Melatonin Attenuates Mitochondrial Damage in Aristolochic AcidInduced Acute Kidney Injury

Aristolochic acid (AA), extracted from Aristolochiaceae plants, plays an essential role in traditional herbal medicines and is used for different diseases. However, AA has been found to be nephrotoxic and is known to cause aristolochic acid nephropathy (AAN).AA-induced acute kidney injury (AKI) is a syndrome in AAN with a high morbidity that manifests mitochondrial damage as a key part of its pathological progression. Melatonin primarily serves as a mitochondria-targeted antioxidant. However, its mitochondrial protective role in AA-induced AKI is barely reported. In this study, mice were administrated 2.5 mg/kg AA to induce AKI. Melatonin reduced the increase in Upro and Scr and attenuated the necrosis and atrophy of renal proximal tubules in mice exposed to AA. Melatonin suppressed ROS generation, MDA levels and iNOS expression and increased SOD activities in vivo and in vitro. Intriguingly, the in vivo study revealed that melatonin decreased mitochondrial fragmentation in renal proximal tubular cells and increased ATP levels in kidney tissues in response to AA. In vitro, melatonin restored the mitochondrial membrane potential (MMP) in NRK-52E and HK-2 cells and led to an elevation in ATP levels. Confocal immunofluorescence data showed that puncta containing Mito-tracker and GFP-LC3A/B were reduced, thereby impeding the mitophagy of tubular epithelial cells. Furthermore, melatonin decreased LC3A/B-II expression and increased p62 expression. The apoptosis of tubular epithelial cells induced by AA was decreased. Therefore, our findings revealed that melatonin could prevent AA-induced AKI by attenuating mitochondrial damage, which may provide a potential therapeutic method for renal AA toxicity.

Effect of 1M3S nursing management mode combined with interventional surgery on intestinal microecological distribution in patients with primary liver cancer / 中国实用护理杂志

Objective:To investigate the effect of 1M3S nursing management mode combined with transcatheter arterial chemoembolization (TACE) on intestinal microecological distribution in patients with primary liver cancer.Methods:A total of 115 patients with primary liver cancer in Hai′an people′s Hospital from January 2017 to January 2020 were enrolled. Patients were divided into two groups according to the admission time. Patients ( n=56) receiving routine nursing care from January 2017 to December 2018 were set as control group, patients ( n=59) receiving 1M3S nursing management from January 2019 to January 2020 were set as observation group. Another 34 healthy individuals were set as healthy group from January 2017 to January 2020 in Hai′an People′s Hospital. The general data were collected in all three groups, and the serum levels of endotoxin (ET), alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were detected. Fecal samples were collected, and 16S rDNA sequencing method was used to analyze the fecal flora structure and species relative abundance among groups, and alpha diversity was analyzed. Results:At the level of phylum, the dominant phylum of the three groups were Bacteroidetes, Proteobacteria and Firmicutes. After TACE, the ET, ALT and AST levels were (9.67±2.12) ng/L, (53.24±8.47) U/L, (55.48±8.15) U/L in the control group, (4.36±2.15) ng/L, (45.31±8.36) U/L, (47.25±8.21) U/L in the observation group ( t value was 13.328, 5.052, 5.392, P<0.05). Compared with the control group, there was an increase in the relative abundance percentage of Firmicutes( t value was 16.426, P<0.01) and Lachnospiraceae in the observation group ( t value was 4.527, P<0.01), and a decrease in the relative abundance percentage of Proteobacteria ( t value was 8.462, P<0.001) after intervention. Conclusions:TACE can affect the intestinal bacteria in patients with primary liver cancer, resulting in a decrease in the relative abundance of Proteobacteria, Lachnospiraceae, and an increase in the relative abundance of Firmicutes, while application of 1M3S nursing management mode can effectively reduce the level of endotoxin, improve liver function, and reduce the imbalance of intestinal flora caused by TACE.

Correlation study of high-sensitivity C-reactive protein with risk factors and target organ damage in hypertensive patients / 中国医师进修杂志

Objective To explore the correlation of high-sensitivity C-reactive protein (hs-CRP) with risk factors and target organ damage in hypertensive patients.Methods The levels of serum hs-CRP of 216 hypertensive cases (hypertension group) and 36 healthy subjects (control group) were tested and compared among different associated diseases, the number of involved target organ and the difference of involved target organ.The relativity between variables such as total cholesterol, high density lipoprotein cholesterol (HDL-C), left ventricular mass index (LVMI) and so on and hs-CRP was analyzed by linear correlation analysis and multiple linear regression analysis.Results The levels of serum hs-CRP in hypertension group were higher than those in control group[( 1.99 ± 0.34) mg/L vs.( 1.10 ± 0.26 ) mg/L](P ＜ 0.01 ).The levels of serum hs-CRP in hypertension combined with coronarv disease and hvoertension combined with diabetes mellitus[(2.39 ± 0.24), (2.10 ± 0.18 ) mg/L, respectively]were higher than those in simple hypertension[( 1.85 ± 0.30 ) mg/L], and the levels of serum hs-CRP in hypertension combined with coronary disease were higher than those in hypertension combined with diabetes mellitus, and there were significant difference (P ＜ 0.05 ).The levels of serum hs-CRP were positively correlated with the number of involved target organ (r =0.747,P ＜0.01 ).There were significant differences among different associated diseases.The levels of serum hs-CRP in hypertension combined with left ventricle thickening were higher than those in hypertension combined with carotid atherosclerosis, renal damage and diabetic retinopathy,and there were significant differences (P ＜ 0.05 ).There was no significant difference in the level of serum hs-CRP between hypertension combined with carotid atherosclerosis and hypertension combined with renal damage (P ＞ 0.05 ).Stepwise regression analysis showed that the dominating factors of the level of serum hs-CRP were LVMI, age and HDL-C, and the level of hs-CRP showed negative correlation with HDL-C.Conclusions The levels of serum hs-CRP in hypertensive patients are higher than those in healthy subjects.The more number of involved target organ, the higher levels of serum hs-CRP.Patients with different involved target organ have different inflammatory degree.The levels of serum hs-CRP in hypertension combined with coronary disease are higher than those in hypertension combined with diabetes mellitus.Stepwise regression analysis shows that the dominating factors for hs-CRP levels are LVMI, HDL-C and age.

Effect of intensive lipid-lowering therapy on the imbalance between inflammatory and anti-inflammtory responses in patients with acute coronary syndrome / 中国医师进修杂志

Objective To investigate the effect of intensive lipid-lowering therapy on the imbalance between inflammatory and anti-inflammatory responses in patients with acute coronary syndrome (ACS).Methods Observed serum levels of hs-CRP and IL-IO in 82 patients with ACS, 17 patients with stable angina, and 22 controls. Forty-one patients with ACS were randomized to take either atorvastatin 10 mg/d (standard lipid-lowering therapy) or atorvastatin 40 mg/d (intensive lipid-lowering therapy) for one month in addition to their routine anti-anginal treatment. Serum levels of hs-CRP, blood lipids, IL-10 were investigat-ed.IL-10 was measured by ELISA. Results The level of hs-CRP in patients with ACS [(11.10 ± 14.30)mg/L] was higher than that in patients with stable angina [(2.47 ± 2.72) mg/L]and controls [(2.34 ± 4.22)mg/L] (P all < 0.05 ). The level of IL- 10 was lower in ACS patients [( 3.94 ± 1.91 ) ng/L] compared with those who had stable angina [(6.31 ± 4.26) ng/L] and controls [(7.76 ± 2.82) ng/L], Pan <0.05. The level of hs-CRP in patients with ACS was decreased and IL-10 was increased after one month treatment with atorvastatin (P < 0.05).The effect of atorvastatin 40 mg/d was more effective than that of atorvastatin 10 mg/d.Conclusions Patients with ACS have higher level of hs-CRP and lower level of IL-10 than those with sta-ble angina. This finding suggests that imbalance of inflammatory and anti-inflammatory responses is related with aggravation of atherosclerotic disease. Intensive lipid-lowering therapy is more effective than standard lipid-lowering therapy on ameliorating the imbalance.

Role of nucleotide binding oligomerization domain receptor 1 as a new innate immune recognition receptor in activation of vascular smooth muscle cells / 中国组织工程研究

AIM: Nucleotide binding oligomerization domain receptor 1 (NOD1) is a recently identified intracellular pathogen pattern recognition receptor of innate immunity. This study was designed to explore the role of NOD1-mediated innate immune signal pathway in the activation of vascular smooth muscle cells (VSMCs), and investigate the effect of peptidoglycan (PGN) on the activation and expression of NOD1 in human VSMCs. METHODS: The experiment was performed in the central laboratory of the Second Affiliated Hospital of Dalian Medical University from June 2006 to March 2007.①Subject: Human coronary artery VSMCs were purchased from Cambrex company.② Methods: Human coronary artery VSMCs were cultured in vitro, and stimulated with NOD1 agonist PGN (10 mg/L) for 0, 3, 6 and 24 hours. ③ Evaluation: The mRNA expression of NOD1 in VSMCs was measured by real time quantitative reverse transcription-polymerase chain reaction. The concentration in the culture supernatants of interleukin-8 (IL-8) and tumor necrosis factor-? (TNF-?) was determined by enzyme linked immunosorbent assay. RESULTS: ①Human VSMCs constitutively expressed a low level of NOD1 at resting condition. Upon PGN stimulation, the expression of NOD1 mRNA was up-regulated in VSMCs, from 0.164?0.005 to 0.231?0.027 (P

Synergistic Effect of Nucleotide binding Oligomerization Domain 2 and Toll-like Receptor Agonists on Proliferation and Release of Proinflammatory Cytokines in Vascular Smooth Muscle Cells / 中华高血压杂志

Objective To investigate the expression of nucleotide-binding oligomerization domain 2(NOD2),an intracelluar pathogen pattern recognition receptor,and Toll like receptor(TLR) 2,4 in human vascular smooth muscle cells(VSMC),and its effect on production of proinflammatory cytokines in VSMC.Methods Human coronary artery smooth muscle cells were in vitro stimulated with NOD2 agonist Muramyl dipeptide(MDP),TLR2 agonist Pam3CSK4(PAM3)and TLR4 agonist lipopolysaccharides(LPS) alone or MDP in cocultured with either PAM3 or LPS.The mRNA expression of NOD2 and fibroblast growth factor-2(FGF-2) were measured by real time RT-PCR.The concentration in the culture supernatants of interleukin-8(IL-8) and tumor necrosis factor-?(TNF-?) was determined by ELISA.VSMC proliferation was analyzed by the MTT assay.Results MDP up-regulate the expression of NOD2 mRNA in VSMC in a time-dependent manner(0 h:0.028?0.001;3 h:0.045?0.002;6 h:0.053?0.002;24 h:0.162?0.013).It up-regulate the expression of FGF-2 mRNA(MDP 9.3?0.4 vs control 7.4?0.2;P

The intracellular pattern recognition receptors-NOD like receptors / 中国病理生理杂志

NODs are cytosolic proteins that contain a nucleotide-binding oligomerization domain(NOD).These intracellular proteins are a class of pattern recognition receptors with unique functions in the innate and the acquired immune systems.NOD like receptors,including NOD1 and NOD2,are associated with host responses to intracellular invasion by bacteria or the intracellular presence of specific bacterial products.Activation of NOD like receptors initiates proinflammatory signalling via NF-?B activation,which is necessary for clearance of infecting pathogens from the host.Several different mutations in the genes encoding NOD1 and NOD2 are associated with susceptibility to inflammatory disorders.