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1.
Chem Biol Drug Des ; 103(2): e14431, 2024 02.
Artículo en Inglés | MEDLINE | ID: mdl-38373741

RESUMEN

Icariin has been shown to promote osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs). However, the underlying molecular mechanism by which Icariin regulates osteogenic differentiation needs to be further revealed. The viability of BMSCs was assessed by cell counting kit 8 assay. BMSC osteogenic differentiation ability was evaluated by detecting alkaline phosphatase activity and performing alizarin red S staining. The protein levels of osteogenic differentiation-related markers, sirtuin 1 (SIRT1), ubiquitin-specific protease 47 (USP47), and Wnt/ß-catenin-related markers were determined using western blot. SIRT1 mRNA level was measured using quantitative real-time PCR. The regulation of USP47 on SIRT1 was confirmed by ubiquitination detection and co-immunoprecipitation analysis. Icariin could promote BMSC osteogenic differentiation. SIRT1 expression was enhanced by Icariin, and its knockdown suppressed Icariin-induced BMSC osteogenic differentiation. Moreover, deubiquitinating enzyme USP47 could stabilize SIRT1 protein expression. Besides, SIRT1 overexpression reversed the inhibiting effect of USP47 knockdown on BMSC osteogenic differentiation, and USP47 knockdown also restrained Icariin-induced BMSC osteogenic differentiation. Additionally, Icariin enhanced the activity of the Wnt/ß-catenin pathway by upregulating SIRT1. Icariin facilitated BMSC osteogenic differentiation via the USP47/SIRT1/Wnt/ß-catenin pathway.


Asunto(s)
Flavonoides , Células Madre Mesenquimatosas , Osteogénesis , Sirtuina 1 , Humanos , beta Catenina/metabolismo , Diferenciación Celular/efectos de los fármacos , Células Cultivadas , Flavonoides/farmacología , Células Madre Mesenquimatosas/citología , Células Madre Mesenquimatosas/efectos de los fármacos , Células Madre Mesenquimatosas/metabolismo , Osteogénesis/efectos de los fármacos , Osteogénesis/genética , Sirtuina 1/genética , Sirtuina 1/metabolismo , Ubiquitina Tiolesterasa/metabolismo , Proteasas Ubiquitina-Específicas/metabolismo , Técnicas de Silenciamiento del Gen
2.
Ecotoxicol Environ Saf ; 270: 115894, 2024 Jan 15.
Artículo en Inglés | MEDLINE | ID: mdl-38171100

RESUMEN

Algal toxins produced by microalgae, such as domoic acid (DA)1, have toxic effects on humans. However, toxicity tests using mice only yield lethal doses of algal toxins without providing insights into the mechanism of action on cells. In this study, a fast segmentation of microfluidic flow cytometry cell images based on the bidirectional background subtraction (BBS)2 method was developed to get the visual evidence of apoptosis in both bright-field and fluorescence images. This approach enables mapping of changes in cell morphology and activity under algal toxins, allowing for fast (within 60 s) and automated biological detection. By combining microfluidics with flow cytometry, the intricate cellular-level reaction process can be observed in micro samples of 293 T cells and mouse spleen cells, offering potential for future in vitro experiments.


Asunto(s)
Microalgas , Microfluídica , Humanos , Animales , Ratones , Citometría de Flujo
3.
J Mater Chem B ; 11(48): 11483-11495, 2023 12 13.
Artículo en Inglés | MEDLINE | ID: mdl-38054245

RESUMEN

Synthetic micro/nanomotors have attracted considerable attention due to their promising potential in the field of biomedicine. Despite their great potential, major micromotors require chemical fuels or complex devices to generate external physical fields for propulsion. Therefore, for future practical medical and environmental applications, Mg-based micromotors that exhibit water-powered movement and thus eliminate the need for toxic fuels, and that display optimal biocompatibility and biodegradability, are attracting attention. In this review, we summarized the recent microarchitectural design of Mg-based micromotors for biomedical applications. We also highlight the mechanism for realizing their water-powered motility. Furthermore, recent biomedical and environmental applications of Mg-based micromotors are introduced. We envision that advanced Mg-based micromotors will have a profound impact in biomedicine.


Asunto(s)
Microtecnología , Agua
4.
Biomacromolecules ; 24(12): 5678-5686, 2023 12 11.
Artículo en Inglés | MEDLINE | ID: mdl-37934694

RESUMEN

Cells use dynamic self-assembly to construct functional structures for maintaining cellular homeostasis. However, using a natural biological small molecule to mimic this phenomenon remains challenging. This work reports the dynamic microfiber formation of nucleopeptide driven by guanosine triphosphate, the small molecule that controls microtubule polymerization in living cells. Deactivation of GTP by enzyme dissociates the fibers, which could be reactivated by adding GTP. Molecular dynamic simulation unveils the mystery of microfiber formation of GBM-1 and GTP. Moreover, the microfiber formation can also be controlled by diffusion-driven GTP gradients across a semipermeable membrane in bulk conditions and the microfluidic method in the defined droplets. This study provides a new platform to construct dynamic self-assembly materials of molecular building blocks driven by GTP.


Asunto(s)
Microtúbulos , Tubulina (Proteína) , Guanosina Trifosfato , Tubulina (Proteína)/química , Hidrólisis , Simulación de Dinámica Molecular
5.
Mater Horiz ; 10(11): 5079-5086, 2023 Oct 30.
Artículo en Inglés | MEDLINE | ID: mdl-37680183

RESUMEN

Ultrasmall CsPbBr3 perovskite quantum dots (PQDs) as promising blue-emitting materials are highly desired for full-color display and lighting applications, but their inferior efficiency and poor ambient stability hinder extensive applications. Herein, a "break-and-repair" strategy has been developed to tightly confine monodispersed ultrasmall CsPbBr3 PQDs in a zeolite. In this strategy, the CsPbBr3 PQDs are introduced into the zeolite via a high temperature evaporation method, wherein the perovskite precursors break the zeolite framework, and amino acids and silane are then used to fix the damaged framework and lock the perovskite QDs within the matrix. By modulating the synthetic conditions to control the growth of CsPbBr3, PQDs with ultrasmall size of 2 nm have been obtained in the zeolite, giving emission centered at 460 nm with a high quantum yield of 76.93%. Strikingly, the PQDs@zeolite composite exhibits water-induced reversible photoluminescence promoted by the coordination between the amino acids and PQDs in a dynamic manner, achieving enhanced water stability (14 days in aqueous solution). This work provides a new perspective for the synthesis of water-stable blue-emitting perovskite composites for potential applications in lighting fields.

6.
Angew Chem Int Ed Engl ; 62(36): e202303455, 2023 09 04.
Artículo en Inglés | MEDLINE | ID: mdl-37409642

RESUMEN

Chirality correction, asymmetry, ring-chain tautomerism and hierarchical assemblies are fundamental phenomena in nature. They are geometrically related and may impact the biological roles of a protein or other supermolecules. It is challenging to study those behaviors within an artificial system due to the complexity of displaying these features. Herein, we design an alternating D,L peptide to recreate and validate the naturally occurring chirality inversion prior to cyclization in water. The resulting asymmetrical cyclic peptide containing a 4-imidazolidinone ring provides an excellent platform to study the ring-chain tautomerism, thermostability and dynamic assembly of the nanostructures. Different from traditional cyclic D,L peptides, the formation of 4-imidazolidinone promotes the formation of intertwined nanostructures. Analysis of the nanostructures confirmed the left-handedness, representing chirality induced self-assembly. This proves that a rationally designed peptide can mimic multiple natural phenomena and could promote the development of functional biomaterials, catalysts, antibiotics, and supermolecules.


Asunto(s)
Nanoestructuras , Péptidos Cíclicos , Péptidos Cíclicos/química , Péptidos/química , Nanoestructuras/química , Materiales Biocompatibles
7.
Nat Commun ; 14(1): 3880, 2023 06 30.
Artículo en Inglés | MEDLINE | ID: mdl-37391398

RESUMEN

The amino acid sequences of peptides determine their self-assembling properties. Accurate prediction of peptidic hydrogel formation, however, remains a challenging task. This work describes an interactive approach involving the mutual information exchange between experiment and machine learning for robust prediction and design of (tetra)peptide hydrogels. We chemically synthesize more than 160 natural tetrapeptides and evaluate their hydrogel-forming ability, and then employ machine learning-experiment iterative loops to improve the accuracy of the gelation prediction. We construct a score function coupling the aggregation propensity, hydrophobicity, and gelation corrector Cg, and generate an 8,000-sequence library, within which the success rate of predicting hydrogel formation reaches 87.1%. Notably, the de novo-designed peptide hydrogel selected from this work boosts the immune response of the receptor binding domain of SARS-CoV-2 in the mice model. Our approach taps into the potential of machine learning for predicting peptide hydrogelator and significantly expands the scope of natural peptide hydrogels.


Asunto(s)
COVID-19 , Animales , Ratones , Humanos , SARS-CoV-2 , Péptidos , Secuencia de Aminoácidos , Hidrogeles
8.
Molecules ; 28(8)2023 Apr 12.
Artículo en Inglés | MEDLINE | ID: mdl-37110631

RESUMEN

In this study, the preparation of covalent polyoxometalate organic frameworks (CPOFs) is introduced using the idea of polyoxometalate and covalent organic frameworks. Firstly, the prepared polyoxometalate was functionalized with an amine group (NH2-POM-NH2), and then the CPOFs were prepared by a solvothermal Schiff base reaction with NH2-POM-NH2 and 2,4,6-trihydroxybenzene-1,3,5-tricarbaldehyde (Tp) as monomers. After the incorporation of PtNPs and MWCNTs into the CPOFs material, the PtNPs-CPOFs-MWCNTs nanocomposites, which possess excellent catalytic activity and electrical conductivity, were formed and utilized as new electrode materials for the electrochemical thymol sensors. The obtained PtNPs-CPOFs-MWCNTs composite exhibits excellent activity toward thymol, which is attributable to its large special surface area, good conductivity and the synergistic catalysis of each component. Under optimal experimental conditions, the sensor presented a good electrochemical response to thymol. The sensor shows two good linear relationships between the current and thymol concentration in the range of 2-65 µM (R2 = 0.996) and 65-810 µM (R2 = 0.997), with the corresponding sensitivity of 72.7 µA mM-1 and 30.5 µA mM-1, respectively. Additionally, the limit of detection (LOD) was calculated to be 0.2 µM (S/N = 3). At the same time, the prepared thymol electrochemical sensor revealed superior stability and selectivity. The constructed PtNPs-CPOFs-MWCNT electrochemical sensor is the first example of thymol detection.

9.
In Vitro Cell Dev Biol Anim ; 59(2): 109-120, 2023 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-36881345

RESUMEN

Osteoporosis is described as an age-associated impairment of bone formation. microRNA (miR)-29b-3p was thought to be linked to osteoblast differentiation; however, the underlying molecular pathways are yet unknown. The study's goal was to look into the involvement of miR-29b-3p in osteoporosis and the pathophysiological mechanisms. A murine model of estrogen deficiency-induced bone loss was established to simulate postmenopausal osteoporosis. Reverse transcription-quantitative PCR (RT-qPCR) was performed to assess the level of miR-29b-3p of bone tissue. Additionally, miR-29b-3p/sirtuin-1 (SIRT1)/peroxisome proliferator-activated receptor γ (PPARγ) axis in the osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) was examined. Osteogenesis-related markers, including alkaline phosphatase (ALP), osteocalcin (OCN), and runt-related transcription factor 2 (RUNX2), were assessed at protein and molecular levels. ALP staining and Alizarin Red staining were used to detect ALP activity and calcium deposition. The ovariectomy group was shown to express miR-29b-3p at higher levels in vitro, and miR-29b-3p mimics suppressed osteogenic differentiation and protein/mRNA expression levels of osteogenesis-related markers in vivo. SIRT1 was identified as a target of miR-29b-3p using luciferase reporter assays. Overexpression of SIRT1 reduced the inhibition of osteogenic differentiation by miR-29b-3p. Rosiglitazone, an activator of PPARγ signaling, was able to reverse the downregulation of the osteogenic differentiation of BMSCs and the protein expression of PPARγ caused by miR-29b-3p inhibitors. The results revealed that osteogenesis was suppressed by miR-29b-3p, which blocks the SIRT1/PPARγ axis. These results suggested that postmenopausal osteoporosis could be treated by targeting miR-29b-3p SIRT1/PPARγ.


Asunto(s)
MicroARNs , Osteoporosis Posmenopáusica , Osteoporosis , Sirtuinas , Femenino , Ratones , Animales , Humanos , Osteogénesis/genética , PPAR gamma/genética , PPAR gamma/metabolismo , Sirtuina 1/genética , Diferenciación Celular/genética , MicroARNs/metabolismo , Osteoporosis/genética , Células Cultivadas
10.
Adv Mater ; 35(6): e2208735, 2023 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-36446033

RESUMEN

Luminescence multiplexing shows promising application prospects in information security, yet even outstanding time division multiplexing can only carry limited luminescence information. Time-space division multiplexing can greatly expand the information capacity by simultaneously transferring luminescence information in both time and space dimensions. Herein, time-dependent polychrome stereoscopic luminescence system has been successfully developed by designing a 3D luminescence system based on resonance energy transfer (RET), in which afterglow lifetime easily regulated carbon dots-in-zeolite composites are used as energy donors and multicolor fluorescence quantum dots (QDs) as energy acceptors. Taking perovskite QDs (PeQDs) as example, by matching the energy donors with different afterglow lifetimes and the energy acceptors with different fluorescence colors, tunable afterglow emission of PeQDs with wavelength within 463-614 nm and lifetime within 232-1500 ms can be realized, in which the maximal RET efficiency reaches 95%. As a proof of concept, such novel luminescence system that carries eight layers of luminescence information involving four dimensions (time and 3D space) is successfully applied in advanced time-space division multiplexing. This work opens a new perspective for the application of time-space integrated luminescence systems in advanced information multiplexing.

11.
Am J Transl Res ; 15(12): 6832-6840, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-38186973

RESUMEN

OBJECTIVES: The long-term trends in crude mortality rates (CMRs) and age-standardized mortality rates characterized by Segi's world standard population (ASMRWs) of DMSCT in Pudong New Area (PNA), Shanghai, were evaluated from 1973 to 2019, and the role of demographic and non-demographic factors in the mortality of diseases of the musculoskeletal system and connective tissue (DMSCT) was explored. METHODS: The PNA district has the largest population and area in Shanghai. Therefore, the mortality registration system of the PNA district was used to calculate and verify the number of deaths. Then, the Joinpoint Regression Program was used to analyze the time trend of mortality. The difference decomposition method was used to visualize the mortality of population and non-population factors, and GraphPad Prism was used for image visualization. RESULTS: A total of 2260 deaths from DMSCT occurred from 1973 to 2019. The CMR and ASMRW of DMSCT were 2.56/105 person-years and 1.57/105 person-years, respectively. The number of people aged ≥80 (696 deaths) who died of DMSCT was the highest among total deaths, the highest number of years of life lost (YLL) was observed in the 45-59 age group, and the YLL rate in the ≥80 age group was the highest. The CMR and YLL rates of DMSCT showed upward trends in the total population from 1973 to 2019. CONCLUSION: The CMR and YLL rates of DMSCT showed upward trends in the total population from 1973 to 2019 in PNA, Shanghai, and age was closely related to the occurrence of DMSCT. Similarly, demographic factors played a role in this process.

12.
Sci Rep ; 12(1): 20793, 2022 12 01.
Artículo en Inglés | MEDLINE | ID: mdl-36456717

RESUMEN

With the economic development and industrialization, the increasingly accumulated tailings ponds in China have become a great risk. Due to the difficulty of selecting proper site for a new reservoir in Yunnan, a sub-dam was built at the downstream original reservoir. This study explored the fracture development and progressive failure characteristics of the tailings reservoir area after capacity expansion based on a similarity experiment and the numerical simulation. The results showed that the primary cracks in the reservoir area were more than those at the top of the sub-dam. With the increase of the upper load, the primary cracks further developed and penetrated the whole sub-dam top, and the sub-cracks were then produced under the concentrate stress of the primary cracks. After the further development of the sub-cracks, the secondary cracks parallel to the primary cracks were formed on the outer slope of the sub-dam. The progressive failure of a tailings dam can be summarized as: the maximum shear stress was firstly generated at the toe of the slope or the top of the dam which then extended to the top of the sub-dam in the form of a curve and finally formed the failure surface by connecting with the primary fracture of the tensile plastic zone at the top of the dam. The study also found that in the process of tailings accumulation in the new reservoir area, tailings would form "back pressure slope protection" at the initial dam of the original reservoir, which not only effectively delayed the occurrence of shear failure, but also inhibited the generation and penetration of tensile plastic zone.


Asunto(s)
Fracturas Óseas , Humanos , China , Desarrollo Industrial , Simulación por Computador , Plásticos
13.
BMJ Open ; 12(11): e056067, 2022 11 15.
Artículo en Inglés | MEDLINE | ID: mdl-36379656

RESUMEN

OBJECTIVES: This study sought to identify the epidemiological investigation challenges of the COVID-19 pandemic and offer insights into the underlying issues. DESIGN: An exploratory qualitative study used thematic analysis of semistructured and in-depth individual interviews. SETTING: This study was conducted in Centers for Disease Control and Prevention in Guangdong Province. PARTICIPANTS: Twenty-four participants consented to participate in an in-depth interview. Transcribed recordings were managed using NVivo software and analysed using inductive thematic analysis. RESULTS: The qualitative analysis revealed five key themes: high-intensity epidemiological investigation task, emergency management requiring improvement in the early stage, respondent uncertainty, impact on work and social life and inadequate early-stage Joint Prevention and Control Mechanism. CONCLUSION: This survey focuses on the epidemiology workforce at the forefront of the COVID-19 pandemic and qualitatively describes their experiences, vocational issues and psychological stressors. We found that the problems of epidemiological investigation posed intense challenges to the epidemiology workforce. These findings highlight the epidemiological investigation challenges associated with this pandemic. We have provided some suggestions that may help improve the efficiency and quality of the epidemiology workforce in China.


Asunto(s)
COVID-19 , Estados Unidos , Humanos , COVID-19/epidemiología , Pandemias , Investigación Cualitativa , Recursos Humanos , Estrés Psicológico
14.
Zhongguo Gu Shang ; 35(10): 921-6, 2022 Oct 25.
Artículo en Chino | MEDLINE | ID: mdl-36280407

RESUMEN

OBJECTIVE: To investigate the clinical effect of NRD assisted Ilizarov technique in the treatment of infected bone and soft tissue defect of tibia. METHODS: All 48 patients with infected bone and soft tissue defect of tibia were randomly divided into study group and control group from March 2013 to December 2020. There were 34 males and 14 females, aged from 24 to 55 years old with an average of (40.54±11.64) years old. There were 25 patients in the study group, including 17 males and 8 females, aged from 31 to 55 years old with an average of (41.36±9.69) years old. The study group were treated with NRD assisted with Ilizarov bone transport technique. There were 23 patients in control group, including 17 males and 6 females, aged from 24 to 53 years old with an average of(38.61±8.76) years old. The control group were treated with traditional bone transport technique. The curative rate, recurrence rate, incidence rate of pin track infection, time of using antibiotics, time of wound healing, time of carrying external fixation, time of bone transport, time of bone healing and postoperative function were used to evaluate the therapeutic effect of the two groups. RESULTS: The follow-up period was from 12 to 62 months with an average of (33.0±7.2) months. At the final follow-up, there was no significant difference in the curative rate between the two groups (P>0.05). The recurrence rate in the study group was lower than that in the control group(P<0.05). The incidence of pin track infection in the study group was lower than that in the control group (P<0.05). The time of using antibiotics and wound healing in the study group was shorter than that in the control group(P<0.05). There was no significant difference in the time of bone transport and carrying of external fixation between the two groups(P>0.05). There was no significant difference in bone healing and postoperative function between the two groups(P>0.05). CONCLUSION: NRD assisted Ilizarov technique can achieve satisfactory results in the treatment of infected bone and soft tissue defect of tibia and shorten the treatment period and the time of using antibiotics. It is worthy of development in clinic.


Asunto(s)
Técnica de Ilizarov , Fracturas de la Tibia , Masculino , Femenino , Humanos , Adulto Joven , Adulto , Persona de Mediana Edad , Tibia/cirugía , Fracturas de la Tibia/cirugía , Cicatrización de Heridas , Antibacterianos , Resultado del Tratamiento , Estudios Retrospectivos , Fijadores Externos
15.
Am J Transl Res ; 14(7): 4698-4708, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35958510

RESUMEN

BACKGROUND: Hip tumors often require tumor-type artificial joint replacement. The selection of the prosthesis stem (hip tumor prosthesis stem) implantation angle during the operation is important to prevent the complication of postoperative prosthesis dislocation. The aim of this study was to evaluate the role of a nickel-titanium (Ni-Ti) shape memory alloy embracing fixator in determination of the implantation angle of a hip tumor prosthesis stem and analyze its efficacy. METHODS: 36 patients with proximal femur tumor were treated with extended tumor resection and prosthetic replacement. 14 patients received prosthetic replacements with the embracing fixators fixing between the junction of the prosthesis stem and the femur temporarily, while the other 22 patients received the same replacements but without the fixators. The two groups were compared regarding occurrence of complications, limb function, and active hip range of motion (ROM). RESULTS: There was no case of hip dislocation in the group that received prosthetic replacements with the use of embracing fixators. Occurrence of deep infection had no difference between the two groups. However, better limb function and higher active (ROM) on abduction or flexion were observed in the group using embracing fixators. CONCLUSION: Ni-Ti shape memory alloy embracing fixator plays a key role in assisting the accurate implantation angle of the prosthesis stem in prosthetic replacement. The prosthesis stem can be adjusted to the optimal angle with the help of the embracing fixator. Patients have a lower risk of dislocation, better limb function, and higher active hip ROM.

16.
Int J Biol Sci ; 18(13): 4824-4836, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35982900

RESUMEN

Long noncoding RNAs (lncRNAs) are dysregulated in many cancers. Here, we identified the molecular mechanisms of lncRNA Cancer Susceptibility Candidate 8 (CASC8) in promoting the malignancy of esophageal squamous cell carcinoma (ESCC). CASC8 was highly overexpressed in ESCC tissues and upregulation of CASC8 predicted poor prognosis in ESCC patients. Moreover, CASC8 decreased the cisplatin sensitivity of ESCC cells and promoted ESCC tumor growth in vivo. Mechanistically, CASC8 interacted with heterogeneous nuclear ribonucleoprotein L (hnRNPL) and inhibited its polyubiquitination and proteasomal degradation, thus stabilizing hnRNPL protein levels and activating the Bcl2/caspase3 pathway. Additionally, AlkB Homolog 5, RNA demethylase (ALKBH5)-mediated m6A demethylation stabilized the CASC8 transcript, resulting in CASC8 upregulation. Taken together, these findings identified an oncogenic function of CASC8 in the progression of ESCC, which suggest that CASC8 might become a potential prognostic biomarker in ESCC.


Asunto(s)
Neoplasias Esofágicas , Carcinoma de Células Escamosas de Esófago , Ribonucleoproteína Heterogénea-Nuclear Grupo L , ARN Largo no Codificante , Ribonucleoproteínas , Línea Celular Tumoral , Proliferación Celular/genética , Resistencia a Antineoplásicos/genética , Neoplasias Esofágicas/patología , Carcinoma de Células Escamosas de Esófago/metabolismo , Regulación Neoplásica de la Expresión Génica/genética , Ribonucleoproteína Heterogénea-Nuclear Grupo L/genética , Ribonucleoproteína Heterogénea-Nuclear Grupo L/metabolismo , Humanos , ARN Largo no Codificante/genética , ARN Largo no Codificante/metabolismo , Ribonucleoproteínas/genética , Ribonucleoproteínas/metabolismo , Regulación hacia Arriba/genética
17.
Nano Lett ; 22(18): 7588-7596, 2022 09 28.
Artículo en Inglés | MEDLINE | ID: mdl-35925772

RESUMEN

Controlling the enzymatic reaction of macromolecules in living systems plays an essential role in determining the biological functions, which remains challenging in the synthetic system. This work shows that host-guest complexation could be an efficient strategy to tune the enzymatic self-assembly of the peptide. The formed host-guest complexation prevents the enzymatic kinetics of peptide assemblies on the cell surface and promotes cellular uptake of assemblies. For uptake inside cells, the host-guest complex undergoes dissociation in the acidic lysosome, and the released peptide further self-assembles inside the mitochondria. Accumulating assemblies at mitochondria induce the ferroptosis of cancer cells, resulting in cancer cell death in vitro and the tumor-bearing mice model. As the first example of using host-guest complexation to modulate the kinetics of enzymatic self-assembly, this work provides a general method to control enzymatic self-assembly in living cells for selective programming cancer cell death.


Asunto(s)
Neoplasias , Animales , Muerte Celular , Sustancias Macromoleculares/química , Ratones , Péptidos/química
18.
J Mater Chem B ; 10(37): 7556-7562, 2022 09 28.
Artículo en Inglés | MEDLINE | ID: mdl-35775603

RESUMEN

The toxicity effects of paclitaxel (PTX)-loaded magnetic neutrophil-hybrid swimming microrobots ("neutrobots") in vivo were assessed after intravenous administration to mice. The mice after 72 hours exhibited minimal immunotoxicity and liver and kidney toxicity at an administration dose of 3 × 106 PTX-loaded neutrobots. The minor toxicity of drug-loaded neutrobots holds considerable promise for biomedical applications.


Asunto(s)
Contención de Riesgos Biológicos , Paclitaxel , Animales , Ratones , Paclitaxel/uso terapéutico
19.
Front Oncol ; 12: 873918, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35669429

RESUMEN

Introduction: The burden of cancer-related mortality of common malignancies has been reported worldwide. However, whether bone cancer (BC), as a highly aggressive and heterogeneous group of rare cancers, followed a similar or distinct epidemiological pattern during such process remains largely unknown. We aimed to analyze the mortality and the temporal trends of BC in relation to gender, age, and premature death in Shanghai, China. Methods: We conducted a population-based analysis of the mortality data of BC in Shanghai Pudong New Area (PNA) from 2005 to 2020. The epidemiological characteristics and long-term trends in crude mortality rates (CMRs), age-standardized mortality rates worldwide (ASMRWs), and rate of years of life lost (YLL) was analyzed using the Joinpoint regression program. The demographic and non-demographic factors affecting the mortality rate were evaluated by the decomposition method. Results: There are 519 BC-specific deaths accounting for 0.15% of all 336,823 deaths and 0.49% of cancer-specific death in PNA. The CMR and ASMRW of BC were 1.15/105 person-year and 0.61/105 person-year, respectively. The YLL due to premature death from BC was 6,539.39 years, with the age group of 60-69 years having the highest YLL of 1,440.79 years. The long-term trend of CMR, ASMRW, and YLL rate significantly decreased by -5.14%, -7.64%, and -7.27%, respectively, per year (all p < 0.05) in the past 16 years. However, the proportion of BC-specific death within the total cancer-specific death dropped to a plateau without further improvement since 2016, and a remarkable gender and age disparity was noticed in the observed reduction in mortality. Specifically, the elderly benefited less but accounted for a larger percentage of BC population in the last decades. Although the overall mortality of BC decreased, there was still a significant upward trend toward an increased mortality rate caused by the aging of the BC patients. Conclusion: Our study provides novel insights on the epidemiological characteristics and longitudinal dynamics of BC in a fast urbanization and transitioning city. As a rare disease affecting all ages, the burden of BC among the elderly emerged to form an understudied and unmet medical need in an aging society.

20.
ACS Nano ; 16(3): 4126-4138, 2022 03 22.
Artículo en Inglés | MEDLINE | ID: mdl-35230089

RESUMEN

Anisotropic structures made by hierarchical self-assembly and crystallization play an essential role in the living system. However, the spontaneous formation of liquid crystalline hydrogel of low molecular weight organic molecules with controlled properties remains challenging. This work describes a rational design of tetrapeptide without N-terminal modification and chemical conjugation that utilizes intermolecular interactions to drive the formation of nanofiber bundles in a two-component system, which could not be accessed by a single component. The diameter of nanofibers can be simply controlled by varying the enantiomer of electrostatic pairs. Mutation of lysine (K) to arginine (R) results in an over 30-fold increase of mechanical property. Mechanistic studies using different techniques unravel the mechanism of self-assembly and formation of anisotropic liquid crystalline domains. All-atom molecular dynamics simulations reveal that the mixture of heterochiral peptides self-assembles into a nanofiber with a larger width compared to the homochiral assemblies due to the different stacking pattern and intermolecular interactions. The intermolecular interactions show an obvious increase by substituting the K with R, facilitating a more stable assembly and further altering the assembly mechanics and bulk material properties. Moreover, we also demonstrated that the hydrogel properties can be easily controlled by incorporating a light-responsive group. This work provides a method to generate the liquid crystalline hydrogel from isotropic monomers.


Asunto(s)
Cristales Líquidos , Nanofibras , Biomimética , Hidrogeles/química , Nanofibras/química , Péptidos/química
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