Alkaline Aerosols: An Initial Investigation of Their Role in Determining Precipitation Acidity

published or submitted for publicationis peer reviewedOpe

Hypothermic manipulation of bone cement can extend the handling time during vertebroplasty

BACKGROUND: Polymethylmethacrylate (PMMA) is commonly used for clinical applications. However, the short handling time increases the probability of a surgeon missing the crucial period in which the cement maintains its ideal viscosity for a successful injection. The aim of this article was to illustrate the effects a reduction in temperature would have on the cement handling time during percutaneous vertebroplasty. METHODS: The injectability of bone cement was assessed using a cement compressor. By twisting the compressor, the piston transmits its axial load to the plunger, which then pumps the bone cement out. The experiments were categorized based on the different types of hypothermic manipulation that were used. In group I (room temperature, sham group), the syringes were kept at 22°C after mixing the bone cement. In group 2 (precooling the bone cement and the container), the PMMA powder and liquid, as well as the beaker, spatula, and syringe, were stored in the refrigerator (4°C) overnight before mixing. In group 3 (ice bath cooling), the syringes were immediately submerged in ice water after mixing the bone cement at room temperature. RESULTS: The average liquid time, paste time, and handling time were 5.1 ± 0.7, 3.4 ± 0.3, and 8.5 ± 0.8 min, respectively, for group 1; 9.4 ± 1.1, 5.8 ± 0.5, and 15.2 ± 1.2 min, respectively, for group 2; and 83.8 ± 5.2, 28.8 ± 6.9, and 112.5 ± 11.3 min, respectively, for group 3. The liquid and paste times could be increased through different cooling methods. In addition, the liquid time (i.e. waiting time) for ice bath cooling was longer than for that of the precooling method (p < 0.05). CONCLUSIONS: Both precooling (i.e. lowering the initial temperature) and ice bath cooling (i.e. lowering the surrounding temperature) can effectively slow polymerization. Precooling is easy for clinical applications, while ice bath cooling might be more suitable for multiple-level vertebroplasty. Clinicians can take advantage of the improved injectability without any increased cost

Src-family kinase-Cbl axis negatively regulates NLRP3 inflammasome activation.

Activation of the NLRP3 inflammasome is crucial for immune defense, but improper and excessive activation causes inflammatory diseases. We previously reported that Pyk2 is essential for NLRP3 inflammasome activation. Here we show that the Src-family kinases (SFKs)-Cbl axis plays a pivotal role in suppressing NLRP3 inflammasome activation in response to stimulation by nigericin or ATP, as assessed using gene knockout and gene knockdown cells, dominant active/negative mutants, and pharmacological inhibition. We reveal that the phosphorylation of Cbl is regulated by SFKs, and that phosphorylation of Cbl at Tyr371 suppresses NLRP3 inflammasome activation. Mechanistically, Cbl decreases the level of phosphorylated Pyk2 (p-Pyk2) through ubiquitination-mediated proteasomal degradation and reduces mitochondrial ROS (mtROS) production by contributing to the maintenance of mitochondrial size. The lower levels of p-Pyk2 and mtROS dampen NLRP3 inflammasome activation. In vivo, inhibition of Cbl with an analgesic drug, hydrocotarnine, increases inflammasome-mediated IL-18 secretion in the colon, and protects mice from dextran sulphate sodium-induced colitis. Together, our novel findings provide new insights into the role of the SFK-Cbl axis in suppressing NLRP3 inflammasome activation and identify a novel clinical utility of hydrocortanine for disease treatment

Pyk2 activates the NLRP3 inflammasome by directly phosphorylating ASC and contributes to inflammasome-dependent peritonitis

The inflammasome adaptor protein, ASC, contributes to both innate immune responses and inflammatory diseases via self-oligomerization, which leads to the activation of the protease, caspase-1. Here, we report that the cytosolic tyrosine kinases, FAK and Pyk2, are differentially involved in NLRP3 and AIM2 inflammasome activation. The inhibition of FAK and Pyk2 with RNA interference or chemical inhibitors dramatically abolished ASC oligomerization, caspase-1 activation, and IL-1β secretion in response to NLRP3 or AIM2 stimulation. Pyk2 is phosphorylated by the kinase Syk and relocalizes to the ASC specks upon NLRP3 inflammasome activation. Pyk2, but not FAK, could directly phosphorylate ASC at Tyr146, and only the phosphorylated ASC could participate in speck formation and trigger IL-1β secretion. Moreover, the clinical-trial-tested Pyk2/FAK dual inhibitor PF-562271 reduced monosodium urate-mediated peritonitis, a disease model used for studying the consequences of NLRP3 activation. Our results suggest that although Pyk2 and FAK are involved in inflammasome activation, only Pyk2 directly phosphorylates ASC and brings ASC into an oligomerization-competent state by allowing Tyr146 phosphorylation to participate ASC speck formation and subsequent NLRP3 inflammation

Serotonin receptor HTR6-mediated mTORC1 signaling regulates dietary restriction-induced memory enhancement

Dietary restriction (DR; sometimes called calorie restriction) has profound beneficial effects on physiological, psychological, and behavioral outcomes in animals and in humans. We have explored the molecular mechanism of DR-induced memory enhancement and demonstrate that dietary tryptophan-a precursor amino acid for serotonin biosynthesis in the brain-and serotonin receptor 5-hydroxytryptamine receptor 6 (HTR6) are crucial in mediating this process. We show that HTR6 inactivation diminishes DR-induced neurological alterations, including reduced dendritic complexity, increased spine density, and enhanced long-term potentiation (LTP) in hippocampal neurons. Moreover, we find that HTR6-mediated mechanistic target of rapamycin complex 1 (mTORC1) signaling is involved in DR-induced memory improvement. Our results suggest that the HTR6-mediated mTORC1 pathway may function as a nutrient sensor in hippocampal neurons to couple memory performance to dietary intake

Study of Atmospheric Pollution Scavenging: Twentieth Progress Report

published or submitted for publicationis peer reviewedOpe

Women with endometriosis have higher comorbidities: Analysis of domestic data in Taiwan

AbstractEndometriosis, defined by the presence of viable extrauterine endometrial glands and stroma, can grow or bleed cyclically, and possesses characteristics including a destructive, invasive, and metastatic nature. Since endometriosis may result in pelvic inflammation, adhesion, chronic pain, and infertility, and can progress to biologically malignant tumors, it is a long-term major health issue in women of reproductive age. In this review, we analyze the Taiwan domestic research addressing associations between endometriosis and other diseases. Concerning malignant tumors, we identified four studies on the links between endometriosis and ovarian cancer, one on breast cancer, two on endometrial cancer, one on colorectal cancer, and one on other malignancies, as well as one on associations between endometriosis and irritable bowel syndrome, one on links with migraine headache, three on links with pelvic inflammatory diseases, four on links with infertility, four on links with obesity, four on links with chronic liver disease, four on links with rheumatoid arthritis, four on links with chronic renal disease, five on links with diabetes mellitus, and five on links with cardiovascular diseases (hypertension, hyperlipidemia, etc.). The data available to date support that women with endometriosis might be at risk of some chronic illnesses and certain malignancies, although we consider the evidence for some comorbidities to be of low quality, for example, the association between colon cancer and adenomyosis/endometriosis. We still believe that the risk of comorbidity might be higher in women with endometriosis than that we supposed before. More research is needed to determine whether women with endometriosis are really at risk of these comorbidities