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1.
Mater Today Bio ; 26: 101092, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38873105

ABSTRACT

Osteoporosis (OP) can result in slower bone regeneration than the normal condition due to the imbalance between osteogenesis and osteoclastogenesis, making osteoporotic bone defects healing a significant clinical challenge. Calcium phosphate cement (CPC) is a promising bone substitute material due to its good osteoinductive activity, however, the drawbacks such as fragility, slow degradation rate and incapability to control bone loss restrict its application in osteoporotic bone defects treatment. Currently, we developed the PLGA electrospun nanofiber sheets to carry alendronate (ALN) and magnesium oxide nanoparticle (nMgO) into CPC, therefore, to obtain a high-strength bone cement (C/AM-PL/C). The C/AM-PL/C bone cement had high mechanical strength, anti-washout ability, good injection performance and drug sustained release capacity. More importantly, the C/AM-PL/C cement promoted the osteogenic differentiation of bone marrow mesenchymal stem cells and neovascularization via the release of Mg2+ (from nMgO) and Ca2+ (during the degradation of CPC), and inhibited osteoclastogenesis via the release of ALN in vitro. Moreover, the injection of C/AM-PL/C cement significantly improved bone healing in an OP model with femur condyle defects in vivo. Altogether, the injectable C/AM-PL/C cement could facilitate osteoporotic bone regeneration, demonstrating its capacity as a promising candidate for treatment of osteoporotic bone defects.

2.
Article in English | MEDLINE | ID: mdl-38866616

ABSTRACT

BACKGROUND AND AIM: Currently, the relationship between dynamic changes in dietary manganese (Mn) intake and risk of hyperuricemia (HU) is still unclear. This study aimed to identify dietary Mn consumption trajectories in the Chinese adults and assess their relation with the risk of HU. METHODS AND RESULTS: Cohort data from the China Health and Nutrition Survey (CHNS) 1997-2009 were employed in this study. Overall, 6886 adult participants were included. Participants were designated into subgroups based on the trajectories of dietary Mn consumption by sex. Cox proportional hazard models were used to explore the associations between different trajectories and the risk of HU. For men, compared with low stable trajectory group, moderate to high trajectory group was significantly related to reduced risk of HU (HR = 0.61, 95% CI: 0.38 to 0.98) with adjustment for covariates. TC, HDL-C, ApoB, and TG exerted partial regulation function between trajectories and HU. For women, compared with low stable trajectory group, high stable trajectory group was significantly related to reduced risk of HU (HR = 0.76, 95% CI: 0.60 to 0.95) with adjustment for covariates. Similarly, TC, HDL-C, ApoB, and ApoA exerted partial regulation function between trajectories and HU. CONCLUSIONS: Long-term relatively high dietary Mn consumption may have a protective effect against HU in Chinese adults. The differences in HU-related factors among different dietary Mn intake trajectories partially regulated the association between these trajectories and HU.

3.
Diagn Microbiol Infect Dis ; 109(3): 116278, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38723451

ABSTRACT

The aim of this study was to evaluate the influence factors of metagenomic next-generation sequencing (mNGS) negative results in the diagnosed patients with spinal infection. mNGS test was applied in a cohort of 114 patients with suspected spinal infection, among which 56 patients had a final diagnosis of spinal infection. mNGS achieved a sensitivity of 75.0% (95% CI, 61.6% to 85.6%) and a specificity of 84.5% (95% CI, 72.6% to 92.7%), using histopathology and culture results as reference. Diagnosed patients with a negative culture result had lower white blood cell account, percentage of neutrophilic granulocyte, C-reactive protein (all P<0.05) and relatively higher rate of prior antimicrobial treatment history (P=0.059). However, diagnosed patients with a negative mNGS result did not have such difference with mNGS-positive patients, suggesting that mNGS was not strictly limited by the above indicators, which presented the advantages of this technique from another point of view.


Subject(s)
High-Throughput Nucleotide Sequencing , Metagenomics , Sensitivity and Specificity , Humans , High-Throughput Nucleotide Sequencing/methods , Male , Female , Metagenomics/methods , Middle Aged , Aged , Adult , Aged, 80 and over , Young Adult , Spinal Diseases/microbiology , Spinal Diseases/diagnosis
4.
Ann Plast Surg ; 92(5): 585-590, 2024 May 01.
Article in English | MEDLINE | ID: mdl-38685498

ABSTRACT

BACKGROUND: Acellular nerve allografts (ANAs) were developed to replace the autologous nerve grafts (ANGs) to fill the peripheral nerve defects. Poor vascularization relative to ANGs has been a limitation of application of ANAs. METHODS: A total of 60 female Sprague-Dawley rats were assigned 3 groups. The rats in A group received ANGs, the rats in B group received ANAs, and the rats in C group were transplanted with ANA carrying endothelial cells (ANA + ECs). In the 1st, 2nd, 4th, and 12th postoperative weeks, 5 rats were selected from each group for evaluating sciatic function index (SFI), electrophysiology, maximum tetanic force recovery rate, tibialis anterior muscle weights recovery rate, and microvessel density. In the 12th postoperative week, the nerves were harvested and stained with toluidine blue and observed under an electron microscope to compare nerve fibers, myelin width, and G-ratio. RESULTS: All the rats survived. In the first and second postoperative weeks, more microvessels were found in the ANA + EC group. In the 12th postoperative week, the nerve fibers were more numerous, and G-ratio was smaller in the C group compared with the B group. The compound muscle action potential and maximum tetanic force recovery rate in the tibialis anterior muscle in the C group were better than those in the B group in the 12th postoperative week. The A group showed better performances in electrophysiology, maximum tetanic force, muscle wet weight, and nerve regeneration. CONCLUSION: ANA + ECs can promote early angiogenesis, promoting nerve regeneration and neurological function recovery.


Subject(s)
Allografts , Endothelial Cells , Nerve Regeneration , Rats, Sprague-Dawley , Sciatic Nerve , Animals , Female , Rats , Sciatic Nerve/surgery , Sciatic Nerve/injuries , Sciatic Nerve/transplantation , Nerve Regeneration/physiology , Peripheral Nerve Injuries/surgery , Recovery of Function , Random Allocation
5.
Acta Biomater ; 180: 82-103, 2024 05.
Article in English | MEDLINE | ID: mdl-38621599

ABSTRACT

The treatment of osteoporotic bone defect remains a big clinical challenge because osteoporosis (OP) is associated with oxidative stress and high levels of reactive oxygen species (ROS), a condition detrimental for bone formation. Anti-oxidative nanomaterials such as selenium nanoparticles (SeNPs) have positive effect on osteogenesis owing to their pleiotropic pharmacological activity which can exert anti-oxidative stress functions to prevent bone loss and facilitate bone regeneration in OP. In the current study a strategy of one-pot method by introducing Poly (lactic acid-carbonate) (PDT) and ß-Tricalcium Phosphate (ß-TCP) with SeNPs, is developed to prepare an injectable, anti-collapse, shape-adaptive and adhesive bone graft substitute material (PDT-TCP-SE). The PDT-TCP-SE bone graft substitute exhibits sufficient adhesion in biological microenvironments and osteoinductive activity, angiogenic effect and anti-inflammatory as well as anti-oxidative effect in vitro and in vivo. Moreover, the PDT-TCP-SE can protect BMSCs from erastin-induced ferroptosis through the Sirt1/Nrf2/GPX4 antioxidant pathway, which, in together, demonstrated the bone graft substitute material as an emerging biomaterial with potential clinical application for the future treatment of osteoporotic bone defect. STATEMENT OF SIGNIFICANCE: Injectable, anti-collapse, adhesive, plastic and bioactive bone graft substitute was successfully synthesized. Incorporation of SeNPs with PDT into ß-TCP regenerated new bone in-situ by moderating oxidative stress in osteoporotic bone defects area. The PDT-TCP-SE bone graft substitute reduced high ROS levels in osteoporotic bone defect microenvironment. The bone graft substitute could also moderate oxidative stress and inhibit ferroptosis via Sirt1/Nrf2/GPX4 pathway in vitro. Moreover, the PDT-TCP-SE bone graft substitute could alleviate the inflammatory environment and promote bone regeneration in osteoporotic bone defect in vivo. This biomaterial has the advantages of simple synthesis, biocompatibility, anti-collapse, injectable, and regulation of oxidative stress level, which has potential application value in bone tissue engineering.


Subject(s)
Bone Regeneration , Bone Substitutes , Calcium Phosphates , Osteoporosis , Oxidative Stress , Oxidative Stress/drug effects , Animals , Bone Substitutes/chemistry , Bone Substitutes/pharmacology , Bone Regeneration/drug effects , Osteoporosis/pathology , Osteoporosis/therapy , Osteoporosis/drug therapy , Calcium Phosphates/pharmacology , Calcium Phosphates/chemistry , Rats, Sprague-Dawley , Selenium/chemistry , Selenium/pharmacology , Female , Osteogenesis/drug effects , Polyesters/chemistry , Polyesters/pharmacology , Mesenchymal Stem Cells/metabolism , Mesenchymal Stem Cells/drug effects , Rats , Injections
6.
Phys Rev Lett ; 132(12): 120201, 2024 Mar 22.
Article in English | MEDLINE | ID: mdl-38579221

ABSTRACT

We consider how to describe Hamiltonian mechanics in generalized probabilistic theories with the states represented as quasiprobability distributions. We give general operational definitions of energy-related concepts. We define generalized energy eigenstates as the purest stationary states. Planck's constant plays two different roles in the framework: the phase space volume taken up by a pure state and a dynamical factor. The Hamiltonian is a linear combination of generalized energy eigenstates. This allows for a generalized Liouville time-evolution equation that applies to quantum and classical Hamiltonian mechanics and more. The approach enables a unification of quantum and classical energy concepts and a route to discussing energy in a wider set of theories.

7.
Adv Sci (Weinh) ; 11(17): e2302988, 2024 May.
Article in English | MEDLINE | ID: mdl-38430538

ABSTRACT

Peripheral nerve injury (PNI) remains a challenging area in regenerative medicine. Nerve guide conduit (NGC) transplantation is a common treatment for PNI, but the prognosis of NGC treatment is unsatisfactory due to 1) neuromechanical unmatching and 2) the intra-conduit inflammatory microenvironment (IME) resulting from Schwann cell pyroptosis and inflammatory-polarized macrophages. A neuromechanically matched NGC composed of regenerated silk fibroin (RSF) loaded with poly(3,4-ethylenedioxythiophene): poly(styrene sulfonate) (P:P) and dimethyl fumarate (DMF) are designed, which exhibits a matched elastic modulus (25.1 ± 3.5 MPa) for the peripheral nerve and the highest 80% elongation at break, better than most protein-based conduits. Moreover, the NGC can gradually regulate the intra-conduit IME by releasing DMF and monitoring sciatic nerve movements via piezoresistive sensing. The combination of NGC and electrical stimulation modulates the IME to support PNI regeneration by synergistically inhibiting Schwann cell pyroptosis and reducing inflammatory factor release, shifting macrophage polarization from the inflammatory M1 phenotype to the tissue regenerative M2 phenotype and resulting in functional recovery of neurons. In a rat sciatic nerve crush model, NGC promoted remyelination and functional and structural regeneration. Generally, the DMF/RSF/P:P conduit provides a new potential therapeutic approach to promote nerve repair in future clinical treatments.


Subject(s)
Fibroins , Nerve Regeneration , Peripheral Nerve Injuries , Animals , Nerve Regeneration/drug effects , Nerve Regeneration/physiology , Rats , Peripheral Nerve Injuries/therapy , Fibroins/chemistry , Fibroins/pharmacology , Disease Models, Animal , Rats, Sprague-Dawley , Schwann Cells/metabolism , Guided Tissue Regeneration/methods , Inflammation , Tissue Scaffolds/chemistry , Sciatic Nerve/injuries
8.
Adv Sci (Weinh) ; 11(12): e2303981, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38224203

ABSTRACT

Coloading adjuvant drugs or biomacromolecules with photosensitizers into nanoparticles to enhance the efficiency of photodynamic therapy (PDT) is a common strategy. However, it is difficult to load positively charged photosensitizers and negatively charged adjuvants into the same nanomaterial and further regulate drug release simultaneously. Herein, a single-component dual-functional prodrug strategy is reported for tumor treatment specifically activated by tumor microenvironment (TME)-generated HOCl. A representative prodrug (DHU-CBA2) is constructed using indomethacin grafted with methylene blue (MB). DHU-CBA2 exhibited high sensitivity toward HOCl and achieved simultaneous release of dual drugs in vitro and in vivo. DHU-CBA2 shows effective antitumor activity against lung cancer and spinal metastases via PDT and cyclooxygenase-2 (COX-2) inhibition. Mechanistically, PDT induces immunogenic cell death but stimulates the gene encoding COX-2. Downstream prostaglandins E2 and Indoleamine 2,3 dioxygenase 1 (IDO1) mediate immune escape in the TME, which is rescued by the simultaneous release of indomethacin. DHU-CBA2 promotes infiltration and function of CD8+ T cells, thus inducing a robust antitumor immune response. This work provides an autoboost strategy for a single-component dual-functional prodrug activated by TME-specific HOCl, thereby achieving favorable tumor treatment via the synergistic therapy of PDT and a COX-2 inhibitor.


Subject(s)
Lung Neoplasms , Photochemotherapy , Prodrugs , Spinal Neoplasms , Humans , Photosensitizing Agents/therapeutic use , Lung Neoplasms/drug therapy , Cyclooxygenase 2 , CD8-Positive T-Lymphocytes , Spinal Neoplasms/drug therapy , Indomethacin , Tumor Microenvironment
9.
Adv Healthc Mater ; 13(4): e2302342, 2024 Feb.
Article in English | MEDLINE | ID: mdl-37975509

ABSTRACT

Intercellular communication between tumor cells and immune cells regulates tumor progression including positive communication with immune activation and negative communication with immune escape. An increasing number of methods are employed to suppress the dominant negative communication in tumors such as PD-L1/PD-1. However, how to effectively improve positive communication is still a challenge. In this study, a nuclear-targeted photodynamic nanostrategy is developed to establish positive spatiotemporal communication, further activating dual antitumor immunity, namely innate and adaptative immunity. The mSiO2 -Ion@Ce6-NLS nanoparticles (NPs) are designed, whose surface is modified by ionic liquid silicon (Ion) and nuclear localization signal peptide (NLS: PKKKRKV), and their pores are loaded with the photosensitizer hydrogen chloride e6 (Ce6). Ion-modified NPs enhance intratumoral enrichment, and NLS-modified NPs exhibit nuclear-targeted characteristics to achieve nuclear-targeted photodynamic therapy (nPDT). mSiO2 -Ion@Ce6-NLS with nPDT facilitate the release of damaged double-stranded DNA from tumor cells to activate macrophages via stimulator of interferon gene signaling and induce the immunogenic cell death of tumor cells to activate dendritic cells via "eat me" signals, ultimately leading to the recruitment of CD8+ T-cells. This therapy effectively strengthens positive communication to reshape the dual antitumor immune microenvironment, further inducing long-term immune memory, and eventually inhibiting tumor growth and recurrence.


Subject(s)
Nanoparticles , Photochemotherapy , Cell Line, Tumor , CD8-Positive T-Lymphocytes , Photosensitizing Agents/pharmacology , Photochemotherapy/methods , Macrophages , Immunotherapy/methods , Tumor Microenvironment
10.
Plant Commun ; 5(2): 100734, 2024 Feb 12.
Article in English | MEDLINE | ID: mdl-37859344

ABSTRACT

Volatile organic compounds (VOCs) play key roles in plant-plant communication, especially in response to pest attack. E-2-hexenal is an important component of VOCs, but it is unclear whether it can induce endogenous plant resistance to insects. Here, we show that E-2-hexenal activates early signaling events in Arabidopsis (Arabidopsis thaliana) mesophyll cells, including an H2O2 burst at the plasma membrane, the directed flow of calcium ions, and an increase in cytosolic calcium concentration. Treatment of wild-type Arabidopsis plants with E-2-hexenal increases their resistance when challenged with the diamondback moth Plutella xylostella L., and this phenomenon is largely lost in the wrky46 mutant. Mechanistically, E-2-hexenal induces the expression of WRKY46 and MYC2, and the physical interaction of their encoded proteins was verified by yeast two-hybrid, firefly luciferase complementation imaging, and in vitro pull-down assays. The WRKY46-MYC2 complex directly binds to the promoter of RBOHD to promote its expression, as demonstrated by luciferase reporter, yeast one-hybrid, chromatin immunoprecipitation, and electrophoretic mobility shift assays. This module also positively regulates the expression of E-2-hexenal-induced naringenin biosynthesis genes (TT4 and CHIL) and the accumulation of total flavonoids, thereby modulating plant tolerance to insects. Together, our results highlight an important role for the WRKY46-MYC2 module in the E-2-hexenal-induced defense response of Arabidopsis, providing new insights into the mechanisms by which VOCs trigger plant defense responses.


Subject(s)
Aldehydes , Arabidopsis Proteins , Arabidopsis , Arabidopsis/genetics , Arabidopsis/metabolism , Arabidopsis Proteins/genetics , Arabidopsis Proteins/metabolism , Flavonoids/metabolism , Saccharomyces cerevisiae/metabolism , Calcium/metabolism , Hydrogen Peroxide/metabolism , Plants/metabolism , Basic Helix-Loop-Helix Leucine Zipper Transcription Factors/genetics , Basic Helix-Loop-Helix Leucine Zipper Transcription Factors/metabolism
11.
ACS Nano ; 17(21): 21153-21169, 2023 11 14.
Article in English | MEDLINE | ID: mdl-37921421

ABSTRACT

Innate and adaptive immunity is important for initiating and maintaining immune function. The nucleotide-binding oligomerization domain-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome serves as a checkpoint in innate and adaptive immunity, promoting the secretion of pro-inflammatory cytokines and gasdermin D-mediated pyroptosis. As a highly inflammatory form of cell death distinct from apoptosis, pyroptosis can trigger immunogenic cell death and promote systemic immune responses in solid tumors. Previous studies proposed that NLRP3 was activated by translocation to the mitochondria. However, a recent authoritative study has challenged this model and proved that the Golgi apparatus might be a prerequisite for the activation of NLRP3. In this study, we first developed a Golgi apparatus-targeted photodynamic strategy to induce the activation of NLRP3 by precisely locating organelles. We found that Golgi apparatus-targeted photodynamic therapy could significantly upregulate NLRP3 expression to promote the subsequent release of intracellular proinflammatory contents such as IL-1ß or IL-18, creating an inflammatory storm to enhance innate immunity. Moreover, this acute NLRP3 upregulation also activated its downstream classical caspase-1-dependent pyroptosis to enhance tumor immunogenicity, triggering adaptive immunity. Pyroptosis eventually led to immunogenic cell death, promoted the maturation of dendritic cells, and effectively activated antitumor immunity and long-lived immune memory. Overall, this Golgi apparatus-targeted strategy provided molecular insights into the occurrence of immunogenic pyroptosis and offered a platform to remodel the tumor microenvironment.


Subject(s)
NLR Family, Pyrin Domain-Containing 3 Protein , Pyroptosis , Inflammasomes/metabolism , Immunity, Innate , Golgi Apparatus/metabolism , Interleukin-1beta , Caspase 1/metabolism
12.
Front Plant Sci ; 14: 1269090, 2023.
Article in English | MEDLINE | ID: mdl-37780524

ABSTRACT

Fruit ripening is a crucial stage in quality development, influenced by a diverse array of internal and external factors. Among these factors, epigenetic regulation holds significant importance and has garnered substantial research attention in recent years. Here, this review aims to discuss the breakthrough in epigenetic regulation of tomato (Solanum lycopersicum) fruit ripening, including DNA methylation, N6-Methyladenosine mRNA modification, histone demethylation/deacetylation, and non-coding RNA. Through this brief review, we seek to enhance our understanding of the regulatory mechanisms governing tomato fruit ripening, while providing fresh insights for the precise modulation of these mechanisms.

13.
Plants (Basel) ; 12(19)2023 Sep 25.
Article in English | MEDLINE | ID: mdl-37836119

ABSTRACT

As an important member of the plant receptor-like kinases, Catharanthus roseus receptor-like kinase 1-like (CrRLK1L) plays vital roles in plant growth and development, as well as biotic and abiotic stress response. Numerous CrRLK1Ls have been identified and analyzed in various plant species, while our knowledge about eggplant (Solanum melongena L.) CrRLK1Ls is still scarce. Utilizing state-of-the-art genomic data, we conducted the first genome-wide identification and analysis of CrRLK1L proteins in eggplant. In this study, 32 CrRLK1L proteins were identified and analyzed in eggplant. A subsequent gene structure and protein domain analysis showed that the identified eggplant CrRLK1Ls possessed typical features of CrRLK1Ls. A subcellular localization prediction demonstrated that these proteins mostly localized on the plasma membrane. A collinearity analysis showed that some eggplant CrRLK1L genes had predicted intraspecies or interspecies evolutionary duplication events. Promoter analysis suggests that eggplant CrRLK1Ls may be involved in plant hormone signaling, host-pathogen interactions, and environmental responses. Based on transcriptomic gene expression analysis, it is indicated that eggplant CrRLK1Ls may be involved in the resistance response of eggplant to Botrytis cinerea. Together, these results will give us a theoretical foundation and guidance for elaborating the biological functions of CrRLK1Ls in eggplant growth, development, and resistance response.

14.
ACS Nano ; 17(18): 17858-17872, 2023 09 26.
Article in English | MEDLINE | ID: mdl-37656882

ABSTRACT

Replicating the controlled nanofibrillar architecture of collagenous tissue represents a promising approach in the design of tendon replacements that have tissue-mimicking biomechanics─outstanding mechanical strength and toughness, defect tolerance, and fatigue and fracture resistance. Guided by this principle, a fibrous artificial tendon (FAT) was constructed in the present study using an engineering strategy inspired by the fibrillation of a naturally spun silk protein. This bioinspired FAT featured a highly ordered molecular and nanofibrillar architecture similar to that of soft collagenous tissue, which exhibited the mechanical and fracture characteristics of tendons. Such similarities provided the motivation to investigate FAT for applications in Achilles tendon defect repair. In vitro cellular morphology and expression of tendon-related genes in cell culture and in vivo modeling of tendon injury clearly revealed that the highly oriented nanofibrils in the FAT substantially promoted the expression of tendon-related genes combined with the Achilles tendon structure and function. These results provide confidence about the potential clinical applications of the FAT.


Subject(s)
Tissue Engineering , Tissue Scaffolds , Tissue Scaffolds/chemistry , Tissue Engineering/methods , Regeneration , Tendons , Silk/chemistry
15.
Adv Healthc Mater ; 12(32): e2301724, 2023 Dec.
Article in English | MEDLINE | ID: mdl-37767893

ABSTRACT

The bone matrix has distinct architecture and biochemistry which present a barrier to synthesizing bone-mimetic regenerative scaffolds. To mimic the natural structures and components of bone, biomimetic structural decellularized extracellular matrix (ECM)/regenerated silk fibroin (RSF) scaffolds incorporated with magnetic nanoparticles (MNP) are prepared using a facile synthetic methodology. The ECM/RSF/MNP scaffold is a hierarchically organized and interconnected porous structure with silk fibroin twined on the collagen nanofibers. The scaffold demonstrates saturation magnetization due to the presence of MNP, along with good cytocompatibility. Moreover, the ß-sheet crystalline domain of RSF and the chelated MNP could mimic the deposition of hydroxyapatite and enhance compressive modulus of the scaffold by ≈20%. The results indicate that an external static magnetic field (SMF) with a magnetic responsive scaffold effectively promotes cell migration, osteogenic differentiation, neogenesis of endotheliocytes in vitro, and new bone formation in a critical-size femur defect rat model. RNA sequencing reveals that the molecular mechanisms underlying this osteogenic effect involve calsequestrin-2-mediated Ca2+ release from the endoplasmic reticulum to activate Ca2+ /calmodulin/calmodulin-dependent kinase II signaling axis. Collectively, bionic magnetic scaffolds with SMF stimulation provide a potent strategy for bone regeneration through internal structural cues, biochemical composition, and external physical stimulation on intracellular Ca2+ homeostasis.


Subject(s)
Fibroins , Tissue Scaffolds , Rats , Animals , Tissue Scaffolds/chemistry , Fibroins/chemistry , Osteogenesis , Calcium , Biomimetics , Calmodulin , Bone Regeneration/physiology , Magnetic Phenomena , Tissue Engineering/methods
16.
Nat Commun ; 14(1): 4628, 2023 08 02.
Article in English | MEDLINE | ID: mdl-37532754

ABSTRACT

Chemotherapy remains as the first-choice treatment option for triple-negative breast cancer (TNBC). However, the limited tumor penetration and low cellular internalization efficiency of current nanocarrier-based systems impede the access of anticancer drugs to TNBC with dense stroma and thereby greatly restricts clinical therapeutic efficacy, especially for TNBC bone metastasis. In this work, biomimetic head/hollow tail nanorobots were designed through a site-selective superassembly strategy. We show that nanorobots enable efficient remodeling of the dense tumor stromal microenvironments (TSM) for deep tumor penetration. Furthermore, the self-movement ability and spiky head markedly promote interfacial cellular uptake efficacy, transvascular extravasation, and intratumoral penetration. These nanorobots, which integrate deep tumor penetration, active cellular internalization, near-infrared (NIR) light-responsive release, and photothermal therapy capacities into a single nanodevice efficiently suppress tumor growth in a bone metastasis female mouse model of TNBC and also demonstrate potent antitumor efficacy in three different subcutaneous tumor models.


Subject(s)
Hyperthermia, Induced , Nanoparticles , Triple Negative Breast Neoplasms , Animals , Humans , Mice , Female , Triple Negative Breast Neoplasms/therapy , Triple Negative Breast Neoplasms/pathology , Biomimetics , Cell Line, Tumor , Phototherapy , Tumor Microenvironment
17.
ACS Biomater Sci Eng ; 9(9): 5293-5303, 2023 09 11.
Article in English | MEDLINE | ID: mdl-37606611

ABSTRACT

L-poly(lactic acid) (PLLA) is a biodegradable material with multiple biomedical application potentials, especially as a membrane for guided bone regeneration. In terms of its low strength and poor osteogenic activity, improving these two properties is the key to resolve the limitations of PLLA for bone-associated applications. Herein, an orientation-strengthening technology (OST) was developed to reinforce PLLA's mechanical strength by introducing biocompatible ß-tricalcium phosphate (ß-TCP) to improve the crystallinity of PLLA, allowing for the formation of a highly oriented architecture to acquire an advanced membrane with high mechanical property. Furthermore, the addition of ß-TCP nanoparticles significantly promotes the osteogenic activity of the composites. The tensile strength of the membrane containing 5 wt % ß-TCP was 220 MPa, which was 4-folds that of the native polylactic acid fabricated via the conventional method. The oriented microstructure enhanced both the mechanical strength and the osteogenic activity of the material. The parallel grooves on the material surface are similar to the mineralized collagen fibers on the bone surface, which promoted the growth and differentiation of osteoblasts, with ß-TCP further contributing to the osteoconductive effect. The combination of ß-TCP and orientation-strengthening effect endows the material with higher mechanical properties and bioactivities, which provides an advanced manufacturing strategy for the preparation of PLLA-based materials for bone repair.


Subject(s)
Bone Regeneration , Osteogenesis , Calcium Phosphates/pharmacology , Lactic Acid
19.
Indian J Hematol Blood Transfus ; 39(3): 371-375, 2023 Jul.
Article in English | MEDLINE | ID: mdl-37304473

ABSTRACT

To assess the diagnostic value of circ-ANAPC7 expression levels in MDS and its risk stratification. This is a retrospective observational study. This study enrolled 125 patients diagnosed with MDS and divided them into five groups according to IPSS-R (very high group, 25; high group, 25; intermediate group, 25; low group, 25; and very low group, 25), and 25 patients with IDA were studied as control group from our bone marrow cell bank. Bone marrow cell were used as material in this study to measure the expression level of circ-ANAPC7 by qRT-PCR. An evaluation of diagnostic value was conducted using ROC curves. Circ-ANAPC7 expression levels were 5.623 ± 4.483, 28.396 ± 12.938, 91.867 ± 37.010, 202.525 ± 54.911, 337.633 ± 86.013, and 502.269 ± 98.410 from the control group to the very high group, respectively (p < 0.05). Circ-ANAPC7 expression was gradually upregulated with the risk stratification of MDS. The AUCs of circ-ANAPC7 were 0.973, 0.996, 0.951, 0.920, and 0.907 in the control group/very low group, very low group/low group, low group/intermediate group, intermediate group/high group, and high group/very high group, respectively. In this study, the expression level of circ-ANAPC7 was found to be a promising biomarker for MDS. It may be added to the scoring system to better identify risk groups.

20.
Molecules ; 28(9)2023 Apr 25.
Article in English | MEDLINE | ID: mdl-37175103

ABSTRACT

The aroma, taste, and flavour profiles of mango cultivars vary, directly influencing their marketability and consumer acceptance. In this study, we explored the effects of volatile organic compounds (VOCs) on the distinct aromas of two mango cultivars during storage using GC-IMS and HS-SPME-GC-MS combined with OPLS-DA analysis. Our findings revealed that the terpene and aldehyde contents were higher in the 'Tainong' mango cultivar, compared to the 'Hongyu' mango, while the ester content was lower. The aroma was attributed to the presence of terpinolene, 2-nonenal, delta-carene, and alpha-phellandrene in the early stages of storage, and later-between 5 and 11 days-to ethyl acetate, ethyl butyrate, and ethyl propanoate. Further analysis of characteristic VOCs using OPLS-DA demonstrated and explained the strong grassy aroma of the 'Tainong' mango, and the strong fruity and sweet aromas of the 'Hongyu' mango. Additionally, esters mainly accumulated during the later periods of storage, especially propyl butyrate, which was produced and accumulated when fruit quality deteriorated in the later storage period. Our study provides a theoretical basis for detecting mango VOCs during storage to determine the appropriate marketing time for the two mango cultivars and enables informed consumer choice.


Subject(s)
Mangifera , Volatile Organic Compounds , Odorants/analysis , Taste , Gas Chromatography-Mass Spectrometry , Taste Perception , Flavoring Agents , Volatile Organic Compounds/analysis , Esters
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