Int. J. Transl. Med., Volume 4, Issue 1 (March 2024) – 11 articles

For 80 years, high-intensity focused ultrasound (HIFU) has been the subject of interest in medical research. It is a non-invasive procedure that causes the death of cells in a very select area through one of two mechanisms, either heat or cavitation. While diagnostic ultrasound is well known in the medical profession and ultrasound is also used in physiotherapy, high-intensity focused ultrasound is less known but is becoming increasingly important as a non-invasive tool that can be used in many ways, including in the treatment of several cancers as well as benign uterine fibroids. Other interesting developments are underway, including its use in the treatment through an intact skull of essential tremors and the tremor associated with Parkinson’s disease, and in a modified form, it is used to target drug delivery to the brain due to its potential opening of the blood–brain barrier. The depth of penetration of HIFU is variable depending on the type of transducer used and the distance from it. Clinical trials of abdominal malignancies and benign uterine fibroids are reviewed in this article along with potential side effects of the procedure. Over the past two decades, the technology has improved considerably, and the clinical indications have broadened. The current limitations of the technology are also discussed, along with the potential advances in the field that may be made over the next decade. Full article

Major depressive disorder (MDD), a prevalent mental illness, is marked by a complex mixture of biological factors. This review focuses on the roles of oxidative stress, tryptophan-serotonin metabolism, brain-derived neurotrophic factor (BDNF), and the hypothalamic–pituitary–adrenal (HPA) axis in MDD’s pathophysiology. Oxidative stress, defined as an imbalance between pro-oxidants and antioxidants, is closely linked to MDD’s neurobiological changes. The tryptophan (TRP)-/serotonin (5-HT) metabolic pathway is also known to be crucial in mood regulation, with its dysregulation being a central aspect of MDD. Additionally, BDNF, key for neuronal growth and plasticity, often shows alterations in MDD patients, supporting its role in the disorder’s progression. Furthermore, the HPA axis, which manages stress response, is frequently disrupted in MDD, further contributing to its complex pathology. In addition to exploring these biological mechanisms, this review also explores the pharmacotherapy of MDD, including new advances. These advancements in treatment strategies are crucial for managing MDD effectively. Understanding these mechanisms and the latest pharmacological interventions is essential for developing more effective treatments for MDD. Full article

Background: Low-quality tumoral surgical excision is the major relapse factor in rectal cancer. If the surgery is highly difficult, the quality of the resection might be compromised. In the literature, it is described how low pelvic dimensions can make this type of surgery difficult. The main aim was to study the influence of pelvic measures in surgical difficulty on the patients submitted to tumoral surgical resection with curative intent. Methods: A retrospective, observational and analytic study was conducted. A total of 73 patients over a period of 3 years were included. Demographic and surgical data, as well as measurements of the pelvis taken from MRI, were collected. An univariate and multivariate analysis was performed. Results: 11 (15.1%) patients were classified as having highly difficult surgeries. All 11 patients were male. Significant differences were found between groups regarding gender (p = 0.013), transverse diameter of the pelvis (p < 0.001), interspinal distance (p = 0.014) and intertuberous distance (p < 0.001). The logistic regression revealed that a small transverse diameter (O.R. 0.919, 95% I.C. 0.846–0.999, p = 0.047) increases the degree of difficulty of the surgery. Conclusions: Male patients with a small pelvic measurement deserve a thorough surgical plan that predicts a quality resection. Full article

Previous research has already shown that apolipoprotein (apo)A-I is adsorbed from the bloodstream onto the surface of certain colloidal lipid particles after the intravenous injection of such colloidal nanocarriers. As a result, various blood–brain barrier (BBB) scavenger receptors are targeted by these (apoA-I-coated) colloidal nanocarriers. This targeted molecular interaction is mediated/facilitated by the adsorbed apoA-I, which is then followed by receptor-mediated endocytosis and subsequent transcytosis of the nanocarrier particles across the BBB. A multifunctional combination therapy is obtained by adding the appropriate drug(s) to these biomimetic (lipid cubic phase) nanocarriers. This therapeutic targets specific cell-surface scavenger receptors, primarily class B type I (SR-BI), and crosses the blood–brain barrier. The lipid contents of artificial biomimetic (nanoemulsion) nanocarrier particles and of naturally occurring high-density lipoproteins (HDL) have been shown to be similar, which enables these nanocarrier particles to partially imitate or simulate the known heterogeneity (i.e., subpopulations or subspecies) of HDL particles. Hence, colloidal drug nanocarriers have the potential to be used in the biomedical treatment of complicated medical conditions including dementia, as well as certain elements of aging. Widespread inflammation and oxidative stress—two processes that include several pathophysiological cascades—are brought on by dementia risk factors. More recent studies suggest that proinflammatory cytokines may be released in response to a prolonged inflammatory stimulus in the gut, for example through serum amyloid A (SAA). Therefore, pharmacologically targeting a major SAA receptor implicated in the SAA-mediated cell signaling processes that cause aging and/or cognitive decline, and ultimately Alzheimer’s disease or (late-onset) dementia, could be an effective preventive and therapeutic approach. Full article

Pulmonary arterial hypertension (PAH) is a fatal disease that primarily affects women. In PAH, endothelial cells become dysfunctional, reducing production of the vasodilator nitric oxide while increasing proliferation. Other studies suggest altered glucose metabolism in PAH. Our recent study showed that increased endothelial glucose metabolism in disturbed flow increased O-GlcNAcylation of endothelial nitric oxide synthase (eNOS), the enzyme that makes nitric oxide, which then reduced nitric oxide production. We therefore hypothesized that elevated endothelial glycolytic activity in PAH endothelial cells would reduce nitric oxide production by increasing eNOS O-GlcNAcylation. We cultured human pulmonary artery endothelial cells (HPAECs) from failed lung transplant (“non-PAH”) and idiopathic PAH patients (“PAH”) and quantified glycolytic activity, nitric oxide production, and eNOS O-GlcNAcylation in each cell type. Our data show that PAH HPAECs had higher glucose uptake and glycolytic metabolites, as well as decreased nitric oxide production, compared to non-PAH HPAECs. However, PAH HPAECs had lower eNOS O-GlcNAcylation and UDP-GlcNAc, the substrate for O-GlcNAcylation. Interestingly, both glucose uptake and eNOS O-GlcNAcylation were higher in female as compared to male HPAECs. These data suggest that although endothelial glycolytic metabolism is altered in PAH, eNOS O-GlcNAcylation is not connected to decreased nitric oxide. In addition, differences in glucose metabolism and protein O-GlcNAcylation in HPAECs from male and female donors could relate to PAH sexual dimorphism. Full article

The present study examined the effects of foods containing lipopolysaccharides from Pantoea agglomerans (LPSp) on eye–nose allergic symptoms using a double-blind, placebo-controlled, randomized, parallel-group comparative research design. Sixty-three Japanese individuals aged 20–65 years with eye–nose allergic symptoms were included in this study and assigned to the LPS (480 μg/day)-containing food and placebo groups. Data on the subjective eye–nose allergic symptoms and antiallergic medication during the 8-week period were evaluated. The immunoglobulin E (IgE) and eosinophil counts were measured as indicators that may be correlated with allergy. No significant group differences were found in the change in eye–nose allergic symptoms from baseline. However, the LPS group showed a significantly shorter duration of antiallergic medication use and lower total antiallergic drug score than the placebo group. The corrected nasal allergy score calculated by taking into account the antiallergic drug score at week 8 was predominantly lower in the LPS group. The IgE to house dust and cedar pollen and eosinophil counts tended to be lower in the LPS group, and the total IgE and eosinophil counts were significantly lower in the LPS group at week 4. In conclusion, our results indicate that LPS-containing foods alleviate eye–nose allergic symptoms and consequently lower the use of antiallergic drugs (UMIN000049974). Full article

Background: The tooth is a repository of stem cells, garnering interest in recent years for its therapeutic potential. The aim of this systematic review and meta-analysis was to test the hypothesis that dental stem cell administration can reduce blood glucose and ameliorate polyneuropathy in diabetes mellitus. The scope of clinical translation was also assessed. Methods: PubMed, Cochrane, Ovid, Web of Science, and Scopus databases were searched for animal studies that were published in or before July 2023. A search was conducted in OpenGrey for unpublished manuscripts. Subgroup analyses were performed to identify potential sources of heterogeneity among studies. The risk for publication bias was assessed by funnel plot, regression, and rank correlation tests. Internal validity, external validity, and translation potential were determined using the SYRCLE (Systematic Review Center for Laboratory Animal Experimentation) risk of bias tool and comparative analysis. Results: Out of 5031 initial records identified, 17 animal studies were included in the review. There was a significant decrease in blood glucose in diabetes-induced animals following DSC administration compared to that observed with saline or vehicle (SMD: −3.905; 95% CI: −5.633 to −2.177; p = 0.0004). The improvement in sensory nerve conduction velocity (SMD: 4.4952; 95% CI: 0.5959 to 8.3945; p = 0.035) and capillary-muscle ratio (SMD: 2.4027; 95% CI: 0.8923 to 3.9132; p = 0.0095) was significant. However, motor nerve conduction velocity (SMD: 3.1001; 95% CI: −1.4558 to 7.6559; p = 0.119) and intra-epidermal nerve fiber ratio (SMD: 1.8802; 95% CI: −0.4809 to 4.2413; p = 0.0915) did not increase significantly. Regression (p < 0.0001) and rank correlation (p = 0.0018) tests indicated the presence of funnel plot asymmetry. Due to disparate number of studies in subgroups, the analyses could not reliably explain the sources of heterogeneity. Interpretation: The direction of the data indicates that DSCs can provide good glycemic control in diabetic animals. However, methodological and reporting quality of preclinical studies, heterogeneity, risk of publication bias, and species differences may hamper translation to humans. Appropriate dose, mode of administration, and preparation must be ascertained for safe and effective use in humans. Longer-duration studies that reflect disease complexity and help predict treatment outcomes in clinical settings are warranted. This review is registered in PROSPERO (number CRD42023423423). Full article

The coronavirus SARS-CoV-2 is the causative pathogen of the COVID-19 pandemic that has been causing global upheaval since 2019. The widespread administration of vaccines has partially deterred the spread of SARS-CoV-2, yet the virus is mutating its genome to reduce its antigenicity and evade the human herd immunity. It seems that SARS-CoV-2 will co-exist with the human population for many decades to come. While most infected individuals only experience mild to moderate symptoms, some develop severe pulmonary and systemic disease that can result in hospitalization or even death. The natural history model of SARS-CoV-2 infection has been proposed which includes three sequential stages: the early infection stage, pulmonary stage, and hyper-inflammatory stage. Recently, it has been observed that many people who recovered from an acute infection still experience persistent symptoms for weeks or months, a condition known as long COVID. Furthermore, some COVID-19 patients display escalated rates of both macro- and micro-thrombosis due to endotheliopathy. Hence, we added the thrombosis and convalescent stages to the natural history model, encompassing the entire period from early infection to long COVID. The early infection stage is characterized by symptomatic or asymptomatic elevation of viral titers. Some patients progress to the pulmonary stage characterized by opacities in chest X-rays and computed tomography. The thrombosis stage is characterized by heightened rates of pulmonary thrombosis and consistently elevated D-dimer levels. The hyper-inflammatory stage is characterized by storms of cytokines, such as IL-6, IL-17, and interferons, which is a systemic effect. In the convalescent stage, some people recover completely, while others suffer from long COVID with persistent symptoms such as fatigue, shortness of breath, or brain fog. The natural history model of SARS-CoV-2 infection can be used to elucidate treatment and care. Full article

MicroRNAs (miRNAs), or small non-coding RNAs, modulate the expression of mRNAs and, consequently, a variety of signal transduction pathways. Due to their dysregulation in cancer, they exert oncogenic pressure and have an impact on the immune system with their protective functions. These immunosuppressive characteristics of miRNAs in cancer promote cancer progression and metastasis, causing the dysregulation of immune cells and the immune escape of tumor cells. In contrast, there are also tumor suppressor miRNAs that are able to activate the immune system. Therefore, studies on the altered expression of miRNAs that consider both the oncogenic and tumor-suppressive aspects of miRNAs have become an important research field for advancing immunotherapeutic interventions using miRNAs or their inhibitors as therapeutics. In the current review, their potential in the immunomodulation of immune cells and their use as immune stimulatory molecules to elicit specific cytotoxic responses against the tumor are discussed. Full article

Background: Preterm birth (PTB) is a leading cause of childhood disability, and it has become a key public health priority recognized by the World Health Organization and the United Nations. Objectives: This review will: (1) summarize current practice in the diagnosis and management of PTB, (2) outline developments in precision-based medicine for diagnostics to improve the care provided to pregnant women at risk of PTB, and (3) discuss the implications of current research in personalized medicine and the potential of future advances to influence the clinical care of women at risk of PTB. Methodology: This is a narrative literature review. Relevant journal articles were identified following searches of computerized databases. Key Results: Current and emerging technologies for the utility of personalized medicine in the context of PTB have the potential for applications in: (1) direct diagnostics to identify and target infection as one of the main known causes of PTB, (2) identifying novel maternal and fetal biomarkers, (3) the use of artificial intelligence and computational modeling, and (4) combining methods to enhance diagnosis and treatment. Conclusions: In this paper, we show how current research has moved in the direction of the targeted use of biomarkers in the context of PTB, with many novel approaches. Full article

Intermediate-thickness melanomas display highly variable outcomes influenced by both clinical and histopathological characteristics. This study investigates several clinicopathological prognostic factors for pT3 cutaneous melanomas, focusing on a novel parameter, the width of invasion. This is a retrospective study of 49 patients diagnosed with cutaneous melanoma between 2012 and 2018 who were followed up for at least five years. We evaluated the age, gender, tumor location, Breslow depth of invasion, width of invasion, mitotic index, the presence/absence of ulceration, regression, microsatellites, lymphovascular invasion, and perineural invasion for their association with disease progression and survival. Cox univariate analysis revealed that progression-free survival (PFS) was significantly associated with age, depth of invasion, width of invasion, lymphovascular invasion, microsatellites, and perineural invasion. Overall survival (OS) was significantly associated with age, depth of invasion, width of invasion, microsatellites, and perineural invasion. Through multivariate Cox proportional hazards regression, the only factor associated with both PFS and OS was the width of the invasion. This is one of the few studies to assess the width of invasion and we have demonstrated that this parameter could become an important prognostic factor for cutaneous melanomas. Full article