Abstract MicroRNAs (miRNAs) regulate fundamental biological processes by silencing mRNA targets and are dysregulated in many diseases. Therefore, miRNA replacement or inhibition can be harnessed as potential therapeutics. However, existing strategies for modulation using oligonucleotides gene therapies challenging, especially neurological diseases, none have yet gained clinical approval. We explore a different approach screening biodiverse library of small molecule compounds their ability to...

Significance Wolfram syndrome is a rare multisystem disease characterized by diabetes insipidus, mellitus, optic nerve atrophy, and deafness (DIDMOAD). It primarily caused mutations in the 1 gene, WFS1 . As monogenetic disorder, model for neurodegeneration. There no effective treatment this invariably fatal disease. Here we characterize as regulator of calcium homeostasis subsequently target signaling to reverse deficits cellular syndrome.

Three types of commercially derived methylsilicone materials, Sylgard-184, QVQH (an MQ-based silicone containing no dimethylsiloxane, D units), and DVDH (a D-based with additives), were judiciously chosen to study the conditions under which long-lasting hydrophilicity after oxygen plasma treatment can be obtained. A 30 s time controlled was found optimal in terms achieving lowest initial advancing receding contact angles θA/θR = 10°/5° undetectable surface damage. Vacuum treatment, a...

Tumor cell heterogeneity in neuroblastoma, a pediatric cancer arising from neural crest–derived progenitor cells, presents clinical challenges. Unlike adrenergic (ADRN) neuroblastoma cells with mesenchymal (MES) identity are resistant to chemotherapy and retinoid therapy, which contributes relapses treatment failures. We explored whether up-regulation of the neurogenic, tumor suppressor microRNA miR-124 could promote differentiation retinoic acid–resistant MES cells. Leveraging our screen...

Abstract Background After chemotherapy, many cancer survivors suffer from long-lasting cognitive impairment, colloquially known as “chemobrain.” However, the trajectories of changes and underlying mechanisms remain unclear. We previously established paclitaxel-induced inositol trisphosphate receptor (InsP3R)-dependent calcium oscillations a mechanism for peripheral neuropathy, which was prevented by lithium pretreatment. Here, we investigated if similar also underlay chemobrain. Method Mice...

Inositol 1,4,5-trisphosphate receptors (InsP3Rs) are endoplasmic reticulum-localized channels that mediate Ca2+ release from the reticulum into cytoplasm. We previously reported an EF-hand Ca2+-binding protein, neuronal calcium sensor 1 (NCS1), binds to InsP3R and thereby increases channel open probability, event associated with chemotherapy-induced peripheral neuropathy. However, exact NCS1-binding site on remains unknown. Using protein docking, co-immunoprecipitation, blocking peptides, we...

1.4.8Lung histology confirms higher tumor burden in mice xenografted with NCS1 overexpressing cells 1.4.9NCS1 protects cancer from necrosis within mature tumors 1.5 Discussion 1.

Adsorption of poly(vinyl alcohol) (PVOH), 99% and 88% hydrolyzed acetate), to poly(dimethylsiloxane) (PDMS) substrates was studied. The were prepared by covalently attaching linear PDMS polymers 2, 9, 17, 49, 116 kDa onto silicon wafers. As the molecular weight/thickness increases, adsorbed PVOH thin films progressively transition from continuous discontinuous morphologies, including honeycomb fractal/droplet. structures are result film dewetting that occurs upon exposure air. thickness does...

Neuronal calcium sensor-1 (NCS-1 Var1) is a calcium-binding protein expressed in most tissues. We examined poorly characterized variant of NCS-1 (Var2), identified only humans where the N-terminal 22 amino acid residues native NCS-1(MGKSNSKLKPEVVEELTRKTY) were replaced with 4 different (MATI). Because alterations level expression Var1 and variants have been correlated several neurological diseases, relative functional role Var2 was examined. found that mRNA levels are not mouse tissues at...

Calcium (Ca2+ ) signaling is critical for neuronal functioning and requires the concerted interplay of numerous Ca2+ -binding proteins, including calcium sensor 1 (NCS1). Although an important role NCS1 in processes neurodevelopmental neurodegenerative diseases has been established, underlying mechanisms remain enigmatic. Here, we systematically investigated functions brain. Using Golgi-Cox staining, observed a reduction dendritic complexity spine density prefrontal cortex dorsal hippocampus...

<title>Abstract</title> MicroRNAs (miRNAs) regulate fundamental biological processes by silencing mRNA targets and are dysregulated in many diseases. Therefore, miRNA replacement or inhibition can be harnessed as potential therapeutics. However, existing strategies for modulation using oligonucleotides gene therapies challenging, especially neurological diseases, none have yet gained clinical approval. We explore a different approach screening biodiverse library of small molecule compounds...

Objectives: The aim of this study is to analyze the compositions urinary stones and investigate their distributions in different ages, genders, seasons, clinical features Northern Vietnamese patients. Methods: A total 231 patients with from Vietnam were collected analyzed composition 1/2021-12/2022. For all patients, age, sex, stone location, side, urine pH, hospitalized date (month) collected. Results: Kidney are more frequently found men than women male: female ratio being 1.96:1. highest...

Neuronal calcium sensor 1 (NCS1) regulates a wide range of cellular functions throughout the mammalian nervous systems. Altered NCS1 expression is associated with neurodevelopmental and neurodegenerative diseases. Previous studies focused on affective cognitive behaviors in knockout (KO) mice, but little known about physiological pathological states loss peripheral system. We previously reported that was reduced following paclitaxel-induced neuropathy. Here, we comprehensively investigated...

Abstract Tumor cell heterogeneity in neuroblastoma, a pediatric cancer arising from neural crest-derived progenitor cells, poses significant clinical challenge. In particular, unlike adrenergic (ADRN) neuroblastoma mesenchymal (MES) cells are resistant to chemotherapy and retinoid therapy thereby significantly contribute relapses treatment failures. Previous research suggested that overexpression or activation of miR-124, neurogenic microRNA with tumor suppressor activity, can induce the...

SUMMARY MicroRNAs (miRNAs) are short RNAs that regulate fundamental biological processes. miR-132, a key miRNA with established functions in Tau homeostasis and neuroprotection, is consistently downregulated Alzheimer’s disease (AD) other tauopathies. miR-132 overexpression rescues neurodegenerative phenotypes several AD models. To complement research on miRNA-mimicking oligonucleotides targeting the central nervous system, we developed high-throughput-screen coupled...

Wolfram syndrome (WS) is an orphan, autosomal recessive neuroendocrinological disease that affects approximately 1 in 500,000 people worldwide. Patients develop diabetes mellitus, insipidus, optical atrophy, and hearing loss usually die their 30s. The majority of cases are attributed to mutations a single gene, WFS1, which encodes for the protein wolframin. Despite known genetic cause, there currently no direct treatment WS. This lack therapy because regular functions wolframin,...

Chemotherapy, a life‐saving treatment for cancer patients, is often associated with debilitating, sometimes irreversible, side effects. Approximately 40% of survivors suffer from cognitive impairments, symptoms including memory lapses, learning difficulties, and troubles focusing, planning, multi‐tasking, verbal communication. However, essential questions concerning the specific functions affected, trajectories changes, underlying mechanisms remain unclear. We aimed to investigate these by...

Many chemotherapy drugs induce peripheral neuropathy (PN), a painful and irreversible side effect. Previous results reported in the literature show that Paclitaxel vincristine, which are anti-microtubule targeting drugs, PN by mechanisms not fully understood. The Ehrlich group has neuronal cell line primary rat dorsal root ganglia, paclitaxel binds to protein calcium sensor-1 (NCS-1) triggers calpain-dependent decrease intracellular signaling via degradation of NCS-1 subsequent dependent...