RESUMO
Spermiogenesis is considered to be crucial for the production of haploid spermatozoa with normal morphology, structure and function, but the mechanisms underlying this process remain largely unclear. Here, we demonstrate that SPEM family member 2 (Spem2), as a novel testis-enriched gene, is essential for spermiogenesis and male fertility. Spem2 is predominantly expressed in the haploid male germ cells and is highly conserved across mammals. Mice deficient for Spem2 develop male infertility associated with spermiogenesis impairment. Specifically, the insufficient sperm individualization, failure of excess cytoplasm shedding, and defects in acrosome formation are evident in Spem2-null sperm. Sperm counts and motility are also significantly reduced compared to controls. In vivo fertilization assays have shown that Spem2-null sperm are unable to fertilize oocytes, possibly due to their impaired ability to migrate from the uterus into the oviduct. However, the infertility of Spem2-/- males cannot be rescued by in vitro fertilization, suggesting that defective sperm-egg interaction may also be a contributing factor. Furthermore, SPEM2 is detected to interact with ZPBP, PRSS21, PRSS54, PRSS55, ADAM2 and ADAM3 and is also required for their processing and maturation in epididymal sperm. Our findings establish SPEM2 as an essential regulator of spermiogenesis and fertilization in mice, possibly in mammals including humans. Understanding the molecular role of SPEM2 could provide new insights into future therapeutic treatment of human male infertility and development of non-hormonal male contraceptives.
Assuntos
Infertilidade Masculina , Espermatogênese , Testículo , Animais , Masculino , Camundongos , Fertilinas , Infertilidade Masculina/genética , Mamíferos , Sêmen , Interações Espermatozoide-Óvulo , Espermatogênese/genética , Testículo/metabolismoRESUMO
Signaling via the T cell antigen receptor (TCR) during the CD4(+)CD8(+) double-positive developmental stage determines thymocyte selection and lineage commitment. Here we describe a previously uncharacterized T cell-expressed protein, Tespa1, with critical functions during the positive selection of thymocytes. Tespa1(-/-) mice had fewer mature thymic CD4(+) and CD8(+) T cells, which reflected impaired thymocyte development. Tespa1 associated with the TCR signaling components PLC-γ1 and Grb2, and Tespa1 deficiency resulted in attenuated TCR signaling, as reflected by defective activation of the Erk-AP-1 and Ca(2+)-NFAT pathways. Our findings demonstrate that Tespa1 is a component of the TCR signalosome and is essential for T cell selection and maturation through the regulation of TCR signaling during T cell development.
Assuntos
Receptores de Antígenos de Linfócitos T/imunologia , Linfócitos T/imunologia , Timo/imunologia , Proteínas Adaptadoras de Transdução de Sinal/imunologia , Sequência de Aminoácidos , Animais , Sequência de Bases , Diferenciação Celular/imunologia , Clonagem Molecular , Proteína Adaptadora GRB2/imunologia , Ativação Linfocitária , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Camundongos Transgênicos , Dados de Sequência Molecular , Fosfolipase C gama/imunologia , RNA Mensageiro/química , RNA Mensageiro/genética , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Alinhamento de Sequência , Transdução de Sinais/imunologia , Timo/citologiaRESUMO
BACKGROUND: Syntaxin6 (STX6) is a SNARE (Soluble N-ethylmaleimide-sensitive factor attachment protein receptors) protein complex located in the trans-Golgi network and endosomes, which is closely associated with a variety of intracellular membrane transport events. STX6 has been shown to be overexpressed in a variety of human malignant tumors such as esophageal, colorectal, and renal cell carcinomas, and participates in tumorigenesis and development. METHODS: Based on clinical public database and clinical liver samples analysis, the expression of STX6 in hepatocellular carcinoma (HCC) tissues was investigated. The effects of STX6 on proliferation, migration and invasion of HCC cell in vitro and in vivo were evaluated through gain- and loss-of-function studies. We further performed RNA-seq analysis and protein interactome analysis, to further decifer the detailed mechanisms of STX6 in the regulation of the JAK-STAT pathway in HCC. RESULTS: STX6 expression was upregulated in HCC tissues and its expression was highly correlated with the high histological grade of the tumor. STX6 promoted HCC cell proliferation, migration and invasion both in vitro and in vivo. Mechanistically, STX6 mediated tumor progression depending on promoting the activation of JAK-STAT signaling pathway. Receptor for activated protein kinase C (RACK1) as an essential adaptor protein mediating STX6 regulation of JAK-STAT pathway. Specifically, STX6 interacted with RACK1 and then recruited signal transducer and activator of transcription 3 (STAT3) to form a protein-binding complex and activates STAT3 transcriptional activity. CONCLUSIONS: This study provided a novel concept that STX6 exerted oncogenic effects by activating the STAT3 signaling pathway, and STX6 might be a promising therapeutic target for HCC.
RESUMO
INTRODUCTION: This study aimed to use 3-dimensional data to investigate the factors affecting local alveolar bone thickness in unilateral maxillary canine-lateral incisor transposition. METHODS: Pretreatment cone-beam computed tomography data of 34 patients with unilateral maxillary canine-lateral transposition were imported into Dolphin Imaging software (version 11.8; Dolphin Imaging and Management Solutions, Chatsworth, Calif) for 3-dimensional reconstruction. The age, gender, and type of transposition at the beginning of treatment were recorded. The thickness and height of the transposed canine, the labiopalatal and distomedial distance from the transposed canine to the apex of the lateral incisor, the inclination of the transposed lateral incisor, the apical height of the lateral incisor, and the alveolar bone thickness in the apical plane were measured. Multiple linear regression analyses were applied to investigate the factors affecting alveolar bone thickness in the apical plane of the transposed lateral incisor. Two sample t test were applied to assess the difference of alveolar bone thickness in patients of different ages. RESULTS: The 10 boys and 24 girls had a mean age of 12.26 ± 2.34 years. In all 34 participants, the apical alveolar bone thickness of transposed lateral incisors was significantly higher than that of the unaffected side (P <0.05). Based on multiple regression analyses, factors associated with a wider alveolar bone thickness were as follows: age (ß = -0.237; P = 0.008), the labiopalatal distance from the transposed canine to the apex of the lateral incisor (ß = 0.675; P <0.001), and the inclination of the transposed lateral incisor (ß = 0.048; P = 0.032). Patients aged <11 years had significantly thicker alveolar bone than that of patients aged >11 years (P <0.05). CONCLUSIONS: Patients with younger age, greater lateral incisor inclination, and greater labiopalatal distance between canine and lateral incisor had more alveolar bone thickness. Early treatment permits tooth movement within the thicker alveolar bone.
Assuntos
Processo Alveolar , Tomografia Computadorizada de Feixe Cônico , Dente Canino , Incisivo , Maxila , Humanos , Masculino , Feminino , Incisivo/diagnóstico por imagem , Dente Canino/diagnóstico por imagem , Tomografia Computadorizada de Feixe Cônico/métodos , Adolescente , Criança , Maxila/diagnóstico por imagem , Processo Alveolar/diagnóstico por imagem , Processo Alveolar/patologia , Imageamento Tridimensional/métodos , Técnicas de Movimentação Dentária/métodos , Erupção Ectópica de Dente/diagnóstico por imagemRESUMO
Cinnamomi ramulus (CR) and Cinnamomi cortex (CC), both sourced from Cinnamomum cassia Presl, are commonly used Chinese medicines in the Chinese Pharmacopeia. However, while CR functions to dissipate cold and to resolve external problems of the body, CC functions to warm the internal organs. To clarify the material basis of these different functions and clinical effects, a simple and reliable UPLC-Orbitrap-Exploris-120-MS/MS method combined with multivariate statistical analyses was established in this study with the aim of exploring the difference in chemical compositions of aqueous extracts of CR and CC. As the results indicated, a total of 58 compounds was identified, including nine flavonoids, 23 phenylpropanoids and phenolic acids, two coumarins, four lignans, four terpenoids, 11 organic acids and five other components. Of these compounds, 26 significant differential compounds were identified statistically including six unique components in CR and four unique components in CC. Additionally, a robust HPLC method combined with hierarchical clustering analysis (HCA) was developed to simultaneously determine the concentrations and differentiating capacities of five major active ingredients in CR and CC: coumarin, cinnamyl alcohol, cinnamic acid, 2-methoxycinnamic acid and cinnamaldehyde. The HCA results showed that these five components could be used as markers for successfully distinguishing CR and CC. Finally, molecular docking analyses were conducted to obtain the affinities between each of the abovementioned 26 differential components, focusing on targets involved in diabetes peripheral neuropathy (DPN). The results indicated that the special and high-concentration components in CR showed high docking scores of affinities with targets such as HbA1c and proteins in the AMPK-PGC1-SIRT3 signaling pathway, suggesting that CR has greater potential than CC for treating DPN.
Assuntos
Medicamentos de Ervas Chinesas , Espectrometria de Massas em Tandem , Simulação de Acoplamento Molecular , Medicamentos de Ervas Chinesas/química , Cinnamomum zeylanicumRESUMO
INTRODUCTION: This study aimed to investigate the height and thickness of alveolar bone by cone-beam computed tomography imaging after orthodontic treatment in the unilateral maxillary anterior region and speculate on reasons for the difference in alveolar bone morphology. METHODS: This study selected 11 patients (3 males and 8 females; mean age, 9.42 ± 1.45 years). Cone-beam computed tomography was performed for these 11 patients before and after treatment using Dolphin Imaging software (Dolphin Imaging and Management Solutions, Chatsworth, Calif). Labial and palatal alveolar bone thickness (BT) at root apices and different levels along the roots and loss of alveolar bone height was measured for each impacted tooth and its contralateral homonymous tooth. RESULTS: After orthodontic therapy, all 3 impacted anterior teeth had different degrees of loss of labial alveolar bone height compared with the normal side (central incisor: -1.5 mm, P <0.005; lateral incisor: -1.06 mm, P <0.01; canine: -0.59 mm, P < 0.01). The lateral incisors also showed palatal alveolar bone height loss compared with the unaffected side (-0.8 mm, P <0.005). Alveolar BT at root apices of impacted canines was 1.14 mm thicker than the normal side (P <0.005). Central and lateral incisors were similar to the normal side. The thickness of the alveolar bone at 8, 10, and 12 mm of the impacted canine position was still larger than that on the healthy side, whereas the difference in average thickness between the healthy and affected side had been significantly reduced compared with pretreatment measurements. CONCLUSIONS: There is satisfactory retention of alveolar bone height in canines after orthodontic treatment; however, alveolar bone loss is slightly worse at central and lateral incisors. Retention of alveolar BT was normal for impacted anterior teeth, whereas excess apical alveolar BT at the canines, although still present, was substantially less significant than had been observed before treatment.
Assuntos
Perda do Osso Alveolar , Dente Impactado , Masculino , Feminino , Humanos , Criança , Dente Impactado/diagnóstico por imagem , Dente Impactado/terapia , Raiz Dentária , Maxila/diagnóstico por imagem , Perda do Osso Alveolar/diagnóstico por imagem , Perda do Osso Alveolar/etiologia , Palato , Tomografia Computadorizada de Feixe Cônico/métodosRESUMO
Six compounds were isolated from aqueous extract of wine-processed Corni Fructus through silica gel, ODS column chromatography, Sephadex LH-20 gel column chromatography, reverse phase preparative HPLC and other chromatographic separation technologies. Their structures were identified with multiple spectroscopical methods including HR-ESI-MS, UV, IR, NMR and ECD and so on. Their structures were established as pinoresinoside B(1), cornusgallicacid A(2),(+)-isolariciresinol-9'-O-ß-glucopyranoside(3),(-)-isolariciresinol 3α-O-ß-D-glucopyranoside(4),(7R,8S)-dihydrodehydrodiconiferyl alcohol 9-O-ß-D-glucopyranoside(5), and(-)-seco isolariciresinol-9'-O-ß-D-glucopyranoside(6). Among them, compounds 1 and 2 were two new compounds. The biological activity evaluation results showed that compounds 2 and 6 had strong DPPH free radical scavenging ability, with EC_(50) values of(4.18±1.96) and(21.45±1.19) µmol·L~(-1), respectively. Compounds 1 and 2 had protective effects on H_2O_2-induced oxidative damage in NRK-52E cells in a dose-dependent manner, and the cell survival rate of compound 2 at 100 µmol·L~(-1) was 96.09%±1.77%.
Assuntos
Cornus , Vinho , Naftóis , LigninaRESUMO
Sarglaromatics A-E (1-5, respectively), five unprecedented naphthalene-like architecture-fused norlindenane sesquiterpene dimers, were discovered from the roots of Sarcandra glabra. The unique naphthalene core skeleton was obtained from classical lindenane [4 + 2] dimers via a free-radical-mediated C11-C11' bond formation reaction and 12'-decarboxylation. The highly fused octonary ring skeleton was elucidated by HRMS, NMR, ECD, quantum chemical calculations, and biogenetic inspiration. Compounds 1 and 2 showed significant anti-nonalcoholic steatohepatitis (NASH) activity by inhibiting lipid deposition in L02 cells.
Assuntos
Sesquiterpenos , Naftalenos , Raízes de Plantas/química , Polímeros , Sesquiterpenos/químicaRESUMO
Nine new cadinane-type sesquiterpenoids (1-9) and three new eucalyptane -type sesquiterpenes (10-12) were isolated from the ethyl acetate extract of Burdock leaves, which were commonly used for preventing or treating atherosclerosis in China. Their structures were confirmed by extensive spectroscopic analysis, single-crystal X-ray diffraction analysis and ECD calculations. Compound 1 possessed the rare large conjugated skeleton. All the isolates were evaluated for anti-inflammatory and cholesterol-lowering activities by the LPS- and oxidized-low-density-lipoprotein-stimulated RAW 264.7 cells, respectively. As the results, all isolates could decrease the productions of NO, and down-regulate the accumulation of cholesterol. Among them, 4 showed the most potent cholesterol-lowering effect. For the high content of 4 in the herb, mechanistic study of 4 was performed and the results showed that 4 markedly reduced the release of pro-inflammatory mediators which was probably associated with inhibition of the PI3K/Akt and 5-LOX signaling pathways. The findings of this study demonstrated the anti-inflammatory/cholesterol-lowering effects of the new sesquiterpenes from burdock leaves, which provides chemical basis and scientific evidence for the herb used as anti-atherosclerosis agents for the further study. The sesquiterpene lactones of burdock leaves are expected to become new small molecule inhibitors for the treatment of AS.
Assuntos
Arctium , Sesquiterpenos , Anti-Inflamatórios/química , Colesterol , Estrutura Molecular , Fosfatidilinositol 3-Quinases , Sesquiterpenos/químicaRESUMO
The main causes of damage to industrial machinery are aging, corrosion, and the wear of parts, which affect the accuracy of machinery and product precision. Identifying problems early and predicting the life cycle of a machine for early maintenance can avoid costly plant failures. Compared with other sensing and monitoring instruments, sound sensors are inexpensive, portable, and have less computational data. This paper proposed a machine tool life cycle model with noise reduction. The life cycle model uses Mel-Frequency Cepstral Coefficients (MFCC) to extract audio features. A Deep Neural Network (DNN) is used to understand the relationship between audio features and life cycle, and then determine the audio signal corresponding to the aging degree. The noise reduction model simulates the actual environment by adding noise and extracts features by Power Normalized Cepstral Coefficients (PNCC), and designs Mask as the DNN's learning target to eliminate the effect of noise. The effect of the denoising model is improved by 6.8% under Short-Time Objective Intelligibility (STOI). There is a 3.9% improvement under Perceptual Evaluation of Speech Quality (PESQ). The life cycle model accuracy before denoising is 76%. After adding the noise reduction system, the accuracy of the life cycle model is increased to 80%.
Assuntos
Redes Neurais de Computação , Ruído , Fala , AprendizagemRESUMO
INTRODUCTION: This study investigated the position and morphologic characteristics of multiple impacted anterior teeth in the unilateral maxillary area. METHODS: Cone-beam computed tomography images of 21 patients (11 males and 10 females; median age 9.42 years [9.08-11.29]) with multiple teeth impacted were collected and imported into Dolphin Imaging software (Dolphin Imaging and Management Solutions, Chatsworth, Calif). The vertical height, crown orientation, twist direction, and root curvature of each impacted tooth were described. The crown length, root length, and root canal width of impacted and homonym teeth were measured. RESULTS: The positions of the impacted lateral incisors are lower than that of the other 2 anterior teeth. Most crowns of impacted central incisors are positioned distally, labial surfaces in mesial torsion, with most roots, bent toward the distal and labial. Crowns of impacted lateral incisors are positioned mesiolabially, with labial surfaces mostly in distal torsion, and most roots bent toward the mesial and labial. Crowns of impacted canines are mostly positioned mesiolabially, with labial surfaces in mesial torsion. The crowns and roots of the impacted central and lateral incisors were shorter than those of the homonym (P <0.05); however, the difference in crown length is clinically negligible, and there was no difference in root canal widths. There was no difference in the comparison of parameters for the canine group. CONCLUSIONS: There are certain rules in the vertical height, crown orientation, twist direction, and root curvature of multiple impacted anterior teeth in the unilateral maxillary area. Root development of impacted central and lateral incisors was restricted.
Assuntos
Dente Impactado , Masculino , Feminino , Humanos , Dente Impactado/diagnóstico por imagem , Estudos Retrospectivos , Raiz Dentária/diagnóstico por imagem , Maxila/diagnóstico por imagem , Tomografia Computadorizada de Feixe Cônico/métodos , Dente Canino/diagnóstico por imagemRESUMO
INTRODUCTION: This study aimed to use 3-dimensional data to analyze the relationship between local alveolar bone housing and canine size in maxillary canine-lateral incisor transposition. METHODS: Cone-beam computed tomography study data from 31 patients with maxillary canine-lateral incisor transposition were imported into Dolphin Imaging software (version 11.8; Dolphin Imaging and Management Solutions, Chatsworth, Calif) for measurement. The buccal and palatal alveolar thickness of lateral incisor roots at different heights, the maximal thickness of displaced canine, and canine height were measured. Alveolar height-thickness variation curves at the lateral incisor region and maximal thickness of displaced canine were plotted to calculate the appropriate theoretical minimum alveolar heights of total alveolar housing, buccal alveolar housing after concentrating the bone buccally (TMAH-B1), and original buccal alveolar housing (TMAH-B2) required for correcting the transposition of 2 teeth. RESULTS: Canines could only be moved distally above lateral incisors in 5 patients. The mean value of theoretical minimum alveolar heights of total alveolar housing was 14.57 ± 1.75 mm. It was possible to reposition canines distally by concentrating the alveolar bone buccally in the remaining 26 patients. The mean value of TMAH-B1 was 10.86 ± 3.70 mm. Canines could be repositioned distally directly over the buccal aspect of the lateral incisor in 17 patients. The mean value of TMAH-B2 was 9.30 ± 2.35 mm. Canine height was greater than TMAH-B1 in 18 patients; however, only 10 patients were greater than TMAH-B2. CONCLUSIONS: Correction of transposition was difficult in some patients because of the lack of alveolar bone housing. Repositioning was possible when the height of the canine was higher than a certain height. An accurate assessment of the relationship between alveolar housing and tooth size is recommended.
Assuntos
Dente Canino , Incisivo , Tomografia Computadorizada de Feixe Cônico/métodos , Dente Canino/diagnóstico por imagem , Habitação , Incisivo/diagnóstico por imagem , Maxila/diagnóstico por imagem , Estudos RetrospectivosRESUMO
INTRODUCTION: The purpose of this trial was to use 3-dimensional data to analyze the differences of root morphology and root length between 3 different types of impacted maxillary central incisors. METHODS: Cone-beam computed tomography images of 126 patients with impacted maxillary central incisors were included in this retrospective study. On the basis of the angle of the impacted incisor to the palatal plane, we categorized the tooth as labial inversely impacted, labially positioned, or palatal impacted incisor. In each category, the early and late dental age groups were classified according to the method of Nolla. The total root length of both impacted and homonym teeth, length of the nondilacerated part of the root, length of the dilacerated part of the root, the angle between the crown and root, and root direction, were measured in the sagittal-view sections using Dolphin Imaging software (version 11.9; Dolphin Imaging and Management Solutions, Chatsworth, Calif). RESULTS: Compared with the early dental age groups, the length of the dilacerated portion of the root and rate of dilaceration for inverse labial and labially positioned impactions increases, and crown-root angle decreases (P <0.05). The dilacerated part of the root bent labially, and the root morphology shows an obvious L-shaped curve. The length of the nondilacerated part of the root for palatal impactions is greater(P <0.05). The dilacerated part of the root bends palatally, and the root morphology shows a continuous C-shaped curve. CONCLUSIONS: Obstruction from the alveolar bone will cause different root morphology. Root morphology of labial impactions shows an obvious L-shaped curve; palatal impactions show a continuous C-shaped curve.
Assuntos
Incisivo , Dente Impactado , Tomografia Computadorizada de Feixe Cônico/métodos , Humanos , Incisivo/diagnóstico por imagem , Maxila/diagnóstico por imagem , Estudos Retrospectivos , Dente Impactado/diagnóstico por imagemRESUMO
A new iridoid glycoside, cornushmf A(1) and nine known iridoids(2-10) were isolated from the water extract of the wine-processed Corni Fructus by various column chromatographies. Their chemical structures were identified by comprehensive spectroscopic methods as 7ß-O-(2â³-formylfuran-5â³-methylene)-morroniside(1), 7-dehydrologanin(2), sweroside(3), 7ß-O-methylmorroniside(4), 7α-O-methylmorroniside(5), 7ß-O-ethylmorroniside(6), 7α-O-ethylmorroniside(7), cornuside(8), sarracenin(9), and loganin(10).
Assuntos
Cornus , Medicamentos de Ervas Chinesas , Vinho , Cornus/química , Medicamentos de Ervas Chinesas/química , IridoidesRESUMO
Four new gallate derivatives-ornusgallate A, ent-cornusgallate A, cornusgallate B and C (1a, 1b, 2, 3)-were isolated from the wine-processed fruit of Cornus officinalis. Among them, 1a and 1b are new natural compounds with novel skeletons. Their chemical structures were elucidated by comprehensive spectroscopy methods including NMR, IR, HRESIMS, UV, ECD spectra and single-crystal X-ray diffraction analysis. The in vitro anti-inflammatory activities of all compounds were assayed in RAW 264.7 cells by assessing LPS-induced NO production. As the result, all compounds exhibited anti-inflammatory activities at attested concentrations. Among the tested compounds, compound 2 exhibited the strongest anti- inflammatory activity.
Assuntos
Anti-Inflamatórios , Cornus/química , Frutas/química , Ácido Gálico , Animais , Anti-Inflamatórios/química , Anti-Inflamatórios/isolamento & purificação , Anti-Inflamatórios/farmacologia , Ácido Gálico/análogos & derivados , Ácido Gálico/química , Ácido Gálico/isolamento & purificação , Ácido Gálico/farmacologia , Lipopolissacarídeos/toxicidade , Camundongos , Óxido Nítrico/metabolismo , Células RAW 264.7RESUMO
In view of the current inadequate standards for Gleditsiae Spina in the Chinese Pharmacopoeia, this study put forward some new items of the quality standards of Gleditsiae Spina. Thin-layer chromatography(TLC) was performed for identification with the reference substance of taxifolin and the reference material of Gleditsiae Spina as the control. According to the general principles of the Chinese Pharmacopoeia(2020 edition, Vol. 4), the moisture, total ash content, and alcohol-soluble extract of medicinal materials and decoction pieces of Gleditsiae Spina were determined. The content determination method for medicinal materials and decoction pieces of Gleditsiae Spina was established using high-performance liquid chromatography(HPLC), with taxifolin as the quality control index. Based on the determination results of 30 batches of samples of Gleditsiae Spina from different habitats, the draft quality standards of Gleditsiae Spina were developed, which provided suggestions for the revision of the quality standards of Gleditsiae Spina in the Chinese Pharmacopoeia.
Assuntos
Medicamentos de Ervas Chinesas , Cromatografia Líquida de Alta Pressão , Controle de Qualidade , Padrões de ReferênciaRESUMO
BACKGROUND: Long non-coding RNAs (lncRNAs) have been reported to be prognostic biomarkers in many types of cancer. We aimed to identify a lncRNA signature that can predict the prognosis in patients with esophageal squamous cell carcinoma (ESCC). METHODS: Using a custom microarray, we retrospectively analyzed lncRNA expression profiles in 141 samples of ESCC and 81 paired non-cancer specimens from Sun Yat-Sen University Cancer Center (Guangzhou, China), which were used as a training cohort to identify a signature associated with clinical outcomes. Then we conducted quantitative RT-PCR in another 103 samples of ESCC from the same cancer center as an independent cohort to verify the signature. RESULTS: Microarray analysis showed that there were 338 lncRNAs significantly differentially expressed between ESCC and non-cancer esophagus tissues in the training cohort. From these differentially expressed lncRNAs, we found 16 lncRNAs associated with overall survival (OS) of ESCC patients using Cox regression analysis. Then a 7-lncRNA signature for predicting survival was identified from the 16 lncRNAs, which classified ESCC patients into high-risk and low-risk groups. Patients with high-risk have shorter OS (HR: 3.555, 95% CI 2.195-5.757, p < 0.001) and disease-free survival (DFS) (HR: 2.537, 95% CI 1.646-3.909, p < 0.001) when compared with patients with low-risk in the training cohort. In the independent cohort, the 7 lncRNAs were detected by qRT-PCR and used to compute risk score for the patients. The result indicates that patients with high risk also have significantly worse OS (HR = 2.662, 95% CI 1.588-4.464, p < 0.001) and DFS (HR 2.389, 95% CI 1.447-3.946, p < 0.001). The univariate and multivariate Cox regression analyses indicate that the signature is an independent factor for predicting survival of patients with ESCC. Combination of the signature and TNM staging was more powerful in predicting OS than TNM staging alone in both the training (AUC: 0.772 vs 0.681, p = 0.002) and independent cohorts (AUC: 0.772 vs 0.660, p = 0.003). CONCLUSIONS: The 7-lncRNA signature is a potential prognostic biomarker in patients with ESCC and may help in treatment decision when combined with the TNM staging system.
Assuntos
Neoplasias Esofágicas , Carcinoma de Células Escamosas do Esôfago , Neoplasias de Cabeça e Pescoço , RNA Longo não Codificante , Biomarcadores Tumorais/genética , China , Neoplasias Esofágicas/genética , Carcinoma de Células Escamosas do Esôfago/genética , Perfilação da Expressão Gênica , Humanos , Prognóstico , RNA Longo não Codificante/genética , Estudos RetrospectivosRESUMO
OBJECTIVES: Postoperative recurrences, especially anastomotic recurrence and regional lymph node recurrence were common in patients even with curative esophageal cancer surgery. Endobronchial ultrasound-guided transbronchial needle aspiration is an alternative to mediastinoscopy in patients with lung cancer and mediastinal lymphadenopathy. The aim of our study is to evaluate the utility of endobronchial ultrasound-guided transbronchial needle aspiration in postoperative patients suffered from esophageal malignancy. METHODS: All endobronchial ultrasound-guided transbronchial needle aspiration cases performed between August 2015 and December 2018 in our center were all retrospective reviewed. The patients with enlarged mediastinal lymph node and/or unknown intrathoracic mass after esophageal cancer surgery were enrolled. Final diagnoses were determined by the result of endobronchial ultrasound-guided transbronchial needle aspiration, second surgery and/or clinical follow-up for at least 6 months. RESULTS: Overall 29 patients were included in the analysis with 30 lesions sampled. No endobronchial ultrasound-guided transbronchial needle aspiration related complications were observed. In total, 22 of these (73.3%) had a diagnosis of tumor recurrence, whereas eight (26.7%) had a different diagnosis: two (6.7%) had a second primary malignancy and three (10.0%) had non-neoplastic diagnosis. Cases were false-negative in 3 (10.0%) out of 30 lesions. The overall sensitivity, negative predicted value and diagnostic accuracy were 88.9, 50.0 and 90.0%, respectively. CONCLUSIONS: Given its safety, low invasiveness, high sensitivity and diagnostic accuracy, endobronchial ultrasound-guided transbronchial needle aspiration could be considered for mediastinal lymphadenopathy and intrathoracic masses of unknown origin in patients after radical esophageal cancer resection, and its strategic role in the management of these patients was confirmed.
Assuntos
Aspiração por Agulha Fina Guiada por Ultrassom Endoscópico , Neoplasias Esofágicas/diagnóstico , Neoplasias Esofágicas/cirurgia , Esôfago/patologia , Esôfago/cirurgia , Recidiva Local de Neoplasia/patologia , Idoso , Neoplasias Esofágicas/diagnóstico por imagem , Neoplasias Esofágicas/patologia , Esôfago/diagnóstico por imagem , Feminino , Humanos , Neoplasias Pulmonares/patologia , Linfonodos/patologia , Masculino , Mediastinoscopia , Pessoa de Meia-Idade , Estudos Retrospectivos , UltrassonografiaRESUMO
INTRODUCTION: To determine the value of whole-tumor histogram analysis of apparent diffusion coefficient (ADC) maps in differentiating nasopharyngeal carcinoma (NPC) from lymphoma (NPL) at the primary site METHOD AND MATERIALS: One hundred forty-seven patients with nasopharyngeal tumors (89 NPCs and 38 NPLs) who had undergone magnetic resonance imaging (MRI) and diffusion-weighted imaging were retrospectively analyzed. ADC histogram-derived parameters were compared between the NPC and NPL groups by using the Mann-Whitney U test. Receiver operating characteristic (ROC) curves of the histogram parameters were plotted for diagnostic accuracy. Sensitivity and specificity were calculated for each histogram parameter. RESULTS: In whole-tumor histogram analysis, the mean, median, and 10th and 25th percentiles of ADC were all significantly higher in NPC than NPL (P = 0.045, P = 0.035, P = 0.005, and P = 0.016, respectively). Uniformity was significantly higher in NPC than NPL (P = 0.001). Skewness was significantly lower in NPC than NPL (P = 0.039). For the conventional ROI-based method, ADCmean values were significantly higher in NPC than in NPL (P = 0.009). The ROC curve analysis showed that uniformity yielded the largest area under the curve (AUC = 0.768) for differentiating NPC from NPL among all ADC metrics, followed by 10th percentiles of ADC (AUC = 0.725); sensitivity and specificity were 76.5% and 71.4%, respectively. CONCLUSION: Whole-tumor histogram analysis of ADC maps could be helpful for differentiating NPC from NPL.
Assuntos
Imagem de Difusão por Ressonância Magnética/métodos , Linfoma/diagnóstico por imagem , Carcinoma Nasofaríngeo/diagnóstico por imagem , Neoplasias Nasofaríngeas/diagnóstico por imagem , Adulto , Idoso , Idoso de 80 Anos ou mais , Diagnóstico Diferencial , Feminino , Humanos , Linfoma/patologia , Masculino , Pessoa de Meia-Idade , Carcinoma Nasofaríngeo/patologia , Neoplasias Nasofaríngeas/patologia , Estudos Retrospectivos , Sensibilidade e EspecificidadeRESUMO
The theoretical analysis and biomimetic conversion confirmed that the oxidative cleavage of the Δ8,9 double bond of chloranthalactone A (I), an abundant lindenane-type sesquiterpenoid in Chloranthaceae plants, generates 8,9-secolindenane (II) with active aldehyde and maleic anhydride fragments that can capture other fragments and produce oligomeric molecules. A careful phytochemical investigation of the leaves of Sarcandra glabra led to the discovery of eight novel 8,9-secolindenane-type sesquiterpenoid oligomers (sarglalactones A-H, compounds 1-8), including three unprecedented trimers (1-3), five unusual dimers (4-8), and five 8,9-secolindenane monomers (sarglalactones I-M, 9-13). Their structures were determined by comprehensive HRMS, NMR, circular dichroism, and X-ray diffraction analyses. Bioassay results showed that these oligomers significantly reversed the multidrug resistance of MCF-7/doxorubicin (DOX) cells and increased the sensitivity of U2 OS cells to DOX by downregulating the HMGB1 expression.