Effects of chitooligosaccharide-zinc on the ovarian function of mice with premature ovarian failure via the SESN2/NRF2 signaling pathway / 中国天然药物

Chitooligosaccharide-zinc (COS·Zn) is a powerful anti-oxidant and anti-aging scavenger, whose anti-oxidative ability immensely exceeds vitamin C. Therefore, this study was aimed to investigate the protective effects of COS·Zn against premature ovarian failure (POF) and potential mechanisms. Female KM adult mice were divided into the following groups: a treatment group (150 mg·kg

Microencapsulation of immunoglobulin Y: optimization with response surface morphology and controlled release during simulated gastrointestinal digestion / 浙江大学学报（英文版）（B辑：生物医学和生物技术）

Immunoglobulin Y (IgY) is an effective orally administered antibody used to protect against various intestinal pathogens, but which cannot tolerate the acidic gastric environment. In this study, IgY was microencapsulated by alginate (ALG) and coated with chitooligosaccharide (COS). A response surface methodology was used to optimize the formulation, and a simulated gastrointestinal (GI) digestion (SGID) system to evaluate the controlled release of microencapsulated IgY. The microcapsule formulation was optimized as an ALG concentration of 1.56% (15.6 g/L), COS level of 0.61% (6.1 g/L), and IgY/ALG ratio of 62.44% (mass ratio). The microcapsules prepared following this formulation had an encapsulation efficiency of 65.19%, a loading capacity of 33.75%, and an average particle size of 588.75 µm. Under this optimum formulation, the coating of COS provided a less porous and more continuous microstructure by filling the cracks on the surface, and thus the GI release rate of encapsulated IgY was significantly reduced. The release of encapsulated IgY during simulated gastric and intestinal digestion well fitted the zero-order and first-order kinetics functions, respectively. The microcapsule also allowed the IgY to retain 84.37% immune-activity after 4 h simulated GI digestion, significantly higher than that for unprotected IgY (5.33%). This approach could provide an efficient way to preserve IgY and improve its performance in the GI tract.

Anti-melanoma effect of intratumoral injection of PD-L1-siRNA-loaded phenylboronic acid-modified chitooligosaccharide nanoparticles: a preliminary study / 国际药学研究杂志

Objective: To prepare phenylboronic acid-modified chitooligosaccharide(PBA-COS)nanoparticles(PBA-COS/ siPD-L1) loaded with PD-L1-siRNA(siPD-L1) and investigate the properties and in vivo anti -melanoma(B16F10) effect of the nanoparticles in mice. Methods: PBA-COS/siPD-L1 nanoparticles were prepared by the complex coacervation method. The particle size and Zeta potential of nanoparticles were investigated by dynamic light scattering. Agarose gel electrophoresis was used to evaluate the binding capacity of PBA-COS carriers to siRNA. The morphology of nanoparticles was observed by transmission electron microscope. In vitro cell uptake efficiency was analyzed by flow cytometry. The mouse subcutaneous B16F10 melanoma model was used to in- vestigate the in vivo effect of intratumoral injection of the nanoparticles on the tumor growth and metastasis. The apoptosis of tumor cells and the lung metastasis of tumors were analyzed and examined by TUNEL staining and HE staining, respectively. Results: The particle size of the PBA-COS/siPD-L1 nanoparticles was(101.9±1.89)nm and the Zeta potential was(25.6±1.52)mV. The nanoparticles were observed to be spherical under the transmission electron microscope. The nanoparticles were efficiently ingestible by B16F10 cells, and the intratumoral injection of the nanoparticles could inhibit tumor growth and lung metastasis of B16F10 melanoma in vivo in mice by inducing the B16F10 cell apoptosis. Conclusion: The intratumoral injection of PBA-OS/siPD-L1 nanoparticles could significantly inhibit tumor growth(the tumor inhibition rate was 42.4%, P<0.01)and lung metastasis of melanoma in mice.

Microencapsulation of immunoglobulin Y: optimization with response surface morphology and controlled release during simulated gastrointestinal digestion / 浙江大学学报（英文版）（B辑：生物医学和生物技术）

Immunoglobulin Y (IgY) is an effective orally administered antibody used to protect against various intestinal pathogens, but which cannot tolerate the acidic gastric environment. In this study, IgY was microencapsulated by alginate (ALG) and coated with chitooligosaccharide (COS). A response surface methodology was used to optimize the formulation, and a simulated gastrointestinal (GI) digestion (SGID) system to evaluate the controlled release of microencapsulated IgY. The microcapsule formulation was optimized as an ALG concentration of 1.56% (15.6 g/L), COS level of 0.61% (6.1 g/L), and IgY/ALG ratio of 62.44% (mass ratio). The microcapsules prepared following this formulation had an encapsulation efficiency of 65.19%, a loading capacity of 33.75%, and an average particle size of 588.75 μm. Under this optimum formulation, the coating of COS provided a less porous and more continuous microstructure by filling the cracks on the surface, and thus the GI release rate of encapsulated IgY was significantly reduced. The release of encapsulated IgY during simulated gastric and intestinal digestion well fitted the zero-order and first-order kinetics functions, respectively. The microcapsule also allowed the IgY to retain 84.37% immune-activity after 4 h simulated GI digestion, significantly higher than that for unprotected IgY (5.33%). This approach could provide an efficient way to preserve IgY and improve its performance in the GI tract.

Preparation of gadolinium-loaded stearic acid grafted chitooligosaccharide and application in pancreatic tumor imaging / 中国医学影像技术

Objective To prepare gadolinium-loaded stearic acid grafted chitooligosaccharide (COSSA-DTPA-Gd) and evaluate its micelle properties,cytotoxicity,relaxation rate in vitro,and pancreatic tumor in vivo imaging.Methods Stear ic acid grafted chitooligosaccharide (COSSA) was synthesized by acetylation reaction between stearic acid and chitooligosaccharide.Diethylenetriaminepentaacetic dianhydride (DTPA) was conjugated to the residual amino groups of COSSA,then Gd3+ was chelated to obtain the final product.The micelle properties were measured using an electron microscopy and a laser particle sizer.The MTT assay was adopted to determine cytotoxicity.The in vitro relaxation rate and in vivo imaging of pancreatic tumor were evaluated using an MR scanner.Results COSSA-DTPA-Gd could self-assemble into stable micelles in aqueous solutions with a critical micelle concentration of (5.12±0.43)μg/ml.The micelles had positive charge and exhibited roughly spherical shape with a mean diameter of (58.3± 5.7)nm.The content of Gd3+ in COSSA-DTPA-Gd was 330.31 μmol/g.The nanoprobe and Magnevist,the commercial formulation,showed similar cytotoxicity (P＞0.05).The cell survival rate within 24 h were higher than 85％.The in vitro relaxation rate of COSSA-DTPA-Gd was 8.23 mM-1 ·s-1.After intravenous injection,COSSA-DTPA-Gd showed a better positive contrast-enhancing effect for pancreatic tumor than Magnevist.The MR images at the tumor periphery was rapidly enhanced,while a slow increase in image quality was observed in tumor core.Conclusion The prepared COSSA-DTPA-Gd can be used for efficient MR imaging of pancreatic tumor.

Modulation of lipid metabolism by mixtures of protamine and chitooligosaccharide through pancreatic lipase inhibitory activity in a rat model / 한국실험동물학회지

Overweight and obesity are usually related with high fat and calorie intake, and seriously causative of lifestyle-related diseases such as cardiovascular disorders, arteriosclerosis, and colon cancer. In this study, we propose a novel dietary therapy against overweight and obesity using mixtures of protamine and chitooligosaccharide (COS), which are known to interrupt the lipid metabolism in the body. Protamine is a dietary protein originated from salmon reproductive organ, and COS is an oligosaccharide made from chitin or chitosan by chemical or enzymatic hydrolysis. In the enzyme activity analysis in vitro, protamine and COS strongly suppressed the activity of pancreatic lipase, which is the primary enzyme for the digestion and absorption of lipids in the intestine. In in vivo animal test, the mixtures of protamine and COS significantly reduced the serum levels of triglyceride (TG), total cholesterol (T-CHO), and low density lipoprotein-cholesterol (LDLC) and inhibited the accumulation of lipids in liver tissue of Sprague Dawley (SD) rats fed high fat diets. On the other hand, they increased fecal TG and T-CHO contents. From these alterations in lipid metabolism, we verified that protamine and COS mixtures could effectively interrupt the digestion and absorption of dietary lipids in the body by inhibiting pancreatic lipase activity. In addition, protamine and COS mixtures increased the serum level of high density lipoprotein-cholesterol (HDLC), responsible for removing cholesterol from cells and protecting atherosclerosis, and therefore decreased the potential risks of cardiovascular diseases by lowering values of the atherogenic index (AI) and cardiac risk factor (CRF). Taken together, we suggest protamine and COS mixtures as a prominent dietary therapy for the prevention of overweight, obesity, and further cardiovascular diseases related with hyperlipidemia.

Solubility effects on antibacterial activity of chemically modified chitooligosaccharides of fungal origin / Efectos de la solubilidad sobre la actividad antibacteriana de quitooligosacáridos modificados químicamente de origen fúngico

Chitin and chitosan are a class of metabolites that occurring in some fungi species that are associated with commercial and medicinal plants, this is in Mucor sp. for example with an ample number of biological activities, being antibacterial and antifungal one of the most important. Into our program of search of biopesticides and natural compounds with biological activities, we have studying chitosan that was obtained from the culture medium of the fungus Mucor ruoxii. Chitooligosaccharides were prepared by partial acid hydrolysis of native chitosan and an aminoglycosylated derivative was obtained by reductive amination of the chitooligosaccaride. The solubilities of these compounds were measured at different pHs and its antibacterial activity against Escherichia coli (gram-negative) and Staphylococcus aureus (gram-positive). Chitosan and the derivatives tested exhibited a good antibacterial activity against S. aureus.

Quitina y quitosano son una clase de metabolitos que producen algunas especies de hongos que están asociados con plantas medicinales y comerciales, esto es por ejemplo en Mucor sp., con un amplio número de actividades biológicas, siendo la antibacteriana y antifúngica unas de las más importantes. En nuestro programa de investigación de biopesticidas y compuestos naturales, estamos estudiando quitosano obtenido de el medio de cultivo del hongo Mucor ruoxii. Quitooligosacáridos fueron preparados por hidrólisis parcial ácida de quitosano nativo y un derivado aminoglicosilado fue obtenido por aminación reductiva del quitooligosacárido. Las solubilidades de estos compuestos fueron medidas a diferentes pHs y su actividad antibacteriana frente a Escherichia coli (gram-negative) and Staphylococcus aureus (gram-positive). Quitosano y los derivados testeados exhiben una buena actividad antibacteriana frente a S. aureus.