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1.
Small Methods ; : e2400078, 2024 Mar 27.
Artigo em Inglês | MEDLINE | ID: mdl-38537103

RESUMO

As one of the most promising renewable energies, wind energy is abundant in the natural environment. However, it is still challenging to effectively collect wind energy because of its variable wind speed and unpredictable direction. Here, a triboelectric nanogenerator, which is inspired by ancient Chinese wind bells, has been developed to collect energy from variable-speed and multi-directional wind. The wind-bell-inspired triboelectric nanogenerator (W-TENG) has the capability to generate electricity even at a very low wind speed of 0.5 m s-1. Furthermore, it is able to harvest wind energy effectively from all directions (0-360 degrees). The parameter-optimized W-TENG achieves a maximum output voltage of 9.3 V and a maximum current of 0.63 µA. Electronic devices including a digital watch and 40 light-emitting diodes (LEDs) are successfully powered by the designed W-TENG, demonstrating its applicability. In this study, it is believed that a novel and effective strategy is provided to harvest energy from variable-speed and multi-directional wind.

2.
CNS Neurosci Ther ; 30(2): e14630, 2024 02.
Artigo em Inglês | MEDLINE | ID: mdl-38348765

RESUMO

OBJECTIVE: Induced pluripotent stem cells (iPSCs) hold a promising potential for rescuing dopaminergic neurons in therapy for Parkinson's disease (PD). This study clarifies a TREM2-dependent mechanism explaining the function of iPSC differentiation in neuronal repair of PD. METHODS: PD-related differentially expressed genes were screened by bioinformatics analyses and their expression was verified using RT-qPCR in nigral tissues of 6-OHDA-lesioned mice. Following ectopic expression and depletion experiments in iPSCs, cell differentiation into dopaminergic neurons as well as the expression of dopaminergic neuronal markers TH and DAT was measured. Stereotaxic injection of 6-OHDA was used to develop a mouse model of PD, which was injected with iPSC suspension overexpressing TREM2 to verify the effect of TREM2 on neuronal repair. RESULTS: TREM2 was poorly expressed in the nigral tissues of 6-OHDA-lesioned mice. In the presence of TREM2 overexpression, the iPSCs showed increased expression of dopaminergic neuronal markers TH and DAT, which facilitated the differentiation of iPSCs into dopaminergic neurons. Mechanistic investigations indicated that TREM2 activated the TGF-ß pathway and induced iPSC differentiation into dopaminergic neurons. In vivo data showed that iPSCs overexpressing TREM2 enhanced neuronal repair in 6-OHDA-lesioned mice. CONCLUSION: This work identifies a mechanistic insight for TREM2-mediated TGF-ß activation in the regulation of neuronal repair in PD and suggests novel strategies for neurodegenerative disorders.


Assuntos
Células-Tronco Pluripotentes Induzidas , Doença de Parkinson , Animais , Camundongos , Diferenciação Celular/fisiologia , Modelos Animais de Doenças , Neurônios Dopaminérgicos/metabolismo , Oxidopamina/toxicidade , Doença de Parkinson/genética , Doença de Parkinson/terapia , Doença de Parkinson/metabolismo , Fator de Crescimento Transformador beta/metabolismo
3.
Genes Dis ; 11(3): 100977, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38292193

RESUMO

Glioma is a common tumor originating in the brain that has a high mortality rate. Temozolomide (TMZ) is the first-line treatment for high-grade gliomas. However, a large proportion of gliomas are resistant to TMZ, posing a great challenge to their treatment. In the study, the specific functions and mechanism(s) by which cortistatin (CORT) regulates TMZ resistance and glioma progression were evaluated. The decreased expression of CORT was detected in glioma tissues, and highly expressed CORT was associated with a better survival rate in patients with glioma. CORT overexpression notably decreased the capacity of glioma cells to proliferate and migrate in vitro and to form tumors in vivo. CORT overexpression also markedly suppressed the viability and enhanced the apoptosis of TMZ-resistant U251 cells by regulating MGMT, p21, and Puma expression. Importantly, CORT overexpression reduced the resistance of gliomas to TMZ in vivo. CORT expression was negatively correlated with MGMT expression in both glioma tissues and cells, and it was found that CORT inhibited NF-κB pathway activation in glioma cells, thereby inhibiting MGMT expression. In conclusion, CORT regulates glioma cell growth, migration, apoptosis, and TMZ resistance by weakening the activity of NF-κB/p65 and thereby regulating MGMT expression. The CORT/NF-κB/MGMT axis might be regarded as a molecular mechanism contributing to the resistance of glioma to TMZ. Our data also suggest that CORT regulates the viability and metastatic potential of glioma cells, independent of its effects on TMZ resistance, providing evidence of novel therapeutic targets for glioma that should be evaluated in further studies.

4.
Front Neurol ; 14: 1221335, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37920838

RESUMO

Aim: Prognostic assessment plays an important role in the effective management of patients with spontaneous intracerebral hemorrhage (ICH). The study aimed to investigate whether elevated red cell distribution width-to-platelet ratio (RPR) at admission was related to 30-day death in patients with spontaneous intracerebral hemorrhage (ICH). Methods: This retrospective cohort study included 2,823 adult patients with ICH from the Multiparameter Intelligent Monitoring in Intensive Care (MIMIC) III and IV databases between 2001 and 2019. The Cox proportional hazard model was utilized to evaluate the relationship between RPR levels and 30-day death risk. The area under receiver-operating characteristic curve (AUC) was used to assess the predictive ability of RPR for 30-day death in patients with ICH. Results: At the end of the 30-day follow-up, 799 (28.30%) patients died, and the median RPR level was 0.066 (0.053, 0.087). After adjusting for confounders, the tertile 3 of RPR levels [hazard ratio (HR) = 1.37, 95% confidence interval (CI): 1.15-1.64] were associated with a higher risk of 30-day death in patients with ICH compared with tertile 1. In the stratified analyses, elevated RPR levels were found to be associated with an increased risk of 30-day death in patients aged <65 years (HR = 1.77, 95%CI: 1.29-2.43), aged ≥65 years (HR = 1.30, 95%CI: 1.05-1.61), with Glasgow Coma Score (GCS) <14 (HR = 1.65, 95%CI: 1.27-2.14), with Charlson comorbidity index (CCI) ≥4 (HR = 1.45, 95%CI: 1.17-1.80), with (HR = 1.66, 95%CI: 1.13-2.43) or without sepsis (HR = 1.32, 95%CI: 1.08-1.61), and female patients (HR = 1.75, 95%CI: 1.35-2.26) but not in male patients (P = 0.139) and patients with GCS ≥14 (P = 0.058) or CCI <4 (P = 0.188). The AUC for RPR to predict 30-day death in patients with ICH was 0.795 (95%CI: 0.763-0.828) in the testing set, indicating a good predictive ability. Conclusion: Elevated RPR levels were correlated with an increased risk of 30-day death in patients with ICH, and RPP levels showed good predictive ability for 30-day death.

5.
Neurosurg Rev ; 46(1): 280, 2023 Oct 25.
Artigo em Inglês | MEDLINE | ID: mdl-37875636

RESUMO

Extracerebral tumors often occur on the surface of the brain or at the skull base. It is important to identify the peritumoral sulci, gyri, and nerve fibers. Preoperative visualization of three-dimensional (3D) multimodal fusion imaging (MFI) is crucial for surgery. However, the traditional 3D-MFI brain models are homochromatic and do not allow easy identification of anatomical functional areas. In this study, 33 patients with extracerebral tumors without peritumoral edema were retrospectively recruited. They underwent 3D T1-weighted MRI, diffusion tensor imaging (DTI), and CT angiography (CTA) sequence scans. 3DSlicer, Freesurfer, and BrainSuite were used to explore 3D-color-MFI and preoperative planning. To determine the effectiveness of 3D-color-MFI as an augmented reality (AR) teaching tool for neurosurgeons and as a patient education and communication tool, questionnaires were administered to 15 neurosurgery residents and all patients, respectively. For neurosurgical residents, 3D-color-MFI provided a better understanding of surgical anatomy and more efficient techniques for removing extracerebral tumors than traditional 3D-MFI (P < 0.001). For patients, the use of 3D-color MFI can significantly improve their understanding of the surgical approach and risks (P < 0.005). 3D-color-MFI is a promising AR tool for extracerebral tumors and is more useful for learning surgical anatomy, developing surgical strategies, and improving communication with patients.


Assuntos
Realidade Aumentada , Neoplasias , Humanos , Imagem de Tensor de Difusão , Estudos Retrospectivos , Imageamento Tridimensional/métodos
6.
Nanomaterials (Basel) ; 13(9)2023 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-37177117

RESUMO

Acetaminophen (N-acetyl-p-aminophenol, APAP) is regularly used for antipyretic and analgesic purposes. Overdose or long-term exposure to APAP could lead to liver damage and hepatotoxicity. In this study, the approach of enhanced electrochemical detection of APAP by nanostructured biomass carbon/silver was developed. Porous biomass carbon derived from Elaeagnus Angustifolia gum was prepared by pyrolysis with co-doping of electron-rich elements of nitrogen, sulfur, and phosphorus. The electrodeposition of silver onto a glassy carbon electrode modified with porous carbon could enhance the sensing signal towards APAP. Two linear ranges from 61 nM to 500 µM were achieved with a limit of detection of 33 nM. The developed GCE sensor has good anti-interference, stability, reproducibility, and human urine sample analysis performance. The silver-enhanced biomass carbon GCE sensor extends the application of biomass carbon, and its facile preparation approach could be used in constructing disposable sensing chips in the future.

7.
Neurosci Lett ; 805: 137222, 2023 05 14.
Artigo em Inglês | MEDLINE | ID: mdl-37019269

RESUMO

Spinal cord injury (SCI) is a destructive and disabling nerve injury from which complete recovery has not yet been achieved due to complex pathology. Casein kinase II (CK2) is a pleiotropic serine/threonine protein kinase that plays an essential role in the nervous system. This study aimed to investigate the role of CK2 in SCI to understand the pathogenesis of SCI and explore new therapeutic methods. The SCI rat model of C5 unilateral clamp was established by modified clamp method in male adult SD rats. Then, CK2 inhibitor DMAT was used to treat SCI rats, and the behaviour, pathological changes in the spinal cord and microglial polarization were analysed. Additionally, the effects of DMAT on the polarization and autophagy of microglial BV-2 cells were investigated in vitro, and the effects of BV-2 polarization on spinal cord neuronal cells were analysed by Transwell coculture. Results showed that DMAT significantly increased the BBB score, improved histopathological injury, decreased the expression of inflammatory cytokines, and promoted M2 polarization of microglia in SCI rats. In vitro experiments further confirmed that DMAT could promote the polarization of BV-2 to the M2 type, promote autophagy, and reverse the LPS-induced decline in cell viability and increase in apoptosis of neuronal cells. The use of 3-MA confirmed that autophagy plays an important role in DMAT promoting M2 polarization of BV-2 to improve neuronal cell viability. In conclusion, CK2 inhibitor DMAT improved SCI by inducing anti-inflammatory polarization of microglia through autophagy and is a potential therapeutic target for SCI.


Assuntos
Microglia , Traumatismos da Medula Espinal , Animais , Masculino , Ratos , Anti-Inflamatórios/farmacologia , Autofagia , Caseína Quinase II/metabolismo , Macrófagos/metabolismo , Microglia/metabolismo , Ratos Sprague-Dawley , Medula Espinal/metabolismo , Traumatismos da Medula Espinal/metabolismo
8.
Ann Med ; 55(1): 2200033, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-37086071

RESUMO

BACKGROUND: Glioma is a common primary central nervous system tumor with complex pathogenesis. DNA damage and repair (DDR) is widely involved in regulating cell proliferation and tumorigenesis by correcting and repairing DNA damage mechanisms. Recent studies have reported the following properties in cancer cells in glioma, increased DNA damage and reduced DNA repair capacity. However, the relationship between glioma and DDR-related genes was unclear. METHODS: DDR-related risk score model was built. The validity of this model was validated in detail through the Kaplan-Meier survival analysis, tumor mutational burden (TMB) analysis, immune cell infiltration, sensitivity to treatment regimens. Moreover, the model's adaptability was validated in different glioma data cohorts and different glioma subgroups. To further investigate the molecular mechanism of one of DDR-related gene (NUDT1) in glioma, U251 cell was used for the knockdown experiment, followed by MTT, wound healing and transwell analysis. RESULTS: Ten prognostic-related DDR-related signature genes were obtained, including EID3, MGMT, YWHAG, PMS1, SHPRH, HUS1, NUDT1, GADD45G, APEX1 and FAM175A. The RT-qPCR results suggested that the latter five genes were highly expressed in glioma patients. Interestingly, high TMB score had longer survival. In high-risk score groups, reduced immune cell infiltration in the tumor microenvironment lead to poorer patient outcomes. Sensitivity to treatment regimens analysis indicated that low-risk score groups were more sensitive to chemotherapeutics. Moreover, the risk score model had a good prediction effect on different glioma datasets and different glioma subgroups. In vitro mechanism study showed that knockdown of NUDT1 reduced tumorigenesis. Furthermore, knockdown of NUDT1 remarkably reduced the expression level of HIF-1α. CONCLUSION: DDR-related risk score model built-in this work has good predictive performance for glioma.Key messagesTen prognostic-related DDR-related signature genes were obtained, including EID3, MGMT, YWHAG, PMS1, SHPRH, HUS1, NUDT1, GADD45G, APEX1 and FAM175A.In high-risk score groups, reduced immune cell infiltration in the tumor microenvironment leads to poorer patient outcomes.The risk score model had a good prediction effect on different glioma datasets and different glioma subgroups.Knockdown of NUDT1 reduced tumorigenesis of glioma and remarkably reduced the expression level of HIF-1α.


Assuntos
Carcinogênese , Glioma , Humanos , Fatores de Risco , Transformação Celular Neoplásica , Dano ao DNA , Glioma/genética , Prognóstico , Microambiente Tumoral/genética , DNA Helicases , Ubiquitina-Proteína Ligases , Proteínas 14-3-3
9.
Artigo em Inglês | MEDLINE | ID: mdl-36965451

RESUMO

A total of 29 batches of R. graveolens were used in this study, their fingerprints were obtained by ultra-performance liquid chromatography (UPLC) and their melanogenesis activities were evaluated. The common peaks were identified by quadrupole-orbitrap high-resolution mass spectrometry (Q-Orbitrap-HRMS). Eleven coumarins, six alkaloids, three flavonoids, three phenolic acids, and four other compounds were found. The spectrum-effect relationships between R. graveolens' chemical fingerprints, the melanin synthesis, and tyrosine's activation activities were established through chemometrics methods which in detail principal component analysis (PCA), gray correlation analysis (GRA), bivariate correlation analysis (BCA) and orthogonal partial least squares analysis (OPLS). The results showed that P18 (bergapten), P22 (isoimperatorin), P15 (kokusaginine), P7 (rutin), P12 (psoralen), and P13 (graveolinine) were relevant to intracellular melanin synthesis activity and tyrosinase activity. Among them, P18 (bergapten), P15 (kokusaginine), and P12 (psoralen) were validated with good melanogenesis activities. This study provides a research basis for future quality control and medicinal application of R. graveolens.


Assuntos
Furocumarinas , Ruta , Melaninas , 5-Metoxipsoraleno , Furocumarinas/química , Ficusina , Cromatografia Líquida , Cromatografia Líquida de Alta Pressão/métodos
11.
J Mater Chem B ; 11(5): 998-1007, 2023 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-36621800

RESUMO

Few glucometers are available to easily and quickly measure low blood glucose levels (≤4 mmol L-1) from a small amount of blood samples. Here, a hybrid reduced graphene oxide (rGO)-based magnetoresistance (MR) sensor has been developed to monitor blood glucose levels to quickly detect hypoglycemia. Hybrid rGO nanosheets, incorporating Fe50Co50 nanoparticles onto rGO nanosheets, with an unusual large negative MR (-5.7%) at room temperature under a small magnetic field (9.5 kOe) have been successfully fabricated through a one-pot reaction. To quickly detect the low concentration of glucose in a small amount of blood (1 µL), a two-step process has been further developed by using the "sandwich" structural MR sensor. The results show that the higher the negative MR value of the sensor, the lower the concentration of glucose that can be detected. A linear relationship between the MR and the concentration of the spiked plasma glucose taken from streptozotocin-induced diabetic rats can be found when the concentration of glucose is in the range of 0-6 mmol L-1. The limit of detection (LOD) of this MR glucose sensor is 0.867 mmol L-1. The accuracy of the rGO-based MR sensor is improved in measuring low concentration of plasma glucose as compared to that of a commercialized glucometer. Furthermore, the selectivity of the rGO-based MR sensor has been studied. The results demonstrate that the rGO-based MR sensor is a flexible and sensitive detection platform and specifically suitable for monitoring low concentrations of plasma glucose to prevent from hypoglycemia.


Assuntos
Diabetes Mellitus Experimental , Hipoglicemia , Animais , Ratos , Glicemia , Diabetes Mellitus Experimental/induzido quimicamente , Diabetes Mellitus Experimental/diagnóstico , Hipoglicemia/diagnóstico , Glucose
13.
Sichuan Da Xue Xue Bao Yi Xue Ban ; 54(6): 1250-1255, 2023 Nov 20.
Artigo em Chinês | MEDLINE | ID: mdl-38162060

RESUMO

Objective: To investigate the surgical treatment strategy of intracranial alveolar echinococcosis (AE) and the clinical outcomes. Methods: The clinical and follow-up data of 15 intracranial AE patients who underwent surgical treatment in the Departments of Neurosurgery of Sichuan Provincial People's Hospital (SPPH) and People's Hospital of Aba Tibetan and Qiang Autonomous Prefecture (a branch hospital of SPPH) between March 2017 and January 2021 were retrospectively analyzed. Full follow-up data were available for each of the 15 cases. The clinical and imaging characteristics, general surgical information, and surgical outcomes were analyzed. Results: In the 15 patients, there were a total of 50 intracranial lesions, with an average of (3.3±3.1)/case. Four cases had solitary intracranial lesions, while 11 cases had multiple lesions, with the number of intracranial lesions per case ranging from 2 to 13. All patients with solitary intracranial lesions received total resection. In 6 patients with multiple intracranial lesions, only the largest lesion was surgically removed, and in 5 patients, 2 to 3 adjacent lesions were surgically removed. All but one patient had extracranial lesions in their liver, lungs, kidneys, adrenal glands, and thoracic vertebrae. The patients were followed up for 12 to 58 months after surgery, with the mean follow-up time being (28.1±13.4) months. Among the 15 cases, 13 showed stable intracranial condition during postoperative follow-up. Intracranial lesions recurred in 2 patients who had deep lesions accompanied by dissemination to the subarachnoid space. Two patients died during follow-up. Conclusion: Microsurgical treatment of intracranial AE is effective, but total surgical resection is difficult to accomplish when patients have echinococcosis lesions located at a depth, especially when the lesions are spreading to the subarachnoid space. The prognosis of patients is closely associated with the extent of lesion invasion and the control of systemic hydatid lesions, especially those in the liver.


Assuntos
Equinococose Hepática , Equinococose , Humanos , Equinococose Hepática/cirurgia , Equinococose Hepática/tratamento farmacológico , Estudos Retrospectivos , Equinococose/cirurgia , Equinococose/patologia , Resultado do Tratamento
14.
J Transl Med ; 20(1): 443, 2022 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-36183123

RESUMO

BACKGROUND: Gliomas account for about 80% of all malignant brain and other central nervous system (CNS) tumors. Temozolomide (TMZ) resistance represents a major treatment hurdle. Adrenomedullin (ADM) has been reported to induce glioblastoma cell growth. METHODS: Cell viability was measured using the CCK-8 assay. The apoptosis analysis was performed using the Annexin V-FITC Apoptosis Detection Kit. The mitochondrial membrane potential was determined by JC-1 staining. A nude mouse tumor assay was used to detect tumor formation. Hematoxylin and eosin (H&E) and immunohistochemical (IHC) staining were performed in tissue sections. Activation of Akt and Erk and expression of apoptosis-related proteins were determined by immunoblotting. RESULTS: ADM expression has been found upregulated in TMZ -resistant glioma samples based on bioinformatics and experimental analyses. Knocking down ADM in glioma cells enhanced the suppressive effects of TMZ on glioma cell viability, promotive effects on cell apoptosis, and inhibitory effects on mitochondrial membrane potential. Moreover, ADM knockdown also enhanced TMZ effects on Bax/Bcl-2, Akt phosphorylation, and Erk1/2 phosphorylation. Bioinformatics and experimental investigation indicated that miR-1297 directly targeted ADM and inhibited ADM expression. miR-1297 overexpression exerted similar effects to ADM knockdown on TMZ-treated glioma cells. More importantly, under TMZ treatment, inhibition of miR-1297 attenuated TMZ treatment on glioma cells; ADM knockdown partially attenuated the effects of miR-1297 inhibition on TMZ-treated glioma cells. CONCLUSIONS: miR-1297 sensitizes glioma cells to TMZ treatment through targeting ADM. The Bax/Bcl-2, Akt, and Erk1/2 signaling pathways, as well as mitochondrial functions might be involved.


Assuntos
Neoplasias Encefálicas , Glioma , MicroRNAs , Adrenomedulina/genética , Adrenomedulina/farmacologia , Adrenomedulina/uso terapêutico , Animais , Antineoplásicos Alquilantes/uso terapêutico , Apoptose/genética , Neoplasias Encefálicas/tratamento farmacológico , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/metabolismo , Linhagem Celular Tumoral , Proliferação de Células , Resistencia a Medicamentos Antineoplásicos , Amarelo de Eosina-(YS)/farmacologia , Amarelo de Eosina-(YS)/uso terapêutico , Glioma/tratamento farmacológico , Glioma/genética , Glioma/metabolismo , Hematoxilina/farmacologia , Hematoxilina/uso terapêutico , Camundongos , MicroRNAs/genética , MicroRNAs/metabolismo , Proteínas Proto-Oncogênicas c-akt , Proteínas Proto-Oncogênicas c-bcl-2 , Temozolomida/farmacologia , Temozolomida/uso terapêutico , Proteína X Associada a bcl-2
15.
Neurol India ; 70(3): 864-871, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35864610

RESUMO

Background: Seizures often herald the clinical appearance of glioma. Temozolomide (TMZ) is the first-line chemotherapeutic agent that has been used to treat glioma. Objective: We conducted a systematic review to determine seizure outcomes in glioma patients treated with TMZ. Methods and Material: We searched EMBASE and PubMed databases (January 1, 2003-August 26, 2021) by using search terms closely related to glioma, seizure, and temozolomide. Titles, abstracts, and full texts were screened and selected using previously established inclusion and exclusion criteria. The research team members reviewed potential articles and reached a consensus on the final articles to be included. Results: Nine studies containing data from three continents met our inclusion criteria. From several descriptive studies on low-grade gliomas (LGGs), the percentage of patients with partial seizure control after TMZ treatment ranged from 29% to 89.7%, and the percentage of patients with complete seizure control after TMZ ranged from 19.4% to 72%. In a retrospective cohort study of patients with LGGs, there was a marked difference in decreased seizure frequency between patients receiving TMZ and those who did not receive TMZ. In a randomized trial, TMZ seemed to have little effect on seizure control in elderly patients with glioblastoma. Conclusions: At present, there are few high-quality and well-designed clinical studies on TMZ for gliomas-related seizures. In terms of the literature included in this review, TMZ has an inhibitory effect on epilepsy. More randomized controlled trials are needed to elucidate the clinical benefits of TMZ in the treatment of gliomas-related seizures.


Assuntos
Neoplasias Encefálicas , Glioma , Idoso , Antineoplásicos Alquilantes/uso terapêutico , Neoplasias Encefálicas/complicações , Neoplasias Encefálicas/tratamento farmacológico , Glioma/complicações , Glioma/tratamento farmacológico , Humanos , Ensaios Clínicos Controlados Aleatórios como Assunto , Estudos Retrospectivos , Convulsões/tratamento farmacológico , Convulsões/etiologia , Temozolomida/uso terapêutico
16.
Hum Pathol ; 123: 59-73, 2022 05.
Artigo em Inglês | MEDLINE | ID: mdl-35219686

RESUMO

Glioblastoma (GBM) is the most malignant subtype of gliomas. GBM resistance to temozolomide (TMZ) remains a huge challenge. O6-methylguanine-DNA methyltransferase (MGMT) is mainly responsible for repairing DNA alkylation damage caused by alkylating drugs such as TMZ; therefore, it has been regarded as the major cause of the resistance to TMZ. Hematoxylin and eosin (H&E) and immunohistochemical (IHC) staining were performed in tissue sections. LncRNA urothelial cancer-associated 1 (UCA1) knockdown was conducted via the transfection of the plasmid containing small interfering RNA (siRNA) targeting lncRNA UCA1. Cell viability and apoptosis were examined using MTT assay and flow cytometry. Nude mouse tumorigenicity assay was performed to detect tumor formation in vivo. MGMT expression and lncRNA UCA1 expression were increased in high-grade glioma tissues and cells. UCA1 knockdown in glioma cells enhanced TMZ efficacies in affecting glioma cell viability, cell apoptosis, MGMT protein level, and DNA damage markers in vitro, as well as tumorigenesis in vivo. Moreover, miR-182-5p targeted UCA1 and MGMT; miR-182-5p inhibited MGMT expression. Similar to UCA1 knockdown, miR-182-5p overexpression also promoted TMZ effects on glioma cell phenotype, MGMT expression level, and the levels of DNA damage markers. Under TMZ treatment, the efficacies of UCA1 knockdown in MGMT expression level and glioma cell sensitivity to TMZ were notably reversed after miR-182-5p overexpression. Taken together, we demonstrate the lncRNA UCA1/miR-182-5p/MGMT axis modulates glioma cell sensitivity to TMZ via MGMT-related DNA damage pathways.


Assuntos
Carcinoma de Células de Transição , Glioblastoma , Glioma , MicroRNAs , RNA Longo não Codificante , Neoplasias da Bexiga Urinária , Animais , Carcinoma de Células de Transição/genética , Linhagem Celular Tumoral , DNA/uso terapêutico , Dano ao DNA , Metilases de Modificação do DNA/genética , Metilases de Modificação do DNA/metabolismo , Enzimas Reparadoras do DNA/genética , Feminino , Regulação Neoplásica da Expressão Gênica , Glioblastoma/genética , Glioma/tratamento farmacológico , Glioma/genética , Glioma/metabolismo , Humanos , Masculino , Camundongos , MicroRNAs/genética , RNA Longo não Codificante/genética , Temozolomida/farmacologia , Temozolomida/uso terapêutico , Proteínas Supressoras de Tumor/genética , Proteínas Supressoras de Tumor/metabolismo , Neoplasias da Bexiga Urinária/genética
18.
J Obstet Gynaecol Res ; 47(11): 3913-3922, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34482592

RESUMO

AIM: G2 and S phase-expressed-1 (GTSE1) has been identified to play a vital role in several kinds of cancers, but its role in cervical cancer development remains unknown. Herein, we aimed to reveal the role and underlying mechanism of GTSE1 in cervical cancer cell growth, migration, and aerobic glycolysis. METHODS: GTSE1 expression levels in cervical cancer tissues and normal cervical tissues were determined by real time PCR and immunohistochemistry. Human short hairpin RNA was used to downregulate GTSE1 level in cervical cancer cells SiHa and HeLa cells. Colony formation, cell counting kit-8, and wound-healing assays were used for cell function evaluation. Lactate production, lactate dehydrogenase activity, and glucose concentration were tested to assess the Warburg effect. RESULTS: GTSE1 expressions at both mRNA and protein levels were significantly elevated in cervical cancer tissues compared with normal tissues. Downregulation of GTSE1 induced significant repressions in cell colony formation, viability and migration, and Warburg effect, as well as reduced expression of lactate dehydrogenase isoform A (LDHA) at mRNA and protein levels. Additionally, downregulation of GTSE1 weakened the tumorigenesis of HeLa and SiHa cells in vivo. CONCLUSION: This study demonstrated that downregulation of GTSE1 led to significant inhibitions in cell proliferation, migration, tumorigenesis, and Warburg effect in cervical cancer by blocking the expression of LHDA.


Assuntos
Neoplasias do Colo do Útero , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Regulação para Baixo , Feminino , Regulação Neoplásica da Expressão Gênica , Células HeLa , Humanos , Proteínas Associadas aos Microtúbulos/genética , Proteínas Associadas aos Microtúbulos/metabolismo , Neoplasias do Colo do Útero/genética
19.
Gland Surg ; 10(5): 1780-1785, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-34164321

RESUMO

For locally advanced right colon cancer (LARCC) invading duodenum, multivisceral resection is a curative surgical treatment, which is technically challenging when performed in a total laparoscopic approach. Herein, we report the first case of LARCC treated by total laparoscopic en bloc right hemicolectomy and pancreaticoduodenectomy with transvaginal specimen extraction. The patient was a 37-year-old female suffering from upper abdominal pain who was diagnosed with LARCC invading the duodenum by preoperative examination. The en bloc resection and digestive tract reconstruction were completed laparoscopically without an assisted abdominal incision. Then the specimen was extracted transvaginally through a 6 cm transverse incision made in the posterior vaginal fornix and the vaginal incision was closed by a continuous suture intracorporeally. The operative time was 470 min and intraoperative blood loss was 130 mL. The postoperative pathological examination showed T4bN0M0 adenocarcinoma of the hepatic flexure of colon with infiltration of duodenal serosa, and all the margins were negative. The patient recovered uneventfully with minimal postoperative pain and was discharged from hospital on postoperative day 7. After 3 years of follow-up, the patient was alive with no recurrence. To the best of our knowledge, this is the most extensive multivisceral resection with natural orifice specimen extraction (NOSE) ever reported. We believe that NOSE surgery, with advantages of minimal invasiveness and enhanced recovery, is a feasible and promising option for LARCC.

20.
Cell Signal ; 79: 109882, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33316386

RESUMO

Identifying biomarkers for the early diagnosis of glioma and elucidating the molecular mechanisms underlying the development of this cancer are of considerable clinical importance. Recently, studies performing microarray profiling of genes to identify distinct gene signatures reported specific subtypes with predictive and prognostic relevance. Thus, we performed deep sequencing on a total of 26 glioma tissue samples to identify the frequently mutated of oncogenes and tumor suppressors in gliomas. A total of 2306 single-nucleotide polymorphisms (SNPs) and 2010 insertion and deletion sites (indels) were found by aligning sequencing information from 26 glioma samples with sequences from the normal human gene database (GRCh37/hg19). GSEA results suggest that an underexpressed gene, calmodulin binding transcription activator 1 (CAMTA1), participates in the cell proliferation and cell cycle regulation of glioma cells. Moreover, overexpression of CAMTA1 in glioma cells notably inhibited cell growth, migration, invasion and cell cycle and enhanced temozolomide (TMZ)-induced cell apoptosis in glioma cells, while CAMTA1 overexpression decreased the ITGA5, ITGB1, p-AKT, p-FAK, and Myc protein levels, suggesting that the signaling pathways of these proteins might be involved in the cellular functions of CAMTA1 in glioma. Moreover, overexpression of CAMTA1 attenuated the growth and tumorigenesis of glioma in vivo. In summary, we identified high-frequency mutant genes in glioma and provided an experimental basis for a novel mechanism by which CAMTA1 may serve as a tumor suppressor in glioma.


Assuntos
Neoplasias Encefálicas/metabolismo , Proteínas de Ligação ao Cálcio/metabolismo , Ciclo Celular , Glioma/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transativadores/metabolismo , Proteínas Supressoras de Tumor/metabolismo , Adulto , Animais , Neoplasias Encefálicas/genética , Proteínas de Ligação ao Cálcio/genética , Linhagem Celular Tumoral , Feminino , Glioma/genética , Humanos , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Pessoa de Meia-Idade , Fosforilação , Proteínas Proto-Oncogênicas c-akt/genética , Transativadores/genética , Proteínas Supressoras de Tumor/genética
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