The NLRP3 inflammasome plays a critical role in various inflammatory conditions. However, despite extensive research in targeted drug development for NLRP3, including MCC950, clinical success remains elusive. Here, we discovered that the activated NLRP3 inflammasome complex (disc-NLRP3) and the activating mutation L351P exhibited resistance to MCC950.
View Article and Find Full Text PDFBackground: Podocytes have limited proliferative capacity, which leads to irreversible glomerular injury in diverse kidney diseases. Magnesium isoglycyrrhizinate (MgIG), a hepatoprotective agent in clinic, has been reported to improve glomerular podocyte injury. However, the underlying mechanism of MgIG in ameliorating podocyte injury remains unclear.
View Article and Find Full Text PDFEthnopharmacological Relevance: Siwu tablet (SWT), derived from a traditional Chinese medicinal formula named Siwu decoction, is widely used for blood deficiency syndrome. Siwu decoction and its derived formulas have been proven to improve renal anemia and prevent senescence. Whether SWT prevents glomerular podocyte senescence and the underlying molecular mechanism remains unknow.
View Article and Find Full Text PDFIntroduction: High fructose intake has been implicated as a risk factor for behavioral disorders, potentially through cell ferroptosis induction in the central nervous system. Neural stem cells (NSCs) are crucial for maintaining hippocampal neurogenesis to resist behavioral alterations. Gastrodin, derived from the traditional Chinese herb Gastrodia elata, has neuroprotective effect.
View Article and Find Full Text PDFBile acids (BAs) are natural metabolites in mammals and have the potential to function as drugs against viral infection. However, the limited understanding of chenodeoxycholic acid (CDCA) receptors and downstream signaling, along with its lower suppression efficiency in inhibiting virus infection limits its clinical application. In this study, we demonstrate that farnesoid X receptor (FXR), the receptor of CDCA, negatively regulates interferon signaling, thereby contributing to the reduced effectiveness of CDCA against virus replication.
View Article and Find Full Text PDFIntroduction: Podocyte senescence causes podocyte loss and glomerulopathy. Excessive fructose intake is a risk factor for podocyte injury. However, whether high fructose promotes podocyte senescence remains unknown.
View Article and Find Full Text PDFAtmospheric aerosol (including total suspended particulate (TSP) samples and fine particulate matter (PM) samples) and precipitation samples were collected in Qingdao from May 2020 to June 2021. The concentrations of metal elements on fog days were 0.28-0.
View Article and Find Full Text PDFHydrogen peroxide (HO) plays a crucial role as an oxidizing agent within the tropospheric environment, making a substantial contribution to sulfate formation in hydrated aerosols and cloud and fog droplets. Field observations show that high levels of HO are often observed in heavy haze events and polluted air. However, the source of HO remains unclear.
View Article and Find Full Text PDFPurpose: The main objective is to quantify the lens nuclear opacity using spectral-domain optical coherence tomography (SD-OCT) and to evaluate its association with Lens Opacities Classification System III (LOCS-III) system, lens thickness (LT), and surgical parameters. The secondary objective is to assess the diagnostic model performance for hard nuclear cataract.
Methods: This study included 70 eyes of 57 adults with cataract, with 49 (70%) and 21 (30%) in training and validation cohort, respectively.
is an invasive weed species found in many countries. Methods to control the spread of this weed have been largely unsuccessful. Soil pH is the most important soil factor affecting the availability of nutrients for plant and impacting its growth.
View Article and Find Full Text PDFIn recent years, among many oxidation pathways studied for atmospheric sulfate formation, the aqueous phase oxidation pathways of HO and organic hydroperoxides (ROOHs) have attracted great scientific attention. Higher concentrations of HO and ubiquitous ROOHs have been observed in atmospheric aqueous phase environments (cloud water, fog droplets, etc.).
View Article and Find Full Text PDFIEEE Trans Pattern Anal Mach Intell
May 2024
With the rapid advances in autonomous driving, it becomes critical to equip its sensing system with more holistic 3D perception. However, widely explored tasks like 3D detection or point cloud semantic segmentation focus on parsing either the objects or scenes. In this work, we propose to address the challenging task of LiDAR-based Panoptic Segmentation, which aims to parse both objects and scenes in a unified manner.
View Article and Find Full Text PDFAlthough STAT3 has been reported as a negative regulator of type I interferon (IFN) signaling, the effects of pharmacologically inhibiting STAT3 on innate antiviral immunity are not well known. Capsaicin, approved for the treatment of postherpetic neuralgia and diabetic peripheral nerve pain, is an agonist of transient receptor potential vanilloid subtype 1 (TRPV1), with additional recognized potencies in anticancer, anti-inflammatory, and metabolic diseases. We investigated the effects of capsaicin on viral replication and innate antiviral immune response and discovered that capsaicin dose-dependently inhibited the replication of VSV, EMCV, and H1N1.
View Article and Find Full Text PDFNeurogenesis decline in hippocampal dentate gyrus (DG) participates in stress-induced depressive-like behaviors, but the underlying mechanism remains poorly understood. Here, we observed low-expression of NOD-like receptor family pyrin domain containing 6 (NLRP6) in hippocampus of stress-stimulated mice, being consistent with high corticosterone level. NLRP6 was found to be abundantly expressed in neural stem cells (NSCs) of DG.
View Article and Find Full Text PDFDietary alkaloid nuciferine isolated from the leaves of can ameliorate dyslipidemia and liver lipid accumulation, but the underlying mechanism remains unclear. Caspase recruitment domain protein family member 6 (CARD6) is suggested to play an important role in metabolic diseases. This study aimed to investigate the role and the upstream regulator of CARD6 in high fructose-induced liver lipid accumulation and whether and how the anti-lipid accumulation effect of nuciferine was related to CARD6.
View Article and Find Full Text PDFActa Pharmacol Sin
September 2023
Inhibition of NLRP3 inflammasome activation produces potent therapeutic effects in a wide array of inflammatory diseases. Bergapten (BeG), a furocoumarin phytohormone present in many herbal medicines and fruits, exibits anti-inflammatory activity. In this study we characterized the therapeutic potential of BeG against bacterial infection and inflammation-related disorders, and elucidated the underlying mechanisms.
View Article and Find Full Text PDFIncreasing evidence suggests that natural antisense transcriptional lncRNAs regulate their adjacent coding genes to mediate diverse aspects of biology. Bioinformatics analysis of the previously identified antiviral gene ZNFX1 revealed neighboring lncRNA ZFAS1 transcribed on the opposite strand from ZNFX1. Whether ZFAS1 exerts antiviral function via regulating the dsRNA sensor ZNFX1 is unknown.
View Article and Find Full Text PDFNatural products, and especially the active ingredients found in traditional Chinese medicine (TCM), have a thousand-year-long history of clinical use and a strong theoretical basis in TCM. As such, traditional remedies provide shortcuts for the development of original new drugs in China, and increasing numbers of natural products are showing great therapeutic potential in various diseases. This paper reviews the molecular mechanisms of action of natural products from different sources used in the treatment of inflammatory diseases and cancer, introduces the methods and newly emerging technologies used to identify and validate the targets of natural active ingredients, enumerates the expansive list of TCM used to treat inflammatory diseases and cancer, and summarizes the patterns of action of emerging technologies such as single-cell multiomics, network pharmacology, and artificial intelligence in the pharmacological studies of natural products to provide insights for the development of innovative natural product-based drugs.
View Article and Find Full Text PDFLong-term high fructose intake drives oxidative stress, causing glomerular podocyte injury. Polydatin, isolated from Chinese herbal medicine , is used as an antioxidant agent that protects kidney function. However, it remains unclear how polydatin prevents oxidative stress-driven podocyte damage.
View Article and Find Full Text PDFAntidepressant fluoxetine can affect cerebral glucose metabolism in clinic, but the underlying molecular mechanism remains poorly understood. Here, we examined the effect of fluoxetine on brain regional glucose metabolism in a rat model of depression induced by repeated corticosterone injection, and explored the molecular mechanism. Fluoxetine was found to recover the decrease of F-fluorodeoxyglucose (F-FDG) signal in prefrontal cortex (PFC), and increased 2-[-(7-Nitrobenz-2-oxa-1,3-diazol-4-yl) amino]-2-deoxy-D-glucose (2-NBDG, a fluorescent glucose analog) uptake in an astrocyte-specific manner in cultured PFC slices from corticosterone-induced depressive rats, which were consistent with its improvement of animal depressive behaviors.
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