Autophagy induction is an effective approach for OA therapy. IL-1β is one of the major inflammatory cytokines linked to OA pathological progression, and its receptor blockade interrupts OA cartilage ...destruction. The objective of this study was to decipher the link between autophagy and regulatory mechanism of IL-1β and to investigate the effect of IL-1β receptor blockade by IL-1 receptor antagonist (IL-1Ra) combined with or without an autophagy inducer (TAT-Beclin1) on extracellular matrix (ECM) in OA chondrocytes in vitro and in vivo.
IL-1β-treated rat and human OA chondrocytes were cultured in response to IL-1Ra. The expression and distribution of signal molecules regulating ECM synthesis and autophagy were investigated via western blotting, immunoprecipitation, real-time PCR, immunofluorescence, and transmission electron microscope technique. Furthermore, after intra-articular injection of IL-1Ra, TAT-Beclin1, and a combination of both in a rat OA model established by anterior cruciate ligament transection and medial meniscus resection, the morphological changes of cartilage and related signal molecule expression levels were monitored using H.E., Safranin O-Fast green, and immunohistochemistry staining.
Reduced autophagy by IL-1β contributed to ECM degradation, and blockade of IL-1β by IL-1Ra restored autophagy and attenuated ECM degradation in rat and human OA chondrocytes, as well as in a rat OA model. Akt/mTOR/ULK1, Akt/mTOR/NF-κB, and LC3B deacetylation were involved in autophagy regulated by IL-1β. Intra-articular injection of IL-1Ra combined with TAT-Beclin1 was more effective than IL-1Ra alone.
IL-1Ra restored autophagy and attenuated ECM degradation, with an implication that blocking IL-1β combined with enhancing autophagy might be a potential therapeutic strategy for OA.
Critically ill patients in intensive care units (ICUs) have restricted exposure to natural light throughout the day. As a result, they are more prone to undergo disruptions in circadian rhythmicity ...and sleep patterns, which may contribute to the development of delirium. As a measure to synchronize to the patterns of natural sunlight, EWINDOW has been proved to prevent delirium in some studies. Hence, the aim of this systematic review to evaluate the effectiveness of EWINDOW so as to prevent delirium.
From January 2012 to December 2021, electronic databases such as China National Knowledge Infrastructure Database, Excerpta Medica database, PubMed, Cochrane Central Register of Controlled Trials, Wan Fang, and Cumulative Index of Nursing and Allied Health Literature are aimed to look for appropriate randomized controlled trials to evaluate the therapeutic impact of EWINDOW on delirium prevention. To be more exact, related studies are chosen, data is retrieved and the risk of bias is examined, then a meta-analysis is carried out in order.
The goal of this study is to show how effective EWINDOW is at preventing delirium in ICU. The incidence and duration of delirium are included in our outcome measures.
This review evaluates related studies on the therapeutic effects of EWINDOW on the prevention of delirium in the ICUs.
The findings of this study will be published in a peer-reviewed journal. As the study relies on publicly available data, no ethical approval is required. Furthermore, throughout the data analysis procedure, anonymity is protected.OSF Registration: https://osf.io/NP3EW/.
Dear Editor, The leucine rich repeat （LRR） is a versatile protein motif （-20-30 amino acids） found in a variety of protein in all life forms. Tandem arrays of two or more repeats in an LRR domain ...form a structure similar to a horseshoe-shaped solenoid. Largely by acting as scaffolds for protein-protein interactions, LRR domains participate in diverse biological processes 1, 2, as exemplified by the large family of LRR-containing receptor like kinases （LRR-RLKs） in plants 3.
Despite various animal serums being used widely to culture chondrocytes, the regulatory mechanism of serum on chondrocyte activities has not been elucidated. In the present study, human ...osteoarthritis (OA) chondrocytes were used to perform in vitro investigations on the effect of different concentrations of bovine fetal serum on extracellular matrix synthesis, cell proliferation and autophagy using the Cell Counting Kit‑8 analysis, a laser‑scanning confocal microscope, and western blot analysis. The results demonstrated that 5% serum exerted a chondroprotective effect more than the other concentrations of serum, as it simultaneously promoted cell proliferation, autophagy, and ECM synthesis in human OA chondrocytes. Furthermore, the decreased mechanistic target of rapamycin (mTOR) and increased Akt were observed in 5% serum‑treated OA chondrocytes. Either mTOR or Akt inhibitor influenced the effect of 5% serum on cell proliferation and autophagy in human OA chondrocytes, which was associated with LC‑3B or B‑cell lymphoma-2 (Bcl‑2) signal molecules. Consistent with previous studies, the present study proposes that 5% serum promotes cell proliferation via the Akt/Bcl‑2 axis and induces autophagy via the mTOR/LC‑3B axis in human OA chondrocytes. Furthermore, the different roles of Akt and mTOR in the cell processes of human OA chondrocytes require consideration for preclinical and clinical therapy of OA.
The effect of â-Casomorphin-7 on intestinal mucosal immunity was investigated in aged mice. Mice were treated without or with different doses of â-Casomorphin-7 for 30 days. All mice were sacrificed ...and intestinal mucosa samples collection at the end of the experiment. Histopathological studies showed the tissue protective role of â-Casomorphin-7 in aged mice. The number of duodenal and jejunal epithelial lymphocytes decreased significantly Pandlt;0.05 The doses of duodenal and jejunal epithelial lymphocytes in mice were significantly Pandlt;0.05 increased in each dose group. The relative expression of TLR4,TRAF6 and NF-êB in the intestinal mucosa of the elderly model group was lower than that of the young control group. The low and middle dose groups significantly Pandlt;0.05 up-regulated the relative expression of TLR4, TRAF6 and NF-êB.The results suggest that â-Casomorphin-7 can improved intestinal mucosal immune decline likely through balancing TLR4\NF-êB signaling pathway.
The Fe- and Mn-rich intermetallics are of great effect on the mechanical properties of the AA5083 type alloy （Al-5Mg-0.8Mn）. The effect of Fe, Si and cooling rate on the formation of the ...intermetallics were investigated by analyzing the microstructures of the alloys with different Fe and Si contents. The results indicated that increasing the Fe content resulted in the increase of the Al6（Fe,Mn） phase in both amount and size. In the alloys with high Fe content, the platelet-like Al6（Fe,Mn） compounds lined up and formed a band. Increasing the content of Si resulted in the increase of the Mg2Si phase which formed a network structure. Increasing the cooling rate significantly refined the intermetallics. However, increasing the cooling rate did not change the characteristic of the intermetallic compounds in the alloys with low or medium Si contents. For the alloys with high contents of Fe and Si under the condition of near-rapid cooling, the Fe- and Mn-rich intermetallic compound changed to the quaternary Al15（Fe,Mn）3Si phase and displayed a fine fish bone or Chinese script structure. The refinement of the intermetallics would allow higher tol- erance of Fe and Si contents in the AA5083 alloy produced, for instance, via the continuous strip casting process.
This paper describes the combinational surface kinetics enhancement and surface states passivation of nickel-borate （Ni-Bi） co-catalyst for a hematite （Fe_2O_3） photoanode. The Ni-Brmodified Fe_2O_3 ...photoanode exhibits a cathodic onset potential shift of 230 mV and a 2.3-fold enhancement of the photocurrent at 1.23 V, versus the reversible hydrogen electrode （RHE）. The borate （Bi） in the Ni-Bi film promotes the release of pro- tons for the oxygen evolution reaction （OER）.
To identify proteins involved in pancreatic development, we used a differential proteomics approach by comparing pancreatic extracts from four biologically significant stages of development: ...embryonic day (E) 15.5, E18.5, postnatal (P) days 0 and adult. By two-dimensional gel electrophoresis (2D-E) and MALDI-TOF MS (Matrix Assisted Laser Desorption/Ionization Time-Of-Flight Mass Spectrometry) following database searching and protein annotation, 15 proteins were identified as being differently expressed in the pancreas between the four phases. The expression pattern and the localization of alpha-fetoprotein (AFP), one of significant changed proteins observed, were further determined. Four isoforms of AFP (72 kDa, 60 kDa, 48 kDa and 37 kDa) were found by Western blotting in the pancreas tested, most of them showed a stronger signal in E18.5 followed by a steady decrease and only a 60-kDa isoform was detected in the adult pancreas. Immunolocalization for AFP revealed that a positive reactivity was detectable at E15.5 pancreas, became stronger in the cytoplasm of mesenchyme cells at E18.5, and declined after birth to a nearly undetectable level in adults. The dynamic expression of AFP in rat pancreas from different stages indicates that AFP might be involved in some aspects of pancreatic development.
Peptide-mediated cell-to-cell signaling has crucial roles in coordination and definition of cellular functions in plants. Peptide-receptor matching is important for understanding the mechanisms ...underlying peptide-mediated sig- naling. Here we report the structure-guided identification of root meristem growth factor （RGF） receptors important for plant development. An assay based on a signature ligand recognition motif （Arg-x-Arg） conserved in a subfamily of leucine-rich repeat receptor kinases CLRR-RKs） identified the functionally uncharacterized LRR-RK At4926540 as a receptor of RGF1 （RGFR1）. We further solved the crystal structure of RGF1 in complex with the LRR domain of RGFR1 at a resolution of 2.6 A, which reveals that the Arg-x-Gly-Gly （RxGG） motif is responsible for specific rec- ognition of the sulfate group of RGF1 by RGFR1. Based on the RxGG motif, we identified additional four RGFRs. Participation of the five RGFRs in RGF-induced signaling is supported by biochemical and genetic data. We also of- fer evidence showing that SERKs function as co-receptors for RGFs. Taken together, our study identifies RGF receptors and co-receptors that can link RGF signals with their downstream components and provides a proof of principle for structure-based matching of LRR-RKs with their peptide ligands.
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