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1.
Chem Commun (Camb) ; 60(29): 3950-3953, 2024 Apr 04.
Article in English | MEDLINE | ID: mdl-38498350

ABSTRACT

In situ AFM observations show that when PILP droplets contact a surface, their initial properties are either a liquid with a high interfacial tension (350 mJ m-2) or a soft gel-like material with a low modulus (less than 0.2 MPa). These findings suggest that PILP may initially be liquid-like to infiltrate collagen fibrils, enabling the production of interpenetrating composites, and/or become viscoelastic, to provide a means for moulding minerals.

2.
Adv Healthc Mater ; 13(10): e2303488, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38265149

ABSTRACT

Amphiphilic biomolecules are abundant in mineralization front of biological hard tissues, which play a vital role in osteogenesis and dental hard tissue formation. Amphiphilic biomolecules function as biosurfactants, however, their biosurfactant role in biomineralization process has never been investigated. This study, for the first time, demonstrates that aggregated amorphous calcium phosphate (ACP) nanoparticles can be reversed into dispersed ultrasmall prenucleation clusters (PNCs) via breakdown and dispersion of the ACP nanoparticles by a surfactant. The reduced surface energy of ACP@TPGS and the electrostatic interaction between calcium ions and the pair electrons on oxygen atoms of C-O-C of D-α-tocopheryl polyethylene glycol succinate (TPGS) provide driving force for breakdown and dispersion of ACP nanoparticles into ultrasmall PNCs which promote in vitro and in vivo biomimetic mineralization. The ACP@TPGS possesses excellent biocompatibility without any irritations to oral mucosa and dental pulp. This study not only introduces surfactant into biomimetic mineralization field, but also excites attention to the neglected biosurfactant role during biomineralization process.


Subject(s)
Nanoparticles , Surface-Active Agents , Biomineralization , Biomimetics , Calcium Phosphates/chemistry , Polyethylene Glycols , Nanoparticles/chemistry
3.
Adv Healthc Mater ; 13(2): e2302418, 2024 Jan.
Article in English | MEDLINE | ID: mdl-37742096

ABSTRACT

Despite significant efforts utilizing advanced technologies, the contentious debate surrounding the intricate mechanism underlying collagen fibril mineralization, particularly with regard to amorphous precursor infiltration and phase transformation, persists. This work proposes an amorphous calcium phosphate (ACP)-mediated pathway for collagen fibril mineralization and utilizing stochastic optical reconstruction microscopy technology, and has experimentally confirmed for the first time that the ACP nanoparticles can infiltrate inside collagen fibrils. Subsequently, the ACP-mediated phase transformation occurs within collagen fibrils to form HAP crystallites, and significantly enhances the mechanical properties of the mineralized collagen fibrils compared to those achieved by the calcium phosphate ion (CPI)-mediated mineralization and resembles the natural counterpart. Furthermore, demineralized dentin can be effectively remineralized through ACP-mediated mineralization, leading to complete restoration of its mechanical properties. This work provides a new paradigm of collagen mineralization via particle-mediated phase transformation, deepens the understanding of the mechanism behind the mineralization of collagen fibrils, and offers a new strategy for hard tissue repair.


Subject(s)
Collagen , Extracellular Matrix , Collagen/metabolism , Extracellular Matrix/metabolism , Calcium Phosphates
4.
Clin Exp Hypertens ; 45(1): 2280758, 2023 Dec 31.
Article in English | MEDLINE | ID: mdl-37963203

ABSTRACT

Circular RNAs (circRNAs) regulate the function of vascular smooth muscle cells (VSMCs) in atherosclerosis (AS) progression. We aimed to explore the role of circUSP9X in oxidized low-density lipoprotein (ox-LDL)-induced VSMCs. Cell proliferation was assessed using cell counting kit-8 and EDU assays. Cell migration was evaluated using Transwell and wound healing assays. The interaction between circUSP9X or STIM1 and miR-599 was analyzed using dual-luciferase reporter and RNA pull-down assays. Their levels were examined using quantitative real-time PCR. CircUSP9X and STIM1 expression was increased, whereas miR-599 expression was reduced in the serum of patients with AS and ox-LDL-stimulated VSMCs. Overexpression of circUSP9X facilitated the proliferation and migration of VSMCs induced by ox-LDL. CircUSP9X sponged miR-599, which targeted STIM1. MiR-599 reversed the effects induced by circUSP9X, and STIM1 reversed the effects induced by miR-599. Taken together, CircUSP9X promoted proliferation and migration in ox-LDL-treated VSMCs via the miR-599/STIM1 axis, providing a theoretical basis for the role of circUSP9X/miR-599/STIM1 axis in AS.


Subject(s)
Atherosclerosis , MicroRNAs , Humans , Muscle, Smooth, Vascular , Atherosclerosis/genetics , Cell Proliferation , Lipoproteins, LDL/pharmacology , MicroRNAs/genetics
5.
Front Pharmacol ; 14: 1249145, 2023.
Article in English | MEDLINE | ID: mdl-37781709

ABSTRACT

Patients diagnosed with cancer face an increased risk of cardiovascular events in the short term, while those experiencing acute myocardial infarction (AMI) have a higher incidence of cancer. Given limitations in clinical resources, identifying shared biomarkers offers a cost-effective approach to risk assessment by minimizing the need for multiple tests and screenings. Hence, it is crucial to identify common biomarkers for both cancer survival and AMI prediction. Our study suggests that monocyte-derived biomarkers, specifically WEE1, PYHIN1, SEC61A2, and HAL, hold potential as predictors for cancer prognosis and AMI. We employed a novel formula to analyze mRNA levels in clinical samples from patients with AMI and cancer, resulting in the development of a new risk score based on expression profiles. By categorizing patients into high-risk and low-risk groups based on the median risk score, we observed significantly poorer overall survival among high-risk patients in cancer cohorts using Kaplan-Meier analysis. Furthermore, calibration curves, decision curve analysis (DCA), and clinical impact curve analyses provided additional evidence supporting the robust diagnostic capacity of the risk score for AMI. Noteworthy is the shared activation of the Notch Signaling pathway, which may shed light on common high-risk factors underlying both AMI and cancer. Additionally, we validated the differential expression of these genes in cell lines and clinical samples, respectively, reinforcing their potential as meaningful biomarkers. In conclusion, our study demonstrates the promise of mRNA levels as biomarkers and emphasizes the significance of further research for validation and refinement.

6.
Adv Sci (Weinh) ; 10(34): e2304216, 2023 Dec.
Article in English | MEDLINE | ID: mdl-37870172

ABSTRACT

Soft and hard tissues possess distinct biological properties. Integrating the soft-hard interface is difficult due to the inherent non-osteogenesis of soft tissue, especially of anterior cruciate ligament and rotator cuff reconstruction. This property makes it difficult for tendons to be mineralized and integrated with bone in vivo. To overcome this challenge, a biomimetic mineralization strategy is employed to engineer mineralized tendons. The strategy involved infiltrating amorphous calcium phosphate precursors into collagen fibrils, resulting in hydroxyapatite deposition along the c-axis. The mineralized tendon presented characteristics similar to bone tissue and induced osteogenic differentiation of mesenchymal stem cells. Additionally, the interface between the newly formed bone and tendon is serrated, suggesting a superb integration between the two tissues. This strategy allows for biomineralization of tendon collagen and replicating the hallmarks of the bone matrix and extracellular niche, including nanostructure and inherent osteoinductive properties, ultimately facilitating the integration of soft and hard tissues.


Subject(s)
Biomimetics , Osteogenesis , Collagen/chemistry , Tendons
7.
Am J Transl Res ; 15(9): 5835-5842, 2023.
Article in English | MEDLINE | ID: mdl-37854199

ABSTRACT

OBJECTIVE: To compare the efficacy of laparoscopy versus laparotomy in the treatment of transverse colon cancer. METHODS: Data from 100 patients with transverse colon cancer treated in our hospital from January 2018 to December 2020 were retrospectively analyzed in this study. According to the treatment methods, these patients were assigned into two groups: a laparotomy group (n=50) and a laparoscopy group (n=50). The intraoperative parameters, postoperative recovery, incidences of complications, postoperative pain, quality of life (QoL) score, postoperative serum inflammatory cytokine (hs-CRP, TNF-α, and IL-6) levels, and prognostic nutritional index (PNI) were analyzed and compared between the two groups. RESULTS: There was no significant difference in number of resected lymph nodes between the two groups. The operation time and intraoperative bleeding in the laparoscopy group were significantly less than those in the laparotomy group (P<0.05). The hospital stay, duration of gastrointestinal function recovery, and time of first postoperative flatus in the laparoscopy group were significantly shorter than those in the laparotomy group (all P<0.001). Moreover, the incidence of overall complications in the laparoscopy group was significantly lower than that in the laparotomy group (P<0.05). Compared with those in the laparotomy group, the VAS score was obviously lower and the QoL score was significantly higher in the laparoscopy group (all P<0.001). Patients in the laparoscopy group exhibited lower levels of postoperative hs-CRP, TNF-α and IL-6 in contrast to those in the laparotomy group (P<0.05). In additional, there was no significant difference in the PNI level before surgery between two groups. After surgery, the PNI level in the laparoscopy group was obviously higher than that in the laparotomy group (P<0.001). CONCLUSION: Laparoscopy is superior to laparotomy in treatment of transverse colon cancer through achieving better intraoperative outcomes, promoting postoperative recovery, reducing the incidence of complications and inflammatory reactions, alleviating postoperative pain, and improving therapeutic effects.

8.
Funct Integr Genomics ; 23(2): 160, 2023 May 13.
Article in English | MEDLINE | ID: mdl-37178159

ABSTRACT

Patients diagnosed with stable coronary artery disease (CAD) are at continued risk of experiencing acute myocardial infarction (AMI). This study aims to unravel the pivotal biomarkers and dynamic immune cell changes, from an immunological, predictive, and personalized viewpoint, by implementing a machine-learning approach and a composite bioinformatics strategy. Peripheral blood mRNA data from different datasets were analyzed, and CIBERSORT was used for deconvoluting human immune cell subtype expression matrices. Weighted gene co-expression network analysis (WGCNA) in single-cell and bulk transcriptome levels was conducted to explore possible biomarkers for AMI, with a particular emphasis on examining monocytes and their involvement in cell-cell communication. Unsupervised cluster analysis was performed to categorize AMI patients into different subtypes, and machine learning methods were employed to construct a comprehensive diagnostic model to predict the occurrence of early AMI. Finally, RT-qPCR on peripheral blood samples collected from patients validated the clinical utility of the machine learning-based mRNA signature and hub biomarkers. The study identified potential biomarkers for early AMI, including CLEC2D, TCN2, and CCR1, and found that monocytes may play a vital role in AMI samples. Differential analysis revealed that CCR1 and TCN2 exhibited elevated expression levels in early AMI compared to stable CAD. Machine learning methods showed that the glmBoost+Enet [alpha=0.9] model achieved high predictive accuracy in the training set, external validation sets, and clinical samples in our hospital. The study provided comprehensive insights into potential biomarkers and immune cell populations involved in the pathogenesis of early AMI. The identified biomarkers and the constructed comprehensive diagnostic model hold great promise for predicting the occurrence of early AMI and can serve as auxiliary diagnostic or predictive biomarkers.


Subject(s)
Myocardial Infarction , Humans , Myocardial Infarction/diagnosis , Myocardial Infarction/genetics , Cluster Analysis , Computational Biology , Machine Learning , RNA, Messenger/genetics
9.
Am J Transl Res ; 15(3): 2075-2083, 2023.
Article in English | MEDLINE | ID: mdl-37056855

ABSTRACT

OBJECTIVE: To investigate the application effect of the county medical community Hospital-Community health service organization-Home (HCH) model in nutritional management of patients with advanced gastrointestinal cancer after surgery. METHODS: This is a retrospective study. A total of 100 postoperative malnutrition patients with advanced gastrointestinal malignant tumors admitted to Lanxi People's Hospital from January 2022 to August 2022 were selected as subjects. All patients were divided into an observation group (n=50) or control group (n=50) according to the different methods of intervention. Patients in the observation group underwent care according to our county medical community HCH model, while those in the control group received routine perioperative nutrition management. The nutritional risk screening scores (NRS2002), Patient-Generated Subjective Global Assessment (PG-SGA) scores, body mass index (BMI), triceps skinfold thickness (TSF), upper arm circumference (AC); a well as levels of serum albumin (ALB), prealbumin (PA), transferrin (TRF), retinol binding protein (RBP), creatinine (Cr) and Free fatty acid (FFA); levels of immunoglobulin G (IgG), immunoglobulin M (IgM) and immunoglobulin A (IgA); and the levels of sodium (Na+), potassium (K+), calcium (Ca+) and lactic acid, and quality of life were recorded and compared between two groups. RESULTS: Compared with those before intervention, NRS2002 scores, PG-SGA score, BMI, TSF and AC after intervention were significantly improved in both groups. Compared with those after intervention in the control group, the NRS2002 score, PG-SGA score, BMI, TSF and AC of the patients in the observation group were significantly improved (all P<0.001). Compared with those before intervention, the levels of ALB, PA, TRF, RBP, Cr, FFA, IgG, IgM and IgA in the two groups were significantly higher after intervention. The levels of ALB, PA, TRF, RBP, Cr, FFA, IgG, IgM and IgA after intervention in the observation group were significantly higher than those in the control group (all P<0.05). Compared with those before management, the levels of Na+, K+ and lactic acid in the two groups were significantly decreased and the level of Ca+ was significantly increased after intervention. Compared with those after intervention in the control group, the patients in the observation group had significantly lower levels of Na+, K+ and lactic acid, and higher levels of Ca+ (all P<0.05). Compared with those before intervention, the scores of mental status, appetite, sleep quality, daily life and family understanding and cooperation in patients from the two groups after intervention were significantly higher. Compared with those after intervention in the control group, the patients in the observation group had significantly higher scores of life quality (P<0.05). CONCLUSION: The county medical community HCH model has a good effect in the nutritional management of patients with advanced gastrointestinal cancer surgery. The HCH model can effectively improve the nutritional status, enhance the immune function, and increase the quality of life. Thus it is worthy of clinical application.

10.
BMC Cardiovasc Disord ; 23(1): 167, 2023 03 29.
Article in English | MEDLINE | ID: mdl-36991345

ABSTRACT

BACKGROUND: Pulmonary arterial hypertension is a common complication in patients with congenital heart disease. In the absence of early diagnosis and treatment, pediatric patients with PAH has a poor survival rate. Here, we explore serum biomarkers for distinguishing children with pulmonary arterial hypertension associated with congenital heart disease (PAH-CHD) from CHD. METHODS: Samples were analyzed by nuclear magnetic resonance spectroscopy-based metabolomics and 22 metabolites were further quantified by ultra-high-performance liquid chromatography-tandem mass spectroscopy. RESULTS: Serum levels of betaine, choline, S-Adenosyl methionine (SAM), acetylcholine, xanthosine, guanosine, inosine and guanine were significantly altered between CHD and PAH-CHD. Logistic regression analysis showed that combination of serum SAM, guanine and N-terminal pro-brain natriuretic peptide (NT-proBNP), yielded the predictive accuracy of 157 cases was 92.70% with area under the curve of the receiver operating characteristic curve value of 0.9455. CONCLUSION: We demonstrated that a panel of serum SAM, guanine and NT-proBNP is potential serum biomarkers for screening PAH-CHD from CHD.


Subject(s)
Heart Defects, Congenital , Hypertension, Pulmonary , Pulmonary Arterial Hypertension , Humans , Child , Pulmonary Arterial Hypertension/diagnosis , Pulmonary Arterial Hypertension/complications , Heart Defects, Congenital/complications , Heart Defects, Congenital/diagnosis , Familial Primary Pulmonary Hypertension , Biomarkers , Metabolomics , Natriuretic Peptide, Brain , Peptide Fragments
11.
Adv Healthc Mater ; 12(19): e2300100, 2023 07.
Article in English | MEDLINE | ID: mdl-36930219

ABSTRACT

Dentin hypersensitivity (DH) is triggered by external stimuli irking fluid flow through exposed dentinal tubules (DTs). Three commercially available desensitizing agents as control in this study only achieve limited occlusion depths of ≈10 µm in the DTs as well as scarce remineralization of demineralized dentin matrix. Herein, polyelectrolyte-calcium complexes pre-precursor (PCCP) process is proposed for managing DH that demineralized dentin with exposed DTs is rubbed with ultrahighly concentrated polyelectrolyte-calcium suspension (4 g L-1 -5.44 m) followed by phosphate solution (3.25 m), each 10 min, leading to heavy remineralization of demineralized dentin and compact occlusion of the DTs over 200 µm after 1 day of in vitro and in vivo incubation. For the first time, it is demonstrated that the PCCP process relies on the pH-dependent electrostatic attraction between electropositive polyelectrolyte-calcium complexes and electronegative inwalls of DTs comprised of collagen fibrils and hydroxyapatite crystals under alkaline condition. The PCCP process might shed light on a promising dentin desensitizing strategy for DH management via rapid in-depth DT occlusion and remineralization of demineralized dentin.


Subject(s)
Calcium , Dentin Sensitivity , Humans , Calcium/analysis , Dentin , Dentin Sensitivity/drug therapy , Polyelectrolytes , Microscopy, Electron, Scanning , Tooth Remineralization
12.
ACS Biomater Sci Eng ; 9(4): 1808-1814, 2023 04 10.
Article in English | MEDLINE | ID: mdl-34855358

ABSTRACT

Controlling oriented crystallization is key to producing bonelike composite materials with a well-organized structure. However, producing this type of composite material using synthetic biopolymers as scaffolds is challenging. Inspired by the molecular structure of collagen-I, a collagenlike peptide─(Pro-Hyp-Gly)10 (POG10)─was designed to produce self-assembled fibrils that resemble the structure of collagen-I fibrils. In addition, the oriented mineralization of HAP crystals is formed in the fibrils that reproduces a bonelike material similar to collagen-I fibril mineralization. Unlike collagen-I fibrils, POG10 fibrils do not contain gap spaces. The molecular simulation results indicate that in addition to space confinement, the molecular field generated by POG10 can also confine the orientation of HAP, enriching our understanding of physical confinement and shedding light on the design of synthetic biopolymer scaffolds for bonelike material fabrication.


Subject(s)
Collagen , Durapatite , Durapatite/chemistry , Crystallization , Extracellular Matrix , Collagen Type I , Peptides/chemistry
13.
ACS Biomater Sci Eng ; 9(4): 1757-1773, 2023 04 10.
Article in English | MEDLINE | ID: mdl-34870411

ABSTRACT

Biomineralization is a process in which natural organisms regulate the crystal growth of inorganic minerals, resulting in hierarchical structured biominerals with excellent properties. Typical biominerals in the human body are the bones and teeth, and damage to these hard tissues directly affect our daily lives. The repair of bones and teeth in a biomimetic way, either by using a biomimetic mineralization strategy or biomimetic materials, is the key for hard tissue regeneration. In this review, we briefly introduce the structure of bone and tooth, and highlight the fundamental role of collagen mineralization in tissue repair. The recent progress on intra-/extrafibrillar collagen mineralization by a biomimetic strategy or materials is presented, and their potential for tissue regeneration is discussed. Then, recent achievements on bone and tooth repair are summarized, and these works are discussed in the view of materials science and biological science, providing a broader vision for the future research of hard tissue repair techniques. Lastly, recent progress on hard tissue regeneration is concluded, and existing problems and future directions are prospected.


Subject(s)
Biomimetic Materials , Tooth , Humans , Biomimetics , Collagen , Bone and Bones , Biomimetic Materials/pharmacology , Biomimetic Materials/chemistry
14.
Aust Endod J ; 49 Suppl 1: 46-57, 2023 Sep.
Article in English | MEDLINE | ID: mdl-36127810

ABSTRACT

This study aimed to evaluate and compare the remineralisation, mechanical, anti-aging, acid resistance and antibacterial properties of calcium phosphate ion clusters (CPICs) materials with those of Duraphat and Icon. The remineralisation and mechanical properties were investigated using scanning electron microscopy, Fourier-transform infrared (FTIR) spectroscopy and nanoindentation. CPICs induced epitaxial crystal growth on the enamel surface, where the regrown enamel-like apatite layers had a similar hardness and elastic modulus to natural enamel (p > 0.05). Acid resistance and anti-aging properties were tested based on ion dissolution and surface roughness. CPICs exhibited similar calcium and phosphate ion dissolution to the control (p > 0.05), and its roughness decreased after thermocycling (p < 0.05), thereby decreasing the risk of enamel surface demineralisation. The minimum inhibitory concentration was 0.1 mg/ml, and the minimum bactericidal concentration ranged from 0.05 to 0.1 mg/ml. Overall, this biomimetic CPICs is a promising alternative to dental demineralisation.


Subject(s)
Fluorides , Tooth Demineralization , Humans , Fluorides/analysis , Fluorides/pharmacology , Tooth Demineralization/prevention & control , Dental Enamel/chemistry , Calcium Phosphates/pharmacology , Calcium Phosphates/analysis , Phosphates/analysis , Phosphates/pharmacology , Hardness
15.
J Mater Chem B ; 10(30): 5826-5834, 2022 08 04.
Article in English | MEDLINE | ID: mdl-35876157

ABSTRACT

Biomineralization of collagen fibers is regulated by non-collagenous proteins and small biomolecules, which are essential in bone and teeth formation. In particular, small biomolecules such as succinic acid (SA) exist at a high level in hard tissues, but their role is yet unclear. Here, our work demonstrated that SA could significantly promote intrafibrillar mineralization in two- and three-dimensional collagen models, where the relative mineralization rate was 16 times faster than the control group. Furthermore, the FTIR spectra and isothermal experimental results showed that collagen molecules could interact with SA via a hydrogen bond and that the interaction energy was about 4.35 kJ mol-1. As expected, the SA-pretreated demineralized dentin obtained full remineralization within two days, whereas it took more than four days in the control group, and their mechanical properties were considerably enhanced compared with those of the demineralized one. The possible mechanism of the promotion effect of SA was ultimately illustrated, with SA modification strengthening the capacity of the collagen matrix to attract more calcium ions, which might create a higher local concentration that could accelerate the mineralization of collagen fibers. These findings not only advance the understanding of the vital role of small biomolecules in collagen biomineralization but also facilitate the development of an effective strategy to repair hard tissues.


Subject(s)
Dentin , Succinates , Biomineralization , Bone and Bones/metabolism , Collagen/chemistry , Succinates/analysis , Succinates/metabolism
16.
Contrast Media Mol Imaging ; 2022: 7021200, 2022.
Article in English | MEDLINE | ID: mdl-35360268

ABSTRACT

Objective: To investigate the protective effect of miR-542-3p on cardiomyocyte injury and related mechanisms. Methods: A cardiomyocyte hypoxia/reoxygenation model was established. The expression levels of miR-542-3p and PDE4D were detected using qRT-PCR; the luciferase reporter assay system was used to detect the targeting relationship between miR-542-3p and PDE4D; overexpressing miR-542-3p was transfected into cardiomyocytes, and ROS release was detected by immunofluorescence while cellular apoptosis was detected by TUNEL; and the western blot assay was applied to detect the expression of PDE4D, phosphorylated protein kinase A (p-PKA), and phosphorylated cyclic adenosine monophosphate (cAMP) response element-binding protein (p-CREB). Results: Compared with the control group, the miR-542-3p expression level was decreased and the PDE4D expression level was increased in the cardiomyocyte hypoxia/reoxygenation model group. The dual-luciferase reporter assay system confirmed that miR-542-3p could target and regulate PDE4D; the transfection with cardiomyocytes using the overexpressing miR-542-3p could downregulate PDE4D expression, attenuate ROS release during cardiomyocyte injury, and reduce cellular apoptosis rate, while upregulating the expression of p-PKA and p-CREB. Conclusion: The miR-542-3p can negatively regulate PDE4D protein expression and attenuate cardiomyocyte injury through a mechanism related to the activation of the cAMP/PKA signaling pathway.


Subject(s)
MicroRNAs , Myocytes, Cardiac , Apoptosis , Cyclic AMP-Dependent Protein Kinases/metabolism , Cyclic AMP-Dependent Protein Kinases/pharmacology , MicroRNAs/genetics , MicroRNAs/metabolism , MicroRNAs/pharmacology , Myocytes, Cardiac/metabolism , Signal Transduction
17.
Bioact Mater ; 18: 199-212, 2022 Dec.
Article in English | MEDLINE | ID: mdl-35387162

ABSTRACT

Although ultra-small nanoclusters (USNCs, < 2 nm) have immense application capabilities in biomedicine, the investigation on body-wide organ responses towards USNCs is scant. Here, applying a novel strategy of single-cell mass cytometry combined with Nano Genome Atlas of multi-tissues, we systematically evaluate the interactions between the host and calcium phosphate (CaP) USNCs at the organism level. Combining single-cell mass cytometry, and magnetic luminex assay results, we identify dynamic immune responses to CaP USNCs at the single cell resolution. The innate immune is initially activated and followed by adaptive immune activation, as evidenced by dynamic immune cells proportions. Furthermore, using Nano Genome Atlas of multi-tissues, we uncover CaP USNCs induce stronger activation of the immune responses in the cartilage and subchondral bone among the five local tissues while promote metabolic activities in the liver and kidney. Moreover, based on the immunological response profiles, histological evaluation of major organs and local tissue, and a body-wide transcriptomics, we demonstrate that CaP USNCs are not more hazardous than the Food and Drug Administration-approved CaP nanoparticles after 14 days of injection. Our findings provide valuable information on the future clinical applications of USNCs and introduce an innovative strategy to decipher the whole body response to implants.

18.
Biosci Rep ; 42(3)2022 03 31.
Article in English | MEDLINE | ID: mdl-35237783

ABSTRACT

Some tumor cells have a high rate of glutamine uptake and exhibit glutamine addiction. Alanine-serine cysteine-preferring transporter 2 (ASCT2) is a major mediator of glutamine supply in many tumor cells, but the underlying effects and mechanisms of ASCT2 in pancreatic cancer (PC) are largely unknown. Our results show that ASCT2 expression is significantly higher in PC than in normal pancreatic duct cells and pancreas. Utilizing the Kaplan-Meier Plotter database, a high expression of SLC1A5 mRNA was significantly associated with poor overall survival (OS) in patients with PC. shRNA-mediated inhibition of ASCT2 function in vitro can significantly decrease glutamine consumption, α-ketoglutarate (α-KG) production and ATP generation and increase the reactive oxygen species (ROS) level. Moreover, the antioxidant N-acetylcysteine partially attenuated the increase in the ROS levels and reduced ATP generation. These data suggest that ASCT2 mediates glutamine metabolism and maintains redox homeostasis in PC. To further investigate whether ASCT2 is involved in PC cell growth, we blocked ASCT2 activity with the ASCT2 inhibitor l-γ-glutamyl-p-nitroanilide (GPNA) and silenced the expression of ASCT2 with specific shRNAs. We found that the growth of PC cells was significantly inhibited. Additionally, knockdown of ASCT2 induced apoptosis through the Akt/mTOR signaling pathway. Furthermore, the loss of ASCT2 in BxPC-3 cell xenografts significantly inhibited tumor growth in vivo, and this effect was associated with an increase in cleaved caspase-3 expression and a decrease in Ki67 staining. Taken together, our results show that ASCT2 may be utilized as a putative therapeutic target for PC.


Subject(s)
Glutamine , Pancreatic Neoplasms , Adenosine Triphosphate , Alanine/pharmacology , Amino Acid Transport System ASC/genetics , Amino Acid Transport System ASC/metabolism , Apoptosis , Cell Line, Tumor , Cell Proliferation , Cysteine , Glutamine/metabolism , Humans , Minor Histocompatibility Antigens/genetics , Minor Histocompatibility Antigens/metabolism , Pancreas/metabolism , Pancreatic Neoplasms/drug therapy , Pancreatic Neoplasms/genetics , Reactive Oxygen Species/metabolism , Serine , Pancreatic Neoplasms
19.
Nanoscale ; 14(3): 642-652, 2022 Jan 20.
Article in English | MEDLINE | ID: mdl-34935821

ABSTRACT

Dentinal tubule (DT) occlusion by desensitizing agents has been widely applied to inhibit the transmission of external stimuli that cause dentin hypersensitivity (DH). However, most desensitizing agents merely accomplish porous blocking or the formation of a superficial tubular occlusion layer, resulting in a lack of mechanical and acid resistance and long-term stability. Herein, combining biomimetic mineralization and mineral overgrowth of the dentinal matrix was shown to effectively occlude DTs, resulting in the formation of a compact and deep occluding mineral layer that is strongly bound to the organic matrix on tubule walls. This DT occlusion method could achieve both mechanical resistance and acid resistance, demonstrating the potential of an inexpensive, long-term, and efficient therapy for treating DH.


Subject(s)
Biomimetics , Dentin , Microscopy, Electron, Scanning , Minerals
20.
Adv Mater ; 34(9): e2107523, 2022 Mar.
Article in English | MEDLINE | ID: mdl-34962676

ABSTRACT

The development of environmentally friendly plastics is critical to ensure sustainable development. In contrast to polymer plastics derived from petrochemicals, inorganic minerals, which are the most abundant matter in Earth's crust, are environmentally friendly. However, the brittleness of these minerals limits their applications as plastics. Here, because of the advantages of both biomineralization and inorganic ionic polymerization, the calcium phosphate (CaP, a typical geological and biological mineral) oligomers are used for biomimetic mineralization under the regulation of polyvinyl alcohol and sodium alginate, resulting in flexible CaP nanofibers with periodic structural defects. The assembly of CaP nanofibers produces a hierarchically structured bulk hybrid mineral (HM), which overcomes the intrinsic brittleness of minerals and exhibits plasticity characteristics. HM exhibits better hardness and thermostability than classical polymer plastics due to its dominant mineral composition. Notably, HM is environmentally friendly and degradable in nature, as it can potentially participate in geological cycles, indicating that this material is an optimal plastic substitute. The construction of periodic structural defects within flexible minerals expands the current understanding of materials science.

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