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Int. J. Transl. Med., Volume 5, Issue 1 (March 2025) – 7 articles

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27 pages, 2692 KiB  
Review
Therapeutic Strategies for MASH: An Update on Drug Candidates Under Investigation in Late-Phase Clinical Trials
by Samuel Dinerman and Yan Shu
Int. J. Transl. Med. 2025, 5(1), 7; https://doi.org/10.3390/ijtm5010007 - 17 Jan 2025
Viewed by 591
Abstract
Metabolic dysfunction-associated steatohepatitis (MASH) is rapidly becoming a leading cause of hepatocellular carcinoma and end-stage liver transplantation. Characterized by hepatic steatosis, lobular inflammation, and hepatocyte ballooning, there is a dire need to develop therapeutic strategies to mitigate MASH alongside the subsequent fibrosis and [...] Read more.
Metabolic dysfunction-associated steatohepatitis (MASH) is rapidly becoming a leading cause of hepatocellular carcinoma and end-stage liver transplantation. Characterized by hepatic steatosis, lobular inflammation, and hepatocyte ballooning, there is a dire need to develop therapeutic strategies to mitigate MASH alongside the subsequent fibrosis and cirrhosis. For years, therapeutic development for the treatment of MASH had been considered a graveyard, with various pharmacotherapies failing to achieve clinical efficacy. However, the recent Food and Drug Administration (FDA) approval of Madrigal Pharmaceuticals’ Resmetirom in the United States provides a positive step in the collective effort to eradicate MASH. Granted, with much about Resmetirom’s long-term efficacy and safety still to be determined and with the multi-factorial nature of MASH pathogenesis, continuing to evaluate alternative therapeutic options remains in the best interest of the field. Currently, therapeutics previously approved for other ailments, alongside novel therapeutics developed specifically for the treatment of MASH, are being evaluated in late-phase clinical trials. However, considering the complex nature of the disease and varying clinical outcomes to assess treatment efficacy, achieving regulatory approval as a MASH therapeutic continues to be a rigorous endeavor. In this review, we summarize notable therapeutics of various mechanistic backgrounds having achieved, or actively undergoing, late-phase clinical trials for the treatment of MASH and offer our perspectives on anti-MASH therapeutic development. Full article
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23 pages, 3539 KiB  
Review
Emerging Strategies to Overcome Chemoresistance: Structural Insights and Therapeutic Targeting of Multidrug Resistance-Linked ATP-Binding Cassette Transporters
by Raghavendra Sashi Krishna Nagampalli, Gangadhar P. Vadla and Eswar Kumar Nadendla
Int. J. Transl. Med. 2025, 5(1), 6; https://doi.org/10.3390/ijtm5010006 - 10 Jan 2025
Viewed by 497
Abstract
The ATP-binding cassette (ABC) transporter superfamily, one of the largest membrane protein families, plays a crucial role in multidrug resistance (MDR) in cancer by mediating the efflux of various chemotherapeutic agents, thereby lowering their intracellular concentrations and diminishing therapeutic effectiveness. Beyond drug efflux, [...] Read more.
The ATP-binding cassette (ABC) transporter superfamily, one of the largest membrane protein families, plays a crucial role in multidrug resistance (MDR) in cancer by mediating the efflux of various chemotherapeutic agents, thereby lowering their intracellular concentrations and diminishing therapeutic effectiveness. Beyond drug efflux, these transporters are also involved in vital biological processes, such as signal transduction in cancer. Over the past few decades, extensive structural and functional research has provided valuable insights into ABC transporters’ broad substrate specificity and transport mechanisms, leading to promising strategies for overcoming MDR. This review will provide a structural understanding of the interactions between ABC transporters and inhibitors to develop novel cancer therapeutics. Additionally, we focus on methods such as irradiation-based immune therapies, thermal therapies, nanomedicine, CRISPR-Cas, and natural therapies that can genetically modify ABC transporters to reduce their expression or reverse the drug efflux ability. Knowledge gained from these approaches can then be translated into the development of new cancer therapeutics that can combat chemotherapy resistance. Full article
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12 pages, 1090 KiB  
Article
Acute Effects of Wild Ginseng Extract on Exercise Performance, Cognitive Function, and Fatigue Recovery: A Randomized Cross-Over, Placebo-Controlled, and Double-Blind Study
by Sukho Lee, Hyun Chul Jung, Michael Sargent and Minsoo Kang
Int. J. Transl. Med. 2025, 5(1), 5; https://doi.org/10.3390/ijtm5010005 - 6 Jan 2025
Viewed by 616
Abstract
This study aimed to investigate the acute effects of wild ginseng extract (Panax ginseng C.A. Meyer) on exercise performance, cognitive function, and fatigue recovery. Methods: Twelve healthy male participants were randomly assigned to receive either wild ginseng extract (WG) or a placebo [...] Read more.
This study aimed to investigate the acute effects of wild ginseng extract (Panax ginseng C.A. Meyer) on exercise performance, cognitive function, and fatigue recovery. Methods: Twelve healthy male participants were randomly assigned to receive either wild ginseng extract (WG) or a placebo prior to exercise trials, utilizing a double-blind, placebo-controlled cross-over design. The exercise protocol included 30 min cycling exercises followed by a 10-mile time trial, during which muscular power, strength, endurance, cognitive function, and fatigue were assessed. Additionally, biomarkers such as glucose, interleukin-6 (IL-6), myoglobin, total antioxidant capacity (TAC), and cortisol were measured. Repeated measures ANOVAs were used to analyze the effects of acute WG intake on the dependent variables. Results: In the placebo condition, both peak and mean power levels significantly decreased over time (p = 0.039 and p = 0.028, respectively), whereas no such decline was observed in the WG condition (p > 0.05). Furthermore, average reaction time (ART) was significantly delayed over time in the placebo trial (p = 0.005), while ART remained stable in the WG trial (p = 0.051). A significant increase in TAC was observed across time in the WG trial (p = 0.036), but no change was found in the placebo trial (p = 0.326). Cortisol levels significantly decreased over time in the WG trial (p = 0.001), while no change was observed in the placebo trial (p = 0.141). No significant differences were found for other variables between the WG and placebo trials (p > 0.05). Conclusions: The acute supplementation with WG positively influenced exercise performance by maintaining muscular power, reducing reaction time delay, and enhancing antioxidant capacity and cortisol regulation. These findings suggest that WG may be a promising ergogenic aid for improving exercise performance and recovery. NCT06679725 (ClinicalTrials.gov). Full article
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9 pages, 1211 KiB  
Review
Challenges of Porcine Wound Models: A Review
by Margarita Elloso, Maria Fernanda Hutter, Nicklas Jeschke, Graham Rix, Yufei Chen, Alisa Douglas and Marc G. Jeschke
Int. J. Transl. Med. 2025, 5(1), 4; https://doi.org/10.3390/ijtm5010004 - 2 Jan 2025
Viewed by 494
Abstract
Pigs are important translational research models for wound healing due to their skin, which is similar to human skin in terms of anatomy and physiology. Porcine wound models have been developed and used for years to study wound healing and evaluate various therapeutic [...] Read more.
Pigs are important translational research models for wound healing due to their skin, which is similar to human skin in terms of anatomy and physiology. Porcine wound models have been developed and used for years to study wound healing and evaluate various therapeutic agents. However, the study of porcine wound healing is multilayered as it involves not just the complex biological processes of wound healing but also cost, animal housing, handling, staff experience, and challenges such as procedural risks and human resources. In this review article, we discuss the various challenges of the model. Investigators using pig models should be well informed of the challenges of the porcine wound model to prevent possible problems and complications. Full article
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8 pages, 4648 KiB  
Case Report
Clinical Course of Parotid Carcinoma with Hepatic and Nodal Metastases: A Case Report
by Antonio Doronzo, Giovanni Musci, Gennaro Gadaleta-Caldarola and Maria Chiara Sergi
Int. J. Transl. Med. 2025, 5(1), 3; https://doi.org/10.3390/ijtm5010003 - 25 Dec 2024
Viewed by 427
Abstract
Background: Salivary gland tumors are relatively rare neoplasms, comprising approximately 3–6% of all head and neck tumors. Parotid gland carcinoma (PGC) represents approximately 70–80% of all salivary gland malignancies. Treatment strategies depend on tumor histology, stage, and molecular characteristics, with surgical resection [...] Read more.
Background: Salivary gland tumors are relatively rare neoplasms, comprising approximately 3–6% of all head and neck tumors. Parotid gland carcinoma (PGC) represents approximately 70–80% of all salivary gland malignancies. Treatment strategies depend on tumor histology, stage, and molecular characteristics, with surgical resection and adjuvant radiotherapy being the mainstays of treatment for localized disease. Conversely, in advanced stages, therapeutic approaches, including chemotherapy and targeted agents, are more challenging. Methods: We present a case report of a 60-year-old patient with hepatic and nodal metastases of parotid gland carcinoma HER2+ who received dual blockade with Pertuzumab and trastuzumab (PH) with addition of Docetaxel, with the aim of highlighting the management and treatment outcomes. Results: Our patient received 4 cycles of chemotherapy and PH with near-complete response. After lymph node dissection (level I–IV) with primitive tumor resection and radiosurgery on the residual liver metastases, currently she continues treatment as maintenance. Conclusions: Based on the patient’s overall condition and response to current treatment, the oncology team ought to consider further targeted therapies, radiotherapy, or surgery as future therapeutic options. Full article
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10 pages, 1235 KiB  
Case Report
Evaluation of the Timed Up and Go Test in Patients with Knee Osteoarthritis Using Inertial Sensors
by Elina Gianzina, Christos K. Yiannakopoulos, Georgios Kalinterakis, Spilios Delis and Efstathios Chronopoulos
Int. J. Transl. Med. 2025, 5(1), 2; https://doi.org/10.3390/ijtm5010002 - 25 Dec 2024
Viewed by 406
Abstract
Background: There has been a growing interest in using inertial sensors to explore the temporal aspects of the Timed Up and Go (TUG) test. The current study aimed to analyze the spatiotemporal parameters and phases of the TUG test in patients with knee [...] Read more.
Background: There has been a growing interest in using inertial sensors to explore the temporal aspects of the Timed Up and Go (TUG) test. The current study aimed to analyze the spatiotemporal parameters and phases of the TUG test in patients with knee osteoarthritis (KOA) and compare the results with those of non-arthritic individuals. Methods: This study included 20 patients with KOA and 60 non-arthritic individuals aged 65 to 84 years. All participants performed the TUG test, and 17 spatiotemporal parameters and phase data were collected wirelessly using the BTS G-Walk inertial sensor. Results: Significant mobility impairments were observed in KOA patients, including slower gait speed, impaired sit-to-stand transitions, and reduced turning efficiency. These findings highlight functional deficits in individuals with KOA compared to their non-arthritic counterparts. Conclusions: The results emphasize the need for targeted physiotherapy interventions, such as quadriceps strengthening, balance training, and gait retraining, to address these deficits. However, the study is limited by its small sample size, gender imbalance, and limited validation of the BTS G-Walk device. Future research should include larger, more balanced cohorts, validate sensor reliability, and conduct longitudinal studies. Despite these limitations, the findings align with previous research and underscore the potential of inertial sensors in tailoring rehabilitation strategies and monitoring progress in KOA patients. Full article
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15 pages, 1648 KiB  
Review
The Druggable Target Potential of NF-κB-Inducing Kinase (NIK) in Cancer
by Yina Wang and Liangyou Rui
Int. J. Transl. Med. 2025, 5(1), 1; https://doi.org/10.3390/ijtm5010001 - 25 Dec 2024
Viewed by 633
Abstract
NF-κB-inducing kinase (NIK) is primarily recognized for its role as the apical kinase that activates non-canonical NF-κB signaling and its involvement in immune system regulation. NIK is crucial for maintaining cellular health by regulating fundamental processes such as differentiation, growth, and survival. Emerging [...] Read more.
NF-κB-inducing kinase (NIK) is primarily recognized for its role as the apical kinase that activates non-canonical NF-κB signaling and its involvement in immune system regulation. NIK is crucial for maintaining cellular health by regulating fundamental processes such as differentiation, growth, and survival. Emerging evidence suggests that dysregulated expression or function of NIK in non-lymphoid cells is a key factor in cancer progression. While NIK deficiency causes severe immune dysfunction, its overexpression or excessive activation is linked to inflammatory diseases, metabolic disorders, and cancer development. The development of small molecule inhibitors targeting NIK has sparked optimism for clinical intervention, positioning NIK as a promising druggable mediator for cancer. The ongoing progress in creating novel small molecule NIK inhibitors offers new opportunities for testing NIK-targeted cancer therapies, potentially advancing the clinical application of NIK-based cancer treatments. Full article
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