Int. J. Transl. Med., Volume 4, Issue 4 (December 2024) – 13 articles

The failure of endogenous repair mechanisms is a key characteristic of neurological diseases, leading to the inability to restore damaged nerves and resulting in functional impairments. Since the endogenously regenerative capacity of damaged nerves is limited, the enhancement of regenerative potential of quiescent neural stem cells (NSCs) presents as a therapeutic option for neural diseases. Our previous studies have shown exciting progress in treating sciatic nerve injury in mice and rats using NSCs in conjunction with neurotrophic factors such as fibroblast growth factor 1 (FGF1). Additionally, a recently discovered neurotrophic factor, IL12p80, has shown significant therapeutic effects in sciatic nerve injury repair via myelinating oligodendrocytes. IL12p80 induces oligodendrocyte differentiation from NSCs through phosphorylation of Stat3. Therefore, it might be possible to alleviate the myelination defects of oligodendrocytes in neurodegenerative diseases such as amyotrophic lateral sclerosis (ALS), multiple sclerosis (MS), and even schizophrenia through the administration of IL12p80. These applications could shed light on IL12p80 and FGF1, not only in damaged nerve repair, but also in rectifying the oligodendrocytes’ defects in neurodegenerative diseases, such as ALS and MS. Finally, the synergistic effects of neurogenesis-induced FGF1 and myelination-induced IL12 might be able to supplant the need of NSCs for nerve repair and neuroregeneration. Full article

Sex differences are a complex and crucial variable in developing and progressing metabolic and cardiovascular disease pathophysiology and clinical outcomes. The female sex, compared to the male sex, is protected from metabolic disturbances and their resulting cardiovascular events. However, the peculiar life phases associated with females, such as puberty, pregnancy, and premenopausal and menopausal stages, are all associated with different risks for the development of cardiovascular disease (CVD). Metabolic dysfunction-associated steatotic liver disease (MASLD), a condition of hepatic steatosis, and at least one feature of metabolic syndrome is associated with an increased risk of cardiovascular events. The risk of MASLD and its progression to the development of CVD differs between men and women. Differences in several factors, including formyl peptide receptor (FPR) 2, adipose tissue distribution, liver pyruvate kinase (LPK), and ketone body production, may underlie the sex differences in the risk of development of MASLD-induced CVD. Understanding the specific risk factors involved in the development and progression of MASLD between the sexes is crucial. This knowledge will provide important insights into the mechanisms responsible for its cardiovascular complications and can potentially lead to therapeutics targeted explicitly for each sex, offering new hope in the fight against MASLD-induced CVD. Full article

The increase in cancer incidence in recent years necessitates urgent exploration of novel and alternative sources of natural bioactives for targeted cancer therapy. Approximately 75% of the Earth’s surface is covered by oceans, which are thought to harbor untapped physiologically active compounds with potential efficacy against cancer. Recently, a growing focus has been on isolating and investigating novel bioactive compounds derived from marine sources. Bioactive metabolites with diverse chemical structures, isolated from various marine species such as algae, mollusks, and actinomycetes, demonstrate potential efficacy against a wide range of cancers. To our knowledge, this is one of the articles that has reviewed recent papers on the application of marine-derived bioactives in targeted cancer therapy. This study aims to showcase some of the most current developments in targeted cancer therapy with various bioactives that have been identified from marine sources. Full article

Cancer discovery is directed at the identification of a specific cancer type which allows for specific therapeutic interventions. Background/Objectives: Recently, similar immune checkpoint therapeutics have been applied with success across several cancer types, opening the field for other immune disruptive interventions that have practical applications. Methods: We have discovered an innate immune system (InImS) biomarker that allows for the characterization of allied cancer subtypes and outliers that might aid with diagnosis, treatment, and prognostication. Results: These InImS biomarkers are related to PD-L1 treatment outcomes and can be potentially manipulated by dietary means. Conclusions: The FERAD (ferritin–fecal p87) and absolute neutrophil/lymphocyte (aNLR) ratios are two such InImS biomarkers and we show herein, that they allow for the discovery of diagnosis and prognostication patterns, as demonstrated by this study. Full article

Background: Organ-on-a-chip models have emerged as transformative tools in ophthalmology, offering physiologically relevant platforms for studying ocular diseases and testing therapeutic interventions. These microfluidic devices replicate human eye tissue architecture, addressing limitations of traditional in vitro and animal models. Methods: A narrative review of recent advancements in organ-on-a-chip technology was conducted, focusing on models simulating ocular structures like the retina and cornea and their applications in studying diseases such as dry eye disease (DED), age-related macular degeneration (AMD), and glaucoma. Results: Advanced organ-on-a-chip models successfully mimic key ocular features, providing insights into disease mechanisms and therapeutic responses. Innovations in microengineering and cellular integration have enhanced these platforms’ translational potential, though challenges like scalability and regulatory validation persist. Conclusions: Organ-on-a-chip models are poised to enhance preclinical research and clinical applications in ophthalmology. Addressing scalability and regulatory hurdles will be key to unlocking their full potential in drug discovery and disease modeling. Full article

Sirtuins are a family of lysine deacetylases that regulate cellular homeostasis and energy sensing. Regeneration is the process that restores structural and functional homeostasis at the cellular, tissue, organ, and appendage levels. Several cellular processes, such as epithelial–mesenchymal transition (EMT), proliferation, migration, and differentiation, contribute to restoration after an injury. This review highlights the role of sirtuins in tissue, organ, and anatomical structure regeneration, showing how sirtuins modulate signalling pathways by deacetylating targets such as transcription factors. Furthermore, understanding the role of this protein family could help elucidate the molecular and cellular mechanisms underlying tissue regeneration, which may hold significant potential for fields such as regenerative medicine. The review compiles evidence suggesting that sirtuins are emerging factors in the regeneration of various organs (e.g., skin, liver, heart) and tissues (e.g., bone, muscle, cornea, spinal cord). Full article

Background: Active recruitment of osteogenic cells by secreted signaling factors, such as stromal-cell-derived factor 1 (SDF-1), has recently been proposed as a novel strategy to enhance osseointegration. However, the intrinsic importance of the SDF-1/C-X-C chemokine receptor type 4 (CXCR4) axis in promoting osseointegration is unknown. To study the role of SDF-1/CXCR4 in osseointegration, we blocked the SDF-1/CXCR4 pathway in a murine tibial implant model through repeated administrations of an antibody against SDF-1. Methods: Using our previously described murine tibial implant model (N = 24), mice were randomized into an anti-SDF-1 group and a control group (N = 12/group). Intraperitoneal injections of CXCL12/SDF-1 monoclonal antibody (84 µg/mouse) or mouse IgG1 isotype were administered on days 2, 4, 7, 10, 13, 16, 19, 22, and 25 post-surgery. Mice were euthanized 4 weeks post-surgery. Peri-implant bone mass and architecture were determined through microcomputed tomography (µ-CT). Bone implant strength was detected through implant pull-out testing. Results: Inhibition of the SDF-1/CXCR4 pathway significantly reduced host bone–implant interface strength but did not significantly change the cancellous architecture surrounding the implant. Conclusion: SDF-1/CXCR4 is an important pathway to achieve maximum implant osseointegration. However, inhibition of the pathway did not completely eliminate osseointegration. Full article

Lung cancer is a leading cause of cancer-related mortality worldwide, characterized by its aggressive nature and poor prognosis. Matrix metalloproteinases (MMPs), a family of zinc-dependent endopeptidases, play a pivotal role in the progression of lung cancer. They contribute to tumor invasion, metastasis, angiogenesis, and the modulation of the tumor microenvironment by degrading extracellular matrix components and regulating various cellular signaling pathways. Elevated levels of specific MMPs, such as MMP-2, MMP-9, and MMP-14, have been associated with advanced disease stages and reduced survival rates. As such, MMPs have emerged as valuable biomarkers for the diagnosis, prognosis, and prediction of treatment responses in lung cancer. This review aims to provide a comprehensive overview of the current understanding of MMPs in lung cancer, highlighting their diagnostic and prognostic significance, as well as their potential as therapeutic targets. Despite the initial setbacks in developing broad-spectrum MMP inhibitors, recent advancements have spurred interest in more selective inhibitors that minimize off-target effects and enhance therapeutic efficacy. Furthermore, combining MMP-targeted therapies with conventional treatments, such as chemotherapy and immunotherapy, holds promise for improving clinical outcomes. Future research directions include exploring novel MMP inhibitors, understanding the regulatory mechanisms of MMP activity, and integrating MMP biomarkers into personalized medicine approaches. As the field progresses, targeting MMPs may offer new therapeutic avenues and improve the prognosis for lung cancer patients, making this a promising area of investigation. Full article

The aggressive nature of gastric cancer often leads to late diagnosis and poor prognosis. Chemotherapy and the more recently added immunotherapy remain key treatments for this disease. Several studies have focused on identifying tissue biomarkers with prognostic and/or predictive roles and therefore the therapeutic options are rapidly growing. In this narrative review, we summarize the major tissue biomarkers routinely assessed in clinical practice. In addition, we focus on new evidence about emerging tissue biomarkers that could have a predictive role in future therapeutic approaches and also on the potential role of liquid biopsy in this neoplasm. Full article

Background: Invasive aspergillosis (IA) is an opportunistic infection that affects immunocompromised patients. While voriconazole is commonly used for IA treatment, it presents the risk of drug interactions, particularly in patients on polytherapy. Isavuconazole may serve as a safer alternative with fewer interactions. However, the use of isavuconazole is typically limited to the parenteral route for patients without access to the enteral route, due to recommendations against tablet handling for enteral administration. The objective of this study was to evaluate the suitability of isavuconazole administration via an enteral tube, by therapeutic drug monitoring of isavuconazole plasma concentrations. Methods: This case study examines a patient with diffuse large B-cell lymphoma who was diagnosed with IA and treated with isavuconazole via an enteral tube. Therapeutic pharmacokinetic monitoring of isavuconazole plasma concentrations was performed to assess the feasibility and safety of enteral administration. Results: The results show that isavuconazole concentrations were maintained within the therapeutic range when administered via an enteral tube. No significant deviations in plasma concentration were noted during the monitoring period. Conclusions: Administering isavuconazole through an enteral tube is a safe and viable alternative for patients that are unable to receive the drug via the oral route. Therapeutic monitoring of plasma concentrations is recommended to ensure proper dosing and efficacy. Full article

Background: Fabry Disease (FD) is an X-linked lysosomal disease, in which, unlike other X-linked disorders, most female carriers manifest signs or symptoms for unknown reasons. Objectives: Herein, we aimed to test the potential role of X-chromosome inactivation (XCI) in leukocytes as a prognostic biomarker of disease in FD female carriers. Moreover, we explored if levels of X-inactive-specific transcript (Xist), a long non-coding RNA driving XCI, were detectable in the leukocytes of FD female carriers. Methods: We tested the XCI pattern in leukocytes on 33 consecutive females carrying pathogenic GLA variants. Disease severity was defined using the Mainz Severity Score Index (MSSI). Xist levels in leukocytes were assessed by real-time PCR and compared to the levels of 22 controls. Results: XCI was obtained for 31 female patients, finding 16 skewed (51.6%) individuals. Global MSSI did not differ in skewed vs. non-skewed FD carriers. In skewed FD females, the renal function and mean cardiologic MSSI subscore were significantly worse, and systemic arterial hypertension was more frequent. Xist levels detected in leukocytes were similar between female patients and controls, and did not differ by phenotype or XCI status. Conclusions: A skewed XCI pattern in leukocytes may represent a prognostic biomarker of worse renal and cardiac outcomes in female FD carriers. Full article

Background: Parkinson’s disease (PD) is a common neurodegenerative disorder characterized by motor impairments, cognitive decline, and affective changes. Beyond the well-described motor symptoms, neuropsychiatric symptoms play a crucial role in PD disability burden. Novelty seeking, a trait extensively studied within various models of personality, may influence the manifestation of these non-motor symptoms. Methods: A narrative review of articles determined relevant by the author(s) was undertaken. Results: The literature indicates that PD patients typically exhibit low novelty seeking initially. However, dopaminergic therapies can increase novelty-seeking behaviors, sometimes leading to impulse control disorders (ICD). Studies using the Temperament and Character Inventory (TCI) suggest a complex interplay between disease state, medication, and baseline personality, which is not fully elucidated. High novelty seeking scores predict a higher risk of ICDs, yet they also correlate with a more benign clinical phenotype and improved quality of life post-DBS surgery. Conclusions: Novelty seeking is a significant trait in PD, influencing non-motor symptoms and treatment responses. Understanding its neurobiological basis and clinical implications could lead to better diagnostic and therapeutic strategies through the use of objective, practical tools for disease monitoring, individualized therapy, and pharmacological development. Full article

Objectives: Various measures have been attempted to prevent infectious diseases in calves, such as environmental improvement and vaccine administration. Probiotics are commonly used to improve the body condition of newborn calves and prevent disease. In our previous research, Lactiplantibacillus plantarum RGU-LP1 (LP1) suppressed the expression of inflammatory cytokines in PBMCs of cattle fed it in the diet. In this study, we evaluated the effect of LP1 on the weights and number of treatments of the calves. Methods: Twenty-six one-week-old Holstein bull calves were divided into two groups (thirteen each), the LP1 group (LP1-treated) and the CN group (no LP1 fed), and tested as follows. The LP1 group was fed lyophilized LP1 (10⁹ CFU/head/day) in milk replacer for 40 days. The CN group was fed the same diet only. Calves were followed for 63 days. The average treatment costs for the LP1 during the period were recorded. Feces and blood were collected from each calf during this period. Feces were examined for gut microbiota, and blood for immune assay and cytokine gene expression. Results: The LP1-treated group showed a decrease in disease incidence and an increase in body weights compared to controls. The average treatment cost during the observation period was significantly reduced compared to the CN group. The expression of TGFβ and IL10, inhibitory cytokines of inflammation, was significantly increased. The simultaneous expression of this set of inhibitory molecules resulted in low serum IL1β levels during the growth period. Conclusions: The Th1-type cytokine IFNγ was also significantly increased in LP1-treated calves. By reducing the amount of disease treatments and increasing dairy gain, LP1 is effective in preventing infectious diseases in calves. In addition, the increase in IFNγ by LP1 indicates improved Th1-type immunity in calves. These results show that LP1 has effects on the regulated inflammatory response and growth of calves. Full article