RESUMO
Grain chalkiness reduces the quality of rice (Oryza sativa) and is a highly undesirable trait for breeding and marketing. However, the underlying molecular cause of chalkiness remains largely unknown. Here, we cloned the F-box gene WHITE-CORE RATE 1 (WCR1), which negatively regulates grain chalkiness and improves grain quality in rice. A functional A/G variation in the promoter region of WCR1 generates the alleles WCR1A and WCR1G, which originated from tropical japonica and wild rice Oryza ruï¬pogon, respectively. OsDOF17 is a transcriptional activator that binds to the AAAAG cis-element in the WCR1A promoter. WCR1 positively affects the transcription of the metallothionein gene MT2b and interacts with MT2b to inhibit its 26S proteasome-mediated degradation, leading to decreased reactive oxygen species production and delayed programmed cell death in rice endosperm. This, in turn, leads to reduced chalkiness. Our findings uncover a molecular mechanism underlying rice chalkiness and identify the promising natural variant WCR1A, with application potential for rice breeding.
Assuntos
Endosperma , Oryza , Grão Comestível/genética , Endosperma/genética , Regulação da Expressão Gênica de Plantas/genética , Homeostase/genética , Oryza/genética , Oryza/metabolismo , OxirreduçãoRESUMO
Residents are one of the most significant stakeholder groups in ecologically vulnerable regions, and the local ecological environmental governance efforts require their active cooperation and participation. To this end, this study leverages the sampled survey data from residents across 14 cities in Guangxi, China, and uses a structural equation modeling analysis to explore the impact of environmental education perception on residents' ecological security behavior. The results indicate that psychological ownership of nature plays a positive mediating role between environmental education perception and residents' ecological security behavior, as well as between ecological consciousness and residents' ecological security behavior, thereby supporting the idea that a sense of stewardship in protecting ecological security is a key factor in residents' conversion of their ecological protection cognition into practical actions. Further research finds that visual fluency has a moderating effect on the relationship between environmental education perception and psychological ownership of nature. This study provides new insights into the theoretical understanding of the formation mechanism of residents' ecological security behavior, enriches the theory of psychological ownership, and offers policy recommendations for governments implementing ecological environmental propaganda programs.
Assuntos
Conservação dos Recursos Naturais , Propriedade , Política Ambiental , China , CidadesRESUMO
Rice grain quality is a multifarious attribute mainly governed by multiple nutritional factors. Grain protein is the central component of rice grain nutrition dominantly affecting eating-cooking qualities. Grain protein content is quantitatively influenced by its protein fractions. Genetic quantification of five protein fractions-albumins, globulins, prolamins, glutelin, and grain protein content-were evaluated by exploiting two BC3F2 mapping populations, derived from Kongyu131/TKM9 (population-I) and Kongyu131/Bg94-1 (population-II), which were grown in a single environment. Correlation studies among protein fractions and grain protein content were thoroughly investigated. A genetic linkage map was developed by using 146 single sequence repeat (SSR) markers in population-I and 167 markers in population-II. In total, 40 QTLs were delineated for five traits in both populations. Approximately 22 QTLs were dissected in population-I, derived from Kongyu131/TKM9, seven QTLs for albumin content, four QTLs for globulin content, three QTLs for prolamin content, four QTLs for glutelin content, and four QTLs for grain protein content. In total, 18 QTLs were detected in population-II, derived from Kongyu131/Bg94-1, five QTLs for albumin content, three QTLs for globulin content, four QTLs for prolamin content, two QTLs for glutelin content, and four QTLs for grain protein content. Three QTLs, qAlb7.1, Alb7.2, and qGPC7.2, derived from population-II (Kongyu131/Bg94-1) for albumin and grain protein content were successfully validated in the near isogenic line (NIL) populations. The localized chromosomal locus of the validated QTLs could be helpful for fine mapping via map-based cloning to discover underlying candidate genes. The functional insights of the underlying candidate gene would furnish novel perceptivity for the foundation of rice grain protein content and trigger the development of nutritionally important rice cultivars by combining marker-assisted selection (MAS) breeding. Supplementary Information: The online version contains supplementary material available at 10.1007/s11032-023-01436-7.
RESUMO
BACKGROUND: Precise quantification of microRNA is challenging since circulating mRNA and rRNA in the blood are usually degraded. Therefore, it is necessary to identify specific biomarkers for ovarian cancer. This study aimed to investigate candidate circular RNAs (circRNAs) involved in the pathogenic process of ovarian cancer after inhibition of chromodomain helicase DNA binding protein 1-like (CHD1L) and the corresponding mechanism. METHODS: CHD1L mRNA-targeted siRNA was designed and induced a decreased level of CHD1L function in SK-OV-3 and OVCAR-3 cells observed via transwell and wound healing assays and assessment of epithelial-mesenchymal transition (EMT)-related protein expression by immunofluorescence (IF) and western blotting (WB). After decreasing the level of CHD1L, RNA-seq was conducted, and the circRNA expression profiles were obtained. cirRNAs were then selected and validated by PCR together with Sanger sequencing, fluorescent in situ hybridization (FISH), and reverse transcriptase-quantitative PCR (RT-qPCR). Selected circRNA function in vitro was adjusted via interference and overexpression and assessed via transwell assay, tube formation, and EMT-related protein assay by IF and WB; tumor formation in vivo was followed via hematoxylin and eosin (HE) staining and immunohistochemistry of EMT-related proteins. Based on the competing endogenous RNA prediction of circRNA targets, candidate miRNAs were found, and their downstream mRNAs targeted by the selected miRNA were identified and validated by luciferase assay. The functions of these selected miRNA and mRNA were then further investigated through transwell and WB assay of EMT-related proteins. RESULTS: CHD1L was significantly upregulated in ovarian cancer tissues and patients with higher expression of CHD1L had a shorter relapse-free survival (P < 0.001) and overall survival (P < 0.001). Inhibiting the level of CHD1L significantly decreased cell migration and invasion (P < 0.05), increased the expression of epithelial markers, and decreased the expression of mesenchymal markers. Following inhibition of CHD1L expression, RNA-seq was conducted and 82 circRNAs had significantly upregulated expression, while 247 had significantly downregulated expression. The circRNAs were validated by PCR, and hsa_circ_0008305 (circ-PTK2) was selected and further validated by Sanger sequencing, FISH, and RT-qPCR. Circ-PTK2 expression was significantly higher in the ovarian cancer tissues compared with normal ovary tissues (P < 0.001). By regulating the level of circ-PTK2 with siRNA and an overexpression vector, expression of circ-PTK2 was found to be positively correlated to cell migration and invasion. Overexpression of circ-PTK2 enhanced tumor formation and was correlated to expression of EMT pathway markers. Prediction of the target of circ-PTK2 was validated with dual luciferase assay and identified miR-639 and FOXC1 as the valid target of circ-PTK2 and miR-639, respectively. The RNA level of miR-639 was negatively correlated to cell proliferation and migration, whereas the mRNA level of FOXC1 was positively correlated to those processes. miR-639 mimics reversed the function of circ-PTK2 overexpression; however, interference of FOXC1 mRNA also reversed the function of circ-PTK2. CONCLUSIONS: circ-PTK2 is an important molecule in regulating the pathogenic processes of ovarian cancer via the miR-639 and FOXC1 regulatory cascade.
RESUMO
In recent time, due to convenient availability of number of over the counter (OTC) drugs, patients are able to treat minor ailments by themselves. The self-medicated regimen has lead to certain health problems in all age groups irrespective of their professions. People are usually unaware about the safe use of NSAIDs (non-steroidal anti-inflammatory drugs) and currently there is no study carried out in COMSATS Institute of Information Technology (CIIT), Abbottabad, regarding the choice of faculty members for NSAIDs to relieve pain and their knowledge about its safety and use. A questionnaire based survey was carried out to collectdata about the choice of CIIT faculty for a specific NSAID and their cognition related to ibuprofen. Two hundred fifty faculty members (comprising of 53 pharmacy faculty members and 197 faculty members who belonged to other departments) of which 87 were females, took part in this study. Average age of participants was 34.86 +/- 9.02 years. Ibuprofen was the drug of choice NSAID among the participants. Four percent participants experienced pain almost every day. Analgesia was the well known indication for ibuprofen (31%) by both the groups and in general more educated and younger participants showed better apprehension related to indications. Sixty one percent participants comprising of non-pharmacy faculty were unaware of any undesirable effects and 79% (comprising of 72% pharmacists and 5% non-pharmacists) were affirmative that ibuprofen had no adverse effects. Fifteen percent participants of department other than pharmacy were not aware of any interactions of ibuprofen. 34% of participants (comprising of 32% non-pharmacists and 2% pharmacists) entrusted their physician for an analgesic. Regardless that many participants suffered from pain almost every day and their drug of choice would be ibuprofen, they had inadequate information related to the safety and use of ibuprofen.
Assuntos
Analgésicos não Narcóticos/uso terapêutico , Conhecimentos, Atitudes e Prática em Saúde , Ibuprofeno/uso terapêutico , Medicamentos sem Prescrição/uso terapêutico , Adulto , Anti-Inflamatórios não Esteroides/efeitos adversos , Anti-Inflamatórios não Esteroides/uso terapêutico , Estudos Transversais , Docentes , Feminino , Humanos , Ibuprofeno/efeitos adversos , Masculino , Pessoa de Meia-Idade , Medicamentos sem Prescrição/efeitos adversos , Dor/tratamento farmacológico , Paquistão , Farmacêuticos/estatística & dados numéricos , Inquéritos e Questionários , Universidades , Adulto JovemRESUMO
Background: Small intestinal neuroendocrine tumors (SI-NETs) are the most common malignant tumors of the small intestine, with many patients presenting with metastases and their incidence increasing. We aimed to find effective diagnostic biomarkers for patients with primary and metastatic SI-NETs that could be applied for clinical diagnosis. Methods: We downloaded GSE65286 (training set) and GSE98894 (test set) from the GEO database and performed differential gene expression analysis to obtain differentially expressed genes (DEGs) and differentially expressed long non-coding RNAs (DElncRNAs). The functions and pathways involved in these genes were further explored by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses. In addition, a global regulatory network involving dysregulated genes in SI-NETs was constructed based on RNAInter and TRRUST v2 databases, and the diagnostic power of hub genes was identified by receiver operating characteristic curve (ROC). Results: A total of 2,969 DEGs and DElncRNAs were obtained in the training set. Enrichment analysis revealed that biological processes (BPs) and KEGG pathways were mainly associated with cancer. Based on gene set enrichment analysis (GSEA), we obtained five BPs (cytokinesis, iron ion homeostasis, mucopolysaccharide metabolic process, platelet degranulation and triglyceride metabolic process) and one KEGG pathway (ppar signaling pathway). In addition, the core set of dysregulated genes obtained included MYL9, ITGV8, FGF2, FZD7, and FLNC. The hub genes were upregulated in patients with primary SI-NETs compared to patients with metastatic SI-NETs, which is consistent with the training set. Significantly, the results of ROC analysis showed that the diagnostic power of the hub genes was strong in both the training and test sets. Conclusion: In summary, we constructed a global regulatory network in SI-NETs. In addition, we obtained the hub genes including MYL9, ITGV8, FGF2, FZD7, and FLNC, which may be useful for the diagnosis of patients with primary and metastatic SI-NETs.
RESUMO
PURPOSE: The role of neoadjuvant chemotherapy (NACT) and primary debulking surgery (PDS) in advanced epithelial ovarian cancer (EOC) remains controversial. This study aimed to investigate the prognosis between NACT and PDS in advanced EOC. We also investigated the prognostic effect of the residual tumor (RT) after NACT and PDS. METHODS: Patients with stage III-IV EOC diagnosed between 2010 and 2017 were included from the Surveillance, Epidemiology, and End Results (SEER) database. Chi-square test, multivariate logistic regression analysis, Kaplan-Meier curves, and Cox proportional hazards model were used for statistical analyses. RESULTS: A total of 5522 women patients were identified, 2017 (36.5%) and 3505 (63.5%) patients received NACT and PDS, respectively. There were 2971 (53.8%), 1637 (29.6%), and 914 (16.6%) patients who had no residual tumor, RT ≤1 cm, and RT >1 cm, respectively. There were 25.5% of patients receiving NACT in 2010 and 48.4% in 2017 (p < 0.001). Women treated with NACT were not related to a higher chance of complete resection than the PDS group (p = 0.098). Patients receiving PDS had significantly better cancer-specific survival (CSS) than those receiving NACT (p < 0.001). The 5-year CSS was 35.3% and 51.1% in those receiving NACT and PDS, respectively. In patients receiving NACT, those who had no residual tumor had significantly better CSS compared to those who had RT ≤1 cm (p < 0.001), while comparable CSS was found between those who had RT ≤1 cm and RT >1 cm (p = 0.442). In those receiving PDS, the CSS was decreased with a RT increase (p < 0.001). CONCLUSIONS: Our study suggests that PDS may be the optimal procedure for the majority of advanced EOC patients. Complete resection of all residual diseases should be the goal with the increased utilization of NACT.
Assuntos
Neoplasias Epiteliais e Glandulares , Neoplasias Ovarianas , Carcinoma Epitelial do Ovário/tratamento farmacológico , Carcinoma Epitelial do Ovário/cirurgia , Quimioterapia Adjuvante , Procedimentos Cirúrgicos de Citorredução , Feminino , Humanos , Terapia Neoadjuvante/métodos , Estadiamento de Neoplasias , Neoplasia Residual/patologia , Neoplasias Epiteliais e Glandulares/tratamento farmacológico , Neoplasias Epiteliais e Glandulares/patologia , Neoplasias Epiteliais e Glandulares/cirurgia , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/patologia , Neoplasias Ovarianas/cirurgia , Prognóstico , Estudos RetrospectivosRESUMO
PURPOSE: The purpose of this study was to develop and initially validate a nomogram model in order to predict the 3-year and 5-year survival rates of neuroendocrine tumor patients. METHODS: Accordingly, 348 neuroendocrine tumor patients were enrolled as study objects, of which 244 (70%) patients were included in the training set to establish the nomogram model, while 104 (30%) patients were included in the validation set to verify the robustness of the model. First, the variables related to the survival rate were determined by univariable analysis. In addition, variables that were sufficiently significant were selected for constructing the nomogram model. Furthermore, the concordance index (C-index), receiver operating characteristic (ROC), and calibration curve analysis were used to evaluate the performance of the proposed nomogram model. The survival analysis was then used to evaluate the return to survival probability as well as the indicators of constructing the nomogram model. RESULTS: According to the multivariable analysis, lymphatic metastasis, international normalized ratio (INR), prothrombin time (PT), tumor differentiation, and the number of tumor metastases were found to be independent predictors of survival rate. Moreover, the C-index results demonstrated that the model was robust in both the training set (0.891) and validation set (0.804). In addition, the ROC results further verified the robustness of the model either in the training set (AUC = 0.823) or training set (AUC = 0.768). Furthermore, the calibration curve results showed that the model can be used to predict the 3-year and 5-year survival probability of neuroendocrine tumor patients. Meaningfully, five variables were found: lymphatic metastasis (p = 0.0095), international standardized ratio (p = 0.024), prothrombin time (p = 0.0036), tumor differentiation (p = 0.0026), and the number of tumor metastases (p = 0.00096), which were all significantly related to the 3-year and 5-year survival probability of neuroendocrine tumor patients. CONCLUSION: In summary, a nomogram model was constructed in this study based on five variables (lymphatic metastasis, international normalized ratio (INR), prothrombin time (PT), tumor differentiation, and number of tumor metastases), which was shown to predict the survival probability of patients with neuroendocrine tumors. Additionally, the proposed nomogram exhibited good ability in predicting survival probability, which may be easily adopted for clinical use.
Assuntos
Tumores Neuroendócrinos/diagnóstico , Tumores Neuroendócrinos/mortalidade , Nomogramas , Idoso , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Sensibilidade e EspecificidadeRESUMO
BACKGROUND: Actual long-term survival rates for advanced epithelial ovarian cancer (EOC) are rarely reported. OBJECTIVE: This study aimed to assess the role of histological subtypes in predicting the prognosis among long-term survivors (≥5 years) of advanced EOC. METHODS: We performed a retrospective analysis of data among patients with stage III-IV EOC diagnosed from 2000 to 2014 using the Surveillance, Epidemiology, and End Results cancer data of the United States. We used the chi-square test, Kaplan-Meier analysis, and multivariate Cox proportional hazards model for the analyses. RESULTS: We included 8050 patients in this study, including 6929 (86.1%), 743 (9.2%), 237 (2.9%), and 141 (1.8%) patients with serous, endometrioid, clear cell, and mucinous tumors, respectively. With a median follow-up of 91 months, the most common cause of death was primary ovarian cancer (80.3%), followed by other cancers (8.1%), other causes of death (7.3%), cardiac-related death (3.2%), and nonmalignant pulmonary disease (3.2%). Patients with the serous subtype were more likely to die from primary ovarian cancer, and patients with the mucinous subtype were more likely to die from other cancers and cardiac-related disease. Multivariate Cox analysis showed that patients with endometrioid (hazard ratio [HR] 0.534, P<.001), mucinous (HR 0.454, P<.001), and clear cell (HR 0.563, P<.001) subtypes showed better ovarian cancer-specific survival than those with the serous subtype. Similar results were found regarding overall survival. However, ovarian cancer-specific survival and overall survival were comparable among those with endometrioid, clear cell, and mucinous tumors. CONCLUSIONS: Ovarian cancer remains the primary cause of death in long-term ovarian cancer survivors. Moreover, the probability of death was significantly different among those with different histological subtypes. It is important for clinicians to individualize the surveillance program for long-term ovarian cancer survivors.
Assuntos
Neoplasias Ovarianas , Carcinoma Epitelial do Ovário/epidemiologia , Carcinoma Epitelial do Ovário/patologia , Feminino , Humanos , Estadiamento de Neoplasias , Neoplasias Ovarianas/epidemiologia , Neoplasias Ovarianas/patologia , Prognóstico , Estudos Retrospectivos , Estados Unidos/epidemiologiaRESUMO
The skeletal system is fundamental for the structure and support of the body consisting of bones, cartilage, and connective tissues. Poor fracture healing is a chief clinical problem leading to disability, extended hospital stays and huge financial liability. Even though most fractures are cured using standard clinical methods, about 10% of fractures are delayed or non-union. Despite decades of progress, the bone-targeted delivery system is still restricted due to the distinctive anatomical bone features. Recently, various novel nanocomposite systems have been designed for the cell-specific targeting of bone, enhancing drug solubility, improving drug stability and inhibiting drug degradation so that it can reach its target site without being removed in the systemic circulation. Such targeting systems could consist of biological compounds i.e. bone marrow stem cells (BMSc), growth factors, RNAi, parathyroid hormone or synthetic compounds, i.e. bisphosphonates (BPs) and calcium phosphate cement. Hydrogels and nanoparticles are also being employed for fracture healing. In this review, we discussed the normal mechanism of bone healing and all the possible drug delivery systems being employed for the healing of the bone fracture.
Assuntos
Remodelação Óssea/efeitos dos fármacos , Sistemas de Liberação de Medicamentos/métodos , Consolidação da Fratura/efeitos dos fármacos , Fraturas Ósseas/tratamento farmacológico , Nanocompostos/administração & dosagem , Animais , Cimentos Ósseos/metabolismo , Remodelação Óssea/fisiologia , Difosfonatos/administração & dosagem , Difosfonatos/metabolismo , Consolidação da Fratura/fisiologia , Fraturas Ósseas/diagnóstico por imagem , Fraturas Ósseas/metabolismo , Humanos , Hidrogéis/administração & dosagem , Hidrogéis/metabolismo , Nanopartículas/administração & dosagem , Nanopartículas/metabolismoRESUMO
PURPOSE: To investigate the effect of 21-gene recurrence score (RS) on chemotherapy-decision making and prognosis in breast cancer patients aged <40 years. METHODS: Using the Surveillance, Epidemiology, and End Results program, we included patients aged <40 years with tumor size ≤5 cm, node negative, and estrogen receptor-positive breast cancer between 2004 and 2015. Correlations among the 21-gene RS, chemotherapy decision-making and prognosis were analyzed. RESULTS: We included 2721 patients in this study. According to TAILORx cutoffs, 352 (12.9%), 1814 (66.7%), and 555 (20.4%) patients were classified as low-, intermediate-, and high-risk cohorts, respectively. The 21-gene RS categories were associated with the probability of receiving chemotherapy, with 7.1%, 33.4%, and 77.1% of patients in low-, intermediate-, and high-risk cohorts treated with chemotherapy, respectively (P < 0.001). Those in the intermediate-risk cohort were significantly less likely to receive chemotherapy over time (P = 0.008), and the trends of chemotherapy receipt were stable in the low-risk and high-risk cohorts over time. Multivariate analysis showed that the 21-gene RS was an independent prognostic indicator for breast cancer specific survival. In the stratified analysis, the receipt of chemotherapy was associated with better breast cancer specific survival in the high-risk cohort (P = 0.028), but not in the intermediate-risk cohort (P = 0.223). CONCLUSIONS: 21-gene RS has clinical implications for young breast cancer patients with respect to optimizing chemotherapy-decisions. Despite increasing rates of chemotherapy receipt in young patients, more studies are needed to determine the definitive effect of chemotherapy in young patients with three RS categories.
Assuntos
Antineoplásicos/uso terapêutico , Neoplasias da Mama/genética , Regras de Decisão Clínica , Tomada de Decisão Clínica/métodos , Testes Genéticos/métodos , Recidiva Local de Neoplasia/genética , Adulto , Fatores Etários , Biomarcadores Tumorais/genética , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/mortalidade , Carcinoma Ductal de Mama/diagnóstico , Carcinoma Ductal de Mama/tratamento farmacológico , Carcinoma Ductal de Mama/genética , Carcinoma Ductal de Mama/mortalidade , Carcinoma Lobular/diagnóstico , Carcinoma Lobular/tratamento farmacológico , Carcinoma Lobular/genética , Carcinoma Lobular/mortalidade , Feminino , Seguimentos , Perfilação da Expressão Gênica , Humanos , Recidiva Local de Neoplasia/diagnóstico , Recidiva Local de Neoplasia/mortalidade , Recidiva Local de Neoplasia/prevenção & controle , Prognóstico , Estudos Retrospectivos , Medição de Risco , Programa de SEER , Análise de SobrevidaRESUMO
BACKGROUND: The value of postoperative radiotherapy in tubular breast carcinoma patients under 65 years is uncertain. METHODS: Data on patients with estrogen receptor positive T1N0M0 tubular breast carcinoma who were younger than 65 years and who received breast-conserving surgery between 2000 and 2013 were retrieved from the Surveillance, Epidemiology and End Results database. Demographic, clinicopathologic features, and receipt of postoperative radiotherapy were analyzed to investigate effects on survival. RESULTS: Data from 2442 patients were analyzed, of whom 2020 (82.7%) received postoperative radiotherapy and 422 (17.3%) did not. The number of patients treated with or without postoperative radiotherapy showed no differences during the study period (p = 0.184). Radiotherapy was more likely to be administered in patients with well differentiated tumors. Multivariate Cox analysis showed that postoperative radiotherapy delivery was significantly correlated with better breast cancer-specific survival (BCSS) (hazard ratio [HR] 0.297, 95% confidence interval [CI] 0.105-0.836, p = 0.022) and overall survival (OS) (HR 0.656, 95% CI 0.441-0.978, p = 0.038). Ten 10-year BCSS was 99.3% in patients who received postoperative radiotherapy and 98.1% in those who did not (p = 0.020), and 10-year OS was 93.4 and 91.0%, respectively (p = 0.029). Postoperative radiotherapy increased BCSS and OS in the subgroups of age < 50 years, non-Hispanic white, well differentiated tumors, and progesterone receptor positive tumors. CONCLUSIONS: Postoperative radiotherapy after breast-conserving surgery improved survival outcomes in tubular breast carcinoma patients aged < 50 years. However, omitting postoperative radiotherapy may not decrease survival in patients aged ≥50 years.