PARK7/DJ-1 inhibition decreases invasion and proliferation of uveal melanoma cells

Introduction: PARK7/DJ-1 is an oncogene that is associated with tumorigenesis in many cancers. Recent studies have demonstrated the importance of DJ-1 in the origin and development of uveal melanoma (UM). We present an analysis of the role of the DJ-1 protein in UM cells, especially in its effect on proliferation and migration. Methods: UM cells from a primary tumor, Mel 270, and its liver metastasis, OMM2.5, were transfected with lentiviral-delivered shRNA against PARK7/DJ-1. Evaluation of cell migration and proliferation was performed using the xCELLigence real-time cell analyzer (RTCA). The effect of DJ-1 inhibition on the PTEN-Akt signaling pathway was also studied by immunoblotting. Results: The silencing of PARK7/DJ-1 oncoprotein expression produced a significant decrease of phosphorylated Akt (S473) in Mel270 and in metastatic OMM2.5 UM cells with no alteration on tumor suppressor PTEN expression. The diminution of PARK7/DJ-1 expression significantly inhibited real-time proliferation and invasion of Mel270 and OMM2.5 and the invasion potential of the metastatic cells. Conclusion: DJ-1 appears to play a key role on the PTEN/Akt pathway in UM. DJ-1 inhibition appears to have a negative effect on proliferation and invasion of UM cells. This suggests DJ-1 as a potential therapeutic target in UM.

Serum Cytokine Profile in Patients with Candidemia Versus Bacteremia

Bloodstream Candida infections constitute a major threat for hospitalized patients in intensive care units and immunocompromised hosts. Certain serum cytokines play a decisive role in anti-microbial host defense. Cytokines may act as discriminatory biomarkers that can significantly increase in candidemia compared to bacteremia patients. The concentration of secreted cytokine/chemokines was determined using a multiplexed cytometric bead array run on a cell analyzer. The cytokines tested during the study were interleukin (IL)-1β, IL-6, IL-17A, IL-10, IFN-?, IL-4, IL-2, IL-8, IL-12p70 and the tumor necrosis factor (TNF)-α. The cytokines of 51 candidemia patients were characterized and compared to the cytokine levels of 20 bacteremia patients. Levels were significantly elevated in patients with bloodstream infections compared to healthy controls. Cytokines comprising IL-2, IL-17A, IL-6 and IL-10 were significantly elevated in the patients with bloodstream Candida infection as compared to the patients having bloodstream bacterial infections. The levels were found to be promising as a potential diagnostic marker for bloodstream Candida infections.

SKIRTINGŲ KRŪTIES VĖŽIO LĄSTELIŲ LINIJŲ ATSPARUMO RADIOTERAPIJAI TYRIMAS

Įvadas. Radioterapija yra vienas iš pagrindinių vėžio gydymo metodų, taikomų daugiau kaip pusei onkologinių pacientų. Manoma, kad pagrindinė onkologinės ligos pasikartojimo ir nesėkmingo gydymo priežastis yra vėžinių ląstelių atsparumas radioterapijai. Viena iš pagrindinių atsparumo radioterapijai priežasčių yra vėžinių ląstelių gebėjimas išvengti apoptozės. Manoma, kad ląstelės ciklas taip pat yra vienas iš procesų, turinčių reikšmės radioatsparumui. Šio tyrimo tikslas – įvertinti skirtingų krūties vėžio ląstelių linijų atsparumą radioterapijai, lyginant jų gyvybingumą, ląstelių pasiskirstymą tarp ciklo fazių ir apoptozės intensyvumą. Metodika. MCF-7 ir MDA-MB-231 ląstelių gyvybingumas buvo ištirtas, naudojant kolonijų formavimo testą. Ląstelės ciklo analizei buvo dažomos propidžio jodidu ir analizuojamos, naudojant tėkmės citometrą Muse Cell Analyzer. Apoptozės intensyvumui nustatyti naudotas aneksinas V ir Guava PCA tėkmės citometras. Rezultatai. Šiame tyrime nustatėme, kad MDA-MB-231 ląstelių gyvybingumas po radioterapijos poveikio buvo didesnis, nei MCF-7 ląstelių. Ciklo analizė parodė, kad po radioterapijos poveikio MCF-7 ląstelių ciklo sustabdymas vyko G0/G1 fazėje, o MDA-MB-231 ląstelių – G2/M fazėje. Po radioterapijos poveikio MCF-7 ląstelėse apoptozė prasidėjo anksčiau ir buvo intensyvesnė, o MDA-MB-231 ląstelės reagavo vėliau ir turėjo uždelstą apoptozinį atsaką. Išvados. MDA-MB-231 ląstelės buvo atsparesnės radioterapijai, negu MCF-7 ląstelės.

N-trans-Feruloyloctopamine Wakes Up BBC3, DDIT3, CDKN1A, and NOXA Signals to Accelerate HCC Cell Apoptosis

N-trans-Feruloyloctopamine (FO), a natural compound, was reported in our previous study to inhibit a tumor cell malignant phenotype by AKT- and EMT-related signals and might be used as a promising drug for HCC treatment. However, the specific targets and detailed mechanisms still need to be clarified. Screening with RNA-Seq in Huh7 cells treated with FO revealed that 317 genes were modulated, of which 188 genes were upregulated and 129 genes were downregulated. Real-time cell analyzer and flow cytometry data reveal that tumor cell proliferation and apoptosis were impacted by FO. DAVID bioinformatic data showed that most of the biological process GO terms are related to proliferation and apoptosis. KEGG enrichment analysis showed that FO mainly regulates PI3K-AKT- and apoptosis-related signals, in which BBC3, DDIT3, NOXA, and CDKN1A on the surface serve as the novel targets of FO inducing HCC cell apoptosis. The result implied that FO might exacerbate HCC cell apoptosis by regulating BBC3, DDIT3, CDKN1A, and NOXA signals. The obstacle effect of FO can provide new targets and new credibility for the treatment of liver cancer.

miR-875-5p exerts tumor-promoting function via down-regulation of CAPZA1 in esophageal squamous cell carcinoma

Esophageal squamous cell carcinoma (ESCC) is one of the leading causes of cancer deaths worldwide. Currently, efficient genetic markers for diagnosis and treatment of ESCC are lacking. MicroRNAs (miRNAs) are global genetic regulators that control cancer gene expression by binding to the 3′untranslated regions (3′UTRs) of targeting mRNAs. In addition, miRNAs function as oncogenes or tumor suppressors in the progression of tumors. In the current study, we found that hsa-miR-875-5p (miR-875-5p) exhibited amplification in ESCC according to the TCGA database. Then, xCELLigence Real-Time Cell Analyzer (RTCA)-MP system and colony formation assays were employed to detect cell proliferationand colony formationability. The results showed that miR-875-5p promoted the proliferation ESCC cells. Subsequently, transwell results indicated that miR-875-5p promoted the invasion and migration of ESCC cells. Furthermore, we showed that miR-875-5p was able to bind to CAPZA13’UTR, which contains the single nucleotide polymorphism (SNP), rs373245753, as reported in our previous study involving WGS and WES on ESCC. Subsequently, mRNA affinity pull-down assays verifiedthat the SNP disrupts miR-875-5p binding to CAPZA1. The current study is the first demonstration that miR-875-5p may function as an oncogene via down-regulation of CAPZA1 expression in ESCC.

Pengaruh Puasa, Olahraga Moderat, Dan Olahraga Moderat Pada Keadaan Puasa Terhadap Sel Limfosit Pada Tikus Putih Jenis Wistar

This study aims to determine the effect of moderate fasting exercise on lymphocyte cells in white wistar strains of rattus norvegicus, with 24 male divided into 4 groups, namely control, fasting, moderate exercise and moderate exercise in fasting conditions. The research method uses Random Control Group Posttest-Only Design. The measurement of lymphocyte cells using Cobas Micros or Hematology Counter Cell Analyzer, while the data analysis uses ANOVA test with a significance level of 0.05. Based on the results of data analysis in the research group, it was interpreted that there was no significant effect between fasting, moderate exercise and moderate exercise in fasting conditions with a result of 0.682 (P> 0.05).Keywords: moderate exercise, fasting, lymphocyteAbstrak: Penelitian ini bertujuan untuk mengetahui pengaruh olahraga moderat saat puasa terhadap sel limfosit pada tikus putih jenis rattus norvegicus strain wistar, dengan jenis kelamin jantan berjumlah 24 ekor yang terbagi menjadi 4 kelompok. yaitu kontrol, puasa, olahraga moderat dan olahraga moderat pada kondisi puasa. Metode penelitian menggunakan Random Control Group Posttest-Only Design. Pengukuran sel limfosit menggunakan alat Cobas Micros atau Hematology Counter Cell Analyzer, sedangkan analisis data menggunakan uji anova dengan taraf signifikasi 0.05. Berdasarkan hasil analisis data pada kelompok peneliti, diartikan bahwa tidak terdapat pengaruhn yang signifikan antara puasa, olahraga moderat dan olahraga moderat pada keadaan puasa dengan hasil 0,682 (P > 0.05).Kata Kunci: olahraga moderat, puasa, limfosit