p38 MAPK对嗜酸性粒细胞和支气管上皮细胞共培养时细胞因子释放的调控作用

目的 了解嗜酸性粒细胞和支气管上皮细胞相互作用诱导细胞因子释放的p38 MAPK信号转导通路.方法 用CD16磁珠抗体分离外周血中嗜酸性粒细胞,以嗜酸性粒细胞和支气管上皮细胞(BEAS-2B)接触共培养为实验模型,观察SB 203580对细胞培养上清液中细胞因子浓度的影响.细胞因子浓度采用ELISA和流式细胞微珠方法测定.结果 SB 203580能够有效抑制BEAS-2B细胞释放IL-6、IL-8(P＜0.05)和嗜酸性粒细胞释放IL-8(P＜0.01).SB 203580对嗜酸性粒细胞与BEAS-2B细胞接触共培养诱导的IL-6、IL-8和IP-10释放具有显著抑制作用(P＜0.001).结论 嗜酸性粒细胞、BEAS-2B细胞单独或相互作用时均通过p38 MAPK信号转导通路释放细胞因子.     

Tryptophan 650 of human granulocyte colony-stimulating factor (G-CSF) receptor, implicated in the activation of JAK2, is also required for G- CSF-mediated activation of signaling complexes of the p21ras route

Granulocyte colony-stimulating factor (G-CSF) induces rapid phosphorylation of JAK kinases as well as activation of the p21ras route through interaction with its specific receptor (G-CSF-R). The cytoplasmic membrane-proximal region of G-CSF-R (amino acids 631 to 684) is necessary for proliferation induction and activation of JAK2. In contrast, activation of Shc and Syp, signaling molecules implicated in the p21ras signaling route, depends on the phosphorylation of tyrosine residues located in the membrane-distal region (amino acids 685 to 813) of G-CSF-R. We investigated whether G-CSF-induced activation of signaling complexes of the p21ras route depends on the function of the membrane-proximal cytoplasmic region of G-CSF-R. A G- CSF-R mutant was constructed in which tryptophan 650 was replaced by arginine and expressed in BAF3 cells (BAF/W650R). In contrast to BAF3 cell transfectants expressing wild-type G-CSF-R, BAF/W650-R cells did not proliferate and did not show activation of JAK2, STAT1, or STAT3 in response to G-CSF. Immunoprecipitations with anti-Shc and anti-Grb2 antisera showed that mutant W650R also failed to activate Syp and Shc. These data indicate that the membrane-proximal cytoplasmic domain of G- CSF-R is not only crucial for proliferative signaling and activation of JAK2 and STATs, but is also required for activation of the p21ras route, which occurs via the membrane-distal region of G-CSF-R.     

Cross-match-compatible platelets improve corrected count increments in patients who are refractory to randomly selected platelets

Background

Cross-match-compatible platelets are used for the management of thrombocytopenic patients who are refractory to transfusions of randomly selected platelets. Data supporting the effectiveness of platelets that are compatible according to cross-matching with a modified antigen capture enzyme-linked immunosorbent assay (MAC-ELISA or MACE) are limited. This study aimed to determine the effectiveness of cross-match-compatible platelets in an unselected group of refractory patients.

Materials and methods

One hundred ABO compatible single donor platelet transfusions given to 31 refractory patients were studied. Patients were defined to be refractory if their 24-hour corrected count increment (CCI) was <5×10⁹/L following two consecutive platelet transfusions. Platelets were cross-matched by MACE and the CCI was determined to monitor the effectiveness of platelet transfusions.

Results

The clinical sensitivity, specificity, positive predictive value and negative predictive value of the MACE-cross-matched platelets for post-transfusion CCI were 88%, 54.6%, 39.3% and 93.2%, respectively. The difference between adequate and inadequate post-transfusion 24-hour CCI for MACE cross-matched-compatible vs incompatible single donor platelet transfusions was statistically significant (p=0.000). The 24-hour CCI (mean±SD) was significantly higher for cross-match-compatible platelets (9,250±026.6) than for incompatible ones (6,757.94±2,656.5) (p<0.0001). Most of the incompatible cross-matches (73.2%) were due to anti-HLA antibodies, alone (55.3% of cases) or together with anti-platelet glycoprotein antibodies (17.9%).

Discussion

The clinical sensitivity and negative predictive value of platelet cross-matching by MACE were high in this study and such tests may, therefore, be used to select compatible platelets for refractory patients. A high negative predictive value demonstrates the greater chance of an adequate response with cross-matched-compatible platelets.     

Coronavirus Disease-2019 (COVID-19) and the Liver

Within a year of its emergence, coronavirus disease-2019 (COVID-19) has evolved into a pandemic. What has emerged during the past 1 year is that, apart from its potentially fatal respiratory presentation from which the severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) derives its name, it presents with a myriad of gastrointestinal (GI) and liver manifestations. Expression of the angiotensin-converting enzyme-2 (ACE-2) receptor throughout the GI tract and liver, which is the receptor for the SARS-CoV-2, may be responsible for the GI and liver manifestations. Besides acting directly via the ACE-2 receptor, the virus triggers a potent immune response, which might have a role in pathogenesis. The virus leads to derangement in liver function tests in close to 50% of the patients. The impact of these derangements in patients with a normal underlying liver seems to be innocuous. Severe clinical presentations include acute decompensation and acute-on-chronic liver failure in a patient with chronic liver disease, leading to high mortality. Evolving data suggests that, contrary to intuition, liver transplant recipients and patients with autoimmune liver disease on immunosuppression do not have increased mortality. The exact mechanism underlying why immunosuppressed patients fare well as compared to other patients remains to be deciphered. With newer variants of COVID-19, which can spread faster than the original strain, the data on hepatic manifestations needs to be updated to keep a step ahead of the virus.     

一叶萩的化学成分

目的：对一叶萩枝叶的化学成分进行研究。方法：应用各种色谱技术从一叶萩总碱部位中分离化合物，根据理化常数和波谱（NMR及MS等）分析方法对化合物的结构进行鉴定。结果：自一叶萩枝叶的总碱部位中分离得到11个化合物。分别鉴定为：（-）-15β-ethoxy-14，15-dihvdroviroallosecurinine（1），一叶萩碱（securinine，2），二氢一叶萩碱（14，15-dihydrosecurinine，3），4-epiph），llanthine（4），securitinine（5），右旋别一叶萩碱（viroallosecurinine，6），一叶萩醇A（securinol A，7），secu’amamineA（8），ent-phyllanthidine（9），（＋）-aquilegiohde（10）和（＋）-menisdaurilide（11）。结论：1为新化合物，4，8，10和11为首次从一叶萩中分离得到。