Search

Psoriasis is a systemic immune-mediated disease associated with an increased risk of comorbidities, such as psoriatic arthritis, cardiovascular disease, metabolic syndrome, inflammatory bowel disease, psychiatric disorders, and malignancy. In recent years, with the advent of biological agents, the efficacy and safety of psoriasis treatments have dramatically improved. Presently, tumor necrosis factor-α inhibitors, interleukin-17 inhibitors, interleukin-12/23 inhibitors, and interleukin-23 inhibitors are approved to treat moderate-to-severe psoriasis. Small-molecule inhibitors, such as apremilast and deucravacitinib, are also approved for the treatment of psoriasis. Although it is still unclear, systemic agents used to treat psoriasis also have a significant impact on its comorbidities by altering the systemic inflammatory state. Data from clinical trials and studies on the safety and efficacy of biologics and small-molecule inhibitors provide important information for the personalized care and treatment for patients with psoriasis. Notably, treatment with interleukin-17 inhibitors is associated with new-onset or exacerbations of inflammatory bowel disease. In addition, great caution needs to be taken when using tumor necrosis factor-α inhibitors in patients with psoriasis with concomitant congestive heart failure, multiple sclerosis, and malignancy. Apremilast may induce weight loss as an adverse effect, presenting also with some beneficial metabolic actions. A better understanding of the characteristics of biologics and small-molecule inhibitors in the treatment of psoriasis comorbidities can provide more definitive guidance for patients with distinct comorbidities.

Synthesis of high-quality metal nanoparticles (NPs) is the premise toward their downstream diverse applications. Although some electrochemical synthesis strategies have been developed, the necessary use of high-concentration electrolyte solution as current pathway and reaction medium severely limits the colloidal stability of the growing NPs in the solution and their tunability in size and shape. Herein, we report a collision electrochemical method for the synthesis of metal NPs without the use of electrolyte solution. To this end, we designed an asymmetrical electrochemical cell to control the potential (i.e., to supply electrons) in the reaction system via a separated electrochemical cell, thereby enabling the electrochemical reaction occurring in an electrolyte-free growth solution. Consequently, this collision electrochemical method, using seed-mediated growth of NPs as examples, allows the synthesis of monodisperse homogeneous Au NPs and heterogeneous Pd- and Pt-coated Au NPs at a yield comparable to that achieved in common chemical synthesis. Furthermore, this method allows readily tailoring the morphology of the resultant metal NPs just by changing the concentration of the growth solution. Therefore, our green synthesis method is important for a variety of nanomaterials beyond metal NPs.

Background Transmembrane emp24 domain containing (TMED) proteins are known to play pivotal roles in normal development, but have been reported to be implicated in pancreatic disease, immune system disorders, and cancers. As far as TMED3 is concerned, its roles in cancers are controversial. However, evidence describing TMED3 in the context of malignant melanoma (MM) is scarce. Results In this study, we characterized the functional significance of TMED3 in MM and identified TMED3 as a tumor-promoting factor in MM development. Depletion of TMED3 arrested the development of MM in vitro and in vivo. Mechanistically, we found that TMED3 could interact with Cell division cycle associated 8 (CDCA8). Knocking down CDCA8 suppressed cell events associated with MM development. On the contrary, elevating CDCA8 augmented cell viability and motility and even reversed the inhibitory effects of TMED3 knockdown on MM development. On the other hand, we found that the levels of P-Akt and P-PI3K were decreased in response to TMED3 downregulation, which was partially abolished following SC79 treatment. Thus, our suspicion was that TMED3 exacerbates MM progression via PI3K/Akt pathway. More notably, previously decreased P-Akt and P-PI3K in TMED3-depleted cells were rescued after overexpressing CDCA8. Also, previously impaired cell events due to CDCA8 depletion were ameliorated after SC79 addition, implying that TMED3 regulates PI3K-AKT pathway via CDCA8, thereby promoting MM development. Conclusions Collectively, this study established the link between TMED3 and MM, and provides a potential therapeutic intervention for patients with MM harboring abundant TMED3.

Lung cancer is the leading cause of cancer‐related death worldwide. Previous studies revealed that endoplasmic reticulum oxidoreductase 1 alpha (ERO1L) played critical roles in the malignant behaviors of several cancer types, but its role in non‐small cell lung cancer (NSCLC) remained unclear. In this study, we identified 26 upregulated and 102 downregulated genes in NSCLC using bioinformatics analyses, and these genes were enriched in the biological processes of the cell cycle. ERO1L was remarkably upregulated in NSCLC and overexpression of ERO1L was associated with poor prognosis of NSCLC. ERO1L deficiency markedly suppressed NSCLC cell proliferation, colony formation, migration, and invasion. ERO1L depletion caused a dramatically decreased expression of cell cycle‐related factors in NSCLC cells. Collectively, our data validated that ERO1L could function as a tumor promoter in NSCLC, indicating the potential of targeting ERO1L for the treatment of NSCLC.

BackgroundThe transient receptor potential vanilloid (TRPV) channels family, TRPV1-6, has been identified to profoundly affect a wide spectrum of pathological processes in various cancers. However, the biological function and prognostic value of TRPVs in clear cell renal cell carcinoma (ccRCC) are still largely unknown.MethodsWe obtained the gene expression data and clinical information of 539 ccRCC patients from The Cancer Genome Atlas (TCGA) database. A series of databases were used for data processing and visualization, including GEPIA, GeneMANIA, MethSurv, GSCA, TIMER, and starBase databases.ResultsThe mRNA expression of TRPV2/3 was upregulated while the expression of TRPV5/6 was downregulated in ccRCC tumor tissues. TRPV family members in ccRCC were rarely mutated (nearly 7 frequencies). The ROC curve showed that TRPV2/5/6 had a high diagnostic ability in discriminating ccRCC from the control samples (AUC>0.9). Higher levels of TRPV3 expression were associated with poor prognosis of ccRCC patients, while higher expression of TRPV4 was associated with favorable prognosis. The expression of TRPV3 in normal and ccRCC tissues was validated by Immunohistochemistry, and its expression was remarkably related to high histologic grade and advanced stage. Besides, TRPV3 exhibit a reduction of DNA methylation level with tumor progression, and 12 CpGs of TRPV3 were associated with a significant prognosis. In addition, TRPV3 expression was significantly associated with the accumulation of several tumor-infiltrating immune cells, especially regulatory T cells. Furthermore, high levels of TRPV3 induced the expression of immune checkpoints such as LAG3, CTLA4, PDCD1, and TIGIT. Finally, we predicted a key SNHG3/AL513497.1-miR-10b-5p-TRPV3 axis linking to carcinogenesis and progression of ccRCC.ConclusionOur study may uncover TRPV channels–associated molecular mechanisms involved in the tumorigenesis and progression of ccRCC. TRPV family members might be diagnosed and prognostic markers and potential therapeutic targets for ccRCC patients.

Accumulating lines of evidence indicate that the deregulation of m6A is involved in various cancer types. The m6A RNA methylation is modulated by m6A methyltransferases, demethylases, and reader proteins. Although the aberrant expression of m6A RNA methylation contributes to the development and progression of multiple cancer types, the roles of m6A regulators across numerous types of cancers remain largely unknown. Here, we comprehensively investigated the expression, genetic alteration, and prognosis significance of 20 commonly studied m6A regulators across diverse cancer types using TCGA datasets via bioinformatic analyses. The results revealed that the m6A regulators exhibited widespread dysregulation, genetic alteration, and the modulation of oncogenic pathways across TCGA cancer types. In addition, most of the m6A regulators were closely relevant with significant prognosis in many cancer types. Furthermore, we also constructed the protein–protein interacting network of the 20 m6A regulators, and a more complex interacting regulatory network including m6A regulators and their corresponding interacting factors. Besides, the networks between m6A regulators and their upstream regulators such as miRNAs or transcriptional factors were further constructed in this study. Finally, the possible chemicals targeting each m6A regulator were obtained by bioinformatics analysis and the m6A regulators–potential drugs network was further constructed. Taken together, the comprehensive analyses of m6A regulators might provide novel insights into the m6A regulators’ roles across cancer types and shed light on their potential molecular mechanisms as well as help develop new therapy approaches for cancers.

Accumulating lines of evidence indicate that the deregulation of m6A is involved in various cancer types. The m6A RNA methylation is modulated by m6A methyltransferases, demethylases, and reader proteins. Although the aberrant expression of m6A RNA methylation contributes to the development and progression of multiple cancer types, the roles of m6A regulators across numerous types of cancers remain largely unknown. Here, we comprehensively investigated the expression, genetic alteration, and prognosis significance of 20 commonly studied m6A regulators across diverse cancer types using TCGA datasets via bioinformatic analyses. The results revealed that the m6A regulators exhibited widespread dysregulation, genetic alteration, and the modulation of oncogenic pathways across TCGA cancer types. In addition, most of the m6A regulators were closely relevant with significant prognosis in many cancer types. Furthermore, we also constructed the protein–protein interacting network of the 20 m6A regulators, and a more complex interacting regulatory network including m6A regulators and their corresponding interacting factors. Besides, the networks between m6A regulators and their upstream regulators such as miRNAs or transcriptional factors were further constructed in this study. Finally, the possible chemicals targeting each m6A regulator were obtained by bioinformatics analysis and the m6A regulators–potential drugs network was further constructed. Taken together, the comprehensive analyses of m6A regulators might provide novel insights into the m6A regulators’ roles across cancer types and shed light on their potential molecular mechanisms as well as help develop new therapy approaches for cancers.

Interferon-induced protein with tetratricopeptide repeats (IFITs) genes, consisting of four members named IFIT1, IFIT2, IFIT3 and IFIT5, are involved in the progression of multiple cancer types, but their roles in skin cutaneous melanoma (SKCM) are still largely unknown. The TCGA-SKCM dataset, GSE15605 dataset and GSE100508 dataset were obtained in our study, and multiple online databases were used for data analysis and visualization, including GEPIA, GSCALite, MethSurv, DAVID, starBase and TIMER database. The mRNA expressing levels of all the four members included in IFIT family were elevated in SKCM tissues. In addition, ROC curve showed that the combined IFITs had a higher tumor prediction performance. Kaplan-Meier survival analysis revealed that the low expression of IFIT1/2/3/5 was associated with poor overall survival (OS) and disease-specific survival (DSS) in SKCM patients. Moreover, univariate and multivariate Cox regression analysis suggested that the low expression of IFIT2/3/5 was an independent risk factor for the prognosis of SKCM patients. Besides, cancer pathway activity analysis certified that the IFITs were involved in the apoptosis pathways, epithelial-mesenchymal transition (EMT) and cell cycle. Furthermore, drug sensitivity analysis indicated that the high expression of IFIT1/2/3 was sensitive to dasatinib drug. Additionally, the expressing levels of IFITs were found to be positively correlated with the level of immune cell infiltrates, immune biomarkers and m6A regulators. Finally, using bioinformatics analysis, we predicted that PAX8-AS1/Z83843.1-miR-92a-3p-IFIT2 axis might play crucial roles in the development and progression of SKCM. This study explored the prognostic values and biological significance of the IFITs in SKCM microenvironment. IFITs may serve as novel biomarkers for the diagnosis and prognosis of melanoma and potential immunotherapeutic targets.

Nanoporous gold film (NPGF) has shown great potential for photonics, catalysis, sensing, and renewable energy. Herein, we report a monolayered NPGF with tunable electrocatalytic activity for improved methanol electrooxidation and H2O2 detection. The NPGFs were fabricated via interfacial self-assembly of Au nanoparticles (NPs) with different sizes and a subsequent light welding process. Amongst the NPGFs made from 16, 30, 55, and 70 nm Au NPs (denoted as x nm-NPGF, where x represents the size for the Au NPs), the 16 nm-NPGF shows the highest electrocatalytic activity, which is attributed to the synergistic contribution from its largest surface area, high conductivity, and the smallest hyperboloid-like ligaments that expose more high-index facets. Consequently, the optimized 16 nm-NPGF delivers a large current density of 151 μA cm−2 (at 0.22 V vs. saturated calomel electrode in 0.1 M KOH and 1.0 M methanol) for methanol electrooxidation. Moreover, it as well shows a good linear range (from 0.005 to 45 mM) for H2O2 detection, reaching a detection limit of 2.56 μM and sensitivity of 156.6 μA mM−1 cm−2. Our studies, thus, offer a low-temperature, solution-processable approach to fabricate monolayered NPGF from easily available Au NPs, without harsh dealloying process.