Flightless-I regulates proinflammatory caspases by selectively modulating intracellular localization and caspase activity

Caspase-1 and caspase-11 are proinflammatory caspases that regulate cytokine production and leukocyte migration during pathogen infection. In an attempt to identify new intracellular regulators of caspase-11, we found that Flightless-I, a member of the gelsolin superfamily of actin-remodeling proteins, interacts and regulates both caspase-11 and caspase-1. Flightless-I targets caspase-11 to the Triton X-100–insoluble cytoskeleton fraction and the cell leading edge. In addition, Flightless-I inhibits caspase-1 activation and caspase-1–mediated interleukine-1β (IL-1β) maturation. The physiological relevance of these findings is supported by the opposing effects of Flightless-I overexpression and knockdown on caspase-1 activity and IL-1β maturation. Our results suggest that Flightless-I may be a bona fide caspase-1 inhibitor that acts through a mechanism similar to that of cytokine response modifier A, a potent caspase-1 inhibitor from the cowpox virus. Our study provides a new mechanism controlling the localization and activation of proinflammatory caspases

Defining key metabolic roles in osmotic adjustment and ROS homeostasis in the recretohalophyte Karelinia caspia under salt stress

The recretohalophyte Karelinia caspia is of forage and medical value and can remediate saline soils. We here assess the contribution of primary/secondary metabolism to osmotic adjustment and ROS homeostasis in Karelinia caspia under salt stress using multi‐omic approaches. Computerized phenomic assessments, tests for cellular osmotic changes and lipid peroxidation indicated that salt treatment had no detectable physical effect on K. caspia. Metabolomic analysis indicated that amino acids, saccharides, organic acids, polyamine, phenolic acids, and vitamins accumulated significantly with salt treatment. Transcriptomic assessment identified differentially expressed genes closely linked to the changes in above primary/secondary metabolites under salt stress. In particular, shifts in carbohydrate metabolism (TCA cycle, starch and sucrose metabolism, glycolysis) as well as arginine and proline metabolism were observed to maintain a low osmotic potential. Chlorogenic acid/vitamin E biosynthesis was also enhanced, which would aid in ROS scavenging in the response of K. caspia to salt. Overall, our findings define key changes in primary/secondary metabolism that are coordinated to modulate the osmotic balance and ROS homeostasis to contribute to the salt tolerance of K. caspia

ROS scavenging and ion homeostasis is required for the adaptation of halophyte Karelinia caspia to high salinity

The halophyte Karelinia caspia has not only fodder and medical value but also can remediate saline-alkali soils. Our previous study showed that salt-secreting by salt glands is one of main adaptive strategies of K. caspia under high salinity. However, ROS scavenging, ion homeostasis, and photosynthetic characteristics responses to high salinity remain unclear in K. caspia. Here, physio-biochemical responses and gene expression associated with ROS scavenging and ions transport were tested in K. caspia subjected to 100–400 mM NaCl for 7 days. Results showed that both antioxidant enzymes (SOD, APX) activities and non-enzymatic antioxidants (chlorogenic acid, α-tocopherol, flavonoids, polyamines) contents were significantly enhanced, accompanied by up-regulating the related enzyme and non-enzymatic antioxidant synthesis gene (KcCu/Zn-SOD, KcAPX6, KcHCT, KcHPT1, Kcγ-TMT, KcF3H, KcSAMS and KcSMS) expression with increasing concentrations of NaCl. These responses are beneficial for removing excess ROS to maintain a stable level of H(2)O(2) and O(2)(−) without lipid peroxidation in the K. caspia response to high salt. Meanwhile, up-regulating expression of KcSOS1/2/3, KcNHX1, and KcAVP was linked to Na(+) compartmentalization into vacuoles or excretion through salt glands in K. caspia. Notably, salt can improve the function of PSII that facilitate net photosynthetic rates, which is helpful to growing normally in high saline. Overall, the findings suggested that ROS scavenging systems and Na(+)/K(+) transport synergistically contributed to redox equilibrium, ion homeostasis, and the enhancement of PSII function, thereby conferring high salt tolerance

Effects of propofol combined with remifentanil on hemodynamics and stress response in children undergoing surgery for oral cancers, tonsil and adenoid surgery

727-733The anesthetic medication to sedate a child during general anesthesia (GA) for oral cancer, adenoidectomy or tonsillectomy is associated with operative complications such as hemodynamic instability and long postoperative recovery period. The current advancement enables combination of different anesthetic medications to decrease operative or postoperative complications associated with GA. In this study assessed the effects of propofol combined with remifentanil on hemodynamics and stress response in children undergoing oral cancer, tonsil and adenoid surgery. Propofol combined with remifentanil is beneficial to anesthesia for children undergoing oral cancer tonsil and adenoid surgery, manifested as stable hemodynamics, rapid recovery, low inflammatory and stress responses, and mild adverse reactions. A total of 106 eligible children treated from May 2017 to December 2019 were randomly divided into observation and control groups (n=53). Observation group was anesthetized by propofol plus remifentanil, while control group was anesthetized by propofol plus esketamine. Mean arterial pressure (MAP), heart rate (HR), serum C-reactive protein (CRP), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), epinephrine (E), cortisol (Cor), CD3+, CD4+ helper and CD8+ inhibitory T lymphocytes, and CD4+/CD8+were compared before anesthesia induction (T1), immediately after intubation (T2), at the beginning of operation (T3), at the end of operation (T4) and 5 min after extubation (T5). Time of anesthetic recovery and adverse reactions after extubation were observed. MAP and HR significantly rose at T2 compared with those at T1. After maintenance of anesthesia, MAP and HR were significantly lower in observation group than those in control group. Serum CRP, IL-6 and TNF-α levels rose with time. E and Cor levels rose from T1 to T4 and declined at T5, with significant differences at each time point. CRP, IL-6, TNF-α, E and Cor levels were lower in observation group from T3 to T5. At T4 and T5, CD3+, CD4+levels and CD4+/CD8+ declined, whileCD8+level rose compared with those at other three time points. Time of recovery of autonomous respiration and limbs and duration from anesthetic withdrawal to extubation were significantly shorter in observation group. Observation group had lower incidence rate of dysphoria during recovery

Effects of propofol combined with remifentanil on hemodynamics and stress response in children undergoing surgery for oral cancers, tonsil and adenoid surgery

The anesthetic medication to sedate a child during general anesthesia (GA) for oral cancer, adenoidectomy or tonsillectomy is associated with operative complications such as hemodynamic instability and long postoperative recovery period. The current advancement enables combination of different anesthetic medications to decrease operative or postoperative complications associated with GA. In this study assessed the effects of propofol combined with remifentanil on hemodynamics and stress response in children undergoing oral cancer, tonsil and adenoid surgery. Propofol combined with remifentanil is beneficial to anesthesia for children undergoing oral cancer tonsil and adenoid surgery, manifested as stable hemodynamics, rapid recovery, low inflammatory and stress responses, and mild adverse reactions. A total of 106 eligible children treated from May 2017 to December 2019 were randomly divided into observation and control groups (n=53). Observation group was anesthetized by propofol plus remifentanil, while control group was anesthetized by propofol plus esketamine. Mean arterial pressure (MAP), heart rate (HR), serum C-reactive protein (CRP), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), epinephrine (E), cortisol (Cor), CD3+, CD4+ helper and CD8+ inhibitory T lymphocytes, and CD4+/CD8+were compared before anesthesia induction (T1), immediately after intubation (T2), at the beginning of operation (T3), at the end of operation (T4) and 5 min after extubation (T5). Time of anesthetic recovery and adverse reactions after extubation were observed. MAP and HR significantly rose at T2 compared with those at T1. After maintenance of anesthesia, MAP and HR were significantly lower in observation group than those in control group. Serum CRP, IL-6 and TNF-α levels rose with time. E and Cor levels rose from T1 to T4 and declined at T5, with significant differences at each time point. CRP, IL-6, TNF-α, E and Cor levels were lower in observation group from T3 to T5. At T4 and T5, CD3+, CD4+levels and CD4+/CD8+ declined, whileCD8+level rose compared with those at other three time points. Time of recovery of autonomous respiration and limbs and duration from anesthetic withdrawal to extubation were significantly shorter in observation group. Observation group had lower incidence rate of dysphoria during recovery