BackgroundEndometrial carcinoma is one of the most common gynecological malignancies in women. The diagnosis of the disease at early or premalignant stages is crucial for the patient's prognosis. To date, diagnosis and follow-up of endometrial carcinoma and hyperplasia require invasive procedures. Therefore, there is considerable demand for the identification of biomarkers to allow non-invasive detection of these conditions.MethodsIn this study, we performed a quantitative proteomics analysis on serum samples from simple endometrial hyperplasia, complex endometrial hyperplasia, atypical endometrial hyperplasia, and endometrial carcinoma patients, as well as healthy women. Serum samples were first depleted of high-abundance proteins, labeled with isobaric tags (iTRAQ™), and then analyzed via two-dimensional liquid chromatography and tandem mass spectrometry. Protein identification and quantitation information were acquired by comparing the mass spectrometry data against the International Protein Index Database using ProteinPilot software. Bioinformatics annotation of identified proteins was performed by searching against the PANTHER database.ResultsIn total, 74 proteins were identified and quantified in serum samples from endometrial lesion patients and healthy women. Using a 1.6-fold change as the benchmark, 12 proteins showed significantly altered expression levels in at least one disease group compared with healthy women. Among them, 7 proteins were found, for the first time, to be differentially expressed in atypical endometrial hyperplasia. These proteins are orosomucoid 1, haptoglobin, SERPINC 1, alpha-1-antichymotrypsin, apolipoprotein A-IV, inter-alpha-trypsin inhibitor heavy chain H4, and histidine-rich glycoprotein.ConclusionsThe differentially expressed proteins we discovered in this study may serve as biomarkers in the diagnosis and follow-up of endometrial hyperplasia and endometrial carcinoma.

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Here we report a series of classical molecular dynamics simulations for the icosahedral Au nanoparticles with four different diameters of 1.0, 1.4, 1.8, and 2.3 nm in 1-butyl-3-methylimidazolium tetrafluoroborate ([bmim]­[BF4]) room-temperature ionic liquid (RTIL). Our simulation results reveal for the first time a size-dependent stabilization mechanism of the Au nanoparticles in the [bmim]­[BF4] RTIL, which may help to clarify the relevant debate on the stabilization mechanism from various experimental observations. By comparison, the alkyl chains in the [bmim]+ cations are found to dominate the stabilization of the smallest Au13 nanoparticle in the RTIL while the imidazolium rings should be mainly responsible for the stabilization of other larger nanoparticles in the RTIL. Compared to the [bmim]+ cations, the [BF4]− anions are found to have an indirect influence on stabilizing the Au nanoparticles in the RTIL because of the weak interaction between the Au nanoparticles and the anions. However, such differences in the stabilization mechanism between the small and the large Au nanoparticles can be attributed to the unique hydrogen bond (HB) network between the cations and the anions in the first solvation shell. Meanwhile, increasing the particle size can lead to the enhanced HBs on the surface of Au nanoparticles, so slower rotational motions and more pronounced orientation distribution of cations can be observed around the larger nanoparticles. Our simulation results in this work provide a molecular-level understanding of the unique size-dependent stabilization mechanism of the Au nanoparticles in the imidazolium-based RTILs.

Radiotherapy is one of the most common treatment options for local or regional advanced prostate cancer (PCa). Importantly, PCa is prone to radioresistance and often develops into malignancies after long-term radiotherapy. Antrocin, a sesquiterpene lactone isolated from Antrodia cinnamomea, possesses pharmacological efficacy against various cancer types; however, its therapeutic potential requires comprehensive exploration, particularly in radioresistant PCa cells. In this study, we emphasized the effects of antrocin on radioresistant PCa cells and addressed the molecular mechanism underlying the radiosensitization induced by antrocin. Our results showed that a combination treatment with antrocin and ionizing radiation (IR) synergistically inhibited cell proliferation and induced apoptosis in radioresistant PCa cells. We further demonstrated that antrocin downregulated PI3K/AKT and MAPK signaling pathways as well as suppressed type 1 insulin-like growth factor 1 receptor (IGF-1R)-mediated induction of β-catenin to regulate cell cycle and apoptosis. Using xenograft mouse models, we showed that antrocin effectively enhanced radiotherapy in PCa. Our study demonstrates that antrocin sensitizes PCa to radiation through constitutive suppression of IGF-1R downstream signaling, revealing that it can be developed as a potent therapeutic agent to overcome radioresistant PCa.

The structures and relevant vibrational spectra of an ethylammonium nitrate (EAN) ionic liquid (IL) confined in single-walled carbon nanotubes (SWCNTs) with various diameters have been investigated in detail by using classical molecular dynamics simulation. Our simulation results demonstrate that the EAN IL confined in larger SWCNTs can form well-defined multishell structures with an additional cation chain located at the center. However, a different single-shell hollow structure has been found for both the cations and the anions in the 1 nm SWCNT. For the cations confined in SWCNTs, the CH3 groups stay closer to the nanotube walls because of their solvophobic nature, while the NH3 + groups prefer to point toward the central axis. Accordingly, the NO3 – anions tend to lean on the SWCNT surface with three O atoms facing the central axis to form hydrogen bonds (HBs) with the NH3 + groups. In addition, in the 1 nm SWCNT, the CH3 groups of cations exhibit an obvious blue shift of around 16 cm–1 for the C–H stretching mode with respect to the bulk value, and the N–H stretching mode of NH3 + groups is split into two characteristic peaks with one peak appearing at a higher frequency. Such a blue shift is attributed to the existence of more free space for the C–H bonds of confined CH3 groups, while the splitting phenomenon is due to the fact that more than 60% of the confined NH3 + groups have one dangling N–H bond. For the anions confined in the 1 nm SWCNT, the N–O stretching mode of NO3 – has a maximum red shift of around 24 cm–1 with respect to the bulk value, which is attributed to enhanced HBs between anions and cations. Our simulation results reveal a molecular-level correlation between confined structural configurations and the corresponding vibrational spectra changes for the ILs confined in nanometer scale environments.

The nucleotide sequences of the dnaQ genes from Salmonella typhimurium and Buchnera aphidicola, encoding the ε-subunit of the DNA polymerase III holoenzyme, have been determined. The Salmonella typhimurium dnaQ protein consists of 243 amino acid residues with a calculated molecular weight of 27224. The Buchnera aphidicola dnaQ protein contains 233 amino acid residues with a calculated molecular weight of 27170. A multiple sequence alignment of the amino acid sequences of the dnaQ proteins and those of DNA polymerase ms from Grampositive bacteria produced six homologous segments. These homologous segments contain highly conserved amino acid sequence motifs involved in catalytically important metal ion bindings (ligands 1,2 and 3). However, metal ligand 4 is found to be altered in the 3'-5' exonuclease domain of the family C DNA polymerases and dnaQ proteins in Gram-negative bacteria. From these results, we propose that the last common ancestor of the dnaQ gene of Gram-negative bacteria and the DNA polymerase ΙΠ gene (pol C gene) of Gram-positive bacteria was a single gene containing both 3'-5' exonuclease and DNA polymerase domains and then the dnaQ gene separated from the polymerase gene in Gram-negative bacteria.

Molecular dynamics simulations have been performed to explore the solvation structures and vibrational spectra of an ethylammonium nitrate (EAN) ionic liquid (IL) around various single-walled carbon nanotubes (SWNTs). Our simulation results demonstrate that both cations and anions show a cylindrical double-shell solvation structure around the SWNTs regardless of the nanotube diameter. In the first solvation shell, the CH 3 groups of cations are found to be closer to the SWNT surface than the NH 3 + groups because of the solvophobic nature of the CH 3 groups, while the NO 3 − anions tend to lean on the nanotube surface, with three O atoms facing the bulk EAN. On the other hand, the intensities of both C−H (the CH 3 group of the cation) and N−O (anion) asymmetric stretching bands at the EAN/SWNT interface are found to be slightly higher than the corresponding bulk values owing to the accumulation and orientation of cations and anions in the first solvation shell. More interestingly, the N−O stretching band exhibits a red shift of around 10 cm −1 with respect to the bulk value, which is quite contrary to the blue shift of the O−H stretching band of water molecules at the hydrophobic interfaces. Such a red shift of the N−O stretching mode can be attributed to the enhanced hydrogen bonds (HBs) of the NO 3 − anions in the first solvation shell. Our simulation results provide a molecular-level understanding of the interfacial vibrational spectra of an EAN IL on the SWNT surface and their connection with the relevant solvation structures and interfacial HBs.