Phosphatases

Mutations in the phosphatase and tensin homolog (PTEN) gene are associated with severe neurodevelopmental disorders. Loss of PTEN leads to hyperactivation of the mechanistic target of rapamycin (mTOR), which functions in two distinct protein complexes, mTORC1 and mTORC2. The downstream signaling mechanisms that contribute to PTEN mutant phenotypes are not well delineated. Here, we show that pluripotent stem cell-derived PTEN mutant human neurons, neural precursors, and cortical organoids recapitulate disease-relevant phenotypes, including hypertrophy, electrical hyperactivity, enhanced proliferation, and structural overgrowth...

Vascular calcification can be triggered by oxidative stress and inflammation. Although boron possesses antioxidant and anti-inflammatory properties, its effect on osteogenic differentiation of vascular smooth muscle cells (VSMCs) has yet to be examined. Therefore, we aimed to investigate the effect of boric acid (BA), the main form of boron in body fluids, on the osteogenic differentiation of VSMCs. Following the isolation of VSMCs, the effects of BA on cell proliferation were determined by MTT. The impact of various BA concentrations on the osteogenic differentiation of VSMCs was evaluated by Alizarin red S and alkaline phosphatase (ALP) stainings and the o-cresolphthalein complexone method...

Myosin phosphatase targeting subunit1 (MYPT1) is a critical subunit of myosin phosphatase (MP), which brings PP1Cδ phosphatase and its substrate together. We previously showed that MYPT1 depletion resulted in oblique chromatid segregation. Therefore, we hypothesized that MYPT1 may control microtubule-dependent motor activity. Dynein, a minus-end microtubule motor, is known to be involved in mitotic spindle assembly. We thus examined whether MYPT1 and dynein may interact. Proximity ligation assay and co-immunoprecipitation revealed that MYPT1 and dynein intermediate chain (DIC) were associated...

Along with an ever-deepening understanding of the catalytic principle of natural enzymes, the rational design of high-activity biomimetic nanozymes has become a hot topic in current research. Inspired by the active centers of natural enzymes consisting of catalytic sites and binding pockets, a Cu-doped CoS2 hollow nanocube (Cu/CoS2 HNCs) nanozyme integrating substitution defects and vacancies is developed through a defect engineering strategy. It is shown that the vacancies and substitution defects in the developed Cu/CoS2 HNC nanozymes serve as binding pockets and catalytic sites, respectively...

OBJECTIVE: To investigate whether visceral adipose tissue-derived serine protease inhibitor (vaspin) can alleviate the inhibitory effect of high-glucose (HG) culture on the proliferation and osteogenic differentiation of human periodontal ligament stem cells (PDLSCs) and to preliminarily explore the underlying mechanisms. BACKGROUND: High glucose produces damage to the regeneration of periodontal tissue of PDLSCs. The expression level of vaspin in periodontal tissue is high in periodontitis patients and effectively reduced after initial therapy of periodontal diseases...

Current cancer vaccines face challenges due to an immunosuppressive tumor microenvironment and their limited ability to produce an effective immune response. To address the above limitations, we develop a 3-(2-spiroadamantyl)-4-methoxy-4-(3-phosphoryloxy)-phenyl-1,2-dioxetane (alkaline phosphatase substrate) and XMD8-92 (extracellular signal-regulated kinase 5 inhibitor)-codelivered copper-tetrahydroxybenzoquinone (Cu-THBQ/AX) nanosized metal-organic framework to in situ-generate therapeutic vaccination. Once inside the early endosome, the alkaline phosphatase overexpressed in the tumor cells' membrane activates the in situ type I photodynamic effect of Cu-THBQ/AX for generating • O2 - , and the Cu-THBQ/AX catalyzes O2 and H2 O2 to • O2 - and • OH via semiquinone radical catalysis and Fenton-like reactions...

Selecting breed-worthy gilts as sow replacements is essential for continuity of pig production cycle. Though vitamin D3 (VD3) is known to enhance reproductive performance of multiparous sows, there is still a knowledge gap on its impact in developing gilts and primiparous sows. This study was aimed to quantify plasma 25-hydroxyvitamin D3 (25(OH)D3), serum alkaline phosphatase (ALP), and examine the reproductive performance of primiparous sows fed diets supplemented with regular VD3, and its 25(OH)D3 epimers...

BACKGROUND: Though the albumin-to-alkaline phosphatase ratio (AAPR) is used as a biomarker in various diseases, little is known about its effect on outcomes after peritoneal dialysis (PD). METHODS: This multicenter retrospective study comprised 357 incident PD patients stratified according to the AAPR. Propensity score matching (PSM) was performed to identify 85 patients for a well-matched comparison of all-cause and cardiovascular mortality. Using Cox regression, we performed univariate and multivariate analyses to investigate the prognostic value of the AAPR and established a Kaplan-Meier curve-predicted nomogram to estimate expected overall survival (OS)...

OBJECTIVES:  Dental pulp, a specialized mesenchymal tissue within teeth, is pivotal in dental health and tissue repair. Capsaicin, the primary pungent component of chili peppers, is known for its diverse pharmacological properties. While capsaicin's effects on various cell types have been studied, its impact on dental pulp cells remains relatively unexplored. This study investigated the influence of pure capsaicin extract on dental pulp cell behavior, focusing on cell viability, proliferation, migration, and alkaline phosphatase (ALP) activity...

BACKGROUND: Ossification of the posterior longitudinal ligament (OPLL), an emerging heterotopic ossification disease, causes spinal cord compression, resulting in motor and sensory dysfunction. The etiology of OPLL remains unclear but may involve integrin αVβ3 regulating the process of osteogenesis and angiogenesis. In this study, we focused on the role of integrin αVβ3 in OPLL and explored the underlying mechanism by which the c(RGDyk) peptide acts as a potent and selective integrin αVβ3 inhibitor to inhibit osteogenesis and angiogenesis in OPLL...

To explore the impacts of continuous Ganoderma lucidum cultivation on soil physicochemical factors, soil enzyme activity, and the metabolome of Ganoderma lucidum fruiting bodies, this study conducted two consecutive years of cultivation on the same plot of land. Soil physicochemical factors and enzyme activity were assessed, alongside non-targeted metabolomic analysis of the Ganoderma lucidum fruiting bodies under continuous cultivation. The findings unveiled that in the surface soil layer (0-15 cm), there was a declining trend in organic matter, ammonium nitrogen, available phosphorus, available potassium, pH, polyphenol oxidase, peroxidase, alkaline phosphatase, and sucrase, whereas nitrate nitrogen, electrical conductivity (EC), and salt content exhibited an upward trend...

Cilia and Wnt signaling have a complex relationship, wherein Wnt regulates cilia and, conversely, cilia may affect Wnt signaling. Recently, it was shown that Wnt receptors are present in flagella, primary cilia, and multicilia, where they transmit an intraciliary signal that is independent of β-catenin. Intraciliary Wnt signaling promotes ciliogenesis, affecting male fertility, adipogenesis, and mucociliary clearance. Wnt also stimulates the beating of motile cilia, highlighting that these nanomotors, too, are chemosensory...

Fumigants and fungicides are effective at controlling soil-borne pathogens but might also adversely affect soil beneficial microbes, such as soil phosphorus (P) solubilizing microbes, further altering nutrient cycling processes. Therefore, this study investigated the effects of the fumigant chloropicrin (CP) and the fungicide azoxystrobin (AZO) on soil microeukaryotes and P-cycling related soil bacteria through a greenhouse experiment. Soil microeukaryotic communities and bacterial communities containing two phosphomonoesterase encoding genes (phoC and phoD) were analysed using high-throughput sequencing methods...

Current therapeutic options for renal cell carcinoma (RCC) are very limited, which is largely due to inadequate comprehension of molecular pathological mechanisms as well as RCC's resistance to chemotherapy. Dual-specificity phosphatase 6 (DUSP6) has been associated with numerous human diseases. However, its role in RCC is not well understood. Here, we show that diminished DUSP6 expression is linked to RCC progression and unfavorable prognosis. Mechanistically, DUSP6 serves as a tumor suppressor in RCC by intervening the TAF10 and BSCL2 via the ERK-AKT pathway...

Dimethyl nitrosamine (DMN), a potent hepatotoxin, exerts carcinogenic effects and induces hepatic necrosis in experimental animals via CYP2E1 metabolic activation, and generation of reactive oxygen species (ROS). Protocatechuic acid (PCA), a plant-based simple phenolic compound and potent antioxidant, has been shown to affect the development of neoplasia in the rat liver and inhibit the initiation or progression phases of most cancers. In this study, the modulatory effects of PCA on DMN-induced hepatotoxicity, oxidative stress, inflammation, and selected phase I xenobiotic metabolizing enzymes were investigated in male Wistar rats...

Hepatocellular carcinoma (HCC) is the most common primary liver cancer worldwide and no pharmacological treatment is available that can achieve complete remission of HCC. Phospholysine phosphohistidine inorganic pyrophosphate phosphatase (LHPP) is a recently identified HCC tumor suppressor gene which plays an important role in the development of HCC and its inactivation and reactivation has been shown to result in respectively HCC tumorigenesis and suppression. Small activating RNAs (saRNAs) have been used to achieve targeted activation of therapeutic genes for the restoration of their encoded protein through the RNAa mechanism...

The Rab small GTPases are characterized by the distinct intracellular localization and modulate various endocytic, transcytic and exocytic transport pathways. Rab proteins function as scaffolds that connect signaling pathways and intracellular membrane trafficking processes through the recruitment of effectors, such as tethering factors, phosphatases, motors and kinases. In different cancers, Rabs play as either an onco-protein or a tumor suppressor role, highly dependending on the context. The molecular mechanistic research has revealed that Rab proteins are involved in cancer progression through influences on migration, invasion, metabolism, exosome secretion, autophagy, and drug resistance of cancer cells...

The RAF kinases are required for signal transduction through the RAS-RAF-MEK-ERK pathway, and their activity is frequently up-regulated in human cancer and the RASopathy developmental syndromes. Due to their complex activation process, developing drugs that effectively target RAF function has been a challenging endeavor, highlighting the need for a more detailed understanding of RAF regulation. This review will focus on recent structural and biochemical studies that have provided 'snapshots' into the RAF regulatory cycle, revealing structures of the autoinhibited BRAF monomer, active BRAF and CRAF homodimers, as well as HSP90/CDC37 chaperone complexes containing CRAF or BRAFV600E...

INTRODUCTION: The objective of the current study was to investigate the association between lower body bone fractures occurring during maintenance hemodialysis and prognosis. METHODS: This study included 151 hemodialysis patients at the dialysis center of our hospital as of December 2017, and data were systematically gathered from medical records over a period of 5 years, concluding in December 2022. RESULTS: Fourteen patients, 3.0 per 100 person-years, in 151 hemodialysis patients suffered from lower body bone fractures...

Poor cellular permeability greatly hampers the utilization of anionic Ir(III) complexes, though efficiently emissive and remarkably stable, in cell-based diagnosis. To overcome this barrier, we present the development of an alkaline phosphatase (ALP)-responsive, anionic, and aggregation-induced emission (AIE)-active Ir(III) complex (Ir1) for specific recognition of osteosarcoma cells. Containing phosphate moieties, Ir1 exhibits a net -1 charge, enabling charge repulsion from the cell membrane and resulting in low cellular uptake and good biocompatibility in normal osteoblast cells...