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Int. J. Transl. Med., Volume 5, Issue 2 (June 2025) – 10 articles

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18 pages, 4077 KiB  
Article
Phosphate Peritoneal Equilibration Test, Hypothesizing New Parameters to Classify Peritoneal Phosphate Handling Through the Peritoneal Membrane
by Francesca K. Martino, Chiara Ciotti, Anna Basso, Ruggero Zanella, Lucia F. Stefanelli, Dorella Del Prete and Federico Nalesso
Int. J. Transl. Med. 2025, 5(2), 22; https://doi.org/10.3390/ijtm5020022 - 10 Jun 2025
Abstract
Background/Objectives: Phosphate level is a critical factor in the health of dialysis patients, as it is linked to cardiovascular risk. In peritoneal dialysis (PD), phosphate removal is related to residual kidney function, dietary intervention, and the ability of the visceral peritoneum to transport [...] Read more.
Background/Objectives: Phosphate level is a critical factor in the health of dialysis patients, as it is linked to cardiovascular risk. In peritoneal dialysis (PD), phosphate removal is related to residual kidney function, dietary intervention, and the ability of the visceral peritoneum to transport phosphate. The role of dialysis prescriptions in phosphate management is not sufficiently enhanced. Standardizing a phosphate removal propensity marker could optimize the peritoneal dialytic program. Our preliminary report aims to evaluate a simple model of phosphate handling and to assess which marker during the peritoneal equilibration test (PET) could better describe the propensity of phosphate removal through the peritoneal membrane. Methods: We hypothesized a simple two-compartment model to describe phosphate removal driven by diffusion. We performed an explorer study on 10 PD patients to assess the reliability of the two-compartment model. In each patient, we evaluated the basal condition and performed a PET with 2 L of 3.86% glucose exchange to assess phosphate handling. We collected blood and peritoneal effluent samples at the beginning of the test (t0), after 1 h (t1), and after 4 h (t4). We proposed and examined the following biomarkers: the ratio between dialysis effluent phosphate and plasma at t4 (PHO-D/P4); the difference between dialysis effluent phosphate at t0 and t4 (PHOΔd0-d4); and phosphate permeability–area product at t4 (PHO-PxA4). Results: 9 men and one woman with a mean age of 58.7 ± 16.7 years and a mean dialysis vintage of 25 ± 18.3 months were enrolled. The PHO-D/P4 mean was 0.68 ± 0.18, the PHO-Δd0-d4 median was 0.89 mmol/L [0.7–1.19], and the PHO-PxA4 mean was 1.7 ± 0.85. PHO-D/P4was significantly related to creatinine D/P4 (beta 1.49, p < 0.001), PHO-Δd0-d4 was significantly influenced by plasma phosphate at t0 (beta 0.56, p < 0.001), and the PHO-PxA4 was significantly influenced by ultrafiltration (beta 0.003, p < 0.001). Conclusions: In our two-compartment model, we observed the independence of the PHO-D/P4marker, which could serve as a potential marker for standardizing phosphate handling. However, PHO-Δd0-d4 and PHO-PxA4 normalized by plasma phosphate at t0 and ultrafiltration rate were able to reserve a potential good performance as markers in phosphate handling standardization. Full article
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12 pages, 1124 KiB  
Article
Urine Metabolites as Biomarkers and Metabolism Mechanism Studies of Alcohol-Associated Liver Disease
by Liqing He, Vatsalya Vatsalya, Raobo Xu, Xinmin Yin, Xipeng Ma, Seongho Kim, Eugene G. Mueller, Wenke Feng, Craig J. McClain and Xiang Zhang
Int. J. Transl. Med. 2025, 5(2), 21; https://doi.org/10.3390/ijtm5020021 - 10 Jun 2025
Abstract
Background/Aims: We explored the possibility of using urine polar metabolites as non-invasive biomarkers of alcohol-associated liver disease (ALD) for early-stage diagnosis and severity assessment, as well as the possible changes in metabolic pathways in ALD patients. Methods: Polar metabolites were extracted with 80% [...] Read more.
Background/Aims: We explored the possibility of using urine polar metabolites as non-invasive biomarkers of alcohol-associated liver disease (ALD) for early-stage diagnosis and severity assessment, as well as the possible changes in metabolic pathways in ALD patients. Methods: Polar metabolites were extracted with 80% methanol, and parallel 2DLC-MS was used for polar metabolite quantification. Results: Data from untargeted metabolomics showed that 194 metabolites were significantly changed in patients, and three metabolites can differentiate healthy controls (HC), non-severe ALD, and severe alcohol-associated hepatitis (severe AH) with high accuracy (0.92–0.97). Pathway analysis showed that arginine biosynthesis and histidine metabolism pathways were among the pathways containing the metabolites that were most altered in the urine of patients. Metabolites in the urea cycle, histidine catabolism, and histidine dipeptides pathways were notably increased in the urine of ALD patients, but none of the metabolites in these two pathways can simultaneously differentiate patients from healthy volunteers and non-severe ALD from severe AH. As the top differentiated pathways, the alterations of arginine biosynthesis and histidine metabolism indicate their importance in the metabolic dysfunction of ALD. Conclusions: Our results show that the abundance changes of specific metabolites can differentiate the disease severity of ALD, showing the potential of urine polar metabolites as non-invasive biomarkers for early-stage diagnosis and disease severity assessment of ALD. Full article
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1 pages, 157 KiB  
Correction
Correction: Elmelid et al. Effects of Phototherapy on Free Vitamin D Levels in Ten Patients with Atopic Dermatitis. Int. J. Transl. Med. 2022, 2, 586–596
by Andrea Elmelid, Amra Osmancevic, Martin Gillstedt and Mikael Alsterholm
Int. J. Transl. Med. 2025, 5(2), 20; https://doi.org/10.3390/ijtm5020020 - 6 Jun 2025
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Abstract
In the original publication [...] Full article
14 pages, 4427 KiB  
Case Report
Horizontal Guided Bone Regeneration Using Titanium-Reinforced Dense PTFE Membrane and Synthetic Nanocrystalline Hydroxyapatite: A Case Study Reporting Clinical and Histological Outcomes with 5-Year Follow-Up
by Fabrizio Belleggia, Luca Signorini, Mirko Martelli and Marco Gargari
Int. J. Transl. Med. 2025, 5(2), 19; https://doi.org/10.3390/ijtm5020019 - 31 May 2025
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Abstract
Background/Objectives: Guided bone regeneration (GBR) is a regenerative technique used to treat maxillary osseous defects to enable implant placement for prosthetic rehabilitation. It is generally performed with the use of barrier membranes and bone substitute materials of human or animal origin. Here, [...] Read more.
Background/Objectives: Guided bone regeneration (GBR) is a regenerative technique used to treat maxillary osseous defects to enable implant placement for prosthetic rehabilitation. It is generally performed with the use of barrier membranes and bone substitute materials of human or animal origin. Here, we report the clinical and histological outcomes of a horizontal GBR, treated using only synthetic biomaterials. Methods: A graft of nanocrystalline hydroxyapatite (NH) embedded in a silica gel matrix was used to fill a horizontal bone defect. The graft was covered with a titanium-reinforced dense polytetrafluoroethylene (TR-dPTFE) membrane, and primary closure was completed and maintained for 10 months. Then, the site was re-opened for membrane removal and implant insertion. During implant bed preparation, a bone biopsy was obtained for histological evaluation. A metal–ceramic crown was fitted, and the 5-year follow-up after prosthetic loading showed clinical and radiographically healthy tissues. Results: Histological examination revealed good integration of the biomaterial into the surrounding tissues, which were composed of lamellar bone trabeculae and connective tissue. New bone formation occurred not only around the NH granules but even inside the porous amorphous particles. Conclusions: The combination of NH and the TR-dPTFE membrane produced good clinical and histological results, which remained stable for 5 years. Full article
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19 pages, 249 KiB  
Article
Socioeconomic Disparities and Other Factors in Dyslipidemia: Insights from NHANES 2017–2020 Data
by Tanvir Ahmed, Akhi Nath, Nusrat Jahan, Aakanksha Khadka, Jaimala Kishore, Ashley Farokhrouz and Rodney G. Bowden
Int. J. Transl. Med. 2025, 5(2), 18; https://doi.org/10.3390/ijtm5020018 - 22 May 2025
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Abstract
Introduction: Dyslipidemia, characterized by abnormal blood lipid levels, is a key risk factor for cardiovascular disease. Socioeconomic status can play a role in the development of chronic disease, including as an influence on risk factors for chronic diseases such as cardiovascular disease. [...] Read more.
Introduction: Dyslipidemia, characterized by abnormal blood lipid levels, is a key risk factor for cardiovascular disease. Socioeconomic status can play a role in the development of chronic disease, including as an influence on risk factors for chronic diseases such as cardiovascular disease. Methods: This study analyzes the relationship between socioeconomic status and dyslipidemia using a population-based cross-sectional survey (NHANES 2017–2020 data). A cohort of 5862 adults was examined, focusing on socioeconomic factors (income, education, occupation) and their association with lipid profiles while controlling for sociodemographic, lifestyle, and medical variables, contributing to understanding how health disparities may affect chronic disease outcomes. Results: Low socioeconomic status was consistently associated with higher dyslipidemia risk, while high socioeconomic status demonstrated a modest protective effect. Age, BMI, hypertension, and diabetes were key predictors, highlighting the need for targeted interventions. Conclusions: This study underscores the critical role of socioeconomic status in dyslipidemia risk. Low socioeconomic status consistently increased the odds of dyslipidemia. While high socioeconomic status demonstrated some protective effects, these were diminished when accounting for lifestyle and clinical factors, highlighting the complex interplay of socioeconomic status and health behaviors. Full article
12 pages, 861 KiB  
Article
Identifying High-Risk Bacteria with Active Nasal Swab Surveillance in Intensive Care Units to Prevent Ventilator-Associated Pneumonia
by Yu Kuramasu, Yu Suzuki, Daisuke Akaneya, Yoshikazu Okuma, Yuta Tsujimoto, Daisuke Ishizawa, Kazunori Moriya, Parichart Hongsing, Mohan Amarasiri, Cameron Hurst, Paul G. Higgins, Kenji Shibuya, Anthony Kicic, Yoshitaka Shimotai, Hiroshi Hamamoto, Dhammika Leshan Wannigama and Shuichi Abe
Int. J. Transl. Med. 2025, 5(2), 17; https://doi.org/10.3390/ijtm5020017 - 25 Apr 2025
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Abstract
Background: Active nasal surveillance culture (ANSC) is recognized to enable rapid detection of antibiotic-resistant bacteria in the intensive care unit (ICU), which can contribute to the prevention of Ventilator-associated pneumonia (VAP). This study aims to evaluate the usefulness of ANSC in assessing the [...] Read more.
Background: Active nasal surveillance culture (ANSC) is recognized to enable rapid detection of antibiotic-resistant bacteria in the intensive care unit (ICU), which can contribute to the prevention of Ventilator-associated pneumonia (VAP). This study aims to evaluate the usefulness of ANSC in assessing the development of VAP in ICU patients. Methods: Patients admitted to the Yamagata Prefectural Central Hospital ICU from January 2017 to 2018 (Term 1) or January 2020 to December 2021 (Term 2) and underwent invasive mechanical ventilation supports were eligible for this study. Nasal swab samples were collected from the patients upon their admission to the ICU. The diagnosis of VAP was made according to the criteria set by the Centers for Disease Control and Prevention. Results: A total of 467 patients (156 women) in term 1, and 312 patients (113 women) in term 2 were enrolled. The incidence of VAP in term 2 was higher than in term 1 (7.1% vs. 12.8%, respectively). ANSC isolated several causative pathogens from the patients on admission who later developed VAP. Haemophilus influenza, Streptococcus pneumoniae, Stenotrophomonas maltophilia, and Pseudomonas aeruginosa had a 100% match rate with the sputum culture, indicating a perfect relation between ANSC results and sputum culture in VAP (+) cases. Conclusions: The isolation of high-risk bacterial species by ANSC could foresee the development of VAP in ICU patients and efficiently prevent VAP in critically ill patients. Full article
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29 pages, 6419 KiB  
Article
Concentration-Dependent Pleiotropic Effects of Thymosin Beta4 and Cofilin on the Migratory Activity of Carcinoma Cells
by Abdulatif Al Haj, Kamila Ćwikłowska, Antonina Joanna Mazur, Beate Brand-Saberi, Ewald Hannappel and Hans Georg Mannherz
Int. J. Transl. Med. 2025, 5(2), 16; https://doi.org/10.3390/ijtm5020016 - 18 Apr 2025
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Abstract
Background/Objectives: Tumor cell migration depends on the actin cytoskeleton modified by actin-binding proteins (ABPs). Overexpression of cofilin or thymosin beta4 (Tß4) has been correlated with an increase or decrease in their migratory activity, respectively. Methods: Immunostaining of tumor cells and transfection with EGFP-tagged [...] Read more.
Background/Objectives: Tumor cell migration depends on the actin cytoskeleton modified by actin-binding proteins (ABPs). Overexpression of cofilin or thymosin beta4 (Tß4) has been correlated with an increase or decrease in their migratory activity, respectively. Methods: Immunostaining of tumor cells and transfection with EGFP-tagged cofilin or bicistronic vectors leading to independent expression of EGFP and Tß4. Determination of cell migration by transwell or agarose drop assay. Results: We modulated by transfection the intracellular concentrations of cofilin and Tß4 of two colon (3LNLN and EB3) and one breast carcinoma (MDA-MB-231) cell line and analyzed their migratory activity. Increasing wild-type cofilin did not alter their migratory activity, whereas the constitutively active S3A–cofilin mutant elevated migration. Transfection leading to an up- or downregulation of Tß4 showed that MDA-MB-231 and 3LNLN cells responded with a decrease or increase in migration, respectively. Exposure of MDA-MB-231 and 3LNLN cells to increasing concentrations of extracellular Tβ4 (or His-tagged Tß4) induced a biphasic response of migration, being highest around 0.24 µM and decreased at higher extracellular Tß4. Immunostaining of 3LNLN cells exposed to 0.24 µM extracellular His-tagged Tß4 with anti-His antibody indicated its uptake co-localizing with integrin-linked kinase at cell attachment points. Furthermore, the exposure to 0.24 µM His-tagged Tß4 led to increased phosphorylation of AKT1/2 and secretion of matrix metalloproteases. These effects and tumor cell migration were abrogated after exposure of 3LNLN cells to 2.8 µM His-Tß4, also inducing apoptosis in a number of cells. Conclusions: Tumor cell migration can be inhibited by high extracellular Tß4. Full article
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12 pages, 1410 KiB  
Article
Mutation-Specific Cardiomyocyte Lines from Patients with Fabry Disease: A Sustainable In Vitro Model to Investigate Structure, Function, and Disease Mechanisms
by Kathleen Nicholls, Andrea Wise, David Elliot, Menno ter Huurne, Maria Fuller and Sharon Ricardo
Int. J. Transl. Med. 2025, 5(2), 15; https://doi.org/10.3390/ijtm5020015 - 15 Apr 2025
Viewed by 446
Abstract
Background: Fabry disease (FD) results from pathogenic GLA variants, causing lysosomal α-galactosidase A (α-GalA) deficiency and sphingolipid ceramide trihexoside (Gb3 or THC) accumulation. Disease phenotype varies widely but cardiomyopathy is commonly life-limiting. As a multisystemic disorder, FD initiates at the cellular level; however, [...] Read more.
Background: Fabry disease (FD) results from pathogenic GLA variants, causing lysosomal α-galactosidase A (α-GalA) deficiency and sphingolipid ceramide trihexoside (Gb3 or THC) accumulation. Disease phenotype varies widely but cardiomyopathy is commonly life-limiting. As a multisystemic disorder, FD initiates at the cellular level; however, the mechanism/s underlying Gb3-induced cell dysfunction remains largely unknown. This study established an in vitro mutation-specific model of Fabry cardiomyopathy using human-induced pluripotent stem cell (iPSC)-derived cardiomyocytes to explore underlying cell pathology. Methods: Skin biopsies from consenting Fabry patients and normal control subjects were reprogrammed to iPSCs then differentiated into cardiomyocytes. The GLA mutations in Fabry cell lines were corrected using CRISP-Cas9. Phenotypic characteristics, α-Gal A activity, Gb3 accumulation, functional status, and lipid analysis were assessed. Cardiomyocytes derived from two patients with severe clinical phenotype and genotypes, GLAc.851T>C, GLAc.1193_1196del, and their respective corrected lines, GLAcorr c.851T>C, GLAcorr c.1193_1196del, were selected for further studies. Results: Cardiomyocytes derived from individuals with FD iPSCs exhibited stable expression of cardiomyocyte markers and spontaneous contraction, morphological features of FD, reduced α-Gal A activity, and accumulation of Gb3. Lipidomic profiling revealed differences in the Gb3 isoform profile between the control and FD patient iPSC-derived cardiomyocytes. Contraction strength was unchanged but relaxation after contraction was delayed, mimicking the diastolic dysfunction typical of Fabry cardiomyopathy. Conclusions: iPSC-derived cardiomyocytes provide a useful model to explore aspects of Fabry cardiomyopathy, including disruptions in sphingolipid pathways, proteomics, and multigene expression that together link genotype to phenotype. The platform potentially offers broad applicability across many genetic diseases and offers the prospect of testing and implementation of individualised therapies. Full article
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17 pages, 352 KiB  
Review
Liquid Biopsy for Colorectal Cancer: Advancing Detection and Clinical Application
by Yan Li, Qiong Zhang and Shelly Cook
Int. J. Transl. Med. 2025, 5(2), 14; https://doi.org/10.3390/ijtm5020014 - 26 Mar 2025
Viewed by 1114
Abstract
Colorectal cancer (CRC) is the third most common cancer and a leading cause of cancer-related mortality worldwide, with prognosis significantly deteriorating at advanced stages. While current diagnostic methods, such as colonoscopy and tissue biopsy, are widely employed in clinical practice, they are invasive, [...] Read more.
Colorectal cancer (CRC) is the third most common cancer and a leading cause of cancer-related mortality worldwide, with prognosis significantly deteriorating at advanced stages. While current diagnostic methods, such as colonoscopy and tissue biopsy, are widely employed in clinical practice, they are invasive, expensive, and limited in assessing tumor heterogeneity and monitoring disease processes, including therapy response. Therefore, early and accurate detection, coupled with minimal invasion and cost-effective strategies, are critical for improving patient outcomes. Liquid biopsy has emerged as a promising, minimally invasive alternative, enabling the detection of tumor-derived components. This approach is increasingly utilized in clinical settings. The current key liquid biopsy modalities in CRC include circulating tumor DNA (ctDNA), circulating tumor cells (CTCs), and RNA-based biomarkers such as long non-coding RNAs (lncRNAs), microRNAs(miRNAs), and circular RNAs (circRNAs), and tumor-educated platelets (TEPs). These methods provide valuable insights into genetic and epigenetic tumor alterations, and serve as indicators for early detection, treatment monitoring, and recurrence prediction. However, challenges such as assay standardization and variability in sensitivity persist. This review delves into the clinical applications of liquid biopsy in CRC management, highlighting the transformative roles of ctDNA, CTCs, and non-coding RNAs, TEPs in early detection, prognostic assessment, and personalized therapy. In addition, it addresses current limitations and explores potential advancements to facilitate their integration into routine clinical practice. Full article
11 pages, 2218 KiB  
Article
Systemic Administration of Docosahexaenoic Acid Suppresses Trigeminal Secondary Nociceptive Neuronal Activity in Rats
by Hanano Takahashi, Yukito Sashide and Mamoru Takeda
Int. J. Transl. Med. 2025, 5(2), 13; https://doi.org/10.3390/ijtm5020013 - 25 Mar 2025
Viewed by 420
Abstract
Background and Objectives: Docosahexaenoic acid (DHA) has been shown to modulate various voltage-gated ion channels and both excitatory and inhibitory synapses. Nonetheless, its exact effect on nociceptive signaling in the trigeminal system has yet to be elucidated. The purpose of the current investigation [...] Read more.
Background and Objectives: Docosahexaenoic acid (DHA) has been shown to modulate various voltage-gated ion channels and both excitatory and inhibitory synapses. Nonetheless, its exact effect on nociceptive signaling in the trigeminal system has yet to be elucidated. The purpose of the current investigation was to assess if acute DHA given intravenously to rats diminished the excitability of wide dynamic range spinal trigeminal nucleus caudalis (SpVc) neurons in response to mechanical stimulation in vivo. Methods: Single-unit extracellular activity was recorded from SpVc neurons in response to mechanical stimulation of the whisker pad in anesthetized rats. Responses to both non-noxious and noxious mechanical stimuli were analyzed in the present study. Results: The mean firing frequency of SpVc wide dynamic range neurons in response to both non-noxious and noxious mechanical stimuli was significantly dose-dependently inhibited by DHA, and the effect was seen within 5 min. After approximately 20 min, the inhibiting effects dissipated. Conclusions: These results suggest that, in the absence of inflammatory or neuropathic pain, the acute intravenous administration of DHA reduces the activity of trigeminal sensory neurons, including those responsible for pain, indicating that DHA could be utilized as an adjunct and alternative therapeutic agent for managing trigeminal nociceptive pain, including hyperalgesia. Full article
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