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Nanotechnology provides the platform to develop functional nanocomposites with outstanding features, such as persistent luminescence (PL), photothermal conversion, magnetic resonance (MR), and so on, that has been incorporated in nanomedicine for diagnosis and therapy. Herein, the nanocomposites of ZnGa2O4:Cr3+ embedded in mesoporous silica coating surrounding gold nanorods (cGNR@MSNs) were developed for the codelivery of chemotherapeutic drugs and anti-CD40 antibodies. The nanocomposites were functionalized with tetrazaheterocycle linking divinylpyrimidine derivatives (DOTVs), which covalently capture anti-CD40 by disulfide re-bridging on the surface of cGNR@MSNs. The anti-CD40-mediated dual drug delivery system simultaneously realized the combination of chemo-, immuno-, and photothermal therapies, enhancing the synergistic effect of combination therapy for multiple tumor cells. Moreover, the nanodrug delivery system achieved multimodality imaging with fluorescence, PL, and MR modes for precise diagnosis. This study provides fascinating insights into the development of nanocomposite-based multimodality imaging strategies and imaging-guided combination therapies. [ABSTRACT FROM AUTHOR]

Metabolic disorder is one of the hallmarks of cancers, and reprogramming of metabolism is becoming a novel strategy for cancer treatment. Citrate is a key metabolite and critical metabolic regulator linking glycolysis and lipid metabolism in cellular energy homeostasis. Here it is reported that citrate treatment (both sodium citrate and citric acid) significantly suppresses tumor cell proliferation and growth in various tumor types. Mechanistically, citrate promotes excessive lipid biosynthesis and induces disruption of lipid metabolism in tumor cells, resulting in tumor cell senescence and growth inhibition. Furthermore, ATM‐associated DNA damage response cooperates with MAPK and mTOR signaling pathways to control citrate‐induced tumor cell growth arrest and senescence. In vivo studies further demonstrate that citrate administration dramatically inhibits tumor growth and progression in a colon cancer xenograft model. Importantly, citrate administration combined with the conventional chemotherapy drugs exhibits synergistic antitumor effects in vivo in the colon cancer models. These results clearly indicate that citrate can reprogram lipid metabolism and cell fate in cancer cells, and targeting citrate can be a promising therapeutic strategy for tumor treatment. [ABSTRACT FROM AUTHOR]

DNA microarray and high‑throughput sequencing have been widely used to identify the differentially expressed genes (DEGs) in systemic lupus erythematosus (SLE). However, the big data from gene microarrays are also challenging to work with in terms of analysis and processing. The presents study combined data from the microarray expression profile (GSE65391) and bioinformatics analysis to identify the key genes and cellular pathways in SLE. Gene ontology (GO) and cellular pathway enrichment analyses of DEGs were performed to investigate significantly enriched pathways. A protein‑protein interaction network was constructed to determine the key genes in the occurrence and development of SLE. A total of 310 DEGs were identified in SLE, including 193 upregulated genes and 117 downregulated genes. GO analysis revealed that the most significant biological process of DEGs was immune system process. Kyoto Encyclopedia of Genes and Genome pathway analysis showed that these DEGs were enriched in signaling pathways associated with the immune system, including the RIG‑I‑like receptor signaling pathway, intestinal immune network for IgA production, antigen processing and presentation and the toll‑like receptor signaling pathway. The current study screened the top 10 genes with higher degrees as hub genes, which included 2'‑5'‑oligoadenylate synthetase 1, MX dynamin like GTPase 2, interferon induced protein with tetratricopeptide repeats 1, interferon regulatory factor 7, interferon induced with helicase C domain 1, signal transducer and activator of transcription 1, ISG15 ubiquitin‑like modifier, DExD/H‑box helicase 58, interferon induced protein with tetratricopeptide repeats 3 and 2'‑5'‑oligoadenylate synthetase 2. Module analysis revealed that these hub genes were also involved in the RIG‑I‑like receptor signaling, cytosolic DNA‑sensing, toll‑like receptor signaling and ribosome biogenesis pathways. In addition, these hub genes, from different probe sets, exhibited significant co‑expressed tendency in multi‑experiment microarray datasets (P<0.01). In conclusion, these key genes and cellular pathways may improve the current understanding of the underlying mechanism of development of SLE. These key genes may be potential biomarkers of diagnosis, therapy and prognosis for SLE. [ABSTRACT FROM AUTHOR]

Regulatory factor X-5 (RFX5) was previously characterized as an essential and highly specific regulator of major histocompatibility class II (MHCII) gene expression in the immune system. We found that RFX5 is significantly upregulated in hepatocellular carcinoma (HCC) tumors and cell lines compared with non-tumor tissues in mRNA expression levels, but it fails to induce the expression of MHCII. However, RFX5 can strongly bind to the tripeptidyl peptidase 1 (TPP1) promoter region and then increase its transcriptional activity. We also found that manipulation the expression of RFX5 can significantly affect the expression of TPP1 in HepG2, which suggested that RFX5 can transcriptionally activate TPP1 in HCC. Moreover, TPP1 is overexpressed in HCC tissues and significantly correlated with poor prognosis of HCC patients, suggesting that it may have potential biological implications in HCC.