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1.
BMC Cancer ; 24(1): 696, 2024 Jun 06.
Artigo em Inglês | MEDLINE | ID: mdl-38844884

RESUMO

OBJECTIVE: Inflammation, malnutrition, and cancer are intricately interconnected. Despite this, only a few studies have delved into the relationship between inflammatory malnutrition and the risk of death among cancer survivors. This study aimed to specifically investigate the association between the categorically defined Naples prognostic score (NPS) and the prognosis of cancer survivors. METHODS: Data from 42,582 participants in the National Health and Nutrition Examination Survey (NHANES, 1999-2018) were subjected to analysis. Naples prognostic scores (NPS) were computed based on serum albumin (ALB), total cholesterol (TC), neutrophil to lymphocyte ratio (NLR), and lymphocyte to monocyte ratio (LMR), and participants were stratified into three groups accordingly. Cancer status was ascertained through a self-administered questionnaire, while mortality data were sourced from the National Death Index up to December 31, 2019. Multiple logistic regression was employed to estimate the odds ratio (OR) with a 95% confidence interval (CI) between NPS and cancer prevalence within the U.S. community population. Kaplan-Meier survival analysis and the Log-rank test were utilized to compare survival disparities among the three groups. Additionally, Cox proportional regression was utilized to estimate the hazard ratio (HR) with a 95% CI. RESULTS: The incidence of cancers was 9.86%. Among the participants, 8140 individuals (19.1%) were classified into Group 0 (NPS 0), 29,433 participants (69.1%) into Group 1 (NPS 1 or 2), and 5009 participants (11.8%) into Group 2 (NPS 3 or 4). After adjusting for confounding factors, the cancer prevalence for the highest NPS score yielded an odds ratio (OR) of 1.64 (95% CI: 1.36, 1.97) (P(for trend) < 0.05). In comparison to cancer survivors in Group 0, those with the highest NPS had adjusted hazard ratios (HRs) of 2.57 (95% CI: 1.73, 3.84) for all-cause mortality, 3.44 (95% CI: 1.64, 7.21) for cardiovascular mortality, 1.60 (95% CI: 1.01, 2.56) for cancer mortality, and 3.15 (95% CI: 1.74, 5.69) for other causes of mortality (All P(for trend) < 0.05). These associations remained consistent when stratified by age, sex, race, and body mass index. CONCLUSIONS: This study indicates that the Naples prognostic score (NPS), serving as a novel prognostic metric integrating inflammation and nutritional status, is closely linked to cancer prognosis within the general population.


Assuntos
Sobreviventes de Câncer , Neoplasias , Inquéritos Nutricionais , Humanos , Feminino , Masculino , Sobreviventes de Câncer/estatística & dados numéricos , Prognóstico , Pessoa de Meia-Idade , Neoplasias/mortalidade , Idoso , Adulto , Inflamação , Neutrófilos , Desnutrição/epidemiologia , Colesterol/sangue , Estados Unidos/epidemiologia , Albumina Sérica/análise , Albumina Sérica/metabolismo , Monócitos/metabolismo , Linfócitos/metabolismo
2.
J Mol Model ; 30(2): 26, 2024 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-38191945

RESUMO

CONTEXT: The reaction between Na and HF is a typical harpooning reaction which is of great interest due to its significance in understanding the elementary chemical reaction kinetics. This work aims to investigate the detailed reaction mechanisms of sodium with hydrogen fluoride and the adsorption of HF on the resultant NaF as well as the (NaF)4 tetramer. The results suggest that the reaction between Na and HF leads to the formation of sodium fluoride salt NaF and hydrogen gas. Na interacts with HF to form a complex HF···Na, and then the approaching of F atom of HF to Na results in a transition state H···F···Na. Accompanied by the broken of H-F bond, the bond forms between F and Na atoms as NaF, then the product NaF is yielded due to the removal of H atom. The resultant NaF can further form (NaF)4 tetramer. The interaction of NaF with HF leads to the complex NaF···HF; the form I as well as II of (NaF)4 can interact with HF to produce two complexes (i.e., (NaF)4(I-1)···HF, (NaF)4(I-2)···HF, (NaF)4(II-1)···HF and (NaF)4(II-2)···HF), but the form III of (NaF)4 can interact with HF to produce only one complex (NaF)4(III)···HF. These complexes were explored in terms of noncovalent interaction (NCI) and quantum theory of atoms in molecules (QTAIM) analyses. NCI analyses confirm the existences of attractive interactions in the complexes HF···Na, NaF···HF, (NaF)4(I-1)···HF, (NaF)4(I-2)···HF, (NaF)4(II-1)···HF and (NaF)4(II-2)···HF, and (NaF)4(III)···HF. QTAIM analyses suggest that the F···Na interaction forms in the HF···Na complex while the F···H hydrogen bonds form in NaF···HF, (NaF)4(I-1)···HF, (NaF)4(I-2)···HF, (NaF)4(II-1)···HF and (NaF)4(II-2)···HF, and (NaF)4(III)···HF complexes. Natural bond orbital (NBO) analyses were also applied to analyze the intermolecular donor-acceptor orbital interactions in these complexes. These results would provide valuable insight into the chemical reaction of Na and HF and the adsorption interaction between sodium fluoride salt and HF. METHODS: The calculations were carried out at the M06-L/6-311++G(2d,2p) level of theory which were performed using the Gaussian16 program. Intrinsic reaction coordinate (IRC) calculations were carried out at the same level of theory to confirm that the obtained transition state was true. The molecular surface electrostatic potential (MSEP) was employed to understand how the complex forms. Quantum theory of atoms in molecules (QTAIM) and noncovalent interaction (NCI) analysis was used to know the topology parameters at bond critical points (BCPs) and intermolecular interactions in the complex and intermediate. The topology parameters and the BCP plots were obtained by the Multiwfn software.

3.
Acta Otorhinolaryngol Ital ; 44(2): 83-90, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38165205

RESUMO

Objective: This study aimed to investigate the global research status, hot topics, and prospects in the field of sinonasal inverted papilloma (SNIP) through bibliometric analysis. Methods: The literature on SNIP was retrieved and downloaded from the Web of Science Core Collection from 2002 to 2021. The bibliometric and visualisation networks of SNIP were constructed using VOSviewer 1.6.18, CiteSpace 6.1. R2, and a bibliometric online analysis platform. Results: A total of 560 original articles about SNIP research were included, involving 2,457 authors from 610 institutions in 45 countries. The number of SNIP publications showed an overall rising trend, with an average annual output of 28 articles and almost 3 times as many articles published in 2020 as in 2002. The analysis of keyword burst detection indicated that EGFR mutation, malignant transformation and infection are emerging research hotspots. Moreover, EGFR mutation, KRAS mutation, malignant tumour, metallothionein 2a gene, pre-operative diagnosis, HPV-negative tumour, and expression were among the 11 key clusters of co-cited references. Conclusions: This study provided a comprehensive, systematic, and objective analysis and visualised knowledge map of SNIP over the past 2 decades. In particular, current hotspots and prospective trends in the field of SNIP have been identified. These results highlight the future direction of SNIP research for rhinologists.


Assuntos
Bibliometria , Papiloma Invertido , Neoplasias dos Seios Paranasais , Papiloma Invertido/patologia , Humanos , Neoplasias dos Seios Paranasais/patologia , Pesquisa Biomédica , Fatores de Tempo
4.
Talanta ; 270: 125526, 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38091748

RESUMO

Logic gate-based fluorescent probes are powerful tools for the discriminative sensing of multiple signaling molecules that are expressed in concert during the progression of many diseases such as inflammation, cancer, aging, and other disorders. To achieve logical sensing, multiple functional groups are introduced to the different substitution sites of a single fluorescent dye, which increases the complexity of chemical synthesis. Herein, we report a simple strategy that incorporates just one responsive unit into a hemicyanine dye achieving the logic gate-based sensing of two independent analytes. We introduce boronic acid to hemicyanine to quench the fluorescence, and in the presence of hydrogen peroxide (H2O2), the fluorescence is recovered due to removal of the boronate. Interestingly, the subsequent decrease in pH turned the red fluorescence of hemicyanine to green emissive because of protonation of the phenolic alcohol. This unique feature of the probe enables us to construct "INHIBIT" and "AND" logical gates for the accurate measuring of intracellular H2O2 and acidic pH in tandem. This study offers insight into the simple construction of logic-gate based fluorescent probes for the tandem sensing of multiple analytes that are correlatively produced during disease progression.


Assuntos
Corantes Fluorescentes , Peróxido de Hidrogênio , Corantes Fluorescentes/química , Carbocianinas/química , Concentração de Íons de Hidrogênio
5.
Proc Natl Acad Sci U S A ; 120(45): e2309032120, 2023 Nov 07.
Artigo em Inglês | MEDLINE | ID: mdl-37903267

RESUMO

Tryptophan and its derivatives perform a variety of biological functions; however, the role and specific mechanism of many tryptophan derivatives in intestinal inflammation remain largely unclear. Here, we identified that an Escherichia coli strain (Ec-TMU) isolated from the feces of tinidazole-treated individuals, and indole-3-lactic acid (ILA) in its supernatant, decreased the susceptibility of mice to dextran sulfate sodium-induced colitis. Ec-TMU and ILA contribute to the relief of colitis by inhibiting the production of epithelial CCL2/7, thereby reducing the accumulation of inflammatory macrophages in vitro and in vivo. Mechanistically, ILA downregulates glycolysis, NF-κB, and HIF signaling pathways via the aryl hydrocarbon receptor, resulting in decreased CCL2/7 production in epithelial cells. Clinical evidence suggests that the fecal ILA level is negatively correlated with the progression indicator of inflammatory bowel diseases. These results demonstrate that ILA has the potential to regulate intestinal homeostasis by modulating epithelium-macrophage interactions.


Assuntos
Colite , Triptofano , Animais , Camundongos , Triptofano/metabolismo , Colite/metabolismo , Macrófagos/metabolismo , Epitélio/metabolismo , Sulfato de Dextrana/toxicidade , Camundongos Endogâmicos C57BL , Mucosa Intestinal/metabolismo
6.
Front Mol Neurosci ; 16: 1195327, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37520430

RESUMO

Introduction: Recombinant adeno-associated viruses (rAAVs) are widely used in genetic therapeutics. AAV5 has shown superior transduction efficiency, targeting neurons and glial cells in primate brains. Nonetheless, the comprehensive impact of AAV5 transduction on molecular and behavioral alterations remains unexplored. This study focuses on evaluating the effects of AAV5 transduction in the hippocampus, a critical region for memory formation and emotional processes. Methods: In this experiment, fluorescence-activated cell sorting (FACS) was utilized to isolate the mCherry-labeled pyramidal neurons in the hippocampus of CaMkIIα-cre mice following three different doses rAAV5-mCherry infusion after 3 weeks, which were then subjected to RNA sequencing (RNA-seq) to assess gene expression profiles. The cytokines concentration, mRNA expression, and glial response in hippocampi were confirmed by ELASA, digital droplet PCR and immunohistochemistry respectively. Locomotion and anxiety-like behaviors were elevated by Open Field Test and Elevated Plus Maze Test, while the Y-Maze were used to assessed spatial working memory. Recognition memory and fear responses were examined by the Novel Object Recognition Test and Fear Conditioning Test, respectively. Results: We found that 2.88 × 1010 v.g rAAV5 transduction significantly upregulated genes related to the immune response and apoptosis, and downregulated genes associated with mitochondrial function and synaptic plasticity in hippocampal pyramidal neurons, while did not induce neuronal loss and gliosis compared with 2.88 × 109 v.g and 2.88 × 108 v.g. Furthermore, the same doses impaired working memory and contextual fear memory, without effects on locomotion and anxiety-related behaviors. Discussion: Our findings highlight the detrimental impact of high-dose administration compared to median-dose or low-dose, resulting in increased neural vulnerability and impaired memory. Therefore, when considering the expression effectiveness of exogenous genes, it is crucial to also take potential side effects into account in clinical settings. However, the precise molecular mechanisms underlying these drawbacks of high-dose rAAV5-mCherry still require further investigation in future studies.

7.
Carcinogenesis ; 44(8-9): 682-694, 2023 12 02.
Artigo em Inglês | MEDLINE | ID: mdl-37294054

RESUMO

EphB6 belongs to the receptor tyrosine kinase, whose low expression is associated with shorter survival of colorectal cancer (CRC) patients. But the role and mechanism of EphB6 in the progression of CRC need further study. In addition, EphB6 was mainly expressed in intestinal neurons. But how EphB6 is involved in functions of intestinal neurons has not been known. In our study, we constructed a mouse xenograft model of CRC by injecting CMT93 cells into the rectum of EphB6-deficient mice. We found that the deletion of EphB6 in mice promoted tumor growth of CMT93 cells in a xenograft model of CRC, which was independent of changes in the gut microbiota. Interestingly, inhibition of intestinal neurons by injecting botulinum toxin A into rectum of EphB6-deficient mice could eliminate the promotive effect of EphB6 deficiency on tumor growth in the xenograft model of CRC. Mechanically, the deletion of EphB6 in mice promoted the tumor growth in CRC by increasing GABA in the tumor microenvironment. Furthermore, EphB6 deficiency in mice increased the expression of synaptosomal-associated protein 25 in the intestinal myenteric plexus, which mediated the release of GABA. Our study concluded that EphB6 knockout in mice promotes tumor growth of CMT93 cells in a xenograft model of CRC by modulating GABA release. Our study found a new regulating mechanism of EphB6 on the tumor progression in CRC that is dependent on intestinal neurons.


Assuntos
Comunicação Celular , Neoplasias Colorretais , Humanos , Animais , Camundongos , Neoplasias Colorretais/metabolismo , Intestinos/patologia , Neurônios/metabolismo , Neurônios/patologia , Ácido gama-Aminobutírico , Microambiente Tumoral
8.
Biochim Biophys Acta Mol Cell Res ; 1870(5): 119461, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-36931607

RESUMO

As an anticancer drug, cisplatin is widely used, but its clinical application is restricted due to its severe side effects of ototoxicity. Therefore, this study was dedicated to assessing the benefit of ginsenoside extract, 20(S)-Ginsenoside Rh1 (Rh1), on cisplatin-induced ototoxicity. HEI-OC1 cells and neonatal cochlear explants were cultured. Cleaved caspase-3, TUNEL, and MitoSOX Red were observed in vitro by immunofluorescence staining. CCK8 and LDH cytotoxicity assays were detected to measure cell viability and cytotoxicity. Our results showed that Rh1 significantly increased cell viability, reduced cytotoxicity, and alleviated cisplatin-induced apoptosis. In addition, Rh1 pretreatment decreased the excessive accumulation of intracellular reactive oxygen species. Mechanistic studies indicated that Rh1 pretreatment reversed the increase of apoptotic protein expression, accumulation of mitochondrial ROS, and activation of the MAPK signaling pathway. These results suggested that Rh1 can act as an antioxidant and anti-apoptotic agent against cisplatin-induced hearing loss by suppressing the excessive accumulation of mitochondrial ROS, activation of MAPK signaling pathway and apoptosis.


Assuntos
Ginsenosídeos , Perda Auditiva , Ototoxicidade , Humanos , Recém-Nascido , Cisplatino/efeitos adversos , Ginsenosídeos/efeitos adversos , Ginsenosídeos/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Ototoxicidade/metabolismo , Células Ciliadas Auditivas , Perda Auditiva/induzido quimicamente , Apoptose , Sistema de Sinalização das MAP Quinases
9.
Curr Oncol ; 30(2): 1708-1719, 2023 01 31.
Artigo em Inglês | MEDLINE | ID: mdl-36826093

RESUMO

BACKGROUND: The high recurrence rate of hepatocellular carcinoma (HCC) after hepatectomy usually results in poor prognosis. To the best of our knowledge, no study has reported the efficacy of immune checkpoint inhibitors (ICIs) plus targeted therapies on preventing HCC recurrence after hepatectomy. Thus, the aim of this study was to investigate the benefits and safety of applying adjuvant ICIs plus targeted therapies after hepatectomy for patients at high risk of HCC recurrence. METHODS: A total of 196 patients with any risk factors for recurrence who underwent hepatectomy for HCC were reviewed in this retrospective study. RESULTS: Compared with the control group (n = 158), ICIs plus targeted therapies (n = 38) had a significantly higher recurrence-free survival (RFS) rate in univariate analysis (HR, 0.46; 95% confidence interval [CI], 0.24-0.90; p = 0.020), multivariate analysis (adjusted HR, 0.62; 95%CI, 0.49-0.79; p < 0.001) and propensity score-matched analysis (HR, 0.35; 95%CI, 0.16-0.75; p = 0.005). Subgroup analyses also showed that postoperative adjuvant ICIs plus targeted therapies might reduce HCC recurrence in patients with the most of risk factors. CONCLUSION: Postoperative adjuvant ICI plus targeted therapies may reduces early HCC recurrence in patients with a high risk of recurrence, and the treatments are well tolerated.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/tratamento farmacológico , Neoplasias Hepáticas/tratamento farmacológico , Hepatectomia , Estudos Retrospectivos , Quimioterapia Adjuvante
10.
Infect Agent Cancer ; 18(1): 2, 2023 Jan 17.
Artigo em Inglês | MEDLINE | ID: mdl-36650583

RESUMO

BACKGROUND: Recent studies have proved that tenofovir disoproxil fumarate (TDF) is associated with a lower risk of hepatocellular carcinoma (HCC) occurrence in chronic hepatitis B (CHB) patients and HCC recurrence in patients who underwent hepatectomy when compared to ETV. However, it is unclear whether TDF and ETV treatment, which are both recommended as first-line antiviral agents to prevent the hepatitis B (HBV) recurrence after liver transplantation (LT), are associated with equivalent prognosis. We aim to compare risk of HCC recurrence and survival of patients recieving TDF or ETV after LT for HBV-related HCC. METHOD: We performed a retrospective study including 316 patients who received treatment with ETV or TDF after LT for HBV-related HCC from 2015 January to 2021 Augest. The Recurrence-free survival (RFS) and overall survival (OS) of TDF and ETV groups were analyzed and compared by propensity score-matched (PSM), multivariable Cox regression analysis, competing risk analysis, sensitivity analyses and subgroup analyses. RESULT: Compared with ETV, TDF therapy was associated with significantly higher RFS rates in the entire cohort (P < 0.01), PSM cohort (P < 0.01) and beyond-Milan cohort (P < 0.01). By multivariable analysis, TDF group was associated with significantly lower rates of HCC recurrence (HR, 0.33; 95%CI, 0.14-0.75; P < 0.01). In subgroup analyses, the similar results were observed in patients with following tumor characteristics: Maximum diameter plus number of viable tumor ≥ 5, with MIV or MAT, AFP at LT ≥ 20 ng/ml, and well or moderate tumor grade. CONCLUSION: Tenofovir decrease risk of HBV-Related Hepatocellular Carcinoma recurrence after liver transplantation compared to Entecavir.

11.
Microb Ecol ; 86(1): 460-473, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-35596751

RESUMO

Reasonable fertilization management can increase nutrient content and enzyme activity in rhizosphere soil, and even increase soil microbial richness. However, different fertilizers could raise distinct influences on the soil properties, including soil environmental factors (physicochemical properties and enzymatic activities) and microbial community. Here, the effects of two soil amendments (microbial fertilizer and woody peat) on environmental factors and microbial community structure in tobacco rhizosphere soil were evaluated, with the correlations between microbes and environmental factors explored. As the results, microbial fertilizer could effectively alleviate soil acidification, increase available potassium and organic matter contents in soil, and was also beneficial to increase nitrate reductase activity in rhizosphere soil. Fertilizers cause changes in the abundance of certain microbes in the soil. Besides, it was shown that the candidate phyla Gal15, Acidobacterota, Latescibacterota, Mortierellommycota, Basidiomycota, and Rozellomycota in tobacco rhizosphere soil had significant correlation with soil environmental factors. Through the functional analysis of these populations, it can be deduced that the changes in the abundance of certain microorganisms may be an important reason for the differences in environmental factors. All these indicated that the differences of environmental factors in different treatments are closely related to the abundance of some special soil microorganisms. Studying the life activities of these microbes would provide good guidance for exploring the interaction among crops, soil, and microorganisms and improving crop yields.


Assuntos
Fertilizantes , Solo , Solo/química , Fertilizantes/análise , Nicotiana , Rizosfera , Microbiologia do Solo
12.
Autophagy ; 19(1): 75-91, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-35471096

RESUMO

Aminoglycosides exhibit ototoxicity by damaging mitochondria, which in turn generate reactive oxygen species that induce hair cell death and subsequent hearing loss. It is well known that damaged mitochondria are degraded by mitophagy, an important mitochondrial quality control system that maintains mitochondrial homeostasis and ensures cell survival. However, it is unclear whether dysregulation of mitophagy contributes to aminoglycoside-induced hair cell injury. In the current study, we found that PINK1-PRKN-mediated mitophagy was impaired in neomycin-treated hair cells. Our data suggested that mitochondrial recruitment of PRKN and phagophore recognition of damaged mitochondria during mitophagy were blocked following neomycin treatment. In addition, the degradation of damaged mitochondria by lysosomes was significantly decreased as indicated by the mitophagic flux reporter mt-mKeima. Moreover, we demonstrated that neomycin disrupted mitophagy through transcriptional inhibition of Pink1 expression, the key initiator of mitophagy. Moreover, we found that neomycin impaired mitophagy by inducing ATF3 expression. Importantly, treatment with a mitophagy activator could rescue neomycin-treated hair cells by increasing mitophagy, indicating that genetic modulation or drug intervention in mitophagy may have therapeutic potential for aminoglycoside-induced hearing loss.Abbreviations: AAV: adeno-associated virus; ABR: auditory brainstem response; ATF3: activating transcription factor 3; ATOH1/MATH1: atonal bHLH transcription factor 1; BafA1: bafilomycin A1; CCCP: carbonyl cyanide m-chlorophenyl hydrazone; COX4I1/COXIV: cytochrome c oxidase subunit 4I1; CTBP2/RIBEYE: C-terminal binding protein 2; DFP: deferiprone; EGFP: enhanced green fluorescent protein; FOXO3: forkhead box O3; GRIA2/GLUR2: glutamate receptor, ionotropic, AMPA2 (alpha 2); HC: hair cell; HSPD1/HSP60: heat shock protein 1 (chaperonin); IHC: inner hair cell; MAP1LC3B/LC3B: microtubule-associated protein 1 light chain 3 beta; MYO7A: myosin VIIA; OPTN: optineurin; OMM: outer mitochondrial membrane; PRKN: parkin RBR E3 ubiquitin protein ligase; PINK1: PTEN induced putative kinase 1; RT-qPCR: real-time quantitative polymerase chain reaction; TOMM20/TOM20: translocase of outer mitochondrial membrane 20; TUNEL: Terminal deoxynucleotidyl transferase (TdT) dUTP nick-end labeling; USP30: ubiquitin specific peptidase 30; XBP1: X-box binding protein 1.


Assuntos
Autofagia , Mitofagia , Mitofagia/genética , Aminoglicosídeos/toxicidade , Proteínas Quinases/metabolismo , Ubiquitina-Proteína Ligases/metabolismo , Antibacterianos/farmacologia , Neomicina/toxicidade , Células Ciliadas Auditivas
13.
Transplant Proc ; 55(1): 153-163, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36522222

RESUMO

BACKGROUND: Current selection tools were not precise enough to predict recurrence of hepatocellular carcinoma (HCC) and benefit of adjuvant lenvatinib for patients who received liver transplant (LT) for HCC. Thus, we aim at developing a risk classifier to predict recurrence of HCC and benefit of adjuvant Lenvatinib for those who underwent LT for HCC. METHODS: Cox regression model was applied to selected predictors and created the final model in a training cohort of 287 patients who underwent LT for HCC, which was tested in an internal validation cohort of 72 patients by using C-statistic and net classification index (NRI) compared with the following HCC selection criteria: the Milan criteria, the Up-to-7 criteria, and the University of California, San Francisco criteria. RESULTS: We built a Risk Classifier of South China Cohort (RCOSC) based on 4 variables: the maximum diameter plus number of viable tumors, alpha-fetoprotein, microvascular invasion, and highest alanine aminotransferase in 7 days after LT. In validation analyses, our RCOSC showed good predictive performance (C-statistic, 0.866; 95% confidence interval [CI], 0.833-0.899) and had better prognostic value than Milan criteria (NRI, 0.406; P < .001), University of California, San Francisco (NRI, 0.497; P < .001), and Up-to-7 (NRI, 0.527; P < .001). By applying the RCOSC, we were able to accurately categorize patients into high-risk and low-risk groups. Further survival analysis revealed that the patients in the high-risk group might have a better therapeutic response to preventive regimen of lenvatinib after LT for HCC (hazard ratio, 0.38; 95% CI, 0.161-0.871, P = .018). CONCLUSIONS: Our RCOSC presented favorable predictive performance for HCC recurrence. It might be capable of sifting out patients who benefit from adjuvant therapy after LT for HCC, providing a reliable tool for precise clinical decision-making of patients with HCC with LT.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Transplante de Fígado , Humanos , Carcinoma Hepatocelular/patologia , Neoplasias Hepáticas/patologia , Transplante de Fígado/efeitos adversos , Recidiva Local de Neoplasia/etiologia , Estudos Retrospectivos , alfa-Fetoproteínas
14.
Appl Microbiol Biotechnol ; 107(2-3): 663-676, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36525041

RESUMO

Our previous study's introduction of the malonic acid assimilation pathway into Escherichia coli enabled biosynthesis of 3-Hydroxypropionate (3-HP) from malonate. However, the relatively low uptake activity of tripartite ATP-independent periplasmic (TRAP) malonic acid transporter (MatPQM) is considered rate-limiting in malonate utilization. Here, to improve the transport performance of this importer, MatP variants were obtained via directed evolution and a novel developed enzyme-inhibition-based high throughput screening approach. This plate chromogenic screening method is based on the fact that malonic acid inhibits both of succinate dehydrogenase activity and further the capability of the reduction of methylene-blue to methylene-white. The best mutant E103G/S194G/Y218H/L235P/N272S showed twofold increased transport efficiency compared to the wild-type. ITC assay and structural analysis revealed that increased binding affinity of the mutant to the ligand was the reason for improved uptake activity of MatPQM. Finally, the engineered strain harboring the evolved mutant produced 20.08 g/L 3-HP with the yield of 0.87 mol/mol malonate in a bioreactor. Therefore, the well-established directed evolution strategy can be regarded as the reference work for other TRAP-type transporters engineering. And, this transporter mutant with enhanced malonic acid uptake activity has broad applications in the microbial biosynthesis of malonyl-CoA-derived valuable compounds in bacteria. KEY POINTS: • We reported directed evolution of a TRAP-type malonic acid transporter. • We found the enhanced malonate uptake activity of mutant lies in improved affinity. • We enhanced 3-HP bioproduction with high yield by employing the best mutant.


Assuntos
Malonatos , Proteínas de Membrana Transportadoras , Proteínas de Membrana Transportadoras/genética , Proteínas de Membrana Transportadoras/metabolismo , Trifosfato de Adenosina/metabolismo
15.
Eur Arch Otorhinolaryngol ; 280(3): 1403-1410, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36208332

RESUMO

PURPOSE: The aim of this study was to determine whether interleukin-6 (IL-6) could be used as a predictor for surgical drainage in deep neck space infection (DNSI). METHODS: A retrospective study was conducted to analyze 69 adult patients newly diagnosed as DNSI from January 2017 to December 2021 at a single center. The patients were treated with either surgical drainage or not. The following clinical data including age, gender, maximum diameter of abscess (MDA), laboratory data, therapeutic modalities, comorbidities, duration of hospitalization and complications were collected and evaluated. RESULTS: Patients in drained group had significantly elevated MDA, IL-6, procalcitonin, C-reactive protein and neutrophil to lymphocyte ratio compared to patients in non-drained group (all P < 0.01). Significant predictors for surgical drainage were IL-6 and MDA as independent factors, with the optimum cutoff values of 52.5 pg/mL and 14.4 mm, respectively. Moreover, the IL-6 had a wider area under the curve than MDA for prediction of surgical drainage in DNSI. CONCLUSIONS: IL-6 as a promising predictor of the need for surgical drainage can be effectively used for routine assessment in the early stage of DNSI to determine the optimal treatments.


Assuntos
Interleucina-6 , Pescoço , Adulto , Humanos , Abscesso/cirurgia , Drenagem , Interleucina-6/uso terapêutico , Pescoço/cirurgia , Estudos Retrospectivos
16.
Eur Arch Otorhinolaryngol ; 280(4): 1919-1926, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-36422670

RESUMO

OBJECTIVE: To determine the value of a questionnaire as a screening tool for benign paroxysmal position vertigo (BPPV). STUDY DESIGN: Retrospective chart review. SETTING: Tertiary care centers. METHODS: A total of 520 vertigo adults completed the questionnaire before the diagnosis was confirmed. After vestibular function examination and other diagnostic examination, the diagnosis of all participants was confirmed by experts. By validating valuable items from the questionnaire with 47 items, a new questionnaire of 5 items was formed to quickly diagnose BPPV. The internal consistency of the new questionnaire and validity were evaluated. The correlation between the score obtained from the new questionnaire and diagnosis was investigated. The mean score was also compared between groups with and without BPPV and diagnostic precision measures were calculated. RESULTS: 520 vertigo participants answered all the question completely and BPPV was identified in 138 participants (26.5%). The responses to questionnaire revealed preferable reproducibility (r = 0.898, P < 0.05) and internal consistency (Cronbach's α = 0.702) as well as the validity (Kaiser-Meyer-Olkin, KMO = 0.731). The higher the individual score, the more likely to be BPPV (B = 2.082; P < 0.05). The mean score of answers was greater in the group with a clinical diagnosis of BPPV compared to those without BPPV (F = 58.459, P < 0.05). The sensitivity of the screening tool was 92.8% and specificity was 88.5%, with an area under the ROC curve of 0.946 (95% confidence interval 0.926-0.965; P < 0.05). CONCLUSION: The questionnaire proved to be of great value to screen for individuals with possible BPPV.


Assuntos
Vertigem Posicional Paroxística Benigna , Adulto , Humanos , Estudos Retrospectivos , Reprodutibilidade dos Testes , Vertigem Posicional Paroxística Benigna/diagnóstico , Inquéritos e Questionários , Curva ROC
17.
Appl Microbiol Biotechnol ; 106(24): 8053-8066, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36374331

RESUMO

ß-Elemene is the major component of a traditional Chinese medicine (Rhizoma Curcumae) for cancer treatment, and plant extraction is the major methods currently. Biosynthesis of ß-elemene is a promising and attractive route due to its advantages, including environmentally friendly processes, renewable resources, and sustainable development. In this research, biosynthesis of germacrene A, direct precursor of ß-elemene, in Escherichia coli was successfully performed and 11.99 mg/L germacrene A was obtained. Thereafter, a cobiosynthesis system for germacrene A and lycopene, another kind of isoprenoid, was constructed. Furthermore, the cultivation conditions were optimized. The germacrene A production was increased to the highest level reported to date, 364.26 mg/L, threefold increase to the strain with only germacrene A production. The cobiosynthesis system was suggested to promote the metabolic flux for germacrene A production. This research enabled germacrene A production in E. coli, and it highlights the promoting mechanism of the cobiosynthesis system for two chemicals which are both belonging to isoprenoids. KEY POINTS : • Co-production of germacrene A and lycopene in E. coli. • Promoting mechanism of cobiosynthesis of two isoprenoid compounds in E. coli. • Shake-flask production of germacrene A reached to the highest 364.26 mg/L in E. coli.


Assuntos
Escherichia coli , Medicina Tradicional Chinesa , Licopeno , Escherichia coli/genética
18.
Biomed Res Int ; 2022: 9236822, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36212710

RESUMO

Objective: Tinnitus, as a common clinical symptom, has the characteristics of high incidence and great heterogeneity among different patients. As one of the common treatment strategies for tinnitus, this study is aimed at exploring the factors influencing tinnitus sound therapy and the correlation between different tinnitus acoustic characteristics. Methods: 315 patients with chronic tinnitus were enrolled and divided into three groups according to the tinnitus multielement integration sound therapy (T-MIST): (1) vanishing, (2) remission, and (3) unchanged. The general characteristics, psychoacoustic scores (tinnitus handicap inventory (THI) and visual analog scale (VAS)), residual inhibition (RI), degree of hearing loss, and tinnitus characteristics of each group were compared. Finally, we analyze the predictive significance of different features for acoustic effects. Results: The frequency of tinnitus in the vanishing group was higher than that in the remission and unchanged groups (P < 0.05). There were no differences in age, initial onset time, course of the disease, and VSAD between the vanishing group and the unchanged group (P > 0.05). High-frequency tinnitus may predict the vanishing of tinnitus after treatment (P < 0.05), but the degree of hearing loss, tinnitus characteristics (loudness and frequency), and psychoacoustic score (THI and VAS) were only weakly correlated (P < 0.05). Residual inhibition test (RI) was an independent risk factor for the efficacy of acoustic therapy (P < 0.001). Conclusion: The patients were divided into three groups by T-MIST treatment effect; Kruskal-Wallis test and chi-square test were used to compare the baseline information of each group. Then, we analyzed the correlation between patient characteristics and psychoacoustic scores. Finally, logistic regression was performed to explore predictors that might influence the treatment effect. High-frequency tinnitus may have a better therapeutic effect; age, disease course, and other factors can not be stable explanation factors for a poor therapeutic effect of tinnitus. The residual inhibition (RI) test was an independent factor in predicting the efficacy of T-MIST.


Assuntos
Surdez , Perda Auditiva , Zumbido , Humanos , Som , Zumbido/terapia , Escala Visual Analógica
19.
Front Microbiol ; 13: 924137, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36171748

RESUMO

During agricultural production, plowing affects the existing traits of the planted soil, including environmental factors (physicochemical properties and soil enzymatic activity) and microbial community, but whether deep tillage and conventional tillage cause differences in soil microecology are unknown. In this study, the 16S rRNA high-throughput sequencing technology was combined with soil environmental factor detection to analyze the differences in microbial diversity of smokey soils at different depths. As a result, the composition and structure of microbial community varied in different soil depth after plowing. Two dominant phyla, Actinobacteria and Acidobacteria, have varied a lot between the deep-plowing treatment HS3 (the sample in 10-20 cm depth after deep-plowing treatment) sample and the conventional tillage HC3 (treatment the sample in 10-20 cm depth after conventional tillage) sample. The abundance of Actinobacteria has increased significantly, while the abundance of Acidobacteria has decreased significantly. Moreover, deep tillage increased the activity of sucrase (S-SC) and nitrate reductase (NR) in samples with soil depth below 20 cm. In summary, deep tillage disturbed spatial microbial diversity and environmental factors significantly. This would provide new guidance for improving farmland management strategies, optimizing the activation methods of soil layers, further improving crop planting soil, and increasing crop yield.

20.
BMC Genomics ; 23(1): 611, 2022 Aug 23.
Artigo em Inglês | MEDLINE | ID: mdl-35999496

RESUMO

BACKGROUND: Emerging transcriptome-wide high-throughput screenings reveal the landscape and functions of RNAs, such as circular RNAs (circRNAs), in human cancer. In addition, the post-transcriptional RNA internal modifications, especially N6-methyladenosine (m6A), greatly enrich the variety of RNAs metabolism. However, the m6A modification on circRNAs has yet to be addressed. RESULTS: Here, we report an epitranscriptome-wide mapping of m6A-modified circRNAs (m6A-circRNA) in oral squamous cell carcinoma (OSCC). Utilizing the data of m6A methylated RNA immunoprecipitation sequencing (MeRIP-seq) and m6A-circRNAs microarray, we found that m6A-circRNAs exhibited particular modification styles in OSCC, which was independent of m6A-mRNA. Besides, m6A modification on circRNAs frequently occurred on the long exons in the front part of the coding sequence (CDS), which was distinct from m6A-mRNA that in 3'-UTR or stop codon. CONCLUSION: In conclusion, our work preliminarily demonstrates the traits of m6A-circRNAs, which may bring enlighten for the roles of m6A-circRNAs in OSCC.


Assuntos
Carcinoma de Células Escamosas , Neoplasias de Cabeça e Pescoço , Neoplasias Bucais , Carcinoma de Células Escamosas/patologia , Humanos , Neoplasias Bucais/genética , Neoplasias Bucais/metabolismo , Neoplasias Bucais/patologia , RNA/metabolismo , RNA Circular , RNA Mensageiro/genética , Carcinoma de Células Escamosas de Cabeça e Pescoço
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