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1.
J Vet Med Sci ; 2024 Mar 14.
Artigo em Inglês | MEDLINE | ID: mdl-38479882

RESUMO

The study aimed to investigate the effect of Grid1, encoding the glutamate ionotropic receptor delta type subunit 1(GluD1), on puberty onset in female rats. Grid1 mRNA and protein expression was detected in the hypothalamus of female rats at prepuberty and puberty. Additionally, the expression of Grid1 was suppressed in primary hypothalamus cells and prepubertal rat. Finally, investigated the effect of Grid1 knockdown on puberty onset and reproductive performance. The levels of Grid1 mRNA in the hypothalamus, the fluorescence intensity in the arcuate nucleus and paraventricular nucleus of the prepubertal rats was significantly lower than pubertal. Treatment of hypothalamic neurons with LV-Grid1 decreased the level of Grid1 and Rfrp-3 (encoding RFamide-related peptide 3) mRNA expression, but increased the Gnrh (encoding gonadotropin-releasing hormone) mRNA levels. After an ICV injection, the time for the rat vaginal opening occurred earlier. Moreover, Gnrh mRNA expression was increased, whereas Rfrp-3 mRNA expression was decreased in the hypothalamus. The concentration of progesterone(P4) in the serum was significantly decreased compare with control group. Ovary hematoxylin-eosin staining revealed that the LV-Grid1 group mainly contained primary and secondary follicles. The reproductive performance of the rats was not affected by the Grid1 knockdown. Therefore, Grid1 may affect the onset of puberty in female rats by regulating the levels of Gnrh, and Rfrp-3 in the hypothalamus, as well as the concentrations of P4, but not reproduction performance.

2.
J Pers Med ; 14(2)2024 Jan 23.
Artigo em Inglês | MEDLINE | ID: mdl-38392565

RESUMO

BACKGROUND: Colorectal cancer (CRC) is the leading cause of cancer deaths, and treatment, especially in the metastatic stage, is challenging. Immune checkpoint inhibitors (ICIs) have revolutionized CRC treatment, but response varies, emphasizing the need for effective biomarkers. This study explores SPEN mutations as potential biomarkers. METHODS: Using data from the Memorial Sloan Kettering Cancer Center (MSKCC) and The Cancer Genome Atlas (TCGA)-Colorectal Cancer, this research applied bioinformatics tools and statistical analysis to SPEN (Split Ends) mutant and wild-type CRC patients treated with ICIs. Focus areas included mutation rates, immune cell infiltration, and DNA damage response pathways. RESULTS: The SPEN mutation rate was found to be 13.8% (15/109 patients) in the MSKCC cohort and 6.65% (35/526 patients) in the TCGA cohort. Our findings indicate that CRC patients with SPEN mutations had a longer median overall survival (OS) than the wild-type group. These patients also had higher tumor mutational burden (TMB), microsatellite instability (MSI) scores, and programmed death-ligand 1 (PD-L1) expression. SPEN mutants also exhibited increased DNA damage response (DDR) pathway mutations and a greater presence of activated immune cells, like M1 macrophages and CD8+ T cells, while wild-type patients had more resting/suppressive immune cells. Furthermore, distinct mutation patterns, notably with TP53, indicated a unique molecular subtype in SPEN-mutated CRC. CONCLUSIONS: We conclude that SPEN mutations might improve ICI efficacy in CRC due to increased immunogenicity and an inflammatory tumor microenvironment. SPEN mutations could be predictive biomarkers for ICI responsiveness, underscoring their value in personalized therapy and highlighting the importance of genomic data in clinical decisions. This research lays the groundwork for future precision oncology studies.

3.
J Trace Elem Med Biol ; 83: 127387, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38237425

RESUMO

BACKGROUND: Biogenic selenium nanoparticles (SeNPs) show numerous advantages including their high stability, low toxicity, and high bioactivity. While metabolism of SeNPs remains not well studied and need more investigation to reveal the process. PURPOSE: The objective of the study was to investigate the relationship between nitrate reductase and selenite reduction in Rahnella aquatilis HX2, characterize the properties of HX2 produced SeNPs, and explore their potential applications, particularly their anticancer activity. PROCEDURES: Selenium species were measured by high-performance liquid chromatography coupled to inductively coupled plasma - Mass spectrometry (HPLC-ICP-MS). Transcription level of nitrate reductase was determined by Real-time quantitative PCR. Morphology, particle size, crystal structure and surface chemistry of SeNPs were determined by electron microscopy, dynamic light scattering method, Raman scattering, X-ray photoelectron spectroscopy, respectively. Anti cancer cell activity was measured by CCK-8 assay. MAIN FINDINGS: SeNP production in R. aquatilis HX2 was correlated with the cell growth. The products of selenite reduction in HX2 detected by HPLC-ICP-MS included SeNPs, selenocysteine (SeCys), Se-Methylselenocysteine (MeSeCys), and 7 unknown compounds. Nitrate addition experiments suggested the involvement of nitrate reductase in selenite reduction in HX2. Both the cellular membrane and cytoplasm of HX2 exhibited selenite-reducing ability, indicating that membrane-associated nitrate reductase was not the sole selenite reductase in HX2. Characterization of the biogenic SeNPs revealed a spherical morphology and amorphous structure of them. Surface chemistry analysis implicated the binding of extracellular polymeric substances to the biogenic SeNPs, and the presence of Se0, Se2-, and electron-rich Se atoms on the surface of SeNPs. Finally, the IC50 values of the biogenic SeNPs were 36.49 µM for HepG2 and 3.70 µM for HeLa cells. CONCLUSIONS: The study first revealed that the nitrate reductase is involving in selenite reduction in R. aquatilis HX2. The biogenic SeNPs coordinated with organic substances in the surface. And SeNPs produced by R. aquatilis HX2 showed excellent anticancer activities on HepG2 and HeLa cells.


Assuntos
Nanopartículas , Rahnella , Selênio , Humanos , Selênio/metabolismo , Ácido Selenioso/farmacologia , Rahnella/metabolismo , Nitrato Redutase , Células HeLa , Nanopartículas/química
4.
Bioresour Technol ; 395: 130335, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38242237

RESUMO

This study presented the effects of hydrochar on humification, heavy metals (HMs) bioavailability and bacterial community succession during composting. Results indicated that hydrochar addition led to elevated composting temperature, 7.3% increase in humic acid (HA), and 52.9% increase in ratio of humic acid to fulvic acid. The diethylene triamine pentacetic acid extractable Zn, Cu, Pb, and Ni were reduced by 19.2%, 36.3%, 37.8%, and 27.1%, respectively, in hydrochar-involved composting system. Furthermore, main mechanisms driving the reduced HMs bioavailability by hydrochar addition were revealed. The addition of hydrochar significantly modified the microbial community structure. Correlation analysis and microbial analysis demonstrated that relative abundance of bacterial groups connected with humification and HMs passivation were increased. Consequently, the HA formation was promoted and the HMs bioavailability were reduced through bacterial bioremediation and HA complexation. This study demonstrates the addition of hydrochar as a promising strategy to mitigate the HMs bioavailability during composting.


Assuntos
Compostagem , Metais Pesados , Microbiota , Substâncias Húmicas , Solo/química , Disponibilidade Biológica , Esterco , Metais Pesados/análise
5.
Bioresour Technol ; 387: 129672, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37586429

RESUMO

Animal manure is a primary repository of antibiotic resistance genes (ARGs) and mobile genetic elements (MGEs). This work explored the efficiency of ARGs and MGEs removal during pig manure composting after thermal pretreatment (TPC) and the underlying mechanisms. TPC resulted in a decrease of 94.7% and 92.3% in the relative abundance of ARGs and MGEs which was 48.9% and 76.6% lower than control, respectively. Network analysis indicated that reductions of ARGs and MGEs in TPC were relevant to decrease in the amount and abundance of bacterial hosts. Furthermore, total ARGs abundance in TPC was correlated with that of intI1 and Tn916/1545 (P < 0.001). Redundancy analysis supported a leading role of MGEs in ARGs dynamics in TPC. Reduction of MGEs rather than bacterial hosts contributed mainly to ARGs removal in TPC, as revealed by structural equation modeling. In conclusion, TPC was an effective method to treat animal manure containing ARGs.


Assuntos
Compostagem , Genes Bacterianos , Animais , Suínos , Genes Bacterianos/genética , Esterco/microbiologia , Antibacterianos , Bactérias/genética , Resistência Microbiana a Medicamentos/genética , Sequências Repetitivas Dispersas/genética
6.
Foods ; 12(9)2023 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-37174401

RESUMO

Chinese bayberry (Myrica rubra Sieb. et Zucc.) pomace wine (CPW) is fruity and rich in bioactive compounds, with high nutritional value and antioxidant activities. This study aims to investigate the protective effect of CPW on the oxidative damage induced by hydrogen peroxide in human hepatocellular carcinoma (HepG2) cells and CPW's possible underlying mechanism. The fluorescence assay results revealed that CPW pre-treatment inhibited intracellular reactive oxygen species (ROS) accumulation in H2O2-induced HepG2 cells and cell membrane injury. Meanwhile, CPW remarkably enhanced the activity of antioxidant enzymes including superoxide dismutase (SOD), catalase (CAT), glutathione reductase (GR), and the content of glutathione (GSH). Moreover, CPW pretreatment significantly regulated the expression of Kelch-like ECH-associated protein 1 (Keap1)/nuclear factor erythroid 2-related factor 2 (Nrf2) pathway-associated genes (Keap1, Nrf2, NADPH quinone oxidoreductase I (NQO1), and heme oxygenase-1 (HO-1)) and its downstream antioxidant genes (SOD, CAT, GSH, and the glutamate-cysteine ligase catalytic (GCLC) subunit) in HepG2 cells. These data demonstrated that CPW prevented H2O2-induced oxidative stress by regulating the Keap1/Nrf2 signaling pathway.

7.
J Ovarian Res ; 16(1): 69, 2023 Apr 06.
Artigo em Inglês | MEDLINE | ID: mdl-37024956

RESUMO

BACKGROUND: Age at puberty is an important factor affecting goat fertility, with endocrine and genetic factors playing a crucial role in the onset of puberty. To better understand the relationship between endocrine and genetic factors and mechanisms underlying puberty onset in goats, reproductive hormone levels were analyzed by ELISA and ultraperformance liquid chromatography-multiple reaction monitoring-multistage/mass spectrometry and RNA sequencing was performed to analyze ovarian genes. RESULTS: Serum follicle stimulating hormone, luteinizing hormone, estradiol, 11-deoxycortisol, 11-deoxycorticosterone, corticosterone, cortisone, and cortisol levels were found to be higher but progesterone were lower in pubertal goats as compared to those in prepubertal goats (P < 0.05). A total of 18,139 genes were identified in cDNA libraries, and 75 differentially expressed genes (DEGs) were identified (|log2 fold change|≥ 1, P ≤ 0.05), of which 32 were significantly up- and 43 were down-regulated in pubertal goats. Gene ontology enrichment analyses indicated that DEGs were mainly involved in "metabolic process," "signaling," "reproduction," and "growth." Further, DEGs were significantly enriched in 91 Kyoto Encyclopedia of Genes and Genomes pathways, including estrogen signaling pathway, steroid hormone biosynthesis, and cAMP signaling pathway. Bioinformatics analysis showed that PRLR and THBS1 were highly expressed in pubertal ovaries, and ZP3, ZP4, and ASTL showed low expression, suggesting their involvement in follicular development and lutealization. CONCLUSIONS: To summarize, serum hormone changes and ovarian DEGs expression were investigated in our study. Further studies are warranted to comprehensively explore the functions of DEGs in goat puberty.


Assuntos
Cabras , Ovário , Animais , Feminino , Ovário/metabolismo , Cabras/genética , Hormônio Luteinizante , Hormônio Foliculoestimulante , Estradiol , Perfilação da Expressão Gênica
8.
Front Oncol ; 13: 1085188, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37051536

RESUMO

Introduction: Hepatocellular carcinoma (HCC) is one of the most invasive cancers with a low 5-year survival rate. Pyroptosis, a specialized form of cell death, has shown its association with cancer progression. However, its role in the prognosis of HCC has not been fully understood. Methods: In our study, clinical information and mRNA expression for 1076 patients with HCC were obtained from the five public cohorts. Pyroptotic clusters were generated by unsupervised clustering based on 40 pyroptosis-related genes (PRGs) in the TCGA and ICGC cohort. A pyroptosis-related signature was constructed using least absolute shrinkage and selection operator (LASSO) regression according to differentially expressed genes (DEGs) of pyroptotic clusters. The signature was then tested in the validation cohorts (GES10142 and GSE14520) and subsequently validated in the CPTAC cohort (n=159) at both mRNA and protein levels. Response to sorafenib was explored in GSE109211. Results: Three clusters were identified based on the 40 PRGs in the TCGA cohort. A total of 24 genes were selected based on DEGs of the above three pyroptotic clusters to construct the pyroptotic risk score. Patients with the high-risk score showed shorter overall survival (OS) compared to those with the low-risk score in the training set (P<0.001; HR, 3.06; 95% CI, 2.22-4.24) and the test set (P=0.008; HR, 1.61; 95% CI, 1.13-2.28). The predictive ability of the risk score was further confirmed in the CPTAC cohort at both mRNAs (P<0.001; HR, 2.99; 95% CI, 1.67-5.36) and protein levels (P<0.001; HR, 2.97; 95% CI 1.66-5.31). The expression of the model genes was correlated with immune cell infiltration, angiogenesis-related genes, and sensitivity to antiangiogenic therapy (P<0.05). Discussion: In conclusion, we established a prognostic signature of 24 genes based on pyroptosis clusters for HCC patients, providing insight into the risk stratification of HCC.

9.
Heliyon ; 9(3): e13984, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36925554

RESUMO

VFAs accumulation in anaerobic digestion systems can lead to disturbance of the acid base balance, which has brought major challenges for methane production. Meanwhile, less research explored the potential of biochar derived from wood wastes of oriental plane tree (Platanus orientalis L.) for stimulating methanization in mesophilic anaerobic digestion. In this study, the effects of pyrochar and hydrochar derived from sawdust of oriental plane tree on mesophilic anaerobic digestion of swine manure were compared for the first time. Fourier infrared transform analysis indicated that more functional groups existed on the surface of hydrochar, whereas higher ash content and BET specific surface area were found in pyrochar. The maximum methane production rate during anaerobic digestion was observed in the pyrochar treatment, which increased by 59.5% compared with the control without biochar. Although stimulative effects on dissolved organic carbon and volatile fatty acids production were both observed in the pyrochar and hydrochar treatments, the pyrochar treatment was much easier to trigger multipath methanogenesis and direct interspecific electron transport and subdue propionic acid accumulation compared to the hydrochar treatment. Moreover, redundancy analysis indicated that the variations in acetic acid and dissolved organic carbon were mostly associated with microbial succession. These results suggest that pyrochar has better promoting effects than HC in terms of methane generation and propionic acid inhibition alleviation owing to its special porous structures, functional groups (e.g., C=O, C-O and O-H), and physicochemical properties. These excellent properties play a greater role in recruiting functional archaea and bacteria to regulate the levels of volatile fatty acids and dissolved organic carbon to enhance the methane yield of anaerobic digestion. This study provides novel and valuable information for further engineering applications of pyrochar and hydrochar derived from sawdust of oriental plane tree in energy production and environmental waste treatment.

10.
medRxiv ; 2023 Feb 24.
Artigo em Inglês | MEDLINE | ID: mdl-36865297

RESUMO

Androgen Receptor (AR) signaling inhibitors, including enzalutamide, are treatment options for patients with metastatic castration-resistant prostate cancer (mCRPC), but resistance inevitably develops. Using metastatic samples from a prospective phase II clinical trial, we epigenetically profiled enhancer/promoter activities with H3K27ac chromatin immunoprecipitation followed by sequencing, before and after AR-targeted therapy. We identified a distinct subset of H3K27ac-differentially marked regions that associated with treatment responsiveness. These data were successfully validated in mCRPC patient-derived xenograft models (PDX). In silico analyses revealed HDAC3 as a critical factor that can drive resistance to hormonal interventions, which we validated in vitro . Using cell lines and mCRPC PDX tumors in vitro , we identified drug-drug synergy between enzalutamide and the pan-HDAC inhibitor vorinostat, providing therapeutic proof-of-concept. These findings demonstrate rationale for new therapeutic strategies using a combination of AR and HDAC inhibitors to improve patient outcome in advanced stages of mCRPC.

11.
Reprod Biol Endocrinol ; 20(1): 100, 2022 Jul 12.
Artigo em Inglês | MEDLINE | ID: mdl-35821045

RESUMO

Insulin-like growth factor-binding protein-5 (IGFBP-5) has recently been shown to alter the reproductive capacity by regulating insulin-like growth factor (IGF) bioavailability or IGF-independent effects. The present study aimed to investigate the effect and mechanism of IGFBP-5 on the onset of puberty in female rats. Immunofluorescence and real-time quantitative PCR were used to determine the expression and location of IGFBP-5 mRNA and protein distribution in the infant's hypothalamus-pituitary-ovary (HPO) axis prepuberty, peripuberty, puberty and adult female rats. Prepubertal rats with IGFBP-5 intracerebroventricular (ICV) were injected to determine the puberty-related genes expression and the concentrations of reproductive hormones. Primary hypothalamic cells were treated with IGFBP-5 to determine the expression of puberty-related genes and the Akt and mTOR proteins. Results showed that Igfbp-5 mRNA and protein were present on the HPO axis. The addition of IGFBP-5 to primary hypothalamic cells inhibited the expression of Gnrh and Igf-1 mRNAs (P < 0.05) and increased the expression of AKT and mTOR protein (P < 0.01). IGFBP-5 ICV-injection delayed the onset of puberty, reduced Gnrh, Igf-1, and Fshß mRNAs, and decreased the concentrations of E2, P4, FSH,serum LH levels and the ovaries weight (P < 0.05). More corpus luteum and fewer primary follicles were found after IGFBP-5 injection (P < 0.05).


Assuntos
Proteína 5 de Ligação a Fator de Crescimento Semelhante à Insulina , Puberdade , Animais , Feminino , Hormônio Liberador de Gonadotropina/metabolismo , Proteína 5 de Ligação a Fator de Crescimento Semelhante à Insulina/biossíntese , Proteína 5 de Ligação a Fator de Crescimento Semelhante à Insulina/genética , Proteínas Proto-Oncogênicas c-akt/metabolismo , Puberdade/genética , Puberdade/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Ratos
12.
BMC Genomics ; 23(1): 507, 2022 Jul 13.
Artigo em Inglês | MEDLINE | ID: mdl-35831802

RESUMO

BACKGROUND: Changes in the abundance of ovarian proteins play a key role in the regulation of reproduction. However, to date, no studies have investigated such changes in pubescent goats. Herein we applied isobaric tags for relative and absolute quantitation (iTRAQ) and liquid chromatography-tandem mass spectrometry to analyze the expression levels of ovarian proteins in pre-pubertal (n = 3) and pubertal (n = 3) goats. RESULTS: Overall, 7,550 proteins were recognized; 301 (176 up- and 125 downregulated) were identified as differentially abundant proteins (DAPs). Five DAPs were randomly selected for expression level validation by Western blotting; the results of Western blotting and iTRAQ analysis were consistent. Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis indicated that DAPs were enriched in olfactory transduction, glutathione metabolism, and calcium signaling pathways. Besides, gene ontology functional enrichment analysis revealed that several DAPs enriched in biological processes were associated with cellular process, biological regulation, metabolic process, and response to stimulus. Protein-protein interaction network showed that proteins interacting with CDK1, HSPA1A, and UCK2 were the most abundant. CONCLUSIONS: We identified 301 DAPs, which were enriched in olfactory transduction, glutathione metabolism, and calcium signaling pathways, suggesting the involvement of these processes in the onset of puberty. Further studies are warranted to more comprehensively explore the function of the identified DAPs and aforementioned signaling pathways to gain novel, deeper insights into the mechanisms underlying the onset of puberty.


Assuntos
Cabras , Proteômica , Animais , Feminino , Glutationa , Ovário , Proteômica/métodos , Maturidade Sexual
13.
Ecotoxicol Environ Saf ; 240: 113681, 2022 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-35653978

RESUMO

Biosynthetic nano-selenium (bio-SeNP), as a plant growth regulator, has better bioavailability and lower toxicity than selenite and selenate. This study investigated the beneficial role of bio-SeNP in mitigating the adverse effects of multiple heavy metals (HMs, e.g., Cd, Pb, and Hg) on growth and yield of pak choi (Brassica chinensis) grown in slightly or heavily polluted (SP or HP) soil by regulating metabolic and antioxidant systems. The results revealed that foliar application of bio-SeNP (5, 10, 20 mg L-1 Se) at the 6-leaf stage greatly reduced the levels of Cd, Pb, and Hg in shoots and roots of pak choi. Application of 5 mg L-1 bio-SeNP significantly (p < 0.05) decreased the translocation factor (TF) of Cd, Pb, and Hg from root to shoot by 9.83%, 44.21%, and 46.99% for SP soil, 24.17%, 56.00%, and 39.36% for HP soil, respectively. Meanwhile, all bio-SeNP treatments led to a significant improvement in plants growth by enhancing the antioxidant defense system (e.g., AsA-GSH) and promoting chlorophyll synthesis as well as suppressed the lipid peroxidation products contents (MDA) in shoots. Moreover, the enhanced levels of mineral nutrient elements (e.g., Ca, Mg, Fe, or Zn) and organic selenium (e.g., selenocystine, Se-methylselenocysteine, and selenomethionine) in the edible shoots of bio-SeNP-treated pak choi plant under multiple HMs stress indicated the positive impacts of bio-SeNP on the improvement of shoot quality and nutritional values. Collectively, our results indicated that bio-SeNP play an important role in the management of multiple HMs-induced adverse effects on pak choi. Foliar application of bio-SeNP at appropriate concentration (≤ 5 mg L-1 Se) can be considered as a promising agronomic measure for safety leafy vegetable production in multiple HMs polluted soils when bio-SeNP application.


Assuntos
Brassica , Mercúrio , Metais Pesados , Selênio , Poluentes do Solo , Adsorção , Antioxidantes/metabolismo , Antioxidantes/farmacologia , Brassica/metabolismo , Cádmio/metabolismo , Chumbo/metabolismo , Mercúrio/metabolismo , Mercúrio/toxicidade , Metais Pesados/metabolismo , Selênio/metabolismo , Selênio/farmacologia , Solo , Poluentes do Solo/análise
14.
Foods ; 11(5)2022 Feb 24.
Artigo em Inglês | MEDLINE | ID: mdl-35267304

RESUMO

In this study, a novel method to clarify bayberry juice with composite clarifiers, chitosan and sodium alginate, has been designed. The optimal conditions were as follows: using chitosan 0.05 g/L first and then sodium alginate 0.05 g/L as composite clarifiers, standing for 2 h at 25 °C. The transmittance increased from 0.08 to 91.2% after treating by composite clarifiers, which was significantly higher than using chitosan (44.29%) and sodium alginate (38.46%) alone. It was also found that sedimentation time of juice treated by composite clarifiers was about 60% shorter than using single clarifiers. Meanwhile, the reduction of anthocyanin in juice was 9.16% for composite clarifiers treatment, being less than that for the single sodium alginate and previous related researches. In addition, the color and aroma of bayberry juice treated by composite clarifiers were improved. Juice treated by composite clarifiers had the highest L* value with 52.48 and looked more attractive. The present research revealed that content of beta-damascenone and dihydro-5-pentyl-2(3H)-furanone increased after treatment with composite clarifiers which contributed more to the pleasant aroma. Overall, the developed method improved the clarification effect and sensory quality, and reduced the sedimentation time, which may be promising in the production of clear bayberry juice.

15.
World J Clin Cases ; 9(33): 10265-10272, 2021 Nov 26.
Artigo em Inglês | MEDLINE | ID: mdl-34904098

RESUMO

BACKGROUND: Metastasis of pancreatic cancer to the colon is rare and the features need to be further elucidated. Herein, we report a rare case of pancreatic cancer with simultaneous liver and colon metastases. CASE SUMMARY: A 48-year-old man with intrahepatic space-occupying lesions based on a computed tomography scan was admitted to our hospital for further treatment. Abdominal magnetic resonance imaging revealed a 6.4 cm × 4.2 cm mass in the tail of the pancreas and multiple low-density masses in the liver parenchyma. In addition, a mass of 2.2 cm × 1.6 cm with surface congestive erosions in the sigmoid colon was detected by colonoscopy. Histopathological examination of biopsies from both the liver and colon lesions revealed a moderately to poorly differentiated adenocarcinoma. Immunohistochemical staining of the colon tumor was positive for cytokeratin (CK) 7 and CK, but negative for colorectal adenocarcinoma-related markers CK 20, CDX2, and SATB2, thus indicating that the metastasis originated from the pancreas. Next-generation sequencing for genomic profiling of the liver and colon metastases both found mutations in KRAS (p.G12D) and TP53 (c.376-1delG), with microsatellite stable and low tumor mutational burden without actionable or cancer-predisposing gene mutations detected. The patient was subsequently treated with 12 cycles of FOLFIRINOX which led to a sustainable response, followed by ongoing maintenance treatment with irinotecan plus fluorouracil. CONCLUSION: For this rare case, careful evaluation of histopathological and immunohistochemical staining results are required. The genomic profiling of colon lesions was revealed for the first time, and FOLFIRINOX showed good treatment efficacy in this patient.

16.
Nat Commun ; 12(1): 6377, 2021 11 04.
Artigo em Inglês | MEDLINE | ID: mdl-34737261

RESUMO

Endocrine therapies for prostate cancer inhibit the androgen receptor (AR) transcription factor. In most cases, AR activity resumes during therapy and drives progression to castration-resistant prostate cancer (CRPC). However, therapy can also promote lineage plasticity and select for AR-independent phenotypes that are uniformly lethal. Here, we demonstrate the stem cell transcription factor Krüppel-like factor 5 (KLF5) is low or absent in prostate cancers prior to endocrine therapy, but induced in a subset of CRPC, including CRPC displaying lineage plasticity. KLF5 and AR physically interact on chromatin and drive opposing transcriptional programs, with KLF5 promoting cellular migration, anchorage-independent growth, and basal epithelial cell phenotypes. We identify ERBB2 as a point of transcriptional convergence displaying activation by KLF5 and repression by AR. ERBB2 inhibitors preferentially block KLF5-driven oncogenic phenotypes. These findings implicate KLF5 as an oncogene that can be upregulated in CRPC to oppose AR activities and promote lineage plasticity.


Assuntos
Fatores de Transcrição Kruppel-Like/metabolismo , Células Neuroendócrinas/metabolismo , Neoplasias de Próstata Resistentes à Castração/metabolismo , Receptor ErbB-2/metabolismo , Receptores Androgênicos/metabolismo , Linhagem Celular Tumoral , Humanos , Masculino , Estadiamento de Neoplasias , Células Neuroendócrinas/patologia , Neoplasias de Próstata Resistentes à Castração/genética , Neoplasias de Próstata Resistentes à Castração/patologia , Transdução de Sinais , Ativação Transcricional
17.
Sheng Wu Gong Cheng Xue Bao ; 37(8): 2825-2835, 2021 Aug 25.
Artigo em Chinês | MEDLINE | ID: mdl-34472300

RESUMO

Biosynthesis of nanomaterials has attracted much attention for its excellent characteristics such as low energy consumption, high safety, and environmental friendliness. As we all know, the toxic selenite can be transformed into higher-value nanomaterials by using bacteria. In this study, nano-selenium was synthesized by halophilic Bacillus subtilis subspecies stercoris strain XP in LB medium supplemented with selenite (electron acceptor). The physicochemical characteristics of nano-selenium were analyzed by scanning electron microscope (SEM), X-ray energy dispersive spectral analysis (EDAX), X-ray diffraction (XRD), and fourier transform infrared spectroscopy (FTIR). Meanwhile, the antifungal activity of nano-selenium to strawberry pathogens (fusarium wilt, erythema, and purple spot fungi) was determined. The products from reduction of selenite by strain XP was amorphous spherical selenium nanoparticles (SeNPs) with a diameter range of 135-165 nm. The production of SeNPs was positively correlated with time (0-48 h) and no changes were observed on cell morphology. Selenium was dominant in the surface of SeNPs where the organic elements (C, O, N, and S) existed at the same time. SeNPs were coated with biomolecules containing functional groups (such as -OH, C=O, N-H, and C-H) which were associated with the stability and bioactivity of particles. Although the highest concentration of SeNPs had significant (P<0.05) inhibitory effects on three strains of strawberry pathogens, antifungal activity to erythema and fusarium wilt pathogenic fungi was higher than that to purple spot pathogenic fungi from strawberry. In conclusion, strain XP not only has strong tolerance to high salt stress, but can be also used to synthesize biological SeNPs with good stability and biological activity. Thus, the strain XP has bright perspectives and great potential advantage in pathogens control and green selenium-rich strawberry planting as well as other fields.


Assuntos
Fragaria , Nanopartículas , Selênio , Bacillus subtilis , Ácido Selenioso
18.
Bioresour Technol ; 341: 125842, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34469819

RESUMO

This study explored the effects of single-stage inoculation (SSI) versus two-stage inoculation (TSI) on organic carbon components, product quality and fungal community during co-composting of cattle manure and rice straw. Both inoculation methods accelerated the temperature increase and elevated the composting temperature. TSI resulted in a second fermentation stage and extended the thermophilic stage from 22 to 29 days. Compared with SSI, TSI promoted the degradation degree of cellulose, hemicellulose and lignin by 25.9%, 16.5% and 47.4%, and increased the content of total nutrients and humus carbon by 5.9% and 10.5% in final products, respectively. TSI significantly increased the relative abundance of Aspergillus, Trichoderma, Neurospora, Mycothermus, Malbranchea and Gloeophyllum in the second fermentation stage. Spearman correlation analysis indicated that Aspergillus, Neurospora, Trichoderma and Gloeophyllum were the key fungi for lignocellulose degradation and humification. Redundancy analysis showed that temperature was the major environmental factor affecting fungal community succession in TSI.


Assuntos
Compostagem , Micobioma , Oryza , Trichoderma , Animais , Carbono , Bovinos , Esterco , Solo
19.
Antioxidants (Basel) ; 10(8)2021 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-34439565

RESUMO

Using ultrasound (US) in proanthocyanidin (PA) extraction has become one of the important emerging technologies. It could be the next generation for studying the US mechnophore impact on the bioactive compound's functionality. The objective of this study was to demonstrate the potential of US treatment on PAs extracted from kiwifruit (Actinidia chinensis) leaves, and to provide a comprehensive chemical composition and bioactivity relationship of the purified kiwifruit leaves PAs (PKLPs). Several methods like single-factor experiments and response surface methodology (RSM) for the four affected factors on US extraction efficiency were constructed. HPLC-QTOF-MS/MS, cytotoxicity analysis, and antioxidant activity were also demonstrated. In the results, the modeling of PA affected factors showed that 40% US-amplitude, 30 mL/g dry weight (DW) solvent to solid ration (S/S), and 70 °C for 15 min were the optimum conditions for the extraction of PAs. Furthermore, PKLPs exhibited significant radical scavenging and cellular antioxidant activity (p < 0.05). In conclusion, this study's novelty comes from the broad prospects of using US in PKLP green extraction that could play an important role in maximizing this phytochemical functionality in drug discovery and food science fields.

20.
Bioresour Technol ; 337: 125427, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34217022

RESUMO

The present study investigated the effect of brown-rot fungus Gloeophyllum trabeum inoculation on lignocellulose degradation, enzyme activities and fungal community during co-composting of swine manure and wheat straw. G. trabeum inoculation shortened the maturation period of composting from 39 to 30 days. Composting piles inoculated with G. trabeum showed a higher degree of maturity as indicated by 31.6% lower C/N ratio and 29.4% higher GI. The decomposition rate of cellulose, hemicellulose and lignin was increased by 181.1%, 49.4% and 109.4%, respectively, due to higher activities of filter paper enzyme, xylanase, manganese peroxidase and laccase. Redundancy analysis showed that inoculating G. trabeum influenced the succession of fungal communities by changing the main physicochemical parameters, resulting in the increased relative abundance of Aspergillus, Mycothermus and Melanocarpus. Pearson correlation analysis indicated that more dominant fungal genera were involved in the production of lignocellulose-degrading enzymes after G. trabeum inoculation.


Assuntos
Compostagem , Animais , Basidiomycota , Fungos , Lignina , Esterco , Solo , Suínos
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