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Rheumatoid arthritis (RA) is a chronic inflammatory joint disease accompanied by energy depletion and accumulation of reactive oxygen species (ROS). Inorganic nanoparticles (NPs) offer great promise for the treatment of RA because they mostly have functions beyond being drug carriers. However, conventional nanomaterials become coated with a protein corona (PC) or lose their cargo prematurely in vivo, reducing their therapeutic efficacy. To avoid these problems, we loaded methotrexate (MTX) into hollow structured manganese dioxide nanoparticles (H-MnO2 NPs), then coated them with a ‘pseudo-corona’ of human serum albumin (HSA) at physiological concentrations to obtain HSA-MnO2@MTX NPs. Efficacy of MTX, MnO2@MTX, and HSA-MnO2@MTX NPs was compared in vitro and in vivo. Compared to MnO2@MTX, HSA-coated NPs were taken up better by lipopolysaccharide-activated RAW264.7 and were more effective at lowering levels of pro-inflammatory cytokines and preventing ROS accumulation. HSA-MnO2@MTX NPs were also more efficient at blocking the proliferation and migration of fibroblast-like synoviocytes from rats with collagen-induced arthritis. In this rat model, HSA-MnO2@MTX NPs showed better biodistribution than other treatments, specifically targeting the ankle joint. Furthermore, HSA-MnO2@MTX NPs reduced swelling in the paw, regulated pro-inflammatory cytokine production, and limited cartilage degradation and signs of inflammation. These results establish the therapeutic potential of HSA-MnO2@MTX NPs against RA.

Ultraviolet (UV) radiation causes skin damage including oxidative stress, inflammation, and photoaging. Extremophile fermentation products have been found to effectively protect the skin from UV-induced damage. This study aimed to investigate the impact of acid-induced stress on the content of bioactive compounds, as well as the anti-inflammatory and anti-photoaging properties of sorghum fermentation by the extremophilic Monascus pilosus. The study compared acid-stress fermentation (ASF) of sorghum with conventional fermentation (CF) and examined differences in total phenolic content, antioxidant activity, and short-chain fatty acid levels. Using gas chromatography–mass spectrometry assay, the ASF sample had lower total phenolic content compared to CF, but significantly higher levels of short-chain fatty acids. Butyric acid was the predominant metabolite in the ASF sample, followed by propionic acid. The ASF sample exhibited superior protection for UV-irradiated human keratinocytes by inhibiting apoptosis, reducing ROS, and downregulating inflammatory mediators. It also decreased metalloproteinases expression levels, increased collagen and elastin production, and mitigated UV-induced photoaging. The effects of ASF samples were evaluated in volunteers, and the results confirmed the ASF sample's effectiveness in ameliorating UV-induced skin symptoms, including pigmentation, redness, and wrinkles. These findings conclude that acid-stress enhances the anti-inflammatory and anti-photoaging capabilities of Monascus pilosus fermented sorghum.

Abstract Background Due to oral nano-delivery systems for the treatment of inflammatory bowel disease (IBD) are often failed to accumulated to the colonic site and could not achieve controlled drug release, it’s urgent to develop a microenvironment responsive drug delivery to improve therapy efficacy. Inflammation at the IBD site is mainly mediated by macrophages, which are the key effector cells. Excessive inflammation leads to oxidative stress and intestinal mucosal damage. The use of curcumin (CUR) and emodin (EMO) together for the treatment of IBD is promising due to their respective anti-inflammatory and intestinal mucosal repair effects. In view of the pH gradient environment of gastrointestinal tract, here we prepared pH-responsive sodium alginate (SA) hydrogel-coated nanoemulsions to co-deliver CUR and EMO (CUR/EMO NE@SA) to achieve controlled drug release and specifically target macrophages of the colon. Results In this study, a pH-responsive CUR/EMO NE@SA was successfully developed, in which the CUR/EMO NE was loaded by chitosan and further crosslinked with sodium alginate. CUR/EMO NE@SA had a pH-responsive property and could achieve controlled drug release in the colon. The preparation could significantly alleviate and improve the colon inflammatory microenvironment by decreasing TNF-α and IL-6 expression, increasing IL-10 expression, scavenging reactive oxygen species in macrophages, and by ameliorating the restoration of intestinal mucosal tight junction protein expression. Furthermore, we revealed the molecular mechanism of the preparation for IBD treatment, which might due to the CUR and EMO synergic inhibition of NF-κB to improve the pro-inflammatory microenvironment. Our study provides a new IBD therapy strategy via synergically inhibiting inflammatory, repairing mucosal and clearing ROS by pH-sensitive hydrogel-encapsulated nanoemulsion drug delivery system, which might be developed for other chronic inflammatory disease treatment. Conclusions It’s suggested that pH-sensitive hydrogel-coated nanoemulsion-based codelivery systems are a promising combinatorial platform in IBD. Graphical Abstract

Myeloid RNA regulator of Bim-induced death (Morrbid) is a newly identified leukocyte-specific long noncoding RNA (lncRNA). However, the expression and biological functions of Morrbid in cardiomyocytes and heart disease are currently unclear. This study was meant to determine the role of cardiac Morrbid in acute myocardial infarction (AMI) and to identify the potential cellular and molecular mechanisms involved. We found that both human and mouse cardiomyocytes could express a significant amount of Morrbid and that its expression was increased in cardiomyocytes with hypoxia or oxidative stress as well as in mouse hearts with AMI. Overexpression of Morrbid reduced the myocardial infarct size and cardiac dysfunction, whereas the infarct size and cardiac dysfunction deteriorated in cardiomyocyte-specific Morrbid-KO (Morrbidfl/fl/Myh6-Cre) mice. We identified that Morrbid had a protective effect against hypoxia- or H2O2-induced apoptosis; this was also confirmed in vivo in mouse hearts after AMI. We further discovered that serpine1 was a direct target gene of Morrbid that was involved in the Morrbid-mediated protective effect on cardiomyocytes. In summary, we have found, for the first time to our knowledge, that the cardiac Morrbid is a stress-enhanced lncRNA that protects hearts from AMI via antiapoptosis through its target gene serpine1. Morrbid may be a novel promising therapeutic target for ischemic heart diseases such as AMI.