Association between plasma adiponectin levels and left ventricular systolic dysfunction in sepsis patients.

PURPOSE: As a well-known cardioprotective factor, the relevance of adiponectin (APN) to heart function following sepsis remains largely unknown. The present study evaluated the effects of plasma APN levels on heart function and 28-day mortality in sepsis patients. MATERIALS AND METHODS: This was a prospective study that was performed with 98 patients with sepsis and 32 controls. Left ventricular systolic dysfunction (LVSD) was defined as a left ventricular ejection fraction (LVEF) ≤ 45% based on echocardiography. The effects of APN on the development of sepsis-related LVSD and prediction of 28-day mortality were evaluated. RESULTS: Plasma APN levels significantly decreased in sepsis patients compared with controls, with rising severity of illness, and positively correlated with the LVEF and stroke volume index. Sepsis patients with LVSD had lower APN levels than patients without LVSD. According to the receiver operating characteristic curve, plasma APN levels had the comparable value in prediction of LVSD incidence than those conditional factors, including brain natriuretic peptide (BNP) and highly sensitive cardiac troponin T (hsTnT). Twenty-three of the 98 sepsis patients (23.47%) died at 28 days. Adiponectin levels were an independent predictive factor for 28-day mortality. CONCLUSIONS: Low APN levels were associated with the incidence of LVSD and 28-day mortality in sepsis patients. Adiponectin may be a novel factor that may be useful for the diagnosis of LVSD.

Melatonin attenuates nicotine-induced autophagy and neurological changes by decreasing the production of reactive oxygen species.

Purpose: The aim of this study was to explore the mechanism of neurological changes underlying the toxicity of nicotine.Materials and methods: Rat pheochromocytoma 12 (PC12) cells and human neuroglia (HM) cells were used. The ROS levels of the cells were detected by the FACScan. Autophagy flux was monitored by a tandem monomeric RFP-GFP-tagged LC3 lentivirus. The autophagic proteins LC3, SQSTM1/p62 and Beclin1 were detected by western blot assay. In order to evaluate the effects of nicotine and melatonin on the morphological changes of neurons, primary cortical neurons were obtained and immunocytochemistry of TUBB3 tubulin were conducted.Results: Nicotine increased the levels of reactive oxygen species (ROS) in PC12 and HM cells in a concentration-dependent manner. Microscopy showed increased autophagic flux in nicotine-treated PC12 cells. Subsequent western blotting results showed that nicotine induced increase in the levels of LC3B-II and Beclin1, and decreased SQSTM1/p62 in a concentration-dependent manner. Finally, nicotine treatment reduced the length of TUBB3-positive axons and dendrites. Melatonin, a mitochondrially targeted antioxidant, reduced the ROS level, and blocked autophagy activation and the morphologic structural changes induced by nicotine.Conclusions: Our results suggested that the role of nicotine in neuronal toxicity maybe through the induction of ROS and the subsequent activation of autophagy. These effects could be restored by melatonin.

Inhibitory effects of PGA1 and TRI on the apoptosis of cardiac microvascular endothelial cells of rats.

The present study investigated the protective effects and molecular mechanism of prostaglandin A1 (PGA1) and triptolide (TRI) on apoptosis of cardiac microvascular endothelial cells (CMVECs) in rats. CMVECs of rats were isolated and then cultured. MTT method was used to select and establish a cell hypoxia reoxygenation cell model. The cells were divided into four groups: Normoxia control group (C, normal oxygen), hypoxia reoxygenation group (H/R, hypoxia for 12 h/reoxygenation for 6 h), PGA1 group (H/R+PGA1) and TRI group (H/R+TRI). The growth of cells in each of the group was observed. B-cell lymphoma 2 (Bcl-2) mRNA expression in CMVECs and expression of Bcl-2 mRNA after PGA1 and TRI treatment were determined by RT-PCR. Cell apoptosis was detected by terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL) assay. Bcl-2 mRNA decreased significantly after hypoxia stimulation of CMVECs of rats. The expression of Bcl-2 mRNA was significantly higher in comparison to hypoxia stimulation group after treatment with PGA1 and TRI (P<0.01). The elevated effect of PGA1 on Bcl-2 mRNA was stronger than that of the TRI group (P<0.05). The number of CMVECs reduced significantly after hypoxia. By contrast, DNA fragmentation and the number of endothelial cell apoptosis were increased significantly. However, Bcl-2 mRNA expression decreased significantly, after PGA1 and TRI treatments. Furthermore, the number of apoptotic cells reduced and Bcl-2 mRNA expression increased (P<0.01). PGA1 and TRI significantly upregulated the expression of Bcl-2 mRNA, inhibited the activation of CMVECs and were able to achieve the protective effect on apoptosis of CMVECs in hypoxia-oxygenated rats.

Effect of Dialysis on Antiplatelet Drug Efficacy in Uremic Patients with Coronary Heart Disease.

BACKGROUND: Coronary intervention therapy is the main treatment for uremic patients with coronary heart disease. The studies on whether dialysis reduces the efficacy of dual antiplatelet drugs are limited. The aim of this study was to examine the effect of dialysis on antiplatelet drugs in uremic patients with coronary heart disease. METHODS: This study included 26 uremic patients who had undergone percutaneous coronary intervention in China-Japan Friendship Hospital from November 2015 to May 2017. We examined their thromboelastography results before and after hemodialysis. Self-paired t-tests were employed to analyze changes in the inhibition rate of platelet aggregation. RESULTS: The mean inhibition rates of arachidonic acid-induced platelet aggregation before and after hemodialysis were 82.56 ± 2.79% and 86.42 ± 3.32%, respectively (t= -1.278, P= 0.213). The mean inhibition rates of adenosine diphosphate-induced platelet aggregation before and after hemodialysis were 67.87 ± 5.10% and 61.94 ± 5.90%, respectively (t = 1.425, P= 0.167). There was no significant difference in the inhibition rates of platelet aggregation before or after hemodialysis. These results also applied to patients with different sensitivity to aspirin and clopidogrel. CONCLUSION: Dialysis did not affect the antiplatelet effects of aspirin and clopidogrel in uremic patients with coronary heart disease.

[Interaction of fish collagen peptide with epigallocatechin gallate].

Fish collagen is known to have good moisturising property and antioxidant ability, which has been increasingly added into cosmetics, foods and drinks as thicker agent and to increase dietary supply of collagen. Fish collagen peptide (FCP) is a white or pale yellow powder, obtained by extracting collagen from sources including the scales and bones of fish such as bonito, halibut, tuna, and sea bream. It is identical to human collagen and 100% absorbable through the skin. (-)-Epigallocatechin-3-gallate (EGCG), the major constituent of green tea, has lots of beneficial biological and pharmacological effects, including antioxidant, antimutagenic, antiviral and antiinflammatory activities. Because proteins have the desirable formulation of EGCG-fortified food, the interaction between proteins and EGCG molecules has been widely studied. At the same time, the interaction of proteins and EGCG was known to affect the content of free EGCG, structure of proteins, antioxidant capacity of EGCG in foods. But, to our knowledge, the interaction between FCP and EGCG has not been characterised clearly, and little is known about their interaction mechanism. Therefore, a better understanding of the interaction between FCP and EGCG would help to control their functional properties in food products during processing, transportation and storage when we facilitate FCP as the vehicles for EGCG. In view of the above, we planned to study the interaction of FCP with EGCG by using different spectroscopic techniques, such as fluorescence spectroscopic, FTIR, CD and Raman. EGCG caused a concentration dependent quenching of the intrinsic fluorescence of tyrosine residue in the FCP, indicating the occurrence of interactions between FCP and EGCG. Excimer-like species and dityrosine were regularly formed with the addition of EGCG into the solution, and the interaction of FCP and EGCG partly disrupted the structure-of the protein. Synchronous fluorescence results indicate that the interaction caused decrease of the polarity around tyrosine residues resulting in FCP conformation alteration. FTIR showed that the frequency of 3 281 and 1 248 cm-1 declined, the absorption peaks at 3 076 and 1 547 cm-1 had a slight red-shift, the absorption peaks at 1 659 and 1 689 cm-1 had a slight blue-shift in the FCP-EGCG complexes. It is interesting to observe that the CD intensity of FCP around 198 nm decreased with high EGCG concentration, and the peak maximum shifted to a larger wavelength (red shift). Raman spectra showed that peaks at 863 and 932 cm-1 had a slight red-shift, and decreased intensities near 932 cm-1 suggested that more exposure of proline when FCP-EGCG complexes formed. This study provides a theoretical basis for fortifying FCP products with EGCG.

Resveratrol improves hepatic steatosis by inducing autophagy through the cAMP signaling pathway.

SCOPE: Resveratrol (RSV), a natural polyphenol, has been reported to attenuate nonalcoholic fatty liver disease (NAFLD); however, its underlying mechanism is unclear. Autophagy was recently identified as a critical protective mechanism during NAFLD development. Therefore, we investigated the role of autophagy in the beneficial effects of RSV on hepatic steatosis. METHODS AND RESULTS: Via Oil red O staining, triglyceride, and ß-hydroxybutyrate detection, we found that RSV decreased palmitate-induced lipid accumulation and stimulated fatty acid ß-oxidation in hepatocytes. Based on Western blot assay, confocal microscopy and transmission electron microscopy, we found that RSV induced autophagy in hepatocytes, whereas autophagy inhibition markedly abolished RSV-mediated hepatic steatosis improvement. Moreover, RSV increased cAMP levels and the levels of SIRT1 (sirtuin 1), pPRKA (phosphorylated protein kinase A), and pAMPK (phosphorylated AMP-activated protein kinase), as well as SIRT1 activity in HepG2 cells. Incubation with inhibitors of AC (adenylyl cyclase), PRKA, AMPK, SIRT1, or with AC, PRKA, AMPK, or SIRT1 siRNA abolished RSV-mediated autophagy. Similar results were obtained in mice with hepatic steatosis. CONCLUSION: RSV improved hepatic steatosis partially by inducing autophagy via the cAMP-PRKA-AMPK-SIRT1 signaling pathway, which provides new evidence regarding RSV's effects on NAFLD treatment.

ADAMTS-7 expression increases in the early stage of angiotensin II-induced renal injury in elderly mice.

BACKGROUND/AIMS: We investigated the recently described family of proteinases, a disintegrin and metalloproteinase with thrombospondin motifs (ADAMTs), and matrix metalloproteinases (MMPs) as inflammatory mediators in inflammatory kidney damage by studying ADAMTS-1, -4, and -7 and MMP-9 expression in elderly mouse kidneys after angiotensin II (Ang II) administration. METHODS: Ang II (2.5 µg/kg/min) or norepinephrine (8.3 µg/kg/min) was subcutaneously infused in old mice. Renal injury was assessed by hematoxylin-eosin staining, 24-h albuminuria, and immunohistochemistry to evaluate inflammatory cell markers. The mRNA and protein expression of ADAMTS-1, -4, and -7 and MMP-9 were determined using real-time PCR, Western blot, and immunohistochemistry 3 days after Ang II or norepinephrine administration. RESULTS: Elderly mice in the Ang II group developed hypertension and pathological kidney damage. The mRNA and protein levels of ADAMTS-7 in the Ang II group were 3.3 ± 1.1 (P = 0.019) and 1.6 ± 0.1 (P = 0.047) vs. 1.0 ± 0.1 and 1.0 ± 0.1 in the control group on day 3. In contrast, treatment with the hypertensive agent norepinephrine did not lead to obvious renal damage or an increase in renal ADAMTS-7 expression. CONCLUSIONS: Renal ADAMTS-7 expression was induced by Ang II in elderly mice. The overexpression of ADATMTS-7 might contribute to early inflammatory kidney damage associated with aging.

Investigation into the antioxidant activity and chemical composition of alcoholic extracts from defatted marigold (Tagetes erecta L.) residue.

The influence of various solvents on the yield of polyphenols from defatted marigold residue, the antioxidant activity of the extracts and the composition of antioxidant compounds in the extracts were investigated. The content of total phenolics and flavonoids in the extracts was significantly varied with different solvents (P<0.05) and the extract by ethyl alcohol (EtOH)/water (7:3, v/v) has the highest content of total phenolics and flavonoids, 62.33 mg gallic acid equivalents (GAE)/g and 97.00 mg rutin equivalent (RE)/g, respectively. The antioxidant activity of the extracts was evaluated by radical (2,2'-azino-bis-(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS), 1,1-diphenyl-2-picrylhydrazyl (DPPH)) scavenging and ferric reducing antioxidant power (FRAP) assays. The results of the correlation analysis showed that the antioxidant activity was well correlated with the content of total phenolics and flavonoids (R²>0.900). Antioxidant components in the extracts were identified by combined on-line HPLC-ABTS·+ post-column assay and HPLC-DAD-MS method. Gallic acid, gallicin, quercetagetin, 6-hydroxykaempferol-O-hexoside, patuletin-O-hexoside and quercetin were the dominant antioxidant compounds in the extracts, and quercetagetin was identified as the strongest antioxidant capacity.

Application of targeted drug delivery system in Chinese medicine.

Targeted drug delivery system of traditional Chinese medicine (TCM) refers to those using different carriers to make the effective parts or monomer extracted from TCM or natural medicine into agents which can directly concentrate on the target site. This system is an ideal delivery approach and has became a hot spot in the field of TCM pharmaceutical research since it can improve the pharmacological effects and reduce the adverse reactions. This paper reviews literatures on TCM targeted agents which were published in the past 10 years. In accordance with the different carriers, four types of agents, liposome, nanoparticle, microsphere, and emulsion are analyzed. Liposomes were studied most profoundly and a variety of new types of liposomes was developed on the basis of the traditional liposomes. Using natural or synthetic polymer materials to carry drugs, nanoparticles and microspheres can promote the drug through the blood-brain barrier and enhance its bioavailability. Emulsion has lymphatic affinity and the drug is coated in the internal phase, which can protect the drugs from hydrolysis. All these delivery agents are proved to be effective ways to improve the clinical efficacy of drugs, and each is discussed in detail with examples. At present, TCM targeted agents are still in the exploratory stage and many problems need to be solved. Especially, it is a huge challenge to research the targeted delivery systems for the effective parts of Chinese medicines and compound prescriptions, and the paper gives a particular discussion on this point. In the future, more attention should be paid to the research on the particle agents of TCM effective parts, and the development of new carrier materials in order to enhance the overall quality of TCM targeted agents.