Although the cytokines tumor necrosis factor (TNF), interleukin-1 (IL-1), and interleukin-6 (IL-6) are important mediators of hemodynamic, metabolic, and immunologic alterations in the host during sepsis, it is not known whether there is any association between the release of these cytokines and prostanoids during sepsis. Sepsis induced by cecal ligation and puncture in rats led to a persistent elevation (p less than 0.05) of plasma TNF until 10 hours, steadily increasing (p less than 0.05) IL-1 plasma levels, and enhanced (p less than 0.05) IL-6 plasma levels at all time points compared to the sham group. Prostaglandin E2 plasma levels were elevated (p less than 0.05) at 5 hours (153 +/- 29 pg/mL; control: 47 +/- 11 pg/mL) and 10 hours (96 +/- 16 pg/mL; control: 21 +/- 5 pg/mL). Prostaglandin E2 production by splenic macrophages (sM phi) from septic animals was increased (p less than 0.05) at 5 hours (9.1 +/- 2.2 ng/mL) and 10 hours (5.6 +/- 1.5 ng/mL) compared to controls (3.3 +/- 0.3 ng/mL at 5 hours; 1.3 +/- 1.3 ng/mL at 10 hours). Incubation of sM phi from septic animals with ibuprofen enhanced (p less than 0.05) IL-1 and TNF synthesis, while IL-6 production was reduced (p less than 0.05). These results indicate that the alterations in prostanoid release and elevated plasma prostanoids may regulate the release and consequently the circulating levels of cytokines during sepsis.
Objective. After replantation of severed fingers in infants, the utility model patent upper limb restrictive brace-assisted bed rest braking, combined with psychological intervention, can alleviate children’s anxiety, so as to reduce the occurrence of vascular crisis. Methods. The study period was from April 2015 to July 2018. In this paper, 30 children with finger injuries in hand surgery in the CIS electronic medical record system of Cangzhou Integrated Traditional Chinese and Western Medicine Hospital were selected as the research objects. Replantation was performed in 30 infants with severed fingers. Among them, 15 cases were applied with the method of aircraft chest arm gypsum splint combined with sedative drug braking and the utility model patented product upper limb restrictive brace fixation-assisted bed rest braking, and the method of psychological intervention was applied at the same time. Results. Among the 15 fingers in the control group, 6 had vascular crisis and 1 in the experimental group. The incidence of vascular crisis in the experimental group was lower, and the difference between the two groups was statistically significant ( P<0.05 ). The patients were followed up for 9~18 months, with an average of 9.72±1.07 months. In the control group, 15 cases of severed fingers survived, and there were 13 cases of replantation finger necrosis in 2 cases of intractable arterial crisis. In the experimental group, 14 cases of severed fingers survived in 15 cases and there was 1 case of replanted finger necrosis in intractable arterial crisis after operation. There was no significant difference in the survival rate between the two groups ( P>0.05 ). In addition, the replanted finger function was evaluated. In the control group, 9 cases were excellent, 4 cases were good, and 1 case was fair. In the experimental group, 14 cases were excellent, 1 case was good, and 0 case was fair. The functional evaluation of the experimental group was better than that of the control group, and the difference between the two groups was statistically significant ( P<0.05 ). Conclusion. For infants after replantation of severed fingers, the application of the utility model patented product upper limb restrictive brace can effectively make up for the insufficient fixation of aircraft chest arm gypsum splint, reduce the occurrence of vascular crisis, and assist children in bed. In addition, the application of psychological intervention can reduce children’s postoperative crying and is conducive to children’s postoperative recovery.
To identify diagnostic markers related to oxidative stress in chronic rhinosinusitis with nasal polyps (CRSwNP) by analyzing transcriptome sequencing data, and to investigate their roles in CRSwNP.
To investigate the effect and possible mechanism of curcumin to induce apoptosis in ovarian cancer resistant cell lines COC1/DDP.COC1/DDP cells were treated with different concentration of curcumin, with or without the combination of chemotherapy drugs cisplatin (DDP) and paclitaxel (PIX) for 48 hours. The growth inhibition rates of COC1/DDP cells were studied by MTT method, and the apoptotic ratios were measured with flow cytometry. The expression of phosphoinositide 3-kinase catalytic subunit (PI3KCA) mRNA was studied by RT-PCR in curcumin treated cells, DDP treated cells and their combination treated cells.After the treatment of different concentration of curcumin for 48 hours, the growth inhibition rates and the apoptotic rate of COC1/DDP cells were gradually increased accordingly with increasing curcumin concentration. Furthurmore, curcumin in combination with chemotherapy drug obtained higher inhibition rate and apoptosis rate than single chemotherapy drug did (P < 0.05). The expression of PI3KCA mRNA of COC1/DDP cells treated with curcumin combined DDP was much lower than that treated only with DDP (P < 0.05).Curcumin can increase the apoptotic rate of COC1/DDP cells, so has synergistic effect on with chemotherapy drugs on the induction of cell apoptosis. Its possible mechanism may be related to the down-regulation of PI3KCA.
Tumor necrosis factor (TNF) and interleukin 6 (IL-6) are purported to be important mediators of inflammatory responses. It is not known whether the plasma levels of these cytokines are altered after trauma and hemorrhage. Our objectives were to determine whether there is any elevation of plasma TNF or IL-6 after trauma and hemorrhage and to what extent these changes are due to tissue trauma vs. simple hemorrhage. Trauma was induced in Sprague-Dawley rats under light ether anesthesia by performing a 5-cm midline laparotomy. On closure, animals were catheterized, awakened, hemorrhaged to a mean blood pressure of 40 mmHg, and maintained at that pressure until 40% of maximum shed blood volume was returned in the form of Ringer lactate (RL). Animals were then resuscitated with RL equivalent to four times shed blood volume. Blood samples (0.5 ml) were taken before inducing hemorrhage, at maximal bleed out (45 min), and at 4 and 6 h posthemorrhage to obtain plasma. IL-6 and TNF levels were measured using cytokine-dependent cellular assays. TNF levels were significantly elevated at 45 min into hemorrhage and remained so up to 4 h after hemorrhage. IL-6 levels were also elevated 45 min into hemorrhage and remained so up to 6 h posthemorrhage. IL-6, unlike TNF, was already significantly increased after midline laparotomy and before initiation of hemorrhage compared with unmanipulated animals. Thus induction of IL-6 by trauma may be partially independent of those mechanisms in hemorrhage that are involved in the release of TNF.
We recently demonstrated that early administration of rat adrenomedullin (AM), a vasoactive peptide, in combination with its binding protein (human AMBP-1) produces various beneficial effects in sepsis. Human AM is a 52-amino acid peptide, but rat AM differs from human AM, having only 50 amino acid residues, with two amino acid deletions and six substitutions. It remains unknown whether a combination of human AM and human AMBP-1 (AM/AMBP-1) is also beneficial in sepsis and, if so, whether human AM/AMBP-1 reverses established sepsis in rats. To test the effects of human AM/AMBP-1, we induced sepsis in male adult rats by cecal ligation and puncture (CLP). At 10 h after CLP (i.e., severe sepsis), human AM (12–48 µg/kg body weight) was administered in combination with human AMBP-1 (40–160 µg/kg body weight). Vehicle-treated animals received a nonspecific human plasma protein (albumin). Blood and intestinal samples were collected at 20 h for various measurements. In additional groups of septic animals, the gangrenous cecum was surgically excised at 20 h after CLP The 10-day survival was recorded. Our results showed that tissue injury, as evidenced by increased levels of transaminases and lactate, was present at 20 h after CLP Proinflammatory cytokines tumor necrosis factor-α and interleukin-6 were significantly elevated. Gut barrier dysfunction, manifested by increased mucosal permeability to hydrophilic macromolecules and increased bacterial translocation to mesenteric lymph nodes, also occurred at 20 h after CLP Administration of human AM/AMBP-1 in established sepsis markedly attenuated tissue injury, reduced proinflammatory cytokine levels, ameliorated intestinal-barrier dysfunction, and improved the survival rate from 47% to 67%–80%. Thus, human AM/AMBP-1 can be further developed as a safe and effective therapy for patients with established sepsis.
Abstract Background Chronic kidney disease (CKD) is a leading cause of death in the United States, and renal fibrosis represents a pathologic hallmark of CKD. Extracellular cold-inducible RNA-binding protein (eCIRP) is a stress response protein involved in acute inflammation, tissue injury and regulated cell death. However, the role of eCIRP in chronic inflammation and tissue injury has not been elucidated. We hypothesize that eCIRP is involved in renal ischemia/reperfusion (RIR)-induced CKD and that C23, an antagonist to eCIRP, is beneficial in attenuating renal fibrosis and ferroptosis in RIR-induced CKD. Methods C57BL/6 (WT) or CIRP −/− mice underwent renal injury with total blockage of blood perfusion by clamping bilateral renal pedicles for 28 min. In the WT mice at the time of reperfusion, they were treated with C23 (8 mg/kg) or vehicle. Blood and kidneys were harvested for further analysis at 21 days thereafter. In a separate cohort, mice underwent bilateral RIR and treatment with C23 or vehicle and were then subjected to left nephrectomy 72 h thereafter. Mice were then monitored for additional 19 days, and glomerular filtration rate (GFR) was assessed using a noninvasive transcutaneous method. Results In the RIR-induced CKD, CIRP −/− mice showed decreased collagen deposition, fibronectin staining, and renal injury as compared to the WT mice. Administration of C23 ameliorated renal fibrosis by decreasing the expression of active TGF-β1, α-SMA, collagen deposition, fibronectin and macrophage infiltration to the kidneys. Furthermore, intervention with C23 significantly decreased renal ferroptosis by reducing iron accumulation, increasing the expression of glutathione peroxidase 4 (GPX4) and lipid peroxidation in the kidneys of RIR-induced CKD mice. Treatment with C23 also attenuated BUN and creatinine. Finally, GFR was significantly decreased in RIR mice with left nephrectomy and C23 treatment partially prevented their decrease. Conclusion Our data show that eCIRP plays an important role in RIR-induced CKD. Treatment with C23 decreased renal inflammation, alleviated chronic renal injury and fibrosis, and inhibited ferroptosis in the RIR-induced CKD mice.
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