Int. J. Transl. Med., Volume 3, Issue 4 (December 2023) – 9 articles

Due to global population growth, age-related disorders like cardiovascular disease and dementia are anticipated to increase. Recent data suggests a connection between cardiovascular disease and neurodegeneration, especially focusing on arterial stiffness (AS) and Alzheimer’s disease (AD). In light of this, we conducted a study to explore the impact of long-term nitric oxide synthase (NOS) isoform inhibition, which leads to AS, on neurobehavioral performance. We also compared these effects in an AD model and control mice. C57BL/6 and hAPP23+/− mice (an established AD model) were given 0.5 mg/mL N(G)-Nitro-L-Arginine Methyl Ester (L-NAME) in their drinking water for 16 weeks. Our findings indicate that chronic non-selective NOS inhibition increased AS and reduced spatiotemporal learning and memory in both C57BL/6 and hAPP23+/− mice. These effects were consistent across both groups, emphasizing the role of neuronal NOS (nNOS) in cognitive aging, regardless of genetic predisposition to AD. Full article

Amphiphilic dendritic copolymers of arborescent poly(γ-benzyl L-glutamate) (PBG) of generations G1 and G2, grafted at their chain ends with poly(ethylene oxide) (PEO) segments (PBG-eg-PEO) were synthesized, characterized, and evaluated as nanocarriers for doxorubicin (DOX). The copolymers were designed with hydrophobic PBG cores having three different branching densities and were characterized by proton nuclear magnetic resonance (¹H NMR) spectroscopy, size exclusion chromatography (SEC), transmission electron microscopy (TEM), and atomic force microscopy (AFM). Dynamic light scattering (DLS) measurements revealed that these amphiphilic molecules behaved like unimolecular micelles without significant aggregation in aqueous media such as phosphate-buffered saline (PBS), with diameters in the 13–29 nm range depending on the generation number and the core structure. Efficient encapsulation of DOX by these unimolecular micelles was demonstrated with drug loading capacities of up to 11.2 wt%, drug loading efficiencies of up to 67%, and pH-responsive sustained drug release, as determined by UV spectroscopy. The generation number of the copolymers and the branching density of the dendritic PBG core were found to have influenced the encapsulation and release properties of the micelles. Given the tailorable characteristics, good water dispersibility, and biocompatibility of the components used to synthesize the amphiphilic arborescent copolymers, these systems should be useful as robust nanocarriers for a broad range of therapeutic and diagnostic agents. Full article

Inhibitory effects of 4,5-didehydrogeranylgeranoic acid (dGGA) on the development of tumors were investigated in spontaneous hepatoma mice, C3H/HeNCrj. Experiment 1: Male mice at 8 weeks of age were raised on a basal diet, and then provided with a diet containing 0.02% dGGA from 32 to 91 weeks of age. Experiment 2: dGGA was administered to the animals only once at different time points, from 2 months to 17 months after birth, respectively. Experiment 3: dGGA was administered twice to the mice at different time points: at 5 months and 11 months, and at 8 months and 11 months, respectively. When the inhibitory effects on tumor development were evaluated with the incidences of tumors, average numbers, and weight of tumors per mouse, there was a marked relationship between the time of single or dual dosing and the inhibitory effects of dGGA. The greatest inhibitory effects were observed in Experiment 3 in the group of animals given dGGA at the ages of 8 and 11 months, which were far superior to the results with a large dose of the compounds for a long time. These results might indicate that dGGA administered at the right time in the right amount effectively prevents the development of cancer. Full article

Background: Up to now, endometrial cancer (EC) treatments are mainly represented by surgery followed by adjuvant chemotherapy or radiotherapy. The updated guidelines give a 2A recommendation for the use of hormone therapy only in advanced low-grade ECs, underlying the need for more data on the role of hormone therapy in the adjuvant setting. Methods: The clinicopathological data of 158 early-stage EC patients was retrospectively collected. A Ki-67 cut-off value of 40% was established based on literature data. Disease-free survival (DFS) and Overall survival (OS) were evaluated. Results: Results: Multivariate analysis of DFS and OS showed a significantly increased risk of progression in patients with >40% Ki-67 [HR = 3.13 (95% CI; 1.35–7.14); p = 0.007] and a significantly higher relative risk of death [HR = 3.70 (95% CI; 1.69–8.33); p = 0.001]. The predictive role of the Ki-67 index was highlighted by the clinical benefit of adjuvant hormone in patients with high Ki-67. Conclusions: Our results suggest a positive role of the Ki-67 index as a prognostic and potentially predictive marker in EC, although further studies are warranted to reach a definitive conclusion. Full article

This comprehensive review explores two antiretroviral drugs, Etravirine (ETV) and Darunavir (DRV), a non-nucleoside reverse transcriptase inhibitor and a protease inhibitor, that are commonly used in human immunodeficiency virus (HIV) infection treatment, often in combination with each other. The pharmacokinetic properties of these drugs are covered as well as the clinical trials of these two drugs combined. This paper also delves into the possible repurposing of these two drugs for other diseases, with drug repurposing being a significant factor in addressing global health challenges. DRV was extensively studied for treating COVID-19, as well as other infections, such as candidiasis and cryptococcosis, while ETV proved to be efficient in hampering Zika virus brain infection. The focus on cancer repurposing is also explored, with the results revealing that ETV has a particular inhibitory effect on ovarian cancer in vitro and on cancer molecules, such as anterior gradient protein 2 homolog (AGR2) and casein kinase 1 (CK1ε), and that DRV has an in silico inhibitory effect on human lactate dehydrogenase A (LDHA) and induces the in vitro and in vivo inhibition of pepsin, consequent laryngopharyngeal reflux, and possible laryngeal and hypopharyngeal carcinomas. The significance of fresh methods of drug development is emphasized in this work, as is the enormous potential for new therapeutic uses of the antiretroviral drugs ETV and DRV in viral and non-viral disorders. Full article

Inborn errors of immunity (IEI) are multifaced diseases which can present with a variety of phenotypes, ranging from infections to autoimmunity, lymphoproliferation, and neoplasms. In recent decades, research has investigated the relationship between autoimmunity and IEI. Autoimmunity is more prevalent in primary humoral immunodeficiencies than in most other IEI and it can even be their first manifestation. Among these, the two most common primary immunodeficiencies are selective IgA deficiency and common variable immunodeficiency. More than half of the patients with these conditions develop non-infectious complications due to immune dysregulation: autoimmune, autoinflammatory, allergic disorders, and malignancies. Around 30% of these patients present with autoimmune phenomena, such as cytopenia, gastrointestinal and respiratory complications, and endocrine and dermatologic features. Complex alterations of the central and peripheral mechanisms of tolerance are involved, affecting mainly B lymphocytes but also T cells and cytokines. Not only the immunophenotype but also advances in genetics allow us to diagnose monogenic variants of these diseases and to investigate the pathogenetic basis of the immune dysregulation. The diagnosis and therapy of the primary humoral immunodeficiencies has been mostly focused on the infectious complications, while patients with predominant features of immune dysregulation and autoimmunity still present a challenge for the clinician and an opportunity for pathogenetic and therapeutic research. Full article

Primary lymphomas of the salivary gland are rare. The most common subtype is MALT lymphoma. MALT lymphoma has an indolent clinical course, and patients often present with a prolonged history. Evaluations of parotid masses begin initially with radiological imaging, but pathological and histological examination remains the mainstay of definitive diagnosis. This case describes a primary non-Hodgkin’s lymphoma of the parotid gland in a healthy 32-year-old male. This case report will evaluate the prevalence of primary MALT lymphoma and discuss the possible presentation. Full article

Naturopathy or herbal medicine has been widely used as an alternative treatment for several illnesses, such as cancer, as they are generally acknowledged as a treatment with lesser side effects. This research evaluated the bioactive compounds profiling, antioxidant, and anticancer potential in Mentha longifolia L. (essential oil and extract), using different solvent polarities (hexane, methanol, and diethyl ether). Meanwhile, the caspase 3 gene expression and cell cycle status of methanolic extract were determined in colorectal cancer cells (Caco-2 and SW48). The overall findings showed that methanolic extraction exhibited the highest total phenolic and flavonoid with respective values of 59.25 mg GAE (Gallic acid) eq./g DW (dry weight) and 20.02 mg RE (Rutin) eq./g DW, respectively, compared to hexane and diethyl ether. Furthermore, piperitenone oxid and piperitonone were found to be the dominant volatile compounds in methanolic extracts and essential oils. Additionally, the methanolic extract possesses higher antioxidant and anticancer activities. The molecular analysis indicated that methanolic extract up-regulated the expression of caspase 3 and increased the SubG1 (method to detecting cell death) peaks in treated Caco-2 and SW48 cell lines. To conclude, M. longifolia L. could serve as an effective therapeutic agent and a remedy for several illnesses, such as cancer caused by oxidative stress. Full article

The 2019 coronavirus disease (COVID-19) pandemic is affecting millions of people worldwide. Chest high-resolution computed tomography (HRCT) is commonly used as a diagnostic test for suspected COVID-19; however, despite numerous attempts, there is no single scoring system that is widely accepted and used in clinical practice to estimate the probability of SARS-CoV-2 pneumonia. The aim of this single-center retrospective study is to develop a radiological score to predict the probability of COVID-19 with HRCT. Patients admitted to the emergency department with symptoms suggestive of COVID-19 who underwent both HRCT and RT-PCR on nasopharyngeal swab to detect SARS-CoV-2 infection between 1 March and 30 April 2020 were included. A multivariable regression analysis was conducted to identify all HRCT signs independently associated with a positive RT-PCR assay for SARS-CoV-2 and build the HRCT score. A total of 1153 patients were enrolled in this study. The number of segments with ground glass opacities (OR 1.18, 95% CI 1.11–1.26), number of segments with linear opacities (OR 1.21, 95% CI 1.05–1.42), crazy paving patterns (OR 6, 95% CI 3.79–9.76), and vascular ectasia in each segment (OR 2.46, 95% CI 1.1.5–5.8) were included in the score. The HRCT score showed high discriminatory power (area under the ROC curve of 0.8267 [95% CI 0.8–0.85]) with 72.2% sensitivity, 86.6% specificity, 78% PPV, and 83% NPV for its best cut-off. In summary, the HRCT score has good diagnostic and discriminatory accuracy for COVID-19 and is easy and quick to perform. Full article