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1.
J Biol Chem ; 300(10): 107813, 2024 Sep 23.
Artigo em Inglês | MEDLINE | ID: mdl-39322015

RESUMO

The formin protein Diaph3 is an actin nucleator that regulates numerous cytoskeleton-dependent cellular processes through the activation of actin polymerization. Expression and activity of Diaph3 is tightly regulated: lack of Diaph3 results in developmental defects and embryonic lethality in mice, while overexpression of Diaph3 causes auditory neuropathy. It is known that Diaph3 homophilic interactions include the intramolecular interaction of its Dia-inhibitory domain (DID)-diaphanous autoregulatory domain (DAD) domains and the intermolecular interactions of DD-DD domains or FH2-FH2 domains. However, the physiological significance of these interactions in Diaph3 protein stability and activity is not fully understood. In this study, we show that FH2-FH2 interaction promotes Diaph3 activity, while DID-DAD and DD-DD interactions inhibit Diaph3 activity through distinct mechanisms. DID-DAD interaction is responsible for the autoinhibition of Diaph3 protein, which is disrupted by binding of Rho GTPases. Interestingly, we find that DID-DAD interaction stabilizes the expression of each DID or DAD domain against proteasomal-mediated degradation. Disruption of DID-DAD interaction by RhoA binding or M1041A mutation causes increased Diaph3 activity and accelerated degradation of the activated Diaph3 protein. Further, the activated Diaph3 is ubiquitinated at K1142/1143/1144 lysine residues by the E3 ligase Stub1. Expression of Stub1 is causally related to the stability and activity of Diaph3. Knockdown of Stub1 in mouse cochlea results in hair cell stereocilia defects, neuronal degeneration, and hearing loss, resembling the phenotypes of mice overexpressing Diaph3. Thus, our study reports a novel regulatory mechanism of Diaph3 protein expression and activity whereby the active but not inactive Diaph3 is readily degraded to prevent excessive actin polymerization.

2.
Crit Rev Immunol ; 44(4): 61-78, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38505922

RESUMO

We aimed to identify an effective metabolic subtype and risk score to predict survival and immunotherapy response in head and neck squamous cell carcinoma (HNSCC). Data were obtained from an online database. We screened significant prognostic metabolism-related genes between the normal and tumor groups using a series of bioinformatics methods. Based on the selected prognostic genes, we conducted a subtype analysis to identify significantly different subtypes in HNSCC. We then investigated survival, immune features, and hallmark differences among different subtypes. LASSO was utilized to identify optimal genes for the risk score model construction. Finally, distribution of the risk score samples was analyzed for different subtypes. A total of 32 significantly prognostic metabolism-related genes were screened, and all samples were grouped into two subtypes: cluster 1 and cluster 2. Cluster 1 had worse survival. Different immune cell infiltration (CD8 T cells, macrophages, and regulatory T cells) and immune checkpoint gene expression (PD-1 and CLAT-4) were observed between the two clusters. Twelve optimal genes were involved in risk score model, and high-risk group had poorer survival. Cluster 1 contained more high-risk samples (60%). Finally, four genes CAV1, GGT6, PYGL, and HS3ST1 were identified as significantly related to immune cells, and these genes were differentially expressed in the normal oral epithelial cells and HNSCC cells. The subtypes and risk score model in the study provide a promising biomarker for prognosis and immunotherapy response.


Assuntos
Células Epiteliais , Neoplasias de Cabeça e Pescoço , Humanos , Carcinoma de Células Escamosas de Cabeça e Pescoço/diagnóstico , Carcinoma de Células Escamosas de Cabeça e Pescoço/genética , Prognóstico , Linfócitos T CD8-Positivos , Neoplasias de Cabeça e Pescoço/diagnóstico , Neoplasias de Cabeça e Pescoço/genética , Neoplasias de Cabeça e Pescoço/terapia
3.
World J Surg Oncol ; 20(1): 348, 2022 Oct 19.
Artigo em Inglês | MEDLINE | ID: mdl-36261844

RESUMO

OBJECTIVE: This study focused on evaluating whether high-intensity interval training (HIIT) had an effect on aerobic capacity and fatigue among patients with prostate cancer (PCa) and exploring its effect on the immune system of PCa patients. METHODS: To investigate the potential effect of HIIT on patients with prostate cancer, a meta-analysis was carried out. From January 2012 to August 2022, studies that met predefined criteria were searched in the Scopus, PubMed, Web of Science, and EBSCO databases. Analysis of the standardized mean differences was performed using Review Manager 5.4.1 software with a 95% confidence interval. RESULTS: This review examined a total of 6 articles. There were 215 male patients with PCa involved, and the mean age was 64.4 years. According to the results of the meta-analysis, the HIIT group (n = 63) had greater VO2peak (P<0.01) than the control group (CON) (n = 52) (P = 0.30, I2 = 19% in the heterogeneity test; MD, 1.39 [0.50, 2.27]). Moreover, fatigue was significantly different (P<0.01) between the HIIT (n = 62) and CON (n = 61) groups (P = 0.78, I2 = 0% in the heterogeneity test; SMD, -0.52 [-0.88, -0.16]). Furthermore, among PCa patients, HIIT showed higher efficacy (P < 0.01) in decreasing PSA than the CON regimen (P=0.22, I2 = 34% in the heterogeneity test; MD, -1.13 [-1.91, -0.34]). CONCLUSIONS: HIIT improves aerobic capacity, fatigue, and PSA levels among PCa patients but does not significantly affect IL-6 or TNF-α content. Therefore, HIIT may be a novel and potent intervention scheme for PCa patients.


Assuntos
Treinamento Intervalado de Alta Intensidade , Neoplasias da Próstata , Humanos , Masculino , Pessoa de Meia-Idade , Treinamento Intervalado de Alta Intensidade/métodos , Fator de Necrose Tumoral alfa , Interleucina-6 , Antígeno Prostático Específico , Fadiga/etiologia , Fadiga/terapia , Neoplasias da Próstata/complicações , Neoplasias da Próstata/terapia
4.
Food Microbiol ; 105: 104009, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35473971

RESUMO

In this study, we examined the effects of different salt stress application methods on the Lactiplantibacillus plantarum LIP-1 freeze-drying survival rate. The application of salt stress during the stationary phase significantly improved Lactiplantibacillus plantarum LIP-1 freeze-drying survival rates (P < 0.05). The indirect application of salt stress via phosphate-buffered saline containing 0.4 mol/L NaCl (NB group) led to significantly higher freeze-drying survival rates compared to when salt stress was directly applied (NA group: the concentration of NaCl is 0.4 mol/L) (P < 0.05). Following exposure to salt stress, Lactiplantibacillus plantarum LIP-1 cells exuded excessive Na+ out of the cell and transported extracellular K+ into the cell, resulting in upregulation of the trkA gene, which is related to K+ transport, thereby significantly upregulating the expression of a lysR-type transcription factor, which increased the cell membrane unsaturated fatty acid content, reducing the degree of cell membrane damage and improving the freeze-drying survival rate. When the concentration of NaCl is 0.4 mol/L, compared with direct salt stress application, indirect application led to higher intracellular pH and ATP content, which effectively reduced DNA and cell membrane damage, respectively. Together, these results demonstrate that appropriate indirect salt stress application can improve Lactiplantibacillus plantarum LIP-1 freeze-drying resistance.


Assuntos
Lactobacillus , Cloreto de Sódio , Liofilização/métodos , Estresse Salino , Cloreto de Sódio/farmacologia , Taxa de Sobrevida
5.
J Sci Food Agric ; 100(5): 2007-2017, 2020 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-31849068

RESUMO

BACKGROUND: Previous studies have shown that Lactobacillus plantarum LIP-1 (hereafter LIP-1) has an obvious hypolipidemic effect, and microencapsulated probiotics can ensure the strains live through the gastrointestinal tract. Although there has been much research on both preparation and assessment methods for probiotics microcapsules, most assessments were made in vitro and few were validated in vivo. In this study, the protective effect of microencapsulation and the possible hypolipidemic mechanisms of probiotic LIP-1 were evaluated in rats. Treatments included rats fed on a normal diet, a high-fat diet, and a high-fat diet with an intragastric supplement of either non-microencapsulated LIP-1 cells (NME LIP-1) or microencapsulated LIP-1 (ME LIP-1). Lipid metabolism indicators were measured during the experiment and following euthanasia. RESULTS: Microencapsulation increased survival and colonization of LIP-1 in the colon. ME LIP-1 was superior to NME LIP-1 in reducing cholesterol. The mechanisms behind the hypolipidemic effect exerted by LIP-1 are possibly due to promoting the excretion of cholesterol, improving antioxygenic potentials, enhancing recovery from the injury in the liver, cardiovascular intima and intestinal mucosa, promoting the generation of short-chain fatty acids, and improving lipid metabolism. CONCLUSIONS: This study confirms that microencapsulation provides effective protection of LIP-1 in the digestive system and the role of LIP-1 in the prevention and cure of hyperlipidaemia, providing theoretical support for probiotics to enter clinical applications. © 2019 Society of Chemical Industry.


Assuntos
Hiperlipidemias/tratamento farmacológico , Hipolipemiantes/administração & dosagem , Lactobacillus plantarum/metabolismo , Probióticos/administração & dosagem , Animais , Cápsulas/administração & dosagem , Dieta Hiperlipídica/efeitos adversos , Humanos , Hiperlipidemias/metabolismo , Lactobacillus plantarum/química , Metabolismo dos Lipídeos/efeitos dos fármacos , Masculino , Ratos , Ratos Wistar
6.
Ophthalmic Res ; 57(3): 186-193, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28190007

RESUMO

OBJECTIVE: This study aimed to identify differentially expressed microRNAs (miRNAs) and to explore their potential roles in form-deprivation myopia. METHODS: The microarray data set GSE58124 of miRNAs was downloaded from the Gene Expression Omnibus, and form-deprivation myopia was induced in C57BL/6J mice over the right eye; the contralateral, left eyes were used as controls. Differential expression analysis was done using the LIMMA package. miRDB was used to predict targets for miRNAs. The target genes were put into DAVID to identify significant pathways and biological processes of miRNAs. A functionally collaborative network was constructed using Cytoscape. RESULT: In total, 24 and 20 upregulated miRNAs, respectively, were screened out in retina and whole-eye tissue. However, there was no dramatic expression change of miRNAs in sclera tissue. By taking intersections, 8 common upregulated miRNAs were obtained in both the retina and the whole-eye samples. According to miRDB, 1,805 target genes were screened out for the 8 differentially expressed miRNAs, including MAPK10 (mitogen-activated protein kinase 10). The functionally collaborative network revealed that "regulation of transcription" was significantly enriched. The pathways "Axon guidance" and "TGF-ß signaling pathway" were also enriched. Importantly, miR-466h-5p and miR-466j were significantly enriched in some synaptic transmission-related biological processes. CONCLUSION: This study identified an upregulation of 8 miRNAs, which may function by disturbing their enriched pathways or biological processes in the progression of myopia.


Assuntos
MicroRNAs/fisiologia , Miopia/genética , Animais , Biologia Computacional , Modelos Animais de Doenças , Progressão da Doença , Perfilação da Expressão Gênica , Redes Reguladoras de Genes , Camundongos Endogâmicos C57BL , MicroRNAs/metabolismo , Análise em Microsséries , Regulação para Cima
7.
Eur Arch Otorhinolaryngol ; 273(6): 1477-80, 2016 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-26370235

RESUMO

The present study was aimed to investigate the effects of DNS on the structure of nasal cavity. The paranasal sinus coronal view CT of 108 patients with DNS and 129 hospitalized patients without DNS was retrospectively analyzed. The transverse diameter of nasal cavity (a), transverse diameter of nasal cavity and paranasal sinus (b), angle between maxillary and palatal bone, interalveolar distance, and maxillary rotation distance were measured. The ratio of a/b in experimental group was 0.367 ± 0.006 which was significantly (P = 0.0023) less than that in control group (0.391 ± 0.005). For the angle between maxillary and palatal bone, there was no significant difference found between DNS and control group for both right and left sides. The interalveolar distance was 40.75 mm in experimental group, and 38.8 mm in control (P = 0.0002). For the maxillary rotation distance, findings were considered as significant (P < 0.0001) in experimental group (11.25 mm) compared with control (10.1 mm). The present study demonstrates that long-term DNS affects the development of nasal cavity and paranasal sinus, as well as increases the interalveolar distance and maxillary rotation distance. These influences may be caused by the alteration of airflow inside the nasal cavities.


Assuntos
Cavidade Nasal/diagnóstico por imagem , Septo Nasal/anormalidades , Seios Paranasais/diagnóstico por imagem , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Septo Nasal/diagnóstico por imagem , Estudos Retrospectivos , Tomografia Computadorizada por Raios X , Adulto Jovem
8.
Artigo em Inglês | MEDLINE | ID: mdl-25791913

RESUMO

AIMS: Compared with those in other head and neck regions, schwannomas in the nasal cavity or paranasal sinuses are rare. The aim of this study was to present the experience of the authors in 11 schwannoma cases of the sinonasal tract and pterygopalatine fossa over a decade. METHODS: A retrospective study from 2003 to 2014. RESULTS: Three female and 8 male patients from 22 to 61 years of age (mean age 42 years) were admitted. The most common complaints were unilateral nasal congestion. A total of 10 of the patients received surgery, including 6 functional endoscopic sinus surgeries (FESS). The postoperative course was generally uneventful. Among the patients, 10 remained regionally asymptomatic, and there has been no clinical or radiological evidence of recurrence or residual tumor. CONCLUSION: Surgical treatment is effective for schwannomas of the sinonasal tract and the pterygopalatine fossa with a low recurrence rate. Conducting CT and MRI (particularly fluid-attenuated inversion recovery) before surgery is mandatory. FESS could become the primary treatment of choice.


Assuntos
Cavidade Nasal/patologia , Neurilemoma/cirurgia , Neoplasias Nasais/patologia , Neoplasias dos Seios Paranasais/cirurgia , Seios Paranasais/patologia , Fossa Pterigopalatina/patologia , Adulto , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Cavidade Nasal/cirurgia , Recidiva Local de Neoplasia , Neoplasias Nasais/cirurgia , Neoplasias dos Seios Paranasais/patologia , Seios Paranasais/cirurgia , Estudos Retrospectivos , Tomografia Computadorizada por Raios X , Adulto Jovem
9.
J Food Sci ; 2024 Oct 22.
Artigo em Inglês | MEDLINE | ID: mdl-39437221

RESUMO

The purpose of this study was to prepare and evaluate the formulation of nanoemulsions (NEs) to encapsulate phloretin (PT) to improve its stability, antioxidant, and tyrosinase inhibitory competence. The aim of this study was to improve the stability, antioxidant, and tyrosinase inhibitory effects of PT via NEs. The formulations were prepared using low energy emulsification method for PT-VE-NEs, α-tocopherol (Vitamin E) and medium chain triglycerides (MCT) were used as the oil phase, and Tween 60 was used as the emulsifier and PEG-400 as the co-emulsifier. The droplet size and zeta potential of oil-in-water NEs were evaluated using dynamic light scattering. The PT-VE-NEs were also characterized by transmission electron microscopy and Fourier transform infrared spectroscopy. The mean droplet diameter was 14.85 ± 0.14 nm, with a zeta potential of -2.47 ± 0.51 mV. Fourier transform infrared spectroscopy revealed the formation of molecular interactions in the NEs formulations. PT-VE-NEs size was maintained the same during the in vitro digestion study. The particle size of PT-VE-NE remained stable during in vitro digestion. The addition of VE significantly improved the antioxidant, tyrosinase inhibitory effects, as well as thelion and physical stability of PT-VE-NE. The results revealed that NEs is a promising strategy to improve the functionality and stability of PT and VE. PT-VE-NEs will be applied for the preservation of fruits.

10.
Food Chem ; 453: 139656, 2024 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-38788646

RESUMO

Oxidative stability is a key quality characteristic of edible oils, and the oil's antioxidant capacity decreases during the deodorization stage. This study explores the changes in radical formation, molecular structure, oxidative characteristics, fatty acids, and main bioactive compounds in soybean oil during deodorization. The lag phase decreased, whereas the total amount of spins of free radicals increased as the deodorization time increased from 90 to 150 min. The total amount of spins and percentage of alkyl radicals varied dramatically under different times and temperatures (220 âˆ¼ 260 ℃). Results showed that identifying and quantifying the formed radicals can provide useful information for monitoring and controlling oil oxidation in vegetable oil refining systems. Therefore, to control early oxidation events, maximize refined oil product yield, and reduce energy consumption in the refining plant, the priority should be to minimize temperature during the oil refining process and then shorten the deodorization time.


Assuntos
Ácidos Graxos , Oxirredução , Óleo de Soja , Óleo de Soja/química , Ácidos Graxos/química , Radicais Livres/química , Lipídeos/química , Antioxidantes/química
11.
Neurosci Bull ; 40(10): 1519-1528, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-38589712

RESUMO

Deafness is the prevailing sensory impairment among humans, impacting every aspect of one's existence. Half of congenital deafness cases are attributed to genetic factors. Studies have shown that Luzp2 is expressed in hair cells (HCs) and supporting cells of the inner ear, but its specific role in hearing remains unclear. To determine the importance of Luzp2 in auditory function, we generated mice deficient in Luzp2. Our results revealed that Luzp2 has predominant expression within the HCs and pillar cells. However, the loss of Luzp2 did not result in any changes in auditory threshold. HCs or synapse number and HC stereocilia morphology in Luzp2 knockout mice did not show any notable distinctions. This was the first study of the role of Luzp2 in hearing in mice, and our results provide important guidance for the screening of deafness genes.


Assuntos
Perda Auditiva , Camundongos Knockout , Animais , Perda Auditiva/genética , Perda Auditiva/patologia , Camundongos , Células Ciliadas Auditivas/patologia , Células Ciliadas Auditivas/metabolismo , Camundongos Endogâmicos C57BL , Limiar Auditivo/fisiologia , Estereocílios/patologia , Estereocílios/metabolismo
12.
Plant Cell ; 22(7): 2336-52, 2010 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-20639449

RESUMO

Genetic screening identified a suppressor of ros1-1, a mutant of REPRESSOR OF SILENCING1 (ROS1; encoding a DNA demethylation protein). The suppressor is a mutation in the gene encoding the largest subunit of replication factor C (RFC1). This mutation of RFC1 reactivates the unlinked 35S-NPTII transgene, which is silenced in ros1 and also increases expression of the pericentromeric Athila retrotransposons named transcriptional silent information in a DNA methylation-independent manner. rfc1 is more sensitive than the wild type to the DNA-damaging agent methylmethane sulphonate and to the DNA inter- and intra- cross-linking agent cisplatin. The rfc1 mutant constitutively expresses the G2/M-specific cyclin CycB1;1 and other DNA repair-related genes. Treatment with DNA-damaging agents mimics the rfc1 mutation in releasing the silenced 35S-NPTII, suggesting that spontaneously induced genomic instability caused by the rfc1 mutation might partially contribute to the released transcriptional gene silencing (TGS). The frequency of somatic homologous recombination is significantly increased in the rfc1 mutant. Interestingly, ros1 mutants show increased telomere length, but rfc1 mutants show decreased telomere length and reduced expression of telomerase. Our results suggest that RFC1 helps mediate genomic stability and TGS in Arabidopsis thaliana.


Assuntos
Arabidopsis/genética , Inativação Gênica , Genoma de Planta , Transcrição Gênica , Clonagem Molecular , Dano ao DNA , Metilação de DNA , Mutação , Recombinação Genética
13.
Heliyon ; 8(10): e11051, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-36281415

RESUMO

Objective: To investigate the acute effects of blood flow restriction (BFR) with single-leg low load resistance exercise and high load resistance exercise on serum insulin-like growth factor-1 (IGF-1), growth hormone (GH), and testosterone in patients with unilateral knee osteoarthritis (OA). Methods: This study recruited 18 postmenopausal female patients with mild to moderate unilateral knee OA, which was then followed by randomly conducting three resistance exercise protocols by drawing lots: 1. A 30% 1-repetition maximum (1-RM) resistance exercise with BFR of 70% arterial occlusive pressure (AOP) (BFR group); 2. A 70% 1-RM resistance exercise without BFR (RES group); 3. A 30% 1-RM resistance exercise without BFR (CON group). Blood lactate (BLA) and muscle growth related hormone levels were tested at 4-time points: before exercise, immediately after exercise, 15 min after exercise, and 30 min after exercise. Results: There was no statistical difference between the indexes in each group before exercise, but the different exercise had different effects on each index and also an interactive effect (P < 0.05). The increase of rating of perceived exertion in the BFR and RES groups, which were of similar magnitude, was greater compared to the levels in the CON group (P < 0.05). Post-exercise BLA levels were lower in the CON group in comparison to the BFR and RES groups (P < 0.05). Rather than the RES group, GH levels of the BFR group were also significantly higher than the CON group (P < 0.05) at 15 min post-exercise. At post- and 15 min after exercise, the CON group recorded significantly lower IGF-1 levels compared to the BFR and RES groups (P < 0.05). At post- and 15 min after exercise, the CON group (P < 0.05) reflected the lowest testosterone levels, followed by the RES group (P < 0.05), and the highest in the BFR group (P < 0.05). Conclusions: Myogenesis-related hormones in women with unilateral knee OA could be increased by high load resistance exercise and low load resistance exercise with BFR on unaffected limb.

14.
Artigo em Zh | MEDLINE | ID: mdl-35822384

RESUMO

Objective:To investigate the clinicopathological features, treatment and prognosis of Castleman disease in the head and neck. Methods:The clinical and pathological data of 18 patients with Castleman disease of the head and neck in Nanjing Drum Tower Hospital from 2007 to 2021 were retrospectively analyzed. There were 14 cases of unicentric type and 4 cases of multicentric type. The clinical characteristics, treatment and prognosis were analyzed. Results:Among the 18 cases of Castleman disease in the head and neck, 1 case was located in the parotid gland, 1 case was behind the ear, 1 case was in the parapharyngeal space, 3 cases were in the neck region Ⅰ, 2 cases were supraclavicular, 2 cases were in the neck region Ⅲ, the rest were located in more than two subregions of the neck. In patients with unicentric type, no tumor recurrence and progression were found in the postoperative re-examination with neck Doppler ultrasound and CT; in the multicentric type, multiple organ dysfunction, such as edema of both lower extremities, hepatosplenomegaly, and cough, were found. Of the 4 patients with multicentric type, only 1 patient received chemotherapy, and the remaining 3 patients refused chemotherapy and only received symptomatic treatment. All patients survived during follow-up, but the disease of multicentric patients progressed significantly, and the number of involved lymph nodes increased, and hepatosplenomegaly were found in some patients. Conclusion:Castleman disease of the head and neck is mostly unicentric type, which is manifested as multiple asymptomatic enlarged lymph nodes in the neck. The surgical resection is effective and the prognosis is good. Multicentric Castleman disease of the head and neck has complex clinical symptoms and involves multiple organs over time, requiring follow-up treatment.


Assuntos
Hiperplasia do Linfonodo Gigante , Hiperplasia do Linfonodo Gigante/diagnóstico , Hiperplasia do Linfonodo Gigante/terapia , Cabeça , Humanos , Linfonodos/patologia , Pescoço/patologia , Estudos Retrospectivos
15.
Int J Genomics ; 2022: 6022869, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35795712

RESUMO

Head and neck squamous cell carcinoma (HNSCC) is a heterogeneous disease with a high mortality rate. The tumor microenvironment (TME) is composed of numerous noncancerous cells that contribute to tumorigenesis and prediction of therapeutic effects. In this study, we aimed to develop a cell component-related prognostic model based on TME. We screened cell component enrichments from samples in The Cancer Genome Atlas (TCGA) HNSCC cohort using the xCell algorithm. Univariate Cox and multivariate Cox regression analyses were performed to establish an optimal independent risk model. The prognostic value of the model was further validated using Gene Expression Omnibus datasets. We found that patients in the low-risk group had a better outcome and activated immunity and may benefit more from the immune checkpoint inhibitor therapy. We also explored microRNAs (miRNAs) that may regulate these identified cell components, and 11 miRNA expression levels influenced the overall survival time. Moreover, their target mRNAs were differentially expressed in TCGA cohort and enriched in pathways of cell cycle pathways, extracellular matrix receptor interaction, human papillomavirus infection, and cancer. In summary, our cell component-related signature was a promising prognostic biomarker that provides new insights into the predictive value of nontumor components in the TME.

16.
Exp Hematol Oncol ; 11(1): 14, 2022 Mar 14.
Artigo em Inglês | MEDLINE | ID: mdl-35287752

RESUMO

BACKGROUND: N6-methyladenosine (m6A) RNA methylation and its methyltransferase METTL3 have been widely reported to be involved in different cancers by regulating RNA metabolism and function. Here, we aimed to explore the biological function and clinical significance of m6A modification and METTL3 in head and neck squamous cell carcinoma (HNSCC). METHODS: The prognostic value of METTL3 expression was evaluated using tissue microarray and immunohistochemical staining analyses in a human HNSCC cohort. The biological role and mechanism of METTL3 in HNSCC tumour growth, metastasis and angiogenesis were determined in vitro and in vivo. RESULTS: M6A levels and METTL3 expressions in HNSCC tissues were significantly increased compared with paired adjacent tissues. Meanwhile, METTL3 was an independent risk factor for the prognosis of HNSCC patients. Moreover, METTL3 overexpression promoted HNSCC cell proliferation, migration, invasion, and angiogenesis, while knockdown of METTL3 had an opposite effect in vivo and in vitro. Mechanistically, METTL3 enhanced the m6A modification of CDC25B mRNA, which maintained its stability and upregulated its expression, thereby activating G2/M phase of cell cycle and leading to HNSCC malignant progression. CONCLUSIONS: METTL3 may be a potential prognostic biomarker and therapeutic target for HNSCC.

17.
Open Life Sci ; 16(1): 544-557, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34131588

RESUMO

lncRNA-mRNA co-expression pairs and prognostic markers related to the development of laryngeal squamous cell carcinoma (LSCC) were investigated. The lncRNA and mRNA expression data of LSCC in GSE84957 and RNA-seq data of 112 LSCC samples from TCGA database were used. Differentially expressed genes (DEGs) and lncRNAs (DE-lncRNAs) between LSCC and para-cancer tissues were identified. Co-expression analysis of DEGs and DE-lncRNA was conducted. Protein-protein interaction network for co-expressed DEGs of top 25 DE-lncRNA was constructed, followed by survival analysis for key nodes in co-expression network. Finally, expressions of several DE-lncRNAs and DEGs were verified using qRT-PCR. The lncRNA-mRNA network showed that ANKRD20A5P, C21orf15, CYP4F35P, LOC_I2_011146, XLOC_006053, XLOC_I2_003881, and LOC100506027 were highlighted in network. Some DEGs, including FUT7, PADI1, PPL, ARHGAP40, MUC21, and CEACAM1, were co-expressed with above lncRNAs. Survival analysis showed that PLOD1, GLT25D1, and KIF22 were significantly associated with prognosis. qRT-PCR results showed that the expressions of MUC21, CEACAM1, FUT7, PADI1, PPL, ARHGAP40, ANKRD20A5P, C21orf15, CYP4F35P, XLOC_I2_003881, LOC_I2_011146, and XLOC_006053 were downregulated, whereas the expression of LOC100506027 was upregulated in LSCC tissues. PLOD1, GLT25D1, and KIF22 may be potential prognostic markers in the development of LSCC. C21orf15-MUC21/CEACAM1/FUT7/PADI1/PPL/ARHGAP40 are potential lncRNA-mRNA pairs that play significant roles in the development of LSCC.

18.
Ultrason Sonochem ; 80: 105810, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34736116

RESUMO

In this work casein (CN) was used as a carrier system for the hydrophobic agent α-tocopherol (α-TOC), and an amphiphilic self-assembling micellar nanostructure was formed with ultrasound treatment. The interaction mechanism was detected with UV-Vis spectroscopy, fluorescence spectroscopy, proton spectra, and Fourier transform infrared spectroscopy (FTIR). The stability of the nanoparticles was investigated by using typical processing and storage conditions (thermal, photo, 20 ± 2 °C and 4 ± 2 °C). Oil-in-water emulsions containing the self-assembled nanoparticles and grape seed oil were prepared, and the effect of emulsion oxidation stability was studied using the accelerated Rancimat method. The results indicated that the UV-Vis spectra of α-TOC/CN nanoparticles complexes were different for ultrasonic treatments performed with different combinations of power (100, 200, 300 W) and time (5, 10, and 15 min). The results of UV-Vis fluorescence spectrum data indicated that the secondary structure of casein changed in the presence of α-TOC. The nanoparticles exhibited the chemical shifts of conjugated double bonds. Interactions between α-TOC and casein at different molar concentrations resulted in a quenching of the intrinsic fluorescence at 280 nm and 295 nm. Moreover, by performing FTIR deconvolution analysis and multicomponent peak modeling, the relative quantitative amounts of α-helix and ß-sheet protein secondary structures were determined. The self-assembled nanoparticles can improve the stability of α-TOC by protecting them against degradation caused by light and oxygen. The antioxidant activity of the nanoparticles was stronger than those of the two free samples. Lipid hydroperoxides remained at a low level throughout the course of the study in emulsions containing 200 mg α-TOC/kg oil with the nanoparticles. The presence of 100 and 200 mg α-TOC/kg oil led to a 78.54 and 63.54 µmol/L inhibition of TBARS formation with the nanoparticles, respectively, vs the free samples containing control after 180 mins.

19.
Int J Nanomedicine ; 16: 6097-6113, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34511908

RESUMO

Superparamagnetic iron oxide nanoparticles (SPIONs) have been widely investigated and applied in the field of biomedicine due to their excellent superparamagnetic properties and reliable traceability. However, with the optimization of core composition, shell types and transfection agents, the cytotoxicity and metabolism of different SPIONs have great differences, and the labeled cells also show different cellular behaviors. Therefore, a holistic review of the construction and application of SPIONs is desired. This review focuses the advances of SPIONs in the field of biomedicine in recent years. After summarizing the toxicity of different SPIONs, the uptake, distribution and metabolism of SPIONs in vitro were discussed. Then, the regulation of labeled-cells behavior is outlined. Furthermore, the major challenges in the optimization process of SPIONs and insights on its future developments are proposed.


Assuntos
Nanopartículas de Magnetita , Nanopartículas Magnéticas de Óxido de Ferro , Nanopartículas de Magnetita/efeitos adversos
20.
Acta Otolaryngol ; 141(4): 419-423, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33508996

RESUMO

BACKGROUND: There were heterogeneous or even conflicting data regarding the ability of platelet-to-lymphocyte ratio (PLR) for predicting the prognosis of laryngeal/hypopharyngeal squamous cell carcinoma (LHSCC). The discrepancies were found to be largely due to the cutoff value of PLR. AIMS: The aims of this study were to rationally select an optimal PLR cutoff value and to analyze the relationship between pretreatment PLR and the prognosis. METHODS: A total of 180 male patients were eligible for this retrospective study. We included another 180 healthy male individuals as controls. The relationship between PLR and age in patients and the controls was determined. The optimal cutoff values of PLR were identified. PLR value was then dichotomized into two categories, and the relationship between PLR and the clinicopathologic parameters were calculated. Kaplan-Meier curves were used to evaluate the overall survival (OS), and the association between PLR and the OS was analyzed. RESULTS: The linear regression analysis showed a positive correlation between age and PLR in the control group, but not the patients. The optimal cutoff value of PLR was 112.5. The high PLR value group of patients exhibited significantly decreased OS. PLR was related to prognosis, as revealed by the univariate Cox regression. CONCLUSION: Patients with LHSCC have abnormal high PLR, and a high pretreatment PLR portends adverse survival.


Assuntos
Carcinoma de Células Escamosas/sangue , Neoplasias Hipofaríngeas/sangue , Neoplasias Laríngeas/sangue , Contagem de Linfócitos , Contagem de Plaquetas , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Células Escamosas/mortalidade , Carcinoma de Células Escamosas/cirurgia , Humanos , Neoplasias Hipofaríngeas/mortalidade , Neoplasias Hipofaríngeas/cirurgia , Estimativa de Kaplan-Meier , Neoplasias Laríngeas/mortalidade , Neoplasias Laríngeas/cirurgia , Modelos Lineares , Masculino , Pessoa de Meia-Idade , Prognóstico , Modelos de Riscos Proporcionais , Valores de Referência , Estudos Retrospectivos
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