Kidney Cancer and Potential Use of Urinary Extracellular Vesicles.

Kidney cancer is the 14th most common cancer globally. The 5-year relative survival rate of kidney cancer at a localized stage is 92.9% and it declines to 17.4% in metastatic stage. Currently, the most accurate method of its diagnosis is tissue biopsy. However, the invasive and costly nature of biopsies makes it undesirable in many patients. Therefore, novel biomarkers for diagnosis and prognosis should be explored. Urinary extracellular vesicles (uEVs) are small vesicles (50-200 nm) in urine carrying nucleic acids, proteins and lipids as their cargos. These uEVs' cargos can provide non-invasive alternative to monitor kidney health. In this review, we have summarized recent studies investigating potential use of uEVs' cargos as biomarkers in kidney cancer for diagnosis, prognosis and therapeutic intervention.

Apolipoprotein L1 is a tumor suppressor in clear cell renal cell carcinoma metastasis.

The 5-year survival rate of kidney cancer drops dramatically from 93% to 15% when it is metastatic. Metastasis constitutes for 30% of kidney cancer cases, in which clear cell renal cell carcinoma (ccRCC) is the most prominent subtype. By sequencing mRNA of ccRCC patient samples, we found that apolipoprotein L1 (APOL1) was highly expressed in tumors compared to their adjacent normal tissues. This gene has been previously identified in a large body of kidney disease research and was reported as a potential prognosis marker in many types of cancers. However, the molecular function of APOL1 in ccRCC, especially in metastasis, remained unknown. In this study, we modulated the expression of APOL1 in various renal cancer cell lines and analyzed their proliferative, migratory, and invasive properties. Strikingly, APOL1 overexpression suppressed ccRCC metastasis both in vitro and in vivo. We then explored the mechanism by which APOL1 alleviated ccRCC malignant progression by investigating its downstream pathways. APOL1 overexpression diminished the activity of focal adhesive molecules, Akt signaling pathways, and EMT processes. Furthermore, in the upstream, we discovered that miR-30a-3p could inhibit APOL1 expression. In conclusion, our study revealed that APOL1 play a role as a tumor suppressor in ccRCC and inhibit metastasis, which may provide novel potential therapeutic approaches for ccRCC patients.

Characterization of exosomal microRNAs in preterm infants fed with breast milk and infant formula.

Breastfeeding not only reduces infection-related morbidity, but also increases growth of preterm infants. Advantages of breast milk (BM) for preterm infants are significant. They continue to be studied. However, because not all preterm infants can receive breastfeeding, bovine-based infant formula (IF) is used as an alternative, which may increase the risk of several preterm complications. Exosomes isolated from biofluids are emerging as biomarkers in research of various diseases. Here, we characterized miRNA contents of exosomes in urine and serum samples of preterm infants who were BM and IF fed and performed transcriptomic analysis of small RNA libraries. We identified significantly up-regulated 6 miRNAs and 10 miRNAs, respectively. Gene Ontology (GO) analysis revealed that target genes of these miRNAs might participate in neuronal development, immunity modulation, detoxification of reactive oxygen species, and transmembrane exchange. Our data suggest that exosome-based systemic screening for preterm infants with breastfeeding might be a screening tool for identifying target molecules involved in therapy for preterm infants in neonatal intensive care unit (NICU) and for future application as nutraceutical formulations or pharmaceuticals.

Deinococcus ruber sp. nov., a radiation-resistant bacterium isolated from soil.

Two gamma- and UVC-resistant bacterial strains, designated JSH3-1T and 9-2-2, were isolated from garden soil in South Korea. Cells were Gram-stain-positive, aerobic, non-motile and spherical. A polyphasic approach was used to study the taxonomic properties of strains JSH3-1T and 9-2-2. Phylogenetic analysis based on nearly full-length 16S rRNA gene sequences of strains JSH3-1T and 9-2-2 indicated highest similarity with Deinococcus radiomollis PO-04-20-132T (94.7 and 94.9 %, respectively); levels of sequence similarity with the type strains of other Deinococcus species were less than 94.0 %. Strains JSH3-1T and 9-2-2 shared relatively high 16S rRNA gene sequence similarity (98.7 %) and had a high DNA reassociation value of 81±0.5 %. Meanwhile, they showed low levels of DNA reassociation (<25 %) with other closely related species of the genus Deinococcus. The two strains showed chemotaxonomic features typical of the genus Deinococcus, with the presence of menaquinone 8 as the respiratory quinone. The predominant fatty acids were iso-C17 : 0, iso-C13 : 0 and anteiso-C13 : 0. The polar lipids comprised phosphoglycolipid, aminophospholipid, glycolipid and unknown aminolipids. The DNA G+C contents of strains JSH3-1T and 9-2-2 were 62.0 and 61.9 mol%, respectively. On the basis of their phenotypic and genotypic characteristics, and phylogenetic distinction, strains JSH3-1T (=KCTC 33790T=JCM 31311T) and 9-2-2 (=KCTC 33789=JCM 31310) should be classified within a novel species of the genus Deinococcus, for which the name Deinococcus ruber sp. nov. is proposed.

Spirosoma swuense sp. nov., isolated from wet soil.

Strain JBM2-3T, a pale-yellow-coloured, aerobic, catalase-negative, oxidase-positive and Gram-stain-negative bacterium, was isolated from wet soil. The isolate grew aerobically at 25-30 °C (optimum 25 °C), pH 6.0-8.0 (optimum pH 7.0) and in the presence of 0-0.5 % (w/v) NaCl (optimum 0 % NaCl). Phylogenetic analysis based on 16S rRNA gene sequence indicated that strain JBM2-3T belonged to the genus Spirosoma, with a sequence similarity of 96.2 % with Spirosoma panaciterrae Gsoil 1519T. The strain showed the typical chemotaxonomic characteristics of the genus Spirosoma, with the presence of menaquinone 7 as the respiratory quinone; the major fatty acids were summed feature 3 (composed of C16: 1ω6c/ω7c), C16: 1ω5c and iso-C15: 0. The DNA G+C content of strain JBM2-3T was 47.4 mol%. The polar lipid profile contained major amounts of phosphatidylethanolamine and aminophospholipids. On the basis of its phenotypic and genotypic properties, and phylogenetic distinctiveness, strain JBM2-3T should be classified as a representative of a novel species in the genus Spirosoma, for which the name Spirosoma swuense sp. nov. is proposed. The type strain is JBM2-3T (=KCTC 52176T=JCM 31298T).

Deinococcus persicinus sp. nov., a radiation-resistant bacterium from soil.

Two Gram-stain-negative, oxidase-negative, catalase-positive, aerobic and coccus-shaped bacterial strains, KSY3-6T and JSH6-18, were isolated from soil in South Korea. Strains KSY3-6T and JSH6-18 showed high resistance to gamma-ray and UVC irradiation. The 16S rRNA gene sequences of strains KSY3-6T and JSH6-18 showed a novel subline within the genus Deinococcus in the family Deinococcaceae. They shared 94.8-86.4 % nucleotide similarities with other species of the genus Deinococcus. Strain KSY3-6T exhibited high DNA-DNA hybridization values with JSH6-18 (77±0.8 %). The two strains showed typical chemotaxonomic characteristics of the genus Deinococcus, including the presence of menaquinone 8 (MK-8) as predominant respiratory quinone and C16 : 0, C17 : 0cyclo and summed feature 3 (C16 : 1ω7c/C16: 1ω6c) as major fatty acids. The G+C content of the DNA of strains KSY3-6T and JSH6-18 was 62.0 and 62.4 mol%, respectively. Polar lipids in strains KSY3-6T and JSH6-18 were mainly phosphoglycolipids. Based on their phenotypic and genotypic properties, strains KSY3-6T and JSH6-18 should be classified as representatives of a novel species in the genus Deinococcus, for which the name Deinococcus persicinus sp. nov. is proposed. The type strain is KSY3-6T (=KCTC 33787T=JCM 31313T). The reference strain is JSH6-18 (=KCTC 33788=JCM 31312).

Complete genome sequence of Deinococcus actinosclerus BM2(T), a bacterium with Gamma-radiation resistance isolated from soil in South Korea.

A Gram-positive, short-rod shaped and non-motile bacterium Deinococcus actinosclerus BM2(T), resistant to gamma and UV radiation, was isolated from a soil sample collected in South Korea. Strain BM2(T) showed high resistance to gamma radiation with D10 value of 9 kGy. The complete genome of D. actinosclerus BM2(T) consists of a single chromosome (3,264,334bp). The genome features showed the presence of intracellular proteases that help to eliminate radiation-induced ROS during recovery from ionizing radiation damage.

Altererythrobacter terrae sp. nov., isolated from mountain soil.

A Gram-negative, non-motile, non-spore-forming, ovoid-shaped bacterium designated as SWU3(T) was isolated from mountain soil collected at Seoul Women's University, South Korea. Based on 16S rRNA sequence analysis, strain SWU3(T) was found to belong to the genus Altererythrobacter. It shares high sequence similarities with A. dongtanensis JM27(T) (96.6 %), A. epoxidivorans JCS350(T) (96.6 %), and A. troitsensis KMM 6042(T) (96.5 %). Growth was observed between 15 and 37 °C (optimum, 30 °C) with pH of 6-9 (optimum, pH 7.0). It could tolerate 0-2 % (w/v) NaCl. Its predominant quinone was found to be ubiquinone (Q-10). Its major cellular fatty acids were determined to be C17:1 ω6c, C18:1 ω7c, and summed featured 3 (C16:1 ω7c/C16:1 ω6c), all of which are similar characteristics to those of species within the genus Altererythrobacter. Its G + C molar content was found to be 58.4 mol%. Phylogenetic evidence, together with phenotypic characteristics showed that strain SWU3(T) represents a new species of the genus Altererythrobacter. The name Altererythrobacter terrae sp. nov. is proposed and the type strain is SWU3(T) (=KEMB 9004-128(T) = JCM 19177(T)).

Hymenobacter rubidus sp. nov., bacterium isolated from a soil.

Strain DG7B(T) was isolated from a soil sample collected in Seoul, Republic of Korea and was observed to be a gram-negative, short-rod shaped and non-motile bacterium. Its 16S rRNA gene sequence is closely related to those of Hymenobacter terrae DG7A(T) (97.8 % similarity), H. soli PB17(T) (97.5 %), H. glaciei VUG-A130(T) (96.4 %), H. saemangeumensis GSR0100(T) (95.7 %), H. ruber PB156(T) (95.3 %), and H. antarcticus VUG-A42aa(T) (95.3 %). The low levels of DNA-DNA relatedness (<50.3 %) with the above species identified strain DG7B(T) as a novel species in the genus Hymenobacter. The genomic DNA G+C content was determined to be 54.9 %. Growth of strain DG7B(T) was observed at 12-30 °C (optimum at 25 °C) and pH 6.0-11.0 (optimum at pH 7). The cells tolerate <0.5 % NaCl. A UV-visible scan of an ethanol extract of the whole cell pigment showed absorbance peaks at 264.5, 320.0, and 481.5 nm, so the pigment type was determined to be 2'-hydroxyflexixanthin. Chemotaxonomic data showed that strain DG7B(T) possesses menaquinone-7 as the predominant isoprenoid quinone, sym-homospermidine as the major polyamine, phosphatidylethanolamine as the predominant polar lipid and iso-C15:0, anteiso-C15:0 and summed feature 3 (C16:1 ω7c/C16:1 ω7c) as the major fatty acids. Strain DG7B(T) showed low-level resistance to ultraviolet C. Based on the polyphasic analysis, it is concluded that strain DG7B(T) (=KCTC 32553(T) = KEMB 9004-166(T) = JCM 30008(T)) should be classified as the type strain of a novel Hymenobacter species, for which the name Hymenobacter rubidus sp. nov. is proposed.

Complete genome sequence of Deinococcus soli N5(T), a gamma-radiation- resistant bacterium isolated from rice field in South Korea.

A Gram-negative, non-motile and short-rod shaped and gamma-radiation-resistant bacterium Deinococcus soli N5(T), isolated from a rice field soil in South Korea. The complete genome of D. soli N5(T) consists of a chromosome (3,236,984bp). The key enzymes for the central DNA repair mechanisms were present in the genome. The enzyme coding genes has been identified which is involving in the nucleotide excision repair (NER) pathway. The gene cluster in the genome sequence suggest that the D. soli N5(T) use (NER) pathways for efficient removal of pyrimidine dimers that are the most abundant type of UV- induced damage.