Circ_0001806 relieves LPS-induced HK2 cell injury by regulating the expression of miR-942-5p and TXNIP.

Sepsis is a systemic inflammatory disease that can cause a variety of diseases, including septic acute kidney injury (AKI). Circular RNAs (circRNAs) are believed to be involved in the development of this disease. This study aims to clarify the function of circ_0001806 in lipopolysaccharide (LPS)-induced HK2 cell model and its related mechanisms. Circ_0001806 was up-regulated in septic AKI serum specimens and LPS-induced HK2 cells. Circ_0001806 knockdown promoted cell proliferation and restrained apoptosis, inflammation and oxidative stress in LPS-induced HK2 cells. In mechanism, circ_0001806 can be used as a sponge for miR-942-5p, and miR-942-5p can directly target TXNIP. Functional experiments revealed that the miR-942-5p inhibitor could reverse the alleviating effect of circ_0001806 knockdown on LPS-induced HK2 cell injury, and TXNIP addition can also reverse the inhibitory effect of miR-942-5p overexpression on LPS-induced HK2 cell injury. In addition, circ_0001806 regulated TXNIP expression through sponging miR-942-5p. Besides, exosome-derived circ_0001806 was upregulated in LPS-induced HK2 cells, while was downregulated by GW4869. The results showed that circ_0001806 knockdown could reduce LPS-induced HK2 cell injury by regulating TXNIP expression via targeting miR-942-5p, indicating that circ_0001806 might be an important biomarker for alleviating sepsis-related AKI. This might provide therapeutic strategy for the treatment of sepsis.

Surgical intervention and outcome for treatment of myocardial bridging refractory to medication.

INTRODUCTION: Myocardial bridging (MB) is a common and usually benign inborn coronary abnormality that may lead to anginal symptoms, acute coronary syndrome, arrhythmias, and rarely sudden cardiac death. MB are most commonly localized in the middle segment of the left anterior descending coronary artery (LAD). The treatment of LAD-MB is still challenging. Our objective was to assess the short- and long-term results of surgical procedures in patients with LAD-MB who had chest pain refractory to medical therapy. METHODS: Between March 2005 and January 2020, 26 patients (19 males and 7 females; mean 55.8 ± 12.4 years) with MB underwent surgery. All MB was located in the mid-segment of the LAD with a mean length of 4.2 ± 1.7 cm. Coronary angiography before surgery demonstrated LAD-MB with systolic compression more than or equal to 70% in all patients. RESULTS: Twenty-five patients underwent myotomy and one patient underwent coronary artery bypass grafting (CABG). All patients survived and recovered uneventfully. Neither hospital or late death nor major complications occurred. Follow-up time was 3-173 months (mean 55.7 months). Follow-up of coronary angiography or computed tomography scan performed in 16 patients demonstrated restoration of coronary blood flow and myocardial perfusion without significant residual compression of the artery. All patients were symptom-free and are currently in NYHA Class I. CONCLUSION: The symptomatic LAD-MB patients who are refractory to medication should actively undergo the surgical intervention such as myotomy and CABG to eliminate the clinical symptoms and achieve satisfactory results by follow-up findings. Myotomy is a preferred procedure because of its safety and satisfactory results.

Modified Peritoneal Dialysis for Treatment of Acute Renal Failure after Complex Congenital Heart Surgery in Infants.

BACKGROUND: Acute kidney injury (AKI) is one of the common complications in infants and children after complex congenital heart surgery. Peritoneal dialysis (PD) is usually applied for renal replacement therapy (RRT), especially in infants. We investigated the efficacy and safety of modified PD for the treatment of acute renal failure and congestive heart failure after cardiac surgery for congenital heart disease in infants. METHODS: We retrospectively analyzed five consecutive patients from October 2015 to February 2017. The patients were aged from four days to five years old, and all had acute renal failure and congestive heart failure after cardiac surgery. In the five patients treated with modified PD (five males; average weight: 11.2 ± 5.5 kg), we used the Seldinger technique percutaneous abdominal puncture 16 G single lumen central venous catheter instead of the Tenckhoff peritoneal dialysis catheter as a PD catheter. Modified PD was intermittent. We recorded and monitored circulation and metabolism index. RESULTS: Five cases (100%) with modified PD were restored to normal renal function. Congestive heart failure was gradually alleviated, and pulmonary and cardiovascular function were improved. Urine volume increased. Neither peritonitis nor catheter leakage occured in any of our cases. Urine volume increased due to PD, from 0.16 + 0.18 mL/kg*h before PD to 2.63 + 1.05 ml/kg*h at the end of PD (P < .05). Serum creatinine, serum urea nitrogen, and serum K+ changed from 85.0 ± 36.5 µmol/L, 17.1 ± 7.5 mmol/L, and 4.57 ± 0.30 mmol/L before PD, to 76.0 ± 36.7 µmol/L, 20.1 ± 11.0 mmol/L, and 4.42 ± 0.42 mmol/L at the end of PD, respectively (P > .05). Acidosis, hyperkalemia, hypoxemia and low cardiac output syndrome were improved. All patients were cured and discharged with normal renal function. CONCLUSION: We conclude that modified single lumen central venous catheter for PD is a safe, feasible, and less invasive therapeutic strategy for AKI in infants undergoing cardiac surgery, and is worthy of being widely applied in clinical practice.

Integration of Low-Cost GNSS and Monocular Cameras for Simultaneous Localization and Mapping.

Low-cost Global Navigation Satellite System (GNSS) receivers and monocular cameras are widely used in daily activities. The complementary nature of these two devices is ideal for outdoor navigation. In this paper, we investigate the integration of GNSS and monocular camera measurements in a simultaneous localization and mapping system. The proposed system first aligns the coordinates between two sensors. Subsequently, the measurements are fused by an optimization-based scheme. Our system can function in real-time and obtain the absolute position, scale, and attitude of the vehicle. It achieves a high accuracy without a preset map and also has the capability to work with a preset map. The system can easily be extended to create other forms of maps or for other types of cameras. Experimental results on a popular public dataset are presented to validate the performance of the proposed system.

PM2.5 induces male reproductive toxicity via mitochondrial dysfunction, DNA damage and RIPK1 mediated apoptotic signaling pathway.

Recent years, air pollution has been a serious problem, and PM2.5 is the main air particulate pollutant. Studies have investigated that PM2.5 is a risky factor to the deterioration of semen quality in males. But, the related mechanism is still unclear. To explore the effect of PM2.5, Sprague Dawley (SD) rats were exposed to PM2.5 (0, 1.8, 5.4 and 16.2mg/kg.bw.) through intratracheal instillation. The exposure was performed once every 3days and continued for 30days. In vitro, GC-2spd cells were treated using 0, 50, 100, 200µg/mL PM2.5 for 24h. The data showed that sperm relative motility rates and density were remarkably decreased, while sperm malformation rates were significantly increased with exposure to the PM2.5. The expression of Fas/FasL/RIPK1/FADD/Caspase-8/Caspase-3 and the level of 8-OHdG expression in testes were significantly increased after exposure to PM2.5. Additionally, in vitro the results showed that PM2.5 inhibited cell viability, increased the release of lactate dehydrogenase (LDH) by increasing reactive oxygen species (ROS) level. And ROS induced-DNA damage led to cell cycle arrest at G0/G1 phases and proliferation inhibition. Similar to the vivo study, the expressions of Fas/FasL/RIPK1/FADD/Caspase-8/Caspase-3 in GC-2spd cells were significantly increased after exposure to PM2.5 for 24-h. In addition, PM2.5 decreased the levels of ATP by impairing mitochondria structures, which led to energy metabolism obstruction resulted in the decrease of sperm motility. The above three aspects together resulted in the decrease in sperm quantity and quality.

Serum sTREM-1, PCT, CRP, Lac as Biomarkers for Death Risk Within 28 Days in Patients with Severe Sepsis.

This study was undertaken to evaluate the clinical efficacy of serum soluble triggering receptors expressed by myeloid cell-1 (sTREM-1), procalcitonin (PCT), C-reactive protein (CRP) and lactic acid (Lac) as biomarkers for death risk within 28 days in patients with severe sepsis. Fifty-one cases of severe sepsis from the department of ICU in Lishui People's Hospital from May 2013 to February 2017 were retrospectively analyzed. These cases were divided into survival (n=39) and death (n=12) groups based on the outcome within 28 days of treatment. Serum levels of sTREM-1, PCT, CRP and Lac were measured on the day of admission and compared between the survival and death groups. And the death prediction value within 28 days were evaluated according to serum sTREM-1, PCT, CRP and Lac. The serum level of TREM-1 and Lac were 128.70±46.10 pg/mL, 7.02±1.56 mmol/L for the death group and 83.69±26.57 pg/mL 4.44±0.45 mmol/L for survival group. The serum levels of sTREM-1 and Lac in death group were significantly higher than those of survival group (p<0.05). However, the serum PCT and CRP between the survival and death group were not statistically different (p>0.05). The death prediction sensitivity, specificity and AUC within 28 days were high for serum sTREM-1 (75.00%, 77.78%, 0.79) and APACHEII (74.89%, 84.62%, 0.84). However, the prediction value of serum level PCT, CRP and Lac were relatively low. A significant positive correlation was found between serum sTREM-1 and APACHEII score rpearson =0.54, (p<0.001). However, no such correlation was observed between serum CRP, Lac and APACHEII scores (p>0.05). CONCLUSION: Serum sTREM-1 was significantly elevated in sepsis patients who died within 28 days of admission, suggesting that this test could be a potential biomarker for severe sepsis patients, and also be used for prognostic evaluation.

Revascularization by carotid artery stenting and off-pump coronary artery bypass.

BACKGROUND: The optimal management of patients with concomitant carotid and coronary artery disease remains controversial currently. The purpose of this study was to evaluate the safety and efficacy of hybrid or staged revascularization by carotid artery stenting (CAS) and off-pump coronary artery bypass (OPCAB) in the treatment of these patients. METHODS: From September 2006 to January 2011, 59 consecutive patients with carotid and coronary artery disease underwent either hybrid (n = 20) or staged (n = 39) CAS and OPCAB, the perioperative and long-term outcomes were analysed. The primary endpoint was the incidence of stroke, perioperative myocardial infarction (MI) or death within 30 days of the procedures. RESULTS: No death occurred post-operatively. Two patients (2/20) in hybrid group and two patients (2/39) in staged group suffered from non-fatal stroke. The combined incidence of stroke, MI or death at 30 days was 10.0% in hybrid group and 5.1% in staged group (P = 0.875). The median follow-up time was 44 months (range, 28 to 80 months) with 57 patients (96.6%) available. During follow-up period, one patient had non-fatal stroke in hybrid group and one patient suffered from MI in staged group, respectively. There was no significant difference of long-term event-free survival between the two groups (log-rank test, P = 0.390). CONCLUSION: Our findings demonstrate that for patients with carotid and coronary artery disease, both hybrid and staged revascularization by CAS and OPCAB are feasible and safe therapeutic strategies with good early and long-term outcomes. However, our results have to be substantiated by larger scale studies and randomized trials.

Apoptosis and fibrosis are early features of heart failure in an animal model of metabolic cardiomyopathy.

In previous experiments, we observed signs of cardiac failure in mice overexpressing lipoprotein lipase (LPL) under the control of a muscle specific promotor and in peroxisome proliferators activated receptor alpha (PPARalpha) knockout mice overexpressing LPL under the control of the same promotor. In our current investigations, we focussed on morphological consequences and changes in mRNA and protein expression in hearts from these animals. mRNA expression was analysed by differential display analysis and Northern blot as well as by cDNA microarray analysis followed by pathway analysis. Protein expression was examined using immunoblot and immunohistochemistry. Fibrosis was determined by chromotrope aniline blue staining for collagen. A distinct increase in the expression of alpha-tubulin mRNA was noted in hearts of all mutant mouse strains compared with the control. This result was paralleled by increased alpha-tubulin protein expression. Using cDNA microarray analysis, we detected an activation of apoptosis, in particular an increase of caspase-3 expression in hearts of mice overexpressing LPL but not in PPARalpha knockout mice overexpressing LPL. This finding was confirmed immunohistochemically. In addition, we identified a distinct interstitial increase in collagen and an increase around blood vessels. In our mouse model, we detect mRNA and protein changes typical for cardiomyopathy even before overt clinical signs of heart failure. In addition, a small but distinct increase in the rate of apoptosis of cardiomyocytes and fibrotic changes contributes to cardiac failure in mice overexpressing LPL, whereas additional deficiency in PPARalpha seems to protect hearts from these effects.

Decreased aortic contractile reaction to 5-hydroxytryptamine in rats with long-term hypertension induced by lead (Pb(2+)) exposure.

Male Wistar rats were exposed to 100ppm Pb(2+) in drinking water for 10 months. Tail blood pressure, serum 5-hydroxytryptamine (5-HT), the expression of 5-HT(2B) receptor in the aorta, the aortic response to 5-HT, and the pathologic changes of aorta were examined. The systolic blood pressure of Pb(2+) exposed group was significantly increased after 2 months of Pb(2+) exposure. After 10 months of Pb(2+) exposure, aortic contractile response to 5-HT was significantly decreased. There was no significant difference in the levels of serum 5-HT and the expression of 5-HT(2B) receptor between these two groups. The aortic media and the media-lumen ratio of Pb(2+) exposed group were significantly increased. These data suggest that long-term Pb(2+) exposure can increase blood pressure, and can alter the function and structure of aortic of rats. The decreased aortic response to 5-HT has little relation to the expression of 5-HT(2B) receptor and the serum level of 5-HT, maybe is a result of the aortic structural alteration.

Inhibition of lipoprotein-associated phospholipase A2 reduces complex coronary atherosclerotic plaque development.

Increased lipoprotein-associated phospholipase A(2) (Lp-PLA(2)) activity is associated with increased risk of cardiac events, but it is not known whether Lp-PLA(2) is a causative agent. Here we show that selective inhibition of Lp-PLA(2) with darapladib reduced development of advanced coronary atherosclerosis in diabetic and hypercholesterolemic swine. Darapladib markedly inhibited plasma and lesion Lp-PLA(2) activity and reduced lesion lysophosphatidylcholine content. Analysis of coronary gene expression showed that darapladib exerted a general anti-inflammatory action, substantially reducing the expression of 24 genes associated with macrophage and T lymphocyte functioning. Darapladib treatment resulted in a considerable decrease in plaque area and, notably, a markedly reduced necrotic core area and reduced medial destruction, resulting in fewer lesions with an unstable phenotype. These data show that selective inhibition of Lp-PLA(2) inhibits progression to advanced coronary atherosclerotic lesions and confirms a crucial role of vascular inflammation independent from hypercholesterolemia in the development of lesions implicated in the pathogenesis of myocardial infarction and stroke.

Direct effects of lead (Pb2+) on the relaxation of in vitro cultured rat aorta to acetylcholine.

Lead (Pb(2+)) exposure is related to increased blood pressure or hypertension of human or animals. Abnormal vascular relaxant responses of low level Pb(2+) exposed animals were reported by several studies. However, it is difficult to tell whether these effects were induced directly by Pb(2+) or not. In this study we hypothesized that Pb(2+) can directly affect the relaxation of vessels. Male Wistar rat aortae were removed and cultured in PMRI 1640 with 1 ppm Pb(2+) (4.8 microM lead acetate) for 0.5, 6, 12 and 24h, and then their responses to acetylcholine (ACh) and sodium nitroprusside (SNP) were examined. After incubated for 24h, the relaxation induced by ACh was significantly decreased in Pb(2+) exposed aortic rings. However, there was not significant difference in relaxation induced by SNP between Pb(2+) exposed and control group. The nitrite in the culture media of aortic rings cultured for 24h, measured with Griess method, was significantly decreased in the Pb(2+) exposed group. The expression of endothelial NOS (eNOS) and isoform NOS (iNOS) in the homogenate of aortic rings cultured for 24h was measured by Western blot. The expression of eNOS of the Pb(2+) exposed group was significantly upregulated compared with that of the control group. However, there was no significant difference in the expression of iNOS in control and Pb(2+) exposed group. In conclusion, Pb(2+) was able to directly affect the relaxation of rat aorta. This effect may have some relation with the lower level of NO in the media, though the expression of eNOS was upregulated.

Influence of lead (Pb2+) on the reactions of in vitro cultured rat aorta to 5-hydroxytryptamine.

Although several studies demonstrated that lead induced abnormal vascular responses in low level lead exposed animals, investigations of the direct effects of lead on blood vessels are limited. In this study we tested the hypothesis that lead was able to directly affect the contractile reactivities of vessels. Male Wistar rat aortae were removed and cultured in PMRI 1640 with 1 ppm lead acetate for 0.5, 6, 12, 24 and 48 h, and then their responses to norepinephrine bitartrate (NE) and serotonin (5-hydroxytryptamine, 5-HT) were examined. The contractile responses to 5-HT of lead exposed aortae were significantly increased when the aortae were cultured for 24 and 48 h. Denudation of endothelium was able to abolish the increased contractile response completely. Diphenyleneiodonium (DPI), an inhibitor of the NAD(P)H oxidase, could abolish the increased contractile response to 5-HT. However, Vitamin C (VC) enhanced the contractile response of both groups to higher dosages of 5-HT. The expression of 5-HT(2B) receptor was not significantly altered by incubation with 1 ppm lead for 24 h. These data suggest that exposure to low levels of lead can directly increase the contraction of aorta to 5-HT. This effect is endothelium dependent, which is not mediated by increased expression of the 5-HT 2B receptor. The increased contraction to 5-HT may be related to increased production of superoxide (O2*-) induced by lead exposure.