Effectiveness of Partially Hydrolyzed Guar Gum on Cognitive Function and Sleep Efficiency in Healthy Elderly Subjects in a Randomized, Double-Blind, Placebo-Controlled, and Parallel-Group Study.

The consumption of functional foods in a daily diet is a promising approach for the maintenance of cognitive health. The present study examines the effects of water-soluble prebiotic dietary-fiber, partially hydrolyzed guar gum (PHGG), on cognitive function and mental health in healthy elderly individuals. Participants consumed either 5 g/day of PHGG or a placebo daily for 12 weeks in this randomized, double-blind, placebo-controlled, and parallel-group study. An assessment of cognitive functions, sleep quality, and subjective mood evaluations was performed at baseline and after 8 and 12 weeks of either PHGG or placebo intake. The visual memory scores in cognitive function tests and sleepiness on rising scores related to sleep quality were significantly improved in the PHGG group compared to the placebo group. No significant differences were observed in mood parameters between the groups. Vigor-activity scores were significantly improved, while the scores for Confusion-Bewilderment decreased significantly in the PHGG group when compared to the baseline. In summary, supplementation with PHGG was effective in improving cognitive functions, particularly visual memory, as well as enhancing sleep quality and vitality in healthy elderly individuals (UMIN000049070).

Hesperetin-7-O-glucoside/ß-cyclodextrin Inclusion Complex Induces Acute Vasodilator Effect to Inhibit the Cold Sensation Response during Localized Cold-Stimulate Stress in Healthy Human Subjects: A Randomized, Double-Blind, Crossover, and Placebo-Controlled Study.

Hesperetin, a citrus flavonoid, exerts vasodilation and is expected to improve endothelial function and alleviate cold sensation by activating nervous system thermal transduction pathways. In this randomized, double-blind, crossover, and placebo-controlled study, the purpose was to assess the effect of an orally administered highly bioavailable soluble inclusion complex of hesperetine-7-O-glucoside with ß-cyclodextrin (HEPT7G/ßCD; SunActive® HES/HCD) on cold sensation response during localized cold-stimulated stress in healthy humans. A significant (p ≤ 0.05) dose-dependent increase in skin cutaneous blood flow following relatively small doses of HEPT7G/ßCD inclusion complex ingestion was confirmed, which led to a relatively effective recovery of peripheral skin temperature. The time delay of an increase in blood flow during rewarming varied significantly between low- and high-dose HEPT7G/ßCD inclusion complex consumption (e.g., 150 mg and 300 mg contain 19.5 mg and 39 mg of HEPT7G, respectively). In conclusion, the substantial alteration in peripheral skin blood flow observed during local cooling stress compared to placebo suggested that deconjugated hesperetin metabolites may have a distinct capacity for thermoregulatory control of human skin blood flow to maintain a constant body temperature during cold stress exposure via cutaneous vasodilation and vasoconstriction systems.

Effects of partially hydrolyzed guar gums of different molecular weights on a human intestinal in vitro fermentation model.

Partially hydrolyzed guar gums (PHGGs) are prebiotic soluble dietary fibers. High molecular-weight PHGGs have rapid fermentation and high short-chain fatty acid (SCFA) productivity rates, compared to low molecular-weight PHGGs. Therefore, low molecular-weight PHGGs may have less pronounced prebiotic effects than high molecular-weight PHGGs. However, the effects of PHGGs of different molecular weights on the human intestinal microbiota, as well as their fermentation ability and prebiotic effects, have not been investigated. The aim of this study was to evaluate the effects of two PHGGs of different molecular weights, Sunfiber-R (SF-R; 20 kDa) and Sunfiber-V (SF-V; 5 kDa), on human colonic microbiota and SCFA production. A human intestinal in vitro fermentation model was operated by fecal samples with and without the PHGGs. The addition of 0.2% SF-R or SF-V increased the relative abundance of Bacteroides spp., especially that of Bacteroides uniformis. This increase corresponded to a significant (p = 0.030) and non-significant (p = 0.073) increase in propionate production in response to SF-R and SF-V addition, respectively. Both fibers increased the relative abundance of Faecalibacterium and stimulated an increase in the abundance of unclassified Lachnospiraceae and Bifidobacterium. In conclusion, the low molecular-weight PHGG exerted prebiotic effects on human colonic microbiota to increase SCFA production and bacteria that are beneficial to human health in a manner similar to that of the high molecular-weight forms of PHGG.

Partially hydrolyzed guar gum is associated with improvement in gut health, sleep, and motivation among healthy subjects.

Partially hydrolyzed guar gum dietary fiber is well recognized for a number of health benefits. In the present study, we aim to investigate the effects of partially hydrolyzed guar gum on constipation, intestinal microbiota as well as mental health in healthy subjects. In the randomized, parallel, double-blind, and placebo-controlled study the enrolled healthy men and women volunteers took either 3 g/day (T3) or 5 g/day (T5) of dietary fiber intakes for eight consecutive weeks compared to placebo (T0). The fecal characteristics, fecal microbiota, defecation characteristics, and quality of life (QOL) questionnaire were investigated. The results revealed a significant suppression in fecal potent harmful mucolytic bacteria in the T3 and T5 groups compared to the T0 group. The defecation frequency, excretory feeling, and scores of sleep and motivation questionnaire were also improved in the dietary fiber intake groups, showing a significant difference in the T5 group compared to the T0 group. In summary, the consumption of partially hydrolyzed guar gum dietary fiber is found effective in suppressing the potent harmful mucolytic bacteria that could be associated with the improvement of constipation-related symptoms including mental health in terms of sleep and motivation among the healthy subjects.

Theanine, a Tea-Leaf-Specific Amino Acid, Alleviates Stress through Modulation of Npas4 Expression in Group-Housed Older Mice.

Group rearing is a common housing condition, but group-housed older mice show increased adrenal hypertrophy, a marker of stress. However, the ingestion of theanine, an amino acid unique to tea leaves, suppressed stress. We aimed to elucidate the mechanism of theanine's stress-reducing effects using group-reared older mice. The expression of repressor element 1 silencing transcription factor (REST), which represses excitability-related genes, was increased in the hippocampus of group-reared older mice, whereas the expression of neuronal PAS domain protein 4 (Npas4), which is involved in the regulation of excitation and inhibition in the brain, was lower in the hippocampus of older group-reared mice than in same-aged two-to-a-house mice. That is, the expression patterns of REST and Npas4 were found to be just inversely correlated. On the other hand, the expression levels of the glucocorticoid receptor and DNA methyltransferase, which suppress Npas4 transcription, were higher in the older group-housed mice. In mice fed theanine, the stress response was reduced and Npas4 expression tended to be increased. These results suggest that Npas4 expression was suppressed by the increased expression of REST and Npas4 downregulators in the group-fed older mice, but that theanine avoids the decrease in Npas4 expression by suppressing the expression of Npas4 transcriptional repressors.

Effect of partially hydrolyzed guar gum on the expression of aquaporin-3 in the colon.

In recent years, the development of functional foods targeting gastrointestinal disorders has been in progress. Partially hydrolyzed guar gum (PHGG), which is a water-soluble dietary fiber, is known to have a constipation-improving effect. However, many aspects of the mechanism remain unclear. In this study, we investigated the role of aquaporin-3 (AQP3), which regulates the water content of feces in ameliorative effect of PHGG on constipation. Rats were allowed to freely consume a normal diet or a diet containing 5% PHGG for 14 days, and defecation parameters were measured. We also analyzed the expression levels of genes involved in water transport in the colon. The defecation frequency and volume of rats treated with PHGG were not different from those from the control group, but the fecal water content was significantly increased, and soft stools were observed. The expressions of claudin-1, tight junction protein-1, and cadherin-1, which are involved in tight junctions or adherens junctions, were almost the same in the PHGG-treated group and the control group. The expression level of AQP3 in the colon was significantly decreased in the PHGG-treated group. In this study, PHGG decreased the colonic AQP3 expression, thereby suppressing water transport from the luminal side to the vascular side and improving constipation.

Lower Rate of Water Absorption of an Oral Rehydration Solution with Partially Hydrolyzed Guar Gum in Conscious Rats.

The purpose of the present study was to elucidate the rate of water absorption of an oral rehydration solution containing partially hydrolyzed guar gum (PHGG) in the small intestine, which is the main site of water absorption when water is drunk. Seven-week-old male SD rats were employed. We prepared four types of an aqueous solution, i.e., containing mineral and sugar, containing PHGG, containing mineral and sugar and PHGG, or containing no additives. After 24 h of food and 4 h of water deprivation, the aqueous solutions were infused into the stomach of conscious rats on their hands using a syringe with a stomach sonde. We sampled the stomach and the small intestine with contents 8 min after the infusions. Causal effects were calculated using a Bayesian network. PHGG increased the residual amount of water in the gastro-intestine, which depends negatively on the absorption of water in the small intestine/the flow rate to the small intestine. The absorption of water in the small intestine depended positively on the flow rate to the small intestine, which depended negatively on the free water in the solutions. PHGG decreased water absorption in the small intestine by decreasing the free water in the aqueous solutions.

Monocaprin Enhances Bioavailability of Fucoxanthin in Diabetic/Obese KK-Ay Mice.

Fucoxanthin is a marine carotenoid found in brown seaweeds and several microalgae. It has been reported that fucoxanthin has health benefits such as anti-obesity and anti-diabetic effects. To facilitate fucoxanthin applications in the food industry, it is important to improve its low bioavailability. We attempted the combined feeding of fucoxanthin-containing seaweed oil (SO) and monocaprin in a powder diet and analyzed the fucoxanthin metabolite contents in the liver, small intestine and serum of diabetic/obese KK-Ay mice. After 4 weeks of feeding with the experimental diets, the serum fucoxanthinol concentrations of the mice fed 0.2% SO and 0.5% monocaprin were higher than those of the 0.2% SO-fed mice. Furthermore, fucoxanthinol accumulation in the liver and small intestine tended to increase in a combination diet of 0.2% SO and 0.125-0.5% monocaprin compared with a diet of 0.2% SO alone, although amarouciaxanthin A accumulation was not different among the 0.2% SO-fed groups. These results suggest that a combination of monocaprin with fucoxanthin-containing SO is an effective treatment for improving the bioavailability of fucoxanthin.

Partially Hydrolyzed Guar Gum Suppresses the Development of Sarcopenic Obesity.

Partially hydrolyzed guar gum (PHGG) is a soluble dietary fiber derived through controlled enzymatic hydrolysis of guar gum, a highly viscous galactomannan derived from the seeds of Cyamopsis tetragonoloba. Here, we examined the therapeutic potential of dietary supplementation with PHGG against sarcopenic obesity using Db/Db mice. Db/Db mice fed a normal diet alone or a fiber-free diet, or supplemented with a diet containing PHGG (5%), were examined. PHGG increased grip strength and the weight of skeletal muscles. PHGG increased the short-chain fatty acids (SCFAs) concentration in feces and sera. Concerning innate immunity, PHGG decreased the ratio of inflammatory cells, while increasing the ratio of anti-inflammatory cells in the small intestine. The present study demonstrated the preventive effect of PHGG on sarcopenic obesity. Changes in nutrient absorption might be involved through the promotion of an anti-inflammatory shift of innate immunity in the intestine accompanied by an increase in SCFA production by PHGG.

Effects of Partially Hydrolyzed Guar Gum Supplementation on the Fecal Microbiotas of Piglets.

Probiotics and prebiotics have become viable alternatives of growth-promoting antimicrobials in animal production. Here, we tested partially hydrolyzed guar gum (PHGG) as a possible prebiotic for piglets in the commercial farm. Five hundred and ninety-four piglets were used for the experiments, with 293 given a normal pig feed (control), while the rest the feed plus 0.06% (w/w) of PHGG (PHGG). One and three months post-PHGG supplementation, fecal samples were collected from randomly selected 20 piglets in each group and analyzed for microbiota and organic acid concentrations. Notably, the abundance of Streptococcus, and unclassified Ruminococcaceae were lower (p < 0.05) in PHGG than in control, one-month post-supplementation. Lactobacillus and Prevotella were higher (p < 0.05), while Streptococcus was lower (p < 0.05), in PHGG than in control, three months post-supplementation. The concentrations of acetate, propionate, and butyrate were greater in PHGG than in control, three months post-supplementation. Finally, PHGG grew faster and had fewer deaths until slaughter time (p < 0.05), than control. We concluded that PHGG not only was an effective prebiotic to alter gut microbiota of weanling piglets but also can possibly promote body weight accretion and health.

Green Tea Catechin Association with Ultraviolet Radiation-Induced Erythema: A Systematic Review and Meta-Analysis.

Catechins are a part of the chemical family of flavonoids, a naturally occurring antioxidant, and a secondary metabolite in certain plants. Green tea catechins are well recognized for their essential anti-inflammatory, photo-protective, antioxidant, and chemo-preventive functions. Ultraviolet radiation is a principal cause of damage to the skin. Studies observed that regular intake of green tea catechins increased the minimal dose of radiation required to induce erythema. The objectives of this systematic review and meta-analysis are to determine the effectiveness of green tea catechins in cutaneous erythema and elucidate whether green tea catechin consumption protects against erythema (sunburn) inflammation. A comprehensive literature search was conducted to identify the relevant studies. Two researchers carried out independent screening, data extraction, and quality assessment according to the guidelines of Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA). The pooled effect of green tea catechins on protection against erythema was assessed using approaches fixed-effects or random-effects model to quantify the effectiveness of green tea catechins in the erythema dose-response. Studies not be included in meta-analyses were summarized narratively. Six randomized controlled studies of enrolled studies regularly administrated green tea catechins orally for 6 to 12 weeks involving healthy volunteers comprising a total of 100 participants were included in the analysis. The results revealed green tea catechins have favorable protection against erythema inflammation even at increased minimal erythema dose (MED) of ultraviolet radiation. Meta-analysis results confirm oral supplementation of green tea catechins is highly effective at low-intensity ultraviolet radiation-induced erythema response (MED range; 1.25-1.30) compared to placebo, showing a significant pooling difference (p = 0.002) in erythema index (SMD: -0.35; 95% CI, -0.57 to -0.13; I2 = 4%, p = 0.40) in the random-effects model. The pro-inflammatory signaling pathways through oral supplementation with green tea catechins are an attractive strategy for photo-protection in healthy human subjects and could represent a complementary approach to topical sunscreens. Therefore, studies that involved green tea catechin in topical applications to human subjects were also evaluated separately, and their meta-analysis is presented as a reference. The evidence indicates that regular green tea catechin supplementation is associated with protection against UV-induced damage due to erythema inflammation.

Antidepressant Effect of Shaded White Leaf Tea Containing High Levels of Caffeine and Amino Acids.

The young leaves of green tea become lighter in color than usual when protected from sunlight by a shading net for about two weeks while growing. These leaves are called "shaded white leaf tea" or SWLT. In the eluate of SWLT, the amount of amino acids (361 mg/L) was significantly higher than that in regular tea (53.5 mg/L). Since theanine and arginine, the first and second most abundant amino acids in SWLT, have significant antistress effects, we examined the antistress effect of SWLT on humans. SWLT or placebo green tea (3 g) was eluted with room-temperature water (500 mL). Participants consumed the tea for one week prior to pharmacy practice and continued for 10 days in the practice period. The state-trait anxiety inventory, an anxiety questionnaire, tended to be scored lower in the SWLT group than the placebo, but other stress markers showed no differences. The effect of the difference in SWLT components examined with mice showed that aspartic acid and asparagine, which are abundant in SWLT, counteracted the antistress effects of theanine and arginine. Large amounts of caffeine also interfered with SWLT's antistress effect. Thus, SWLT, which is high in caffeine and amino acids, suppressed depressant behavior in mice.

Clinical evaluation of Emblica Officinalis Gatertn (Amla) in healthy human subjects: Health benefits and safety results from a randomized, double-blind, crossover placebo-controlled study.

The preventive efficacies and safety of Emblica Officinalis Gatertn (Amla), a most important and extensively studied plant in the traditional Indian Ayurvedic system of medicine, are presented. Eligible healthy adult subjects (n = 15) were randomized to receive either amla or placebo (500 mg per day) during an 18-week study. The efficacy parameters evaluated were the vascular function, blood hematology, oxidative and inflammatory biomarkers, glucose and lipid profiles, urinalysis, and liver hepatotoxicity. The amla intake showed significant improvements in the primary efficacy parameter of blood fluidity. There were also improvements in the secondary endpoints including lowering of von Willebrand factor (vWF), reduced 8-hydroxy-2'-deoxyguanosine (8-OHdG) as well as thrombin (TM) biomarkers of oxidative stress along with a significant improvement in HDL-cholesterol and lowering the LDL-cholesterol levels. No substantial changes were observed in liver hepatotoxicity, urinalysis, and hematology after consumption of amla compared to baseline or placebo. In addition, no adverse events, changes safety parameters or tolerance issues were observed after consumption of amla. In conclusion, amla supplementation showed acceptable palatability, improved endothelial functions and reduced oxidative stress.

Effects of L-Theanine Administration on Stress-Related Symptoms and Cognitive Functions in Healthy Adults: A Randomized Controlled Trial.

This randomized, placebo-controlled, crossover, and double-blind trial aimed to examine the possible effects of four weeks L-theanine administration on stress-related symptoms and cognitive functions in healthy adults. Participants were 30 individuals (nine men and 21 women; age: 48.3 ± 11.9 years) who had no major psychiatric illness. L-theanine (200 mg/day) or placebo tablets were randomly and blindly assigned for four-week administration. For stress-related symptoms, Self-rating Depression Scale, State-Trait Anxiety Inventory-trait, and Pittsburgh Sleep Quality Index (PSQI) scores decreased after L-theanine administration (p = 0.019, 0.006, and 0.013, respectively). The PSQI subscale scores for sleep latency, sleep disturbance, and use of sleep medication reduced after L-theanine administration, compared to the placebo administration (all p < 0.05). For cognitive functions, verbal fluency and executive function scores improved after L-theanine administration (p = 0.001 and 0.031, respectively). Stratified analyses revealed that scores for verbal fluency (p = 0.002), especially letter fluency (p = 0.002), increased after L-theanine administration, compared to the placebo administration, in individuals who were sub-grouped into the lower half by the median split based on the mean pretreatment scores. Our findings suggest that L-theanine has the potential to promote mental health in the general population with stress-related ailments and cognitive impairments.

Effect of Repeated Consumption of Partially Hydrolyzed Guar Gum on Fecal Characteristics and Gut Microbiota: A Randomized, Double-Blind, Placebo-Controlled, and Parallel-Group Clinical Trial.

Partially hydrolyzed guar gum (PHGG) is a water-soluble dietary fiber and is used in solid and liquid food to regulate gut function. The aim of this study was to investigate effects of PHGG on bowel movements (stool form and frequency), plasma bile acids, quality of life, and gut microbiota of healthy volunteers with a tendency toward diarrhea, i.e., irritable bowel syndrome diarrhea (IBS-D)-like symptoms. A randomized, double-blind, placebo-controlled, and parallel trial was performed on 44 healthy volunteers (22 males, 22 females, 41.9 ± 6.3 years old (average ± SD)) with minimum 7 bowel movements every week, wherein above 50% of their stool was between the Bristol stool scale (BSS) value of 5 and 6. Intake of the PHGG for 3 months significantly improved stool form, evaluated using BSS, and had no effects on stool frequency. BSS was significantly normalized in the group consuming the PHGG compared with the placebo. Comprehensive fecal microbiome analysis by the 16S rRNA-sequence method detected significant changes in the ratio of some bacteria, such as an increase of Bifidobacterium (p < 0.05) in the PHGG group. Our results suggest that intake of PHGG improves human stool form via regulating intestinal microbiota.

Randomized controlled trial of a water-soluble formulation of lutein in humans.

Lutein is poorly absorbed owing to their high hydrophobicity and crystallinity. This double-blind crossover trial involved eight healthy males who were administrated capsules containing either a lutein water-soluble formulation or a lutein oil suspension for 8 days. In the formulation group, plasma and erythrocytes lutein concentrations and baseline-corrected AUC were two-fold higher than those in the oil suspension group.

Dietary supplementation with partially hydrolyzed guar gum helps improve constipation and gut dysbiosis symptoms and behavioral irritability in children with autism spectrum disorder.

Prebiotic dietary water-soluble fiber obtained from partially hydrolyzed guar gum was added to diets of children with autism spectrum disorders who presented constipation symptoms. Supplementation with partially hydrolyzed guar gum altered gut microbiota and significantly increased the frequency of defecation per week and altered the gut microbiota. In addition, supplementation with partially hydrolyzed guar gum significantly (p<0.05) decreased and tended to decrease (p = 0.07) the concentrations of serum interleukin-1ß and tumor necrosis factor-α, respectively. More importantly, supplementation with partially hydrolyzed guar gum significantly ameliorated behavioral irritability as per the Aberrant Behavior Checklist, Japanese Version. The present study demonstrated that supplementation with partially hydrolyzed guar gum to diets of constipated autism spectrum disorders children helped improve constipation and gut dysbiosis symptoms, which in turn helped attenuate the level of serum inflammation cytokines and behavioral irritability.

Partially hydrolysed guar gum ameliorates murine intestinal inflammation in association with modulating luminal microbiota and SCFA.

Partially hydrolysed guar gum (PHGG), a water-soluble dietary fibre produced by the controlled partial enzymatic hydrolysis of guar gum beans, has various physiological roles. This study aimed to elucidate the beneficial effects of PHGG on colonic mucosal damage in a murine 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced colitis model. Acute colitis was induced in male C57BL/6 mice with TNBS after 2 weeks of pre-feeding with PHGG (5 %). The colonic mucosal inflammation was evaluated using macroscopic damage scores, and neutrophil infiltration was assessed by measuring tissue-associated myeloperoxidase (MPO) activity in the colonic mucosa. TNF-α expression in the colonic mucosa was measured by ELISA and real-time PCR. Moreover, the intestinal microbiota and production of SCFA were assessed by real-time PCR and HPLC, respectively. Colonic damage due to TNBS administration was significantly ameliorated by PHGG treatment. Furthermore, PHGG significantly inhibited increases in MPO activity and TNF-α protein and mRNA expression in the colonic mucosa in TNBS-induced colitis. On analysis of intestinal microbiota, we found that the concentration of the Clostridium coccoides group (Clostridium cluster XIVa), the Clostridium leptum subgroup (Clostridium cluster IV) and the Bacteroides fragilis group had significantly increased in PHGG-fed mice. On analysis of SCFA, we found that the caecal content of acetic acid, propionic acid and butyric acid had significantly increased in PHGG-fed mice. Together, these results suggest that chronic ingestion of PHGG prevents the development of TNBS-induced colitis in mice by modulating the intestinal microbiota and SCFA, which may be significant in the development of therapeutics for inflammatory bowel disease.

A local bone anabolic effect of rhFGF2-impregnated gelatin hydrogel by promoting cell proliferation and coordinating osteoblastic differentiation.

UNLABELLED: The bone anabolic effect of rhFGF2 is attributed to activation of proliferation and differentiation of osteoblasts. Concomitant up-regulation of Runx2 and Bmp2 implies a coordinative function of FGF/FGFR signaling on osteoblast differentiation. INTRODUCTION: Duration and tissue concentration of growth factor exposure are important in tissue regeneration. This study analyzed the availability of rhFGF2 using a sustained release gelatin hydrogel system. To examine biological aspects of the bone anabolic effect, we carried out morphological and cell proliferation assays together with gene expression analyses of osteoblast related genes induced by rhFGF2 using localizing and quantifying procedures in vivo. MATERIALS AND METHODS: Bone formation induced by implantation of gelatin hydrogel impregnated with 20 microg rhFGF2 (rhFGF2(+)) onto mice maxillae was analyzed by micro computed tomography, proliferating cell nuclear antigen (PCNA) immunohistochemistry, in situ hybridization and quantitative real time polymerase chain reaction combined with laser microdissection (LMD-QPCR). RESULTS: The bony maxilla was augmented to 1.58 times its original volume (p=0.002) by the implantation of rhFGF2(+) gelatin hydrogel. An increased number of PCNA-positive nuclei were observed among differentiated osteoblasts as well as undifferentiated mesenchymal cells. Fgfr1, Fgfr2 and Runx2 were shown to be co-expressed mainly in differentiated osteoblasts but also in osteoblast marker-negative spindle-shaped cells that were scattered within the outer layer of hyperplastic periosteum. LMD-QPCR revealed up-regulation of Bmp2 expression accompanied by increased transcription of Fgfr1, Fgfr2 and Runx2 by rhFGF2 controlled release. CONCLUSIONS: rhFGF2 sustained release results in bone formation on the maxilla by positively regulating the expansion and differentiation of osteoblastic cells. It is suggested that FGF/FGFR signaling coordinates a bone anabolic effect by simultaneously activating RUNX2 and BMP2 pathways. The gelatin hydrogel system, which enables a sustained slow rate of release of rhFGF2 in tissue has advantages of optimizing bone regeneration.

Controlled-release of epidermal growth factor from cationized gelatin hydrogel enhances corneal epithelial wound healing.

We designed a new ophthalmic drug-delivery system for epidermal growth factor (EGF) from the biodegradable hydrogel of cationized gelatin. We placed a cationized gelatin hydrogel (CGH) with incorporated (125)I-labelled EGF in the conjunctival sac of mice and measured the residual radioactivity at different times to evaluate the in vivo profile of EGF release. Approximately 60-67% and 10-12% of EGF applied initially remained 1 and 7 days after application, respectively; whereas EGF delivered in topically applied solution or via EGF impregnation of soft contact lenses disappeared within the first day. We also placed CGH films with 5.0 mug of incorporated EGF on round corneal defects in rabbits to evaluate the healing process using image analysis software and to assess epithelial proliferation immunohistochemically by counting the number of Ki67-positive cells. The application of a CGH film with incorporated EGF resulted in a reduction in the epithelial defect in rabbit corneas accompanied by significantly enhanced epithelial proliferation compared with the reduction seen after the topical application of EGF solution or the placement of an EGF-free CGH film. The controlled release of EGF from a CGH placed over a corneal epithelial defect accelerated ocular surface wound healing.