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1.
Food Chem X ; 22: 101395, 2024 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-38694544

RESUMO

Xinyu mandarin is popular for its good flavor, but its flavor deteriorates during postharvest storage. To better understand the underlying basis of this change, the dynamics of the sensory profiles were investigated throughout fruit ripening and storage. Sweetness and sourness, determined especially by sucrose and citric acid content, were identified as the key sensory factors in flavor establishment during ripening, but not in flavor deterioration during storage. Postharvest flavor deterioration is mainly attributed to the reduction of retronasal aroma and the development of off-flavor. Furthermore, sugars, acids and volatile compounds were analyzed. Among the 101 detected volatile compounds, 10 changed significantly during the ripening process. The concentrations of 15 volatile components decreased during late postharvest storage, among which α-pinene and d-limonene were likely to play key roles in the reduction of aroma. Three volatile compounds were found to increase during storage, associated with off-flavor development.

2.
Heliyon ; 10(7): e28218, 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38560106

RESUMO

Host-virus interactions can significantly impact the viral life cycle and pathogenesis; however, our understanding of the specific host factors involved in highly pathogenic avian influenza A virus H7N9 (HPAI H7N9) infection is currently restricted. Herein, we designed and synthesized 65 small interfering RNAs targeting host genes potentially associated with various aspects of RNA virus life cycles. Afterward, HPAI H7N9 viruses were isolated and RNA interference was used to screen for host factors likely to be involved in the life cycle of HPAI H7N9. Moreover, the research entailed assessing the associations between host proteins and HPAI H7N9 proteins. Twelve key host proteins were identified: Annexin A (ANXA)2, ANXA5, adaptor related protein complex 2 subunit sigma 1 (AP2S1), adaptor related protein complex 3 subunit sigma 1 (AP3S1), ATP synthase F1 subunit alpha (ATP5A1), COPI coat complex subunit alpha (COP)A, COPG1, heat shock protein family A (Hsp70) member 1A (HSPA)1A, HSPA8, heat shock protein 90 alpha family class A member 1 (HSP90AA1), RAB11B, and RAB18. Co-immunoprecipitation revealed intricate interactions between viral proteins (hemagglutinin, matrix 1 protein, neuraminidase, nucleoprotein, polymerase basic 1, and polymerase basic 2) and these host proteins, presumably playing a crucial role in modulating the life cycle of HPAI H7N9. Notably, ANXA5, AP2S1, AP3S1, ATP5A1, HSP90A1, and RAB18, were identified as novel interactors with HPAI H7N9 proteins rather than other influenza A viruses (IAVs). These findings underscore the significance of host-viral protein interactions in shaping the dynamics of HPAI H7N9 infection, while highlighting subtle variations compared with other IAVs. Deeper understanding of these interactions holds promise to advance disease treatment and prevention strategies.

3.
Sci Rep ; 14(1): 7674, 2024 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-38561370

RESUMO

In the absence of evidence-based guidance on the impact of hydroxychloroquine (HCQ) blood concentration on efficacy and ocular toxicity in systemic lupus erythematosus (SLE), the clinical monitoring of HCQ blood concentration is not yet widely performed, which raised concerns about the necessity of conducting HCQ blood concentration monitoring. In this retrospective study, we consecutively enrolled 135 patients with SLE who received HCQ treatment for more than 6 months from July 2022 to December 2022. Ocular toxicity was evaluated by collecting relevant retinal parameters using optical coherence tomography angiography (OCTA). Therapeutic efficacy was evaluated using the SLE disease activity index (SLEDAI) and relevant clinical parameters. HCQ blood concentration was determined by high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS). Spearman correlation analysis revealed that the cumulative dose of HCQ was positively correlated with the foveal avascular zone (FAZ) perimeter and FAZ area (r = 0.734, P < 0.001; r = 0.784, P < 0.001). Meanwhile, the treatment duration of HCQ was positively correlated with FAZ perimeter and FAZ area (r = 0.761, P < 0.001; r = 0.882, P < 0.001). The univariate and multivariate logistic regression analyses indicated that HCQ blood concentration was associated with the disease activity of patients with SLE (odds ratio 0.994, 95% CI 0.990-0.999). HCQ blood concentration may be an important factor in assessing the therapeutic effectiveness of SLE patients. The HCQ-related ocular toxicity was a long-term effect related to long term exposure, rather than the blood concentration of HCQ at the time of testing. More importantly, when addressing HCQ-related ocular toxicity, it may be crucial to pay attention to the cumulative dose and treatment duration of HCQ.


Assuntos
Antirreumáticos , Lúpus Eritematoso Sistêmico , Humanos , Hidroxicloroquina/efeitos adversos , Antirreumáticos/efeitos adversos , Espectrometria de Massas em Tandem , Estudos Retrospectivos , Neuropatia Óptica Tóxica/tratamento farmacológico , Lúpus Eritematoso Sistêmico/tratamento farmacológico
4.
EBioMedicine ; 98: 104870, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37967508

RESUMO

BACKGROUND: Nasopharyngeal carcinoma (NPC) is a malignant head and neck cancer with a high incidence in Southern China and Southeast Asia. Patients with remote metastasis and recurrent NPC have poor prognosis. Thus, a better understanding of NPC pathogenesis may identify novel therapies to address the unmet clinical needs. METHODS: H3K27ac ChIP-seq and HiChIP was applied to understand the enhancer landscapes and the chromosome interactions. Whole genome sequencing was conducted to analyze the relationship between genomic variations and epigenetic dysregulation. CRISPRi and JQ1 treatment were used to evaluate the transcriptional regulation of SOX2 SEs. Colony formation assay, survival analysis and in vivo subcutaneous patient-derived xenograft assays were applied to explore the function and clinical relevance of SOX2 in NPC. FINDINGS: We globally mapped the enhancer landscapes and generated NPC enhancer connectomes, linking NPC specific enhancers and SEs. We found five overlapped genes, including SOX2, among super-enhancer regulated genes, survival related genes and NPC essential genes. The mRNA expression of SOX2 was repressed when applying CRISPRi targeting different SOX2 SEs or JQ1 treatment. Next, we identified a genetic variation (Chr3:181422197, G > A) in SOX2 SE which is correlated with higher expression of SOX2 and poor survival. In addition, SOX2 was highly expressed in NPC and is correlated with short survival in patients with NPC. Knock-down of SOX2 suppressed tumor growth in vitro and in vivo. INTERPRETATION: Our study demonstrated the super-enhancer landscape with chromosome interactions and identified super-enhancer driven SOX2 promotes tumorigenesis, suggesting that SOX2 is a potential therapeutic target for patients with NPC. FUNDING: A full list of funding bodies that contributed to this study can be found in the Acknowledgements section.


Assuntos
Neoplasias Nasofaríngeas , Humanos , Carcinoma Nasofaríngeo/genética , Carcinoma Nasofaríngeo/patologia , Neoplasias Nasofaríngeas/genética , Neoplasias Nasofaríngeas/patologia , Recidiva Local de Neoplasia/genética , Análise de Sobrevida , Cromatina/genética , Linhagem Celular Tumoral , Regulação Neoplásica da Expressão Gênica , Proliferação de Células , Fatores de Transcrição SOXB1/genética , Fatores de Transcrição SOXB1/metabolismo
5.
Chaos ; 33(8)2023 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-37549113

RESUMO

Epidemics pose a significant threat to societal development. Accurately and swiftly identifying the source of an outbreak is crucial for controlling the spread of an epidemic and minimizing its impact. However, existing research on locating epidemic sources often overlooks the fact that epidemics have an incubation period and fails to consider social behaviors like self-isolation during the spread of the epidemic. In this study, we first take into account isolation behavior and introduce the Susceptible-Exposed-Infected-Recovered (SEIR) propagation model to simulate the spread of epidemics. As the epidemic reaches a certain threshold, government agencies or hospitals will report the IDs of some infected individuals and the time when symptoms first appear. The reported individuals, along with their first and second-order neighbors, are then isolated. Using the moment of symptom onset reported by the isolated individuals, we propose a node-level classification method and subsequently develop the node-level-based source identification (NLSI) algorithm. Extensive experiments demonstrate that the NLSI algorithm is capable of solving the source identification problem for single and multiple sources under the SEIR propagation model. We find that the source identification accuracy is higher when the infection rate is lower, and a sparse network structure is beneficial to source localization. Furthermore, we discover that the length of the isolation period has little impact on source localization, while the length of the incubation period significantly affects the accuracy of source localization. This research offers a novel approach for identifying the origin of the epidemic associated with our defined SEIR model.


Assuntos
Epidemias , Humanos , Surtos de Doenças , Suscetibilidade a Doenças , Algoritmos
6.
Clin Sci (Lond) ; 137(4): 303-316, 2023 02 27.
Artigo em Inglês | MEDLINE | ID: mdl-36749124

RESUMO

BACKGROUND: Postoperative transarterial chemoembolization (PA-TACE) is an effective adjuvant therapy for preventing early postoperative recurrence of hepatocellular carcinoma (HCC); however, many patients are insensitive to it. Therefore, the present study aimed to explore the in-depth reasons for PA-TACE resistance and provide a reliable basis for selecting patients who will benefit the most from PA-TACE. METHODS: The unique gene expression profiles of primary tumors from PA-TACE-sensitive or -insensitive patients were analyzed using microarray data. Combined differential expression analysis, gene set enrichment analysis (GSEA), and weighted correlation network analysis (WGCNA) were used to screen for potential drivers of PA-TACE insensitivity. The expression of ALDOB was silenced or overexpressed in hepatoma cell lines, and changes in glycolytic activity, cycle, apoptosis, and malignant biological phenotypes were observed under normoxia and hypoxia. Finally, an animal model was constructed to verify the effects of ALDOB dysregulation on the tumorigenic ability of HCC cells in vivo. RESULTS: The inhibition of ALDOB promoted the up-regulation of Ki67 expression, and glycolytic activity was significantly enhanced. Moreover, the proliferation, invasion, and migration capabilities were increased in HCC cells and even worse in hypoxia. This advantage of malignant behavior was also validated using in vivo models. CONCLUSION: Down-regulation of ALDOB may underlie the metabolic reprogramming observed in HCC by promoting the malignant behavior of HCC cells. Hypoxia and ALDOB down-regulation acted additively, which was closely related to PA-TACE insensitivity. The use of ALDOB and Ki67 as a combined marker has the potential to identify the 'PA-TACE beneficiary population'.


Assuntos
Carcinoma Hepatocelular , Quimioembolização Terapêutica , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/terapia , Carcinoma Hepatocelular/patologia , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/terapia , Neoplasias Hepáticas/patologia , Regulação para Baixo , Antígeno Ki-67 , Prognóstico , Hepatectomia , Estudos Retrospectivos
8.
BMC Infect Dis ; 22(1): 868, 2022 Nov 21.
Artigo em Inglês | MEDLINE | ID: mdl-36411430

RESUMO

BACKGROUND: Human brucellosis has become one of the major public health problems in China, and increases atypical manifestations, such as fever of unknown origin (FUO), and misdiagnosis rates has complicated the diagnosis of brucellosis. To date, no relevant study on the relationship between brucellosis and FUO has been conducted. METHODS: We retrospectively reviewed the medical charts of 35 patients with confirmed human brucellosis and prospectively recorded their outcomes by telephone interview. The patients were admitted to the Second Affiliated Hospital of Nanchang University between January 01, 2013 and October 31, 2019. Patient data were collected from hospital medical records. RESULTS: The percentage of males was significantly higher than that of female in FUO (78.95% vs. 21.05%, P < 0.05), and 80% of the patients had a clear history of exposure to cattle and sheep. Moreover, 19 (54%) cases were hospitalized with FUO, among which the patients with epidemiological histories were significantly more than those without (P < 0.05). The incidence of toxic hepatitis in FUO patients was higher than that in non-FUO patients (89% vs. 50%, P < 0.05). Meanwhile, the misdiagnosis rate was considerably higher in the FUO group than in the non-FUO group (100% vs. 63%; P < 0.05). CONCLUSION: Brucellosis is predominantly FUO admission in a non-endemic area of China, accompanied by irregular fever and toxic hepatitis. Careful examination of the epidemiological history and timely improvement of blood and bone marrow cultures can facilitate early diagnosis and prevent misdiagnosis.


Assuntos
Brucelose , Doença Hepática Induzida por Substâncias e Drogas , Febre de Causa Desconhecida , Masculino , Humanos , Feminino , Bovinos , Ovinos , Animais , Febre de Causa Desconhecida/diagnóstico , Febre de Causa Desconhecida/epidemiologia , Febre de Causa Desconhecida/etiologia , Estudos Retrospectivos , Brucelose/complicações , Brucelose/diagnóstico , Brucelose/epidemiologia , Hospitalização
9.
Rare Metals ; 41(12): 4138-4148, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36157375

RESUMO

The daily life of people in the intelligent age is inseparable from electronic device, and a number of bacteria on touch screens are increasingly threatening the health of users. Herein, a photocatalytic TiO2/Ag thin film was synthesized on a glass by atomic layer deposition and subsequent in situ reduction. Ultraviolet-visible (UV-Vis) spectra showed that this film can harvest the simulated solar light more efficiently than that of pristine TiO2. The antibacterial tests in vitro showed that the antibacterial efficiency of the TiO2/Ag film against S. aureus and E. coli was 98.2% and 98.6%, under visible light irradiation for 5 min. The underlying mechanism was that the in-situ reduction of Ag on the surface of TiO2 reduced the bandgap of TiO2 from 3.44 to 2.61 eV due to the formation of Schottky heterojunction at the interface between TiO2 and Ag. Thus, TiO2/Ag can generate more reactive oxygen species for bacterial inactivation on the surface of electronic screens. More importantly, the TiO2/Ag film had great biocompatibility with/without light irradiation. The platform not only provides a more convenient choice for the traditional antibacterial mode but also has limitless possibilities for application in the field of billions of touch screens.

10.
Mol Cancer ; 21(1): 153, 2022 07 25.
Artigo em Inglês | MEDLINE | ID: mdl-35879762

RESUMO

BACKGROUND: Cell division cycle 6 (CDC6) has been proven to be associated with the initiation and progression of human multiple tumors. However, it's role in glioma, which is ranked as one of the common primary malignant tumor in the central nervous system and is associated with high morbidity and mortality, is unclear. METHODS: In this study, we explored CDC6 gene expression level in pan-cancer. Furthermore, we focused on the relationships between CDC6 expression, its prognostic value, potential biological functions, and immune infiltrates in glioma patients. We also performed vitro experiments to assess the effect of CDC6 expression on proliferative, apoptotic, migrant and invasive abilities of glioma cells. RESULTS: As a result, CDC6 expression was upregulated in multiple types of cancer, including glioma. Moreover, high expression of CDC6 was significantly associated with age, IDH status, 1p/19q codeletion status, WHO grade and histological type in glioma (all p < 0.05). Meanwhile, high CDC6 expression was associated with poor overall survival (OS) in glioma patients, especially in different clinical subgroups. Furthermore, a univariate Cox analysis showed that high CDC6 expression was correlated with poor OS in glioma patients. Functional enrichment analysis indicated that CDC6 was mainly involved in pathways related to DNA transcription and cytokine activity, and Gene Set Enrichment Analysis (GSEA) revealed that MAPK pathway, P53 pathway and NF-κB pathway in cancer were differentially enriched in glioma patients with high CDC6 expression. Single-sample gene set enrichment analysis (ssGSEA) showed CDC6 expression in glioma was positively correlated with Th2 cells, Macrophages and Eosinophils, and negative correlations with plasmacytoid dendritic cells, CD8 T cells and NK CD56bright cells, suggesting its role in regulating tumor immunity. Finally, CCK8 assay, flow cytometry and transwell assays showed that silencing CDC6 could significantly inhibit proliferation, migration, invasion, and promoted apoptosis of U87 cells and U251 cells (p < 0.05). CONCLUSION: In conclusion, high CDC6 expression may serve as a promising biomarker for prognosis and correlated with immune infiltrates, presenting to be a potential immune therapy target in glioma.


Assuntos
Neoplasias Encefálicas , Glioma , Biomarcadores , Neoplasias Encefálicas/metabolismo , Proteínas de Ciclo Celular/genética , Glioma/patologia , Humanos , NF-kappa B , Proteínas Nucleares/genética , Prognóstico
11.
Quant Imaging Med Surg ; 12(1): 823-837, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34993121

RESUMO

BACKGROUND: To investigate the differences of retinal thickness (RT) and superficial vascular density (SVD) between patients with systemic lupus erythematosus (SLE) and healthy controls using optical coherence tomography angiography (OCTA). METHODS: Individuals with SLE (n=12; 24 eyes) and healthy controls (n=12; 24 eyes) were recruited to this study. The study protocol was in accordance with the tenets of the Declaration of Helsinki (as revised in 2013). The monocular best-corrected visual acuity (BCVA) was determined using a Snellen eye chart. Each image was segmented into 9 early treatment diabetic retinopathy study subregions, within which the macular RT and SVD were measured by OCTA. The vascular perfusion area as a percentage of the measured area was considered to be the vascular density. RESULTS: The mean age of the SLE group was 33.80±9.49 years, and the mean age of the control group was 33.20±9.41 years. The mean duration of SLE was 4.33±2.67 years. The BCVA was significantly different between the SLE and control groups (0.17±0.20 vs. 0.05±0.07, respectively; P=0.021). In the SLE group, inner RT was reduced in the outer superior and temporal regions and full RT was reduced in the outer temporal region, compared with the control group (P<0.05). In the outer temporal region, the area under the receiver operating characteristic curve (AUC) for the inner RT was 0.805 [95% confidence interval (CI): 0.674 to 0.935], and the full RT was 0.828 (95% CI: 0.701 to 0.955). Thinning of RT was negatively correlated with erythrocyte sedimentation rate (ESR) in the inner retina at the outer temporal and outer superior regions and the full retina at the outer temporal region (P<0.05). The SVD was significantly lower in SLE participants than in controls in the central region, all 4 inner quadrants, and 4 outer quadrants (P<0.05). In the SLE group, SVD was positively correlated with inner RT in the outer superior region, inner RT, and full RT in the outer temporal region (P<0.05). CONCLUSIONS: Variations in RT within the macular area may affect visual acuity. The OCTA measurement of RT may be a potential marker for diagnosis of SLE and an indicator of its inflammatory activity.

12.
Mitochondrial DNA B Resour ; 7(1): 273-274, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35097213

RESUMO

Pseudosasa usawae is an endemic species in Taiwan, and grows at an altitude of 600-1200 m. In this study, we fully characterized the complete chloroplast genome of P. usawae. The complete chloroplast sequence was 139,660 bp, including large single-copy (LSC), small single-copy (SSC), and a pair of invert repeats (IR) region of 83,271, 12,803, and 21,793 bp. Besides, the plastid genome comprised a total of 129 genes, including protein-coding, tRNA, and rRNA genes as 83, 38, and 8 genes. Phylogenetic analysis reveals that P. usawae is closely associated with Phyllostachys genus clade, sister to the lineage of Phyllostachys.

13.
Phytochemistry ; 195: 113048, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-34890889

RESUMO

Epigenetic modifiers are proved to be effective specialized products-mining tools by rationally regulating the gene expression of fungal biosynthetic pathways. Chemical investigation on the histone deacetylase inhibitor (HDI) vorinostat (also known as SAHA)-modified cultures of the basidiomycete Cyathus stercoreus (Schwein.) De Toni (Nidulariaceae) led to the isolation of nine previously undescribed sesquiterpenes, and four previously described ones. The structures of the nine undescribed compounds were determined by extensive NMR spectroscopic analysis, HRESIMS analysis, as well as ECD and NMR calculations. Notably, the isolated sesquiterpenes are exclusive or overproduced from the epigenetic modified cultures compared to the negative control cultures. Additionally, the skeleton types of the isolated sesquiterpenes include protoilludalane, illudalane, 1,11-seco-protoilludalane, 10,11-seco-illudalane, and 14(11→10)abeo-illudalane. It is noteworthy that the 14(11→10)abeo-illudalane skeleton is reported for the first time. Cystercorodiol A, 4-O-acetylcybrodol, cystercorotone, and cybrodol showed weak inhibitory activity against the bacterium Escherichia coli ATCC25922 with the inhibitory rates 34.7%, 33.0%, 32.3%, and 29.6% at the concentration 200 µM, respectively. This study suggested that epigenetic modifiers are also an effective tool for specialized metabolite-mining in basidiomycetes.


Assuntos
Agaricales , Basidiomycota , Sesquiterpenos , Cyathus , Inibidores de Histona Desacetilases/farmacologia , Estrutura Molecular , Sesquiterpenos/farmacologia , Esqueleto
14.
Front Med (Lausanne) ; 8: 724283, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34926488

RESUMO

Purpose: To evaluate the conjunctival and fundus retinal vessel density in patients with systemic lupus erythematosus (SLE) with optical coherence tomography angiography (OCTA), and to investigate the relationship between vessel density and clinical indicators. Methods: Twelve patients with SLE (24 eyes) and 12 healthy controls (24 eyes) were recruited. OCTA was used to examine the superficial retina layer (SRL) and deep retina layer (DRL) in the macular retina and conjunctival capillary plexus of each eye. We calculated the density of the temporal conjunctival vessels, fundus microvascular (MIR), macrovascular (MAR) and total MIR(TMI) and compared the results in both groups. We used annular partitioning (C1-C6), hemispheric quadrants, and Early Treatment Diabetic Retinopathy Study partitioning (ETDRS) to analyze changes in the retinal vascular density. Correlation analysis was used to investigate the association between blood capillary density and clinical indicators. Results: OCTA results showed significant differences in the conjunctival microvascular density (p < 0.001). There was no significant difference in MIR, TMI, and MAR in the superficial layers between the SLE and healthy group (p > 0.05). The DRL and DTMI (Deeper TMI) densities were decreased in the macular regions of SLE patients (p < 0.05). In the hemispheric segmentation analysis, the superficial MIR was significantly decreased in the IL (inferior left) region of the SLE patients (p < 0.05), and the deep MIR in the IR (inferior right) region was significantly reduced (p < 0.05). In the ETDRS partitioning analysis, the superficial MIR in the inferior, right, and left subdivisions was significantly decreased in the SLE patients (p < 0.05). In the circular segmentation analysis, the deep MIR in the C1 and C3 regions was significantly reduced in SLE patients (p < 0.05), while the superficial MIR density was decreased only in the C3 region (p < 0.05). The conjunctival vascular density was negatively correlated with the STMI (Superficial TMI) (r = -0.5107; p = 0.0108) and DTMI (r = -0.9418, p < 0.0001). There was no significant correlation between vascular density and SLEDAI-2k (Systemic Lupus Erythematosus Disease Activity Index-2000) (P > 0.05). Conclusion: Clinically, patients with SLE and patients suspected of SLE should receive OCTA examination in a comprehensive eye examination to detect changes in ocular microcirculation at an early stage.

16.
J Transl Med ; 19(1): 301, 2021 07 12.
Artigo em Inglês | MEDLINE | ID: mdl-34247626

RESUMO

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is a fatal disease with molecular heterogeneity, inducing differences in biological behavior, and therapeutic strategy. NGS profiles of pathogenic alterations in the Chinese PDAC population are limited. We conducted a retrospective study to investigate the predictive role of DNA damage repair (DDR) mutations in precision medicine. METHODS: The NGS profiles were performed on resected tissues from 195 Chinese PDAC patients. Baseline clinical or genetic characteristics and survival status were collected. The Kaplan-Meier survival analyses were performed by the R version 3.6.1. RESULTS: The main driver genes were KRAS, TP53, CDKN2A, and SMAD4. Advanced patients with KRAS mutation showed a worse OS than KRAS wild-type (p = 0.048). DDR pathogenic deficiency was identified in 30 (15.38%) of overall patients, mainly involving BRCA2 (n = 9, 4.62%), ATM (n = 8, 4.10%) and RAD50 genes (n = 3, 1.54%). No significance of OS between patients with or without DDR mutations (p = 0.88). But DDR mutation was an independent prognostic factor for survival analysis of advanced PDAC patients (p = 0.032). For DDR mutant patients, treatment with platinum-based chemotherapy (p = 0.0096) or olaparib (p = 0.018) respectively improved the overall survival. No statistical difference between tumor mutation burden (TMB) and DDR mutations was identified. Treatment of PD-1 blockades did not bring significantly improved OS to DDR-mutated patients than the naive DDR group (p = 0.14). CONCLUSIONS: In this retrospective study, we showed the role of germline and somatic DDR mutation in predicting the efficacy of olaparib and platinum-based chemotherapy in Chinese patients. However, the value of DDR mutation in the prediction of hypermutation status and the sensitivity to the PD-1 blockade needed further investigation.


Assuntos
Adenocarcinoma , Neoplasias Pancreáticas , Carcinoma Ductal Pancreático/tratamento farmacológico , Carcinoma Ductal Pancreático/genética , China , Dano ao DNA/genética , Células Germinativas , Humanos , Mutação/genética , Neoplasias Pancreáticas/tratamento farmacológico , Neoplasias Pancreáticas/genética , Estudos Retrospectivos
19.
Carcinogenesis ; 42(4): 631-639, 2021 04 30.
Artigo em Inglês | MEDLINE | ID: mdl-33367515

RESUMO

The TGF-ß receptor kinase inhibitors (TRKI) have been reported to inhibit tumorigenicity in colon cancer. However, there is no direct evidence showing that these inhibitors function through inhibiting the TGF-ß- mediated tumor-promoting effects in vivo. We established a TGF-ß inducible reporter system by inserting a luciferase reporter gene to the vector downstream of TGF-ß-inducible promoter elements, and transfected it into colon cancer cell lines. TRKIs SB431542 and LY2109761 were used to treat TGF-ß inducible cells in vitro and in vivo. The luciferase activity was induced 5.24-fold by TGF-ß in CT26 inducible cells, while it was marginally changed in MC38 inducible cells lacking Smad4 expression. Temporary treatment of mice with SB431542 inhibited the TGF-ß pathway and TGF-ß induced bioluminescence activity in vivo. Long-term treatment with LY2109761 inhibited tumorigenicity and liver metastasis in vivo in concomitant with reduced luciferase activity in the tumor. In this study, we established a model to monitor the TGF-ß pathway in vivo and to compare the antitumor effects of TRKIs. Based on this novel experimental tool, we provided direct evidences that LY2109761 inhibits tumorigenicity and liver metastasis by blocking the pro-oncogenic functions of TGF-ß in vivo.


Assuntos
Carcinogênese/efeitos dos fármacos , Neoplasias do Colo/tratamento farmacológico , Receptores de Fatores de Crescimento Transformadores beta/genética , Fator de Crescimento Transformador beta/genética , Animais , Benzamidas/farmacologia , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Neoplasias do Colo/genética , Neoplasias do Colo/patologia , Dioxóis/farmacologia , Modelos Animais de Doenças , Humanos , Camundongos , Inibidores de Proteínas Quinases/farmacologia , Pirazóis/farmacologia , Pirróis/farmacologia , Receptores de Fatores de Crescimento Transformadores beta/antagonistas & inibidores , Transdução de Sinais/efeitos dos fármacos
20.
Mol Plant Pathol ; 22(1): 3-18, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33151622

RESUMO

CaWRKY40 was previously found to be transcriptionally up-regulated by Ralstonia solanacearum inoculation (RSI) or heat stress (HS), but the underlying mechanism remains unknown. Herein, we report that a double-W box-element (DWE) in the promoter of CaWRKY40 is critical for these responses. The upstream W box unit WI of this composite element is crucial for preferential binding by CaWRKY40 and responsiveness to RSI or HS. DWE-driven CaWRKY40 can be transcriptionally and nonspecifically regulated by itself and by CaWRKY58 and CaWRKY27. The DWE was also found in the promoters of CaWRKY40 orthologs, including AtWRKY40, VvWRKY40, GmWRKY40, CplWRKY40, SaWRKY40, SpWRKY40, NtWRKY40, and NaWRKY40. DWEAtWRKY40 was analogous to DWECaWRKY40 by responding to RSI or HS and AtWRKY40 expression. These data suggest that a conserved response of plants to pathogen infection or HS is probably mediated by binding of the DWE by WRKY40.


Assuntos
Capsicum/genética , Resistência à Doença/genética , Regulação da Expressão Gênica de Plantas , Doenças das Plantas/imunologia , Ralstonia solanacearum/fisiologia , Fatores de Transcrição/metabolismo , Capsicum/imunologia , Capsicum/microbiologia , Capsicum/fisiologia , Resposta ao Choque Térmico , Interações Hospedeiro-Patógeno , Doenças das Plantas/microbiologia , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Regiões Promotoras Genéticas/genética , Fatores de Transcrição/genética
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