Latest articles in this journal
Biomedicines, Volume 11; https://doi.org/10.3390/biomedicines11061632
This article provides a comprehensive narrative review of the history of antiepileptic drugs (AEDs) and their development over time. Firstly, it explores the significant role of serendipity in the discovery of essential AEDs that continue to be used today, such as phenobarbital and valproic acid. Subsequently, it delves into the historical progression of crucial preclinical models employed in the development of novel AEDs, including the maximal electroshock stimulation test, pentylenetetrazol-induced test, kindling models, and other animal models. Moving forward, a concise overview of the clinical advancement of major AEDs is provided, highlighting the initial milestones and the subsequent refinement of this process in recent decades, in line with the emergence of evidence-based medicine and the implementation of increasingly rigorous controlled clinical trials. Lastly, the article explores the contributions of artificial intelligence, while also offering recommendations and discussing future perspectives for the development of new AEDs.
Biomedicines, Volume 11; https://doi.org/10.3390/biomedicines11061631
The prediction of the biological function of non-coding ribonucleic acid (ncRNA) is an important step towards understanding the regulatory mechanisms underlying many diseases. Since non-coding RNAs are present in great abundance in human cells and are functionally diverse, developing functional prediction tools is necessary. With recent advances in non-coding RNA biology and the availability of complete genome sequences for a large number of species, we now have a window of opportunity for studying non-coding RNA biology. However, the computational methods used to predict the non-coding RNA functions are mostly either scarcely accurate, when based on sequence information alone, or prohibitively expensive in terms of computational burden when a secondary structure prediction is needed. We propose a novel computational method to predict the biological function of non-coding RNA genes that is based on a collection of deep network architectures utilizing solely ncRNA sequence information and which does not rely on or require expensive secondary ncRNA structure information. The approach presented in this work exhibits comparable or superior accuracy to methods that employ both sequence and structural features, at a much lower computational cost.
Biomedicines, Volume 11; https://doi.org/10.3390/biomedicines11061630
Background: Although non-target puncture (NPT)-related complications are well known to clinicians performing TIPS, there is no NTP-focused study to assess the true clinical sequalae of NTP-related complications. In this study, the aim was to evaluate the incidence, safety, clinical outcomes and complications related to NTPs during the portal access of TIPS procedures. Methods: A retrospective review of 369 TIPS procedures from October 2007 to September 2019 was performed. We identified inadvertent NTPs, including biliary, hepatic artery, lymphatic and capsular punctures. Next, the medical records and images were reviewed and analyzed to assess the safety and clinical outcomes of these cohorts. Results: A total of 71 NTPs were identified in 56 patients (15.18% of 369 patients). Of 369 TIPS patients, there were (1) 28 biliary punctures (7.6%), (2) 16 extracapsular punctures (4.3%), (3) 15 lymphatic punctures (4.1%) and (4) 12 hepatic artery punctures (3.3%). The overall complication rate was 2.2% (8/369). Based on the Clavien–Dindo classification, three patients (0.8%) had a minor complication. In addition, five patients (1.4%) experienced grade II–V major complications, such as symptomatic hemoperitoneum, arterio-biliary fistula or hemorrhagic shock leading to death. Mortality (0.5%) was only caused by extracapsular puncture combined with other NTP. Conclusions: NTPs during the portal access of TIPS procedures are associated with low complication risk. However, when extracapsular punctures are combined with other NTPs, a more severe complication, including mortality, can occur. Nevertheless, all patients with NTP should be closely monitored at a higher level of care after TIPS placement.
Biomedicines, Volume 11; https://doi.org/10.3390/biomedicines11061629
Purpose: To evaluate the impact of drusen-like deposits (DLD) on retinal layer integrity and retinal function by optical coherence tomography (OCT) and multifocal electroretinography (mfERG) in patients with systemic lupus erythematosus (SLE). Methods: We identified 66 eyes of 33 SLE patients treated with hydroxychloroquine (HCQ) that were categorized into two groups according to whether DLDs were present (34 eyes, Group One) or absent (32 eyes, Group Two). The groups were matched for age, sex, HCQ treatment duration, daily, and cumulative dosage. OCT (retinal layer thicknesses, central retinal thickness, CRT) and mfERG concentric ring analysis were analyzed and compared. Results: CRT was significantly thicker in Group One compared to Group Two (273.21 ± 3.96 vs. 254.5 ± 7.62) (p = 0.023). Group One also demonstrated an overall thicker retinal pigment epithelium compared to Group Two; however, the other outer retinal layers, outer nuclear layer, and photoreceptor layer were found to be significantly thinner in Group One compared to Group Two. We found no differences in mfERG parameters between the two groups. Conclusions: DLDs in SLE patients lead to abnormal central retinal layer thickness, which has no measurable impact on cone-mediated retinal function assessed by mfERG.
Biomedicines, Volume 11; https://doi.org/10.3390/biomedicines11061628
Prostate cancer (PCa) is a critical global public health issue with its incidence on the rise. Radiation therapy holds a primary role in PCa treatment; however, radiation resistance has become increasingly challenging as we uncover more about PCa’s pathogenesis. Our review aims to investigate the multifaceted mechanisms underlying radiation therapy resistance in PCa. Specifically, we will examine how various factors, such as cell cycle regulation, DNA damage repair, hypoxic conditions, oxidative stress, testosterone levels, epithelial–mesenchymal transition, and tumor stem cells, contribute to radiation therapy resistance. By exploring these mechanisms, we hope to offer new insights and directions towards overcoming the challenges of radiation therapy resistance in PCa. This can also provide a theoretical basis for the clinical application of novel ultra-high-dose-rate (FLASH) radiotherapy in the era of PCa.
Biomedicines, Volume 11; https://doi.org/10.3390/biomedicines11061627
Several scoring systems for clinical prediction of the severity of acute pancreatitis (AP) have been proposed. Yet, there is still a need for an easy-to-measure biomarker. Osteopontin (OPN) may be released to the circulation early during tissue injury, but the significance of OPN in AP has not yet been established. We aimed to evaluate plasma levels of OPN in relation to the severity of AP. In 39 individuals with confirmed AP, plasma was collected on the day of admission and consecutively for three days thereafter. Sex- and age-matched healthy blood donors (n = 39) served as controls. Plasma OPN was measured by a commercial enzyme-linked immunosorbent assay. At admission, patients with AP displayed higher OPN, 156.4 ng/mL (IQR 111.8–196.2) compared to controls, 37.4 ng/mL (IQR 11.7–65.7) (p < 0.0001). However, OPN levels on admission could not discriminate between mild and moderate-to-severe disease (132.6 ng/mL vs. 163.4 ng/mL). Nevertheless, the changes in OPN within 24 h of admission and Day 2/3 were higher among patients with moderate/severe AP (33.7%) compared to mild AP (−8.1%) (p = 0.01). This indicates that OPN is a relevant biomarker reflecting tissue injury in AP. The increase in OPN over time suggests that serial OPN measurements could contribute to the early detection of at-risk patients. Prospective studies assessing OPN in relation to outcome in AP are warranted.
Biomedicines, Volume 11; https://doi.org/10.3390/biomedicines11061625
Modern biomedical sensing techniques have significantly increased in precision and accuracy due to new technologies that enable speed and that can be tailored to be highly specific for markers of a particular disease. Diagnosing early-stage conditions is paramount to treating serious diseases. Usually, in the early stages of the disease, the number of specific biomarkers is very low and sometimes difficult to detect using classical diagnostic methods. Among detection methods, biosensors are currently attracting significant interest in medicine, for advantages such as easy operation, speed, and portability, with additional benefits of low costs and repeated reliable results. Single-molecule sensors such as nanopores that can detect biomolecules at low concentrations have the potential to become clinically relevant. As such, several applications have been introduced in this field for the detection of blood markers, nucleic acids, or proteins. The use of nanopores has yet to reach maturity for standardization as diagnostic techniques, however, they promise enormous potential, as progress is made into stabilizing nanopore structures, enhancing chemistries, and improving data collection and bioinformatic analysis. This review offers a new perspective on current biomolecule sensing techniques, based on various types of nanopores, challenges, and approaches toward implementation in clinical settings.
Biomedicines, Volume 11; https://doi.org/10.3390/biomedicines11061626
Over one century after its first military use on the battlefield, sulfur mustard (SM) remains a threatening agent. Due to the absence of an antidote and specific treatment, the management of SM-induced lesions, particularly on the skin and eyes, still represents a challenge. Current therapeutic management is mainly limited to symptomatic and supportive care, pain relief, and prevention of infectious complications. New strategies are needed to accelerate healing and optimize the repair of the function and appearance of damaged tissues. Hydrogels have been shown to be suitable for healing severe burn wounds. Because the same gravity of lesions is observed in SM victims, hydrogels could be relevant dressings to improve wound healing of SM-induced skin and ocular injuries. In this article, we review how hydrogel dressings may be beneficial for improving the wound healing of SM-induced injuries, with special emphasis placed on their suitability as drug delivery devices on SM-induced skin and ocular lesions.
Biomedicines, Volume 11; https://doi.org/10.3390/biomedicines11061624
Epigenetic mechanisms finely regulate gene expression and represent potential therapeutic targets. Cambinol is a synthetic heterocyclic compound that inhibits class III histone deacetylases known as sirtuins (SIRTs). The acetylating action that results could be crucial in modulating cellular functions via epigenetic regulations. The main aim of this research was to investigate the effects of cambinol, and its underlying mechanisms, on cell differentiation by combining wet experiments with bioinformatics analyses and molecular docking simulations. Our in vitro study evidenced the ability of cambinol to induce the differentiation in MCF-7, NB4, and 3T3-L1 cell lines. Interestingly, focusing on the latter that accumulated cytoplasmic lipid droplets, the first promising results related to the action mechanisms of cambinol have shown the induction of cell cycle-related proteins (such as p16 and p27) and modulation of the expression of Rb protein and nuclear receptors related to cell differentiation. Moreover, we explored the inhibitory mechanism of cambinol on human SIRT1 and 2 performing in silico molecular simulations by protein–ligand docking. Cambinol, unlike from other sirtuin inhibitors, is able to better interact with the substrate binding site of SIRT1 than with the inhibition site. Additionally, for SIRT2, cambinol partially interacts with the substrate binding site, although the inhibition site is preferred. Overall, our findings suggest that cambinol might contribute to the development of an alternative to the existing epigenetic therapies that modulate SIRTs.
Biomedicines, Volume 11; https://doi.org/10.3390/biomedicines11061623
Background: Stroke is a significant public health problem and a leading cause of death and long-term disability worldwide. Several treatments for ischemic stroke have been developed, but these treatments have limited effectiveness. One potential treatment for this condition is Actovegin®/AODEJIN, a calf blood deproteinized hemodialysate/ultrafiltrate that has been shown to have pleiotropic/multifactorial and possibly multimodal effects. The actual actions of this medicine are thought to be mediated by its ability to reduce oxidative stress, inflammation, and apoptosis and to enhance neuronal survival and plasticity. Methods: To obtain the most up-to-date information on the effects of Actovegin®/AODEJIN in ischemic stroke, we systematically reviewed the literature published in the last two years. This review builds upon our previous systematic literature review published in 2020, which used the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) method to search for and select related articles over almost two decades, between 1 January 2001 and 31 December 2019. Additionally, we compared the results of our PRISMA search (human intelligence-based) with those obtained from an interrogation of a GPT-based chatbot (ChatGPT) in order to ensure comprehensive coverage of potentially relevant studies. Results: Our updated review found limited new evidence on the use of Actovegin®/AODEJIN in ischemic stroke, although the number of articles on this subject consistently increased compared to that from our initial systematic literature review. Specifically, we found five articles up to 2020 and eight more until December 2022. While these studies suggest that Actovegin®/AODEJIN may have neuroprotective effects in ischemic stroke, further clinical trials are needed to confirm these findings. Consequently, we performed a funnel analysis to evaluate the potential for publication bias. Discussion: Our funnel analysis showed no evidence of publication bias, suggesting that the limited number of studies identified was not due to publication bias but rather due to a lack of research in this area. However, there are limitations when using ChatGPT, particularly in distinguishing between truth and falsehood and determining the appropriateness of interpolation. Nevertheless, AI can provide valuable support in conducting PRISMA-type systematic literature reviews, including meta-analyses. Conclusions: The limited number of studies identified in our review highlights the need for additional research in this area, especially as no available therapeutic agents are capable of curing central nervous system lesions. Any contribution, including that of Actovegin (with consideration of a positive balance between benefits and risks), is worthy of further study and periodic reappraisal. The evolving advancements in AI may play a role in the near future.