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1.
Artigo em Chinês | MEDLINE | ID: mdl-36347579

RESUMO

Objective:To explore the correlation between the parameters of video head impulse test (vHIT)and dizziness handicap inventory (DHI) score in patients with vestibular neuritis. Methods:Clinical data of 46 patients with vestibular neuritis were retrospectively analyzed. All the patients underwent DHI evaluation and vHIT examination. They were divided into mild handicap group, moderate handicap group and severe handicap group according to DHI score. The correlations between the parameters of vHIT and DHI score were compared among the three groups. The important parameters of vHIT were compared including vestibulo-ocular reflex (VOR) gain, gain asymmetry ratio (GA), abnormal saccade dispersion (PR%). Results:Of the 46 patients, 10 were in the mild handicap group, 21 in the moderate handicap group, and 15 in the severe handicap group. ①In the comparison of the mean value of lateral semicircular canal VOR gain, the vHIT gain of patients with mild, moderate and severe handicap were 0.64±0.06, 0.53±0.11 and 0.37±0.10, respectively, the mean value of VOR gain was negatively correlated with DHI score among the three groups(r=-0.545, P<0.001), and the pairwise comparisons among the three groups was statistically significant(P<0.05). In comparison of the mean values of lateral semicircular canal GA, the GA values of mild, moderate and severe handicap groups were 46.40±21.81, 47.59±15.17 and 56.57±17.39, respectively, there was no significant linear correlation between GA values and DHI scores among the three groups(r=0.246, P>0.05), there was no significant difference between the three groups(P>0.05). In comparison of the mean PR% of the lateral semicircular canal, the mean PR% of patients with mild, moderate and severe handicap group were 32.00±10.62, 53.82±17.09 and 76.00±10.01, respectively, PR% was positively correlated with DHI score(r=0.726, P<0.001), and the comparison among the three groups was statistically significant(P<0.05). ②The vertical semicircular canal vHIT gain of patients with mild, moderate and severe handicap was 0.63±0.06, 0.52±0.15 and 0.38±0.16, respectively, the mean of VOR gain was negatively correlated with DHI score among the three groups(r=-0.487, P<0.01), the comparison of mild-severe and moderate-severe group was statistically significant(P<0.05), while there was no significant difference between the mild and moderate group(P>0.05). In the comparison of the mean values of vertical semicircular canal GA, the GA values of mild, moderate and severe handicap groups were 40.40±15.31, 46.10±19.59 and 47.87±18.05, respectively, there was no significant linear correlation between GA values and DHI scores among the three groups(r=0.047, P>0.05), there was no significant difference in GA among the three groups(P>0.05). The PR% of patients with mild, moderate and severe handicap were 42.40±15.39, 54.14±17.60 and 64.93±10.95, respectively, there was a positive significant correlation between PR% and DHI score(r=0.454, P<0.05), there was statistically significant in the comparison of mild-severe group(P<0.05), while there was no statistical significance between the other groups(P>0.05). Conclusion:The VOR gain and PR% value of vHIT in patients with vestibular neuritis are closely related to the DHI score, which can evaluate the vestibular function and the degree of vertigo.


Assuntos
Teste do Impulso da Cabeça , Neuronite Vestibular , Humanos , Neuronite Vestibular/diagnóstico , Estudos Retrospectivos , Reflexo Vestíbulo-Ocular , Vertigem/diagnóstico , Canais Semicirculares , Hiperplasia
2.
Nat Commun ; 13(1): 7160, 2022 Nov 22.
Artigo em Inglês | MEDLINE | ID: mdl-36418319

RESUMO

Aromatase inhibition is an efficient endocrine therapy to block ectopic estrogen production for postmenopausal estrogen receptor (ER)-positive breast cancer patients, but many develop resistance. Here, we show that aromatase inhibitor (AI)-resistant breast tumors display features of enhanced aerobic glycolysis with upregulation of long noncoding RNA (lncRNA) DIO3OS, which correlates with poor prognosis of breast cancer patients on AI therapies. Long-term estrogen deprivation induces DIO3OS expression in ER-positive breast tumor cells, which further enhances aerobic glycolysis and promotes estrogen-independent cell proliferation in vitro and in vivo. Mechanistically, DIO3OS interacts with polypyrimidine tract binding protein 1 (PTBP1) and stabilizes the mRNA of lactate dehydrogenase A (LDHA) by protecting the integrity of its 3'UTR, and subsequently upregulates LDHA expression and activates glycolytic metabolism in AI-resistant breast cancer cells. Our findings highlight the role of lncRNA in regulating the key enzyme of glycolytic metabolism in response to endocrine therapies and the potential of targeting DIO3OS to reverse AI resistance in ER-positive breast cancer.


Assuntos
Neoplasias da Mama , RNA Longo não Codificante , Humanos , Feminino , Inibidores da Aromatase/farmacologia , Inibidores da Aromatase/uso terapêutico , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/genética , Neoplasias da Mama/metabolismo , Resistencia a Medicamentos Antineoplásicos/genética , Glicólise/genética , Estrogênios/farmacologia , Ribonucleoproteínas Nucleares Heterogêneas/metabolismo , Proteína de Ligação a Regiões Ricas em Polipirimidinas/metabolismo
3.
Front Oncol ; 12: 923425, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35898869

RESUMO

Emerging evidence has shown that long non-coding RNAs (lncRNAs) play an important role in colorectal cancer (CRC) carcinogenesis, so more specific mechanisms of key lncRNAs in CRC initiation and development are needed. Here, we evaluated the expression profiles of lncRNAs in CRC tissues and identified a novel lncRNA generated from the pseudogene Wiskott-Aldrich syndrome protein (WASP) family homolog 5, termed lncRNA WASH5P. However, the role and potential molecular mechanism of this novel lncRNA in diseases, including CRC carcinogenesis, is unknown. Our present study found that WASH5P was significantly downregulated in CRC cell lines and tissues compared with normal controls. The ectopic expression of WASH5P in CRC cells could significantly inhibit CRC cell proliferation, invasion, and migration. In addition, WASH5P could increase the expression of E-cadherin and decrease Vimentin expression. WASH5P-overexpressing CRC cells developed tumors more slowly in different mouse models. Meanwhile, the overexpression of WASH5P could significantly inhibit AKT activation via suppressing AKT phosphorylation. The treatment of PI3K/AKT (phosphatidlinositol 3-kinase /protein kinase B) signaling agonist 740Y-P rescued WASH5P-reduced AKT phosphorylation and abolished the inhibitory effects of WASH5P on cell viability, migration, and invasion. Moreover, 740Y-P restored the WASH5P-induced downregulation of p-AKT and vimentin and the upregulation of E-cadherin via Western blot. In summary, our findings suggested that the novel lncRNA WASH5P might be a potential candidate biomarker and therapeutic target that could inhibit CRC by repressing the AKT signaling pathway.

4.
J Appl Microbiol ; 133(5): 2915-2930, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-35882518

RESUMO

Intestinal microbiota is considered to play an integral role in maintaining health of host by modulating several physiological functions including nutrition, metabolism and immunity. Accumulated data from human and animal studies indicate that intestinal microbes can affect lipid metabolism in host through various direct and indirect biological mechanisms. These mechanisms include the production of various signalling molecules by the intestinal microbiome, which exert a strong effect on lipid metabolism, bile secretion in the liver, reverse transport of cholesterol and energy expenditure and insulin sensitivity in peripheral tissues. This review discusses the findings of recent studies suggesting an emerging role of intestinal microbiota and its metabolites in regulating lipid metabolism and the association of intestinal microbiota with obesity. Additionally, we discuss the controversies and challenges in this research area. However, intestinal micro-organisms are also affected by some external factors, which in turn influence the regulation of microbial lipid metabolism. Therefore, we also discuss the effects of probiotics, prebiotics, diet structure, exercise and other factors on intestinal microbiological changes and lipid metabolism regulation.


Assuntos
Microbioma Gastrointestinal , Probióticos , Animais , Humanos , Prebióticos , Metabolismo dos Lipídeos , Obesidade/microbiologia
5.
Front Neurosci ; 16: 888596, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35757527

RESUMO

Compared to normal-hearing (NH) listeners, cochlear implant (CI) listeners have greater difficulty segregating competing speech. Neurophysiological studies have largely investigated the neural foundations for CI listeners' speech recognition in quiet, mainly using the P300 component of event-related potentials (ERPs). P300 is closely related to cognitive processes involving auditory discrimination, selective attention, and working memory. Different from speech perception in quiet, little is known about the neurophysiological foundations for segregation of competing speech by CI listeners. In this study, ERPs were measured for a 1 vs. 2 kHz contrast in 11 Mandarin-speaking bimodal CI listeners and 11 NH listeners. Speech reception thresholds (SRTs) for a male target talker were measured in steady noise or with a male or female masker. Results showed that P300 amplitudes were significantly larger and latencies were significantly shorter for the NH than for the CI group. Similarly, SRTs were significantly better for the NH than for the CI group. Across all participants, P300 amplitude was significantly correlated with SRTs in steady noise (r = -0.65, p = 0.001) and with the competing male (r = -0.62, p = 0.002) and female maskers (r = -0.60, p = 0.003). Within the CI group, there was a significant correlation between P300 amplitude and SRTs with the male masker (r = -0.78, p = 0.005), which produced the most informational masking. The results suggest that P300 amplitude may be a clinically useful neural correlate of central auditory processing capabilities (e.g., susceptibility to informational masking) in bimodal CI patients.

6.
Eur Arch Otorhinolaryngol ; 279(6): 2811-2817, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-34228168

RESUMO

OBJECTIVE: Hearing loss (HL) is the most common sensory organ dysfunction disease. The cause is often complex, though genetics are the main factor. METHODS: In this study, we investigated a Chinese family with non-syndromic delayed post-lingual deafness. Comprehensive data collection was performed on this family's members, including basic information, audiological examinations, blood system examinations and imaging examinations. A pedigree diagram was drawn and the genetic patterns were analyzed. RESULTS: A new gene mutation, c.314A>T:p.Y105F in the MYH9 exon, was confirmed by next generation sequencing and Sanger sequencing. This mutation co-segregated with the phenotype in the pedigree. Patients in this family present bilateral symmetry and gradual and delayed high-frequency sensorineural hearing loss. The age of onset was approximately 30 years old. Except for hearing loss, no lesions were seen in other organs, especially the blood system. CONCLUSION: The identification and detection of a novel MYH9 mutation may be of great significance to provide the basis for gene function research and genetic consultation.


Assuntos
Perda Auditiva Neurossensorial , Perda Auditiva de Alta Frequência , Perda Auditiva Neurossensorial/diagnóstico , Perda Auditiva Neurossensorial/genética , Humanos , Mutação , Cadeias Pesadas de Miosina/genética , Linhagem , Fenótipo
8.
Gene ; 808: 146000, 2022 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-34626719

RESUMO

Hearing loss is a common disease, of which genetic factors are the main cause. The incidence of mild or moderate postlingual deafness in children is not high, and the impact on life and learning is not as severe as that of prelingual deafness. This leads to insufficient attention to the disorder in the clinic. To date, only a few disease-causing genes have been reported. This report describe a case of novel heterozygous mutations in OTOGL that causes nonsyndromic mild sensorineural hearing loss. Basic information, imaging examinations, audiological examination, and vestibular function tests of the proband were collected. Blood samples of the proband's family were collected and analyzed by whole exome sequencing and Sanger sequencing. A pedigree diagram was drawn and the genetic patterns were analyzed. The proband is a 16-year-old female student with mild sensorineural hearing loss. High-resolution CT of the inner ear and vestibular function tests showed no abnormalities. The age of onset was approximately 4 years old. Except for hearing loss, no lesions were seen in other organs. The parents of the proband were not close relatives and had normal hearing. Two novel heterozygous mutations were found in the OTOGL gene. The c.5038del (p.D1680Ifs*6) variant was inherited from the father, and the c.2770C > T (p.R924X) variant from the mother. They enriched the mutation spectrum of OTOGL, which provides the basis for gene function research and genetic consultation.


Assuntos
Perda Auditiva Neurossensorial/genética , Proteínas de Membrana/genética , Adolescente , Adulto , China , Família , Feminino , Genótipo , Heterozigoto , Humanos , Masculino , Proteínas de Membrana/metabolismo , Mutação , Linhagem , Fenótipo
9.
Psychol Res Behav Manag ; 14: 549-562, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34017205

RESUMO

PURPOSE: After a year of the COVID-19 pandemic, countries have repeatedly imposed strict quarantine regimes as the virus mutates and becomes more contagious. Medical undergraduate education has been disrupted and transformed into prolonged home isolation and online learning. Although studies have reported that the COVID-19 pandemic tends to increase perceived stress (PS) and affect the mental health of medical students, the influencing factors are unclear. Therefore, based on the stress process model, this study will comprehensively evaluate the distribution of stressors of medical students and explore the personal and environmental predictors of PS during the epidemic. PARTICIPANTS AND METHODS: An online survey was conducted among medical students (n=369) from three medical universities in western China who engaged in online learning. A stress process conceptual framework was formed to explore the influencing factors of PS. The survey items contained four sections: (a) the potential stressors derived from academic, psychosocial and health-related demands; coping resources such as (b) online learning environment support and (c) personal resilience, including online learning behavior and individual characteristics; and (d) PS, perception of imbalanced demands and coping resources. RESULTS: The mean PS score was 17.39 (SD=4.58), and over four-fifths (82.3%) of the students had moderate to high levels of stress. The average item scores of academic, psychosocial and health-related stressors were 2.72 (SD=0.55), 2.31 (SD=0.55) and 2.07 (SD=0.50), respectively. Gender, grade, psychosocial stressors, health-related stressors, specific online learning behavior (persistence, attitude and flexibility), and the online learning environment (teaching, social and cognitive presence) were predictors of PS. CONCLUSION: Our results specify that a reduction in psychological and health-related stressor stimulation, specific online learning behavior promotion, and well-established online learning environment support could be considered essential for alleviating the negative impacts of COVID-19 on the psychosocial health of medical undergraduates.

10.
Artigo em Inglês | MEDLINE | ID: mdl-33690078

RESUMO

Coronary heart disease (CHD) has a high mortality worldwide. This study aimed to screen lipid metabolism biomarkers in patients with coronary heart disease via ultra-performance liquid chromatography-high resolution mass spectrometry. Extraction and reconstitution solvents, liquid chromatographic and mass spectrometry conditions were optimized to detect more plasma lipid metabolites. In this study, the chromatographic and mass spectra characteristics of lipid metabolites were summarized. A total of 316 lipid metabolites were annotated via diagnostic fragment ion filtration, nitrogen rule filtration, and neutral loss filtration. Glycerophospholipid metabolism and sphingolipid metabolism were revealed as the main lipid disorders of CHD. This study provides a novel insight for high-throughput detection of lipid metabolites in plasma and provides a further understanding of the occurrence of CHD, which can provide valuable suggestions for the prevention of CHD.


Assuntos
Cromatografia Líquida de Alta Pressão/métodos , Doença das Coronárias/metabolismo , Glicerofosfolipídeos , Metabolismo dos Lipídeos/fisiologia , Esfingolipídeos , Idoso , Biomarcadores/sangue , Biomarcadores/metabolismo , Estudos de Casos e Controles , Feminino , Glicerofosfolipídeos/sangue , Glicerofosfolipídeos/metabolismo , Ensaios de Triagem em Larga Escala , Humanos , Lipidômica , Masculino , Espectrometria de Massas/métodos , Pessoa de Meia-Idade , Esfingolipídeos/sangue , Esfingolipídeos/metabolismo
11.
Biomed Pharmacother ; 135: 111185, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33422932

RESUMO

Aminoglycoside antibiotics, such as gentamicin, are known to have vestibulotoxic effects, including ataxia and disequilibrium. To date, however, the underlying cellular and molecular mechanisms are still unclear. In this study, we determined the role of gentamicin in regulating the sustained delayed rectifier K+ current (IDR) and membrane excitability in vestibular ganglion (VG) neurons in mice. Our results showed that the application of gentamicin to VG neurons decreased the IDR in a concentration-dependent manner, while the transient outward A-type K+ current (IA) remained unaffected. The decrease in IDR induced by gentamicin was independent of G-protein activity and led to a hyperpolarizing shift of the inactivation Vhalf. The analysis of phospho-c-Jun N-terminal kinase (p-JNK) revealed that gentamicin significantly stimulated JNK, while p-ERK and p-p38 remained unaffected. Blocking Kv1 channels with α-dendrotoxin or pretreating VG neurons with the JNK inhibitor II abrogated the gentamicin-induced decrease in IDR. Antagonism of JNK signaling attenuated the gentamicin-induced stimulation of PKA activity, whereas PKA inhibition prevented the IDR response induced by gentamicin. Moreover, gentamicin significantly increased the number of action potentials fired in both phasic and tonic firing type neurons; pretreating VG neurons with the JNK inhibitor II and the blockade of the IDR abolished this effect. Taken together, our results demonstrate that gentamicin decreases the IDR through a G-protein-independent but JNK and PKA-mediated signaling pathways. This gentamicin-induced IDR response mediates VG neuronal hyperexcitability and might contribute to its pharmacological vestibular effects.


Assuntos
Proteínas Quinases Dependentes de AMP Cíclico/metabolismo , Canais de Potássio de Retificação Tardia/antagonistas & inibidores , Gânglios Sensitivos/efeitos dos fármacos , Gentamicinas/toxicidade , Proteínas Quinases JNK Ativadas por Mitógeno/metabolismo , Neurônios/efeitos dos fármacos , Bloqueadores dos Canais de Potássio/toxicidade , Nervo Vestibular/efeitos dos fármacos , Potenciais de Ação , Animais , Células Cultivadas , Canais de Potássio de Retificação Tardia/metabolismo , Feminino , Gânglios Sensitivos/enzimologia , Masculino , Camundongos Endogâmicos ICR , Neurônios/enzimologia , Fosforilação , Transdução de Sinais , Nervo Vestibular/enzimologia
12.
J Alzheimers Dis ; 79(1): 141-152, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33216026

RESUMO

BACKGROUND: Patients with Alzheimer's disease (AD) experience various stressors that negatively impact well-being. Most studies have, however, small effect size and are limited by the experiences of severe patients. Therefore, we conducted a single-blind, randomized controlled trial, which has included patients at different stages. OBJECTIVE: The stressor-oriented multicomponent program was designed as an intervention for AD patients to enhance well-being. METHODS: Patients were randomly assigned to control or SOUL-P conditions according to disease severity. The SOUL-P group received 15 intensive sessions over 6 months and 6 maintenance sessions over a 6-month follow-up by a multidisciplinary team comprising psychologists, occupational therapists, and community nurses. The control group received a similar number of sessions by community nurses. Stress-related outcomes (primary stressors and well-being outcomes) were obtained from in-person baseline and follow-up interviews conducted at 6- and 12-months post-baseline. A treatment compliance survey was conducted at the intervention endpoint for patients. RESULTS: Of the 863 patients screened, 218 (25.3%) were eligible. At 6 months, compared to controls, SOUL-P patients had improved quality of life (QoL) (p < 0.001; Cohen d = 0.56), depression (p = 0.020; Cohen d = -0.33), neurobehavioral symptoms (p = 0.034; Cohen d = -0.30), perceived stress (p = 0.030; Cohen d = -0.31), and family conflict (p = 0.026; Cohen d = -0.32). QoL, depression, perceived stress, and family conflict were still significantly different at 12 months. Most patients were satisfied with SOUL-P, while caregivers in the SOUL-P group reported overloading tasks. CONCLUSION: SOUL-P may reduce perceived stress and improve psychological outcomes in AD patients. Stressor-based interventions, patient-oriented goals, and a multidisciplinary team are essential features for a successful SOUL-P.


Assuntos
Doença de Alzheimer/reabilitação , Qualidade de Vida , Estresse Psicológico/reabilitação , Idoso , Idoso de 80 Anos ou mais , Doença de Alzheimer/psicologia , Feminino , Visita Domiciliar , Humanos , Masculino , Enfermeiros de Saúde Comunitária , Terapeutas Ocupacionais , Equipe de Assistência ao Paciente , Psicologia , Índice de Gravidade de Doença , Método Simples-Cego , Estresse Psicológico/psicologia
13.
Iran J Basic Med Sci ; 23(3): 362-367, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32440323

RESUMO

OBJECTIVES: We sought to explore whether neuregulin-1(NRG1) would have a protective effect on the auditory cortices of adult C57BL/6J mice. MATERIALS AND METHODS: We used RTPCR and Western blot (WB) to detect the expression of NRG1 and ERBB4 (the receptor of NRG1) in the auditory cortices of C57BL/6J mice of different ages (6-8 weeks and 42-44 weeks). Three groups of 42-44 week-old C57BL/6J mice were intraperitoneally injected with mouse neurotrophic factor (m-NGF), NRG1, or saline for two months. We observed the ultrastructures of the auditory cortices of adult mice after treatment using transmission electron microscopy. Additionally, we observed expression of NRG1 in the auditory cortices by immunohistochemistry. RESULTS: Expression of NRG1 and ERBB4 in the auditory cortices of C57BL/6J mice at the age of 42-44 weeks was lower compared with 6-8 week-old mice. The ultra-structures of the auditory cortices, including the neurons and myelin sheaths, as revealed by transmission electron microscopy were healthier in the m-NGF and NRG1 treatment groups than those in the saline group. We found that expression of NRG1 in the auditory cortices after treatment in the m-NGF and NRG1 groups, especially in the NRG1 group, was higher than that in the saline group. CONCLUSION: We concluded that with increasing age, NRG1 in the auditory cortices of C57BL/6J mice gradually decreased, and that NRG1 had a protective effect on the auditory cortices in adult C57BL/J mice.

15.
Int J Legal Med ; 134(3): 987-988, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-31729603

RESUMO

The Blang is a minority living in the mountainous areas of Xishuangbanna Dai Autonomous Prefecture, and they also scatter in the neighboring cities of Lincang and Simao. This population is investigated in this study through PowerPlex® 21 System. The frequency distribution of allele, forensic, and population parameters of 20 autosomal short tandem repeat loci were evaluated based on 207 non-related individuals from Blang minority; meanwhile, the genetic relationships between Blang and 11 related populations were also assessed.


Assuntos
Etnicidade/genética , Frequência do Gene , Repetições de Microssatélites , /genética , China/etnologia , Genética Populacional , Humanos
16.
Int J Legal Med ; 134(2): 509-510, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30783753

RESUMO

The Lisu is an ethnic minority living in highlands or mountain valleys in the northern region of the Indo-China Peninsula. The paper presents the frequency distribution of allele and statistical genetic parameters of forensic relevance for 15 autosomal STR loci found in the AmpFℓSTR® Identifiler® PCR Amplification Kit among a population sample constituted by 1854 non-related Lisu minority individuals residing in the southwestern region of China. The genetic relationships between Lisu population and 14 related populations were assessed.


Assuntos
/genética , Etnicidade/genética , Frequência do Gene , Variação Genética , Repetições de Microssatélites , China/etnologia , Genética Populacional , Humanos , Reação em Cadeia da Polimerase
17.
Respir Res ; 20(1): 106, 2019 May 29.
Artigo em Inglês | MEDLINE | ID: mdl-31142317

RESUMO

BACKGROUND: Tumor chemo-resistance is a hallmark of malignant tumors as well as the major cause of poor survival rates in lung cancer. Transmembrane-4 L-six family member-1 (TM4SF1), an antigen that serves as an oncogene, mainly affects tumor invasion and metastasis. We investigated the roles of TM4SF1 in non-small-cell lung cancer progression, particularly in the regulation of chemo-sensitivity. METHODS: TM4SF1 was silenced by small interfering RNA transfection.TM4SF1 expression in cell lines and tissues were determined by Quantitative Real-time PCR. MTS, clonogenic, Transwell assay, Flow cytometry verified cell function. By RT-PCR, Western blot, the mechanisms were studied. RESULTS: TM4SF1 was upregulated in both lung cancer cell lines and tissues, compared with 293 T epithelial cells. Analysis of online databases revealed that high expression of TM4SF1 is associated with the older patient age, smoking habits, and poor patient survival and outcome. Knockdown of TM4SF1 substantially inhibited tumor cell growth, migration, and invasion, and enhanced the chemo-sensitivity of the lung cancer cell lines A549 and H1299 to cisplatin and paclitaxel. Furthermore, the silencing of TM4SF1 induced lung cancer cell apoptosis and arrested cells at the G2/M phase. These results suggest that TM4SF1 is associated with lung cancer progression and appears to be required for tumor cell growth, maintenance of chemo-resistance and metastasis. We further found that TM4SF1 exerts these effects in part by regulating the expression of the discoidin domain receptor DDR1 and its downstream target, the Akt/ERK/mTOR pathway, and consequently alters cell sensitivity to chemo-reagents and contributes to invasion and metastasis. CONCLUSIONS: These findings demonstrate that TM4SF1 may serve as a prognostic factor for lung cancer chemo-response and patient outcome.


Assuntos
Antígenos de Superfície/biossíntese , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Receptor com Domínio Discoidina 1/metabolismo , Neoplasias Pulmonares/metabolismo , Sistema de Sinalização das MAP Quinases/fisiologia , Proteínas de Neoplasias/biossíntese , Proteínas Proto-Oncogênicas c-akt/metabolismo , Serina-Treonina Quinases TOR/metabolismo , Células A549 , Adulto , Idoso , Carcinoma Pulmonar de Células não Pequenas/patologia , Proliferação de Células/fisiologia , Resistencia a Medicamentos Antineoplásicos/fisiologia , Feminino , Células HEK293 , Humanos , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica/patologia
18.
Pathol Oncol Res ; 25(3): 1143-1152, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30478720

RESUMO

All too often, conventional immunocytochemistry (ICC) via an antibody on cytological samples is limited to a few smears due to scant cellularity. To circumvent these limitations, this study employed a cell-type-specific aptamer as the core tool in ICC protocols for a timely and highly specific ICC diagnosis. S6, an aptamer against A549 lung carcinoma cells, was adopted instead of antibodies in this study for differentiating cancer cells in serosal fluids. Here, we developed three different strategies for discriminating the adenocarcinoma cells in effusion cytology specimens using the S6 aptamer in ICC. These strategies included a biotin-labeled S6 aptamer, an FAM-labeled S6 aptamer, and an activatable S6 aptamer. A total of 112 serosal fluid specimens with known diagnoses were evaluated by all three modes of use of the S6 aptamer. ICC procedures based on biotin-labeled or FAM-labeled S6 aptamers required time-consuming washing to avoid interference from nonspecific adsorption. ICC procedures based on an activatable S6 aptamer probe showed a weak fluorescence signal in the absence of target cells, but the procedures showed a strong fluorescence signal due to alteration of the conformation without any complicated washing steps, in the presence of targets. The specificity and sensitivity are higher in all three different ICC protocols based on the S6 aptamer than those for antibody protocols for differentiating adenocarcinoma cells in clinical effusion cytology. ICC based on cell-type-specific aptamers, instead of on a panel of a set of antibodies, is promising as an auxiliary method for the diagnosis of cancer.


Assuntos
Adenocarcinoma de Pulmão/diagnóstico , Aptâmeros de Nucleotídeos/química , Líquido Ascítico/metabolismo , Fluorescência , Imuno-Histoquímica/métodos , Neoplasias Pulmonares/diagnóstico , Membrana Serosa/metabolismo , Células A549 , Adenocarcinoma de Pulmão/metabolismo , Técnicas Biossensoriais , Citodiagnóstico , Humanos , Neoplasias Pulmonares/metabolismo
19.
Hum Immunol ; 79(12): 869-875, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30316971

RESUMO

Interleukin (IL)-35 is a heterodimeric cytokine composed of the IL-12A subunit and the Epstein-Barr virus induced gene 3 (EBI3) subunit. Binding of IL-35 with IL-12 receptor subunit beta 2 (IL-12RB2) and IL-6 signal transducer (IL-6ST) occupies the binding sites of IL-6, IL-12, and IL-27 and prevents their signal transduction. IL-35 is also shown to promote the development of regulatory T cells (Tregs) and regulatory B cells (Bregs). In this study, we investigated B cell-mediated IL-35 production in patients with coronary artery disease (CAD). The expression levels of IL-35 subunits and IL-10 were significantly lower in B cells from CAD patients than in B cells from healthy control individuals. Exogenous IL-35 could effectively increase the IL-10 production by B cells in a concentration-dependent manner. IL-35 promoted the phosphorylation of STAT1 and STAT3 in B cells, and the inhibition of STAT3 phosphorylation suppressed IL-10 production. Raising the IL-35 concentration in cell culture eliminated the difference in IL-10 expression between CAD B cells and healthy B cells. We also demonstrated that B cells from CAD patients presented lower capacity to suppress interferon gamma (IFNG) and tumor necrosis factor (TNF) expression by T cells than B cells from healthy controls. Exogenous IL-35 could significantly improve the suppressive capacity of B cells in both healthy controls and CAD patients. Together, these results demonstrated that a reduction in IL-35 production was associated with Breg defects in CAD patients. IL-35 and IL-35 targets may serve as therapeutic candidates in the treatment of CAD and related diseases.


Assuntos
Linfócitos B/metabolismo , Doença da Artéria Coronariana/metabolismo , Interleucina-10/biossíntese , Interleucinas/metabolismo , Fator de Transcrição STAT3/metabolismo , Estudos de Casos e Controles , Doença da Artéria Coronariana/genética , Doença da Artéria Coronariana/patologia , Feminino , Expressão Gênica , Humanos , Interleucina-10/genética , Masculino , Pessoa de Meia-Idade , Fosforilação
20.
Drug Deliv ; 25(1): 1426-1437, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-29890855

RESUMO

Most antitumor ingredients found in nature have poor solubility. These ingredients are expected to have much better absorption and higher bioavailability than synthetic antitumor agents. Woody oil emulsive nanosystems carrying poorly soluble natural alkaloids were fabricated (evodiamine (EA) carried by fructus bruceae oil-based emulsive nanosystems, or EFEN). Fructus bruceae oil has two excipient-like properties (oil phase and stabilizer) that contribute to the formulation and one drug-like property (antitumor effects) that synergizes with the antitumor effect of EA. The properties of EFEN were compared with free EA, a blank nanoemulsion, an EA-loaded emulsive nanosystem, and a fructus bruceae oil-loaded emulsive nanosystem. For the first time, this suggests that increases in the sensitivity of lung cancer cells to poorly soluble natural alkaloids can be achieved by delivering drugs using woody oil-based emulsive nanosystems. In this study, woody oil-based emulsive nanosystems efficiently deliver poorly soluble natural alkaloids.


Assuntos
Alcaloides/química , Emulsões/administração & dosagem , Emulsões/química , Neoplasias Pulmonares/tratamento farmacológico , Nanopartículas/química , Óleos Vegetais/química , Lã/química , Células A549 , Animais , Antineoplásicos/administração & dosagem , Antineoplásicos/química , Disponibilidade Biológica , Brucea javanica , Linhagem Celular Tumoral , Sistemas de Liberação de Medicamentos/métodos , Medicamentos de Ervas Chinesas/química , Excipientes/química , Humanos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Nus , Quinazolinas/administração & dosagem , Quinazolinas/química , Ratos , Ratos Sprague-Dawley , Solubilidade/efeitos dos fármacos
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