Covalent inhibition of ACSL4 alleviates ferroptosis-induced acute liver injury.

Ferroptosis, a form of regulated cell death, is characterized by iron-dependent phospholipid peroxidation and is closely linked to various liver diseases. Although covalent inhibitors have gained attention for their high potency and prolonged effects, no specific covalent inhibitor for ferroptosis exists. Here, we identify Rociletinib (ROC) as a potent inhibitor of ferroptosis through virtual screening and mechanistic studies.

GNF-5837 attenuates acute liver injury by inhibiting oxidative stress.

Background: Acute liver injury is caused by various reasons and results in abnormal liver function, serving as the basis for various liver diseases. However, there has not been much progress in research on the prevention and treatment of acute liver injury, and drugs directly or specifically used for acute liver injury are still lacking. Recent studies have shown that several types of cell death are closely associated with the onset, progression, and prognosis of liver injury.

Merestinib inhibits cuproptosis by targeting NRF2 to alleviate acute liver injury.

The emergence of cuproptosis, a novel form of regulated cell death, is induced by an excess of copper ions and has been associated with the progression of multiple diseases, including liver injury, cardiovascular disease, and neurodegenerative disorders. However, there are currently no inhibitors available for targeting specific cuproptosis-related pathways in therapy. Here, the compound merestinib (MTB) has been identified as a strong inhibitor of cuproptosis through screening of a kinase inhibitor library.

Rosthornin B alleviates inflammatory diseases via directly targeting NLRP3.

Aberrant activation of the NLRP3 inflammasome contributes to the evolution of diverse inflammatory diseases. Inhibition of the NLRP3 inflammasome has been proven to be an effective treatment strategy for NLRP3-driven diseases. This study revealed that multiple natural diterpenes from Isodon plants can inhibit the NLRP3 inflammasome, among which Rosthornin B (Ros B) exhibited the best inhibitory effect, with an IC of 0.

Identification of a covalent NEK7 inhibitor to alleviate NLRP3 inflammasome-driven metainflammation.

Aberrant activation of NLRP3 inflammasome is associated with a variety of inflammatory diseases. Advances in understanding the molecular mechanisms of NLRP3 inflammasome have revealed that NEK7 is an essential component for its activation, but the development of drugs specifically targeting NEK7 remains challenging. Here we identify rociletinib (ROC), an anticancer drug in phase III clinical trial with high safety profile, as a highly potent and specific small-molecule antagonists of NEK7.

Distinct -Acetylation Patterns of Serum Glycoproteins among Humans, Mice, and Rats.

-Acetylation is a significant chemical modification of sialic acids on glycoproteins with diverse biological functions. As two important animal models, mice and rats have been widely used for various biomedical studies. In this study, we show that the sialic acid types and their -acetylation patterns have large differences among serum glycoproteins of humans, rats, and mice.

High-abundance serum glycoproteins as valuable resources for glycopeptide standards.

High-abundance serum proteins, mostly modified by N-glycans, are usually depleted from human sera to achieve in-depth analyses of serum proteome and sub-proteomes. In this study, we show that these high-abundance glycoproteins (HAGPs) can be used as valuable standard glycopeptide resources, as long as the structural features of their glycans have been well defined at the glycosite-specific level. By directly analyzing intact glycopeptides enriched from serum, we identified 1322 unique glycopeptides at 48 N-glycosites from the top 12 HAGPs (19 subclasses).

Site-specific N-glycan alterations on haptoglobin as potential biomarkers for distinguishing intrahepatic cholangiocarcinoma from hepatocellular carcinoma.

Intrahepatic cholangiocellular carcinoma (ICC) is a challenging malignancy marked by subtle early symptoms and a high mortality rate, making effective diagnostic markers crucial for early detection and improved patient outcomes. Currently, the conventional diagnosis of ICC is not easily distinguishable from Hepatocellular Carcinoma (HCC) and lacks highly specific and sensitive diagnostic markers. Protein glycosylation, pivotal in biological processes, shows promise for cancer biomarkers due to its association with disease progression.

Copper(II)-Based Nano-Regulator Correlates Cuproptosis Burst and Sequential Immunogenic Cell Death for Synergistic Cancer Immunotherapy.

Immunogenic cell death (ICD) of tumor cells serves as a crucial initial signal in the activation of anti-tumor immune responses, holding marked promise in the field of tumor immunotherapy. However, low immunogenicity tumors pose challenges in achieving complete induction of ICD, thereby limiting the response rates of immunotherapy in clinical patients. The emergence of cuproptosis as a new form of regulated cell death has presented a promising strategy for enhanced immunotherapy of low immunogenic tumors.

Isorhamnetin alleviates ferroptosis-mediated colitis by activating the NRF2/HO-1 pathway and chelating iron.

Ferroptosis of intestinal epithelial cells (IECs) had been identified as a key factor in the development of ulcerative colitis (UC). Therefore, targeted inhibition of ferroptosis may provide a new strategy for the treatment of UC. Isorhamnetin (ISO) was an O-methylated flavonol with therapeutic effects on a variety of diseases, such as cardiovascular disease, neurological disorders and tumors.

Site-Specific Analysis of Core and Antenna Fucosylation on Serum Glycoproteins.

Fucosylation is an important structural feature of glycans and plays an essential role in the regulation of glycoprotein functions. Fucosylation can be classified into core- (CF) and antenna-fucosylation (AF, also known as (sialyl-) Lewis) based on the location on -glycans, and they perform distinct biological functions. In this study, core- and antenna-fucosylated -glycans on human serum glycoproteins that hold great clinical application values were systematically characterized at the site-specific level using StrucGP combined with the recently developed fucosylation assignment method.

Identification of a targeted ACSL4 inhibitor to treat ferroptosis-related diseases.

Ferroptosis is a form of iron-dependent, lipid peroxidation-driven regulatory cell death that has been implicated in the pathogenesis of multiple diseases, including organ injury, ischemia/reperfusion, and neurodegenerative diseases. However, inhibitors that directly and specifically target ferroptosis are not yet available. Here, we identify the compound AS-252424 (AS) as a potent ferroptosis inhibitor through kinase inhibitor library screening.

Entrectinib inhibits NLRP3 inflammasome and inflammatory diseases by directly targeting NEK7.

Excessive inflammation caused by abnormal activation of the NLRP3 inflammasome contributes to the pathogenesis of multiple human diseases, but clinical drugs targeting the NLRP3 inflammasome are still not available. In this study, we identify entrectinib (ENB), a US Food and Drug Administration (FDA)-approved anti-cancer agent, as a target inhibitor of the NLRP3 inflammasome to treat related diseases. ENB specifically blocks NLRP3 without affecting activation of other inflammasomes.

Protocol for in vivo and in vitro activation of NLRP3 inflammasome in mice using monosodium urate.

Although intraperitoneal injection of monosodium urate (MSU) is an effective model for studying peritonitis, its establishment remains challenging. Here, we present a protocol for using MSU to activate the NLRP3 inflammasome in bone-marrow-derived macrophages (BMDMs) and to induce peritonitis in mice. We describe steps for isolating and culturing BMDMs, preparing MSU crystals, and activating the NLRP3 inflammasome using western blot and ELISA.

Role of pyroptosis in the pathogenesis and treatment of diseases.

Programmed cell death (PCD) is regarded as a pathological form of cell death with an intracellular program mediated, which plays a pivotal role in maintaining homeostasis and embryonic development. Pyroptosis is a new paradigm of PCD, which has received increasing attention due to its close association with immunity and disease. Pyroptosis is a form of inflammatory cell death mediated by gasdermin that promotes the release of proinflammatory cytokines and contents induced by inflammasome activation.

Serum biomarker panel for disease severity and prognosis in patients with COVID-19.

Background: Coronavirus disease-2019 (COVID-19) has become a worldwide emergency and has had a severe impact on human health. Inflammatory factors have the potential to either enhance the efficiency of host immune responses or damage the host organs with immune overreaction in COVID-19. Therefore, there is an urgent need to investigate the functions of inflammatory factors and serum markers that participate in disease progression.

Application of StrucGP in medical immunology: site-specific N-glycoproteomic analysis of macrophages.

The structure of N-glycans on specific proteins can regulate innate and adaptive immunity via sensing environmental signals. Meanwhile, the structural diversity of N-glycans poses analytical challenges that limit the exploration of specific glycosylation functions. In this work, we used THP-1-derived macrophages as examples to show the vast potential of a N-glycan structural interpretation tool StrucGP in N-glycoproteomic analysis.

Recognition of Core-Fucosylated Glycopeptides Based on the Y1+Fuc/Y1 Ratio in Low-Energy HCD Spectra.

Accurate identification of core fucosylation on -glycopeptides remains challenging due to fucose migration during mass spectrometry analysis. Here, we introduce a simple and straightforward method for core-fucosylated glycopeptide recognition based on the relative intensities of Y1+Fuc ions compared with their corresponding Y1 ions (labeled as Y1+Fuc/Y1 or simply Y1F/Y1 ratio > 0.1) in low-energy HCD-based spectra.

Precision N-glycoproteomics reveals elevated LacdiNAc as a novel signature of intrahepatic cholangiocarcinoma.

Primary liver cancer, mainly comprising hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC), remains a major global health problem. Although ICC is clinically different from HCC, their molecular differences are still largely unclear. In this study, precision N-glycoproteomic analysis was performed on both ICC and HCC tumors as well as paracancer tissues to investigate their aberrant site-specific N-glycosylation.

Site-specific glycoproteomic analysis revealing increased core-fucosylation on FOLR1 enhances folate uptake capacity of HCC cells to promote EMT.

Epithelial-mesenchymal transition (EMT) has been recognized as an important step toward high invasion and metastasis of many cancers including hepatocellular carcinoma (HCC), while the mechanism for EMT promotion is still ambiguous. The dynamic alterations of site-specific glycosylation during HGF/TGF-β1-induced EMT process of three HCC cell lines were systematically investigated using precision glycoproteomic methods. The possible roles of EMT-related glycoproteins and site-specific glycans were further confirmed by various molecular biological approaches.

Antidiabetic effects of water-soluble Korean pine nut protein on type 2 diabetic mice.

Korean pine nut protein (PNP) has a variety of biological activities, which are good for human health, but its ability to preventing diabetes has not been reported. This study evaluated the effects of water-soluble proteins of Korean pine nut obtained from a dilute alkali extract on carbohydrate metabolism of type 2 diabetic mice on a model of diabetes induced using a high fat diet combined with streptozotocin. The results showed that the hypoglycemic effect of PNP at a middle dose was the most significant, which was 38.

The antitumor effect of folic acid conjugated-Auricularia auricular polysaccharide-cisplatin complex on cervical carcinoma cells in nude mice.

A tumor-targeted, folic acid (FA) conjugated-Auricularia auricular polysaccharide (AAP) -cis-diaminedichloroplatinum (CDDP) complex (FA-AAP-CDDP) was used for cervical carcinoma chemotherapy. The drug delivery system was able to enhance the antitumor potency of CDDP, and to reduce the toxic side effects of CDDP. The kidney of mice treated by FA-AAP-CDDP complex had higher superoxide dismutase, catalase, and glutathione peroxidase activities, and lower malondialdehyde.

Effect of polyamines on the grain filling of wheat under drought stress.

Drought inhibits wheat grain filling. Polyamines (PAs) are closely associated with plant resistance due to drought and grain filling of cereals. However, little is known about the effect of PAs on the grain filling of wheat under drought stress.

Effect of plastic film mulching on the grain filling and hormonal changes of maize under different irrigation conditions.

Plastic film mulching (PM) is widely utilized for maize production in China. However, the effect of PM on the grain yield of crops has not been established, and the biochemical mechanism underlying the increase or decrease in grain yield under PM is not yet understood. Grain filling markedly affects the grain yield.