Ameliorative and anti-arthritic potential of arjunolic acid against complete Freund’s adjuvant-induced arthritis in rats

Purpose: To determine the anti-arthritic effect of arjunolic acid against complete Freund’s adjuvant (CFA)-induced arthritis in rats.Methods: Arthritis was induced in male Sprague Dawley rats by intradermal injection of 0.1 mL of CFA at the right footpad. Upon induction of osteoarthritis, arjunolic acid was administered via oral gavage at doses of 40 and 80 mg/kg once daily for 25 successive days. Indomethacin was used as reference drug at a dose of 3 mg/kg via gavage twice weekly for 25 days. Changes in paw swelling, serum hematology, antioxidant enzymes, serum inflammatory mediators, and histopathology were determined using standard procedures.Results: Paw swelling and weight loss in CFA-induced arthritic rats were significantly reversed (p < 0.01) by arjunolic acid. Malondialdehyde (MDA) levels, spleen index and thymus index were significantly reduced in CFA-induced arthritic rats (p < 0.01). Moreover, arjunolic significantly increased superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) activities, while downregulating the expressions of TNF-α, IL-1β and IL-6 in serum (p < 0.01). The hematological and histopathological changes due to CFA-induced arthritis were ameliorated by arjunolic acid.Conclusion: The results obtained in this study indicate that arjunolic acid may possess therapeutic potentials for the management of arthritis. Keywords: Arjunolic acid, Triterpenoid; Oxidative stress, osteoarthritis, Inflammatio

Role of novel histone modifications in cancer

This article briefly discusses post-translational modifications such as neddylation, sumoylation, glycosylation, phosphorylation, polyADP ribosylation, ubiquitination, and transcriptional regulation

The Landscape of Noncoding RNA in Pulmonary Hypertension

The transcriptome of pulmonary hypertension (PH) is complex and highly genetically heterogeneous, with noncoding RNA transcripts playing crucial roles. The majority of RNAs in the noncoding transcriptome are long noncoding RNAs (lncRNAs) with less circular RNAs (circRNAs), which are two characteristics gaining increasing attention in the forefront of RNA research field. These noncoding transcripts (especially lncRNAs and circRNAs) exert important regulatory functions in PH and emerge as potential disease biomarkers and therapeutic targets. Recent technological advancements have established great momentum for discovery and functional characterization of ncRNAs, which include broad transcriptome sequencing such as bulk RNA-sequence, single-cell and spatial transcriptomics, and RNA-protein/RNA interactions. In this review, we summarize the current research on the classification, biogenesis, and the biological functions and molecular mechanisms of these noncoding RNAs (ncRNAs) involved in the pulmonary vascular remodeling in PH. Furthermore, we highlight the utility and challenges of using these ncRNAs as biomarkers and therapeutics in PH

Antioxidant and Anti-Inflammatory Effects of 6,3’,4´- and 7,3´,4´-Trihydroxyflavone on 2D and 3D RAW264.7 Models

Dietary flavones 6,3´,4´-trihydroxyflavone (6,3´,4´-HOFL) and 7,3´,4´-trihydroxyflavone (7,3´,4´-HOFL) showed preliminary antioxidant and anti-inflammatory activities in a two-dimensional (2D) cell culture model. However, their action mechanisms remain unclear, and the anti-inflammatory activities have not been studied in a reliable three-dimensional (3D) cell model. Therefore, in the current study, the antioxidant potency was examined by their scavenging ability of cellular reactive oxygen species. Anti-inflammatory activities were examined via their inhibitory effects on inflammatory mediators in vitro on 2D and 3D macrophage models, and their mechanisms were determined through transcriptome. In the 3D macrophages, two flavones were less bioactive than they were in 2D macrophages, but they both significantly suppressed the overexpression of proinflammatory mediators in two cell models. The divergent position of the hydroxyl group on the A ring resulted in activity differences. Compared to 6,3´,4´-HOFL, 7,3´,4´-HOFL showed lower activity on NO, IL-1β suppression, and c-Src binding (IC50: 12.0 and 20.9 µM) but higher ROS-scavenging capacity (IC50: 3.20 and 2.71 µM) and less cytotoxicity. In addition to the IL-17 and TNF pathways of 6,3´,4´-HOFL, 7,3´,4´-HOFL also exerted anti-inflammatory activity through JAK-STAT, as indicated by the RNA-sequencing results. Two flavones showed prominent antioxidant and anti-inflammatory activities on 2D and 3D models

PKA phosphorylation of HERG protein regulates the rate of channel synthesis

Acute changes in cAMP and protein kinase A (PKA) signaling can regulate ion channel protein activities such as gating. Effects on channels due to chronic PKA signaling, as in stress or disease states, are less understood. We examined the effects of prolonged PKA activity on the human ether-a-go-go-related gene (HERG) K+ channel in stably transfected human embryonic kidney (HEK)293 cells. Sustained elevation of cAMP by either chlorophenylthiol (CPT)-cAMP or forskolin increased the HERG channel protein abundance two- to fourfold within 24 h, with measurable difference as early as 4 h. The cAMP-induced augmentation was not due to changes in transcription and was specific for HERG compared with other cardiac K+ channels (Kv1.4, Kv1.5, Kir2.1, and KvLQT1). PKA activity was necessary for the effect on HERG protein and did not involve other cAMP signaling pathways. Direct PKA phosphorylation of the HERG protein was responsible for the cAMP-induced augmentation. Enhanced abundance of HERG protein was detected in endoplasmic reticulum-enriched, Golgi, and plasma membrane without significant changes in trafficking rates or patterns. An increase in the K+ current density carried by the HERG channel was also observed, but with a delay, suggesting that traffic to the surface is rate-limiting traffic. Acceleration of the HERG protein synthesis rate was the primary factor in the cAMP/PKA effect with lesser effects on protein stability. These results provide evidence for a novel mechanism whereby phosphorylation of a nascent protein dictates its rate of synthesis, resetting its steady-state abundance

Gain enhancement in a V-shaped plasmonic slot waveguide for efficient loss compensation at the subwavelength scale

a b s t r a c t An active plasmonic slot waveguide comprising an inverted triangular metal wedge incorporated inside a V-shaped plasmonic groove with a low-index gain medium embedded between them is presented, and its guiding properties are investigated numerically at the wavelength of 1550 nm. The presented waveguide is shown to be capable of supporting two fundamental plasmonic slot modes with high field localization to the V-shaped low-index slot region. Due to such strong optical confinement and significant field enhancement, the introduced gain in the slot could effectively compensate the propagation loss of the supported plasmonic modes. It is revealed that for the studied channel plasmonic slot and wedge plasmonic slot modes, notable gain enhancements are observable within a wide range of geometric parameters. For the considered structure with a 10-40 nm-wide slot, the enhancements of gain can be as large as 11%-159% for the CPS mode while 43%-174% for the WPS mode. These values could be further improved by adopting even narrower slots. It is shown that, by introducing a gain medium with coefficients around hundreds of cm À 1 , the modal loss can be largely or even fully compensated, with a subwavelength mode area achievable simultaneously. These unique features of the studied V-shaped plasmonic slot waveguide might be useful for its potential applications in compact, active plasmonic components

Preliminary design and analysis of a cubic deployable support structure based on shape memory polymer composite

The deployable structures based on shape memory polymer composites (SMPCs) have been developed for its unique properties, such as high reliability, low-cost, lightweight, and self-deployment without complex mechanical devices compared with traditional deployable structures. In order to increase the inflatable structure system’s robustness and light the weight of it, a cubic deployable support structure based on SMPC is designed and analyzed preliminarily. The cubic deployable support structure based on SMPC consists of four dependent spatial cages, each spatial cage is composed of 12 three-longeron SMPC truss booms and end connections. The shape recovery of arc-shaped deployable laminates drive the three-longeron SMPC truss booms to unfold, thus realize the expansion of the deployable support structure. The concept and operation of the cubic deployable support structure are described in detail. A series of experiments are performed on the three-longeron deployable laminates unit and the simplified cubic deployable support structure to investigate the shape recovery behavior in the deployment process. Results indicate that the cubic deployable support structure has a high deployment-tgo-stowage volume ratio and can achieve self-deployment, package, and deploy without complex mechanical devices

T: Nanowire based hybrid plasmonic structures for low-threshold lasing at the subwavelength scale

a b s t r a c t Novel plasmonic nanolaser structures are proposed by leveraging the efficient guiding properties of hybrid plasmonic modes of nanowire based waveguides. Theoretical investigations reveal that the coupling between the metal nanowire and the high-index dielectric nanostructure with optical gain results in strong field enhancement in the low-index gap region, sufficient modal overlap with the gain medium and low propagation loss, which could enable lasing at the subwavelength scale with low pump threshold. The proposed nanowire-based plasmonic nanolasers are also compatible with standard fabrication technology and could be appealing candidates for active photonic systems