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1.
Carcinogenesis ; 44(8-9): 682-694, 2023 12 02.
Artigo em Inglês | MEDLINE | ID: mdl-37294054

RESUMO

EphB6 belongs to the receptor tyrosine kinase, whose low expression is associated with shorter survival of colorectal cancer (CRC) patients. But the role and mechanism of EphB6 in the progression of CRC need further study. In addition, EphB6 was mainly expressed in intestinal neurons. But how EphB6 is involved in functions of intestinal neurons has not been known. In our study, we constructed a mouse xenograft model of CRC by injecting CMT93 cells into the rectum of EphB6-deficient mice. We found that the deletion of EphB6 in mice promoted tumor growth of CMT93 cells in a xenograft model of CRC, which was independent of changes in the gut microbiota. Interestingly, inhibition of intestinal neurons by injecting botulinum toxin A into rectum of EphB6-deficient mice could eliminate the promotive effect of EphB6 deficiency on tumor growth in the xenograft model of CRC. Mechanically, the deletion of EphB6 in mice promoted the tumor growth in CRC by increasing GABA in the tumor microenvironment. Furthermore, EphB6 deficiency in mice increased the expression of synaptosomal-associated protein 25 in the intestinal myenteric plexus, which mediated the release of GABA. Our study concluded that EphB6 knockout in mice promotes tumor growth of CMT93 cells in a xenograft model of CRC by modulating GABA release. Our study found a new regulating mechanism of EphB6 on the tumor progression in CRC that is dependent on intestinal neurons.


Assuntos
Comunicação Celular , Neoplasias Colorretais , Humanos , Animais , Camundongos , Neoplasias Colorretais/metabolismo , Intestinos/patologia , Neurônios/metabolismo , Neurônios/patologia , Ácido gama-Aminobutírico , Microambiente Tumoral
2.
Phytother Res ; 37(12): 5871-5882, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37646382

RESUMO

Renal tubular injury is a key factor in the progression of diabetic kidney disease to end-stage renal disease. Hyperoside, a natural flavonol glycoside in various plants, is a potentially effective drug for the clinical treatment of diabetic kidney disease. However, the specific mechanisms remain unknown. Therefore, this study will explore the effect and mechanism of hyperoside on renal tubulointerstitium in diabetic kidney disease. db/db mouse (C57BL/KsJ) is a model of type 2 diabetes resulting from Leptin receptor point mutations, with the appearance of diabetic kidney disease. Therefore, db/db mice were used for in vivo experimental studies. In vitro, human renal tubular epithelial cells were incubated with bovine serum albumin to simulate the injury of renal tubular epithelial cells caused by excessive albumin in primary urine. The experimental results showed that hyperoside could improve kidney function and reduce kidney tissue damage in mice, and could inhibit oxidative stress, extracellularly regulated protein kinases 1/2 signaling activation, and pyroptosis in human renal tubular epithelial cells. Therefore, hyperoside inhibited oxidative stress by regulating the activation of the extracellularly regulated protein kinases 1/2/mitogen-activated protein kinase signaling pathway, thereby alleviating proteinuria-induced pyroptosis in renal tubular epithelial cells. This study provides novel evidence that could facilitate the clinical application of hyperoside in diabetic kidney disease treatment.


Assuntos
Diabetes Mellitus Tipo 2 , Nefropatias Diabéticas , Humanos , Camundongos , Animais , Nefropatias Diabéticas/tratamento farmacológico , Espécies Reativas de Oxigênio/metabolismo , Piroptose , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/metabolismo , Camundongos Endogâmicos C57BL , Rim , Transdução de Sinais , Proteínas Quinases/metabolismo
3.
Childs Nerv Syst ; 37(10): 3277-3279, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-33404717

RESUMO

BACKGROUND: Teratoma involving of cerebellopontine angle (CPA) area is extremely rare, only several cases were described based on previous literature. Here we reported uncommon pediatric teratoma located in the left CPA. The purpose of this document is to explore clinical manifestations, diagnosis and and treatment of this disease. METHODS: We accomplish it by analyzing the previous literature and this case report. CONCLUSION: Through clinical manifestations, imaging examination and HE staining, teratoma can be diagnosed and other lesions can be distinguished. The excellent outcome was obtained after tumor was totally removed under microsurgery.


Assuntos
Neoplasias Cerebelares , Teratoma , Neoplasias Cerebelares/diagnóstico por imagem , Neoplasias Cerebelares/cirurgia , Ângulo Cerebelopontino/diagnóstico por imagem , Ângulo Cerebelopontino/cirurgia , Criança , Humanos , Imageamento por Ressonância Magnética , Microcirurgia , Teratoma/diagnóstico por imagem , Teratoma/cirurgia
4.
Int J Biol Macromol ; 276(Pt 1): 134110, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39047994

RESUMO

ß-Carotene is widely used in food systems because of its biological activity; however, ß-carotene has poor chemical stability and low bioavailability. Thus, researchers use encapsulated delivery systems to overcome these disadvantages. In this study, we prepared emulsion gels to encapsulate ß-carotene, using Longzhua mushroom polysaccharide (LMP), which can autonomously form weak gels. The LMP emulsion gel (LEG) exhibited a high water-holding capacity of up to 95.06 %. All samples showed adequate storage stability for 28 days. Increasing the polysaccharide content in the emulsion gel enhanced the encapsulation efficiency of ß-carotene (96.76 %-98.27 %), the release of free fatty acids (68.21 %-81.44 %), and the photostability (80.65 %-91.27 %), thermal stability (73.84 %-97.08 %), and bioaccessibility (18.28 %-30.26 %) of ß-carotene. In conclusion, LEG is a promising fat-soluble material that can be used for food-grade encapsulated delivery systems.


Assuntos
Agaricales , Emulsões , Géis , Polissacarídeos , beta Caroteno , beta Caroteno/química , Géis/química , Agaricales/química , Polissacarídeos/química , Portadores de Fármacos/química , Disponibilidade Biológica , Estabilidade de Medicamentos
5.
J Mater Chem B ; 12(6): 1592-1603, 2024 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-38265091

RESUMO

Osteoporosis is a disease that manifests itself as an abnormality of bone metabolism and is characterized by low bone mass and destruction of the bone microstructure. Since bone resorption occurs more rapidly than new bone formation, osteoporosis leads to reduced orthopedic implant stability. From a microenvironmental point of view, the rationale for this outcome is that osteoclasts are overactive in the bone tissue of patients with osteoporosis, and the large amount of H+ they produce leads to local chronic acidosis, which promotes bone mineral loss. Therefore, we designed a weakly alkaline layered double hydroxide (LDH) coating to modulate the pathologically acidic microenvironment and the osteogenic-osteoclastic coupling by releasing Sr2+. We prepared Sr-Fe LDH coatings on pure titanium implants using a hydrothermal method in this study and characterized the material using SEM, AFM, XRD, XPS, EDS, ICP, pH acidimeter, etc. We found that the coatings had good nanomorphology and were able to efficiently neutralize H+ as well as steadily release Sr2+ for up to 21 days. In vitro, the coating not only significantly promoted the adhesion, proliferation, and differentiation of osteoblasts, but also inhibited the differentiation of osteoclasts at the same time. In addition, in animal experiments, the coating significantly improved the mechanical stability of the implant in osteoporotic rats, increasing Sr-Fe LDH@Ti maximal push-out force by 72.2% compared to Ti. At the same time, the coating was effective in reversing the osteoporotic state, resulting in a 58.5% increase in BV/TV (%), and a 12.4% increase in Tb. N (1 mm-1), a 31.6% increase in Tb. Th (µm), and a 30.9% increase in BA (%). Our results suggest that this Sr-Fe LDH nanocoating material with acid-neutralizing, as well as long-term Sr2+-releasing capabilities, is a novel and effective orthopedic implant coating material under osteoporotic conditions.


Assuntos
Osseointegração , Osteoporose , Ratos , Humanos , Animais , Próteses e Implantes , Osso e Ossos , Osteoclastos
6.
Spectrochim Acta A Mol Biomol Spectrosc ; 281: 121574, 2022 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-35835059

RESUMO

A novel method of Lorentz distribution solution (LDS) from overlapped absorbance profile in time domain (incomplete absorbance profile in frequency domain) based on the direct absorption spectroscopy method (DAS) was experimentally demonstrated. It utilized the ratio of the integral in a certain interval on the lower horizontal axis of the Lorentzian profile to the integral in the entire interval on the horizontal axis has a certain relationship and can be expressed by a formula. This method effectively solves the difficulties of extracting gas concentration from incomplete absorbance profile. Formulation and detection procedure were presented, experiments were carried out to prove the method on the extraction of gas concentration from different overlapped absorbance profile and different concentration. Compared with the conventional DAS (C-DAS), the maximum relative errors on the concentration extraction are minimized from 25.55% to 2.64% at different concentration and absorbance profile. Meanwhile, the experimental results show that the obtained gas concentration by LDS presents a good linear relationship while those measured by C-DAS are significantly different.


Assuntos
Análise Espectral , Análise Espectral/métodos
7.
Front Oncol ; 11: 739714, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-35155179

RESUMO

Craniopharyngiomas (CPs) are rare tumors arising from the sellar region. Although the best outcome for patients with one subtype, adamantinomatous craniopharyngioma (ACP), is obtained by gross total resection, little is known about the roles of long noncoding RNAs (lncRNAs) and transcription factors (TFs) in ACP tumorigenesis. In total, 12 human ACP and 5 control samples were subjected to transcriptome-level sequencing. We built an integrated algorithm for identifying lncRNAs and TFs regulating the CP-related pathway. Furthermore, ChIP-Seq datasets with binding domain information were used to further verify and identify TF-lncRNA correlations. RT-PCR and immunohistochemistry staining were performed to validate the potential targets. Five pathways associated with ACP were identified and defined by an extensive literature search. Based on the specific pathways and the whole gene expression profile, 266 ACP-related lncRNAs and 39 TFs were identified by our integrating algorithm. Comprehensive analysis of the ChIP-Seq datasets revealed that 29 TFs were targeted by 12000 lncRNAs in a wide range of tissues, including 161 ACP-related lncRNAs that were identified by the computational method. These 29 TFs and 161 lncRNAs, constituting 1004 TF-lncRNA pairs, were shown to potentially regulate different ACP-related pathways. A total of 232 TF-lncRNA networks were consequently established based on differential gene expression. Validation by RT-PCR and immunohistochemistry staining revealed positive expression of the ACP-related TFs E2F2 and KLF5 in ACP. Moreover, the expression of the lncRNA RP11-360P21.2 was shown to be upregulated in ACP tissues. In this study, we introduced an integrated algorithm for identifying lncRNAs and TFs regulating the ACP-related pathway. This is the first comprehensive study to systematically investigate the potential TF and lncRNA regulatory network in ACP. The resulting data serve as a valuable resource for understanding the mechanisms underlying ACP-related lncRNAs and TFs.

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