Aims: The study aims to investigate whether WFS1 is involved in the regulation of the exportation and secretion of other peptide hormones, as well as to elucidate the precise molecular mechanisms underlying WS caused by pathogenic mutations in the WFS1 gene.
Materials And Methods: The plasma proteome from the WS patients (n = 2, male) and WFS1-deficient mice (n = 5, male) were analyzed using liquid-chromatography tandem mass spectrometry (LC-MS/MS), while age- and gender-matched healthy individuals and wildtype (WT) mice serve as controls. WFS1-deficient mice were intraperitoneally injected with IGF1 starting from 4 weeks of age.
Acute myeloid leukemia (AML), as the most common malignancy of the hematopoietic system, poses challenges in treatment efficacy, relapse, and drug resistance. In this study, we have utilized 151 RNA sequencing datasets, 194 DNA methylation datasets, and 200 somatic mutation datasets from the AML cohort in the TCGA database to develop a multi-omics stratification model. This model enables comparison of prognosis, clinical features, gene mutations, immune microenvironment and drug sensitivity across subgroups.
View Article and Find Full Text PDFTo reveal the potential mechanism of the effect of Chinese Herbal Medicine Fuzi on Aplastic anaemia (AA) according to the network pharmacology approach and molecular docking. According to Ultra High Performance Liquid Chromatography Mass Spectrometry (UHPLC-MS/MS), 146 chemical ingredients of Fuzi were obtained. By SwissADME online system analysis, a total of 55 compounds such as Magnoflorine, Scutellarein, Luteolin and Gingerol may be the main active components of Fuzi and 145 common targets related to AA were predicted.
View Article and Find Full Text PDFExtracellular vesicles (EVs) have emerged as a promising tool for clinical liquid biopsy. However, the identification of EVs derived from blood samples is hindered by the presence of abundant plasma proteins, which impairs the downstream biochemical analysis of EV-associated proteins and nucleic acids. Here, we employed optimized asymmetric flow field-flow fractionation (AF4) combined with density cushion ultracentrifugation (UC) to obtain high-purity and intact EVs with very low lipoprotein contamination from human plasma and serum.
View Article and Find Full Text PDFVitamin D acts through the vitamin D receptor (VDR), and vitamin D level decreases in multiple myeloma (MM) patients. Single nucleotide polymorphisms in VDR alter its functions to affect the vitamin D status. This raises the question of whether VDR gene polymorphisms are associated with MM risk, which has been investigated in case‒control studies, but the results have been inconsistent.
View Article and Find Full Text PDFBackground: Peripheral neuropathy (PN) is a prevalent complication of multiple myeloma (MM), due to the disease itself or its treatment. Despite extensive research, the optimal treatment for multiple myeloma peripheral neuropathy (MMPN) remains unclear. Clinical practice has shown the potential efficacy of acupuncture in managing MMPN.
View Article and Find Full Text PDFThe angiotensin-converting enzyme 2 (ACE2) is a primary cell surface viral binding receptor for SARS-CoV-2, so finding new regulatory molecules to modulate ACE2 expression levels is a promising strategy against COVID-19. In the current study, we utilized islet organoids derived from human embryonic stem cells (hESCs), animal models and COVID-19 patients to discover that fibroblast growth factor 7 (FGF7) enhances ACE2 expression within the islets, facilitating SARS-CoV-2 infection and resulting in impaired insulin secretion. Using hESC-derived islet organoids, we demonstrated that FGF7 interacts with FGF receptor 2 (FGFR2) and FGFR1 to upregulate ACE2 expression predominantly in β cells.
View Article and Find Full Text PDFObjective: Numerous studies have highlighted the role of clock genes in diabetes disease and pancreatic β cell functions. However, whether rhythmic long non-coding RNAs involve in this process is unknown.
Methods: RNA-seq and 3' rapid amplification of cDNA ends (RACE)-PCR were used to identify the rat LncCplx2 in pancreatic β cells.
Although severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) entry mechanism has been explored, little is known about how SARS-CoV-2 regulates the subcellular structural remodeling to invade multiple organs and cell types. Here, we unveil how SARS-CoV-2 boosts and utilizes filopodia to enter the target cells by real-time imaging. Using SARS-CoV-2 single virus-like particle (VLP) tracking in live cells and sparse deconvolution algorithm, we uncover that VLPs utilize filopodia to reach the entry site in two patterns, "surfing" and "grabbing", which avoid the virus from randomly searching on the plasma membrane.
View Article and Find Full Text PDFInter-organelle membrane contacts are highly dynamic and act as central hubs for many biological processes, but the protein compositions remain largely unknown due to the lack of efficient tools. Here, we developed BiFCPL to analyze the contact proteome in living cells by a bimolecular fluorescence complementation (BiFC)-based proximity labeling (PL) strategy. BiFCPL was applied to study mitochondria-endoplasmic reticulum contacts (MERCs) and mitochondria-lipid droplet (LD) contacts.
View Article and Find Full Text PDFMultiple myeloma (MM) is a malignant clonal proliferative plasma cell tumor. Zinc oxide nanoparticles (ZnO NPs) are used for antibacterial and antitumor applications in the biomedical field. This study investigated the autophagy-induced effects of ZnO NPs on the MM cell line RPMI8226 and the underlying mechanism.
View Article and Find Full Text PDFDiffuse large B-cell lymphoma (DLBCL) is the most common type of lymphoma. Zinc oxide (ZnO) nanoparticles have excellent anti-tumor properties in the biomedical field. The present study aimed to explore the underlying mechanism by which ZnO nanoparticles induce toxicity in DLBCL cells (U2932) via the PINK1/Parkin-mediated mitophagy pathway.
View Article and Find Full Text PDFIntroduction: nutritional status can affect the treatment of hospitalized patients, and malnutrition can even lead to death. However, the nutritional status of patients with aplastic anemia (AA) is unclear. Objective: to assess the nutritional status of aplastic anemia patients with body mass index (BMI) ≥ 24 kg/m2 (high BMI group) and BMI < 24 kg/m2 (low BMI group), and to compare the consistency between different nutritional screening tools.
View Article and Find Full Text PDFAcute promyelocytic leukemia (APL) is a specific subtype of acute myelogenous leukemia (AML) characterized by the proliferation of abnormal promyelocytes. Realgar, a Chinese medicine containing arsenic, can be taken orally. Traditional Chinese medicine physicians have employed realgar to treat APL for over a thousand years.
View Article and Find Full Text PDFAging (Albany NY)
September 2022
Background: Heat shock factor 1 (HSF1) is now considered to have the potential to be used as a prognostic biomarker in cancers. However, its clinical significance and potential function in acute myeloid leukemia (AML) remain underexplored.
Methods: In this study, the expression pattern and clinical significance of HSF1 in AML were examined by integrating data from databases including The Cancer Genome Atlas (TCGA), The Genotype-Tissue Expression (GTEx), Vizome, Cancer Cell Line Encyclopedia (CCLE) and Gene Expression Omnibus (GEO).
Objective: Analyzing the effective connectivity characteristics of brain networks in the process of action observation is helpful for understanding the neurodynamic mechanisms during action observation.
Method: In this study, functional magnetic resonance imaging (fMRI) images were obtained from 20 participants who performed hand-object interaction observation tasks from the first-person perspective (1PP) and third-person perspective (3PP). On the basis of a meta-analysis, 11 key brain regions were extracted as nodes to build an action observation network.
Zinc oxide nanoparticles (ZnO NPs) have exhibited excellent anti-tumor properties; the present study aimed to elucidate the underlying mechanism of ZnO NPs induced apoptosis in acute myeloid leukemia (AML) cells by regulating mitochondrial division. THP-1 cells, an AML cell line, were first incubated with different concentrations of ZnO NPs for 24 hr. Next, the expression of Drp-1, Bcl-2, Bax mRNA, and protein was detected, and the effects of ZnO NPs on the levels of reactive oxygen species (ROS), mitochondrial membrane potential (Δψm), apoptosis, and ATP generation in THP-1 cells were measured.
View Article and Find Full Text PDFThe sorting of soluble secretory proteins from the endoplasmic reticulum (ER) to the Golgi complex is mediated by coat protein complex II (COPII) vesicles and thought to required specific ER membrane cargo-receptor proteins. However, these receptors remain largely unknown. Herein, we show that ER to Golgi transfer of vesicular cargo proteins requires WFS1, an ER-associated membrane protein whose loss of function leads to Wolfram syndrome.
View Article and Find Full Text PDFGlaucoma is a leading cause of irreversible blindness worldwide due to elevated intraocular pressure, and filtering surgery can efficiently control intraocular pressure of glaucoma patients. However, failure of filtering surgery commonly results from scarring formation at the surgical site, in which fibroblast proliferation plays an essential role in the scarring process. Our previous study has demonstrated that zinc oxide (ZnO) nanoparticles could efficiently inhibit human tenon fibroblasts (HTFs) proliferation.
View Article and Find Full Text PDFBackground: Acute myeloid leukemia (AML) is the most common malignant tumor of the hematopoietic system, which seriously threatens the lives of patients. Most AML patients have acute onset, severe condition, and poor prognosis. The present study aimed to comprehensively evaluate the effectiveness and safety of chemotherapy combined with different doses of interleukin-2 (IL-2) maintenance treatments in AML by Bayesian network meta-analysis (NMA).
View Article and Find Full Text PDFThis study aimed to investigate the dynamic effects of the traditional Chinese medicine compound Longdan Xiegan Decoction (LXD) on the inhibition of Notch signaling pathway activation and T helper (Th) cell differentiation in rats with experimental autoimmune uveitis (EAU). Based on a network pharmacology strategy, we conducted protein interaction network analysis to construct an active ingredient-disease treatment network. Gene Ontology (GO) enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were further used to screen out the possible signaling pathways regulated by LXD in the treatment of uveitis.
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