Prognostic value of geriatric nutritional risk index and prognostic nutritional index in hepatocellular carcinoma.

BACKGROUND: The geriatric nutritional risk index (GNRI) and prognostic nutritional index (PNI) are considered prognostic factors for several cancers. This study aimed to investigate the relationship between the GNRI and PNI for survival outcomes in patients with hepatocellular carcinoma (HCC). METHODS: We retrospectively analyzed 1666 patients with HCC who underwent hepatectomy. Restricted cubic spline regression was used to analyze the relationship between the GNRI and PNI for recurrence and mortality. Cox proportional hazards regression analysis was used to evaluate the risk factors associated with overall survival (OS) and recurrence-free survival (RFS). Interaction analysis was performed to investigate the comprehensive effects of the GNRI, PNI, and subgroup parameters on the prognosis of patients with HCC. RESULTS: The risks of death and recurrence decreased rapidly and gradually stabilized as the GNRI and PNI scores increased. Patients with lower GNRI and PNI scores had significantly shorter OS and RFS rates than those with higher scores. Multivariate analysis showed that high GNRI [HR and 95%CI = 0.77 (0.70-0.85), P < 0.001] and PNI [HR and 95%CI = 0.77 (0.70-0.86), P < 0.001] scores were associated with decreased mortality risk. This trend was maintained by confounding variables in adjusted models despite partial interactions with clinical factors. The combined GNRI and PNI analysis showed that HCC patients with high GNRI and PNI had longer OS and RFS. CONCLUSIONS: The GNRI and PNI showed good survival predictions in patients with HCC. Combining the GNRI with PNI may help predict the prognosis of patients (age>18 years) with HCC after hepatectomy.

Outer dynein arm docking complex subunit 2 polymorphism rs7893462 modulates hepatocellular carcinoma susceptibility and can serve as an overall survival biomarker for hepatitis B virus-related hepatocellular carcinoma after hepatectomy: a cohort study with a long-term follow-up.

BACKGROUND: Genetic variants of outer dynein arm docking complex subunit 2 (ODAD2) have been reported to be closely associated with primary ciliary dyskinesia and colorectal cancer in previous studies, but the association of genetic variants of ODAD2 with hepatocellular carcinoma (HCC) has not been reported. METHODS: We enrolled 80 healthy subjects and 468 Guangxi hepatitis B virus (HBV)-related HCC patients in this study. A case-control study method was used to explore the association of different ODAD2-rs7893462 genotypes with hepatocarcinogenesis. A comprehensive survival analysis was used to explore the association of rs7893462 with the prognosis of HBV-related HCC in Guangxi. RESULTS: Through a case-control study, we observed that patients carrying the G allele of rs7893462 had a markedly increased susceptibility to hepatocarcinogenesis (odds ratio = 1.712, 95% confidence interval = 1.032-2.839, P = 0.037). We found that there were significant prognosis differences among three different genotypes of rs7893462. Nomogram analysis suggested that the contribution of rs7893462 polymorphisms to the prognosis of HBV-related HCC was second only to the BCLC stage. Stratified survival analysis suggested that the AG genotype of rs7893462 was an independent prognostic risk factor for HBV-related HCC. Joint effect survival analysis also observed that the AG genotype of rs7893462 combined with clinical parameters could significantly identify HBV-related HCC patients with different prognostic outcomes more accurately, and the AG genotype was also observed to be independent of clinical factors in HBV-related HCC survival. CONCLUSION: The ODAD2-rs7893462 polymorphisms can be used as an independent prognostic indicator of HBV-related HCC overall survival and are significantly associated with susceptibility to hepatocarcinogenesis.

Robust analysis of a novel PANoptosis-related prognostic gene signature model for hepatocellular carcinoma immune infiltration and therapeutic response.

PANoptosis, an interplay between pyroptosis, apoptosis, and necroptosis, is deeply involved in cancer development and immunity. However, the influence of PANoptosis in hepatocellular carcinoma (HCC) remains to be further investigated. The differentially expressed PANoptosis-related genes (PANRGs) was screened in The Cancer Genome Atlas (TCGA) database. Accordingly, mutation, bioinformatics, and consensus clustering analyses were performed. Then, a prognostic risk model was developed by least absolute shrinkage and selection operator (LASSO) Cox regression. Furthermore, the prognostic value, immunity correlation and therapeutic response prediction ability of risk model were explored. A total of 18 PANRGs were differently expressed in the TCGA-HCC cohort and were mainly involved in cancer- and cell death-related signal pathways. Using unsupervised clustering method, we identified two PANRGs-mediated clustering patterns. The remarkable differences between the two clusters on overall survival (OS) and clinical features were demonstrated respectively. Based on the five-gene prognostic risk model, the calculated PANRG-scores were used to categorize the subgroups as high- and low-risk. Notably, the high-risk subgroup had a dismal prognosis and exhibited much lower immune infiltration levels of mast cells, nature killer cells and pDCs, but higher levels of aDCs, iDCs and Treg cells than those in the low-risk subgroup. Furthermore, we constructed a reliable nomogram combining clinical traits and PANRG-score to predict the OS of HCC patients. The significantly negative correlation between PANoptosis and tumor mutation burden (TMB), ferroptosis were revealed. In drug sensitivity analysis, the high-risk subgroup had a considerably lower TIDE score, suggesting a preferable response to immunotherapy, and may be more sensitive to Tipifarnib, Imatinib, Doxorubicin, and Gemcitabine. The upregulated mRNA expressions of FADD were validated in 16 paired HCC tissues of Guangxi cohort. Based on PANoptosis-related genes, an integrated risk signature was constructed to provide a roadmap for patient stratification and predict HCC patient's prognosis. The patients with the higher PANRG-score may carry a dismal survival and relatively low immune infiltration, but a potential better immunotherapy response. Therefore, future HCC therapy perspectives should emphasize the setting of PANoptosis to achieve a personalized, practicable and effective therapeutic regimen.

Effects of garcinol supplementation on the performance, egg quality, and intestinal health of laying hens in the late laying period.

The problem of rapid decline in egg production performance and poor egg quality is a key obstacle to improving the economic benefits of laying hens. Garcinol is an antioxidant polyphenol plant extract that has multiple physiological functions. Diets with the appropriate amount of garcinol might be able to improve the performance traits and health of late laying hens. Therefore, this study was conducted to evaluate the utilization of garcinol in late laying hens. A total of 400 healthy 59-wk-old Tingfen No. 6 hens were randomly allocated into 4 dietary treatment groups and fed a basal diet supplemented with 0, 100, 300, and 500 mg/kg garcinol for 12 wk, denoted the Con, LG, MG, and HG groups, respectively. The results showed that the addition of garcinol in the diet tended to increase the egg production rate compared with that of the control group (P = 0.080), while the average egg weight was significantly lower (P < 0.05) during the whole period of the experiment. The results showed that MG group hens had higher egg quality and strengthened antioxidant capacity in their serum (P < 0.05). Moreover, the laying hens in the MG group had significantly decreased crypt depth (CD) and increased villus height (VH) in the jejunum and ileum (P < 0.05), as well as an increased ratio of VH to CD (P < 0.05) and increased expression levels of Occludin (P < 0.05) and Claudin-2 (P < 0.05) in the jejunum to improve intestinal barrier function. In addition, dietary supplementation with garcinol influenced the cecal microbiota of laying hens, which was characterized by changes in the microbial community composition, including increased abundances of Firmicutes, Romboutsia, and Ruminococcus torques. In conclusion, dietary 300 mg/kg garcinol supplementation could increase the egg production and egg quality of late laying hens, which may be attributed to the antioxidant effects of garcinol and the improvement of intestinal morphology and epithelial barrier function as well as the regulation of mucosal immune status by altering microbial composition.

Lactiplantibacillus plantarum attenuates Coxsackievirus B3-induced pancreatitis through the BAX/BCL2/CASP3 signaling pathway.

Lactiplantibacillus plantarum is a lactic acid bacterium widely used in food production. Coxsackievirus B3 (CVB3) is an important human pathogen associated with acute pancreatitis development, and no antiviral therapeutics or vaccines are approved to treat or prevent its infection. However, whether L. plantarum could inhibit CVB3 infection remains unclear. Here, L. plantarum FLPL05 showed antiviral activity against CVB3 infection in vivo and in vitro. Pretreatment with L. plantarum FLPL05 reduced serum amylase levels, CVB3 viral load in the pancreas, serum pro-inflammatory cytokine levels, and macrophage infiltration in CVB3-infected mice. In mice, L. plantarum FLPL05 inhibited CVB3-induced pancreas apoptosis via the B cell leukemia/lymphoma 2 (BCL2)/BCL2-associated X protein (BAX)/caspase-3 (CASP3) signaling pathway. Furthermore, L. plantarum FLPL05 reduced CVB3 replication, protected cells from the cytopathic effect of CVB3 infection, and inhibited cell apoptosis. Moreover, L. plantarum FLPL05's exopolysaccharide (EPS) had activity against CVB3 in vitro, reducing the CVB3 titer and improving cell activity. Therefore, L. plantarum FLPL05 pretreatment improved CVB3-induced pancreatitis by partially reversing pancreatitis, which might be associated with EPS. Consequently, L. plantarum FLPL05 could be a potential probiotic with antiviral activity against CVB3.

PUS1 May Be a Potential Prognostic Biomarker and Therapeutic Target for Hepatocellular Carcinoma.

Objective: The mechanisms of pseudouridine synthase (PUS) are not definite in hepatocellular carcinoma (HCC), the objective of this study is to investigate the effect of PUS genes in HCC. Materials and Methods: Differentially expressed and prognostic gene of PUS enzymes was identified based on The Cancer Genome Atlas (TCGA), International Cancer Genome Consortium (ICGC) and Gene Expression Profiling Interactive Analysis (GEPIA) databases. For the identified gene, pseudouridine synthase 1 (PUS1), was used for further research. The clinicopathological feature of PUS1 was analyzed by Student's t-test. Prognostic significance was explored by Kaplan-Meier (KM) analysis and Cox proportional hazards regression model. Receiver operating characteristic (ROC) curve was applied to appraise diagnostic and prognostic value. The Database for Annotation, Visualization, and Integrated Discovery (DAVID) and Gene Set Enrichment Analysis (GSEA) were implemented to explore mechanism of PUS1. A Guangxi cohort was applied to verify differential expression. In vitro cell experiments were implemented to investigate the influence for proliferation, reactive oxygen species (ROS) level, migration, and invasion of HCC cells after a knockdown of PUS1. Results: PUS1 was significantly overexpressed in HCC tissues, and patients with high PUS1 were related to unpromising clinicopathological features. Survival analysis revealed high PUS1 expression was associated with a poor overall survival (OS) and 1 year-recurrence free survival (RFS), was an independent risk factor. Meanwhile, ROC curve showed that PUS1 had a diagnostic and prognostic significance to HCC. Functional enrichment analysis implied that PUS1 may be involved in metabolic pathways, mitochondrial function, non-alcoholic fatty liver disease (NAFLD), and some important carcinogenic pathways. Cell assays revealed that knockdown of PUS1 significantly constrained the migration, proliferation, invasion and improved the ROS level of HCC cells. Conclusion: PUS1 may be a prognostic biomarker and a underlying treatment target for HCC.

Enhanced silage pretreatment improving the biochemical methane potential of Miscanthus sinensis.

The choice of silage additives is an important factor for the storage of silage. One standard ensiling method and two enhanced ensiling methods (using natural silage, silage with mixed lactic acid bacteria, and silage with acetic acid, respectively) were carried out on Miscanthus sinensis. To determine the effects of these different methods, the biochemical methane potential (BMP) was determined. The results revealed that ensiling with acetic acid was the best method among the three ensiling methods. Acetic acid could quickly reduce the pH of the system to inhibit the growth of harmful bacteria. The rate of loss of dry matter was 0.92% when acetic acid was added, and the cumulative methane production was 149.6 mL·g-1 volatile solids. From an analysis of correlations between the properties and BMP of silage, the contents of acetic acid and total volatile fatty acids were significantly correlated with the BMP. This study provides a theoretical basis for improving the BMP of M. sinensis and achieving better effects of silage.

Identification of hub genes and transcription factor-miRNA-mRNA pathways in mice and human renal ischemia-reperfusion injury.

BACKGROUND: Renal ischemia-reperfusion injury (IRI) is a disease with high incidence rate in kidney related surgery. Micro RNA (miRNA) and transcription factors (TFs) are widely involved in the process of renal IRI through regulation of their target genes. However, the regulatory relationships and functional roles of TFs, miRNAs and mRNAs in the progression of renal IRI are insufficiently understood. The present study aimed to clarify the underlying mechanism of regulatory relationships in renal IRI. METHODS: Six gene expression profiles were downloaded from Gene Expression Omnibus (GEO). Differently expressed genes (DEGs) and differently expressed miRNAs (DEMs) were identified through RRA integrated analysis of mRNA datasets (GSE39548, GSE87025, GSE52004, GSE71647, and GSE131288) and miRNA datasets (GSE29495). miRDB and TransmiR v2.0 database were applied to predict target genes of miRNA and TFs, respectively. DEGs were applied for Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis, followed with construction of protein-protein interaction (PPI) network. Then, the TF-miRNA-mRNA network was constructed. Correlation coefficient and ROC analysis were used to verify regulatory relationship between genes and their diagnostic value in GSE52004. Furthermore, in independent mouse RNA-seq datasets GSE98622, human RNA-seq GSE134386 and in vitro, the expression of hub genes and genes from the network were observed and correlation coefficient and ROC analysis were validated. RESULTS: A total of 21 DEMs and 187 DEGs were identified in renal IRI group compared to control group. The results of PPI analysis showed 15 hub genes. The TF-miRNA-mRNA regulatory network was constructed and several important pathways were identified and further verified, including Junb-miR-223-Ranbp3l, Cebpb-miR-223-Ranbp3l, Cebpb-miR-21-Ranbp3l and Cebpb-miR-181b-Bsnd. Four regulatory loops were identified, including Fosl2-miR-155, Fosl2-miR-146a, Cebpb-miR-155 and Mafk-miR-25. The hub genes and genes in the network showed good diagnostic value in mice and human. CONCLUSIONS: In this study, we found 15 hub genes and several TF-miRNA-mRNA pathways, which are helpful for understanding the molecular and regulatory mechanisms in renal IRI. Junb-miR-223-Ranbp3l, Cebpb-miR-223-Ranbp3l, Cebpb-miR-21-Ranbp3l and Cebpb-miR-181b-Bsnd were the most important pathways, while Spp1, Fos, Timp1, Tnc, Fosl2 and Junb were the most important hub genes. Fosl2-miR-155, Fosl2-miR-146a, Cebpb-miR-155 and Mafk-miR-25 might be the negative feedback loops in renal IRI.

Rotating magnetic field induced oscillation of magnetic particles for in vivo mechanical destruction of malignant glioma.

Magnetic particles that can be precisely controlled under a magnetic field and transduce energy from the applied field open the way for innovative cancer treatment. Although these particles represent an area of active development for drug delivery and magnetic hyperthermia, the in vivo anti-tumor effect under a low-frequency magnetic field using magnetic particles has not yet been demonstrated. To-date, induced cancer cell death via the oscillation of nanoparticles under a low-frequency magnetic field has only been observed in vitro. In this report, we demonstrate the successful use of spin-vortex, disk-shaped permalloy magnetic particles in a low-frequency, rotating magnetic field for the in vitro and in vivo destruction of glioma cells. The internalized nanomagnets align themselves to the plane of the rotating magnetic field, creating a strong mechanical force which damages the cancer cell structure inducing programmed cell death. In vivo, the magnetic field treatment successfully reduces brain tumor size and increases the survival rate of mice bearing intracranial glioma xenografts, without adverse side effects. This study demonstrates a novel approach of controlling magnetic particles for treating malignant glioma that should be applicable to treat a wide range of cancers.

Magnetic virus-like nanoparticles in N. benthamiana plants: a new paradigm for environmental and agronomic biotechnological research.

This article demonstrates the encapsulation of cubic iron oxide nanoparticles (NPs) by Brome mosaic virus capsid shells and the formation, for the first time, of virus-based nanoparticles (VNPs) with cubic cores. Cubic iron oxide NPs functionalized with phospholipids containing poly(ethylene glycol) tails and terminal carboxyl groups exhibited exceptional relaxivity in magnetic resonance imaging experiments, which opens the way for in vivo MRI studies of systemic virus movement in plants. Preliminary data on cell-to-cell and long-distance transit behavior of cubic iron oxide NPs and VNPs in Nicotiana benthamiana leaves indicate that VNPs have specific transit properties, i.e., penetration into tissue and long-distance transfer through the vasculature in N. benthamiana plants, even at low temperature (6 °C), while NPs devoid of virus protein coats exhibit limited transport by comparison. These particles potentially open new opportunities for high-contrast functional imaging in plants and for the delivery of therapeutic antimicrobial cores into plants.