Objective: To investigate the effects of apolipoprotein E deficiency (Apo E^-/-) on plasma and lipoprotein distribution of sphingosine-1-phosphate (S1P) in mice. Methods: Five male or female Apo E^-/- or wild type (WT) mice were fed with chow diet and sacrificed at 32-week-age and plasma was collected. The constituents of lipoprotein(very low density lipoprotein (VLDL), low density lipoprotein (LDL), high density lipoprotein (HDL)) were separated by ultracentrifuge. The protein concentration of constituents was detected by BCA protein quantitative kit, and the S1P concentration in plasma and various lipoprotein constituents was detected by liquid chromatography-tandem mass spectrometry (LC-MS/MS). Western blot was used to determine the plasma, liver, and kidney protein expression of apolipoprotein M(Apo M), which is considered as specific ligand of S1P.The S1P concentration in plasma and various constituents of lipoprotein in the Apo E^-/- mice was compared to respective WT mice. Results: (1)Plasma S1P content was significantly higher in the Apo E^-/- groups than that of WT groups (male: (535.7±78.5)nmol/L vs. (263.3±22.0)nmol/L; female: (601.1±64.0)nmol/L vs. (279.0±33.9)nmol/L; all P<0.01). (2) Compared with WT mice, S1P content in non-HDL(LDL+ VLDL) was significantly higher in Apo E^-/- mice (male: (504.9±52.8)nmol/L vs. (28.7±9.0)nmol/L; female: (427.7±27.4) vs. (27.8±4.7)nmol/L; after standardization of protein concentration, male: (385.0±41.2)pmol/mg protein vs. (71.4±6.6)pmol/mg protein; female: (330.2±22.0)pmol/mg protein vs. (67.2±12.1)pmol/mg protein; all P<0.01). (3) The expression of Apo M in plasma, liver and kidney was significantly higher in Apo E^-/- groups than that of WT groups(all P<0.05). Conclusion The deficiency of Apo E could lead to upregulated S1P expression in the non-HDL, the underlying mechanism might be the increased transfer of HDL into the non-HDL by Apo M-S1P.

Objective    To compare the mortality in lung cancer patients infected with coronavirus disease 2019 (COVID-19) versus other cancer patients infected with COVID-19. Methods    A computer search of PubMed, EMbase, The Cochrane Library, Web of Science, Wanfang database, VIP database and CNKI database was conducted to compare the mortality of lung cancer and other cancers patients infected with COVID-19 from the inception to December 2021. Two thoracic surgeons independently screened the literature, extracted data, and then cross-checked the literature. After evaluating the quality of the included literature, a meta-analysis was performed on the literature using Review Manager 5.4 software. Results    A total of 12 retrospective cohort studies were included, covering 3 065 patients infected with COVID-19, among whom 340 patients suffered from lung cancer and the remaining 2 725 patients suffered from other cancers. Meta-analysis results showed that the lung cancer patients infected with COVID-19 had a higher mortality (OR=1.58, 95%CI 1.24 to 2.02, P<0.001). Subgroup analysis results showed that the mortality of two groups of patients in our country was not statistically different (OR=0.90, 95%CI 0.49 to 1.65, P=0.72). Whereas, patients with lung cancer had a higher mortality than those with other cancers in other countries (Brazil, Spain, USA, France, Italy, UK, Netherlands) (OR=1.78, 95%CI 1.37 to 2.32, P<0.001). Conclusion    There is a negligible difference in mortality between lung cancer and other cancers patients who are infected with COVID-19 in our country; while a higher mortality rate is found in lung cancer patients in other countries. Consequently, appropriate and positive prevention methods should be taken to reduce the risk of infecting COVID-19 in cancer patients and to optimize the management of the infected population.

BACKGROUND: Pancreatic β-cells elevate insulin production and secretion through a compensatory mechanism to override insulin resistance under metabolic stress conditions. Deficits in β-cell compensatory capacity result in hyperglycemia and type 2 diabetes (T2D). However, the mechanism in the regulation of β-cell compensative capacity remains elusive. Nuclear factor-Y (NF-Y) is critical for pancreatic islets' homeostasis under physiological conditions, but its role in β-cell compensatory response to insulin resistance in obesity is unclear. METHODS: In this study, using obese ( ob/ob ) mice with an absence of NF-Y subunit A (NF-YA) in β-cells ( ob , Nf-ya βKO) as well as rat insulinoma cell line (INS1)-based models, we determined whether NF-Y-mediated apoptosis makes an essential contribution to β-cell compensation upon metabolic stress. RESULTS: Obese animals had markedly augmented NF-Y expression in pancreatic islets. Deletion of β-cell Nf-ya in obese mice worsened glucose intolerance and resulted in β-cell dysfunction, which was attributable to augmented β-cell apoptosis and reactive oxygen species (ROS). Furthermore, primary pancreatic islets from Nf-ya βKO mice were sensitive to palmitate-induced β-cell apoptosis due to mitochondrial impairment and the attenuated antioxidant response, which resulted in the aggravation of phosphorylated c-Jun N-terminal kinase (JNK) and cleaved caspase-3. These detrimental effects were completely relieved by ROS scavenger. Ultimately, forced overexpression of NF-Y in INS1 β-cell line could rescue palmitate-induced β-cell apoptosis, dysfunction, and mitochondrial impairment. CONCLUSION Pancreatic NF-Y might be an essential regulator of β-cell compensation under metabolic stress.
Rats ; Mice ; Animals ; Reactive Oxygen Species/metabolism* ; Diabetes Mellitus, Type 2/metabolism* ; Insulin Resistance ; Insulin ; Insulin-Secreting Cells/metabolism* ; Apoptosis ; Stress, Physiological ; Transcription Factors/metabolism* ; Palmitates/pharmacology* ; Obesity/metabolism*