Multifunctional and biodegradable methacrylated gelatin/Aloe vera nanofibers for endodontic disinfection and immunomodulation.

Currently employed approaches and materials used for vital pulp therapies (VPTs) and regenerative endodontic procedures (REPs) lack the efficacy to predictably achieve successful outcomes due to their inability to achieve adequate disinfection and/or lack of desired immune modulatory effects. Natural polymers and medicinal herbs are biocompatible, biodegradable, and present several therapeutic benefits and immune-modulatory properties; thus, standing out as a clinically viable approach capable of establishing a conducive environment devoid of bacteria and inflammation to support continued root development, dentinal bridge formation, and dental pulp tissue regeneration. However, the low stability and poor mechanical properties of the natural compounds have limited their application as potential biomaterials for endodontic procedures. In this study, Aloe vera (AV), as a natural antimicrobial and anti-inflammatory agent, was incorporated into photocrosslinkable Gelatin methacrylate (GelMA) nanofibers with the purpose of developing a highly biocompatible biomaterial capable of eradicating endodontic infection and modulating inflammation. Stable GelMA/AV nanofibers with optimal properties were obtained at the ratio of (70:30) by electrospinning. In addition to the pronounced antibacterial effect against Enterococcus faecalis, the GelMA/AV (70:30) nanofibers also exhibited a sustained antibacterial activity over 14 days and significant biofilm reduction with minimal cytotoxicity, as well as anti-inflammatory properties and immunomodulatory effects favoring healing. Our results indicate that the novel GelMA/AV (70:30) nanofibers hold great potential as a biomaterial strategy for endodontic infection eradication and enhanced healing.

Osteopetrorickets due to Snx10 deficiency in mice results from both failed osteoclast activity and loss of gastric acid-dependent calcium absorption.

Mutations in sorting nexin 10 (Snx10) have recently been found to account for roughly 4% of all human malignant osteopetrosis, some of them fatal. To study the disease pathogenesis, we investigated the expression of Snx10 and created mouse models in which Snx10 was knocked down globally or knocked out in osteoclasts. Endocytosis is severely defective in Snx10-deficient osteoclasts, as is extracellular acidification, ruffled border formation, and bone resorption. We also discovered that Snx10 is highly expressed in stomach epithelium, with mutations leading to high stomach pH and low calcium solubilization. Global Snx10-deficiency in mice results in a combined phenotype: osteopetrosis (due to osteoclast defect) and rickets (due to high stomach pH and low calcium availability, resulting in impaired bone mineralization). Osteopetrorickets, the paradoxical association of insufficient mineralization in the context of a positive total body calcium balance, is thought to occur due to the inability of the osteoclasts to maintain normal calcium-phosphorus homeostasis. However, osteoclast-specific Snx10 knockout had no effect on calcium balance, and therefore led to severe osteopetrosis without rickets. Moreover, supplementation with calcium gluconate rescued mice from the rachitic phenotype and dramatically extended life span in global Snx10-deficient mice, suggesting that this may be a life-saving component of the clinical approach to Snx10-dependent human osteopetrosis that has previously gone unrecognized. We conclude that tissue-specific effects of Snx10 mutation need to be considered in clinical approaches to this disease entity. Reliance solely on hematopoietic stem cell transplantation can leave hypocalcemia uncorrected with sometimes fatal consequences. These studies established an essential role for Snx10 in bone homeostasis and underscore the importance of gastric acidification in calcium uptake.

Effect of anti-inflammatory supplementation with whey peptide and exercise therapy in patients with COPD.

BACKGROUND: One of the major pathophysiologies in advanced chronic obstructive pulmonary disease (COPD) has been attributed to systemic inflammation. Meta-analysis of the 2005 Cochrane Database concluded the effect of nutritional supplementation alone on stable COPD was insufficient to promote body weight gain or exercise capacity. The aim of this study was to investigate the effectiveness of nutritional supplementation therapy using a nutritional supplement containing whey peptide with low-intensity exercise therapy in stable elderly patients with COPD. METHOD: In stable elderly COPD patients with %IBW and %FEV(1) of less than 110 and 80%, respectively, anti-inflammatory nutritional supplementation therapy was added to low-intensity exercise therapy. Thirty-six COPD patients were divided into those with and those without the ingestion of an anti-inflammatory nutritional supplement containing whey peptide, which exhibited an anti-inflammatory effect. These two groups were designated as the nutritional support and the control groups, respectively. The body composition, skeletal muscle strength, exercise tolerance, health-related QOL (HRQOL), and inflammatory cytokines were evaluated before and three months after nutritional support combined with exercise therapy in both the nutritional support group and the control group. RESULTS: In the nutritional support group, the body weight, %IBW, FM, energy intake, %AC, Alb, PImax, PEmax, 6MWD, WBI, emotional function, and CRQ total were significantly increased, and the levels of hsCRP, IL-6, IL-8, and TNF-α were reduced significantly, while no significant change was noted in any item of physiological evaluation or any biomarker in the control group. CONCLUSION: Concomitant use of a anti-inflammatory nutritional supplement containing whey peptide, which exhibits an anti-inflammatory effect, with exercise therapy in stable elderly COPD patients with %IBW<110% and %FEV(1)<80% may not only increase body weight but may also inhibit systemic inflammation and thus improve exercise tolerance and HRQOL.

A new enteral diet, MHN-02, which contains abundant antioxidants and whey peptide, protects against carbon tetrachloride-induced hepatitis.

BACKGROUND: Inflammatory or oxidative stress is related to various diseases, including not only inflammatory diseases, but also diabetes, cancer, and atherosclerosis. The aim of this study was to evaluate the anti-inflammatory effects of a new enteral diet, MHN-02, which contains abundant antioxidants and whey peptide. The study also investigated the ability of MHN-02 to attenuate lethality, liver injury, the production of inflammatory cytokines, and the production of oxidized products using a carbon tetrachloride-induced rat model of severe fulminant hepatitis. METHODS: Male Sprague-Dawley rats were fed either a control diet or the MHN-02 diet for 14 days and injected with 2 mL/kg of carbon tetrachloride. Survival of rats was monitored from day 0 to day 3. To evaluate liver injury, inflammation, and oxidative stress, blood and liver samples were collected, and aspartate aminotransferase, alanine aminotransferase, lactate dehydrogenase, interleukin 6, tumor necrosis factor-α, and superoxide dismutase activity as a free radical scavenger were measured. A portion of the liver was evaluated histologically. RESULTS: The survival rates of rats receiving the MHN-02 diet and the control diet were 90% and 55%, respectively. In the MHN-02 diet group, levels of serum liver enzymes and serum cytokines were significantly lower than in the control group. Superoxide dismutase activity in the MHN-02 diet was significantly higher in the MHN-02 group. Pathological lesions were significantly larger in the control group. CONCLUSION: Supplementation of enteral diets containing whey peptide and antioxidants may protect against severe hepatitis.

Water extract of Cordyceps sinensis (WECS) inhibits the RANKL-induced osteoclast differentiation.

It has been reported that Cordyceps sinensis, a traditional Chinese medicine, has various pharmacological effects. The aim of this study was to clarify the effect of water extract of Cordyceps sinensis (WECS) on osteoclast differentiation in vitro. In mouse bone marrow cells and monocyte/macrophage cell line RAW264.7, WECS dose-dependently inhibited the receptor activator of nuclear factor kappa B (NF-kappaB) ligand (RANKL)-induced osteoclast differentiation by tartrate-resistant acid phosphatase (TRAP) staining. In fact, cytotoxic effect was not observed in the RAW264.7 cells treated with WECS. Moreover, the mRNA expression of osteoclast related genes (calcitonin receptor, cathepsin K, matrix metalloprotease 9 and nuclear factor of activated T cells c1) was also inhibited by WECS. Investigation of inhibitory mechanism by using electrophoretic mobility shift assay (EMSA) and Western blot analysis revealed that WECS inhibited the activation of NF-kappaB through the prevention of IkappaBalpha phosphorylation. In conclusion, the present results demonstrate for the first time that WECS is a potent inhibitor of the RANKL-induced osteoclast differentiation through a mechanism involving the NF-kappaB pathway.

Serum ethanolamine and hepatocyte proliferation in perinatal and partially hepatectomized rats.

It has been shown that the administration of ethanolamine (Etn) to partially hepatectomized rats enhances stimulation of DNA synthesis in regenerating hepatocytes. The present study aimed to test the hypothesis that the level of serum Etn in vivo may be regulated to control the growth of hepatocytes. Concentrations of serum Etn were determined in rats 1) of varying ages (from embryonic-19 (E-19) to 7-week-old), and 2) during regeneration following two-thirds hepatectomy (PH), to investigate whether serum Etn concentration correlates with the rate of proliferation of hepatocytes in growing animals or during regeneration. Serum Etn levels were 3 fold higher in E-19 fetuses and newborns than in adults, and were increased 2 fold 4 h after PH and remained high for at least 24 h. Results in both systems indicated a significant positive correlation between the rate of hepatocyte proliferation and serum Etn levels. Furthermore, Etn supplementation of 0.1 to 1 mmol immediately after PH promoted a significant weight gain and stimulated phosphatidylethanolamine (PE) and phosphatidylcholine (PC) synthesis in the regenerating liver. We also observed that whenever serum Etn levels were elevated, the metabolism of PE and PC in the liver changed dynamically, first by elevating the net synthesis of PE. Taken together, these results suggested that the levels of serum Etn might be regulated based on the physiological state of an animal, which consequently regulates the proliferation of hepatocytes.

Hepatoprotective effects of whey protein on D-galactosamine-induced hepatitis and liver fibrosis in rats.

The hepatoprotective effects of whey protein on two injections of D-galactosamine (300 mg/kg, i.p.) were investigated in rats fed a modified AIN-93M diet formulated with a protein source of casein or whey for 16 d. The whey protein-containing diet clearly suppressed an increase in plasma alanine and aspartate aminotransferase activity, lactate dehydrogenase and bilirubin, which are hepatitis markers, and also hyaluronic acid, a fibrosis marker. In addition, it suppressed histopathological signs of portal fibrosis, bile duct proliferation, and perivenular sclerosis. These results suggest that supplementation with whey protein can help prevent the development of hepatitis and portal fibrosis.