Effect of pectin oligosaccharides supplementation on infant formulas: The storage stability, formation and intestinal absorption of advanced glycation end products.

Pectin oligosaccharides with a molecular weight greater than 700 Da was obtained from the pomace of kiwi (Actinidia arguta). Based on characteristics analysis and inhibitory activity of advanced glycation end products (AGEs) formation in vitro, the target pectin oligosaccharides was added to infant formulas and then subjected to accelerated storage. Results showed that pectin oligosaccharides supplementation inhibited the browning of infant formulas and glassy transition of lactose, and slowed down the increase of water activity under accelerated storage conditions. Pectin oligosaccharides also inhibited the formation of AGEs in infant formulas, such as 5-(hydroxymethyl)furfural, Nε-carboxymethyl-lysine, Nε-carboxyethyl-lysine, methylglyoxal hydromidazolones, glyoxal hydromidazolones, glyoxal-lysine dimer, methylglyoxal-lysine dimer and pyrraline. Besides, permeability studies using Caco-2 cell monolayer also showed that pectin oligosaccharides supplementation inhibited the intestinal absorption of AGEs, especially 5-(hydroxymethyl)furfural, Nε-carboxymethyl-lysine, Nε-carboxyethyl-lysine and glyoxal hydromidazolones. These results provide a reliable theoretical basis for the application of pectin oligosaccharides in infant formulas.

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.

Clinical trial for conventional medicine integrated with traditional Chinese medicine (TCM) in the treatment of patients with chronic kidney disease.

BACKGROUND: The prevalence of chronic kidney disease (CKD) has been rapidly increasing and has become one of the most concerned global health problems. It is of good importance to improve therapeutic efficiency of CKD and delay disease progression to end stage renal disease (ESRD). Traditional Chinese Medicine (TCM) is a widely used complementary therapy for patients with CKD. The aim of this study is to evaluate whether basic treatment combined with Chinese herbs mixture Qi Gui Yi Shen decoction could achieve better therapeutic effect on CKD patients. METHODS: To determine whether traditional Chinese medicine Qi Gui Yi Shen decoction could achieve better therapeutic effect, we will conduct a randomized controlled trial. A total of 100 CKD patients that meet the inclusion criteria will be enrolled and divided into 2 groups: Qi Gui Yi Shen group (QGYS group) and placebo group. Each group will receive 6-monthly basic treatment in combination with TCM or placebo 3 times per day. Efficacy of Qi Gui Yi Shen decoction is evaluated by analyzing renal function and TCM symptoms, other efficacy assessments include serum level of PAI-I, expression of transforming growth factor beta1 (TGF-beta1). Routine blood count, plasma albumin (ALB), and alanine transaminase (ALT) are evaluated as side effect and safety profile. DISCUSSION: The results from the clinical trial will provide evidence for the effectiveness and safety of Qi Gui Yi Shen Decoction as a treatment for CKD patients. Furthermore, this will propose a new theory and method for CKD treatment. TRIAL REGISTRATION: Registered with Chinese Clinical Trials Registry at www.chictr.org. (Registration number: ChiCTR1900021622) on 1 March 2019.

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.

A Trojan horse biomimetic delivery strategy using mesenchymal stem cells for PDT/PTT therapy against lung melanoma metastasis.

Mesenchymal stem cell (MSC)-based biomimetic delivery has been actively explored for drug accumulation and penetration into tumors by taking advantage of the tumor-tropic and penetration properties of MSCs. In this work, we further demonstrated the feasibility of MSC-mediated nano drug delivery, which was characterized by the "Trojan horse"-like transport via an endocytosis-exocytosis-endocytosis process between MSCs and cancer cells. Chlorin e6 (Ce6)-conjugated polydopamine nanoparticles (PDA-Ce6) were developed and loaded into the MSCs. Phototherapeutic agents are safe to the MSCs, and their very low dark toxicity causes no impairment of the inherent properties of MSCs, including tumor-homing ability. The MSCs loaded with PDA-Ce6 (MSC-PDA-Ce6) were able to target and penetrate into tumors and exocytose 60% of the payloads in 72 h. The released PDA-Ce6 NPs could penetrate deep and be re-endocytosed by the cancer cells. MSC-PDA-Ce6 tended to accumulate in the lungs and delivered PDA-Ce6 into the tumors after intravenous injection in the mouse model with lung melanoma metastasis. Phototoxicity can be selectively triggered in the tumors by sequentially treating with near-infrared irradiation to induce photodynamic therapy (PDT) and photothermal therapy (PTT). The MSC-based biomimetic delivery of PDA-Ce6 nanoparticles is a potential method for dual phototherapy against lung melanoma metastasis.

Integrated Hydrogel Platform for Programmed Antitumor Therapy Based on Near Infrared-Triggered Hyperthermia and Vascular Disruption.

Complete tumor regression is a great challenge faced by single therapy of near-infrared (NIR)-triggered hyperthermia or vascular disrupting agents. An injectable nanocomposite (NC) hydrogel is rationally designed for combined anticancer therapy based on NIR-triggered hyperthermia and vascular disruption. The NC hydrogel, codelivered with Prussian blue (PB) nanoparticles and combretastatin A4 (CA4), has good shear-thinning, self-recovery, and excellent photothermal properties. Because of the remarkable tumor-site retention and sustained release of CA4 (about 10% over 12 days), the NC hydrogel has a tumor suppression rate of 99.6%. The programmed combinational therapy conveys the concept of "attack + guard", where PB-based NIR irradiation imposes intensive attack on most of cancer cells, and CA4 serves as a guard against the tumor growth by cutting off the energy supply. Moreover, the biosafety and eco-friendliness of the hydrogel platform pave the way toward clinical applications.

Optimal time for single-stage pull-through colectomy in infants with short-segment Hirschsprung disease.

OBJECTIVE: Short-segment Hirschsprung disease (HSCR) is the predominant type of HSCR that affects approximately 75% of patients. Whether single-stage endorectal pull-through (ERPT) surgery is appropriate for neonatal patients with HSCR has not been definitively determined. This retrospective cohort study concerning infants with short-segment HSCR investigated the optimal age for single-stage ERPT surgery, regardless of the operative approach. METHODS: The 198 patients were stratified by operative age ≤ 3 or > 3 months (groups A or B, respectively, n = 62 and 136, respectively). Diagnoses of short-segment HSCR were conducted by preoperative contrast enema and rectal suction biopsy with acetylcholinesterase immunohistochemical staining. The perioperative clinical course for all patients was reviewed and the accuracy rate of the preoperative diagnoses and postoperative short- and midterm outcomes were assessed. RESULTS: The rates of diagnostic accuracy, according to the results of the preoperative contrast enema or rectal suction biopsy, were lower in group A (67.2 and 93.5%, respectively) than in group B (81.4 and 94.9%, respectively). In groups A and B, 49 (79.1%) and 108 (79.4%) infants, respectively, completed follow-up examinations. The short-term outcomes were postoperative HSCR-associated enterocolitis, adhesive bowel obstruction, anastomosis leakage, and anal stenosis during the first 12 months after surgery. The midterm outcomes were incontinence and constipation at ~24 months after surgery. Compared with group B, group A experienced more incidences of anastomotic leakage in the short-term and more soiling in the midterm. In groups A and B, the rates of constipation recurrence were nil and 1.9%, respectively. CONCLUSION: Infants with HSCR ≤3 months old at the time of single-stage ERPT surgery showed lower rates of accurate and conclusive diagnostic results and poorer postoperative outcomes. Waiting to perform this surgery until infants are older might be more beneficial.

Fabrication of injectable CuS nanocomposite hydrogels based on UCST-type polysaccharides for NIR-triggered chemo-photothermal therapy.

Injectable nanocomposite hydrogels containing small copper sulfide nanoparticles (6-8 nm) with a 54.6% photothermal conversion efficiency have been facilely prepared by applying an upper critical solution temperature (UCST)-type biopolymer gellan. This minimally invasive formulation ablates cancer completely in vivo after NIR-triggered chemo-photothermal therapy.

Fabrication of biopolymeric complex coacervation core micelles for efficient tea polyphenol delivery via a green process.

Nanoencapsulation is a promising method to improve the bioavailability of tea polyphenol (TPP). In this work, we adopted a green process to develop a new kind of complex coacervation core micelles (C3Ms) based on biopolymers for efficient tea polyphenol delivery. First, gelatin-dextran conjugate was synthesized using Maillard reaction. Then the C3Ms were produced by mixing gelatin-dextran conjugate with TPP. Variable factors on the self-assembly of the C3Ms were investigated. Under optimal conditions, the obtained C3Ms are of nanosize (average 86 nm in diameter) with narrow distribution. The formation of the C3Ms is attributed to hydrophobic interaction and hydrogen bonding instead of electrostatic interaction. Transmission electron microscope (TEM) and scanning electron microscope (SEM) results showed that C3Ms have a spherical shape with core-shell structure. ζ-Potential measurement suggested that the core is composed of gelatin with TPP, whereas the shell is composed of dextran segments. The encapsulation efficiency of the C3Ms is pH-independent, but the loading capacity is controllable and as high as 360 wt % (weight/weight of protein). In addition, the C3Ms show sustained release of TPP in vitro. MTT assay revealed that the C3Ms have comparable or even stronger cytotoxicity against MCF-7 cells than free TPP.

Glutamine prevents total parenteral nutrition-associated changes to intraepithelial lymphocyte phenotype and function: a potential mechanism for the preservation of epithelial barrier function.

Total parenteral nutrition (TPN) results in a number of derangements to the intestinal epithelium, including a loss of epithelial barrier function (EBF). As TPN supplemented with glutamine has been thought to prevent this loss, this article further defined the impact of glutamine on EBF, and investigated potential mechanisms that contributed to the preservation of EBF. C57BL/6J male mice were randomized to enteral nutrition (control), TPN, or TPN supplemented with glutamine (TPN+GLN). Changes in intraepithelial lymphocyte (IEL)-derived cytokine expression were measured, and EBF was assessed with electrophysiologic methods and assessment of junctional protein expression. TPN resulted in a significant decline in EBF, and this loss of EBF was significantly prevented in the TPN+GLN group. Coincident with these changes was a loss of intraepithelial lymphocyte (IEL, mucosal lymphocyte)-derived IL-10 and increase in interferon-gamma (IFN-gamma) expression, and a decline in IEL numbers in the TPN group. A prevention in the increase in IFN-gamma and decline in IL-10 expression was seen in the TPN+GLN group. To determine the mechanism responsible for these glutamine-associated cytokine changes, we tested whether blockade of the IL-7 signaling pathway between epithelial cells (EC) and IEL would prevent these changes; however, blockade failed to influence IEL-derived cytokine changes. Glutamine-supplemented TPN leads to a specific IEL-derived cytokine profile, which may account for the preservation of EBF; and such action may be due to a direct action of glutamine on the IEL.