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1.
Zhongguo Zhong Yao Za Zhi ; 46(19): 4936-4944, 2021 Oct.
Artigo em Chinês | MEDLINE | ID: mdl-34738387

RESUMO

In this study, liquid chromatography-mass spectrometry(LC-MS) and high performance liquid chromatography(HPLC) were employed for qualitative and quantitative analysis of the steroidal saponins in rhizomes of Paris polyphylla var. yunnanensis from three different habitats cultured in vitro, in an attempt to explore whether the rhizomes of the medicinal herb cultured in vitro can synthesize the steroidal saponins, including polyphyllinsⅠ, Ⅱ, and Ⅶ, the quality markers specified in Chinese Pharmacopoeia(2020 edition). A total of 20 steroidal saponins were identified in the rhizomes from Changxin, Yunlong(S1), Fengyi, Dali(S2), and Niujie, Eryuan(S3): parisyunnanoside A and parisyunnanoside D or E, proto-polyphyllin Ⅱ, polyphyllins G and H, polyphyllinsⅠ, Ⅱ, Ⅴ, Ⅵ, and Ⅶ, dioscin, gracillin, prosapogenin A, Tg, isomer of Th, saponin Th, reclinatoside, proto-pairs D, pseudoproto-dioscin, and 23-O-glc-(23S,25R)-spirost-5-en-3ß,23α,27-triol-3-O-rha-(1→2)-[ara(1→4)]-glc or 27-O-glc-(23S,25R)-spirost-5-en-3ß,27α-diol-3-O-rha-(1→2)-[ara(1→4)]-glc. Among them, polyphyllinsⅠ, Ⅱ, and Ⅶ were detected in the rhizomes from S1, with the mass fraction of 0.109 1%, 0.165 2%, and 0.051 03%, respectively(total 0.325 3%). Polyphyllins Ⅱ and Ⅶ were identified in the rhizomes from S2 with the respective mass fraction of 0.192 2% and 0.074 23% and total content of 0.266 5%. Moreover, polyphyllins Ⅱ and Ⅶ were also found in the rhizomes from S3, which had the mass fraction of 0.207 7% and 0.186 9%, separately, with the total content of 0.394 6%. Thus, steroidal saponins, including the quality makers polyphyllins Ⅰ, Ⅱ, and Ⅶ recorded in Chinese Pharmacopoeia(2020 edition) can be synthesized in rhizomes of Paris polyphylla var. yunnanensis cultured in vitro, but their total content fails to meet the standard(0.60% in Chinese Pharmacopoeia). Therefore, in vitro culture of the Paris polyphylla var. yunnanensis is feasible, but the culture conditions need to be further improved.


Assuntos
Liliaceae , Melanthiaceae , Saponinas , Cromatografia Líquida de Alta Pressão , Rizoma
2.
Front Oncol ; 11: 739134, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34604084

RESUMO

Background: Malignant urachal tumor is a rare subtype of genitourinary cancer. Our aim was to explore the optimal chemotherapy regimens for relapsed or metastatic urachal carcinoma. Materials and Methods: We retrospectively enrolled 24 adult patients with relapsed or metastatic urachal carcinoma from January 2014 to September 2020 at Sun Yat-sen University Cancer Center. We summarized the chemotherapy regimens and classified them as fluorouracil based, platinum based, and paclitaxel based. Nine patients received XELOX (capecitabine and oxaliplatin) regimens, seven patients received TX (paclitaxel and capecitabine) regimens, and eight of them received chemotherapy including GP (gemcitabine and cisplatin), TP (paclitaxel and cisplatin), TN (paclitaxel and nedaplatin), and tislelizumab. Results: The disease control rate was 75%. Among all patients, one patient treated with XELOX achieved partial remission (PR), while 17 patients showed stable disease. The median progression-free survival (PFS) and overall survival (OS) in all treated patients was 7.43 and 29.7 months, respectively. The patients receiving first-line platinum-based chemotherapy presented better PFS than those without platinum (median PFS 8.23 vs. 3.80 months, p = 0.032), but not significant for OS between two groups. There is no significant difference in PFS and OS for fluorouracil-based and paclitaxel-based groups as first-line regimen. Next-generation gene sequencing revealed TP53 mutation and low tumor mutational burden in five out of seven cases. Conclusion: The platinum-based chemotherapy regimen is effective for relapsed or metastatic urachal carcinoma.

3.
World J Clin Cases ; 9(16): 3919-3926, 2021 Jun 06.
Artigo em Inglês | MEDLINE | ID: mdl-34141748

RESUMO

BACKGROUND: Open reduction and internal fixation (ORIF) is the traditional surgical treatment for patellar fractures, and unicompartmental knee arthroplasty (UKA), especially Oxford UKA, has been increasingly used in patients with medial knee osteoarthritis (OA). However, the process of choosing treatment for patients with both patellar fractures and anteromedial knee OA remains unclear. We present the case of a patient with a patellar fracture and anteromedial OA. CASE SUMMARY: We present the case of a 72-year-old woman with a history of bilateral medial compartment OA of the knees and a right Oxford UKA. She also experienced a recent left patellar fracture. ORIF and Oxford UKA were performed in a single stage. The patient showed excellent postoperative clinical results. CONCLUSION: ORIF and Oxford UKA can be performed simultaneously for patients with patellar fracture and anteromedial OA on the same knee.

4.
Transl Pediatr ; 10(4): 790-806, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-34012829

RESUMO

Background: The composition of intestinal flora in Chinese and Japanese has been reported in many studies but that in infants aged 0-6 years old has not been studied yet. Methods: The distribution characteristics of the fecal flora of infants in Beijing (n=84) and Japan (n=53) were analyzed using 16S rRNA gene sequencing analysis. Results: This study showed the higher relative abundance of Erysipelotrichaceae_ UCG-003 and Anaerostipes in male group that of Ruminiclostridium, Eubacterium, Senegalimassilia and Senegalimassilia in female group, especially Senegalimassilia, which was not detected in male group. Defecation trait groups indicated significantly higher relative abundance of Bifidobacterium in abnormal bowel trait group than that in the normal group (P<0.05). The feeding groups' analysis showed significantly higher relative abundance of Bifidobacterium and Enterococcus and lower abundance of Bacteroides and Lacetospirillaceae in the breast-feeding group than that in the formula feeding and mixed-feeding groups. The relative abundance of Parasutterella and Ruminococcaceae_UCG-003 in the halitosis group was significantly higher than that in the normal group. The comparison of cold and fever group and normal group indicated significantly higher relative abundance of Erysipelatoclostridium and lower relative abundance of Lachnospiraceae _UCG-001 in the fever and cold group than that in the normal group (P<0.05). The regional comparison of intestinal flora of Beijing and Japan showed significant increase in the relative abundance of Bacillus, Lactobacillus, Prevotella, megamonas and Veillonella in the intestinal flora of 0-6 years old infants in Beijing. Conclusions: These findings improve the understanding of intestinal bacterial and viral communities of infants from the two Asian countries.

5.
Front Pediatr ; 9: 598805, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33777860

RESUMO

Prior studies have examined the influence of MTHFR C677T on autism susceptibility, however, there are no consensus conclusions and specific analyses of a Chinese population. This meta-analysis included a false-positive report probability (FPRP) test to comprehensively evaluate the association of MTHFR C677T polymorphism with autism susceptibility among a Chinese Han population. A large-scale literature retrieval was conducted using various databases including PubMed, Embase, Wan Fang, and the Chinese National Knowledge Infrastructure (CNKI) up to July 31, 2020, with a total of 2,258 cases and 2,073 controls included. The strength of correlation was assessed by odds ratios (ORs) and 95% confidence intervals (95% CIs). MTHFR C677T showed a significant correlation with increased ASD susceptibility under all genetic models (T vs. C, OR = 1.89, 95% CI 1.28 to 2.79; TT vs. CC: OR = 2.44, 95% CI 1.43 to 4.15; CT vs. CC, OR = 1.73; 95% CI 1.19 to 2.51; CT + TT vs. CC: OR = 2.03, 95% CI 1.31 to 3.15; TT vs. CT + CC, OR = 1.95, 95% CI 1.21 to 3.13). Stratification analysis by region also revealed a consistent association in the Northern Han subgroup, but not in the Southern Han subgroup. Pooled minor allele frequency (MAF) of 30 studies were 45% in Northern Han and 39% in Southern Han. To avoid a possible "false positive report," we further investigated the significant associations observed in the present meta-analysis using the FPRP test, which consolidated the results. In conclusion, MTHFR C677T polymorphism is associated with the increased risk of autism in China, especially in Northern Han. For those mothers and children who are generally susceptible to autism, prenatal folate and vitamin B12 may reduce the risk that children suffer from autism, especially in Northern Han populations. In the future, more well-designed studies with a larger sample size are expected.

6.
Front Neurol ; 12: 604052, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33633666

RESUMO

Myasthenia gravis (MG) is an autoimmune disease in which antibodies bind to acetylcholine receptors (AChR) or other functional molecules in the postsynaptic membrane at the neuromuscular junction. Vitamin D (VD) has a number of pluripotent effects, which include immune-regulation and bone metabolism. The immunomodulatory actions of 1,25(OH)2D3 are mediated by its binding to a vitamin D receptor (VDR). In the study, we undertook a case-control study to explore the association between VDR gene polymorphism and the susceptibility and severity of MG patients. Four hundred and eighty MG patients and 487 healthy controls were included and gene polymorphisms of VDR were determined with improved multiplex ligation detection reaction technique and SNPscanTM technique. MG patients were classified into subgroups by essential clinical features and by a comprehensive classification. The frequencies of alleles and genotypes were compared between the MG group and the control group, between each MG subgroup and the control group, and between each pair of MG subgroups. There were no significant differences in frequencies of alleles and genotypes between MG patients and healthy controls, between MG subgroups and healthy controls, or between each pair of MG subgroups in the analysis of subgroups classified by essential clinical features (onset age, gender, thymoma, AChRAb positivity, onset involvement) and the maximal severity (modified Oosterhuis score). In the analysis of subgroups with a comprehensive classification, the frequencies of alleles and genotypes in rs731236 showed significant differences between adult non-thymoma AChRAb negative MG subgroup and the control group, as well as the adult non-thymoma AChRAb positive MG group. In the Chinese Han population, rs731236 was found to be possibly associated with adult non-thymoma AChRAb negative MG patients, although this needs further confirmation.

7.
J Neuroimmunol ; 353: 577487, 2021 04 15.
Artigo em Inglês | MEDLINE | ID: mdl-33578311

RESUMO

Complement component 3 (C3) had been proved to be involved in the pathogenesis and exacerbation of both myasthenia gravis (MG) patients and experimental autoimmune myasthenia gravis (EAMG) models. We evaluated the underlying association between five SNPs (rs344555, rs7951, rs3745568, rs366510 and rs163913) in C3 gene and Chinese adult MG patients. Our study consisted of 409 adult MG patients and 487 healthy controls. Subgroups were classified by gender, onset age, thymoma, anti-AChR antibody, onset muscle involvement (ocular/generalized) and severity (Oosterhuis score at the maximal severity during the initial two years after the onset of MG). We found significant differences in allele frequencies between MG and the control group, between various MG subgroups and the control group in rs344555 and rs3745568. There were significant differences in genotype frequencies between MG group and the control group, between MG subgroups and the control group under the codominant and additive inheritance models in rs344555 and rs3745568. No association was found between the frequencies of these SNPs and the severity of MG. We also used a comprehensive classification which was close to the clinical scenario to minimize the interaction among clinical features. In rs344555, the T allele frequency in thymoma (-) AChR-Ab (+) subgroup was significantly higher than that in the control group. Our results indicated that rs344555 was associated with the susceptibility of Chinese adult MG patients; rs3745568 was probably associated with the susceptibility of Chinese adult MG patients. No association was found between the frequencies of these SNPs and the severity of MG.


Assuntos
Complemento C3/genética , Predisposição Genética para Doença/genética , Miastenia Gravis/genética , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Grupo com Ancestrais do Continente Asiático/genética , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , Adulto Jovem
8.
BMC Musculoskelet Disord ; 22(1): 83, 2021 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-33451309

RESUMO

BACKGROUND: Previous research and published literature indicate that some patients with spinal diseases who underwent percutaneous transforaminal endoscopic decompression (PTED) still suffer some discomfort in the early recovery stage in the form of pain, stiffness, and swelling. These are usually considered minor residual symptoms or normal postoperative phenomenon (NPF) in the clinic, occur frequently, and are acknowledged by surgeons worldwide. To the best of our knowledge, we report the first case of a patient who had an osteoporotic vertebral fracture (OVF) misdiagnosed as NPF after she underwent PTED as a result of lumbar disc herniation (LDH). CASE PRESENTATION: A 71-year-old female with Parkinson's disease who presented with lower back pain radiating to the legs was diagnosed as LDH in L4-5, after which a PTED of L4-5 was performed, with temporary alleviation of symptoms. However, severe lower back pain recurred. Unfortunately, the recurred pain initially misdiagnosed as NPF, in fact, was finally confirmed to be OVF by CT-scan. OVF in the early stage of post-PTED seldom occurs and is rarely reported in the literature. With a percutaneous vertebroplasty, the pain was significantly relieved, and she resumed walking. After 36-weeks of follow-up, the pain improved satisfactorily. CONCLUSION: Doctors should not immediately diagnose a relapse of back pain following PTED as NPF, and hands-on careful physical and imaging examinations are necessary to manage recurring pain rightly and timely.


Assuntos
Discotomia Percutânea , Fraturas da Coluna Vertebral , Idoso , Descompressão Cirúrgica , Erros de Diagnóstico , Feminino , Humanos , Vértebras Lombares/diagnóstico por imagem , Vértebras Lombares/cirurgia , Medição da Dor , Fraturas da Coluna Vertebral/diagnóstico por imagem , Fraturas da Coluna Vertebral/etiologia , Fraturas da Coluna Vertebral/cirurgia
10.
In Vivo ; 35(1): 249-257, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33402471

RESUMO

BACKGROUND/AIM: Curcumin is a polyphenol that exerts a variety of pharmacological activities and plays an anti-cancer role in many cancer cells. It was recently reported that gasdermin E (GSDME) is involved in the progression of pyroptosis. MATERIALS AND METHODS: HepG2 cells were treated with various concentrations of curcumin and cell viability was examined using MTT assay, apoptosis was analysed using flow cytometry, reactive oxygen species (ROS) levels using dihydroethidium, LDH release using an LDH cytotoxicity assay, and protein expression using western blot. RESULTS: Curcumin increased the expression of the GSDME N-terminus and proteins involved in pyrolysis, promoted HspG2 cell pyrolysis and increased intracellular ROS levels. Moreover, inhibition of the production of intracellular ROS with n-acetylcysteine (NAC) improved the degree of apoptosis and pyrolysis induced by curcumin. CONCLUSION: Curcumin induces HspG2 cell death by increasing apoptosis and pyroptosis, and ROS play a key role in this process. This study improves our understanding of the potential anti-cancer properties of curcumin in liver cancer.


Assuntos
Carcinoma Hepatocelular , Curcumina , Neoplasias Hepáticas , Apoptose , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/genética , Curcumina/farmacologia , Células Hep G2 , Humanos , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/genética , Piroptose , Espécies Reativas de Oxigênio
11.
World J Stem Cells ; 12(11): 1354-1365, 2020 Nov 26.
Artigo em Inglês | MEDLINE | ID: mdl-33312403

RESUMO

BACKGROUND: As the third most abundant element, aluminum is widespread in the environment. Previous studies have shown that aluminum has a neurotoxic effect and its exposure can impair neuronal development and cognitive function. AIM: To study the effects of aluminum on epigenetic modification in neural stem cells and neurons. METHODS: Neural stem cells were isolated from the forebrain of adult mice. Neurons were isolated from the hippocampi tissues of embryonic day 16-18 mice. AlCl3 at 100 and 200 µmol/L was applied to stem cells and neurons. RESULTS: Aluminum altered the differentiation of adult neural stem cells and caused apoptosis of newborn neurons while having no significant effects on the proliferation of neural stem cells. Aluminum application also significantly inhibited the dendritic development of hippocampal neurons. Mechanistically, aluminum exposure significantly affected the levels of DNA 5-hydroxy-methylcytosine, 5-methylcytosine, and N6-methyladenine in stem cells and neurons. CONCLUSION: Our findings indicate that aluminum may regulate neuronal development by modulating DNA modifications.

12.
BMJ Open ; 10(11): e037150, 2020 11 10.
Artigo em Inglês | MEDLINE | ID: mdl-33172940

RESUMO

OBJECTIVES: Geographical disparities have been identified as a specific barrier to cancer screening and a cause of worse outcomes for patients with cancer. In the present study, our aim was to assess the influence of geographical disparities on the survival outcomes of patients with nasopharyngeal carcinoma (NPC) treated with intensity-modulated radiation therapy (IMRT). DESIGN: Cohort study. SETTING: Guangzhou, China. PARTICIPANTS: A total of 1002 adult patients with NPC (724 males and 278 females) who were classified by area of residence (rural or urban) received IMRT from 1 January 2010 to 31 December 2014, at Sun Yat-sen University Cancer Center. Following propensity score matching (PSM), 812 patients remained in the analysis. MAIN OUTCOME MEASURES: We used PSM to reduce the bias of variables associated with treatment effects and outcome prediction. Survival outcomes were estimated using the Kaplan-Meier method and compared by the log-rank test. Multivariate Cox regression was used to identify independent prognostic factors. RESULTS: In the matched cohort, 812 patients remained in the analysis. Kaplan-Meier survival analysis revealed that the rural group was significantly associated with worse overall survival (OS, p<0.001), disease-free survival (DFS, p<0.001), locoregional relapse-free survival (LRRFS, p=0.003) and distant metastasis-free survival (DMFS, p<0.001). Multivariate Cox regression showed worse OS (HR=3.126; 95% CI 1.902 to 5.138; p<0.001), DFS (HR=2.579; 95% CI 1.815 to 3.665; p<0.001), LRRFS (HR=2.742; 95% CI 1.359 to 5.533; p=0.005) and DMFS (HR=2.461; 95% CI 1.574 to 3.850; p<0.001) for patients residing in rural areas. CONCLUSIONS: The survival outcomes of patients with NPC who received the same standardised treatment were significantly better in urban regions than in rural regions. By analysing the geographic disparities in outcomes for NPC, we can guide the formulation of healthcare policies.


Assuntos
Carcinoma , Neoplasias Nasofaríngeas , Radioterapia de Intensidade Modulada , Adulto , Carcinoma/radioterapia , China/epidemiologia , Estudos de Coortes , Feminino , Humanos , Masculino , Carcinoma Nasofaríngeo/radioterapia , Neoplasias Nasofaríngeas/radioterapia , Recidiva Local de Neoplasia , Prognóstico , Estudos Retrospectivos
13.
Int J Syst Evol Microbiol ; 70(11): 5950-5957, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33048042

RESUMO

A taxonomic identification using a polyphasic approach was performed on strain NBS58-1T, which was isolated from the interfacial sediment of Taihu Lake in China. Strain NBS58-1T was Gram-stain-negative, aerobic, non-spore-forming and catalase-positive. Phylogenetic analyses based on 16S rRNA gene and three housekeeping genes (rpoB, gyrB and dnaK) sequences supported the position that strain NBS58-1T should be classified within the genus Rufibacter. The 16S rRNA gene sequence of strain NBS58-1T possessed the highest similarity to Rufibacter sediminis H-1T (96.60 %), followed by Rufibacter glacialis MDT1-10-3T (96.17 %). And the ANI value between strain NBS58-1T and R. glacialis MDT1-10-3T was 79.3 %. The respiratory quinone was menaquinone 7 (MK-7). The major cellular fatty acids comprised iso-C15 : 0 and summed feature 3. Phosphatidylethanolamine, two unidentified phospholipids and four unidentified lipids were the main polar lipids. The genomic DNA G+C content was 51.3 mol%. Based on phenotypic features and phylogenetic position, a novel species with the name Rufibacter hautae sp. nov. is proposed. The type strain is NBS58-1T=(KACC 21309T=MCCC 1K04037T). We also proposed Rufibacter quisquiliarum as a latter heterotypic synonym of Rufibacter ruber.


Assuntos
Bacteroidetes/classificação , Sedimentos Geológicos/microbiologia , Lagos/microbiologia , Filogenia , Técnicas de Tipagem Bacteriana , Bacteroidetes/isolamento & purificação , Composição de Bases , China , DNA Bacteriano/genética , Ácidos Graxos/química , Fosfolipídeos/química , Pigmentação , RNA Ribossômico 16S/genética , Análise de Sequência de DNA , Vitamina K 2/análogos & derivados , Vitamina K 2/química
16.
ACS Omega ; 5(27): 16584-16594, 2020 Jul 14.
Artigo em Inglês | MEDLINE | ID: mdl-32685824

RESUMO

We report on single-crystal growths of the SrTb2O4 compound by a super-necking technique with a laser-floating-zone furnace and study the stoichiometry, growth mode, and structural and magnetic properties by scanning electronic microscopy, neutron Laue, X-ray powder diffraction, and the physical property measurement system. We optimized the growth parameters, mainly the growth speed, atmosphere, and the addition of a Tb4O7 raw material. Neutron Laue diffraction displays the characteristic feature of a single crystal. Our study reveals an atomic ratio of Sr:Tb = 0.97(2):2.00(1) and a possible layer by layer crystal growth mode. Our X-ray powder diffraction study determines the crystal structure, lattice constants, and atomic positions. The paramagnetic (PM) Curie-Weiss (CW) temperature θCW = 5.00(4) K, and the effective PM moment M mea eff = 10.97(1) µB per Tb3+ ion. The data of magnetization versus temperature can be divided into three regimes, showing a coexistence of antiferromagnetic and ferromagnetic interactions. This probably leads to the magnetic frustration in the SrTb2O4 compound. The magnetization at 2 K and 14 T originates from both the Tb1 and Tb2 sites and is strongly frustrated with an expected saturation field at ∼41.5 T, displaying an intricate phase diagram with three ranges.

17.
Medicine (Baltimore) ; 99(21): e20117, 2020 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-32481279

RESUMO

INTRODUCTION: Central airway stenosis is a life-threating requiring immediate medical intervention. There are several options for treating central airway stenosis, including rigid bronchoscopy, bronchoscopic high-power laser therapy, high-frequency electric needle knife, and balloon-expanding stents. However, interventional techniques may be unavailable in an emergent situation or at smaller local hospitals. In this case report, we publicly demonstrate for the first time that a tracheal intubation catheter may be applied as a temporary alternative to interventional bronchoscopic treatment. PATIENT CONCERNS: A 72-year old male patient was admitted with a 1-year history of intermittent dyspnea, which was exacerbated for one day. One day prior to admission to our hospital, the patient presented with cyanosis due to an exacerbation of dyspnea.A tracheotomy was performed and the patient had been carrying a tracheotomy cannula for 6 months. DIAGNOSIS: The ventilator alarm indicated high airway resistance and the nurses were unable to insert the suction pipes into the airway. Immediate fiberoptic bronchoscopy showed diffuse edema and stenosis of the inferior tracheal airways. INTERVENTIONS: Tracheal intubation was used to temporarily replace the tracheotomy cannula, which successfully expanded the narrowed airways. OUTCOMES: The blood oxygen saturation returned to normal, and dyspnea was quickly relieved. CONCLUSION: In emergent situations, tracheal intubation catheters may be used in patients with post-tracheotomy central airway stenosis, not only for surviving the most dangerous phase but for also prolonging the survival time for further treatments.


Assuntos
Obstrução das Vias Respiratórias/terapia , Intubação Intratraqueal/métodos , Estenose Traqueal/terapia , Traqueotomia/efeitos adversos , Idoso , Humanos , Masculino
18.
Oncogene ; 39(30): 5307-5322, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32555330

RESUMO

Nasopharyngeal carcinoma (NPC) is a unique head and neck cancer with highly aggressive and metastatic potential in which distant metastasis is the main reason for treatment failure. Till present, the underlying molecular mechanisms of NPC metastasis remains poorly understood. Here, we identified S100 calcium-binding protein A14 (S100A14) as a functional regulator suppressing NPC metastasis by inhibiting the NF-kB signaling pathway and reversing the epithelial-mesenchymal transition (EMT). S100A14 was found to be downregulated in highly metastatic NPC cells and tissues. Immunohistochemical staining of 202 NPC samples revealed that lower S100A14 expression was significantly correlated with shorter patient overall survival (OS) and distant metastasis-free survival (DMFS). S100A14 was also found as an independent prognostic factor for favorable survival. Gain- and loss-of-function studies confirmed that S100A14 suppressed the in vitro and in vivo motility of NPC cells. Mechanistically, S100A14 promoted the ubiquitin-proteasome-mediated degradation of interleukin-1 receptor-associated kinase 1 (IRAK1) to suppress NPC cellular migration. Moreover, S100A14 and IRAK1 established a feedback loop that could be disrupted by the IRAK1 inhibitor T2457. Overall, our findings showed that the S100A14-IRAK1 feedback loop could be a promising therapeutic target for NPC metastasis.


Assuntos
Proteínas de Ligação ao Cálcio/genética , Quinases Associadas a Receptores de Interleucina-1/genética , Neoplasias Pulmonares/genética , NF-kappa B/genética , Carcinoma Nasofaríngeo/genética , Neoplasias Nasofaríngeas/genética , Animais , Proteínas de Ligação ao Cálcio/metabolismo , Linhagem Celular Tumoral , Movimento Celular/genética , Transição Epitelial-Mesenquimal/genética , Retroalimentação Fisiológica , Regulação Neoplásica da Expressão Gênica , Xenoenxertos , Humanos , Quinases Associadas a Receptores de Interleucina-1/metabolismo , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/secundário , Camundongos Nus , NF-kappa B/metabolismo , Carcinoma Nasofaríngeo/metabolismo , Carcinoma Nasofaríngeo/patologia , Neoplasias Nasofaríngeas/metabolismo , Neoplasias Nasofaríngeas/patologia , Complexo de Endopeptidases do Proteassoma/metabolismo , Interferência de RNA , Transdução de Sinais/genética , Análise de Sobrevida
19.
Biochem Biophys Res Commun ; 527(3): 770-777, 2020 06 30.
Artigo em Inglês | MEDLINE | ID: mdl-32446561

RESUMO

Nasopharyngeal carcinoma (NPC) is relatively sensitive to ionizing radiation, and radiotherapy is the main treatment modality for non-metastatic NPC. Radiation therapy generates overproduction of reactive oxygen species (ROS), which can cause DNA damage and induce apoptosis in tumors, thereby killing the malignant cells. Although dietary antioxidant supplementation reduces oxidative stress and promotes tumor progression, the effects of antioxidants on the NPC cells upon radiation have not been reported. In the present study, we showed that antioxidants (ß-Carotene, NAC, GSH) played an anti-apoptotic role in response to radiation via decreasing ROS production and inhibiting MAPK pathway in NPC cells. Based on that, we conclude that the use of supplemental antioxidants during radiotherapy should be avoided because of the possibility of tumor protection and reduced treatment efficacy.


Assuntos
Antioxidantes/farmacologia , Apoptose/efeitos dos fármacos , Apoptose/efeitos da radiação , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Carcinoma Nasofaríngeo/radioterapia , Neoplasias Nasofaríngeas/radioterapia , Linhagem Celular Tumoral , Humanos , Carcinoma Nasofaríngeo/tratamento farmacológico , Carcinoma Nasofaríngeo/metabolismo , Neoplasias Nasofaríngeas/tratamento farmacológico , Neoplasias Nasofaríngeas/metabolismo , Espécies Reativas de Oxigênio/metabolismo
20.
J Control Release ; 322: 274-285, 2020 06 10.
Artigo em Inglês | MEDLINE | ID: mdl-32234511

RESUMO

Nanocrystals have exhibited great advantage for enhancing the dissolution rate of water insoluble drugs due to the reduced size to nanoscale. However, current pharmaceutical approaches for nanocrystals formulation development highly depend on the expert experience and trial-and-error attempts which remain time and resource consuming. In this research, we utilized machine learning techniques to predict the particle size and polydispersity index (PDI) of nanocrystals. Firstly, 910 nanocrystal size data and 341 PDI data by three preparation methods (ball wet milling (BWM) method, high-pressure homogenization (HPH) method and antisolvent precipitation (ASP) method) were collected for the construction of the prediction models. The results demonstrated that light gradient boosting machine (LightGBM) exhibited well performance for the nanocrystals size and PDI prediction with BWM and HPH methods, but relatively poor predictions for ASP method. The possible reasons for the poor prediction refer to low quality of data because of the poor reproducibility and instability of nanocrystals by ASP method, which also confirm that current commercialized products were mainly manufactured by BWM and HPH approaches. Notably, the contribution of the influence factors was ranked by the LightGBM, which demonstrated that milling time, cycle index and concentration of stabilizer are crucial factors for nanocrystals prepared by BWM, HPH and ASP, respectively. Furthermore, the model generalizations and prediction accuracies of LightGBM were confirmed experimentally by the newly prepared nanocrystals. In conclusion, the machine learning techniques can be successfully utilized for the predictions of nanocrystals prepared by BWM and HPH methods. Our research also reveals a new way for nanotechnology manufacture.


Assuntos
Nanopartículas , Preparações Farmacêuticas , Composição de Medicamentos , Aprendizado de Máquina , Tamanho da Partícula , Reprodutibilidade dos Testes , Solubilidade
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