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2.
Odontology ; 2024 Jul 03.
Artículo en Inglés | MEDLINE | ID: mdl-38961043

RESUMEN

Periodontitis (PD) is a multifactorial inflammatory disease associated with periodontopathic bacteria. Lysine-specific demethylase 1 (LSD1), a type of histone demethylase, has been implicated in the modulation of the inflammatory response process in oral diseases by binding to miRNA targets. This study investigates the molecular mechanisms by which miRNA binds to LSD1 and its subsequent effect on osteogenic differentiation. First, human periodontal ligament stem cells (hPDLSCs) were isolated, cultured, and characterized. These cells were then subjected to lipopolysaccharide (LPS) treatment to induce inflammation, after which osteogenic differentiation was initiated. qPCR and western blot were employed to monitor changes in LSD1 expression. Subsequently, LSD1 was silenced in hPDLSCs to evaluate its impact on osteogenic differentiation. Through bioinformatics and dual luciferase reporter assay, miR-708-3p was predicted and confirmed as a target miRNA of LSD1. Subsequently, miR-708-3p expression was assessed, and its role in hPDLSCs in PD was evaluated through overexpression. Using chromatin immunoprecipitation (ChIP) and western blot assay, we explored the potential regulation of osterix (OSX) transcription by miR-708-3p and LSD1 via di-methylated H3K4 (H3K4me2). Finally, we investigated the role of OSX in hPDLSCs. Following LPS treatment of hPDLSCs, the expression of LSD1 increased, but this trend was reversed upon the induction of osteogenic differentiation. Silencing LSD1 strengthened the osteogenic differentiation of hPDLSCs. miR-708-3p was found to directly bind to and negatively regulate LSD1, leading to the repression of OSX transcription through demethylation of H3K4me2. Moreover, overexpression of miR-708-3p was found to promote hPDLSCs osteogenic differentiation in inflammatory microenvironment. However, the protective effect was partially attenuated by reduced expression of OSX. Our findings indicate that miR-708-3p targetedly regulates LSD1 to enhance OSX transcription via H3K4me2 methylation, ultimately promoting hPDLSCs osteogenic differentiation.

4.
J Cell Mol Med ; 28(5): e18083, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38393307

RESUMEN

The connection between head and neck squamous cell carcinoma (HNSC) and M2 tumour-associated macrophages is not yet fully understood. We gathered gene expression profiles and clinical data from HNSC patients in the TCGA database. Using Consensus Clustering, we categorized these patients into M2 macrophage-related clusters. We developed a M2 macrophage-related signature (MRS) through statistical analyses. Additionally, we assessed gene expression in HNSC cells using single-cell sequencing data (GSE139324). We identified three distinct M2 macrophage-related clusters in HNSC, each with different prognostic outcomes and immune characteristics. Patients with different MRS profiles exhibited variations in immune infiltration, genetic mutations and prognosis. FCGR2A may play a role in creating an immunosuppressive tumour microenvironment and could potentially serve as a therapeutic target for HNSC. Our study demonstrated that M2 macrophage-related genes significantly impact the development and progression of HNSC. The M2 macrophage-related model offered a more comprehensive assessment of HNSC patient prognosis, genetic mutations and immune features. FCGR2A was implicated in immunosuppressive microenvironments and may hold promise for the development of novel immunotherapeutic strategies for HNSC.


Asunto(s)
Regulación Neoplásica de la Expresión Génica , Macrófagos , RNA-Seq , Análisis de la Célula Individual , Carcinoma de Células Escamosas de Cabeza y Cuello , Microambiente Tumoral , Humanos , Análisis de la Célula Individual/métodos , Carcinoma de Células Escamosas de Cabeza y Cuello/genética , Carcinoma de Células Escamosas de Cabeza y Cuello/inmunología , Carcinoma de Células Escamosas de Cabeza y Cuello/patología , Macrófagos/metabolismo , Macrófagos/inmunología , Microambiente Tumoral/genética , Microambiente Tumoral/inmunología , Pronóstico , RNA-Seq/métodos , Neoplasias de Cabeza y Cuello/genética , Neoplasias de Cabeza y Cuello/inmunología , Neoplasias de Cabeza y Cuello/patología , Receptores de IgG/genética , Receptores de IgG/metabolismo , Perfilación de la Expresión Génica , Mutación , Transcriptoma/genética , Masculino , Femenino , Análisis de Expresión Génica de una Sola Célula
5.
J Nanobiotechnology ; 21(1): 488, 2023 Dec 18.
Artículo en Inglés | MEDLINE | ID: mdl-38105218

RESUMEN

BACKGROUND: Lung cancer is a highly prevalent malignancy and has the highest mortality rate among all tumors due to lymph node metastasis. Bone marrow and umbilical cord-derived mesenchymal stem cells (MSCs) have demonstrated tumor-suppressive effects on lung cancer. This study investigated the effects of DPSC lysate on proliferation, apoptosis, migration and invasion of cancer cells were studied in vivo and in vitro. METHODS: The proliferation, apoptosis, and migration/metastasis were evaluated by cell counting kit-8 assay, Annexin-V and propidium iodide staining, and the transwell assay, respectively. The expression levels of apoptosis-, cell cycle-, migration-, and adhesion-related mRNA and proteins were measured by qRT-PCR and western blot. The level and mRNA expression of tumor markers carcino embryonic antigen (CEA), neuron-specific enolase (NSE), and squamous cell carcinoma (SCC) were measured by Enzyme-linked immunosorbent assay (ELISA) and qRT-PCR. Finally, a tumor-bearing mouse model was constructed to observe the tumor-suppressive effect of DPSC lysate after intraperitoneal injection. RESULTS: DPSC lysate decreased the viability of A549 cells and induced apoptosis in lung cancer cells. Western blot confirmed that levels of Caspase-3, Bax, and Bad were increased, and Bcl-2 protein levels were decreased in A549 cells treated with DPSC lysate. In addition, DPSC lysate inhibited the migration and invasion of A549 cells; downregulated key genes of the cell cycle, migration, and adhesion; and significantly suppressed tumor markers. Xenograft results showed that DPSC lysate inhibited tumor growth and reduced tumor weight. CONCLUSIONS: DPSC lysate inhibited proliferation, invasion, and metastasis; promoted apoptosis in lung cancer cells; and suppressed tumor growth- potentially providing a cell-based alternative therapy for lung cancer treatment.


Asunto(s)
Neoplasias Pulmonares , Células Madre Mesenquimatosas , Humanos , Ratones , Animales , Neoplasias Pulmonares/patología , Pulpa Dental/metabolismo , Pulpa Dental/patología , Proliferación Celular , Células Madre Mesenquimatosas/metabolismo , ARN Mensajero/farmacología , Biomarcadores de Tumor , Apoptosis , Movimiento Celular , Línea Celular Tumoral
6.
Front Cell Dev Biol ; 11: 1225449, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37842095

RESUMEN

Introduction: Curcumin has broad application prospects in the prevention and treatment of periodontal diseases. Periodontal ligament stem cell-derived extracellular vesicles (PDLSC-EV) can effectively promote periodontal tissue regeneration and possess good drug delivery capability. Superior pharmacological effects can be exerted using PDLSC-EV as a curcumin carrier. Methods: In the present study, we constructed curcumin-primed PDLSCs-derived extracellular vesicles (Cur-PDLSC-EV) from cell culture supernatants of curcumin-pretreated PDLSCs by ultracentrifugation and investigated their effects on the proliferation, migration, and osteogenic ability of PDLSCs and the corresponding downstream molecular pathways. Results: Both Cur-PDLSC-EV and PDLSC-EV promoted osteoblast proliferation and migration. Compared with PDLSC-EV, Cur-PDLSC-EV possessed a more potent pro-osteogenic ability. Moreover, the improved osteogenesis of Cur-PDLSC-EV was related to the activation of the Wnt/ß-catenin signaling pathway. Conclusion: This study suggests that Cur-PDLSC-EV can promote osteogenic differentiation by activating Wnt/ß-catenin, providing reference bases for the treatment of periodontal diseases.

7.
J Cell Mol Med ; 27(24): 4133-4144, 2023 12.
Artículo en Inglés | MEDLINE | ID: mdl-37864310

RESUMEN

Cisplatin (CDDP) chemoresistance is one of the predominant factors in oral squamous cell carcinoma (OSCC) treatment failure. Uncovering the mechanisms underlying CDDP resistance is of great importance in OSCC therapy. Circular RNAs (circRNAs) are a newly discovered class of noncoding RNAs, which are reported to participate in the progression of various diseases, including cancer. However, the function of circRNAs in CDDP resistance in OSCC remains unclear. Quantitative reverse transcription PCR was used to search for different circRNAs between OSCC cell lines and CDDP-resistant cell lines. The results showed that circ-ILF2 expression was higher in CDDP-resistant OSCC cell lines. The stability of circ-ILF2 was also confirmed using RNase R and actinomycin D assays. Functional experiments, including cytotoxicity, apoptosis and growth rate assays, showed that upregulation of circ-ILF2 contributes to CDDP resistance. Luciferase reporter-gene, RNA pull-down and quantitative real-time PCR (RT-qPCR) assays showed that circ-ILF2 functions as a microRNA sponge for miR-1252. Luciferase reporter assays, RNA pull-down, RT-qPCR and Western blotting showed that miR-1252 directly targeted and regulated the expression of KLF8. Circ-ILF2 plays an important role in CDDP resistance in OSCC. Circ-ILF2 exerts its function through the miR-1252/KLF8 pathway. In addition, tumour-associated macrophages (TAM) play important roles in cancer progressions, our results showed that circ-ILF2 in OSCC cells induced the M2 polarization of macrophages which provided new thoughts on immunotherapy. Our results suggest that circ-ILF2 may represent a potential therapeutic target in CDDP-resistant OSCC.


Asunto(s)
Cisplatino , Resistencia a Antineoplásicos , ARN Circular , Carcinoma de Células Escamosas de Cabeza y Cuello , ARN Circular/genética , ARN Circular/metabolismo , Cisplatino/farmacología , Resistencia a Antineoplásicos/efectos de los fármacos , Resistencia a Antineoplásicos/genética , MicroARNs/metabolismo , Línea Celular Tumoral , Regulación Neoplásica de la Expresión Génica , Factores de Transcripción de Tipo Kruppel/genética , Factores de Transcripción de Tipo Kruppel/metabolismo , Macrófagos/metabolismo , Carcinoma de Células Escamosas de Cabeza y Cuello/genética , Carcinoma de Células Escamosas de Cabeza y Cuello/fisiopatología , Polaridad Celular/genética , Humanos
8.
J Cell Mol Med ; 28(5): e17888, 2023 Aug 09.
Artículo en Inglés | MEDLINE | ID: mdl-37556099

RESUMEN

Oral squamous cell carcinoma (OSCC) is a type of tumour found in the cavity that is characterized by differentiation and metastasis to the lymph nodes. Although diagnosis strategy and clinical treatment have recently improved, the outcomes for OSCC patients remain unsatisfactory. This study verified the characteristics of circPUM1 in OSCC cells, subsequently generating dysregulated circPUM1 cell models, showing that circPUM1 promoted chemoresistance and natural killer (NK) cell toxicity. Furthermore, the transcription factor SP2 regulated the expression of circPUM1 in OSCC cells, circPUM1 acted as a molecular sponge for miR-770-5p. Moreover, Nucleosome Assembly Protein 1 Like 1 (NAP1L1) is a downstream target for miR-770-5p and essential for circPUM1-mediated cisplatin resistance and NK cell cytotoxicity in OSCC cells. The network composed of SP2, circPUM1, miR-770-5p and NAP1L1 in OSCC appears to be a promising avenue for the development of novel targets for diagnosing or treating OSCC.

9.
J Appl Oral Sci ; 31: e20230158, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37646717

RESUMEN

OBJECTIVE: This study aimed to develop a pro-angiogenic hydrogel with in situ gelation ability for alveolar bone defects repair. METHODOLOGY: Silk fibroin was chemically modified by Glycidyl Methacrylate (GMA), which was evaluated by proton nuclear magnetic resonance (1H-NMR). Then, the photo-crosslinking ability of the modified silk fibroin was assessed. Scratch and transwell-based migration assays were conducted to investigate the effect of the photo-crosslinked silk fibroin hydrogel on the migration of human umbilical vein endothelial cells (HUVECs). In vitro angiogenesis was conducted to examine whether the photo-crosslinked silk fibroin hydrogel would affect the tube formation ability of HUVECs. Finally, subcutaneous implantation experiments were conducted to further examine the pro-angiogenic ability of the photo-crosslinked silk fibroin hydrogel, in which the CD31 and α-smooth muscle actin (α-SMA) were stained to assess neovascularization. The tumor necrosis factor-α (TNF-α) and interleukin-1ß (IL-1ß) were also stained to evaluate inflammatory responses after implantation. RESULTS: GMA successfully modified the silk fibroin, which we verified by our 1H-NMR and in vitro photo-crosslinking experiment. Scratch and transwell-based migration assays proved that the photo-crosslinked silk fibroin hydrogel promoted HUVEC migration. The hydrogel also enhanced the tube formation of HUVECs in similar rates to Matrigel®. After subcutaneous implantation in rats for one week, the hydrogel enhanced neovascularization without triggering inflammatory responses. CONCLUSION: This study found that photo-crosslinked silk fibroin hydrogel showed pro-angiogenic and inflammation inhibitory abilities. Its photo-crosslinking ability makes it suitable for matching irregular alveolar bone defects. Thus, the photo-crosslinkable silk fibroin-derived hydrogel is a potential candidate for constructing scaffolds for alveolar bone regeneration.


Asunto(s)
Fibroínas , Hidrogeles , Humanos , Animales , Ratas , Regeneración Ósea , Células Endoteliales de la Vena Umbilical Humana
10.
Cell Prolif ; 56(3): e13373, 2023 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-36519208

RESUMEN

The Epstein-Barr virus (EBV) is involved in the carcinogenesis of gastric cancer (GC) upon infection of normal cell and induces a highly variable composition of the tumour microenvironment (TME). However, systematic bioinformatics analysis of key genes associated with EBV regulation of immune infiltration is still lacking. In the present study, the TCGA and GEO databases were recruited to analyse the association between EBV infection and the profile of immune infiltration in GC. The weighted gene co-expression analysis (WGCNA) was applied to shed light on the key gene modules associated with EBV-associated immune infiltration in GC. 204 GC tissues were used to analysed the expression of key hub genes by using the immunohistochemical method. Real-time PCR was used to evaluate the association between the expression of EBV latent/lytic genes and key immune infiltration genes. Our results suggested that EBV infection changed the TME of GC mainly regulates the TIICs. The top three hub genes of blue (GBP1, IRF1, and LAP3) and brown (BIN2, ITGAL, and LILRB1) modules as representative genes were associated with EBV infection and GC immune infiltration. Furthermore, EBV-encoded LMP1 expression is account for the overexpression of GBP1 and IRF1. EBV infection significantly changes the TME of GC, and the activation of key immune genes was more dependent on the invasiveness of the whole EBV virion instead of single EBV latent/lytic gene expression.


Asunto(s)
Carcinoma , Infecciones por Virus de Epstein-Barr , Neoplasias Gástricas , Humanos , Herpesvirus Humano 4/genética , Infecciones por Virus de Epstein-Barr/complicaciones , Infecciones por Virus de Epstein-Barr/genética , Neoplasias Gástricas/patología , Microambiente Tumoral
11.
Oral Dis ; 29(3): 1137-1148, 2023 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-34739163

RESUMEN

OBJECTIVE: Periodontitis is a chronic inflammation of periodontal tissues. This study is expected to assess the effect of LSD1 on the osteogenic differentiation of hPDLSCs in periodontitis. METHODS: hPDLSCs were separated, cultivated, and identified, and then treated by LPS to induce inflammatory microenvironment and subjected to osteogenic differentiation. Subsequently, LSD1 expression was determined, and then silenced to assess its effect on hPDLSCs. Next, the binding relation between LSD1 and miR-590-3p was analyzed. miR-590-3p expression was detected and then overexpressed to evaluate its role in hPDLSCs in periodontitis. Afterward, the relation between LSD1 and OSX was analyzed. H3K4me2 level and OSX transcription were measured, and the role of H3K4me2 was determined. Additionally, the role of OSX in hPDLSCs was verified. RESULTS: LSD1 was poorly expressed after osteogenic differentiation of hPDLSCs while it was rescued upon LPS induction. The osteogenic differentiation of hPDLSC in periodontitis was strengthened upon LSD1 downregulation. Besides, miR-590-3p targeted LSD1 transcription, and LSD1 inhibited OSX transcription via H3K4me2 demethylation. miR-590-3p overexpression improved osteogenic differentiation of hPDLSCs in periodontitis. But this improvement was annulled by OSX inhibition. CONCLUSION: miR-590-3p targeted LSD1 transcription and upregulated H3K4me2 methylation to promote OSX transcription, thereby encouraging osteogenic differentiation of hPDLSCs in periodontitis.


Asunto(s)
MicroARNs , Periodontitis , Humanos , Diferenciación Celular , Células Cultivadas , Histona Demetilasas/genética , Histona Demetilasas/metabolismo , Lipopolisacáridos/farmacología , MicroARNs/genética , MicroARNs/metabolismo , Osteogénesis/genética , Ligamento Periodontal , Periodontitis/genética , Periodontitis/metabolismo , Células Madre
12.
J. appl. oral sci ; J. appl. oral sci;31: e20230158, 2023. graf
Artículo en Inglés | LILACS-Express | LILACS | ID: biblio-1506563

RESUMEN

Abstract Objective: This study aimed to develop a pro-angiogenic hydrogel with in situ gelation ability for alveolar bone defects repair. Methodology: Silk fibroin was chemically modified by Glycidyl Methacrylate (GMA), which was evaluated by proton nuclear magnetic resonance (1H-NMR). Then, the photo-crosslinking ability of the modified silk fibroin was assessed. Scratch and transwell-based migration assays were conducted to investigate the effect of the photo-crosslinked silk fibroin hydrogel on the migration of human umbilical vein endothelial cells (HUVECs). In vitro angiogenesis was conducted to examine whether the photo-crosslinked silk fibroin hydrogel would affect the tube formation ability of HUVECs. Finally, subcutaneous implantation experiments were conducted to further examine the pro-angiogenic ability of the photo-crosslinked silk fibroin hydrogel, in which the CD31 and α-smooth muscle actin (α-SMA) were stained to assess neovascularization. The tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) were also stained to evaluate inflammatory responses after implantation. Results: GMA successfully modified the silk fibroin, which we verified by our 1H-NMR and in vitro photo-crosslinking experiment. Scratch and transwell-based migration assays proved that the photo-crosslinked silk fibroin hydrogel promoted HUVEC migration. The hydrogel also enhanced the tube formation of HUVECs in similar rates to Matrigel®. After subcutaneous implantation in rats for one week, the hydrogel enhanced neovascularization without triggering inflammatory responses. Conclusion: This study found that photo-crosslinked silk fibroin hydrogel showed pro-angiogenic and inflammation inhibitory abilities. Its photo-crosslinking ability makes it suitable for matching irregular alveolar bone defects. Thus, the photo-crosslinkable silk fibroin-derived hydrogel is a potential candidate for constructing scaffolds for alveolar bone regeneration.

13.
Front Bioeng Biotechnol ; 10: 1025155, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36440435

RESUMEN

Orally administered colon-targeted delivery vehicles are of major importance in the treatment of inflammatory bowel disease (IBD). However, it remains a challenge to maintain the integrity of such delivery vehicles during treatment, particularly in the gastric environment, which may cause untimely drug release before reaching the targeted colon. Herein, an oral colon-targeted drug delivery system (OCDDS) based on acetylated konjac glucomannan (AceKGM) has been developed in this work, which accomplishes colonic localization release and targets local inflammatory macrophages. The AceKGM nanoparticle-loading curcumin (Cur) was successfully fabricated by emulsion solvent evaporation techniques. DLS, AFM, and SEM were used in order to evaluate the nanoparticles' diameter as well as their in vitro drug release profile, and reactive oxygen species (ROS) scavenging results showed that the OCDDS considerably retained the activity of Cur treated with simulated gastric fluid (SGF) and controllably released in simulated intestinal fluid (SIF). In addition, the adhesion experiment results indicated that the nanoparticle could accumulate on the colonic macrophages. Evaluations in colitis mice showed that the treatment significantly alleviated the symptoms of colitis by decreasing the local level of myeloperoxidase (MPO) and the disease activity index (DAI) score in mice. In summary, the results of our research demonstrate that Cur-AceKGM nanoparticles exhibit significantly improved therapeutic efficacy compared to orally administered free Cur and can be developed as an effective drug delivery vehicle for IBD treatment.

14.
Oral Dis ; 2022 Sep 08.
Artículo en Inglés | MEDLINE | ID: mdl-36076350

RESUMEN

OBJECTIVE: Periodontitis is characterized by alveolar bone injury and absorption, with high incidence and poor treatment effect. Proliferation, migration, differentiation and apoptosis of osteoblasts are identified as key factors during the regeneration of alveolar bone tissue processes. Periodontal ligament stem cells (PDLSCs) have been proved to be a possible candidate for the treatment of periodontitis due to its multiple advantages, such as increasing the regenerative capacity of bone tissue. However, the effect of exosomes derived from PDLSCs (PDLSC-Exo) on osteoblasts remains to be further studied. METHODS AND MATERIALS: In this work, cell proliferation, migration, osteogenic differentiation, and H2 O2 -induced apoptosis were detected after cells were exposed to PDLSC-Exo by CCK-8, scratch wound assay, alizarin red S and alkaline phosphatase staining, real-time PCR, flow cytometry, tunel assay, and so on. Moreover, the activation of PI3K/AKT and MEK/ERK signaling pathways was evaluated by western blotting. RESULTS: We found that PDLSC-Exo are capable of promoting hFOB1.19 cell proliferation, migration and osteogenic differentiation, inhibiting H2 O2 -induced apoptosis, and activating the PI3K/AKT and MEK/ERK signaling pathways. CONCLUSION: These results suggest that PDLSC-Exo may be a promising therapeutic for osteoblastic damage.

15.
J Oncol ; 2022: 7574458, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36016581

RESUMEN

Oral squamous cell carcinoma (OSCC) is one of the most lethal cancers worldwide. The high morbidity and mortality of OSCC are a great burden to global health-care systems. Therefore it is important to understand the underlying molecular mechanisms of OSCC initiation and progression. This study aimed to investigate the role of circMAT2B in OSCC progression and its molecular mechanisms. First, the expression and circularization of circMAT2B in OSCC cells were verified. Subsequently, knockdown of circMAT2B was shown to inhibit OSCC cell proliferation, migration, invasion, and the Warburg effect. Bioinformatics prediction, RNA-pull down, and luciferase reporter gene assays led to the identification of a novel TEAD1/circMAT2B/miR-942-5p/HSPD1 axis in OSCC progression. In conclusion, the novel TEAD1/circMAT2B/miR-942-5p/HSPD1 axis is a potential target for OSCC.

16.
Cell Prolif ; 55(10): e13293, 2022 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-35822247

RESUMEN

OBJECTIVES: As a result of the current limitation of therapeutic strategies, the repair and regeneration of oviduct injuries required an alternative treatment. We present a novel approach to treat oviduct injuries through a dental pulp stem cells (DPSCs)-based therapy. MATERIALS AND METHODS: In vitro and in vivo models have been established. Immunofluorescence staining, flow cytometry and enzyme-linked immunosorbent assay (ELISA) analysis were used to investigate the features and angiogenic properties of DPSCs, as well as their impact on macrophages, in vitro. For the in vivo experiment with female SD rat model, immunohistochemical staining and ELISA analysis were used to assess the effects of DPSCs on the repair and regeneration of damaged oviducts. RESULTS: The present data showed that intraperitoneal injection of DPSCs reduced the expression of IL-6 and TNF-α to inhibit the immunoreaction in injured sites, as well as increased the expression of VEGF to promote the in situ formation of vessel-like structures, thus the repair and recovery process could be initiated. CONCLUSIONS: We concluded that DPSCs-based therapy could be a novel potential technique for restoring the structure and function of damaged oviduct by enhancing immuno-regulated effect and promoting angiogenic property.


Asunto(s)
Células Madre , Factor A de Crecimiento Endotelial Vascular , Animales , Diferenciación Celular , Proliferación Celular , Células Cultivadas , Pulpa Dental/metabolismo , Femenino , Humanos , Inmunomodulación , Interleucina-6/metabolismo , Oviductos/metabolismo , Ratas , Ratas Sprague-Dawley , Factor de Necrosis Tumoral alfa/metabolismo , Factor A de Crecimiento Endotelial Vascular/metabolismo
17.
Int J Biol Macromol ; 218: 335-345, 2022 Oct 01.
Artículo en Inglés | MEDLINE | ID: mdl-35870629

RESUMEN

Chitosan-based nanogels are effective carriers for drug delivery due to their biocompatibility and biodegradability. However, the chemically cross-linked nanogels usually require complicated procedures or tough conditions. Herein, we report a simple approach to generate chitosan-based nanogels by photo-crosslinking of poor solvent-induced nanoaggregates without requiring any emulsifying agent, catalyst, or external crosslinker. O-nitrobenzyl alcohol-modified carboxymethyl chitosan was synthesized and self-crosslinked into the nanogels in a mixed solution of ethanol and water under 365 nm light irradiation due to UV-induced primary amine and o-nitrobenzyl alcohol cyclization. The nanogels (CMC-NBA NPs) and lactobionic acid-decorated nanogels (LACMC-NBA NPs) displayed a uniform diameter (~200 nm) and excellent stability under physiological conditions. Notably, the nanogels exhibited a high loading content (~28 %) due to π-π stacking and electrostatic interactions between doxorubicin (DOX) and the carriers. These DOX-loaded nanogels showed rapid drug release under slightly acidic conditions. The cell and animal experiments confirmed that LACMC-NBA NPs increased cellular uptake, improved cytotoxicity in tumor cells, and enhanced growth inhibition in vivo than CMC-NBA NPs. Thus, these photo-crosslinked nanogels possess great potential for DOX delivery.


Asunto(s)
Quitosano , Animales , Quitosano/química , Doxorrubicina/química , Doxorrubicina/farmacología , Portadores de Fármacos/química , Geles , Concentración de Iones de Hidrógeno , Nanogeles
18.
Front Cell Dev Biol ; 10: 888598, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35663398

RESUMEN

Objective: To explore the repair effect of the prepared drug-loaded AM1241 poly(ethylene glycol)-dithiothreitol (PEG-DTT) hydrogel on cranial bone defects in SD rats. Methods: The PEG-DTT hydrogel under borax catalysis was quickly prepared, and the characterization of the material was observed by a scanning electron microscope. The effect of AM1241 on cell activity and bone tissue differentiation was tested. The SD rat model of cranial bone defect was established, and the defect was repaired by injecting the prepared hydrogel into the defect. The defect was divided into four groups, namely, sham group, blank group, PEG-DTT group, and PEG-DTT + AM1241 group. The rats were euthanized, and whole cranial bone was taken out for micro-CT and histological observation. Results: The prepared hydrogel is porous; it is liquid when heated to 80°C and a hydrogel when cooled to 25°C. 5-10 µM AM1241 increased osteoblast activity. A moderate amount of AM1241 can promote osteogenic differentiation. Both the PEG-DTT group and PEG-DTT + AM1241 group showed obvious new bone tissue formation, but the PEG-DTT + AM1241 group had a better effect. In addition, the new bone tissue in the PEG-DTT + AM1241 group was significantly more than that in the other groups. Conclusion: The prepared AM1241-loaded PEG-DTT hydrogel showed a good repair effect on SD rats with cranial bone defects. It can be used as materials for cranial bone repair in SD rats with cranial bone defects, but the repair effect is weaker than that of normal bone. These results provide a theoretical and practical basis for its further clinical application.

19.
J Oncol ; 2022: 7453185, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35586208

RESUMEN

Objectives: Many studies have shown that dysregulation of metabolism contributes to oncogenesis. However, the exact roles of metabolism-related genes (MRGs) in oral squamous cell carcinoma (OSCC) remain unclear. Thus, we aimed to identify a prognostic signature related to MRGs in OSCC. Methods: The gene sequencing data of OSCC samples and the MRG set were downloaded from The Cancer Genome Atlas (TCGA) and the Molecular Signatures Database (MSigDB). The Wilcoxon rank-sum test was used to identify differentially expressed MRGs. Then, a prognostic signature was established by multivariate Cox regression analysis. Finally, prognosis-related MRGs were selected and further validated in OSCC tissues and cell lines. Results: A prognostic signature that included 8 MRGs was constructed. Multiple survival analysis revealed that only HPRT1 might be an independent biomarker and indicator of poor overall survival in OSCC patients. The expression of HPRT1 was then found to be upregulated in OSCC tissues and cell lines, and suppression of HPRT1 gene expression by siRNA inhibited the proliferation, migration, and invasion of OSCC cells in vitro. Conclusions: MRGs play an important role in the development of OSCC. Furthermore, HPRT1 might be an independent biomarker of OSCC and enhance OSCC proliferation, migration, and invasion in vitro; these results emphasize the potential utility of HPRT1 in OSCC therapy.

20.
J Oral Pathol Med ; 51(5): 474-482, 2022 May.
Artículo en Inglés | MEDLINE | ID: mdl-35377493

RESUMEN

BACKGROUND: Oral submucosal fibrosis (OSF) is a precancerous condition that closely related to the habit of chewing betel nut. The OSF patients of 3%-19% may develop cancer, and this probability is increasing year by year. Epigenetics modifications have been reported as part of the pathogenesis of OSF. However, in OSF field, the role and mechanism of arecoline-induced activation of transforming growth factor ß (TGF-ß) signaling on N6-methyladenosine (m6A) modification remain unclear. In this study, we investigated the effect and mechanism of arecoline on m6A modification. METHODS: MeRIP-Seq and RNA-seq were performed in arecoline-stimulated cells. Quantitative polymerase chain reaction and western blot were performed to detect the expression of m6A writers and erasers. CCK-8 and flow cytometry analyses were performed to measure the cell viability and apoptosis. RESULTS: m6A level was increased in OSF tissues compared to normal tissues; arecoline promoted the m6A methyltransferase Mettl3 and Mettl14 through TGF-ß. MeRIP-seq and RNA-seq analyses found that MYC was the target gene of Mettl14. In addition, Mettl14 silence reversed the effects of arecoline on cell proliferation and apoptosis in Hacat cells. CONCLUSION: TGF-ß-METTL14-m6A-MYC axis was crucially implicated in arecoline-mediated OSF and may be an effective therapeutic strategy for OSF treatment.


Asunto(s)
Arecolina , Fibrosis de la Submucosa Bucal , Adenosina/análogos & derivados , Adenosina/metabolismo , Arecolina/farmacología , Humanos , Metiltransferasas/genética , Fibrosis de la Submucosa Bucal/inducido químicamente , Fibrosis de la Submucosa Bucal/genética , Factor de Crecimiento Transformador beta
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