Malnutrition, which is often underestimated in patients with hepatocellular carcinoma (HCC), has a proven adverse effect on survival rates. The purpose of this study was to verify the effectiveness of the cholesterol-modified prognostic nutritional index (CPNI) in determining the nutritional status and predicting overall survival (OS) and recurrence-free survival (RFS) in patients with HCC by comparing it with several other nutritional indicators. This retrospective single-center study enrolled 1450 consecutive HCC patients who underwent curative liver resection from January 2015 to November 2019. We evaluated the prognostic significance of several nutritional indicators, including CPNI, the controlling nutritional status (CONUT), the nutritional risk index (NRI), and the prognostic nutritional index (PNI), by applying time-dependent receiver operating characteristic (ROC) curves, Kaplan-Meier survival analysis, and Cox proportional hazards regression analysis. Among several objective nutrition evaluations (including CPNI, CONUT, NRI, and PNI), CPNI demonstrated the greatest prognostic predictive power for predicting OS. Meanwhile, CPNI demonstrated marginally higher accuracy in predicting RFS compared to PNI, and significantly outperformed CONUT and NRI. Univariate and multivariate analyses suggested that CPNI was an independent risk factor for the OS and RFS of patients with HCC undergoing curative liver resection. In most subgroups, malnutrition as identified by CPNI demonstrates strong stratification ability in predicting both OS and RFS. CPNI serves as an accurate and stable instrument for evaluating nutritional status and forecasting survival outcomes in HCC patients following liver resection, which has the potential to markedly influence clinical decision-making processes and the management of patient care.
Abstract Rheumatoid arthritis (RA) is the most prevalent inflammatory joint disease worldwide, leading to irreversible disability and even mortality. Unfortunately, current treatment regimens fail to cure RA due to low therapeutic responses and off‐target side effects. Herein, a neutrophil membrane‐cloaked, natural anti‐arthritic agent leonurine (Leo), and catalase (CAT) co‐loaded nanoliposomal system (Leo@CAT@NM‐Lipo) is constructed to remodel the hostile microenvironment for RA remission. Due to the inflammation tropism inherited from neutrophils, Leo@CAT@NM‐Lipo can target and accumulate in the inflamed joint cavity where high‐level ROS can be catalyzed into oxygen by CAT to simultaneously accelerate the drug release and alleviate hypoxia at the lesion site. Besides, the neutrophil membrane camouflaging also enhances the anti‐inflammatory potentials of Leo@CAT@NM‐Lipo by robustly absorbing pro‐arthritogenic cytokines and chemokines. Consequently, Leo@CAT@NM‐Lipo successfully alleviated paw swelling, reduced arthritis score, mitigated bone and cartilage damage, and reversed multiple organ dysfunctions in adjuvant‐induced arthritis rats (AIA) rats by synergistic effects of macrophage polarization, inflammation resolution, ROS scavenging, and hypoxia relief. Furthermore, Leo@CAT@NM‐Lipo manifested excellent biocompatibility both at the cellular and animal levels. Taken together, the study provided a neutrophil‐mimetic and ROS responsive nanoplatform for targeted RA therapy and represented a promising paradigm for the treatment of a variety of inflammation‐dominated diseases.
Abstract Oxidative stress and local overactive inflammation have been considered major obstacles in diabetic wound treatment. Although antiphlogistic tactics have been reported widely, they are also challenged by pathogen contamination and compromised angiogenesis. Herein, a versatile integrated nanoagent based on 2D reductive covalent organic frameworks coated with antibacterial immuno‐engineered exosome (PCOF@E‐Exo) is reported to achieve efficient and comprehensive combination therapy for diabetic wounds. The E‐Exo is collected from TNF‐α‐treated mesenchymal stem cells (MSCs) under hypoxia and encapsulated cationic antimicrobial carbon dots (CDs). This integrated nanoagent not only significantly scavenges reactive oxygen species and induces anti‐inflammatory M2 macrophage polarization, but also stabilizes hypoxia‐inducible factor‐1α (HIF‐1α). More importantly, the PCOF@E‐Exo exhibits intriguing bactericide capabilities toward Gram‐negative, Gram‐positive, and drug‐resistant bacteria, showing favorable intracellular bacterial destruction and biofilm permeation. In vivo results demonstrate that the synergetic impact of suppressing oxidative injury and tissue inflammation, promoting angiogenesis and eradicating bacterial infection, could significantly accelerate the infected diabetic fester wound healing with better therapeutic benefits than monotherapy or individual antibiotics. The proposed strategy can inspire further research to design more delicate platforms using the combination of immunotherapy with other therapeutic methods for more efficient ulcerated diabetic wounds treatments.
Consumers’ low-carbon preferences will affect the decision-making behavior of supply chain members; an understanding of the influence mechanism of reciprocal altruistic preferences and reference low-carbon-level effect on carbon emission transfers in a supply chain is of great significance for optimizing transfer and reducing emissions and enhancing the overall emission reduction effect of the supply chain. By constructing a manufacturer-led differential game model, we analyzed the carbon emission transfer strategy of a supply chain under the influence of the reference low-carbon level effect and reciprocal altruistic preferences in scenarios with and without such preferences. The results showed that the reference low-carbon-level effect had a positive influence on the manufacturer’s transfers but not on the supplier’s acceptance of them. Moreover, reciprocal altruistic preferences increased both the transfer and acceptance of emissions while improving the low-carbon level of products. Under the influence of reciprocal preferences, the difference in the degree of altruism will also affect the carbon emission transfer and acceptance behavior of the manufacturer and supplier. When the supplier’s reciprocal altruism coefficient and the consumer’s memory parameter remain within a certain range, the transfers positively affect cooperation in the supply chain.
Transfer RNA-derived small RNAs, a recently identified class of small noncoding RNAs, play a crucial role in regulating gene expression and are implicated in cerebrovascular diseases. However, the specific biological roles and mechanisms of transfer RNA-derived small RNAs in intracranial aneurysms (IAs) remain unclear. In this study, we identified that the transfer RNA-Asp-GTC derived fragment (tRF-AspGTC) is highly expressed in the IA tissues of both humans and mice. tRF-AspGTC promotes IA formation by facilitating the phenotypic switching of vascular smooth muscle cells, increasing of matrix metalloproteinase 9 expression, and inducing of oxidative stress and inflammatory responses. Mechanistically, tRF-AspGTC binds to galectin-3, inhibiting tripartite motif 29-mediated ubiquitination and stabilizing galectin-3. This stabilization activates the toll-like receptor 4/MyD88/nuclear factor kappa B pathway, further driving phenotypic switching and inflammation. Clinically, circulating exosomal tRF-AspGTC demonstrates strong diagnostic efficacy for IAs and is identified as an independent risk factor for IA occurrence. These findings highlight the potential of tRF-AspGTC as a promising diagnostic biomarker and therapeutic target for IAs.
Extracellular vesicles (EVs), including exosomes, play a crucial role in intercellular communication and have emerged as important mediators in the development and progression of gastric cancer. This review discusses the current understanding of the role of EVs, particularly exosomal lncRNA and microRNA, in gastric cancer and their potential as diagnostic and therapeutic targets. Exosomes are small membrane-bound particles secreted by both cancer cells and stromal cells within the tumor microenvironment. They contain various ncRNA and biomolecules, which can be transferred to recipient cells to promote tumor growth and metastasis. In this review, we highlighted the importance of exosomal lncRNA and microRNA in gastric cancer. Exosomal lncRNAs have been shown to regulate gene expression by interacting with transcription factors or chromatin-modifying enzymes, which regulate gene expression by binding to target mRNAs. We also discuss the potential use of exosomal lncRNAs and microRNAs as diagnostic biomarkers for gastric cancer. Exosomes can be isolated from various bodily fluids, including blood, urine, and saliva. They contain specific molecules that reflect the molecular characteristics of the tumor, making them promising candidates for non-invasive diagnostic tests. Finally, the potential of targeting exosomal lncRNAs and microRNAs as a therapeutic strategy for gastric cancer were reviewed as wee. Inhibition of specific molecules within exosomes has been shown to suppress tumor growth and metastasis in preclinical models. In conclusion, this review article provides an overview of the current understanding of the role of exosomal lncRNA and microRNA in gastric cancer. We suggest that further research into these molecules could lead to new diagnostic tools and therapeutic strategies for this deadly disease.
Background: Targeting the mRNA splicing process has been identified as a therapeutic strategy for human cancer. PRPF19 is an RNA binding protein that is involved in pre-mRNA processing and repairing DNA damage; the aberrant expression of PRPF19 is potentially associated with carcinogenesis. However, the biological role of PRPF19 in hepatocellular carcinoma (HCC) is still elusive. Methods: Data obtained from TCGA, Oncomine, and GEO were used to investigate the PRPF19 expression level and its role in tumor immune infiltration, prognosis, and the tumor progression of cohorts from HCC. Using various databases and tools (UALCAN, TIMER, TISMO, and PathCards), we presented the potential mechanisms of PFPF19 upregulation, PRPF19-related pathways, and its biological functions in liver cancer. Results: For HCC, PRPF19 expression was found upregulated both in single tumor cells and tissues. Furthermore, the increased expression of PRPF19 was significantly correlated to clinical characteristics: advanced stage, vascular invasion, high AFP, and poor prognosis of HCC. According to the tumor-immunological analysis, we found that PRPF19 is positively correlated with infiltrating myeloid-derived suppressor cells (MDSCs). Moreover, the microenvironment of HCC tissues with high expression of PRPF19 is highly immunosuppressive (lower T-lymphocytes, multiple immune checkpoints upregulated). Patients with high expression of PRPF19 and high MDSCs had a worse survival prognosis as well. TP53 mutation may have a positive effect on PRPF19 expression via decreased promoter methylation of PRPF19. By TF-mRNA network analysis, key transcription factors (TFs) in TC-NER and PCS pathways (PRPF19 involved) were identified. Conclusion: This work implied that PRPF19 is associated with tumor immune evasion and progression, and serves as a prognostic marker for worse clinical outcomes with HCC. Thus, this critical regulator could serve as a potential therapeutic target of HCC.
'/%3e%3cuse xlink:href='%23a' transform='rotate(23.036 .093 25.536)'/%3e%3cuse xlink:href='%23a' transform='rotate(45.87 1.273 16.18)'/%3e%3cuse xlink:href='%23a' transform='rotate(69.945 .996 12.078)'/%3e%3cuse xlink:href='%23a' transform='rotate(20.66 -19.689 31.932)'/%3e%3c/svg%3e)