Targeted protein degradation has been widely adopted as a new approach to eliminate both established and previously recalcitrant therapeutic targets. Here, it is reported that the development of small molecule degraders of the envelope (E) protein of dengue virus. Two classes of bivalent E-degraders are developed by linking two previously reported E-binding small molecules, GNF-2, and CVM-2-12-2, to a glutarimide-based recruiter of the CRL4 ligase to effect proteosome-mediated degradation of the E protein.
View Article and Find Full Text PDFObjectives: Emerging evidence indicate that long noncoding RNAs (lncRNAs) may play an important role in the pathogenesis of systemic lupus erythematosus (SLE) however, the contribution of lncRNAs to SLE remains largely unclear. Our study aimed to explore the lncRNA expression profiles in peripheral blood mononuclear cells (PBMCs) from SLE patients.
Methods: LncRNA sequencing was used to detect differentially expressed genes in PBMCs from 5 SLE-MIX samples and 3 healthy controls (HC)-MIX samples, and the expression of selected lncRNAs was further verified by real-time quantitative polymerase chain reaction (RT‒qPCR).
Cyclin-dependent kinase 7, along with cyclin H and MAT1, forms the CDK-activating complex (CAK), which directs cell cycle progression via T-loop phosphorylation of cell cycle CDKs. Pharmacological inhibition of CDK7 leads to selective anti-cancer effects in cellular and in vivo models, motivating several ongoing clinical investigations of this target. Current CDK7 inhibitors are either reversible or covalent inhibitors of its catalytic activity.
View Article and Find Full Text PDFTargeted protein degradation has been widely adopted as a new approach to eliminate both established and previously recalcitrant therapeutic targets. Here we report the development of small molecule degraders of the envelope (E) protein of dengue virus. We developed two classes of bivalent E-degraders, linking two previously reported E-binding small molecules, GNF-2 and CVM-2-12-2, to a glutarimide-based recruiter of the CRL4 ligase to effect proteosome-mediated degradation of the E protein.
View Article and Find Full Text PDFObjective: Human gamma-delta T cells (γδ-T cells) play crucial roles in both innate and adaptive immune responses. However, much less is known about the immune status of γδT cells in systemic lupus erythematosus (SLE) patients. The objective of this study was to explore potential relationships between the frequency of γδ-T-cell subpopulations and disease activity, autoantibody titres and renal involvement in patients with SLE.
View Article and Find Full Text PDFInt J Biol Macromol
February 2024
Flavonoids have been shown to be beneficial in a variety of inflammatory and metabolic diseases because of their anti-inflammatory and antioxidant properties. However, previous epidemiological studies have only demonstrated a negative correlation between flavonoid intake on inflammatory markers, and the optimal intake of dietary flavonoids and subclasses in terms of dietary anti-inflammatory efficacy remains undetermined. This study was based on 3 cycles (2007-2010, 2017-2018) of the National Health and Nutrition Examination Survey and the corresponding expanded flavonoid database.
View Article and Find Full Text PDFThe c-Jun N-terminal kinases (JNKs) are members of the mitogen-activated protein kinase (MAPK) family, which includes JNK1-JNK3. Interestingly, JNK1 and JNK2 show opposing functions, with JNK2 activity favoring cell survival and JNK1 stimulating apoptosis. Isoform-selective small molecule inhibitors of JNK1 or JNK2 would be useful as pharmacological probes but have been difficult to develop due to the similarity of their ATP binding pockets.
View Article and Find Full Text PDFInt J Biol Macromol
October 2022
Long-term retrogradation of amylopectin always leads to the quality deterioration of starch-based food. In this paper, the purified maize amylopectin was co-crystallized with NaCl to obtain anti-retrograded amylopectin. The results showed that the retrogradation rate of maize amylopectin dropped directly from 27.
View Article and Find Full Text PDFObjective: T cells display significant phenotypical changes and play multiple roles in promoting the immune response in SLE. The frequencies of T cell subpopulations in SLE are still not well understood. To better understanding the phenotypic abnormalities of T cells in SLE will help us to clarify disease immunopathology and to find promising biomarkers for disease monitoring and control.
View Article and Find Full Text PDFTo evaluate the association of inflammatory markers and depression in RA patients and the risk factors in RA with depression, a cross-sectional study was conducted in a cohort of RA patients from southern China.Two hundred-fifteen RA patients were enrolled. The demographic and disease-related characteristics were recorded and inflammatory markers in sera were measured.
View Article and Find Full Text PDFSepsis is an organ dysfunction caused by the dysregulated inflammatory response to infection. Lipopolysaccharide-binding protein (LBP) binds to lipopolysaccharide (LPS) and modulates the inflammatory response. A rare systematic study has been reported to detect the effect of LBP gene during LPS-induced sepsis.
View Article and Find Full Text PDFTargeted protein degradation represents a rapidly growing area in drug discovery and development. Moreover, small molecules that induce the targeted degradation of a given protein also represent an important addition to the chemical probes toolbox as these compounds can achieve selective protein knockdown, thus providing an approach that is orthogonal to genetic knockdowns. In order to develop degradation-inducing chemical probes for studying cereblon (CRBN) biology, we generated six CRBN-CRBN (homo-PROTAC) degraders and six CRBN-VHL (hetero-PROTAC) degraders.
View Article and Find Full Text PDFThe fatigue behaviors of metals are different under different in-service environment and loading conditions. This study was devoted to investigating the combined effects of high and low cycle fatigue loads on the performance of the low alloy steel Q345. Three kinds of experiments were carried out, including the pure high cycle fatigue (HCF) tests, the pure low cycle fatigue (LCF) tests, and the combined high and low cycle fatigue (HLCF) tests.
View Article and Find Full Text PDFObjectives: To explore the role of LPS binding protein (LBP) in metabolism and optimize sepsis treatment.
Design: A sepsis model was established by injecting LPS into LBP-/- rats and WT rats and observing changes in the liver over time (0, 1, 6, and 24 h).
Setting: Detecting liver inflammation and injury.
This study investigated the anti-fibrotic effects of reversine and Chinese medicine Xiang-Sha-Liu-Jun-Zi decoction (XSLJZD) on thioacetamide (TAA)-induced hepatic injury. Sprague-Dawley rats were intraperitoneally administered with TAA, then injected with reversine intraperitoneally, and/or orally provided with XSLJZD. TAA resulted in liver injury with increases in the liver index and levels of serum aspartate aminotransferase (AST) and alanine aminotransferase.
View Article and Find Full Text PDFMedicine (Baltimore)
December 2020
Background:: Whether the bone graft is needed in treating the displaced intra-articular calcaneal fractures (DIACFs) is still controversial. Therefore, in our study, we will explore the results of 2 approaches for the DIACFs surgical treatment.
Methods:: The present report follows the Consolidated Standards of Reporting Trials (CONSORT) guidelines.
Lead-zinc (Pb-Zn) mine tailings pose a great risk to the natural environment and human health because of their high toxicity. In this study, the responses of photosynthesis, chlorophyll fluorescence, and antioxidative enzyme of and in the soil contaminated by Pb-Zn mine tailings were investigated. Results showed that Pb-Zn mine tailings significantly reduced net photosynthetic rates and leaf photosynthetic pigment content of both trees, and the reduction of net photosynthetic rates was mainly caused by their biochemical limitation (BL).
View Article and Find Full Text PDF