Malignant phyllodes tumors display mesenchymal stem cell features and aldehyde dehydrogenase/disialoganglioside identify their tumor stem cells.

IntroductionAlthough breast phyllodes tumors are rare, there is no effective therapy other than surgery. Little is known about their tumor biology. A malignant phyllodes tumor contains heterologous stromal elements, and can transform into rhabdomyosarcoma, liposarcoma and osteosarcoma. These versatile properties prompted us to explore their possible relationship to mesenchymal stem cells (MSCs) and to search for the presence of cancer stem cells (CSCs) in phyllodes tumors.MethodsParaffin sections of malignant phyllodes tumors were examined for various markers by immunohistochemical staining. Xenografts of human primary phyllodes tumors were established by injecting freshly isolated tumor cells into the mammary fat pad of non-obese diabetic-severe combined immunodeficient (NOD-SCID) mice. To search for CSCs, xenografted tumor cells were sorted into various subpopulations by flow cytometry and examined for their in vitro mammosphere forming capacity, in vivo tumorigenicity in NOD-SCID mice and their ability to undergo differentiation.ResultsImmunohistochemical analysis revealed the expression of the following 10 markers: CD44, CD29, CD106, CD166, CD105, CD90, disialoganglioside (GD2), CD117, Aldehyde dehydrogenase 1 (ALDH), and Oct-4, and 7 clinically relevant markers (CD10, CD34, p53, p63, Ki-67, Bcl-2, vimentin, and Globo H) in all 51 malignant phyllodes tumors examined, albeit to different extents. Four xenografts were successfully established from human primary phyllodes tumors. In vitro, ALDH+ cells sorted from xenografts displayed approximately 10-fold greater mammosphere-forming capacity than ALDH- cells. GD2+ cells showed a 3.9-fold greater capacity than GD2- cells. ALDH+/GD2+cells displayed 12.8-fold greater mammosphere forming ability than ALDH-/GD2- cells. In vivo, the tumor-initiating frequency of ALDH+/GD2+ cells were up to 33-fold higher than that of ALDH+ cells, with as few as 50 ALDH+/GD2+ cells being sufficient for engraftment. Moreover, we provided the first evidence for the induction of ALDH+/GD2+ cells to differentiate into neural cells of various lineages, along with the observation of neural differentiation in clinical specimens and xenografts of malignant phyllodes tumors. ALDH+ or ALDH+/GD2+ cells could also be induced to differentiate into adipocytes, osteocytes or chondrocytes.ConclusionsOur findings revealed that malignant phyllodes tumors possessed many characteristics of MSC, and their CSCs were enriched in ALDH+ and ALDH+/GD2+ subpopulations

Molecular mechanism of ethylene stimulation of latex yield in rubber tree (Hevea brasiliensis) revealed by de novo sequencing and transcriptome analysis

Differential expression of unigenes involved in hormone signaling in E8 and E24 compared to C samples of Hevea brasiliensis. Ethylene signalling pathway: ETR1: ETHYLENE RESPONSE 1; CTR1: CONSTITUTIVE TRIPLE RESPONSE 1; EIN2: ETHYLENE INSENSITIVE 2; EIN3: ETHYLENE INSENSITIVE 3; ERF1/2: ETHYLENE RESPONSE FACTOR 1/2; EBF1/2: EIN3 binding F-Box protein 1/2; BR signaling pathway: BRI1: Brassinosteroid-Insensitive 1; BAK1: BRI1-associated kinase 1; BKI1: BRI1 KINASE INHIBITOR 1; BSK: BR SIGNALING KINASE; BSU1: bri1 SUPPRESSOR 1; BIN2: BRASSINOSTEROID-INSENSITIVE 2; BZR1/2: BRASSINAZOLE RESISTANT 1/2; TCH: TOUCH genes; CYCD3: CYCLIN D3; GA signaling pathway: GID1: GIBBERELLIN INSENSITIVE DWARF 1; GID2: GIBBERELLIN INSENSITIVE DWARF 2; DELLAs: DELLA growth inhibitors; TF: transcriptional factor; Auxin signaling pathway: AUX1: AUXIN1; TIR1: TRANSPORT INHIBITOR RESPONSE 1; IAA: INDOLE ACETIC ACID; ARF: AUXIN RESPONSE FACTOR; SAUR: Small Auxin-Up RNA; G10H: geraniol 10-hydroxylase gene; Cytokinin signaling pathway: CRE1: CYTOKININ RESPONSE 1; AHP: histidine phosphotransfer protein; B-ARR: type-B response regulator (ARR); A-ARR: type-A response regulator (ARR); SA signalling pathway: NPR1: Non-expressor of pathogenesis-related genes 1; TGA: the bZIP transcription factors; PR1: pathogenesis related protein 1; JA signaling pathway: JAR1: JASMONATES RESISTANT 1; JA-Ile: jasmonoyl isoleucine; JAZ: Jasmonate ZIM-domain-containing protein; MYC2: a basic helix-loop-helix (bHLH) transcription factor; ORCA3: Octadecanoid-derivative Responsive Catharanthus AP2-domain gene; ABA signalling pathway: PYR1/PYLs: Pyrabactin Resistance Protein1/PYR-Like proteins; PP2Cs: protein phosphatases which fall under the category of type 2C; SnRK2: SNF1 (Sucrose-Nonfermenting Kinase1)-related protein kinase 2: ABF: ABA responsive element (ABRE) binding factors. Cells with gray border lines in the upper rows represent differentially expressed unigenes in E8 compared to C and cells with green border lines in the lower rows represent differentially expressed unigenes in E24 compared to C. Relative levels of expression are showed by a color gradient from low (blue) to high (red). (JPG 249 kb

Poly[(acetato-κ2 O,O′)aqua­(μ4-1H-benzimidazole-5,6-dicarboxyl­ato-κ5 N 3:O 5,O 5′:O 5,O 6:O 6′)praseodymium(III)]

In the title complex, [Pr(C9H4N2O4)(C2H3O2)(H2O)]n, the PrIII ion is coordinated by five O atoms and one N atom from four benzimidazole-5,6-dicarboxyl­ate ligands, two O atoms from an acetate ligand and one water mol­ecule, giving a tricapped trigonal-prismatic geometry. The benzimidazole-5,6-dicarboxyl­ate and acetate ligands connect the PrIII ions, forming a layer in the ac plane; the layers are further linked by N—H⋯O and O—H⋯O hydrogen bonding and π–π stacking inter­actions between neighboring pyridine rings [the centroid–centroid distance is 3.467 (1) Å], assembling a three-dimensional supra­molecular network. The acetate methyl group is disordered over two positions with site-occupancy factors of 0.75 and 0.25

Glechoma longituba (Lamiaceae) alleviates apoptosis in calcium oxalate-induced oxidative stress in kidney proximal tubule epithelial cell line, HK-2

Purpose: To investigate the effects of Glechoma longituba on calcium oxalate (CaOx)-induced stress in HK-2 cells as a possible treatment strategy for nephrolithiasis (kidney stones).Methods: Human kidney HK-2 cells were treated with CaOx and Glechoma longituba at different concentrations. The levels of reactive oxygen species (ROS), lactate dehydrogenase (LDH), and malondialdehyde (MDA) were measured. Cell apoptosis and viability were assessed by flow cytometry and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assays, respectively, while apoptosis-related proteins were determined using western blotting. The levels of the nuclear factorerythroid 2-related factor 2 (Nrf2), heme oxygenase-1 (HO-1), and NADPH-quinone-oxidoreductase 1 (NQO-1) genes were evaluated using quantitative real-time polymerase chain reaction (qRT-PCR). Using lentivirus, Nrf2 was knocked down in HK-2 cells, and this was confirmed by both qRT-PCR and western blotting. Scramble and si-Nrf2 transfected HK-2 cells were treated with CaOx and Glechoma longituba, and ROS levels and apoptosis were also assessed.Results: CaOx significantly increased the levels of ROS, LDH and MDA, while Glechoma longituba pretreatment attenuated these elevations in a dose-dependent manner. CaOx treatment increased cell apoptosis and decreased cell viability (p < 0.05), while Glechoma longituba pre-treatment abolished these effects in a dose-dependent manner. Glechoma longituba pre-treatment significantly upregulated the expressions of Nrf2, HO-1 and NQO-1 (p < 0.05). In HK-2 cells, Si-Nrf-2 attenuated the effects of Glechoma longituba pre-treatment on cell oxidative stress and apoptosis induced by CaOx.Conclusion: Glechoma longituba pre-treatment attenuates cell apoptosis and oxidative stress induced by CaOx via Nrf2/HO-1 signalling pathway. Thus, the plant is a potential source of agents for the treatment of nephrolithiasis.Keywords: Glechoma longituba, Nephrolithiasis, Nuclear factor-erythroid 2-related factor 2, Oxidative stress, Apoptosi

Benzoyl­methyl 4-chloro­benzoate

The asymmetric unit of the title compound, C15H11ClO3, contains three mol­ecules, A, B, and C. Mol­ecules A and B are aligned edge-to-face, whereas mol­ecules B and C are aligned almost parallel to each other. The crystal structure displays C—H⋯π and π–π [centroid–centroid distances of 3.960 (4), 3.971 (4) and 3.971 (4) for mol­ecules A, B and C, respectively] parallel-displaced inter­actions, and C—H⋯O hydrogen bonds

Benzoyl­methyl pyridine-4-carboxyl­ate

In the crystal structure of the title compound, C14H11NO3, isolated from the reaction of 2-bromo-1-phenyl­ethanone and pyridine-4-carboxylic acid using triethyl­amine as a base to deprotonate the organic acid, the mol­ecular packing is stabilized by C—H⋯π inter­actions involving the phenyl and pyridine rings. The C—C—O—C torsion angle for the linkage between the two carbonyl groups is −80.8 (2)°, and the planes of the phenyl and pyridyl rings form a dihedral angle of 65.8 (1)°

Sulforaphane induces adipocyte browning and promotes glucose and lipid utilization

Scope: Obesity is closely related to the imbalance of white adipose tissue storing excess calories, and brown adipose tissue dissipating energy to produce heat in mammals. Recent studies revealed that acquisition of brown characteristics by white adipocytes, termed “browning,” may positively contribute to cellular bioenergetics and metabolism homeostasis. The goal was to investigate the putative effects of natural antioxidant sulforaphane (1-isothiocyanate-4-methyl-sulfonyl butane; SFN) on browning of white adipocytes. Methods and Results: 3T3-L1 mature white adipocytes were treated with SFN for 48 h, and then the mitochondrial content, function, and energy utilization were assessed. SFN was found to induce 3T3-L1 adipocytes browning based on the increased mitochondrial content and activity of respiratory chain enzymes, whereas the mechanism involved the upregulation of nuclear factor E2-related factor 2/ sirtuin1/ peroxisome proliferator-activated receptor gamma coactivator 1 alpha signaling. SFN enhanced uncoupling protein 1 expression, a marker for brown adipocyte, leading to the decrease in cellular ATP. SFN also enhanced glucose uptake and oxidative utilization, lipolysis and fatty acid oxidation in 3T3-L1 adipocytes. Conclusion: SFN-induced browning of white adipocytes enhanced the utilization of cellular fuel, and the application of SFN is a promising strategy to combat obesity and obesity-related metabolic disorder

Alternative O-GlcNAcylation/O-Phosphorylation of Ser16 Induce Different Conformational Disturbances to the N Terminus of Murine Estrogen Receptor β

SummarySerine and threonine residues in many proteins can be modified by either phosphorylation or GlcNAcylation. To investigate the mechanism of O-GlcNAc and O-phosphate's reciprocal roles in modulating the degradation and activity of murine estrogen receptor β (mER-β), the conformational changes induced by O-GlcNAcylation and O-phosphorylation of Ser16 in 17-mer model peptides corresponding to the N-terminal intrinsically disordered (ID) region of mER-β were studied by NMR techniques, circular dichroism (CD), and molecular dynamics simulations. Our results suggest that O-phosphorylation discourages the turn formation in the S15STG18 fragment. In contrast, O-GlcNAcylation promotes turn formation in this region. Thus, we postulate that the different changes of the local structure in the N-terminal S15STG18 fragment of mER-β caused by O-phosphate or O-GlcNAc modification might lead to the disturbances to the dynamic ensembles of the ID region of mER-β, which is related to its modulatory activity

Current reversals and metastable states in the infinite Bose-Hubbard chain with local particle loss

We present an algorithm which combines the quantum trajectory approach to open quantum systems with a density-matrix renormalization group scheme for infinite one-dimensional lattice systems. We apply this method to investigate the long-time dynamics in the Bose-Hubbard model with local particle loss starting from a Mott-insulating initial state with one boson per site. While the short-time dynamics can be described even quantitatively by an equation of motion (EOM) approach at the mean-field level, many-body interactions lead to unexpected effects at intermediate and long times: local particle currents far away from the dissipative site start to reverse direction ultimately leading to a metastable state with a total particle current pointing away from the lossy site. An alternative EOM approach based on an effective fermion model shows that the reversal of currents can be understood qualitatively by the creation of holon-doublon pairs at the edge of the region of reduced particle density. The doublons are then able to escape while the holes move towards the dissipative site, a process reminiscent---in a loose sense---of Hawking radiation