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1.
Oncoimmunology ; 10(1): 1929727, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34350061

RESUMO

Background: The present study aimed to evaluate the effects of concomitant proton pump inhibitor (PPI) use on immune checkpoint inhibitor (ICI) efficacy among advanced cancer patients. Methods and Materials: A systematic literature search of electronic database was performed to identify all potential reports. Then, meta-analyses were conducted to obtain pooled HRs with 95% CIs, which reveal the influence of PPI use on PFS and OS in patients receiving ICI treatment. Results: A total of 7 studies with 3,647 advanced cancer patients fulfilled the inclusion criteria. The impact of PPI use was then evaluated on 3,340 patients for PFS and 3,647 patients for OS. Concomitant PPI use has a detrimental effect on the efficacy of ICIs that PPI use increased the risk of progression by 28% (HR = 1.28, 95% CI 1.17-1.40; I2 = 31.3%, Q test P = .21) when compared to those not receiving PPIs. Similarly, the meta-analysis showed that PPI use was also associated with shorter OS of advanced cancer patients receiving ICIs that PPI use increased risk of death by 39% (HR = 1.39, 95% CI 1.26-1.54; I2 = 36.5%, Q test P = .16). Sensitivity analysis showed that the pooled HRs were constant after excluding one study at a time, and no significant publication biases were detected. Conclusion: The meta-analysis suggested that concomitant PPI use is significantly associated with low clinical benefit in ICI treatment, revealing a significantly reduced PFS and OS in advanced cancer patients receiving ICIs who are also exposed to PPI.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Humanos , Inibidores de Checkpoint Imunológico , Neoplasias Pulmonares/tratamento farmacológico , Inibidores da Bomba de Prótons/efeitos adversos
2.
BMC Plant Biol ; 21(1): 376, 2021 Aug 16.
Artigo em Inglês | MEDLINE | ID: mdl-34399701

RESUMO

BACKGROUND: Glycolytic pathway is common in all plant organs, especially in oxygen-deficient tissues. Phosphofructokinase (PFK) is a rate-limiting enzyme in the glycolytic pathway and catalyses the phosphorylation of fructose-6-phosphate to fructose-1,6-bisphosphate. Cassava (M. esculenta) root is a huge storage organ with low amount of oxygen. However, less is known about the functions of PFK from M. esculenta (MePFK). We conducted a systematic analysis of MePFK genes to explore the function of the MePFK gene family under hypoxic stress. RESULTS: We identified 13 MePFK genes and characterised their sequence structure. The phylogenetic tree divided the 13 genes into two groups: nine were MePFKs and four were pyrophosphate-fructose-6-phosphate phosphotransferase (MePFPs). We confirmed by green fluorescent protein fusion protein expression that MePFK03 and MePFPA1 were localised in the chloroplast and cytoplasm, respectively. The expression profiles of the 13 MePFKs detected by quantitative reverse transcription polymerase chain reaction revealed that MePFK02, MePFK03, MePFPA1, MePFPB1 displayed higher expression in leaves, root and flower. The expression of MePFK03, MePFPA1 and MePFPB1 in tuber root increased gradually with plant growth. We confirmed that hypoxia occurred in the cassava root, and the concentration of oxygen was sharply decreasing from the outside to the inside root. The expression of MePFK03, MePFPA1 and MePFPB1 decreased with the decrease in the oxygen concentration in cassava root. Waterlogging stress treatment showed that the transcript level of PPi-dependent MePFP and MeSuSy were up-regulated remarkably and PPi-dependent glycolysis bypass was promoted. CONCLUSION: A systematic survey of phylogenetic relation, molecular characterisation, chromosomal and subcellular localisation and cis-element prediction of MePFKs were performed in cassava. The expression profiles of MePFKs in different development stages, organs and under waterlogging stress showed that MePFPA1 plays an important role during the growth and development of cassava. Combined with the transcriptional level of MeSuSy, we found that pyrophosphate (PPi)-dependent glycolysis bypass was promoted when cassava was under waterlogging stress. The results would provide insights for further studying the function of MePFKs under hypoxic stress.


Assuntos
Genoma de Planta , Manihot/enzimologia , Manihot/genética , Fosfofrutoquinases/genética , Fosfofrutoquinases/metabolismo , Cloroplastos/enzimologia , Mapeamento Cromossômico , Cromossomos de Plantas , Sequência Conservada , Citoplasma/enzimologia , Éxons , Flores/enzimologia , Íntrons , Família Multigênica , Oxigênio/metabolismo , Filogenia , Folhas de Planta/enzimologia , Raízes de Plantas/enzimologia , Regiões Promotoras Genéticas , Estresse Fisiológico/genética , Transcriptoma
3.
BMC Plant Biol ; 21(1): 318, 2021 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-34217217

RESUMO

BACKGROUND: Cassava (Manihot esculenta Crantz) efficiently accumulates starch in its storage roots. However, how photosynthates are transported from the leaves to the phloem (especially how they are unloaded into parenchymal cells of storage roots) remains unclear. RESULTS: Here, we investigated the sucrose unloading pattern and its impact on cassava storage root development using microstructural and physiological analyses, namely, carboxyfluorescein (CF) and C14 isotope tracing. The expression profiling of genes involved in symplastic and apoplastic transport was performed, which included enzyme activity, protein gel blot analysis, and transcriptome sequencing analyses. These finding showed that carbohydrates are transported mainly in the form of sucrose, and more than 54.6% was present in the stem phloem. Sucrose was predominantly unloaded symplastically from the phloem into storage roots; in addition, there was a shift from apoplastic to symplastic unloading accompanied by the onset of root swelling. Statistical data on the microstructures indicated an enrichment of plasmodesmata within sieve, companion, and parenchyma cells in the developing storage roots of a cultivar but not in a wild ancestor. Tracing tests with CF verified the existence of a symplastic channel, and [14C] Suc demonstrated that sucrose could rapidly diffuse into root parenchyma cells from phloem cells. The relatively high expression of genes encoding sucrose synthase and associated proteins appeared in the middle and late stages of storage roots but not in primary fibrous roots, or secondary fibrous roots. The inverse expression pattern of sucrose transporters, cell wall acid invertase, and soluble acid invertase in these corresponding organs supported the presence of a symplastic sucrose unloading pathway. The transcription profile of genes involved in symplastic unloading and their significantly positive correlation with the starch yield at the population level confirmed that symplastic sucrose transport is vitally important in the development of cassava storage roots. CONCLUSIONS: In this study, we revealed that the cassava storage root phloem sucrose unloading pattern was predominantly a symplastic unloading pattern. This pattern is essential for efficient starch accumulation in high-yielding varieties compared with low-yielding wild ancestors.


Assuntos
Manihot/metabolismo , Floema/fisiologia , Fotossíntese/fisiologia , Raízes de Plantas/metabolismo , Amido/metabolismo , Transporte Biológico , Biomassa , Parede Celular/metabolismo , Difusão , Fluoresceínas/metabolismo , Regulação da Expressão Gênica de Plantas , Manihot/genética , Modelos Biológicos , Floema/citologia , Floema/ultraestrutura , Plasmodesmos/metabolismo , Frações Subcelulares/metabolismo , Sacarose/metabolismo , Açúcares/metabolismo
4.
Oncologist ; 26(9): 717-721, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-33896090

RESUMO

The addition of trastuzumab to chemotherapy regimen is the standard of care for human epidermal growth factor receptor 2 (HER2)-positive advanced gastric cancer; however, most patients eventually acquire trastuzumab resistance. Although some resistance mechanisms to trastuzumab-based regimens have been proposed, further understanding is required for developing therapeutic strategies to overcome the resistance. In the present work, we attempted to determine the possible resistance mechanism to trastuzumab in a patient with HER2-positive stage IV gastric adenocarcinoma. In this study, we first report the nucleotide change c.1899-1G>A at the intron 15 acceptor splice site promoting exon 16 deletion of HER2 as the potential mechanism of trastuzumab resistance in HER2-positive gastric adenocarcinoma. KEY POINTS: The combination of trastuzumab with chemotherapy is considered to be the standard therapy for HER2-positive advanced gastric cancer (GC), but most of the patients eventually acquire trastuzumab resistance. The mechanisms of resistance to trastuzumab in GC are poorly characterized. To the best of the authors' knowledge, this study is the first to implicate HER2 c.1899-1G>A, which results in exon 16 skpping, as the acquired resistance mechanism to trastuzumab in HER2-positive gastric adenocarcinoma. This work provides insights into the potential molecular mechanism of trastuzumab resistance, which is crucial in developing effective therapeutic strategies for HER2-positive GC patients refractory to trastuzumab.


Assuntos
Adenocarcinoma , Neoplasias Gástricas , Adenocarcinoma/tratamento farmacológico , Adenocarcinoma/genética , Humanos , Mutação , Receptor ErbB-2/genética , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/genética , Trastuzumab/uso terapêutico
5.
Hortic Res ; 8(1): 14, 2021 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-33419990

RESUMO

Passion fruit (Passiflora edulis Sims) is an economically valuable fruit that is cultivated in tropical and subtropical regions of the world. Here, we report an ~1341.7 Mb chromosome-scale genome assembly of passion fruit, with 98.91% (~1327.18 Mb) of the assembly assigned to nine pseudochromosomes. The genome includes 23,171 protein-coding genes, and most of the assembled sequences are repetitive sequences, with long-terminal repeats (LTRs) being the most abundant. Phylogenetic analysis revealed that passion fruit diverged after Brassicaceae and before Euphorbiaceae. Ks analysis showed that two whole-genome duplication events occurred in passion fruit at 65 MYA and 12 MYA, which may have contributed to its large genome size. An integrated analysis of genomic, transcriptomic, and metabolomic data showed that 'alpha-linolenic acid metabolism', 'metabolic pathways', and 'secondary metabolic pathways' were the main pathways involved in the synthesis of important volatile organic compounds (VOCs) in passion fruit, and this analysis identified some candidate genes, including GDP-fucose Transporter 1-like, Tetratricopeptide repeat protein 33, protein NETWORKED 4B isoform X1, and Golgin Subfamily A member 6-like protein 22. In addition, we identified 13 important gene families in fatty acid pathways and eight important gene families in terpene pathways. Gene family analysis showed that the ACX, ADH, ALDH, and HPL gene families, especially ACX13/14/15/20, ADH13/26/33, ALDH1/4/21, and HPL4/6, were the key genes for ester synthesis, while the TPS gene family, especially PeTPS2/3/4/24, was the key gene family for terpene synthesis. This work provides insights into genome evolution and flavor trait biology and offers valuable resources for the improved cultivation of passion fruit.

6.
J Environ Sci (China) ; 88: 72-80, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31862081

RESUMO

Selective catalytic reduction (SCR) denitration may increase the emission of NH4+ and NH3. The removal and transformation characteristics of ammonium sulfate aerosols and ammonia slip during the wet flue gas desulfurization (WFGD) process, as well as the effect of desulfurization parameters, were investigated in an experimental system equipped with a simulated SCR flue gas generation system and a limestone-based WFGD system. The results indicate that the ammonium sulfate aerosols and ammonia slip in the flue gas from SCR can be partly removed by slurry scrubbing, while the entrainment and evaporation of desulfurization slurry with accumulated NH4+ will generate new ammonium-containing particles and gaseous ammonia. The ammonium-containing particles formed by desulfurization are not only derived from the entrainment of slurry droplets, but also from the re-condensation of gaseous ammonia generated by slurry evaporation. Therefore, even if the concentration of NH4+ in the desulfurization slurry is quite low, a high level of NH4+ was still contained in the fine particles at the outlet of the scrubber. When the accumulated NH4+ in the desulfurization slurry was high enough, the WFGD system promoted the conversion of NH3 to NH4+ and increased the additional emission of primary NH4+ aerosols. With the decline of the liquid/gas ratio and flue gas temperature, the removal efficiency of ammonia sulfate aerosols increased, and the NH4+ emitted from entrainment and evaporation of the desulfurization slurry decreased. In addition, the volatile ammonia concentration after the WFGD system was reduced with the decrease of the NH4+ concentration and pH values of the slurry.


Assuntos
Aerossóis/análise , Poluentes Atmosféricos/análise , Sulfato de Amônio/química , Centrais Elétricas , Aerossóis/química , Poluentes Atmosféricos/química , Poluição do Ar/prevenção & controle , Amônia , Catálise , Gases
7.
Front Plant Sci ; 9: 503, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29725343

RESUMO

Cassava (Manihot esculenta Crantz) is a major tuberous crop produced worldwide. In this study, we sequenced 158 diverse cassava varieties and identified 349,827 single-nucleotide polymorphisms (SNPs) and indels. In each chromosome, the number of SNPs and the physical length of the respective chromosome were in agreement. Population structure analysis indicated that this panel can be divided into three subgroups. Genetic diversity analysis indicated that the average nucleotide diversity of the panel was 1.21 × 10-4 for all sampled landraces. This average nucleotide diversity was 1.97 × 10-4, 1.01 × 10-4, and 1.89 × 10-4 for subgroups 1, 2, and 3, respectively. Genome-wide linkage disequilibrium (LD) analysis demonstrated that the average LD was about ∼8 kb. We evaluated 158 cassava varieties under 11 different environments. Finally, we identified 36 loci that were related to 11 agronomic traits by genome-wide association analyses. Four loci were associated with two traits, and 62 candidate genes were identified in the peak SNP sites. We found that 40 of these genes showed different expression profiles in different tissues. Of the candidate genes related to storage roots, Manes.13G023300, Manes.16G000800, Manes.02G154700, Manes.02G192500, and Manes.09G099100 had higher expression levels in storage roots than in leaf and stem; on the other hand, of the candidate genes related to leaves, Manes.05G164500, Manes.05G164600, Manes.04G057300, Manes.01G202000, and Manes.03G186500 had higher expression levels in leaves than in storage roots and stem. This study provides basis for research on genetics and the genetic improvement of cassava.

8.
Sci Rep ; 7: 41232, 2017 01 25.
Artigo em Inglês | MEDLINE | ID: mdl-28120898

RESUMO

Cassava (Manihot esculenta Crantz) is an important tropical starchy root crop that is adapted to drought but extremely cold sensitive. A cold-tolerant, high-quality, and robust supply of cassava is urgently needed. Here, we clarify genome-wide distribution and classification of CCGG hemi-methylation and full-methylation, and detected 77 much candidate QTLsepi for cold stress and 103 much candidate QTLsepi for storage root quality and yield in 186 cassava population, generated by crossing two non-inbred lines with female parent KU50 and male parent SC124 (KS population). We developed amplified-fragment single nucleotide polymorphism and methylation (AFSM) genetic map in this population. We also constructed the AFSM QTL map, identified 260 much candidate QTL genes for cold stress and 301 much candidate QTL genes for storage root quality and yield, based on the years greenhouse and field trials. This may accounted for a significant amount of the variation in the key traits controlling cold tolerance and the high quality and yield of cassava.


Assuntos
Metilação de DNA , Epigênese Genética , Ligação Genética , Manihot/genética , Característica Quantitativa Herdável , Resposta ao Choque Frio , Genoma de Planta , Raízes de Plantas/genética , Raízes de Plantas/metabolismo , Polimorfismo de Nucleotídeo Único , Locos de Características Quantitativas
9.
Front Plant Sci ; 7: 680, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27242878

RESUMO

Reverse transcription quantitative real-time polymerase chain reaction (real-time PCR, also referred to as quantitative RT-PCR or RT-qPCR) is a highly sensitive and high-throughput method used to study gene expression. Despite the numerous advantages of RT-qPCR, its accuracy is strongly influenced by the stability of internal reference genes used for normalizations. To date, few studies on the identification of reference genes have been performed on cassava (Manihot esculenta Crantz). Therefore, we selected 26 candidate reference genes mainly via the three following channels: reference genes used in previous studies on cassava, the orthologs of the most stable Arabidopsis genes, and the sequences obtained from 32 cassava transcriptome sequence data. Then, we employed ABI 7900 HT and SYBR Green PCR mix to assess the expression of these genes in 21 materials obtained from various cassava samples under different developmental and environmental conditions. The stability of gene expression was analyzed using two statistical algorithms, namely geNorm and NormFinder. geNorm software suggests the combination of cassava4.1_017977 and cassava4.1_006391 as sufficient reference genes for major cassava samples, the union of cassava4.1_014335 and cassava4.1_006884 as best choice for drought stressed samples, and the association of cassava4.1_012496 and cassava4.1_006391 as optimal choice for normally grown samples. NormFinder software recommends cassava4.1_006884 or cassava4.1_006776 as superior reference for qPCR analysis of different materials and organs of drought stressed or normally grown cassava, respectively. Results provide an important resource for cassava reference genes under specific conditions. The limitations of these findings were also discussed. Furthermore, we suggested some strategies that may be used to select candidate reference genes.

10.
Nat Commun ; 5: 5110, 2014 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-25300236

RESUMO

Cassava is a major tropical food crop in the Euphorbiaceae family that has high carbohydrate production potential and adaptability to diverse environments. Here we present the draft genome sequences of a wild ancestor and a domesticated variety of cassava and comparative analyses with a partial inbred line. We identify 1,584 and 1,678 gene models specific to the wild and domesticated varieties, respectively, and discover high heterozygosity and millions of single-nucleotide variations. Our analyses reveal that genes involved in photosynthesis, starch accumulation and abiotic stresses have been positively selected, whereas those involved in cell wall biosynthesis and secondary metabolism, including cyanogenic glucoside formation, have been negatively selected in the cultivated varieties, reflecting the result of natural selection and domestication. Differences in microRNA genes and retrotransposon regulation could partly explain an increased carbon flux towards starch accumulation and reduced cyanogenic glucoside accumulation in domesticated cassava. These results may contribute to genetic improvement of cassava through better understanding of its biology.


Assuntos
Evolução Molecular , Genoma de Planta , Manihot/genética , Variação Genética , Manihot/classificação , Manihot/metabolismo , Dados de Sequência Molecular , Fotossíntese , Filogenia , Proteínas de Plantas/genética , Seleção Genética , Amido/metabolismo
11.
Int J Clin Exp Pathol ; 7(5): 2421-9, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24966952

RESUMO

Inflammatory pseudotumor (IPT)-like follicular dendritic cell (FDC) sarcoma is a recently described rare tumor and considered a unique entity, with different histologic appearances and behavior from those of the classical FDC sarcoma. This study analyzed the clinical and pathological findings of two such cases that the authors encountered and 36 previously reported cases identified in the literature. Assessment of all 38 cases showed a slight female predominance (2.2:1) with a median age of 56.5 years. Seventeen patients complained of abdominal discomfort or pain, while fifteen patients had no clinical symptom. Almost all cases occurred in liver (n=20) or spleen (n=17). Except in one case, all patients underwent surgical resection of the tumor alone. Histologic features showed a mixture of chronic inflammatory cells and variable amounts of spindle cells with vesicular nuclei and distinct nucleoli. The tumor cells expressed conventional FDC markers such as CD21 (75%), CD35 (92%), CD23 (62%), clusterin (75%), and CNA.42 (100%). EBV was detected in thirty-five cases (92.1%) by Epstein-Barr virus (EBV)-encoded RNA in situ hybridization, and EBV-latent membrane protein-1 was expressed in 90% of the cases. With a median follow-up of 21 months, 29 patients (85.3%) were alive and well, 4 (11.8%) were alive with disease, one patient (2.9%) died of disease. Only four patients with hepatic tumors underwent recurrence or metastasis after initial treatment. Epstein-Barr virus is thought to play a role in the development of the tumor; however, the pathogenesis of the disease and the origin of tumor cells remain unclear.


Assuntos
Sarcoma de Células Dendríticas Foliculares/patologia , Células Dendríticas Foliculares/patologia , Granuloma de Células Plasmáticas/patologia , Neoplasias Hepáticas/patologia , Neoplasias Esplênicas/patologia , Dor Abdominal/etiologia , Idoso , Biomarcadores Tumorais/análise , Biópsia , DNA Viral/genética , Sarcoma de Células Dendríticas Foliculares/complicações , Sarcoma de Células Dendríticas Foliculares/metabolismo , Sarcoma de Células Dendríticas Foliculares/mortalidade , Sarcoma de Células Dendríticas Foliculares/cirurgia , Sarcoma de Células Dendríticas Foliculares/virologia , Células Dendríticas Foliculares/química , Células Dendríticas Foliculares/virologia , Feminino , Granuloma de Células Plasmáticas/complicações , Granuloma de Células Plasmáticas/metabolismo , Granuloma de Células Plasmáticas/mortalidade , Granuloma de Células Plasmáticas/cirurgia , Granuloma de Células Plasmáticas/virologia , Hepatectomia , Herpesvirus Humano 4/genética , Humanos , Imuno-Histoquímica , Hibridização In Situ , Neoplasias Hepáticas/química , Neoplasias Hepáticas/complicações , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/cirurgia , Neoplasias Hepáticas/virologia , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Recidiva Local de Neoplasia , Valor Preditivo dos Testes , Fatores de Risco , Esplenectomia , Neoplasias Esplênicas/química , Neoplasias Esplênicas/complicações , Neoplasias Esplênicas/mortalidade , Neoplasias Esplênicas/cirurgia , Neoplasias Esplênicas/virologia , Fatores de Tempo , Resultado do Tratamento
12.
Transgenic Res ; 19(3): 461-72, 2010 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-19789991

RESUMO

Chinese cabbage (Brassica rapa L. ssp. pekinensis) is a common and economically important crop in Asia. Specific targets of plant breeding programs for cabbage have been improvement in yield, resistance to environment stresses, and nutrition quality by means of genetic manipulation. To obtain information on yield improvement applicable for the genetic engineering approach, we have attempted to dissect the molecular pathways that regulate organ size. We first isolated a putative homolog of ARGOS full-length cDNA from Chinese cabbage leaves, which we designated BrARGOS. At the transcription level, BrARGOS was detected in all organs tested in Chinese cabbage. To test the function of this gene, we then engineered Arabidopsis plants that would overexpress BrARGOS ectopically. The organs of the transgenic Arabidopsis plants were significantly larger than those of the control plants. This increase in size was due to enhanced cell proliferation, with no contribution from cell expansion. The molecular analysis revealed that overexpression of BrARGOS up-regulated the transcription of several genes involved in the control of organ size. These results suggest that the BrARGOS gene may function as one of the regulators of organ size in Chinese cabbage. As such, manipulation of the BrARGOS gene may significantly increase the size of Chinese cabbage organs, such as Chinese cabbage heads.


Assuntos
Agricultura/métodos , Arabidopsis/crescimento & desenvolvimento , Brassica rapa/genética , Genes de Plantas/genética , Engenharia Genética/métodos , Folhas de Planta/citologia , Regulação para Cima , Arabidopsis/genética , Arabidopsis/metabolismo , Sequência de Bases , Proliferação de Células , Primers do DNA/genética , Vetores Genéticos/genética , Dados de Sequência Molecular , Tamanho do Órgão/genética , Folhas de Planta/crescimento & desenvolvimento , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Análise de Sequência de DNA , Transformação Genética
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