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Neutrophil extracellular traps (NETs) are produced by neutrophil activation and usually have both anti-infective and pro-damage effects. Streptococcus uberis (S. uberis), one of the common causative organisms of mastitis, can lead to the production of NETs. Taurine, a free amino acid abundant in the organism, has been shown to have immunomodulatory effects. In this study, we investigated the molecular mechanisms of S. uberis-induced NETs formation and the regulatory role of taurine. The results showed that NETs had a disruptive effect on mammary epithelial cells and barriers, but do not significantly inhibit the proliferation of S. uberis. S. uberis induced NADPH oxidase-dependent NETs. TLR2-mediated activation of the MAPK signaling pathway was involved in this process. Taurine could inhibit the activation of MAPK signaling pathway and NADPH oxidase by modulating the activity of TAK1, thereby inhibiting the production of ROS and NETs. The effects of taurine on NADPH oxidase and NETs in S. uberis infection were also demonstrated in vivo. These results suggest that taurine can protect mammary epithelial cells and barriers from damage by reducing S. uberis-induced NETs. These data provide new insights and strategies for the prevention and control of mastitis.

Background Pancreatic ductal adenocarcinoma (PDAC) has the worst five-year overall survival rate among all cancer types. Acquired chemoresistance is considered one of the main reasons for this dismal prognosis, and the mechanism of chemoresistance is unknown. Methods We previously identified a subpopulation of chemoresistant CD44high-expressing PDAC cells. Subsequently, we selected the candidate gene, gamma-aminobutyric acid receptor subunit Pi (GABRP), from three Gene Expression Omnibus datasets as the potential CD44 downstream target mediating the gemcitabine resistance. Loss and gain of function such as stable knockdown of CD44 by small hairpin (sh) RNA-mediated silencing technique and overexpression (O/E) of CD44s had been studied for comparing the gemcitabine resistance among CD44high-expressing cells, shCD44 cells, CD44low-expressing cells and O/E CD44s expressing cells. Functional assays including cell viability, colony formation, invasion, quantitative PCR and western blotting techniques were performed to validate the roles of CD44 and GABRP playing in mediating the gemcitabine resistance in pancreatic cancer cells. Results CD44s depletion significantly reduced gemcitabine resistance in shCD44 single clone cells compared to CD44high-expressing cells. Knockdown of CD44 cells formed less colonies, became less invasive and remarkably decreased the mRNA level of GABRP. While overexpression of CD44s had the opposite effect on gemcitabine resistance, colony formation and invasive property. Of note, long term gemcitabine resistant pancreatic cancer cells detected increased expression of CD44 and GABRP. Clinically, GABRP expression was significantly upregulated in the tissues of patients with pancreatic cancer compared to the normal samples, and the overall survival rate of patients with low GABRP expression was longer. CD44 and GABRP co-expression was positively correlated in 178 pancreatic cancer patients. Conclusion Our findings suggest that GABRP may serve as a CD44s downstream target to diminish gemcitabine resistance in pancreatic cancer, and both CD44s and GABRP molecules have the potential to become prognostic biomarkers for PDAC patients with gemcitabine resistance.

The paper uses a magnetic modulation current transformer method to detect transient waveform residual currents containing pulsating DC components and even smooth DC components. At the same time, it uses IIR-based digital low-pass filters to filter the collected signals, which improves Filtering accuracy. The software design is based on the floating-point DSP-TMS320F28335, which realizes the accurate sampling and analysis of the transient waveform residual current, and the transient waveform residual current detection meets the standard requirements.

Neutrophil extracellular traps (NETs) are produced by neutrophil activation and usually have both anti-infective and pro-damage effects. Streptococcus uberis (S. uberis), one of the common causative organisms of mastitis, can lead to the production of NETs. Taurine, a free amino acid abundant in the organism, has been shown to have immunomodulatory effects. In this study, we investigated the molecular mechanisms of S. uberis-induced NETs formation and the regulatory role of taurine. The results showed that NETs had a disruptive effect on mammary epithelial cells and barriers, but do not significantly inhibit the proliferation of S. uberis. S. uberis induced NADPH oxidasedependent NETs. TLR2-mediated activation of the MAPK signaling pathway was involved in this process. Taurine could inhibit the activation of MAPK signaling pathway and NADPH oxidase by modulating the activity of TAK1, thereby inhibiting the production of ROS and NETs. The effects of taurine on NADPH oxidase and NETs in S. uberis infection were also demonstrated in vivo. These results suggest that taurine can protect mammary epithelial cells and barriers from damage by reducing S. uberis-induced NETs. These data provide new insights and strategies for the prevention and control of mastitis. [ABSTRACT FROM AUTHOR]