2025

Abstract

The ability to walk is often lost after neural injury, leading to multiple secondary complications that reduce quality of life and increase healthcare costs. The current rehabilitation interventions primarily focus on restoring leg movements through intensive training on a treadmill or using robotic [...] Read more.

The ability to walk is often lost after neural injury, leading to multiple secondary complications that reduce quality of life and increase healthcare costs. The current rehabilitation interventions primarily focus on restoring leg movements through intensive training on a treadmill or using robotic devices, but ignore engaging the arms. Several groups have recently shown that simultaneous arm and leg (A&L) cycling improves walking function and interlimb connectivity. These findings highlight the importance of neuronal pathways between the arm (cervical) and leg (lumbar) control regions in the spinal cord during locomotion, and emphasize the need for activating these pathways to improve walking after neural injury or disease. While the findings to date provide important evidence about actively including the arms in walking rehabilitation, these strategies have yet to be optimized. Moreover, improvements beyond A&L cycling alone may be possible with conjunctive targeted strategies to enhance spinal interlimb connectivity. The aim of this review is to highlight the current evidence for improvements in walking function and neural interlimb connectivity after neural injury or disease with cycling-based rehabilitation paradigms. Furthermore, strategies to enhance the outcomes of A&L cycling as a rehabilitation strategy are explored. These include the use of functional electrical stimulation-assisted cycling in acute care settings, utilizing non-invasive transcutaneous spinal cord stimulation to activate previously inaccessible circuitry in the spinal cord, and the use of paired arm and leg rehabilitation robotics. This review aims to consolidate the effects of exercise interventions that incorporate the arms on improved outcomes for walking, functional mobility, and neurological integrity, underscoring the importance of integrating the arms into the rehabilitation of walking after neurological conditions affecting sensorimotor function. Full article

(This article belongs to the Special Issue Neuromodulation: From Theories to Therapies)

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15 pages, 678 KiB

Open AccessArticle

Retinal Thickness in Patients with Parkinson’s Disease and Dopa Responsive Dystonia—Is There Any Difference?

by Marko Svetel, Gorica Marić, Marija Božić, Una Lazić, Andona Milovanović, Jana Jakšić, Igor Petrović, Ana Dimitrijević, Milica Knežević and Tatjana Pekmezović

Biomedicines 2025, 13(5), 1227; https://doi.org/10.3390/biomedicines13051227 - 19 May 2025

Abstract

Background/Objectives: Certain aspects of retinal thickness assessed by optical coherence tomography (OCT) in patients with Parkinson’s disease (PD) require additional clarification. It is supposed that attributing reduced retinal thickness in PD to dopaminergic loss may not be acceptable as it also happens [...] Read more.

Background/Objectives: Certain aspects of retinal thickness assessed by optical coherence tomography (OCT) in patients with Parkinson’s disease (PD) require additional clarification. It is supposed that attributing reduced retinal thickness in PD to dopaminergic loss may not be acceptable as it also happens in diseases where dopaminergic loss does not occur. The objective of our study is to compare the ganglion cell/inner plexiform layer (GCIPL), peripapillary retinal nerve fiber layer (pRNFL), and macular thickness of PD and dopa responsive dystonia (DRD) patients with healthy controls (HC), to investigate whether DRD patients, as a distinctive model of genetically induced dopamine deficiency, have reduced retinal thickness in comparison with PD, and to analyze correlation between retinal thickness and various PD clinical parameters. Methods: We analyzed 86 patients with PD, 10 patients with DRD, and 96 age- and sex-matched HC. Results: GCIPL, pRNFL, and central macula thickness (CMT) are statistically significantly thinner in PD patients compared to HC (p < 0.001, all). GCIPL and CMT are also statistically significantly thinner in DRD patients compared to HC (p = 0.012, p = 0.001, respectively). GCIPL thickness correlates positively with the daily dose of levodopa (r = 0.244, p < 0.01). The thickness of GCIPL and pRNFL correlate negatively with current age (r = −0.219; p < 0.01 and r = −0.358; p < 0.05, respectively). All retinal parameters are statistically significantly thinner in females than in males (p < 0.05). Conclusions: Patients with PD and DRD did not differ in GCIPL and pRNFL thickness when compared to one another. These results, supported by positive correlation of levodopa dose and GCIPL thickness in PD patients, emphasize the importance of dopamine in maintaining retinal thickness. Full article

(This article belongs to the Section Neurobiology and Clinical Neuroscience)

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17 pages, 1186 KiB

Open AccessArticle

Ultrasound Predictors for Persistence or a Change in the Diagnosis of Rheumatoid Arthritis After 5 Years—A Prospective Cohort Study of Patients with Early Rheumatoid Arthritis

by Tanya Sapundzhieva, Lyubomir Sapundzhiev, Martin Mitev, Rositsa Karalilova and Anastas Batalov

Biomedicines 2025, 13(5), 1226; https://doi.org/10.3390/biomedicines13051226 - 19 May 2025

Abstract

Aim: To identify ultrasound (US) predictors of persistence or change in the diagnosis of rheumatoid arthritis (RA) after five years in a cohort of patients with early RA. Patients and Methods: One hundred and twenty patients with early arthritis who met the 2010 [...] Read more.

Aim: To identify ultrasound (US) predictors of persistence or change in the diagnosis of rheumatoid arthritis (RA) after five years in a cohort of patients with early RA. Patients and Methods: One hundred and twenty patients with early arthritis who met the 2010 ACR/EULAR classification criteria for RA were followed for a period of five years. The US assessment at baseline included a bilateral evaluation of the wrists, second to fifth metacarpophalangeal (MCP) joints, second to fifth proximal interphalangeal (PIP) joints, the IV and VI extensor compartments of the wrists, and the flexor tendons of the second to fifth fingers. This evaluation was conducted using both grayscale ultrasound (GSUS) and power Doppler ultrasound (PDUS). The following scores were recorded for each patient: synovitis score, mini-enthesitis score (including paratenonitis of the finger extensor tendon at the MCP joint, central slip enthesitis at the PIP joint, pseudotenosynovitis, and the A1 pulley of the second finger), finger flexor tenosynovitis score, and tenosynovitis score for the IV and VI wrist extensor compartments. The receiver operating characteristic (ROC) curve was utilized to identify the ultrasound predictors for either maintaining or revising an initial diagnosis of RA. Results: At month 6, 82 (68%) patients were classified as having RA according to 1987 ACR RA criteria, 23 (19.2%) were diagnosed with psoriatic arthritis (PsA), 10 (8.3%) with systemic connective tissue disease (SCTD)–8 (6.7%) patients with Sjogren Syndrome and 2 (1.7%) patients with systemic lupus erythematosus (SLE)–and 5 (4.2%) patients with calcium pyrophosphate deposition disease (CPPD). The most significant predictor of RA in the fifth year was the VI extensor compartment tenosynovitis score, with an AUC of 0.915 and a criterion value > 0, associated with a sensitivity of 82.93% and a specificity of 100% (p < 0.001). The PDUS synovitis score demonstrated the second-best prognostic ability with an AUC of 0.823, a criterion value > 2, a sensitivity of 82.93%, and a specificity of 73.68% (p < 0.001). The mini-enthesitis score showed the best prognostic ability of a PsA diagnosis with an AUC of 0.998, a criterion value > 1, a sensitivity of 95.65%, and a specificity of 100% (p < 0.001). The paratenonitis score, pseudotenosynovitis score, and thickened A1 pulley were also predictive of PsA diagnosis with AUCs of 0.977, 0.955, and 0.919, respectively (p < 0.001 for all). Conclusions: Nearly one-third of the patients who were initially classified as having RA had their diagnosis revised at the end of the fifth year. Ultrasound of joints, tendons, and mini-entheses at baseline may serve as potential imaging predictive biomarkers for persistence or change in diagnosis after 5 years. Full article

(This article belongs to the Section Molecular and Translational Medicine)

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16 pages, 4441 KiB

Open AccessArticle

Inhibition of TPI1 Sensitizes Cisplatin-Resistant Oral Cancer to Ferroptosis

by Dandan Wang, Huimin Zheng, Yumin Chen, Jialin Hao, Yuan Zhou and Nan Li

Biomedicines 2025, 13(5), 1225; https://doi.org/10.3390/biomedicines13051225 - 19 May 2025

Abstract

Background: Iron metabolism has emerged as a critical factor in cancer biology, with elevated intracellular iron levels contributing to increased oxidative stress and tumorigenesis. However, the molecular determinants governing ferroptosis sensitivity remain incompletely understood. Triosephosphate isomerase 1 (TPI1), a key glycolytic enzyme, has [...] Read more.

Background: Iron metabolism has emerged as a critical factor in cancer biology, with elevated intracellular iron levels contributing to increased oxidative stress and tumorigenesis. However, the molecular determinants governing ferroptosis sensitivity remain incompletely understood. Triosephosphate isomerase 1 (TPI1), a key glycolytic enzyme, has been implicated in cancer progression, but its role in ferroptosis regulation, particularly in the context of chemoresistance, is largely unexplored. In this study, we investigated the impact of TPI1 silencing on ferroptosis in cisplatin-resistant oral squamous cell carcinoma (OSCC), aiming to elucidate its mechanistic role and therapeutic potential. Methods: We conducted in vitro and in vivo analyses to evaluate the functional consequences of TPI1 knockdown in cisplatin-resistant OSCC cell lines and tumor xenograft models. The effects of TPI1 silencing and/or cisplatin treatment were assessed with respect to cell proliferation, migration, and invasion, along with ferroptosis-associated markers, including lipid ROS, free iron levels, lipid peroxidation, and the expression of key ferroptosis-related genes. Additionally, we analyzed the clinical relevance of TPI1 expression in human OSCC tissue samples, examining its association with clinicopathological features and patient prognosis. Results: TPI1 was found to be significantly upregulated in both OSCC tissues and cell lines, and high TPI1 expression correlated with poor clinical outcomes. Multivariate analysis identified TPI1 as an independent prognostic factor for tumor progression. Functionally, TPI1 knockdown suppressed OSCC cell proliferation, migration, and invasion, while its overexpression enhanced these oncogenic behaviors. Mechanistically, silencing TPI1 led to increased intracellular ROS accumulation, elevated free iron, and enhanced lipid peroxidation, collectively promoting ferroptotic cell death in cisplatin-resistant OSCC cells. In vivo, TPI1 depletion resulted in marked tumor growth inhibition and synergized with cisplatin to further suppress tumor burden in xenograft models. Moreover, TPI1 silencing disrupted the epithelial–mesenchymal transition (EMT), a key driver of cancer metastasis and drug resistance. Conclusions: Our study reveals a previously unrecognized role of TPI1 in protecting oral cancer cells from ferroptosis, especially in the setting of cisplatin resistance. These findings suggest that TPI1 not only contributes to tumor aggressiveness but also mediates resistance to ferroptosis. Targeting TPI1 may therefore represent a promising therapeutic strategy to overcome chemoresistance and enhance ferroptosis-based therapies in oral cancer. Full article

(This article belongs to the Section Cancer Biology and Oncology)

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22 pages, 10999 KiB

Open AccessArticle

The Development and Assessment of a Unique Disulfidptosis-Associated lncRNA Profile for Immune Microenvironment Prediction and Personalized Therapy in Gastric Adenocarcinoma

by Jiyue Zhu, Xiang Zhu, Tingting Su, Huiqing Zhou, Shouhua Wang and Weibin Shi

Biomedicines 2025, 13(5), 1224; https://doi.org/10.3390/biomedicines13051224 - 19 May 2025

Abstract

Background: Long non-coding RNAs (lncRNAs) are crucial factors affecting the occurrence, progression, and prognosis of gastric carcinoma (GC). The accumulation of disulfide bonds to excessive levels in cells expressing high SLC7A11 triggers disulfidptosis, which functions as a regulated form of cellular death. Research [...] Read more.

Background: Long non-coding RNAs (lncRNAs) are crucial factors affecting the occurrence, progression, and prognosis of gastric carcinoma (GC). The accumulation of disulfide bonds to excessive levels in cells expressing high SLC7A11 triggers disulfidptosis, which functions as a regulated form of cellular death. Research has demonstrated that upregulated SLC7A11 is common in human cancers, but the effect of disulfidptosis on GC remains unclear. Identifying lncRNAs associated with disulfidptosis (drlncRNAs) and establishing a prognostic risk profile holds considerable importance for advancing GC research and treatment. Methods: Clinical records and transcriptomic datasets from individuals with GC were acquired from The Cancer Genome Atlas (TCGA) repository. A three-drlncRNA risk model was built using three common regression analysis methods. Then we used receiver operating characteristic (ROC) curves, independent prognostic analysis, and additional statistical approaches to assess the precision of the model. This investigation additionally encompassed Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis, immune cell infiltration evaluation, and pharmacological sensitivity predictions. To further investigate immunotherapy response disparities between patient cohorts with elevated- and reduced-risk scores, analyses of tumor mutational burden (TMB), tumor immune dysfunction and exclusion (TIDE), and microsatellite instability (MSI) were implemented. Results: We constructed a unique model composed of three drlncRNAs (AC107021.2, AC016394.2, and AC129507.1). Its independent prognostic capability for GC patients was validated through both single-variable and multivariable Cox regression analyses. GO and KEGG pathway assessments revealed predominant enrichment within the elevated-risk cohort, particularly in pathways involving sulfur compound interactions, traditional Wnt signaling mechanisms, cell-substrate adherens junctions, and cAMP signaling cascades, among others. Tumor microenvironment (TME) evaluation demonstrated elevated ImmuneScores, StromalScores, and ESTIMATEScores within the high-risk patient population. Concurrently, this elevated-risk cohort exhibited enhanced immune cell infiltration patterns, whereas the reduced-risk group displayed superior expression of immune checkpoints (ICPs). Additional investigations revealed that patients categorized into the reduced-risk classification possessed greater tumor mutational burden, increased MSI-high proportions, and diminished tumor immune dysfunction and exclusion scores compared to their high-risk counterparts. Pharmacological sensitivity assessments confirmed the superior efficacy of several therapeutic agents, including gemcitabine and veliparib (ABT.888), in patients with lower risk classifications. Conclusions: Our established risk stratification system demonstrates independent prognostic predictive capacity while offering personalized clinical intervention guidance for individuals diagnosed with GC. Full article

(This article belongs to the Section Molecular and Translational Medicine)

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15 pages, 3838 KiB

Open AccessArticle

Extended Toxicity, Genotoxicity, and Mutagenicity of Combination of pBudK-coVEGF-coANG and pBudK-coGDNF Plasmids in Preclinical Trials

by Igor V. Samatoshenkov, Alexander M. Aimaletdinov, Elena Y. Zakirova, Egan L. Kalmykov, Rustam Khodzhibaev, Yulia M. Samatoshenkova, Ilnur M. Ganiev, Marat S. Kadyrov and Yana O. Mukhamedshina

Biomedicines 2025, 13(5), 1223; https://doi.org/10.3390/biomedicines13051223 - 18 May 2025

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Abstract

Chronic lower limb ischemia is a debilitating condition, particularly prevalent among elderly patients and individuals ineligible for revascularization procedures. Gene therapy aimed at promoting therapeutic angiogenesis presents a promising alternative treatment strategy. Objectives: This study evaluated the preclinical safety of a gene therapy [...] Read more.

Chronic lower limb ischemia is a debilitating condition, particularly prevalent among elderly patients and individuals ineligible for revascularization procedures. Gene therapy aimed at promoting therapeutic angiogenesis presents a promising alternative treatment strategy. Objectives: This study evaluated the preclinical safety of a gene therapy drug composed of the plasmids pBudK-coVEGF-coANG and pBudK-coGDNF in laboratory animals. Safety assessment followed a single intramuscular injection at a dose 30 times higher than the proposed therapeutic level. Methods: Acute toxicity was monitored over a 24-h period. Genotoxicity was assessed using the micronucleus test at doses of 200, 1000, and 5000 μg/kg. Bone marrow cytology was analyzed to detect hematopoietic toxicity. Delayed toxicity was evaluated over a two-week recovery period. Results: No signs of acute toxicity were observed, even at the highest dose. The micronucleus test revealed no genotoxic effects, with no significant increase in micronucleated polychromatic erythrocytes compared to control groups. Bone marrow erythroblast parameters remained within normal physiological ranges. Additionally, no delayed adverse effects were detected during the recovery period. Conclusions: The gene therapy drug demonstrated a favorable preclinical safety profile, exhibiting no evidence of toxicity or genotoxicity, even at substantially elevated doses. These findings support the continued development of this therapy as a potential treatment for chronic lower limb ischemia in patients who are not candidates for surgical intervention. Full article

(This article belongs to the Section Gene and Cell Therapy)

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14 pages, 298 KiB

Open AccessArticle

Genetic Analysis of CYP1B1 and Other Anterior Segment Dysgenesis-Associated Genes in Latvian Cohort of Primary Congenital Glaucoma

by Eva Elksne, Baiba Lace, Janis Stavusis, Anastasija Tvoronovica, Pawel Zayakin, Eriks Elksnis, Arturs Ozolins, Ieva Micule, Sandra Valeina and Inna Inashkina

Biomedicines 2025, 13(5), 1222; https://doi.org/10.3390/biomedicines13051222 - 18 May 2025

Viewed by 154

Abstract

Background: Primary congenital glaucoma (PCG) is a rare disease with an incidence of 1 in 12,000 to 18,000 in Europeans. The scarcity of the disease and limited access to genetic testing have hindered research, particularly within the Latvian population. Objectives: This [...] Read more.

Background: Primary congenital glaucoma (PCG) is a rare disease with an incidence of 1 in 12,000 to 18,000 in Europeans. The scarcity of the disease and limited access to genetic testing have hindered research, particularly within the Latvian population. Objectives: This study aims to present the preliminary results of a molecular genetic investigation into PCG in a Latvian cohort and to compare the prevalence of gene CYP1B1 variants with other European studies as well as to the general population in Latvia. Methods: Twenty probands with clinically diagnosed PCG and 36 family members enrolled in the study. Genetic testing was conducted using genomic DNA from peripheral blood using next generation sequencing (NGS) of seven selected genes: CYP1B1, FOXC1, FOXE3, PXDN, PITX2, PITX3, PAX6, and CPAMD8. Four probands had whole-genome sequencing (WGS). Results: All participants were of European ancestry, with no family history of PCG. Most probands were diagnosed in their first year of life, with a female to male ratio of 1:1.2 and with 80.0% of cases being unilateral. No CYP1B1 pathogenic variants were identified in the screened subjects. However, a heterozygous missense variant c.4357C>A (p.Pro4357Thr) in the PXDN gene was found in one proband and one of her parents that was classified as a variant of uncertain significance. Conclusions: This study represents the first genetic characterization of PCG in the Latvian population. Using NGS, we identified no pathogenic variants in the CYP1B1 gene among affected individuals. Preliminary evidence from this cohort does not support CYP1B1 variants as a predominant cause of PCG, though larger studies are needed to confirm this observation. Comprehensive genetic screening using whole-exome or whole-genome sequencing will be essential to identify the underlying genetic etiology of PCG in Latvia. Full article

(This article belongs to the Special Issue Ophthalmic Genetics: Unraveling the Genomics of Eye Disorders)

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Biomedicines, Volume 13, Issue 5 (May 2025) – 243 articles

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