Mitigation of malondialdehyde-induced protein lipoxidation by epicatechin in whey protein isolate.

Malondialdehyde (MDA) can induce lipoxidation in whey protein isolate (WPI). The physicochemical changes in this reaction with or without the presence of a phenolic compound epicatechin (EC) were characterized in this study. Results suggested the content of MDA was significantly reduced during co-incubation of MDA and EC. The addition of EC dose-dependently alleviated MDA-induced protein carbonylation, Schiff base formation and loss of tryptophan fluorescence. The interruption of MDA-binding to WPI was directly visualized by immunoblotting analysis. Observation of the surface microstructure of WPI showed that MDA-induced protein aggregation was partially restored by EC. Meanwhile, EC was found to promote loss of both protein sulfhydryls and surface hydrophobicity due to possible phenol-protein interactions. These observations suggested the potential of EC in the relief of MDA-mediated protein lipoxidation.

SIRT1 Asn346 sugar chain promoting collagen deacetylation protective effect on osteoblasts under stress.

Silencing type information regulator homolog 1 (SIRT1) is a class of nicotinamide adenine dinucleotide (NAD+) dependent deacetylases, which is the convergence point of important physiological processes in vivo, namely, osteoblast aging, energy metabolism, and bone remodeling. To verify whether the O-acetylglucosamine (O-GlcNAc) modification of SIRT1 in the nucleus of osteoblasts enhances its deacetylase activity under stress and protects osteoblasts through the RANK/RANKL signaling pathway by collagen deacetylation. The R language and online data research identified SIRT1 as being involved in bone metabolism. Enrichment analysis showed that SIRT1 is involved in osteoblast transcription, apoptosis, and deacetylation pathways. Interactive Immuno-blotting and immunofluorescence experiments revealed that SIRT1 and O-glycosylation catalytic enzyme (OGT) were localized in the nucleus. Mass Spectrometry analysis showed that O-glycosylation occurred on the asparagine at the 346th position of SIRT1, and N346th was located in the central domain of SIRT1. Furthermore, the protein structure analysis of PyMol also proved that the OGT binding region was in the central domain of SIRT1. Under physiological conditions, both wtSIRT1 and SIRT1N346R can inhibit RANKL-mediated transcriptional activation. The RT-PCR detection results showed that wtSIRT1 reduced RANKL transcription under the conditions of apoptotic agent treatment. The finding that SIRT1 can regulate the physiological process of bone remodeling through the RANK/RANKL signaling pathway in osteoblasts under stress. The O-glycosylation and deacetylation activity of SIRT1 significantly increased, regulating the balance between osteoblast survival and apoptosis by deacetylation of key proteins such as RANKL.

7-Hydroxyflavone Alleviates Myocardial Ischemia/Reperfusion Injury in Rats by Regulating Inflammation.

Inflammation is the primary pathological process of myocardial ischemia/reperfusion injury (MI/RI). 7-Hydroxyflavone (HF), a natural flavonoid with a variety of bioactivities, plays a crucial role in various biological processes. However, its cardioprotective effects and the underlying mechanisms of MI/RI have not been investigated. This study aimed to explore whether pretreatment with HF could attenuate MI/RI-induced inflammation in rats and investigate its potential mechanisms. The results showed that pretreatment with HF could significantly improve the anatomic data and electrocardiograph parameters, reduce the myocardial infarct size, decrease markers of myocardial injury (aspartate transaminase, creatine kinase, lactate dehydrogenase, and cardiac troponin I), inhibit inflammatory cytokines (IL-1ß, IL-6, and TNF-α), suppress oxidative stress, and recover the architecture of the cardiomyocytes. The cardioprotective effect of HF was connected with the regulation of the MAPK/NF-κB signaling pathway. What is more, molecular docking was carried out to prove that HF could be stably combined with p38, ERK1/2, JNK, and NF-κB. In summary, this is a novel study demonstrating the cardioprotective effects of HF against MI/RI in vivo. Consequently, these results demonstrate that HF can be considered a promising potential therapy for MI/RI.

Acute glucose fluctuation promotes RAGE expression via reactive oxygen species­mediated NF­κB activation in rat podocytes.

Diabetic nephropathy (DN) is a common chronic complication of diabetes, for which acute glucose fluctuation (AGF) is a potential risk factor. Fluctuating hyperglycemia has been confirmed to induce more serious kidney damage than hyperglycemia in diabetic rats; however, the mechanism remains unknown. The purpose of this study was to explore the potential role of AGF in the progression of DN. Viability of rat podocytes following 72­h AGF treatment was detected using Cell Counting­Kit­8. The rates of apoptosis and the level of reactive oxygen species (ROS) in rat podocytes were assessed by flow cytometry. Western blotting and reverse transcription­quantitative PCR were performed to measure relative protein and mRNA expression levels, respectively. Transfection with an mRFP­GFP­LC3 adenoviral vector was used to track autophagic flux under confocal microscopy. The results indicated that AGF could inhibit cell proliferation, promote TNF­α, interleukin­1ß (IL­1ß), and reactive oxygen species (ROS) generation, and increase autophagy in rat podocytes. Moreover, AGF upregulated receptor for advanced glycation end products (RAGE) expression via activation of NF­κB/p65 and IκBα. Pretreatment with 5 mM N­Acetyl­L­cysteine or 10 µM pyrrolidine dithiocarbamate effectively reduced cellular damage and inhibited activation of the NF­κB/RAGE signaling pathway. Thus, AGF induces rat podocyte injury by aggravating oxidative stress, promoting the inflammatory response, and regulating ROS­mediated NF­κB/RAGE activation.

Comparison of Interlaminar and Transforaminal Approaches for Treatment of L5 /S1 Disc Herniation by Percutaneous Endoscopic Discectomy.

OBJECTIVE: The aim of this study was to compare the clinical efficacy of percutaneous endoscopic interlaminar discectomy (PEID) and percutaneous endoscopic transforaminal discectomy (PETD) in treating L5 /S1 disc herniation. METHODS: A retrospective analysis of 76 patients with L5 /S1 intervertebral disc herniation was performed. There were two surgical treatment groups: one with patients receiving PEID and the other with patients receiving PETD. The two groups were compared by length of surgery, times of intraoperative X-ray exposure, postoperative time in bed, length of hospital stay, operative complications, patient's assessment of pain using a visual analogue scale (VAS), and disability using the Oswestry disability index (ODI) before and after surgery. RESULTS: Subjects in the PEID group were in surgery for 60.90 ± 13.11 min and needed intraoperative X-ray exposure 4.10 ± 1.09 times. Patients in this group were ambulatory by 7.52 ± 1.08 h after surgery and were hospitalized for 5.05 ± 0.92 days. In contrast, patients in the PETD group were in surgery for 84.06 ± 15.58 min and needed intraoperative X ray exposure 12.81 ± 8.46 times. These patients were ambulatory by 7.06 ± 0.91 h after surgery and remained in the hospital for 4.94 ± 0.80 days. Based on these data, operation time and fluoroscopy time were significantly less (P < 0.002 and P < 0.001, respectively) for subjects in the PEID group. However, ambulatory time and hospitalization were similar for both in terms of pain relief and decreased disability, and subjects in both groups responded well to the surgery and showed a significant decrease in both VAS and ODI scores at their 1-year follow-up (P < 0.01). Furthermore, there were no statistically significant differences between the two surgeries in terms of pain relief and decrease in disability. CONCLUSION: For L5 /S1 disc herniation, PEID and PETD provide similar results for patients. However, PEID has the advantage over PETD in that it is a shorter procedure and exposes the patient to less radiation.