-
Peritoneal Dialysis: Phosphate Handling Model and Biomarkers in the Four-Hour Peritoneal Equilibration Test
-
Current and Future Directions in Immunotherapy for Gastrointestinal Malignancies
-
Novel Roles and Therapeutic Approaches Linking Platelets and Megakaryocytes to Non-Hemostatic and Thrombotic Disease
-
Protein Engineering Paving the Way for Next-Generation Therapies in Cancer
-
Urine Metabolites as Biomarkers and Metabolism Mechanism Studies of Alcohol-Associated Liver Disease
Journal Description
International Journal of Translational Medicine
International Journal of Translational Medicine
is an international, peer-reviewed, open access journal on major advances in both experimental and clinical medicine, with a particular emphasis on translational research published quarterly online by MDPI.
- Open Access— free for readers, with article processing charges (APC) paid by authors or their institutions.
- High Visibility: indexed within Scopus and other databases.
- Journal Rank: CiteScore - Q2 (Medicine (miscellaneous))
- Rapid Publication: manuscripts are peer-reviewed and a first decision is provided to authors approximately 25.9 days after submission; acceptance to publication is undertaken in 2.7 days (median values for papers published in this journal in the first half of 2025).
- Recognition of Reviewers: APC discount vouchers, optional signed peer review, and reviewer names published annually in the journal.
- IJTM is a companion journal of Biomedicines.
Latest Articles
Heavy Increase in Erythrocyte Protoporphyrin IX During Treatment with Teriflunomide in a Patient with Erythropoietic Protoporphyria: A Case Report
Int. J. Transl. Med. 2025, 5(3), 41; https://doi.org/10.3390/ijtm5030041 (registering DOI) - 23 Aug 2025
Abstract
►
Show Figures
Background/Objectives: Patients with erythropoietic protoporphyria (EPP) have a decreased activity of the ferrochelatase enzyme which converts protoporphyrin IX (PpIX) into heme, causing PpIX to accumulate in erythrocytes. The ensuing release of PpIX to the skin when exposed to visible light causes a phototoxic
[...] Read more.
Background/Objectives: Patients with erythropoietic protoporphyria (EPP) have a decreased activity of the ferrochelatase enzyme which converts protoporphyrin IX (PpIX) into heme, causing PpIX to accumulate in erythrocytes. The ensuing release of PpIX to the skin when exposed to visible light causes a phototoxic reaction with severe pain, erythema, and edema. Erythrocyte PpIX levels in adult EPP patients are rather stable and largely unaffected by pharmaceutical treatments. It is important to be aware of drugs causing an increase in PpIX as this may increase the risk of liver toxicity. Method: The patient had blood samples taken regularly for analyses of PpIX, znPpIX, ALT, ALP, iron, leucocytes, C-reactive protein, and hemoglobin before, during, and after treatment with teriflunomide. Additionally, we tested if teriflunomide increased PpIX in vitro. Results: A female EPP patient was treated for 7 years with teriflunomide for multiple sclerosis attacks. During treatment, her natural PpIX level increased from about 30 µmol/L to about 200 µmol/L, without significant simultaneous changes in hemoglobin, iron levels, alanine transaminase (ALT), or alkaline phosphatase (ALP). The patient experienced no increase in photosensitivity. In vitro addition of teriflunomide did not affect PpIX levels. Discussion: In patients with lead intoxication, the release of PpIX from erythrocytes is very slow. The increase in PpIX during treatment with teriflunomide compared to periods with no medication could be caused by a similar slow PpIX release from the erythrocytes. This theory is supported by the patient’s unchanged light sensitivity and stable levels of hemoglobin, iron, and liver enzymes.
Full article
Open AccessReview
Fluorescence-Guided Surgery in Head and Neck Squamous Cell Carcinoma (HNSCC)
by
Albrecht Blosse, Markus Pirlich, Andreas Dietz, Christin Möser, Katrin Arnold, Jessica Freitag, Thomas Neumuth, David M. Smith, Hans Kubitschke and Maximilian Gaenzle
Int. J. Transl. Med. 2025, 5(3), 40; https://doi.org/10.3390/ijtm5030040 - 22 Aug 2025
Abstract
►▼
Show Figures
Head and neck squamous cell carcinomas (HNSCCs) are the seventh most common form of cancer worldwide, typically characterized by high mortality and significant morbidity, including pain and speech and swallowing disorders. Complete tumor tissue resection, the common first line of therapy, remains a
[...] Read more.
Head and neck squamous cell carcinomas (HNSCCs) are the seventh most common form of cancer worldwide, typically characterized by high mortality and significant morbidity, including pain and speech and swallowing disorders. Complete tumor tissue resection, the common first line of therapy, remains a surgical challenge with room for improvements. Because tumor cells express highly specific surface molecules serving as receptors for ligands, specific targeting ligands can be conjugated to fluorescent molecules in order to better visualize tumor borders. Targeted fluorescence-guided surgery (T-FGS) as well as tumor-targeted and near-infrared (NIR) fluorescence imaging are emerging techniques for real-time intraoperative cancer imaging. Targeting agents include nanodots or fluorophores, which have been conjugated to specific ligands like antibodies, peptides, or other synthetic moieties. This article surveys tumor-targeted ligands in recent and current preclinical studies and clinical trials related to HNSCC, highlighting common NIRF dyes used for molecular imaging and their physical properties, working concentrations, and associated risks. Smaller ligands, nanodots, dual-modality NIR dyes, and activatable agents can enhance tumor-targeting processes, resulting in faster, more penetrable, and clearer imaging, which could lead to improved clinical applications and better tumor removal rates in the future.
Full article

Figure 1
Open AccessReview
Circulating Extracellular Vesicle-Based Biomarkers: Advances, Clinical Implications and Challenges in Coronary Artery Disease
by
Valeria Carcia, Alessandro Vincenzo De Salve, Chiara Nonno and Maria Felice Brizzi
Int. J. Transl. Med. 2025, 5(3), 39; https://doi.org/10.3390/ijtm5030039 - 22 Aug 2025
Abstract
►▼
Show Figures
Coronary artery disease (CAD) is a leading cause of death worldwide, encompassing a broad spectrum of pathological conditions ranging from chronic to acute coronary syndromes. It underlies complex biological mechanisms, among which an emerging role is played by extracellular vesicles (EVs). EVs are
[...] Read more.
Coronary artery disease (CAD) is a leading cause of death worldwide, encompassing a broad spectrum of pathological conditions ranging from chronic to acute coronary syndromes. It underlies complex biological mechanisms, among which an emerging role is played by extracellular vesicles (EVs). EVs are non-replicable cell-derived particles enclosed by lipid bilayers acting as mediators of cellular interactions. In the past two decades, there has been a growing interest in EVs as potential diagnostic, prognostic and therapeutic tools in cardiovascular disease. We reviewed the most recent studies on circulating EVs in CAD with a particular focus on their role in biomarker discovery. Our aim was to evaluate the feasibility of translating these findings into routine clinical practice. To this end, we underlie the development and application of integrated indicators, referred to as “Bioscores”, which combine clinical, laboratory, and molecular data to enhance diagnostic and prognostic accuracy. We briefly discuss the opportunity and pitfalls related to the emerging use of Machine Learning (ML) algorithms. Moreover, we highlight that further investigation of mechanistic pathways is required beyond the initially predicted associations generated by in silico studies. Finally, we analyzed the key limitations, challenges, and unmet needs in the field, including small and unrepresentative sample sizes, a lack of external validation, overlapping and often contradictory effects on targeted pathways, difficulties in standardizing EV isolation and characterization methods, as well as concerns regarding affordability and clinical reliability.
Full article

Figure 1
Open AccessReview
The Importance of an Adequate Diet in the Treatment and Maintenance of Health in Children with Cystic Fibrosis
by
Michał Mazur, Agnieszka Malik, Monika Pytka and Joanna Popiołek-Kalisz
Int. J. Transl. Med. 2025, 5(3), 38; https://doi.org/10.3390/ijtm5030038 - 20 Aug 2025
Abstract
►▼
Show Figures
This review focuses specifically on pediatric patients with cystic fibrosis. Cystic fibrosis (CF) is a serious inherited disease that affects the respiratory and gastrointestinal systems in children and adolescents, causing chronic inflammation, infections, and impaired nutrient absorption. A key component of patient care
[...] Read more.
This review focuses specifically on pediatric patients with cystic fibrosis. Cystic fibrosis (CF) is a serious inherited disease that affects the respiratory and gastrointestinal systems in children and adolescents, causing chronic inflammation, infections, and impaired nutrient absorption. A key component of patient care is monitoring nutritional status, particularly based on BMI, which correlates with lung function and life expectancy. This paper presents the latest guidelines for dietary therapy, including a high-calorie and fat-rich diet supported by pancreatic enzymes, as well as the importance of vitamin and mineral supplementation in the context of CF pathophysiology. The role of modern therapies that modulate CFTR function to improve patients’ quality of life and support antimicrobial therapy is discussed. Particular attention is paid to the role of the gut microbiota and the potential for its modulation by probiotics, highlighting their potential to alleviate inflammation and support the immune system. The conclusions underscore the need for a comprehensive, individualized approach to diagnosis and therapy, which is crucial for improving the quality of life and health prognosis of children with CF. New visual tools and a clinical case study enhance the practical applicability of current recommendations, while emerging areas such as microbiome-targeted interventions and treatment inequalities are also addressed.
Full article

Graphical abstract
Open AccessReview
Nanocarrier-Assisted Delivery of Drug(s) for the Targeted Treatment of Neurodegenerative Disease
by
Joseph S. D’Arrigo
Int. J. Transl. Med. 2025, 5(3), 37; https://doi.org/10.3390/ijtm5030037 - 19 Aug 2025
Abstract
►▼
Show Figures
Apolipoprotein A-I (apoA-I)-coated nanoemulsion particles target scavenger receptors. Adsorbed apoA-I (from the bloodstream) mediates/facilitates this targeted molecular contact, which is followed by receptor-mediated endocytosis and subsequent transcytosis of these same nanoemulsion (nanocarrier) particles across the blood–brain barrier (BBB). When the right drugs are
[...] Read more.
Apolipoprotein A-I (apoA-I)-coated nanoemulsion particles target scavenger receptors. Adsorbed apoA-I (from the bloodstream) mediates/facilitates this targeted molecular contact, which is followed by receptor-mediated endocytosis and subsequent transcytosis of these same nanoemulsion (nanocarrier) particles across the blood–brain barrier (BBB). When the right drugs are added in advance to these high-density lipoprotein (HDL)-like nanocarriers, multifunctional combination treatment is achieved. This medication penetrates the BBB and targets particular cell-surface scavenger receptors, mainly class B type I (SR-BI). As a result, these (drug-carrying) nanoemulsions may find application in the biomedical therapy of complex medical disorders, such as dementia, as well as some aspects of aging. According to recent research, sustained inflammatory stimulation in the gut, such as via serum amyloid A (SAA), may cause the release of proinflammatory cytokines. Thus, using this “HDL-like” nanoemulsion vehicle to target drugs early (or even proactively) toward a major SAA receptor (like SR-BI), which is implicated in SAA-mediated cell-signaling processes that lead to aging and/or cognitive decline (and eventually Alzheimer’s disease or dementia), may be a useful preventive and therapeutic strategy.
Full article

Figure 1
Open AccessArticle
Comparison of the Differing Impacts of Lowered N-Acetylglucosaminyltransferase-Ia/b Activity on Motor and Sensory Function in Zebrafish
by
M. Kristen Hall, Cody J. Hatchett, Haris A. Khan, Hannah Lewis and Ruth A. Schwalbe
Int. J. Transl. Med. 2025, 5(3), 36; https://doi.org/10.3390/ijtm5030036 - 18 Aug 2025
Abstract
►▼
Show Figures
Background/Objectives: Perturbation in terminal N-glycan processing is a feature of congenital disorders of glycosylation and neurological disorders. Since treatment options are limited, N-glycans are plausible therapeutic targets. Here, we investigated the consequences of substituting complex/hybrid with oligomannose types of N-glycans on nervous and
[...] Read more.
Background/Objectives: Perturbation in terminal N-glycan processing is a feature of congenital disorders of glycosylation and neurological disorders. Since treatment options are limited, N-glycans are plausible therapeutic targets. Here, we investigated the consequences of substituting complex/hybrid with oligomannose types of N-glycans on nervous and musculature systems, employing mgat1a and mgat1b mutant zebrafish models. Methods: CRISPR Cas9 technology was employed to engineer the mgat1a zebrafish model. The N-glycan populations in Wt AB, mgat1a−/− and mgat1b−/− zebrafish were characterized via lectin blotting. Motor and sensory functions were measured by tail-coiling and touch-evoked response assays in embryos and larvae. Swimming locomotion and anxiety-like behavior were characterized in adult Wt AB, and mutant zebrafish using motility and novel tank dive assays. Results: The mgat1a−/− model had increased oligomannosylated proteins compared to Wt AB in embryos and dissected brain, spinal cord, skeletal muscle, heart, swim bladder, and skin from adults, supporting a global knockdown of GnT-I activity. Higher levels were also observed in mgat1a−/− relative to mgat1b−/−, except in the brain. Band patterns for oligomannosylated proteins were different between all three zebrafish lines. The mgat1−/− embryos and larvae had deficient motor and sensory functions which persisted into adulthood, with a higher deficiency in mgat1b−/−. Anxiety-like behavior was decreased and increased in adult mgat1a−/− and mgat1b−/−, respectively, compared to Wt AB. Conclusions: Taken together, this study revealed that aberrant terminal N-glycan processing impacts brain, spinal and muscle control, and hence will enhance our understanding of the vital role of complex/hybrid N-glycans in nervous system health.
Full article

Figure 1
Open AccessReview
Various Approaches Employed to Enhance the Bioavailability of Antagonists Interfering with the HMGB1/RAGE Axis
by
Harbinder Singh
Int. J. Transl. Med. 2025, 5(3), 35; https://doi.org/10.3390/ijtm5030035 - 2 Aug 2025
Abstract
►▼
Show Figures
High-mobility group box 1 (HMGB1) is a nuclear protein that can interact with a transmembrane cell surface receptor for advanced glycation end products (RAGEs) and mediates the inflammatory pathways that lead to various pathological conditions like cancer, diabetes, cardiovascular diseases, and neurodegenerative disorders.
[...] Read more.
High-mobility group box 1 (HMGB1) is a nuclear protein that can interact with a transmembrane cell surface receptor for advanced glycation end products (RAGEs) and mediates the inflammatory pathways that lead to various pathological conditions like cancer, diabetes, cardiovascular diseases, and neurodegenerative disorders. Blocking the HMGB1/RAGE axis using various small synthetic or natural molecules has been proven to be an effective therapeutic approach to treating these inflammatory conditions. However, the low water solubility of these pharmacoactive molecules limits their clinical use. Pharmaceutically active molecules with low solubility and bioavailability in vivo convey a higher risk of failure for drug development and drug innovation. The pharmacokinetic and pharmacodynamics parameters of these compounds are majorly affected by their solubility. Enhancement of the bioavailability and solubility of drugs is a significant challenge in the area of pharmaceutical formulations. This review mainly describes various technologies utilized to improve the bioavailability of synthetic or natural molecules which have been particularly used in various inflammatory conditions acting specifically through the HMGB1/RAGE pathway.
Full article

Figure 1
Open AccessReview
Parental Cigarette Smoke Exposure and Its Impact on Offspring Reproductive Health: A Systematic Review of Maternal, Paternal, and Dual-Smoking Effects
by
Yasmin Azizbayli, Amanda Tatler, Victoria James, Adam Watkins and Lucy C. Fairclough
Int. J. Transl. Med. 2025, 5(3), 34; https://doi.org/10.3390/ijtm5030034 - 2 Aug 2025
Abstract
►▼
Show Figures
Objectives: Parental exposure to tobacco smoke is a significant public health concern, with over 1.1 billion smokers worldwide. The aim of this systematic review was to evaluate the impact of maternal, paternal, and dual-parental cigarette smoke exposure on offspring reproductive health. Methods: Original
[...] Read more.
Objectives: Parental exposure to tobacco smoke is a significant public health concern, with over 1.1 billion smokers worldwide. The aim of this systematic review was to evaluate the impact of maternal, paternal, and dual-parental cigarette smoke exposure on offspring reproductive health. Methods: Original human clinical and animal research studies were included; titles and abstracts were manually scanned for relevance to the effect of parental smoking on offspring reproductive outcomes (Date of search:18/03/2025). Results: This systematic review incorporates 30 studies identified from three databases (PubMed, Web of Science, and Scopus). The results indicate that male offspring exhibit reduced spermatogenic capacity, characterized by decreased testicular size, lower sperm count, and impaired hormonal biosynthesis, with reductions of 30–40% in sperm production. Dual-parental smoking exacerbates these effects, with sperm counts averaging 85 million per ml in human male offspring from dual-smoking households, compared to 111 million per ml in single-smoking households. Animal studies provide mechanistic insights, revealing reduced testis weight in nicotine-exposed male rats and increased oxidative stress in offspring. Conclusions: This review highlights the dose-dependent and sex-specific effects of smoking on the fertility of offspring and underscores the need for standardized protocols to enhance the consistency and comparability of future research in both human and animal studies.
Full article

Figure 1
Open AccessReview
Current and Future Directions in Immunotherapy for Gastrointestinal Malignancies
by
Catherine R. Lewis, Yazan Samhouri, Christopher Sherry, Neda Dadgar, Moses S. Raj and Patrick L. Wagner
Int. J. Transl. Med. 2025, 5(3), 33; https://doi.org/10.3390/ijtm5030033 - 31 Jul 2025
Abstract
Gastrointestinal (GI) malignancies are diverse and particularly challenging in terms of current immunotherapy but hold great opportunity for impact given that they constitute the highest cancer incidence and mortality rates worldwide. Traditional treatment options for solid GI malignancies include surgical intervention, chemotherapy, radiation,
[...] Read more.
Gastrointestinal (GI) malignancies are diverse and particularly challenging in terms of current immunotherapy but hold great opportunity for impact given that they constitute the highest cancer incidence and mortality rates worldwide. Traditional treatment options for solid GI malignancies include surgical intervention, chemotherapy, radiation, or a combination of these treatments. Emerging modalities within immunotherapy are anticipated to extend the results with conventional therapy by stimulating the patient’s own intrinsic potential for tumor-specific immunologic rejection. Combination regimens of chemotherapy and tumor-infiltrating lymphocyte (TIL) therapy in advanced colorectal cancer and pancreatic cancer, autologous monocyte therapy in advanced gastric cancer, and CAR-T therapy trained against GI-selective tumor antigens such as carcinoembryonic antigen are currently being studied. Clinical trials are underway to study the combination of various chemotherapeutic agents along with immunotherapy in the management of cholangiocarcinoma, hepatocellular carcinoma, and esophageal cancer. Alternative therapies are needed based on the tumor immune microenvironment, which can lead to a personalized approach to treatment. In this review, we discuss the current status of various modalities of immunotherapy in common GI malignancies, along with their mechanisms of immune activation and cancer suppression. We will also discuss the use of immunotherapy in less common solid GI malignancies and touch on recent advancements and clinical trials.
Full article
(This article belongs to the Special Issue Gene and Cell Therapy: New Findings from Medical Research and Treatment)
►▼
Show Figures

Graphical abstract
Open AccessArticle
Magnetic Resonance Imaging Evaluation of Photodynamic Therapy with Indocyanine Green in Atherosclerosis Plaques Before and After Gadovist Administration
by
Piotr Wańczura, Wiktoria Mytych, Dorota Bartusik-Aebisher, Dawid Leksa, Adrian Truszkiewicz and David Aebisher
Int. J. Transl. Med. 2025, 5(3), 32; https://doi.org/10.3390/ijtm5030032 - 25 Jul 2025
Abstract
►▼
Show Figures
Background: Singlet oxygen (1O2) generation in biological samples remains a significant challenge. Studying the mechanism of 1O2 action during photodynamic therapy (PDT) in atherosclerotic plaques in vitro represents an innovative cardiological approach. Atherosclerosis, a chronic and progressive
[...] Read more.
Background: Singlet oxygen (1O2) generation in biological samples remains a significant challenge. Studying the mechanism of 1O2 action during photodynamic therapy (PDT) in atherosclerotic plaques in vitro represents an innovative cardiological approach. Atherosclerosis, a chronic and progressive disease, is characterized by plaque buildup inside arterial walls. Objectives: This study focused on the use of spin–lattice (T1) and spin–spin (T2) relaxation times measured by Magnetic Resonance Imaging (MRI) before and after the administration of indocyanine green-mediated PDT (ICG-PDT). Methods: To enhance visualization of morphological changes in atherosclerotic plaques, the clinically approved MRI contrast agent Gadovist was utilized. A total of 12 atherosclerotic plaque samples were collected from six patients undergoing endarterectomy. The generation of 1O2 in these plaques was assessed using quantitative MRI measurements and microscopic imaging, which visualized structural changes induced by PDT. Results: This research explores the potential of T1 and T2 relaxation times as indicators of PDT efficacy, while Gadovist helped provide evidence of 1O2 diffusion within the samples. Conclusions: Considering advancements in modern treatment, PDT may offer a novel approach for targeting atherosclerosis.
Full article

Figure 1
Open AccessReview
Targeting Drug-Resistant Epilepsy: A Narrative Review of Five Novel Antiseizure Medications
by
Guillermo de Jesús Aguirre-Vera, Luisa Montufar, María Fernanda Tejada-Pineda, María Paula Fernandez Gomez, Andres Alvarez-Pinzon, José E. Valerio and Eder Luna-Ceron
Int. J. Transl. Med. 2025, 5(3), 31; https://doi.org/10.3390/ijtm5030031 - 22 Jul 2025
Abstract
►▼
Show Figures
Epilepsy remains a major therapeutic challenge, with approximately one-third of patients experiencing drug-resistant epilepsy (DRE) despite the availability of multiple antiseizure medications (ASMs). This review aims to evaluate emerging ASMs—cenobamate, fenfluramine, ganaxolone, ezogabine (retigabine), and perampanel—with a focus on their mechanisms of action,
[...] Read more.
Epilepsy remains a major therapeutic challenge, with approximately one-third of patients experiencing drug-resistant epilepsy (DRE) despite the availability of multiple antiseizure medications (ASMs). This review aims to evaluate emerging ASMs—cenobamate, fenfluramine, ganaxolone, ezogabine (retigabine), and perampanel—with a focus on their mechanisms of action, pharmacological profiles, and potential role in precision medicine. A comprehensive literature search was conducted using PubMed, Scopus, and Web of Science to identify preclinical and clinical studies evaluating the pharmacodynamics, pharmacokinetics, efficacy, and safety of the selected ASMs. Relevant trials, reviews, and mechanistic studies were reviewed to synthesize the current understanding of their application in DRE and specific epilepsy syndromes. Each ASM demonstrated unique mechanisms targeting hyperexcitability, including the modulation of γ-aminobutyric acid receptor A (GABA-A) receptors, sodium and potassium channels, α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPA receptors), and serotonin systems. These mechanisms correspond with specific pathophysiological features in syndromes such as Dravet and Lennox–Gastaut. Evidence from clinical trials supports their use as adjunctive therapies with generally favorable tolerability, though adverse events and variable efficacy profiles were noted. The mechanistic diversity of these emerging ASMs supports their value in personalized epilepsy management, particularly in treatment-resistant cases. While the promise of precision medicine is evident, further studies are required to address challenges related to long-term safety, cost, and equitable access.
Full article

Figure 1
Open AccessReview
Hyperuricemia and Insulin Resistance: Interplay and Potential for Targeted Therapies
by
Opeyemi. O. Deji-Oloruntoba, James Onoruoiza Balogun, Taiwo. O. Elufioye and Simeon Okechukwu Ajakwe
Int. J. Transl. Med. 2025, 5(3), 30; https://doi.org/10.3390/ijtm5030030 - 10 Jul 2025
Abstract
Hyperuricemia, defined as elevated serum uric acid (SUA) levels (>6.8 mg/dL), is traditionally linked to gout and nephrolithiasis but is increasingly implicated in insulin resistance (IR) and type 2 diabetes mellitus (T2DM). Epidemiological studies, such as NHANES, suggest hyperuricemia increases the risk of
[...] Read more.
Hyperuricemia, defined as elevated serum uric acid (SUA) levels (>6.8 mg/dL), is traditionally linked to gout and nephrolithiasis but is increasingly implicated in insulin resistance (IR) and type 2 diabetes mellitus (T2DM). Epidemiological studies, such as NHANES, suggest hyperuricemia increases the risk of T2DM by 1.6 to 2.5 times. Mechanistically, uric acid promotes IR via oxidative stress, chronic inflammation, endothelial dysfunction, and adipocyte dysregulation. Despite growing evidence, significant gaps remain in understanding these pathways, with existing studies often limited by observational designs and short intervention durations. A bibliographic analysis of studies from 2004–2024 using Web of Science and VOSviewer highlights a growing focus on hyperuricemia’s interplay with inflammation, oxidative stress, and metabolic disorders. However, inconsistencies in therapeutic outcomes and limited exploration of causality underscore the need for further research. We also explored the importance of gender stratification and the limitations of the binary model for the relationship between hyperuricemia and insulin resistance. This review emphasizes the importance of addressing these gaps to optimize hyperuricemia management as a potential strategy for diabetes prevention and metabolic health improvement.
Full article
(This article belongs to the Collection Feature Papers in International Journal of Translational Medicine)
►▼
Show Figures

Figure 1
Open AccessArticle
Loss of 4.1B Drives PRMT3-Mediated Regulation of GBM Brain Tumour Stem Cell Growth
by
Ravinder K. Bahia, Kyle Heemskerk, Samir Assaf, Orsolya Cseh, Xiaoguang Hao, Rozina Hassam, Panagiotis Prinos, H. Artee Luchman and Samuel Weiss
Int. J. Transl. Med. 2025, 5(3), 29; https://doi.org/10.3390/ijtm5030029 - 7 Jul 2025
Abstract
►▼
Show Figures
Background: Protein arginine methyltransferase 3 (PRMT3), a type I family PRMT, regulates the activity of downstream substrates by catalyzing the asymmetric dimethylation of arginine residues. While PRMT3 activity has been reported to be deregulated in many cancers, including glioblastoma (GBM), the underlying signalling
[...] Read more.
Background: Protein arginine methyltransferase 3 (PRMT3), a type I family PRMT, regulates the activity of downstream substrates by catalyzing the asymmetric dimethylation of arginine residues. While PRMT3 activity has been reported to be deregulated in many cancers, including glioblastoma (GBM), the underlying signalling mechanisms that contribute to disease progression are largely unknown. Methods: We tested the efficacy of a PRMT3 chemical probe, SGC707, in a cohort of GBM patient-derived primary and recurrent brain tumour stem cell (BTSC) lines. RNA-sequencing, CRISPR-cas9 knockout, and inducible overexpression methods were used to investigate the molecular mechanisms regulated by the aberrant activity of PRMT3 in different BTSC lines. Results: We show that expression of the tumour suppressor protein 4.1B, a negative regulator of PRMT3, predicts the response of GBM BTSCs to the PRMT3 chemical probe, SGC707. Furthermore, PRMT3 modulates the stability and subcellular localization of the downstream effector, UHRF1, a member of the DNA methylation complex. These findings suggest that UHRF1 and DNMT1 may suppress the expression of 4.1B through the increased promoter methylation of EPB4.1L3. Intriguingly, the inducible overexpression of EPB4.1L3 in the BT248EPB4.1L3low BTSC line mimicked the effects of the pharmacologic and genetic inhibition of PRMT3. In contrast, knockout of EPB4.1L3 in BT143EPB4.1L3high cells reduced the interactions between PRMT3 and 4.1B proteins, resulting in increased sensitivity of knockout cells to SGC707 treatment. Conclusions: These findings show that 4.1B, PRMT3, and UHRF1/DNMT1 function together to promote BTSC growth. Thus, targeting PRMT3 or UHRF1/DNMT1, especially in tumours with low endogenous 4.1B protein, may have high therapeutic relevance.
Full article

Figure 1
Open AccessReview
Protein Engineering Paving the Way for Next-Generation Therapies in Cancer
by
Zahra Naderiyan and Alireza Shoari
Int. J. Transl. Med. 2025, 5(3), 28; https://doi.org/10.3390/ijtm5030028 - 6 Jul 2025
Abstract
►▼
Show Figures
Cancer continues to be a leading cause of global mortality, necessitating innovative therapeutic strategies to address its complexity and heterogeneity. Protein engineering has emerged as a transformative approach in developing cancer biotherapeutics, enabling the creation of highly specific, potent, and adaptable treatments. This
[...] Read more.
Cancer continues to be a leading cause of global mortality, necessitating innovative therapeutic strategies to address its complexity and heterogeneity. Protein engineering has emerged as a transformative approach in developing cancer biotherapeutics, enabling the creation of highly specific, potent, and adaptable treatments. This paper provides a comprehensive review of the state-of-the-art in protein engineering, highlighting key techniques such as directed evolution, rational design, and hybrid approaches that underpin the development of monoclonal antibodies, bispecific antibodies, and novel fusion proteins. Case studies of FDA-approved therapies, including engineered monoclonal antibodies like trastuzumab and bispecific T-cell engagers such as blinatumomab, are discussed to illustrate the impact of these advancements. Furthermore, emerging trends, including AI-driven protein design and synthetic biology applications, are explored alongside their potential to revolutionize future cancer treatments. Challenges such as immunogenicity, stability, and scalability are critically evaluated, offering insights into potential solutions and future research directions. By synthesizing advancements in protein science and oncology, this paper aims to guide researchers and clinicians in harnessing the full potential of engineered proteins for cancer therapy.
Full article

Figure 1
Open AccessReview
Exploiting Synthetic Lethality of PRMT5 for Precision Treatment of MTAP-Deficient Glioblastoma
by
Trang T. T. Nguyen, Eunhee Yi and Christian E. Badr
Int. J. Transl. Med. 2025, 5(3), 27; https://doi.org/10.3390/ijtm5030027 - 29 Jun 2025
Abstract
Glioblastoma (GBM) is the most aggressive primary brain tumor in adults, characterized by a dismal prognosis and limited therapeutic options. Its highly invasive nature and pronounced intratumoral heterogeneity underscores the urgent need for innovative and targeted therapeutic strategies. One promising approach is synthetic
[...] Read more.
Glioblastoma (GBM) is the most aggressive primary brain tumor in adults, characterized by a dismal prognosis and limited therapeutic options. Its highly invasive nature and pronounced intratumoral heterogeneity underscores the urgent need for innovative and targeted therapeutic strategies. One promising approach is synthetic lethality, which exploits cancer-specific genetic vulnerabilities to selectively eliminate tumor cells. A well-characterized example involves the deletion of methylthioadenosine phosphorylase (MTAP), commonly observed in GBM and other malignancies. This review focuses on synthetic lethality targeting protein arginine methyltransferase 5 (PRMT5) in MTAP-deleted GBM. Loss of MTAP leads to the accumulation of methylthioadenosine (MTA), a metabolite that partially inhibits PRMT5, thereby creating a selective vulnerability to PRMT5 inhibition which is used to inhibit the residual function of PRMT5. We critically evaluate preclinical and clinical data on both first- and second-generation PRMT5 inhibitors, with particular emphasis on MTA-cooperative compounds that selectively exploit MTAP deficiency. Despite promising anti-tumor activity in vitro, the clinical efficacy of PRMT5 inhibitors is often limited by the tumor microenvironment, particularly the impact of non-malignant cells that attenuate drug activity. Finally, we explore rational combination strategies that integrate PRMT5 inhibition with existing therapies to enhance clinical outcomes in GBM.
Full article
(This article belongs to the Collection Feature Papers in International Journal of Translational Medicine)
►▼
Show Figures

Figure 1
Open AccessArticle
Decoding the CD36-Centric Axis in Gastric Cancer: Insights into Lipid Metabolism, Obesity, and Hypercholesterolemia
by
Preyangsee Dutta, Dwaipayan Saha, Atanu Giri, Aseem Rai Bhatnagar and Abhijit Chakraborty
Int. J. Transl. Med. 2025, 5(3), 26; https://doi.org/10.3390/ijtm5030026 - 23 Jun 2025
Abstract
►▼
Show Figures
Background: Gastric cancer is a leading cause of cancer-related mortality worldwide, with approximately one million new cases diagnosed annually. While Helicobacter pylori infection remains a primary etiological factor, mounting evidence implicates obesity and lipid metabolic dysregulation, particularly in hypercholesterolemia, as emerging drivers of
[...] Read more.
Background: Gastric cancer is a leading cause of cancer-related mortality worldwide, with approximately one million new cases diagnosed annually. While Helicobacter pylori infection remains a primary etiological factor, mounting evidence implicates obesity and lipid metabolic dysregulation, particularly in hypercholesterolemia, as emerging drivers of gastric tumorigenesis. This study investigates the molecular intersections between gastric cancer, obesity, and hypercholesterolemia through a comprehensive multi-omics and systems biology approach. Methods: We conducted integrative transcriptomic analysis of gastric adenocarcinoma using The Cancer Genome Atlas (TCGA) RNA-sequencing dataset (n = 623, 8863 genes), matched with standardized clinical metadata (n = 413). Differential gene expression between survival groups was assessed using Welch’s t-test with Benjamini–Hochberg correction (FDR < 0.05, |log2FC| ≥ 1). High-confidence gene sets for obesity (n = 128) and hypercholesterolemia (n = 97) were curated from the OMIM, STRING (confidence ≥ 0.7), and KEGG databases using hierarchical evidence-based prioritization. Overlapping gene signatures were identified, followed by pathway enrichment via Enrichr (KEGG 2021 Human) and protein–protein interaction (PPI) analysis using STRING v11.5 and Cytoscape v3.9.0. CD36’s prognostic value was evaluated via Kaplan–Meier and log-rank testing alongside clinicopathological correlations. Results: We identified 36 genes shared between obesity and gastric cancer, and 31 genes shared between hypercholesterolemia and gastric cancer. CD36 emerged as the only gene intersecting all three conditions, marking it as a unique molecular integrator. Enrichment analyses implicated dysregulated fatty acid uptake, adipocytokine signaling, cholesterol metabolism, and NF-κB-mediated inflammation as key pathways. Elevated CD36 expression was significantly correlated with higher tumor stage (p = 0.016), reduced overall survival (p = 0.001), and race-specific expression differences (p = 0.007). No sex-based differences in CD36 expression or survival were observed. Conclusions: CD36 is a central metabolic–oncogenic node linking obesity, hypercholesterolemia, and gastric cancer. It functions as both a mechanistic driver of tumor progression and a clinically actionable biomarker, particularly in metabolically comorbid patients. These findings provide a rationale for targeting CD36-driven pathways as part of a precision oncology strategy and highlight the need to incorporate metabolic profiling into gastric cancer risk assessment and treatment paradigms.
Full article

Figure 1
Open AccessReview
Novel Roles and Therapeutic Approaches Linking Platelets and Megakaryocytes to Non-Hemostatic and Thrombotic Disease
by
Ana Kasirer-Friede
Int. J. Transl. Med. 2025, 5(3), 25; https://doi.org/10.3390/ijtm5030025 - 22 Jun 2025
Abstract
►▼
Show Figures
Historically, pharmacological interventions aimed at platelets have targeted their canonical hemostatic and thrombotic roles. The therapeutic vision, however, has minimally embraced alternate mechanisms by which anucleate platelets, their parent cells, megakaryocytes, and cellular derivatives may be utilized to yield novel and effective therapies.
[...] Read more.
Historically, pharmacological interventions aimed at platelets have targeted their canonical hemostatic and thrombotic roles. The therapeutic vision, however, has minimally embraced alternate mechanisms by which anucleate platelets, their parent cells, megakaryocytes, and cellular derivatives may be utilized to yield novel and effective therapies. Platelets contain storage granules rich in a wide variety of proteins, chemicals, growth factors, and lipid particles that can modulate the fate and activity of diverse cell types, and impact diseases not previously thought to have a platelet component. In this article, we will address unconventional platelet contributions to health and disease development. Recent studies indicate extensive platelet roles in neurodegeneration, insulin secretion, and bone marrow fibrosis, along with a recognition of platelets as immune cells in their own right, partially based on the presence of surface MHC, Toll-like receptors, and stored immunomodulatory molecules. Recent technological advances have produced iPS-derived gene-editable megakaryocytes (MKs) that have been differentiated to clinical-grade platelets for transfusion; however, such successes are still rare. Continued improvements in the standardization of cell isolation, iPS differentiation protocols, technology for the utilization of platelet derivatives, and platelet Omics will expand our understanding of underlying platelet and MK heterogeneity and direct novel therapeutic applications. Furthermore, additional roles for these cells as microniche sensors that monitor systemic pathology by endocytosing shed particles as they circulate through the vasculature will be explored. Taken together, novel insights into the many exciting potential uses of platelets outside of their canonical roles are on the horizon, and continued amelioration of existing protocols and enhanced understanding of communication pathways between platelets and specific cells will help expand opportunities for platelet-related clinical trials to yield improved health outcomes.
Full article

Figure 1
Open AccessReview
Management of Chronic Pain Associated with Small Fiber Neuropathy Secondary to SARS-CoV-2
by
Anirudh Bhimavarapu, Hana Mucevic, Sadiq Rahman and Amruta Desai
Int. J. Transl. Med. 2025, 5(2), 24; https://doi.org/10.3390/ijtm5020024 - 13 Jun 2025
Abstract
►▼
Show Figures
Neuropathic pain has emerged as a significant concern for patients dealing with persistent post-COVID-19 symptoms. Small fiber neuropathy (SFN) has been identified as a potential underlying mechanism contributing to long-term pain in these patients. Despite an increasing body of evidence associating post-COVID-19 SFN
[...] Read more.
Neuropathic pain has emerged as a significant concern for patients dealing with persistent post-COVID-19 symptoms. Small fiber neuropathy (SFN) has been identified as a potential underlying mechanism contributing to long-term pain in these patients. Despite an increasing body of evidence associating post-COVID-19 SFN with immune dysregulation and neuroinflammation, the exact pathophysiology and optimal treatment remains unclear. This review aims to explore the pathophysiology, diagnosis, proposed mechanisms, and treatment of post-COVID-19 SFN. A comprehensive literature review was conducted, examining studies on SFN, as well as SFN in the context of COVID-19, including clinical manifestations, diagnostic criteria, and potential treatment modalities. Evidence was gathered from case studies, observational reports, and clinical trials addressing post-COVID-19 neuropathy and SFN. SFN in long COVID presents a heterogeneous range of sensory and autonomic symptoms. Diagnosis relies on clinical evaluation, quantitative sensory testing, and confirmatory skin biopsy. Proposed mechanisms include autoimmune dysregulation, molecular mimicry, direct viral invasion of neural structures, and inflammatory responses. Pharmacological treatments—such as gabapentin, antidepressants, and corticosteroids—have demonstrated symptom relief, while immunomodulatory therapies show promise in immune-mediated cases. Non-pharmacological strategies warrant further investigation. Post-COVID-19 SFN represents a complex and multifactorial condition requiring a multidisciplinary approach to diagnosis and management. While merging evidence supports immune-mediated pathogenesis, further research is needed to establish definitive mechanisms and optimize targeted therapeutic strategies. Continued investigation into post-COVID-19 SFN will be crucial in addressing the long-term neurological sequelae of SARS-CoV-2 infection.
Full article

Figure 1
Open AccessArticle
A Randomized, Placebo-Controlled, Double-Blind Trial to Assess the Effects of Apocynum venetum L. (A. venetum) Venetron® on Sleep and Stress in Those Expressing Feelings of Anxiety
by
Kaitlyn P. White, Susan Hewlings, Corey Bryant, Megan Moseley, Christopher R. D’Adamo, Christopher S. Colwell, Jeff Chen and Emily K. Pauli
Int. J. Transl. Med. 2025, 5(2), 23; https://doi.org/10.3390/ijtm5020023 - 13 Jun 2025
Abstract
►▼
Show Figures
Background/Objectives: Anxiety and stress are interrelated and connected to reduced health-related quality of life. Botanicals such as Apocynum venetum L. (A. venetum) have been shown to improve health outcomes. No human studies have been conducted in a diverse large group of
[...] Read more.
Background/Objectives: Anxiety and stress are interrelated and connected to reduced health-related quality of life. Botanicals such as Apocynum venetum L. (A. venetum) have been shown to improve health outcomes. No human studies have been conducted in a diverse large group of healthy adults in the US. The purpose of this randomized, double-blind, placebo-controlled study was to evaluate the effects of Venetron® Rafuma (A. venetum leaf extract) on self-reported anxiety levels and overall health outcomes compared to placebo. Methods: Healthy adults (N = 476) seeking improvement in self-reported anxiety and stress were randomly assigned to receive 50 mg of A. venetum (n = 234) or placebo (n = 242) for 6 weeks. Feelings of anxiety were assessed at baseline and weekly using Patient-Reported Outcomes Measurement Information System (PROMIS™) Anxiety 8A. Perceived stress, sleep quality, and cognitive function were evaluated at baseline and weekly using validated assessments. A linear mixed-effects regression model was used to compare the change in health outcome scores between active and placebo groups. Results: A total of 370 participants completed at least one additional assessment and were included in the analysis: 179 in the active arm and 191 in the placebo arm. There was a significant difference between the groups in the rate of improvement in perceived stress and sleep disturbance. The active group was significantly more likely to experience a Minimal Clinically Important Difference (MCID) in their perceived stress and marginally significantly more likely to experience an MCID in their feelings of anxiety. Participants who reported experiencing side effects did not significantly differ between arms. Conclusions: Venetron® may be safe and effective therapy for stress and sleep disturbance among those suffering from feelings of anxiety.
Full article

Figure 1
Open AccessArticle
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
►▼
Show Figures
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

Figure 1
Highly Accessed Articles
Latest Books
E-Mail Alert
News
Topics
Topic in
Biophysica, CIMB, Diagnostics, IJMS, IJTM
Molecular Radiobiology of Protons Compared to Other Low Linear Energy Transfer (LET) Radiation
Topic Editors: Francis Cucinotta, Jacob RaberDeadline: 20 December 2025
Topic in
IJMS, Metabolites, Molecules, Proteomes, Biomedicines, IJTM
Liquid Biopsy: A Modern Method Transforming Biomedicine
Topic Editors: Michele Costanzo, Marianna CaterinoDeadline: 31 March 2026
Topic in
Cancers, CIMB, Current Oncology, Sci. Pharm., Antibodies, IJMS, IJTM
Antibody-Mediated Therapy and Other Emerging Therapies in Cancer Treatment
Topic Editors: Won Sup Lee, Yaewon Yang, Seil GoDeadline: 31 July 2026

Conferences
Special Issues
Special Issue in
IJTM
Bacterial Based Cancer Treatment
Guest Editor: Haim LevyDeadline: 31 August 2025
Special Issue in
IJTM
Gene and Cell Therapy: New Findings from Medical Research and Treatment
Guest Editors: Lorella Tripodi, Antonio Di StasiDeadline: 31 October 2025
Topical Collections
Topical Collection in
IJTM
Feature Papers in International Journal of Translational Medicine
Collection Editor: Joan Oliva