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BACKGROUND: Locoregional treatment with transarterial chemoembolization (TACE) or hepatic artery infusion chemotherapy (HAIC) and systemic targeted immunotherapy with tyrosine kinase inhibitors (TKI) and programmed cell death protein-1 (PD-1) inhibitors in the treatment of unresectable hepatocellular carcinoma (uHCC) have achieved promising efficacy. The retrospective study aimed to evaluate the efficacy and safety of TACE and HAIC plus TKI with or without PD-1 for uHCC. PATIENTS AND METHODS: From November 2020 to February 2024, the data of 44 patients who received TACE-HAIC + TKI + PD-1 (THKP group) and 34 patients who received TACE-HAIC + TKI (THK group) were retrospectively analyzed. Primary outcomes were overall survival (OS) and progress-free survival (PFS), and secondary outcomes were objective response rate (ORR), disease control rate (DCR), conversion rates, and adverse events (AEs). RESULTS: A total of 78 patients were recruited in our single-center study. The patients in THKP group had prolonged median OS [25 months, 95% confidence interval (CI) 24.0-26.0 vs 18 months, 95% CI 16.1-19.9; p = 0.000278], median PFS [16 months, 95% CI 14.1-17.9 vs 12 months 95% CI 9.6-14.4; p = 0.004] and higher ORR (38.6% vs 23.5%, p = 0. 156) and DCR (88.6% vs 64.7%, p = 0.011) compared with those in THK group. Multivariate analysis showed that treatment option and alpha-fetoprotein (AFP) level were independent prognostic factors of OS and PFS. The frequency of AEs were similar between the two groups. CONCLUSIONS: The THKP group had better efficacy for uHCC than the THK group, with acceptable safety.
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Zika virus, a mosquito-borne arbovirus, has repeatedly caused large pandemics with symptoms worsening from mild and self-limiting diseases to Guillain-Barré syndrome in adults and fetal microcephaly in newborns. In recent years, Zika virus diseases have posed a serious threat to human health. The shortage of susceptible small animal models makes it difficult to study pathogenic mechanisms and evaluate potential therapies for Zika virus infection. Therefore, we chose immunocompromised mice (AG129 mice) deficient in IFN-α/ß and IFN-γ receptors, which can abolish the innate immune system that prevents Zika virus infection early. AG129 mice were infected with the Zika virus, and this mouse model exhibited replication dynamics, tissue tropism, pathological lesion and immune activation of the Zika virus. Our results suggest that the inoculum dose of Zika virus can affect the viral replication dynamics, cytokine responses and survival rate in AG129 mice. By testing the potential antiviral drug favipiravir, several critical indicators, including replication dynamics and survival rates, were identified in AG129 mice after Zika virus infection. It is suggested that the model is reliable for drug evaluation. In brief, this model provides a potential platform for studies of the infectivity, virulence, and pathogenesis of the Zika virus. Moreover, the development of an accessible mouse model of Zika virus infection will expedite the research and deployment of therapeutics and vaccines.
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Citocinas , Modelos Animais de Doenças , Hospedeiro Imunocomprometido , Replicação Viral , Infecção por Zika virus , Zika virus , Animais , Zika virus/imunologia , Zika virus/patogenicidade , Infecção por Zika virus/imunologia , Infecção por Zika virus/virologia , Replicação Viral/efeitos dos fármacos , Camundongos , Citocinas/metabolismo , Taxa de Sobrevida , Receptor de Interferon alfa e beta/genética , Antivirais/farmacologia , Antivirais/uso terapêutico , Receptores de Interferon/deficiência , Receptores de Interferon/genética , Receptores de Interferon/metabolismo , Receptor de Interferon gama , Células VeroRESUMO
Recent microbiome-brain axis findings have shown evidence of the modulation of microbiome community as an environmental mediator in brain function and psychiatric illness. This work is focused on the role of the microbiome in understanding a rarely investigated environmental involvement in schizophrenia (SZ), especially in relation to brain circuit dysfunction. We leveraged high throughput microbial 16s rRNA sequencing and functional neuroimaging techniques to enable the delineation of microbiome-brain network links in SZ. N = 213 SZ and healthy control subjects were assessed for the oral microbiome. Among them, 139 subjects were scanned by resting-state functional magnetic resonance imaging (rsfMRI) to derive brain functional connectivity. We found a significant microbiome compositional shift in SZ beta diversity (weighted UniFrac distance, p = 6 × 10-3; Bray-Curtis distance p = 0.021). Fourteen microbial species involving pro-inflammatory and neurotransmitter signaling and H2S production, showed significant abundance alterations in SZ. Multivariate analysis revealed one pair of microbial and functional connectivity components showing a significant correlation of 0.46. Thirty five percent of microbial species and 87.8 % of brain functional network connectivity from each component also showed significant differences between SZ and healthy controls with strong performance in classifying SZ from healthy controls, with an area under curve (AUC) = 0.84 and 0.87, respectively. The results suggest a potential link between oral microbiome dysbiosis and brain functional connectivity alteration in relation to SZ, possibly through immunological and neurotransmitter signaling pathways and the hypothalamic-pituitary-adrenal axis, supporting for future work in characterizing the role of oral microbiome in mediating effects on SZ brain functional activity.
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Encéfalo , Imageamento por Ressonância Magnética , Microbiota , Boca , Esquizofrenia , Humanos , Esquizofrenia/fisiopatologia , Esquizofrenia/diagnóstico por imagem , Esquizofrenia/microbiologia , Feminino , Masculino , Adulto , Microbiota/fisiologia , Encéfalo/diagnóstico por imagem , Encéfalo/fisiopatologia , Boca/microbiologia , Boca/fisiopatologia , Boca/diagnóstico por imagem , RNA Ribossômico 16S/genética , Conectoma , Pessoa de Meia-Idade , Descanso , Adulto JovemRESUMO
Fine-tuning nucleation and growth of colloidal liquid crystalline (LC) droplets, also known as tactoids, is highly desirable in both fundamental science and technological applications. However, the tactoid structure results from the trade-off between thermodynamics and nonequilibrium kinetics effects, and controlling liquid-liquid crystalline phase separation (LLCPS) in these systems is still a work in progress. Here, a single-step strategy is introduced to obtain a rich palette of morphologies for tactoids formed via nucleation and growth within an initially isotropic phase exposed to a gradient of depletants. The simultaneous appearance is shown of rich LC structures along the depleting potential gradient, where the position of each LC structure is correlated with the magnitude of the depleting potential. Changing the size (nanoparticles) or the nature (polymers) of the depleting agent provides additional, precise control over the resulting LC structures through a size-selective mechanism, where the depletant may be found both within and outside the LC droplets. The use of depletion gradients from depletants of varying sizes and nature offers a powerful toolbox for manipulation, templating, imaging, and understanding heterogeneous colloidal LC structures.
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Pancreatic cancer is one of the most fatal cancers in the world. A growing number of studies have begun to demonstrate that mitochondria play a key role in tumorigenesis. Our previous study reveals that NDUFS2 (NADH: ubiquinone oxidoreductase core subunit S2), a core subunit of the mitochondrial respiratory chain complex I, is upregulated in Pancreatic adenocarcinoma (PAAD). However, its role in the development of PAAD remains unknown. Here, we showed that NDUFS2 played a critical role in the survival, proliferation and migration of pancreatic cancer cells by inhibiting mitochondrial cell death. Additionally, protein mass spectrometry indicated that the NDUFS2 was interacted with a deubiquitinase, OTUB1. Overexpression of OTUB1 increased NDUFS2 expression at the protein level, while knockdown of OTUB1 restored the effects in vitro. Accordingly, overexpression and knockdown of OTUB1 phenocopied those of NDUFS2 in pancreatic cancer cells, respectively. Mechanically, NDUFS2 was deubiquitinated by OTUB1 via K48-linked polyubiquitin chains, resulted in an elevated protein stability of NDUFS2. Moreover, the growth of OTUB1-overexpressed pancreatic cancer xenograft tumor was promoted in vivo, while the OTUB1-silenced pancreatic cancer xenograft tumor was inhibited in vivo. In conclusion, we revealed that OTUB1 increased the stability of NDUFS2 in PAAD by deubiquitylation and this axis plays a pivotal role in pancreatic cancer tumorigenesis and development.
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Microdroplets are a class of soft matter that has been extensively employed for chemical, biochemical, and industrial applications. However, fabricating microdroplets with largely controllable contact-area shape and apparent contact angle, a key prerequisite for their applications, is still a challenge. Here, by engineering a type of surface with homocentric closed-loop microwalls/microchannels, we can achieve facile size, shape, and contact-angle tunability of microdroplets on the textured surfaces by design. More importantly, this class of surface topologies (with universal genus value = 1) allows us to reveal that the conventional Gibbs equation (widely used for assessing the edge effect on the apparent contact angle of macrodroplets) seems no longer applicable for water microdroplets or nanodroplets (evidenced by independent molecular dynamics simulations). Notably, for the flat surface with the intrinsic contact angle ~0°, we find that the critical contact angle on the microtextured counterparts (at edge angle 90°) can be as large as >130°, rather than 90° according to the Gibbs equation. Experiments show that the breakdown of the Gibbs equation occurs for microdroplets of different types of liquids including alcohol and hydrocarbon oils. Overall, the microtextured surface design and topological wetting states not only offer opportunities for diverse applications of microdroplets such as controllable chemical reactions and low-cost circuit fabrications but also provide testbeds for advancing the fundamental surface science of wetting beyond the Gibbs equation.
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The development of diabetes mellitus (DM) is generally accompanied by erectile dysfunction (ED) and pulmonary arterial hypertension (PAH), which increases the use of combination drug therapy and the risk of drug-drug interactions. Saxagliptin for the treatment of DM, sildenafil for the treatment of ED and PAH, and macitentan for the treatment of PAH are all substrates of CYP3A4, which indicates their potential involvement in drug-drug interactions. Therefore, we investigated potential pharmacokinetic interactions between saxagliptin and sildenafil/macitentan. We investigated this speculation both in vitro and in vivo, and explored the underlying mechanism using in vitro hepatic metabolic models and molecular docking assays. The results showed that sildenafil substantially inhibited the metabolism of saxagliptin by occupying the catalytic site of CYP3A4 in a competitive manner, leading to the alterations in the pharmacokinetic properties of saxagliptin in terms of increased maximum plasma concentration (Cmax), area under the plasma concentration-time curve from time 0 to 24 h (AUC(0-t)), area under the plasma concentration-time curve from time 0 extrapolated to infinite time (AUC(0-∞)), decreased clearance rate (CLz/F), and prolonged terminal half-life (t1/2). In contrast, a slight inhibition was observed in saxagliptin metabolism when concomitantly used with macitentan, as no pharmacokinetic parameters were altered, except for CLz/F. Thus, dosage adjustment of saxagliptin may be required in combination with sildenafil to achieve safe therapeutic plasma concentrations and reduce the risk of potential toxicity, but it is not necessary for co-administration with macitentan.
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Adamantano , Dipeptídeos , Interações Medicamentosas , Pirimidinas , Citrato de Sildenafila , Sulfonamidas , Citrato de Sildenafila/farmacocinética , Citrato de Sildenafila/farmacologia , Sulfonamidas/farmacocinética , Sulfonamidas/farmacologia , Dipeptídeos/farmacocinética , Dipeptídeos/farmacologia , Pirimidinas/farmacocinética , Pirimidinas/farmacologia , Humanos , Adamantano/análogos & derivados , Adamantano/farmacocinética , Adamantano/farmacologia , Masculino , Animais , Citocromo P-450 CYP3A/metabolismo , Simulação de Acoplamento Molecular , Microssomos Hepáticos/metabolismo , Microssomos Hepáticos/efeitos dos fármacos , Inibidores da Dipeptidil Peptidase IV/farmacocinética , Inibidores da Dipeptidil Peptidase IV/farmacologiaRESUMO
Rational manipulation and assembly of discrete colloidal particles into architected superstructures have enabled several applications in materials science and nanotechnology. Optical manipulation techniques, typically operated in fluid media, facilitate the precise arrangement of colloidal particles into superstructures by using focused laser beams. However, as the optical energy is turned off, the inherent Brownian motion of the particles in fluid media impedes the retention and reconfiguration of such superstructures. Overcoming this fundamental limitation, we present on-demand, three-dimensional (3D) optical manipulation of colloidal particles in a phase-change solid medium made of surfactant bilayers. Unlike liquid crystal media, the lack of fluid flow within the bilayer media enables the assembly and retention of colloids for diverse spatial configurations. By utilizing the optically controlled temperature-dependent interactions between the particles and their surrounding media, we experimentally exhibit the holonomic microscale control of diverse particles for repeatable, reconfigurable, and controlled colloidal arrangements in 3D. Finally, we demonstrate tunable light-matter interactions between the particles and 2D materials by successfully manipulating and retaining these particles at fixed distances from the 2D material layers. Our experimental results demonstrate that the particles can be retained for over 120 days without any change in their relative positions or degradation in the bilayers. With the capability of arranging particles in 3D configurations with long-term stability, our platform pushes the frontiers of optical manipulation for distinct applications such as metamaterial fabrication, information storage, and security.
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BACKGROUND: NUDT21 (Nudix Hydrolase 21) has been shown to play an essential role in multiple biological processes. Pancreatic adenocarcinoma (PAAD) is one of the most fatal cancers in the world. However, the biological function of NUDT21 in PAAD remains rarely understood. The aim of this research was to identify the prediction value of NUDT21 in diagnosis, prognosis, immune infiltration, and signal pathway in PAAD. METHODS: Combined with the data in online databases, we analyzed the expression, immune infiltration, function enrichment, signal pathway, diagnosis, and prognosis of NUDT21 in PAAD. Then, the biological function of NUDT21 and its interacted protein in PAAD was identified through plasmid transduction system and protein mass spectrometry. Expression of NUDT21 was further verified in clinical specimens by immunofluorescence. RESULTS: We found that NUDT21 was upregulated in PAAD tissues and was significantly associated with the diagnosis and prognosis of pancreatic cancer through bioinformatic data analysis. We also found that overexpression of NUDT21 enhanced PAAD cells proliferation and migration, whereas knockdown NUDT21 restored the effects through in vitro experiment. Moreover, NDUFS2 was recognized as a potential target of NUDT21.We further verified that the expression of NDUFS2 was positively correlated with NUDT21 in PAAD clinical specimens. Mechanically, we found that NUDT21 stabilizes NDUFS2 and activates the PI3K-AKT signaling pathway. CONCLUSION: Our investigation reveals that NUDT21 is a previously unrecognized oncogenic factor in the diagnosis, prognosis, and treatment target of PAAD, and we suggest that NUDT21 might be a novel therapeutic target in PAAD.
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Adenocarcinoma , Fator de Especificidade de Clivagem e Poliadenilação , NADH Desidrogenase , Neoplasias Pancreáticas , Humanos , Adenocarcinoma/genética , Proliferação de Células , NADH Desidrogenase/genética , Neoplasias Pancreáticas/genética , Fosfatidilinositol 3-Quinases , Proteínas Proto-Oncogênicas c-akt , Fator de Especificidade de Clivagem e Poliadenilação/genéticaRESUMO
Nowadays, hepatocellular carcinoma (HCC) is still a major threat to human health globally, with a disappointing prognosis. Regular monitoring of patients at high risk, utilizing abdominal ultrasonography combined with alpha-fetoprotein (AFP) serum analysis, enables the early detection of potentially treatable tumors. However, the approach has limitations due to its lack of sensitivity. Meanwhile, the current standard procedure for obtaining a tumor biopsy in cases of HCC is invasive and lacks the ability to assess the dynamic progression of cancer or account for tumor heterogeneity. Hence, there is a pressing need to develop non-invasive, highly sensitive biomarkers for HCC which can improve the accuracy of early diagnosis, assess treatment response and accurately predict the prognosis. In contrast to the conventional method of tissue biopsy, liquid biopsy offers a non-invasive approach that can be readily repeated. As a liquid biopsy approach, the analysis of cell-free DNA (cfDNA) offers real-time insights that can accurately portray the tumor burden and provide a comprehensive depiction of the genetic profile associated with HCC. In this review, we present a comprehensive summary of the recent research findings pertaining to the significance and potential practicality of cfDNA analysis in the early detection and effective management of HCC.
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Carcinoma Hepatocelular , Ácidos Nucleicos Livres , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/diagnóstico , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/terapia , Ácidos Nucleicos Livres/genética , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/terapia , Biomarcadores Tumorais/genética , Detecção Precoce de Câncer/métodosRESUMO
Bandpass microwave photonic filter (MPF) can be achieved based on the well-known phase to intensity conversion method by using phase modulation and single micro-ring resonator (MRR) notch filter. Since MRR could introduce residual phase in handling one optical sideband, the out-of-band radio frequency (RF) rejection ratio and the shape factor of the bandpass MPF are very limited. Here, by introducing another MRR to handle the other optical sideband, the residual phase can be greatly suppressed, thus the filter's performance can be greatly improved. The proposed bandpass MPF was both verified theoretically and experimentally. Compared with the single MRR, the out-of-band RF rejection ratio and the shape factor were improved by 20â dB and 1.67, respectively. Furthermore, the bandpass MPF's bandwidth is reconfigurable by adjusting the optical carrier's frequency or the two MRRs' amplitude coupling coefficients. The bandpass MPF's center frequency is also tunable by changing the resonant wavelengths of two MRRs in the opposite direction simultaneously. Experimentally, bandwidth reconfiguration from 0.38â GHz to 15.74â GHz, the shape factor optimization from 2 to 1.23, and frequency tuning from 4â GHz to 21.5â GHz were achieved. We believe that the proposed bandpass MPF has great potential for microwave photonic signal processing.
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BACKGROUND: Primary central nervous system lymphoma (PCNSL) is a non-Hodgkin lymphoma that occurs in the CNS. With the advancement of medical care, its prognosis and treatment have also undergone tremendous changes. This study aimed to construct a prognostic model and compare the effects of different treatments for intracranial PCNSL. METHODS: Cases diagnosed as PCNSL between 2004 and 2015 were obtained from the Surveillance, Epidemiology, and End Results (SEER) database. Data were analyzed using Kaplan-Meier method and Cox regression analysis. Nomogram was built and validated using the R program. RESULTS: A total of 2861 PCNSL patients were included in the analysis. Age, year of diagnosis, surgery and chemotherapy were independent predictors for both overall survival (OS) and cancer-specific survival (CSS). A nomogram was established to predict 3-, 5- and 10-year OS and CSS for patients. Receiver operating characteristic (ROC) curves and decision curve analysis (DCA) showed the nomogram had good predictive performance and clinical application value. We also revealed that gross total resection had significantly better OS and CSS than biopsy alone (P < 0.001). Patients who received only chemotherapy had the best prognosis and did not benefit from additional radiotherapy. CONCLUSION: We developed a nomogram to predict patient survival rates based on independent predictors. It is an effective tool to help clinicians make survival predictions. Our results showed that patients can benefit from gross total resection of tumor, if it is feasible, and chemotherapy. The role of radiotherapy remained to be further assessed.
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DNA methylation (DNAme) alterations are known to initiate from the precancerous stage of tumorigenesis. Herein, we investigated the global and local patterns of DNAme perturbations in tumorigenesis by analysing the genome-wide DNAme profiles of the cervix, colorectum, stomach, prostate, and liver at precancerous and cancer stages. We observed global hypomethylation in tissues of both two stages, except for the cervix, whose global DNAme level in normal tissue was lower than that of the other four tumour types. For alterations shared by both stages, there were common hyper-methylation (sHyperMethyl) and hypo-methylation (sHypoMethyl) changes, of which the latter type was more frequently identified in all tissues. Biological pathways interrupted by sHyperMethyl and sHypoMethyl alterations demonstrated significant tissue specificity. DNAme bidirectional chaos indicated by the enrichment of both sHyperMethyl and sHypoMethyl changes in the same pathway was observed in most tissues and was a common phenomenon, particularly in liver lesions. Moreover, for the same enriched pathways, different tissues may be affected by distinct DNAme types. For the PI3K-Akt signalling pathway, sHyperMethyl enrichment was observed in the prostate dataset, but sHypoMethyl enrichment was observed in the colorectum and liver datasets. Nevertheless, they did not show an increased possibility in survival prediction of patients in comparison with other DNAme types. Additionally, our study demonstrated that gene-body DNAme changes of tumour suppressor genes and oncogenes may persist from precancerous lesions to the tumour. Overall, we demonstrate the tissue specificity and commonality of cross-stage alterations in DNA methylation profiles in multi-tissue tumorigenesis.
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Metilação de DNA , Lesões Pré-Cancerosas , Masculino , Feminino , Humanos , Especificidade de Órgãos , Fosfatidilinositol 3-Quinases/genética , Lesões Pré-Cancerosas/genética , Carcinogênese/genéticaRESUMO
Background: In-stent restenosis (ISR) is an adverse and notable event in the treatment of intracranial atherosclerotic stenosis (ICAS) with percutaneous transluminal angioplasty and stenting (PTAS). The incidence and contributing factors have not been fully defined. This study was performed to evaluate factors associated with ISR after PTAS. Data source: We identified studies on ISR after PTAS from an electronic search of articles in PubMed, Ovid MEDLINE, and the Cochrane Central Database (dated up to July 2022). Results: A total of 19 studies, including 452 cases of ISR after 2,047 PTAS, were included in the meta-analysis. The pooled incidence rate of in-stent restenosis was 22.08%. ISR was more likely to occur in patients with coronary artery disease (OR = 1.686; 95% CI: 1.242-2.288; p = 0.0008), dissection (OR = 6.293; 95% CI: 3.883-10.197; p < 0.0001), and higher residual stenosis (WMD = 3.227; 95% CI: 0.142-6.311; p = 0.0404). Patients treated with Wingspan stents had a significantly higher ISR rate than those treated with Enterprise stents (29.78% vs. 14.83%; p < 0.0001). Conclusions: The present study provides the current estimates of the robust effects of some risk factors for in-stent restenosis in intracranial atherosclerotic stenosis. The Enterprise stent had advantages compared with the Wingspan stent for ISR. The significant risk factors for ISR were coronary artery disease, dissection, and high residual stenosis. Local anesthesia was a suspected factor associated with ISR.
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Hepatocellular carcinoma (HCC) is the predominant pathological type of liver cancer. Several therapeutic treatments, including sorafenib and regorafenib, have only modestly improved survival in patients with HCC. The aim of this study was to investigate the expression profiles and the regulation of competitive endogenous RNAs (ceRNAs) of the sorafenib-related target genes in HCC. Based on clinical information and expression profiles of HCC clinical samples from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases, shared differentially expressed genes (DEGs) were analyzed and identified. Sorafenib-associated DEGs (SADs) were obtained by intersecting the DEGs with the sorafenib target genes from SuperTarget database. The expression patterns of SADs were verified in the Oncomine database. The biological functions of the SADs were annotated by gene set enrichment analysis (GSEA). In addition, a ceRNA network associated with SADs was constructed. Long non-coding RNAs (lncRNAs) in network that were significantly associated with overall survival were identified as prognosis of patients by Cox regression analysis. Finally, the expression levels of prognostic genes in HCC tissues and cell lines were verified using qRT-PCR. Gene expression differential analysis yielded a total of 146 common DEGs were obtained, including 21 upregulated and 125 downregulated DEGs. Among them, ten SADs were detected to be differentially expressed between tumor and normal tissues, including AXL, CYP2C19, CYP2C8, CYP2C9, CYP3A4, FGFR2, GMNN, PDGFRA, and TTK. GSEA analysis grouped them into three categories by function. The first category (CYP2C19, CYP2C8, CYP2C9 and CYP3A4) and second category (GMNN, TTK and EGER2) had the opposite roles in the enriched terms and pathways, while the third class (AXL and PDGFRA) has enrichment terms and pathways that intersect with those of the first and second categories. A ceRNA network associated with SADs was also constructed including 49 lncRNAs, 14 miRNAs, and 8 mRNAs. Three of these lncRNAs, SNHG7, GAS5 and HCP5, were found upregulated in HCC tissues and to be independent predictors in HCC patients. Significant correlations were found in expression between the prognostic lncRNAs and SADs. Ten SADs were systematically identified using expression data from HCC and normal tissues from TCGA and GEO datasets. GSEA analysis provided us with insight into the function of SADs. In the future, we will continue to explore the mechanisms of coordinated regulation of SADs-related prognostic lncRNAs and SADs at the ceRNA axis level and their potential functions in the development of HCC.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , MicroRNAs , RNA Longo não Codificante , Humanos , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/metabolismo , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/metabolismo , Sorafenibe/farmacologia , Citocromo P-450 CYP2C8/genética , Citocromo P-450 CYP2C8/metabolismo , Citocromo P-450 CYP2C19/genética , Citocromo P-450 CYP2C19/metabolismo , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Citocromo P-450 CYP2C9/genética , Citocromo P-450 CYP2C9/metabolismo , Citocromo P-450 CYP3A/genética , Citocromo P-450 CYP3A/metabolismo , Redes Reguladoras de Genes , MicroRNAs/genética , Expressão Gênica , Regulação Neoplásica da Expressão GênicaRESUMO
Nowadays, primary liver cancer is still a major threat to human health. Anoikis is a particular form of programed cell death that has an inhibitory effect on neoplasm metastasis. Although several prognostic models based on anoikis-related genes for Hepatocellular carcinoma (HCC) have been established, signatures associated with anoikis-related lncRNAs have not been identified. To fill this blank space, the authors built up a prognostic signature and appraised its value in guiding immunotherapy. Eleven prognostic anoikis-related lncRNAs were identified through Least Absolute Shrinkage and Selection Operator Cox analysis. The accuracy of the risk signature in predicting prognosis was verified by K-M survival analysis and Receiver operating characteristic analysis. We further discovered that the high-risk group was often enriched in signal pathways related to cell growth and death and immune response; in addition, in the low-risk group, cells often undergo metabolic changes through gene set enrichment analysis. Finally, we realised that HCC patients in the high-risk group were upregulated in immune-checkpoint molecules and tend to have a higher tumour mutation burden level which indicated a higher sensitivity to immunotherapy. All in all, the anoikis-related lncRNAs risk signature showed excellent ability in predicting prognosis and may guide the application of immunotherapy in future clinical practice.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , RNA Longo não Codificante , Humanos , Anoikis/genética , RNA Longo não Codificante/genética , Carcinoma Hepatocelular/diagnóstico , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/terapia , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/terapia , ImunoterapiaRESUMO
Background: The size and function of the future liver remnant (FLR) is an essential consideration for both eligibility for treatment and postoperative prognosis when planning surgical hepatectomy. Over time, a variety of preoperative FLR augmentation techniques have been investigated, from the earliest portal vein embolization (PVE) to the more recent Associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) and liver venous deprivation (LVD) procedures. Despite numerous publications on this topic, no bibliometric analysis has yet been conducted. Methods: Web of Science Core Collection (WoSCC) database was searched to identify studies related to preoperative FLR augmentation techniques published from 1997 to 2022. The analysis was performed using the CiteSpace [version 6.1.R6 (64-bit)] and VOSviewer [version 1.6.19]. Results: A total of 973 academic studies were published by 4431 authors from 920 institutions in 51 countries/regions. The University of Zurich was the most published institution while Japan was the most productive country. Eduardo de Santibanes had the most published articles, and Masato Nagino was the most frequently co-cited author. The most frequently published journal was HPB, and the most cited journal was Ann Surg, with 8088 citations. The main aspects of preoperative FLR augmentation technique is to enhance surgical technology, expand clinical indications, prevent and treat postoperative complications, ensure long-term survival, and evaluate the growth rate of FLR. Recently, hot keywords in this field include ALPPS, LVD, and Hepatobiliary Scintigraphy. Conclusion: This bibliometric analysis provides a comprehensive overview of preoperative FLR augmentation techniques, offering valuable insights and ideas for scholars in this field.
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BACKGROUND: Assess the effectiveness and safety of treatment options atezolizumab plus bevacizumab (Atez/Bev) or lenvatinib in clinical practice for patients with advanced hepatocellular carcinoma (HCC) patients. METHODS: To compare the effectiveness of Atez/Bev and lenvatinib in treating advanced HCC, we systematically searched the PubMed, EMBASE, and Web of Science databases. We utilized Review Manager 5.3 to extract and analyze the data. RESULTS: The present systematic review included 8 nonrandomized studies comprising a total of 6628 cases. There was no significant difference in 0.5-, 1-, 1.5-year OS rates and 0.5-, 1-year PFS rates between the 2 groups. However, patients with HCC caused by viral hepatitis would benefit more from the Atez/Bev therapy (hazard ratioâ =â 0.75, 95% confidence interval: 0.63-0.89) but patients with a Child-Pugh class B liver function would benefit more from lenvatinib (hazard ratioâ =â 1.70, 95% confidence interval: 1.07-2.70). At the same time, there are no major differences in safety between the 2 treatment options. CONCLUSION: Our study did not find any significant difference in effectiveness and safety between Atez/Bev and lenvatinib. However, Additional verification is required to determine whether these 2 therapeutic approaches have varying effects on distinct populations.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/tratamento farmacológico , Bevacizumab/efeitos adversos , Neoplasias Hepáticas/tratamento farmacológico , Resultado do TratamentoRESUMO
Insoluble amyloid fibrils made from proteins and peptides are difficult to be degraded in both living and artificial systems. The importance of studying their physical stability lies primarily with their association with human neurodegenerative diseases, but also owing to their potential role in multiple bio-nanomaterial applications. Here, gold nanorods (AuNRs) were utilized to investigate the plasmonic heating properties and dissociation of amyloid-ß fibrils formed by different peptide fragments (Aß16-22/Aß25-35/Aß1-42) related to the Alzheimer's disease. It is demonstrated that AuNRs were able to break mature amyloid-ß fibrils from both the full length (Aß1-42) and peptide fragments (Aß16-22/Aß25-35) within minutes by triggering ultrahigh localized surface plasmon resonance (LSPR) heating. The LSPR energy absorbed by the amyloids to unfold and move to higher levels in the protein folding energy landscape can be measured directly and in situ by luminescence thermometry using lanthanide-based upconverting nanoparticles. We also show that Aß16-22 fibrils, with the largest persistence length, displayed the highest resistance to breakage, resulting in a transition from rigid fibrils to short flexible fibrils. These findings are consistent with molecular dynamics simulations indicating that Aß16-22 fibrils possess the highest thermostability due to their highly ordered hydrogen bond networks and antiparallel ß-sheet orientation, hence affected by an LSPR-induced remodeling rather than melting. The present results introduce original strategies for disassembling amyloid fibrils noninvasively in liquid environment; they also introduce a methodology to probe the positioning of amyloids on the protein folding and aggregation energy landscape via nanoparticle-enabled plasmonic and upconversion nanothermometry.