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Cancer remains a severe threat to human health. To date, although various therapeutic methods, including radiotherapy (RT), chemotherapy, chemodynamic therapy (CDT), phototherapy, starvation therapy, and immunotherapy, have entered a new stage of rapid progress in cancer theranostics, their limited therapeutic effect and significant side effects need to be considered carefully. With the rapid development of nanotechnology, the marriage of nanomaterials and therapeutic methods provides the practical possibility to improve the deficiencies in cancer therapy. Notably, metal-organic frameworks (MOFs) composed of ions/clusters and bridging ligands through coordination bonds have been widely applied in cancer therapy to deal with the drawbacks of different therapeutic methods, such as severe side effects, low stability, and poor efficacy, owing to their controllable morphologies, tailorable diameters, diverse compositions, tunable porosities, high specific surface areas, facile functionalization, and good biocompatibility. This review summarizes the recent advanced developments and achievements of multifunctional MOF-based nanoplatforms for cancer therapy through single therapy methods, including RT, chemotherapy, CDT, phototherapy (photodynamic and photothermal therapy), starvation therapy and immunotherapy, and combination therapy methods. Moreover, the prospects and challenges of MOF-based nanoplatforms used in tumor therapy are also discussed.

MicroRNAs (miRNAs or miRs) regulate gene expression at the posttranscriptional level and are involved in many biological processes such as cell proliferation and migration, stem cell differentiation, inflammation, and apoptosis. In particular, miR-144-3p is downregulated in various cancers, and its overexpression inhibits the proliferation and metastasis of cancer cells. However, the role of miR-144-5p in non-small-cell lung cancer (NSCLC), especially radiosensitivity, is unknown. In this study, we found that miR-144-5p was downregulated in NSCLC clinical specimens as well as NSCLC cell lines exposed to radiation. Enhanced expression of miR-144-5p promoted the radiosensitivity of NSCLC cells in vitro and A549 cell mouse xenografts in vivo. Furthermore, we identified activating transcription factor 2 (ATF2) as the direct and functional target of miR-144-5p using integrated bioinformatics analysis and a luciferase reporter assay. In addition, restoration of ATF2 expression inhibited miR-144-5p-induced NSCLC cell sensitivity to radiation in vitro and in vivo. Our findings suggest that deregulation of the miR-144-5p/ATF2 axis plays an important role in NSCLC cell radiosensitivity, thus representing a new potential therapeutic target for NSCLC.

Osteogenesis from preosteoblasts is important for bone tissue engineering. MicroRNAs are a class of endogenous small RNA molecules that potentially modulate osteogenesis. In this study, we found that miR-155 expression was downregulated in a time-dependent manner in cells of the preosteoblast cell line MC3T3-E1 after osteogenic induction using bone morphogenetic protein 2 (BMP2). Transfection with miR-155 decreased alkaline phosphatase (ALP) activity, ALP expression, and the staining intensity of Alizarin Red in MC3T3-E1 cells treated with BMP2, whereas treatment with miR-155 inhibitor promoted BMP2-induced osteoblast differentiation. The luciferase assay confirmed that miR-155 can bind to the 3′ untranslated region of SMAD5 mRNA. miR-155 transfection significantly decreased the expression of SMAD5 protein and mRNA in MC3T3-E1 cells under control media and the p-SMAD5 protein level during osteogenesis. After transfecting cells with the SMAD5 overexpression plasmids, the inhibitory effect of miR-155 on osteogenesis was significantly attenuated. In conclusion, miR-155 inhibited osteoblast differentiation by downregulating the translation of SMAD5 in mouse preosteoblast cells. Inhibition of miR-155 promoted osteogenic potential and thus it can be used as a potential target in the treatment of bone defects.

This study aims at assessing the potential association between non-alcoholic fatty liver disease (NAFLD) and colorectal neoplasms (CRN). PubMed, Cochrane Library, and Embase were searched for cohort studies. 14 cohort studies with a total population of 38,761,773 were included for meta-analysis after selection. The results showed that NAFLD is related to an increased risk of CRN (OR = 1.23; 95% CI: 1.14–1.32; I 2 = 70.7%, p < 0.001). In the subgroup analysis, NAFLD were found to be the independent risk factor of colorectal adenoma (CRA) (OR = 1.29; 95% CI = 1.15–1.45; I 2 = 66.4%) and colorectal cancer (CRC) (OR = 1.13; 95% CI = 1.12–1.15; I 2 = 69.4%). There is no close correlation between smoking status of NAFLD patients and CRN. Interestingly, bioinformatics analysis revealed that there were overlap of dysregulated gene sets among NAFLD, CRC, and two recently identified regulated cell death types, ferroptosis and cuproptosis, respectively. Our meta- and bioinformatics analysis shows that NAFLD increases the risk of CRN. Ferroptosis and cuproptosis may be the critical links between NAFLD and CRN, respectively. These findings here support that NAFLD is necessary to be considered as an emerging risk factor for CRN.

Background and aimsMost submucosal tumors (SMTs) in the esophagogastric junction (EGJ) are irregularly shaped and different from those in the esophagus, where submucosal tunneling endoscopic resection (STER) has been proven effective and safe. However, few reports paid attention to STER for SMTs in the EGJ. The aim of the study was not only to evaluate the effect of STER in patients with SMTs in the EGJ but to analyze the risk factors for failure of en bloc resection.MethodsA consecutive of 47 patients with SMTs originating from the muscularis propria (MP) layer in the EGJ underwent STER were retrospectively included between September 2012 and December 2016. Thirty-five tumors underwent en bloc resection, and the other 12 tumors received piecemeal resection. The tumor size, operation time, en bloc resection rate, complications, residual, and local recurrence were achieved and compared between the two groups.ResultsForty-six of 47 lesions (97.9%) were successfully resected. The mean lesion size was 29.7 ± 16.3 mm. Both the en bloc resection rate and complete resection rate were 74.5% (35/47). No severe complications occurred in the 47 patients. Patients in the piecemeal resection group had more irregularly shaped lesions, longer tumor diameter, larger tumor size (≥40 mm), longer operation time, and longer hospital stay after procedure (P < 0.05), and there were no statistically differences between the two groups in in-operative complications, post-operative complications, and residual rate (P > 0.05). By univariate analysis and stepwise logistic regression analysis, irregular shape and tumor diameter ≥20 mm were two risk factors for failure of en bloc resection.ConclusionsSTER is an effective and safe technique for the treatment of SMTs arising from the MP layer in the EGJ. Irregular shape and tumor diameter ≥20 mm are the reliable risk factors for en bloc resection failure.

Background: Colorectal adenocarcinoma (COAD) is a common malignant tumor with little effective prognostic markers. Cuproptosis is a newly discovered mode of cell death that may be related to epigenetic regulators. This study aimed to explore the association between epigenetic regulators and cuproptosis, and to establish a prognostic prediction model for COAD based on epigenetic regulators associated with cuproptosis (EACs). Methods: RNA sequencing data and clinical data of 524 COAD patients were obtained from the TCGA-COAD database, cuproptosis-related genes were from the FerrDb database, and epigenetic-related genes were from databases such as GO and EpiFactors. LASSO regression analysis and other methods were used to screen out epigenetic regulators associated with cuproptosis and prognosis. The risk score of each patient was calculated and the patients were divided into high-risk group and low-risk group. Next, the survival difference, functional enrichment analyses, tumor mutation burden, chemotherapy drug sensitivity and other indicators between the two groups were compared and analyzed. Results: We found 716 epigenetic regulators closely related to cuproptosis, among which 35 genes were related to prognosis of COAD. We further screened out 7 EACs from the 35 EACs to construct a prognostic prediction model. We calculated the risk score of each patient based on these 7 genes, and divided the patients into high-risk group and low-risk group. We found that the overall survival rate and progression-free survival rate of the high-risk group were significantly lower than those of the low-risk group. This model showed good predictive ability in the training set, test set and overall data set. We also constructed a prognostic prediction model based on risk score and other clinical features, and drew the corresponding Nomogram. In addition, we found significant differences between the high-risk group and the low-risk group in tumor mutation burden, chemotherapy drug sensitivity and other clinical aspects. Conclusion: We established an effective predictive prediction model for COAD based on EACs, revealing the association between epigenetic regulators and cuproptosis in COAD. We hope that this model can not only facilitate the treatment decision of COAD patients, but also promote the research progress in the field of cuproptosis.

Gastric cancer (GC) is among the deadliest diseases with countless incidences and deaths each year. (Hp) is the primary type of microbe that colonizes the stomach. In recent years, increasing evidence has demonstrated that Hp infection is one of the main risk factors for GC. Elucidating the molecular mechanism of how Hp leads to GC will not only benefit the treatment of GC, but also boost the development of therapeutics for other gastric disorders caused by Hp infection. In this study, we aimed to identify innate immunity-related genes in GC and investigate their potentials as prognostic markers and therapeutic targets for Hp-related GC. Firstly, we analyzed the differentially expressed innate immunity-related genes in GC samples from the TCGA database. Then prognostic correlation analysis was carried out to explore the prognostic value of these candidate genes. By combing transcriptome data, somatic mutation data, and clinical data, co-expression analysis, functional enrichment analysis, tumor mutational burden analysis, and immune infiltration analysis were performed to reveal the pathological relevance of the candidate gene. Finally, ceRNA network was constructed to identify the genes and pathways for the regulation of the candidate gene. We revealed that protein tyrosine phosphatase non-receptor type 20 (PTPN20) is a significant prognostic marker in Hp-related GC. Thus, PTPN20 levels have the potential to efficiently predict the survival of Hp-related GC patients. In addition, PTPN20 is associated with immune cell infiltration and tumor mutation burden in these GC patients. Moreover, we have also identified PTPN20-related genes, PTPN20 protein-protein interactions, and the PTPN20 ceRNA network. Our data suggest that PTPN20 may have critical functions in Hp-related GC. Targeting PTPN20 may be a promising way to treat Hp-related GC.

Self‐assembled metallacages with stimuli‐responsive structural transformation and optical tunability present great potential in sensing and detection applications. Herein, the design and synthesis of a multi‐stimuli‐responsive Pd2L4‐type metallacage (MC) are reported, which is constructed through the coordination‐driven self‐assembly of triphenylamine‐based dipyridyl ligand and Pd(II) ions. MC undergoes reversible disassembly upon interaction with specific basic organic ligands and reassembles in the presence of acidic reagents. MC demonstrates an apparent fluorescence resonance energy transfer (FRET) emission enhancement in the presence of naphthalene disulfonate (NDS) isomers and highly selective binding towards four NDS isomers, where, only upon binding with 2,6‐NDS, a solution‐to‐gel transition is observed, due to the specific electrostatic and π–π interactions between MC and 2,6‐NDS. Significantly, MC enables highly selective and rapid detection of thiol‐containing amino acids with a detection limit of 1.22 × 10−6 M via a self‐destructive fluorescence detection mechanism. A facile test strip based on this cage has also been developed to detect cysteine visually. This work widens the application scopes of self‐assembled metallacages and opens new perspectives for building stimuli‐responsive supramolecular coordination complexes. A multi‐stimuli‐responsive metallacage was constructed via a bottom‐up design strategy, and its stimuli‐responsive behaviors were investigated in response to basic/acidic reagents, naphthalene disulfonate, and thiol‐containing amino acids, accompanied by remarkable structural transformations and fluorescence variations. This work presents a promising platform for developing innovative supramolecular coordination complexes with practical applications.

Background Lung cancer is a highly aggressive and lethal cancer requiring prognostic and predictive biomarkers for improving patient outcomes. Here, a prognostic signature for lung cancer was developed and prognostic programmed cell death (PCD)-related genes were identified. Methods In this study, we performed comprehensive bioinformatic analyses on diverse datasets, such as Gene Expression Omnibus and The Cancer Genome Atlas. Consensus clustering, Weighted Gene Co-expression Network Analysis, and Gene Set Enrichment Analysis were applied to gain valuable insights from the data, and survival analysis was performed to determine the genes associated with prognosis PCD and construct a prognostic signature. Results PCD-related genes (n = 46), significantly correlated with lung cancer prognosis, including ACSL3 and BID, were evaluated. A prognostic gene signature was constructed using 12 genes, which showed excellent overall survival prediction for 1, 3, and 5 years (AUC: 0.687, 0.699, and 0.627). The analysis focused on the nine ley mutant PCD risk model genes and their pan-cancer and elevated mutation frequencies were noted in ALK across several cancer types. The drug sensitivity and immune cell infiltration of the two risk groups were analyzed and revealed noteworthy differences. Patients classified as high-risk demonstrated increased susceptibility to drugs and elevated infiltration of Th2, Tcm, and T helper cells. A prognostic nomogram was developed to predict patient survival at 1, 3, and 5 years, and variables such as age, grading, stage, and the PCD risk score were incorporated. The relationship between PCD-associated genes, genes involved in cell proliferation, and immune cell phenotypes were evaluated. HSPA4 exhibited a significant positive correlation with T helper cells, Th2 cells, and Tcm cells and a negative association with pDCs, TFH, and B cells. In stage III tumors, compared to stage I/II tumors, HSPA4 expression was also significantly upregulated. Conclusion Prognostic PCD-related genes for lung cancer were identified and a prognostic signature was constructed. Our findings are invaluable for lung cancer prognostic prediction and personalized treatment.

An improved understanding of the molecular mechanism of colorectal adenocarcinoma is necessary to predict the prognosis and develop new target gene therapy strategies. This study aims to identify hub genes associated with colorectal adenocarcinoma and further analyze their prognostic significance. In this study, The Cancer Genome Atlas (TCGA) COAD-READ database and the gene expression profiles of GSE25070 from the Gene Expression Omnibus were collected to explore the differentially expressed genes between colorectal adenocarcinoma and normal tissues. The weighted gene co-expression network analysis (WGCNA) and differential expression analysis identified 82 differentially co-expressed genes in the collected datasets. Enrichment analysis was applied to explore the regulated signaling pathway in colorectal adenocarcinoma. In addition, 10 hub genes were identified in the protein–protein interaction (PPI) network by using the cytoHubba plug-in of Cytoscape, where five genes were further proven to be significantly related to the survival rate. Compared with normal tissues, the expressions of the five genes were both downregulated in the GSE110224 dataset. Subsequently, the expression of the five hub genes was confirmed by the Human Protein Atlas database. Finally, we used Cox regression analysis to identify genes associated with prognosis, and a 3-gene signature (CLCA1–CLCA4–GUCA2A) was constructed to predict the prognosis of patients with colorectal cancer. In conclusion, our study revealed that the five hub genes and CLCA1–CLCA4–GUCA2A signature are highly correlated with the development of colorectal adenocarcinoma and can serve as promising prognosis factors to predict the overall survival rate of patients.