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1.
Front Oncol ; 14: 1388626, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38863643

RESUMO

Background: Robot-assisted surgery has shown remarkable progress as a minimally invasive procedure for gastric cancer. This study aimed to compare the pre-emptive suprapancreatic approach without duodenal transection and the conventional approach in terms of perioperative feasibility and short-term surgical outcomes. Methods: We retrospectively analyzed all patients who underwent robotic distal gastrectomy with D2 lymph node dissection using the da Vinci Xi robotic system between December 2021 and April 2023 and categorized them into two groups for comparison. Patients treated using the pre-emptive suprapancreatic approach (observation group) were compared with those who received the conventional approach (control group). Employing one-to-one propensity score matching, we evaluated the postoperative morbidity and short-term outcomes in these two distinct groups to assess the efficacy and safety of the novel surgical technique. Results: This study enrolled 131 patients: 70 in the observation group and 61 in the control group. After propensity score matching, the operative times were significantly longer in the control group than in the observation group (229.10 ± 33.96 vs. 174.84 ± 18.37, p <0.001). The mean blood loss was lower in the observation group than in the control group (25.20 ± 11.18 vs. 85.00 ± 38.78, p <0.001). Additionally, the observation group exhibited a higher number of retrieved lymph nodes, including suprapyloric, perigastric, and superior pancreatic lymph nodes (28.69 ± 5.48 vs. 19.21 ± 2.89, p <0.001; 4.98 ± 1.27 vs. 4.29 ± 1.21, p = 0.012; 10.52 ± 2.39 vs. 5.50 ± 1.62, p <0.001; 6.26 ± 2.64 vs. 5.00 ± 1.72, p = 0.029). Drain amylase levels in the observation group were significantly lower than those in the control group (30.08 ± 33.74 vs. 69.14 ± 66.81, p <0.001). Conclusion: This study revealed that using the pre-emptive suprapancreatic approach without duodenal transection in the dissection of D2 lymph nodes for gastric cancer is a safe and feasible procedure in terms of surgical outcomes.

2.
iScience ; 27(2): 108822, 2024 Feb 16.
Artigo em Inglês | MEDLINE | ID: mdl-38303721

RESUMO

Alternative polyadenylation (APA) is an important post-transcriptional regulatory mechanism and is involved in many diseases, but its function and mechanism in regulating pancreatic cancer (PC) pathogenesis remain unclear. In this study, we found that the 3' UTR shortening of MZT1 was the most prominent APA event in PC liver metastases. The short-3'UTR isoform exerted a stronger effect in promoting cell proliferation and migration both in vitro and in vivo. NUDT21, a core cleavage factor involved in APA, promoted the usage of proximal polyadenylation sites (PASs) on MZT1 mRNA by binding to the UGUA element located upstream of the proximal PAS. High percentage of distal polyA site usage index of MZT1 was significantly associated with a better prognosis. These findings demonstrate a crucial mechanism that NUDT21-mediated APA of MZT1 could promote the progression of PC. Our findings provided a better understanding of the connection between PC progression and APA machinery.

3.
Chin Med J (Engl) ; 137(3): 283-293, 2024 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-37386732

RESUMO

BACKGROUND: The conversion of adenosine (A) to inosine (I) through deamination is the prevailing form of RNA editing, impacting numerous nuclear and cytoplasmic transcripts across various eukaryotic species. Millions of high-confidence RNA editing sites have been identified and integrated into various RNA databases, providing a convenient platform for the rapid identification of key drivers of cancer and potential therapeutic targets. However, the available database for integration of RNA editing in hematopoietic cells and hematopoietic malignancies is still lacking. METHODS: We downloaded RNA sequencing (RNA-seq) data of 29 leukemia patients and 19 healthy donors from National Center for Biotechnology Information (NCBI) Gene Expression Omnibus (GEO) database, and RNA-seq data of 12 mouse hematopoietic cell populations obtained from our previous research were also used. We performed sequence alignment, identified RNA editing sites, and obtained characteristic editing sites related to normal hematopoietic development and abnormal editing sites associated with hematologic diseases. RESULTS: We established a new database, "REDH", represents RNA editome in hematopoietic differentiation and malignancy. REDH is a curated database of associations between RNA editome and hematopoiesis. REDH integrates 30,796 editing sites from 12 murine adult hematopoietic cell populations and systematically characterizes more than 400,000 edited events in malignant hematopoietic samples from 48 cohorts (human). Through the Differentiation, Disease, Enrichment, and knowledge modules, each A-to-I editing site is systematically integrated, including its distribution throughout the genome, its clinical information (human sample), and functional editing sites under physiological and pathological conditions. Furthermore, REDH compares the similarities and differences of editing sites between different hematologic malignancies and healthy control. CONCLUSIONS: REDH is accessible at http://www.redhdatabase.com/ . This user-friendly database would aid in understanding the mechanisms of RNA editing in hematopoietic differentiation and malignancies. It provides a set of data related to the maintenance of hematopoietic homeostasis and identifying potential therapeutic targets in malignancies.


Assuntos
Neoplasias , RNA , Humanos , Animais , Camundongos , Edição de RNA/genética , Adenosina/genética , Adenosina/metabolismo , Análise de Sequência de RNA
4.
BMC Med ; 21(1): 489, 2023 12 08.
Artigo em Inglês | MEDLINE | ID: mdl-38066552

RESUMO

BACKGROUND: Pancreatic cancer (PC) is influenced by both genetic and lifestyle factors. However, further research is still needed to comprehensively clarify the relationships among lifestyle, genetic factors, their combined effect on PC, and how these associations might be age-dependent. METHODS: We included 340,631 participants from the UK Biobank. Three polygenic risk score (PRS) models for PC were applied, which were derived from the previous study and were categorized as low, intermediate, and high. Two healthy lifestyle scores (HLSs) were constructed using 9 lifestyle factors based on the World Cancer Research Fund/American Institute of Cancer Research (WCRF/AICR) lifestyle score and the American Cancer Society (ACS) guidelines and were categorized as unfavorable, intermediate, and favorable. Data were analyzed using Cox proportional hazards models. RESULTS: There were 1,129 cases of incident PC during a median follow-up of 13.05 years. Higher PRS was significantly associated with an increased risk of PC (hazard ratio [HR], 1.58; 95% confidence intervals [CI], 1.47-1.71). Adhering to a favorable lifestyle was associated with a lower risk (HR, 0.48; 95% CI, 0.41-0.56). Participants with an unfavorable lifestyle and a high PRS had the highest risk of PC (HR, 2.84; 95% CI, 2.22-3.62). Additionally, when stratified by age, a favorable lifestyle was most pronounced associated with a lower risk of PC among participants aged ≤ 60 years (HR, 0.35; 95% CI, 0.23-0.54). However, the absolute risk reduction was more pronounced among those aged > 70 years (ARR, 0.19%, 95% CI, 0.13%-0.26%). A high PRS was more strongly associated with PC among participants aged ≤ 60 years (HR, 1.89; 95% CI, 1.30-2.73). Furthermore, we observed a significant multiplicative interaction and several significant additive interactions. CONCLUSIONS: A healthy lifestyle was associated with a lower risk of PC, regardless of the participants' age, sex, or genetic risk. Importantly, our findings indicated the age-dependent association of lifestyle and genetic factors with PC, emphasizing the importance of early adoption for effective prevention and potentially providing invaluable guidance for setting the optimal age to start preventive measures.


Assuntos
Neoplasias Pancreáticas , Humanos , Pessoa de Meia-Idade , Estudos Prospectivos , Bancos de Espécimes Biológicos , Fatores de Risco , Estilo de Vida , Estilo de Vida Saudável , Neoplasias Pancreáticas/epidemiologia , Neoplasias Pancreáticas/genética
5.
Phytomedicine ; 119: 154977, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37506573

RESUMO

BACKGROUND: Dengue virus (DENV) is a major public health threat. However, there are no specific therapeutic drugs for DENV. Many Chinese heat-cleaning formulas, such as Liang-Ge-San (LGS), have been frequently used in the virus-induced diseases. The antiviral effect of LGS has not been reported yet. PURPOSE: In this study, the effect of LGS on the inhibition of dengue virus serotype 2 (DENV-2) was investigated and the relevant mechanism was explored. METHODS: High-performance liquid chromatography was applied to analyze the chemical characterization of LGS. The in vitro antiviral activities of LGS against DENV-2 were evaluated by time-of-drug-addition assay. The binding of heat shock protein 70 (Hsp70) and envelope (E) protein or caveolin1 (Cav1) were analyzed by immunofluorescence and immunoprecipitation assays. Then the role of Cav1 in the anti-DENV-2 effects of LGS was further examined. DENV-2 infected Institute of Cancer Research suckling mice (n = 10) and AG129 mice (n = 8) were used to examine the protective effects of LGS. RESULTS: It was found that geniposide, liquiritin, forsythenside A, forsythin, baicalin, baicalein, rhein, and emodin maybe the characteristic components of LGS. LGS inhibited the early stage of DENV-2 infection, decreased the expression levels of viral E and non-structural protein 1 (NS1) proteins. LGS also reduced E protein and Hsp70 binding and attenuated the translocation of Hsp70 from cytoplasm to the cell membrane. Moreover, LGS decreased the binding of Hsp70 to Cav1. Further study showed that the overexpression of Cav1 reversed LGS-mediated E protein and Hsp70 inhibition in the plasma membrane. In the in vivo study, LGS was highly effective in prolonging the survival time, reducing viral loads. CONCLUSION: This work demonstrates for the first time that LGS exerts anti-DENV-2 activity in vitro and in vivo. LGS decreases DENV-2-stimulated cytoplasmic Hsp70 translocation into the plasma membrane by Cav1 inhibition, thereby inhibiting the early stage of virus infection. These findings indicate that LGS may be a candidate for the treatment of DENV.


Assuntos
Vírus da Dengue , Dengue , Animais , Camundongos , Dengue/tratamento farmacológico , Proteínas de Choque Térmico HSP70 , Sorogrupo , Membrana Celular , Antivirais/farmacologia , Antivirais/uso terapêutico , Citoplasma/metabolismo
6.
Aging (Albany NY) ; 15(11): 5190-5214, 2023 06 13.
Artigo em Inglês | MEDLINE | ID: mdl-37315301

RESUMO

Clear cell renal cell carcinoma (ccRCC) is a common urological malignancy with diverse histological types. This study aimed to detect neoantigens in ccRCC to develop mRNA vaccines and distinguish between ccRCC immunological subtypes for construction of an immune landscape to select patients suitable for vaccination. Using The Cancer Genome Atlas SpliceSeq database, The Cancer Genome Atlas, and the International Cancer Genome Consortium cohorts, we comprehensively analysed potential tumour antigens of ccRCC associated with aberrant alternative splicing, somatic mutation, nonsense-mediated mRNA decay factors, antigen-presenting cells, and overall survival. Immune subtypes (C1/C2) and nine immune gene modules of ccRCC were identified by consistency clustering and weighted correlation network analysis. The immune landscape as well as molecular and cellular characteristics of immunotypes were assessed. Rho-guanine nucleotide exchange factor 3 (ARHGEF3) was identified as a new ccRCC antigen for development of an mRNA vaccine. A higher tumour mutation burden, differential expression of immune checkpoints, and immunogenic cell death were observed in cases with the C2 immunotype. Cellular characteristics increased the complexity of the immune environment, and worse outcomes were observed in ccRCC cases with the C2 immunotype. We constructed the immune landscape for selecting patients with the C2 immunotype suitable for vaccination.


Assuntos
Carcinoma de Células Renais , Carcinoma , Neoplasias Renais , Humanos , Carcinoma de Células Renais/genética , Seleção de Pacientes , Vacinas Sintéticas , RNA Mensageiro/genética , Neoplasias Renais/genética , Vacinas de mRNA
7.
Cancer Res ; 83(18): 3077-3094, 2023 09 15.
Artigo em Inglês | MEDLINE | ID: mdl-37363990

RESUMO

Circular RNAs (circRNA) contribute to cancer stemness, proliferation, and metastasis. The biogenesis of circRNAs can be impacted by the genetic landscape of tumors. Herein, we identified a novel circRNA, circARFGEF2 (hsa_circ_0060665), which was upregulated in KRASG12D pancreatic ductal adenocarcinoma (PDAC) and positively associated with KRASG12D PDAC lymph node (LN) metastasis. CircARFGEF2 overexpression significantly facilitated KRASG12D PDAC LN metastasis in vitro and in vivo. Mechanistically, circARFGEF2 biogenesis in KRASG12D PDAC was significantly activated by the alternative splicing factor QKI-5, which recruited U2AF35 to facilitate spliceosome assembly. QKI-5 bound the QKI binding motifs and neighboring reverse complement sequence in intron 3 and 6 of ARFGEF2 pre-mRNA to facilitate circARFGEF2 biogenesis. CircARFGEF2 sponged miR-1205 and promoted the activation of JAK2, which phosphorylated STAT3 to trigger KRASG12D PDAC lymphangiogenesis and LN metastasis. Importantly, circARFGEF2 silencing significantly inhibited LN metastasis in the KrasG12D/+Trp53R172H/+Pdx-1-Cre (KPC) mouse PDAC model. These findings provide insight into the mechanism and metastasis-promoting function of mutant KRAS-mediated circRNA biogenesis. SIGNIFICANCE: Increased splicing-mediated biogenesis of circARFGEF2 in KRAS-mutant pancreatic ductal adenocarcinoma activates JAK2-STAT3 signaling and triggers lymph node metastasis, suggesting circARFGEF2 could be a therapeutic target to inhibit pancreatic cancer progression.


Assuntos
Carcinoma Ductal Pancreático , MicroRNAs , Neoplasias Pancreáticas , Animais , Camundongos , Carcinoma Ductal Pancreático/patologia , Linhagem Celular Tumoral , Regulação Neoplásica da Expressão Gênica , Metástase Linfática , MicroRNAs/genética , Neoplasias Pancreáticas/patologia , Proteínas Proto-Oncogênicas p21(ras)/genética , RNA Circular , Humanos , Neoplasias Pancreáticas
8.
Front Immunol ; 14: 1076587, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37006288

RESUMO

Background: Metabolic reprogramming is a well-known hallmark of cancer. Systematical identification of clinically relevant metabolic subtypes of Hepatocellular carcinoma (HCC) is critical to understand tumor heterogeneity and develop efficient treatment strategies. Methods: We performed an integrative analysis of genomic, transcriptomic, and clinical data from an HCC patient cohort in The Cancer Genome Atlas (TCGA). Results: Four metabolic subtypes were defined: mHCC1, mHHC2, mHCC3, and mHCC4. These subtypes had distinct differences in mutations profiles, activities of metabolic pathways, prognostic metabolism genes, and immune features. The mHCC1 was associated with poorest outcome and was characterized by extensive metabolic alterations, abundant immune infiltration, and increased expression of immunosuppressive checkpoints. The mHHC2 displayed lowest metabolic alteration level and was associated with most significant improvement in overall survival in response to high CD8+ T cell infiltration. The mHHC3 was a "cold-tumor" with low immune infiltration and few metabolic alterations. The mHCC4 presented a medium degree of metabolic alteration and high CTNNB1 mutation rate. Based on our HCC classification and in vitro study, we identified palmitoyl-protein thioesterase 1 (PPT1) was a specific prognostic gene and therapeutic target for mHCC1. Conclusion: Our study highlighted mechanistic differences among metabolic subtypes and identified potential therapeutic targets for subtype-specific treatment strategies targeting unique metabolic vulnerabilities. The immune heterogeneities across metabolic subtypes may help further clarify the association between metabolism and immune environment and guide the development of novel strategies through targeting both unique metabolic vulnerabilities and immunosuppressive triggers.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/terapia , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/terapia , Linfócitos T CD8-Positivos , Perfilação da Expressão Gênica , Genômica , Imunossupressores
10.
Cancers (Basel) ; 15(5)2023 Feb 24.
Artigo em Inglês | MEDLINE | ID: mdl-36900234

RESUMO

The hallmark of pancreatic ductal adenocarcinoma (PDAC) is an exuberant tumor microenvironment (TME) comprised of diverse cell types that play key roles in carcinogenesis, chemo-resistance, and immune evasion. Here, we propose a gene signature score through the characterization of cell components in TME for promoting personalized treatments and further identifying effective therapeutic targets. We identified three TME subtypes based on cell components quantified by single sample gene set enrichment analysis. A prognostic risk score model (TMEscore) was established based on TME-associated genes using a random forest algorithm and unsupervised clustering, followed by validation in immunotherapy cohorts from the GEO dataset for its performance in predicting prognosis. Importantly, TMEscore positively correlated with the expression of immunosuppressive checkpoints and negatively with the gene signature of T cells' responses to IL2, IL15, and IL21. Subsequently, we further screened and verified F2R-like Trypsin Receptor1 (F2RL1) among the core genes related to TME, which promoted the malignant progression of PDAC and has been confirmed as a good biomarker with therapeutic potential in vitro and in vivo experiments. Taken together, we proposed a novel TMEscore for risk stratification and selection of PDAC patients in immunotherapy trials and validated effective pharmacological targets.

11.
Chembiochem ; 24(3): e202200506, 2023 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-36450656

RESUMO

Bioorthogonal prodrugs with both fast reaction kinetics and multiple outputs are highly desirable but are only found sporadically. Herein, we report a novel photoclick-and-release strategy for the co-activation of carbon monoxide and a self-reporter, carbonyl sulfide, or sulfonamide with fast reaction kinetics (k: 1.4-22.6 M-1 s-1 ). Such a photoclick-and-release strategy was successfully applied in live cells to deliver carbon monoxide and a fluorescent self-reporter, both of which exhibited pronounced antiproliferative activity against 4T1 cancer cells. It is conceivable that this photoclick-and-release strategy could find applications in other fields, in which a controlled bond cleavage is preferred.


Assuntos
Monóxido de Carbono , Pró-Fármacos , Estrutura Molecular , Monóxido de Carbono/química , Cinética , Sulfonamidas , Corantes , Pró-Fármacos/química , Sulfanilamida
13.
Bioresour Technol ; 364: 128068, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36202280

RESUMO

Ionic liquids (ILs) have been considered as promising alternatives to traditional reagent for lignocellulosic biomass pretreatment because of their tunable physicochemical and "green" properties. In the study, the influence of 1-Butyl-3-methylimidazolium acetate ([Bmim]acetate) pretreatment of giant reed on H2 yield improvement via photo-fermentation (PF) was evaluated. Under the optimal pretreatment conditions (6 g/L [Bmim]acetate at 70 °C for 4 h), the delignification of giant reed was up to 26.7 %. In addition, the sugar yield (9.5 g/L) and hydrogen yield (72.3 mL/g TS) from giant reed were enhanced by 1.7-fold and 61.7 % over those of untreated giant reed, respectively. Moreover, ternary analysis showed that retention time had the strongest effect on delignification, sugar yield and hydrogen yield of giant reed compared to pretreatment temperature and [Bmim]acetate loading. These experimental results indicated that [Bmim]acetate pretreatment of giant reed is an effective approach to enhance the hydrogen yield via PF.

14.
Front Immunol ; 13: 876195, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36091047

RESUMO

Lactate can play an immunosuppressive role in the tumor microenvironment and promote tumor development by recruiting and inducing the activity of immunosuppressive cells and molecules. High lactate concentrations are important for tumor cell metastasis, angiogenesis, and treatment resistance. With the in-depth studies on tumor metabolism, lactate, one of the key factors involved in glycolysis, has been increasing emerged its characteristic clinical value in colorectal cancer (CRC). In this study, lactate genes were screened based on lactate metabolism pathways. Subsequently, the lactate subtypes were determined by clustering and analysis of the subtypes at all levels, including immune checkpoints, immune infiltration, and clinical characteristics, which revealed the biological significance of lactate metabolism in CRC. Subtype-based differential gene analysis resulted in a lactate score, which stratifies the prognosis of CRC. We discovered that 27 lactate genes and 61 lactate-phenotype genes are associated with immune cell infiltration and have a significant prognostic efficacy. The CRC patients were clustered into four subtypes and five clusters, based on lactate genes and lactate-phenotype genes, respectively. There are significant differences in survival time and activities of hallmark pathways, namely immune-related signatures and chemokines, among these subtypes and clusters. Particularly, cluster 2 and subtype 1 have significantly higher lactate scores than that of the others. In conclusion, lactate score is an independent prognostic factor for cancer that can be used as a clinical guide for predicting CRC progression and as an evaluation factor for the effect of immunotherapy in CRC.


Assuntos
Neoplasias Colorretais , Ácido Láctico , Neoplasias Colorretais/patologia , Humanos , Neovascularização Patológica , Prognóstico , Microambiente Tumoral/genética
15.
J Clin Invest ; 132(14)2022 07 15.
Artigo em Inglês | MEDLINE | ID: mdl-35579947

RESUMO

Lymph node (LN) metastasis occurs frequently in pancreatic ductal adenocarcinoma (PDAC) and predicts poor prognosis for patients. The KRASG12D mutation confers an aggressive PDAC phenotype that is susceptible to lymphatic dissemination. However, the regulatory mechanism underlying KRASG12D mutation-driven LN metastasis in PDAC remains unclear. Herein, we found that PDAC with the KRASG12D mutation (KRASG12D PDAC) sustained extracellular vesicle-mediated (EV-mediated) transmission of heterogeneous nuclear ribonucleoprotein A1 (hnRNPA1) in a SUMOylation-dependent manner and promoted lymphangiogenesis and LN metastasis in vitro and in vivo. Mechanistically, hnRNPA1 bound with SUMO2 at the lysine 113 residue via KRASG12D-induced hyperactivation of SUMOylation, which enabled its interaction with TSG101 to enhance hnRNPA1 packaging and transmission via EVs. Subsequently, SUMOylation induced EV-packaged-hnRNPA1 anchoring to the adenylate- and uridylate-rich elements of PROX1 in lymphatic endothelial cells, thus stabilizing PROX1 mRNA. Importantly, impeding SUMOylation of EV-packaged hnRNPA1 dramatically inhibited LN metastasis of KRASG12D PDAC in a genetically engineered KrasG12D/+ Trp53R172H/+ Pdx-1-Cre (KPC) mouse model. Our findings highlight the mechanism by which KRAS mutant-driven SUMOylation triggers EV-packaged hnRNPA1 transmission to promote lymphangiogenesis and LN metastasis, shedding light on the potential application of hnRNPA1 as a therapeutic target in patients with KRASG12D PDAC.


Assuntos
Carcinoma Ductal Pancreático , Vesículas Extracelulares , Neoplasias Pancreáticas , Animais , Carcinoma Ductal Pancreático/metabolismo , Linhagem Celular Tumoral , Células Endoteliais/metabolismo , Vesículas Extracelulares/metabolismo , Humanos , Linfangiogênese/genética , Metástase Linfática , Camundongos , Neoplasias Pancreáticas/metabolismo , Proteínas Proto-Oncogênicas p21(ras)/genética , Proteínas Proto-Oncogênicas p21(ras)/metabolismo , Sumoilação , Neoplasias Pancreáticas
16.
Cancer Res ; 82(12): 2239-2253, 2022 06 15.
Artigo em Inglês | MEDLINE | ID: mdl-35395674

RESUMO

Circular RNAs (circRNA) containing retained introns are normally sequestered in the nucleus. Dysregulation of cellular homeostasis can drive their nuclear export, which may be involved in cancer metastasis. However, the mechanism underlying circRNA nuclear export and its role in lymph node (LN) metastasis of bladder cancer remain unclear. Here, we identify an intron-retained circRNA, circNCOR1, that is significantly downregulated in LN metastatic bladder cancer and is negatively associated with poor prognosis of patients. Overexpression of circNCOR1 inhibited lymphangiogenesis and LN metastasis of bladder cancer in vitro and in vivo. Nuclear circNCOR1 epigenetically promoted SMAD7 transcription by increasing heterogeneous nuclear ribonucleoprotein L (hnRNPL)-induced H3K9 acetylation in the SMAD7 promoter, leading to inhibition of the TGFß-SMAD signaling pathway. Nuclear retention of circNCOR1 was regulated by small ubiquitin-like modifier (SUMO)ylation of DDX39B, an essential regulatory factor responsible for circRNA nuclear-cytoplasmic transport. Reduced SUMO2 binding to DDX39B markedly increased circNCOR1 retention in the nucleus to suppress bladder cancer LN metastasis. By contrast, SUMOylated DDX39B activated nuclear export of circNCOR1, impairing the suppressive role of circNCOR1 on TGFß-SMAD cascade activation and bladder cancer LN metastasis. In patient-derived xenograft (PDX) models, overexpression of circNCOR1 and inhibition of TGFß signaling significantly repressed tumor growth and LN metastasis. This study highlights SUMOylation-induced nuclear export of circNCOR1 as a key event regulating TGFß-SMAD signaling and bladder cancer lymphangiogenesis, thus supporting circNCOR1 as a novel therapeutic agent for patients with LN metastatic bladder cancer. SIGNIFICANCE: This study identifies the novel intron-retained circNCOR1 and elucidates a SUMOylation-mediated DDX39B-circNCOR1-SMAD7 axis that regulates lymph node metastasis of bladder cancer.


Assuntos
Correpressor 1 de Receptor Nuclear/genética , RNA Circular , Neoplasias da Bexiga Urinária , Transporte Ativo do Núcleo Celular/genética , Humanos , Metástase Linfática , RNA Circular/genética , Proteína Smad7/metabolismo , Fator de Crescimento Transformador beta/genética , Fator de Crescimento Transformador beta/metabolismo , Neoplasias da Bexiga Urinária/patologia
17.
Bioresour Technol ; 347: 126743, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-35066127

RESUMO

Substances harmful to photo-fermentative biological hydrogen production (PFHP) were produced during cellulose hydrolysis. This study aimed to evaluate the effect of by-products (5-hydroxymethylfurfural (5-HMF) and furfural) released from lignocellulose during enzymatic hydrolysis process on PFHP. The exist of 5-HMF inhibited the hydrogen production. However, 0.2 g/L furfural improved the hydrogen production by 19 % compared to no addition (511.6 mL) with a maximum concentration of nitrogenase (109.96 IU/L) at 96 h. Furthermore, a 18.7 % enhancement of hydrogen production was also observed when 0.2 g/L 5-HMF and furfural were mixed at a ratio of 1:1, while decrement of hydrogen production at higher addition was observed as well. Through the scatter matrix analysis, it was concluded that 5-HMF and furfural additives had significant effects on PFHP. This study gave an insight into effect of lignocellulosic by-products on biohydrogen production.


Assuntos
Furaldeído , Hidrogênio , Fermentação
18.
Bioresour Technol ; 343: 126088, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34624469

RESUMO

Ionic liquids (ILs) pretreatment has been regarded as a promising green way to treat lignocellulosic biomass. 1-Butyl-3-methylimidazolium tetrafluoroborate ([Bmim]BF4), 1-allyl-3-methylimidazolium chloride ([Amim]Cl), and 1-Butyl-3-methylimidazolium Hydrogen Sulfate ([Bmim]HSO4) with different loadings (2, 4, 8, and 16 g/L) were adopted to pretreat the Arundo donax L.. 16 g/L [Bmim]HSO4 pretreated Arundo donax L. obtained the highest sugar yield of 7.9 g/L during the enzymatic hydrolysis and hydrogen yield of 106.1 mL/g TS during the photo-fermentation, which were 68.8 % and 35.3 % higher than those of untreated Arundo donax L., respectively. Moreover, volatile fatty acids (VFAs) distribution revealed that acetic acid was the main by-product during hydrogen production process with ILs pretreated Arundo donax L.. Besides, the relationship between sugar yield and hydrogen yield was the closest based on scatter matrix analysis. This study helps to understand of correlation between ILs pretreatment with the behavior of bioenergy production.


Assuntos
Líquidos Iônicos , Fermentação , Hidrogênio , Hidrólise , Poaceae
19.
J Gastrointest Surg ; 26(3): 659-661, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-34545544

RESUMO

INTRODUCTION: Pylorus-preserving gastrectomy (PPG) has been accepted as a representative function-preserving procedure for early gastric cancer (EGC) in the middle stomach. Totally, intracorporeal laparoscopic gastrectomy can provide better aesthetics, be less invasive, and allow faster postoperative recovery. Here, we first describe the surgical procedure of totally laparoscopic pylorus-preserving gastrectomy with intracorporeal hand-sewn anastomosis (TLPPG-IHSA). METHODS: After standard procedure of lymph node dissection and middle stomach resection, we used two double-needle barbed sutures to perform a layer-to-layer manual anastomosis of the anterior and posterior walls in the abdominal cavity. Twelve patients with preoperatively diagnosed clinical EGC located in the middle third of the stomach underwent TLPPG-IHSA between August 2019 and January 2021. RESULTS: A total of 12 patients with EGC successfully underwent TLPPG-IHSA. Only one patient (8.3%) suffered postoperative gastric stasis. No complications or recurrence occurred in other patients during half a year after surgery. CONCLUSION: TLPPG-IHSA is considered technically feasible to treat EGC located in the middle third of the stomach.


Assuntos
Laparoscopia , Neoplasias Gástricas , Anastomose Cirúrgica/métodos , Gastrectomia/métodos , Humanos , Laparoscopia/métodos , Piloro/cirurgia , Neoplasias Gástricas/patologia , Neoplasias Gástricas/cirurgia
20.
Bioresour Technol ; 344(Pt B): 126302, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34752886

RESUMO

Suitable illumination project would help in achieving high light conversion efficiency (LCE) for photo-fermentation. This study proposed an improvement strategy for LCE of photo-fermentative hydrogen production (PFHP) with a photosynthetic consortium by adopting light-dark duration alternation. For this purpose, 6 projects (continues light, 24 h light + 24 h dark, 24 h dark + 24 h light, 48 h light + 48 h light, 48 h dark + 48 h light, and continues dark) light disturbances were carried out to estimate the strategy. The fluctuation of cell growth (OD660) was corresponded to the light-dark alternation. 24 h dark + 24 h light alternation achieved the maximum hydrogen yield (HY) of 390.9 mL/g TS cell (6.7 % higher than continuous light) and maximum improvement of LCE of 114.7%. Moreover, heat map analysis revealed that the light period after inoculation had the closest relation (Pearson's r = 1) with the average hydrogen production rate (HPR) of photo-fermentation. Besides, decreased dark period after inoculation would increase the hydrogen yield of photo-fermentation.


Assuntos
Hidrogênio , Poaceae , Fermentação , Concentração de Íons de Hidrogênio , Iluminação
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