Microbiome in Bladder Cancer: A Systematic Review.

Although many studies on bladder cancer and the microbiome have been conducted so far, useful strains at the species level have not yet been identified. In addition, in the case of urine studies, methodological heterogeneity is too great, and in tissue studies, the species level through shotgun analysis has not been revealed, and studies using stool samples have provided only limited information. In this review, we will review all the microbiome studies related to bladder cancer so far through a systematic review.

The Positive Correlations between the Expression of Histopathological Ubiquitin-Conjugating Enzyme 2O Staining and Prostate Cancer Advancement.

BACKGROUND: The mTOR signaling pathway is inactivated by AMPK's tumor-suppressing function. It is recognized that ubiquitin conjugating enzyme 2O (UBE2O), which directly targets AMPK for ubiquitination and degradation, is intensified in human cancers. METHODS: This study investigated the clinical data about prostate cancer. Examination was also carried out into tissue microarrays (TMA) of human prostate cancer (n = 382) and adjacent non-neoplastic tissues around prostate cancer (n = 61). The TMA slides were incubated with antibodies against UBE2O, and the cores were scored by the pathologist blind to cancer results. RESULTS: Very strong positive correlations were identified between the expression of UBE2O staining and high PSA and pathological stage of prostate cancer. Cox's proportional hazard analysis established correlations between the following: (1) positive surgical margin and biochemical recurrence free survival, (2) PSA grade and clinical recurrence free survival, (3) regional lymph node positive and clinical recurrence free survival, (4) adjuvant treatment and overall survival, and (5) pathological T stage and overall survival. CONCLUSION: There is a positive correlation between the expression of UBE2O staining and prognosis for prostate cancer. Thus, a prostate cancer prognosis can be assessed with the expression of UBE2O staining.

Intraoperative Observation of the Degree and Pattern of Urine Leakage before Adjustment of the Mesh during a Transobturator Tape Procedure.

Most intraoperative provocative tests previously reported were performed after mesh adjustment to confirm the absence of urine leakage. Instead, our test was performed before adjustment of the mesh to control the tape tension after observing the pattern of the urine leakage. We studied whether this method had an effect on the success rate of transobturator tape (TOT) procedures. A total of 96 patients were included: 47 patients underwent TOT procedures without intraoperative testing (Group I) and 49 patients underwent TOT procedures with testing (Group II). Bladder filling was performed with at least 300 ml of normal saline during the test. After observing the pattern of the urine leakage before adjustment of the mesh by coughing or manual pressure on the suprapubic area, we controlled the mesh tension. In Group I, which did not undergo the intraoperative test, the Valsalva leak-point pressure, cough leak-point pressure, preoperative and postoperative peak flow velocity (Qmax), and postvoiding residual urine (PVR) were 86.46 cmH2O, 101.91 cmH2O, 20.82 ml/s, 22.74 ml/s, 19.77 ml, and 45.98 ml, respectively. Changes in the postoperative and preoperative Qmax and PVR were 1.92 ml/s and 26.21 ml, respectively. In Group II, in which the test was applied, the corresponding results were 85.50 cmH2O, 100.45 cmH2O, 25.60 ml/s, 26.90 ml/s, 17.16 ml, and 29.67 ml, respectively. Changes in the postoperative and preoperative Qmax and PVR were 1.3 ml/s and 12.51 ml, respectively. The two groups showed no significant differences in any of the variables. In Group I, the cure and improvement rates were 70.2% and 27.7%, respectively. In Group II, the rates were 91.8% and 8.2%, respectively. Group II had a significantly higher success rate than Group I (p value= 0.011). In the univariable logistic regression analysis, Group II exhibited a higher odds ratio (4.771) than Group I in terms of cure rate, and Group II had a higher success rate than Group I (p value=0.011). In the multivariable logistic regression analysis, Group II exhibited a higher odds ratio (4.700) than Group I in terms of cure rate under calculation of the variables (namely, age, hypertension, preoperative Qmax, and PVR), and the cure rate of Group II was verified to be significantly higher than that of Group I (p value=0.019). We suggest that our test is an effective method to confirm whether adequate tension is being applied to the tape. Our method presents some advantages in that surgeons can control and adjust the tension of the mesh after observing the degree and pattern of the urine leakage.

A hamburger-shaped helical stacking of disk-shaped ligands mediated by silver(II) ions.

We describe a hamburger-shaped helical structure of chiral and achiral C3-symmetric disk-shaped ligands mediated by silver ions.

Porous metal-organic frameworks based on metal-organic polyhedra with nanosized cavities as supramolecular building blocks: two-fold interpenetrating primitive cubic networks of [Cu6L8]12+ nanocages.

Discrete metal-organic polyhedra (MOP) with nanosized cavities and/or clusters of MOP could be prepared when C3-symmetric facial ligands and a potential hexatopic Cu(II) ion are combined in the presence of perchlorate as a weak linker, while similar reaction conditions in the presence of a nitrate linker led to extended metal-organic frameworks made of MOP as supramolecular building blocks.

High-affinity pyrophosphate receptor by a synergistic effect between metal coordination and hydrogen bonding in water.

We have developed the tightest binding PPi receptor reported to date by a combination of metal coordination and hydrogen bonding interaction in water.

Total synthesis of (-)-blepharocalyxin D.

[reaction: see text] The Prins cyclization strategy was successfully applied in the total synthesis of (-)-blepharocalyxin D, a cytotoxic dimeric diarylheptanoid isolated from Alpinia blepharocalyx.

Thin sectioning of slice preparations for immunohistochemistry.

Many investigations in neuroscience, as well as other disciplines, involve studying small, yet macroscopic pieces or sections of tissue that have been preserved, freshly removed, or excised but kept viable, as in slice preparations of brain tissue. Subsequent microscopic studies of this material can be challenging, as the tissue samples may be difficult to handle. Demonstrated here is a method for obtaining thin cryostat sections of tissue with a thickness that may range from 0.2-5.0 mm. We routinely cut 400 micron thick Vibratome brain slices serially into 5-10 micron coronal cryostat sections. The slices are typically first used for electrophysiology experiments and then require microscopic analysis of the cytoarchitecture of the region from which the recordings were observed. We have constructed a simple device that allows controlled and reproducible preparation and positioning of the tissue slice. This device consists of a cylinder 5 cm in length with a diameter of 1.2 cm, which serves as a freezing stage for the slice. A ring snugly slides over the cylinder providing walls around the slice allowing the tissue to be immersed in freezing compound (e.g., OCT). This is then quickly frozen with crushed dry ice and the resulting wafer can be position easily for cryostat sectioning. Thin sections can be thaw-mounted onto coated slides to allow further studies to be performed, such as various staining methods, in situ hybridization, or immunohistochemistry, as demonstrated here.

Encapsulation of a guest molecule in a strained form: an extended 36-membered dodecanuclear manganese metallamacrocycle that accommodates a cyclooctane in the S4 symmetry conformation.

An extended 36-membered dodecanuclear manganese metallamacrocycle with S12 symmetry has been synthesized using the ligand N-cyclohexanoylsalicylhydrazide (H3chxshz) by a self-assembly that accommodates a cyclooctane of conformationally strained S4 symmetry in its hydrophobic cavity.

Solid-state NMR spectroscopy of silicon-treated rice with enhanced host resistance against blast.

Silicon is the second-most abundant element on the surface of the earth, and has been considered important for plant growth and development. As for its role in enhanced plant disease resistance, silicon has been reported to reinforce the physical barrier against the penetration and colonization of pathogens. Rice leaves of silicon-treated plants and control plants at the eight- and twelve-leaf growth stages were analyzed by 29Si solid-state nuclear magnetic resonance spectroscopy to characterize the silicon-induced, cell wall fortification of rice leaves, which demonstrated an ability to counter a pathogen attack.

Face-driven corner-linked octahedral nanocages: M6L8 cages formed by C3-symmetric triangular facial ligands linked via C4-symmetric square tetratopic Pd(II) ions at truncated octahedron corners.

The face-driven corner-linked truncated octahedral nanocages, [Pd6L8]12+ (1, L1 = N,N',N' '-tris(3-pyridinyl)-1,3,5-benzenetricarboxamide; 2, L2 = N,N',N' '-tris(4-pyridinylmethyl)-1,3,5-benzenetricarboxamide), were prepared with eight C3-symmetric tridentate ligands and six square planar tetratopic palladium(II) ions. The combination of the nitrogen donor atom at a approximately 120 degrees kink position of the carboxamido pyridinyl group and the tilted pyridyl versus the facial plane of the ligands can provide the needed curvature for the formation of octahedral cages. The nitrogen atoms can coordinate to the square planar palladium(II) ions to form kinks with approximately 120 degrees angles at the C4-symmetric square planar corners of the truncated octahedron. Depending on the conformation of the ligand, L1, two different truncated octahedral cages of around 2.4 nm in diameters were formed. The major form of 1 with syn-conformational ligands has a cavity volume of approximately 1600 A3. The cage has 12 ports (3.4 x 3.5 A2) at all edges of the octahedron. The minor form of cage 1 with anti-conformational ligands has a slightly increased cavity volume ( approximately 1900 A3) and port size (3.3 x 8.0 A2). The insertion of a methylene group in L2 has not only increased the cavity volume of 2 to approximately 2200 A3 but also enlarged the port size to 4.1 x 8.0 A2. However, an atomic force microscopy (AFM) study of cage 2 showed that the cages had a height of 1.8 +/- 0.1 nm. This value is about 30% smaller than the calculated size of 2.6 nm from the crystal structure. This tip-induced decrease in height in cage 2 suggests the nonrigidity of cage 2.

Stromal cell-derived inducing activity, Nurr1, and signaling molecules synergistically induce dopaminergic neurons from mouse embryonic stem cells.

To induce differentiation of embryonic stem cells (ESCs) into specialized cell types for therapeutic purposes, it may be desirable to combine genetic manipulation and appropriate differentiation signals. We studied the induction of dopaminergic (DA) neurons from mouse ESCs by overexpressing the transcription factor Nurr1 and coculturing with PA6 stromal cells. Nurr1-expressing ESCs (N2 and N5) differentiated into a higher number of neurons (approximately twofold) than the naïve ESCs (D3). In addition, N2/N5-derived cells contained a significantly higher proportion (>50%) of tyrosine hydroxylase (TH)+ neurons than D3 (<30%) and an even greater proportion of TH+ neurons (approximately 90%) when treated with the signaling molecules sonic hedgehog, fibroblast growth factor 8, and ascorbic acid. N2/N5-derived cells express much higher levels of DA markers (e.g., TH, dopamine transporter, aromatic amino acid decarboxylase, and G protein-regulated inwardly rectifying K+ channel 2) and produce and release a higher level of dopamine, compared with D3-derived cells. Furthermore, the majority of generated neurons exhibited electrophysiological properties characteristic of midbrain DA neurons. Finally, transplantation experiments showed efficient in vivo integration/generation of TH+ neurons after implantation into mouse striatum. Taken together, our results show that the combination of genetic manipulation(s) and in vitro cell differentiation conditions offers a reliable and effective induction of DA neurons from ESCs and may pave the way for future cell transplantation therapy in Parkinson's disease.

Genetic engineering of mouse embryonic stem cells by Nurr1 enhances differentiation and maturation into dopaminergic neurons.

Nurr1 is a transcription factor critical for the development of midbrain dopaminergic (DA) neurons. This study modified mouse embryonic stem (ES) cells to constitutively express Nurr1 under the elongation factor-1alpha promoter. The Nurr1-expression in ES cells lead to up-regulation of all DA neuronal markers tested, resulting in about a 4- to 5-fold increase in the proportion of DA neurons. In contrast, other neuronal and glial markers were not significantly changed by Nurr1 expression. It was also observed that there was an additional 4-fold increase in the number of DA neurons in Nurr1-expressing clones following treatment with Shh, FGF8 and ascorbic acid. Several lines of evidence suggest that these neurons may represent midbrain DA neuronal phenotypes; firstly, they coexpress midbrain DA markers such as aromatic L-amino acid decarboxylase, calretinin, and dopamine transporter, in addition to tyrosine hydroxylase and secondly, they do not coexpress other neurotransmitters such as GABA or serotonin. Finally, consistent with an increased number of DA neurons, the Nurr1 transduction enhanced the ability of these neurons to produce and release DA in response to membrane depolarization. This study demonstrates an efficient genetic manipulation of ES cells that facilitates differentiation to midbrain DA neurons, and it will serve as a framework of genetic engineering of ES cells by key transcription factor to regulate their cell fate.

A proximal promoter domain containing a homeodomain-binding core motif interacts with multiple transcription factors, including HoxA5 and Phox2 proteins, and critically regulates cell type-specific transcription of the human norepinephrine transporter gene.

Expression of the norepinephrine transporter (NET), which mediates the reuptake of norepinephrine into presynaptic nerve terminals, is restricted to noradrenergic (NA) neurons. We have demonstrated previously that the 9.0 kb upstream sequences and the first intron residing in the 5' untranslated area are critical for high-level and NA cell-specific transcription. Here, using transient transfection assays, we show that 4.0 kb of the 5' upstream sequences contains sufficient genetic information to drive reporter gene expression in an NA cell type-specific manner. Three functional domains appear to be potentially important for the regulation of human NET (hNET) gene transcription: an upstream enhancer region at -4.0 to -3.1 kb, a proximal domain at -133 to -75 bp, and a middle silencer region between these two domains. DNase I footprinting analysis of the proximal promoter region shows that a subdomain at -128 to -80 bp is protected in a cell-specific manner. We provide evidence that multiple protein factors interact with the proximal promoter domain to critically regulate the transcriptional activity of the hNET gene. In the middle of this proximal subdomain resides a homeodomain (HD)-binding core motif, which interacts with HD factors, including Phox2a and HoxA5, in an NA-specific manner. Cotransfection analyses suggest that HoxA5 and Phox2a may transactivate the hNET gene promoter. Together with previous studies indicating direct activation of dopamine beta-hydroxylase transcription by Phox2a/2b, the present results support a model whereby Phox2 proteins may coordinately regulate the phenotypic specification of NA neurons by activating both NA biosynthetic and reuptake genes.