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1.
Nanoscale Adv ; 2024 Aug 20.
Artículo en Inglés | MEDLINE | ID: mdl-39247870

RESUMEN

Triple-negative breast cancer (TNBC) is the most malignant subtype of breast cancer, characterized by aggressive malignancy and a poor prognosis. Emerging nanomedicine-based combination therapy represents one of the most promising strategies for combating TNBC. Polypyrrole nanoparticles (PPY) are excellent drug delivery vehicles with outstanding photothermal performances. However, the impact of morphology on PPY's drug loading efficiency and photothermal properties remains largely unexplored. In this study, we propose that pluronic P123 can assist in the synthesis of polypyrrole nanoparticles with rough surfaces (rPPY). During the synthesis, P123 formed small micelles around the nanoparticle surface, which were later removed, resulting in small pits and cavities in rPPY. Subsequently, the rPPY was loaded with the chemotherapy drug gemcitabine (Gem@rPPY) for chemo-photothermal therapy against TNBCs. Our results demonstrate that rPPY exhibited superior photothermal performance and significantly enhanced drug loading efficiency by five times compared to smooth PPY nanoparticles. In vitro assessments confirmed Gem@rPPY's robust photothermal properties by efficiently converting light into heat. Cell culture experiments with 4T1 cells and a TNBC mice model revealed significant tumor suppression upon Gem@rPPY administration, emphasizing its efficacy in inducing apoptosis. Toxicity evaluations demonstrated minimal adverse effects both in vitro and in vivo, highlighting the biocompatibility of Gem@rPPY. Overall, this study introduces a promising combination therapy nanoplatform that underscores the importance of surface engineering to enhance therapeutic outcomes and overcome current limitations in TNBC therapy.

2.
Stem Cells ; 2024 Aug 22.
Artículo en Inglés | MEDLINE | ID: mdl-39169713

RESUMEN

Human dental pulp stem cells (HDPSCs) showed an age-dependent decline in proliferation and differentiation capacity. Decline in proliferation and differentiation capacity affect the dental stromal tissue homeostasis and impair the regenerative capability of HDPSCs. However, which age-correlated proteins regulate the senescence of HDPSCs remain unknown. Our study investigated the proteomic characteristics of HDPSCs isolated from subjects of different ages and explored the molecular mechanism of age-related changes in HDPSCs. Our study showed that the proliferation and osteogenic differentiation of HDPSCs were decreased, while the expression of aging-related genes (p21, p53) and proportion of senescence-associated ß-galactosidase (SA-ß-gal)-positive cells were increased with aging. The bioinformatic analysis identified that significant proteins positively correlated with age were enriched in response to the mTOR signaling pathway (ILK, MAPK3, mTOR, STAT1 and STAT3). We demonstrated that OSU-T315, an inhibitor of integrin-linked kinase (ILK), rejuvenated aged HDPSCs, similar to rapamycin (an inhibitor of mTOR). Treatment with OSU-T315 decreased the expression of aging-related genes (p21, p53) and proportion of SA-ß-gal-positive cells in HDPSCs isolated from old (O-HDPSCs). Additionally, OSU-T315 promoted the osteoblastic differentiation capacity of O-HDPSCs in vitro and bone regeneration of O-HDPSCs in rat calvarial bone defects model. Our study indicated that the proliferation and osteoblastic differentiation of HDPSCs were impaired with aging. Notably, the ILK/AKT/mTOR/STAT1 signaling pathway may be a major factor in the regulation of HDPSC senescence, which help to provide interventions for HDPSC senescence.

3.
Regen Biomater ; 11: rbae082, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39055307

RESUMEN

In recent years, the regulation of the cell microenvironment has opened up new avenues for bone defect repair. Researchers have developed novel biomaterials to influence the behavior of osteoblasts and immune cells by regulating the microenvironment, aiming to achieve efficient bone repair. Mitochondria, as crucial organelles involved in energy conversion, biosynthesis and signal transduction, play a vital role in maintaining bone integrity. Dysfunction of mitochondria can have detrimental effects on the transformation of the immune microenvironment and the differentiation of stem cells, thereby hindering bone tissue regeneration. Consequently, targeted therapy strategies focusing on mitochondria have emerged. This approach offers a wide range of applications and reliable therapeutic effects, thereby providing a new treatment option for complex and refractory bone defect diseases. In recent studies, more biomaterials have been used to restore mitochondrial function and promote positive cell differentiation. The main directions are mitochondrial energy metabolism, mitochondrial biogenesis and mitochondrial quality control. In this review, we investigated the biomaterials used for mitochondria-targeted treatment of bone defect repair in recent years from the perspective of progress and strategies. We also summarized the micro-molecular mechanisms affected by them. Through discussions on energy metabolism, oxidative stress regulation and autophagy regulation, we emphasized the opportunities and challenges faced by mitochondria-targeted biomaterials, providing vital clues for developing a new generation of bone repair materials.

4.
Sci Rep ; 14(1): 93, 2024 01 02.
Artículo en Inglés | MEDLINE | ID: mdl-38168591

RESUMEN

Periodontitis is a chronic inflammatory disease that affects the tissues surrounding the teeth, including the gums and the bones supporting the teeth. Early detection and intervention are crucial for effective management of periodontitis. Our study aims to identify a diagnostic biomarker for periodontitis and explore the pathways associated with the occurrence and development of periodontitis. The expression of gingival tissue from periodontitis and healthy control were downloaded from the Gene Expression Omnibus. The weighted gene co-expression network analysis (WGCNA) were used to analyze module genes associated with periodontitis and DESeq2 were performed to identify differently expressed genes (DEGs) between periodontitis and healthy control. Then the candidate genes were obtained by intersecting the genes from interest modules and DEGs. Functional enrichment analysis was performed using gene ontology and kyoto encyclopedia of gene and genomes, followed by the protein-protein interaction (PPI) network analysis. The hub genes were identified by the cytoCNA plugin in Cytoscape. Finally, immunohistochemical staining of the hub genes was performed to validate the findings. WGCNA analysis found that the expression of the MEblack module was significantly higher in individuals with periodontitis compared to those in the healthy control group. A total of 888 DEGs, including 750 upregulated and 138 downregulated genes, were identified. Finally, 427 candidate genes were identified potentially associated with periodontitis after intersecting the DEGs and the black module genes. Several critical signaling pathways were identified associated with periodontitis by functional enrichment analysis, including cytokine-cytokine receptor interaction, neutrophil extracellular trap formation, Staphylococcus aureus infection, and Interleukin-17 signaling pathway. The PPI network analysis revealed that C-X-C motif chemokine ligand 5 (CXCL5) and C-X-C motif chemokine ligand 6 (CXCL6) could play an important role in the process of periodontitis. The gene expression level of CXCL5 and CXCL6 detected using immunohistochemical verified the findings. In conclusion, we found that CXCL5 and CXCL6 are closely associated with the occurrence of periodontitis. Our present pilot study suggests that CXCL5 and CXCL6 have the potential to be used as a diagnostic biomarker of periodontitis.


Asunto(s)
Redes Reguladoras de Genes , Periodontitis , Humanos , Ligandos , Proyectos Piloto , Periodontitis/diagnóstico , Periodontitis/genética , Perfilación de la Expresión Génica , Biomarcadores , Biología Computacional , Quimiocinas/genética
5.
J Biol Eng ; 17(1): 72, 2023 Nov 23.
Artículo en Inglés | MEDLINE | ID: mdl-37996886

RESUMEN

Biomimetic materials are able to mimic the structure and functional properties of native tissues especially natural oral tissues. They have attracted growing attention for their potential to achieve configurable and functional reconstruction in oral medicine. Though tremendous progress has been made regarding biomimetic materials, significant challenges still remain in terms of controversy on the mechanism of tooth tissue regeneration, lack of options for manufacturing such materials and insufficiency of in vivo experimental tests in related fields. In this review, the biomimetic materials used in oral medicine are summarized systematically, including tooth defect, tooth loss, periodontal diseases and maxillofacial bone defect. Various theoretical foundations of biomimetic materials research are reviewed, introducing the current and pertinent results. The benefits and limitations of these materials are summed up at the same time. Finally, challenges and potential of this field are discussed. This review provides the framework and support for further research in addition to giving a generally novel and fundamental basis for the utilization of biomimetic materials in the future.

6.
Front Pharmacol ; 14: 1269096, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-38313074

RESUMEN

Breast cancer is one of the most common female malignant tumors today and represents a serious health risk for women. Although the survival rate and quality of life of patients with breast cancer are improving with the continuous development of medical technology, metastasis, recurrence, and drug resistance of breast cancer remain a significant problem. Huaier, a traditional Chinese medicine (TCM) fungus, is a type of Sophora embolism fungus growing on old Sophora stems. The polysaccharides of Trametes robiniophila Murr (PS-T) are the main active ingredient of Huaier. There is increasing evidence that Huaier has great potential in breast cancer treatment, and its anti-cancer mechanism may be related to a variety of biological activities, such as the inhibition of cell proliferation, metastasis, tumor angiogenesis, the promotion of cancer cell death, and regulation of tumor-specific immunity. There is growing evidence that Huaier may be effective in the clinical treatment of breast cancer. This review systematically summarizes the basic and clinical studies on the use of Huaier in the treatment of breast cancer, providing useful information to guide the clinical application of Huaier and future clinical studies.

7.
J Fungi (Basel) ; 8(11)2022 Nov 20.
Artículo en Inglés | MEDLINE | ID: mdl-36422045

RESUMEN

Arbuscular mycorrhizal (AM) fungi can improve the lead (Pb) tolerance of host plants and accumulate intensive Pb in mycorrhizal roots. However, the detailed contribution of AM fungal extraradical hyphae to the plants' Pb uptake remains unknown. In this study, mulberry (Morus alba) colonized by the AM fungus (Rhizophagus irregularis) with light treatments were linked by fungal extraradical hyphae using a three-compartment system (pot test), and their differences in responding to Pb application were compared. Shading inhibited mulberry photosynthesis and the growth of mulberry. In this study, Pb application did not affect the colonization of R. irregularis when symbiosis had already formed as the root was not exposed to Pb during the colonization and formation of the AM fungal hyphae network. The R. irregularis preferred to transfer more Pb to the unshaded mulberry than to the shaded mulberry, a condition capable of providing more C supply for fungal survival than to low-light mulberry. The Pb transferred through the mycorrhizal pathway to mulberry had low mobility and might be compartmented in the root by R. irregularis until exceeding a threshold. The relatively high expressions of MaABCG16 with high Pb concentrations in plants suggest that MaABCG16 might play an important role in Pb translocation.

8.
Carcinogenesis ; 43(11): 1071-1082, 2022 12 25.
Artículo en Inglés | MEDLINE | ID: mdl-36179220

RESUMEN

Alpha-synuclein (SNCA) is a pathological hallmark of Parkinson's disease, known to be involved in cancer occurrence and development; however, its specific effects in breast cancer remain unknown. Data from 150 patients with breast cancer were retrieved from tissue microarray and analyzed for SNCA protein level using immunohistochemistry. Functional enrichment analysis was performed to investigate the potential role of SNCA in breast cancer. SNCA-mediated inhibition of epithelial-mesenchymal transition (EMT) was confirmed with western blotting. The effects of SNCA on invasion and migration were evaluated using transwell and wound-healing experiments. Furthermore, the potential influence of SNCA expression level on drug sensitivity and tumor infiltration by immune cells was analyzed using the public databases. SNCA is lowly expressed in breast cancer tissues. Besides, in vitro and in vivo experiments, SNCA overexpression blocked EMT and metastasis, and the knockdown of SNCA resulted in the opposite effect. A mouse model of metastasis verified the restriction of metastatic ability in vivo. Further analysis revealed that SNCA enhances sensitivity to commonly used anti-breast tumor drugs and immune cell infiltration. SNCA blocks EMT and metastasis in breast cancer and its expression levels could be useful in predicting the chemosensitivity and evaluating the immune microenvironment in breast cancer.


Asunto(s)
Transición Epitelial-Mesenquimal , Neoplasias , Animales , Ratones , Línea Celular Tumoral , Transición Epitelial-Mesenquimal/genética , Sinucleínas , Pronóstico , Movimiento Celular/genética , alfa-Sinucleína/farmacología
9.
Cell Biosci ; 11(1): 170, 2021 Sep 04.
Artículo en Inglés | MEDLINE | ID: mdl-34481526

RESUMEN

BACKGROUND: Triple-negative breast cancer (TNBC) is the most aggressive subtype of breast cancer, and the targeted therapies are lacking for this type of cancer. We previously demonstrated that Huaier effectively improve 5-year OS and DFS in stage III TNBC patients, and the polysaccharides of Huaier (PS-T) have been identified as the major components of Huaier. However, the mechanisms of anti-tumor action of PS-T is unclear. This study aimed to investigate the effect of PS-T on TNBC cell invasion and migration. RESULTS: This study showed that PS-T inhibited cell invasion and migration both in vitro and in vivo by inducing autophagy to suppress epithelial-mesenchymal transition (EMT). Autophagy inhibitor LY294002 or knockdown of ATG5 suppressed the inhibitory effects of PS-T. In addition, as a key transcription factor controlling EMT initiation, Snail was found to be degraded by PS-T induced autophagy. In addition, overexpression of Snail reversed the inhibitory effects of PS-T. Furthermore, it was confirmed that the expression of Snail was inversely correlated with LC3 and associated with poor prognosis using immunohistochemistry and TCGA database analysis, respectively. CONCLUSIONS: This study demonstrated that PS-T could inhibit EMT in breast cancer cells by inducing autophagy to degrade Snail protein, thus improving the prognosis of TNBC, offering potential treatment alternatives for TNBC patients.

10.
Acta Biomater ; 119: 444-457, 2021 01 01.
Artículo en Inglés | MEDLINE | ID: mdl-33129987

RESUMEN

Dual-functional regulation for angiogenesis and osteogenesis is crucial for desired bone regeneration especially in large-sized bone defects. Exosomes have been demonstrated to facilitate bone regeneration through enhanced osteogenesis and angiogenesis. Moreover, functional stimulation to mesenchymal stromal cells (MSCs) was reported to further boost the pro-angiogenic ability of exosomes secreted. However, whether the stimulation by bioactive trace elements of biomaterials could enhance pro-angiogenic capability of bone marrow stromal cells (BMSCs)-derived exosomes and consequently promote in vivo vascularized bone regeneration has not been investigated. In this study, strontium-substituted calcium silicate (Sr-CS) was chosen and the biological function of BMSCs-derived exosomes after Sr-CS stimulation (Sr-CS-Exo) was systemically investigated. The results showed that Sr-CS-Exo could significantly promote in vitro angiogenesis of human umbilical vein endothelial cells (HUVECs), which might be attributed to elevated pro-angiogenic miR-146a cargos and inhibition of Smad4 and NF2 proteins. Moreover, the in vivo study confirmed that Sr-CS-Exo possessed superior pro-angiogenic ability, which contributed to the accelerated developmental vascularization in zebrafish along with the neovascularization and bone regeneration in rat distal femur defects. Our findings may provide new insights into the mechanisms underlying Sr-containing biomaterials-induced angiogenesis, and for the first time, proposed that Sr-CS-Exo may serve as the candidate engineered-exosomes with dual-functional regulation for angiogenesis and osteogenesis in vascularized bone regeneration.


Asunto(s)
Compuestos de Calcio , Cerámica , Células Madre Mesenquimatosas , MicroARNs , Osteogénesis , Estroncio , Animales , Células de la Médula Ósea , Cerámica/farmacología , Células Endoteliales de la Vena Umbilical Humana , Humanos , Neovascularización Fisiológica , Ratas , Silicatos , Estroncio/farmacología , Pez Cebra
11.
Biomed Microdevices ; 22(2): 24, 2020 03 12.
Artículo en Inglés | MEDLINE | ID: mdl-32166408

RESUMEN

The porous TiO2 coatings containing Ca/P/Ag were separately prepared on titanium (Ti) surface by one-step (micro-arc oxidation) and two-step methods (micro-arc oxidation and cathodic deposition), and then their surface morphology, composition, biological and antibacterial properties were compared. The results showed that the porous coatings containing Ca/P/Ag achieved by different methods showed similar surface morphology and elemental composition, however, by one-step method, silver existed in the coating as silver phosphate, while in the coatings prepared by two-step method, silver existed as metallic silver. Although both coatings showed excellent antibacterial property (the antimicrobial rate is over 99.9%), the surface coating prepared by one-step method had a more suitable release curve of Ag. In addition, the surface coating prepared by one-step method also presented better biological property, which was due to its enhanced surface roughness and hydrophilicity. Combining with its easy operation and long-term antibacterial property, its prospect for clinical application is more promising.


Asunto(s)
Antibacterianos/química , Antibacterianos/farmacología , Calcio/química , Fósforo/química , Plata/química , Titanio/química , Titanio/farmacología , Electrodos , Oxidación-Reducción , Porosidad , Propiedades de Superficie
12.
Biomater Sci ; 7(10): 4075-4087, 2019 Oct 01.
Artículo en Inglés | MEDLINE | ID: mdl-31355387

RESUMEN

Titanium (Ti) is a widely used implant material in clinics; however, failures still frequently occur due to its bioinertness and poor antibacterial capability. Post-implant infections most likely occur within the first two weeks. Thereafter, the host immune system lowers the infection risk, and biosafety becomes the first consideration. Therefore, endowing biomedical Ti with a time-dependent bactericidal effect is of considerable interest. In this study, Ag nanoparticles (NPs) as the antibacterial agent were incorporated deeply into TiO2 nanotubes prepared on the sandblasted and etched (SLA) Ti surface. The incorporated Ag NPs were verified to automatically transform from a free state to an immobilized state, rendering the constructed platform exhibit a self-adjusting antibacterial effect. It showed strong "release bactericidal" activity in the early phase that gradually changed to the "contact bactericidal" ability. Such a smart alteration could satisfy the varied antibacterial requirements in different periods after biomaterial implantation. Moreover, the nanotubular structure could accelerate apatite formation and improve cell adhesion and proliferation when compared with those of commercially used SLA implants. Based on these results, it can be concluded that Ag-NP-incorporated micro-nanostructured Ti has worthwhile biological and time-dependent antibacterial properties, and it can have promising applications in orthopedics, dentistry, and fabrication of other biomedical devices.


Asunto(s)
Antibacterianos/administración & dosificación , Nanopartículas del Metal/administración & dosificación , Nanotubos , Plata/administración & dosificación , Titanio/administración & dosificación , Animales , Línea Celular , Proliferación Celular/efectos de los fármacos , Escherichia coli/efectos de los fármacos , Escherichia coli/crecimiento & desarrollo , Ratones , Staphylococcus aureus/efectos de los fármacos , Staphylococcus aureus/crecimiento & desarrollo
13.
J Mater Sci Mater Med ; 25(1): 199-205, 2014 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-24113889

RESUMEN

Anodic oxidation was applied to produce nanostructures on the surface of titanium (Ti) implants. The bioactivity of the Ti implants was evaluated by simulated body fluid soaking test. The biocompatibility was investigated by in vitro cell culture test. The results showed that bone-like apatite was formed on the anodized Ti surface, but not on the as-polished Ti surface after immersion in simulated body fluid for 2 weeks. Cells cultured on the anodized Ti surface showed enhanced cell adhesion and proliferation, compared to those cultured on the as-polished Ti surface. Based on these results, it can be concluded that anodic oxidation improved the bioactivity and biocompatibility of Ti surface, which was attributed to the formation of nanostructures as well as the nanostructure induced high surface roughness and hydrophilicity.


Asunto(s)
Materiales Biocompatibles Revestidos/química , Nanoestructuras/química , Prótesis e Implantes , Titanio/química , Células 3T3 , Animales , Adhesión Celular , Proliferación Celular , Células Cultivadas , Fluoruros/química , Interacciones Hidrofóbicas e Hidrofílicas , Ensayo de Materiales , Ratones , Nanoporos/ultraestructura , Nanoestructuras/ultraestructura , Oseointegración , Oxidación-Reducción , Propiedades de Superficie
14.
Appl Biochem Biotechnol ; 172(3): 1147-57, 2014 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-24218183

RESUMEN

Laccases from fungal origin are typically unstable at high temperatures and alkaline conditions. This characteristic limits their practical applications. In this study, a new bacterial strain exhibiting laccase activity was isolated from raw fennel honey samples and identified as Bacillus subtilis X1. The CotA-laccase gene was cloned from strain X1 and efficiently expressed in Escherichia coli in a biologically active form. The purified recombinant laccase demonstrated an extensive pH range for catalyzing substrates and high stability toward alkaline pH and high temperatures. No loss of laccase activity was observed at pH 9.0 after 10 days of incubation, and approximately 21 % of the initial activity was detected after 10 h at 80 °C. Two anthraquinonic dyes (reactive blue 4 and reactive yellow brown) and two azo dyes (reactive red 11 and reactive brilliant orange) could be partially decolorized by purified laccase in the absence of a mediator. The decolorization process was efficiently promoted when methylsyringate was present, with more than 90 % of color removal occurring in 3 h at pH 7.0 or 9.0. These unusual properties indicated a high potential of the novel CotA-laccase for industrial applications.


Asunto(s)
Bacillus subtilis/enzimología , Biodegradación Ambiental , Lacasa/genética , Estabilidad Proteica , Compuestos Azo/química , Clonación Molecular , Calor , Concentración de Iones de Hidrógeno , Lacasa/química
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