Int. J. Transl. Med., Volume 5, Issue 1 (March 2025) – 12 articles

Background/Objectives: Cancer-associated fibroblasts (CAFs), which are an important component of the tumor microenvironment, have been reported to have an adverse effect on conventional radiotherapy. This study aims to elucidate the effects of CAFs in boron neutron capture therapy (BNCT) using a three-dimensional (3D) oral cancer model. Methods: Three-dimensional cancer models were fabricated using patient-derived CAFs or patient-derived normal oral fibroblasts (NOFs) and a human oral squamous cell carcinoma cell line. Each 3D cancer model was performed with either a conventional X-ray treatment or BNCT and additionally analyzed histomorphologically. Results: The 3D oral cancer-CAFs model demonstrated a greater depth of cancer cell invasion than the 3D oral cancer-NOFs model. Radiation therapy for the 3D oral cancer models indicated a trend for decreasing cancer cell invasion and cell number with dose dependence in both X-ray and BNCT. In comparison with X-rays, BNCT showed a consistent increase in the number of NOFs and a significant reduction in the number of CAFs. Conclusions: BNCT for the 3D oral cancer model was shown to be effective against cancer cells and CAFs but not against NOFs, indicating its usefulness as a minimally invasive treatment for advanced cancer. Furthermore, it is indicated that the 3D oral cancer-CAFs model is a valuable tool to evaluate cancer treatment and research, particularly in high-grade malignant tumors with invasion. Full article

Background: Cystic Fibrosis is an inherited disorder caused by mutations in the Cystic Fibrosis Transmembrane conductance Regulator (CFTR) gene, encoding a chloride and bicarbonate channel widely expressed in epithelia. Loss of CFTR function leads to dehydration of the epithelium surface with thicker mucus secretions from tissues. The lungs, pancreas, liver, intestines, and sweat glands are the most common affected organs. However, pulmonary disease remains the main cause of morbidity and mortality. Fortunately, elexacaftor/tezacaftor/ivacaftor (ETI) therapy is showing unprecedented clinical benefits in patients with Cystic Fibrosis (CF) carrying at least one F508del mutation in the Cystic Fibrosis Transmembrane conductance Regulator (CFTR) gene. However, almost 35% of the CF population living in the Mediterranean area still lacks effective CFTR modulator therapies because of the elevated incidence of patients with (pw)CF harboring CFTR rare mutations (RMs), different from F508del. Methods: Twenty-three pwCF harboring RM including the N1303K underwent off-label ETI treatment for 6-12 months. Respiratory function in terms of FEV1 and FVC was measured after 3, 6, and 12 months of treatment. In addition, we analyzed sweat chloride concentration, body mass index (BMI), and quality of life before and after treatment. Possible adverse effects were recorded. Results: All patients included in this off-label program displayed a substantial improvement in respiratory function. In particular, patients carrying the N1303K mutation showed an improvement in FEV1 and FVC similar to that observed in subjects harboring the F508del mutation, although sweat chloride concentration was not significantly decreased. No severe adverse effect was reported. Conclusions: This study strengthens the clinical efficacy of ETI in pwCF harboring the N1303K and other CFTR rare variants. Since these CFTR RMs have not been approved for ETI therapy in Europe, this study may promote the inclusion of these variants in the list of CFTR mutations responsive to ETI. Full article

Background: The spontaneous rupture of the internal iliac artery (IIA) is an exceedingly rare vascular event, typically associated with congenital anomalies or degenerative conditions. This report details an unprecedented case of isolated IIA rupture in an elderly patient with evidence of plaque rupture but devoid of congenital vascular pathology. Case Presentation: An 81-year-old Caucasian male presented to the Emergency Department following a syncopal episode and acute right iliac fossa pain. His significant medical history was atrial fibrillation managed with anticoagulation (Apixaban), non-insulin-dependent diabetes mellitus, and recent hospitalization for multidrug-resistant Klebsiella pneumoniae pneumonia. Initial imaging with contrast-enhanced computed tomography revealed an aneurysmatic dilatation of the right IIA, indicative of rupture. An endovascular repair was performed, employing a combination of stent grafts to achieve proximal and distal sealing and to restore vascular continuity. Outcome: The patient exhibited hemodynamic stability throughout the perioperative period and was transferred to the general ward postoperatively. However, he suffered a recurrent rupture on the 30th postoperative day, prompting a second endovascular intervention to extend the graft landing zone into the common iliac artery. Intraoperative findings confirmed localized plaque rupture as the underlying trigger for the initial vessel rupture. He ultimately achieved clinical stability and was discharged on the 35th postoperative day. Discussion: This case illustrates the critical importance of recognizing spontaneous IIA rupture as a potential complication in elderly patients, particularly in the context of recent severe infections. While the relationship between the rupture and the Klebsiella pneumoniae infection remains speculative, this report underscores the necessity of further research into the role of infectious processes in vascular integrity and susceptibility to rupture. Conclusions: The successful management of this rare and complex vascular emergency using endovascular techniques underscores the evolving landscape of minimally invasive interventions. This case contributes to the limited existing literature on spontaneous IIA rupture and highlights the need for increased clinical vigilance regarding atypical presentations in similar patient populations. Full article

Background: Biomarkers have emerged as a cost-effective tool to risk stratify patients presenting to the emergency department with chest pain. The measurement of serum N-terminal pro-B-type natriuretic peptide (NT-proBNP) and myeloperoxidase (MPO) may improve the identification of patients who are more likely to have abnormal stress test results and require revascularization. Methods: In this prospective observational study, we evaluated the use of NT-proBNP and MPO in predicting abnormal stress testing results and revascularization in patients presenting to the ED with chest pain and an intermediate TIMI risk score. The serum levels of NT-proBNP and MPO were obtained at enrollment. Stress testing or coronary angiography was performed at the discretion of the treating physician. Clinical outcomes were followed at index hospitalization, 6 months, and 1 year. Results: A total of 485 patients were enrolled. NT-proBNP had a fair ability to predict abnormal stress testing results (AUC 0.69, p < 0.001). Based on the Mann–Whitney U test, there was a detectable difference in the median serum levels of both biomarkers among patients who did not undergo revascularization compared to patients who did undergo revascularization (NT-proBNP 70.5 vs. 250, p < 0.001, MPO 341 vs. 471, p < 0.001). NT-proBNP and MPO revealed a meaningful ability to predict revascularization in all patients (NT-proBNP AUC = 0.725, p < 0.001, MPO AUC = 0.653 p < 0.001). Conclusion: Elevated serum NT-proBNP was a fair predictor of abnormal stress test results. Furthermore, higher serum NT-proBNP and MPO levels were associated with revascularization events up to 1-year follow-up and were found to be meaningful predictors of coronary revascularization. Full article

(1) Background/Objectives: This pilot study aims to address the research gap on the interplay between ocular and systemic parameters as well as sex hormones in men. (2) Methods: We measured intraocular pressure (IOP), central corneal thickness (CCT), and macular thickness (CMT) in nine healthy male volunteers. These measures, along with blood glucose; blood pressure; and sex steroid hormones (testosterone, estrogen, and progesterone), were measured twice for each subject. Linear regression was used to determine the individual effects of these measures as well as self-reported age, height, and weight. (3) Results: Height, weight, systolic blood pressure, blood glucose, and estrogen significantly predicted IOP and CMT. CCT models were more limited, with systolic blood pressure and estrogen as the most significant predictors. (4) Conclusions: Our findings suggest that height, weight, blood pressure, and estrogen levels have the most substantial impact on ocular measurements. Testosterone levels were strongly associated with systemic health markers, a common result in the literature. However, ours appears to be the first study demonstrating estrogen’s effects on ocular structure or physiology in men. As many of our comparisons were statistically underpowered, future research with larger populations is needed to confirm these relationships and elucidate underlying mechanisms. Full article

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

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

Background: 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

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

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

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

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