Systematic analysis of cuproptosis abnormalities and functional significance in cancer.

BACKGROUND: Cuproptosis is a recently discovered type of cell death, but the role and behavior of cuproptosis-related genes (CuRGs) in cancers remain unclear. This paper aims to address these issues by analyzing the multi-omics characteristics of cancer-related genes (CuRGs) across various types of cancer. METHOD: To investigate the impact of somatic copy number alterations (SCNA) and DNA methylation on CRG expression, we will analyze the correlation between these factors. We developed a cuproptosis index (CPI) model to measure the level of cuproptosis and investigate its functional roles. Using this model, we assessed the clinical prognosis of colorectal cancer patients and analyzed genetic changes and immune infiltration features in different CPI levels. RESULTS: The study's findings indicate that the majority of cancer-related genes (CuRGs) were suppressed in tumors and had a positive correlation with somatic copy number alterations (SCNA), while having a negative correlation with DNA methylation. This suggests that both SCNA and DNA methylation have an impact on the expression of CuRGs. The CPI model is a reliable predictor of survival outcomes in patients with colorectal cancer and can serve as an independent prognostic factor. Patients with a higher CPI have a worse prognosis. We conducted a deeper analysis of the genetic alterations and immune infiltration patterns in both CPI positive and negative groups. Our findings revealed significant differences, indicating that CuRGs may play a crucial role in tumor immunity mechanisms. Additionally, we have noticed a positive correlation between CuRGs and various crucial pathways that are linked to the occurrence, progression, and metastasis of tumors. CONCLUSIONS: Overall, our study systematically analyzes cuproptosis and its regulatory genes, emphasizing the potential of using cuproptosis as a basis for cancer therapy.

Colonic stent as a bridge to surgery versus emergency rection for malignant left-sided colorectal obstruction: A systematic review and meta-analysis of randomized controlled trials.

INTRODUCTION: The role of self-expanding metal stent (SEMS) implantation as a bridge to surgery in malignant left-sided colorectal obstruction (MLCO) remains controversial. OBJECTIVE: To evaluate the safety of SEMS implantation versus emergency surgery (ER) in the treatment of MLCO. METHODS: Four major literature databases (Cochrane Library, Embase, PubMed, and Web of Science) were searched to collect articles published before April 20, 2023. After determining random or fixed-effect models based on heterogeneity tests, odds ratios (RR) or standardized mean differences (SMD) with their respective 95% confidence intervals (CI) were calculated. RESULTS: Nineteen randomized controlled studies were included. The main outcomes included overall tumor recurrence rate, 30-day mortality rate, and overall incidence of complications. Secondary outcomes included mortality-related indicators, tumor recurrence-related indicators, surgery-related indicators, and other relevant indicators. The study found that there was no significant difference in the 30-day mortality rate between the SEMS group and the er group. However, the SEMS group had a lower overall incidence of complications (RR = 0.787, P = .004), lower incision infection rate (RR = 0.472, P = .003), shorter operation time (SMD = -0.591, P = .000), lower intraoperative blood loss (SMD = -1.046, P = .000), lower intraoperative transfusion rate (RR = 0.624, P = .021), lower permanent stoma rate (RR = 0.499, P = .000), lower overall stoma rate (RR = 0.520,P = .000), shorter hospital stay (SMD = -0.643, P = .014), and more lymph node dissections during surgery (SMD = 0.222, 95% CI: 0.021-0.423, P = .031), as well as a higher primary anastomosis rate (RR = 0.472, 95% CI: 0.286-0.7 77, P = .003), among other advantages. However, the SEMS group had a higher overall tumor recurrence rate (RR = 1.339, P = .048). CONCLUSION: SEMS has significant advantages over er in relieving clinical symptoms and facilitating postoperative recovery in MLCO, but does not reduce the tumor recurrence rate. Neoadjuvant chemotherapy combined with SEMS may provide a new approach to the treatment of MLCO.

A Polymeric Hydrogel to Eliminate Programmed Death-Ligand 1 for Enhanced Tumor Radio-Immunotherapy.

Programmed death-ligand 1 (PD-L1) is a specialized shield on tumor cells that evades the immune system. Even inhibited by PD-L1 antibodies, a cycling process constantly transports PD-L1 from inside to outside of cells, facilitating the renewal and replenishment of PD-L1 on the cancer cell membrane. Herein, we develop a sodium alginate hydrogel consisting of elesclomol-Cu and galactose to induce persistent cuproptosis, leading to the reduction of PD-L1 for radio-immunotherapy of colon tumors. First, a prefabricated hydrogel is synthesized by immobilizing elesclomol onto a sodium alginate saccharide chain through the coordination with bivalent copper ions (Cu2+), followed by incorporation of galactose. After implantation into the tumors, this prefabricated hydrogel can be further cross-linked in the presence of physiological calcium ions (Ca2+), resulting in the formation of a hydrogel with controlled release of elesclomol-Cu2+ (ES-Cu) and galactose. The hydrogel effectively induces the oligomerization of DLAT and cuproptosis in colorectal cancer cells. Interestingly, radiation-induced PD-L1 upregulation is abrogated in the presence of the hydrogel, releasing ES-Cu and galactose. Consequently, the sensitization of tumor to radiotherapy and immunotherapy is significantly improved, further prolonging the survival of tumor-bearing mice in both local and metastatic tumors. Our study introduces an approach that combines cuproptosis with immunotherapy and radiotherapy.

Hsa_circ_0046430 promotes the progression of colorectal cancer by targeting miR-6785-5p/SRCIN1 axis as a ceRNA.

The correlation among circular RNAs (circRNAs), microRNAs, and messenger RNAs have gained increasing attention in recent years. However, the mechanism of such discoveries in colorectal cancer (CRC) is not yet elucidated. The present study aimed to clarify whether the novel circRNAs regulate the prognosis-related genes through the competing endogenous RNAs (ceRNA). An analysis of the Weighted Gene Co-Expression Network Analysis was conducted to screen a module-trait circRNAs, and other big data mining technologies were used to predict the related microRNAs and the downstream genes. Prognosis-related gene model was built using the Cox regression analysis for the 138 messenger RNAs associated with hsa circ 0046430. The qRT-PCR was adopted to verify ceRNA network. Immunohistochemistry verified the correlation between SRCIN1 and patient prognosis. In summary, these results demonstrated that hsa_circ_0046430 is a tumor-related circRNA based on the clinical characteristics module of Weighted Gene Co-Expression Network Analysis. The prognostic risk score signature model analysis indicated that CRC risk was independently related to the risk score and SRCIN1 was independently associated with overall survival. Therefore, the hsa_circ_0046430/miR-6785-5p/SRCIN1 axis was constructed. Hsa_circ_0046430/miR-6785-5p/SRCIN1 axis relative expression level was determined by qRT-PCR. Immunohistochemical staining further validated that SCRIN1 was significantly higher in cancer than in adjacent normal tissues. Our study identified and primarily validated the hsa_circ_0046430/miR-6785-5p/SRCIN1 regulatory axis impacted on CRC prognosis, suggesting novel biomarkers and therapeutic targets for CRC patients. Further in-depth studies are essential to confirm the underlying ceRNA mechanism.

P4HA1 Regulates CD31 via COL6A1 in the Transition of Glioblastoma Stem-Like Cells to Tumor Endothelioid Cells.

Glioblastoma multiforme (GBM) is a common intracranial malignancy characterized by abundant and aberrant vasculature. The efficiency of existing antivascular treatments remains unsatisfactory. The transition of glioblastoma stem-like cells (GSCs) into tumor endothelioid cells (ECs) has been thought to cause glioma neovascularization and anti-angiogenesis tolerance, but the mechanisms regulating glioma transdifferentiation remains unclear. Our previous study found that P4HA1 regulates GSCs vascular mimicry in a hypoxic microenvironment, but the detailed molecular mechanism has not been determined. In this study, candidate protein COL6A1 was screened by mass spectrometry. In vitro experiments show that P4HA1 regulates the expression of CD31 via COL6A1, with the levels of expression of P4HA1, COL6A1 and the vascular endothelial molecular markers CD31 showing positive correlations in vivo assay. Altering the expression of P4HA1 in GSCs altered the expression of COL6A1 and CD31, thereby inducing glioma angiogenesis. In conclusion, this study revealed that the P4HA1/COL6A1 axis modulates the transdifferentiation process of GSCs into ECs. Interrupting this signaling axis can inhibit glioma angiogenesis, suggesting that this axis may be a novel target for antivascular therapy in patients with glioma.

Role of H2A.Z.1 in epithelial-mesenchymal transition and radiation resistance of lung adenocarcinoma in vitro.

Radiation resistance reduces patient survival and is an important challenge in treating lung adenocarcinoma (LUAD). Previous studies have shown that histone H2A variants can affect the radiosensitivity of tumors; however, the main role of histone H2A variants in LUAD remains unclear. Using the TCGA database, we found that histone H2A variant H2A.Z.1 is positively associated with the progression and poor prognosis of LUAD. Colony formation, scratch wound-healing, and transwell assays as well as Western blot were performed to assess the role of H2A.Z.1 in vitro. Results suggested that H2A.Z.1 promoted cell migration and invasion, epithelial-mesenchymal transition, stemness, and radiation resistance in LUAD cells. Targeting H2A.Z.1 in combination with radiation therapy could be a potential therapeutic approach for radiation resistant LUAD.

P4HA1 Down-Regulation Inhibits Glioma Invasiveness by Promoting M1 Microglia Polarization.

BACKGROUND: Polarization of microglia cells in the glioma microenvironment is closely related to the malignant progression and invasion of gliomas. Prolyl 4-hydroxylase subunit α1 (P4HA1) is the rate-limiting subunit of prolyl 4-hydroxylase (P4H). In previous studies, we showed that P4HA1 could promote the proliferation, migration, and invasion of glioma cells, but the specific mechanisms through which this occurs have not been fully elucidated. MATERIALS AND METHODS: Interactions between glioma and microglia cells were analyzed using bioinformatics. Then, co-culture models were used to obtain conditioned media. To characterize microglial cell polarization, we used PCR and immunofluorescence. Proliferation and invasion assays were used to explore the biological behavior of glioma cells affected by microglia. Finally, marker expression was detected using immunohistochemistry in glioblastoma multiform (GBM) specimens. RESULTS: Knockdown of P4HA1 resulted in reduced chemotaxis of microglia toward GBM cells and increased polarization of microglia toward the M1 phenotype. The changed microglial polarization state, in turn, inhibited the proliferation and invasion of GBM cells. Moreover, in GBM tissue specimens, the P4HA1 expression level is negatively correlated with that of the CD86 microglia M1-specific marker. CONCLUSION: Our results show that P4HA1 promotes immunosuppressive microenvironment formation by cross-talk between GBM and microglia cells and indirectly increases the aggressiveness of GBM.

Resonance light scattering study on the interaction of benproperine phosphate with eriochrome blue black R in the presence of sodium dodecylbenzene sulphonate and its analytical application.

The interaction of benproperine phosphate (BPP) with eriochrome blue black R (EBBR) in the presence of sodium dodecylbenzene sulphonate (SDBS) was studied using resonance light scattering (RLS) technology and ultraviolet-visual (UV-vis) spectrophotometry. Under optimum conditions, BPP reacts with EBBP and SDBS to form a three-component complex, which results in strong RLS signal and a new RLS peak. The enhanced RLS intensities are proportional to the concentration of BPP over the range 0.6-28.0 microg/mL, with a detection limit of 0.053 microg/mL. The affecting factors as well as the influence of coexisting substances were investigated. The results indicate that this assay method could be applied to the determination of BPP in pharmaceuticals, serum and urine samples with satisfactory results.