ABSTRACT
Pluripotent stem cells (PSCs) can immortally self-renew in culture with a high proliferation rate, and they possess unique metabolic characteristics that facilitate pluripotency regulation. Here, we review recent progress in understanding the mechanisms that link cellular metabolism and homeostasis to pluripotency regulation, with particular emphasis on pathways involving amino acid metabolism, lipid metabolism, the ubiquitin-proteasome system and autophagy. Metabolism of amino acids and lipids is tightly coupled to epigenetic modification, organelle remodeling and cell signaling pathways for pluripotency regulation. PSCs harness enhanced proteasome and autophagy activity to meet the material and energy requirements for cellular homeostasis. These regulatory events reflect a fine balance between the intrinsic cellular requirements and the extrinsic environment. A more complete understanding of this balance will pave new ways to manipulate PSC fate.
ABSTRACT
Pluripotent stem cells (PSCs) can immortally self-renew in culture with a high proliferation rate, and they possess unique metabolic characteristics that facilitate pluripotency regulation. Here, we review recent progress in understanding the mechanisms that link cellular metabolism and homeostasis to pluripotency regulation, with particular emphasis on pathways involving amino acid metabolism, lipid metabolism, the ubiquitin-proteasome system and autophagy. Metabolism of amino acids and lipids is tightly coupled to epigenetic modification, organelle remodeling and cell signaling pathways for pluripotency regulation. PSCs harness enhanced proteasome and autophagy activity to meet the material and energy requirements for cellular homeostasis. These regulatory events reflect a fine balance between the intrinsic cellular requirements and the extrinsic environment. A more complete understanding of this balance will pave new ways to manipulate PSC fate.
ABSTRACT
Pluripotent stem cells (PSCs) can immortally self-renew in culture with a high proliferation rate, and they possess unique metabolic characteristics that facilitate pluripotency regulation. Here, we review recent progress in understanding the mechanisms that link cellular metabolism and homeostasis to pluripotency regulation, with particular emphasis on pathways involving amino acid metabolism, lipid metabolism, the ubiquitin-proteasome system and autophagy. Metabolism of amino acids and lipids is tightly coupled to epigenetic modification, organelle remodeling and cell signaling pathways for pluripotency regulation. PSCs harness enhanced proteasome and autophagy activity to meet the material and energy requirements for cellular homeostasis. These regulatory events reflect a fine balance between the intrinsic cellular requirements and the extrinsic environment. A more complete understanding of this balance will pave new ways to manipulate PSC fate.
ABSTRACT
Objective To investigate the effects of α7 nicotinic acetylcholine receptor (α7nAChR) on the inflammatory response induced by lipopolysaccharide (LPS) in RAW264.7 macrophages and its molecular mechanisms. Methods RAW264.7 macrophages were culturedin vitro. Inflammatory cell model was constructed by LPS stimulation. Cells were challenged by LPS (1, 10, 100 and 500μg/L) for 5 hours or 100μg/L LPS for 0, 2, 4, 8, 12, 24, 48 and 72 hours, and the release of tumor necrosis factor-α (TNF-α) was detected by the enzyme linked immunosorbent assay (ELISA). The location of α7nAChR was examined in RAW264.7 macrophages by immunofluorescence. Then the cell proliferation and toxicity kit (CCK-8) was used to detect 1, 10, 100, 1000μmol/L GTS-21, a α7nAchR agonist, on the cell viability after LPS stimulation. ELISA was used to detect 1, 10, 100, 1000μmol/L GTS-21 on the levels of TNF-α, interleukin 1β (IL-1β) after LPS stimulation. Cells were challenged with 100μg/L LPS and 100μmol/L GTS-21, then, the level of high mobility group box 1 (HMGB1) was detected by Western Blot and the intracellular location of HMGB1 and nuclear factor-κB p65 (NF-κB p65) was tested by immunofluorescence.Results LPS increased the level of TNF-α to a peak at the concentration of 100μg/L and at 24 hours after stimulation. Theα7nAChR expressed on the macrophages. The cell viability was decreased in a dose-dependent manner [(96.2±1.0)%, (92.0±1.1)% vs. (86.5±2.2)%, bothP < 0.05]. Compared with the control group, the levels of TNF-α and IL-1βin the supernatant of LPS group were significantly increased [TNF-α (ng/L): 453.0±60.6 vs. 100.8±3.2, IL-1β(μg/L): 8.21±0.31 vs. 0.87±0.16, bothP < 0.05]. TNF-α and IL-1β were significantly decreased by 10μmol/L and 100μmol/L GTS-21 in a dose-dependent manner [TNF-α (ng/L): 227.5±17.5, 81.0±8.8 vs. 453.0±60.6;IL-1β (μg/L): 4.86±0.72, 2.32±0.45 vs. 8.21±0.31, allP < 0.05]. GTS-21 significantly reduced the expression of HMGB1 which was induced by LPS management (gray value: 0.788±0.130 vs. 2.061±0.330,P < 0.05) and reversed LPS-induced HMGB1 cytoplasmic transfer. GTS-21 also reversed LPS-induced nuclear translocation of NF-κB p65. Conclusion GTS-21 reduces the inflammatory response via inhibiting the activation of NF-κB.
ABSTRACT
Objective To summarize the causes of death and to analyze the risk factors in a surgical intensive care unit (SICU).Methods The relevant information of patients died in the SICU of Xijing Hospital of Fourth Military Medical University in past 15 years (from December 1999 to February 2015) was retrospectively analyzed.The gender,age, reason and date of hospitalization, date of transfer SICU, past medical history, whether or not admitted directly from emergency department, or transferred from other department, operated or not, date of death, the main cause of death, acute physiology and chronic health evaluation Ⅱ (APACHE Ⅱ) score, the history of undergoing mechanical ventilation, continuous renal replacement therapy (CRRT), or antifungal therapy, as well as the ratio of the patients with body temperature higher than 39 ℃, white blood cell (WBC) count higher than 10 × 109/L, platelet (PLT) count below 100 × 109/L, albumin (Alb) below 35 g/L of two periods, namely from December 1999 to July 2007 (the first period),and from August 2007 to February 2015 (the second period) were compared.The above parameters were compared with those of 201 survivors in SICU, and the risk factors leading to death were analyzed by logistic regression.Results From December 1999 to February 2015, 4 317 patients were taken care of in the SICU.Among them, the number of death was 186, and the mortality rate was 4.3％.In the first time period (from December 1999 to July 2007), the total number of patients was 1 356, and the number of death were 109 (the mortality rate was 8.0％).In the second period, i.e.from August 2007 to February 2015, the number of SICU patients was 2 961, and 77 died (the mortality rate was 2.6％).The difference of mortality rate between the two periods was statistically significant (x2 =66.707, P =0.001).The death rate of patients transferred directly from emergency department in tle first period was 79.8％ (87/109), and it was lower in the second period (51.9％, 40/77, x2 =16.181, P =0.001).The death rate of the patients with blood Alb below 35 g/L in the second period (59.7％, 46/77) was higher than that of the first period (41.3％, 45/109, x2 =6.151, P =0.017).The top three causes of death from December 1999 to February 2015 were sepsis (38.2％), trauma (16.7％), and operation for cancer (14.0％).In the first period, the top three causes of death were sepsis (35.8％), trauma (22.0％),and operation for cancer (13.8％).In the second period, the top three causes of death were sepsis (41.6％), damage of the central nervous system (16.9％), and operation for cancer (14.3％).Top three reasons for SICU admission were trauma (29.03％), abdominal pain (20.97％) and other reasons (18.82％).Top three departments from which the patients were transferred were the emergency department (19.35％), orthopedics department (17.20％), and hepatobiliary department (16.13％).Logistic regression analysis showed that age [odds ratio (OR) =2.025, 95％ confidence interval (95％CI) =1.500-2.734, P =0.000], mechanical ventilation (OR =3.514, 95％CI =1.701-7.259, P =0.001), CRRT (OR =5.604,95％CI =3.003-10.459, P =0.000), body temperature higher than 39 ℃ (OR =1.992, 95％CI =1.052-3.771, P =0.034) were the risk factors of death in SICU patients.Conclusion Sepsis and severe trauma are the leading causes of death in severe SICU patients, to whom with risk factors of death enough attention should be given.