Emerging nanoscience allows us to take advantage of the improved evolutionary components and apply today’s advanced characterization and fabrication techniques to solve environmental and biological problems. Despite the promise that nanotechnology will improve our lives, the potential risks of technology remain largely uncertain. The lack of information on bio-impacts and the absence of consistent standards are the limitations of using metal-based nanoparticles (mNPs) for existing applications. To analyze the role played by the mNPs physicochemical characteristics and tactics to protect live beings, the field of nanotoxicology nowadays is focused on collecting and analyzing data from in vitro and in vivo investigations. The degree of reactive oxygen species (ROS) and oxidative stress caused by material nanoparticles (NPs) depends on many factors, such as size, shape, chemical composition, etc. These characteristics enable NPs to enter cells and interact with biological macromolecules and cell organelles, resulting in oxidative damage, an inflammatory response, the development of mitochondrial dysfunction, damage to genetic material, or cytotoxic effects. This report explored the mechanisms and cellular signaling cascades of mNPs-induced oxidative stress and the relevant health consequences.
Achyranthes japonica Nakai root (AJNR) is used to treat osteoarthritis (OA) and rheumatoid arthritis (RA) owing to its anti-inflammatory and antioxidant effects. This study investigated the inhibitory effects of AJNR on arthritis. AJNR was extracted using supercritical carbon dioxide (CO2), and its main compounds, pimaric and kaurenoic acid, were identified. ANJR’s inhibitory effects against arthritis were evaluated using primary cultures of articular chondrocytes and two in vivo arthritis models: destabilization of the medial meniscus (DMM) as an OA model, and collagenase-induced arthritis (CIA) as an RA model. AJNR did not affect pro-inflammatory cytokine (IL-1β, TNF-α, IL-6)-mediated cytotoxicity, but attenuated pro-inflammatory cytokine-mediated increases in catabolic factors, and recovered pro-inflammatory cytokine-mediated decreases in related anabolic factors related to in vitro. The effect of AJNR is particularly specific to IL-6-mediated catabolic or anabolic alteration. In a DMM model, AJNR decreased cartilage erosion, subchondral plate thickness, osteophyte size, and osteophyte maturity. In a CIA model, AJNR effectively inhibited cartilage degeneration and synovium inflammation in either the ankle or knee and reduced pannus formation in both the knee and ankle. Immunohistochemistry analysis revealed that AJNR mainly acted via the inhibitory effects of IL-6-mediated matrix metalloproteinase-3 and -13 in both arthritis models. Therefore, AJNR is a potential therapeutic agent for relieving arthritis symptoms.
Estrogen-related receptors (ERRs) are the first identified orphan nuclear receptors. The ERR family consists of ERRα, ERRβ, and ERRγ, regulating diverse isoform-specific functions. We have reported the importance of ERRγ in osteoarthritis (OA) pathogenesis. However, therapeutic approaches with ERRγ against OA associated with inflammatory mechanisms remain limited. Herein, we examined the therapeutic potential of a small-molecule ERRγ inverse agonist, GSK5182 (4-hydroxytamoxifen analog), in OA, to assess the relationship between ERRγ expression and pro-inflammatory cytokines in mouse articular chondrocyte cultures. ERRγ expression increased following chondrocyte exposure to various pro-inflammatory cytokines, including interleukin (IL)-1β, IL-6, and tumor necrosis factor (TNF)-α. Pro-inflammatory cytokines dose-dependently increased ERRγ protein levels. In mouse articular chondrocytes, adenovirus-mediated ERRγ overexpression upregulated matrix metalloproteinase (MMP)-3 and MMP-13, which participate in cartilage destruction during OA. Adenovirus-mediated ERRγ overexpression in mouse knee joints or ERRγ transgenic mice resulted in OA. In mouse joint tissues, genetic ablation of Esrrg obscured experimental OA. These results indicate that ERRγ is involved in OA pathogenesis. In mouse articular chondrocytes, GSK5182 inhibited pro-inflammatory cytokine-induced catabolic factors. Consistent with the in vitro results, GSK5182 significantly reduced cartilage degeneration in ERRγ-overexpressing mice administered intra-articular Ad-Esrrg. Overall, the ERRγ inverse agonist GSK5182 represents a promising therapeutic small molecule for OA.
For more than a decade, next-generation sequencing (NGS) has been emerging as the mainstay of agrigenomics research. High-throughput technologies have made it feasible to facilitate research at the scale and cost required for using this data in livestock research. Scale frameworks of sequencing for agricultural and livestock improvement, management, and conservation are partly attributable to innovative informatics methodologies and advancements in sequencing practices. Genome-wide sequence-based investigations are often conducted worldwide, and several databases have been created to discover the connections between worldwide scientific accomplishments. Such studies are beginning to provide revolutionary insights into a new era of genomic prediction and selection capabilities of various domesticated livestock species. In this concise review, we provide selected examples of the current state of sequencing methods, many of which are already being used in animal genomic studies, and summarize the state of the positive attributes of genome-based research for cattle (Bos taurus), sheep (Ovis aries), pigs (Sus scrofa domesticus), horses (Equus caballus), chickens (Gallus gallus domesticus), and ducks (Anas platyrhyncos). This review also emphasizes the advantageous features of sequencing technologies in monitoring and detecting infectious zoonotic diseases. In the coming years, the continued advancement of sequencing technologies in livestock agrigenomics will significantly influence the sustained momentum toward regulatory approaches that encourage innovation to ensure continued access to a safe, abundant, and affordable food supplies for future generations.