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1.
Cancer Sci ; 2024 May 12.
Artigo em Inglês | MEDLINE | ID: mdl-38735837

RESUMO

Metaplastic breast cancer is a rare, aggressive, and chemotherapy-resistant subtype of breast cancers, accounting for less than 1% of invasive breast cancers, characterized by adenocarcinoma with spindle cells, squamous epithelium, and/or mesenchymal tissue differentiation. The majority of metaplastic breast cancers exhibit the characteristics of triple-negative breast cancer and have unfavorable prognoses with a lower survival rate. This subtype often displays gene alterations in the PI3K/AKT pathway, Wnt/ß-catenin pathway, and cell cycle dysregulation and demonstrates epithelial-mesenchymal transition, immune response changes, TP53 mutation, EGFR amplification, and so on. Currently, the optimal treatment of metaplastic breast cancer remains uncertain. This article provides a comprehensive review on the clinical features, molecular characteristics, invasion and metastasis patterns, and prognosis of metaplastic breast cancer, as well as recent advancements in treatment strategies.

2.
Small ; : e2402412, 2024 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-38647117

RESUMO

The industrialization of lithium-sulfur (Li-S) batteries faces challenges due to the shuttling effect of lithium polysulfides (LiPSs) and the growth of lithium dendrites. To address these issues, a simple and scalable method is proposed to synthesize 2D membranes comprising a single layer of cubic graphitic cages encased with few-layer, curved MoS2. The distinctive 2D architecture is achieved by confining the epitaxial growth of MoS2 within the open cages of a 2D-ordered mesoporous graphitic framework (MGF), resulting in MoS2@MGF heterostructures with abundant sulfur vacancies. The experimental and theoretical studies establish that these MoS2@MGF membranes can act as a multifunctional interlayer in Li-S batteries to boost their comprehensive performance. The inclusion of the MoS2@MGF interlayer facilitates the trapping and conversion kinetics of LiPSs, preventing their shuttling effect, while simultaneously promoting uniform lithium deposition to inhibit dendrite growth. As a result, Li-S batteries with the MoS2@MGF interlayer exhibit high electrochemical performance even under high sulfur loading and lean electrolyte conditions. This work highlights the potential of designing advanced MoS2-encased heterostructures as interlayers, offering a viable solution to the current limitations plaguing Li-S batteries.

3.
Anticancer Drugs ; 33(7): 686-690, 2022 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-35324515

RESUMO

Thymic lymphoepithelioma-like carcinoma (LELC) is a rare primary malignant neoplasm originating from the thymus. Thymic LELC diagnosis is often terminal when diagnosed, some patients have lost the opportunity for surgery. Platinum- and anthracycline-based systemic chemotherapy are the first-line treatment plan; however, there is no clear consensus on therapy when first-line treatment fails because of the lack of cases of advanced thymic LELC. Here was a rare case of advanced thymic LELC with bone marrow metastasis at relapse, which is reported in a patient who responded well to toripalimab combined with anlotinib therapy. The treatment showed tolerable toxicity with good antitumor activity in the patient. As far as we know, this is the first case that the combination of toripalimab with anlotinib is effective in controlling advanced thymic LELC with bone marrow metastasis. The case reports represent an essential means by which an effective therapy for advanced thymic LELC may not be practical given the low frequency of a thymic LELC with multiple metastases.


Assuntos
Neoplasias da Medula Óssea , Neoplasias Ósseas , Carcinoma de Células Escamosas , Humanos , Imunoterapia , Platina
4.
Pharm Res ; 36(11): 157, 2019 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-31493066

RESUMO

PURPOSE: Although pharmacokinetic (PK) interaction effects of methotrexate (MTX) on adalimumab have been found, the mechanism of these effects is still unclear. In this work, effects of MTX on the concentration of neonatal Fc receptor (FcRn) and the role of FcRn in the interaction between MTX and adalimumab were investigated. METHODS: The experiment was performed in rats whose FcRn had normal physiological function and also in rats whose FcRn was blocked with FcRn antibody. Rats were randomly assigned to receive placebo or 0.2 mg/kg MTX orally every week while taking one abdominal subcutaneous injection of 0.5 mg/kg adalimumab. The FcRn concentration in tissues and the PK parameters of adalimumab were compared between MTX-treated and placebo groups. RESULTS: In rats with normally functioning FcRn, the concentrations of FcRn were significantly increased in the liver (F=105.5, p=0.000) and kidney (F=996.312, p=0.000) after treatment with MTX, and the clearance (CL/F) of adalimumab was decreased accordingly (F=4.423, p=0.048). However, in rats injected with FcRn antibody, the concentrations of FcRn in MTX-treated rats were close to that of the placebo rats in the tissues of the liver (F=1.279, p=0.268) and kidney (F=0.661, p=0.424). The CL/F of adalimumab in rats was also not affected by MTX (F=0.002, p=0.961). CONCLUSIONS: FcRn may play a vital role in the interaction between adalimumab and MTX.


Assuntos
Adalimumab/farmacocinética , Antígenos de Histocompatibilidade Classe I/metabolismo , Metotrexato/metabolismo , Receptores Fc/metabolismo , Adalimumab/administração & dosagem , Animais , Feminino , Humanos , Injeções Subcutâneas , Rim/metabolismo , Fígado/metabolismo , Masculino , Metotrexato/administração & dosagem , Metotrexato/farmacologia , Ratos Sprague-Dawley
5.
Clin Exp Pharmacol Physiol ; 45(7): 643-651, 2018 07.
Artigo em Inglês | MEDLINE | ID: mdl-29436715

RESUMO

Etanercept (ETN) is a widely used anti-tumour necrosis factor-α (TNF-α) agent, which relieves the symptoms of ankylosing spondylitis (AS) by binding to TNF-α to inhibit its inflammation effects. In this study, the effect of TNF-α level on ETN clearance (CL) was investigated, and the TNF-α concentration was initially set as a correction factor for allometric scaling to improve the predictions of individual ETN CLs. Individual ETN CLs and TNF-α concentrations in healthy volunteers and patients with AS were determined by performing ETN pharmacokinetic studies in the two cohorts. Accordingly, individual ETN CLs in both healthy volunteers and patients with AS were predicted from data of two animal species using different methods, including simple allometric scaling, scaling with a correction factor of maximum life span potential or brain weight, and scaling with a correction factor of the TNF-α concentration. The accuracies of such predictions were evaluated by the percentage errors. Consequently, increased TNF-α concentration was shown to improve ETN CL, by comparing both ETN CLs and TNF-α concentrations between healthy volunteers and patients with AS. More importantly, better predictions of individual ETN CLs were achieved in patients with AS using allometric scaling with TNF-α concentration as the correction factor. In conclusion, in vivo levels of TNF-α can affect ETN CL, and allometric scaling corrected with the TNF-α concentration can be used to estimate the individual CLs of anti-TNF-α monoclonal antibodies based on preclinical data.


Assuntos
Etanercepte/farmacocinética , Espondilite Anquilosante/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Adulto , Animais , Feminino , Voluntários Saudáveis , Humanos , Masculino , Pessoa de Meia-Idade , Ratos , Distribuição Tecidual , Adulto Jovem
6.
Regen Biomater ; 11: rbae050, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38872841

RESUMO

Pulp regeneration remains a crucial target in the preservation of natural dentition. Using decellularized extracellular matrix is an appropriate approach to mimic natural microenvironment and facilitate tissue regeneration. In this study, we attempted to obtain decellularized extracellular matrix from periapical lesion (PL-dECM) and evaluate its bioactive effects. The decellularization process yielded translucent and viscous PL-dECM, meeting the standard requirements for decellularization efficiency. Proteomic sequencing revealed that the PL-dECM retained essential extracellular matrix components and numerous bioactive factors. The PL-dECM conditioned medium could enhance the proliferation and migration ability of periapical lesion-derived stem cells (PLDSCs) in a dose-dependent manner. Culturing PLDSCs on PL-dECM slices improved odontogenic/angiogenic ability compared to the type I collagen group. In vivo, the PL-dECM demonstrated a sustained supportive effect on PLDSCs and promoted odontogenic/angiogenic differentiation. Both in vitro and in vivo studies illustrated that PL-dECM served as an effective scaffold for pulp tissue engineering, providing valuable insights into PLDSCs differentiation. These findings pave avenues for the clinical application of dECM's in situ transplantation for regenerative endodontics.

7.
J Hazard Mater ; 466: 133636, 2024 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-38309166

RESUMO

The toxic Cr(VI) from industrial wastewater pose serious threat to the human beings and eco-systems. To reduce the operation processes and enhance the removal efficiency of Cr(VI), targeted design of functionalized material is critical in practical applications. Herein, we developed a one-step strategy for simultaneous Cr(VI) reduction and total Cr capture by a novel phytate modified zero-valent iron (PA-ZVI). The reaction kinetics of Cr(VI) removal by PA-ZVI (0.2225 min-1) was 53 times higher compared to ZVI (0.0042 min-1). The Fe(0) content on the surface of PA-ZVI increased from 2.2% to 15.6% compared to ZVI. Meanwhile, Cr(VI) was liable to adsorb on the surface of PA-ZVI due to its lower adsorption energy compared with the original ZVI (-2.09 eV vs -0.85 eV). The incorporation of the phytate ligand promoted electron transfer from iron core to Cr(VI), leading to the rapid in-situ reduction of Cr(VI) adsorbed on the surface of PA-ZVI to Cr(III). PA-ZVI exhibited a satisfactory performance for Cr(VI) removal at a broad pH range (3-11) and in the presence of coexisting ions and humic acid. Moreover, the reactor with the addition of PA-ZVI achieved more than 90% Cr(VI) removal within 72 h in continuous flow experiments. The feasibility of PA-ZVI for the removal of Cr(VI) is also validated in authentic wastewater. This work provides novel ZVI materials that can effectively address decontamination challenges from Cr(VI) pollution.

8.
Zool Res ; 45(2): 367-380, 2024 Mar 18.
Artigo em Inglês | MEDLINE | ID: mdl-38485506

RESUMO

Osteoporosis is a prevalent metabolic bone disease. While drug therapy is essential to prevent bone loss in osteoporotic patients, current treatments are limited by side effects and high costs, necessitating the development of more effective and safer targeted therapies. Utilizing a zebrafish ( Danio rerio) larval model of osteoporosis, we explored the influence of the metabolite spermine on bone homeostasis. Results showed that spermine exhibited dual activity in osteoporotic zebrafish larvae by increasing bone formation and decreasing bone resorption. Spermine not only demonstrated excellent biosafety but also mitigated prednisolone-induced embryonic neurotoxicity and cardiotoxicity. Notably, spermine showcased protective attributes in the nervous systems of both zebrafish embryos and larvae. At the molecular level, Rac1 was identified as playing a pivotal role in mediating the anti-osteoporotic effects of spermine, with P53 potentially acting downstream of Rac1. These findings were confirmed using mouse ( Mus musculus) models, in which spermine not only ameliorated osteoporosis but also promoted bone formation and mineralization under healthy conditions, suggesting strong potential as a bone-strengthening agent. This study underscores the beneficial role of spermine in osteoporotic bone homeostasis and skeletal system development, highlighting pivotal molecular mediators. Given their efficacy and safety, human endogenous metabolites like spermine are promising candidates for new anti-osteoporotic drug development and daily bone-fortifying agents.


Assuntos
Osteoporose , Doenças dos Roedores , Humanos , Camundongos , Animais , Peixe-Zebra , Espermina/uso terapêutico , Osteoporose/tratamento farmacológico , Osteoporose/metabolismo , Osteoporose/prevenção & controle , Osteoporose/veterinária , Prednisolona/efeitos adversos , Glucocorticoides , Doenças dos Roedores/induzido quimicamente , Doenças dos Roedores/tratamento farmacológico
9.
Transl Oncol ; 28: 101614, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36584488

RESUMO

OBJECTIVE: Follicular lymphoma (FL) occurring progression within 24 months (POD24) after initial immunochemotherapy has poor prognosis. GLUT1 affects glycolysis within tumor microenvironment (TME) and promotes tumor progression. However, its specific mediated mechanism remains unclear in FL. METHODS: Baseline GLUT1 expression, infiltrations of M2 macrophage, and CD8+ T-cells were assessed by immunohistochemistry in FL with POD24 and long-term remission respectively. The spatial features of TME were assessed by MIBI-TOF and proteomics. Predictive immunophenotypes for POD24 occurrence was analyzed by random forest algorithm. The lactate production and the induction of M2 macrophages were detected when GLUT1 was transfected or knocked down in DOHH2. The activation of PI3K/Akt/mTOR signaling in DOHH2 and WSU-FSCCL cells co-cultured with induced inhibitory immunocytes was tracked by western blotting. RESULTS: The FL with POD24 exhibited higher baseline GLUT1 expression and increased infiltration of various inhibitory immunocytes. Spatial signatures of 69 immunophenotypes could predict POD24 occurrence. The activation of PI3K/ Akt /mTOR signaling pathway was not significant in both groups. The supernatant of DOHH2-GLUT1 cells which had more lactate content could induce more M2-type macrophages than that of DOHH2/siRNA GLUT1 cells. When co-cultured with exhausted CD8+ T cells, M2-type macrophages and Tregs, compared with WSU-FSCCL cells, DOHH2 cells with high GLUT1 expression induced more M2-type macrophages and was triggered activation of PI3K/ Akt /mTOR signaling pathway. CONCLUSION: Tumor cells overexpressing GLUT1 could domesticate immunocytes to form an immunosuppressive TME, which promotes occurrence of POD24 and gradually activates PI3K/ Akt /mTOR pathway of tumor cells in FL. SIGNIFICANCE: Tumor cells overexpressing GLUT1 could domesticate immunocytes to form an immunosuppressive microenvironment, which in turn promoted the growth of tumor cells and was related to the progression of disease within 24 months in FL. Suppressive immunocytes gradually activated PI3K/ Akt /mTOR pathway of tumor cells in later stage. Distinguishing spatial features of immunocytes could well predict POD24 occurrence, hoping to benefit these patients from early anti-metabolism therapy based on GLUT1 in the future.

10.
Front Endocrinol (Lausanne) ; 14: 1154931, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37008900

RESUMO

Objectives: Periodontium regeneration remains a significant challenge in clinics and research, and it is essential to understand the stage-specific biological process in situ. However, differing findings have been reported, and the mechanism has yet to be elucidated. The periodontium of adult mice molars is considered to be stable remodeling tissue. At the same time, the continuously growing incisors and the developing dental follicle (DF) of postnatal mice highly represent fast remodeling tissue. In this study, we attempted to explore different clues of temporal and spatial comparisons to provide improved references for periodontal regeneration. Methods: Periodontal tissues from the developing periodontium (DeP) of postnatal mice, and continuously growing periodontium (CgP) and stable remodeling periodontium (ReP) of adult mice were isolated and compared using RNA sequencing. Based on the Dep and CgP separately compared with the ReP, differentially expressed genes and signaling pathways were analyzed using GO, KEGG databases, and Ingenuity Pathway Analysis (IPA). The results and validation were obtained by immunofluorescence staining and RT-PCR assays. Data were expressed as means ± standard deviation (SD) and analyzed by GraphPad Prism 8 software package, and one-way ANOVA was used to test multiple groups. Results: Principal component analysis showed that the three groups of periodontal tissue were successfully isolated and had distinct expression profiles. A total of 792 and 612 DEGs were identified in the DeP and CgP groups compared with the ReP. Upregulated DEGs in the DeP were closely related to developmental processes, while the CgP showed significantly enhanced cellular energy metabolism. The DeP and CgP showed a common downregulation of the immune response, with activation, migration, and recruitment of immune cells. IPA and further validation jointly suggested that the MyD88/p38 MAPK pathway played an essential regulatory role in periodontium remodeling. Conclusion: Tissue development, energy metabolism, and immune response were critical regulatory processes during periodontal remodeling. Developmental and adult stages of periodontal remodeling showed different expression patterns. These results contribute to a deeper understanding of periodontal development and remodeling and may provide references for periodontal regeneration.


Assuntos
Ligamento Periodontal , Periodonto , Camundongos , Animais , Periodonto/metabolismo , Ligamento Periodontal/metabolismo , Transcriptoma
11.
Front Cell Infect Microbiol ; 13: 1321855, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38125907

RESUMO

Introduction: Microbiota and their interaction with hosts have been of great interest in brain research in recent years. However, the role of oral microbiota in mental illness and the underlying mechanism of oral-brain communication remains elusive. Sleep bruxism (SB) is an oral parafunctional activity related to the nervous system and is considered a risk factor for harmful clinical consequences and severe systemic conditions. Exploring the connection between oral microbiota and sleep bruxism may deepen our understanding of the complex relationship between oral-brain axis and provide insights for treatment. Methods: In this study, salivary samples were collected from 22 individuals with SB and 21 healthy controls, and metagenomics with metabolomics was performed. Nonparametric Wilcoxon test were applied for the statistical analysis between the two groups. Microbial dysbiosis and altered oral metabolites were found in the SB individuals. Results: The characteristic metabolite N-acetylglucosamine (GlcNAc) (VIP=8.4823, P<0.05) was correlated to a statistically lower Streptococcus mitis level in SB individuals. Salivary IFN-g level and IFN-g/IL-4 ratio were detected with significant changes in a chip assay. Amino acid metabolism pathways were upregulated, and the pathway with the largest number of differentially expressed genes is related to amino-tRNA charging pathway, while the most significantly enriched pathway is related to arginine biosynthesis. Neurotransmitter-associated pathways with glutamatergic and GABAergic synapses and cardiovascular system-related pathways were enriched in the SB group. Discussion: These results indicate a possible neuroimmune regulatory network of oral-brain communication in SB, which helps explain the mechanism of the oral microbiome with the host in sleep bruxers and provides a reference for early clinical and therapeutic intervention to improve the diagnosis and treatment of SB and similar diseases.


Assuntos
Bruxismo do Sono , Humanos , Bruxismo do Sono/complicações , Bruxismo do Sono/diagnóstico , Sono , Encéfalo/metabolismo , Fatores de Risco
12.
Heliyon ; 9(8): e18498, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37533997

RESUMO

Purpose: Endocrine resistance hormone receptor-positive (HR+) advanced breast cancer (ABC) is generally insensitive to immunecheckpoint inhibitors (ICIs). This study sought to determine whether PI3Kδ inhibitor could enhance the sensitivity of endocrine resistance HR + advanced BC to ICIs by reducing immune evasion. Methods: Patient-derived HR + ABC xenografts were implanted into immune-humanized NSG mice and subsequently treated with YY20394 (PI3Kδ inhibitor) and camrelizumab. The mice were monitored for tumor progression, biochemical blood indicators, and peripheral blood T-cell subsets. The xenografted tumors were collected at the end of the treatment cycle and subjected to HE staining, immunohistochemistry and protein phosphorylation analysis. Besides, the xenografted tumors were also used to isolate primary breast cancer cells (BCCs) and regulatory T-cells (Tregs), which were subsequently used to evaluate drug sensitivity in vitro. Results: The humanized PDX model showed a favorable initial treatment response to camrelizumab combined with YY20394 and manageable toxicity. YY20394 plus camrelizumab showed a strong inhibitory effect on HR + BC in vivo mediated by suppression of Treg activity and an increased proportion of CD8+ T cells. Mice bearing tumors treated with YY20394 and camrelizumab had less invasion, mitotic figures, and ki67 expression, while having higher IL-12 expression compared with other groups. Mechanistically, YY20394 only effectively inhibited the PI3K pathway and proliferation activity in Tregs but not in BCCs. Conclusion: Our study suggests PI3Kδ inhibitor could the enhance the efficacy of ICIs in HR + BC PDX models by combating immune suppression and provides a feasible approach that may overcome the resistance of ICIs in HR + BC patients.

13.
NPJ Breast Cancer ; 9(1): 57, 2023 Jul 12.
Artigo em Inglês | MEDLINE | ID: mdl-37438419

RESUMO

Some triple-negative breast cancer (TNBC) patients evaluated as Miller-Payne 4 with ypN0 after neoadjuvant chemotherapy (NACT) who have better prognoses should avoid escalation of therapy. We aim to identify these patients by evaluating pretherapeutic spatial distributions of immunophenotypes. Our retrospective study in patients with TNBC assessed as Miller-Payne grade 4/5 with ypN0 showed that Miller-Payne 4 with ypN0 group had poorer 5-year disease-free survival (DFS, 63.8% vs. 83.0%, p = 0.003) and the 5-year overall survival (OS, 71.0% vs. 85.5%, p = 0.007) than Miller-Payne 5 with ypN0 group. High TILs were significantly associated with better DFS and OS in patients with Miller-Payne 4 and ypN0 (both p = 0.016). Spatially, detected by multiplexed ion beam imaging by the time of flight combined with proteomics, tumors assessed as Miller-Payne 4 and ypN0 with good prognosis exhibited an inflamed phenotype, with dominant CD8+ T cells on tumor center, few scattered CD68+ myeloid-derived cells far away from T cells, and deposit of increased activated molecules of lymphocyte. While those with poor prognoses presented excluded phenotypes, with few CD8+ T cells restricted to invasive margins and a high density of CD14+CD68+CD11c+ myeloid cells. A good classifier model based on 29 spatial immunophenotypes was established by the random forest algorithm (AUC = 0.975), for identifying patients with Miller-Payne 4 and ypN0 who had favorable prognoses. We also observed similar signatures in patients with Miller-Payne 5 and ypN0. Taken together, spatial immunophenotypes may assess the prognosis in TNBC patients with Miller-Payne 4 and ypN0 after NACT.

14.
Adv Sci (Weinh) ; 10(25): e2302136, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37400369

RESUMO

Tissue regeneration is regulated by morphological clues of implants in bone defect repair. Engineered morphology can boost regenerative biocascades that conquer challenges such as material bioinertness and pathological microenvironments. Herein, a correlation between the liver extracellular skeleton morphology and the regenerative signaling, namely hepatocyte growth factor receptor (MET), is found to explain the mystery of rapid liver regeneration. Inspired by this unique structure, a biomimetic morphology is prepared on polyetherketoneketone (PEKK) via femtosecond laser etching and sulfonation. The morphology reproduces MET signaling in macrophages, causing positive immunoregulation and optimized osteogenesis. Moreover, the morphological clue activates an anti-inflammatory reserve (arginase-2) to translocate retrogradely from mitochondria to the cytoplasm due to the difference in spatial binding of heat shock protein 70. This translocation enhances oxidative respiration and complex II activity, reprogramming the metabolism of energy and arginine. The importance of MET signaling and arginase-2 in the anti-inflammatory repair of biomimetic scaffolds is also verified via chemical inhibition and gene knockout. Altogether, this study not only provides a novel biomimetic scaffold for osteoporotic bone defect repair that can simulate regenerative signals, but also reveals the significance and feasibility of strategies to mobilize anti-inflammatory reserves in bone regeneration.


Assuntos
Regeneração Óssea , Inflamação , Fígado , Macrófagos , Osseointegração , Osteoporose , Alicerces Teciduais , Animais , Feminino , Camundongos , Ratos , Respiração Celular , Metabolismo Energético , Inflamação/prevenção & controle , Fígado/citologia , Fígado/metabolismo , Macrófagos/metabolismo , Camundongos Endogâmicos C57BL , Mitocôndrias/metabolismo , Osteoporose/metabolismo , Proteínas Proto-Oncogênicas c-met/metabolismo , Ratos Sprague-Dawley , Transdução de Sinais , Alicerces Teciduais/química
15.
Adv Healthc Mater ; 12(22): e2300229, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37186211

RESUMO

Pulp exposure often leads to pulp necrosis, root fractures, and ultimate tooth loss. The repair of the exposure site with pulp capping treatment is of great significance to preserving pulp vitality, but its efficacy is impaired by the low bioactivity of capping materials and cell injuries from the local accumulation of oxidative stress. This study develops a Wnt3a-loaded hydroxyapatite nanowire@mesoporous silica (Wnt3a-HANW@MpSi) core-shell nanocomposite for pulp capping treatments. The ultralong and highly flexible hydroxyapatite nanowires provide the framework for the composites, and the mesoporous silica shell endows the composite with the capacity of efficiently loading/releasing Wnt3a and Si ions. Under in vitro investigation, Wnt3a-HANW@MpSi not only promotes the oxidative stress resistance of dental pulp stem cells (DPSCs), enhances their migration and odontogenic differentiation, but also exhibits superior properties of angiogenesis in vitro. Revealed by the transcriptome analysis, the underlying mechanisms of odontogenic enhancement by Wnt3a-HANW@MpSi are closely related to multiple biological processes and signaling pathways toward pulp/dentin regeneration. Furthermore, an animal model of subcutaneous transplantation demonstrates the significant reinforcement of the formation of dentin-pulp complex-like tissues and blood vessels by Wnt3a-HANW@MpSi in vivo. These results indicate the promising potential of Wnt3a-HANW@MpSi in treatments of dental pulp exposure.

16.
Virulence ; 13(1): 1101-1110, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-35801633

RESUMO

The global pandemic of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus causing COVID-19, has led to more than 170 million confirmed cases in 223 countries and regions, claiming 3,872,457 lives. Some patients with COVID-19 have mild clinical symptoms despite severe respiratory failure, which greatly increases the difficulty of diagnosis and treatment. It is therefore necessary to identify biological characteristics of SARS-CoV-2, screen novel diagnostic and prognostic biomarkers, as well as to explore potential therapeutic targets for COVID-19. In this comprehensive review, we discuss the current published literature on COVID-19. We find that the comprehensive application of genomics, transcriptomics, proteomics and metabolomics is becoming increasingly important in the treatment of COVID-19. Multi-omics analysis platforms are expected to revolutionize the diagnosis and classification of COVID-19. This review aims to provide a reference for diagnosis, surveillance and clinical decision making related to COVID-19.


Assuntos
COVID-19 , COVID-19/diagnóstico , Humanos , Pandemias , SARS-CoV-2
17.
Artigo em Inglês | MEDLINE | ID: mdl-35329253

RESUMO

The healthcare sector throughout the world is identified for its outsized carbon footprint. Despite the mounting importance of employees' pro-environmental behavior (PEB) for decarbonization, the role of PEB in a healthcare context was less emphasized previously, especially in a developing country context. To address this knowledge gap, the current work was carried out to examine the relationship between a hospital's corporate social responsibility (CSR) initiatives and PEB with the mediating effect of environmental-specific transformational leadership (ESTL). At the same time, the conditional indirect effect of altruistic values (AV) was also considered in the above relationship. The data were collected through a questionnaire by employing a paper-pencil method from the hospital employees (n = 293). By considering the structural equation modeling, the hypothesized relationships were validated. The results indicated that CSR directly (ß1 = 0.411) and indirectly, via ESTL, (ß4 = 0.194) influenced the PEB of employees. It was also realized that A.V produced a conditional indirect effect in this relationship (ß5 = 0.268). This work tends to help a hospital to improve its environmental footprint through CSR and ESTL. Moreover, the current work also highlights the role of employees' values (e.g., A.V) to guide the environment-specific behavior of employees.


Assuntos
Liderança , Organizações , Altruísmo , Hospitais , Responsabilidade Social
18.
Adv Mater ; 34(10): e2109145, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-34982834

RESUMO

Self-assembled nanocrystal superlattices represent an emergent class of designer materials with potentially programmable functionalities. The ability to construct hierarchically structured nanocrystal superlattices with tailored geometry and porosity is critical for extending their applications. Here, 2D superlattices comprising monolayer FeP nanoframes are synthesized through a space-confined topochemical transformation approach induced by the Kirkendall effect, using carbon-coated Fe3 O4 nanocube superlattices as a precursor. The particle shape and the close-packed nature of Fe3 O4 nanocubes as well as the interconnected carbon layer network contribute to the topochemical transformation process. The resulting 2D FeP nanoframe superlattices possess several unique and advantageous structural features that are unavailable in conventional 3D nanocrystal superlattices, which make them particularly attractive for catalytic applications. As a proof of concept, such 2D FeP nanoframe superlattices are harnessed as highly efficient and durable electrocatalysts for the hydrogen evolution reaction, the performance of which is superior to that of most FeP-based catalysts reported previously. This topochemical transformation approach is scalable and general, representing a new route of designing hierarchical superlattices with highly open features that cannot be accessible by traditional self-assembly methods.

19.
Int J Oral Sci ; 14(1): 41, 2022 08 10.
Artigo em Inglês | MEDLINE | ID: mdl-35948539

RESUMO

Medication-related osteonecrosis of the jaw (MRONJ) is primarily associated with administering antiresorptive or antiangiogenic drugs. Despite significant research on MRONJ, its pathogenesis and effective treatments are still not fully understood. Animal models can be used to simulate the pathophysiological features of MRONJ, serving as standardized in vivo experimental platforms to explore the pathogenesis and therapies of MRONJ. Rodent models exhibit excellent effectiveness and high reproducibility in mimicking human MRONJ, but classical methods cannot achieve a complete replica of the pathogenesis of MRONJ. Modified rodent models have been reported with improvements for better mimicking of MRONJ onset in clinic. This review summarizes representative classical and modified rodent models of MRONJ created through various combinations of systemic drug induction and local stimulation and discusses their effectiveness and efficiency. Currently, there is a lack of a unified assessment system for MRONJ models, which hinders a standard definition of MRONJ-like lesions in rodents. Therefore, this review comprehensively summarizes assessment systems based on published peer-review articles, including new approaches in gross observation, histological assessments, radiographic assessments, and serological assessments. This review can serve as a reference for model establishment and evaluation in future preclinical studies on MRONJ.


Assuntos
Osteonecrose da Arcada Osseodentária Associada a Difosfonatos , Conservadores da Densidade Óssea , Animais , Osteonecrose da Arcada Osseodentária Associada a Difosfonatos/diagnóstico por imagem , Osteonecrose da Arcada Osseodentária Associada a Difosfonatos/tratamento farmacológico , Conservadores da Densidade Óssea/efeitos adversos , Difosfonatos/uso terapêutico , Humanos , Reprodutibilidade dos Testes , Roedores
20.
Biomater Adv ; 138: 212935, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-35913256

RESUMO

Parthenolide (PTL), a germacrane sesquiterpene lactone extracted from the "Yin" Chinese traditional herb feverfew, has gained interest due to its lethal effects on tumor cells and its pharmacological effects within traditional Chinese medicine theory. To overcome low, non-targeted accumulation and uncontrolled release of PTL administration, a dual-responsive PTL-liposomes@chitosan@gold nanoshells (PTL-Lips@CS@GNS) system was fabricated. Hyperthermia generated under light irradiation in the near-infrared region via local surface plasmon resonance of gold nanoshells induced photothermal therapy, which also stimulated PTL release due to the liposomes gel-to-liquid crystalline phase transition. Additionally, PTL-Lips@CS@GNS exhibited a pH-responsive release in the acidic tumor microenvironment. Collectively, this study provides a realistic strategy for an effective combination of traditional Chinese medicine and current nanotechnology for tumor therapy.


Assuntos
Antineoplásicos , Hipertermia Induzida , Neoplasias , Antineoplásicos/farmacologia , Ouro/química , Humanos , Lipossomos/química , Fototerapia , Sesquiterpenos , Microambiente Tumoral
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