A Bi2S3-embedded gellan gum hydrogel for localized tumor photothermal/antiangiogenic therapy.

An injectable gellan gum-based nanocomposite hydrogel (Bi2S3@GG) was designed for X-ray computed tomography (CT) imaging and photothermal/antiangiogenic therapy. The linear anionic polysaccharide gellan gum (GG) was used as a stabilizer, embedded with ultra-small bismuth sulfide (Bi2S3) nanodots (∼2 nm) through a one-pot synthesis method. The as-prepared Bi2S3@GG hydrogel displays excellent capability for both photothermal therapy (PTT) (with a photothermal conversion efficiency of 44.3%) and X-ray computed tomography (with an X-ray absorption coefficient of 51.5 HU L g-1), integrated with real-time monitoring drug retention and tunable therapeutic functions. After the incorporation of sorafenib (SF), the hydrogel shows a sustained release of SF over 15 days. A tumor suppression rate of 98.2% is shown at day 22 postinjection in the mice received the combined treatments of photothermal/antiangiogenic therapy. In contrast, tumor growth and recurrence are observed in the single treatment. Our work presents a new strategy to construct a multifunctional hydrogel platform for a safe and precise antitumor therapy.

Sandalwood seed oil ameliorates hepatic insulin resistance by regulating the JNK/NF-κB inflammatory and PI3K/AKT insulin signaling pathways.

Sandalwood (santalum spicatum) seed oil (SSO) is rich in ximenynic acid. The aim of the present study was to investigate the effect of SSO on high-fat/high-sucrose diet (HFHSD) induced insulin resistance (IR) in comparison with fish oil (FO), sunflower oil (SO) and linseed oil (LO). Fifty male Sprague-Dawley rats were randomly divided into five dietary groups: standard chow diet (controls), HFHSD plus 7% SSO, HFHSD plus 7% FO, HFHSD plus 7% SO and HFHSD plus 7% LO. After 12 weeks of feeding, the rats were sacrificed, and the serum parameters, hepatic lipids and underlying molecular mechanisms were studied. SSO, FO or LO significantly prevented glucose intolerance, hyperglycaemia, obesity, and hepatic lipid accumulation, and decreased the homeostasis model assessment of IR (HOMA-IR) and the serum levels of pro-inflammatory factors (IL-6, IL-1ß and TNF-α) compared with SO. In addition, SSO activated the PI3K/AKT insulin signaling pathway and down-regulated the JNK/NF-κB inflammatory signaling pathway in the liver. In summary, our results proved that SSO exerted an ameliorative effect on IR by regulating the hepatic inflammation related blockage of the insulin signaling pathway in the rats.

A robust hybrid nanozyme@hydrogel platform as a biomimetic cascade bioreactor for combination antitumor therapy.

The development of highly effective and minimally invasive approaches for cancer treatment is the ultimate goal. Herein, an injectable hybrid hydrogel as a biomimetic cascade bioreactor is designed for combination antitumor therapy by providing spatiotemporally-controlled and long-term delivery of therapeutic agents. This hybrid nanozyme@hydrogel (hPB@gellan) is doped with Prussian blue (PB) nanoparticles via the in situ nanoprecipitation method in the polysaccharide gellan matrix. The obtained PB nanoparticles have a small size of 10 nm and play dual roles as a photothermal agent with a photothermal conversion efficiency of 59.6% and as a nanozyme to decompose hydrogen peroxide into oxygen. By incorporating glucose oxidase (GOD) into the hybrid hydrogel, a cascade bioreactor is formed for PB-promoted glucose consumption. Owing to its shear-thinning and self-recovery properties, the hybrid hydrogel is locally administered into tumors, and shows long-term resistance against body clearance and metabolism. The in vivo antitumor results demonstrate that the tumors in the group of combined photothermal and starvation therapy (GOD/hPB@gellan + NIR) are greatly eliminated with a tumor suppression rate of 99.7% 22 days after the treatment. The outstanding antitumor performance is attributed to the main attack by NIR-triggered hyperthermia and the holding attack by GOD-mediated starvation from the catalytic bioreactor of the hybrid hydrogel. Taking into consideration the advantages of biosafety, simple synthetic approaches and facile manipulation in treatment, the hybrid hydrogel has great potential for clinical translation.

Ximenynic Acid Regulation of n-3 PUFA Content in Liver and Brain.

BACKGROUND/AIMS: Ximenynic acid is a rare conjugated enyne fatty acid found primarily in plants in the Santalaceae family. It has been reported that sandalwood seed oil (SWSO) affects fatty acid metabolism in animal studies; however, the effects of pure ximenynic acid remain unclear. The present study aimed to study the impact of SWSO and ximenynic acid on n-3 fatty acid metabolism in the liver and brain. METHODS: Thirty C57BL/6 male mice aged 4 weeks were fed SWSO (1.0 mL/20 g bodyweight), olive oil (OO), or a combination of SWSO and OO (n = 10/group) for 8 weeks. Liver and brain fatty acid compositions were determined using gas chromatography. HepG2 cells were treated with up to 150 µM ximenynic acid and oleic acid for 48-72 h. The expression and abundance of genes and proteins relevant to n-3 fatty acid metabolism pathways were investigated. RESULTS: The intake of SWSO in mice elevated the levels of total n-3 fatty acids and decreased total n-9 fatty acids in the liver (p < 0.05) compared with the OO group. In contrast, total n-3 fatty acids were significantly decreased in the brain (p < 0.05). HepG2 cells treated with ximenynic acid for 48 h showed significant reductions in n-9 fatty acids and docosahexaenoic acid (C22:6n-3) (p < 0.05) compared with HepG2 cells treated with oleic acid. In HepG2 cells, stearoyl-CoA desaturase (SCD) and fatty acid desaturase 2 (FADS2) gene expression, as well as FADS2 protein expression, were significantly down-regulated after a 72-h incubation with 150 µM of ximenynic acid compared with the vehicle (p < 0.05). CONCLUSION: Ximenynic acid may regulate fatty acid metabolism by suppressing the expression of key enzymes of lipid metabolism. In contrast, SWSO, which has a high level of C18:3n-3, positively affected n-3 fatty acid synthesis in mouse liver compared to pure ximenynic acid. We hypothesize that a high level of precursor C18:3n-3 in SWSO promotes the endogenous synthesis of C22:6n-3 despite the presence of ximenynic acid.

Ulcerative colitis with mucosal lesions in duodenum: Two case reports.

RATIONALE: Ulcerative colitis (UC) is a chronic, nonspecific, inflammatory disease of the colon. Colorectal is the main target organ of UC, while other digestive tract involvement is rare. This report describes 2 rare cases of duodenal mucosa lesions in patients with UC after total colectomy. PATIENT CONCERNS: In case 1, a patient of 45-year-old with intermittent diarrhea and bloody mucosanguineous feces who was diagnosed as UC, revealed diffuse erosive ulcers in the descending duodenum through gastroscopy after total colectomy. In case 2, a 55-year-old Chinese female with UC, aggravated to colon cancer and received total colectomy. Eighteen months after surgery, the patient was admitted to hospital following upper abdominal pain and acid regurgitation. A gastroscopy found inflammation in the descending part of the duodenum. DIAGNOSIS: UC, duodenal mucosa lesions INTERVENTIONS:: In case 1, the patient was treated with oral mesalazine (1 g/tid) and hydrocortisone (0.3 g/d) but symptoms did not improve, and the treatment was changed to oral methylprednisolone (0.6 g/d) and a hydrocortisone enema (0.1 g/late). Finally, the patient underwent a total colectomy and ileostomy. In case 2, the patient was treated with sulfasalazine, mesalazine, and intermittent hormone enemas. A total colectomy and ileostomy were performed with the patient after diagnosed as colon cancer. After surgery, the patient received N1-(2 tetrahydrofuryl)-5-fluorouracil (FT-207), 8 g, 300 mg, and 100 mg oxaliplatin chemotherapy, and biologic therapy. OUTCOMES: In case 1, the patient presented with duodenal necrosis and died of septic shock. In case 2, the patient recovered well without recurrence by taking proton pump inhibitor. LESSONS: The occurrence of UC related ulcerative gastroduodenal mucosal lesions may be associated with progressing UC or total colitis that does not respond to hormone therapy, leading to requirement of total colectomy.

Comparative effects of sandalwood seed oil on fatty acid profiles and inflammatory factors in rats.

The aim of the present study was to investigate the effect of sandalwood seed oil on fatty acid (FA) profiles and inflammatory factors in rats. Fifty male Sprague-Dawley rats were randomly divided into five different dietary groups: 10 % soybean oil (SO), 10 % olive oil (OO), 10 % safflower oil (SFO), 10 % linseed oil (LSO) and 8 % sandalwood seed oil blended with 2 % SO (SWSO) for 8 weeks. The SWSO group had a higher total n-3 polyunsaturated fatty acids (PUFA) levels but lower n-6:n-3 PUFA ratios in both adipose tissue and liver than those in the SO, OO and SFO groups (p < 0.05). Although the SWSO group had a much lower 18:3n-3 level (4.51 %) in their dietary lipids than the LSO group (58.88 %), the levels of docosahexaenoic acid (DHA: 22:6n-3) in liver lipids and phospholipids of the SWSO group (7.52 and 11.77 %) were comparable to those of the LSO group (7.07 and 13.16 %). Ximenynic acid, a predominant acetylenic FA in sandalwood seed oil, was found to be highly incorporated into adipose tissue (13.73 %), but relatively lower in liver (0.51 %) in the SWSO group. The levels of prostaglandin F(2α), prostaglandin E2, thromboxane B2, leukotriene B4, tumor necrosis factor-α and interleukin-1ß in both liver and plasma were positively correlated with the n-6:n-3 ratios, suggesting that increased n-6 PUFA appear to increase the formation of pro-inflammatory cytokines, whereas n-3 PUFA exhibit anti-inflammatory activity. The present results suggest that sandalwood seed oil could increase tissue levels of n-3 PUFA, DHA and reduce the n-6:n-3 ratio, and may increase the anti-inflammatory activity in rats.