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  • Zhao Potts posted an update 4 months, 2 weeks ago

    Seomae mugwort, a Korean native variety of Artemisia argyi, exhibits physiological effects against various diseases. However, its effects on osteoarthritis (OA) are unclear. In this study, a Seomae mugwort extract prevented cartilage destruction in an OA mouse model. In vitro and ex vivo analyses revealed that the extract suppressed MMP3, MMP13, ADAMTS4 and ADAMTS5 expression induced by IL-1β, IL-6 and TNF-α and inhibited the loss of extracellular sulphated proteoglycans. In vivo analysis revealed that oral administration of the extract suppressed DMM-induced cartilage destruction. We identified jaceosidin in Seomae mugwort and showed that this compound decreased MMP3, MMP13, ADAMTS4 and ADAMTS5 expression levels, similar to the action of the Seomae mugwort extract in cultured chondrocytes. Interestingly, jaceosidin and eupatilin combined had similar effects to Seomae mugwort in the DMM-induced OA model. Induction of IκB degradation by IL-1β was blocked by the extract and jaceosidin, whereas JNK phosphorylation was only suppressed by the extract. These results suggest that the Seomae mugwort extract and jaceosidin can attenuate cartilage destruction by suppressing MMPs, ADAMTS4/5 and the nuclear factor-κB signalling pathway by blocking IκB degradation. Thus, the findings support the potential application of Seomae mugwort, and particularly jaceosidin, as natural therapeutics for OA.Introduction The high ill-health burden associated with musculoskeletal (MSK) disease has been widely reported, and various treatment approaches proposed. Increasingly, treatments have sought to reflect personalised care and incorporate self-management (SM). However, the range of SM approaches proposed for foot and ankle MSK problems, and their relative clinical or cost-effectiveness, has not been reviewed. A scoping review is required to understand the need/appropriateness of a systematic review on this topic. Methods and analysis The scoping review will be conducted in line with the PRISMA-ScR framework. We will perform an initial search across two databases to confirm search syntax. find more We will then complete a full search across three databases (Embase [Ovid], CINAHL [EBSCO], and Medline [EBSCO]) and grey literature (Cochrane Library, The British Library, The Canadian Agency for Drugs and Technologies in Health [CADTH], The Health Foundation, The Kings Fund, and MedNar). We will use a snowballing strategy to review the reference list of retrieved texts, as per inclusion criteria, to identify previously unretrieved texts of potential relevance. In an iterative process, the protocol outlined above will be refined and repeated as new key terms come to light. Ethics and dissemination The scoping review will synthesise what is known and not known about SM approaches for MSK foot and ankle problems. The review will form the first step in outlining future research recommendations and areas of potentially unmet clinical need. The findings will be submitted for publication and shared in written form with stakeholder groups involved in the design of future research.Scope It is hypothesized that decreased advanced glycation end products (AGEs) levels could affect type 2 diabetes mellitus (T2DM) remission in newly diagnosed patients through the consumption of two healthy diets. Methods and results Patients from CORDIOPREV study, all with previous cardiovascular events, with T2DM at the beginning of the study are included. link2 Patients are randomized to a Mediterranean or a low-fat diet for five years. No different diabetes remission rates are found among diets. Serum methylglioxal (MG) and carboximethyllysine (CML), levels dietary AGE, as well as gene expression of AGER1 and RAGE are measured. Serum MG decreases only after the consumption of the Mediterranean diet. Moreover, a COX regression analysis shows that each SD decrease in the MG, occurring after the Mediterranean diet, increases the probability of T2DM remission with HR2.56(1.02-6.25) and p = 0.046 and each SD increase in disposition index at baseline increases the probability of remission with HR1.94(1.32-2.87) and p = 0.001. Conclusions It is demonstrated that the reduction of serum AGEs levels and the modulation of its metabolism, occurring after the consumption of a Mediterranean diet, might be involved in the molecular mechanism underlying the T2DM remission of newly diagnosed patients with coronary heart disease.Dynamic Covalent Chemistry (DCC) – combining the robustness of covalent bonds with the self-correcting nature of supramolecular chemistry – facilitates the modular synthesis of complex molecular assemblies in high yields. Although numerous reactions form covalent bonds, only a small set of chemical transformations affect covalent bond formation reversibly under suitable conditions for DCC. Further progress in this area still requires the identification of dynamic motifs and greater insights into their reversibility. We have fruitfully employed DCC of both thiolate coordination to main-group elements and disulfide formation for the facile self-assembly of (1) metal/metalloid-thiolate assemblies, and (2) purely organic cyclic and caged disulfides, thioethers, and even hydrocarbons, many of which have remained elusive by traditional stepwise synthesis yet form readily through our methods. In this Minireview, we highlight the approaches to prepare these unusual compounds and the factors inducing structural transformations or favoring the formation of certain products over others, given a set of external stimuli or reaction conditions.Introduction The aim of this study was to explore whether the antibrain edema of hypertonic saline (HS) is associated with alleviating ischemic blood-brain barrier (BBB) permeability by downregulating astrocyte-derived vascular endothelial growth factor (VEGF), which is mediated by microglia-derived NOD-like receptor protein 3 (NLRP3) inflammasome. Methods The infarct volume and BBB permeability were detected. The protein expression level of VEGF in astrocytes in a transient focal brain ischemia model of rats was evaluated after 10% HS treatment. Changes in the NLRP3 inflammasome, IL-1β protein expression, and the interleukin-1 receptor (IL1R1)/pNF-кBp65/VEGF signaling pathway were determined in astrocytes. Results HS alleviated the BBB permeability, reduced the infarct volume, and downregulated the expression of VEGF in astrocytes. HS downregulates IL-1β expression by inhibiting the activation of the NLRP3 inflammasome in microglia and then downregulates VEGF expression by inhibiting the phosphorylation of NF-кBp65 mediated by IL-1β in astrocytes. Conclusions HS alleviated the BBB permeability, reduced the infarct volume, and downregulated the expression of VEGF in astrocytes. HS downregulated IL-1β expression via inhibiting the activation of the NLRP3 inflammasome in microglia and then downregulated VEGF expression through inhibiting the phosphorylation of NF-кBp65 mediated by IL-1β in astrocytes.Reactive oxygen species (ROS) play an important role in cellular metabolism and many oxidative stress related diseases. Oxidative stress results from toxic effects of ROS and plays a critical role in the pathogenesis of a variety of diseases like cancers and many important biological processes. It is known that the unique feature of high intracellular ROS level in cancer cells can be considered as target and utilized as a useful cancer-related stimulus to mediate intracellular drug delivery. Therefore, biomaterials responsive to excess level of ROS are of great importance in biomedical applications. In this study, a novel ROS-responsive polymer based on L-methionine poly(ester amide) (Met-PEA-PEG) was designed, synthesized, characterized and self-assembled into nano-micellar-type nanoparticles (NP). link3 The Met-PEA-PEG NP exhibited responsiveness to an oxidative environment. The size and morphology of the nanoparticle changed rapidly in the presence of H2 O2 . The Nile Red dye was loaded into the Met-PEA-PEG NP to demonstrate a H2 O2 concentration induced time-dependent release behavior. The Met-PEA-PEG NP was sensitive to high intracellular ROS level of PC3 prostate cancer cells. Furthermore, the Met-PEA-PEG NP was investigated as a carrier of a Chinese medicine-based anticancer component, gambogic acid (GA). Compared to free GA, the GA-loaded nanocomplex (GA-NP) showed enhanced cytotoxicity toward PC3 and HeLa cells. The GA-NP also induced a higher level of apoptosis and mitochondrial depolarization in PC3 cells than free GA. The Met-PEA-PEG NP improved the therapeutic effect of GA and may serve as a potential carrier for anticancer drug delivery.Background Deeply divided ideological positions challenge collaboration when engaging youth with mental disorders, caregivers and providers in mental health research. The integrative dynamics (ID) approach can restructure relationships and overcome ‘us vs them’ thinking. Objective To assess the extent to which an experience-based co-design (EBCD) approach to patient and family engagement in mental health research aligned with ID processes. Methods A retrospective case study of EBCD data in which transitional-aged youth (n = 12), caregivers (n = 8) and providers (n = 10) co-designed prototypes to improve transitions from child to adult services. Transcripts from focus groups and a co-design event, co-designed prototypes, the resulting model, evaluation interviews and author reflections were coded deductively based on core ID concepts, while allowing for emergent themes. Analysis was based on pattern matching. Triangulation across data sources, research team, and youth and caregiver reflections enhanced rigour. Findings The EBCD focus group discussions of touchpoints in experiences aligned with ID processes of acknowledging the past, by revealing the perceived identity mythos of each group, and allowing expression of and working through emotional pain. These ID processes were briefly revisited in the co-design event, where the focus was on the remaining ID processes building cross-cutting connections and reconfiguring relationships. The staged EBCD approach may facilitate ID, by working within one’s own perspective prior to all perspectives working together in co-design. Conclusion Researchers can augment patient engagement approaches by applying ID principles with staged integration of groups to improve relations in mental health systems, and EBCD shows promise to operationalize this.Various cancer therapies have been developed, but tumor recurrence with incomplete tumor killing and remaining tumor cells/tissues is frequent in monotherapies. Herein, a nano-bio therapeutic emulsion formulated with multifunctional nanoscintillators and anaerobic Clostridium novyi-NT spores for synergistic image-guided combinational cancer therapy is reported. MRI visible nanoscintillators (NSs) are synthesized with a NaGdF4 Tb,Ce@NaGdF4 core/shell structure for an image-guided X-ray photodynamic therapy (PDT) of the normoxic peripheral tumor. An anaerobic oncolytic bacterium (C. novyi-NT) therapy is combined to treat the hypoxic central tumor tissues. Photosensitizer-coated NSs (PS-NSs) and C. novyi-NT spores are emulsified with clinically available ethiodized oil (Lipiodol) to be the nano-bio therapeutic emulsion and injected into the tumor with computed tomography image guidance. The distribution of nano-bio therapeutic emulsion, including PS-NSs and anaerobic C. novyi-NT spores in the tumor site, is confirmed by both X-ray and T1 -weighted magnetic resonance imaging.

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