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1.
Ecotoxicol Environ Saf ; 257: 114946, 2023 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-37105096

RESUMO

BACKGROUND: Bisphenol A (BPA) is known to exhibit endocrine disrupting activities and is associated with adiposity. We examined the obesogenic effect of prenatal BPA exposure in the present study. METHODS: Pregnant ICR mice were exposed to vehicle or BPA via the drinking water at a dose of 0.5 µg/kg·d throughout the gestation. Obesity-related indexes were investigated in the 12-wk-old offspring. Primary mouse embryonic fibroblasts (MEFs) collected from treated embryos were used to test effects of BPA on adipocyte differentiation. RESULTS: Offspring presented a significantly higher rate of weight gain than the control, with impaired insulin sensitivity and increased adipocyte size. Differentiation of MEFs from BPA-treated mice showed a higher propensity for the adipocyte commitment as well as up-regulation of genes enriched in lipid biosynthesis. TGF-ß signaling pathway was found to modulate obesogenic effect of BPA in MEF model, but estrogen signaling pathway had no effect. CONCLUSIONS: The present study provides strong evidence of the association between prenatal exposure to low dose of BPA and a significant increase in body weight in the offspring mice with a critical role played by TGF-ß signaling pathway. The potential interactions modulating the binding of BPA and TGF-ß that activate its obesogenic effects need to be examined.


Assuntos
Adiposidade , Efeitos Tardios da Exposição Pré-Natal , Gravidez , Humanos , Animais , Masculino , Camundongos , Feminino , Efeitos Tardios da Exposição Pré-Natal/induzido quimicamente , Camundongos Endogâmicos ICR , Fibroblastos , Obesidade , Compostos Benzidrílicos/toxicidade
2.
J Org Chem ; 87(22): 15703-15712, 2022 11 18.
Artigo em Inglês | MEDLINE | ID: mdl-36331418

RESUMO

Installing a fluoroalkyl group onto the nitrogen atom of azoles represents a potential strategy for lead optimization in medicinal chemistry. Herein, we describe a method for the N-trifluoropropylation of azoles. This process is accomplished using a combination of regioselective N-vinylation and sequential hydrogenation. The two-step sequence is applicable to a diverse set of azoles and tolerates a wide range of functionalities. In addition, we showcase its practicability and utility through the gram-scale synthesis and the late-stage modification of a complex molecule.


Assuntos
Azóis , Nitrogênio , Azóis/química , Hidrogenação , Catálise
3.
BMC Public Health ; 22(1): 1378, 2022 07 19.
Artigo em Inglês | MEDLINE | ID: mdl-35854262

RESUMO

BACKGROUND: Infertility has troubled millions of people worldwide while always being an ignored issue. The high cost of treatment or lack of services placed a barrier to the alleviation of infertility status. Governments play a significant role to promote infertility-related policies for better access to infertility services and comprehensive supports for infertile people. METHODS: Data of infertility status indicators and infertility-related policies in ten representative countries were collected. An infertility-related policy system was established, then classification and quantification were processed according to specific criteria, and different policy implementation patterns were identified. The effectiveness of specific infertility-related policy and various patterns on infertility prevalence relief between 1990 and 2017 were evaluated via generalized linear models and analyses of covariance for the first time. RESULTS: Economic support policies would be less prioritized compared with social security policies, while economic support policy had a significant positive role in the decline of female infertility prevalence (ß = -2·16, p = 0·042). In detail, insurance coverage and economic reward policies were crucial (ß = -3·31, p = 0·031; ß = -4·10, p = 0·025) with adjusted with covariates. The effect of economic support-oriented pattern was relatively better than other patterns for both male and female infertility prevalence relief. Nevertheless, the effectiveness of gradual-promotion pattern seemed preferable for male infertility prevalence relief while was similar with simultaneous-promotion pattern for females. CONCLUSIONS: Our data-driven analysis revealed that insurance coverage and economic reward policies played the pivotal role in moderation of female infertility status. Economic support-oriented pattern and gradual-promotion pattern were preferable when promoting infertility-related policies.


Assuntos
Infertilidade Feminina , Feminino , Humanos , Cobertura do Seguro , Masculino , Políticas , Prevalência
4.
Lasers Med Sci ; 37(1): 279-286, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33442853

RESUMO

Cafe-au-lait macules (CALMs) affect the appearance of patients and can result in serious psychological problems. Successful treatments without adverse effects remain challenging. We designed a prospective, randomized, controlled, evaluator-blinded trial on 40 pediatric patients to compare the efficacy between a low-fluence 1064-nm Q-switched Nd:YAG laser and a Q-switched Nd:YAG 532-nm laser for the treatment of solitary CALMs in children. We randomly assigned participants into 2 groups. We treated those in the first group with 3 sessions of 532-nm QS laser at 1-month intervals, and those in the second group with 6 sessions of 1064-nm LFQS laser at 2-week intervals. We found no significant differences in treatment efficacy (p = 0.14). The 1064-nm laser group referred significantly less pain than the 532-nm laser group (p = 0.0001). Side effects were detected in 5 patients in the 532-nm laser group. The difference of the side effects was statistically significant (p = 0.04). Two patients in 532-nm laser group were recurred and none in 1064-nm laser group. On a univariate logistic regression analysis, lesions with brown color, small size, and irregular edges were significantly associated with better outcomes (> 50% clearance). Multivariate logistic regression analysis found that brown lesions and lesions with irregular edges had higher odds of getting > 50% clearance (p < 0.05). In conclusion, the 1064-nm LFQS laser produced fewer side effects, less pain, and shorter recovery time than the 532-nm laser. Irregular-bordered, smaller, brown lesions improved better than smooth-bordered, larger, light brown lesions. Moreover, the 1064-nm laser may be a better choice for treating large size CALMs. However, no significant differences were found in terms of the treatment efficacy and recurrence.


Assuntos
Lasers de Estado Sólido , Terapia com Luz de Baixa Intensidade , Manchas Café com Leite , Criança , China , Humanos , Lasers de Estado Sólido/efeitos adversos , Estudos Prospectivos , Resultado do Tratamento
5.
Orthopade ; 49(4): 338-349, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30989258

RESUMO

PURPOSE: The aim of this study was to systematically compare the safety and effectiveness of percutaneous endoscopic transforaminal discectomy (PETD) versus percutaneous endoscopic interlaminar discectomy (PEID) for the treatment of lumbar disc herniation (LDH). MATERIAL AND METHODS: All studies that were performed to compare PETD with PEID to treat LDH and published until 31 August 2017 were acquired through a comprehensive search in various databases. A meta-analysis was performed using the Cochrane Collaboration's RevMan 5.3 software. RESULTS: A total of 13 trials with 974 cases consisting of 3 randomized controlled trials, 3 prospective studies and 7 retrospective studies were included. The results suggest that patients treated with PEID experienced more significant advantages with shorter operation time, less intraoperative blood loss and less intraoperative fluoroscopy times but more complications than those treated with PETD; however, the two operative approaches did not significantly differ in terms of LDH recurrence, hospital stay, Oswestry disability index (ODI) scores, visual analogue scale (VAS) scores, Japanese Orthopaedic Association (JOA) scores and MacNab criteria at the final follow-up. CONCLUSION: Based on the results of this study, although PEID may be superior to PETD in certain ways, some of its advantages have yet to be verified and the two interventions were not significantly different in terms of relief of symptoms and functional recovery. Therefore, PEID would be recommended for treating LDH especially at L5/S1 under certain conditions but a prudent attitude is necessary to choose between the two operative approaches before a large sample and high quality randomized controlled trials have been performed.


Assuntos
Discotomia Percutânea/métodos , Deslocamento do Disco Intervertebral/cirurgia , Vértebras Lombares/cirurgia , Procedimentos Cirúrgicos Minimamente Invasivos , Endoscopia/métodos , Feminino , Humanos , Masculino , Ensaios Clínicos Controlados Aleatórios como Assunto , Resultado do Tratamento
6.
Sensors (Basel) ; 19(4)2019 Feb 22.
Artigo em Inglês | MEDLINE | ID: mdl-30813259

RESUMO

Recently, extensive convolutional neural network (CNN)-based methods have been used in remote sensing applications, such as object detection and classification, and have achieved significant improvements in performance. Furthermore, there are a lot of hardware implementation demands for remote sensing real-time processing applications. However, the operation and storage processes in floating-point models hinder the deployment of networks in hardware implements with limited resource and power budgets, such as field-programmable gate arrays (FPGAs) and application-specific integrated circuits (ASICs). To solve this problem, this paper focuses on optimizing the hardware design of CNN with low bit-width integers by quantization. First, a symmetric quantization scheme-based hybrid-type inference method was proposed, which uses the low bit-width integer to replace floating-point precision. Then, a training approach for the quantized network is introduced to reduce accuracy degradation. Finally, a processing engine (PE) with a low bit-width is proposed to optimize the hardware design of FPGA for remote sensing image classification. Besides, a fused-layer PE is also presented for state-of-the-art CNNs equipped with Batch-Normalization and LeakyRelu. The experiments performed on the Moving and Stationary Target Acquisition and Recognition (MSTAR) dataset using a graphics processing unit (GPU) demonstrate that the accuracy of 8-bit quantized model drops by about 1%, which is an acceptable accuracy loss. The accuracy result tested on FPGA is consistent with that of GPU. As for the resource consumptions of FPGA, the Look Up Table (LUT), Flip-flop (FF), Digital Signal Processor (DSP), and Block Random Access Memory (BRAM) are reduced by 46.21%, 43.84%, 45%, and 51%, respectively, compared with that of floating-point implementation.

8.
Sensors (Basel) ; 18(5)2018 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-29693585

RESUMO

With the development of remote-sensing technology, optical remote-sensing imagery processing has played an important role in many application fields, such as geological exploration and natural disaster prevention. However, relative radiation correction and geometric correction are key steps in preprocessing because raw image data without preprocessing will cause poor performance during application. Traditionally, remote-sensing data are downlinked to the ground station, preprocessed, and distributed to users. This process generates long delays, which is a major bottleneck in real-time applications for remote-sensing data. Therefore, on-board, real-time image preprocessing is greatly desired. In this paper, a real-time processing architecture for on-board imagery preprocessing is proposed. First, a hierarchical optimization and mapping method is proposed to realize the preprocessing algorithm in a hardware structure, which can effectively reduce the computation burden of on-board processing. Second, a co-processing system using a field-programmable gate array (FPGA) and a digital signal processor (DSP; altogether, FPGA-DSP) based on optimization is designed to realize real-time preprocessing. The experimental results demonstrate the potential application of our system to an on-board processor, for which resources and power consumption are limited.

9.
Sensors (Basel) ; 18(11)2018 Nov 06.
Artigo em Inglês | MEDLINE | ID: mdl-30404224

RESUMO

Due to strong ocean waves, broken clouds, and extensive cloud cover interferences, ocean ship detection performs poorly when using optical remote sensing images. In addition, it is a challenge to detect small ships on medium resolution optical remote sensing that cover a large area. In this paper, in order to balance the requirements of real-time processing and high accuracy detection, we proposed a novel ship detection framework based on locally oriented scene complexity analysis. First, the proposed method can separate a full image into two types of local scenes (i.e., simple or complex local scenes). Next, simple local scenes would utilize the fast saliency model (FSM) to rapidly complete candidate extraction, and for complex local scenes, the ship feature clustering model (SFCM) will be applied to achieve refined detection against severe background interferences. The FSM considers a fusion enhancement image as an input of the pulse response analysis in the frequency domain to achieve rapid ship detection in simple local scenes. Next, the SFCM builds the descriptive model of the ship feature clustering algorithm to ensure the detection performance on complex local scenes. Extensive experiments on SPOT-5 and GF-2 ocean optical remote sensing images show that the proposed ship detection framework has better performance than the state-of-the-art methods, and it addresses the tricky problem of real-time ocean ship detection under strong waves, broken clouds, extensive cloud cover, and ship fleet interferences. Finally, the proposed ocean ship detection framework is demonstrated on an onboard processing hardware.

10.
Sensors (Basel) ; 17(7)2017 Jun 22.
Artigo em Inglês | MEDLINE | ID: mdl-28640236

RESUMO

With the rapid development of optical remote sensing satellites, ship detection and identification based on large-scale remote sensing images has become a significant maritime research topic. Compared with traditional ocean-going vessel detection, inshore ship detection has received increasing attention in harbor dynamic surveillance and maritime management. However, because the harbor environment is complex, gray information and texture features between docked ships and their connected dock regions are indistinguishable, most of the popular detection methods are limited by their calculation efficiency and detection accuracy. In this paper, a novel hierarchical method that combines an efficient candidate scanning strategy and an accurate candidate identification mixture model is presented for inshore ship detection in complex harbor areas. First, in the candidate region extraction phase, an omnidirectional intersected two-dimension scanning (OITDS) strategy is designed to rapidly extract candidate regions from the land-water segmented images. In the candidate region identification phase, a decision mixture model (DMM) is proposed to identify real ships from candidate objects. Specifically, to improve the robustness regarding the diversity of ships, a deformable part model (DPM) was employed to train a key part sub-model and a whole ship sub-model. Furthermore, to improve the identification accuracy, a surrounding correlation context sub-model is built. Finally, to increase the accuracy of candidate region identification, these three sub-models are integrated into the proposed DMM. Experiments were performed on numerous large-scale harbor remote sensing images, and the results showed that the proposed method has high detection accuracy and rapid computational efficiency.

11.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi ; 33(5): 708-12, 2016 Oct.
Artigo em Chinês | MEDLINE | ID: mdl-27577229

RESUMO

Ultraviolet light(UV)-sensitive disorders refer to a group of diseases due to damages to the nucleotide excision repair mechanism which cannot effectively repair DNA damage caused by ultraviolet radiation. The inheritance pattern of such diseases, mainly including xeroderma pigmentosum, Cockayne syndrome and trichothiodystrophy, is autosomal recessive and known to involve 13 genes. As proteins encoded by such genes are involved in DNA repair and transcription pathways. There is overlap between the symptoms of such diseases, and their genotype - phenotype correlations are quite complex. To facilitate genetic and prenatal diagnosis for such diseases, a summary of the research progress is provided, which mainly focused on mutation research and genotype - phenotype correlation studies. We also propose a strategy for their genetic diagnosis based on recent findings of our group.


Assuntos
Pesquisa Biomédica/métodos , Síndrome de Cockayne/genética , Predisposição Genética para Doença/genética , Síndromes de Tricotiodistrofia/genética , Xeroderma Pigmentoso/genética , Pesquisa Biomédica/tendências , Dano ao DNA , Reparo do DNA/genética , Humanos , Pele/metabolismo , Pele/patologia , Pele/efeitos da radiação , Raios Ultravioleta
12.
World J Surg Oncol ; 12: 208, 2014 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-25022487

RESUMO

Inflammatory myofibroblastic tumors are rare, and those located in the extremities without bone involvement are even rarer. We present the case of a 61-year-old Chinese male patient with an inflammatory myofibroblastic tumor of the right thigh. It was excised and a histopathologic examination revealed an inflammatory myofibroblastic tumor. This case is presented by virtue of its rare location.


Assuntos
Osso e Ossos , Granuloma de Células Plasmáticas/diagnóstico , Inflamação/diagnóstico , Neoplasias de Tecido Muscular/diagnóstico , Coxa da Perna/patologia , Granuloma de Células Plasmáticas/cirurgia , Humanos , Inflamação/cirurgia , Masculino , Pessoa de Meia-Idade , Neoplasias de Tecido Muscular/cirurgia , Prognóstico , Coxa da Perna/cirurgia , Tomografia Computadorizada por Raios X
13.
Int Med Case Rep J ; 17: 301-309, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38618188

RESUMO

This study describes a patient with an intradural extramedullary (IDEM) tumor removed entirely using the unilateral biportal endoscopic technique (UBE), achieving satisfactory clinical outcomes. A 60-year-old woman had a diagnosis of meningioma with sensations and motor dysfunction in the lower extremities and perineum and gait disturbances for three years, which has worsened over the last month. Preoperative imaging data showed a sizeable IDEM tumor at the T10 level, significantly compressing the thoracic spinal cord to the right side, with 80% intraspinal encroachment. The IDEM tumor was removed entirely by UBE surgery. To the best of our knowledge, this study may be the first to report the application of UBE techniques for IDEM tumor treatment. In this case, UBE provides a magnified and clear surgical field, greater maneuverability, and a less invasive surgical procedure. The procedure objectives were pathological confirmation, spinal cord decompression, and complete tumor removal; all were met. The patient was satisfied with her dramatically improved clinical symptoms. UBE may be an alternative surgical treatment option for benign IDEM tumors presenting with symptomatic, especially the non-giant lateral and posterior tumors.

14.
Medicine (Baltimore) ; 103(18): e37943, 2024 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-38701305

RESUMO

BACKGROUND: Lumbar disc herniation was regarded as an age-related degenerative disease. Nevertheless, emerging reports highlight a discernible shift, illustrating the prevalence of these conditions among younger individuals. METHODS: This study introduces a novel deep learning methodology tailored for spinal canal segmentation and disease diagnosis, emphasizing image processing techniques that delve into essential image attributes such as gray levels, texture, and statistical structures to refine segmentation accuracy. RESULTS: Analysis reveals a progressive increase in the size of vertebrae and intervertebral discs from the cervical to lumbar regions. Vertebrae, bearing weight and safeguarding the spinal cord and nerves, are interconnected by intervertebral discs, resilient structures that counteract spinal pressure. Experimental findings demonstrate a lack of pronounced anteroposterior bending during flexion and extension, maintaining displacement and rotation angles consistently approximating zero. This consistency maintains uniform anterior and posterior vertebrae heights, coupled with parallel intervertebral disc heights, aligning with theoretical expectations. CONCLUSIONS: Accuracy assessment employs 2 methods: IoU and Dice, and the average accuracy of IoU is 88% and that of Dice is 96.4%. The proposed deep learning-based system showcases promising results in spinal canal segmentation, laying a foundation for precise stenosis diagnosis in computed tomography images. This contributes significantly to advancements in spinal pathology understanding and treatment.


Assuntos
Aprendizado Profundo , Canal Medular , Estenose Espinal , Tomografia Computadorizada por Raios X , Humanos , Estenose Espinal/diagnóstico por imagem , Tomografia Computadorizada por Raios X/métodos , Canal Medular/diagnóstico por imagem , Masculino , Vértebras Lombares/diagnóstico por imagem , Feminino , Pessoa de Meia-Idade , Processamento de Imagem Assistida por Computador/métodos , Adulto , Deslocamento do Disco Intervertebral/diagnóstico por imagem
15.
Biotechnol Genet Eng Rev ; : 1-17, 2023 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-37035918

RESUMO

Platelet-rich plasma (PRP) with skin booster is a popular treatment for improving skin quality and reducing the signs of aging. However, few studies have evaluated its clinical efficacy in patients with aging face. This study aimed to evaluate the clinical efficacy, adverse reactions, and follow-up results of targeted injection of PRP with skin booster in treating patients with aging face. The study included 80 patients treated with targeted injection of PRP with skin booster from July 2022 to February 2023. The doctors compared the changes of the patients' facial skin indicators, quality of life, and satisfaction with their appearance before and after treatment, and analyzed the clinical efficacy, adverse reactions, and follow-up results of the patients after treatment. After one course of treatment, the patients' facial skin indicators, quality of life, and satisfaction with their appearance improved significantly, with P < 0.05. The total clinical effective rate was 88.75%, and the incidence of adverse reactions was 6.25%. After half a year of follow-up, 48.75% of the patients were willing to receive further treatment, and their facial soft feel, natural expression, and self-feeling comfort had significantly improved. Targeted injection of PRP with skin booster is an effective and safe treatment for improving facial skin symptoms such as coarse pores and wrinkles in patients with aging face. The results of this study provide evidence for the clinical use of PRP with skin booster in aesthetic medicine.

16.
Chin Med ; 18(1): 80, 2023 Jun 29.
Artigo em Inglês | MEDLINE | ID: mdl-37386638

RESUMO

BACKGROUND: Knee osteoarthritis (KOA) has a complex pathological mechanism and is difficult to cure. The traditional medicine Du Huo Ji Sheng Tang (DHJST) has been used for the treatment of KOA for more than one thousand years, but its mechanism for treating KOA has not been revealed. In our previous study, we confirmed that DHJST inhibited the activation of NLRP3 signaling in rats and humans. In the current study, we aimed to determine how DHJST inhibits NLRP3 to alleviate knee cartilage damage. METHODS: Mice were injected with NLRP3 shRNA or Notch1-overexpressing adenovirus into the tail vein to construct systemic NLRP3 low-expressing or Notch1 high-expressing mice. Mice were injected with papain into the knee joint to replicate the KOA model. DHJST was used to treat KOA model mice with different backgrounds. The thickness of the right paw was measured to evaluate toe swelling. The pathohistological changes and the levels of IL-1ß, MMP2, NLRP3, Notch1, collagen 2, collagen 4, HES1, HEY1, and Caspase3 were detected by HE staining, ELISA, immunohistochemical staining, western blotting, or real-time qPCR. RESULTS: DHJST reduced tissue swelling and serum and knee cartilage IL-1ß levels, inhibited cartilage MMP2 expression, increased collagen 2 and collagen 4 levels, decreased Notch1 and NLRP3 positive expression rates in cartilage, and decreased HES1 and HEY1 mRNA levels in KOA model mice. In addition, NLRP3 interference decreased cartilage MMP2 expression and increased collagen 2 and collagen 4 levels without affecting the expression levels of notch1, HES1 and HEY1 mRNA levels in the synovium of KOA mice. In KOA mice with NLRP interference, DHJST further reduced tissue swelling and knee cartilage damage in mice. Finally, Notch1-overexpressing mice not only showed more severe tissue swelling and knee cartilage degradation but also abolished the therapeutic effect of DHJST on KOA mice. Importantly, the inhibitory effects of DHJST on the mRNA expression of NLRP3, Caspase3 and IL-1ß in the knee joint of KOA mice were completely limited after Notch1 overexpression. CONCLUSION: DHJST significantly reduced inflammation and cartilage degradation in KOA mice by inhibiting Ntoch1 signaling and its subsequent NLRP3 activation in the knee joint.

17.
Photodiagnosis Photodyn Ther ; 42: 103545, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-37001715

RESUMO

BACKGROUND: Hemoporfin-mediated photodynamic therapy (Hemoporfin-PDT) has been approved for port-wine stain (PWS) in China in 2017. This study evaluated the efficacy and safety of Hemoporfin-PDT for PWS in a real life setting and investigated factors that influence the efficacy. METHODS: A multicenter retrospective study included patients with PWS who underwent Hemoporfin-PDT in 29 hospitals across China and completed at least two months of follow-up. The efficacy was evaluated based on patien photographs. RESULTS: A total of 1679 patients were included. After the first and second sessions of Hemoporfin-PDT, 63.5 and 75.3% of patients responded, respectively. The response rate of purple-type PWS was significantly lower than that of pink-type PWS (OR: 0.71, 95% CI: 0.54-0.94, P < 0.05), and there was no significant difference between thick- and pink-type (OR: 0.72, 95% CI: 0.42-1.22, P > 0.05). The response rate of PWS on the limbs was significantly lower than that on the mid-face (OR: 0.35, 95% CI: 0.23-0.53, P < 0.0001), while no significant difference was observed between PWS on the peripheral part of the face, neck or other parts of the body and PWS on the mid-face (P > 0.05). The response rate was lower in male patients with an age > 3 years or ≤ 6 years (P < 0.05). Previous treatment history did not affect the efficacy (P > 0.05). Hemoporfin-PDT was well tolerated. CONCLUSION: Patients with PWS have a good response and good tolerance to Hemoporfin-PDT.


Assuntos
Fotoquimioterapia , Mancha Vinho do Porto , Humanos , Masculino , Pré-Escolar , Fotoquimioterapia/métodos , Mancha Vinho do Porto/tratamento farmacológico , Fármacos Fotossensibilizantes/uso terapêutico , Estudos Retrospectivos , Hematoporfirinas
19.
Org Lett ; 24(50): 9301-9305, 2022 Dec 23.
Artigo em Inglês | MEDLINE | ID: mdl-36516238

RESUMO

A new class of Michael acceptor, tetrazolyl-trifluoromethyl alkenes, has been discovered. They readily undergo Michael-type addition instead of addition-elimination reaction with aliphatic amines and azoles to furnish ß-trifluoromethyl alkylamines and CF3-substituted 1,2-bisazole derivatives, respectively. Additionally, some of the products are capable of engaging in microwave-assisted intramolecular denitrogenative annulation, leading to the formation of CF3-substituted 1,4,5,6-tetrahydro-1,2,4-triazines that are otherwise difficult to access by other methodologies.

20.
Life Sci ; 277: 119408, 2021 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-33781831

RESUMO

OBJECTIVE: MicroRNAs are well-established players in post-transcriptional gene modulation. We aim to explore the role of microRNA-15a-5p (miR-15a-5p)/sex determining region Y-box 9 (Sox9)/nuclear factor-κB (NF-κB) axis in inflammation and apoptosis of murine nucleus pulposus cells (NPCs) in intervertebral disc degeneration (IVDD). METHODS: Expression levels of miR-15a-5p and Sox9 in disc tissues from IVDD patients were determined. The IVDD mouse models were established by disc puncture, and the modeled mice were accordingly injected with miR-15a-5p antagomir and/or overexpressed Sox9 plasmid, or their negative controls. Then, the expression of miR-15a-5p, Sox9 and p-p65, pathological changes and the apoptosis of NPCs in IVDD mouse intervertebral disc tissues were measured. The NPCs were isolated and cultured, which were then transfected with miR-15a-5p inhibitor, overexpressed or silenced Sox9 plasmids, or the NCs. Next, the expression of miR-15a-5p and Sox9, apoptosis, proliferation and cell cycle distribution of NPCs, and the contents of inflammatory factors in the NPCs were evaluated. RESULTS: MiR-15a-5p expression was increased while Sox9 expression was reduced in intervertebral disc tissues from IVDD patients and mice. Mouse NPCs were successfully isolated. The down-regulated miR-15a-5p could elevate Sox9 to activate p-p65 expression, suppress NPC apoptosis and inflammatory factor contents, promote proliferation of NPCs, and arrest the NPCs at S and G2/M phases. However, these effects could be reversed by silencing Sox9. CONCLUSION: Reduction of miR-15a-5p elevated Sox9 to inhibit the inflammatory response and apoptosis of NPCs in IVDD mice through the NF-κB pathway. This study may be helpful for IVDD treatment.


Assuntos
Apoptose , Degeneração do Disco Intervertebral/patologia , MicroRNAs/genética , NF-kappa B/metabolismo , Núcleo Pulposo/patologia , Fatores de Transcrição SOX9/metabolismo , Adulto , Animais , Estudos de Casos e Controles , Modelos Animais de Doenças , Feminino , Humanos , Mediadores da Inflamação/metabolismo , Degeneração do Disco Intervertebral/genética , Degeneração do Disco Intervertebral/imunologia , Degeneração do Disco Intervertebral/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , NF-kappa B/genética , Núcleo Pulposo/imunologia , Núcleo Pulposo/metabolismo , Fatores de Transcrição SOX9/genética , Adulto Jovem
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