Effect of atmospheric pressure non-thermal pin to plate plasma on the functional, rheological, thermal, and morphological properties of mango seed kernel starch.

This study aimed to investigate the effect of atmospheric pressure non-thermal pin-to-plate plasma on the functional, rheological, thermal, and morphological properties of mango seed kernel starch. As cold plasma contains highly reactive species and free radicals, it is expected to cause noticeable modifications in the attributes of starch treated. The isolated mango seed kernel starch was subjected to the plasma treatment of input voltages 170 and 230 V for 15 and 30 min of exposure. Water adsorption, swelling, and solubility at lower temperatures. There has been a significant reduction (p < 0.05) in pH values of starch from 7.09 to 6.16 and also the desirable reduction in turbidity values by 42.60%. However, there has been no significant change in the oil and water binding behavior of the starch. The FTIR spectra of MSKS demonstrate the formation of amines which contributes to the better hydrophilic nature of the starch. The structural modification has been adequately confirmed by SEM images. The maximum voltage and time combination, lead to depolymerization of starch which is supported by NMR spectra thus affecting thermal and rheological properties. The application of cold plasma-modified MSKS in food would facilitate stable and smooth textural development.

Shear Stress Alterations Activate BMP4/pSMAD5 Signaling and Induce Endothelial Mesenchymal Transition in Varicose Veins.

Chronic venous diseases, including varicose veins, are characterized by hemodynamic disturbances due to valve defects, venous insufficiency, and orthostatism. Veins are physiologically low shear stress systems, and how altered hemodynamics drives focal endothelial dysfunction and causes venous remodeling is unknown. Here we demonstrate the occurrence of endothelial to mesenchymal transition (EndMT) in human varicose veins. Moreover, the BMP4-pSMAD5 pathway was robustly upregulated in varicose veins. In vitro flow-based assays using human vein, endothelial cells cultured in microfluidic chambers show that even minimal disturbances in shear stress as may occur in early stages of venous insufficiency induce BMP4-pSMAD5-based phenotype switching. Furthermore, low shear stress at uniform laminar pattern does not induce EndMT in venous endothelial cells. Targeting the BMP4-pSMAD5 pathway with small molecule inhibitor LDN193189 reduced SNAI1/2 expression in venous endothelial cells exposed to disturbed flow. TGFß inhibitor SB505124 was less efficient in inhibiting EndMT in venous endothelial cells exposed to disturbed flow. We conclude that disturbed shear stress, even in the absence of any oscillatory flow, induces EndMT in varicose veins via activation of BMP4/pSMAD5-SNAI1/2 signaling. The present findings serve as a rationale for the possible use of small molecular mechanotherapeutics in the management of varicose veins.

Steatosis Alters the Activity of Hepatocyte Membrane Transporters in Obese Rats.

Fat accumulation (steatosis) in ballooned hepatocytes alters the expression of membrane transporters in Zucker fatty (fa/fa) rats. The aim of the study was to quantify the functions of these transporters and their impact on hepatocyte concentrations using a clinical hepatobiliary contrast agent (Gadobenate dimeglumine, BOPTA) for liver imaging. In isolated and perfused rat livers, we quantified BOPTA accumulation and decay profiles in fa/+ (normal) and fa/fa hepatocytes by placing a gamma counter over livers. Profiles of BOPTA accumulation and decay in hepatocytes were analysed with nonlinear regressions to characterise BOPTA influx and efflux across hepatocyte transporters. At the end of the accumulation period, BOPTA hepatocyte concentrations and influx clearances were not significantly different in fa/+ and fa/fa livers. In contrast, bile clearance was significantly lower in fatty hepatocytes while efflux clearance back to sinusoids compensated the low efflux into canaliculi. The time when BOPTA cellular efflux impacts the accumulation profile of hepatocyte concentrations was slightly delayed (2 min) by steatosis, anticipating a delayed emptying of hepatocytes. The experimental model is useful for quantifying the functions of hepatocyte transporters in liver diseases.

Molecular weight effects of low acyl gellan gum on antioxidant capacity and rheological properties.

The current study investigated the antioxidant capacity of enzymatically cleaved low acyl gellan gum (LA-GAGR) fragments, named midi-GAGR (MWv : 1.2 × 105  Da) and mini-GAGR (MWv : 2.5 × 104  Da). Three different methods-hydroxide assay, superoxide assay, and DPPH assay-were used to measure the antioxidant capacity of the low acyl gellan gum fragments. Both mini-GAGR and midi-GAGR showed similar antioxidant capacities, 27.1% and 25.6%, respectively, for hydroxide radicals, whereas ascorbic acid showed 9.8%. For superoxide radicals, the fragments scavenged 41.7% (mini) and 35.6% (midi) of free radicals compared to 10.6% removal by ascorbic acid. Mini- and midi-GAGR displayed modest scavenging capabilities with DPPH radicals (8.5% and 6.6%, respectively) as compared to ascorbic acid (96.3%). Both midi- and mini-GAGR showed less gel-like behaviors than LA-GAGR. Midi-GAGR was observed to have a transition from liquid to gel at 63 rad/s. PRACTICAL APPLICATION: The results in the manuscript are helpful when gellan gum and its derivatives are directly applied to food processing as a dietary fiber supplement or a stabilizer for functional beverages. The antioxidant capacity results can be used to promote the functionality of gellan gum as a food additive and for controlling cell adhesion and growth on gellan gum scaffolds. The rheology results will be useful for synthesis of scaffolds for bone tissue generation and facilitating clinical treatments when gellan gum is injected as an adsorbent or a filler for treating bone fractures. In the pharmaceutical industry, they are useful when controlling the therapeutic effects of drug delivery systems.

Cress seed gum improves rheological, textural and physicochemical properties of native wheat starch-sucrose mixture.

In this paper, the impact of different substitution levels of cress seed gum (CSG, 0, 5, 10, and 15%) and sucrose (SUC, 0, 5, and 10%) on the rheological properties, textural attributes, syneresis, FTIR and microstructure of native wheat starch (NWS, 4%) gel was investigated. According to the rheological tests, the NWS-CSG and NWS-CSG-SUC gels showed thixotropic behavior and all the samples exhibited shear-thinning flow behavior. Increasing the CSG substitution level up to 15% elevated the apparent viscosity, consistency coefficient whereas the SUC substitution with NWS reduced these values. The higher apparent viscosity, consistency coefficient, and stronger pseudoplastic behavior were obtained for NWS-CSG-SUC gel than NWS gel. The addition of CSG greatly decreased hardness and consistency from 140 to 55.5 g and from 6.9 to 3.0 mJ, respectively during storage at 4 °C for 14 days; while in the presence of SUC these values slightly decreased. After storage, syneresis of NWS and NWS-10%SUC gels increased by 46.78% and 32.11%, respectively; whereas it decreased 19.88% for NWS-15%CSG gel. The SEM images showed that the mixed gels had a denser structure with a smaller pore size. The results indicated that CSG had positive effect in modifying the properties of NWS-SUC mixed gels.

Effects of plasticizer type and concentration on rheological, physico-mechanical and structural properties of chitosan/zein film.

The purpose of this study was to evaluate the effect of plasticizer type (glycerol, PEG-400, and sorbitol) and concentration (0%, 15%, 30% and 45%, w/w dry polymer weight) on rheological and physico-mechanical and structural properties of chitosan/zein blend film. Based on the analysis of rheological properties of chitosan/zein film-forming solutions, all film-forming solutions exhibited non-Newtonian behavior. The flow index of film-forming solution increased and apparent viscosity decreased with the increase of plasticizer concentration. The storage modulus (G') and the loss modulus (G″) decreased when plasticizer was added. The permeability of films increased significantly with the increase of plasticizer concentration, but the C/Z-P film (plasticized chitosan/zein film with PEG-400) had better barrier performance compared with the other two. The C/Z-P film had better mechanical properties and light transmission. Scanning electron microscopy (SEM) and X-ray diffraction (XRD) revealed chitosan and zein had good compatibility due to the addition of the plasticizer, and crystallinity decreased with the increase of plasticizer concentration.

Enhanced Tumor Synergistic Therapy by Injectable Magnetic Hydrogel Mediated Generation of Hyperthermia and Highly Toxic Reactive Oxygen Species.

Nanoparticle-mediated tumor magnetic induction hyperthermia has received tremendous attention. However, it has been a challenge to improve the efficacy at 42 °C therapeutic temperatures without resistance to induced thermal stress. Therefore, we designed a magnetic hydrogel nanozyme (MHZ) utilizing inclusion complexation between PEGylated nanoparticles and α-cyclodextrin, which can enhance tumor oxidative stress levels by generating reactive oxygen species through nanozyme-catalyzed reactions based on tumor magnetic hyperthermia. MHZ can be injected and diffused into the tumor tissue due to shear thinning as well as magnetocaloric phase transition properties, and magnetic heat generated by the Fe3O4 first gives 42 °C of hyperthermia to the tumor. Fe3O4 nanozyme exerts peroxidase-like properties in the acidic environment of tumor to generate hydroxyl radicals (•OH) by the Fenton reaction. The hyperthermia promotes the enzymatic activity of Fe3O4 nanozyme to produce more •OH. Simultaneously, •OH further damages the protective heat shock protein 70, which is highly expressed in hyperthermia to enhance the therapeutic effect of hyperthermia. This single magnetic nanoparticle exerts dual functions of hyperthermia and catalytic therapy to synergistically treat tumors, overcoming the resistance of tumor cells to induced thermal stress without causing severe side effects to normal tissues at 42 °C hyperthermia.

The inhibitory effect of silk sericin against ultraviolet-induced melanogenesis and its potential use in cosmeceutics as an anti-hyperpigmentation compound.

Ultraviolet radiation (UVR)-induced redox imbalance in melanocytes triggers the activation of tyrosinase that results in melanogenesis and its related skin disorders. Supplementation of biological reductants or anti-tyrosinase compounds inhibits such melanogenesis. Silk sericin (SS), a globular protein, is known to possess antioxidant and anti-tyrosinase activities along with other biological attributes. However, its inhibitory activity against UVR-induced melanogenesis has yet to be explored. In the current study, we have scientifically explored the inhibitory activity of SS against UVR-induced melanogenesis. Anti-tyrosinase activity of SS was assessed using mushroom tyrosinase, showing that Antheraea assamensis sericin (AAS) and Philosamia ricini sericin (PRS) inhibited 50% of its activity. Inhibitory activity of SS against UVR-induced melanogenesis was assessed by measuring the cellular melanin content, intracellular tyrosinase activity, and reactive oxygen species (ROS) levels in mouse melanoma. SS pretreatment significantly reduced cellular melanin and ROS production in UV irradiated melanocytes compared with SS untreated cells. AAS treatment before UVA or UVB irradiation significantly inhibited tyrosinase activity. Rheological studies showed that the skin care formulation prepared by the addition of AAS to the basic formulation minimally affected its flow properties. Altogether, our results validate that AAS efficiently inhibited UVR-induced melanogenesis and it could be used as a potential antioxidant molecule in skin care cosmeceutics.

Characterization of bound water in skin hydrators prepared with and without a 3D3P interpenetrating polymer network.

BACKGROUND: Hyaluronic acid (HA) has been considered the gold standard ingredient for improving skin hydration and combating age-related effects, however it is an inefficient polymer with inconsistent results partially due to its poor skin penetration, surface deposition, and rapid degradation. Herein we report the synthesis and in vitro characterization of a newly developed, topical super-humectant with the goal of attracting and binding water molecules more efficiently than traditional, cosmetic-grade forms of HA. METHODS: A modified interpenetrating polymer network (IPN) was developed using three polymers into a three-dimensional formation (3D3P) for entrapping HA and water. This 3D3P-IPN functions as a super-humectant, attracting and binding water molecules more efficiently than the traditional cosmetic-grade forms of HA. We compare 3D3P-IPN serum samples to a traditional commercial benchmark product of similar ingredients using microscopic analysis, rheology, Karl Fischer (KF) titration, differential scanning calorimetry (DSC), thermal gravimetric analysis (TGA), and dynamic vapor sorption (DVS) techniques. RESULTS: The 3D3P-IPN samples appeared to bind water tighter than the benchmark sample as evidenced by maximum endpoints of endotherms occurring at significantly higher temperatures. The DVS results further confirm this speculation as the 3D3P-IPN samples lost approximately 10% less water up to 35% RH than the benchmark. The 3D3P-IPN samples also absorbed more water as the humidity level increased,demonstrating superior humectant properties. KF titration indicated that all three samples had similar water concentrations; however, TGA results demonstrated that the benchmark (a viscous, humectant-rich hydrating masque) did not have much bound water. CONCLUSION: Through the synthesis of a 3D3P-IPN using simplified methods, we were able to increase the water-binding and HA-delivery capabilities of a thin serum. This 3D3P-IPN serum has potential to deliver more hydration to the skin's surface compared to traditional HA formulations.

The optimization of prebiotic sucrose-free mango nectar by response surface methodology: The effect of stevia and inulin on physicochemical and rheological properties.

The reduction of sugar consumption is one of the major challenges for nutritionists and food industry. Therefore, it is significant to replace sucrose with other types of sweeteners, especially, natural ones. The aim of the present study is to produce low-calorie, sucrose-free mango nectar and to optimize the formulation by employing response surface methodology. The two independent variables were stevia, as a low-calorie sugar replacer (0, 1.5, and 3% w/w) and inulin as a prebiotic texturizer (0, 3, and 6% w/w) in order to compensate sugar elimination defect on viscosity and °Brix. The fitted models indicated a high coefficient of determination. The results revealed that stevia and inulin are as the independent variables which had significant effects on °Brix, viscosity, and sensory scores (p < 0.05). Also, pH was affected by stevia concentration. The rheological behavior of the sucrose-free mango nectar was non-Newtonian, shear thinning as Herschel-Bulkley model which was not different from the reported behavior for normal mango nectar-containing sucrose. The optimization of the variables, based on the response surface three-dimensional plots, demonstrated that utilizing 6% w/w inulin and 3% w/w stevia produced the optimum mango nectar with the desirability of 0.85 without undesirable changes in the physicochemical and organoleptic properties. The optimum sample was produced in triplicate to validate the optimum model as well.

Impact of PEGylation on the mucolytic activity of recombinant human deoxyribonuclease I in cystic fibrosis sputum.

Highly viscous mucus and its impaired clearance characterize the lungs of patients with cystic fibrosis (CF). Pulmonary secretions of patients with CF display increased concentrations of high molecular weight components such as DNA and actin. Recombinant human deoxyribonuclease I (rhDNase) delivered by inhalation cleaves DNA filaments contained in respiratory secretions and thins them. However, rapid clearance of rhDNase from the lungs implies a daily administration and thereby a high therapy burden and a reduced patient compliance. A PEGylated version of rhDNase could sustain the presence of the protein within the lungs and reduce its administration frequency. Here, we evaluated the enzymatic activity of rhDNase conjugated to a two-arm 40 kDa polyethylene glycol (PEG40) in CF sputa. Rheology data indicated that both rhDNase and PEG40-rhDNase presented similar mucolytic activity in CF sputa, independently of the purulence of the sputum samples as well as of their DNA, actin and ions contents. The macroscopic appearance of the samples correlated with the DNA content of the sputa: the more purulent the sample, the higher the DNA concentration. Finally, quantification of the enzymes in CF sputa following rheology measurement suggests that PEGylation largely increases the stability of rhDNase in CF respiratory secretions, since 24-fold more PEG40-rhDNase than rhDNase was recovered from the samples. The present results are considered positive and provide support to the continuation of the research on a long acting version of rhDNase to treat CF lung disease.

Design of a vascularized synthetic poly(ethylene glycol) macroencapsulation device for islet transplantation.

The use of immunoisolating macrodevices in islet transplantation confers the benefit of safety and translatability by containing transplanted cells within a single retrievable device. To date, there has been limited development and characterization of synthetic poly(ethylene glycol) (PEG)-based hydrogel macrodevices for islet encapsulation and transplantation. Herein, we describe a two-component synthetic PEG hydrogel macrodevice system, designed for islet delivery to an extrahepatic islet transplant site, consisting of a hydrogel core cross-linked with a non-degradable PEG dithiol and a vasculogenic outer layer cross-linked with a proteolytically sensitive peptide to promote degradation and enhance localized vascularization. Synthetic PEG macrodevices exhibited equivalent passive molecular transport to traditional microencapsulation materials (e.g., alginate) and long-term stability in the presence of proteases in vitro and in vivo, out to 14 weeks in rats. Encapsulated islets demonstrated high viability within the device in vitro and the incorporation of RGD adhesive peptides within the islet encapsulating PEG hydrogel improved insulin responsiveness to a glucose challenge. In vivo, the implementation of a vasculogenic, degradable hydrogel layer at the outer interface of the macrodevice enhanced vascular density within the rat omentum transplant site, resulting in improved encapsulated islet viability in a syngeneic diabetic rat model. These results highlight the benefits of the facile PEG platform to provide controlled presentation of islet-supportive ligands, as well as degradable interfaces for the promotion of engraftment and overall graft efficacy.

Effects of molecular weight of hyaluronic acid on its viscosity and enzymatic activities of lysozyme and peroxidase.

OBJECTIVES: To investigate the effects of the molecular weight of hyaluronic acid on its viscosity and enzymatic activities of lysozyme and peroxidase in solution and on the hydroxyapatite surface. DESIGN: Hyaluronic acids of four different molecular weights (10 kDa, 100 kDa, 1 MDa, and 2 MDa), hen egg-white lysozyme, bovine lactoperoxidase, and human whole saliva were used. Viscosity values of hyaluronic acids were measured using a cone-and-plate viscometer at six different concentrations (0.1-5.0 mg/mL). Enzymatic activities of lysozyme and peroxidase were examined by hydrolysis of fluorescein-labeled Micrococcus lysodeikticus and oxidation of fluorogenic 2',7'-dichlorofluorescein to fluorescing 2',7'-dichlorofluorescein, respectively. RESULTS: In solution assays, only 2 MDa-hyaluronic acid significantly inhibited lysozyme activities in saliva. In surface assays, hyaluronic acids inhibited lysozyme and peroxidase activities; the inhibitory activities were more apparent with high-molecular-weight ones in saliva than in purified enzymes. The 100 kDa-hyaluronic acid at 5.0 mg/mL, 1 MDa-one at 0.5 mg/mL, and 2 MDa-one at 0.2 mg/mL showed viscosity values similar to those of human whole saliva at a shear rate range required for normal oral functions. The differences among the influences of the three conditions on the enzymatic activities were not statistically significant. CONCLUSIONS: High-molecular-weight hyaluronic acids at low concentration and low-molecular-weight ones at high concentration showed viscosity values similar to those of human whole saliva. Inhibitory effects of hyaluronic acids on lysozyme and peroxidase activities were more significant with high-molecular-weight ones on the surface and in saliva compared with in solution and on purified enzymes.

Micromotion-induced peri-prosthetic fluid flow around a cementless femoral stem.

Micromotion-induced interstitial fluid flow at the bone-implant interface has been proposed to play an important role in aseptic loosening of cementless implants. High fluid velocities are thought to promote aseptic loosening through activation of osteoclasts, shear stress induced control of mesenchymal stem cells differentiation, or transport of molecules. In this study, our objectives were to characterize and quantify micromotion-induced fluid flow around a cementless femoral stem using finite element modeling. With a 2D model of the bone-implant interface and full-factorial design, we first evaluated the relative influence of material properties, and bone-implant micromotion and gap on fluid velocity. Transverse sections around a femoral stem were built from computed tomography images, while boundary conditions were obtained from experimental measurements on the same femur. In a second step, a 3D model was built from the same data-set to estimate the shear stress experienced by cells hosted in the peri-implant tissues. The full-factorial design analysis showed that local micromotion had the most influence on peak fluid velocity at the interface. Remarkable variations in fluid velocity were observed in the macrostructures at the surface of the implant in the 2D transverse sections of the stem. The 3D model predicted peak fluid velocities extending up to 2.2 mm/s in the granulation tissue and to 3.9 mm/s in the trabecular bone. Peak shear stresses on the cells hosted in these tissues ranged from 0.1 to 12.5 Pa. These results offer insight into mechanical stimuli encountered at the bone-implant interface.

Biomimetic sulphated alginate hydrogels suppress IL-1ß-induced inflammatory responses in human chondrocytes.

Loss of articular cartilage from ageing, injury or degenerative disease is commonly associated with inflammation, causing pain and accelerating degradation of the cartilage matrix. Sulphated glycosaminoglycans (GAGs) are involved in the regulation of immune responses in vivo, and analogous polysaccharides are currently being evaluated for tissue engineering matrices to form a biomimetic environment promoting tissue growth while suppressing inflammatory and catabolic activities. Here, we characterise physical properties of sulphated alginate (S-Alg) gels for use in cartilage engineering scaffolds, and study their anti-inflammatory effects on encapsulated chondrocytes stimulated with IL-1ß. Sulphation resulted in decreased storage modulus and increased swelling of alginate gels, whereas mixing highly sulphated alginate with unmodified alginate resulted in improved mechanical properties compared to gels from pure S-Alg. S-Alg gels showed extensive anti-inflammatory and anti-catabolic effects on encapsulated chondrocytes induced by IL-1ß. Cytokine-stimulated gene expression of pro-inflammatory markers IL-6, IL-8, COX-2 and aggrecanase ADAMTS-5 were significantly lower in the sulphated gels compared to unmodified alginate gels. Moreover, sulphation of the microenvironment suppressed the protein expression of COX-2 and NF-κB as well as the activation of NF-κB and p38-MAPK. The sulphated alginate matrices were found to interact with IL-1ß, and proposed to inhibit inflammatory induction by sequestering cytokines from their receptors. This study shows promising potential for sulphated alginates in biomimetic tissue engineering scaffolds, by reducing cytokine-mediated inflammation and providing a protective microenvironment for encapsulated cells.

Niosome-based hydrogel of resveratrol for topical applications: An effective therapy for pain related disorder(s).

The present work endeavors for development and evaluation of resveratrol loaded niosomal hydrogel system for its anti-inflammatory action. Niosomes were prepared by thin film hydration and ether injection methods employing Span 80 as a surfactant at three different levels. Best optimized formulation was selected on the basis of entrapment efficiency (% EE), mean particle size, sedimentation volume, and microscopy. The vesicular and spherical nature of the niosomes was confirmed by optical microscopy and transmission electron microscope (TEM). Further, resveratrol entrapped niosomal gel was prepared by gelling in Carbopol 934, and evaluated for pH, viscosity, and in vitro release, employing dialysis membrane method. The in vitro release data after fitting to various models revealed it to follow Korsmeyer-Pappas model. Ex vivo permeation studies witnessed high permeation and deposition of resveratrol in skin when compared to plain resveratrol. Dermatokinetic studies elaborated that niosomal gel enhanced the biological half-life and reduced Tmax of the drug, in both the skin layers. Finally, in vivo anti-inflammatory activity of niosomal gel was evaluated by carrageenan induced paw edema model and compared with standard sodium diclofenac gel. The resveratrol entrapped niosomal gel sufficiently reduced the edema and revealed prolonged therapeutic action vis-a-vis the marketed anti-inflammatory gel formulation. Our findings suggest that a topical drug delivery system using niosomal hydrogel could lead to expansion in the anti-inflammatory use of resveratrol.

Mycelium transformation of Streptomyces toxytricini into pellet: Role of culture conditions and kinetics.

The present study envisages the role of different carbon sources, nitrogen sources, metals, pH, inoculum volume and agitation rate in pellet formation of S. toxytricini at shake-flask level. It was found that galactose, ammonium sulphate, sodium nitrate, Cu2+, Zn2+, higher inoculum volume (5% v/v) and agitation rate at 300rpm caused significant reduction in pellet size (up to the range of 30µm-0.5mm) but biomass formations was also reduced subsequently. Interestingly diffused type of morphology was obtained in Fe2+ supplemented medium with reduced biomass (1.5gL-1). Rheological study revealed that non-Newtonian behaviour of culture broth. Besides this, kinetics study was also made to understand the growth kinetics (0.39gL-1h-1), oxygen uptake rate (0.1146mgL-1h-1), and production of lipstatin (0.0072gh-1).

Protective effects of traditional Tibetan medicine Zuo-Mu-A Decoction () on the blood parameters and myocardium of high altitude polycythemia model rats.

OBJECTIVE: To explore the protective effects of Tibetan medicine Zuo-Mu-A Decoction (, ZMAD) on the blood parameters and myocardium of high altitude polycythemia (HAPC) model rats. METHODS: Forty male Wistar rats were randomly divided into 4 groups by a random number table, including the normal, model, Rhodiola rosea L. (RRL) and ZMAD groups (10 in each group). Every group was raised in Lhasa to create a HAPC model except the normal group. After modeling, rats in the RRL and the ZMAD groups were administered intragastrically with RRL (20 mL/kg) and ZMAD (7.5 mL/kg) once a day for 2 months, respectively; for the normal and the model groups, 5 mL of distilled water was administered intragastrically instead of decoction. Then routine blood and hematologic rheology parameters were taken, levels of erythropoietin and 8-hydroxy-2'-deoxyguanosine (8-OHdG) were tested, and ultrastructural change in the left ventricular myocardium was observed using transmission electron microscopy. RESULTS: Compared with the model group, ZMAD significantly reduced the red blood cell count, hemoglobin levels, whole blood viscosity at low/middle shear rates, plasma viscosity, erythrocyte electrophoretic time, erythropoietin and 8-OHdG levels, and also increased the erythrocyte deformation index (P<0.05). There was no difference in all results between the RRL and the ZMAD groups. The cardiac muscle fibers were well-protected, mitochondrial matrix swelled mildly and ultrastructure changes were less prominent in the ZMAD group compared with the model group. CONCLUSION: ZMAD has significant protective effects on the blood parameters against HAPC, and also has the beneficial effect in protecting against myocardial injury.

Use of 5-Fluorouracil Loaded Micelles and Cisplatin in Thermosensitive Chitosan Hydrogel as an Efficient Therapy against Colorectal Peritoneal Carcinomatosis.

Colorectal peritoneal carcinomatosis (CRPC) is a common systemic metastasis of intra-abdominal cancers. Intraperitoneal chemotherapy against CRPC is at present the preferred treatment. The aim of this study is to develop a novel hydrogel drug delivery system through the combination of 5-fluorouracil (5-FU) loaded polymeric micelles and cisplatin (DDP) in biodegradable thermosensitive chitosan (CS) hydrogel. The prepared CS hydrogel drug is a free-flowing solution at room temperature and forms a stationary gel at body temperature. Therefore, a CRPC mouse model is established to investigate the antitumor activity of CS hydrogel drug system. The results suggest that intraperitoneal administration of CS hydrogel drug can inhibit tumor growth and metastasis, and prolong survival time compared with other groups, thus improving the chemotherapeutic effect. Ki-67 immunohistochemical analysis reveals that tumors in the CS hydrogel drug group has lower cell proliferation in contrast to other groups (P < 0.001). Furthermore, hematoxylin-eosin staining of liver and lung tissue indicates that the CS hydrogel drug has also a certain inhibitory effect on colorectal cancer metastasis to the liver and lung. Hence, the work highlights the potential clinical applications of the CS hydrogel drug.

On the biological performance of graphene oxide-modified chitosan/polyvinyl pyrrolidone nanocomposite membranes: In vitro and in vivo effects of graphene oxide.

Nanofibrous structures that mimic the native extracellular matrix and promote cell adhesion have attracted considerable interest for biomedical applications. In this study, GO-modified nanofibrous biopolymers (GO) were prepared by electrospinning blended solutions of chitosan (80vol%), polyvinyl pyrrolidone (15vol%), polyethylene oxide (5vol%) containing GO nanosheets (0-2wt%). It is shown that GO nanosheets significantly change the conductivity and viscosity of highly concentrated chitosan solutions, so that ultrafine and uniform fibers with an average diameter of 60nm are spinnable. The GO-reinforced nanofibers with controlled pore structure exhibit enhanced elastic modulus and tensile strength (150-300%) with a controllable water permeability to meet the required properties of natural skins. Potential use of the GO-modified biocomposites for tissue engineering is demonstrated in mesenchymal stem cell lines extracted from rat's bone marrow. The biocompatibility assay and SEM imaging reveal that the nanofibrous structure promotes the attachment and maintained characteristic cell morphology and viability up to 72h. In-vivo evaluations in rats show that a faster and more efficient wound closure rate (about 33%) are attained for the 1.5% GO nanofibrous membrane as compared with control (sterile gauze sponges).