OBJECTIVES: Endothelium-dependent vasodilation dysfunction is the pathological basis of diabetic macroangiopathy. The utilization and adaptation of endothelial cells to high glucose determine the functional status of endothelial cells. Glycolysis pathway is the major energy source for endothelial cells. Abnormal glycolysis plays an important role in endothelium-dependent vasodilation dysfunction induced by high glucose. Pyruvate kinase isozyme type M2 (PKM2) is one of key enzymes in glycolysis pathway, phosphorylation of PKM2 can reduce the activity of pyruvate kinase and affect the glycolysis process of glucose. TEPP-46 can stabilize PKM2 in its tetramer form, reducing its dimer formation and phosphorylation. Using TEPP-46 as a tool drug to inhibit PKM2 phosphorylation, this study aims to explore the impact and potential mechanism of phosphorylated PKM2 (p-PKM2) on endothelial dependent vasodilation function in high glucose, and to provide a theoretical basis for finding new intervention targets for diabetic macroangiopathy. METHODS: The mice were divided into 3 groups: a wild-type (WT) group (a control group, C57BL/6 mice) and a db/db group (a diabetic group, db/db mice), which were treated with the sodium carboxymethyl cellulose solution (solvent) by gavage once a day, and a TEPP-46 group (a treatment group, db/db mice+TEPP-46), which was gavaged with TEPP-46 (30 mg/kg) and sodium carboxymethyl cellulose solution once a day. After 12 weeks of treatment, the levels of p-PKM2 and PKM2 protein in thoracic aortas, plasma nitric oxide (NO) level and endothelium-dependent vasodilation function of thoracic aortas were detected. High glucose (30 mmol/L) with or without TEPP-46 (10 μmol/L), mannitol incubating human umbilical vein endothelial cells (HUVECs) for 72 hours, respectively. The level of NO in supernatant, the content of NO in cells, and the levels of p-PKM2 and PKM2 protein were detected. Finally, the effect of TEPP-46 on endothelial nitric oxide synthase (eNOS) phosphorylation was detected at the cellular and animal levels. RESULTS: Compared with the control group, the levels of p-PKM2 in thoracic aortas of the diabetic group increased (P<0.05). The responsiveness of thoracic aortas in the diabetic group to acetylcholine (ACh) was 47% lower than that in the control group (P<0.05), and that in TEPP-46 treatment group was 28% higher than that in the diabetic group (P<0.05), while there was no statistically significant difference in the responsiveness of thoracic aortas to sodium nitroprusside (SNP). Compared with the control group, the plasma NO level of mice decreased in the diabetic group, while compared with the diabetic group, the phosphorylation of PKM2 in thoracic aortas decreased and the plasma NO level increased in the TEPP-46 group (both P<0.05). High glucose instead of mannitol induced the increase of PKM2 phosphorylation in HUVECs and reduced the level of NO in supernatant (both P<0.05). HUVECs incubated with TEPP-46 and high glucose reversed the reduction of NO production and secretion induced by high glucose while inhibiting PKM2 phosphorylation (both P<0.05). At the cellular and animal levels, TEPP-46 reversed the decrease of eNOS (ser1177) phosphorylation induced by high glucose (both P<0.05). CONCLUSIONS p-PKM2 may be involved in the process of endothelium-dependent vasodilation dysfunction in Type 2 diabetes by inhibiting p-eNOS (ser1177)/NO pathway.
Animals ; Humans ; Mice ; Carboxymethylcellulose Sodium/pharmacology* ; Diabetes Mellitus, Type 2/metabolism* ; Endothelium, Vascular/metabolism* ; Glucose/metabolism* ; Human Umbilical Vein Endothelial Cells ; Mice, Inbred C57BL ; Nitric Oxide/metabolism* ; Nitric Oxide Synthase Type III/metabolism* ; Phosphorylation ; Pyruvate Kinase/metabolism* ; Vasodilation

The present study prepared a new type of Ginkgo biloba ketone ester(GBE50) preparation from polyethylene glycol and croscarmellose sodium with good biocompatibility and a certain viscosity by fused deposition modeling(FDM)-type 3D printing technique. Firstly, a cylindrical 3D printing model with a diameter of 9.00 mm and a height of 4.50 mm was established. Subsequently, the 3D-GBE50 preparations with three paths(concentric, zigzag, and grid), different layer heights, and different filling gaps were designed and prepared after the optimization of the proportions of excipients. The morphology, size, chemical properties, and dissolution activity of the 3D-GBE50 preparations were fully characterized and investigated. The results showed that 3D-GBE50 preparations had smooth appearance, clear texture, standard friability, good thermal stability, and stable chemical properties. Moreover, the printing path, layer height, and filling gap were directly related to the release rate of 3D-GBE50 preparations. The dissolution of 3D-GBE50 tablets with zigzag printing path was the fastest, while the dissolution rates of 3D-GBE50 tablets with concentric circle and grid-shaped printing paths were slower than that of commercially available G. biloba Ketone Ester Tablets. In addition, the dissolution of 3D-GBE50 tablets was faster with higher layer height and wider filling gap. As revealed by the results, th FDM-type 3D printing technique can flexibly regulate the drug release activity via controlling the printing parameters, providing effective ideas and methods for the pre-paration of personalized pharmaceutical preparations.
Carboxymethylcellulose Sodium ; Esters ; Excipients/chemistry* ; Ginkgo biloba ; Ketones ; Polyethylene Glycols/chemistry* ; Printing, Three-Dimensional ; Tablets/chemistry* ; Technology, Pharmaceutical/methods*

Avicel is made of a mixture of microcrystalline cellulose (MCC) and carboxymethyl cellulose (CMC), and used for virus plaque assay. The avicel in common use is produced by FMC Biopolymer. Due to the relatively fixed proportion of MCC and CMC, avicel in common use is not suitable for plaque determination experiment of all types of viruses. In this study, we evaluated the effect of avicel made of different proportions of MCC and CMC on virus plaque assay, and developed an improved avicel virus plaque assay featured with simple and convenient operation, good practicability and high stability. To generate avicel overlays with different proportions of MCC and CMC, twelve different 2×avicel solutions were prepared. Their overall viscosity and bottom viscosity were measured to evaluate the ease of operation. The results showed that most of the 2×avicel solutions (except the 4.8% MCC+1.4% CMC and 4.8% MCC+1.0% CMC group) were easy to absorb and prepare nutrient overlap than 2×CMC solution. In order to find the best scheme to detect the titer of porcine epidemic diarrhea virus (PEDV), these avicel overlay solutions with different proportion of MCC and CMC were used as a replacement in the standard plaque assay. By comparing the size, clarity, stability and titer accuracy of virus plaque, we identified that 0.6% MCC and 0.7% CMC was the most preferable composition of avicel overlay for PEDV plaque assay. In conclusion, we developed an improved virus plaque assay based on avicel, which may facilitate the research of virus etiology, antiviral drugs and vaccines.
Animals ; Carboxymethylcellulose Sodium/chemistry* ; Cellulose/chemistry* ; Swine

To evaluate the effects of Hydroxypropyl methylcellulose acetate succinate(HPMCAS MF) on absorption of silybin(SLB) from supersaturable self-nanoemulsifying drug delivery system which was pre-prepared at the early stage experiment. The cell toxicity of self-emulsifying preparation was evaluated by the MTT method, and the in vitro membrane permeability and absorption promoting effect of the self-emulsifying preparation were evaluated by establishing a Caco-2 cell monolayer model. The in vivo and in vitro supersaturation correlation was evaluated via the blood concentration of SLB. The results of MTT showed that the concentration of the preparation below 2 mg·mL~(-1)(C_(SLB) 100 μg·mL~(-1)) was not toxic to Caco-2 cells, and the addition of polymer had no significant effect on Caco-2 cells viability. As compared with the solution group, the transport results showed that the P_(app)(AP→BL) of the self-emulsifying preparation had a very significant increase; the transport rate of silybin can be reduced by polymer in 0-30 min; however, there was no difference in supersaturated transport between supersaturated SLB self-nanoemulsion drug delivery system(SLB-SSNEDDS) and SLB self-nanoemulsion drug delivery system(SLB-SNEDDS) within 2 hours. As compared with SLB suspension, pharmacokinetic parameters showed that the blood concentration of both SLB-SNEDDS and SLB-SSNEDDS groups were significantly increased, and C_(max) was 5.25 times and 9.69 times respectively of that in SLB suspension group, with a relative bioavailability of 578.45% and 1 139.44% respectively. C_(max) and relative bioavailability of SLB-SSNEDDS were 1.85 times and 197% of those of SLB-SNEDDS, respectively. Therefore, on the one hand, SSNEDDS can increase the solubility of SLB in gastrointestinal tract by maintaining stability of SLB supersaturation state; on the other hand, the osmotic transport process of SLB was regulated through the composition of its preparations, and both of them could jointly promote the transport and absorption of SLB to improve the oral bioavailability of SLB.
Administration, Oral ; Biological Availability ; Caco-2 Cells ; Drug Delivery Systems ; Emulsions ; Humans ; Methylcellulose/analogs & derivatives* ; Nanoparticles ; Particle Size ; Silybin ; Solubility

To enhance in vitro dissolution of Cur by preparing Cur solid dispersions. The ability of HPMCAS-HF,HPMCAS-MF,HPMCAS-LF and PVPK30 to maintain supersaturated solution was investigated by supersaturation test. Amorphous solid dispersions were prepared by the solvent-evaporation method. The prepared samples were characterized using infrared spectroscopy( IR) and differential scanning calorimetry( DSC),and in vitro dissolution was investigated. DSC and IR results showed that in 1 ∶3 and 1 ∶9 solid dispersions,Cur was amorphously dispersed in the carrier,and the interaction existed between drug and carrier. The supersaturation test showed that the order of the ability of polymer to inhibit crystallization of Cur was MF>HF>LF>K30. The dissolution results showed that Cur-K30 amorphous solid dispersion had the highest drug release rate; Cur-K30 and Cur-LF amorphous solid dispersions had a quicker but not stable dissolution rate,and the drug concentration decrease after 4 h; Cur-MF and Cur-HF solid dispersions had a low dissolution,which however increased steadily,attributing to the strong ability of the polymers to inhibit the crystallization of Cur. HPMCAS could inhibit the degradation of Cur better than K30,especially MF and HF. The amorphous solid dispersions of cur significantly enhanced the dissolution of Cur and improved the chemical stability of Cur. This study can provide a basis for the rational selection of the polymer used for Cur solid dispersion.
Chemistry, Pharmaceutical ; Curcumin ; chemistry ; Drug Stability ; Methylcellulose ; analogs & derivatives ; chemistry ; Polymers ; Solubility

Hydrogen sulfide is well-known to exhibit anti-inflammatory and cytoprotective activities, and also has protective effects in the liver. This study aimed to examine the protective effect of hydrogen sulfide in rats with hepatic encephalopathy, which was induced by mild bile duct ligation. In this rat model, bile ducts were mildly ligated for 26 days. Rats were treated for the final 5 days with sodium hydrosulfide (NaHS). NaHS (25 µmol/kg), 0.5% sodium carboxymethyl cellulose, or silymarin (100 mg/kg) was administered intraperitoneally once per day for 5 consecutive days. Mild bile duct ligation caused hepatotoxicity and inflammation in rats. Intraperitoneal NaHS administration reduced levels of aspartate aminotransferase and alanine aminotransferase, which are indicators of liver disease, compared to levels in the control mild bile duct ligation group. Levels of ammonia, a major causative factor of hepatic encephalopathy, were also significantly decreased. Malondialdehyde, myeloperoxidase, catalase, and tumor necrosis factor-α levels were measured to confirm antioxidative and anti-inflammatory effects. N-Methyl-D-aspartic acid (NMDA) receptors with neurotoxic activity were assessed for subunit NMDA receptor subtype 2B. Based on these data, NaHS is suggested to exhibit hepatoprotective effects and guard against neurotoxicity through antioxidant and anti-inflammatory actions.
Alanine Transaminase ; Ammonia ; Animals ; Aspartate Aminotransferases ; Bile Ducts ; Carboxymethylcellulose Sodium ; Catalase ; Hepatic Encephalopathy ; Hydrogen Sulfide ; Inflammation ; Ligation ; Liver ; Liver Diseases ; Malondialdehyde ; Models, Animal ; N-Methylaspartate ; Necrosis ; Peroxidase ; Rats ; Silymarin ; Sodium

Nonthermal atmospheric plasma has been studied for its many biomedical effects, such as tooth bleaching, wound healing, and coagulation. In this study, the effects of dentinal tubules occlusion were investigated using fluoride-carboxymethyl cellulose (F-CMC) gel, nano-sized hydroxyapatite (n-HA), and nonthermal atmospheric plasma. Human dentin specimens were divided to 5 groups (group C, HA, HAF, HAP, and HAFP). Group HA was treated with n-HA, group HAF was treated with n-HA after a F-CMC gel application, group HAP was treated with n-HA after a plasma treatment and group HAFP was treated with n-HA after a plasma and F-CMC gel treatment. The occlusion of dentinal tubules was investigated using scanning electron microscopy (SEM) and energy dispersive x-ray spectroscopy (EDS), which shows Ca/P ratio. In the EDS results, a higher Ca/P ratio was shown in the groups including n-HA than in the control group. The specimens of group HAP and HAFP had a higher Ca/P ratio in retentivity. In the SEM results, there was not a significant difference in the amount of times applied. Therefore, this study suggests F-CMC gel and n-HA treatment using nonthermal atmospheric plasma will be a new treatment method for decreasing hypersensitivity.
Carboxymethylcellulose Sodium ; Cellulose ; Dentin Sensitivity ; Dentin ; Durapatite ; Fluorides ; Humans ; Hydroxyapatites ; Hypersensitivity ; Methods ; Microscopy, Electron, Scanning ; Plasma Gases ; Plasma ; Spectrometry, X-Ray Emission ; Tooth Bleaching ; Wound Healing

Canine mammary tumors are among the most frequently observed cutaneous tumors in female dogs. Cancer stem cells (CSCs), referred to as tumor-initiating cells, are thought to have properties similar to normal stem cells such as the ability to self-renewal and to differentiate into various cell types. Biological understanding of CSCs and the critical pathways involved in their maintenance are important in research and therapy for mammary tumors. We conducted the present study on sphere formation from REM134 cells by using methylcellulose to produce tumorspheres on a large scale and compared the specific markers of the spheres-formed and plating-cultured REM134 cells. The results revealed that the tumorspheres cultured in methylcellulose had higher seeding density and improved morphology compared to those produced in normal sphere formation medium. Expression levels of stemness markers and CSC-related markers were higher in tumorsphere-forming cells than in plating-cultured cells. Subsequently, we transplanted the tumorsphere-forming and plating-cultured cells into female nude mice to examine their tumorigenic potential. Tumor volume increased rapidly in mice transplanted with tumorsphere-derived cells compared to plating-cultured cells. We observed a novel sphere-forming condition for REM134 cells and showed that REM134 cell tumorspheres can exhibit improved CSC properties.
Animals ; Carcinogenesis ; Critical Pathways ; Dogs ; Female ; Humans ; Mammary Neoplasms, Animal ; Methylcellulose ; Mice ; Mice, Nude ; Neoplastic Stem Cells ; Stem Cells ; Tumor Burden

BACKGROUND AND OBJECTIVES: Although polyvinyl acetate (Merocel®) has been widely used as a packing material after septoplasty, removable nasal packing can increase patient discomfort, local pain, and pressure. Furthermore, the removal of nasal packing has been described as the most uncomfortable and distressing feature associated with septoplasty. The purpose of this study was to investigate the efficacy of polyvinyl acetate with carboxymethyl cellulose sheet (Rhinocel®) nasal packing on patient subjective symptoms, degree of bleeding, hemostasis, and wound healing following septoplasty. SUBJECTS AND METHOD: Forty patients with nasal septum deviation requiring septoplasty were included. Following surgery, one nasal cavity was packed with Rhinocel® and the other one with Merocel®. Patient subjective symptoms while the packing was in situ, hemostatic properties, pain on removal, degree of bleeding on removal, duration of hemostasis after removal, postoperative wound healing, and the cost of the pack were evaluated. RESULTS: Although the two types of packing materials were equally effective in controlling postoperative bleeding after septoplasty, Rhinocel® was significantly more comfortable while in situ and less painful on removal than Merocel®, which was associated with significantly more bleeding on removal and so more time was needed to control hemorrhage. There was no significant difference in postoperative wound healing or pack cost. CONCLUSIONS: The use of Rhinocel® after septoplasty has less discomfort, greater patient satisfaction, and less bleeding on removal with no adverse reactions compared to Merocel® packing. Therefore, Rhinocel® may be a useful packing material after septoplasty.
Biocompatible Materials ; Carboxymethylcellulose Sodium* ; Hemorrhage ; Hemostasis ; Humans ; Methods ; Nasal Cavity ; Nasal Septum ; Nose ; Patient Satisfaction ; Polyvinyls* ; Postoperative Care ; Wound Healing

PURPOSE: Various absorbable anti-adhesion agents have been used to prevent postoperative synechia formation after endonasal surgery. The purpose of this study was to evaluate the anti-adhesion effects of HyFence and Mediclore after endonasal dacryocystorhinostomy (DCR) compared to a mixed solution of hyaluronic acid and sodium carboxymethylcellulose (Guardix-Sol). METHODS: In this retrospective study, endonasal DCR and silicone tube intubation were performed on 198 eyes of 151 patients. Three different anti-adhesion adjuvants were applied to the osteotomy site in the nasal cavity after standard endonasal DCR procedures. The subjects were classified into three respective groups: group A (71 eyes, Guardix-Sol 1.5 g), group B (89 eyes, HyFence 1.5 mL), and group C (38 eyes, Mediclore 1 cc). The three groups were evaluated by asking patients about subjective symptoms and by performing lacrimal irrigation tests and endoscopic examinations. RESULTS: There were no statistically significant differences in age, sex, timing of tube removal, or follow-up period among the three groups. There were no statistically significant differences in success rates among the three groups (p = 0.990, 91.5% [65 / 71], 92.1% [82 / 89], and 92.1% [35 / 38], respectively). CONCLUSIONS: HyFence and Mediclore are safe and effective adjunctive modalities following endonasal DCR compared to Guardix-Sol. Therefore, these agents can be considered good alternatives to Guardix-Sol to increase the success rate of endonasal DCR in treating patients with poor prognosis.
Carboxymethylcellulose Sodium ; Dacryocystorhinostomy* ; Follow-Up Studies ; Humans ; Hyaluronic Acid ; Intubation ; Nasal Cavity ; Osteotomy ; Prognosis ; Retrospective Studies ; Silicon ; Silicones