Nisch

Argonaute (AGO) proteins execute microRNA (miRNA)-mediated gene silencing. However, it is unclear whether all 4 mammalian AGO proteins (AGO1, AGO2, AGO3, and AGO4) are required for miRNA activity. We generate Ago1, Ago3, and Ago4-deficient mice (Ago134Δ ) and find AGO1/3/4 to be redundant for miRNA biogenesis, homeostasis, or function, a role that is carried out by AGO2. Instead, AGO1/3/4 regulate the expansion of type 2 immunity via precursor mRNA splicing in CD4+ T helper (Th) lymphocytes. Gain- and loss-of-function experiments demonstrate that nuclear AGO3 interacts directly with SF3B3, a component of the U2 spliceosome complex, to aid global mRNA splicing, and in particular the isoforms of the gene Nisch, resulting in a dysregulated Nisch isoform ratio...

BACKGROUND:   With the help of statements from contemporary witnesses, it shall be deduced, if and to what extent Psychiatry was experienced as a shelter for employees and patients in the state controlled society of the GDR and which effort of adaptation to the authoritarian regime was needed to organize protected and protective spaces, here called "niches". METHOD:   74 guide-based interviews from subjects including former patients and different staff groups of the East german Psychiatry were analyzed qualitatively...

Mercury (Hg) fulminate was used as a primary fuse in World War (WW) munitions, and may consequently be a Hg source for impacted environments. Mercury is a conspicuous and persistent pollutant, with methylmercury (MeHg) acting as a notorious neurotoxin. Considerable amounts of munitions were intentionally dumped in the North Sea and Baltic Sea following the First and Second WWs. After more than 70 years on the seafloor many munitions have corroded and likely release explosive compounds, including Hg fulminate...

Neonatal ichthyosis and sclerosing cholangitis syndrome (NISCH), also known as ichthyosis, leukocyte vacuoles, alopecia, and sclerosing cholangitis (ILVASC), is an extremely rare disease of autosomal recessive inheritance, resulting from loss of function of the tight junction protein claudin-1. Its clinical presentation is highly variable, and is characterized by liver and ectodermal involvement. Although most ILVASC cases described to date were attributed to homozygous truncating variants in CLDN1, a single missense variant CLDN1 p...

BACKGROUND: Opiate abuse has been critically increased in the world, especially in Iran. Owing to the association of opiate use with multiple human cancers and neurological disorders, seeking for genetic and epigenetic effects of opium can pave the way for early diagnosis of major health defects in addicted users. Accordingly, the present study aimed to determine the methylation status of the promoter of two genes, which are actively involved in neurodevelopment and cancer evolution. METHODS: DNA was isolated from peripheral blood of 28 opium abusers and 19 healthy controls and then subjected to sonication...

BACKGROUND: Schizophrenia and bipolar disorder (BD) are believed to share clinical symptoms, genetic risk, etiological factors, and pathogenic mechanisms. We previously reported that single nucleotide polymorphisms spanning chromosome 3p21.1 showed significant associations with both schizophrenia and BD, and a risk SNP rs2251219 was in linkage disequilibrium with a human specific Alu polymorphism rs71052682, which showed enhancer effects on transcriptional activities using luciferase reporter assays in U251 and U87MG cells...

Due to the development of resistance to previously effective therapies, there is a constant need for novel treatment modalities for metastatic melanoma. Nischarin (NISCH) is a druggable scaffolding protein reported as a tumor suppressor and a positive prognostic marker in breast and ovarian cancers through regulation of cancer cell survival, motility and invasion. The aim of this study was to examine the expression and potential role of nischarin in melanoma. We found that nischarin expression was decreased in melanoma tissues compared to the uninvolved skin, and this was attributed to the presence of microdeletions and hyper-methylation of the NISCH promoter in the tumor tissue...

Invited for the cover of this issue are the groups of Carsten von Hänisch and Crispin Lichtenberg at the Philipps University of Marburg. The image depicts a bismuth kraken, eagerly grabbing Lewis basic substrates, thereby solving scientific puzzles about bismuth-based Lewis acidity. Read the full text of the article at 10.1002/chem.202204012.

Invited for the cover of this issue is the group of Carsten von Hänisch at the Philipps-University Marburg. The image depicts a bismuth crystal, a chain formed from it and the molecular structures of different chain molecules with diaryl-bismuth groups. Read the full text of the article at 10.1002/chem.202202932.

We evaluated the presence of tight junction (TJ) remnants in the stratum corneum (SC) of in vitro reconstructed human epidermis and human skin explants subjected or not to an aggressive topical treatment with beta-lipohydroxy salicylic acid (LSA) for 24 h. LSA-treated samples showed an increased presence of TJ remnants in the two lowermost layers of the SC, as quantified with standard electron microscopy. The topical aggression-induced overexpression of TJ-like cell-cell envelope fusions may influence SC functions: (1) directly, through an enhanced cohesion, and (2) indirectly, by impeding accessibility of peripheral corneodesmosomes to extracellular hydrolytic enzymes and, thus, slowing down desquamation...

Ferroptosis, a type of iron-dependent programmed cell death distinct from apoptosis, necroptosis, and other types of cell death, is characterized by lipid peroxidation, reactive oxygen species production, and mitochondrial dysfunction. Accumulating evidence has highlighted vital roles for ferroptosis in multiple diseases, including acute kidney injury. Therefore, ferroptosis has become a major focus for translational research. However, despite its involvement in pathological conditions, there are no pharmacologic inhibitors of ferroptosis in clinical use...

Increasing research interests have been aroused in exploring the function of long non-coding RNA (lncRNA) in breast cancer and developing lncRNA-targeted diagnosis, treatment and prognosis. In GEPIA2 database, we compared the expression pattern of the lncRNA RP11-214F16.8 in normal mammary tissues and breast cancer tumors and its correlation with the overall death rate of breast cancer patients. Gain- and loss-of function assays were employed to study function of the lncRNA in breast cancer cell lines in vitro while xenograft tumor growth assay was performed to investigate its function in tumorigenesis in vivo...

Nischarin has been demonstrated to have tumor suppressor functions. In this review, we comprehensively discuss up to date information about Nischarin. In addition, this paper aims to report the prognostic value, clinical relevance, and biological significance of the Nischarin gene (NISCH) in breast cancer (BCa) patients using the Molecular Taxonomy of Breast Cancer International Consortium (METABRIC) and The Cancer Genome Atlas (TCGA) datasets. We evaluated NISCH gene expression and its correlation to patient survival, baseline expression, and expression variation based on age groups, tumor stage, tumor size, tumor grade, and lymph node status in different subtypes of BCa...

BACKGROUND: Recently, overwhelming evidence supports that long noncoding RNAs (lncRNAs) play crucial roles in the occurrence and progression of tumors. However, the role and mechanism of lncRNA TFAP2A-AS1 in human gastric cancer (GC) remains unclear. Thus, the biological role and regulatory mechanisms of TFAP2A-AS1 in GC were explored. METHODS: Quantitative real-time PCR (qPCR) was applied to detect gene expression. Western blot was used to measure protein expression...

Nischarin is an integrin-binding protein, which is well known as a novel tumor suppressor. In breast cancer, Nischarin serves a critical role in breast cancer cell migration and invasion. However, the molecular mechanism underlying the role of Nischarin remains unclear. Recent findings have demonstrated that epithelial-mesenchymal transition (EMT) increases the capacity of cell migration and invasion. As a member of the integrin family, it was hypothesized that Nischarin may regulate cellular processes via various signaling pathways associated with the EMT process...

Nischarin (NISCH) is a key protein functioning as a molecular scaffold and thereby hosting interactions with several protein partners. Here, we aimed to investigate whether NISCH downregulation could protect rat pheochromocytoma (PC12) cells against oxidative stress-induced injury using a model of cell injury induced by hydrogen peroxide (H2O2). Cell viability was evaluated using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Cell apoptosis rate was evaluated using flow cytometry. The expressions of apoptosis-related proteins Bax, Bcl-2, caspase-3 and NISCH were examined via Western blot analysis and immunofluorescence staining analyses...

The development of breast cancer (BC) subtypes is controlled by distinct sets of candidate genes, and the expression of these genes is regulated by the binding of their mRNAs with miRNAs. Predicting miRNA associations and target genes is thus essential when studying breast cancer. The MirTarget program identifies the initiation of miRNA binding to mRNA, the localization of miRNA binding sites in mRNA regions, and the free energy from the binding of all miRNA nucleotides with mRNA. Candidate gene mRNAs have clusters (miRNA binding sites with overlapping nucleotide sequences)...

Lung cancer has very high mortality due to late stage diagnosis not amenable to curative resection. Cancer specific methylation patterns of tumor suppressor genes may precede precursor lesions of lung cancer. Our aim was to evaluate the promoter hypermethylation of tumor suppressor gene NISCH and CDH1 in cfDNA from plasma of lung cancer patients and its possible correlation with smoking status and various clinicopathological parameters. Forty histopathologically confirmed lung cancer cases, thirty smoker and thirty nonsmoker controls were enrolled...

Previously, our lab discovered the protein Nischarin and uncovered its role in regulating cell migration and invasion via its interactions with several proteins. We subsequently described a role for Nischarin in breast cancer, in which it is frequently underexpressed. To characterize Nischarin's role in breast tumorigenesis and mammary gland development more completely, we deleted a critical region of the Nisch gene (exons 7-10) from the mouse genome and observed the effects. Mammary glands in mutant animals showed delayed terminal end bud formation but did not develop breast tumors spontaneously...

Nischarin (NISCH) is a cytoplasmic protein known to serve an inhibitory role in breast cancer cell apoptosis, migration and invasion. Recently, NISCH has been reported to be involved in the regulation of spinal cord injury (SCI). However, the molecular mechanism is still unclear. Oxidative stress contributes to tissue injury and cell apoptosis during the development of various diseases, including SCI. The aim of the present study was to investigate the role of NISCH in the regulation of apoptosis induced by oxidative stress in PC12 cells...