Effects of Enterocytozoon hepatopenaei single-infection or co-infection with Vibrio parahaemolyticus on the hepatopancreas of Penaeus vannamei

Aquaculture, Год журнала: 2021, Номер 549, С. 737726 - 737726

Опубликована: Ноя. 20, 2021

Язык: Английский

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Behind every smile there's teeth: Cathepsin B's function in health and disease with a kidney view

Biochimica et Biophysica Acta (BBA) - Molecular Cell Research, Год журнала: 2021, Номер 1869(4), С. 119190 - 119190

Опубликована: Дек. 27, 2021

Cathepsin B (CatB) is a very abundant lysosomal protease with endo- and carboxydipeptidase activities even ligase features. In this review, we will provide general characterization of CatB describe structure, structure-derived properties location-dependent proteolytic actions. We depict action within lysosome its important roles in biogenesis, homeostasis autophagy rendering key player orchestrating functions. Lysosomal leakage subsequent escape into the cytosol lead to harmful actions, e.g. role activating NLPR3 inflammasome, affecting immune responses cell death. The second focus review addresses functions kidney, i.e. glomerulus, proximal tubule collecting duct strong emphasis pathology respective segment. Finally, observations regarding that need be considered culture discussed. conclusion, physiologically molecule may, upon aberrant expression different cellular context, become effectively showing teeth behind smile.

Язык: Английский

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Transcriptomic profiling identifies differentially expressed genes and related pathways associated with wound healing and cuproptosis-related genes in Ganxi goats

Frontiers in Veterinary Science, Год журнала: 2023, Номер 10

Опубликована: Май 3, 2023

Introduction Wound healing is very important for the maintenance of immune barrier integrity, which has attracted wide attention in past 10 years. However, no studies on regulation cuproptosis wound have been reported. Methods In this study, skin injury model was constructed Gnxi goats, and function, regulatory network hub genes before after were comprehensively analyzed by transcriptomics. Results The results showed that there 1,438 differentially expressed (DEGs), up-regulated 545 down-regulated 893, detected comparing day 0 5 posttraumatic skin. Based GO-KEGG analysis, DEGs tended to be enriched lysosome, phagosome, leukocyte transendothelial migration pathways, while significantly adrenergic signaling cardiomyocytes calcium pathway. There 166 overlapped (DE-CUGs) between cuproptosis-related genes, with 72 DE-CUGs 94 DE-CUGs. GOKEGG analysis ferroptosis, lysosome Apelin pathway tyrosine metabolism pathways. By constructing analyzing protein–protein interaction (PPI) networks DE-CUGs, (ENSCHIG00000020079, PLK1, AURKA, ASPM, CENPE, KIF20A, CCNB2, KIF2C, PRC1 KIF4A) (MMP2, TIMP1, MMP9, MMP14, TIMP3, MMP1, EDN1, GCAT, SARDH, DCT) obtained, respectively. Discussion This study revealed pathways Ganxi identified correlation first time, found MMP2, EDN1 core associated. transcriptome data goats expanded research direction cuproptosis.

Язык: Английский

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Hematopoietic Disorders, Renal Impairment and Growth in Mucopolysaccharidosis-Plus Syndrome

International Journal of Molecular Sciences, Год журнала: 2022, Номер 23(10), С. 5851 - 5851

Опубликована: Май 23, 2022

Mucopolysaccharidoses (MPS) are rare lysosomal storage disorders (LSD) characterized by the excessive accumulation of glycosaminoglycans (GAG). Conventional MPS, caused inborn deficiencies enzymes involved in GAG degradation, display various multisystemic symptoms-including progressive neurological complications, ophthalmological disorders, hearing loss, gastrointestinal and hepatobiliary issues, cardiorespiratory problems, bone joint abnormalities, dwarfism, coarse facial features. Mucopolysaccharidosis-Plus Syndrome (MPSPS), an autosomal recessive disease a mutation endo-lysosomal tethering protein VPS33A, shows additional renal hematopoietic abnormalities ("Plus symptoms") uncommon conventional MPS. Here, we analyze data from biochemical, histological, physical examinations-particularly blood counts kidney function-to further characterize clinical phenotype MPSPS. A series tests indicate symptoms including anemia thrombocytopenia, which correlate with histological observations hypoplastic marrow. High urinary excretion (caused impairments filtration), hypoalbuminemia, elevated levels creatinine, cholesterol, uric acid dysfunction. Histological analyses MPSPS kidneys similarly suggest extensive destruction glomerular structures foamy podocytes. Height weight did not significantly deviate average, but some cases, growth began to decline at around six months or one year age.

Язык: Английский

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Nanotechnology Utilizing Ferroptosis Inducers in Cancer Treatment

Anti-Cancer Agents in Medicinal Chemistry, Год журнала: 2024, Номер 24(8), С. 571 - 589

Опубликована: Янв. 25, 2024

Abstract: Current cancer treatment options have presented numerous challenges in terms of reaching high efficacy. As a result, an immediate step must be taken to create novel therapies that can achieve more than satisfying outcomes the fight against tumors. Ferroptosis, emerging form regulated cell death (RCD) is reliant on iron and reactive oxygen species, has garnered significant attention field therapy. Ferroptosis been reported induced by variety small molecule compounds known as ferroptosis inducers (FINs), well several licensed chemotherapy medicines. These compounds' low solubility, systemic toxicity, limited capacity target tumors are some limitations hindered their clinical effectiveness. A therapy paradigm created hypothesis nanoparticles superior preclinical properties drugs overcome apoptosis resistance. Knowing different ideas behind preparation nanomaterials very helpful generating new ideas. Simultaneously, improvement nanomaterial design needed make them appropriate for therapeutic treatment. This paper first discusses fundamentals nanomedicine-based highlight potential characteristics context The latest study nanomedicine applications ferroptosis-based anticancer then highlighted.

Язык: Английский

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Mucopolysaccharidosis-Plus Syndrome: Is This a Type of Mucopolysaccharidosis or a Separate Kind of Metabolic Disease?

International Journal of Molecular Sciences, Год журнала: 2024, Номер 25(17), С. 9570 - 9570

Опубликована: Сен. 4, 2024

Several years ago, dozens of cases were described in patients with symptoms very similar to mucopolysaccharidosis (MPS). This new disease entity was as mucopolysaccharidosis-plus syndrome (MPSPS). The name the indicates that addition typical conventional MPS, develop other features such congenital heart defects and kidney hematopoietic system disorders. are highly advanced, usually do not survive past second year life. MPSPS is inherited an autosomal recessive manner caused by a homozygous-specific mutation gene encoding VPS33A protein. To date, it has been 41 patients. Patients exhibited excessive excretion glycosaminoglycans (GAGs) urine exceptionally high levels heparan sulfate plasma, but accumulation substrates decrease activity any lysosomal enzymes. Here, we discuss pathomechanisms MPSPS, comparing them those MPS. Moreover, asked question whether should be classified type MPS or separate disease, contrary ‘classical’ types, despite GAG accumulation, no enzymes responsible for degradation these compounds could detected MPSPS. molecular mechanism appearance suggested on basis results available literature.

Язык: Английский

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Consensus draft of the native mouse podocyte-ome

AJP Renal Physiology, Год журнала: 2022, Номер 323(2), С. F182 - F197

Опубликована: Июль 7, 2022

The podocyte is a key cell in maintaining renal filtration barrier integrity. Several recent studies have analyzed the genome and transcriptome at deep resolution. This avenue of "podocyte-ome" research was enabled by variety techniques, including 1) single-cell transcriptomics, 2) FACS with without genetically encoded markers, 3) proteomics. However, data across various omics techniques are currently not well integrated each other. Here, we aimed to establish common, simplified knowledge base for mouse podocyte-ome integrating bulk RNA sequencing, proteomics FACS-sorted podocytes, transcriptomics. Three publicly available datasets technique from different laboratories were bioinformatically visualized. Our approach only revealed conserved processes podocytes but also sheds light on benefits limitations used technologies. We identified that high expression glycan glycosylphosphatidylinositol anchor synthesis turnover, as retinol metabolism, relatively understudied features podocytes. In addition, actin-binding molecules organized podocyte-specific manner, evidenced differential compared other glomerular cells. compiled Web-based "PodIent" application illustrates dataset. enables user-driven exploratory analysis querying genes interest identity absolute relative quantification while linking functional annotation using keywords, Gene Ontology terms, gene set enrichments. consensus draft first step toward common molecular kidney cells.NEW & NOTEWORTHY Podocytes components affected diseases. present an integrated, robust definition proteomic, transcriptomic native created "PodIdent" app, novel promoting access presence specific proteins

Язык: Английский

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Synthesis and mechanism of biological action of morpholinyl-bearing arylsquaramides as small-molecule lysosomal pH modulators

RSC Advances, Год журнала: 2022, Номер 12(35), С. 22748 - 22759

Опубликована: Янв. 1, 2022

A family of small-molecule arylsquaramides were synthesized as transmembrane anion transporters for modulating lysosomal pH.

Язык: Английский

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GSK3β-dependent lysosome biogenesis: An effective pathway to mitigate renal fibrosis with LM49

Frontiers in Pharmacology, Год журнала: 2022, Номер 13

Опубликована: Сен. 26, 2022

Renal fibrosis is an incurable disorder characterised by imbalance of the extracellular matrix (ECM) favouring excess production over degradation. The identification actionable pathways and agents that promote ECM degradation to restore homeostasis may help mitigate renal fibrosis. In this study, we identified 5,2'-dibromo-2,4',5'-trihydroxydiphenylmethanone (LM49), a compound previously synthesised, as small-molecule inducer LM49 administration efficiently reduced deposition in tissue diabetic nephropathy rats transforming growth factor β-treated fibroblast cells. promoted cytosol-to-nucleus translocation transcription EB (TFEB) increase lysosome biogenesis, leading lysosome-based ECM. TFEB-mediated biogenesis was induced directly inhibiting activity glycogen synthase kinase 3β (GSK3β) rather than mammalian target rapamycin complex 1. inhibited GSK3β concentration-dependently via competing with ATP. Direct binding between confirmed bio-layer interferometry assay, cellular thermal shift drug affinity responsive stability. A molecular docking dynamic simulation revealed occupied ATP pocket GSK3β, which consistent assay. summary, enhances lysosomes. enhancement GSK3β-dependent rebalance be novel strategy counteract fibrosis, viable clinical candidate for treating disorder.

Язык: Английский

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Knockout of the neonatal Fc receptor alters immune complex trafficking and lysosomal function in cultured podocytes

PLoS ONE, Год журнала: 2023, Номер 18(4), С. e0284636 - e0284636

Опубликована: Апрель 18, 2023

Podocytes are key to preventing the filtration of serum proteins into urine. Recent evidence also suggests that in immune mediated kidney diseases, podocytes targets complexes (ICs). The mechanisms whereby handle and respond ICs remain unknown. neonatal Fc receptor (FcRn) is involved IgG handling required dendritic cells traffic lysosome for proteolytic degradation antigen presentation on MHC II. Here we examine role FcRn podocytes. We show knockout results decreased trafficking increases IC recycling endosomes. KO alters lysosomal distribution, decreases surface area cathepsin B expression activity. demonstrate signaling pathways cultured differ after treatment with alone versus podocyte proliferation both WT suppressed by treatment. Our findings suggest differentially modifies response ICs. Elucidating underlying may provide novel modulate disease progression.

Язык: Английский

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