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Ferroptosis is a type of regulated cell death characterized by its non-apoptotic, iron-dependent and oxidative nature. Since its discovery in 2012, extensive research has demonstrated its pivotal roles in tumorigenesis, metastasis and cancer therapy. The tumor microenvironment (TME) is a complex ecosystem comprising cancer cells, non-cancer cells, extracellular matrix, metabolites and cytokines. Recent studies have underscored a new paradigm in which non-cancer cells in the TME, such as immune and stromal cells, also play significant roles in regulating tumor progression and therapeutic resistance typically through complicated crosstalk with cancer cells. Notably, this crosstalk in the TME were partially mediated through ferrotopsis-related mechanisms. This review provides a comprehensive and systematic summary of the current findings concerning the roles of ferroptosis in the TME and how ferroptosis-mediated TME reprogramming impacts cancer therapeutic resistance and progression. Additionally, this review outlines various ferroptosis-related therapeutic strategies aimed at targeting the TME.

We aimed to determine and compare the effects of music therapy and music medicine on depression, and explore the potential factors associated with the effect. PubMed (MEDLINE), Ovid-Embase, the Cochrane Central Register of Controlled Trials, EMBASE, Web of Science, and Clinical Evidence were searched to identify studies evaluating the effectiveness of music-based intervention on depression from inception to May 2020. Standardized mean differences (SMDs) were estimated with random-effect model and fixed-effect model. A total of 55 RCTs were included in our meta-analysis. Music therapy exhibited a significant reduction in depressive symptom (SMD = -0.66; 95% CI = -0.86 to -0.46; P<0.001) compared with the control group; while, music medicine exhibited a stronger effect in reducing depressive symptom (SMD = -1.33; 95% CI = -1.96 to -0.70; P<0.001). Among the specific music therapy methods, recreative music therapy (SMD = -1.41; 95% CI = -2.63 to -0.20; P<0.001), guided imagery and music (SMD = -1.08; 95% CI = -1.72 to -0.43; P<0.001), music-assisted relaxation (SMD = -0.81; 95% CI = -1.24 to -0.38; P<0.001), music and imagery (SMD = -0.38; 95% CI = -0.81 to 0.06; P = 0.312), improvisational music therapy (SMD = -0.27; 95% CI = -0.49 to -0.05; P = 0.001), music and discuss (SMD = -0.26; 95% CI = -1.12 to 0.60; P = 0.225) exhibited a different effect respectively. Music therapy and music medicine both exhibited a stronger effects of short and medium length compared with long intervention periods. A different effect of music therapy and music medicine on depression was observed in our present meta-analysis, and the effect might be affected by the therapy process.

Mitochondrial malic enzyme 2 (ME2), which catalyzes the conversion of malate to pyruvate, is frequently upregulated during tumorigenesis and is a potential target for cancer therapy. However, the regulatory mechanism underlying ME2 activity is largely unknown. In this study, we demonstrate that ME2 is highly expressed in human colorectal cancer (CRC) tissues, and that ME2 knockdown inhibits the proliferation of CRC cells. Furthermore, we reveal that ME2 is succinylated and identify Sirtuins 5 (SIRT5) as an ME2 desuccinylase. Glutamine deprivation directly enhances the interaction of SIRT5 with ME2 and thus promotes SIRT5-mediated desuccinylation of ME2 at lysine 346, activating ME2 enzymatic activity. Activated ME2 significantly enhances mitochondrial respiration, thereby counteracting the effects of glutamine deprivation and supporting cell proliferation and tumorigenesis. Additionally, the levels of succinylated ME2 at K346 and SIRT5 in CRC tissues, which are negatively correlated, are associated with patient prognosis. These observations suggest that SIRT5-catalyzed ME2 desuccinylation is a key signaling event through which cancer cells maintain mitochondrial respiration and promote CRC progression under glutamine deficiency conditions, offering the possibility of targeting SIRT5-mediated ME2 desuccinylation for CRC treatment.

Recent preliminary studies reported the in vitro tumor-promoting effects of long non-coding RNA urothelial carcinoma associated 1 (UCA1) in colorectal cancer (CRC). However, the in vivo functions and molecular mechanism of UCA1 in CRC remain unclear. Therefore, we investigated the detailed role and mechanism of UCA1 in CRC. We found that UCA1 was up-regulated in CRCs and negatively correlated with survival time in two CRC cohorts. Functional assays revealed the in vitro and in vivo growth-promoting function of UCA1 and revealed that UCA1 can decrease the sensitivity of CRC cells to 5-FU by attenuating apoptosis. Further mechanistic studies revealed that UCA1 could sponge endogenous miR-204-5p and inhibit its activity. We also identified CREB1 as a new target of miR-204-5p. The protein levels of CREB1 were significantly up-regulated in CRCs, negatively associated with survival time and positively correlated with the UCA1 expression. The present work provides the first evidence of a UCA1-miR-204-5p- CREB1 / BCL2 / RAB22A regulatory network in CRC and reveals that UCA1 and CREB1 are potential new oncogenes and prognostic factors for CRC.

Tumor‐associated macrophages (TAMs) are one of the most abundant cell types in colorectal cancer (CRC) tumor microenvironment (TME). Recent studies observed complicated “cross‐talks” between cancer cells and macrophages in TME. However, the underlying mechanisms are still poorly elucidated. Here, PD‐L1 levels are very low in CRC cells but highly abundant in TAMs, and a specific PD‐L1+CD206+ macrophage subpopulation are identified, which is induced by tumor cells and associated with a poor prognosis. Mechanistic investigations reveal that CRC cells can secrete small extracellular vesicles (sEVs) taken up by macrophages that induce M2 like polarization and PD‐L1 expression, resulting in increased PD‐L1+CD206+ macrophage abundance and decreased T cell activity in CRC TME. sEV‐derived miR‐21‐5p and miR‐200a are identified as key signaling molecules mediating the regulatory effects of CRC on macrophages. Further studies reveal that CRC‐derived miR‐21‐5p and miR‐200a synergistically induces macrophage M2 like polarization and PD‐L1 expression by regulating the PTEN/AKT and SCOS1/STAT1 pathways, resulting in decreased CD8+ T cell activity and increased tumor growth. This study suggests that inhibiting the secretion of specific sEV‐miRNAs from CRC and targeting PD‐L1 in TAMs may serve as novel methods for CRC treatment as well as a sensitization method for anti‐PD‐L1 therapy in CRC. A specific PD‐L1+CD206+ macrophage risk subgroup is identified in colorectal cancer, which is induced by tumor‐derived sEV‐miRNAs. This subgroup promotes tumor growth by inducing an immunosuppressive tumor microenvironment. Hence, targeting specific tumor sEV‐miRNAs that regulate PD‐L1 in tumor‐associated macrophages may serve as a novel treatment strategy and a sensitization method for anti‐PD‐L1 therapy in colorectal cancer.

BackgroundChemoresistance is a common problem for cancer treatment worldwide. Circulating exosomal microRNAs (miRNAs) have been considered as promising biomarkers of cancers. However, few studies have assessed the relationship between serum/plasma exosomal microRNAs and chemoresistance in colorectal cancer (CRC).MethodsBased on previous microarray analysis, we selected 30 miRNAs which are aberrantly expressed during CRC progression and then detected their expression levels in three pairs of oxaliplatin/5-fluorouracil-resistant CRC cell lines and the corresponding secreted exosomes. Six candidate exosomal miRNAs were identified for further evaluating potential value in predicting chemotherapeutic effect in advanced CRC patients. Finally, the molecular mechanisms of these miRNAs in drug resistance were explored by bioinformatics preliminarily.ResultsWe observed that the expression of 14 miRNAs was significantly higher in three drug-resistant CRC cells comparing with their parental cells. Among these miRNAs, miR-21-5p, miR-1246, miR-1229-5p, miR-135b, miR-425 and miR-96-5p are also up-regulated in exosomes from culture media of resistant cells. Clinical sample analysis confirmed that the expression levels of miR-21-5p, miR-1246, miR-1229-5p and miR-96-5p in serum exosomes were significantly higher in chemoresistant patients in contrast with chemosensitive controls. ROC curve showed that the combination of the four miRNAs had an area of under the curve (AUC) of 0.804 (P < 0.05). In addition, GO analysis and KEGG pathway analysis revealed that these miRNAs were enriched in PI3K-Akt signaling pathway, FoxO signaling pathway and autophagy pathway.ConclusionsOur study demonstrates that a panel of serum exosomal miRNAs containing miR-21-5p, miR-1246, miR-1229-5p and miR-96-5p could significantly distinguish the chemotherapy-resistant group from advanced colorectal cancer patients. Targeting these miRNAs may promote chemosensitivity to oxaliplatin and 5-fluorouracil, and might be promising strategy for CRC treatment.

Colorectal cancer (CRC) is a major cause of death worldwide. Sensitive, non-invasive diagnostic screen methods are urgently needed to improve its survival rates. Stable circulating microRNA offers unique opportunities for the early diagnosis of several diseases, including cancers. Our aim has been to find new plasma miRNAs that can be used as biomarkers for the detection of CRC. According to the results of miRNA profiling performed on pooling plasma samples form 10 CRC patients or 10 healthy controls, a panel of miRNAs (hsa-miR-10a, -19a, -22*, -24, -92a, 125a-5p, -141, -150, -188-3p, -192, -210, -221, -224*, -376a, -425*, -495, -572, -601, -720, -760 and hsa-let-7a, -7e) were deregulated in CRC plasma with fold changes >5. After large scale validation by qRT-PCR performed on another 191 independent individuals (90 CRC, 43 advanced adenoma and 58 healthy participants), we found that the levels of plasma miR-601 and miR-760 were significantly decreased in colorectal neoplasia (carcinomas and advanced adenomas) compared with healthy controls. ROC curve analysis showed that plasma miR-601 and miR-760 were of significant diagnostic value for advanced neoplasia. These two miRNAs together yield an AUC of 0.792 with 83.3% sensitivity and 69.1% specificity for separating CRC from normal controls, and yield an AUC of 0.683 with 72.1% sensitivity and 62.1% specificity in discriminating advanced adenomas from normal controls. Plasma miR-601 and miR-760 can potentially serve as promising non-invasive biomarkers for the early detection of CRC.

MicroRNAs (miRNAs) are a class of non‐coding single‐stranded RNA molecules with a length of approximately 18‐25 nt nucleotides that regulate gene expression post‐transcriptionally. MiR‐204‐5p originates from the sixth intron of the transient receptor potential cation channel subfamily M member 3 (TRPM3) gene. MiR‐204‐5p is frequently downregulated in various cancer types and is related to the clinicopathological characteristics and prognosis of cancer patients. So far, many studies have determined that miR‐204‐5p functions as a tumor suppressor for its extensive and powerful capacity to inhibit tumor proliferation, metastasis, autophagy, and chemoresistance in multiple cancer types. MiR‐204‐5p appears to be a promising prognostic biomarker and a therapeutic target for human cancers. This review summarized the latest advances on the role of miR‐204‐5p in human cancers. MiR‐204‐5p regulates tumorigenesis and progression via various target genes in human cancers.

Background Colorectal cancer (CRC) is a major cause of cancer-related deaths worldwide, and chemoresistance is a major obstacle in its treatment. Despite advances in therapy, the molecular mechanism underlying chemoresistance in CRC is not fully understood. Recent studies have implicated the key roles of long noncoding RNAs (lncRNAs) in the regulation of CRC chemoresistance. Methods In this study, we investigated the role of the lncRNA LINC01852 in CRC chemoresistance. LINC01852 expression was evaluated in multiple CRC cohorts using quantitative reverse transcription PCR. We conducted in vitro and in vivo functional experiments using cell culture and mouse models. RNA pull-down, RNA immunoprecipitation, chromatin immunoprecipitation, and dual luciferase assays were used to investigate the molecular mechanism of LINC01852 in CRC. Results Our findings revealed that a lncRNA with tumor-inhibiting properties, LINC01852, was downregulated in CRC and inhibited cell proliferation and chemoresistance both in vitro and in vivo. Further mechanistic investigations revealed that LINC01852 increases TRIM72-mediated ubiquitination and degradation of SRSF5, inhibiting SRSF5-mediated alternative splicing of PKM and thereby decreasing the production of PKM2. Overexpression of LINC01852 induces a metabolic switch from aerobic glycolysis to oxidative phosphorylation, which attenuates the chemoresistance of CRC cells by inhibiting PKM2-mediated glycolysis. Conclusions Our results demonstrate that LINC01852 plays an important role in repressing CRC malignancy and chemoresistance by regulating SRSF5-mediated alternative splicing of PKM, and that targeting the LINC01852/TRIM72/SRSF5/PKM2 signaling axis may represent a potential therapeutic strategy for CRC.

The high price of noble metal resources limits its commercial application and stimulates the potential for developing new catalysts that can replace noble metal catalysts. Tungsten-based catalysts have become the most important substitutes for noble metal catalysts because of their rich resources, friendly environment, rich valence and better adsorption enthalpy. However, some challenges still hinder the development of tungsten-based catalysts, such as limited catalytic activity, instability, difficult recovery, and so on. At present, the focus of tungsten-based catalyst research is to develop a satisfactory material with high catalytic performance, excellent stability and green environmental protection, mainly including tungsten atomic catalysts, tungsten metal nanocatalysts, tungsten-based compound nanocatalysts, and so on. In this work, we first present the research status of these tungsten-based catalysts with different sizes, existing forms, and chemical compositions, and further provide a basis for future perspectives on tungsten-based catalysts.