No abstract

Our group was the first one reporting that autophagy could be triggered by airborne fine particulate matter (PM) with a mean diameter of less than 2.5 μm (PM2.5) in human lung epithelial A549 cells, which could potentially lead to cell death. In the present study, we further explored the potential interactions between autophagy and apoptosis because it was well documented that PM2.5 could induce apoptosis in A549 cells. Much to our surprise, we found that PM2.5-exposure caused oxidative stress, resulting in activation of multiple cell death pathways in A549 cells, that is, the tumor necrosis factor-alpha (TNF-α)-induced pathway as evidenced by TNF-α secretion and activation of caspase-8 and -3, the intrinsic apoptosis pathway as evidenced by increased expression of pro-apoptotic protein Bax, decreased expression of anti-apoptotic protein Bcl-2, disruption of mitochondrial membrane potential, and activation of caspase-9 and -3, and autophagy as evidenced by an increased number of double-membrane vesicles, accompanied by increases of conversion and punctuation of microtubule-associated proteins light chain 3 (LC3) and expression of Beclin 1. It appears that reactive oxygen species (ROS) function as signaling molecules for all the three pathways because pretreatment with N-acetylcysteine, a scavenger of ROS, almost completely abolished TNF-α secretion and significantly reduced the number of apoptotic and autophagic cells. In another aspect, inhibiting autophagy with 3-methyladenine, a specific autophagy inhibitor, enhanced PM2.5-induced apoptosis and cytotoxicity. Intriguingly, neutralization of TNF-α with an anti-TNF-α special antibody not only abolished activation of caspase-8, but also drastically reduced LC3-II conversion. Thus, the present study has provided novel insights into the mechanism of cytotoxicity and even pathogenesis of diseases associated with PM2.5 exposure.

A 9-year-old bitch was presented because of lethargy and abdominal distension. Abdominal ultrasound revealed an enlarged, fluid-filled uterus and associated mass. Subsequent exploratory laparotomy revealed unilateral uterine torsion involving the mass. Recovery following ovariohysterectomy was uneventful and the histopathological diagnosis was of a benign endometrial inflammatory polyp. Reports of uterine torsion in the English-language literature are reviewed to identify factors associated with the incidence of uterine torsion. The aetiology of the cystic endometrial hyperplasia/pyometra complex and its possible role in the development of inflammatory polypoid lesions in the bitch is also discussed.

We demonstrate that electron-vibration-vibration two-dimensional infrared spectroscopy (EVV 2DIR) can be used to detect the binding of a drug to a target protein-active site. The EVV 2DIR spectrum of the FGFR1 kinase target protein is found to have ∼200 detectable cross-peaks in the spectral region 1250–1750 cm–1/2600–3400 cm–1, with additional 63 peaks caused by the addition of a drug, SU5402. Of these 63 new peaks, it is shown that only six are due to protein–drug interactions, with the other 57 being due to vibrational coupling within the drug itself. Quantum mechanical calculations employing density functional theory are used to support assignment of the six binding-dependent peaks, with one being assigned to a known interaction between the drug and a backbone carbonyl group which forms part of the binding site. None of the 57 intramolecular coupling peaks associated with the drug molecule change substantially in either intensity or frequency when the drug binds to the target protein. This strongly suggests that the structure of the drug in the target binding site is essentially identical to that when it is not bound.

A transverse pressure pulse decay (TPPD) method is presented to measure transverse permeability of tight reservoir cores in a cell with finite volume. Given appropriate assumptions, a mathematical model based on the specially designed experiment is formulated, and its general solution is proposed. Early‐time and late‐time techniques are further presented for convenient postprocessing applications of experimental data. Meanwhile, sensitivity analysis of TPPD method is given. It is found that a good TPPD experimental principle can be obtained by adjusting test gas, experimental pressure, dimension of core sample, and volume ratio (λ). The volume ratio error (λerror) analysis reveals the following: (1) a larger λerror results in increased transverse permeability error (kerror); (2) the volume ratio (λ) is better not very close to 0.754; (3) when λ is equal to or greater than 1, the kerror resulting from λerror is monotonic decreasing as the volume ratio increases. In practice, λ is usually equal to or greater than 1 due to the very small pore volume of a tight core. But this does not mean that the volume ratio should be as large as possible. The reason for this is that a pressure transducer with higher resolution is needed to record pressure change. That means experimental apparatus is much more costly. And such a TPPD experiment requires a much longer time to attain the late‐time straight line behavior. The best choice is to find an optimal balance point among experimental cost, time, and accuracy.