Search Results (84)

Alphaviruses are transmitted by Aedes mosquitoes and cause large-scale epidemics worldwide. Chikungunya virus (CHIKV) infection can cause febrile seizures known as chikungunya fever (CHIKF), which ultimately leads to severe joint pain and myalgia. While a vaccine has recently been introduced against CHIKV, at present, no anti-viral drug is available. CHIKV, like other alphaviruses, has a short 6K protein capable of forming an ion channel. Blocking this ion channel with drugs can therefore serve as a potential way to curtail CHIKV infection. To that end, we screened a repurposed drug library using three bacteria-based channel assays to detect blockers against 6K viroporin, yielding several hits. Interestingly, several of the blockers were able to inhibit the 6K protein from the similar Eastern equine encephalitis virus (EEEV), while others were not, pointing to structural specificity which may be explained by modeling studies. In conclusion, our study provides a starting point for developing a new route to potentially inhibit CHIKV. Full article

Type 2 diabetes mellitus (T2D) and cardiovascular disease (CVD) are not merely coexisting epidemics but co-evolving manifestations of a shared cardiometabolic continuum. Despite advances in glycemic, lipid, and blood pressure control, residual cardiovascular risk remains high, underscoring the limitations of siloed approaches. In this perspective, we argue for reframing T2D and CVD as interconnected conditions driven by inflammation, adipose tissue dysfunction, and organ crosstalk. Beyond metformin, which remains foundational, several glucose-lowering drug classes are now evaluated not only for glycemic control but also for their cardiovascular and renal impact. Landmark trials and recent meta-analyses confirm that sodium-glucose co-transporter 2 inhibitors and glucagon-like peptide-1 (GLP-1) receptor agonists improve cardiorenal outcomes. More recently, tirzepatide, a dual glucose-dependent insulinotropic polypeptide (GIP)/GLP-1 receptor agonist, has shown unprecedented efficacy in weight and glucose management, with potential to further transform cardiometabolic risk reduction. Yet enthusiasm for these therapies must be tempered by heterogeneity of response, treatment costs, and inequitable access. Integrated care models, supported by multidisciplinary teams, digital health tools, and value-based reimbursement, are essential to close the gap between trial efficacy and real-world outcomes. Attention to sex, age, ethnicity, and comorbidity profiles is critical to ensure equity, as is the adaptation of strategies to low- and middle-income countries where the burden of cardiometabolic disease is rapidly rising. Ultimately, advancing cardiometabolic medicine requires not only novel therapies but also a unifying framework that integrates biology, behavior, economics, and health systems to deliver the right treatment to the right patient at the right time. Full article

Diabetes mellitus, both type 1 (T1D) and type 2 (T2D), has become the epidemic of the century and a major public health concern given its rising prevalence and the increasing adoption of a sedentary lifestyle globally. This multifaceted disease is characterized by impaired pancreatic beta cell function and insulin resistance (IR) in peripheral organs, namely the liver, skeletal muscle, and adipose tissue. Additional insulin target tissues, including cardiomyocytes and neuronal cells, are also affected. The advent of stem cell research has opened new avenues for tackling this disease, particularly through the regeneration of insulin target cells and the establishment of disease models for further investigation. Human-induced pluripotent stem cells (iPSCs) have emerged as a valuable resource for generating specialized cell types, such as hepatocytes, myocytes, adipocytes, cardiomyocytes, and neuronal cells, with diverse applications ranging from drug screening to disease modeling and, importantly, treating IR in T2D. This review aims to elucidate the significant applications of iPSC-derived insulin target cells in studying the pathogenesis of insulin resistance and T2D. Furthermore, recent differentiation strategies, protocols, signaling pathways, growth factors, and advancements in this field of therapeutic research for each specific iPSC-derived cell type are discussed. Full article

Recent outbreaks of highly pathogenic human RNA viruses from probable zoonotic origin have highlighted the relevance of epidemic preparedness as a society. However, research in vaccinology and virology, as well as epidemiologic surveillance, is often constrained by the biological risk that live virus experimentation entails. These also involve expensive costs, time-consuming procedures, and advanced personnel expertise, hampering market access for many drugs. Most of these drawbacks can be circumvented with the use of pseudotyped viruses, which are surrogate, non-pathogenic recombinant viral particles bearing the surface envelope protein of a virus of interest. Pseudotyped viruses significantly expand the research potential in virology, enabling the study of non-culturable or highly infectious pathogens in a safer environment. Most are derived from lentiviral vectors, which confer a series of advantages due to their superior efficiency. During the past decade, many studies employing pseudotyped viruses have evaluated the efficacy of vaccines or monoclonal antibodies for relevant pathogens such as HIV-1, Ebolavirus, Influenza virus, or SARS-CoV-2. In this review, we aim to provide an overview of the applications of pseudotyped viruses when evaluating the neutralization capacity of exposed individuals, or candidate vaccines and antivirals in both preclinical models and clinical trials, to further help develop effective countermeasures against emerging neutralization-escape phenotypes. Full article

The opioid drug overdose death rate remains a significant public health crisis in the U.S., where an opioid epidemic has led to a dramatic rise in overdose deaths over the past two decades. Since 1999, opioids have been implicated in approximately 75% of the nearly one million drug-related deaths. Research indicates that the epidemic is caused by both over-prescribing and social and psychological determinants such as economic stability, hopelessness, and social isolation. Impeding this research is the lack of measurements of these social and psychological constructs at fine-grained spatial and temporal resolution. To address this issue, we sourced data from Reddit, where people share self-reported experiences with opioid substances, specifically using opioid drugs through different routes of administration. To achieve this objective, an opioid overdose dataset is created and manually annotated in binary and multi-classification, along with detailed annotation guidelines. In traditional manual investigations, the route of administration is determined solely through biological laboratory testing. This study investigates the efficacy of an automated tool leveraging natural language processing and transformer model, such as RoBERTa, to analyze patterns of substance use. By systematically examining these patterns, the model contributes to public health surveillance efforts, facilitating the identification of at-risk populations and informing the development of targeted interventions. This approach ultimately aims to enhance prevention and treatment strategies for opioid misuse through data-driven insights. The findings show that our proposed methodology achieved the highest cross-validation score of 93% for binary classification and 91% for multi-class classification, demonstrating performance improvements of 9.41% and 10.98%, respectively, over the baseline model (XGB, 85% in binary class and 81% in multi-class). Full article

Porcine epidemic diarrhea virus (PEDV) causes a highly contagious intestinal disease with severe economic impacts on the global swine industry. The non-structural protein 13 (nsp13), a viral helicase, is essential for viral replication, making it a promising target for antiviral drug development. In this study, through virtual screening and molecular dynamics simulations, Vancomycin, a small-molecule drug also clinically used as an antibacterial agent, was identified to exhibit a stable binding affinity for PEDV nsp13. The NTPase and ATP-dependent RNA helicase activities of PEDV nsp13 were confirmed in vitro, and the optimal biochemical reaction conditions for its dsRNA unwinding activity were established. Further experiments demonstrated that Vancomycin effectively inhibited the dual enzymatic activities of PEDV nsp13 and reduced PEDV infections in vitro. This research highlights Vancomycin as a novel inhibitor of PEDV nsp13, providing valuable mechanistic insights and serving as a model for antiviral drug discovery. While this study suggests its potential for repurposing as a therapeutic agent against PEDV, further investigations are required to evaluate its feasibility in vivo, particularly in terms of safety, efficacy, and practical applicability. Full article

Amphetamine abuse is a global health epidemic that is difficult to treat due to individual differences in response to environmental factors, including stress reactivity and anxiety levels, as well as individual neuronal differences, which may result in increased/decreased vulnerability to addiction. In the present study, we investigated whether the Wistar rats behavioral traits of high (HR) and low (LR) locomotor activity to novelty influence motivational behavior (induced feeding model; iFR by electrical stimulation of the ventral tegmental area; Es-VTA) supported by amphetamine injection into the nucleus accumbens shell (AcbSh) (HR_Amph, n = 5; LR_Amph, n = 5). A correlation was found between the novelty test’s locomotor activity score and the frequency threshold percentage change (p < 0.001, Rs = −0.867). In HR_Amph, there was a shortening (−24.16%), while in LR_Amph, there was a lengthening (+51.84%) of iFR latency. Immunofluorescence studies showed differential neuronal density (activity of tyrosine hydroxylase, choline acetyltransferase, and cFos protein) in the selected brain structures in HR_Amph and LR_Amph animals as well as in comparison to a control group (HR_ACSF, n = 5; LR_ACSF, n = 5). These results contribute to expanding the state of knowledge of the behavioral and neuronal propensity to take drug abuse. Full article

Juvenile idiopathic arthritis (JIA) is a chronic autoimmune condition in children that often requires long-term pain management, which can include opioid use. In the context of Canada’s ongoing overdose crisis, youth with JIA face risks due to potential opioid dependency and exposure to toxic drug supplies. This commentary proposes an integrated approach combining chronic disease management with harm reduction strategies specifically tailored for JIA patients. By incorporating multidisciplinary care, opioid stewardship, and harm reduction measures, this approach aims to address the dual challenges of managing chronic pain and mitigating substance use risks. Key recommendations include the development of integrated care models, enhanced access to multidisciplinary services, allocation of resources for specialized pain management, research, and mental health support, and investment in harm reduction initiatives. Additionally, comprehensive training for healthcare providers on the intersection of chronic pain, substance use, and mental health is essential. This integrated strategy not only supports the medical and psychosocial needs of youth with JIA but also offers a model for addressing the broader challenges faced by vulnerable populations in the overdose crisis. Adopting these measures will help protect this at-risk group, improve their quality of life, and contribute to the overall public health response to the overdose epidemic. Full article

Over the years, the growing “epidemic” spread of cocaine use represents a crucial public health and social problem worldwide. According to the 2023 World Drug Report, 0.4% of the world’s population aged 15 to 64 report using cocaine; this number corresponds to approximately 24.6 million cocaine users worldwide and approximately 1 million subjects with cocaine use disorder (CUD). While we specifically know the short-term side effects induced by cocaine, unfortunately, we currently do not have exhaustive information about the medium/long-term side effects of the substance on the body. The scientific literature progressively highlights that the chronic use of cocaine is related to an increase in cardio- and cerebrovascular risk and probably to a greater incidence of psychomotor symptoms and neurodegenerative processes. Several studies have highlighted an increased risk of antipsychotic-induced extrapyramidal symptoms (EPSs) in patients with psychotic spectrum disorders comorbid with psychostimulant abuse. EPSs include movement dysfunction such as dystonia, akathisia, tardive dyskinesia, and characteristic symptoms of Parkinsonism such as rigidity, bradykinesia, and tremor. In the present paper, we propose a model of interpretation of the neurobiological mechanisms underlying the hypothesized increased vulnerability in chronic cocaine abusers to neurodegenerative disorders with psychomotor symptoms. Specifically, we supposed that the chronic administration of cocaine produces significant neurobiological changes, causing a complex dysregulation of various neurotransmitter systems, mainly affecting subcortical structures and the dopaminergic pathways. We believe that a better understanding of these cellular and molecular mechanisms involved in cocaine-induced neuropsychotoxicity may have helpful clinical implications and provide targets for therapeutic intervention. Full article

Salmonella species are causal pathogens instrumental in human food-borne diseases. The pandemic survey related to multidrug resistant (MDR) Salmonella genomics enables the prevention and control of their dissemination. Currently, serotype Mbandaka is notorious as a multiple host-adapted non-typhoid Salmonella. However, its epidemic and MDR properties are still obscure, especially its genetic determinants accounting for virulence and MD resistance. Here, we aim to characterize the genetic features of a strain SMEH pertaining to Salmonella Mbandaka (S. Mbandaka), isolated from the patient’s hydropericardium, using cell infections, a mouse model, antibiotic susceptibility test and comparative genomics. The antibiotic susceptibility testing showed that it could tolerate four antibiotics, including chloramphenicol, tetracycline, fisiopen and doxycycline by Kirby–Bauer (K-B) testing interpreted according to the Clinical and Laboratory Standards Institute (CLSI). Both the reproducibility in RAW 264.7 macrophages and invasion ability to infect HeLa cells with strain SMEH were higher than those of S. Typhimurium strain 14028S. In contrast, its attenuated virulence was determined in the survival assay using a mouse model. As a result, the candidate genetic determinants responsible for antimicrobial resistance, colonization/adaptability and their transferability were comparatively investigated, such as bacterial secretion systems and pathogenicity islands (SPI-1, SPI-2 and SPI-6). Moreover, collective efforts were made to reveal a potential role of the plasmid architectures in S. Mbandaka as the genetic reservoir to transfer or accommodate drug-resistance genes. Our findings highlight the essentiality of antibiotic resistance and risk assessment in S. Mbandaka. In addition, genomic surveillance is an efficient method to detect pathogens and monitor drug resistance. The genetic determinants accounting for virulence and antimicrobial resistance underscore the increasing clinical challenge of emerging MDR Mbandaka isolates, and provide insights into their prevention and treatment. Full article

COVID-19, generated by SARS-CoV-2, has significantly affected healthcare systems worldwide. The epidemic has highlighted the urgent need for vaccine development. Besides the conventional vaccination models, which include live-attenuated, recombinant protein, and inactivated vaccines, nanovaccines present a distinct opportunity to progress vaccine research and offer convenient alternatives. This review highlights the many widely used nanoparticle vaccine vectors, outlines their benefits and drawbacks, and examines recent developments in nanoparticle vaccines to prevent SARS-CoV-2. It also offers a thorough overview of the many advantages of nanoparticle vaccines, including an enhanced host immune response, multivalent antigen delivery, and efficient drug delivery. The main objective is to provide a reference for the development of innovative antiviral vaccines. Full article

The future paradigm of early cardiac diagnostics is shifting the focus towards heart attack preventive medicine based on non-invasive medical imaging with the support of artificial intelligence. It is necessary to preventively detect its increased risk early and respond with preventive drugs before moving on to more effective, but also more invasive, forms of therapy. The main motivation of our study was to improve existing and develop new AI-based solutions for cardiac preventive medicine, with particular emphasis on the prevention of heart attacks. This is due to the fact that the epidemic of lifestyle diseases (including cardiologic ones) has been stopped but not reversed; hence, automatically supervised prevention using AI seems to be a key opportunity to introduce progress in the above-mentioned areas. This can have major effects not only scientific and clinical in nature, but also economic and social. The aim of this article is to develop and test an AI-based tool designed to predict the occurrence of a heart attack for the purposes of preventive medicine. It used the combination and comparison of multiple AI methods and techniques to determine a personalized heart attack probability based on a wide range of patient characteristics and, from a computational point of view, determine the minimum set of characteristics necessary to do so. When applied to a specific patient, this represents progress in this field of research, resulting in improvements in preclinical care and diagnostics, as well as predictive accuracy in preventive medicine. After an initial selection based on the authors’ knowledge and experience, four solutions turned out to be the best: linear support vector machine (Linear SVC), logistic regression, k-nearest neighbors algorithm (KNN, k-NN), and random forest. A comparison of the models developed in the study shows that models based on logistic regression proved to be the most accurate, although their predictive value is moderate, but sufficient for the initial screening diagnosis—selecting patients who require further, more accurate testing. In addition, this can be performed based on a reduced set of parameters, particularly heart rate, age, BMI, and cholesterol. This allows the development of a prevention strategy based on modifiable factors (e.g., in the form of diet, activity modification, or a hybrid combining different factors) combined with the monitoring of heart attack risk by the proposed system. The novelty and contribution of the described system lies in the use of AI for a widely available, cheap, and quick predictive analysis of cardiovascular functions in a group of patients classified as at risk, and over time in all patients as a standard periodic examination qualifying them for further, more advanced diagnosis of heart diseases. Full article

Influenza antiviral drugs are important tools in our fight against both annual influenza epidemics and pandemics. Polyphenols are a group of compounds found in plants, some of which have demonstrated promising antiviral activity. Previous in vitro and mouse studies have outlined the anti-influenza virus effectiveness of the polyphenol epigallocatechin-3-gallate (EGCG); however, no study has utilised the ferret model, which is considered the gold-standard for influenza antiviral studies. This study aimed to explore the antiviral efficacy of EGCG in vitro and in ferrets. We first performed studies in Madin-Darby Canine Kidney (MDCK) and human lung carcinoma (Calu-3) cells, which demonstrated antiviral activity. In MDCK cells, we observed a selective index (SI, CC50/IC50) of 77 (290 µM/3.8 µM) and 96 (290 µM/3.0 µM) against A/California/07/2009 and A/Victoria/2570/2019 (H1N1)pdm09 influenza virus, respectively. Calu-3 cells demonstrated a SI of 16 (420 µM/26 µM) and 18 (420 µM/24 µM). Ferrets infected with A/California/07/2009 influenza virus and treated with EGCG (500 mg/kg/day for 4 days) had no change in respiratory tissue viral titres, in contrast to oseltamivir treatment, which significantly reduced viral load in the lungs of treated animals. Therefore, we demonstrated that although EGCG showed antiviral activity in vitro against influenza viruses, the drug failed to impair viral replication in the respiratory tract of ferrets. Full article

In the 21st century, the effects of HIV-associated neurocognitive disorders (HAND) have been significantly reduced in individuals due to the development of antiretroviral therapies (ARTs). However, the growing epidemic of polysubstance use (PSU) has led to concern for the effects of PSU on HIV-seropositive individuals. To effectively treat individuals affected by HAND, it is critical to understand the biological mechanisms affected by PSU, including the identification of novel markers. To fill this important knowledge gap, we used an in vivo HIV-1 Transgenic (HIV-1 Tg) animal model to investigate the effects of the combined use of chronic methamphetamine (METH) and oxycodone (oxy). A RNA-Seq analysis on the striatum—a brain region that is primarily targeted by both HIV and drugs of abuse—identified key differentially expressed markers post-METH and oxy exposure. Furthermore, ClueGO analysis and Ingenuity Pathway Analysis (IPA) revealed crucial molecular and biological functions associated with ATP-activated adenosine receptors, neuropeptide hormone activity, and the oxytocin signaling pathway to be altered between the different treatment groups. The current study further reveals the harmful effects of chronic PSU and HIV infection that can subsequently impact neurological outcomes in polysubstance users with HAND. Full article

In this article, we mainly consider the dynamic analysis of a stochastic infectious disease model with negative feedback, a symmetric and compatible distribution family. Based on the sir epidemic model taking into account the isolation (y) and the death (v), we consider adding a new variable (w) to control the information of non-drug interventions, which measures transformations in isolation performance that determine the epidemic, and establish a new model. We have demonstrated various properties of the model solution using Lyapunov functions for this model. To begin with, we demonstrate the existence and uniqueness of the global positive solution. After that, we obtained the conditions that need to be met for the extinction of the disease and verified the correctness of the conclusion by simulating numerical values. Afterwards, we prove the stochastic boundedness and stationary distribution of the model solution. Full article