Warifteine Alleviates ALI and Inhibits NETosis by Decreasing ROS-induced GSDMD Oligomerization.

Acute lung injury (ALI) is characterized by exaggerated inflammatory reactions and high clinical mortality rates, but targeted therapeutic interventions are lacking. Warifteine, which is a traditional remedy known for its anti-inflammatory properties, has been identified, but its potential effects on ALI remain unexplored. In this study, a murine model of ALI was established by injecting lipopolysaccharide (LPS) into wild-type or neutrophil-specific Gasdermin D (Gsdmd)-deficient mice.

Gαq/11 aggravates acute lung injury in mice by promoting endoplasmic reticulum stress-mediated NETosis.

Background: Acute lung injury (ALI) is distinguished by exaggerated neutrophil extracellular traps (NETs), elevated clinical mortality rates, and a paucity of targeted therapeutic interventions. The Gαq/11 protein, a member of the G protein subfamily, is an effective intervention target for a variety of diseases, but little is known about its role in ALI.

Methods: In this study, a murine model of ALI induced by lipopolysaccharide (LPS) was utilized, employing myeloid cell-specific Gna11 knockout mice.

N-homocysteinylation of β-arrestins biases GPCR signaling and promotes platelet activation.

Hyperhomocysteinemia (HHcy) is strongly associated with cardiovascular diseases (CVDs), and HHcy has been identified as a risk factor for thrombotic diseases. Most patients with HHcy die from various complications closely related to thrombotic diseases. However, the underlying mechanisms have not been fully elucidated.

Tyrosine phosphorylation and palmitoylation of TRPV2 ion channel tune microglial beta-amyloid peptide phagocytosis.

Alzheimer's disease (AD) is the leading form of dementia, characterized by the accumulation and aggregation of amyloid in brain. Transient receptor potential vanilloid 2 (TRPV2) is an ion channel involved in diverse physiopathological processes, including microglial phagocytosis. Previous studies suggested that cannabidiol (CBD), an activator of TRPV2, improves microglial amyloid-β (Aβ) phagocytosis by TRPV2 modulation.

Neuronostatin regulates neuronal function and energetic metabolism in Alzheimer's disease in a GPR107-dependent manner.

Alzheimer's disease (AD) is the most prevalent neurodegenerative disease, which is characterized by the accumulation and aggregation of amyloid in brain. Neuronostatin (NST) is an endogenous peptide hormone that participates in many fundamental neuronal processes. However, the metabolism and function of NST in neurons of AD mice are not known.

Tirzepatide shows neuroprotective effects via regulating brain glucose metabolism in APP/PS1 mice.

Tirzepatide (LY3298176), a GLP-1 and GIP receptor agonist, is fatty-acid-modified and 39-amino acid linear peptide, which ameliorates learning and memory impairment in diabetic rats. However, the specific molecular mechanism remains unknown. In the present study, we investigated the role of tirzepatide in the neuroprotective effects in Alzheimer's disease (AD) model mice.

A Pilot Study to Determine the Effect of Individualized Enteral Nutrition Management Based on Prognostic Nutrition Index on Surgical Patients With Oral Malignancies.

This study aimed to assess the effect of individualized enteral nutrition management based on the prognostic nutrition index (PNI) on surgical patients with oral malignancies. This quasi-experimental pilot study consecutively included patients diagnosed with oral malignancies who underwent radical surgery in Ningbo No. 2 Hospital between January 2020 and May 2023.

ROCK1 inhibition improves wound healing in diabetes via RIPK4/AMPK pathway.

Refractory wounds are a severe complication of diabetes mellitus that often leads to amputation because of the lack of effective treatments and therapeutic targets. The pathogenesis of refractory wounds is complex, involving many types of cells. Rho-associated protein kinase-1 (ROCK1) phosphorylates a series of substrates that trigger downstream signaling pathways, affecting multiple cellular processes, including cell migration, communication, and proliferation.

Unsaturated bond recognition leads to biased signal in a fatty acid receptor.

Individual free fatty acids (FAs) play important roles in metabolic homeostasis, many through engagement with more than 40G protein-coupled receptors. Searching for receptors to sense beneficial omega-3 FAs of fish oil enabled the identification of GPR120, which is involved in a spectrum of metabolic diseases. Here, we report six cryo-electron microscopy structures of GPR120 in complex with FA hormones or TUG891 and G or G trimers.

Prognostic and therapeutic implication of m6A methylation in Crohn disease.

Background: N6-methyladenosine (m6A) methylation has been reported to participate in inflammatory bowel disease (including Crohn disease [CD]). However, the prognostic and therapeutic implication of m6A methylation modification in CD is still unclear.

Methods: Genomic information of CD patients was integrated to assess disease-related m6A regulators, and difference and correlation analyses of m6A regulators were explored by using the R packages.

Reducing PDK1/Akt Activity: An Effective Therapeutic Target in the Treatment of Alzheimer's Disease.

Alzheimer's disease (AD) is a common age-related neurodegenerative disease that leads to memory loss and cognitive function damage due to intracerebral neurofibrillary tangles (NFTs) and amyloid-β (Aβ) protein deposition. The phosphoinositide-dependent protein kinase (PDK1)/protein kinase B (Akt) signaling pathway plays a significant role in neuronal differentiation, synaptic plasticity, neuronal survival, and neurotransmission via the axon-dendrite axis. The phosphorylation of PDK1 and Akt rises in the brain, resulting in phosphorylation of the TNF-α-converting enzyme (TACE) at its cytoplasmic tail (the C-terminal end), changing its internalization as well as its trafficking.

Emerging functions of neuronostatin in physiology, pathology, and potential therapeutics.

Neuronostatin, a bioactive peptide hormone, was encoded by pro-somatostatin and discovered using a bioinformatic method in 2008. Neuronostatin is widely expressed in the central nervous system (CNS) and peripheral tissues, it is also highly conserved among humans, rodents, and even goldfish. The 13 and 19 amino acids and the C-terminal amidation type play important roles in physiological and pathological functions.

Cannabidiol Enhances Microglial Beta-Amyloid Peptide Phagocytosis and Clearance via Vanilloid Family Type 2 Channel Activation.

Alzheimer's disease (AD) is associated with the accumulation and aggregation of amyloid in the brain. The cation channel TRPV2 may mediate the pathological changes in mild cognitive impairment. A high-affinity agonist of TRPV2 named cannabidiol is one of the candidate drugs for AD.

Endogenous Lipid-GPR120 Signaling Modulates Pancreatic Islet Homeostasis to Different Extents.

Long-chain fatty acids (LCFAs) are not only energy sources but also serve as signaling molecules. GPR120, an LCFA receptor, plays key roles in maintaining metabolic homeostasis. However, whether endogenous ligand-GPR120 circuits exist and how such circuits function in pancreatic islets are unclear.

Transient receptor potential ankyrin 1 mediates cisplatin-induced apoptosis in renal tubular cells via calcium-dependent signaling pathway.

Background: Cisplatin has been a vital drug used for tumor treatment because of its excellent effect on numerous malignant solid cancers. Nonetheless, its nephrotoxicity is non-negligible in clinical practice. This study aims to provide a new understanding of the molecular mechanism of transient receptor potential ankyrin 1 (TRPA1) in cisplatin-induced renal apoptosis.

Influence of graphene on the multiple metabolic pathways of Zea mays roots based on transcriptome analysis.

Graphene reportedly exerts positive effects on plant root growth and development, although the corresponding molecular response mechanism remains to be elucidated. Maize seeds were randomly divided into a control and experimental group, and the roots of Zea mays L. seedlings were watered with different concentrations (0-100 mg/L) of graphene to explore the effects and molecular mechanism of graphene on the growth and development of Z.

Effective prevention and management of COVID-19 in outpatient hemodialysis patients.

The authors introduce a mobile phone app that may effectively prevent and manage coronavirus disease 2019 (COVID-19) in outpatient hemodialysis patients in Sichuan Province, China.

Gender-specific associations of CD36 polymorphisms with the lipid profile and susceptibility to premature multi-vessel coronary artery heart disease in the Northern Han Chinese.

Background: The aim of the present study was to detect potential gender-specific associations between some common CD36 single nucleotide polymorphisms (SNPs) and the lipid profile, as well as the susceptibility to premature multi-vessel coronary artery heart disease (CHD) in the Han population of Northern China.

Methods: A systematic three-step study process was employed to detect associations between CD36 gene variants and blood lipid profiles, as well as premature multi-vessel CHD in a gender-specific manner.

Results: The current study documented the following novel findings: (I) the full population-based association study in 329 Northern Han Chinese showed that four common CD36 polymorphisms were significantly related to extreme lipid profiles, with statistically significant effects based on gender interactions (rs1049673: P = 0.

Mitofusin1 Is a Major Mediator in Glucose-Induced Epithelial-to-Mesenchymal Transition in Lung Adenocarcinoma Cells.

Background: Epithelial-to-mesenchymal transition (EMT) has been considered a latent mediator of diverse biological processes in cancer. However, the mechanisms involved in high glucose-associated EMT in lung adenocarcinoma (LAD) have not been fully clarified. In this study, we aimed to investigate whether mitofusin1 (MFN1) is involved in the EMT of LAD cells induced by glucose and to identify the molecular mechanism involved in this process.

In vitro expansion of pancreatic islet clusters facilitated by hormones and chemicals.

Tissue regeneration, such as pancreatic islet tissue propagation in vitro, could serve as a promising strategy for diabetes therapy and personalised drug testing. However, such a strategy has not been realised yet. Propagation could be divided into two steps, in vitro expansion and repeated passaging.

Correction to: Efficient derivation of extended pluripotent stem cells from NOD-scid Il2rg mice.

In the original publication Fig. 1D and supplementary material is incorrect. The correct figure and supplementary material is provided in this correction.

Rapid generation of gene-targeted EPS-derived mouse models through tetraploid complementation.

One major strategy to generate genetically modified mouse models is gene targeting in mouse embryonic stem (ES) cells, which is used to produce gene-targeted mice for wide applications in biomedicine. However, a major bottleneck in this approach is that the robustness of germline transmission of gene-targeted ES cells can be significantly reduced by their genetic and epigenetic instability after long-term culturing, which impairs the efficiency and robustness of mouse model generation. Recently, we have established a new type of pluripotent cells termed extended pluripotent stem (EPS) cells, which have superior developmental potency and robust germline competence compared to conventional mouse ES cells.

Efficient derivation of extended pluripotent stem cells from NOD-scid Il2rg mice.

Recently we have established a new culture condition enabling the derivation of extended pluripotent stem (EPS) cells, which, compared to conventional pluripotent stem cells, possess superior developmental potential and germline competence. However, it remains unclear whether this condition permits derivation of EPS cells from mouse strains that are refractory or non-permissive to pluripotent cell establishment. Here, we show that EPS cells can be robustly generated from non-permissive NOD-scid Il2rg mice through de novo derivation from blastocysts.

Derivation of Pluripotent Stem Cells with In Vivo Embryonic and Extraembryonic Potency.

Of all known cultured stem cell types, pluripotent stem cells (PSCs) sit atop the landscape of developmental potency and are characterized by their ability to generate all cell types of an adult organism. However, PSCs show limited contribution to the extraembryonic placental tissues in vivo. Here, we show that a chemical cocktail enables the derivation of stem cells with unique functional and molecular features from mice and humans, designated as extended pluripotent stem (EPS) cells, which are capable of chimerizing both embryonic and extraembryonic tissues.