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1.
BMC Musculoskelet Disord ; 24(1): 430, 2023 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-37254081

RESUMO

BACKGROUND: Galeazzi fracture dislocation is a compound injury that encompasses fractures of the distal third of the radius and dislocation of the distal radial ulnar joint (DRUJ). Clinically, this condition is rare and often leads to distal ulnar bifurcation. In previous similar reports, patients were effectively managed through surgery. CASE PRESENTATION: In this case report, we describe an 11-year-old male child who presented with an ulnar bifida following trauma to the hand, and was treated with manipulation and conservative treatment without surgery. A follow-up performed over the years demonstrated that the patient recovered well, and had normal wrist movements without significant pain, and the patient expressed great satisfaction. CONCLUSIONS: Ulnar diaphyseal fracture may occur in children or adolescents due to injuries, and may be accompanied with manipulation and repositioning. Conservative treatment can be applied to avoid the trauma associated with surgery especially in the absence of severe joint mobility impairment with good outcomes.


Assuntos
Luxações Articulares , Fraturas do Rádio , Fraturas da Ulna , Traumatismos do Punho , Masculino , Adolescente , Humanos , Criança , Fixação Interna de Fraturas/efeitos adversos , Ulna/cirurgia , Fraturas da Ulna/cirurgia , Luxações Articulares/diagnóstico por imagem , Luxações Articulares/etiologia , Luxações Articulares/cirurgia , Rádio (Anatomia) , Fraturas do Rádio/cirurgia , Traumatismos do Punho/cirurgia , Articulação do Punho/cirurgia
2.
Int J Mol Sci ; 24(2)2023 Jan 11.
Artigo em Inglês | MEDLINE | ID: mdl-36674964

RESUMO

In this study, a series of novel tryptanthrin derivatives were synthesized and their inhibitory activities against selected human cancer cell lines, namely, lung (A549), chronic myeloid leukemia (K562), prostate (PC3), and live (HepG2), were evaluated using a methyl thiazolyl tetrazolium colorimetric (MTT) assay. Among the tested compounds, compound C1 exhibited a promising inhibitory effect on the A549 cell line with an IC50 value of 0.55 ± 0.33 µM. The observation of the cell morphological result showed that treatment with C1 could significantly inhibit the migration of A549 cells through the cell migration assay. Moreover, after treatment with C1, the A549 cells exhibited a typical apoptotic morphology and obvious autophagy. In addition, the detection of apoptosis and the mitochondrial membrane potential indicated that C1 induced A549 cell apoptosis via modulating the levels of Bcl2 family members and disrupted the mitochondrial membrane potential. Compound C1 also suppressed the expression of cyclin D1 and increased the expression of p21 in the A549 cells, inducing cell cycle arrest in the G2/M phase in a dose dependent manner. The further mechanism study found that C1 markedly increased the transformation from LC3-I to LC3-II. Taken together, our results suggest that C1 is capable of inhibiting the proliferation of non-small cell lung cancer (NSCLC) cells, inducing cell apoptosis, and triggering autophagy.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Humanos , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Apoptose , Autofagia , Proliferação de Células , Linhagem Celular Tumoral
3.
Int J Mol Sci ; 24(13)2023 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-37446077

RESUMO

Rice bacterial leaf blight is a destructive bacterial disease caused by Xanthomonas oryzae pv. oryzae (Xoo) that seriously threatens crop yields and their associated economic benefits. In this study, a series of improved dissolubility 7-aliphatic amine tryptanthrin derivatives was designed and synthesized, and their potency in antibacterial applications was investigated. Notably, compound 6e exhibited excellent activity against Xoo, with an EC50 value of 2.55 µg/mL, compared with the positive control bismerthiazol (EC50 = 35.0 µg/mL) and thiodiazole copper (EC50 = 79.4 µg/mL). In vivo assays demonstrated that 6e exhibited a significant protective effect on rice leaves. After exposure, the morphology of the bacteria was partially atrophied by SEM. Furthermore, 6e increased the accumulation of intracellular reactive oxygen species, causing cell apoptosis and the formation of bacterial biofilms. All the results indicated that 6e could be a potential agrochemical bactericide for controlling phytopathogenic bacteria.


Assuntos
Oryza , Xanthomonas , Oxidiazóis/farmacologia , Testes de Sensibilidade Microbiana , Doenças das Plantas/prevenção & controle , Doenças das Plantas/microbiologia , Antibacterianos/farmacologia , Antibacterianos/química , Oryza/microbiologia
4.
J Mater Sci Mater Med ; 33(2): 16, 2022 Jan 24.
Artigo em Inglês | MEDLINE | ID: mdl-35072786

RESUMO

The MR/FI bimodal imaging has attracted widely studied due to combining the advantages of MRI and FI can bridge gaps in sensitivity and depth between these two modalities. Herein, a novel MR/FI bimodal imaging probe is facile fabricated by coating the Mn-phenolic coordination polymer on the surface of the carbon quantum dots. The structure of the as-prepared nanocomposite probe is carefully validated via SEM, TEM, and XPS. The content of Mn2+ is calculated through the EDS and TGA. The quantum yield (QY) and emission wavelength of the probe are about 7.24% and 490 nm, respectively. The longitudinal r1 value (2.43 mM-1 s-1) with low r2/r1 (4.45) of the probe is obtained. Subsequently, fluorescence and MR imaging are performed. The metabolic pathways in vivo are inferred by studying the bio-distribution of the probe in major organs. Thus, these results indicate that probe would be an excellent dual-modal imaging probe for enhanced MR imaging and fluorescence imaging. MR/FI bimodal imaging probe is built via in-situ coated Mn-phenolic coordination polymer on the surface of the carbon quantum dots. The in vitro and vivo image property of the probe is evaluated.


Assuntos
Manganês/química , Nanocompostos/química , Polímeros/química , Pontos Quânticos/química , Taninos/química , Células Hep G2 , Humanos , Imageamento por Ressonância Magnética , Imagem Óptica
5.
Cell Biol Int ; 43(5): 565-573, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30958604

RESUMO

Heterotopic ossification (HO) is a common disturbing complication of intra-articular fractures. Its prevention and treatment are still difficult as its pathogenesis is unclear. It was reported that PDGFRα+ muscle cells in skeletal muscle may participate in the formation of HO; however, the specific mechanism is still unknown. This study investigated the function of miR-19b-3p in osteogenic differentiation of PDGFRα+ muscle cells. MiR-19b-3p was upregulated during PDGFRα+ muscle cell osteogenic differentiation. The exogenous expression of miR-19b-3p led to an increase in osteogenic marker gene transcription and translation during the osteogenic differentiation of PDGFRα+ muscle cells. Furthermore, both alkaline phosphatase and alizarin red staining increased in miR-19b-3p mimic transfected cells. Over-expression of miR-19b-3p led to the down-regulation of gene of phosphate and tension homology deleted on chromosome ten (PTEN). Additionally, the dual luciferase reporter assay demonstrated that PTEN was a direct target of miR-19b-3p. The increase of osteocalcin, osteopontin, and Runt-related transcription factor 2 protein levels induced by ectopic miR-19b-3p expression could be partially reversed by PTEN over-expression. In conclusion, our results suggested that miR-19b-3p may be a promising target in inhibiting PDGFRα+ muscle cell osteogenic differentiation and treatment of HO.


Assuntos
MicroRNAs/metabolismo , Ossificação Heterotópica/metabolismo , PTEN Fosfo-Hidrolase/metabolismo , Receptor alfa de Fator de Crescimento Derivado de Plaquetas/metabolismo , Diferenciação Celular/fisiologia , Subunidade alfa 1 de Fator de Ligação ao Core/metabolismo , Regulação para Baixo , Humanos , MicroRNAs/genética , Músculo Esquelético/metabolismo , Músculo Esquelético/patologia , Ossificação Heterotópica/genética , Ossificação Heterotópica/patologia , Osteocalcina/metabolismo , PTEN Fosfo-Hidrolase/genética , Receptor alfa de Fator de Crescimento Derivado de Plaquetas/genética
6.
J Bone Miner Metab ; 37(6): 987-995, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30919130

RESUMO

Osteoporosis is the most common bone disease in humans. During bone remodeling, specialized blood vessels influenced by the endothelial cells (CD31hiEmcnhi, also called type H cells) are formatted to supply nutrients. Reductions in vascular supply are associated with bone loss resulting in osteoporosis. Therefore, the objective of the present study was to explore the association between the CD31hiEmcnhi endothelial cells and bone mineral density (BMD). In this prospective study, 134 Chinese women were enrolled and examined. BMD was measured by DEXA method while the percentage of CD31hiEmcnhi endothelial cells in the intertrochanteric part was measured by flow cytometry. The percentage of CD31hiEmcnhi endothelial cells in postmenopausal subjects was significantly lower compared with premenopausal women (8.7 ± 4.0% vs 13.2 ± 5.6%, P < 0.01). Meanwhile, the CD31hiEmcnhi endothelial cell levels in osteopenia and osteoporosis were significantly lower compared with subjects with normal BMD (9.84 ± 4.2% in osteopenia and 7.11 ± 3.2% in osteoporosis vs 12.7 ± 5.6% in subjects with normal T score, P < 0.01). Multiple regression analyses showed that the CD31hiEmcnhi endothelial cells level was positively associated with femur neck and total hip BMD, but not with lumbar BMD. Our study suggests a significantly positive association between CD31hiEmcnhi endothelial cells and local BMD in Chinese women. The proportion of CD31hiEmcnhi endothelial cells is a marker of bone quality and represents a potential target for treatment of bone loss.


Assuntos
Povo Asiático , Densidade Óssea , Células Endoteliais/metabolismo , Molécula-1 de Adesão Celular Endotelial a Plaquetas/metabolismo , Sialoglicoproteínas/metabolismo , Adulto , Idoso , Feminino , Colo do Fêmur/fisiologia , Quadril/fisiologia , Humanos , Vértebras Lombares/fisiologia , Pessoa de Meia-Idade , Análise Multivariada , Estudos Prospectivos , Análise de Regressão
7.
Cancer Sci ; 109(8): 2412-2422, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-29845707

RESUMO

Osteosarcoma is the most common primary bone malignancy. Recently, studies showed chemokine receptor 4 (CXCR4) played a critical role in osteosarcoma. However, the regulation of CXCR4 is not fully understood. microRNAs are short, non-coding RNAs that play an important roles in post-transcriptional regulation of gene expression in a variety of diseases including osteosarcoma. miR-613 is a newly discovered miRNA and has been reported to function as a tumor suppressor in many cancers. In this study, we confirmed that both Stromal Cell-Derived Factor (SDF-1) and CXCR4 could be prognostic markers for osteosarcoma. Meanwhile this study found that SDF-1/CXCR4 pathway regulated osteosarcoma cells proliferation, migration and reduced apoptosis. Besides, we demonstrated that miR-613 was significantly downregulated in osteosarcoma patients. Elevated expression of miR-613 directly suppressed CXCR4 expression and then decreased the proliferation, migration and induced apoptosis of osteosarcoma cells. Moreover, our study found that CXCR4 promoted the development of lung metastases and inhibition of CXCR4 by miR-613 reduced lung metastases. These data indicated that CXCR4 mediated osteosarcoma cell growth and lung metastases and this effect can be suppressed by miR-613 through directly downregulating CXCR4.


Assuntos
Neoplasias Ósseas/genética , Genes Supressores de Tumor/fisiologia , Neoplasias Pulmonares/genética , MicroRNAs/genética , Osteossarcoma/genética , Osteossarcoma/patologia , Receptores CXCR4/genética , Adolescente , Adulto , Idoso , Animais , Apoptose/genética , Neoplasias Ósseas/patologia , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células/genética , Criança , Regulação para Baixo/genética , Feminino , Regulação Neoplásica da Expressão Gênica/genética , Humanos , Neoplasias Pulmonares/patologia , Masculino , Camundongos Nus , Pessoa de Meia-Idade , Adulto Jovem
8.
Molecules ; 23(4)2018 Mar 31.
Artigo em Inglês | MEDLINE | ID: mdl-29614741

RESUMO

[Co2(L)Ce(OAc)3(CH3CH2OH)]·1.5CH3OH∙0.5CH2Cl2, a heterotrinuclear Co(II)-Ce(III) bis(salamo)-type complex with a symmetric bi(salamo)-type ligand H4L and an acyclic naphthalenediol moiety, was designed, synthesized and characterized by elemental analyses, FT-IR, UV-Vis and fluorescence spectroscopy and X-ray crystallography. The X-ray crystallographic investigation revealed the heterotrinuclear complex consisted of two Co(II) atoms, one Ce(III) atom, one (L)4‒ unit, three µ2-acetate ions, one coordinated ethanol molecule, one and half crystallization methanol molecule and half crystallization dichloromethane molecule. Two Co(II) atoms located in the N2O2 coordination spheres, are both hexacoordinated, with slightly distorted octahedral geometries. The Ce(III) atom is nine-coordinated and located in the O6 cavity possesses a single square antiprismatic geometry. In addition, supramolecular interactions exist in the Co(II)-Ce(III) complex. Two infinite 2D supramolecular structures are built via intermolecular O-H···O, C-H···O and C-H···π interactions, respectively.


Assuntos
Cério/química , Cobalto/química , Complexos de Coordenação/síntese química , Oximas/química , Complexos de Coordenação/química , Cristalografia por Raios X , Fluorescência , Ligação de Hidrogênio , Ligantes , Espectrometria de Fluorescência
9.
Zhong Nan Da Xue Xue Bao Yi Xue Ban ; 42(4): 445-450, 2017 Apr 28.
Artigo em Chinês | MEDLINE | ID: mdl-28490704

RESUMO

OBJECTIVE: To establish a database for pelvic trauma in Hunan Province, and to start the work of multicenter pelvic trauma registry.
 Methods: To establish the database, literatures relevant to pelvic trauma were screened, the experiences from the established trauma database in China and abroad were learned, and the actual situations for pelvic trauma rescue in Hunan Province were considered. The database for pelvic trauma was established based on the PostgreSQL and the advanced programming language Java 1.6.
 Results: The complex procedure for pelvic trauma rescue was described structurally. The contents for the database included general patient information, injurious condition, prehospital rescue, conditions in admission, treatment in hospital, status on discharge, diagnosis, classification, complication, trauma scoring and therapeutic effect. The database can be accessed through the internet by browser/servicer. The functions for the database include patient information management, data export, history query, progress report, video-image management and personal information management.
 Conclusion: The database with whole life cycle pelvic trauma is successfully established for the first time in China. It is scientific, functional, practical, and user-friendly.


Assuntos
Pelve/lesões , Sistema de Registros , China , Humanos
10.
Rapid Commun Mass Spectrom ; 30 Suppl 1: 173-8, 2016 08.
Artigo em Inglês | MEDLINE | ID: mdl-27539434

RESUMO

RATIONALE: As a key signal transducer and transcription activator, STAT3 plays a very important role in many cell processes. We found that there were many G-rich sequences existing in the STAT3 gene including its promoter, intron, exon and 3'-flanking regions. These G-rich tracts can form G-quadruplexes under near physiological conditions. In this research, we systemically studied the G-quadruplexes in the STAT3 gene at a whole gene scale for the first time. METHODS: In this research, the formation of G-quadruplexes in the STAT3 gene was probed by electrospray ionization mass spectrometry (ESI-MS) and circular dichroism (CD). Their structures were constructed and refined by a molecular modeling method. We also used ESI-MS to study the recognition of the G-quadruplexes in the promoter of the STAT3 gene by flexible molecules which do not have a planar core like the other common quadruplex ligands. RESULTS: The results based on ESI-MS suggested that the G-quadruplexes in the promoter of the STAT3 gene formed and were further recognized by some small molecules. CONCLUSION: Our research proved that the G-rich sequences in the STAT3 gene could form G-quadruplexes under near physiological conditions. This provides a promising target to study the regulation of cell signal transduction in vivo and drug design that aims to target STAT3 G-quadruplexes. Copyright © 2016 John Wiley & Sons, Ltd.


Assuntos
Quadruplex G , Fator de Transcrição STAT3/genética , Espectrometria de Massas por Ionização por Electrospray/métodos , Dicroísmo Circular , Pegada de DNA/métodos , Humanos , Modelos Moleculares , Conformação de Ácido Nucleico
11.
J Am Chem Soc ; 136(6): 2583-91, 2014 Feb 12.
Artigo em Inglês | MEDLINE | ID: mdl-24450937

RESUMO

Four putative G-quadruplex sequences (PGSs) in the HIF1α promoter and the 5'UTR were evaluated for their G-quadruplex-forming potential using ESI-MS, CD, FRET, DMS footprinting, and a polymerase stop assay. An important G-quadruplex (S1) has been proven to inhibit HIF1α transcription by blocking AP2 binding. A benzo[c]phenanthridine derivative was found to target the S1 G-quadruplex and induce its conformational conversion from antiparallel to parallel orientation. The transcriptional suppression of HIF1α by this compound was demonstrated using western blotting, Q-RT-PCR, luciferase assay, and ChIP. Our new findings provided a novel strategy for HIF1α regulation and potential insight for cancer therapy.


Assuntos
Benzoatos/química , Desenho de Fármacos , Quadruplex G/efeitos dos fármacos , Subunidade alfa do Fator 1 Induzível por Hipóxia/efeitos dos fármacos , Subunidade alfa do Fator 1 Induzível por Hipóxia/genética , Fenantridinas/química , Regiões Promotoras Genéticas , Benzoatos/farmacologia , Western Blotting , Dicroísmo Circular , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , Subunidade alfa do Fator 1 Induzível por Hipóxia/antagonistas & inibidores , Espectroscopia de Ressonância Magnética , Modelos Biológicos , Modelos Moleculares , Fenantridinas/farmacologia
12.
Int J Biol Macromol ; 270(Pt 2): 132187, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38723827

RESUMO

Injectable hydrogels fabricated from natural polymers have attracted increasing attentions for their potential in biomedical application owing to the biocompatibility and biodegradability. A new class of natural polymer based self-healing hydrogel is constructed through dynamic covalent bonds. The injectable self-healing hydrogels are fabricated by introducing alginate aldehyde to form Schiff base bonds with the chitin nanofibers. These hydrogels demonstrate excellent self-healing properties, injectability, and pH-responsive sol-gel transition behaviors. As a result, they can serve as carriers to allow an effective encapsulation of doxorubicin (DOX) for drug delivery. Furthermore, these hydrogels exhibit excellent biocompatibility and degradability in vitro and in vivo. The sustained release of DOX from the hydrogels effectively suppresses tumor growth in animal models without causing significant systemic toxicity, suggesting their potential application in anti-tumor therapies.


Assuntos
Alginatos , Antineoplásicos , Quitina , Doxorrubicina , Hidrogéis , Nanofibras , Quitina/química , Quitina/análogos & derivados , Alginatos/química , Nanofibras/química , Animais , Doxorrubicina/química , Doxorrubicina/farmacologia , Hidrogéis/química , Antineoplásicos/farmacologia , Antineoplásicos/química , Humanos , Camundongos , Sistemas de Liberação de Medicamentos , Portadores de Fármacos/química , Liberação Controlada de Fármacos , Materiais Biocompatíveis/química , Injeções , Linhagem Celular Tumoral
13.
Adv Sci (Weinh) ; 11(3): e2304053, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38029340

RESUMO

Hepatectomy, a surgical procedure for liver cancer, is often plagued by high recurrence rates worldwide. The recurrence of liver cancer is primarily attributed to microlesions in the liver, changes in the immune microenvironment, and circulating tumor cells in the bloodstream. To address this issue, a novel intervention method that combines intraoperative hemostasis with mild photothermal therapy is proposed, which has the potential to ablate microlesions and improve the immune microenvironment simultaneously. Specifically, the integrated strategy is realized based on the fibrous chitosan/polydopamine sponge (CPDS), which is constructed from shearing-flow-induced oriented hybrid chitosan fibers and subsequent self-assembly of polydopamine. The CPDS demonstrates high elasticity, excellent water absorption, and photothermal conversion performance. The results confirm the efficient hemostatic properties of the fibrous CPDS in various bleeding models. Notably, in subcutaneous and orthotopic postoperative recurrence and metastasis models of hepatocellular carcinoma, the fibrous CPDS significantly inhibits local tumor recurrence and distant metastasis. Moreover, the combination with lenvatinib can substantially enhance the antitumor effect. This comprehensive treatment strategy offers new insights into hepatectomy of liver cancer, representing a promising approach for clinical management.


Assuntos
Carcinoma Hepatocelular , Quitosana , Indóis , Neoplasias Hepáticas , Polímeros , Humanos , Carcinoma Hepatocelular/cirurgia , Neoplasias Hepáticas/cirurgia , Quitosana/farmacologia , Recidiva Local de Neoplasia/prevenção & controle , Hemostasia , Microambiente Tumoral
14.
Spectrochim Acta A Mol Biomol Spectrosc ; 314: 124187, 2024 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-38547781

RESUMO

A bis(salamo)-like chemical sensor H3L ((1E,3E)-2-hydroxy-5-methylisophthalaldehyde O,O -di(3-((((E)-(2-hydroxynaphthalen-1-yl)methylene)amino)oxy)propyl) dioxime) was constructed. H3L is capable of recognizing B4O72- in H2O/DMF (1:9, v/v) solution by both fluorescent and colorimetric channels, bright green fluorescence was turned on when B4O72- was added to H3L and changed from colorless to yellow in natural light. The detection limit was 3.21 × 10-8 M. The identification has good anti-interfering ability, quickly responsive time (5 S) and broad pH detecting range (pH = 5-12). The mechanism of action was determined by 1H NMR titration, infrared spectrometry, HRMS spectra and further elucidated by theory calculations. The fluorescence imaging of bean sprouts and spiked recovery assays of actual water samples demonstrated the practical use of sensor H3L for the detection of B4O72-, which is expected to have applications for the detection of B4O72- in plants and the environment.

15.
Tissue Cell ; 86: 102279, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38007880

RESUMO

Injectable hydrogels are currently a topic of great interest in bone tissue engineering, which could fill irregular bone defects in a short time and avoid traditional major surgery. Herein, we developed an injectable gellan gum (GG)-based hydrogel for bone defect repair by blending nano-hydroxyapatite (nHA) and magnesium sulfate (MgSO4). In order to acquire an injectable GG-based hydrogel with superior osteogenesis, nHA were blended into GG solution with an optimized proportion. For the aim of endowing this hydrogel capable of angiogenesis, MgSO4 was also incorporated. Physicochemical evaluation revealed that GG-based hydrogel containing 5% nHA (w/v) and 2.5 mM MgSO4 (GG/5%nHA/MgSO4) had appropriate sol-gel transition time, showed a porosity-like structure, and could release magnesium ions for at least 14 days. Rheological studies showed that the GG/5%nHA/MgSO4 hydrogel had a stable structure and repeatable self-healing properties. In-vitro results determined that GG/5%nHA/MgSO4 hydrogel presented superior ability on stimulating bone marrow mesenchymal stem cells (BMSCs) to differentiate into osteogenic linage and human umbilical vein endothelial cells (HUVECs) to generate vascularization. In-vivo, GG/5%nHA/MgSO4 hydrogel was evaluated via a rat cranial defect model, as shown by better new bone formation and more neovascularization invasion. Therefore, the study demonstrated that the new injectable hydrogel, is a favorable bioactive GG-based hydrogel, and provides potential strategies for robust therapeutic interventions to improve the repair of bone defect.


Assuntos
Hidrogéis , Osteogênese , Polissacarídeos Bacterianos , Ratos , Humanos , Animais , Hidrogéis/farmacologia , Hidrogéis/química , Angiogênese , Regeneração Óssea , Engenharia Tecidual , Células Endoteliais da Veia Umbilical Humana
16.
Adv Sci (Weinh) ; 11(6): e2306428, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38060833

RESUMO

In order to repair critical-sized bone defects, various polylactic acid-glycolic acid (PLGA)-based hybrid scaffolds are successfully developed as bone substitutes. However, the byproducts of these PLGA-based scaffolds are known to acidify the implanted site, inducing tiresome acidic inflammation. Moreover, these degradation productions cannot offer an osteo-friendly microenvironment at the implanted site, matching natural bone healing. Herein, inspired by bone microenvironment atlas of natural bone-healing process, an osteo-microenvironment stage-regulative scaffold (P80/D10/M10) is fabricated by incorporating self-developed decellularized bone matrix microparticles (DBM-MPs) and multifunctional magnesium hydroxide nanoparticles (MH-NPs) into PLGA with an optimized proportion using low-temperature rapid prototyping (LT-RP) 3D-printing technology. The cell experiments show that this P80/D10/M10 exhibits excellent properties in mechanics, biocompatibility, and biodegradability, meanwhile superior stimulations in osteo-immunomodulation, angiogenesis, and osteogenesis. Additionally, the animal experiments determined that this P80/D10/M10 can offer an osteo-friendly microenvironment in a stage-matched pattern for enhanced bone regeneration, namely, optimization of early inflammation, middle neovascularization, and later bone formation. Furthermore, transcriptomic analysis suggested that the in vivo performance of P80/D10/M10 on bone defect repair is mostly attributed to regulating artery development, bone development, and bone remodeling. Overall, this study reveals that the osteo-microenvironment stage-regulative scaffold provides a promising treatment for bone defect repair.


Assuntos
Materiais Biocompatíveis , Glicolatos , Osteogênese , Animais , Alicerces Teciduais , Regeneração Óssea , Neovascularização Patológica , Inflamação
17.
Pest Manag Sci ; 80(6): 2710-2723, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38358029

RESUMO

BACKGROUND: Xanthomonas oryzae pv. oryzae (Xoo) is often considered one of the most destructive bacterial pathogens causing bacterial leaf blight (BLB), resulting in significant yield and cost losses in rice. In this study, a series of novel derivatives containing the isopropanolamine moiety linked to various substituted phenols and piperazines were designed, synthesized and screened. RESULTS: Antibacterial activity results showed that most compounds had good inhibitory effects on Xoo, among which compound W2 (EC50 = 2.74 µg mL-1) exhibited the most excellent inhibitory activity, and W2 also had a certain curative effect (35.89%) on rice compared to thiodiazole copper (TC) (21.57%). Scanning electron microscopy (SEM) results indicated that compound W2 could cause rupture of the Xoo cell membrane. Subsequently, proteomics and quantitative real-time polymerase chain reaction revealed that compound W2 affected the physiological processes of Xoo and may exert antibacterial activity by targeting the two-component system pathway. Interestingly, W2 upregulated Xoo's methyltransferase to impact on its pathogenicity. CONCLUSION: The present study offers a promising phenolic-piperazine-sopropanolamine compound as an innovative antibacterial strategy by specifically targeting the two-component system pathway and inducing upregulation of methyltransferase to effectively impact Xoo's pathogenicity. © 2024 Society of Chemical Industry.


Assuntos
Antibacterianos , Xanthomonas , Xanthomonas/efeitos dos fármacos , Antibacterianos/farmacologia , Antibacterianos/síntese química , Antibacterianos/química , Fenóis/farmacologia , Fenóis/química , Desenho de Fármacos , Piperazinas/farmacologia , Piperazinas/química , Piperazinas/síntese química , Oryza/microbiologia , Doenças das Plantas/microbiologia
18.
Int J Nanomedicine ; 18: 8131-8141, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38169995

RESUMO

Background: Combination therapy employing multiple drugs has been shown to enhance the efficacy of cancer treatment. Chlorambucil (Chl) and 6-mercaptopurine (6MP) are the first-line medicines for chronic lymphocytic leukemia and ovarian cancer. However, both were limited by their short half-life of disintegration, unsatisfactory water solubility, and adverse reactions. Methods: In this work, the drug Chl and 6MP were introduced into the polymerized N-(2-hydroxypropyl) methacrylamide (polyHPMA) by pH and glutathione responsive linker to construct the polymer nanodrug delivery system for effective co-delivery. Results: The drug load capacities, release, morphology, and cytotoxicity of the pro-drug were systematic. The two drugs showed satisfactory synergism with a combination index of 0.81, and a better ability to induce apoptosis. In and ex vivo fluorescence imaging showed a rapid systemic distribution of the conjugate within mice, majorly metabolized by liver and kidneys and eliminated after 24 hr. No significant pathological damage was observed in the major organs. This polymeric prodrug system holds promise for improved therapeutic efficiency and reduced side effects through the synergistic delivery of various chemotherapeutics. Conclusion: The introduction of HPMA as a carrier not only enhanced the solubility and biocompatibilities of Chl and 6 MP but also improved their drug effect. This strategy might be a promising alternative for constructing multi-drug-release system.


Assuntos
Neoplasias Ovarianas , Pró-Fármacos , Humanos , Feminino , Camundongos , Animais , Mercaptopurina , Clorambucila , Neoplasias Ovarianas/patologia , Pró-Fármacos/farmacologia , Liberação Controlada de Fármacos , Linhagem Celular Tumoral , Doxorrubicina
19.
Carbohydr Polym ; 306: 120575, 2023 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-36746566

RESUMO

Infections caused by bacteria have long constituted a major threat to human health and the economy. Therefore, there is an urgent need to design broad-spectrum antibacterial materials possessing good biocompatibility to treat such infections. Herein, inspired by the good biocompatibility of chitin and antibacterial properties of imidazolium salts, a polysaccharide-based material, imidazolium salt chitin (IMSC), was homogeneously prepared using a facile method with epichlorohydrin as a chemical crosslinker to combine chitin with imidazole to enhance Staphylococcus aureus (S. aureus)-infected wound healing. The characteristics, antimicrobial properties, and biosafety of IMSC were evaluated. The results demonstrated successful grafting of imidazole onto chitin. Furthermore, IMSC exhibited good water solubility, broad-spectrum antimicrobial activity, hemocompatibility, and biocompatibility. Moreover, IMSC enabled complete healing of S. aureus-infected wound in Sprague-Dawley rats within 15 days of application, thus demonstrating that IMSC could reduce wound inflammation and remarkably accelerate wound healing owing to its efficient antibacterial activity and ability to promote collagen deposition in and around the wound area. Therefore, this study provides a promising and potential therapeutic strategy for infected wound healing by synthesizing a water-soluble and broad-spectrum antimicrobial material exhibiting good biocompatibility.


Assuntos
Anti-Infecciosos , Infecção dos Ferimentos , Ratos , Animais , Humanos , Staphylococcus aureus , Ratos Sprague-Dawley , Escherichia coli , Cicatrização , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Antibacterianos/química , Quitina/farmacologia , Quitina/uso terapêutico , Quitina/química , Cloreto de Sódio , Água/química , Infecção dos Ferimentos/tratamento farmacológico
20.
Bone Res ; 11(1): 37, 2023 07 20.
Artigo em Inglês | MEDLINE | ID: mdl-37474577

RESUMO

In this study, we aimed to investigate the causal associations of brain structure with bone mineral density (BMD). Based on the genome-wide association study (GWAS) summary statistics of 1 325 brain imaging-derived phenotypes (BIDPs) of brain structure from the UK Biobank and GWAS summary datasets of 5 BMD locations, including the total body, femoral neck, lumbar spine, forearm, and heel from the GEFOS Consortium, linkage disequilibrium score regression (LDSC) was conducted to determine the genetic correlations, and Mendelian randomization (MR) was then performed to explore the causal relationship between the BIDPs and BMD. Several sensitivity analyses were performed to verify the strength and stability of the present MR outcomes. To increase confidence in our findings, we also performed confirmatory MR between BIDPs and osteoporosis. LDSC revealed that 1.93% of BIDPs, with a false discovery rate (FDR) < 0.01, were genetically correlated with BMD. Additionally, we observed that 1.31% of BIDPs exhibited a significant causal relationship with BMD (FDR < 0.01) through MR. Both the LDSC and MR results demonstrated that the BIDPs "Volume of normalized brain," "Volume of gray matter in Left Inferior Frontal Gyrus, pars opercularis," "Volume of Estimated Total Intra Cranial" and "Volume-ratio of brain segmentation/estimated total intracranial" had strong associations with BMD. Interestingly, our results showed that more left BIDPs were causally associated with BMD, especially within and around the left frontal region. In conclusion, a part of the brain structure causally influences BMD, which may provide important perspectives for the prevention of osteoporosis and offer valuable insights for further research on the brain-bone axis.


Assuntos
Densidade Óssea , Osteoporose , Humanos , Densidade Óssea/genética , Estudo de Associação Genômica Ampla , Correlação de Dados , Análise da Randomização Mendeliana , Polimorfismo de Nucleotídeo Único , Osteoporose/diagnóstico por imagem , Colo do Fêmur , Córtex Pré-Frontal
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