Deciphering the therapeutic potential of trimetazidine in rheumatoid arthritis via targeting mi-RNA128a, TLR4 signaling pathway, and adenosine-induced FADD-microvesicular shedding: In vivo and in silico study

Rheumatoid arthritis (RA) is a debilitating autoimmune condition characterized by chronic synovitis, joint damage, and inflammation, leading to impaired joint functionality. Existing RA treatments, although effective to some extent, are not without side effects, prompting a search for more potent therapies. Recent research has revealed the critical role of FAS-associated death domain protein (FADD) microvesicular shedding in RA pathogenesis, expanding its scope beyond apoptosis to include inflammatory and immune pathways. This study aimed to investigate the intricate relationship between mi-RNA 128a, autoimmune and inflammatory pathways, and adenosine levels in modulating FADD expression and microvesicular shedding in a Freund’s complete adjuvant (FCA) induced RA rat model and further explore the antirheumatoid potency of trimetazidine (TMZ). The FCA treated model exhibited significantly elevated levels of serum fibrogenic, inflammatory, immunological and rheumatological diagnostic markers, confirming successful RA induction. Our results revealed that the FCA-induced RA model showed a significant reduction in the expression of FADD in paw tissue and increased microvesicular FADD shedding in synovial fluid, which was attributed to the significant increase in the expression of the epigenetic miRNA 128a gene in addition to the downregulation of adenosine levels. These findings were further supported by the significant activation of the TLR4/MYD88 pathway and its downstream inflammatory IkB/NFB markers. Interestingly, TMZ administration significantly improved, with a potency similar to methotrexate (MTX), the deterioration effect of FCA treatment, as evidenced by a significant attenuation of fibrogenic, inflammatory, immunological, and rheumatological markers. Our investigations indicated that TMZ uniquely acted by targeting epigenetic miRNA128a expression and elevating adenosine levels in paw tissue, leading to increased expression of FADD of paw tissue and mitigated FADD microvesicular shedding in synovial fluid. Furthermore, the group treated with TMZ showed significant downregulation of TLR4/MYD88 and their downstream TRAF6, IRAK and NF-kB. Together, our study unveils the significant potential of TMZ as an antirheumatoid candidate, offering anti-inflammatory effects through various mechanisms, including modulation of the FADD-epigenetic regulator mi-RNA 128a, adenosine levels, and the TLR4 signaling pathway in joint tissue, but also attenuation of FADD microvesicular shedding in synovial fluid. These findings further highlight the synergistic administration of TMZ and MTX as a potential approach to reduce adverse effects of MTX while improving therapeutic efficacy.Peer Reviewe

Self-assembly of precisely defined DNA nanotube superstructures using DNA origami seeds

We demonstrate a versatile process for assembling micron-scale filament architectures by controlling where DNA tile nanotubes nucleate on DNA origami assemblies. "Nunchucks," potential mechanical magnifiers of nanoscale dynamics consisting of two nanotubes connected by a dsDNA linker, form at yields sufficient for application and consistent with models

Deciphering the therapeutic potential of trimetazidine in rheumatoid arthritis via targeting mi-RNA128a, TLR4 signaling pathway, and adenosine-induced FADD-microvesicular shedding: In vivo and in silico study

Rheumatoid arthritis (RA) is a debilitating autoimmune condition characterized by chronic synovitis, joint damage, and inflammation, leading to impaired joint functionality. Existing RA treatments, although effective to some extent, are not without side effects, prompting a search for more potent therapies. Recent research has revealed the critical role of FAS-associated death domain protein (FADD) microvesicular shedding in RA pathogenesis, expanding its scope beyond apoptosis to include inflammatory and immune pathways. This study aimed to investigate the intricate relationship between mi-RNA 128a, autoimmune and inflammatory pathways, and adenosine levels in modulating FADD expression and microvesicular shedding in a Freund’s complete adjuvant (FCA) induced RA rat model and further explore the antirheumatoid potency of trimetazidine (TMZ). The FCA treated model exhibited significantly elevated levels of serum fibrogenic, inflammatory, immunological and rheumatological diagnostic markers, confirming successful RA induction. Our results revealed that the FCA-induced RA model showed a significant reduction in the expression of FADD in paw tissue and increased microvesicular FADD shedding in synovial fluid, which was attributed to the significant increase in the expression of the epigenetic miRNA 128a gene in addition to the downregulation of adenosine levels. These findings were further supported by the significant activation of the TLR4/MYD88 pathway and its downstream inflammatory IkB/NFB markers. Interestingly, TMZ administration significantly improved, with a potency similar to methotrexate (MTX), the deterioration effect of FCA treatment, as evidenced by a significant attenuation of fibrogenic, inflammatory, immunological, and rheumatological markers. Our investigations indicated that TMZ uniquely acted by targeting epigenetic miRNA128a expression and elevating adenosine levels in paw tissue, leading to increased expression of FADD of paw tissue and mitigated FADD microvesicular shedding in synovial fluid. Furthermore, the group treated with TMZ showed significant downregulation of TLR4/MYD88 and their downstream TRAF6, IRAK and NF-kB. Together, our study unveils the significant potential of TMZ as an antirheumatoid candidate, offering anti-inflammatory effects through various mechanisms, including modulation of the FADD-epigenetic regulator mi-RNA 128a, adenosine levels, and the TLR4 signaling pathway in joint tissue, but also attenuation of FADD microvesicular shedding in synovial fluid. These findings further highlight the synergistic administration of TMZ and MTX as a potential approach to reduce adverse effects of MTX while improving therapeutic efficacy

Review: The increasing importance of carbon nanotubes and nanostructured conducting polymers in biosensors

The growing need for analytical devices requiring smaller sample volumes, decreased power consumption and improved performance have been driving forces behind the rapid growth in nanomaterials research. Due to their dimensions, nanostructured materials display unique properties not traditionally observed in bulk materials. Characteristics such as increased surface area along with enhanced electrical/optical properties make them suitable for numerous applications such as nanoelectronics, photovoltaics and chemical/biological sensing. In this review we examine the potential that exists to use nanostructured materials for biosensor devices. By incorporating nanomaterials, it is possible to achieve enhanced sensitivity, improved response time and smaller size. Here we report some of the success that has been achieved in this area. Many nanoparticle and nanofibre geometries are particularly relevant, but in this paper we specifically focus on organic nanostructures, reviewing conducting polymer nanostructures and carbon nanotubes

Ecotoxicity of Ag-nanoparticles on two microalgae, Chlorella vulgaris and Dunaliella tertiolecta

The increasing application of nanotechnology highlights the need to clarify and understand it. In this work, the subacute toxicity of Ag-NPs to the fresh water microalga Chlorella vulgaris and marine microalga Dunaliella tertiolecta were assessed. The effect of Ag-NPs was induced by exposing both algae to increasing concentrations of Ag-NPs (0, 10, 50, 100 and 200 mg/L). Cellular viability and reactive oxygen species (ROS) formation were determined to evaluate the toxic effect of Ag-NPs on algal growth. Superoxide dismutase (SOD), catalase (CAT) and peroxidase (POD) activities and lipid peroxidation (MDA) levels in the algal cells varied with the concentration of Ag-NPs suspensions and exposure times (up to 8 d). As a result, 100 and 200 mg/L Ag-NPs caused a statistically significant decrease in cell viability, as well as SOD, CAT and POD activities, and a significant increase in ROS formation and MDA levels in tissues (P <0.05), suggesting that the algal cells exposed to these two concentrations of Ag-NPs suffered from oxidative stress. The extent of depletion of antioxidant enzyme activities and the elevation of MDA in Dunaliella tertiolecta was the greatest, indicating that Dunaliella tertiolecta might be the most susceptible to Ag-NP exposure. These results indicated a potential risk from Ag-NPs released into the aqueous environment

Designing, Modeling, and Fabrication of a Novel Solar-Concentrating Spittoon against COVID-19 for Antibacterial Sustainable Atmosphere

Spreading infectious illnesses such as viral meningitis, hepatitis, and cytomegalovirus among people is facilitated by spitting in public. India is more prone to transferring infectious illnesses. Recent research discovered that the new Coronavirus may also be transmitted via an infected person’s saliva. Self-collected saliva from 91.7% of patients contains COVID-19. Numerous nations have prioritized preventing individuals from spitting in open or public areas such as hospitals, parks, airports, train stations, etc. The UVC range has a greater damaging effect on microbial cells because microorganisms’ intracellular components, such as RNA, DNA, and proteins, are sensitive to UVC photon absorption. In this article, the design and construction of a solar-concentrating spittoon is attempted. At its receiver, it can create a temperature of 390 K and 176 W of heat. At this temperature, most viruses (including Coronavirus), bacteria, and pathogens are inactivated. Daily, from 8:00 a.m. until 5:00 p.m., the solar-concentrating spittoon is functional. The solar-concentrating spittoon performance was best for nine hours. The receiver thermal efficiency was 80% and 20% of heat was lost to the surroundings. The overall efficiency was found to be 70%. During this time, most people spend their time outside, where this solar-powered spittoon can incinerate human cough and spit within one minute. The installation of this solar-concentrated spittoon will aid in preventing the spread of fatal dangerous diseases and cleaning the city

The Effectiveness of Online Education in Basic Medical Sciences Courses during the COVID-19 Pandemic in Saudi Arabia: Cross-Sectional Study

Coronavirus-19 (COVID-19) is an emerging pandemic that has caused significant disruptions to education, resulting in marked scholar closures across the world. The present study documents the student perception of the online educational process at six universities in Saudi Arabia during the COVID-19 lockdown period. The individual variable factors, i.e., institution, sex, and blended learning, that might influence student perception were also investigated. In this respect, a questionnaire that assessed the impact of COVID-19 on the online learning process and student perception was emailed to a total of 17,230 students from 3 institutions (medical, applied health and dental students) affiliated with six universities in Saudi Arabia. Principal component analysis (PCA) was performed to determine the validity of the questionnaire. A total of 4850 (28%) students responded to the questionnaire and 46.9% (n = 2275) of the respondents were highly satisfied with their online education. Analyses of the scores from the students showed a highly significant difference (p = 0.000) between the male and female students. Applied health students (highly satisfied score = 63.13) were the most satisfied with their online education, while medical students (highly satisfied score = 39.3) were the least satisfied with this education. In addition, applied health, dental and medical students showed a significantly higher score in favor of blended learning after schools re-open (p = 0.000). Collectively, student satisfaction with online education was common, and blended learning was preferred over the traditional format by both genders and all the students. The present data provide interesting contributions and evidence for policy makers and implementers, which might be helpful for the judgment side of decision making