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

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

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

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, GLA^c.851T>C, GLA^{c.1193_1196del}, and their respective corrected lines, GLA^{corr c.851T>C}, GLA^{corr 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

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

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