Morusin-Cu(II)-indocyanine green nanoassembly ignites mitochondrial dysfunction for chemo-photothermal tumor therapy.

Nanoscale drug delivery systems derived from natural bioactive materials accelerate the innovation and evolution of cancer treatment modalities. Morusin (Mor) is a prenylated flavonoid compound with high cancer chemoprevention activity, however, the poor water solubility, low active pharmaceutical ingredient (API) loading content, and instability compromise its bioavailability and therapeutic effectiveness. Herein, a full-API carrier-free nanoparticle is developed based on the self-assembly of indocyanine green (ICG), copper ions (Cu2+) and Mor, termed as IMCNs, via coordination-driven and π-π stacking for synergistic tumor therapy. The IMCNs exhibits a desirable loading content of Mor (58.7 %) and pH/glutathione (GSH)-responsive motif. Moreover, the photothermal stability and photo-heat conversion efficiency (42.8 %) of IMCNs are improved after coordination with Cu2+ and help to achieve photothermal therapy. Afterward, the released Cu2+ depletes intracellular overexpressed GSH and mediates Fenton-like reactions, and further synergizes with ICG at high temperatures to expand oxidative damage. Furthermore, the released Mor elicits cytoplasmic vacuolation, expedites mitochondrial dysfunction, and exerts chemo-photothermal therapy after being combined with ICG to suppress the migration of residual live tumor cells. In vivo experiments demonstrate that IMCNs under laser irradiation could excellently inhibit tumor growth (89.6 %) through the multi-modal therapeutic performance of self-enhanced chemotherapy/coordinated-drugs/ photothermal therapy (PTT), presenting a great potential for cancer therapy.

Dietary fiber of Tartary buckwheat bran modified by steam explosion alleviates hyperglycemia and modulates gut microbiota in db/db mice.

Type 2 diabetes is a serious threat to human health. Tartary buckwheat bran dietary fiber has good hypoglycemic activity, with its modification widely studied. However, the hypoglycemic activity of steam explosion modified Tartary buckwheat bran soluble dietary fiber (SE-SDF) has not been reported. This research aimed at investigating the hypoglycemic effect with its underlying mechanism of SE-SDF on type 2 diabetic db/db mice. Results found SE-SDF decreased the levels of fasting blood glucose and glycosylated hemoglobin while improved oral glucose tolerance, insulin resistance, and injuries of liver, pancreas, and colon in diabetic db/db mice. Additionally, SE-SDF up-regulated the protein expression levels of hepatic phosphatidylinositol 3 kinase (PI3K), G protein-coupled receptor43 (GPR43), and phospho-adenosine monophosphate activated protein kinase (p-AMPK), whereas inhibited the protein expression levels of hepatic fork-head transcription factor O1 (FoxO1), phosphoenolpyruvate carboxy kinase (PEPCK) and glucose-6-phosphatase (G-6-Pase). Moreover, SE-SDF increased the production of fecal short chain fatty acids (SCFAs) and the expression of colon GPR43 and the concentration of serum glucagon like peptide-1 (GLP-1), leading to reduced ratio of Firmicutes/Bacteroidetes but increased relative abundance of Parabacteroides, norank_f_Muribaculaceae, Alloprevotella, Ruminiclostridium_9, unclassified_f_Ruminococcaceae, and Lachnospiraceae_NK4A136_group. These findings suggested that SE-SDF ameliorated type 2 diabetes via activating the liver PI3K/Akt/FoxO1 and GPR43/AMPK signaling pathways and modulating the gut microbiota-SCFAs-GPR43/GLP-1 signaling axis.

Premna microphylla Turcz pectin protected UVB-induced skin aging in BALB/c-nu mice via Nrf2 pathway.

Excessive exposure to ultraviolet B (UVB) irradiation is one of the major risk factors for skin photoaging. The aim of this study was to investigate the protective effect of Premna microphylla Turcz pectin (PMTP) against UVB-induced skin aging in BALB/c-nu mice. PMTP was characteristic of a low methoxyl RG-I pectin with Mw was 26.60 kDa, mainly composed of galacturonic acid. PMTP-containing cream efficiently inhibited the water loss, epidermal hyperplasia, matrix metalloproteinases-1 (MMP-1), and collagen destruction in UVB-induced skin injury mice. Additionally, topical administration of PMTP-containing cream significantly increased protein levels of the nuclear factor erythroid 2-related factor 2 (Nrf2), Kelch-like ECH-associated protein 1 (Keap1), macrophage-activating factor (Maf), and heme oxygenase 1 (HO-1), and the expression of antioxidant enzymes including superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px). In contrast, application of PMTP-containing cream on mice skin decreased the protein levels of nuclear factor-kappa B (NF-κB), inhibitor kappa B kinase ß (IKKß), and cyclooxygenase-2 (COX-2), and pro-inflammatory cytokines. Taken togethmier, these findings suggest that PMTP might protect UVB-induced skin aging via activating Nrf2 pathway and suppressing NF-κB pathway.

Anti-aging effects of the fermented anthocyanin extracts of purple sweet potato on Caenorhabditis elegans.

Anthocyanins have anti-inflammatory, anticarcinogenic and antioxidant properties and anti-aging effects as well as potential application as pigments. The metabolism of anthocyanins in fermented food has attracted increasing attention. However, the effect of lactic acid bacteria (LAB) fermentation on its anti-aging activity remains mostly unknown. The current study aimed to investigate the compositions, antioxidant activities and anti-aging effect of fermented purple sweet potato anthocyanins (FSPA) on aging Caenorhabditis elegans compared to raw purple sweet potato anthocyanins (PSPA). Results showed that anthocyanins were degraded into more bioavailable phenolic acids by Weissella confusa fermentation. PSPA and FSPA can extend the lifespan of C. elegans by 26.7% and 37.5%, respectively, through improving the activity of antioxidant enzymes as well as decreasing MDA content, ROS levels and lipofuscin accumulation. Pretreatment of the worms with PSPA and FSPA induced their potential to resist to thermal tolerance and oxidative stress, and FSPA exerted a higher anti-stress effect than PSPA. Moreover, FSPA supplementation upregulated the mRNA expressions of genes daf-16, hsp-16.2, sir-2.1, skn-1 and sod-3 and downregulated the expression of daf-2 in the nematodes, whereas PSPA only induced the increase in the expressions of sir-2.1, skn-1 and sod-3. Overall, FSPA can improve stress resistance and extend the lifespan of C. elegans by both insulin/IGF-1 signaling pathway and dietary restriction pathway, providing a theoretical basis for the application of PSPA in fermented food as functional pigments.

Influence of Anesthetic Techniques on Perioperative Outcomes after Endovascular Aneurysm Repair.

BACKGROUND: The purpose of the study was to explore the influence of anesthetic techniques on perioperative outcomes after endovascular aneurysm repair (EVAR) for infrarenal abdominal aortic aneurysm (AAA) in a Chinese population. METHODS: A retrospective review was performed in patients after elective EVAR for infrarenal AAA at our single center. Patients were classified into general anesthesia (GA), regional anesthesia (RA), and local anesthesia (LA) groups. The primary outcomes (30-day mortality and morbidity) and secondary outcomes [procedure time, mean arterial pressure (MAP), and length of hospital stay (LOS)] were collected and analyzed. RESULTS: From January 2006 to December 2015, 486 consecutive patients underwent elective EVAR at our center. GA was used in 155 patients (31.9%), RA in 56 (11.5%), and LA in 275 (56.6%). The GA patients had fewer respiratory comorbidities, shorter and more angulated proximal necks, and more concomitant iliac aneurysms. LA during EVAR was significantly associated with a shorter procedure time (GA, P < 0.001; RA, P < 0.001) and shorter LOS (GA, P = 0.002; RA, P = 0.001), but a higher MAP (GA, P < 0.001; RA, P < 0.001) compared with GA and RA. LA was associated with a significantly lower risk of cardiac (odds ratio (OR) 4.27, 95% confidence interval (CI) 1.21-15.04), pulmonary (OR 5.37, 95% CI 1.58-18.23), and systemic complications (OR 4.15, 95% CI 1.85-9.33) compared with GA. RA was also associated with a decreased risk of systemic complications (OR 4.74, 95% CI 1.19-18.92) compared with GA. There was no difference in the 30-day mortality, neurologic complications, renal complications, and intraoperative extra procedures among the 3 groups. CONCLUSIONS: Anesthetic techniques for EVAR have no influence on the 30-day mortality. LA for EVAR appears to be beneficial concerning the procedure time, LOS, and 30-day systemic complications for patients after elective EVAR for infrarenal AAA in the Chinese population.

Effects of steam explosion pretreatment on the composition and biological activities of tartary buckwheat bran phenolics.

Steam explosion (SE) is an efficient technology to disrupt materials for improving their quality. In this study, SE was applied to release phenolics and improve the roughening of tartary buckwheat bran. The results showed that SE promoted the dissolution of phenolics, particularly, the content of the bound fraction was nearly increased by two times (0.36 vs. 0.99 mg GAE per g DW). The analysis of the phenolic composition showed that SE improved the liberation of bound pyrogallic acid, protocatechuic acid and caffeic acid. The biological activity tests indicated that SE effectively enhanced the oxygen radical absorbance capacity (ORAC) in vitro of the extract of bound phenolics by 270%. It also improved the cellular antioxidant activity (CAA) in vitro of the extract of free phenolics by 215%. Furthermore, SE showed potential in improving the antiproliferative activity of the total phenolic extract against Caco-2 cells as well as the bound phenolic extract against HepG2 cells in vitro.

Inhibition of AAA in a rat model by treatment with ACEI perindopril.

BACKGROUND: The purpose of the present study was to evaluate the effect of a new angiotensin converting enzyme inhibitor perindopril on the formation of experimental abdominal aortic aneurysms (AAAs) in a rat model induced by intraluminal elastase infusion and extraluminal calcium chloride (CaCl2) application. MATERIALS AND METHODS: Thirty-six male Sprague-Dawley rats were randomly distributed into three groups (n = 12 per group): model (A), sham (B), and perindopril (C). Rats in model and perindopril groups underwent intra-aortic elastase perfusion and extraluminal CaCl2 application to induce AAAs. Rats in the sham group received aortic perfusion and extraluminal application of saline. A dose of 3 mg/kg/d of perindopril was fed orally in the perindopril group. The maximum abdominal aortic diameter was measured in vivo on days 0 and 28 and by ultrasound on days 7, 14, and 21. The arterial blood pressure was measured directly using a pressure transducer after cannulation in surgery and before death. AAA tissue samples were harvested at day 28 and evaluated using normal hematoxylin and eosin stain, Verhoeff-van Gieson stain for elastin, and image analysis technique. RESULTS: Aortic diameters of rats in the model group consistently increased within 28 d, coinciding with the development of a transmural inflammatory response, thickening of intima, and destruction of the elastic media. Without alteration in blood pressure, the AAA formation rate and mean maximal diameter of aorta at day 28 were significantly lower in the perindopril group compared with the control group (1.71 ± 0.20 versus 2.70 ± 0.69 mm, P < 0.001; 0% versus 90.91%, P < 0.001) and were similar to those in the sham group (1.79 ± 0.29 mm, P = 0.175; 0%, P = 1). The thickness of intima in the perindopril group was lower than that in the model group (20.68 ± 9.96 versus 58.49 ± 32.01 µm, P = 0.001), but higher than that in the sham group (7.23 ± 2.68 µm, P = 0.005). The intensity of elastin fiber showed the opposite trend (0.8541 ± 0.0495 in sham group versus 0.7376 ± 0.1024 in perindopril group versus 0.5413 ± 0.0912 in model group, P < 0.001). CONCLUSIONS: Perindopril inhibited the aortic degeneration and AAA formation in the experimental AAA model induced by elastase and CaCl2. This effect, which was independent of its influence on hemodynamics, appeared to be induced by the suppression of the inflammatory cell influx and intimal thickening and the preservation of aortic medial elastin.