1,10-Phenanthroline promotes copper complexes into tumor cells and induces apoptosis by inhibiting the proteasome activity.

Indole-3-acetic acid and indole-3-propionic acid, two potent natural plant growth hormones, have attracted attention as promising prodrugs in cancer therapy. Copper is known to be a cofactor essential for tumor angiogenesis. We have previously reported that taurine, L-glutamine, and quinoline-2-carboxaldehyde Schiff base copper complexes inhibit cell proliferation and proteasome activity in human cancer cells.

Normal hearing sensitivity at low-to-middle frequencies with 34% prestin-charge density.

The mammalian outer hair cells (OHCs) provide a positive mechanical feedback to enhance the cochlea's hearing sensitivity and frequency selectivity. Although the OHC-specific, somatic motor protein prestin is required for cochlear amplification, it remains unclear whether prestin can provide sufficient cycle-by-cycle feedback. In cochlear mechanical modeling, varying amounts of OHC motor activity should provide varying degrees of feedback efficiency to adjust the gain of cochlear amplifier at resonant frequencies.

40-De-oxy-40(S)-iodo-rapamycin.

The title compound, C(51)H(78)INO(12), contains a 29-membered ring incorporating amide, lactone and ester groups. It contains a total of 15 stereogenic centres. In the crystal, mol-ecules are linked by O-H⋯O hydrogen bonds, forming C(8) chains propagating in [100].

Regulation of p27Kip1 by Sox2 maintains quiescence of inner pillar cells in the murine auditory sensory epithelium.

Sox2 plays critical roles in cell fate specification during development and in stem cell formation; however, its role in postmitotic cells is largely unknown. Sox2 is highly expressed in supporting cells (SCs) of the postnatal mammalian auditory sensory epithelium, which unlike non-mammalian vertebrates remains quiescent even after sensory hair cell damage. Here, we induced the ablation of Sox2, specifically in SCs at three different postnatal ages (neonatal, juvenile and adult) in mice.

2-Amino-5-methyl-pyridinium nitrate.

In the title salt, C(6)H(9)N(2) (+)·NO(3) (-), the 2-amino-5-methyl-pyridinium cation and the nitrate anion are cyclically linked through pyridinium and amine N-H⋯O hydrogen bonds [graph set R(4) (3)(12)]. These units are extended into a zigzag chain structure lying parallel to the a axis, through a second cyclic R(2) (2)(8) association involving amine N-H⋯O and aromatic C-H⋯O hydrogen bonds to nitrate O-atom acceptors.

(E)-2-[2-(4-Chloro-benzyl-idene)hydrazin-yl]-4-[3-(morpholin-4-ium-4-yl)propyl-amino]-quinazolin-1-ium bis-(perchlorate).

In the title compound, C(22)H(27)ClN(6)O(2) (2+)·2ClO(4) (-), the mol-ecule adopts an E conformation about the C=N double bond. The quinazoline ring is approximately planar, with an r.m.

(2,2'-Bipyridine-κ(2)N,N'){N-[(2-oxidonaphthalen-1-yl-κO)methyl-idene]-l-valinato-κO}copper(II) trihydrate.

In the title complex, [Cu(C(16)H(15)NO(3))(C(10)H(8)N(2))]·3H(2)O, the Cu(II) atom is five coordinated by O,N,O'-donor atoms of the Schiff base ligand and by two N atoms of the 2,2'-bipyridine ligand in a distorted square-pyramidal geometry. In the crystal, mol-ecules are linked into a two-dimensional network parallel to (011) by O-H⋯O hydrogen bonds.

[Far-IR and THz absorption spectra studies of metronidazole, tinidazole and ornidazole].

Metronidazole, tinidazole and ornidazole are 5-nitro-imidazole medicines used particularly for anaerobic bacteria and protozoa infections. The present paper reports that terahertz time-domain spectroscopy (THz-TDS) and Fourier transform infrared spectroscopy (Far-FTIR) were used to measure the fingerprint spectra of metronidazole, tinidazole and ornidazole in the frequency range of 0.9 - 19.

41-Azido-41-de-oxy-rapamycin.

The title compound, C(51)H(78)N(4)O(12), is a derivative of rapamycin, a triene macrolide anti-biotic mol-ecule isolated from Streptomyces hygroscopicus. The macrocyclic ring structure has 15 chiral centres, with one of the substituent hy-droxy groups giving an intra-molecular hydrogen bond to a ketone O-atom acceptor. The mol-ecules also form inter-molecular hy-droxy-ketone O-H⋯O hydrogen-bonding associations, giving one-dimensional chains extending along (010).

(E)-2-[2-(4-Chloro-benzyl-idene)hydrazin-1-yl]-4-{[3-(dimethyl-aza-nium-yl)prop-yl]amino}-quinazolin-1-ium bis-(perchlorate).

In the title compound, C(20)H(25)ClN(6) (2+)·2ClO(4) (-), the organic cation is roughly planar, as shown by the dihedral angle of 3.78 (3)° between the quinazoline and chloro-phenyl rings. The quinazoline ring is itself approximately planar, with an average deviation of 0.

Age-dependent in vivo conversion of mouse cochlear pillar and Deiters' cells to immature hair cells by Atoh1 ectopic expression.

Unlike nonmammalian vertebrates, mammals cannot convert inner ear cochlear supporting cells (SCs) into sensory hair cells (HCs) after damage, thus causing permanent deafness. Here, we achieved in vivo conversion of two SC subtypes, pillar cells (PCs) and Deiters' cells (DCs), into HCs by inducing targeted expression of Atoh1 at neonatal and juvenile ages using novel mouse models. The conversion only occurred in ∼10% of PCs and DCs with ectopic Atoh1 expression and started with reactivation of endogenous Atoh1 followed by expression of 11 HC and synaptic markers, a process that took approximately 3 weeks in vivo.

In vivo proliferative regeneration of balance hair cells in newborn mice.

The regeneration of mechanoreceptive hair cells occurs throughout life in non-mammalian vertebrates and allows them to recover from hearing and balance deficits that affect humans and other mammals permanently. The irreversibility of comparable deficits in mammals remains unexplained, but often has been attributed to steep embryonic declines in cellular production. However, recent results suggest that gravity-sensing hair cells in murine utricles may increase in number during neonatal development, raising the possibility that young mice might retain sufficient cellular plasticity for mitotic hair cell regeneration.

Wnt signaling induces proliferation of sensory precursors in the postnatal mouse cochlea.

Inner ear hair cells are specialized sensory cells essential for auditory function. Previous studies have shown that the sensory epithelium is postmitotic, but it harbors cells that can behave as progenitor cells in vitro, including the ability to form new hair cells. Lgr5, a Wnt target gene, marks distinct supporting cell types in the neonatal cochlea.

Conditional gene expression in the mouse inner ear using Cre-loxP.

In recent years, there has been significant progress in the use of Cre-loxP technology for conditional gene expression in the inner ear. Here, we introduce the basic concepts of this powerful technology, emphasizing the differences between Cre and CreER. We describe the creation and Cre expression pattern of each Cre and CreER mouse line that has been reported to have expression in auditory and vestibular organs.

Myosin light-chain kinase is necessary for membrane homeostasis in cochlear inner hair cells.

The structural homeostasis of the cochlear hair cell membrane is critical for all aspects of sensory transduction, but the regulation of its maintenance is not well understood. In this report, we analyzed the cochlear hair cells of mice with specific deletion of myosin light chain kinase (MLCK) in inner hair cells. MLCK-deficient mice showed impaired hearing, with a 5- to 14-dB rise in the auditory brainstem response (ABR) thresholds to clicks and tones of different frequencies and a significant decrease in the amplitude of the ABR waves.

Enoxacin directly inhibits osteoclastogenesis without inducing apoptosis.

Enoxacin has been identified as a small molecule inhibitor of binding between the B2-subunit of vacuolar H+-ATPase (V-ATPase) and microfilaments. It inhibits bone resorption by calcitriol-stimulated mouse marrow cultures. We hypothesized that enoxacin acts directly and specifically on osteoclasts by disrupting the interaction between plasma membrane-directed V-ATPases, which contain the osteoclast-selective a3-subunit of V-ATPase, and microfilaments.

Overactivation of Notch1 signaling induces ectopic hair cells in the mouse inner ear in an age-dependent manner.

Background: During mouse inner ear development, Notch1 signaling first specifies sensory progenitors, and subsequently controls progenitors to further differentiate into either hair cells (HCs) or supporting cells (SCs). Overactivation of NICD (Notch1 intracellular domain) at early embryonic stages leads to ectopic HC formation. However, it remains unclear whether such an effect can be elicited at later embryonic or postnatal stages, which has important implications in mouse HC regeneration by reactivation of Notch1 signaling.

Novel Polypyridyl chelators deplete cellular zinc and destabilize the X-linked inhibitor of apoptosis protein (XIAP) prior to induction of apoptosis in human prostate and breast cancer cells.

X-linked inhibitor of apoptosis protein (XIAP), inhibits the initiation and execution phases of the apoptotic pathway. XIAP is the most potent member of the inhibitor of apoptosis protein (IAP) family of the endogenous caspase inhibitors. Therefore, targeting XIAP may be a promising strategy for the treatment of apoptosis-resistant malignancies.

In vivo Notch reactivation in differentiating cochlear hair cells induces Sox2 and Prox1 expression but does not disrupt hair cell maturation.

Background: Notch signaling is active in mouse cochlear prosensory progenitors but declines in differentiating sensory hair cells (HCs). Overactivation of the Notch1 intracellular domain (NICD) in progenitors blocks HC fate commitment and/or differentiation. However, it is not known whether reactivation of NICD in differentiating HCs also interrupts their developmental program and reactivates its downstream targets.

[Ultrastructural study on the facial nerve of rabbit after (125)I seed implantation].

Objective: To investigate the ultrastructural variation of the facial nerve of rabbit with different dosage of (125)I seed brachytherapy.

Methods: Fifty-four big ear rabbits were divided into 3 groups randomly and given 40 Gy, 80 Gy, 120 Gy respectively. Radioactive seeds were implanted in one side of parotid gland, the other side was implanted with vacant shell as a control group.

Transcriptional profiling identifies upregulated genes following induction of epithelial-mesenchymal transition in squamous carcinoma cells.

During the progression of head and neck squamous cell carcinoma (HNSCC), the induction of an epithelial-mesenchymal transition (EMT) program may play a critical role in the dissemination of cells from the primary tumor to distant metastatic foci. The process of EMT involves the activation of several important genes and pathways to help maintain survival and growth and evolve into highly invasive and metastatic variants. In this study, expression microarray analysis identified a set of 145 upregulated genes in EMT-like HNSCC cells.

(E)-3-(2-Hy-droxy-5-methyl-phenyl-imino)-indolin-2-one.

In the title compound, C(15)H(12)N(2)O(2), the dihedral angle between the two benzene rings is 83.55 (11)° In the crystal, the molecules are linked by O-H⋯O and N-H⋯O hydrogen bonds.

Assessment of the fecal lactobacilli population in patients with hepatitis B virus-related decompensated cirrhosis and hepatitis B cirrhosis treated with liver transplant.

This study aims to provide an overview of the diversity of intestinal Lactobacillus among Chinese patients with hepatitis B virus (HBV)-related decompensated cirrhosis and who received liver transplant for hepatitis B cirrhosis. Fecal samples were collected from 38 healthy volunteers, 61 patients with HBV-related decompensated cirrhosis (group LC) and 74 patients who had liver transplant for hepatitis B cirrhosis (group LT). Quantitative polymerase chain reaction technology with species-specific primers was applied to investigate lactobacilli 16S rDNA in crude DNA, extracted from fecal samples.