Search

Rheumatoid arthritis (RA) is a heterogeneous inflammatory disease with an autoimmune origin and an incompletely elucidated pathophysiological mechanism. RA pharmacotherapy is based on chemically or biologically active substances that provide clinical alleviation and remission, but the disease is still incurable. As a result, there remains a need for significant therapeutic development, and adjuvant therapies may play an essential role in the search for novel RA treatment strategies. The aim of the present study was to investigate potential phytocompounds and phytocompound derivates as RA treatment agents, using in silico methodologies. In this regard, five phytoconstituents identified in different structures of Embelia ribes were evaluated by in silico methods for their potential action on target proteins of therapeutic interest in RA. The methodology involved identifying the phytocompound with the highest binding toward the target protein via molecular docking using AutoDock Vina 1.5.7, followed by a ligand-based virtual screening based on the structure of the most promising phytocompound using SwissSimilarity. This process led to the identification of ligands that are not currently utilized in medical practice, but that might have the potential to be used in the management of RA after further extensive experimental endorsements. ZINC000004024651 showed the highest binding affinity for the Bruton's tyrosine kinase protein, followed by ZINC000000434197 for p38 mitogen-activated protein kinases, ZINC000087606977 for interleukin-1 receptor-associated kinase 4, and ZINC000014728393 for matrix metallopeptidase 9, the latter two showing higher affinity than the co-crystallized compound. The relatively high affinities to target proteins and the pharmacokinetic data obtained by in silico studies using SwisADME suggest a first step for the inclusion of promising new compounds in various more advanced studies, leading to the evaluation of efficacy and safety profiles. [ABSTRACT FROM AUTHOR]

Alzheimer's disease (AD), once considered a rare disease, is now the most common form of dementia in the elderly population. Current drugs (cholinesterase inhibitors and glutamate antagonists) are safe but of limited benefit to most patients, offering symptomatic relief without successful cure of the disease. Since the last several decades, there has been a great need for the development of a treatment that might cure the underlying causes of AD and thereby slow its progression in vulnerable individuals. That is why phase I, II, and III studies that act on several fronts, such as cognitive improvement, symptom reduction, and enhancing the basic biology of AD, are imperative to stop the disease. This review discusses current treatment strategies, summarizing the clinical features and pharmacological properties, along with molecular docking analyses of the existing medications. [ABSTRACT FROM AUTHOR]

Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) is considered the etiological agent of the disease that caused the COVID-19 pandemic, and for which there is currently no effective treatment. This pandemic has shown that the rapid identification of therapeutic compounds is critical (when a new virus with high transmissibility occurs) to prevent or reduce as much as possible the loss of human lives. To meet the urgent need for drugs, many strategies were applied for the discovery, respectively the identification of potential therapies / drugs for SARS-CoV-2. Molecular docking and virtual screening are two of the in silico tools/techniques that provided the identification of few SARS-CoV-2 inhibitors, removing ineffective or less effective drugs and thus preventing the loss of resources such as time and additional costs. The main target of this review is to provide a comprehensive overview of how in-silico tools have been used in the crisis management of anti-SARS-CoV-2 drugs, especially in virtual screening of substances used in the treatment of SARS-CoV-2 infection and analysis of compounds with known action on structurally similar proteins from other viruses; also, completions were added to the way in which these methods came to meet the requirements of biomedical research in the field. Moreover, the importance and impact of the topic approached for researchers was highlighted by conducting an extensive bibliometric analysis. [Display omitted] • Our review focused on compounds proposed/evaluated by in silico techniques as anti-viral agents against SARS-CoV-2. • Much scientific effort has been put into making this field a cornerstone in the drug discovery and repositioning process • These approaches can significantly reduce the number of chemicals that must be examined in-vivo / in-vitro • The cost of the drug discovery progress will decrease using these methods. • SARS-CoV-2 pandemic shown that the necessity of quick identification of therapeutic compounds is mandatory [ABSTRACT FROM AUTHOR]

Coronavirus disease 2019 (COVID-19) represents an unmet clinical need, due to a high mortality rate, rapid mutation rate in the virus, increased chances of reinfection, lack of effectiveness of repurposed drugs and economic damage. COVID-19 pandemic has created an urgent need for effective molecules. Clinically proven efficacy and safety profiles have made favipiravir (FVP) and remdesivir (RDV) promising therapeutic options for use against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Even though both are prodrug molecules with an antiviral role based on a similar mechanism of action, differences in pharmacological, pharmacokinetic and pharmacotoxicological mechanisms have been identified. The present study aims to provide a comprehensive comparative assessment of FVP and RDV against SARS-CoV-2 infections, by centralizing medical data provided by significant literature and authorized clinical trials, focusing on the importance of a better understanding of the interactions between drug molecules and infectious agents in order to improve the global management of COVID-19 patients and to reduce the risk of antiviral resistance. [Display omitted] ● COVID-19 pandemic created an urgent need for effective molecules. ● Clinically efficacy revealed favipiravir and remdesivir as promising therapeutic options. ● Both are prodrug molecules with antiviral role based on similar mechanism of action. ● Differences: pharmacological, pharmacokinetic and pharmacotoxicological mechanisms. ● This study is a comprehensive comparative assessment of FVP / RDV against SARS-CoV-2. [ABSTRACT FROM AUTHOR]

Patients with diabetes are particularly susceptible to COVID-19 infection, which can result in severe respiratory illness. This study conducted a comparative assessment of the impact of antiviral therapy using molnupiravir and favipiravir in COVID-19 patients with underlying diabetes. A cohort of one hundred individuals infected with SARS-CoV-2, diagnosed with diabetes, and consecutively admitted, was included in the present study. These patients were treated with antivirals according to local guidelines: Group F (51 cases) was treated with favipiravir - 10 days and Group M (49 cases) was treated with molnupiravir - 5 days. In Group F, the average hospitalization was higher than in Group M (11.29±2.27 vs. 7.14±3.16, p<0.001). The risk score for severe evolution was less statistically significant at the end point of treatment in group M (156.29±61.32; 160.59±59.41, p<0.001). Administration of molnupiravir led to a decrease in the number of deaths among patients with COVID-19 compared to those treated with favipiravir [2 (4.08%) vs. 9 (17.65%), p=0.034]. Molnupiravir demonstrated superiority over favipiravir in treating SARS-CoV-2 infection in diabetic patients, and controlling or diagnosing diabetes is crucial to prevent the critical progression of COVID-19 patients. Further research is needed to confirm its potential in the management of infected individuals with SARS-CoV-2. [ABSTRACT FROM AUTHOR]

Stroke is a significant disability and death cause worldwide and is conventionally defined as a neurological impairment relating to the intense focal harm of the central nervous system (CNS) by vascular causative components. Although the applicability of robotic rehabilitation is a topic with considerable practical significance because it has produced noticeably higher improvements in motor function than regular (physical and occupational) therapy and exempted the therapists, most of the existing bibliometric papers were not focused on stroke survivors. Additionally, a modular system is designed by joining several medical end-effector devices to a single limb segment, which addresses the issue of potentially dangerous pathological compensatory motions. Searching the Web of Science database, 31,930 papers were identified, and using the VOSviewer software and science mapping technology, data were extracted on the most prolific countries, the connections between them, the most valuable journals according to certain factors, their average year of publication, the most influential papers, and the most relevant topical issues (bubble map of term occurrence). The most prolific country in the analyzed field and over the entire period evaluated (1975–2022) is the United States, and the most prolific journal is Neurorehabilitation and Neural Repair, observing a marked increase in the three periods of scientific interest for this field. The present paper assesses numerous scientific publications to provide, through statistical interpretation of the data, a detailed description of the use of robotic rehabilitation in stroke survivors. The findings may aid scientists, academics, and clinicians in establishing precise goals in the optimization of the management of stroke survivors via robotic rehabilitation, but also through easier access to scientifically validated literature. [ABSTRACT FROM AUTHOR]

Rheumatoid arthritis (RA) is a chronic multifactorial disorder of autoimmune etiology with a complex pathophysiological mechanism that is not yet fully elucidated. RA pharmacotherapy includes active molecules of chemical or biological nature that offer symptomatic relief and a slowing of progression, but still in a context of incurability. Therefore, the development of continuous research and multidisciplinary collaboration is essential. Although the management of RA is a topic of significant scientific relevance, existing bibliometric analyses are insufficient to assess this vast field. Consequently, the present study examines numerous manuscripts indexed in the Web of Science database using the VOSviewer software to provide through statistical interpretation of the data a comprehensive description of RA pharmacotherapy in terms of scientific impact, current state of research, number and frequency of citations, most prolific journals, authors, and countries, along with their relationships and other useful data for the literature search/publication process. Furthermore, the use of bubble maps of term occurrence has applicability in identifying current research trends in the field of RA pharmacotherapy as well as their evolution over the years. The leader in this field in terms of published papers is the United States, and the most prolific journal is Annals of the rheumatic diseases. The global management of RA, which is characterized by extensiveness and depth due to many variables, suggests the need for a conceptual framework based on pharmacotherapy coupled with comprehensive bibliometric studies, and the results may be useful for researchers in setting specific objectives that contribute to improving RA outcomes. [Display omitted] • Rheumatoid arthritis (RA) pharmacotherapy includes active molecules that offer symptomatic relief and slowing of progression. • This research examines 44832 manuscripts indexed in the Web of Science database using the VOSviewer software. • It provides through statistical interpretation of the data the description of RA pharmacotherapy scientific impact. • Bubble maps of term occurrence identify current research trends and evolution of RA pharmacotherapy. • The leader in publishing papers is the US, and the most prolific journal is Annals of the rheumatic diseases. [ABSTRACT FROM AUTHOR]

Approximately two-thirds of Romanian HIV patients were parenterally infected with the F subtype of HIV in early childhood. They are now in the context of immunological aging, with immunosuppression posing an additional challenge in developing the most effective and well-tolerated regimens. The risk of an improper immune recovery is higher in these patients than in newly diagnosed patients. The primary goal of this retrospective study was to conduct a comparative analysis of the immune recovery, measured at three time points, on 462 HIV-infected patients who were registered at the "Matei Balş National Institute of Infectious Diseases", Bucharest, Romania, between 2018 and 2021, as follows: darunavir (DRV) 600 mg plus ritonavir (RTV) 100 mg (twice daily) was given to 384 patients, while DRV 800 mg plus cobicistat (COBI) 150 mg was given to 78 patients (once daily). The immune response was assessed by counting T lymphocytes, CD4 count cells/mm3, and the CD4/CD8 lymphocyte count ratio. Additionally, the study assessed the relationship between the immune and virological responses to therapy. Using various statistical tests, the results revealed that the immune response is normal in both groups, but with a statistically significant difference (p < 0.05) for the DRV/c group. Statistical associations between RNA viral plasma load and immune response (CD4 count and CD4/CD8 ratio) were assessed at all three visits and showed an insignificant association for the first two time points; however, at the final visit, the outcomes changed and reached statistical significance for both groups. [Display omitted] • The natural physiological implication of aging is an additional challenge for HIV patients. • A comparative analysis of the immune recovery, measured in three time points of 2 groups of patients, is provided. • Treatment regimens also contained pharmacokinetically enhanced DRV with RTV or COBI. • By determining the T lymphocytes no., CD4 count cells/mm3, and the lymphocyte ratio CD4/CD8, the immune response was obtained. • The study analyzed the correlation regarding the immune/virological response to therapy. [ABSTRACT FROM AUTHOR]