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1.
Acta Neuropathol Commun ; 12(1): 84, 2024 May 31.
Article En | MEDLINE | ID: mdl-38822421

Alpha-synuclein (αsyn) is an intrinsically disordered protein that aggregates in the brain in several neurodegenerative diseases collectively called synucleinopathies. Phosphorylation of αsyn at serine 129 (PSER129) was considered rare in the healthy human brain but is enriched in pathological αsyn aggregates and is used as a specific marker for disease inclusions. However, recent observations challenge this assumption by demonstrating that PSER129 results from neuronal activity and can be readily detected in the non-diseased mammalian brain. Here, we investigated experimental conditions under which two distinct PSER129 pools, namely endogenous-PSER129 and aggregated-PSER129, could be detected and differentiated in the mammalian brain. Results showed that in the wild-type (WT) mouse brain, perfusion fixation conditions greatly influenced the detection of endogenous-PSER129, with endogenous-PSER129 being nearly undetectable after delayed perfusion fixation (30-min and 1-h postmortem interval). Exposure to anesthetics (e.g., Ketamine or xylazine) before perfusion did not significantly influence endogenous-PSER129 detection or levels. In situ, non-specific phosphatase calf alkaline phosphatase (CIAP) selectively dephosphorylated endogenous-PSER129 while αsyn preformed fibril (PFF)-seeded aggregates and genuine disease aggregates (Lewy pathology and Papp-Lantos bodies in Parkinson's disease and multiple systems atrophy brain, respectively) were resistant to CIAP-mediated dephosphorylation. The phosphatase resistance of aggregates was abolished by sample denaturation, and CIAP-resistant PSER129 was closely associated with proteinase K (PK)-resistant αsyn (i.e., a marker of aggregation). CIAP pretreatment allowed for highly specific detection of seeded αsyn aggregates in a mouse model that accumulates non-aggregated-PSER129. We conclude that αsyn aggregates are impervious to phosphatases, and CIAP pretreatment increases detection specificity for aggregated-PSER129, particularly in well-preserved biological samples (e.g., perfusion fixed or flash-frozen mammalian tissues) where there is a high probability of interference from endogenous-PSER129. Our findings have important implications for the mechanism of PSER129-accumulation in the synucleinopathy brain and provide a simple experimental method to differentiate endogenous-from aggregated PSER129.


Brain , Mice, Inbred C57BL , alpha-Synuclein , Animals , Humans , Male , Mice , Alkaline Phosphatase/metabolism , alpha-Synuclein/metabolism , Brain/metabolism , Brain/pathology , Mice, Transgenic , Phosphoric Monoester Hydrolases/metabolism , Phosphorylation , Protein Aggregates/physiology , Protein Aggregation, Pathological/metabolism , Protein Aggregation, Pathological/pathology , Synucleinopathies/metabolism , Synucleinopathies/pathology
3.
Food Res Int ; 186: 114356, 2024 Jun.
Article En | MEDLINE | ID: mdl-38729722

The quality of Pacific oyster (Crassostrea gigas) can be affected by many factors during depuration, in which temperature is the major element. In this study, we aim to determine the quality and plasmalogen changes in C. gigas depurated at different temperatures. The quality was significantly affected by temperature, represented by varying survival rate, glycogen content, total antioxidant capacity, alkaline phosphatase activity between control and stressed groups. Targeted MS analysis demonstrated that plasmalogen profile was significantly changed during depuration with PUFA-containing plasmalogen species being most affected by temperature. Proteomics analysis and gene expression assay further verified that plasmalogen metabolism is regulated by temperature, specifically, the plasmalogen synthesis enzyme EPT1 was significantly downregulated by high temperature and four plasmalogen-related genes (GPDH, PEDS, Pex11, and PLD1) were transcriptionally regulated. The positive correlations between the plasmalogen level and quality characteristics suggested plasmalogen could be regarded as a quality indicator of oysters during depuration.


Crassostrea , Plasmalogens , Temperature , Animals , Plasmalogens/metabolism , Plasmalogens/analysis , Crassostrea/genetics , Crassostrea/metabolism , Shellfish/analysis , Proteomics/methods , Antioxidants/metabolism , Antioxidants/analysis , Alkaline Phosphatase/metabolism , Food Quality
4.
Nan Fang Yi Ke Da Xue Xue Bao ; 44(4): 697-705, 2024 Apr 20.
Article Zh | MEDLINE | ID: mdl-38708503

OBJECTIVE: To explore the role of zinc finger protein 36(ZFP36) in regulating osteogenic differentiation of bone marrow-derived mesenchymal stem cells (BMSCs) and preosteoblasts. METHODS: ZFP36 expression was observed in primary mouse BMSCs and mouse preosteoblasts (MC3T3-E1 cells) during induced osteogenic differentiation. Zfp36-deficient cell models were constructed in the two cells using RNA interference technique and the changes in differentiation capacities of the transfected cells into osteoblasts were observed. Transcriptome sequencing was used to investigate the potential mechanisms of ZFP36 for regulating osteoblast differentiation of the two cells. U0126, a ERK/MAPK signal suppressor, was used to verify the regulatory mechanism of Zfp36 in osteogenic differentiation of Zfp36-deficient cells. RESULTS: During the 14-day induction of osteogenic differentiation, both mouse BMSCs and MC3T3-E1 cells exhibited increased expression of ZFP36, and its mRNA expression reached the peak level on Day 7(P < 0.0001). The Zfp36-deficient cell models showed reduced intensity of alkaline phosphatase (ALP) staining and alizarin red staining with significantly lowered expressions of the osteogenic marker genes including Alpl, Sp7, Bglap and Ibsp (P < 0.01). Transcriptome sequencing verified the reduction of bone mineralization-related gene expressions in Zfp36-deficient cells and indicated the involvement of ERK signaling in the potential regulatory mechanism of Zfp36. Immunoblotting showed that pERK protein expression increased significantly in Zfp36-deficient cells compared with the control cells. In Zfp36-deficient MC3T3-E1 cells, inhibition of activated ERK/MAPK signaling with U0126 resulted in obviously enhanced ALP staining and significantly increased expressions of osteoblast differentiation markers Runx2 and Bglap (P < 0.05). CONCLUSIONS: ZFP36 is involved in the regulation of osteoblast differentiation of mouse BMSCs and preosteoblasts, and ZFP36 deficiency causes inhibition of osteoblast differentiation of the cells by activating the ERK/MAPK signaling pathway.


Cell Differentiation , MAP Kinase Signaling System , Mesenchymal Stem Cells , Osteoblasts , Osteogenesis , Animals , Mice , Alkaline Phosphatase/metabolism , Bone Marrow Cells/cytology , Bone Marrow Cells/metabolism , Butyrate Response Factor 1/metabolism , Butyrate Response Factor 1/genetics , Mesenchymal Stem Cells/cytology , Mesenchymal Stem Cells/metabolism , Osteoblasts/cytology , Osteoblasts/metabolism
5.
Proc Natl Acad Sci U S A ; 121(20): e2312892121, 2024 May 14.
Article En | MEDLINE | ID: mdl-38713622

Marine picocyanobacteria of the genera Prochlorococcus and Synechococcus, the two most abundant phototrophs on Earth, thrive in oligotrophic oceanic regions. While it is well known that specific lineages are exquisitely adapted to prevailing in situ light and temperature regimes, much less is known of the molecular machinery required to facilitate occupancy of these low-nutrient environments. Here, we describe a hitherto unknown alkaline phosphatase, Psip1, that has a substantially higher affinity for phosphomonoesters than other well-known phosphatases like PhoA, PhoX, or PhoD and is restricted to clade III Synechococcus and a subset of high light I-adapted Prochlorococcus strains, suggesting niche specificity. We demonstrate that Psip1 has undergone convergent evolution with PhoX, requiring both iron and calcium for activity and likely possessing identical key residues around the active site, despite generally very low sequence homology. Interrogation of metagenomes and transcriptomes from TARA oceans and an Atlantic Meridional transect shows that psip1 is abundant and highly expressed in picocyanobacterial populations from the Mediterranean Sea and north Atlantic gyre, regions well recognized to be phosphorus (P)-deplete. Together, this identifies psip1 as an important oligotrophy-specific gene for P recycling in these organisms. Furthermore, psip1 is not restricted to picocyanobacteria and is abundant and highly transcribed in some α-proteobacteria and eukaryotic algae, suggesting that such a high-affinity phosphatase is important across the microbial taxonomic world to occupy low-P environments.


Alkaline Phosphatase , Prochlorococcus , Alkaline Phosphatase/metabolism , Alkaline Phosphatase/genetics , Prochlorococcus/genetics , Prochlorococcus/metabolism , Phosphorus/metabolism , Bacterial Proteins/metabolism , Bacterial Proteins/genetics , Synechococcus/genetics , Synechococcus/metabolism , Phylogeny , Seawater/microbiology
6.
Acta Biomater ; 181: 415-424, 2024 Jun.
Article En | MEDLINE | ID: mdl-38704115

Host defense peptide-mimicking cationic oncolytic polymers have attracted increasing attention for cancer treatment in recent years. However, polymers with large amounts of positive charge may cause rapid clearance and severe off-target toxicity. To facilitate in vivo application, an alkaline phosphatase (ALP)-responsive oncolytic polypeptide precursor (C12-PLL/PA) has been reported in this work. C12-PLL/PA could be hydrolyzed into the active form of the oncolytic polypeptide (C12-PLL) by the extracellular alkaline phosphatase within solid tumors, thereby resulting in the conversion of the negative charge to positive charge and restoring its membrane-lytic activity. Detailed mechanistic studies showed that C12-PLL/PA could effectively destroy cancer cell membranes and subsequently result in rapid necrosis of cancer cells. More importantly, C12-PLL/PA significantly inhibited the tumor growth in the 4T1 orthotopic breast tumor model with negligible side effects. In summary, these findings demonstrated that the shielding of the amino groups with phosphate groups represents a secure and effective strategy to develop cationic oncolytic polypeptide, which represents a valuable reference for the design of enzyme-activated oncolytic polymers. STATEMENT OF SIGNIFICANCE: Recently, there has been a growing interest in fabricating host defense peptide-mimicking cationic oncolytic polymers for cancer therapy. However, there remain concerns about the tumor selectivity and off-target toxicity of these cationic polymers. In this study, an alkaline phosphatase-responsive oncolytic polypeptide precursor (C12-PLL/PA) has been developed to selectively target cancer cells while sparing normal cells. Mechanistic investigations demonstrated that C12-PLL/PA effectively disrupted cancer cell membranes, leading to rapid necrosis. Both in vitro and in vivo experiments showed promising anticancer activity and reliable safety of C12-PLL/PA. The findings suggest that this synthetic enzyme-responsive polypeptide holds potential as a tumor-specific oncolytic polymer, paving the way for future applications in cancer therapy.


Alkaline Phosphatase , Peptides , Animals , Alkaline Phosphatase/metabolism , Peptides/chemistry , Peptides/pharmacology , Cell Line, Tumor , Female , Humans , Mice , Mice, Inbred BALB C , Antineoplastic Agents/pharmacology , Antineoplastic Agents/therapeutic use
7.
Int J Mol Sci ; 25(10)2024 May 07.
Article En | MEDLINE | ID: mdl-38791142

Placenta Accreta Spectrum (PAS) is a life-threatening condition in which placental trophoblastic cells abnormally invade the uterus, often up to the uterine serosa and, in extreme cases, tissues beyond the uterine wall. Currently, there is no clinical assay for the non-invasive detection of PAS, and only ultrasound and MRI can be used for its diagnosis. Considering the subjectivity of visual assessment, the detection of PAS necessitates a high degree of expertise and, in some instances, can lead to its misdiagnosis. In clinical practice, up to 50% of pregnancies with PAS remain undiagnosed until delivery, and it is associated with increased risk of morbidity/mortality. Although many studies have evaluated the potential of fetal biomarkers circulating in maternal blood, very few studies have evaluated the potential of circulating placental extracellular vesicles (EVs) and their miRNA contents for molecular detection of PAS. Thus, to purify placental EVs from maternal blood, we customized our robust ultra-sensitive immuno-purification assay, termed EV-CATCHER, with a monoclonal antibody targeting the membrane Placental Alkaline Phosphatase (PLAP) protein, which is unique to the placenta and present on the surface of placental EVs. Then, as a pilot evaluation, we compared the miRNA expression profiles of placental EVs purified from the maternal plasma of women diagnosed with placenta previa (controls, n = 16); placenta lying low in uterus but not invasive) to those of placental EVs purified from the plasma of women with placenta percreta (cases, n = 16), PAS with the highest level of invasiveness. Our analyses reveal that miRNA profiling of PLAP+ EVs purified from maternal plasma identified 40 differentially expressed miRNAs when comparing these two placental pathologies. Preliminary miRNA pathway enrichment and gene ontology analysis of the top 14 upregulated and top nine downregulated miRNAs in PLAP+ EVs, purified from the plasma of women diagnosed with placenta percreta versus those diagnosed with placenta previa, suggests a potential role in control of cellular invasion and motility that will require further investigation.


Extracellular Vesicles , Placenta Accreta , Placenta , Humans , Female , Extracellular Vesicles/metabolism , Pregnancy , Placenta/metabolism , Placenta Accreta/diagnosis , Placenta Accreta/blood , Biomarkers/blood , Adult , MicroRNAs/blood , MicroRNAs/genetics , MicroRNAs/metabolism , Placenta Previa/diagnosis , Placenta Previa/blood , Alkaline Phosphatase/metabolism , Alkaline Phosphatase/blood , Isoenzymes , GPI-Linked Proteins
8.
Mikrochim Acta ; 191(6): 316, 2024 05 10.
Article En | MEDLINE | ID: mdl-38724679

An ultra-sensitive photoelectrochemical (PEC) sensor based on perovskite composite was developed for the determination of alkaline phosphatase (ALP) in human serum. In contrast to CsPbBr3 or Y6 that generated anodic current, the heterojunction of CsPbBr3/Y6 promoted photocarriers to separate and generated cathodic photocurrent. Ascorbic acid (AA) was produced by ALP hydrolyzing L-ascorbic acid 2-phosphate trisodium salt (AAP), which can combine with the holes on the photoelectrode surface, accelerating the transmission of photogenerated carriers, leading to enhanced photocurrent intensity. Thus, the enhancement of PEC current was linked to ALP activity. The PEC sensor exhibits good sensitivity for detection of ALP owing to the unique photoelectric properties of the CsPbBr3/Y6 heterojunction. The detection limit of the sensor was 0.012 U·L-1 with a linear dynamic range of 0.02-2000 U·L-1. Therefore, this PEC sensing platform shows great potential for the development of different PEC sensors.


Alkaline Phosphatase , Ascorbic Acid , Electrochemical Techniques , Electrodes , Limit of Detection , Oxides , Photochemical Processes , Titanium , Alkaline Phosphatase/chemistry , Alkaline Phosphatase/blood , Alkaline Phosphatase/metabolism , Humans , Electrochemical Techniques/methods , Electrochemical Techniques/instrumentation , Ascorbic Acid/chemistry , Ascorbic Acid/blood , Ascorbic Acid/analogs & derivatives , Titanium/chemistry , Oxides/chemistry , Calcium Compounds/chemistry , Biosensing Techniques/methods
9.
Dalton Trans ; 53(20): 8633-8641, 2024 May 21.
Article En | MEDLINE | ID: mdl-38695060

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. Upon ALP-mediated hydrolysis of phosphate groups, the resulting dephosphorylated product, Ir2, demonstrates a positive charge and increased lipophilicity, promoting cellular uptake and activating its AIE properties for specific recognition of osteosarcoma cells that express elevated levels of ALP. This study elucidates the role of ALP as an ideal trigger for enhancing the cellular permeability of phosphate ester-containing Ir(III) complexes, thus expanding the potential of anionic Ir(III) complexes for biomedical applications.


Alkaline Phosphatase , Anions , Coordination Complexes , Iridium , Osteosarcoma , Iridium/chemistry , Humans , Osteosarcoma/pathology , Osteosarcoma/metabolism , Alkaline Phosphatase/metabolism , Coordination Complexes/chemistry , Coordination Complexes/chemical synthesis , Coordination Complexes/pharmacology , Anions/chemistry , Cell Line, Tumor
10.
Sci Rep ; 14(1): 12536, 2024 05 31.
Article En | MEDLINE | ID: mdl-38822011

This study investigated whether Ki-Patlak derived from a shortened scan time for dynamic 18F-NaF PET/CT in chronic kidney disease (CKD) patients undergoing hemodialysis can provide predictive accuracy comparable to that obtained from a longer scan. Twenty-seven patients on chronic hemodialysis, involving a total of 42 scans between December 2021 and August 2023 were recruited. Dynamic 18F-NaF PET/CT scans, lasting 60-90 min, were immediately acquired post-injection, covering the mid-twelfth thoracic vertebra to the pelvis region. Ki-Patlak analysis was performed on bone time-activity curves at 15, 30, 45, 60, and 90 min in the lumbar spine (L1-L4) and both anterior iliac crests. Spearman's rank correlation (rs) and interclass correlation coefficient were used to assess the correlation and agreement of Ki-Patlak between shortened and standard scan times. Bone-specific alkaline phosphatase (BsAP) and tartrate-resistant acid phosphatase isoform 5b (TRAP5b) were tested for their correlation with individual Ki-Patlak. Strong correlations and good agreement were observed between Ki-Patlak values from shortened 30-min scans and longer 60-90-min scans in both lumbar spine (rs = 0.858, p < 0.001) and anterior iliac crest regions (rs = 0.850, p < 0.001). The correlation between BsAP and Ki-Patlak in the anterior iliac crests was weak and statistically insignificant. This finding suggests that a proposed shortened dynamic 18F-NaF PET/CT scan is effective in assessing bone metabolic flux in CKD patients undergoing hemodialysis, offering a non-invasive alternative approach for bone turnover prediction.


Positron Emission Tomography Computed Tomography , Renal Dialysis , Renal Insufficiency, Chronic , Sodium Fluoride , Humans , Positron Emission Tomography Computed Tomography/methods , Male , Female , Middle Aged , Renal Insufficiency, Chronic/therapy , Renal Insufficiency, Chronic/metabolism , Renal Insufficiency, Chronic/complications , Renal Insufficiency, Chronic/diagnostic imaging , Aged , Fluorine Radioisotopes , Bone Remodeling , Lumbar Vertebrae/diagnostic imaging , Lumbar Vertebrae/metabolism , Adult , Alkaline Phosphatase/metabolism , Tartrate-Resistant Acid Phosphatase/metabolism , Ilium/diagnostic imaging , Ilium/metabolism
11.
Clin Exp Dent Res ; 10(3): e885, 2024 Jun.
Article En | MEDLINE | ID: mdl-38798048

OBJECTIVES: Calcifying nanoparticles (CNPs), referred to as nanobacteria (NB), are recognized to be associated with ectopic calcification. This study aims to isolate and culture CNPs from the dental plaque of patients with periodontal disease and investigate their possible role in unravelling the aetiology of periodontal disease. MATERIAL AND METHODS: Supragingival and subgingival plaques were sampled from 30 periodontitis patients for CNPs isolation and culture. Alkaline phosphatase (ALP) content changes were tracked over time. Positive samples underwent thorough morphological identification via hematoxylin and eosin (HE) staining, Alizarin red S (ARS), and transmission electron microscopy (TEM). The chemical composition of CNPs analysis involved calcium (Ca) and phosphorus (P) content determination, Fourier transform infrared spectroscopy (FTIR), and X-ray diffraction (XRD). RESULTS: The subgingival plaque dental group exhibited a higher CNPs isolation rate at 36.67% (11/30) compared to the supragingival dental plaque group at 66.67% (20/30). ALP activity varied among the positive, negative and control groups. Morphological observation characterized the CNPs as round, oval, and ellipsoid particles with Ca deposits. Chemical analysis revealed the Ca/P ratio was 0.6753. Hydroxyl, methyl, carbonate, phosphate, hydrogen phosphate, and dihydrogen phosphate were detected by FTIR; the main chemical components detected by XRD were hydroxyapatite and tricalcium phosphate. CONCLUSION: CNPs were found in periodontitis-related dental plaque and exhibited the potential to develop calcified structures resembling dental calculus. However, the potential involvement of ALP in CNPs formation requires deeper exploration, as does the precise nature of its role and the interrelation with periodontitis demand a further comprehensive investigation.


Alkaline Phosphatase , Calcifying Nanoparticles , Dental Plaque , X-Ray Diffraction , Humans , Calcifying Nanoparticles/metabolism , Dental Plaque/microbiology , Dental Plaque/chemistry , Spectroscopy, Fourier Transform Infrared/methods , Alkaline Phosphatase/metabolism , Phosphorus/analysis , Phosphorus/metabolism , Periodontitis/microbiology , Periodontitis/pathology , Microscopy, Electron, Transmission , Female , Adult , Calcium/metabolism , Calcium/analysis , Male , Middle Aged
12.
Mikrochim Acta ; 191(6): 341, 2024 05 25.
Article En | MEDLINE | ID: mdl-38795199

The construction of gating system in artificial channels is a cutting-edge research direction in understanding biological process and application sensing. Here, by mimicking the gating system, we report a device that easily synthesized single-glass micropipettes functionalized by three-dimensional (3D) DNA network, which triggers the gating mechanism for the detection of biomolecules. Based on this strategy, the gating mechanism shows that single-glass micropipette assembled 3D DNA network is in the "OFF" state, and after collapsing in the presence of ATP, they are in the "ON" state, at which point they exhibit asymmetric response times. In the "ON" process of the gating mechanism, the ascorbic acid phosphate (AAP) can be encapsulated by a 3D DNA network and released in the presence of adenosine triphosphate (ATP), which initiates a catalyzed cascade reaction under the influence of alkaline phosphatase (ALP). Ultimately, the detection of ALP can be responded to form the fluorescence signal generated by terephthalic acid that has captured hydroxyl radicals, which has a detection range of 0-250 mU/mL and a limit of detection of 50 mU/mL. This work provides a brand-new way and application direction for research of gating mechanism.


Adenosine Triphosphate , Alkaline Phosphatase , DNA , Adenosine Triphosphate/analysis , Adenosine Triphosphate/chemistry , Adenosine Triphosphate/metabolism , Alkaline Phosphatase/metabolism , Alkaline Phosphatase/chemistry , DNA/chemistry , Glass/chemistry , Biosensing Techniques/methods , Limit of Detection , Ascorbic Acid/chemistry , Ascorbic Acid/analogs & derivatives
13.
Sci Rep ; 14(1): 10227, 2024 05 03.
Article En | MEDLINE | ID: mdl-38702443

Hydrolyzed egg yolk peptide (YPEP) was shown to increase bone mineral density in ovariectomized rats. However, the underlying mechanism of YPEP on osteoporosis has not been explored. Recent studies have shown that Wnt/ß-catenin signaling pathway and gut microbiota may be involved in the regulation of bone metabolism and the progression of osteoporosis. The present study aimed to explore the preventive effect of the YPEP supplementation on osteoporosis in ovariectomized (OVX) rats and to verify whether YPEP can improve osteoporosis by regulating Wnt/ß-catenin signaling pathway and gut microbiota. The experiment included five groups: sham surgery group (SHAM), ovariectomy group (OVX), 17-ß estradiol group (E2: 25 µg /kg/d 17ß-estradiol), OVX with low-dose YPEP group (LYPEP: 10 mg /kg/d YPEP) and OVX with high-dose YPEP group (HYPEP: 40 mg /kg/d YPEP). In this study, all the bone samples used were femurs. Micro-CT analysis revealed improvements in both bone mineral density (BMD) and microstructure by YPEP treatment. The three-point mechanical bending test indicated an enhancement in the biomechanical properties of the YPEP groups. The serum levels of bone alkaline phosphatase (BALP), bone gla protein (BGP), calcium (Ca), and phosphorus (P) were markedly higher in the YPEP groups than in the OVX group. The LYPEP group had markedly lower levels of alkaline phosphatase (ALP), tartrate-resistant acid phosphatase (TRAP) and C-terminal telopeptide of type I collagen (CTX-I) than the OVX group. The YPEP groups had significantly higher protein levels of the Wnt3a, ß-catenin, LRP5, RUNX2 and OPG of the Wnt/ß-catenin signaling pathway compared with the OVX group. Compared to the OVX group, the ratio of OPG/RANKL was markedly higher in the LYPEP group. At the genus level, there was a significantly increase in relative abundance of Lachnospiraceae_NK4A136_group and a decrease in Escherichia_Shigella in YPEP groups, compared with the OVX group. However, in the correlation analysis, there was no correlation between these two bacteria and bone metabolism and microstructure indexes. These findings demonstrate that YPEP has the potential to improve osteoporosis, and the mechanism may be associated with its modulating effect on Wnt/ß-catenin signaling pathway.


Bone Density , Osteoporosis , Ovariectomy , Wnt Signaling Pathway , Animals , Female , Rats , Alkaline Phosphatase/metabolism , beta Catenin/metabolism , Bone Density/drug effects , Egg Proteins/pharmacology , Egg Proteins/metabolism , Egg Yolk/chemistry , Egg Yolk/metabolism , Femur/drug effects , Femur/metabolism , Low Density Lipoprotein Receptor-Related Protein-5/metabolism , Osteoporosis/prevention & control , Osteoporosis/metabolism , Peptides/pharmacology , Rats, Sprague-Dawley , Wnt Signaling Pathway/drug effects , X-Ray Microtomography
14.
Chemosphere ; 359: 142307, 2024 Jul.
Article En | MEDLINE | ID: mdl-38734252

Agrochemicals play a vital role in protecting crops and enhancing agricultural production by reducing threats from pests, pathogens and weeds. The toxicological status of honey bees can be influenced by a number of factors, including pesticides. While extensive research has focused on the lethal and sublethal effects of insecticides on individual bees and colonies, it is important to recognise that fungicides and herbicides can also affect bees' health. Unfortunately, in the field, honey bees are exposed to mixtures of compounds rather than single substances. This study aimed to evaluate the effects of a commercial fungicide and a commercial herbicide, both individually and in combination, on honey bees. Mortality assays, biomarkers and learning and memory tests were performed, and the results were integrated to assess the toxicological status of honey bees. Neurotoxicity (acetylcholinesterase and carboxylesterase activities), detoxification and metabolic processes (glutathione S-transferase and alkaline phosphatase activities), immune system function (lysozyme activity and haemocytes count) and genotoxicity biomarkers (Nuclear Abnormalities assay) were assessed. The fungicide Sakura® was found to activate detoxification enzymes and affect alkaline phosphatase activity. The herbicide Elegant 2FD and the combination of both pesticides showed neurotoxic effects and induced detoxification processes. Exposure to the herbicide/fungicide mixture impaired learning and memory in honey bees. This study represents a significant advance in understanding the toxicological effects of commonly used commercial pesticides in agriculture and contributes to the development of effective strategies to mitigate their adverse effects on non-target insects.


Biomarkers , Fungicides, Industrial , Herbicides , Animals , Bees/drug effects , Bees/physiology , Fungicides, Industrial/toxicity , Herbicides/toxicity , Biomarkers/metabolism , Acetylcholinesterase/metabolism , Cognition/drug effects , Alkaline Phosphatase/metabolism , Glutathione Transferase/metabolism
15.
Acta Biochim Pol ; 71: 12433, 2024.
Article En | MEDLINE | ID: mdl-38721304

The study aimed to determine the osteointegration markers after dental implantation and evaluate their predictive value. The study was performed on 60 practically healthy persons who needed teeth rehabilitation using dental implants. The conical-shaped implants (CI) and hexagonal implants (HI) were used. The content of Osteopontin (OPN), Osteocalcin (OC), Alkaline Phosphatase (ALP), Osteoprotegerin (OPG), and nitric oxide (NO) was determined in patients' gingival crevicular fluid (GCF) and peri-implant sulcular fluid (PISF), collected 1, 3, and 6 months after implantation. During the 3-6 months of observation level of OPN increased in patients with CIs (<50 years > 50 years) and HIs (<50 years) (CI: <50 years F = 36.457, p < 0.001; >50 years F = 30.104, p < 0.001; HI < 50 years F = 2.246, p < 0.001), ALP increased in patients with CIs (<50 years: F = 19.58, p < 0.001; >50 years: F = 12.01; p = 0.001) and HIs (<50 years) (F = 18.51, p < 0.001), OC increased in patients <50 years (CI: F = 33.72, p < 0.001; HI: F = 55.57, p < 0.001), but in patients >50 years - on the 3 days month (CI: F = 18.82, p < 0.001; HI: F = 26.26, p < 0.001), but sharply decreased at the end of sixth month. OPG increased during 1-3 months of the observation in patients <50 years (CI: F = 4.63, p = 0.037; HI: F = 2.8927, p = 0.046), but at the end of the sixth month returned to the initial level; NO content in PISF increased in patients with CI (>50 years) during 1-6 months of the observation (F = 27.657, p < 0.001). During the post-implantation period, age-related differences in osteointegration were observed. Patients <50 years old had relatively high levels of OPN, ALP, OC, and OPG in PISF, resulting in less alveolar bone destruction around dental implants and more intensive osteointegration. These indicators may be used as biological markers for monitoring implant healing. The process of osseointegration was more intense in CIs due to their comparatively high mechanical loading.


Alkaline Phosphatase , Biomarkers , Dental Implants , Gingival Crevicular Fluid , Osseointegration , Osteocalcin , Osteopontin , Osteoprotegerin , Humans , Middle Aged , Biomarkers/metabolism , Female , Male , Osteoprotegerin/metabolism , Gingival Crevicular Fluid/metabolism , Alkaline Phosphatase/metabolism , Osteocalcin/metabolism , Adult , Osteopontin/metabolism , Prognosis , Nitric Oxide/metabolism , Dental Implantation/methods , Time Factors
16.
Chemosphere ; 359: 142288, 2024 Jul.
Article En | MEDLINE | ID: mdl-38750729

Helicoverpa armigera, a ubiquitous polyphagous pest, poses a significant threat to global agriculture, causing substantial economic losses and demonstrating resistance to synthetic pesticides. This study investigates the potential of emamectin benzoate (EMB), an avermectin derivative, as an effective control agent against H. armigera. The larvae of the NBII-MP-NOC-01 strain of H. armigera were reared on an artificial diet. The impact of dietary EMB was examined on four midgut enzymes; alanine aminotransferase (ALT), aspartate aminotransferase (AST), acid phosphatase (ACP), and alkaline phosphatase (ALP). Results showed a dose-dependent and time-dependent reduction in ALT and AST activity, while an initial increase and subsequent decline in ACP and ALP activity at higher EMB concentrations. Computational modelling of enzyme structures and molecular docking studies revealed differential binding of EMB with the midgut enzymes. The strongest interaction was observed between EMB and ALT residues, contrasting with weakest interactions observed with AST. The study also showed that decreased activity of transaminases in H. armigera caused by EMB may be because of stability-activity trade-off, while in phosphatases reverse may be the case. This research provides crucial insights into the biochemical responses and the intricate insecticide-enzyme interactions in H. armigera caused by EMB exposure. This study lays the foundation for further research aimed at developing environmentally friendly approaches for managing H. armigera, addressing the challenges associated with conventional pesticides.


Acid Phosphatase , Alanine Transaminase , Alkaline Phosphatase , Aspartate Aminotransferases , Insecticides , Ivermectin , Larva , Molecular Docking Simulation , Moths , Animals , Ivermectin/analogs & derivatives , Ivermectin/toxicity , Larva/drug effects , Moths/drug effects , Insecticides/toxicity , Insecticides/chemistry , Insecticides/metabolism , Alkaline Phosphatase/metabolism , Acid Phosphatase/metabolism , Alanine Transaminase/metabolism , Aspartate Aminotransferases/metabolism , Helicoverpa armigera
17.
Hua Xi Kou Qiang Yi Xue Za Zhi ; 42(2): 172-180, 2024 Apr 01.
Article En, Zh | MEDLINE | ID: mdl-38597077

OBJECTIVES: The effect of TiO2 nanotube morphology on the differentiation potency of senescent periodontal ligament stem cells was investigated. METHODS: Two types of titanium sheets with TiO2 nanotube morphology (20V-NT and 70V-NT) were prepared via anodic oxidation at 20 and 70 V separately, and their surface morphology was observed. Young periodontal ligament stem cells were cultivated in an osteogenic induction medium, and the most effective surface morphology in promoting osteogenic differentiation was selected. RO3306 and Nutlin-3a were used to induce the aging of young periodontal ligament stem cells, and senescent periodontal ligament stem cells were obtained. The osteogenic differentiation of senescent periodontal ligament stem cells was induced, and the effect of surface morphology on osteogenic differentiation was observed. RESULTS: Nanotube morphology was achieved on the surfaces of titanium sheets through anodic oxidation, and the diameters of the nanotubes increased with voltage. A significant difference in the effect of nanotube morphology was found among nanotubes with different diameters in the young periodontal ligament stem cells. The surface nanotube morphology of 20V-NT had a more significant effect that promoted osteogenic differentiation. Compared with a smooth titanium sheet, the surface nanotube morphology of 20V-NT increased the number of alkaline phosphatase-positive senescent periodontal ligament stem cells and promoted calcium deposition and the expression of osteogenic marker genes Runt-related transcription factor 2, osteopontin, and osteocalcin. CONCLUSIONS: A special nanotube morphology enhances the differentiation ability of senescent periodontal ligament stem cells, provides an effective method for periodontal regeneration, and further improves the performance of implants.


Dental Implants , Osteogenesis , Periodontal Ligament/metabolism , Titanium/metabolism , Titanium/pharmacology , Stem Cells , Cell Differentiation , Cell Proliferation , Cells, Cultured , Alkaline Phosphatase/genetics , Alkaline Phosphatase/metabolism , Alkaline Phosphatase/pharmacology
18.
Chem Commun (Camb) ; 60(34): 4581-4584, 2024 Apr 23.
Article En | MEDLINE | ID: mdl-38576349

A study of an integrated OPECT biosensor gate and the EC color-changing region on the same chip was carried out, achieving sensitive detection through bioetching-induced signal changes. Enzymatic bioetching enables specific alkaline phosphatase (ALP) detection by catalyzing the production of CdS, which modulates the channel current and generates a visual signal.


Alkaline Phosphatase , Biosensing Techniques , Electrochemical Techniques , Alkaline Phosphatase/metabolism , Alkaline Phosphatase/analysis , Transistors, Electronic , Cadmium Compounds/chemistry , Sulfides/chemistry , Photochemical Processes
19.
Mol Biol Rep ; 51(1): 596, 2024 Apr 29.
Article En | MEDLINE | ID: mdl-38683461

BACKGROUND: Arnica montana and Bellis perennis are two medicinal plants that are thought to accelerate bone repair in homoeopathic literature. Mesenchymal stem cells (MSCs) are multipotent stem cells with the ability to differentiate and regenerate bone or osteogenesis. Hence, we aimed to determine the role of Arnica montana and Bellis perennis on the osteogenic differentiation of the C3H10T1/2 stem cell line. METHODS AND RESULTS: The cell proliferation of Arnica montana and Bellis perennis was evaluated by MTT assay. Osteogenic differentiation of C3H10T1/2 was induced by the addition of ß-glycerophosphate, ascorbic acid and dexamethasone in the differentiation medium over 3 weeks. Cells were treated with Arnica montana and Bellis perennis individually as well as in combination. The osteogenic differentiation potential of Arnica montana and Bellis perennis to differentiate C3H10T1/2 into osteoblasts was measured by alkaline phosphatase activity, alizarin red staining and the expression of Osteocalcin using immunostaining and qRT-PCR. Arnica montana and Bellis perennis could enhance C3H10T1/2 cell proliferation at 1600 µg. Further, the compound showed the ability to augment osteogenesis as confirmed by increased expression of alkaline phosphatase and enhanced calcium accumulation as seen by the Alizarin Red staining and quantification. Enhanced osteogenesis was further supported by the increased expression of osteocalcin in the treated cells with individual and combined doses of Arnica montana and Bellis perennis. Therefore, the findings provide additional support for the positive impact of Arnica montana and Bellis perennis on bone formation. CONCLUSIONS: Our findings suggest that homoeopathic compounds Arnica montana and Bellis perennis can augment osteogenesis individually as well as in combination.


Arnica , Cell Differentiation , Cell Proliferation , Mesenchymal Stem Cells , Osteogenesis , Plant Extracts , Osteogenesis/drug effects , Mesenchymal Stem Cells/metabolism , Mesenchymal Stem Cells/drug effects , Mesenchymal Stem Cells/cytology , Cell Differentiation/drug effects , Animals , Cell Proliferation/drug effects , Mice , Plant Extracts/pharmacology , Cell Line , Osteoblasts/drug effects , Osteoblasts/metabolism , Osteoblasts/cytology , Alkaline Phosphatase/metabolism , Multipotent Stem Cells/drug effects , Multipotent Stem Cells/cytology , Multipotent Stem Cells/metabolism , Osteocalcin/metabolism , Osteocalcin/genetics
20.
Korean J Gastroenterol ; 83(4): 163-166, 2024 Apr 25.
Article En | MEDLINE | ID: mdl-38659253

Malignant melanoma (MM) is an aggressive tumor that can metastasize to any organ, but biliary tract metastasis is scarce. We describe a very rare case of MM metastasis to the common bile duct (CBD), presented with only dyspeptic symptoms. The patient had mildly elevated alkaline phosphatase and gamma-glutamyl transferase levels. Magnetic resonance cholangiopancreatography demonstrated a dilated common bile duct with a distal stricture. The MM diagnosis was established with the ampulla of Vater biopsy specimens obtained by endoscopic retrograde cholangiopancreatography (ERCP), and the patient's symptoms were resolved after biliary stenting. Both primary CBD cancer and other cancer types like MM that metastasize to CBD can cause obstruction and can be manifested only by dyspeptic symptoms. MM metastasis to CBD can cause obstruction manifested only by dyspeptic symptoms without obstructive jaundice. ERCP can be employed as a promising option for treatment and diagnosis. New-onset dyspeptic symptoms in patients with a history of MM should be investigated thoroughly, especially in the context of biliary metastasis.


Cholangiopancreatography, Endoscopic Retrograde , Cholangiopancreatography, Magnetic Resonance , Dyspepsia , Melanoma , Tomography, X-Ray Computed , Humans , Melanoma/diagnosis , Melanoma/secondary , Melanoma/pathology , Melanoma/complications , Dyspepsia/diagnosis , Dyspepsia/etiology , Male , Middle Aged , Common Bile Duct/pathology , gamma-Glutamyltransferase/blood , Common Bile Duct Neoplasms/diagnosis , Common Bile Duct Neoplasms/pathology , Common Bile Duct Neoplasms/complications , Common Bile Duct Neoplasms/secondary , Alkaline Phosphatase/blood , Alkaline Phosphatase/metabolism
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