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1.
Environ Sci Technol ; 58(26): 11707-11717, 2024 Jul 02.
Artículo en Inglés | MEDLINE | ID: mdl-38871667

RESUMEN

Antimicrobial resistance (AMR) undermines the United Nations Sustainable Development Goals of good health and well-being. Antibiotics are known to exacerbate AMR, but nonantibiotic antimicrobials, such as quaternary ammonium compounds (QACs), are now emerging as another significant driver of AMR. However, assessing the AMR risks of QACs in complex environmental matrices remains challenging due to the ambiguity in their chemical structures and antibacterial activity. By machine learning prediction and high-resolution mass spectrometric analysis, a list of antibacterial QACs (n = 856) from industrial chemical inventories is compiled, and it leads to the identification of 50 structurally diverse antibacterial QACs in sediments, including traditional hydrocarbon-based compounds and new subclasses that bear additional functional groups, such as choline, ester, betaine, aryl ether, and pyridine. Urban wastewater, aquaculture, and hospital discharges are the main factors influencing QAC distribution patterns in estuarine sediments. Toxic unit calculations and metagenomic analysis revealed that these QACs can influence antibiotic resistance genes (particularly sulfonamide resistance genes) through cross- and coresistances. The potential to influence the AMR is related to their environmental persistence. These results suggest that controlling the source, preventing the co-use of QACs and sulfonamides, and prioritizing control of highly persistent molecules will lead to global stewardship and sustainable use of QACs.


Asunto(s)
Antibacterianos , Estuarios , Aprendizaje Automático , Compuestos de Amonio Cuaternario , Antibacterianos/farmacología , Compuestos de Amonio Cuaternario/química , Espectrometría de Masas , China , Pueblos del Este de Asia
2.
Environ Sci Technol ; 57(49): 20854-20863, 2023 Dec 12.
Artículo en Inglés | MEDLINE | ID: mdl-38010983

RESUMEN

The limited information in existing mass spectral libraries hinders an accurate understanding of the composition, behavior, and toxicity of organic pollutants. In this study, a total of 350 polycyclic aromatic compounds (PACs) in 9 categories were successfully identified in fine particulate matter by gas chromatography high resolution mass spectrometry. Using mass spectra and retention indexes predicted by in silico tools as complementary information, the scope of chemical identification was efficiently expanded by 27%. In addition, quantitative structure-activity relationship models provided toxicity data for over 70% of PACs, facilitating a comprehensive health risk assessment. On the basis of extensive identification, the cumulative noncarcinogenic risk of PACs warranted attention. Meanwhile, the carcinogenic risk of 53 individual analogues was noteworthy. These findings suggest that there is a pressing need for an updated list of priority PACs for routine monitoring and toxicological research since legacy polycyclic aromatic hydrocarbons (PAHs) contributed modestly to the overall abundance (18%) and carcinogenic risk (8%). A toxicological priority index approach was applied for relative chemical ranking considering the environmental occurrence, fate, toxicity, and analytical availability. A list of 39 priority analogues was compiled, which predominantly consisted of high-molecular-weight PAHs and alkyl derivatives. These priority PACs further enhanced source interpretation, and the highest carcinogenic risk was attributed to coal combustion.


Asunto(s)
Contaminantes Atmosféricos , Hidrocarburos Policíclicos Aromáticos , Compuestos Policíclicos , Compuestos Policíclicos/análisis , Contaminantes Atmosféricos/análisis , Flujo de Trabajo , Monitoreo del Ambiente/métodos , Material Particulado/análisis , Medición de Riesgo , China
3.
Nano Lett ; 22(12): 5046-5054, 2022 Jun 22.
Artículo en Inglés | MEDLINE | ID: mdl-35579571

RESUMEN

The rapid development of solid-state lighting technology has attracted much attention for searching efficient and stable luminescent materials, especially the single-component white-light emitter. Here, we adopt a facile ion-doping technology to synthesize vacancy-ordered double perovskite Cs2ZrCl6:Sb. The introduction of Sb3+ ions with a 5s2 active lone pair into Cs2ZrCl6 host stimulates the singlet (blue) and triplet (orange) states emission of Sb3+ ions, and their relative emission intensity can be tuned through the energy transfer from singlet to triplet states. Benefiting from the dual-band emission as a pair of perfect complementary colors, the optimum Cs2ZrCl6:1.5%Sb exhibits a high-quality white emission with a color-rendering index of 96. By employing Cs2ZrCl6:1.5%Sb as the down-conversion phosphor, stable single-component white light-emitting diodes with a record half-lifetime of 2003 h were further fabricated. This study puts forward an effective ion-doping strategy to design single-component white-light emitter, making practical applications of them in lighting technologies a real possibility.

4.
Environ Sci Technol ; 56(23): 16759-16767, 2022 12 06.
Artículo en Inglés | MEDLINE | ID: mdl-36334087

RESUMEN

Benzotriazole UV stabilizers (BZT-UVs), including 2-(3,5-di-tert-amyl-2-hydroxyphenyl)benzotriazole (UV-328) that is currently under consideration for listing under the Stockholm Convention, are applied in many commodities and industrial products. However, limited information is available on the interannual variation of their environmental occurrence. In this study, an all-in-one strategy combining target, suspect, and nontarget screening analysis was established to comprehensively explore the temporal trends of BZT-UVs in mollusks collected from the Chinese Bohai Sea between 2010 and 2018. Significant residue levels of the target analytes were determined with a maximum total concentration of 6.4 × 103 ng/g dry weight. 2-(2-Hydroxy-3-tert-butyl-5-methyl-phenyl)-5-chloro-benzotriazole (UV-326), 5-chloro-2-(3,5-di-tert-butyl-2-hydroxyphenyl)benzotriazole (UV-327), and 2-(2-hydroxy-5-methylphenyl) benzotriazole (UV-P) were the predominant analogues, and UV-328 was the most frequently detected BZT-UV with a detection frequency (DF) of 87%. Whereas five biotransformation products and six impurity-like BZT-UVs were tentatively identified, their low DFs and semi-quantified concentrations suggest that the targeted analytes were the predominant BZT-UVs in the investigated area. A gradual decrease in the total concentrations of BZT-UVs was observed, accompanied by downward trends of the abundant compounds (e.g., UV-326 and UV-P). Consequently, the relative abundance of UV-327 increased because of its consistent environmental presence. These results suggest that continuous monitoring and risk assessment of BZT-UVs other than UV-328 are of importance in China.


Asunto(s)
Monitoreo del Ambiente , Contaminantes Químicos del Agua , Animales , Moluscos , Rayos Ultravioleta , Contaminantes Químicos del Agua/química , China , Océanos y Mares
5.
Environ Sci Technol ; 56(15): 10681-10690, 2022 08 02.
Artículo en Inglés | MEDLINE | ID: mdl-35839457

RESUMEN

Stress from mixtures of synthetic chemicals is among the key issues that have significant adverse impacts on the marine ecosystems. A robust screening workflow integrating toxicological-based ranking schemes is still deficient for comprehensive investigation on the main constituents in chemical mixtures that contribute to the ecological risks. In this study, the presence and compositions of a collection of priority pollutants were monitored by suspect screening analysis of seawater and estuarine water samples from the semiclosed Bohai Sea. In total, 108 organic pollutants in nine use categories were identified. Pesticides, intermediates, plastic additives, and per- and polyfluoroalkyl substances were the extensively detected chemical groups. Varied distribution patterns of the pollutants were illustrated intuitively in distinctive sampling areas by hierarchical cluster analysis, which were mainly influenced by run-off inputs, ocean currents, and chemical use history. Ecological risks of chemicals with quantified residue levels were first assessed by the toxicity-weighted concentration ranking scheme, and pentachlorophenol was found as the main contributor in the investigating areas. By optimization of multiple alternative variables (e.g., instrumental response and detection frequency), extended ranking of all the identified pollutants was plausible under the toxicological priority index framework. Similarity in toxicological endpoints of the prioritized pollutants could further been screened by ToxAlerts. Aromatic amine was highlighted as the most frequently detected structural alert (SA) for genotoxic carcinogenicity and mutagenicity. These findings fully demonstrate rationality of the ranking schemes integrated into the suspect screening analysis for profiling contamination characteristics, assessing ecological risk potentials, and prioritizing SAs.


Asunto(s)
Contaminantes Ambientales , Plaguicidas , Contaminantes Químicos del Agua , Ecosistema , Monitoreo del Ambiente/métodos , Contaminantes Ambientales/análisis , Plaguicidas/toxicidad , Contaminantes Químicos del Agua/análisis , Contaminantes Químicos del Agua/toxicidad
6.
Cell Tissue Res ; 386(3): 445-454, 2021 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-34665321

RESUMEN

Bone remodeling, expressed as bone formation and turnover, is a complex and dynamic process closely related to its form and function. Different events, such as development, aging, and function, play a critical role in bone remodeling and metabolism. The ability of the bone to adapt to new loads and forces has been well known and has proven useful in orthopedics and insightful for research in bone and cell biology. Mechanical stimulation is one of the most important drivers of bone metabolism. Interestingly, different types of forces will have specific consequences in bone remodeling, and their beneficial effects can be traced using different biomarkers. In this narrative review, we summarize the major mediators and events in bone remodeling, focusing on the effects of mechanical stimulation on bone metabolism, cell populations, and ultimately, bone health.


Asunto(s)
Remodelación Ósea/genética , Huesos/metabolismo , Osteoporosis/fisiopatología , Animales , Humanos
7.
Environ Sci Technol ; 55(14): 9508-9517, 2021 07 20.
Artículo en Inglés | MEDLINE | ID: mdl-33764750

RESUMEN

Chemical mixtures in surface waters could have significant impacts on exposure risks to human beings and pollution stress to aquatic system. By suspect screening analysis of high-resolution mass spectrometry data, occurrence, and compositions of ToxCast chemicals were investigated in grab estuarine water samples from a combination of 20 rivers that represents approximately 70% of the total river flow discharge along the east coast of China. In total, 59 ToxCast chemicals in seven use categories were identified, in which pesticides, intermediates, and pharmaceuticals were the abundant analogues. Significant differences in pollutant composition profiles were noticed, which possibly reflected singular release pattern and geographical-relevant usage preference (especially for herbicides and fungicides in the pesticide category). With the aid of tentative quantitative/semiquantitative measurement, essential contributors to the cumulative pollutant mass discharges and aquatic acute toxicity potentials were focused onto few particular chemicals. Existence of transformation products was further explored, which indicated that the fates of the selected parent ToxCast chemicals could be influenced by dominating transformation reactions (e.g., N-dealkylation and hydroxylation) and possible environmental factors (i.e., microbial activity). The results emphasize the necessity of suspect screening analysis for assessing the influence of terrestrial emissions of pollutants to the surrounding environment.


Asunto(s)
Herbicidas , Plaguicidas , Contaminantes Químicos del Agua , China , Monitoreo del Ambiente , Humanos , Plaguicidas/análisis , Ríos , Contaminantes Químicos del Agua/análisis
8.
Cell Mol Biol Lett ; 26(1): 3, 2021 Jan 20.
Artículo en Inglés | MEDLINE | ID: mdl-33472580

RESUMEN

Mesenchymal stem cells (MSCs) show homing capacity towards tumor sites. Numerous reports indicate that they are involved in multiple tumor-promoting processes through several mechanisms, including immunosuppression; stimulation of angiogenesis; transition to cancer-associated fibroblasts; inhibition of cancer cell apoptosis; induction of epithelial-mesenchymal transition (EMT); and increase metastasis and chemoresistance. However, other studies have shown that MSCs suppress tumor growth by suppressing angiogenesis, incrementing inflammatory infiltration, apoptosis and cell cycle arrest, and inhibiting the AKT and Wnt signaling pathways. In this review, we discuss the supportive and suppressive impacts of MSCs on tumor progression and metastasis. We also discuss MSC-based therapeutic strategies for cancer based on their potential for homing to tumor sites.


Asunto(s)
Citocinas/metabolismo , Células Madre Mesenquimatosas/metabolismo , Neoplasias/metabolismo , Neoplasias/patología , Animales , Apoptosis , Humanos , Inmunidad , Neoplasias/inmunología , Microambiente Tumoral/inmunología
9.
Ecotoxicol Environ Saf ; 212: 111968, 2021 Apr 01.
Artículo en Inglés | MEDLINE | ID: mdl-33550083

RESUMEN

Despite the fact that copper (Cu) is a vital micronutrient to maintain body function, high doses of Cu through environmental exposure damage various organs, especially the liver, which is the main metabolic organ. To investigate the influence of long-term Cu-induced toxicity on mitophagy and apoptosis in rat liver, 96 seven-month-old male Sprague-Dawley rats were fed TBCC for 24 weeks. The results revealed that exposure to high Cu concentrations could promote oxidative stress liver injury by increasing the hepatic function index (ALT, AST and ALP) and MDA content, while reducing the activity of antioxidant enzymes (T-SOD, GSH-Px and CAT) related to oxidative stress. Consistent with histopathological observations, proper dietary Cu (15-60 mg/kg) could improve antioxidant stress levels and induce a dose-dependent increase in the mRNA expression of mitophagy-related genes, whereas a high Cu concentration (120 mg/kg) could cause severe liver impairment and ultrastructural changes and a reduction in mitophagosomes, accompanied by downregulation of Atg5, Beclin1, Pink1, Parkin, NIX, P62 and LC3B. The expression of apoptosis-related genes (Bax, Bax/Bcl-2, Caspase3, Cytc and p53) and proteins (Caspase3 and p53) was upregulated with the addition of dietary Cu. The results demonstrated that an appropriate dose of TBCC could improve liver function by promoting mitophagy and Cu enzymes that play antioxidative roles, while the accumulation of excess Cu could induce liver lesions by enhancing apoptosis and inhibiting mitophagy pathways.


Asunto(s)
Cloruros/toxicidad , Cobre/toxicidad , Animales , Antioxidantes/metabolismo , Apoptosis/efectos de los fármacos , Sulfato de Cobre/análisis , Dieta , Hígado/metabolismo , Masculino , Mitofagia/efectos de los fármacos , Estrés Oxidativo/efectos de los fármacos , Ratas , Ratas Sprague-Dawley , Pruebas de Toxicidad Crónica
10.
Cell Biol Toxicol ; 36(6): 517-536, 2020 12.
Artículo en Inglés | MEDLINE | ID: mdl-32875398

RESUMEN

Chemoresistance is a complex phenomenon responsible for failure in response to chemotherapy agents and more than 90% of deaths in cancer patients. MicroRNAs (miRNAs), as a subgroup of non-coding RNAs with lengths between 21 and 25 nucleotides, are involved in various cancer processes like chemoresistance via interacting with their target mRNAs and suppressing their expression. Autophagy is a greatly conserved procedure involving the lysosomal degradation of cytoplasmic contents and organelles to deal with environmental stresses like hypoxia and starvation. Autophagy contributes to response to chemotherapy agents: autophagy can act as a protective mechanism for mediating the resistance in response to chemotherapy or can induce autophagic cell death and mediate the sensitivity to chemotherapy. On the other hand, one of the processes targeted by microRNAs in the regulation of chemoresistance is autophagy. Hence, we studied the literatures on chemoresistance mechanisms, the miRNAs' role in cancer, and the miRNAs' role in chemoresistance by modulating autophagy. Graphical Abstract.


Asunto(s)
Antineoplásicos/uso terapéutico , Autofagia/efectos de los fármacos , Resistencia a Antineoplásicos , MicroARNs/metabolismo , Neoplasias/tratamiento farmacológico , Animales , Resistencia a Antineoplásicos/efectos de los fármacos , Regulación Neoplásica de la Expresión Génica , Humanos , MicroARNs/genética , Neoplasias/genética , Neoplasias/metabolismo , Neoplasias/patología , Transducción de Señal
11.
J Artif Organs ; 23(3): 191-202, 2020 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-32100147

RESUMEN

Recent advances in biomaterial designing techniques offer immense support to tailor biomimetic scaffolds and to engineer the microstructure of biomaterials for triggering bone regeneration in challenging bone defects. The current review presents the different categories of recently explored strontium-integrated biomaterials, including calcium silicate, calcium phosphate, bioglasses and polymer-based synthetic implants along with their in vivo bone formation efficacies and/or in vitro cell responses. The role and significance of controlled drug release scaffold/carrier design in strontium-triggered osteogenesis was also comprehensively described. Furthermore, the effects of stem cells and growth factors on bone remodeling are also elucidated.


Asunto(s)
Materiales Biocompatibles , Regeneración Ósea/fisiología , Osteogénesis/fisiología , Estroncio , Animales , Compuestos de Calcio , Fosfatos de Calcio , Cerámica , Humanos , Silicatos , Células Madre , Andamios del Tejido
12.
Biotechnol Lett ; 41(3): 305-318, 2019 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-30680496

RESUMEN

Mesenchymal stem cells (MSCs), a class of adult stem cells, are considered a promising source for bone regeneration. Although combining MSCs with biomaterial scaffolds offers an interesting clinical strategy for bone tissue engineering, the presence of the scaffolds could induce an undesirable effect on cell-cell interactions. Moreover, before the application of scaffold materials in bone tissue reconstruction, cells must be manipulated with proteolytic enzymes, such as trypsin or dispase that degrade extracellular matrix (ECM) molecules and cell surface proteins, which can result in the cell damage and loss of cellular activity. Therefore, the development of alternative strategies for bone regeneration is required to solve these problems. Recently, a novel tissue engineering technology named 'cell sheet' has been efficaciously utilized in the regeneration of bone, corneal, cardiac, tracheal and periodontal ligament-like tissues. The cell sheet is a layer of cells, which contains intact ECM and cell surface proteins such as growth factor receptors, ion channels and cell-to-cell junction proteins. MSC sheets can be easily fabricated by layering the recovered cell sheets without any scaffolds or complicated manipulation. This review summarizes the current state of the literature regarding the use of MSCs to produce cell sheets and assesses their applicability in bone tissue regeneration and repair.


Asunto(s)
Células Madre Adultas/fisiología , Células Madre Mesenquimatosas/fisiología , Medicina Regenerativa/métodos , Ingeniería de Tejidos/métodos , Animales , Regeneración Ósea , Humanos , Trasplante de Células Madre Mesenquimatosas/métodos
13.
Biochem Biophys Res Commun ; 497(2): 499-505, 2018 03 04.
Artículo en Inglés | MEDLINE | ID: mdl-29432734

RESUMEN

mTOR over-activation is important for human osteosarcoma (OS) tumorigenesis and progression. RES-529 is a mTORC1/2 dual inhibitor. Here, our results show that RES-529 inhibited viability, cell cycle progression and proliferation of the established (U2OS line) and primary human OS cells. RES-529 induced apoptosis activation in OS cells. It was yet non-cytotoxic to OB-6 osteoblastic cells and the primary human osteoblasts. RES-529 disrupted assembling of mTORC1 (mTOR-Raptor association) and mTORC2 (mTOR-Rictor-mLST8 association) in human OS cells, blocking mTORC1/2 activation. Significantly, RES-529 induced reactive oxygen species (ROS) production and mitochondrial depolarization in U2OS cells as well. RES-529-induced anti-OS cell activity was more potent than other known Akt-mTOR inhibitors. In vivo, RES-529 intraperitoneal injection significantly inhibited U2OS xenograft tumor growth in severe combined immunodeficiency (SCID) mice. mTORC1/2 activation in RES-529-treated tumor tissues was largely inhibited. Collectively, the mTOR inhibitor RES-529 efficiently inhibits human OS cell growth in vitro and in vivo.


Asunto(s)
Antineoplásicos/uso terapéutico , Benzopiranos/uso terapéutico , Neoplasias Óseas/tratamiento farmacológico , Diana Mecanicista del Complejo 1 de la Rapamicina/antagonistas & inhibidores , Diana Mecanicista del Complejo 2 de la Rapamicina/antagonistas & inhibidores , Osteosarcoma/tratamiento farmacológico , Inhibidores de Proteínas Quinasas/uso terapéutico , Animales , Antineoplásicos/farmacología , Benzopiranos/farmacología , Neoplasias Óseas/metabolismo , Neoplasias Óseas/patología , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Humanos , Masculino , Diana Mecanicista del Complejo 1 de la Rapamicina/metabolismo , Diana Mecanicista del Complejo 2 de la Rapamicina/metabolismo , Ratones SCID , Terapia Molecular Dirigida , Osteosarcoma/metabolismo , Osteosarcoma/patología , Inhibidores de Proteínas Quinasas/farmacología
14.
Biochem Biophys Res Commun ; 499(4): 913-919, 2018 05 23.
Artículo en Inglés | MEDLINE | ID: mdl-29626476

RESUMEN

Long non-coding RNA (LncRNA) dysregulation is associated with human osteosarcoma (OS) cell progression. Recent studies have characterized a novel but ultra-conserved LncRNA THOR ("Lnc-THOR") as a cancer-specific LncRNA, mediating cell growth. In the current study, we show that Lnc-THOR is expressed in established and primary human OS cells. It is also detected in human OS tissues, but not in the surrounding normal bone tissues. siRNA-induced knockdown or CRSIPR/Cas9-mediated knockout Lnc-THOR significantly inhibited human OS cell survival and proliferation. Insulin-like growth factor 2 mRNA-binding protein 1 (IGF2BP1) target mRNAs, including IGF2, GLI1 and CD44, were downregulated in Lnc-THOR-silenced OS cells as well. Conversely, forced over-expression of Lnc-THOR enhanced IGF2BP1 target mRNA expression, promoting OS cell survival and proliferation. In vivo, xenograft tumors of Lnc-THOR-knockout U2OS cells grew significantly slower than the control U2OS tumors. Together, these results show that Lnc-THOR expression is essential for human OS cell growth. Lnc-THOR could be a novel therapeutic target and/or diagnosis marker for human OS.


Asunto(s)
Osteosarcoma/genética , Osteosarcoma/patología , ARN Largo no Codificante/metabolismo , Animales , Línea Celular Tumoral , Proliferación Celular/genética , Supervivencia Celular , Regulación Neoplásica de la Expresión Génica , Técnicas de Inactivación de Genes , Humanos , Ratones SCID , ARN Largo no Codificante/genética , ARN Interferente Pequeño/metabolismo
15.
Cell Physiol Biochem ; 43(2): 768-774, 2017.
Artículo en Inglés | MEDLINE | ID: mdl-28950256

RESUMEN

BACKGROUND/AIMS: Increasing evidence has shown that miR-125a plays important role in human cancer progression. However, little is known about the function of miR-125a in osteosarcoma. METHODS: The expression of miR-125a in osteosarcoma tissues and cell lines were examined by qRT-PCR. The biological role of miR-125a in osteosarcoma cell proliferation was examined in vitro. The targets of miR-125a were identified by a dual-luciferase reporter assay. RESULTS: The results showed that the expression of miR-125a expression is significantly lower in osteosarcoma tissues and cell lines. Survival curves showed that the survival of patients in high miR-125a expression was significantly longer than that of patients with low miR-125a expression, and multivariate analysis suggested that miR-125a is an independent prognostic factor for osteosarcoma patients. In addition, it was found in this study that miR-125a can inhibit the growth of osteosarcoma cells. The dual-luciferase reporter assay demonstrated that E2F2 is a novel target gene for miR-125a. In addition, in a recovery experiment, it was shown that miR-125a inhibits the biological function of osteosarcoma cells by inhibiting the expression of E2F2. CONCLUSION: Our results suggest that miR-125a acts as a tumor suppressor via regulation of E2F2 expression in osteosarcoma progression, and miR-125a may represent a novel therapeutic target for the treatment of osteosarcoma.


Asunto(s)
Neoplasias Óseas/genética , Huesos/patología , Proliferación Celular , Factor de Transcripción E2F2/genética , Regulación Neoplásica de la Expresión Génica , MicroARNs/genética , Osteosarcoma/genética , Adulto , Neoplasias Óseas/patología , Línea Celular Tumoral , Femenino , Humanos , Masculino , Osteosarcoma/patología , Adulto Joven
16.
Cell Physiol Biochem ; 37(6): 2101-14, 2015.
Artículo en Inglés | MEDLINE | ID: mdl-26599628

RESUMEN

BACKGROUND/AIMS: The slow healing process of tendon-to-bone junctions can be accelerated via implanted tendon-derived stem cells (TDSCs) with silenced transforming growth interacting factor 1 (TGIF1) gene. Tendon-to-bone insertion site is the special form of connective tissues derivatives of common connective progenitors, where TGF-ß plays bidirectional effects (chondrogenic or fibrogenic) through different signaling pathways at different stages. A recent study revealed that TGF-ß directly induces the chondrogenic gene Sox9. However, TGIF1 represses the expression of the cartilage master Sox9 gene and changes its expression rate against the fibrogenesis gene Scleraxis (Scx). METHODS: TGIF1 siRNA was transduced or TGIF1 was over-expressed in tendon-derived stem cells. Following suprapinatus tendon repair, rats were either treated with transduced TDSCs or nontransduced TDSCs. Histologic examination and Western blot were performed in both groups. RESULTS: In this study, the silencing of TGIF1 significantly upregulated the chondrogenic genes and markers. Similarly, TGIF1 inhibited TDSC differentiation into cartilage via interactions with TGF-ß-activated Smad2 and suppressed the phosphorylation of Smad2. The area of fibrocartilage at the tendon-bone interface was significantly increased in the TGIF1 (-) group compared with the control and TGIF1-overexpressing groups in the early stages of the animal model. The interface between the tendon and bone showed a increase of new bone and fibrocartilage in the TGIF1 (-) group at 4 weeks. Fibrovascular scar tissue was observed in the TGIF1-overexpressing group and the fibrin glue only group. Low levels of fibrocartilage and fibrovascular scar tissue were found in the TDSCs group. CONCLUSION: Collectively, this study shows that the tendon-derived stem cell modified with TGIF1 gene silencing has promising effects on tendon-to-bone healing which can be further explored as a therapeutic tool in regenerative medicine.


Asunto(s)
Huesos/fisiología , Silenciador del Gen , Proteínas de Homeodominio/genética , Proteínas Represoras/genética , Tendones/metabolismo , Animales , Biomarcadores/metabolismo , Regulación hacia Abajo , Fosforilación , ARN Interferente Pequeño/genética , Ratas , Ratas Sprague-Dawley , Proteína Smad2/metabolismo , Tendones/citología , Tendones/fisiología , Factor de Crecimiento Transformador beta/metabolismo , Regulación hacia Arriba
17.
Cell Physiol Biochem ; 34(6): 2070-80, 2014.
Artículo en Inglés | MEDLINE | ID: mdl-25562155

RESUMEN

AIMS: Osteosarcoma (OS) is an aggressive bone malignancy with poor prognosis. Many OS cells are resistant to apoptotic induction by tumor necrosis factor-related apoptosis inducing ligand (TRAIL). In our previous study, we found that the serum level of cytochrome c1 (CYC1) is significantly higher in OS patients than in healthy subjects. Our aim was to investigate the effects of CYC1 silencing on TRAIL-induced apoptosis in human OS in vitro and in vivo along with the underlying mechanisms. METHODS: First, we determined the expression of CYC1 in human OS tumors and cell lines versus normal adjacent tissues and cell line. We then studied the effects of CYC1 silencing alone or in combination with TRAIL on OS cell growth and apoptosis in vitro and OS tumorigenesis in vivo. RESULTS: We found that CYC1 is overexpressed in human OS tissues and cell lines. CYC1 silencing by shRNA transfection inhibits proliferation, slightly induces apoptosis in human OS cells in vitro, and suppresses human OS tumor growth in a mouse xenograft model in vivo. Additionally, CYC1 silencing sensitizes OS to TRAIL-induced apoptosis in vitro and in vivo. Our results also showed that CYC1 silencing significantly reduces complex III activity and potentiates TRAIL-induced cytochrome c release and caspase-9 activation in OS cells, suggesting that CYC1 silencing acts via the mitochondria-dependent apoptotic pathway. CONCLUSION: Taken together, our results provide evidence that CYC1 plays an important role in OS tumorigenesis, and modulation of CYC1 may be an effective strategy to potentiate OS to apoptotic induction by TRAIL.


Asunto(s)
Apoptosis/genética , Citocromos c1/genética , Osteosarcoma/genética , Ligando Inductor de Apoptosis Relacionado con TNF/genética , Animales , Carcinogénesis , Caspasa 9/biosíntesis , Línea Celular Tumoral , Proliferación Celular/genética , Citocromos c1/antagonistas & inhibidores , Regulación Neoplásica de la Expresión Génica , Humanos , Ratones , Osteosarcoma/patología
18.
Front Bioeng Biotechnol ; 12: 1328997, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38405378

RESUMEN

Recent advancements in orthopedic surgery have greatly improved the management of musculoskeletal disorders and injuries. This review discusses the latest therapeutic approaches that have emerged in orthopedics. We examine the use of regenerative medicine, including stem cell therapy and platelet-rich plasma (PRP) injections, to accelerate healing and promote tissue regeneration. Additionally, we explore the application of robotic-assisted surgery, which provides greater precision and accuracy during surgical procedures. We also delve into the emergence of personalized medicine, which tailors treatments to individual patients based on their unique genetic and environmental factors. Furthermore, we discuss telemedicine and remote patient monitoring as methods for improving patient outcomes and reducing healthcare costs. Finally, we examine the growing interest in using artificial intelligence and machine learning in orthopedics, particularly in diagnosis and treatment planning. Overall, these advancements in therapeutic approaches have significantly improved patient outcomes, reduced recovery times, and enhanced the overall quality of care in orthopedic surgery.

19.
Front Bioeng Biotechnol ; 12: 1292171, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38282892

RESUMEN

Globally, an annual count of more than two million bone transplants is conducted, with conventional treatments, including metallic implants and bone grafts, exhibiting certain limitations. In recent years, there have been significant advancements in the field of bone regeneration. Oxygen tension regulates cellular behavior, which in turn affects tissue regeneration through metabolic programming. Biomaterials with oxygen release capabilities enhance therapeutic effectiveness and reduce tissue damage from hypoxia. However, precise control over oxygen release is a significant technical challenge, despite its potential to support cellular viability and differentiation. The matrices often used to repair large-size bone defects do not supply enough oxygen to the stem cells being used in the regeneration process. Hypoxia-induced necrosis primarily occurs in the central regions of large matrices due to inadequate provision of oxygen and nutrients by the surrounding vasculature of the host tissues. Oxygen generating biomaterials (OGBs) are becoming increasingly significant in enhancing our capacity to facilitate the bone regeneration, thereby addressing the challenges posed by hypoxia or inadequate vascularization. Herein, we discussed the key role of oxygen in bone regeneration, various oxygen source materials and their mechanism of oxygen release, the fabrication techniques employed for oxygen-releasing matrices, and novel emerging approaches for oxygen delivery that hold promise for their potential application in the field of bone regeneration.

20.
Front Bioeng Biotechnol ; 12: 1389071, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38860139

RESUMEN

A developing use of nanotechnology in medicine involves using nanoparticles to administer drugs, genes, biologicals, or other materials to targeted cell types, such as cancer cells. In healthcare, nanotechnology has brought about revolutionary changes in the treatment of various medical and surgical conditions, including in orthopedic. Its clinical applications in surgery range from developing surgical instruments and suture materials to enhancing imaging techniques, targeted drug delivery, visualization methods, and wound healing procedures. Notably, nanotechnology plays a significant role in preventing, diagnosing, and treating orthopedic disorders, which is crucial for patients' functional rehabilitation. The integration of nanotechnology improves standards of patient care, fuels research endeavors, facilitates clinical trials, and eventually improves the patient's quality of life. Looking ahead, nanotechnology holds promise for achieving sustained success in numerous surgical disciplines, including orthopedic surgery, in the years to come. This review aims to focus on the application of nanotechnology in orthopedic surgery, highlighting the recent development and future perspective to bridge the bridge for clinical translation.

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