Nano-elemental selenium particle developed via supramolecular self-assembly of chondroitin sulfate A and Na2SeO3 to repair cartilage lesions.

Cartilage repair is a significant clinical issue due to its restricted ability to regenerate and self-heal after cartilage lesions or degenerative disease. Herein, a nano-elemental selenium particle (chondroitin sulfate A­selenium nanoparticle, CSA-SeNP) is developed by the supramolecular self-assembly of Na2SeO3 and negatively charged chondroitin sulfate A (CSA) via electrostatic interactions or hydrogen bonds followed by in-situ reducing of l-ascorbic acid for cartilage lesions repair. The constructed micelle exhibits a hydrodynamic particle size of 171.50 ± 2.40 nm and an exceptionally high selenium loading capacity (9.05 ± 0.03 %) and can promote chondrocyte proliferation, increase cartilage thickness, and improve the ultrastructure of chondrocytes and organelles. It mainly enhances the sulfation modification of chondroitin sulfate by up-regulating the expression of chondroitin sulfate 4-O sulfotransferase-1, -2, -3, which in turn promotes the expression of aggrecan to repair articular and epiphyseal-plate cartilage lesions. The micelles combine the bio-activity of CSA with selenium nanoparticles (SeNPs), which are less toxic than Na2SeO3, and low doses of CSA-SeNP are even superior to inorganic selenium in repairing cartilage lesions in rats. Thus, the developed CSA-SeNP is anticipated to be a promising selenium supplementation preparation in clinical application to address the difficulty of healing cartilage lesions with outstanding repair effects.

Network Pharmacology Study of Bioactive Components and Molecular Mechanisms of the Glycoside Fraction from Picrorhiza scrophulariiflora Against Experimental Colitis.

Purpose: To explore the potential mechanism of glycosidic fraction of Picrorhiza scrophulariiflora Pennell (GPS) extract for the treatment of colitis using UPLC-QTOF-MS analysis, network pharmacology and experimental research. Methods: The active components of GPS extract were identified by UPLC-QTOF-MS analysis and extracted their targets from the databases, which was used for network pharmacology analysis. Kyoto Encyclopedia of genes and genomes (KEGG) pathway analysis was performed to discover potential therapeutic mechanisms, and the network pharmacology results were then validated by in vivo and in vitro experiments. Results: The results showed that GPS extract significantly alleviated the clinical signs of colitis, including body weight, disease activity index, colon shortening, and colon tissue damage, and inhibited the transcription and production of colonic IL-1ß and IL-6 in DSS-induced colitis mice. In vitro, GPS extract also significantly suppressed nitric oxide (NO) production, iNOS expression, IL-1ß and IL-6 transcription of LPS-activated RAW 264.7 cells. Network pharmacology integrated with experimental validation identified that GPS extract significantly suppressed Akt, p38, ERK, and JNK phosphorylation in vivo and in vitro, and luteolin, apocynin, caffeic acid, caffeic acid methyl ester, luteoloside, picroside II, aucubin, cinnamic acid, vanillic acid, and sweroside were the main components responsible for the anti-inflammatory effect of GPS. These findings demonstrate that the potential anti-inflammatory effect of GPS extract against colitis is achieved through suppressing PI3K/Akt and MAPK pathways, and that the abovementioned active components mainly exerted its anti-inflammatory effect. Conclusion: The therapeutic effect of GPS extract on colitis is related to PI3K/Akt and MAPK pathways, which is a promising remedy for colitis therapy.

Selenium nanoparticles: Properties, preparation methods, and therapeutic applications.

Selenium nanoparticles (SeNPs) are a unique type of nano-sized elemental selenium that have recently found wide application in biomedicine. It has been shown that the properties of SeNPs can be varied by different fabrication methods. Moreover, SeNPs have various therapeutic effects in medical applications due to their excellent biological and adaptable physical properties. At the same time, SeNPs can be used as a carrier medium for various therapeutic substances, which can bring out the full curative effects of the drugs. In this review, the differences in bioactivity properties of SeNPs prepared from different substances were reviewed; the therapeutic effects and mechanisms of SeNPs in cancer, inflammation, neurodegenerative diseases, diabetes, reproductive diseases, cardiovascular diseases, and other diseases were discussed; and the importance of the development of SeNPs was further emphasized.

Single and Combined Effects of Short-Term Selenium Deficiency and T-2 Toxin-Induced Kidney Pathological Injury Through the MMPs/TIMPs System.

The single and combined effects of short-term selenium (Se) deficiency and T-2 toxin-induced kidney pathological injury through the MMPs/TIMPs system were investigated. Forty-eight rats were randomly divided into control, 10 ng/g T-2 toxin, 100 ng/g T-2 toxin, Se-deficient, 10 ng/g T-2 toxin and Se deficiency combined, and 100 ng/g T-2 toxin and Se deficiency combined groups for a 4-week intervention. The kidney Se concentration was measured to evaluate the construction of animal models of Se deficiency. Kidney tissues were analyzed by hematoxylin-eosin staining, Masson staining, and transmission electron microscope to observe the pathological changes, the severity of kidney fibrosis, and ultrastructural changes, respectively. Meanwhile, quantitative polymerase chain reaction and immunohistochemical staining were used to analyze the gene and protein expression levels of matrix metallopeptidase 2/3 (MMP2/3) and tissue inhibitor of metalloproteinase 1 (TIMP1). The results showed that short-term Se deficiency and T-2 toxin exposure can cause kidney injury through tubular degeneration and even lead to kidney fibrosis. And the combination of T-2 toxin and Se deficiency had a synergistic effect on the kidney. A dose-response effect of the T-2 toxin was also observed. At the gene and protein levels, the expression of MMP2/3 in the intervention group increased, while the expression of TIMP1 decreased compared with the control group. In conclusion, short-term Se deficiency and T-2 toxin exposure might lead to injury and even the development of fibrosis in the kidneys, and combined intervention can increase the severity with a dose-dependent trend. MMP2/3 and TIMP1 likely play a significant role in the development of kidney fibrosis.

Health-promoting properties of barley: A review of nutrient and nutraceutical composition, functionality, bioprocessing, and health benefits.

Barley is one of the world's oldest cereal crops forming an important component of many traditional diets. Barley is rich in a variety of bioactive phytochemicals with potentially health-promoting effects. However, its beneficial nutritional attributes are not being fully realized because of the limited number of foods it is currently utilized in. It is therefore crucial for the food industry to produce novel barley-based foods that are healthy and cater to customers' tastes. This article reviews the nutritional and functional characteristics of barley, with an emphasis on its ability to improve glucose/lipid metabolism. Then, recent trends in barley product development are discussed. Finally, current limitations and future research directions in glucolipid modulation mechanisms and barley bioprocessing are discussed.

Investigating the Mechanism of Rhizoma Coptidis-Eupatorium fortunei Medicine in the Treatment of Type 2 Diabetes Based on Network Pharmacology and Molecular Docking.

Objective: This study systematically explored the mechanism of Rhizoma Coptidis-Eupatorium fortunei in treating type 2 diabetes mellitus (T2DM) by using network pharmacology and molecular docking methods. Methods: The TCMSP database was used to screen out the active ingredients and related targets of Rhizoma Coptidis-Eupatorium fortunei (R-E) drug pair. GeneCards, OMIM, DrugBank, and other databases were used to screen the related targets of T2DM, and then, the UniProt database was used to standardize the relevant targets of T2DM. Then, the Venn analysis was performed on the active ingredient-related targets and disease-related targets of R-E drugs to find the intersection targets. Using the STRING database and Cytoscape software, the PPI network and "drug-active ingredient-target-disease" network are constructed by intersecting targets and corresponding active ingredients. Through the cluster profiler package in the R software, GO function enrichment analysis and KEGG pathway enrichment analysis were carried out on the intersection targets and the screened core targets, and the prediction results were verified by molecular docking. Results: Taking OB ≥ 30% and DL ≥ 0.18 as the standard, a total of 25 effective active ingredients of R-E drug pairs were screened, including berberine, palmatine, coptisine, and so on. After corresponding, 19 effective chemical components and 284 targets of the R-E drug pair were obtained. After searching multiple disease databases, 1289 T2DM-related targets were screened. After the summary, 159 common targets were obtained in this study. Finally, in the bioinformatics analysis, this study concluded that quercetin, luteolin, berberine, palmatine, and coptisine are the main chemical components of the R-E drug pair. ESR1, MAPK1, AKT1, TP53, IL6, and JUN are the important core targets. GO and KEGG enrichment analyses showed that Rhizoma Coptidis-Eupatorium fortunei could improve T2DM by regulating multiple biological processes and pathways. Molecular docking results showed that berberine, palmatine, and coptisine had higher binding to the core target, and MAPK1, AKT1, and IL6 could stably bind to the active ingredients of Rhizoma Coptidis-Eupatorium fortunei. Conclusion: Rhizoma Coptidis-Eupatorium fortunei may have therapeutic effects on T2DM such as anti-inflammatory and regulating glucose and lipid metabolism through multiple components, multiple targets, and multiple signaling pathways, which provides a scientific basis for further research on the hypoglycemic effect of Rhizoma Coptidis-Eupatorium fortunei drug pair.

Purification and Identification of Lipid-Lowering Protein from Barley Extract after Lactiplantibacillus plantarum dy-1 fermentation.

Previous studies have found that the protein in barley extract fermented by Lactiplantibacillus plantarum dy-1 has the ability to inhibit lipid accumulation. However, the isolation, purification, and structural identification of the protein with lipid-lowering activity were still needed. In the present study, barley protein fermented by L. plantarum dy-1 with the optimal lipid-lowering ability was isolated and purified in three steps: using ammonium sulfate precipitation, anion-exchange chromatography, and size-exclusion chromatography. Combined with the model of HepG2 cells induced by oleic acid, the results showed that the pure protein LFBEP-C1 had the best lipid-lowering potential. Furthermore, our research found that LFBEP-C1 enriched the content of hydrophobic amino acids in LFBEP-C1. Ultraviolet spectroscopy analysis indicated that the glycosidic bond in LFBEP-C1 was an O-type glycosidic bond. The FTIR and circular dichroism spectra indicated that α-helix and random coil were the main secondary structures of LFBEP-C1. Mass spectrometry determined the theoretical molecular weight of LFBEP-C1 as 48 kDa, and its amino acid coverage was 63%. These findings suggest that the protein LFBEP-C1 with the best lipid-lowering activity was isolated and purified, and its structural characteristics were identified.

Protective Effect of Mitophagy Regulated by mTOR Signaling Pathway in Liver Fibrosis Associated with Selenium.

BACKGROUND: As a central organ of energy metabolism, the liver is closely related to selenium for its normal function and disease development. However, the underlying roles of mitochondrial energy metabolism and mitophagy in liver fibrosis associated with selenium remain unclear. METHODS: 28 rats were randomly divided into normal, low-selenium, nano-selenium supplement-1, and supplement-2 groups for a 12-week intervention. We observed pathological and ultrastructural changes in the liver and analyzed the effects of selenium deficiency and nano-selenium supplementation on liver metabolic activities and crucial proteins expression of mammalian target of the rapamycin (mTOR) signaling pathway. RESULTS: Selenium deficiency caused liver pathological damage and fibrosis with the occurrence of mitophagy by disrupting normal metabolic activities; meanwhile, the mTOR signaling pathway was up-regulated to enhance mitophagy to clear damaged mitochondria. Furthermore, nano-selenium supplements could reduce the severity of pathological damage and fibrosis in livers and maintain normal energy metabolic activity. With the increased concentrations of nano-selenium supplement, swelling mitochondria and mitophagy gradually decreased, accompanied by the higher expression of mTOR and phosphorylation-modified mTOR proteins and lower expression of unc-51 like autophagy activating kinase 1 (ULK1) and phosphorylation-modified ULK1 proteins. CONCLUSIONS: Mitophagy regulated by the mTOR signaling pathway plays a dual protective role on low-selenium inducing liver fibrosis and nano-selenium supplements preventing liver fibrosis. Mitochondrial energy metabolism plays an important role in these processes as well.

The Leaves of Cyclocarya paliurus: A Functional Tea with Preventive and Therapeutic Potential of Type 2 Diabetes.

Type 2 diabetes mellitus (T2DM) has become a universal and chronic global public health concern and causes multiple complex complications. In order to meet the rapidly growing demand for T2DM treatment, increased research has been focused on hypoglycemic drugs. Cyclocarya paliurus (Batal.) Iljinsk is the only living species of the genus Cyclocarya Iljinskaja, whose leaves have been extensively used as a functional tea to treat obesity and diabetes in China. An enormous amount of very recent pharmacological research on the leaves of C. paliurus has demonstrated that they carry out numerous biological activities, such as hypoglycemic, anti-inflammatory, and intestinal microbiota regulation. Multiple in vitro and in vivo studies have also shown that the extracts of C. paliurus leaves are innocuous and safe. This study aims to provide an up-to-date review of the botany, traditional uses, phytochemistry, pharmacological effects against diabetes, toxicology, and clinical studies of C. paliurus leaves, in hopes of promoting a better understanding of their role in the prevention and treatment of T2DM.

Progress of Selenium Deficiency in the Pathogenesis of Arthropathies and Selenium Supplement for Their Treatment.

Selenium, an essential trace element for human health, exerts an indispensable effect in maintaining physiological homeostasis and functions in the body. Selenium deficiency is associated with arthropathies, such as Kashin-Beck disease, rheumatoid arthritis, osteoarthritis, and osteoporosis. Selenium deficiency mainly affects the normal physiological state of bone and cartilage through oxidative stress reaction and immune reaction. This review aims to explore the role of selenium deficiency and its mechanisms existed in the pathogenesis of arthropathies. Meanwhile, this review also summarized various experiments to highlight the crucial functions of selenium in maintaining the homeostasis of bone and cartilage.

Protective Effect of Keluoxin against Diabetic Nephropathy in Type 2 Diabetic Mellitus Models.

Diabetic nephropathy (DN) is a chronic kidney disease that develops in patients with diabetes mellitus (DM). Renal dysfunction and persistent proteinuria are the main clinical features of DN. Podocyte injury is an important cause of persistent proteinuria and diabetic kidney disease (DKD) progression. Traditional Chinese patent medicines can improve renal function by enhancing autophagy and promoting apoptosis. Keluoxin is a Chinese patent medicine that has the effect of invigorating qi and nourishing yin, activating blood, and eliminating blood stasis. Therefore, we hypothesized that Keluoxin may have a protective effect against diabetic nephropathy in rats with type 2 DM. Rats induced with diabetes through streptozocin (STZ) injection and a high-fat and high-sugar diet were treated with Keluoxin (0.63 g/kg/day) for 8 weeks, and renal function, biochemical indicators, and histopathological changes in renal tissues were observed. Immunofluorescence staining and western blot analysis were used to detect the expression of autophagy-related proteins. The results showed that Keluoxin reduced blood glucose and lipid levels, improved renal function, and alleviated renal histopathological changes in rats with DN. The therapeutic effect was similar to that of Irbesartan (15.6 mg/kg/day). It is inferred that the mechanism works through reducing the obstruction of downstream pathways of autophagy by improving the lysosomal degradation function and alleviating podocyte injury. This study demonstrates that Keluoxin could regulate autophagy in podocytes, alleviate kidney injury in rats with DN, and have a protective effect on renal function; its mechanism can thus be a potential therapy for DN.

Protective effect of chondroitin sulfate nano-selenium on chondrocyte of patients with Kashin-Beck disease.

OBJECTIVE: To investigate the protective effect of chondroitin sulfate nano-selenium (SeCS) on chondrocyte of Kashin-Beck disease (KBD). METHODS: Chondrocyte samples were isolated from the cartilage of three male KBD patients (54-57 years old). The chondrocytes were respectively divided into four groups: (a) control group, (b) SeCS supplement group (100 ng/mL SeCS), (c) T-2 + SeCS supplement group (20 ng/mL T-2 + 100 ng/mL SeCS), and (d) T-2 group (20 ng/mL T-2). Live/dead staining and transmission electron microscopy (TEM) were used to observe cell viability and ultrastructural changes in chondrocytes respectively. Expressions of Caspase-9, cytochrome C (Cyt-C), and chondroitin sulfate (CS) structure-modifying sulfotransferases including carbohydrate sulfotransferase 3, 15 (CHST-3, CHST-15), and uronyl 2-O-sulfotransferase (UST) were examined by quantitative real-time polymerase chain reaction. RESULTS: After one- or three-days intervention, the number of living chondrocytes in the SeCS supplement group was higher than that in the control group, while it is opposite in the T-2 + SeCS supplement group and T-2 group. The cellular villi number in the surface increased in the SeCS supplement group compared with the control group. Mitochondrial morphology density was improved in the T-2 + SeCS supplement group compared with the T-2 group. Expressions of CHST-3, CHST-15, UST, Caspase-9, and Cyt-C on the mRNA level significantly increased in the T-2 + SeCS supplement group and T-2 group compared with the control group. CONCLUSIONS: SeCS supplement increased the number of living chondrocytes, improved the ultrastructure, and altered the expressions of CS structure-modifying sulfotransferases, Caspase-9, and Cyt-C.

Thymoquinone inhibits the proliferation and invasion of esophageal cancer cells by disrupting the AKT/GSK-3ß/Wnt signaling pathway via PTEN upregulation.

Although thymoquinone (TQ) has been reported to exert antitumor activity against various types of human cancers without evident toxicity, limited studies have reported the effects of TQ on esophageal cancer. Here, we showed that TQ induced cell cycle arrest in the G2/M phase and significantly inhibited cell proliferation and invasion. Further investigation of the potential mechanism revealed that TQ increased the levels of p53 and p21 but significantly reduced the expression of Cyclin B1, Cyclin A, and Cyclin E. Moreover, TQ led to a decrease in Bcl-2 and an increase in cleaved caspase-3, cleaved caspase-7, cleaved caspase-9, and Bax, indicating that TQ induced apoptosis by activating the intrinsic mitochondrial apoptosis pathway. Western blotting showed that TQ disrupted the PI3K/AKT pathway by upregulating PTEN, thus modulating GSK-3ß activity, increasing ß-catenin degradation, and decreasing decreased MMP-2 and MMP-9 levels in Eca109 cells. However, these changes were attenuated by disrupting PTEN function (using a potent inhibitor) or downregulating PTEN expression. In addition, in vivo results showed that the efficacy of TQ as an antitumor agent in a mouse xenograft tumor model. In conclusion, TQ suppressed human esophageal cancer cells proliferation and invasion both in vitro and in vivo and could provide a novel therapeutic approach for esophageal cancer.

Imperatorin ameliorates learning and memory deficits through BDNF/TrkB and ERK/CaMKIIα/CREB signaling in prenatally-stressed female offspring.

Prenatal stress (PS) can lead to impaired spatial learning and memory in offspring. Imperatorin (IMP) is a naturally occurring furanocoumarin with many pharmacological properties. However, the effects of IMP on cognitive impairment induced by PS and the underlying molecular mechanisms remain unclear. We investigated the protective effect of IMP treatment after PS on learning and memory deficits in female offspring at postnatal 60 days. After treating prenatally-stressed offspring with IMP (15 and 30 mg/kg) for 28 days, we found that IMP increased body weight and ameliorated spatial learning and memory and working memory deficits in female offspring rats. Meanwhile, hippocampal Glu and serum corticosterone levels in prenatally-stressed offspring were significantly decreased after IMP administration. Additionally, IMP treatment significantly increased BDNF, TrkB, CaMKII, and CREB mRNA expression in the hippocampus of offspring rats. Furthermore, PS-mediated induction of RKIP protein and mRNA expression and glucocorticoid receptor protein expression in the hippocampus of offspring rats were significantly decreased by IMP treatment, and the protein expression of BDNF and TrkB and relative levels of p-EKR/ERK, p-CaMKIIα/CaMKIIα, and p-CREB/CREB were remarkably increased after IMP treatment. Taken together, IMP can ameliorate PS-induced learning and memory deficits through BDNF/TrkB and ERK/CaMKIIα/CREB signaling pathway and hypothalamic-pituitary-adrenal axis.

Association of magnesium consumption with type 2 diabetes and glucose metabolism: A systematic review and pooled study with trial sequential analysis.

Prevention of type 2 diabetes (T2D) with diet or diet supplementation is challenging. This article aims to draw conclusive associations between magnesium intake and T2D incidence and evaluate the effect of magnesium supplementation on glucose metabolism. Databases were searched for related articles from inception to May 15, 2019. Prospective cohort studies investigating the relevant relationship as well as randomized controlled trials (RCTs) assessing the effect of magnesium supplementation were eligible. We conducted trial sequential analysis (TSA) to prove the sufficiency of the current evidence. Twenty-six publications involving 35 cohorts were included in the analysis. Compared to the lowest magnesium intake, the highest level was associated with a 22% lower risk for T2D; the risk was reduced by 6% for each 100 mg increment in daily magnesium intake. Additional analysis of 26 RCTs (1168 participants) was performed, revealing that magnesium supplementation significantly reduced the fasting plasma glucose (FPG) level (SMD, -0.32 [95% CI, -0.59 to -0.05], 2-hour oral glucose tolerance test (2-h OGTT) result (SMD, -0.30 [-0.58 to -0.02]), fasting insulin level (SMD, -0.17 [-0.30 to -0.04]), homeostatic model assessment-insulin resistance (HOMA-IR) score (SMD, -0.41 [-0.71 to -0.11]), triglyceride (TG) level, systolic blood pressure (SBP) and diastolic blood pressure (DBP). TSA showed an inverse association, with most benefits of magnesium supplementation on glucose metabolism being stable. In conclusion, magnesium intake has an inverse dose-response association with T2D incidence, and supplementation appears to be advisable in terms of glucose parameters in T2D/high-risk individuals.

M2 macrophages mediate sorafenib resistance by secreting HGF in a feed-forward manner in hepatocellular carcinoma.

BACKGROUND: Sorafenib is the only approved first line systemic therapy for advanced hepatocellular carcinoma (HCC) in the last decade. Tumour resistance to sorafenib has been of major obstacles to improve HCC patient survival. METHODS: We polarised THP-1 cells to M1 and M2 macrophages, performed various in vitro assays and developed sorafenib-resistant xenograft models to investigate the role of tumour-associated macrophages (TAM)-secreted molecules in HCC resistance to the targeted therapy. RESULTS: We demonstrated M2, but not M1, macrophages not only promote proliferation, colony formation and migration of hepatoma cells but also significantly confer tumour resistance to sorafenib via sustaining tumour growth and metastasis by secreting hepatocyte growth factor (HGF). HGF activates HGF/c-Met, ERK1/2/MAPK and PI3K/AKT pathways in tumour cells. Tumour-associated M2 macrophages were accumulated in sorafenib-resistance tumours more than in sorafenib-sensitive tumours in vivo and produced abundant HGF. HGF chemoattracts more macrophages migrated from surrounding area, regulates the distribution of M2 macrophages and increases hepatoma resistance to sorafenib in a feed-forward manner. CONCLUSIONS: Our results provide new insights into the mechanisms of sorafenib resistance in HCC and rationale for developing new trials by combining sorafenib with a potent HGF inhibitor such as cabozantinib to improve the first line systemic therapeutic efficacy.

High sulfide production induced by algae decomposition and its potential stimulation to phosphorus mobility in sediment.

This study is devoted to addressing the effects of algae blooms on sulfur cycle and the consequent phosphorus mobility in the sediments of freshwater lake ecosystems. A mesocosm experiment was conducted to investigate these effects through monitoring the dynamics of sulfur (S), iron (Fe) and phosphorus (P) in water and sediments, and their diffusion fluxes at the sediment-water interface (SWI). In addition, the abundance of sulfate-reducing bacteria (SRB) in the water column was also detected. The addition of the algae lead to an increase of SRB, a drastic decline of sulfate and a significant increase of total dissolved sulfide (ΣS2-, the peak value of near 3.0 mmol/L on day 6) in the water column. These results suggest the sulfate reduction was dramatically promoted during algae decomposition. Indeed the ΣS2- was 2 to 3 times of SO42- initial concentration, and higher ΣS2- was produced with higher algal biomass. Moreover, the diffusive flux of ΣS2- at the SWI was negative, indicating that diffusion of ΣS2- from water column toward sediment was occurring. These results indicated that algae decomposition might also be another important source of ΣS2- (termed "algae-derived ΣS2-") in addition to sulfate reduction. The increase of Fe(II) in surface sediment pore-water was slightly delayed compared to the ΣS2- generation in the water column, which illustrated that Fe oxyhydroxides in sediments were transformed into Fe(II) through chemical reduction of ΣS2-. Concomitantly, the vertical distribution of PO43- in high amounts algae group suggested that desorption and release of iron oxides-bound PO43- occurred in sediments. Collectively, algae bloom can boost the lake eutrophication not only through direct release of nutrients but also through the high production of ΣS2-and indirect promotion of phosphorus mobility in sediment.

The isolation, structural characterization and anti-osteosarcoma activity of a water soluble polysaccharide from Agrimonia pilosa.

A homogenous polysaccharide (APP), with a molecular weight of 120 kDa, was isolated from the dried aerial parts of Agrimonia pilosa. Gas chromatography (GC) and GC-MS analysis revealed that APP has a backbone of 1,3-linked Glcp and 1,3, 6-linked Glcp, and branched with 1-linked Glcp terminal along the main chain in a relative ratio of 2:1:1. We investigated the response of human osteosarcoma U-2 OS cells to APP treatment. MTT result showed that APP significantly inhibited cell viability in a concentration dependent manner via induction of apoptotic death in U-2 OS cells, as determined by annexin V/propidium iodide (PI) staining. Western blot analysis also indicated that APP CRA increased in Bax/Bcl-2 ratios by up-regulating Bax expression and triggered the release of cytochrome c from mitochondria into the cytoplasm. Moreover, APP supplement induced the activation of caspase-3, and -9, but not caspase-8 in U-2 OS cells. Likewise, APP administration significantly suppressed tumor growth in BALB/C nude mice bearing U-2 OS xenograft tumors. All these results indicate that APP-induced apoptosis is associated with the activation of a caspase-3-mediated mitochondrial pathway.

Biomimetic Nanovesicles for Enhanced Antitumor Activity of Combinational Photothermal and Chemotherapy.

The combination of multiple modalities has shown great potential in cancer treatment with improved therapeutic effects and minimized side effects. Here, we fabricated a type of doxorubicin-encapsulated biomimetic nanovesicle (NV) by a facile method with near-infrared dye insertion in the membrane for combinatorial photothermal and chemotherapy. With innate biomimetic properties, NVs enhanced the uptake by tumor cells while reducing the phagocytosis of macrophages. Upon laser irradiation, NVs can convert the absorbed fluorescent energy into heat for effective tumor killing. Hyperthermia can further induce membrane ablation of NVs to accelerate the release of chemotherapeutic drug for potent cytotoxicity to tumor cells. The NVs improved drug accumulation and showed a more efficient in vivo photothermal effect with a rapid temperature increase in tumors. Moreover, the NV-based combinational photothermal and chemotherapy exhibited significant tumor growth suppression with a high inhibitory rate of 91.6% and negligible systemic toxicity. The results indicate that NVs could be an appealing vehicle for combinational cancer treatment.

Effects of scalp electroacupuncture on the PI3K/Akt signalling pathway and apoptosis of hippocampal neurons in a rat model of cerebral palsy.

Background Substantial evidence from clinical reports has established that most cerebral palsy (CP) patients benefit from a comprehensive rehabilitation exercise training programme. Such advances are enhanced when scalp electroacupuncture (EA), applied at a location corresponding to the projection of the motor area, is combined with rehabilitation exercise training. However, little information exists regarding the mechanistic basis for these effects. Objective To examine whether EA stimulation within the scalp projection location of the motor area can inhibit apoptosis of hippocampal neurons by regulating the PI3k/Akt signalling pathway in a rat model of CP. Methods Fifty male Sprague-Dawley rats underwent surgical modelling of CP. Five were used to confirm successful establishment of the model and the remaining 45 rats were randomly divided into one of three groups that remained untreated (CP group, n=15) or received EA treatment alone (CP+EA group, n=15) or EA in combination with a PI3K/Akt inhibitor (CP+EA+LY294002 group, n=15)). An otherwise healthy negative control group of rats undergoing sham surgery was also included (Control group, n=15). In the CP+EA and CP+EA+LY294002 groups, EA was applied to the scalp surface at alocation corresponding to the projection of the motor area. Basso, Beattie and Bresnahan (BBB) locomotor scores, hippocampal protein expression of Akt and p-Akt (by Western blot analysis) and neuronal apoptosis in hippocampal tissue (by histopathology) were assessed at 7, 14 and 21 days post-CP induction. Results CP rats receiving scalp EA treatment demonstrated improved behavioural scores, less hippocampal neuronal apoptosis and higher expression levels of Akt and p-Akt (p<0.05) at all time points studied compared with untreated CP rats. There were no significant differences observed between CP+EA+LY294002 and untreated CP model groups. Conclusions The effects of scalp EA on the PI3K/ Akt signalling pathway may represent one of the mechanisms involved in the inhibition of hippocampal neuronal apoptosis and improvement of deficits associated with CP in a rat model.