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1.
Anticancer Drugs ; 35(6): 535-541, 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38527238

RESUMO

Glioblastoma (GBM) is the most common primary malignant brain tumour and lacks therapeutic options with significant effects. The aberrant activation of STAT3 is a critical factor in glioma progression via activating multiple signalling pathways that promote glioma. Among them, the antiapoptotic gene Bcl-2 could be upregulated by p-STAT3, which is an important reason for the continuous proliferation of glioma. We previously reported that bergaptol, a natural furanocoumarin widely found in citrus products, exerts antineuroinflammatory effects by inhibiting the overactivation of STAT3. Here, we aimed to evaluate whether bergaptol could promote glioma apoptosis by inhibiting the STAT3/Bcl-2 pathway. This study found that bergaptol inhibited the proliferation and migration of GBM cell lines (U87 and A172) and promoted apoptosis in vitro. We also found that bergaptol significantly inhibited the STAT3/Bcl-2 pathway in GBM cells. U87 cells were implanted intracranially into nude mice to establish a glioma model, and glioma-bearing mice were treated with bergaptol (40 mg/kg). Bergaptol treatment significantly inhibited glioma growth and prolonged the glioma-bearing mice's survival time. In addition, bergaptol administration also significantly inhibited the STAT3/Bcl-2 pathway of tumour tissue in vivo. Overall, we found that bergaptol could effectively play an antiglioma role by inhibiting STAT3/Bcl-2 pathway, suggesting the potential efficacy of bergaptol in treating glioma.


Assuntos
Apoptose , Neoplasias Encefálicas , Proliferação de Células , Glioma , Camundongos Nus , Proteínas Proto-Oncogênicas c-bcl-2 , Fator de Transcrição STAT3 , Fator de Transcrição STAT3/metabolismo , Animais , Humanos , Proliferação de Células/efeitos dos fármacos , Apoptose/efeitos dos fármacos , Camundongos , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Neoplasias Encefálicas/tratamento farmacológico , Neoplasias Encefálicas/patologia , Neoplasias Encefálicas/metabolismo , Glioma/tratamento farmacológico , Glioma/patologia , Glioma/metabolismo , Linhagem Celular Tumoral , Transdução de Sinais/efeitos dos fármacos , Ensaios Antitumorais Modelo de Xenoenxerto , Furocumarinas/farmacologia , Camundongos Endogâmicos BALB C , Movimento Celular/efeitos dos fármacos , Flavanonas
2.
BMC Womens Health ; 23(1): 535, 2023 10 11.
Artigo em Inglês | MEDLINE | ID: mdl-37817158

RESUMO

BACKGROUND: Endometriosis (EMS) occurs when normal uterine tissue grows outside the uterus and causes chronic pelvic pain and infertility. Endometriosis-associated infertility is thought to be caused by unknown mechanisms. In this study, using necroptosis-related genes, we developed and validated multigene joint signatures to diagnose EMS and explored their biological roles. METHODS: We downloaded two databases (GSE7305 and GSE1169) from the Gene Expression Omnibus (GEO) database and 630 necroptosis-related genes from the GeneCards and GSEA databases. The limma package in Rsoftware was used to identify differentially expressed genes (DEGs). We interleaved common differentially expressed genes (co-DEGs) and necroptosis-related genes (NRDEGs) in the endometriosis dataset. The DEGs functions were reflected by gene ontology analysis (GO), pathway enrichment analysis, and gene set enrichment analysis (GSEA). We used CIBERSORT to analyze the immune microenvironment differences between EMS patients and controls. Furthermore, a correlation was found between necroptosis-related differentially expressed genes and infiltrating immune cells to better understand the molecular immune mechanism. RESULTS: Compared with the control group, this study revealed that 10 NRDEGs were identified in EMS. There were two types of immune cell infiltration abundance (activated NK cells and M2 macrophages) in these two datasets, and the correlation between different groups of samples was statistically significant (P < 0.05). MYO6 consistently correlated with activated NK cells in the two datasets. HOOK1 consistently demonstrated a high correlation with M2 Macrophages in two datasets. The immunohistochemical result indicated that the protein levels of MYO6 and HOOK1 were increased in patients with endometriosis, further suggesting that MYO6 and HOOK1 can be used as potential biomarkers for endometriosis. CONCLUSIONS: We identified ten necroptosis-related genes in EMS and assessed their relationship with the immune microenvironment. MYO6 and HOOK1 may serve as novel biomarkers and treatment targets in the future.


Assuntos
Endometriose , Infertilidade , Necroptose , Feminino , Humanos , Dor Crônica , Endometriose/diagnóstico , Endometriose/genética , Necroptose/genética , Marcadores Genéticos
3.
Front Pharmacol ; 13: 1038063, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36313284

RESUMO

Although cancer has seriously threatened people's health, it is also identified by the World Health Organization as a controllable, treatable and even curable chronic disease. Traditional Chinese medicine (TCM) has been extensively used to treat cancer due to its multiple targets, minimum side effects and potent therapeutic effects, and thus plays an important role in all stages of tumor therapy. With the continuous progress in cancer treatment, the overall efficacy of cancer therapy has been significantly improved, and the survival time of patients has been dramatically prolonged. In recent years, a series of advanced technologies, including nanotechnology, gene editing technology, real-time cell-based assay (RTCA) technology, and flow cytometry analysis technology, have been developed and applied to study TCM for cancer therapy, which efficiently improve the medicinal value of TCM and accelerate the research progress of TCM in cancer therapy. Therefore, the applications of these advanced technologies in TCM for cancer therapy are summarized in this review. We hope this review will provide a good guidance for TCM in cancer therapy.

4.
Asian J Pharm Sci ; 17(2): 193-205, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-35582642

RESUMO

As an important means of communication among cells, exosomes are being studied more and more widely, especially in the context of cancer immunotherapy. In the phase of tumor immunoediting, exosomes derived from tumor cells and different immune cells have complex and changeable physiological functions, because they carry different proteins and nucleic acid from the source cells. Based on the role of exosomes in the communication between different cells, cancer treatment methods are also under continuous research. This review briefly introduces the molecular composition of exosomes, which is closely related to their secretion mechanism. Subsequently, the role of exosomes encapsulating different information molecules is summarized. The role of exosomes in the three phases of tumor immunoediting is introduced in detail, and the relevant literature of exosomes in the tumor immune microenvironment is summarized by using a novel framework for extracting relevant documents. Finally, it summarizes the various exosome-based immunotherapies currently proposed, as well as the challenges and future prospects of exosomes in tumor immunotherapy.

5.
Hum Cell ; 35(1): 214-225, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34716872

RESUMO

Glioma serves as the most common malignancy influencing modern people and is associated with severe morbidity and high mortality. Long non-coding RNAs (lncRNAs) as crucial regulators participate in multiple cancer progression. However, the role of lncRNA LINC01094 in the development of glioma remains unclear. Here, we aimed to explore the effect of lncRNA LINC01094 on the glioma progression and the underlying mechanism. Significantly, we revealed that the expression levels of LINC01094 were elevated in the glioma patient tissues compared to adjacent normal tissues. The LINC01094 expression was enhanced in the glioma cell lines. The depletion of LINC01094 inhibited cell viability and colony formation in the glioma cells. Meanwhile, the migration and invasion of glioma cells were impaired by the depletion of LINC01094. Mechanically, we identified that LINC01094 was able to sponge the miR-224-5p in the glioma cells and miR-224-5p inhibitor could reverse the effect of LINC01094 on glioma progression. In addition, miR-224-5p targeted CHSY1 and LINC01094 up-regulated CHSY1 by targeting miR-224-5p in the glioma cells. LINC01094 promoted glioma progression by the positive regulation of CHSY1. Moreover, tumorigenicity analysis showed that LINC01094 enhanced tumor growth of glioma in vivo. Thus, we conclude that lncRNA LINC01094 promotes glioma progression by modulating miR-224-5p/CHSY1 axis. Our finding provides new insights into the mechanism by which lncRNA LINC01094 contributes to the development of glioma, improving the understanding of lncRNA LINC01094 and glioma. LncRNA LINC01094, miR-224-5p, and CHSY1 may serve as potential targets for glioma.


Assuntos
Neoplasias Encefálicas/genética , Neoplasias Encefálicas/patologia , Regulação Neoplásica da Expressão Gênica/genética , Expressão Gênica , Glioma/genética , Glioma/patologia , Glucuronosiltransferase/metabolismo , MicroRNAs/metabolismo , Enzimas Multifuncionais/metabolismo , N-Acetilgalactosaminiltransferases/metabolismo , RNA Longo não Codificante/genética , RNA Longo não Codificante/fisiologia , Animais , Neoplasias Encefálicas/terapia , Carcinogênese/genética , Carcinogênese/patologia , Linhagem Celular Tumoral , Sobrevivência Celular/genética , Progressão da Doença , Glioma/terapia , Humanos , Camundongos Nus , Terapia de Alvo Molecular , RNA Longo não Codificante/metabolismo
6.
FEBS Open Bio ; 12(1): 211-220, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34739189

RESUMO

Glioma is the predominant brain malignancy and is correlated with high mortality and severe morbidity. The transcription factor limb-bud and heart (LBH) has been reported to be involved in the development of several cancers, although its role in glioma development remains elusive. Here, we examined the effect of LBH on glioma progression. The expression of LBH was increased in glioma samples from The Cancer Genome Atlas database, and upregulation of LBH was observed to be correlated with the poor survival of glioma patients. We also report that expression of LBH was elevated in clinical glioma tissues compared to adjacent normal tissues, and was also enhanced in glioma cell lines. LBH promotes proliferation and inhibits cell cycle arrest and apoptosis in glioma cells. In addition, LBH increased the migration and invasion of glioma cells in vitro. Moreover, tumorigenicity analysis revealed that LBH could promote the tumor growth of glioma cells in vivo. In conclusion, our findings suggest that LBH contributes to glioma progression in vitro and in vivo. Our findings provide new insights into the mechanism by which LBH promotes the development of glioma, improving our understanding of the correlation between LBH with cancer. LBH may have potential as a target for glioma therapy.


Assuntos
Glioma , Linhagem Celular Tumoral , Regulação da Expressão Gênica , Glioma/genética , Humanos , Fatores de Transcrição/metabolismo , Regulação para Cima
8.
Br J Neurosurg ; 35(2): 229-230, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31452388

RESUMO

Ventriculoperitoneal (VP) shunting is the most widely used procedure for diverting cerebrospinal fluid (CSF) for hydrocephalus. Migration of the distal catheter of VP shunts has been reported but extrusion through the abdominal wall is rare. We report a case involving distal catheter extrusion. The catheter was exteriorized without compromising CSF flow while awaiting reoperation. This controlled hydrocephalus and allowed confirmation of CSF sterility prior to shunt replacement.


Assuntos
Hidrocefalia , Derivação Ventriculoperitoneal , Catéteres/efeitos adversos , Humanos , Hidrocefalia/cirurgia , Complicações Pós-Operatórias/cirurgia , Reoperação , Derivação Ventriculoperitoneal/efeitos adversos
9.
Onco Targets Ther ; 13: 9235-9244, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32982310

RESUMO

BACKGROUND: Galangin (GLN), a pure natural flavonoid compound found in plants, has been shown to exert anti-cancer effects against multiple cancer types, including glioma. However, its underlying molecular mechanism remains unclear. Epithelial-to-mesenchymal transition (EMT) performs an important function in the genesis and development of cancer. Skp2, a pivotal component of SCFSkp2 E3 ubiquitin ligase, has been shown to function as an oncogene in GBM invasion that contributes to the EMT process. Thus, we explored whether GLN inhibited Skp2-mediated EMT and the mechanism underlying the Skp2 degradation pathway. METHODS: CCK-8 assay, wound healing assay and transwell assay were used to examine cell proliferation, migration, and invasion after treatment with or without GLN. RT-PCR and Western blotting analysis were performed to evaluate mRNA and protein expression, respectively. Co-immunoprecipitation was conducted to detect ubiquitinated Skp2 levels in vitro and in vivo after GLN treatment. Bioluminescence imaging was performed to examine the intracranial tumor size of U87 xenograft mice. Microscale thermophoresis (MST) experiment was used to detect interactions between Skp2 and GLN. RESULTS: GLN suppressed GBM cell growth, migration, and invasion, and also downregulated the expression of Skp2 and mesenchymal markers (Zeb1, N-cadherin, snail, vimentin) in vitro. Moreover, the overexpression of Skp2 in GBM cells decreased the effect of GLN on EMT. Furthermore, we demonstrated that GLN degraded skp2 protein through the ubiquitination proteasome pathway and directly interacted with skp2 protein, as shown through the MST assay. CONCLUSION: This study is the first to identify Skp2 as a novel target of GLN for the treatment of GBM and report of Skp2 protein degradation in a ubiquitination proteasome pathway. Results from our study indicated the potential of GLN for the treatment of GBM through ubiquitin-mediated degradation of Skp2.

10.
Neurol Res ; 42(9): 721-729, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32529968

RESUMO

OBJECTIVES: We aimed to investigate the protective effects of cyclosporin A (CsA) against ischemia-reperfusion (I/R) damage in a mouse ischemia model and the possible underlying mechanism. METHODS: Mice were divided equally into five groups: Sham, I/R, Vehicle, I/R plus CsA (10 mg/kg), and I/R plus CsA (20 mg/kg). Nerve function scores, infarct volume, brain water content, and Evans blue (EB) leakage were evaluated, and western blotting was performed to analyze the changes in CypA, p-Akt, NF-κB, MMP-9, and Claudin-5 expression. RESULTS: CsA can attenuate I/R damage in a mouse ischemic stroke model, as indicated by improved neurological function scores and decreased infarct volume, brain water content, and EB leakage. Additionally, high-dose CsA showed better protective effects than low-dose. The molecular mechanisms underlying the effects of CsA were explored, and it was found that CsA could inhibit the increase in CypA, p-Akt, NF-κB, and MMP-9 protein expression after middle cerebral artery occlusion, while Claudin-5 expression was decreased. DISCUSSION: CsA showed potential as a neuroprotective drug for the treatment of ischemic stroke patients; besides interfering with the typical NF-κB signaling pathway, the Akt pathway may also be involved in the effects of CsA.


Assuntos
Isquemia Encefálica/complicações , Ciclosporina/administração & dosagem , AVC Isquêmico/complicações , Fármacos Neuroprotetores/administração & dosagem , Traumatismo por Reperfusão/prevenção & controle , Animais , Comportamento Animal/efeitos dos fármacos , Barreira Hematoencefálica/efeitos dos fármacos , Isquemia Encefálica/patologia , Modelos Animais de Doenças , AVC Isquêmico/patologia , Masculino , Camundongos Endogâmicos C57BL , Estresse Oxidativo/efeitos dos fármacos , Traumatismo por Reperfusão/patologia
11.
Exp Ther Med ; 18(6): 4185-4192, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31772624

RESUMO

Cerebral syphilitic gumma is a rarely reported disease of the central nervous system. Magnetic resonance imaging (MRI) is an important diagnostic method for syphilitic gumma. The present study aimed to describe and characterize neuroimaging results from 6 patients with pathologically diagnosed cerebral syphilitic gumma. The 6 patients (age, 32-61 years) underwent brain CT and MRI, with 1 patient also undergoing whole-body 2-deoxy-2-(fluorine-18)fluoro-D-glucose-positron emission tomography/CT (18F-FDG PET/CT). Non-enhanced CT, conventional T1 weighted imaging (T1WI) and T2WI, diffusion weighted imaging (DWI) and gadolinium-enhanced T1WI images were acquired for all patients. The CT and MRI scans were retrospectively reviewed by two experienced radiologists for consensus on the location, number, size, T1WI, T2WI and DWI signal intensity characteristics, extent of vasogenic oedema, and enhancement patterns. In total, the 6 patients exhibited 10 lesions, nine of which were located in the cerebral hemisphere, primarily in the grey matter. The remaining lesion was located in the fourth ventricle, leading to mild-to-moderate hydrocephalus. The diameters of the identified 10 lesions ranged from 0.9-6.5 cm, with a mean diameter of 3.9 cm. The main feature observed in CT was low density and in MRI the features were T1WI and DWI hypointensity and T2WI hyperintensity. A single case exhibited syphilis gumma with massive haemorrhage. Ring-like or strip-like signs (n=5), accompanied by the dural tail sign (n=2) and homogeneous enhancement (n=1), were noted on T1WI with gadolinium. The 18F-FDG PET/CT performed in one patient of a cerebral syphilis gumma revealed low uptake and metabolism. The present study indicated that gadolinium-enhanced MRI combined with 18F-FDG PET/CT and laboratory examinations are helpful in distinguishing cerebral syphilitic gumma from brain tumors and infectious diseases, therefore avoiding unnecessary surgery.

12.
Int J Pharm ; 564: 214-224, 2019 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-31004717

RESUMO

Gene therapy strategies for liver cancer have broad application prospects but still lack a stable and efficient delivery vehicle. To overcome this obstacle, we designed a multifunctional gene delivery vector, sTPssOLP, which was based on oleylamine (OA)-modified disulfide-containing polyethylenimine (PEI) and incorporated into lipids to prepare a lipid nanoparticle. sTPssOLP consisted of the core of PEI derivative and cationic lipids bound to siRNA. The modified polyethylene glycol (PEG) and transferrin (Tf) were partially embedded in the phospholipid bilayer through the lipid and the other as the outer shell. The aim was to use the redox responsiveness of disulfide to trigger siRNA release in cytoplasm to enhance transfection efficiency. Pegylated lipids and Tf focus on increasing cycle life in the body and increasing accumulation at the tumor site of the carrier. In addition, two vectors were prepared as controls, one based on a PEI derivative containing no disulfide bond (POLP) and the other on the surface of the carrier not linked to Tf (PssOLP). PEI derivatives effectively avoid the toxicity problems caused by the use of PEI alone (25 kDa). Meanwhile, it was confirmed by gel retardation experiments that in the presence of dithiothreitol (DTT), the disulfide bond can indeed be reduced and the siRNA entrapped in the vector can be released. Both HepG2 and SMMC had significant uptake of sTPssOLP. The results of intracellular and lysosomal co-localization indicated that sTPssOLP achieved lysosomal escape. RT-PCR and Western blot results also confirmed that sTPssOLP had the best gene silencing activity. In vivo, the tumor inhibition rate of sTPssOLP in nude mice carrying HepG2 xenografts was 56%, which was significantly greater than that of the saline control group. In vivo imaging results showed that fluorescently labeled siRNA loaded in sTPssOLP was able to deliver more to the tumor site. At the same time, it was observed that sTPssOLP did not show significant damage to normal tissues. Therefore, this multifunctional gene delivery vector warrants further investigation.


Assuntos
Portadores de Fármacos/administração & dosagem , Terapia Genética , Neoplasias Hepáticas/terapia , RNA Interferente Pequeno/administração & dosagem , Aminas/administração & dosagem , Animais , Carbocianinas , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Feminino , Corantes Fluorescentes , Técnicas de Transferência de Genes , Humanos , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/patologia , Camundongos Endogâmicos BALB C , Camundongos Nus , Polietilenoglicóis/administração & dosagem , Polietilenoimina/administração & dosagem , Transferrina/administração & dosagem
13.
Br J Neurosurg ; 33(3): 302-304, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-28658987

RESUMO

Parkinsonism has been reported as a complication of a ventriculoperitoneal shunt (VPS) or clinical symptoms of chronic subdural haematoma (CSDH). We report an interesting case of parkinsonism in a patient with CSDH secondary to placement of a VPS for obstructive hydrocephalus, and we discuss the possible pathophysiological mechanisms and treatment.


Assuntos
Hematoma Subdural Crônico/etiologia , Hidrocefalia/cirurgia , Transtornos Parkinsonianos/etiologia , Derivação Ventriculoperitoneal/efeitos adversos , Humanos , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/etiologia , Próteses e Implantes/efeitos adversos , Tomografia Computadorizada por Raios X
14.
World Neurosurg ; 96: 614.e7-614.e9, 2016 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-27544343

RESUMO

BACKGROUND: Cephalhematoma is more frequently associated with hard labor of infancy, but the incidence of ossified cephalhematoma is a rare clinical entity. CASE DESCRIPTION: This case report presents a 2-month-old infant with an ossified cephalhematoma who was treated successfully by excision. CONCLUSIONS: Cephalhematoma goes to an ossification process rather than a calcification one. Surgery should be used to shave off the ossified cephalhematoma.


Assuntos
Traumatismos do Nascimento/cirurgia , Hematoma/cirurgia , Ossificação Heterotópica/cirurgia , Lobo Parietal/cirurgia , Periósteo/cirurgia , Traumatismos do Nascimento/diagnóstico , Seguimentos , Hematoma/diagnóstico , Humanos , Lactente , Masculino , Ossificação Heterotópica/diagnóstico , Osso Parietal/patologia , Osso Parietal/cirurgia , Lobo Parietal/patologia , Periósteo/patologia , Tomografia Computadorizada por Raios X
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