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1.
BMC Genomics ; 25(1): 494, 2024 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-38764031

RESUMO

BACKGROUND: Mammary gland development is a critical process in mammals, crucial for their reproductive success and offspring nourishment. However, the functional roles of key candidate genes associated with teat number, including ABCD4, VRTN, PROX2, and DLST, in this developmental process remain elusive. To address this gap in knowledge, we conducted an in-depth investigation into the dynamic expression patterns, functional implications, and regulatory networks of these candidate genes during mouse mammary gland development. RESULTS: In this study, the spatial and temporal patterns of key genes were characterized in mammary gland development. Using time-series single-cell data, we uncovered differences in the expression of A bcd4, Vrtn, Prox2, and Dlst in cell population of the mammary gland during embryonic and adult stages, while Vrtn was not detected in any cells. We found that only overexpression and knockdown of Abcd4 could inhibit proliferation and promote apoptosis of HC11 mammary epithelial cells, whereas Prox2 and Dlst had no significant effect on these cells. Using RNA-seq and qPCR, further analysis revealed that Abcd4 can induce widespread changes in the expression levels of genes involved in mammary gland development, such as Igfbp3, Ccl5, Tlr2, and Prlr, which were primarily associated with the MAPK, JAK-STAT, and PI3K-AKT pathways by functional enrichment. CONCLUSIONS: These findings revealed ABCD4 as a candidate gene pivotal for regulating mammary gland development and lactation during pregnancy by influencing PRLR expression.


Assuntos
Glândulas Mamárias Animais , Animais , Glândulas Mamárias Animais/crescimento & desenvolvimento , Glândulas Mamárias Animais/metabolismo , Feminino , Camundongos , Apoptose/genética , Proliferação de Células , Regulação da Expressão Gênica no Desenvolvimento , Redes Reguladoras de Genes , Células Epiteliais/metabolismo , Transdução de Sinais
2.
PLoS Pathog ; 20(3): e1012104, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38512977

RESUMO

The interaction between foot-and-mouth disease virus (FMDV) and the host is extremely important for virus infection, but there are few researches on it, which is not conducive to vaccine development and FMD control. In this study, we designed a porcine genome-scale CRISPR/Cas9 knockout library containing 93,859 single guide RNAs targeting 16,886 protein-coding genes, 25 long ncRNAs, and 463 microRNAs. Using this library, several previously unreported genes required for FMDV infection are highly enriched post-FMDV selection in IBRS-2 cells. Follow-up studies confirmed the dependency of FMDV on these genes, and we identified a functional role for one of the FMDV-related host genes: TOB1 (Transducer of ERBB2.1). TOB1-knockout significantly inhibits FMDV infection by positively regulating the expression of RIG-I and MDA5. We further found that TOB1-knockout led to more accumulation of mRNA transcripts of transcription factor CEBPA, and thus its protein, which further enhanced transcription of RIG-I and MDA5 genes. In addition, TOB1-knockout was shown to inhibit FMDV adsorption and internalization mediated by EGFR/ERBB2 pathway. Finally, the FMDV lethal challenge on TOB1-knockout mice confirmed that the deletion of TOB1 inhibited FMDV infection in vivo. These results identify TOB1 as a key host factor involved in FMDV infection in pigs.


Assuntos
Vírus da Febre Aftosa , Febre Aftosa , Animais , Camundongos , Receptores ErbB/metabolismo , Febre Aftosa/genética , Vírus da Febre Aftosa/genética , Regulação da Expressão Gênica , RNA Guia de Sistemas CRISPR-Cas , Suínos
3.
Jpn J Radiol ; 2024 Feb 27.
Artigo em Inglês | MEDLINE | ID: mdl-38409300

RESUMO

PURPOSE: To investigate the role of magnetic resonance imaging (MRI) based on radiomics using T2-weighted imaging fat suppression (T2WI-FS) and contrast enhanced T1-weighted imaging (CE-T1WI) sequences in differentiating T1-category nasopharyngeal carcinoma (NPC) from nasopharyngeal lymphoid hyperplasia (NPH). MATERIALS AND METHODS: This study enrolled 614 patients (training dataset: n = 390, internal validation dataset: n = 98, and external validation dataset: n = 126) of T1-category NPC and NPH. Three feature selection methods were used, including analysis of variance, recursive feature elimination, and relief. The logistic regression classifier was performed to construct the radiomics signatures of T2WI-FS, CE-T1WI, and T2WI-FS + CE-T1WI to differentiate T1-category NPC from NPH. The performance of the optimal radiomics signature (T2WI-FS + CE-T1WI) was compared with those of three radiologists in the internal and external validation datasets. RESULTS: Twelve, 15, and 15 radiomics features were selected from T2WI-FS, CE-T1WI, and T2WI-FS + CE-T1WI to develop the three radiomics signatures, respectively. The area under the curve (AUC) values for radiomics signatures of T2WI-FS + CE-T1WI and CE-T1WI were significantly higher than that of T2WI-FS (AUCs = 0.940, 0.935, and 0.905, respectively) for distinguishing T1-category NPC and NPH in the training dataset (Ps all < 0.05). In the internal and external validation datasets, the radiomics signatures based on T2WI-FS + CE-T1WI and CE-T1WI outperformed T2WI-FS with no significant difference (AUCs = 0.938, 0.925, and 0.874 for internal validation dataset and 0.932, 0.918, and 0.882 for external validation dataset; Ps > 0.05). The radiomics signature of T2WI-FS + CE-T1WI significantly performed better than three radiologists in the internal and external validation datasets. CONCLUSION: The MRI-based radiomics signature is meaningful in differentiating T1-category NPC from NPH and potentially helps clinicians select suitable therapy strategies.

5.
J Comput Assist Tomogr ; 47(6): 989-995, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37948376

RESUMO

PURPOSE: This study aimed to evaluate the imaging features of maxillary sinus adenoid cystic carcinoma (ACC) on computed tomography (CT) and magnetic resonance imaging (MRI) and to investigate the imaging differences between solid and nonsolid maxillary sinus ACC. METHODS: We retrospectively reviewed 40 cases of histopathologically confirmed ACC of the maxillary sinus. All the patients underwent CT and MRI. Based on the histopathological characteristics, the patients were classified into 2 groups: ( a ) solid maxillary sinus ACC (n = 16) and ( b ) nonsolid maxillary sinus ACC (n = 24). Imaging features such as tumor size, morphology, internal structure, margin, type of bone destruction, signal intensity, enhancement changes, and perineural tumor spread on CT and MRI, were evaluated. The apparent diffusion coefficient (ADC) was measured. Comparisons of imaging features and ADC values were performed between the solid and nonsolid maxillary sinus ACC using χ 2 and nonparametric tests. RESULTS: The internal structure, margin, type of bone destruction, and degree of enhancement significantly differed between solid and nonsolid maxillary sinus ACC (all P < 0.05). The ADC of the solid maxillary sinus ACC was considerably lower than that of the nonsolid maxillary sinus ( P < 0.05). CONCLUSIONS: Computed tomography and MRI may aid in the differentiation of solid and nonsolid types of maxillary sinus ACC.


Assuntos
Carcinoma Adenoide Cístico , Neoplasias dos Seios Paranasais , Humanos , Carcinoma Adenoide Cístico/diagnóstico por imagem , Carcinoma Adenoide Cístico/patologia , Seio Maxilar/diagnóstico por imagem , Seio Maxilar/patologia , Estudos Retrospectivos , Imageamento por Ressonância Magnética/métodos , Tomografia Computadorizada por Raios X/métodos
6.
Neurosurg Rev ; 46(1): 240, 2023 Sep 12.
Artigo em Inglês | MEDLINE | ID: mdl-37698750

RESUMO

Optic canal unroofing (OCU) has gradually become a routine technique for tuberculum sellae meningiomas (TSMs) resection. This meta-analysis aimed to evaluate the efficacy and safety of OCU. A systematic review and meta-analysis of the published literature on this topic from 2003 to 2023 were conducted in accordance with the PRISMA guidelines. Rigorous statistical analysis with a p-value was performed for related change in visual improvement, gross total resection (GTR), visual deterioration, and olfactory nerve damage. The study included 15 articles with 384 patients in whom OCU was performed by the transcranial approach (TCA) or the endoscopic endonasal approach (EEA). Of these, 341 patients had preoperative visual loss, and 266 patients had postoperative visual recovery. The overall rate of visual improvement was 0.803 (95% CI: 0.733-0.874, p < 0.01). The rate of visual improvement in the EEA and TCA groups was 0.884 (95% CI: 0.803-0.965, p < 0.01) and 0.788 (95% CI: 0.700-0.875, p < 0.01). Further analysis of classification shows that the rate of visual improvement in Type I: < 2 cm was 0.889(95% CI: 0.739-0.969), Type II:2-4 cm was 0.844(95% CI: 0.755-0.910), Type III: > 4 cm was 0.500(95% CI: 0.068-0.932) and the total was 0.853(95% CI: 0.779-0.927 p < 0.01) with low heterogeneity of I2 = 20.80%.Twelve studies separately reported GTR with OCU was 293; the rate of GTR was 0.911 (95% CI: 0.848-0.961, p < 0.01). And the rate of GTR in Type I: < 2 cm was 0.933(95% CI: 0.817-0.986), Type II:2-4 cm was 0.880(95% CI: 0.800-0.936), Type III: > 4 cm was 0.600(95% CI: 0.147-0.947). The total was 0.897(95% CI: 0.830-0.965 p < 0.01) with low heterogeneity of I2 = 34.57%. The related complications of OCU were visual deterioration and olfactory nerve damage. Visual decline was reported in nine studies, and the rate was 0.077 (95% CI: 0.041-0.113, p < 0.01). Six studies reported olfactory nerve damage, and the overall rate was 0.054 (95% CI: 0.019-0.090, p < 0.01). OCU could significantly recover preoperative impaired vision and make GTR easier to achieve, which was also a safe and effective technique in TSM.


Assuntos
Neoplasias Meníngeas , Meningioma , Neoplasias da Base do Crânio , Humanos , Meningioma/cirurgia , Período Pós-Operatório , Neoplasias da Base do Crânio/cirurgia , Neoplasias Meníngeas/cirurgia
7.
Eur Radiol ; 33(12): 9052-9062, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37405505

RESUMO

OBJECTIVES: To evaluate the predictive performance of pretreatment dual-energy CT (DECT) for early response to induction chemotherapy and survival in nasopharyngeal carcinoma (NPC). METHODS: In this retrospective study, 56 NPC patients who underwent pretreatment DECT scans with posttreatment follow-up were enrolled. The DECT-derived normalised iodine concentration (nIC), effective atomic number (Zeff), 40-180 keV (20 keV interval), and Mix-0.3 value of the tumour lesions were measured to predict the early response to induction chemotherapy and survival in nasopharyngeal carcinoma. The Mann‒Whitney U test, ROC analysis, Kaplan‒Meier method with log-rank test, and Cox proportional hazards model were performed to evaluate the predictive performance of DECT parameters, respectively. RESULTS: Among all DECT-derived parameters, ROC analysis showed the predictive performances of nIC and Zeff values for early objective response to induction chemotherapy (AUCs of 0.803 and 0.826), locoregional failure-free survival (AUCs of 0.786 and 0.767), progression-free survival (AUCs of 0.856 and 0.731) and overall survival (AUCs of 0.765 and 0.799) in NPC patients, respectively (all p < 0.05). Moreover, multivariate analysis showed that a high nIC value was an independent predictor of poor survival in NPC. In addition, survival analysis indicated that NPC patients with higher nIC values in primary tumours tend to have lower 5-year locoregional failure-free survival, progression-free survival and overall survival rates than those with lower nIC values. CONCLUSIONS: DECT-derived nIC and Zeff values can predict early response to induction chemotherapy and survival in NPC; in particular, a high nIC value is an independent predictive factor of poor survival in NPC. CLINICAL RELEVANCE STATEMENT: Preoperative dual-energy computed tomography may provide predictive value for early response and survival outcomes in patients with nasopharyngeal carcinoma, and facilitate their clinical management. KEY POINTS: • Pretreatment dual-energy computed tomography helps to predict early response to therapy and survival in NPC. • NIC and Zeff values derived from dual-energy computed tomography can predict early objective response to induction chemotherapy and survival in NPC. • A high nIC value is an independent predictive factor of poor survival in NPC.


Assuntos
Quimioterapia de Indução , Neoplasias Nasofaríngeas , Humanos , Carcinoma Nasofaríngeo/diagnóstico por imagem , Carcinoma Nasofaríngeo/tratamento farmacológico , Estudos Retrospectivos , Quimioterapia de Indução/métodos , Tomografia Computadorizada por Raios X/métodos , Neoplasias Nasofaríngeas/diagnóstico por imagem , Neoplasias Nasofaríngeas/tratamento farmacológico
8.
Huan Jing Ke Xue ; 44(7): 4201-4210, 2023 Jul 08.
Artigo em Chinês | MEDLINE | ID: mdl-37438317

RESUMO

Charcoal is a carbonaceous particulate matter with a highly aromatic structure produced by incomplete combustion, and it can cause persistent long-term effects on soil ecological functions. In this study, we determined soil organic carbon pools and associated enzyme activities following five years of different charcoal treatments[charcoal removal (B0), charcoal retained in situ (B1), and the addition of charcoal removed from B0(B2)] and the unburnt control (UB) in a recently harvested Pinus massoniana plantation subjected to broadcast burning. The results showed that dissolved organic carbon (DOC), microbial biomass carbon (MBC), coarse and fine particulate organic carbon (CPOC and FPOC), and recalcitrant carbon (RC) contents were significantly lower in B1 than those in UB soil (P<0.05). The MBC and FPOC contents of B2 soil were comparable to those of UB soil, which were significantly higher than those of B0 soil (P<0.001). There was no difference in MBC/TC between the B2 and UB soils, whereas MBC/TC was significantly lower in B0 than in UB soil (P<0.05). ß-glucosidase and peroxidase activities of B0, B1, and B2 soils were significantly lower than that of UB soil (P<0.01), and polyphenol oxidase activity was significantly lower in B0 and B2 soils than in UB soil (P<0.01). No significant difference in soil TC, DOC, readily oxidized carbon (ROC), CPOC, and RC content as well as associated enzyme activities was observed among the charcoal treatments (P>0.05). Redundancy analysis showed that sucrose and polyphenol oxidase were the key drivers influencing soil organic carbon fractions, accounting for 16.3% and 12.7% of the total variance, respectively. Overall, our findings indicated that fire-deposited charcoal played a positive role in enhancing soil microbial biomass carbon recovery, soil organic carbon accumulation, and stability, highlighting the importance of charcoal in the management of subtropical plantations in the future.


Assuntos
Carbono , Pinus , Carvão Vegetal , Solo , Catecol Oxidase , Matéria Orgânica Dissolvida
9.
Sci Rep ; 13(1): 7288, 2023 05 04.
Artigo em Inglês | MEDLINE | ID: mdl-37142638

RESUMO

This study aimed to explore how kinesin family member 2C (KIF2C) influences the progression of non-small cell lung cancer (NSCLC). The levels of KIF2C and microRNA-186-3p (miR-186-3p) were examined by quantitative real-time polymerase chain reaction (qRT-PCR). Through the utilization of cell counting kit-8 (CCK-8) assay, colony formation assay, wound closure assay, and Transwell assay, NSCLC cell proliferation, migration, and invasion were identified, respectively. NSCLC cell apoptosis was assessed using the TUNEL assay and flow cytometry (FCM) assay. Luciferase reporter analysis was used to investigate the relationship between KIF2C and miR-186-3p. Western blot assays were conducted to investigate the influence of KIF2C on the AKT-GSK3ß-ß-catenin pathway. The results showed that KIF2C was up-regulated in NSCLC cells, which predicted poor prognosis. KIF2C overexpression promoted the proliferation, migration, and invasion of NSCLC cells as well as inhibited NSCLC cell apoptosis. KIF2C was as a key target of miR-186-3p. High expression of KIF2C, meanwhile, increased the levels of ß-catenin, p-GSK-3ß and phosphorylated protein kinase B (p-AKT). KIF2C downregulation and miR-186-3p upregulation reversed these outcomes. As an oncogenic factor, KIF2C is negatively regulated by miR-186-3p and participates in the progression of NSCLC through the AKT-GSK3ß-ß-catenin pathway.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , MicroRNAs , Humanos , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Glicogênio Sintase Quinase 3 beta/genética , Glicogênio Sintase Quinase 3 beta/metabolismo , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/metabolismo , Proteínas Proto-Oncogênicas c-akt/genética , Proteínas Proto-Oncogênicas c-akt/metabolismo , MicroRNAs/metabolismo , beta Catenina/genética , beta Catenina/metabolismo , Linhagem Celular Tumoral , Proliferação de Células/genética , Movimento Celular/genética , Regulação Neoplásica da Expressão Gênica , Cinesinas/genética , Cinesinas/metabolismo
10.
Insights Imaging ; 14(1): 95, 2023 May 24.
Artigo em Inglês | MEDLINE | ID: mdl-37222846

RESUMO

BACKGROUND: Skull base invasion in nasopharyngeal carcinoma (NPC) was shown to be a poor negative prognostic factor, and dual-energy CT (DECT) has heralded a new approach to detect this condition. The study aims to evaluate the value of DECT for detection of skull base invasion in NPC and compare the diagnostic performance of DECT with those of simulated single-energy CT (SECT) and MRI. METHODS: The imaging findings of 50 NPC patients and 31 participants in control group which underwent DECT examinations were assessed in this retrospective study. The skull base invasions were evaluated using 5-point scale by two blind observers. ROC analysis, Mcnemar test, paired t test, weighted K statistics and intraclass correlation coefficient were performed to evaluate the diagnostic performance of simulated SECT, MRI and DECT. RESULTS: Quantitative analysis of DECT parameters showed higher normalized iodine concentration and effective atomic number values in sclerosis and lower values in erosion than those in normal bones (both p < 0.05). Compared with simulated SECT and MRI, the diagnostic sensitivity for DECT was significantly improved from 75% (simulated SECT) and 84.26% (MRI) to 90.74% (DECT) (both p < 0.001), specificity from 93.23% and 93.75% to 95.31 (both p < 0.001), accuracy from 86.67% and 90.33% to 93.67%, and AUC from 0.927 and 0.955 to 0.972 (both p < 0.05), respectively. CONCLUSIONS: DECT demonstrates better diagnostic performance than simulated SECT and MRI for detecting skull base invasions in NPC, even those slight bone invasions in early stage, with higher sensitivity, specificity and accuracy.

11.
Curr Med Imaging ; 2023 Mar 06.
Artigo em Inglês | MEDLINE | ID: mdl-36876841

RESUMO

OBJECTIVE: This study aimed to assess the response of combretastatin-A4-phosphate (CA4P) in rabbit VX2 liver tumors using intravoxel incoherent motion diffusion-weighted MRI (IVIM DW-MRI). METHODS: Forty rabbits with implanted VX2 liver tumors underwent baseline MRI and were then given 10 mg/kg CA4P (n=20) or saline (n=20). After 4 h, 10 rabbits from each group underwent an MRI examination and were then sacrificed. The remaining rabbits underwent MRI after 1, 3, and 7 days and were then sacrificed. Liver samples were processed for H&E and immunohistochemical staining. IVIM parameters (D, f, D*) were compared in the treatment and control groups, and the correlations of IVIM parameters with microvascular density (MVD) were determined. RESULTS: At 4 h, the two treatment groups had significantly different f and D* values (p<0.001), and these values were at their minimum in the treatment group. The treatment group had moderate correlations between MVD and f at 4 h (r=0.676, p=0.032) and 7 days (r=0.656, p=0.039) and with D* at 4 h (r=0.732, p=0.016) and 7 days (r=0.748, p=0.013), but no correlation was reported between MVD and f or D* in the control group (all P>0.05). CONCLUSION: IVIM DW-MRI is a sensitive imaging technique. It successfully evaluated the effect of CA4P on VX2 liver tumors in rabbits. The f and D* values correlated with MVD at 4 h and 7 days after using CA4P, indicating that these parameters have the potential to be used as indicators of tumor angiogenesis after treatment.

12.
Eur J Pharm Biopharm ; 186: 7-17, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-36858245

RESUMO

Chemotherapy is one of the most important treatments for malignant cancers, but most chemotherapeutic drugs are poorly targeted, highly toxic and expensive, resulting in unsatisfactory treatment results for cancer patients. Therefore, intelligent drug delivery platforms are needed to be explored urgently to enhance drug treatment and reduce toxicity on normal cells. Nucleic acid nanomaterials are a class of nanomaterials developed on the basis of the "base complementary pairing principle", which have the advantages of good programmability, high stability, good biocompatibility, and strong targeting. Herein, we present a simple Sgc8 aptamer-modified nucleic acid nanomaterial (Sgc8NM) for the targeted delivery of Doxorubicin (Dox), a widely used chemotherapy drug in clinic. Studies have shown the Sgc8NM-Dox performed a precise treatment effect on target cells and low toxicity on non-target cells, providing a new strategy for the potential application of nanocomposite drugs in targeted cancer delivery.


Assuntos
Aptâmeros de Nucleotídeos , Nanoestruturas , Neoplasias , Ácidos Nucleicos , Humanos , Doxorrubicina , Sistemas de Liberação de Medicamentos/métodos , Neoplasias/tratamento farmacológico , Linhagem Celular Tumoral
13.
Curr Med Imaging ; 19(9): 1063-1070, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36748216

RESUMO

OBJECTIVE: The present study aimed to improve the diagnosis and treatment outcome of cerebrospinal fluid (CSF) rhinorrhea caused by patent meningoencephalocele of Sternberg's canal of the sphenoid sinus by analyzing the clinical data and imaging features of two rare cases of this disease and by reviewing the relevant literature for possible etiology, diagnoses, and treatments. METHODS: Together with the relevant literature, we retrospectively studied the clinical and imaging data of two patients (mother and child) with CSF rhinorrhea caused by patent meningoencephalocele of Sternberg's canal of the sphenoid sinus, analyzed their diagnostic and treatment procedures, and proposed a potential, feasible treatment method. RESULTS: On the 2nd day after surgery, the expansive sponge and iodoform gauze in the nasal cavity were removed in both patients, and the lumbar subarachnoid drainage was removed 3 days after the operation, as no nasal discharge was observed. One week after the operation, head magnetic resonance imaging (MRI) showed that the abnormal tissue in the sphenoid sinus had disappeared, and no accumulation of the CSF was observed. Both patients were discharged after 2 weeks. At the time of discharge, both patients were without nasal drip, fever, headache, and other discomforts, and they had grade 5 muscle strength in their extremities, with normal muscle tension. CONCLUSION: CSF rhinorrhea is usually caused by secondary factors. Spontaneous CSF rhinorrhea caused by encephalocele of the skull base due to congenital dysplasia of the skull base is very rare and easily misdiagnosed. The presence of brain tissue or CSF signal in the sphenoid sinus on preoperative MR images is an important imaging feature of the disease. Conditional cisternography can be used to further detect CSF leaks. Endoscopic transnasal transsphenoidal repair of CSF leaks combined with short-term postoperative lumbar subarachnoid drainage is an effective treatment method. According to previous literature, the possible causes of meningoencephalocele with patent Sternberg's canal of the sphenoid sinus include abnormal development of the sphenoid sinus or the craniopharyngeal canal and bone defects of the skull base. There are no related reports on patent meningoencephalocele caused by Sternberg's canal in direct blood relatives, such as mother-son; therefore, the possibility of this disease having a genetic origin should be considered in future studies on its pathophysiological mechanisms.


Assuntos
Rinorreia de Líquido Cefalorraquidiano , Meningocele , Criança , Humanos , Meningocele/complicações , Meningocele/diagnóstico por imagem , Meningocele/cirurgia , Rinorreia de Líquido Cefalorraquidiano/diagnóstico , Rinorreia de Líquido Cefalorraquidiano/etiologia , Rinorreia de Líquido Cefalorraquidiano/cirurgia , Seio Esfenoidal/diagnóstico por imagem , Seio Esfenoidal/cirurgia , Seio Esfenoidal/patologia , Estudos Retrospectivos , Tomografia Computadorizada por Raios X , Encefalocele/complicações , Encefalocele/diagnóstico por imagem
14.
Am J Transl Res ; 14(8): 5379-5393, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36105012

RESUMO

OBJECTIVES: N6-methyladenosine (m6A), a predominant RNA modification, has been recently linked to messenger RNA splicing, stability and expression, and its dysregulation may be important in the initiation as well as development of human cancers. The current study was proposed to investigate the clinico-pathological value and multiomic characteristics of m6A-linked genes in the diagnosis and prognosis of lung adenocarcinoma (LUAD). METHODS: The expression levels and mutation types of 21 previously identified m6A regulators were analyzed using the TCGA (The Cancer Genome Atlas) database. The patients were categorized into two groups, a training group (n=392) and a testing group (n=98). Next, the prognostic score of m6A regulators was determined by the Cox survival analysis and a regression model of LASSO to develop a risk profile for patients with LUAD. Moreover, features of risk signature, including chemosensitivity, tumor immune microenvironment and genetic mutation, were also explored. RESULTS: In total, 18 of 21 m6A regulators showed significantly differential expression in LUAD (P<0.05). Among them, 6 genes were observed to be associated with the Overall Survival (OS) of patients with LUAD. Three genes (IGF2BP1 and 2, and HNRNPC) were further evaluated as a prognostic signature in LUAD. Patients, grouped as high risk based on the median of risk score, had poorer OS in comparison with those in low-risk group (P<0.05). The accuracy of our prognostic signatures was high: the AUC were 0.67, 0.59, 0.64 (training set), and 0.65, 0.69, 0.64 (testing set) at survival of 1- , 3- and 5-year, respectively. The prognostic performance of IGF2BP1, IGF2BP2 and HNRNPC was successfully validated in two independent external cohorts. High-risk score was an indicator of chemoresistance, TP53 mutation and increased infiltration of immune cells, and in vitro assessment of the cellular function of HNRNPC confirmed that the gene is involved in cell proliferation and invasion. CONCLUSION: The prognostic signature based on m6A regulators might provide novel insights into prognostic assessment and individualized treatment for patients with LUAD.

15.
Anal Chim Acta ; 1221: 340132, 2022 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-35934367

RESUMO

MicroRNAs (miRNAs) and p53 gene can serve as valuable biomarkers for the diagnosis of a variety of cancers. Nevertheless, although the development of the DNA nanostructure on the detection of cancer-related biomarkers was initially demonstrated several years ago, the challenges of developing simpler, cheaper, and multi-level detection DNA biosensors persist. Herein, based on the rolling circle amplification (RCA) coupled with the target-triggered skill, we have developed a well-designed detecting platform. In this study, the dumbbell-shaped probes (DPP) could be cyclized and initiated through targets, thus beginning the target-catalyst RCA (tc-RCA) reaction, therefore engendering numerous dumbbell probe amplicons (DPA). Thereafter the probe primers (PP) mutually complementary to the loop of DPA was introduced, leading to the branch strand displacement reaction (B-SDA). SYBR Green I can effectively bind to the amplified double-stranded structures as a fluorescent reporter. Altering the target-binding sequence of the DPP, this biosensor can also be applied to detect different biomarkers. As a consequence, target miR-21 and p53 gene can be detected down to 0.65 fM and 2.04 fM respectively with a wide dynamic range. Moreover, we have also achieved the qualitative detection of interesting targets in cell lysates as well as the complex biological substrates and compared the results with reverse transcription quantitative PCR (RT-qPCR), thereby indicating the potential application in clinical diagnosis and biomedical research.


Assuntos
MicroRNAs , Técnicas de Amplificação de Ácido Nucleico , Biomarcadores , DNA/química , Genes p53 , Limite de Detecção , MicroRNAs/análise , MicroRNAs/genética , Técnicas de Amplificação de Ácido Nucleico/métodos
16.
Artigo em Inglês | MEDLINE | ID: mdl-35711498

RESUMO

Objective: To compare of the efficacy and safety of neuroendoscopic endonasal transsphenoidal surgeries and intracranial endoscopic pterional approach in resection of tuberculum sellae meningioma. Methods: From January 2014 to June 2021, 60 patients with tuberculum sellae meningioma diagnosed and treated in our hospital were enrolled and randomly divided into study group and control group. The tuberculum sellae meningioma was removed by neuroendoscopic endonasal transsphenoidal surgeries in the study group, while the intracranial endoscopic pterional approach was used in the control group. The chi-square test was used to compare the differences of tumor complete resection rate, visual acuity improvement rate, total effective rate at 3 months after operation, and adverse reactions between the two groups. Results: The clinical characteristics of the two groups were comparable (P > 0.05). After surgical treatment, the complete resection rate in the study group was higher than that in the control group (93.3% vs 70.0%), and the difference was statistically significant (P=0.020). After treatment, the visual acuity improvement rate of the study group was 83.3% (25/30), which was significantly higher than that of the control group (60.0%, 18/30), and the difference was statistically significant (χ 2 = 4.022, P=0.045). After surgical treatment, the total effective rate at 3 months after operation was higher in the study group than in the control group (96.7% vs 83.3%), with statistical significance (P=0.041). There was no significant difference in postoperative adverse reactions between the study group and control group (33.3% vs 30.0%, P=0.781). Conclusion: The neuroendoscopic endonasal transsphenoidal surgeries has significant efficacy and can significantly improve the visual acuity of patients without increasing adverse reactions, which is worthy of clinical promotion.

17.
Talanta ; 244: 123412, 2022 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-35405462

RESUMO

Lung cancer with worldwide distribution, high incidence and low survival rate is significantly and increasingly threatening human health. Thus, the specific detection of lung cancer-associated biomarkers is of crucial importance in early diagnosis and treatment. In this work, taking microRNA-21 as an example, a biosensor is proposed via a stimuli-induced strand displacement amplification (SDA) and cascade signal amplification with the assistance of polymerase. An allosteric molecular beacon (MB) with chemical modification is designed to emit the enhanced fluorescent signal in presence of microRNA target. The sensing system possesses a linear calibration curve from 5 pM to 40 nM with the limit of detection (LOD) of 0.7 pM and displays good specificity to discriminate coexisting microRNAs. In addition, the feasibility is confirmed by performing the detection of miRNA-21 extracted from non-small cell lung cancer (NSCLC) A549 cells, and a good recovery is achieved in complex human serum sample. Therefore, the miRNA-triggered cascaded amplification would be crucial strategy to facilitate microRNA analysis in the biological detection and broad clinical applications.


Assuntos
Técnicas Biossensoriais , Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , MicroRNAs , Biomarcadores Tumorais/genética , Carcinoma Pulmonar de Células não Pequenas/diagnóstico , Carcinoma Pulmonar de Células não Pequenas/genética , Humanos , Limite de Detecção , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/genética , MicroRNAs/análise , Técnicas de Amplificação de Ácido Nucleico
18.
J Comput Assist Tomogr ; 46(2): 264-268, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35297583

RESUMO

PURPOSE: To determine magnetic resonance imaging (MRI) with readout-segmented diffusion-weighted imaging (RESOLVE-DWI) and dual-energy computed tomography (DECT) features of sinonasal extramedullary plasmacytoma (SN-EMP). METHODS: The MRI and/or DECT of 10 patients with SN-EMP confirmed by pathology were retrospectively reviewed. Apparent diffusion coefficient (ADC) values of RESOLVE-DWI were analyzed in 9 patients. The quantitative parameters derived from DECT, including the iodine concentration (IC), effective atomic number, and the slope (k) of spectral attenuation curve, were measured in 3 patients. RESULTS: On conventional MRI, typical lesions were well defined (7 of 9), and isointense to the brain on both T1WI and T2WI (9 of 9). Most lesions presented with marked enhancement on contrast-enhanced T1WI without significant necrosis (8 of 9). Notably, multiple flow-void signals were observed in all lesions (9 of 9). On RESOLVE-DWI, the average ADC value was 0.55 × 10-3 mm2/s, and the normalized ADC value was 0.66 ± 0.04. On DECT, the average values of IC, effective atomic number, and slope (k) was 2.7 mg/mL, 8.62, and 3.8, respectively. CONCLUSIONS: Some typical MRI features (well-defined mass, isointensity to the brain, marked enhancement without obvious cystic changes, multiple flow voids, and a lower ADC value) strongly suggest the diagnosis of SN-EMP. The quantitative parameters derived from RESOLVE-DWI and DECT may provide more information for the diagnosis of SN-EMP.


Assuntos
Plasmocitoma , Encéfalo , Imagem de Difusão por Ressonância Magnética/métodos , Humanos , Imageamento por Ressonância Magnética/métodos , Plasmocitoma/diagnóstico por imagem , Estudos Retrospectivos
19.
Huan Jing Ke Xue ; 43(2): 1059-1068, 2022 Feb 08.
Artigo em Chinês | MEDLINE | ID: mdl-35075880

RESUMO

Soil enzyme activity is an important index to characterize the nutrient requirements and nutrient limitations of soil microorganisms. In this study, Pinus massoniana plantations of different stand ages (9, 17, 26, 34, and 43 a) in mid-subtropical China were taken as the research object; the activities of ß-glucosidase (BG), N-acetyl-ß-glucosaminidase (NAG), leucine amino-peptidase (LAP), acid phosphatase (AP), polyphenol oxidase (POX), and peroxidase (POD) were determined; and soil enzyme stoichiometric ratios were also calculated to investigate the soil microbial nutrient limitations of P. massoniana plantation development. The results showed that the activities of BG, NAG, AP, POX, and POD were enhanced with the increase in stand age, and the activity of LAP was the lowest at 17 a, which showed a significant difference and fluctuated among the neighboring stand ages. The soil enzyme C:N:P stoichiometric ratio was 1:1:0.56, which deviated from the global ecosystem enzyme C:N:P stoichiometric ratio (1:1:1). The enzyme C:N increased, whereas the enzyme N:P decreased, with increasing stand age, and both ratios tended to be stable after 17 a. There was no significant difference in enzyme N:P among different stand ages. The vector length of enzyme stoichiometry was not significantly different among the five stand ages. The vector angles increased with the increase in stand ages and tended to be stable after 17 a of stand age, but the angles were less than 45°. Redundancy analysis (RDA) revealed that soil carbon quality index and pH were the main factors influencing soil enzyme activity and the associated stoichiometric ratio. Our findings indicated that P. massoniana plantation soil microorganisms at different growth stages were all subjected to N limitation, and the N limitation was alleviated with the increase in stand age; however, the P requirement was gradually enhanced. Therefore, the management of P. massoniana plantations should take care to increase nitrogen fertilizer at the early growth stage of P. massoniana, and more phosphorus fertilizers need to be applied with nitrogen at the late growth stage in order to maintain the productivity and sustainable development of P. massoniana plantations.


Assuntos
Pinus , Solo , Carbono/análise , China , Ecossistema , Nitrogênio/análise , Fósforo/análise , Microbiologia do Solo
20.
Acta Pharmacol Sin ; 43(6): 1453-1460, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-34446852

RESUMO

Glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) are regarded as 'incretins' working closely to regulate glucose homeostasis. Unimolecular dual and triple agonists of GLP-1R and GIPR have shown remarkable clinical benefits in treating type 2 diabetes. However, their pharmacological characterization is usually carried out in a single receptor-expressing system. In the present study we constructed a co-expression system of both GLP-1R and GIPR to study the signaling profiles elicited by mono, dual and triple agonists. We show that when the two receptors were co-expressed in HEK 293T cells with comparable receptor ratio to pancreatic cancer cells, GIP predominately induced cAMP accumulation while GLP-1 was biased towards ß-arrestin 2 recruitment. The presence of GIPR negatively impacted GLP-1R-mediated cAMP and ß-arrestin 2 responses. While sharing some common modulating features, dual agonists (peptide 19 and LY3298176) and a triple agonist displayed differentiated signaling profiles as well as negative impact on the heteromerization that may help interpret their superior clinical efficacies.


Assuntos
Diabetes Mellitus Tipo 2 , Peptídeo 1 Semelhante ao Glucagon , Diabetes Mellitus Tipo 2/tratamento farmacológico , Polipeptídeo Inibidor Gástrico , Peptídeo 1 Semelhante ao Glucagon/agonistas , Receptor do Peptídeo Semelhante ao Glucagon 1/genética , Receptor do Peptídeo Semelhante ao Glucagon 1/metabolismo , Glucose , Células HEK293 , Humanos , beta-Arrestina 2
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