Polyethylene glycol crosslinked decellularized single liver lobe scaffolds with vascular endothelial growth factor promotes angiogenesis in vivo.

BACKGROUND: Improving the mechanical properties and angiogenesis of acellular scaffolds before transplantation is an important challenge facing the development of acellular liver grafts. The present study aimed to evaluate the cytotoxicity and angiogenesis of polyethylene glycol (PEG) crosslinked decellularized single liver lobe scaffolds (DLSs), and establish its suitability as a graft for long-term liver tissue engineering. METHODS: Using mercaptoacrylate produced by the Michael addition reaction, DLSs were first modified using N-succinimidyl S-acetylthioacetate (SATA), followed by cross-linking with PEG as well as vascular endothelial growth factor (VEGF). The optimal concentration of agents and time of the individual steps were identified in this procedure through biomechanical testing and morphological analysis. Subsequently, human umbilical vein endothelial cells (HUVECs) were seeded on the PEG crosslinked scaffolds to detect the proliferation and viability of cells. The scaffolds were then transplanted into the subcutaneous tissue of Sprague-Dawley rats to evaluate angiogenesis. In addition, the average number of blood vessels was evaluated in the grafts with or without PEG at days 7, 14, and 21 after implantation. RESULTS: The PEG crosslinked DLS maintained their three-dimensional structure and were more translucent after decellularization than native DLS, which presented a denser and more porous network structure. The results for Young's modulus proved that the mechanical properties of 0.5 PEG crosslinked DLS were the best and close to that of native livers. The PEG-VEGF-DLS could better promote cell proliferation and differentiation of HUVECs compared with the groups without PEG cross-linking. Importantly, the average density of blood vessels was higher in the PEG-VEGF-DLS than that in other groups at days 7, 14, and 21 after implantation in vivo. CONCLUSIONS: The PEG crosslinked DLS with VEGF could improve the biomechanical properties of native DLS, and most importantly, their lack of cytotoxicity provides a new route to promote the proliferation of cells in vitro and angiogenesis in vivo in liver tissue engineering.

Panax notoginseng Alleviates Sepsis-Induced Acute Kidney Injury by Reducing Inflammation in Rats.

Background: Sepsis is defined as a host inflammatory response to infection that can result in end-organ dysfunction. One of the most common consequences of sepsis is acute kidney injury (AKI). Panax notoginseng powder (PNP) has been previously reported to protect against overactive inflammation process. However, the potential effect of PNP on septic AKI is poorly described. The current study was conducted to investigate the protective effects of PNP in septic AKI rats. Methods: A model of septic AKI was established on male SD rats by using the cecal ligation and puncture procedure. PNP was administrated by gavage after the cecal ligation and puncture (CLP) procedure, and the mice were sacrificed at 6, 12, and 72 h after induction of sepsis. The serum and kidney samples were collected and assayed for biochemical tests, histopathological staining, inflammation, and apoptosis-related gene/protein expression. In addition, 15 rats in each group were used to calculate the 7-day survival rate. Results: CLP-induced kidney injury was observed by the histopathological score, which markedly was attenuated by PNP treatment. Consistently, PNP intervention significantly alleviated the elevated levels of serum creatinine and blood urea nitrogen in CLP-induced sepsis rats. The CLP procedure also triggered proinflammatory cytokine production and increased the expression of various inflammation-related proteins in the kidneys. However, PNP inhibited the renal expression of IL-18, IL-1ß, TNF-α, and IL-6 to substantially improve inflammatory response. Mechanistically, CLP induced the increase of the NF-κB p65 level in the injured kidneys, while PNP notably inhibited the corresponding protein expression. Conclusion: PNP attenuated kidney inflammation to protect against CLP-induced septic AKI in rats via inhibiting the NF-κB signaling pathway.

Electroacupuncture Improves Intestinal Dysfunction in Septic Patients: A Randomised Controlled Trial.

OBJECTIVE: To investigate the effects of electroacupuncture (EA) at "Zusanli" (ST36) and "Shangjuxu"(ST37) on reducing inflammatory reaction and improving intestinal dysfunction in patients with sepsis-induced intestinal dysfunction with syndrome of obstruction of the bowels Qi. METHODS: A total of 71 patients with sepsis-induced intestinal dysfunction with syndrome of obstruction of the bowels Qi were randomly assigned to control group (n=36) and treatment group (n=35). Patients in control group were given conventional therapies including fluid resuscitation, anti-infection, vasoactive agents, mechanical ventilation, supply of enteral nutrition, and glutamine as soon as possible. In addition to conventional therapies, patients in treatment group underwent 20 minutes of EA at ST36-ST37 twice a day for five days. At baseline, day 1, day 3, and day 7 after treatment, the plasma levels of procalcitonin (PCT), tumor necrosis factor-α (TNF-α), intestinal fatty acid-binding proteins (I-FABP), D-lactate, citrulline, and TCM quantitative score of intestinal dysfunction were measured and recorded, respectively. And days on mechanical ventilation (MV), length of stay in intensive care unit (ICU), and 28d mortality were recorded. RESULTS: During treatment, the plasma levels of PCT, TNF-α, I-FABP, D-lactate, and TCM quantitative score of intestinal dysfunction were declining in both groups, while the treatment group showed a significant decline (P<0.05). Plasma levels of citrulline were increasing in both groups, while the treatment group showed a significant increase (P<0.05). However, there were no significant differences in the days on MV, length of stay in ICU, and 28d mortality between two groups (P>0.05). CONCLUSIONS: EA at ST36-ST37 can reduce inflammatory reaction and has protective effects on intestinal function in patients with sepsis-induced intestinal dysfunction with syndrome of obstruction of the bowels Qi. TRIAL REGISTRATION: This trial was registered at http://www.chictr.org.cn/(ChiCTR-IOR-17010910).

Electro-acupuncture attenuates inflammatory responses and intraabdominal pressure in septic patients: A randomized controlled trial.

BACKGROUND: A pathological increase in intraabdominal pressure (IAP) and inflammatory responses have negative effects on splanchnic, respiratory, cardiovascular, renal, and neurological function in septic patients with intestinal dysfunction. Electro-acupuncture (EA) has been evidenced to have a bidirectional neuron-endocrine-immune system regulating effect in patients with intestinal dysfunction. The purpose of current study was to evaluate the effects of EA at "Zusanli" (ST36) and "Shangjuxu" (ST37) on inflammatory responses and IAP in septic patients with intestinal dysfunction manifested syndrome of obstruction of the bowels Qi. METHODS: Eighty-two septic patients with intestinal dysfunction manifested syndrome of obstruction of the bowels Qi were randomly assigned to control group (n = 41) and EA group (n = 41). Patients in control group were given conventional therapies including fluid resuscitation, antiinfection, vasoactive agents, mechanical ventilation (MV), supply of enteral nutrition, and glutamine as soon as possible. In addition to conventional therapies, patients in EA group underwent 20-minutes of EA at ST36-ST37 twice a day for 5 days. At baseline, posttreatment 1, 3, and 7 days, serum levels of tumor necrosis factor-α (TNF-α) and interleukin-1ß (IL-1ß) and IAP levels, were measured, respectively. And days on MV, length of stay in intensive care unit (ICU) and 28 days mortality were recorded. RESULTS: The serum levels of TNF-α and IL-1ß and IAP levels at posttreatment 1, 3, and 7 days were lower significantly in the EA group compared with the control group (mean [SD]; 61.03 [20.39] vs 79.28 [20.69]; P < .005, mean [SD]; 35.34 [18.75] vs 66.53 [30.43]; P < .005 and mean [SD]; 20.32 [11.30] vs 32.99 [20.62]; P = .001, respectively, TNF-α. Mean [SD]; 14.11 [5.21] vs 16.72 [5.59]; P = .032, mean [SD]; 9.02 [3.62] vs 12.10 [4.13]; P = .001 and mean [SD]; 5.11 [1.79] vs 8.19 [2.99]; P < .005, respectively, IL-1ß. Mean [SD]; 14.83 [5.58] vs 17.55 [3.37]; P = .009, mean [SD]; 11.20 [2.57] vs 14.85 [3.01]; P < .005 and mean [SD]; 8.62 [2.55] vs 11.25 [2.72]; P < .005, respectively, IAP). There were no significant differences in the duration of MV, length of stay in ICU, and 28d mortality between the groups. CONCLUSION: EA at ST36-ST37 attenuated inflammatory responses through reduction in serum levels of TNF-α and IL-1ß and IAP in septic patients with intestinal dysfunction manifested syndrome of obstruction of the bowels Qi.

Levosimendan Versus Dobutamine in Myocardial Injury Patients with Septic Shock: A Randomized Controlled Trial.

BACKGROUND We aimed to investigate the effect of levosimendan on biomarkers of myocardial injury and systemic hemodynamics in patients with septic shock. MATERIAL AND METHODS After achieving normovolemia and a mean arterial pressure of at least 65 mmHg, 38 septic shock patients with low cardiac output (left ventricular ejective fraction), LEVF £45%) were randomly divided into two groups: levosimendan dobutamine. Patients in the levosimendan and dobutamine groups were maintained with intravenous infusion of levosimendan (0.2 µg/kg/minute) and dobutamine (5 µg/kg/minute) for 24 hours respectively. During treatment we monitored hemodynamics and LVEF, and measured levels of heart-type fatty acid binding protein (HFABP), troponin I (TNI), and brain natriuretic peptide(BNP). In addition, the length of mechanical ventilation, intensive care unit (ICU) stay, hospital stay, and 28-day mortality were compared between the two groups. RESULTS The levosimendan group and the dobutamine group were well matched with respect to age (years, 55.4 ± 1 7.5 versus 50.2 ± 13.6) and gender (males, 68.4% versus 57.9%). Levosimendan-treated patients had higher stroke volume index (SVI), cardiac index (CI), LVEF, and left ventricular stroke work index (LVSWI), and lower extravascular lung water index (EVLWI) compared to dobutamine-treated patients (p<0.05). HFABP, TNI, and BNP in the levosimendan group were less than in the dobutamine group (p<0.05). There was no difference in the mechanical ventilation time, length of stay in ICU and hospital, and 28-day mortality between the two groups. CONCLUSIONS Compared with dobutamine, levosimendan reduces biomarkers of myocardial injury and improves systemic hemodynamics in patients with septic shock. However, it does not reduce the days on mechanical ventilation, length of stay in ICU and hospital, or 28-day mortality.

Effects of Early Continuous Venovenous Hemofiltration on E-Selectin, Hemodynamic Stability, and Ventilatory Function in Patients with Septic-Shock-Induced Acute Respiratory Distress Syndrome.

Objective. To investigate the effects of 72-hour early-initiated continuous venovenous hemofiltration (ECVVH) treatment in patients with septic-shock-induced acute respiratory distress syndrome (ARDS) (not acute kidney injury, AKI) with regard to serum E-selectin and measurements of lung function and hemodynamic stability. Methods. This prospective nonblinded single institutional randomized study involved 51 patients who were randomly assigned to receive or not receive ECVVH, an ECVVH group (n = 24) and a non-ECVVH group (n = 27). Besides standard therapies, patients in ECVVH group underwent CVVH for 72 h. Results. At 0 and 24 h after initiation of treatment, arterial partial pressure of oxygen/fraction of inspired oxygen (PaO2/FiO2) ratio, extravascular lung water index (EVLWI), and E-selectin level were not significantly different between groups (all P > 0.05). Compared to non-ECVVH group, PaO2/FiO2 is significantly higher and EVLWI and E-selectin level are significantly lower in ECVVH group (all P < 0.05) at 48 h and 72 h after initiation of treatment. The lengths of mechanical ventilation and stay in intensive care unit (ICU) were shorter in ECVVH group (all P < 0.05), but there was no difference in 28-day mortality between two groups. Conclusions. In patients with septic-shock-induced ARDS (not AKI), treatment with ECVVH in addition to standard therapies improves endothelial function, lung function, and hemodynamic stability and reduces the lengths of mechanical ventilation and stay in ICU.