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1.
Transl Oncol ; 45: 101972, 2024 May 04.
Artigo em Inglês | MEDLINE | ID: mdl-38705053

RESUMO

BACKGROUND: Accumulating evidence has shown that circular RNAs (circRNAs) are involved in gastric cancer (GC) tumorigenesis. However, specific functional circRNAs in GC remain to be discovered, and their underlying mechanisms remain to be elucidated. METHODS: CircRNAs that were differentially expressed between GC tissues and controls were analyzed using a circRNA microarray dataset. The expression of circVDAC3 in GC was determined using quantitative real-time PCR (qRT-PCR), and the structural features of circVDAC3 were validated. Cell function assays and animal experiments were conducted to explore the effects of circVDAC3 on GC. Finally, bioinformatics analysis, fluorescent in situ hybridization, and dual luciferase assays were used to analyze the downstream mechanisms of circVDAC3. RESULTS: Our results showed that circVDAC3 was downregulated in GC and inhibited the proliferation and metastasis of GC cells. Mechanistically, circVDAC3 acts as a competing endogenous RNA (ceRNA) of miR-592 and deregulates the repression of EIF4E3 by miR-592. EIF4E3 is downregulated in GC and overexpression of miR-592 or knockdown of EIF4E3 in circVDAC3-overexpressing cells weakens the anticancer effect of circVDAC3. CONCLUSION: Our study provides evidence that circVDAC3 affects the growth and metastasis of GC cells via the circVDAC3/miR-592/EIF4E3 axis. Our findings offer valuable insights into the mechanisms underlying GC tumorigenesis and suggest novel therapeutic strategies.

2.
World J Gastrointest Surg ; 16(2): 596-600, 2024 Feb 27.
Artigo em Inglês | MEDLINE | ID: mdl-38463376

RESUMO

BACKGROUND: Hemolymphangioma of the jejunum is rare and lacks clinical specificity, and can manifest as gastrointestinal bleeding, abdominal pain, and intestinal obstruction. Computed tomography, magnetic resonance imaging, and other examinations show certain characteristics of the disease, but lack accuracy. Although capsule endoscopy and enteroscopy make up for this deficiency, the diagnosis also still requires pathology. CASE SUMMARY: A male patient was admitted to the hospital due to abdominal distension and abdominal pain, but a specific diagnosis by computed tomography examination was not obtained. Partial resection of the small intestine was performed by robotic surgery, and postoperative pathological biopsy confirmed the diagnosis of hemolymphangioma. No recurrence in the follow-up examination was observed. CONCLUSION: Robotic surgery is an effective way to treat hemolymphangioma through minimally invasive techniques under the concept of rapid rehabilitation.

3.
Sci Total Environ ; 912: 168924, 2024 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-38036146

RESUMO

The global prevalence of Neurological disorders has increased alarmingly in response to environmental and lifestyle changes. Atrazine (ATZ) is a difficult to degrade soil and water pollutant with well-known neurotoxicity. Melatonin (MT), an antioxidant with chemoprotective properties, has a potential therapeutic effect on cerebellar damage caused by ATZ exposure. The aim of this study was to explore the effects and underlying mechanisms of MT on the cerebellar inflammatory response and pyroptosis induced by ATZ exposure. In this study, C57BL/6J mice were treated with ATZ (170 mg/kg BW/day) and MT (5 mg/kg BW/day) for 28 days. Our results revealed that MT alleviated the histopathological changes, ultrastructural damage, oxidative stress and decrease of mitochondrial membrane potential (ΔΨm) in the cerebellum induced by ATZ exposure. ATZ exposure damaged the mitochondria leading to release of mitochondrial DNA (mtDNA) to the cytoplasm, MT activated the cyclic GMP-AMP synthetase interferon gene stimulator (cGAS-STING) axis to alleviate inflammation and pyroptosis caused by ATZ exposure. In general, our study provided new evidence that the cGAS-STING-NLRP3 axis plays an important role in the treatment of ATZ-induced cerebellar injury by MT.


Assuntos
Atrazina , Melatonina , Nucleotídeos Cíclicos , Animais , Camundongos , Atrazina/toxicidade , Atrazina/metabolismo , Melatonina/metabolismo , Piroptose , Interferons/metabolismo , Interferons/farmacologia , Proteína 3 que Contém Domínio de Pirina da Família NLR , Camundongos Endogâmicos C57BL , Mitocôndrias , DNA Mitocondrial , Nucleotidiltransferases/genética , Nucleotidiltransferases/metabolismo , Nucleotidiltransferases/farmacologia
4.
Nanomaterials (Basel) ; 13(24)2023 Dec 08.
Artigo em Inglês | MEDLINE | ID: mdl-38133000

RESUMO

The colorless and odorless ethylene glycol is prone to unknowingly causing poisoning, making preventive monitoring of ethylene glycol necessary. In this paper, scandium (III) trifluoromethanesulfonate was used as a catalyst to successfully prepare covalent organic framework (COF) nanospheres linked by imines at room temperature. The COF nanospheres were characterized by XRD, SEM, TEM, FT-IR, UV-Vis and BET. The results show that COF nanospheres have rough surfaces and a large number of mesoporous structures, which greatly increase the active sites on the surface of the sensing material and enhance the gas sensing performance. The sensing results showed that the prepared imine-conjugated COF nanospheres exhibited a good response-recovery ability for 10 consecutive response-recovery cycles for ethylene glycol at room temperature and had a theoretical detection limit of 40 ppb. In addition, the responses of COF nanospheres to nearly 20 interfering gases, including HCl, HNO3, phenol, formaldehyde and aniline, are relatively low compared to the response to ethylene glycol, indicating that the COF nanospheres have high selectivity towards ethylene glycol. The COF nanospheres show good sensitivity and selectivity for the detection of ethylene glycol, which should be attributed to the large specific surface area, hydrogen bonding interactions, and high defects. This work provides an effective method for the detection of ethylene glycol and expands the application field of COF materials.

5.
J Comput Assist Tomogr ; 47(5): 729-737, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37707402

RESUMO

OBJECTIVE: The aim of the study is to demonstrate whether radiomics based on an automatic segmentation method is feasible for predicting molecular subtypes. METHODS: This retrospective study included 516 patients with confirmed breast cancer. An automatic segmentation-3-dimensional UNet-based Convolutional Neural Networks, trained on our in-house data set-was applied to segment the regions of interest. A set of 1316 radiomics features per region of interest was extracted. Eighteen cross-combination radiomics methods-with 6 feature selection methods and 3 classifiers-were used for model selection. Model classification performance was assessed using the area under the receiver operating characteristic curve (AUC), accuracy, sensitivity, and specificity. RESULTS: The average dice similarity coefficient value of the automatic segmentation was 0.89. The radiomics models were predictive of 4 molecular subtypes with the best average: AUC = 0.8623, accuracy = 0.6596, sensitivity = 0.6383, and specificity = 0.8775. For luminal versus nonluminal subtypes, AUC = 0.8788 (95% confidence interval [CI], 0.8505-0.9071), accuracy = 0.7756, sensitivity = 0.7973, and specificity = 0.7466. For human epidermal growth factor receptor 2 (HER2)-enriched versus non-HER2-enriched subtypes, AUC = 0.8676 (95% CI, 0.8370-0.8982), accuracy = 0.7737, sensitivity = 0.8859, and specificity = 0.7283. For triple-negative breast cancer versus non-triple-negative breast cancer subtypes, AUC = 0.9335 (95% CI, 0.9027-0.9643), accuracy = 0.9110, sensitivity = 0.4444, and specificity = 0.9865. CONCLUSIONS: Radiomics based on automatic segmentation of magnetic resonance imaging can predict breast cancer of 4 molecular subtypes noninvasively and is potentially applicable in large samples.


Assuntos
Neoplasias da Mama , Neoplasias de Mama Triplo Negativas , Humanos , Feminino , Neoplasias da Mama/patologia , Estudos Retrospectivos , Imageamento por Ressonância Magnética/métodos , Neoplasias de Mama Triplo Negativas/patologia , Curva ROC , Redes Neurais de Computação
6.
Cells ; 11(17)2022 09 03.
Artigo em Inglês | MEDLINE | ID: mdl-36078162

RESUMO

Angiogenesis is a vital endogenous brain self-repair processes for neurological recovery after intracerebral hemorrhage (ICH). Increasing evidence suggests that leptin potentiates angiogenesis and plays a beneficial role in stroke. However, the proangiogenic effect of leptin on ICH has not been adequately explored. Moreover, leptin triggers post-ICH angiogenesis through pericyte, an important component of forming new blood vessels, which remains unclear. Here, we reported that exogenous leptin infusion dose-dependent promoted vascular endothelial cells survival and proliferation at chronic stage of ICH mice. Additionally, leptin robustly ameliorated pericytes loss, enhanced pericytes proliferation and migration in ICH mice in vivo, and in ICH human brain microvascular pericytes (HBVPC) in vitro. Notably, we showed that pericytes-derived pro-angiogenic factors were responsible for enhancing the survival, proliferation and tube formation followed leptin treatment in human brain microvascular endothelial cells (HCMEC/D3)/HBVPC co-culture models. Importantly, considerable improvements in neurobehavioral function and hostile microenvironment were observed in leptin treatment ICH mice, indicating that better vascular functionality post ICH improves outcome. Mechanistically, this study unveiled that leptin boost post-ICH angiogenesis potentially through modulation of leptin receptor (leptinR)/Signal Transducer and Activator of Transcription 3 (STAT3) signaling pathway in pericyte. Thus, leptin may be a lucrative option for the treatment of ICH.


Assuntos
Hemorragia Cerebral , Leptina , Neovascularização Fisiológica , Pericitos , Animais , Hemorragia Cerebral/metabolismo , Células Endoteliais/metabolismo , Humanos , Leptina/metabolismo , Leptina/farmacologia , Camundongos , Pericitos/metabolismo , Fator de Transcrição STAT3/metabolismo
7.
Artigo em Inglês | MEDLINE | ID: mdl-35942377

RESUMO

Objective: The aim of this study is to investigate the effect of paclitaxel combined with doxorubicin hydrochloride liposome injection (DHLI) in the treatment of osteosarcoma and the MRI changes before and after treatment. Methods: A total of 108 osteosarcoma patients treated in our hospital (January 2020-April 2022) were selected to carry out a single-center retrospective study. Among them, 54 patients receiving the combination chemotherapy (MDT) with high-dose methotrexate, ifosfamide, cisplatin, and ADM were selected as the control group (COG), while 54 patients receiving MDT with high-dose methotrexate, ifosfamide, cisplatin, paclitaxel, and DHLI were chosen as the study group (STG). The COG and STG had the same dose intensity and chemotherapy cycles, and clinical and MRI evaluations were performed after treatment. Results: The evaluation of postoperative clinical efficacy showed that the disease control rate (DCR) of the STG was markedly higher than that of the COG (P < 0.05). The incidence of cardiac toxicity was remarkably lower in the STG than that in the COG (P < 0.05), with no between-group differences in the incidence of fever, abnormal liver function, myelosuppression, stomatitis, and alopecia (P > 0.05). Obvious differences were found in the semiquantitative parameters of MRI in the STG before and after chemotherapy (P < 0.05) and were also found in the SImax, TTP, SEE, PPE, WOR, and R values in the COG before and after chemotherapy (P < 0.05). After chemotherapy, statistical differences were observed in the semiquantitative parameters of MRI between the two groups, with lower parameters such as Slope, SImax, SEE, and R values and higher parameters such as TTP, PPE, and WOR values in the STG than those in the COG (P < 0.05). Conclusion: Paclitaxel combined with DHLI has definite efficacy in osteosarcoma chemotherapy, which is conducive to narrowing the lesion, controlling the disease, and reducing the occurrence of cardiac-related risk events. In addition, the semiquantitative parameters of dynamic contrast-enhanced MRI (DCE-MRI) have a high predictive value for the efficacy of chemotherapy, which can reflect the degree of tumor necrosis and contribute to a timely and objective assessment of the efficacy of osteosarcoma chemotherapy.

8.
Biomed Pharmacother ; 154: 113545, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-36007274

RESUMO

Magnetic nanoparticles(NPs) are characterized by a rich variety of properties. Because of their excellent physical and chemical properties, they have come to the fore in biomedicine and other fields. The magnetic NPs were extensively studied in magnetic separation of cells, targeted drug delivery, tumor hyperthermia, chemo-photothermal therapy, magnetic resonance imaging (MRI) and other biomedical fields. Magnetic NPs are increasingly used in magnetic resonance imaging (MRI) based on their inherent magnetic targeting, superparamagnetic enzyme-like catalytic properties and nanoscale size. Poly(lactic-co-glycolic acid) (PLGA) is a promising biodegradable material approved by FDA and EU for drug delivery. Currently, PLGA-based magnetic nano-drug delivery systems have attracted the attention of researchers. Herein, we achieved the effective encapsulation of sized-controlled polyethylene glycol-3,4-dihydroxy benzyl-amine-coated superparamagnetic iron oxide nanoparticles (SPIO NPs) and euphorbiasteroid into PLGA nanospheres via a modified multiple emulsion solvent evaporation method (W1/O2/W2). NPs with narrow size distribution and acceptable magnetic properties were developed that are very useful for applications involving cancer therapy and MRI. Furthermore, SPIO-PLGA NPs enhanced the MRI T2 relaxation properties of tumor sites.The prepared SPIO NPs and magnetic PLGA nanospheres can be promising magnetic drug delivery systems for tumor theranostics. This study has successfully constructed a tumor-targeting and magnetic-targeting smart nanocarrier with enhanced permeability and retention, multimodal anti-cancer therapeutics and biodegradability, which could be a hopeful candidate for anti-tumor therapy in the future.


Assuntos
Hipertermia Induzida , Nanopartículas , Neoplasias , Portadores de Fármacos/química , Sistemas de Liberação de Medicamentos/métodos , Compostos Férricos , Humanos , Nanopartículas/química , Neoplasias/diagnóstico por imagem , Neoplasias/tratamento farmacológico , Tamanho da Partícula , Medicina de Precisão
9.
Front Oncol ; 12: 984626, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36033453

RESUMO

Purpose: In clinical work, accurately measuring the volume and the size of breast cancer is significant to develop a treatment plan. However, it is time-consuming, and inter- and intra-observer variations among radiologists exist. The purpose of this study was to assess the performance of a Res-UNet convolutional neural network based on automatic segmentation for size and volumetric measurement of mass enhancement breast cancer on magnetic resonance imaging (MRI). Materials and methods: A total of 1,000 female breast cancer patients who underwent preoperative 1.5-T dynamic contrast-enhanced MRI prior to treatment were selected from January 2015 to October 2021 and randomly divided into a training cohort (n = 800) and a testing cohort (n = 200). Compared with the masks named ground truth delineated manually by radiologists, the model performance on segmentation was evaluated with dice similarity coefficient (DSC) and intraclass correlation coefficient (ICC). The performance of tumor (T) stage classification was evaluated with accuracy, sensitivity, and specificity. Results: In the test cohort, the DSC of automatic segmentation reached 0.89. Excellent concordance (ICC > 0.95) of the maximal and minimal diameter and good concordance (ICC > 0.80) of volumetric measurement were shown between the model and the radiologists. The trained model took approximately 10-15 s to provide automatic segmentation and classified the T stage with an overall accuracy of 0.93, sensitivity of 0.94, 0.94, and 0.75, and specificity of 0.95, 0.92, and 0.99, respectively, in T1, T2, and T3. Conclusions: Our model demonstrated good performance and reliability for automatic segmentation for size and volumetric measurement of breast cancer, which can be time-saving and effective in clinical decision-making.

10.
Curr Med Sci ; 42(3): 597-605, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35648284

RESUMO

OBJECTIVE: The present study aimed to develop an autophagy-related gene prognostic prediction model to provide survival risk prediction for head and neck squamous cell carcinoma (HNSCC) patients. METHODS: The K-mean cluster analysis was performed on HNSCC samples based on the expression values of 210 autophagy-related genes for candidate signature gene selection. LASSO Cox regression analysis was generated using the potential genes and the risk score was calculated from the prognosis model. The risk score was processed as an independent prognostic indicator to construct the nomogram model. The immune status including immune cell infiltration ratio and checkpoints of patients with HNSCC in high- and low-risk groups was also explored. RESULTS: LASSO Cox regression analysis was performed on the selected autophagy-related genes. According to the lambda value corresponding to the number of different genes in the LASSO Cox analysis, six genes (GABARAPL2, SAR1A, ST13, GAPDH, FADD and LAMP1) were finally chosen. The risk score based on the genes was generated, which was an independent prognostic marker for HNSCC. The prognostic prediction model (nomogram) was further optimized by the independent prognostic factors (risk score), which can better predict the prognosis and survival of patients. With the risk score and prognosis model, eight types of immune cells and six key immune checkpoints (CTLA4, PD1, IDO1, TDO2, LAG3, TIGIT) displayed expression specificity. CONCLUSION: This study identified several potential prognostic biomarkers and established an autophagy-related prognostic prediction model for HNSCC, which provides a valuable reference for future clinical research.


Assuntos
Neoplasias de Cabeça e Pescoço , Autofagia/genética , Análise por Conglomerados , Neoplasias de Cabeça e Pescoço/genética , Humanos , Prognóstico , Carcinoma de Células Escamosas de Cabeça e Pescoço/genética
11.
Front Oncol ; 12: 807507, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35223488

RESUMO

BACKGROUND: Lung adenocarcinoma (LUAD) is the most common histological subtype of lung cancer. The role of the long non-coding RNA (lncRNA) LINC00958, which regulates the malignant behavior of multiple tumors, in LUAD has not been elucidated. METHODS: Tissue microarray, FISH, and qRT-PCR were used to detect the expression of LINC00958. Plasmid and viral infections were used to manipulate gene expression. The role of LINC00958 in LUAD was studied by cell proliferation analysis, cell apoptosis analysis, cell migration and invasion analysis, and subcutaneous inoculation of animal models. At the same time, RNA-Seq, RNA pull-down, ChIRP, ChIP, and luciferase reporter gene assays were performed to clarify the mechanism. RESULTS: The expression of LINC00958 in LUAD tissues was significantly upregulated when compared with that in adjacent tissues and could independently predict poor survival of patients with LUAD. LINC00958 knockdown significantly inhibited the growth and metastasis of lung cancer cells in vitro and in vivo. LINC00958 localized to the nucleus, regulated oncogenes and metabolism-related and immune response-related genes, and interacted with histones. The targets of LINC00958 were TRPV3, STAP2, and EDN2 promoters with motifs of HOXA1, NANOG, FOSL2, JUN, and ATF4. Moreover, HOXA1 overexpression mitigated the LINC00958 knockdown-induced oncogenic phenotype. MYC/MAX motif, which was detected at the cis-element of LINC00958, trans-activated the LINC00958 promoter. CONCLUSIONS: MYC/MAX-trans-activated LINC00958 promotes the malignant behavior of LUAD by recruiting HOXA1 and inducing oncogenic reprogramming.

12.
J Plast Reconstr Aesthet Surg ; 74(12): 3431-3436, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34226132

RESUMO

BACKGROUND: Buried-suture double-eyelid blepharoplasty is very popular in Asia, especially in China, but there are few reports related to the cause, management, and prevention of suture-related complications of corneal injury and other damages to the eye. The study aims to determine the cause, management, and prevention of suture-related complications after buried-suture double-eyelid blepharoplasty. METHODS: A retrospective study was conducted from January 2016 to January 2019 on 12 patients with corneal and other injuries to the eye after they underwent buried-suture double-eyelid blepharoplasty. The study included patients who underwent intermittent and continuous buried-suture double-eyelid blepharoplasty with the following symptoms: red eye, foreign body sensation, photophobia, pain, tears, and decreased vision. The clinical characteristics, examination method, and treatment were noted. RESULTS: The patients were all females. Ocular injuries included: corneal epithelial punctate or diffuse injury in nine patients, corneal ulcer in two patients, and a perforating eye injury in one patient. The corneal injury was repaired after exposed nylon thread ends were removed. A suture on the surface of the eye penetrating the sclera was detected in one patient, who then had a vitrectomy caused by endophthalmitis. CONCLUSION: Suture-removal surgery is indicated to treat suture-related complications. Less experienced clinicians should use an eyelid protection plate to protect the cornea and eyeball during surgery. The conjunctiva of the fornix should be examined after surgery. The clinician should inquire about the operation history in detail and check the conjunctiva of the fornix with an eyelid retractor to avoid misdiagnosis.


Assuntos
Blefaroplastia/métodos , Traumatismos Oculares/etiologia , Técnicas de Sutura/efeitos adversos , Suturas/efeitos adversos , Adulto , China , Feminino , Humanos , Pessoa de Meia-Idade , Reoperação , Estudos Retrospectivos
13.
World J Clin Cases ; 9(2): 476-481, 2021 Jan 16.
Artigo em Inglês | MEDLINE | ID: mdl-33521118

RESUMO

BACKGROUND: Fat embolism syndrome (FES) is a rare disease characterized by pulmonary distress, neurologic symptoms, and petechial rash and seriously threatens human life and health. It is still neglected clinically because of the lack of verifiable diagnostic criteria and atypical clinical symptoms. No studies on FES with pulmonary embolism (PE) and tympanic membrane perforation have been reported to date. Here, we report a rare case of concomitant FES, PE and tympanic membrane perforation after surgery in a patient with a tibiofibular fracture. CASE SUMMARY: A 39-year-old man presented with right lower extremity pain due to a car accident while driving a motorbike on the road. X-ray and computed tomography scans revealed a fracture of the right mid-shaft tibia and proximal fibula categorized as a type A2 fracture according to the AO classification. A successful minimally invasive operation was performed 3 d after the injury. Postoperatively, the patient developed sudden symptoms of respiratory distress and hearing loss. Early diagnosis was made, and supportive treatments were used at the early stage of FES. Seven days after surgery, he presented a clear recovery from respiratory symptoms. The outcome of fracture healing was excellent, and his hearing of the left ear was mildly impaired at the last follow-up of 4 mo. CONCLUSION: Concomitant FES, PE and tympanic membrane perforation are very rare but represent potentially fatal complications of trauma or orthopedic surgery and present with predominantly pulmonary symptoms. Early diagnosis and treatment can reduce the mortality of FES, and prevention is better than a cure.

14.
ACS Omega ; 5(32): 20653-20663, 2020 Aug 18.
Artigo em Inglês | MEDLINE | ID: mdl-32832819

RESUMO

Clinically diagnosing low-grade gliomas and microscopic metastatic tumors in the spinal cord using magnetic resonance imaging (MRI) is challenging, as the blood-brain barrier (BBB) almost completely excludes the MRI contrast agent gadopentetate dimeglumine, GdDTPA (Magnevist), from the brain. The development of a more efficient, safe, and broad-spectrum glioma diagnosis and treatment would therefore have a great clinical value. Based on the high expression levels of both transferrin receptor 1 (TfR1) and low-density lipoprotein receptor-related protein 1 (LRP1) in BBB-related cells and glioma cells, we designed a novel protein nanoparticle, ferritin-HREV107-Angiopep-2 (Fn-Rev-Ang). We found that Fn-Rev-Ang rapidly crossed the BBB in mice and had drug-loading properties. Moreover, the brain MRI signal intensity ratio associated with Fn-Rev-Ang-GdDTPA was higher than that associated with Fn-GdDTPA alone. Importantly, gliomas with diameters below 1 mm and microscopic metastatic tumors in the spinal cord were successfully detected in mice by MRI with Fn-Rev-Ang-GdDTPA, which is not possible using the current clinical MRI technology. In addition, Fn-Rev-Ang-loaded doxorubicin had a strong inhibitory effect on mouse brain gliomas and their metastasis, which significantly prolonged the animal survival time. Thus, our newly constructed Fn-Rev-Ang nanodelivery carrier may help expand the use of MRI to the early diagnosis and treatment of microscopic tumors, thereby offering a possible basis for improving the survival rate of patients with gliomas and microscopic spinal metastatic tumors.

15.
Sci Total Environ ; 741: 140293, 2020 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-32610232

RESUMO

An increasing number of epidemiologic studies show that women have a special exposure profile to phthalates, and the exposures have attracted attention regarding their potential health hazards. Here, we developed a model for studying the ovarian action of di-(2-ethylhexyl) phthalate (DEHP) and its major metabolite monoethylhexyl phthalate (MEHP). In vivo, treatment with DEHP (250, 500, and 1000 mg kg^-1) induced decreased thickness of ovarian granulosa cell layer and mitochondrial damage in quail, caused oxidative stress, interfered with the transcription of hypothalamic-pituitary-ovarian axis (HPOA) steroid hormone-related factors (increased transcription of StAR, 3ß-HSD, P450scc, and LH and decreased transcription of 17ß-HSD, P450arom, FSH, and ERß), and blocked the secretion of steroid hormones (decreased FSH, E2, and T levels and increased LH, P, and PRL levels). In vitro, granulosa cells were cultured with MEHP (50, 100, and 200 µM), activator of PPARγ (rosiglitazone, 50 µM), or antagonist of PPARγ (GW9662, 10 µM) for 24 h and gene and protein expression were analyzed by real time RT-PCR and western blot. Rosiglitazone, like MEHP, significantly decreased mRNA and protein levels of P450arom. Antagonist GW9662 partially blocked the suppression of P450arom by MEHP, suggesting that MEHP acts through PPARγ, but not exclusively. Our model shows that MEHP acts on granulosa cells in quail by stimulating PPARs, which leads to decreased gene and protein expression of P450arom. Therefore, the environmental endocrine disruptor DEHP and its major metabolite MEHP act through a receptor-mediated signaling pathway to inhibit the production of estradiol, interfere with the modulation of HPOA, suppress the synthesis of sex hormones, and cause sex hormone secretion disorders, resulting in severe toxicity in the female reproductive system. A framework for an adverse outcome pathway of DEHP/MEHP-induced ovarian toxicity was constructed, which can facilitate an improved understanding of the mechanism of female reproductive toxicity.


Assuntos
Dietilexilftalato , Ovário , Codorniz , Animais , Coturnix , Feminino , Ovário/anormalidades , Ácidos Ftálicos
16.
BMC Mol Cell Biol ; 21(1): 51, 2020 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-32620073

RESUMO

BACKGROUND: Methotrexate (MTX) is an antifolate agent which is widely used in clinic for treating malignancies, rheumatoid arthritis and ectopic pregnancy. As reported, MTX has side effects on gastrointestinal system, nervous system and reproductive system, while its potential damages on oocyte quality are still unclear. It is known that oocyte quality is essential for healthy conception and the forthcoming embryo development. Thus, this work studied the effects of MTX on the oocyte quality. RESULTS: We established MTX model mice by single treatment with 5 mg/Kg MTX. Both morphological and molecular biology studies were performed to assess the in-vivo matured oocytes quality and to analyze the related mechanisms. The in-vivo matured oocytes from MTX-treated mice had poor in-vitro fertilization ability, and the resulting embryo formation rates and blastocyst quality were lower than the control group. We found that the in-vivo matured MTX-treated mouse oocytes displayed abnormal transcript expressions for genes of key enzymes in the folate cycles. MTX increased the rate of abnormal chromosome alignment and affected the regulation of chromosome separation via disrupting the spindle morphology and reducing the mRNA expressions of MAD2 and Sgo1. MTX reduced the DNA methylation levels in the in-vivo matured oocytes, and further studies showed that MTX altered the expressions of DNMT1 and DNMT 3b, and may also affect the levels of the methyl donor and its metabolite. CONCLUSIONS: MTX impaired the in-vivo matured mouse oocyte quality by disturbing folate metabolism and affecting chromosome stability and methylation modification.


Assuntos
Diferenciação Celular/efeitos dos fármacos , Metotrexato/efeitos adversos , Oócitos/patologia , Animais , Diferenciação Celular/genética , Cromossomos de Mamíferos/efeitos dos fármacos , Cromossomos de Mamíferos/metabolismo , DNA (Citosina-5-)-Metiltransferase 1/metabolismo , Metilação de DNA/efeitos dos fármacos , Metilação de DNA/genética , Desenvolvimento Embrionário/efeitos dos fármacos , Fertilização in vitro , Ácido Fólico/metabolismo , Regulação da Expressão Gênica no Desenvolvimento/efeitos dos fármacos , Camundongos Endogâmicos ICR , Oócitos/efeitos dos fármacos , Oócitos/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Fuso Acromático/efeitos dos fármacos , Fuso Acromático/metabolismo , Transcrição Gênica/efeitos dos fármacos
17.
J Nanosci Nanotechnol ; 20(10): 6561-6567, 2020 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-32385014

RESUMO

Objective: This study aimed to determine the effects of dimer captosuccinic acid-coated Fe3O4 (super paramagnetic) nanoparticles (NP) on 2-deoxy-d-glucose in targeted cancer cells with high rates of glucose metabolism. Methods: We prepared Fe3O4@DMSA NP and 2-DG-conjugated Fe3O4@DMSA NP, γ-FE, O, and @DMSA-DG NP. Glucose consumption in MDA-MB-231 and MCF-7 breast cancer cells was determined using γ-Fe2O3@DMSA NP or Fe3O4@DMSA-DG NP, and absorption was tested using Prussian blue staining, ultraviolet colorimetry, and magnetic resonance imaging. Results: Glucose consumption was the highest in MDA-MB-231, and the lowest in human mammary epithelial cells (HMEPiC). The significant uptake of Fe2O3@DMSA-DG NP by MDA-MB-231 and MCF-7 cells within two hours was inhibited by glucose. The uptake of Fe3O4@DMSA-DG NP was significantly higher in MDA-MB-231 than in MCF-7 cells, whereas Fe3O4@DMSA NP was not obviously uptaken by either cell line. Absorption was also not evident in HMEPiC incubated with Fe3O4@DMSA-DG NP and Fe3O4@DMSA NP. Conclusions: The tumor targeting efficacy of 2-DG coated Fe3O4@DMSA NP was improved over Fe3O4,@DMSA NP in cancer cells with high rates of glucose metabolism.


Assuntos
Neoplasias da Mama , Nanopartículas , Neoplasias da Mama/diagnóstico por imagem , Linhagem Celular Tumoral , Compostos Férricos , Humanos , Imageamento por Ressonância Magnética , Titânio
18.
Eur J Pharmacol ; 874: 172988, 2020 May 05.
Artigo em Inglês | MEDLINE | ID: mdl-32032599

RESUMO

Traumatic brain injury (TBI) is a major public health concern with high rates of morbidity and mortality worldwide. Currently used medications, though effective, are also associated with several adverse effects. Development of effective neuroprotective agents with fewer side-effects would be of clinical value. Previous studies have shown that withaferin compounds have a potential neuroprotective effect in nervous system disorders. However, the effect of withaferin compounds, especially withaferin A (WFA), on traumatic brain injury is unclear. In the present study, both in vivo and in vitro models were used to assess whether WFA could exert a neuroprotective effect after TBI and were used to explore the associated mechanisms. The results showed that WFA significantly improved neurobehavioral function in a dose-dependent fashion and alleviated histological alteration of injury to tissues in TBI mice. In vitro models of TBI revealed that dose-dependent WFA treatment increased the viability of SH-SY5Y cells. In addition, WFA treatment could attenuate blood-brain barrier disruption and brain edema via suppressing apoptosis in endothelial cells. Furthermore, both our in vivo and in vitro results reveal that WFA treatment could significantly reduce levels of several neuroinflammation cytokines (IL-1ß, IL-6, and TNF-α), which correlate with an overall reduction in microglial activation. These data suggest that the neuroprotection by WFA is, at least in part, related to regulation of microglial activation and inhibition of vascular endothelial cell apoptosis. Taken together, these findings support further investigation of WFA as a promising therapeutic agent for promoting functional recovery after traumatic brain injury.


Assuntos
Edema Encefálico/tratamento farmacológico , Lesões Encefálicas Traumáticas/tratamento farmacológico , Fármacos Neuroprotetores/uso terapêutico , Vitanolídeos/uso terapêutico , Animais , Apoptose/efeitos dos fármacos , Comportamento Animal/efeitos dos fármacos , Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , Encéfalo/patologia , Edema Encefálico/metabolismo , Edema Encefálico/patologia , Lesões Encefálicas Traumáticas/metabolismo , Lesões Encefálicas Traumáticas/patologia , Linhagem Celular Tumoral , Citocinas/genética , Citocinas/metabolismo , Modelos Animais de Doenças , Células Endoteliais/efeitos dos fármacos , Humanos , Masculino , Camundongos Endogâmicos C57BL , Microglia/efeitos dos fármacos , Microglia/metabolismo , Fármacos Neuroprotetores/farmacologia , Vitanolídeos/farmacologia
19.
J Colloid Interface Sci ; 566: 69-78, 2020 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-31991366

RESUMO

Scald is a kind of common injury for human beings caused by contacting with hot liquids and/or vapor. Herein, we report the preparation of an advanced fabric for efficient scald-preventing by dip-coating a common polyester fabric in a hexadecyl polysiloxane (HD-POS) aqueous suspension, which was synthesized via a waterborne and nonfluorinated approach. Thanks to the hierarchical micro-/nanostructure of the fabric, stable bonding of the compact HD-POS layer on the polyester microfibers, and inherent high stability and elasticity of HD-POS, the fabric features excellent hot water repellency even for dynamic boiling water with a high water impalement resistance of up to 5 grades according to the water repellency grade test. In addition, the fabric shows extraordinary mechanical stability, e.g., its superhydrophobicity remained nearly unchanged after 200 cycles washing, 10,000 cycles Martindale abraison or 1000 cycles 100% streching and releasing. It also exhibits superior environmental robustness (117 d outdoor test) and chemical robustness (7 d immersion in 1 M HCl or NaOH solution, 60 min ultrosonication in both water and anchol immersion) in various harsh conditions. By applying as an advanced fabric for efficient scald-preventing, it can avoid direct contact of hot water and vapor with rat skin by preventing penetration of hot water and most of vapor. It could also significantly reduce heat conduction and radiation to rat skin by reducing contact time of hot water with the fabric (decreased 10 s more quickly than the pristine fabric to 60 °C when encountering 100 mL of 92 °C water). As a result, the fabric in contact with the skin keeps dry and the fabric temperature is much lower than that of the pristine fabric once encountering hot water, thus showing great potentials as an advanced fabric for efficient scald-preventing applications.


Assuntos
Poliésteres/química , Siloxanas/química , Água/química , Tamanho da Partícula , Poliésteres/síntese química , Propriedades de Superfície
20.
FASEB J ; 34(2): 2774-2791, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31912591

RESUMO

Immunologic changes in the hematoma of patients with intracerebral hemorrhage (ICH) and the contribution of these changes to prognosis are unknown. We collected the blood samples and hematoma fluid from 35 patients with acute ICH (<30 hours from symptom onset) and 55 age-matched healthy controls. Using flow cytometry and ELISA, we found that the percentages of granulocytes, regulatory T cells, helper T (Th) 17 cells, and dendritic cells were higher in the peripheral blood of patients with ICH than in healthy controls, whereas the percentages of lymphocytes, M1-like macrophages, and M2-like macrophages were lower. Levels of IL-6, IL-17, IL-23, TNF-α, IL-4, IL-10, and TGF-ß were higher in the peripheral blood of patients with ICH. The absolute counts of white blood cells, lymphocytes, monocytes, and granulocytes in the hematoma tended to be greater at 12-30 hours than they were within 12 hours after ICH, but the percentage of Th cells decreased in peripheral blood. Increased levels of IL-10 in the serum and hematoma, and a reduction in M1-like macrophages in hematoma were independently associated with favorable outcome on day 90. These results indicate that immunocytes present in the hematoma may participate in the acute-phase inflammatory response after ICH.


Assuntos
Hemorragia Cerebral/imunologia , Hematoma/imunologia , Inflamação/imunologia , Macrófagos/imunologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Hemorragia Cerebral/diagnóstico , Feminino , Hematoma/diagnóstico , Humanos , Interleucina-17/sangue , Masculino , Pessoa de Meia-Idade , Monócitos/imunologia , Prognóstico
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