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1.
J Biol Chem ; 300(6): 107394, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38768813

RESUMO

Periprosthetic osteolysis and subsequent aseptic loosening are the primary causes of failure following total joint arthroplasty. Wear particle-induced osteogenic impairment is recognized as an important contributing factor in the development of osteolysis, with endoplasmic reticulum (ER) stress emerging as a pivotal underlying mechanism. Hence, searching for potential therapeutic targets and agents capable of modulating ER stress in osteoblasts is crucial for preventing aseptic loosening. Kaempferol (KAE), a natural flavonol compound, has shown promising osteoprotective effects and anti-ER stress properties in diverse diseases. However, the influence of KAE on ER stress-mediated osteogenic impairment induced by wear particles remains unclear. In this study, we observed that KAE effectively relieved TiAl6V4 particles-induced osteolysis by improving osteogenesis in a mouse calvarial model. Furthermore, we demonstrated that KAE could attenuate ER stress-mediated apoptosis in osteoblasts exposed to TiAl6V4 particles, both in vitro and in vivo. Mechanistically, our results revealed that KAE mitigated ER stress-mediated apoptosis by upregulating the IRE1α-XBP1s pathway while concurrently partially inhibiting the IRE1α-regulated RIDD and JNK activation. Collectively, our findings suggest that KAE is a prospective therapeutic agent for treating wear particle-induced osteolysis and highlight the IRE1α-XBP1s pathway as a potential therapeutic target for preventing aseptic loosening.


Assuntos
Estresse do Retículo Endoplasmático , Endorribonucleases , Quempferóis , Osteoblastos , Osteogênese , Osteólise , Proteínas Serina-Treonina Quinases , Proteína 1 de Ligação a X-Box , Animais , Estresse do Retículo Endoplasmático/efeitos dos fármacos , Quempferóis/farmacologia , Proteínas Serina-Treonina Quinases/metabolismo , Proteína 1 de Ligação a X-Box/metabolismo , Proteína 1 de Ligação a X-Box/genética , Camundongos , Osteogênese/efeitos dos fármacos , Endorribonucleases/metabolismo , Endorribonucleases/genética , Osteoblastos/metabolismo , Osteoblastos/efeitos dos fármacos , Osteólise/metabolismo , Osteólise/induzido quimicamente , Osteólise/patologia , Osteólise/tratamento farmacológico , Apoptose/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Masculino , Humanos , Camundongos Endogâmicos C57BL
2.
ACS Appl Mater Interfaces ; 14(51): 56510-56524, 2022 Dec 28.
Artigo em Inglês | MEDLINE | ID: mdl-36516041

RESUMO

Shikonin (Shik), a natural pigment, has received growing interest in various biomedical fields due to its anti-inflammatory, antitumor, antimicrobial, and antioxidant ability. However, some inherent characteristics of Shik, such as its virulence, low bioavailability, and poor solubility, have limited its biomedical applicability. Here, we reported a facile synthetic method to produce the Shik-iron (III) nanoparticles (Shik-Fe NPs), which could overcome these limitations of Shik. The synthesized Shik-Fe NPs possessed a uniform size range of 110 ± 10 nm, negative surface charges, good water dispersity, and high safety. Iron distributed uniformly inside Shik-Fe NPs, and iron constituted 20% of total mass in PEGylated Shik-Fe NPs. When interacting with activated macrophages, Shik-Fe NPs significantly reduced the level of cellular inflammatory factors, for example, iNOS, IL-1ß, and TNF-α. Furthermore, the Shik-Fe NPs demonstrated synergistic anti-inflammation and anti-bacterial properties in vivo, since they could release Fe3+ and Shik to eradicate bacteria (Staphylococcus aureus and P. aeruginosa were used as model microbes here) during wound infections and provide full recovery for scald wounds. Collectively, the study established a dual-functional Shik-derived nanoplatform, which could be useful for the treatment of various inflammation-involved diseases.


Assuntos
Anti-Infecciosos , Nanopartículas , Compostos Férricos , Staphylococcus aureus , Anti-Inflamatórios , Ferro , Antibacterianos/farmacologia
3.
Mitochondrial DNA B Resour ; 6(7): 1875-1876, 2021 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-34151006

RESUMO

Phoebe minutiflora H. W. Li, is a member of the Lauraceae family, while its generic relationship has been long-term controversial. The complete chloroplast (cp) genome of P. minutiflora was first reported in this paper. The cp genome was 152,654 bp in length with four typical quadripartite structures, which was consisted of a large single-copy (LSC) region of 93,697 bp, a small single-copy (SSC) region of 18,809 bp, and two inverted repeats (IRs) of 20,074 bp. In addition, there were a total of 112 unique genes, including 79 protein-coding genes, 29 tRNA genes, and four rRNA genes. The phylogenetic analysis indicated that P. minutiflora should be placed into Machilus.

4.
J Plant Physiol ; 246-247: 153142, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32112957

RESUMO

WRKY transcription factors have been suggested to play important roles in response and adaptation to drought stress. However, how sorghum WRKY transcription factors function in drought stress is still unclear. Here, we identify a WRKY transcription factor of sorghum, SbWRKY30, which is induced significantly by drought stress. SbWRKY30 is mainly expressed in sorghum taproot and leaf. SbWRKY30 has transcriptional activation activity and functions in the nucleus. Heterologous expression of SbWRKY30 confers tolerance to drought stress in Arabidopsis (Arabidopsis thaliana) and rice by affecting root architecture. In addition, SbWRKY30 transgenic Arabidopsis and rice plants have higher proline contents and SOD, POD, and CAT activities but lower MDA contents than wild-type plants after drought stress. As a homologous gene of the drought stress-responsive gene RD19 of Arabidopsis, SbRD19 overexpression in Arabidopsis improved the drought tolerance of plants relative to wild-type plants. Further analysis demonstrated that SbWRKY30 could induce SbRD19 expression through binding to the W-box element in the promoter of SbRD19. These results suggest that SbWRKY30 functions as a positive regulator in response to drought stress. Therefore, SbWRKY30 may serve as a promising candidate gene for molecular breeding to generate drought-tolerant crops.


Assuntos
Adaptação Fisiológica/genética , Secas , Regulação da Expressão Gênica de Plantas , Proteínas de Plantas/genética , Sorghum/fisiologia , Fatores de Transcrição/genética , Arabidopsis/genética , Proteínas de Plantas/metabolismo , Plantas Geneticamente Modificadas/genética , Sorghum/genética , Fatores de Transcrição/metabolismo
5.
Sci Total Environ ; 643: 785-792, 2018 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-29960222

RESUMO

A high prevalence of infectious diseases (mostly lungworms) is found in finless porpoises (genus Neophocaena) in the coastal waters of China, which is one of the most dichlorodiphenyltrichloroethane (DDT)-polluted areas worldwide, while its association with contaminant exposure remains undetermined. To address this gap, we investigated blubber levels of polychlorinated diphenyls (PCBs), organochlorine pesticides (OCPs) and polycyclic aromatic hydrocarbons in Indo-Pacific finless porpoises (Neophocaena phocaenoides) stranded in the Pearl River Estuary (PRE) of China. In the post-mortem examinations, lungworms (Halocercus species) were found to be the most common parasites, with a high density observed in lungs and bronchi. Severe infections by nematode parasites were also found in the uterus (Cystidicola species), intestine (Anisakis typica) and muscle (A. typica). For all the pollutant compounds analyzed, only the concentrations of p,p'-DDT, p,p'-dichlorodiphenyldichloroethane (DDD) and o,p'-DDD were significantly higher in porpoises died of infectious diseases than in the "healthy" individuals (died from physical trauma). Contrasted accumulation pattern of DDTs and their metabolites was found between animals with different health status. The proportion of p,p'-DDT in ΣDDTs was higher than that of p,p'-dichlorodiphenyldichloroethylene (DDE) in diseased animals, whereas an opposite pattern was shown for "healthy" ones. While this study is the first to describe a significant positive correlation between parasitic diseases and high levels of DDTs in cetaceans, the direction of causality cannot be determined in our data: either a parasitic infection affected the porpoises' ability to metabolize DDTs, resulting in high levels of p,p'-DDT in their blubber, or the pollutant burden rendered them more susceptible to parasitic infection.


Assuntos
Monitoramento Ambiental , Estuários , Toninhas/metabolismo , Poluentes Químicos da Água/metabolismo , Animais , Carga Corporal (Radioterapia) , China , DDT/metabolismo , Feminino , Hidrocarbonetos Clorados/metabolismo , Toninhas/parasitologia , Rios , Poluentes Químicos da Água/análise
6.
Theriogenology ; 74(8): 1467-75, 2010 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-20708252

RESUMO

Most male mammals in temperate regions demonstrate seasonal sexual behaviors that coincide with seasonal variations in gonadal activities and androgen hormones. The Yangtze finless porpoise is a temperate freshwater cetacean species and an obvious seasonal breeder. To investigate the relationship between sexual behavior and gonadal activity in this animal, testicular size (volume) and structure (ultrasonogram pixel intensity) of two adult male porpoises (AF, AB) and one sub-adult male (TT) were longitudinally monitored from November 2008 to November 2009. Serum testosterone concentration was also monitored during the same period. Variations in the frequency of sexual behavior in AF and AB had similar, but seasonal trends. Their testicular size and pixel intensity also varied seasonally. Testicular size increased in March, peaked from April through June, and decreased gradually from August through September, whereas testicular pixel intensity started to increase in early February. The frequency of sexual behavior was positively correlated with testicular volume and pixel intensity (P = 0.000018 and P = 0.00012, respectively) in AF. Serum testosterone concentrations also varied. The sub-adult male porpoise, TT, was undergoing puberty, as evidenced by its marked increase in testicular volume, testicular pixel intensity, and serum testosterone concentrations from the beginning of 2009. Interestingly, TT exhibited the highest frequency of sexual behavior, most of which was same-sex pairing. However, its oversexed behavior neither quantitatively correlated with its smaller testicular volume (P = 0.61) nor with its testicular pixel intensity (P = 0.69).


Assuntos
Toninhas/fisiologia , Estações do Ano , Comportamento Sexual Animal , Fatores Etários , Animais , Estudos Longitudinais , Masculino , Toninhas/metabolismo , Testículo/anatomia & histologia , Testículo/diagnóstico por imagem , Testosterona/sangue , Ultrassonografia
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