Int. J. Transl. Med., Volume 6, Issue 1 (March 2026) – 11 articles

Background: Mitotane is the cornerstone adjuvant and palliative treatment for adrenocortical carcinoma (ACC), requiring strict therapeutic drug monitoring (TDM) due to its narrow therapeutic window and high inter- and intra-individual pharmacokinetic variability. As a highly lipophilic compound, mitotane may be influenced by plasma lipid levels; however, current TDM protocols do not systematically incorporate lipid profile assessment. We report a case illustrating the clinical impact of hypertriglyceridemia on measured mitotane plasma concentrations. Methods: We retrospectively analyzed clinical, biochemical, and pharmacokinetic data from a patient with metastatic ACC treated with oral mitotane. Plasma mitotane concentrations were correlated with triglyceride and cholesterol levels using Spearman’s rank correlation analysis. Results: A 50-year-old male with metastatic ACC experienced abrupt fluctuations in mitotane plasma concentrations despite stable dosing. Supratherapeutic mitotane levels coincided with episodes of marked hypertriglyceridemia. A significant positive correlation was observed between triglyceride levels and plasma mitotane concentrations (ρ = 0.802, p < 0.001), as well as with total cholesterol (ρ = 0.658, p < 0.001). Conclusions: This case highlights a clinically relevant interaction between triglyceride levels and measured mitotane concentrations. Incorporating routine lipid profile assessment into mitotane TDM protocols may improve interpretation of plasma levels and therapeutic decision-making. Prospective studies are warranted to validate these findings and refine monitoring strategies. Full article

Background: Chronic shoulder pain is a frequent musculoskeletal complaint that significantly affects function, productivity, and quality of life. Mesenchymal stem cell (MSC)-based therapies have emerged as a potential regenerative option due to their anti-inflammatory and tissue-repair properties. This study aims to evaluate the safety and short-term effectiveness of intra-articular injections of umbilical cord-derived MSCs (UC-MSCs) in patients with chronic shoulder pain. Methods: A retrospective pragmatic observational study was conducted at the Regenerative Medicine Institute in Costa Rica. Medical records were reviewed to extract clinical, sociodemographic, and treatment-related variables. The primary outcome was functional improvement measured with the American Shoulder and Elbow Surgeons (ASES) score. Changes between baseline and the 3-month follow-up were analyzed using paired tests, effect size calculations, and regression models to explore predictors of treatment response. Results: Twenty patients met the inclusion criteria. A significant improvement in shoulder function was observed, with a mean ASES increase of 17.17 points, exceeding the minimum clinically important difference of 12. Sixty percent of patients achieved clinically meaningful improvement. Effect size estimates indicated a large magnitude of change. Regression analyses showed that baseline ASES predicted follow-up scores, while higher UC-MSC doses were associated with greater functional improvement. No adverse events were documented during the study period. Conclusions: The study shows that UC-MSC therapy is a safe, minimally invasive, and clinically beneficial option for chronic shoulder pain. These findings support the therapeutic potential of MSCs and highlight the need for larger controlled studies to validate long-term efficacy and optimize treatment protocols. Full article

Introduction: Early HIV replication in the gastrointestinal tract plays an important role in HIV pathogenesis. We have followed the onset of the acquired immune deficiency disease (AIDS) pandemic and human immunodeficiency virus (HIV) infection from its recognition in the US. Patients and Methods: We followed 34 adult HIV positive Veterans on cART comparing colon Innate Immune System (InImS) expression of a Paneth cell product (p87; the denominator) and blood ferritin (the numerator) to derive the FERAD ratio, and p87 expression by immunohistochemistry available in some of our HIV patients and compare the expression to 2252 without HIV. Stool and colonoscopically obtained tissue specimens were run in a p87 ELISA and immunohistochemistry for both fixed and native antigens, using the Adnab-9 antibody. Results: There were no significant differences in demographics aside from lower BMI in HIV patients (24.93 ± 6.30 vs. 28.0 ± 6.13 kg/m²) p < 0.0001. Native p87 antigen was elevated in HIV patients compared to controls in the ascending, transverse, and descending colon (0.794 ± 0.890 vs. 0.170 ± 0.201 respectively; p < 0.000004; 1.062 ± 0.730 vs. 0.202 ± 0.377 respectively; p < 0.000003; and 0.611 ± 0.182 vs. 0.174 ± 0.251 respectively; p < 0.0009), respectively; and Helicobacter pylori (H. pylori) detection was higher in HIV patients (84.6% vs. 36%; p < 0.0002). We also ran these assays in cancer patients for comparison. Conclusions: Colonic inflammation as expressed by p87, a Paneth cell product, is significantly elevated in HIV patients and likely represents continued HIV activity leading to inflammation. Full article

Zebrafish (ZF) have gained increasing attention in developmental neuroscience due to their experimental tractability, favorable ethical profile, and translational value. However, the expanding use of the ZF model has also highlighted the need to consider species-specific differences in relation to early social and emotional development. This review adopts a comparative and ethological perspective to examine early social interactions in ZF and mammals, integrating evidence from non-altricial vertebrates and teleost species with parental care (cichlids). Selected illustrative ZF papers were discussed, while Cichlids fish were chosen as a complementary, translationally consistent subject for developmental behavioral studies. The analysis focuses on developmental stages that are relevant for behavioral phenotyping in models of neuropsychiatric conditions. Zebrafish offer multiple methodological advantages, including suitability for high-throughput experimentation and substantial genetic and neurobiological homologies with humans. Nevertheless, the absence of mother–offspring bonding limits the modeling of neurodevelopmental processes shaped by early caregiving, such as imprinting and reciprocal regulatory interactions, instead observed in cichlids. Accumulating evidence indicates that early interactions among age-matched ZF are measurable, developmentally regulated, and sensitive to environmental and experimental manipulations. Within a comparative approach, these early conspecific interactions could be analogs of early social bonding observed in altricial mammals. Rather than representing a critical limitation, such species-specific features can inform the investigation of fundamental mechanisms of social development and support the complementary use of ZF and mammalian models. A contextualized and integrative approach may therefore enhance the translational relevance of ZF-based research, particularly for the study of neurodevelopmental disorders involving early social dysfunction. Full article

Background: Scattering of the sclera limits optical coherence tomography (OCT) imaging of deeper targets including lesions, malignancies, and other surgical targets. While existing applications of fluorescein dye are currently focused on fluorescence properties for tissue labeling, the absorption characteristics of the dye also hold potential for scleral tissue clearing. Methods: Fluorescein is investigated here to gauge the potential impact of its optical clearing on intrasurgical OCT guidance. Fluorescein was applied topically to ex vivo porcine and human eye models. OCT imaging was conducted over time to assess the increases in imaging depth due to fluorescein clearing. High-speed microscope-integrated OCT was used during pilot trabeculectomy surgery on cleared eye models to assess clearing applications in a surgical context. Results: The OCT depth of imaging increased with fluorescein concentration and application time. The effect saturates at a near-20% concentration with 50 min of application time, with a maximum signal increase of +15 dB. Reversal of the effect was observed following 10 min of rinsing. Conclusions: High-concentration fluorescein dye has novel applications as an optical clearing agent, increasing the OCT imaging depth through highly scattering biological tissue. These properties can be leveraged for improved image guidance in surgical contexts. Full article

Oncofetal reprogramming has recently emerged as a critical concept in translational cancer research, particularly for its role in driving therapeutic resistance across a variety of malignancies. This biological process refers to a pattern of gene expression that is restricted to embryogenesis, but becomes expressed again in a subpopulation of cancer cells. These genes are typically suppressed after embryogenesis, and their aberrant re-expression in tumors endows cancer cells with stem-like properties and enhanced adaptability. The goal of this review is the following: (i) comprehensively examine the multifaceted nature of oncofetal reprogramming; (ii) elucidate its underlying molecular mechanisms, including its regulators and effectors; and (iii) evaluate its consequences for the therapeutic response in different cancer types. We comprehensively integrate the latest findings from colorectal, breast, lung, liver, and other cancers to provide a detailed understanding of how oncofetal programs interfere with tumor response to treatment. Among the candidates, YAP1 and AP-1 have emerged as central transcriptional drivers of this reprogramming process, especially in colorectal and breast cancers. We also explore the distinct expression patterns of oncofetal genes across different tumor types and how these patterns correlate with treatment outcomes and patient survival. Lastly, we propose a dual-targeting therapeutic strategy that simultaneously targets both cancer stem cells and oncofetal-reprogrammed populations as a more effective approach to overcome resistance and limit recurrence. Full article

Background: We describe the post-mortem analysis of a CARD11 variant allele, p.Ser995Leu, identified in fraternal twins who died in early infancy with no identifiable cause of death. CARD11 variants through varied inheritance models can alter immune function through loss- or gain-of-function mechanisms, involving distinct protein domains; yet the significance of GUK domain variants remains poorly characterized. Twin autopsies showed non-specific findings, such as pulmonary macrophage accumulation and splenic white pulp expansion, but without infection or structural abnormalities. Methods: Whole-exome sequencing, performed as part of molecular autopsies, identified the shared CARD11 p.Ser995Leu variant, previously classified as a variant of uncertain significance (VUS). We assessed evolutionary conservation across CARD family proteins and species and predicted functional impact using in silico tools, which estimate the likelihood that a variant is deleterious. AlphaFold-based structural modeling emphasized qualitative biophysical assessment. Using epidemiological data, population allele frequency, and Bayesian ACMG variant classification, we assessed competing hypotheses under an autosomal dominant model. Results: The p.Ser995Leu substitution affects a conserved, surface-exposed β-sheet within the GUK domain. While CADD scores exceeded 20, other predictive algorithms offered only partial support of pathogenicity. Structural modeling suggested a potential GUK domain destabilization. Integrating genetic, pathologic, immunologic, and probabilistic modeling, we propose a biologically plausible model in which the variant, like other GUK variants, may alter NF-κB or other signaling pathways and is likely pathogenic. Conclusions: While the CARD11 p.Ser995Leu variant’s contribution to disease is uncertain without functional validation or parental testing, and phenotypic findings are non-specific, the presence of an ultra-rare GUK domain variant in both twins, combined with in silico and statistical modeling, supports its interpretation as likely pathogenic or high risk. The results highlight the challenges of data-limited post-mortem variant interpretation. Full article

Idiopathic inflammatory myopathies (IIM) comprise a heterogeneous group of autoimmune disorders with variable systemic involvement. Among them, dermatomyositis (DM) is the subtype with the most extensive biomarker characterization due to its defined immunopathology and frequent association with interstitial lung disease (ILD). This narrative review summarizes studies retrieved from PubMed, Scopus, and Web of Science up to March 2025, focusing on non-autoantibody biomarkers in DM. Reported categories include soluble proteins, cytokines, chemokines, muscle-specific microRNAs, and transcriptomic signatures reflecting interferon activation, tissue injury, and fibrotic remodeling. Among the most validated molecules, interferon-stimulated genes, ferritin, KL-6, SP-D, and CXCL10 demonstrate diagnostic and prognostic value, particularly in anti-MDA5-positive DM, where they support early identification of patients at risk for rapidly progressive ILD. However, despite increasing evidence, most biomarkers lack disease specificity, standardized cutoffs, and multicenter validation, while molecular assays remain confined to specialized laboratories. Clinically accessible markers such as ferritin, KL-6, and CXCL10 currently offer the highest translational potential. Nevertheless, the heterogeneity of study designs and analytical methods continues to limit comparability and routine clinical integration. Future research should prioritize the validation of composite biomarker panels through standardized, multicentric studies to enhance diagnostic precision and enable precision medicine approaches in DM and related inflammatory myopathies. Full article

Background/Objectives: GATA-binding protein 3 (GATA-3) is a crucial transcription factor that drives type 2 immune responses, and it is actively involved in allergic conditions such as asthma, allergic rhinitis (AR), and atopic dermatitis (AD). However, the molecular mechanisms GATA-3 uses to modulate immune responses and its potential therapeutic targeting are not fully understood. This systematic review aimed to summarize studies on the role of GATA-3 in immune responses, particularly in allergic diseases, and evaluate GATA-3’s potential as a therapeutic target. Methods: We searched PubMed, Scopus, Web of Science, Cochrane, and Science Direct for studies published before April 2025. Articles were sifted through using predefined criteria, and risk of bias was measured with RoB 2 for clinical trials and SYRCLE for animal models and in vitro studies; evidence was graded using the GRADE system. Results: Twenty-nine eligible studies reported that GATA-3 is a key regulator of Th2 and ILC2 differentiation, promoting the production of IL-4, IL-5, and IL-13. Animal models and in vitro studies demonstrated its role in exacerbating allergic inflammation and highlighted the promise of targeting strategies such as DNAzymes and nanocapsules. Clinical trials showed that targeting GATA-3, particularly with DNAzymes, can reduce allergic responses in asthma. Conclusions: GATA-3’s role in driving allergic inflammation through Th2 and ILC2 pathways suggests it as a promising therapeutic target. Understanding its broader regulatory mechanisms is imperative for designing effective GATA-3 targeting-based therapies. Full article

Background/Objective: Early hemodynamic instability in sepsis arises from endothelial dysfunction and vasoplegia before capillary leakage and organ failure occur. Albumin administration guided by serum concentration or shock criteria has not improved outcomes. This review synthesized evidence supporting an early, physiology-guided framework for albumin and norepinephrine use in pre-δ vasoplegic sepsis. Methods: A narrative synthesis of experimental and clinical studies examined endothelial injury, sepsis phenotypes, hemodynamic monitoring, biochemical markers, and intravascular albumin mass. Evidence from phenotype cohorts was integrated to construct a physiology-based therapeutic framework. Results: The δ phenotype consistently emerged as a vasoplegic, hyperinflammatory endotype with hypoalbuminemia, elevated lactate, and the highest mortality. Studies showed 20–25% of patients with community-acquired sepsis exhibit early vasoplegia, with low systemic vascular resistance and high cardiac output. Mass-balance analyses showed intravascular albumin mass declines early in sepsis, correlate inversely with fluid balance, and predict mortality. These findings suggest early low-dose norepinephrine may stabilize perfusion pressure, while albumin use should follow intravascular albumin mass trajectories. A dynamic exclusion concept proposes withholding albumin during capillary leak and reintroducing it when intravascular albumin mass stabilizes. Conclusions: Albumin therapy in sepsis should shift from late concentration-based to early physiology-guided endothelial protection. Monitoring intravascular albumin mass, lactate, and fluid balance may guide targeted norepinephrine and albumin use before δ-type endothelial failure occurs. This framework needs phenotype-stratified validation. Full article

Background: Takotsubo cardiomyopathy (TTC), also known as stress-induced cardiomyopathy, is an acute but reversible form of left ventricular dysfunction, most commonly triggered by physical or emotional stress. Although well documented in cardiology practice, its occurrence following hepatobiliary surgery is rarely reported. Case presentation: We describe the case of a 67-year-old woman with a history of arterial hypertension and prior cholecystectomy who was admitted for elective hepatobiliary surgery due to choledocholithiasis complicated by a liver abscess. She underwent laparotomy with choledocholithotomy, hepaticojejunostomy, and abdominal drainage. The postoperative course was complicated by intra-abdominal bleeding, requiring reoperation, and subsequent intestinal leakage, necessitating a second re-laparotomy. On the tenth postoperative day after the second surgery, she developed chest discomfort and dyspnea upon minimal exertion. Electrocardiography revealed T-wave inversions in leads V3–V6, while echocardiography demonstrated a reduced ejection fraction of 45% with apical akinesis. Plasma levels of N-terminal pro-B-type natriuretic peptide (NT–proBNP) were elevated, whereas troponin remained within normal limits. Coronary angiography excluded obstructive coronary artery disease, and ventriculography confirmed apical ballooning consistent with Takotsubo cardiomyopathy. Conclusions: This case highlights Takotsubo cardiomyopathy as a rare but important postoperative complication of major hepatobiliary surgery. Awareness of this condition in surgical patients presenting with acute chest symptoms is essential, as timely recognition and differentiation from acute coronary syndrome directly influence management and prognosis. Full article