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1.
Oncogene ; 2021 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-33863999

RESUMO

Colorectal cancer (CRC) is one of the leading cancers worldwide, accounting for high morbidity and mortality. The mechanisms governing tumor growth and metastasis in CRC require detailed investigation. The results of the present study indicated that the transcription factor (TF) myocyte enhancer factor 2A (MEF2A) plays a dual role in promoting proliferation and metastasis of CRC by inducing the epithelial-mesenchymal transition (EMT) and activation of WNT/ß-catenin signaling. Aberrant expression of MEF2A in CRC clinical specimens was significantly associated with poor prognosis and metastasis. Functionally, MEF2A directly binds to the promoter region to initiate the transcription of ZEB2 and CTNNB1. Simultaneous activation of the expression of EMT-related TFs and Wnt/ß-catenin signaling by MEF2A overexpression induced the EMT and increased the frequency of tumor formation and metastasis. The present study identified a new critical oncogene involved in the growth and metastasis of CRC, providing a potential novel therapeutic target for CRC intervention.

2.
BMC Cancer ; 21(1): 367, 2021 Apr 07.
Artigo em Inglês | MEDLINE | ID: mdl-33827486

RESUMO

BACKGROUND: An important mechanism that promoter methylation-mediated gene silencing for gene inactivation is identified in human tumorigenesis. Methylated genes have been found in breast cancer (BC) and beneficial biomarkers for early diagnosis. Prognostic assessment of breast cancer remain little known. Zinc finger protein 132 (ZNF132) is downregulated by promoter methylation in prostate cancer and esophageal squamous cell carcinoma. However, no study provides information on the status of ZNF132, analyzes diagnosis and prognostic significance of ZNF132 in BC. METHODS: In the present study, the expression of ZNF132 mRNA and protein level was determined based on the Cancer Genome Atlas (TCGA) RNA-Seq database and clinical samples analysis and multiple cancer cell lines verification. P rognostic significance of ZNF132 in BC was assessed using the Kaplan-Meier plotter. Molecular mechanisms exploration of ZNF132 in BC was performed using the multiple bioinformatic tools. Hypermethylated status of ZNF132 in BC cell lines was confirmed via Methylation specific polymerase chain reaction (MSP) analysis. RESULTS: The expression of ZNF132 both the mRNA and protein levels was downregulated in BC tissues. These results were obtained based on TCGA database and clinical sample analysis. Survival analysis from the Kaplan-Meier plotter revealed that the lower level of ZNF132 was associated with a shorter Relapse Free Survival (RFS) time. Receiver operating characteristic curve (ROC) of 0.887 confirmed ZNF132 had powerful sensitivity and specificity to distinguish between BC and adjacent normal tissues. Bioinformatic analysis showed that 6% ((58/960)) alterations of ZNF132 were identified from cBioPortal. ZNF132 participated in multiple biological pathways based on the Gene Set Enrichment Analysis (GSEA) database including the regulation of cell cycle and glycolysis. Finally, MSP analysis demonstrated that ZNF132 was hypermethylated in a panel of breast cancer cell lines and 5-aza-2'-deoxycytidine (5-Aza-dC) treatment restored ZNF132 expression in partial cell lines. CONCLUSIONS: Results revealed that hypermethylation of ZNF132 contributed to its downregulated expression and could be identified as a new diagnostic and prognostic marker in BC.

3.
Zhongguo Gu Shang ; 34(2): 160-4, 2021 Feb 25.
Artigo em Chinês | MEDLINE | ID: mdl-33666005

RESUMO

Shoulder arthroscopic as a conventional method usually is applied to repair rotator cuff tears. In clinical, plenty single-row, double-row and transosseous tunnels suture technique are performed, but the ideal suture technique for rotator cuff repair is not found. Compared with single-row, double-row has better strength in biomechanics property. As the two best suture technique among the single-row, massive cuff stitch and modified Mason-Allen suture have the strongest biomechanics property. Clinical trials indicate that double-row could improve healing rates, but there are no significant difference in clinical outcome functional scores. Transosseous tunnel techniques possess a better bio-mechanic property, which could improve regional micro-environment and induce tendon-bone healing. Transosseous tunnel techniques are better for small to media size rotator cuff tears and osteoporosis patient. The author suggest that optimal rotator cuff repair technique should performed according to skill of performer and individual of patient by analysing bio-mechanic properties, clinical outcome, operative complexity and patient situation. The technique should follow simple opertaion, rapid, less trauma, stable fixation and utility to perform.


Assuntos
Lesões do Manguito Rotador , Manguito Rotador , Artroscopia , Humanos , Manguito Rotador/cirurgia , Lesões do Manguito Rotador/cirurgia , Âncoras de Sutura , Técnicas de Sutura , Suturas
4.
Medicine (Baltimore) ; 100(12): e25199, 2021 Mar 26.
Artigo em Inglês | MEDLINE | ID: mdl-33761703

RESUMO

INTRODUCTION: Lumbar disc herniation (LDH) is the most common cause of low back pain and severely affects people's quality of life and ability to work. Although many clinical trials and medical reports conducted over the years have shown that acupuncture treatments are effective for LDH, the comparative effectiveness of these different acupuncture therapies is still unclear. This protocol of a network meta-analysis was designed to compare the effects and safety of acupuncture treatment regimens on LDH using both direct and indirect evidence. METHODS AND ANALYSIS: This protocol is reported according to the 2015 PRISMA-P and PRISMA guidelines for acupuncture. Eight databases and two platforms will be searched for articles published from their establishment to 1 December 2020 with medical subject heading terms and keywords. Three reviewers will verify the eligible randomized controlled trials independently. NoteExpress (3.2.0) software will be utilized to manage the literature. The overall quality of evidence will be evaluated by Confidence In Network Meta-Analysis (CINeMA). Additionally, we will conduct a meta-analysis of the effectiveness, recurrence rate, and symptom score of acupuncture in treating LDH using Review Manager (RevManV.5.4.1) and R4.0.2 software (The R Foundation for Statistical Computing). RESULTS: The results of the study will be published in journals or relevant conferences. CONCLUSION: This proposed systematic review will evaluate the comparative efficacy and safety of various acupuncture methods and combination protocols for LDH.


Assuntos
Terapia por Acupuntura/efeitos adversos , Terapia por Acupuntura/métodos , Deslocamento do Disco Intervertebral/terapia , Metanálise em Rede , Revisões Sistemáticas como Assunto , Humanos , Vértebras Lombares , Projetos de Pesquisa
5.
Artigo em Inglês | MEDLINE | ID: mdl-33719146

RESUMO

Despite allene derivatives have been always regarded as a radical accepter in traditional radical chemistry for decades, the reactivity of allene derivatives under excited state in radical chemistry was rarely explored. Herein, we wish to report an example to engage triplet-excited state of allene moiety as hydrogen-atom-transfer (HAT) partner in the activation of remote sp3 C-H bond via visible-light irradiation under mild reaction conditions with broad substrate scope and good functional-group tolerance. The reaction mechanism involving the generation of triplet excited state of allene derivative and the subsequent HAT process was supported by deuterium labeling, kinetic analysis experiments and DFT calculations.

6.
Adv Mater ; 33(11): e2003852, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33554373

RESUMO

Photodetectors selective to the polarization empower breakthroughs in sensing technology for target identification. However, the realization of polarization-sensitive photodetectors based on intrinsically anisotropic crystal structure or extrinsically anisotropic device pattern requires complicated epitaxy and etching processes, which limit scalable production and application. Here, solution-processed PEA2 MA4 (Sn0.5 Pb0.5 )5 I16 (PEA= phenylethylammonium, MA= methylammonium) polycrystalline film is probed as photoactive layer toward sensing polarized photon from 300 to 1050 nm. The growth of the PEA2 MA4 (Sn0.5 Pb0.5 )5 I16 crystal occurs in confined crystallographic orientation of the (202) facet upon the assistance of NH4 SCN and NH4 Cl, enhancing anisotropic photoelectric properties. Therefore, the photodetector achieves a polarization ratio of 0.41 and dichroism ratio (Imax /Imin ) of 2.4 at 900 nm. At 520 nm, the Imax /Imin even surpasses the one of the perovskite crystalline films, 1.8 and ≈1.2, respectively. It is worth noting that the superior figure-of-merits possess a response width of 900 kHz, Ion /Ioff ratio of ≈3 × 108 , linear dynamic range from 0.15 nW to 12 mW, noise current of 8.28 × 10-13 A × Hz-0.5 , and specific detectivity of 1.53 × 1012 Jones, which demonstrate high resolution and high speed for weak signal sensing and imaging. The proof of concept in polarized imaging confirms that the polarization-sensitive photodetector meets the requirements for practical application in target recognition.

7.
Ann Palliat Med ; 10(2): 1928-1949, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33548996

RESUMO

BACKGROUND: The coronavirus disease 2019 (COVID-19) is an emerging pandemic of global public health concern. We aimed to summarize the characteristics of COVID-19 patients in the early stage of the pandemic and explore the risk factors of disease progression. METHODS: We conducted a systematic review with meta-analysis, searching three databases for studies published between January 1, 2020, and March 18, 2020. We used random-effects models to calculate the 95% confidence intervals of pooled estimated prevalence and the odds ratio between the severe and nonsevere cases. RESULTS: Ninety studies involving 16,526 COVID-19 patients were included. Hypertension (19.1%) and diabetes (9.5%) were the most common comorbidities. The most prevalent clinical symptoms were fever (78.4%), cough (58.5%), and fatigue (26.4%). Increased serum ferritin (74.2%), high C-reactive protein (73.3%), and high erythrocyte sedimentation rate (ESR) (72.2%) were the most frequently reported laboratory abnormalities. Most patients had bilateral lung involvement (82.2%) and showed peripheral (66.9%) and subpleural (62.1%) distribution, with multifocal involvement (73.1%). And the most common CT features were vascular enlargement (64.3%), ground-glass opacity (GGO) (60.7%), and thickened interlobular septa (55.1%). Respiratory failure was the most common complication (30.7%) and the overall case-fatality rate (CFR) was 4.2%. Moreover, male, history of smoking, and comorbidities might influence the prognosis. Most clinical symptoms such as fever, high fever, cough, sputum production, fatigue, shortness of breath, dyspnoea, and abdominal pain were linked to the severity of disease. Some specific laboratory indicators implied the deterioration of disease, such as leucocytosis, lymphopenia, platelet, alanine aminotransferase (ALT), aspartate aminotransferase (AST), albumin, creatinine, creatine kinase (CK), lactic dehydrogenase (LDH), C-reactive protein, procalcitonin (PCT), and D-dimer. Besides, the risk of bilateral pneumonia, consolidation, pleural effusion, and enlarged mediastinal nodes was higher in severe cases. CONCLUSIONS: Most COVID-19 patients have fever and cough with lymphopenia and increased inflammatory indices, and the main CT feature is GGO involved bilateral lung. Patients with comorbidities and worse clinical symptoms, laboratory characteristics, and CT findings tend to have poor disease progression.


Assuntos
/diagnóstico , Biomarcadores/sangue , /patologia , Comorbidade , Tosse , Febre , Humanos , Inflamação , Pulmão/diagnóstico por imagem , Pulmão/patologia , Linfopenia , Estudos Retrospectivos , Fatores de Risco , Tomografia Computadorizada por Raios X
8.
J Biomater Appl ; 35(10): 1347-1354, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33487067

RESUMO

OBJECTIVE: To investigate the protective effect of chondroitin sulfate nano-selenium (SeCS) on chondrocyte of Kashin-Beck disease (KBD). METHODS: Chondrocyte samples were isolated from the cartilage of three male KBD patients (54-57 years old). The chondrocytes were respectively divided into four groups: (a) control group, (b) SeCS supplement group (100 ng/mL SeCS), (c) T-2 + SeCS supplement group (20 ng/mL T-2 + 100 ng/mL SeCS), and (d) T-2 group (20 ng/mL T-2). Live/dead staining and transmission electron microscopy (TEM) were used to observe cell viability and ultrastructural changes in chondrocytes respectively. Expressions of Caspase-9, cytochrome C (Cyt-C), and chondroitin sulfate (CS) structure-modifying sulfotransferases including carbohydrate sulfotransferase 3, 15 (CHST-3, CHST-15), and uronyl 2-O-sulfotransferase (UST) were examined by quantitative real-time polymerase chain reaction. RESULTS: After one- or three-days intervention, the number of living chondrocytes in the SeCS supplement group was higher than that in the control group, while it is opposite in the T-2 + SeCS supplement group and T-2 group. The cellular villi number in the surface increased in the SeCS supplement group compared with the control group. Mitochondrial morphology density was improved in the T-2 + SeCS supplement group compared with the T-2 group. Expressions of CHST-3, CHST-15, UST, Caspase-9, and Cyt-C on the mRNA level significantly increased in the T-2 + SeCS supplement group and T-2 group compared with the control group. CONCLUSIONS: SeCS supplement increased the number of living chondrocytes, improved the ultrastructure, and altered the expressions of CS structure-modifying sulfotransferases, Caspase-9, and Cyt-C.

9.
Signal Transduct Target Ther ; 6(1): 28, 2021 Jan 22.
Artigo em Inglês | MEDLINE | ID: mdl-33479196

RESUMO

The immune system initiates robust immune responses to defend against invading pathogens or tumor cells and protect the body from damage, thus acting as a fortress of the body. However, excessive responses cause detrimental effects, such as inflammation and autoimmune diseases. To balance the immune responses and maintain immune homeostasis, there are immune checkpoints to terminate overwhelmed immune responses. Pathogens and tumor cells can also exploit immune checkpoint pathways to suppress immune responses, thus escaping immune surveillance. As a consequence, therapeutic antibodies that target immune checkpoints have made great breakthroughs, in particular for cancer treatment. While the overall efficacy of immune checkpoint blockade (ICB) is unsatisfactory since only a small group of patients benefited from ICB treatment. Hence, there is a strong need to search for other targets that improve the efficacy of ICB. Ubiquitination is a highly conserved process which participates in numerous biological activities, including innate and adaptive immunity. A growing body of evidence emphasizes the importance of ubiquitination and its reverse process, deubiquitination, on the regulation of immune responses, providing the rational of simultaneous targeting of immune checkpoints and ubiquitination/deubiquitination pathways to enhance the therapeutic efficacy. Our review will summarize the latest findings of ubiquitination/deubiquitination pathways for anti-tumor immunity, and discuss therapeutic significance of targeting ubiquitination/deubiquitination pathways in the future of immunotherapy.

10.
J Exp Clin Cancer Res ; 40(1): 44, 2021 Jan 26.
Artigo em Inglês | MEDLINE | ID: mdl-33499877

RESUMO

BACKGROUND: Transcriptional coactivator with PDZ-binding motif (TAZ) has been reported to be involved in tumor progression, angiogenesis, epithelial-mesenchymal transition (EMT), glycometabolic modulation and reactive oxygen species (ROS) buildup. Herein, the underlying molecular mechanisms of the TAZ-induced biological effects in bladder cancer were discovered. METHODS: qRT-PCR, western blotting and immunohistochemistry were performed to determine the levels of TAZ in bladder cancer cells and tissues. CCK-8, colony formation, tube formation, wound healing and Transwell assays and flow cytometry were used to evaluate the biological functions of TAZ, miR-942-3p and growth arrest-specific 1 (GAS1). QRT-PCR and western blotting were used to determine the expression levels of related genes. Chromatin immunoprecipitation and a dual-luciferase reporter assay were performed to confirm the interaction between TAZ and miR-942. In vivo tumorigenesis and colorimetric glycolytic assays were also conducted. RESULTS: We confirmed the upregulation and vital roles of TAZ in bladder cancer. TAZ-induced upregulation of miR-942-3p expression amplified upstream signaling by inhibiting the expression of large tumor suppressor 2 (LATS2, a TAZ inhibitor). MiR-942-3p attenuated the impacts on cell proliferation, angiogenesis, EMT, glycolysis and ROS levels induced by TAZ knockdown. Furthermore, miR-942-3p restrained the expression of GAS1 to modulate biological behaviors. CONCLUSION: Our study identified a novel positive feedback loop between TAZ and miR-942-3p that regulates biological functions in bladder cancer cells via GAS1 expression and illustrated that TAZ, miR-942-3p and GAS1 might be potential therapeutic targets for bladder cancer treatment.

11.
Life Sci ; 268: 118967, 2021 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-33417951

RESUMO

AIMS: Sensory nerve activation modulates ureteral contractility by releasing neuropeptides including CGRP and neurokinin A (NKA). TRPM3 is a recently discovered thermosensitive channel expressed in nociceptive sensory neurons, and plays a key role in heat nociception and chronic pain. The aim of this study is to examine the role of TRPM3 activation in human ureter motility. MAIN METHOD: Human proximal ureters were obtained from fourteen patients undergoing nephrectomy. Spontaneous or NKA-evoked contractions of longitudinal ureter strips were recorded in an organ bath. Ureteral TRPM3 expression was examined by immunofluorescence. KEY FINDINGS: Spontaneous contractions were observed in 60% of examined strips. TRPM3 activation using pregnenolone sulphate (PS) or CIM0216 (specific TRPM3 agonists) dose-dependently reduced the frequency of spontaneous and NKA-evoked contractions, with IC50s of 241.7 µM and 4.4 µM, respectively. The inhibitory actions of TRPM3 agonists were mimicked by CGRP (10 to 100 nM) or a cAMP analogue (8-Br-cAMP; 1 mM). The inhibitory actions of TRPM3 agonists (300 µM PS or 30 µM CIM0216) were blocked by pretreatment with primidone (TRPM3 antagonist; 30 µM), tetrodotoxin (sodium channel blocker; 1 µM), olcegepant (CGRP receptor antagonist; 10 µM), or H89 (non-specific PKA inhibitor; 30 µM). TRPM3 was co-expressed with CGRP in nerves in the sub-urothelial and intermuscular regions of the ureter. SIGNIFICANCE: TRPM3 channels expressed on sensory terminals of the human ureter involve in inhibitory sensory neurotransmission and modulate ureter motility via the CGRP-cAMP-PKA signal pathway. Targeting TRPM3 may be a pharmacological strategy for promoting the ureter stone passage.


Assuntos
Peptídeo Relacionado com Gene de Calcitonina/metabolismo , Células Receptoras Sensoriais/metabolismo , Canais de Cátion TRPM/metabolismo , Ureter/fisiologia , Adulto , Idoso , Capsaicina/farmacologia , Relação Dose-Resposta a Droga , Feminino , Compostos Heterocíclicos de 4 ou mais Anéis/farmacologia , Humanos , Masculino , Pessoa de Meia-Idade , Contração Muscular/efeitos dos fármacos , Contração Muscular/fisiologia , Nefrectomia , Neurocinina A/metabolismo , Neurocinina A/farmacologia , Técnicas de Cultura de Órgãos , Pregnenolona/farmacologia , Primidona/farmacologia , Células Receptoras Sensoriais/efeitos dos fármacos , Canais de Cátion TRPM/agonistas , Canais de Cátion TRPM/antagonistas & inibidores , Ureter/efeitos dos fármacos
12.
Hum Immunol ; 2020 Dec 04.
Artigo em Inglês | MEDLINE | ID: mdl-33288226

RESUMO

BACKGROUND: As the survival rate of premature infants increases, the incidence of bronchopulmonary dysplasia (BPD), a chronic complication of premature infants, is also higher than before. The pathogenesis of BPD is complicated, and immune imbalance and inflammatory response may play important roles in it. OBJECTIVE: To investigate the correlation between lymphocyte subsets in peripheral blood, especially γδ-T cells, and BPD of preterm infants. MATERIALS AND METHOD: The study was carried out with the peripheral blood of premature infants (GA < 32 weeks, BW < 1500 g), which were collected at 24 h or 3-4 weeks after birth. The infants were divided into non-BPD groups and BPD groups that were classified as mild or moderate and severe in preterm infants based on the magnitude of respiratory support at 28 days age and 36 weeks postmenstrual age. The γδ-T, CD3+, CD4+, CD8+ and total lymphocyte subsets in peripheral blood were detected by flow cytometry. RESULTS: The percentages of T lymphocyte subsets in peripheral blood were not different between BPD and non-BPD within 24 h after birth. And no significant difference was found in T lymphocyte subsets among neonates with BPD of different severities. However, the infants who developed BPD had a significant increase in γδ-T cells compared to non-BPD ones within 3-4 weeks after birth. CONCLUSIONS: It seems that γδ-T cells in peripheral blood are correlated with BPD. However, the causality of BPD and various lymphocytes remains unclear, which need to be further studied.

13.
Zhongguo Gu Shang ; 33(12): 1175-8, 2020 Dec 25.
Artigo em Chinês | MEDLINE | ID: mdl-33369328

RESUMO

Titanium alloy has good biological properties and is commonly used in orthopedics, but its bone integrity and antibacterial properties are poor, so surface modification is needed to make up for its shortcomings. Chitosan has good biocompatibility and film forming ability, and can be used as a carrier to introduce the target drug to the surface of titanium alloy, which can effectively improve the biological properties of titanium alloy materials and increase its application range. In this paper, the related research of chitosan surface modified titanium alloy materials in recent years is summarized. The modification methods of chitosan coating, the improvement of osteogenesisand antibacterial properties of titanium alloy materials are discussed in order to provide guidance for the clinical application of coating modification of titanium alloy materials.


Assuntos
Quitosana , Ortopedia , Ligas , Antibacterianos/farmacologia , Propriedades de Superfície , Titânio
14.
Sensors (Basel) ; 21(1)2020 Dec 25.
Artigo em Inglês | MEDLINE | ID: mdl-33375654

RESUMO

In order to obtain desirable crop yields, grain seeds need to be sown at the optimal seed amount per hectare with uniform distribution in the field. In previous grain sowing processes, the seeding rates are controlled by the rotational speed of the flute roller which significantly effects the uniform distribution of the seeds due to disturbances, such as the reduction of the seeds' mass in the hopper and the change of working length of the flute roller. In order to overcome the above problem, we developed an adaptive roller speed control system based on the seed flow rate sensor. The developed system can monitor and feedback actual seeding rates. In addition, based on the monitoring value of the real-time seeding rates, an adaptive roller speed control method (ARSCM), which contains an algorithm for calculating the seeding rate with a compensation, was proposed. Besides, the seeding performance of the ARSCM and that of the conventional roller speed control method (CRSCM) were compared. The results of constant-velocity experiments demonstrated that the accuracy (SA) and the coefficient of variation (SCV) of the seeding rates controlled by the ARSCM were 94.12% and 6.77%, respectively. As for the CRSCM, the SA and SCV were 89.00% and 8.95%, respectively. Under variable-velocity conditions, the SA and SCV of the proposed system were 91.58% and 11.08%, respectively, while those of the CRSCM were 88.48% and 13.08%, respectively. Based on the above results, this study concluded that the ARSCM is able to replace the CRSCM in practical sowing processes for the optimal and uniform seed distribution in the field.

15.
Mol Ther Nucleic Acids ; 22: 815-831, 2020 Dec 04.
Artigo em Inglês | MEDLINE | ID: mdl-33230478

RESUMO

Circular RNAs (circRNAs), a subclass of noncoding RNAs, are reportedly involved in the progression of various diseases. However, the exact role of circRIMS1, also termed hsa_circ_0132246, in human bladder cancer remains unknown. By performing RNA sequencing comparing bladder cell lines and normal uroepithelial cells, circRIMS1 was selected as a research object. We further verified by qRT-PCR that circRIMS1 is upregulated in both bladder cancer tissue and cell lines. Proliferation, colony-formation, Transwell migration, invasion, apoptosis, western blotting, and in vivo experiments were utilized to clarify the roles of circRIMS1, microRNA (miR)-433-3p, and cell cycle and apoptosis regulator 1 (CCAR1). For mechanistic investigation, RNA pulldown, fluorescence in situ hybridization (FISH), and luciferase reporter assay confirmed the binding of circRIMS1 with miR-433-3p. Inhibition of circRIMS1 suppressed the proliferation, migration, and invasion of bladder cancer cells both in vitro and in vivo. Moreover, the circRIMS1/miR-433-3p/CCAR1 regulatory axis was confirmed to be responsible for the biological functions of circRIMS1. Taken together, our research demonstrated that circRIMS1 promotes tumor growth, migration, and invasion through the miR-433-3p/CCAR1 regulatory axis, representing a potential therapeutic target and biomarker in bladder cancer.

16.
Onco Targets Ther ; 13: 11183-11192, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33173310

RESUMO

Purpose: Anaplastic thyroid cancer (ATC) is a kind of rare thyroid cancer with very poor prognosis. Doxorubicin has been approved in ATC treatment as a single agent, but monotherapy still shows no improvement of the total survival in advanced ATC. Lenvatinib was investigated with encouraging results in treating patients with radioiodine-refractory differentiated thyroid cancer (DTC). However, antitumor efficacy of combination therapy with lenvatinib and doxorubicin remains largely unclear. Materials and Methods: The antitumor efficacy of combination therapy with lenvatinib and doxorubicin on ATC cell proliferation was assessed by the MTT assay and colony formation. Flow cytometry was employed to assess ATC cells' apoptosis and cell cycle arrest in response to combination therapy. Transwell assay was used to test the migration and invasion in response to combination therapy. Xenograft models were used to test its in vivo antitumor activity. Results: Lenvatinib monotherapy was less effective than doxorubicin in treating ATC cell lines and xenograft model. The combination therapy of lenvatinib and doxorubicin significantly inhibited ATC cell proliferation and tumor growth in nude mice, and induced cell apoptosis and cell cycle arrest as compared to lenvatinib or doxorubicin monotherapy. Conclusion: Lenvatinib promotes the antitumor effect of doxorubicin in ATC cell and xenograft model. The lenvatinib/doxorubicin combination may be a potential candidate therapeutic approach for anaplastic thyroid cancer.

17.
Clin Nephrol ; 2020 Nov 19.
Artigo em Inglês | MEDLINE | ID: mdl-33210998

RESUMO

INTRODUCTION: Atypical hemolytic uremic syndrome (aHUS) is characterized by hemolytic anemia, thrombocytopenia, and acute kidney injury. Uncontrolled activation of the complement system induced by single or combined complement gene mutations is one of the mechanisms leading to the pathogenesis of aHUS. CASE PRESENTATION: We report a case of a 26-year-old female with a C3 heterozygous gene mutation (p.Asn153Asn). The patient was found to have low complement H factor (CFH) but normal levels of anti-CFH autoantibody. She was treated primarily with plasma exchange and plasma infusion. The patient did not relapse during a 1-year follow-up. CONCLUSION: This is the first case of a novel C3 mutation (p.Asn153Asn) in a patient with aHUS. Further studies are needed to confirm the association between this mutation and the CFH level.

18.
Chem Biol Interact ; 331: 109273, 2020 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-33002460

RESUMO

Artesunate is a kind of derivative of artemisinin, which possesses potent anti-cancer effect in addition to its anti-malarial property. And autophagy was a highly conserved process, exerting a double-edged effect in cancer cell survival. Besides, apoptosis is a programmed cell death program, crucial to cell homeostasis. However, the relations between autophagy and apoptosis, and the role of artesunate in this interaction have not been elucidated in bladder cancer. In present study, we used human bladder cancer cells (T24 and EJ cell lines) to investigate that how artesunate would influence autophagy and apoptosis processes. We found that artesunate could inhibit the viability, proliferation and migration of bladder cancer cells, as well as induce autophagy in a time and dose dependent manner, in addition, the artesunate induced autophagy subsequently activated cells apoptosis. Furthermore, we pretreated T24 and EJ cells with 3-Methyladenine or Rapamycin to inhibit or promote autophagy, respectively, leading to inhibited or increased apoptosis. Moreover, pretreatment of these cell lines with Acadesine or Dorsomorphin to activate or inhibit the AMPK-mTOR-ULK1 pathway, respectively, also resulting in promotion or suppression in both autophagy and apoptosis. In the upstream, ROS upregulation triggered by ART initiated AMPK-mTOR-ULK1 axis. However, this initiative effect of ROS can be reversed by N-Acetyl-l-cysteine. Therefore, this study indicated that Artesunate induces autophagy dependent apoptosis through upregulating ROS and activating AMPK-mTOR-ULK1 pathway in human bladder cancer cells.


Assuntos
Apoptose/efeitos dos fármacos , Artesunato/farmacologia , Autofagia/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Proteínas Quinases Ativadas por AMP/metabolismo , Artesunato/química , Proteína Homóloga à Proteína-1 Relacionada à Autofagia/metabolismo , Caspase 3/metabolismo , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Humanos , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Serina-Treonina Quinases TOR/metabolismo , Regulação para Cima/efeitos dos fármacos , Neoplasias da Bexiga Urinária/metabolismo , Neoplasias da Bexiga Urinária/patologia
19.
Sci Rep ; 10(1): 16862, 2020 10 08.
Artigo em Inglês | MEDLINE | ID: mdl-33033344

RESUMO

The prevalence of a novel ß-coronavirus (SARS-CoV-2) was declared as a public health emergency of international concern on 30 January 2020 and a global pandemic on 11 March 2020 by WHO. The spike glycoprotein of SARS-CoV-2 is regarded as a key target for the development of vaccines and therapeutic antibodies. In order to develop anti-viral therapeutics for SARS-CoV-2, it is crucial to find amino acid pairs that strongly attract each other at the interface of the spike glycoprotein and the human angiotensin-converting enzyme 2 (hACE2) complex. In order to find hot spot residues, the strongly attracting amino acid pairs at the protein-protein interaction (PPI) interface, we introduce a reliable inter-residue interaction energy calculation method, FMO-DFTB3/D/PCM/3D-SPIEs. In addition to the SARS-CoV-2 spike glycoprotein/hACE2 complex, the hot spot residues of SARS-CoV-1 spike glycoprotein/hACE2 complex, SARS-CoV-1 spike glycoprotein/antibody complex, and HCoV-NL63 spike glycoprotein/hACE2 complex were obtained using the same FMO method. Following this, a 3D-SPIEs-based interaction map was constructed with hot spot residues for the hACE2/SARS-CoV-1 spike glycoprotein, hACE2/HCoV-NL63 spike glycoprotein, and hACE2/SARS-CoV-2 spike glycoprotein complexes. Finally, the three 3D-SPIEs-based interaction maps were combined and analyzed to find the consensus hot spots among the three complexes. As a result of the analysis, two hot spots were identified between hACE2 and the three spike proteins. In particular, E37, K353, G354, and D355 of the hACE2 receptor strongly interact with the spike proteins of coronaviruses. The 3D-SPIEs-based map would provide valuable information to develop anti-viral therapeutics that inhibit PPIs between the spike protein of SARS-CoV-2 and hACE2.


Assuntos
Betacoronavirus/metabolismo , Biologia Computacional/métodos , Infecções por Coronavirus/epidemiologia , Peptidil Dipeptidase A/metabolismo , Pneumonia Viral/epidemiologia , Mapas de Interação de Proteínas , Glicoproteína da Espícula de Coronavírus/metabolismo , Anticorpos Antivirais/metabolismo , Sítios de Ligação , Infecções por Coronavirus/virologia , Coronavirus Humano NL63/metabolismo , Humanos , Pandemias , Pneumonia Viral/virologia , Prevalência , Domínios Proteicos , Receptores Virais/metabolismo , Vírus da SARS/metabolismo , Síndrome Respiratória Aguda Grave/virologia
20.
Eur J Clin Invest ; : e13425, 2020 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-33037614

RESUMO

BACKGROUND: Myofibroblast differentiation and extracellular matrix (ECM) deposition are observed in chronic obstructive pulmonary disease (COPD). However, the mechanisms of regulation of myofibroblast differentiation remain unclear. MATERIALS AND METHODS: We detected let-7 levels in peripheral lung tissues, serum and primary bronchial epithelial cells of COPD patients and cigarette smoke (CS)-exposed mice. IL-6 mRNA was explored in lung tissues of COPD patients and CS-exposed mice. IL-6 protein was detected in cell supernatant from primary epithelial cells by ELISA. We confirmed the regulatory effect of let-7 on IL-6 by luciferase reporter assay. Western blotting assay was used to determine the expression of α-SMA, E-cadherin and collagen I. In vitro, cell study was performed to demonstrate the role of let-7 in myofibroblast differentiation and ECM deposition. RESULTS: Low expression of let-7 was observed in COPD patients, CS-exposed mice and CS extract (CSE)-treated human bronchial epithelial (HBE) cells. Increased IL-6 was found in COPD patients, CS-exposed mice and CSE-treated HBE cells. Let-7 targets and silences IL-6 protein coding genes through binding to 3' untranslated region (UTR) of IL-6. Normal or CSE-treated HBE cells were co-cultured with human embryonic lung fibroblasts (MRC-5 cells). Reduction of let-7 in HBE cells caused myofibroblast differentiation and ECM deposition, while increase of let-7 mimics decreased myofibroblast differentiation phenotype and ECM deposition. CONCLUSION: We demonstrate that CS reduced let-7 expression in COPD and, further, identify let-7 as a regulator of myofibroblast differentiation through the regulation of IL-6, which has potential value for diagnosis and treatment of COPD.

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