Identification of key necroptosis-related genes and immune landscape in patients with immunoglobulin A nephropathy.

Background: Immunoglobulin A nephropathy (IgAN) is a major cause of chronic kidney disease (CKD) and kidney failure. Necroptosis is a novel type of programmed cell death that has been proved to be associated with the pathogenesis of infectious disease, cardiovascular disease, neurological disorders and so on. However, the role of necroptosis in IgAN remains unclear.

Oroxylin A suppressed colorectal cancer metastasis by inhibiting the activation of the TGF-β/SMAD signal pathway.

Metastatic colorectal cancer continues to have a high fatality rate, with approximately only 14% of patients surviving more than 5 years. To improve the survival rate of these patients, the development of new therapeutic drugs is a priority. In this study, we investigated the effects of Oroxylin A on the metastasis of human colorectal cancer cells and its potential molecular mechanism.

Arctigenin inhibits the progression of colorectal cancer through epithelial-mesenchymal transition via PI3K/Akt/mTOR signaling pathway.

Background: Colorectal cancer (CRC) is a significant disease worldwide, with high mortality rates. Conventional treatment methods often lead to metastasis and drug resistance, highlighting the need to explore new drugs and their potential molecular mechanisms. In this study, we investigated the effects of arctigenin on CRC cell proliferation, migration, invasion, apoptosis, and related protein expression, as well as its potential molecular mechanisms.

Advances of Antisense Oligonucleotide Technology in the Treatment of Hereditary Neurodegenerative Diseases.

Antisense nucleic acids are single-stranded oligonucleotides that have been specially chemically modified, which can bind to RNA expressed by target genes through base complementary pairing and affect protein synthesis at the level of posttranscriptional processing or protein translation. In recent years, the application of antisense nucleic acid technology in the treatment of neuromuscular diseases has made remarkable progress. In 2016, the US FDA approved two antisense nucleic acid drugs for the treatment of Duchenne muscular dystrophy (DMD) and spinal muscular atrophy (SMA), and the development to treat other neurodegenerative diseases has also entered the clinical stage.

Cyclin A2/cyclin-dependent kinase 1-dependent phosphorylation of Top2a is required for S phase entry during retinal development in zebrafish.

Cyclin-dependent kinase 1 (CDK1) plays an essential role in cell cycle regulation. However, as mouse Cdk1 embryos die early, the role of CDK1 in regulating the cell cycle and embryo development remains unclear. Here, we showed that zebrafish cdk1 embryos exhibit severe microphthalmia accompanied by multiple defects in S phase entry, M phase progression, and cell differentiation but not in interkinetic nuclear migration.

Author Correction: Hydrophobic pore gates regulate ion permeation in polycystic kidney disease 2 and 2L1 channels.

The original version of this Article contained an error in the spelling of the author David Bulkley, which was incorrectly given as David Bulkey. This has now been corrected in both the PDF and HTML versions of the Article.

Mutagenesis of putative ciliary genes with the CRISPR/Cas9 system in zebrafish identifies genes required for retinal development.

Cilia are conserved microtubule-based organelles that function as mechanical and chemical sensors in various cell types. By bioinformatic, genomic, and proteomic studies, more than 2000 proteins have been identified as cilium-associated proteins or putative ciliary proteins; these proteins are referred to as the ciliary proteome or the ciliome. However, little is known about the function of these numerous putative ciliary proteins in cilia.

Apical PtdIns(4,5)P is required for ciliogenesis and suppression of polycystic kidney disease.

Cilia are hair-like structures that function like antennae to detect chemical and mechanical signals in the environment. Recently, phosphoinositides were shown to play an important role in cilia assembly and disassembly. However, the precise molecular and cellular mechanisms underlying this process remain unknown.

Hydrophobic pore gates regulate ion permeation in polycystic kidney disease 2 and 2L1 channels.

PKD2 and PKD1 genes are mutated in human autosomal dominant polycystic kidney disease. PKD2 can form either a homomeric cation channel or a heteromeric complex with the PKD1 receptor, presumed to respond to ligand(s) and/or mechanical stimuli. Here, we identify a two-residue hydrophobic gate in PKD2L1, and a single-residue hydrophobic gate in PKD2.

Identification and characterization of hydrophobic gate residues in TRP channels.

Transient receptor potential (TRP) channels, subdivided into 6 subfamilies in mammals, have essential roles in sensory physiology. They respond to remarkably diverse stimuli, comprising thermal, chemical, and mechanical modalities, through opening or closing of channel gates. In this study, we systematically substituted the hydrophobic residues within the distal fragment of pore-lining helix S6 with hydrophilic residues and, based on Xenopus oocyte and mammalian cell electrophysiology and a hydrophobic gate theory, identified hydrophobic gates in TRPV6/V5/V4/C4/M8.

Using local chromatin structure to improve CRISPR/Cas9 efficiency in zebrafish.

Although the CRISPR/Cas9 has been successfully applied in zebrafish, considerable variations in efficiency have been observed for different gRNAs. The workload and cost of zebrafish mutant screening is largely dependent on the mutation rate of injected embryos; therefore, selecting more effective gRNAs is especially important for zebrafish mutant construction. Besides the sequence features, local chromatin structures may have effects on CRISPR/Cas9 efficiency, which remain largely unexplored.

The Joubert Syndrome Protein Inpp5e Controls Ciliogenesis by Regulating Phosphoinositides at the Apical Membrane.

Phosphoinositides, a family of phosphorylated derivatives of phosphatidylinositol (PtdIns), are tightly regulated both temporally and spatially by PtdIns phosphatases and kinases. Mutations in inositol polyphosphate 5-phosphatase E (INPP5E) cause Joubert syndrome, a human disorder associated with numerous ciliopathic defects, including renal cyst formation, linking phosphoinositides to ciliopathies. However, the molecular mechanism by which INPP5E-mediated PtdIns signaling regulates ciliogenesis and cystogenesis is unclear.

Far Upstream Element-Binding Protein 1 Binds the 3' Untranslated Region of PKD2 and Suppresses Its Translation.

Autosomal dominant polycystic kidney disease pathogenesis can be recapitulated in animal models by gene mutations in or dosage alterations of polycystic kidney disease 1 (PKD1) or PKD2, demonstrating that too much and too little PKD1/PKD2 are both pathogenic. Gene dosage manipulation has become an appealing approach by which to compensate for loss or gain of gene function, but the mechanisms controlling PKD2 expression remain incompletely characterized. In this study, using cultured mammalian cells and dual-luciferase assays, we found that the 3' untranslated region (3'UTR) of PKD2 mRNA inhibits luciferase protein expression.